Datasets:

farleyknight

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big_patent_10_percent

like 1

the following description of the preferred embodiment ( s ) is merely exemplary in nature and is in no way intended to limit the disclosure , its application , or uses . fig1 and 2 show the soft tissue manipulator instrument 10 of the present disclosure . the instrument 10 includes a handle 11 and a shaft 12 coupled to the handle 11 . the instrument 10 includes a cannulation 14 that extends the entire length of the instrument 10 . the shaft 12 includes a proximal portion 12 a coupled to the handle 11 and a distal portion 12 b . the distal portion 12 b includes a tip 13 having prongs 13 a and a channel 13 b located between the prongs 13 b . fig3 a - 3c show three tips 13 , all of which have a different outer width w . for the purposes of this disclosure , the widths w of the tips 13 are 4 . 5 mm , 5 . 0 mm , and 5 . 5 mm . however , other widths w may be used . as will be described further below , the choice of which instrument 10 to use will depend on the diameter of the soft tissue that is being repaired . in addition , fig1 a shows markings 12 b ′, and numbers correlating with those markings , located at the distal portion 12 b of the shaft 12 . as will be further described below , the markings 12 b ′ are used to determine the depth of a bone hole during repair . fig4 a and 4b show the guide assembly 20 of the present disclosure . the assembly 20 includes a guide wire 21 having a proximal portion 21 a and a distal portion 21 b . coupled to the proximal portion 21 a of the guide wire 21 is a wire vice 22 . the vice 22 includes a top portion 22 a , a bottom portion 22 b , a channel 22 c that houses the proximal portion 21 a of the guide wire 21 , a hole 22 d extending perpendicular to the channel 22 c and having threads on an inner surface 22 d ′ of the hole 22 d , and a knob assembly 22 e housed within the hole 22 d . the assembly 22 e includes a knob 22 f and a pin 22 g coupled to the knob 22 f . the pin 22 g includes a proximal portion 22 g ′ coupled to the knob 22 f and a distal portion 22 g ″ having threads that are engaged with the threads on the inner surface 22 d ′ of the hole 22 d . prior to use of the guide assembly 20 during repair , the proximal portion 21 a of the guide wire 21 is disposed within the channel 22 c of the vice 22 and the knob 22 f of the knob assembly 22 e is rotated until the distal portion 22 g ″ of the pin 22 g abuts the proximal portion 21 a of the guide wire 21 , thereby coupling the assembly 22 e to the proximal portion 21 a of the guide wire 21 . fig5 a and 5b show the soft tissue manipulator assembly 30 of the present disclosure . as will be further described below , the assembly 30 is used to insert tissue into bone . fig6 - 12 show a method of soft tissue repair . fig6 and 6a show the soft tissue instrument 10 and a drill bit 40 disposed within the cannulation 14 of the instrument 10 . the drill bit 40 includes a proximal portion 41 and a distal portion 42 having threads 43 . the instrument 10 is used as a guide for placement of the drill bit 40 into bone 50 . once the drill bit 40 is disposed in the instrument 10 , as shown in fig6 , a drill ( not shown ) coupled to the proximal portion 41 of the bit 40 and is operated to rotate the bit 40 and advance the bit 40 into the bone 50 . for the purposes of this disclosure , the drill bit 40 is 2 . 4 mm in diameter , but other diameter drill bits may be used . once the bit 40 is advanced into the bone 50 , the instrument 10 is removed while the drill bit 40 is maintained in bone 50 . as shown in fig7 and 7a , a cannulated reamer 60 is disposed over the drill bit 40 and is used to provide the create a hole 51 in the bone 50 . the reamer 60 includes a distal portion 61 having threads 61 a and a proximal portion 62 . once the reamer 60 is disposed over the drill bit 40 , a drill ( not shown ) is then coupled to the proximal portion 62 and operated to rotate the reamer 60 and advance the reamer 60 into the bone 50 , thereby creating the hole 51 . for the purposes of this disclosure , the diameter of the reamer 60 is 6 - 8 mm , however the diameter is dependent on the diameter of the soft tissue that is placed within the hole 50 , as will be further described below . therefore , other diameter reamers may be used . in addition , the distal portion 61 of the reamer 60 may include number markings , similar to the markings 12 b ′ described above , for measuring the depth of the reamer 60 as it is being advanced into the bone 50 . once the reamer 60 and the drill bit 40 have been removed from the bone 50 , the soft tissue manipulator instrument 10 is used to manipulate the soft tissue 70 and place the soft tissue 70 within the channel 13 b . the shaft 12 of the instrument 10 and the soft tissue 70 are then placed within the hole 51 and the guide assembly 20 is placed within the cannulation 14 of the instrument 10 until the bottom portion 22 b of the vice 22 abuts the handle 11 of the instrument 10 , as shown in fig8 . at the same time , the distal portion 21 b of the wire 21 is inserted through the soft tissue 70 and subsequently disposed within the bone 50 lying beneath the hole 51 , as shown in fig8 a . the distal portion 21 b of the wire 21 is inserted into the bone 50 by tapping the top portion 22 a of the vice 22 with a mallet , or another striking force , until the bottom portion 22 b abuts the handle 11 . the vice 22 acts as a depth stop in limiting the depth of the distal portion 21 b of the wire 21 into the bone 50 . other factors that limit the depth of the distal portion 21 b into the bone 50 include , without limitation , the length of the wire 21 , the length of the instrument 10 , and the depth of the channel 22 a . fig9 and 9a show that the vice 22 has been removed from the proximal portion 21 a of the wire 21 by disengaging the pin 22 g from the wire 21 and uncoupling the vice 22 from the proximal portion 21 a . the instrument 10 has also been removed from the hole 51 , thereby leaving the wire 21 alone in the hole 51 . the wire 21 is subsequently used to guide the insertion of a fixation device 80 , such as an interference screw , into the hole 51 , as shown in fig1 and 10a . a driver assembly 90 , which includes a cannulated driver 91 having a handle 91 a and a shaft 91 b coupled to the handle 91 a and the cannulated fixation device 80 coupled to the shaft 91 b , is disposed over the wire 21 . the driver 91 is rotated to insert the device 80 into the hole 51 , such that the threaded outer surface 81 of the device 80 is engaged with the soft tissue 70 , thereby fixating the soft tissue 70 to the bone 50 . after insertion of the device 80 into the hole 51 , the driver 91 and the wire 21 are both removed from the bone 50 , thereby leaving the device 80 within the hole , as shown in fig1 - 11a and 12 - 12 a . the wire 21 is removed by placing the proximal portion 21 a into the channel 22 c of the vice 22 , rotating the knob 22 f to couple the assembly 22 e to the wire 21 , and then using the assembly 22 e to remove the wire 21 from the hole 50 . other methods of removing the wire 21 are also within the scope of this disclosure . the soft tissue manipulator instrument 10 and drill hit 40 are made from a biocompatible material , such as titanium , stainless steel , or other biocompatible material and via a machining process or other process known to one of skill in the art . a combination of processes may also be used to make the instrument 10 and drill bit 40 . the cannulation 14 and channel 13 b are formed during or after the machining process via a method , such as drilling . the markings 12 b ′ and associated numbers are formed by a laser or another method and the threads 43 are formed via a machining process . the guide assembly 20 and its components and the reamer 60 are also made from a biocompatible material , such as titanium , stainless steel , or other biocompatible material and via a machining process or other process known to one of skill in the art . a combination of processes may also be used to make the assembly 20 and reamer 60 . the channel 22 c , hole 22 d , cannulation , and threads on the inner surface 22 d ′ of the hole 22 d , the distal portion 22 g ″ of the pin 22 g , and the reamer 60 are formed during or after the machining process via a process , such as drilling or other process known to one of skill in the art . the fixation device 80 is made from a resorbable polymer material . however , a metal material and other non - metal materials , either resorbable or non - resorbable , are also within the scope of this disclosure . in addition , the device 80 may be made via a molding process or other process known to one of skill in the art . the cannulation and threads on the outer surface 81 of the device 80 may be formed during the molding process or after the molding process by drilling or machining . as various modifications could be made to the exemplary embodiments , as described above with reference to the corresponding illustrations , without departing from the scope of the disclosure , it is intended that all matter contained in the foregoing description and shown in the accompanying drawings shall be interpreted as illustrative rather than limiting . thus , the breadth and scope of the present disclosure should not be limited by any of the above - described exemplary embodiments , but should be defined only in accordance with the following claims appended hereto and their equivalents .

the present disclosure relates to an instrument and method of manipulating soft tissue during a soft tissue repair procedure . the instrument and related method may include use of a handle and a shaft coupled to the handle , the shaft including a proximal portion and a distal portion , wherein the distal portion of the shaft comprises a tip including at least two prongs and a channel located between the prongs .

now with reference to the drawings , a golf target trainer comprising a golf stance machine incorporating the principles and concepts of the present invention and generally referred to by the reference numeral 10 will be described in detail . with particular reference to fig1 through 4 , the golf stance machine 10 will be seen to include a main elongated linear frame element in the form of tubular bar 12 which mounts the various components of the machine . a first foot stance indicator bar 14 is fixedly attached to bar 12 and extends obliquely from the bar for indicating the appropriate position for the golfer &# 39 ; s forward foot . bar 14 is also a rectangular tubular member . a second foot stance indicator 16 is attached to a rectangular sleeve 18 which slides longitudinally of the bar 12 . graduations generally shown at 20 extend along bar 12 to indicate the distance or separation between the foot stance indicators 14 and 16 . a thumbscrew 22 can be tightened to secure bar 16 in place . assuming the golfer to be right handed , the inside of the golfer &# 39 ; s left foot would be disposed against foot stance indicator 14 with the tip of the left foot being placed directly against bar 12 . the outside of the golfer &# 39 ; s right foot would be placed against the bar 16 . in order to prevent the golfer from shifting the body weight to the outside of the right foot during the back swing and to prevent the right knee from straightening up during the back swing , a wedge 24 can be laid on bar 16 as shown in fig1 and 9 . wedge 24 has a rectangular recess 26 formed in the bottom thereof in order to fit snugly on bar 16 and prevent sideways movement of the wedge due to the golfer &# 39 ; s weight disposed thereon . the golfer merely puts his right foot on the wedge instead of placing the outside of the right foot against bar 16 . wedge 24 is preferably made from hardwood and is small enough to store easily in a golf bag . a brace 27 also comprises a hollow tube and is fixedly mounted to foot stance indicator bar 14 and bar 12 . brace 27 receives telescopically therein a ball location indicator bar 28 which is held in position by a thumbscrew 30 . indicator bar 28 is used to align the golf ball 32 with the heel of the golfer &# 39 ; s left foot . if the ball is to be placed between the left and right feet of the golfer , a second indicator bar 34 is used . bar 34 is received in a tubular member 36 which is slidably mounted to frame member 12 by sleeve 38 attached about the frame . thumbscrews 40 and 42 secure the indicator to the tubular member 36 and the sleeve 38 to frame member 12 , respectively . accordingly , it can be seen that the ball 32 is to be positioned between the feet of the golfer , sleeve 38 is simply located at the appropriate position between the golfer &# 39 ; s feet with scale 20 providing an accurate measure . in this manner , the same ball position can be accurately reproduced each time a similar shot is to be taken . at the front end of the frame member 12 , a sliding tubular bar 44 is mounted in sleeve 46 and held in place by thumbscrew 48 . bar 44 extends perpendicular to bar 12 and serves to measure the distance that ball 32 is placed from the golfer &# 39 ; s feet . bar 44 contains graduated markings 50 to serve as a visual indicator for setting bar 44 . an alignment element 52 is slidably received in the sleeve 54 through which a thumbscrew 56 extends . element 52 serves two purposes . first , it serves to locate more accurately the exact position which the golf ball 32 is to be placed away from the golfer &# 39 ; s feet . second , by sighting along element 52 , the golfer can be made aware of the exact target line along which the shot is to be taken . element 52 can be adjusted toward the ball as close as the golfer chooses , but most golfers will not want that element closer than about 12 &# 34 ;. on the opposite end of the main frame element 12 , there is mounted an additional graduated bar 58 which extends perpendicularly to the element 12 through sleeve 60 and is held in place by thumbscrew 62 . a second alignment element 64 slides through sleeve 66 and is held in place by thumbscrew 68 . alignment element 64 can be aligned with element 52 by proper adjustment of bar 58 . this position will enable the golfer to see and identify the correct target line on the back swing . accordingly , element 52 gives the forward swing line while element 64 gives the correct back swing line . alternatively , element 64 can be moved approximately 2 &# 34 ; further from the golfer &# 39 ; s feet by adjustment of bar 58 . this disposition is shown in fig1 . element 64 can then be extended up to and past the golf ball and defines the outside line of the back swing . the fundamentally correct back swing will start and move along element 64 in a straight line for the first 6 &# 34 ; to 12 &# 34 ;. after the golf stroke has been taken , the golfer can look at the divot in relation to element 64 and get additional feedback on what actually happens during the swing . fig5 shows the set up for the drive and all full shots . in fig5 it can be seen that ball location indicator 28 is used to align the ball 32 with the inside of the left heel of the golfer . the golfer will set his feet into position by placing the inside of the left foot against element 14 and the tip of his left foot about 1 &# 34 ; back from element 12 . the outside of the right foot should be placed against element 16 with the tip of the right foot 1 &# 34 ; from element 12 . the toes of both feet should be set back approximately 1 &# 34 ; from the frame member 12 so that the golfer can move his feet normally during a golf swing . foot stance indicator element 16 should be adjusted to the proper width of the golfer &# 39 ; s stance . element 16 will adjust to any width that is necessary for different club lengths and for varied physical makeup of the golfer . the adjustment is effected by loosening the thumbscrew 22 and sliding the element to the desired position . the markings on element 12 are in inches so that the golfer can learn how far to set his feet apart for each club by looking at these inch markings . the position of alignment elements 52 and 64 should be set according to the discussion had hereinabove . fig6 shows the set up for chip and pitch shots using a normal trajectory . the set up in fig6 is similar to that in fig5 except that element 16 is moved slightly closer to element 14 so that the golfer &# 39 ; s feet are slightly closer together . further , elements 44 and 52 are moved in toward the golfer &# 39 ; s feet to compensate for the shorter length of the golf club . again , the ball 32 is aligned with the heel of the golfer &# 39 ; s left foot by placing the ball in alignment with element 28 . fig7 shows a set up of the golf stance machine for use in putting . in the set up of fig7 elements 16 , 34 and 36 should be removed so that the alignment element 52 can be placed in close proximity to the golfer &# 39 ; s feet . element 52 is then set approximately 2 &# 34 ; inside the eye line of the golfer . element 64 should be set approximately 2 &# 34 ; outside of the eye line of the golfer . element 64 should be extended up to element 44 and element 52 should be extended to element 58 . the golfer should set his feet toward the right end of element 12 with the toes of both feet against element 12 . to execute a putt , the golfer should place the ball 32 between elements 52 and 64 and take the putter straight back in the channels formed between the elements 52 and 64 . the golfer should also keep the putter going straight forward along that channel after he has actually hit the putt . the middle of the opening formed by the ends of elements 52 and 64 visually provide a perfect intermediate target . if the golfer can roll the ball straight through the middle of this opening labelled 70 , the ball should continue to roll straight for the target . fig8 shows the golf stance machine set for a typical shot having a lower than normal trajectory . in such circumstances , the machine 10 is set for the shot using standard set up procedures . ball location indicator 28 is slid into brace 27 and elements 34 and 36 are placed on the frame member 12 . using the inch markings on member 12 , the second ball position indicator comprising elements 34 and 36 is slid between the golfer &# 39 ; s feet to the desired location . the further to the right indicator 34 , 36 is positioned , the lower the flight trajectory will be . element 34 is extended out from element 36 to provide an accurate indicator to position the golf ball 32 . this procedure can be used for any golf club . fig9 shows the use of wedge 24 with the golf stance machine . as discussed above , wedge 24 is placed on foot stance indicator 16 in order that the right foot of the golf will be slightly inward . wedge 24 can help train the golfer to keep the weight on the inside of the right foot throughout the back swaying or to stop swing . wedge 24 will also help train the golfer to keep his right knee flexed throughout the back swing . these results can be accomplished by the golfer placing his right foot completely on wedge 24 initially . as the golfer improves , he can place less of his foot on the wedge and place more of his foot on the ground , until his entire right foot is almost completely on the ground . it should also noted that by loosening all of the thumbscrews , the elements of the golf stance machine 10 can be completely disassembled and carried easily in a golf bag . when assembling , the machine 10 can be put together for use either by right handed or left handed golfers by merely properly orienting main frame member 12 . the foregoing is cosidered as illustrative only of the principles of the invention . further , since numerous modifications and changes will readily occur to those skilled in the art , it is not desired to limit the invention to the exact construction and operation shown and described , and accordingly , all suitable modifications and equivalents may be resorted to , falling within the scope of the invention .

a device for properly orienting the feet of a golfer with respect to the golf ball to be struck . indicators are provided which mount to a longitudinally extending main frame member . one indicator is fixed to the main frame member and extends laterally therefrom at a predetermined angle . the player &# 39 ; s left foot is placed against this indicator . a second indicator slides along the frame member and the right foot abuts this indicator . further indicators are provided for pointing out the location between the player &# 39 ; s feet at which the ball is to be placed and the distance that the ball should be placed from the feet . the various indicators can be moved to positions for aligning a broad range of golf shots from drives to putts .

the preferred embodiment of the present invention is illustrated in fig1 - 8 . fig1 shows an imaging system 1 having a control room 2 , a scan room 3 and a penetration panel 4 situated between control room 2 and scan room 3 . scan room 3 includes scan table 5 upon which is placed a patient 6 undergoing imaging . in this case , a set of inflatable cuffs 40 is placed around the lower extremities 7 of patient 6 . inflatable cuffs 40 include a right upper cuff 41 , a left upper cuff 42 , a right middle cuff 43 , a left middle cuff 44 , a right lower cuff 45 , and a left lower cuff 46 . the inflatable cuffs 40 may be wide like a blood pressure cuff or narrow like a tourniquet band . although inflatable cuffs are preferred , it will be understood by those skilled in the art that any cuff or band capable of tightening around an extremity to impede blood flow through the extremity can be used . for instance , the cuff or band may be made out of a resilient and stretchable material such as rubber . inflatable cuffs 40 are connected to a cuff controller unit 30 by way of a control line system 50 . control line system 50 includes a first control line 51 for controlling right upper cuff 41 and left upper cuff 42 , a second control line 52 for controlling right middle cuff 43 and left middle cuff 44 , and a third control line 53 for controlling right lower cuff 45 and left lower cuff 46 . each of the control lines 51 , 52 and 53 incorporates separate control lines for the right and left cuff thereby allowing each cuff to be activated and controlled independently , if desired . cuff controller unit 30 inflates and deflates inflatable cuffs 40 at predetermined times relative to the injection of intravenous contrast agent , depending on the imaging detail wanted . the amount of inflation pressure required to impair blood flow in the arteries of the lower extremity to enhance imaging may vary . for instance , raising pressure above the venous pressure by just a few millimeters of mercury may be sufficient to achieve the desired effect . in other cases , it might be necessary to totally occlude the arterial blood flow , in which case it would be necessary to raise the pressure just above the arterial systolic blood pressure , i . e . approximately 110 mm to approximately 200 mm hg . a fluid material such as gases or liquids may be used to operate inflatable cuffs 40 . examples of usable gases are air , compressed air , helium , nitrogen , carbon dioxide , and the like . examples of usable liquids are water , oil and the like . preferably , a compressor is used to inflate inflatable cuffs 40 using compressed air . control room 2 includes the system controller 10 that controls the operation of imaging system 1 . system controller 10 , which is programmed by an operator , controls and activates cuff controller unit 30 . coupling of system controller 10 to cuff controller unit 30 is accomplished though an interface coupler 20 . interface coupler 20 may couple system controller 10 to cuff controller unit 30 in any number of ways . examples of such interface coupling are the use of cabling through penetration panel 4 , the use of electromagnetic control ( e . g . infrared ) through a window ( not shown ), or the use of optical fiber through a wave - guide . turning now to fig2 inflatable cuff system 40 is shown incorporated into a lower extremity peripheral vascular rf coil array . because an entire lower extremity is too long to be imaged in its entirety at one instant by an imaging system , the scanner and table area must be moved and be able to follow the contrast material as it flows from thigh to lower leg to foot . the system may have a single coil or multiple coil arrays for imaging the entire lower extremity . in the present invention , patient table 5 includes inflatable cuffs 41 , 42 , 43 , 44 , 45 , and 46 as well as the five pairs of rf coils 8 a , 8 b , 8 c , 8 d , and 8 e that comprise the lower half of the phased - array rf coils 8 . the lower rf coils 8 are paired to image the right and left extremity simultaneously , if desired . each pair of rf coils is activated when the contrast agent is within the segment of the extremity that is within the field of view of that particular pair . generally , only one pair of rf coils is activated at a time . each inflatable cuff can be activated independent of the other cuffs . fig3 shows placement of the lower extremities 7 within inflatable cuffs 40 . fig4 shows the relationship among the inflatable cuffs 40 , the lower extremities 7 , and the upper and lower halves of rf coils 8 and 9 . the inflatable cuffs may also be entirely separate and secured to the lower extremity by simple wrapping . alternatively , the inflatable cuffs can be incorporated into the patient table by way of pivoting bands or leg enclosures . fig5 a and 5b illustrate one embodiment of such a pivoting band enclosure . fig5 a ( closed position ) and 5 b ( open position ) show a pivoting band enclosure system 120 having an outer rigid frame 121 that has an arcuate shape with a pivot 126 affixed to patient table 5 . within the outer rigid frame 121 is situated an inflatable cuff 122 . patient table 5 may include one or more of pivoting band enclosure system 120 . inflatable cuff 122 has mating fasteners 124 that allow inflatable cuff 122 to fasten upon itself and completely encircle the extremity . preferably , the mating fasteners 124 are hook and loop type fasteners . where a leg enclosure embodiment is used , patient table 5 would include a pivoting leg enclosure for each extremity and each enclosure would include one or more of inflatable cuff 122 positioned along the inside of the leg enclosure at appropriate and predetermined locations . an alternative embodiment of the band or leg enclosure system shown in fig5 a and 5b is the band or leg enclosure system shown in fig6 a and 6b . the band enclosure system 130 includes a first cuff frame 131 connected to patient table 5 by first frame pivot 135 , a second cuff frame 132 connected to patient table 5 by second frame pivot 136 , and an inflatable cuff 134 . inflatable cuff 134 is coupled to first cuff frame 131 and second cuff frame 132 so that ends 137 of band enclosure system 130 are in an opposed relationship when first and second cuff frames 131 and 132 swing from an open position as shown in fig6 b to a closed position as shown in fig6 a thereby encircling the patient &# 39 ; s extremity when in use . where a full - length extremity enclosure system is used having a similar first and second cuff frame structure , one or more inflatable cuffs are situated at predetermined locations along the extremity cuff frame of the extremity enclosure system . an alternative local coil and cuff structure that moves with the patient may also be used . referring now to fig7 a and 7b , this alternative local coil and cuff is a coil array comprised of five coil segments 80 - 84 , each comprised of four coil elements . coil segments 80 - 84 are positioned on the patient and distributed along the entire region of interest to be imaged . in this case , it is the legs and the feet . also incorporated is an inflatable cuff array comprised of three cuff components 90 - 92 , each comprised of two cuff elements , one for each extremity . cuff components 90 - 92 are positioned along the extremity to provide pressure before , during or after the infusion of an intravenous contrast agent . the coils and cuffs are supported by fabric ( not shown ) that is sewn into a stocking - like or pant - like garment that clothes one or more of the patient &# 39 ; s legs . each coil segment 80 - 84 has four coil elements that acquire nmr data from the field of view . two of the coil elements are positioned on top , or anterior , of the lower extremity as seen in fig7 b , and the other two elements are positioned below , or posterior , of the lower extremity . the coil elements connect together to form one of the coil segments 80 - 84 and each is separately connected through terminals 85 to the imaging system 1 . each cuff component 90 - 92 has two cuff elements that are capable of obstructing blood flow to a portion of each extremity . one of the cuff elements is positioned around one extremity and the other cuff element is positioned around the other extremity . each cuff element is connected to the compressor by way of terminals 95 and each can be individually controlled , or can be controlled simultaneously , to obstruct blood flow to a portion of the extremity before , during or after introduction of the intravenous contrast agent . another embodiment of the present invention for use with existing imaging machines is illustrated in fig8 . this particular embodiment incorporates one or more compression bands or cuffs 102 , 104 and 106 in a stocking - like or pant - like structure 100 that extends from the foot to either the inguinal or waist area . the stocking - like or pant - like garment is worn by the patient and each compression band or cuff 102 , 104 and 106 is connected by way of couplers 108 to the cuff controlling unit . in the stocking - like embodiment , the stocking may be slipped on over the extremity like a tube of fabric , or the garment may have a releasable seam along its length , or the garment may be more like a wrap that wraps around the extremity much like a blood - pressure cuff wraps around the upper arm . the releasable seam allows the extremity to be enclosed without sliding the stocking - like or pant - like garment over the entire length of the extremity . the releasable seam may be fastened using a zipper , a plurality of snaps or buttons , or hook and loop fasteners placed along the length of the seam or strategically placed to coincide with the inflatable cuffs like that used for blood pressure cuffs . as described earlier , the timing for activating one or more of the pressure cuffs in any of the embodiments depends on the image optimization required , i . e . the pressure is optimized to image certain portions of the lower extremity vasculature such as proximal arteries versus distal arteries , arteries versus veins , etc . although the preferred embodiments of the present invention have been described herein , the above description is merely illustrative . further modification of the invention herein disclosed will occur to those skilled in the respective arts and all such modifications are deemed to be within the scope of the present invention as defined by the appended claims .

the apparatus and method alters the intravenous delivery of pharmaceuticals to enhance imaging of the vasculature of an animal . the apparatus includes a pressure - inducing component that is sized to attach circumferentially to an extremity of an animal thereby impeding arterial blood flow causing said pharmaceuticals to remain at selected levels within the vasculature .

fig1 labels the disposable gloves according to a first embodiment of this invention with reference number 5 . they have two congruent plastic films 6 , 7 which are rectangular in a plan view and which are joined to one another securely by cementing or by bonding or by sealing in the edge areas 8 with the formation of an outside ( back side ) 9 and an inside ( palm side ) 10 , leaving a glove opening 11 . furthermore , the glove 5 as claimed in the invention is provided on the inside 10 externally with an absorbent outside layer 12 which consists of paper ( mat ). the plastic films 6 , 7 are conversely made of polyethylene ( pe ) and are microperforated so that a glove 5 which can to a certain extent breathe is made available which allows air exchange ; this has the positive consequence that unpleasant sweating of the hand in the glove 5 can be prevented . the congruent plastic films 6 , 7 are formed from a plastic web which extends in the lengthwise direction 13 and which is folded in the form of a hose , the folded edge 14 which extends in the lengthwise direction 13 forming the top of the glove 5 in the area of the fingertips and the two edges 15 , 16 which lie opposite the fold edge 14 forming the glove opening 11 . as can be taken from fig2 (= representation along the section line ii — ii from fig1 ) the two edges 15 , 16 which form the glove opening 11 and which lie opposite the fold edge 14 are arranged offset to one another . in this way especially comfortable insertion of the hand into the glove 5 is enabled , since the user of the glove 5 can optionally compensate for the fact that the two plastic films 6 , 7 may adhere to one another by his grasping the projecting edge 16 and gently pulling the two plastic films 6 , 7 apart . the congruent plastic films 6 , 7 which are joined to one another on the lateral edge areas 8 by bonding or by sealing furthermore have in areas a seal seam 17 which runs at a distance from the edge areas 8 and / or from the fold edge 14 , in the first embodiment shown in fig1 to 3 in the form of a mitten . as fig1 shows , there is a host of disposable gloves 5 next to one another in the lengthwise direction 13 of the plastic web , which can be easily separated by one linear perforation 18 at a time which runs essengially at a right angle to the lengthwise direction 13 , but are still joined to one another . as fig1 to 3 further show , on the outside 9 of the glove 5 there are two carrier strips 23 a , 23 b which are located parallel to one another . these carrier strips 23 a , 23 b on the one hand have a stabilizing function , especially when the gloves 5 are unrolled in the lengthwise direction 13 ( compare fig1 and 2 ) and are delivered individually by means of a dispensing device ; on the other hand , the carrier strips 23 a , 23 b can also be used as a holder for the glove 5 , and in an inventive manner also such that there is or are a carrier strip 23 or carrier strips 23 a , 23 b instead of the plastic film 6 which forms the outside 9 ( see fig6 ). in the latter case the hand of the user is inserted between the carrier strips 23 a , 23 b and the plastic film 7 which forms the inside 10 , i . e . the carrier strips 23 a , 23 b then act as holding strips which are pulled over the back of the hand . in the second embodiment which is alternative to fig1 to 3 , in contrast to the first embodiment in which the gloves 5 are arranged horizontally crosswise next to one another , the gloves 50 are arranged in succession horizontally in the lengthwise direction 13 . here the top of the glove 50 which is adjacent to the fingertips is provided with a seal seam 8 which runs transversely to the lengthwise direction 13 . parallel to this seal seam 8 , but on the side facing away from the top of the glove 50 there is a linear perforation 18 which forms the glove opening 11 upon separation . as follows from fig4 the seal seam 17 of the glove 50 in a plan view on both sides of the finger area ( defined by the little finger , ring finger , middle finger and index finger ) has a thumb section 51 which is used to accommodate the thumb and moreover a glove 50 which is to a certain extent mirror - symmetrical with respect to the lengthwise direction 13 . it furthermore follows from fig4 that in the area of the glove opening 11 there is a locking closure with a fixing or closing strip 19 which extends transversely to the insertion direction of the hand . this fixing or closing strip 19 has two ends 19 a , 19 b , one end 19 a being on the side of the glove opening 11 which is the left side in fig4 and the other end 19 b being on the side of the glove opening 11 which is the right side in fig4 . on the one hand , there is no additional material cost associated with providing this fixing or closing strip 19 which is located in the area of the so - called “ turnback ” of the glove 50 and with which the glove opening 11 can be closed after insertion of the hand into the glove 50 , because the material which is necessary for the fixing or closing strip 19 is made available anyway by the plastic films 6 and 7 and otherwise would only be scrap ; on the other hand , by providing the fixing or closing strip 19 and the resulting closing function in the area of the glove opening 11 the hand is reliably prevented from slipping out of the glove 50 since the turnback area which may otherwise tend to uncontrolled flapping and under unfavorable conditions in the extreme case to unwanted incipient tearing , i . e . the area of the glove opening 11 , can be fixed and closed by the fixing or closing strip 19 . in the special embodiment of fig4 one end 19 a is on the side of the glove opening 11 which is the left side in fig4 and the other end 19 b is on the side of the glove opening 11 which is the right side in fig4 . an especially good closing action with reference to the glove opening 11 can be achieved here by the fact that one end 19 a can be turned down onto the other end 19 b and that the two ends 19 a , 19 b can be detachably secured to one another by means of two adhesive strips which are protected against fouling first of all by silicone - treated coverings . in addition , fig5 shows in cross section that on the side of the glove 50 which is opposite the electrostatically chargeable outer layer 12 which is provided with a disinfecting additive , another congruent plastic film 20 with another seal seam 21 which encloses a larger area than the seal seam 17 , but which runs at a distance to the latter to a certain extent parallel , is applied to the two congruent plastic films 6 , 7 . this yields another glove which is produced in one process with a glove opening 52 , this glove being made larger than the glove formed by the two congruent plastic films 6 , 7 . to impart stability of shape to the glove 50 , outside the area of the seal seam 17 ( compare the first embodiment as shown in fig1 to 3 ) or outside the other seal seam 21 ( compare the second embodiment as shown in fig4 and 5 ) there are stabilization connections 22 which are made as seal seams in the second embodiment shown . fig6 shows a cross - sectional view of another embodiment in which the outside layer 12 is applied externally only to the inside or palm side 10 . thus , the area of the parts which are rectangular in a plan view , and which can be separated along the perforation 18 , i . e . the area which remains outside the actual glove 5 or 50 , is stable and is not disruptive when the globe 5 or 50 is being used .

the invention relates to a glove , especially a disposable glove . said glove comprises at least two plastic films of substantially the same dimensions that are firmly linked with each other at least in the lateral marginal zones , thereby defining the inner and the outer face of the glove and leaving free a glove opening . said glove is further characterized by an absorbing exterior layer that is applied on the outer surface that pertains to the back of the hand and / or the inner surface that permits to the palm .

referring more particularly to the drawings by characters of reference , fig1 illustrates the versatile bola assembly of the invention and indicates the alternate use of the specially contrived bola ornament as a pendant to be supported from a chain . as shown in fig1 the bola ornament 10 , which preferably should have a concave rear side to provide room for a clip , may be adjustably attached to the bola cord 11 or it may be supported as a pendant from a separate body attachment means or chain 12 . affixed by soldering or cement to the rear of ornament 10 , as shown in fig2 and 3 , is a retaining wire or frame 13 and a loop or eyelet 14 . frame 13 and eyelet 14 should have low profiles which enhances utility of the ornament 10 for use as a pendant . the retaining wire frame 13 is shaped in the general form of a rectangular picture frame which is longer than it is wide and also somewhat wider at the top than at the bottom . it is attached along the lower two thirds of its two sides by soldering or cement to the rear surface of ornament 10 with frame 13 positioned approximately in the center of the rear surface of ornament 10 . approximately the upper third portion of frame 13 is inclined away from the rear surface of ornament 10 by virtue of a 30 ° to 45 ° bend in each of the side members of frame 13 at positions 15 and 16 , these points lying roughly two - thirds of the way from the bottom to the top of frame 13 . the inclination of the top of frame 13 away from the rear surface of ornament 10 forms a passage 17 between the upper portion of frame 13 and ornament 10 . at the center of the lower member of frame 13 an arched bridge 18 extends perpendicularly from the surface of ornament 10 forming a second smaller passage 19 through the bridge 18 . the eyelet 14 is of a type commonly applied to the rear of pendants for attachment to chains . it is located at the top center of the rear of ornament 10 with its two legs attached one above the other along the centerline of the rear surface of ornament 10 . the frame or clasp member 21 shown in fig5 is formed from a flat piece of metal 22 shown in fig4 . piece 22 has its lower portion shaped in the form of a cross with lower vertical member or tab 23 , upper vertical member 24 and horizontal arms 25 and 26 . projecting upward from the top of member 24 is a center wedge - shaped member 27 which supports at its tapered sides , members 28 and 29 . the division between member 27 and members 28 and 29 are bending lines 31 and 32 , respectively . tapered member 27 is nearly twice as wide at its lower end as at its upper end . members 28 and 29 are elongated and rectangular . member 28 is attached along approximately two - thirds of the length of one of its long edges to one of the tapered edges of member 27 , the lower one - third of the length of member 28 extending beyond the lower extremity of member 27 . member 29 is similarly attached to the opposite tapered side of member 27 . a tab 33 comprising the extension of member 28 beyond the lower extremity of member 27 is separated from the remainder of member 28 by a transverse bending line 34 . similarly , a tab 35 is defined at the lower end of member 29 by a bending line 36 . to form the member 21 from piece 22 , arms 25 and 26 are curled forward so that they will form recesses partially encircling the bola cord 11 . the curved ends 37 and 38 of arms 25 and 26 stop short of completing a circle , however , so that the cord 11 may be forced in and out of these grips with moderate effort . members 28 and 29 are bent forwardly at right angles along lines 31 and 32 and tabs 33 and 35 are then bent inward at right angles along lines 34 and 36 , the members 28 and 29 and the tabs 33 and 35 thus forming a wedge shaped clamping means or block 39 smaller at the top than at the bottom . to assemble the bola cord 11 with the clasp member 21 and the ornament 10 , the cord 11 and the member 21 are first attached to each other . with clasp member 21 oriented as shown in fig5 the block 39 directed upward , and with the loop of the cord 11 held upward , the two halves of the cord 11 are slipped into the encircling grips formed by members 25 and 26 of clasp member 21 . member 23 of clasp member 21 is then passed downward through passage 19 of ornament 10 as formed by the arch 18 of frame 13 . finally , the loop of cord 11 is passed upward through passage 17 and drawn tautly upward until the two sides of the cord 11 fall into position between the outer surfaces of block 39 and the inside surfaces of frame 13 as shown in fig6 . when thus assembled , the cord is gripped between block 39 and the inside of frame 13 , the projection of block 39 being of sufficient height to prevent its passing through passage 17 . the gripping force applied to cord 11 is increased as wedge - shaped block 39 is forced upward and is released as block 39 is forced downward . during normal use as suspended by cord 11 around the wearer &# 39 ; s neck , the weight of ornament 10 urges ornament 10 downward against the block 39 thereby sustaining the gripping pressure . a simple and effective bola clasp is thus provided in the combination of the second frame member 21 and the first frame member 13 as attached to ornament 10 . each of the two parts 13 and 21 is of simple and inexpensive construction , each comprising a single member . both the assembly of the cord 11 and clasp member 21 to the ornament 10 and their disassembly by the reverse procedure may be performed quickly and easily without the hazard of excessive wear , fatigue or damage to any of the parts . with the clasp member 21 and cord 11 removed , the ornament 10 may readily be suspended from a chain 12 utilizing the eyelet 14 , the ornament 10 thus serving alternately as a pendant in accordance with the primary object of the invention . in a second embodiment of the invention as illustrated in fig7 and 9 , a different type of clasp 41 is substituted for the clasp member 21 of fig4 and 6 . the clasp 41 forming a second frame means is an adaptation of a commonly used clasp known as a bennet clip . the bennet clip is a two - part assembly including a channel - shaped body 42 and a pivoting clamping means or tab 43 . as shown in fig7 the channel - shaped body 42 is typically wider at the upper end than at the lower end . the sides 44 and 45 of the body 42 are also tapered , being wider at the upper end . at the center of each of the sides 44 and 45 a semicircular projection 46 extends in the plane of the side member , and in the center of the projection 46 is a small circular hole 47 . the tab 43 is made from a flat piece of metal cut with a slight flare at the outer end and rounded at the outer edge to provide a comfortable grip to be grasped by the fingers . near the opposite end there are two lateral projections , 48 and 49 , one at each side which fit pivotally into the two holes 47 . at the pivotal axis defined by tabs 48 and 49 the end of tab 43 is terminated in a short projection 51 which curls around the pivotal axis stopping just short of a 90 ° bend . the direction taken by the projection 51 is such that as the outer end of tab 43 is directed downward , the direction of the projection 51 is generally inward toward the body 42 . thus , when the cord 11 is passed through the clip 41 , its two sides passing through the channel formed by body 42 and under the tab 43 , the projection 51 is forced against the cord 11 as the tabs 43 is pivoted downward . the force of the projection 51 thus pinches the cord 11 and holds it in place . with the outer end of the tab 43 forced all the way downward , the projection 51 has moved past the point at which it was perpendicular with the edge of the cord so that the tab position is stabilized or locked and cannot come undone by itself . a slight outward bend 50 of the outer end of the main body of tab 43 aids in this locking action . the taper of body 42 with its wider upper end accommodates the spreading of the two halves of the cord 11 as they extend upward and outward to encircle the wearer &# 39 ; s neck . the adaptation of the bennet clip for application in this invention includes two modifications : the first is the addition of a tab 52 extending downward from the lower end of the body 42 . the second modification is the increased height of the channel sides 44 and 45 at the upper end of the body 42 . the utility of these modifications becomes apparent when the assembled cord 11 and clip 41 are attached to the ornament 10 as shown in fig9 . the procedure for attaching the ornament 11 to the clip 41 is essentially the same as in the case of the clip 21 : the tab 52 of clip 41 is first passed downward through passage 19 of ornament 10 . the looped end of cord 11 is then passed upward through passage 17 and drawn taut , whereupon the clip 41 falls into position inside the frame 13 . because of the height of the upper ends of the sides 44 and 45 , the clip 41 is restrained from passing upward through the frame 13 while the cord 11 is held against the body of ornament 10 by the upper portion of frame 13 . the combined actions of the tab 52 , the sides 44 and 45 , the frame 13 and the cord 11 thus secure the ornament 10 to the cord 11 and the clip 41 . it will be noted that in the first embodiment the tapered block 39 cooperated with the frame 13 to grip the cord while in the second embodiment the clip 41 provides the total cord gripping action without help from frame 13 . aside from this difference , however , the functions of the two embodiments are substantially the same , both conforming in all respects with the stated objects of the invention . although but two embodiments of the invention have been illustrated and described , it will be apparent to those skilled in the art that various changes and modifications may be made therein without departing from the spirit of the invention or from the scope of the appended claims .

a detachable clip for bola tie together with a fixed cooperative means attached to the rear surface of the ornamental mount thereof for providing a quick and easy conversion of a bola tie to a chain - and - pendant arrangement with the common use of the ornamental portion of the bola tie .

for the purposes of promoting an understanding of the principles of the invention , reference will now be made to the embodiments illustrated in the drawings and described in the following written specification . it is understood that no limitation to the scope of the invention is thereby intended . it is further understood that the present invention includes any alterations and modifications to the illustrated embodiments and includes further applications of the principles of the invention as would normally occur to one skilled in the art to which this invention pertains . in a particular procedure that may incorporate the present invention , an injectable nucleus is surgically introduced into the spine as a replacement for or augment to the natural nucleus pulposus . the injectable nucleus is preferably a curable biocompatible polymer with properties that emulate those of the natural human disc . a suitable injectable nucleus material is disclosed in u . s . pat . nos . 6 , 423 , 333 ; 6 , 033 , 654 ; and 5 , 817 , 303 , which issued to protein polymer technologies , inc . the disclosures of these patents are incorporated herein by reference . these patents disclose a proteinaceous curable polymer that has physical properties close to those of the human disc nucleus pulposus and that includes certain adhesive properties that allow the polymer to adhere to the disc annulus and any remaining disc nucleus pulposus . in a first step of the technique , the constituents of the injectable nucleus material are prepared in a mixing system , such as the mixing system disclosed in co - pending , commonly assigned patent application ser . no . 10 / 803 , 214 , entitled “ systems and methods for mixing fluids ”, the disclosure of which is incorporated herein by reference . the mixing system is placed on the sterile table until it is needed for the mixing and injection step . where the biomaterial is an injectable nucleus , access to the intradiscal space is required . while many surgical approaches may be used , in one specific embodiment , the surgeon will use an extraforaminal mini - open approach to the disc . this may be either by a lateral retroperitoneal approach or a paramedian approach through the paraspinal muscles of the back . access to the nucleus is gained through an extraforaminal annulotomy , so as to not expose the spinal canal or foramen to any undue risk . the annulus is identified and a minimal annulotomy is performed to gain access to the intradiscal space . the nucleus pulposus is then partially or completely removed using known techniques , such as using pituitary rongeurs and / or curettes . the nucleotomy should be fully irrigated once all loose fragments have been manually removed . once a predetermined amount of disc nucleus is removed , the size of the space may be verified , such as by visualization and / or use of a saline injected balloon . when the disc space is ready to receive the injectable nucleus , the disc space may be distracted using several techniques . in one technique , distraction of the disc is accomplished using a non - compliant inflatable spherical balloon , such as a 15 mm diameter spherical balloon . once the desired amount of distraction has been obtained , the distraction tool , such as the spherical balloon , may be removed from the disc . at this point , a trial balloon may be used again to estimate the volume of injectable nucleus needed to the fill the distracted space . with the disc space maintained in distraction ( whether by physical positioning of the patient or by external instrumentation ), the injectable nucleus composition may be mixed and injected into the disc space . thus , an injection needle may be provided as part of an injection assembly 40 , as shown in fig1 . details of the injection assembly 40 may be gleaned from previously incorporated co - pending application ser . no . 11 / 170 , 010 , and particularly the description associated with fig1 - 16 thereof , the disclosure of which is incorporated herein by reference . the injection needle 42 extends through a seal element 46 that is configured to provide an essentially fluid tight seal against the disc annulus a . a vent 44 also extends through the seal 46 . the seal 46 is shown in more detail in fig2 . in a particular form of the construction , the seal 46 includes a body 48 that is preferably formed of a resilient material that can be compressed slightly under manual pressure to conform to the irregular external surface of the disc . the body 48 defines a sealing face 50 that bears against the disc annulus a ( fig1 ) to create a fluid tight seal . extending from the sealing face 50 is an engagement boss 52 . the boss 52 is preferably configured in accordance with the shape of the annulotomy cut into the annulus . as illustrated in fig2 , the boss 52 is also cruciate in shape with wings 53 that are sized to fit within corresponding legs of a cruciate cut into the annulus a . the leading edges 53 a of the wings 53 can be rounded to facilitate placement of the boss 52 within the annulotomy . the vent 44 provides an additional wing 57 for the boss 52 . the wing 57 includes a channel 58 that integrates with the hollow vent 44 . preferably , the vent wing 57 is co - extensive with the other wings of the boss 52 . alternatively , the working end of the wing 57 can project slightly farther into the disc space . the injection needle 42 feeds to a channel 55 defined in the boss 52 to provide a pathway for the injectable nucleus into the disc cavity . in accordance with another aspect of the procedure , the needle is introduced through the annulotomy , while carefully retracting the nerve root , until the seal 46 seats against the annulus . preferably , the needle is positioned so that the vent 44 is facing upward during the injection , as depicted in fig1 . pressure is applied to the seal 46 to ensure that no injectable nucleus leaks out between the seal and annulus . preferably , this pressure is applied manually by the surgeon by simply pressing the injection catheter 42 toward the annulus . since the injectable nucleus injection occurs at low pressures , the amount of force required to maintain a fluid - tight seal between the seal face 50 and the annulus is minimal . the injectable nucleus is injected into the space until injectable nucleus is seen flowing through or out of the vent tube . at this point , the injection is stopped and the needle is held in place until the injectable nucleus takes its initial set . a microscope or loupe may be used to visualize the injection process . the injectable nucleus composition is preferably allowed to substantially completely cure before the injection needle assembly 40 is removed and the surgical site is closed . the cure period depends upon the particular injectable nucleus material . for the specific proteinaceous polymer discussed above , the cure period is a minimum of about five minutes . the seal 46 is formed of a resilient and deformable material so that it can be compressed against the annulus a to form a fluid tight seal . in a particular form , the seal 46 is formed of silastic ® or a similar elastomeric material . the seal 46 in the illustrated embodiment is cylindrical with a circular sealing face 50 ; however , other configurations are contemplated provided they can adequately conform to the outer surface of the disc annulus . the procedures described heretofore are particularly well suited for open surgical procedures where a microdiscectomy is performed to remove all or a portion of the disc nucleus . one such procedure is for the treatment of degenerative disc disease ( ddd ) where a total or partial nucleotomy is indicated . in such an open procedure access to the spinal disc is accomplished through an incision made through the skin and subcutaneous body tissue down to the surgical site is displaced and retracted . in the case of ddd , the annulus is typically relatively intact so that a minimal annulotomy is required to gain access to the intradiscal space . it is preferred that the opening is as small as feasible to minimize damage to the annulus . in one embodiment , access can be via a k - wire over which a dilator , or a series of dilators , is passed . however , the nucleus pulposus may be significantly under - hydrated or may contain fissures throughout the nucleus material , producing patient pain and giving rise to the need for a total or substantially total discectomy . in such a ddd procedure , in addition to the steps described hereinabove , the surgeon may also chose to perform an intraoperative step of determining the integrity of the annulus , to confirm that the annulus is competent to withstand the distraction and injectable nucleus injection pressures . to accomplish this test , upon completion of the partial or total nucleotomy and creation of an intradiscal space within the disc annulus , a saline solution may be injected into the intradiscal space through the annulotomy opening . a saline solution is preferred since it is relatively easy to aspirate for removal from the intradiscal space . however , other suitable solutions may also be used . the saline solution may be injected through a vented needle , in design and construction similar to the needle 40 shown in fig1 - 2 . when the saline injection is under relatively low pressure ( on the order of 25 - 40 psi under thumb pressure from the syringe and pressing the seal 46 against the external surface of the annulus ), this step evaluates the integrity of the disc annulus — i . e ., detects whether fissures or rents may be present in the annulus . this detection may be by tactile feel and / or by observation of leakage only at the injection needle site . alternatively , or additionally , the injected saline solution may be used to determine the volume of the disc space to be filled with injectable nucleus material . if preferred , a trial balloon may be used to ascertain the volume of the intradiscal space to be filled . after the annulus integrity and volume tests have been completed , suction is applied to aspirate the nuclear cavity and a surgical swab may be used to wick away excess moisture that may interfere with the injection of the injectable nucleus material . thereafter , the surgeon may use a distraction balloon to apply a distraction force within the intradiscal space to distract the opposing vertebral bodies on either side of the intradiscal space , further separating apart such vertebral bodies . a subsequent saline test may be conducted to further verify the integrity of the annulus . the injectable nucleus may then be sealably injected under pressure using the vented needle 40 as described hereinabove . such injection of injectable nucleus is preferred to be at a pressure that is not greater than the pressure under which the saline solution is injected and is typically on the order of 25 - 40 psi . while the saline solution has been described as preferably being injected with a vented needle such as described herein , it should be appreciated that a needle without a vent , but with a sealing element , could also be used in the practice of the annulus integrity test . other open surgical procedures are also contemplated , such as an adjunct to microdiscectomy ( amd ) procedure . an amd procedure is indicated where a total discectomy is not required , or more particularly where only a partial discectomy is necessary to restore normal or near normal function to the affected disc . in a typical case , the affected disc has a herniation or tear in the disc annulus . access to the intradiscal space is thus available through the tear in the annulus . prior to the start of the surgery , the injectable curable polymer constituents are pre - loaded into the mixing assembly , as described above , and left on the sterile instrument table until the appropriate time for injection of the injectable nucleus material . the surgeon uses a traditional open or microdiscectomy technique of preference for access to the disc herniation site . typically , the patient will be placed on a laminectomy frame in the prone position with the spine flexed to aid intraoperative exposure . the ligamentum flavum and laminar edge are identified . a hemilaminectomy / medial facetectomy may be performed as necessary , with the aid of lateral fluoroscopy . exposure of the hernia proceeds in a known manner , taking care to protect the dura and nerve root . the epidural space is explored to ensure that all disc fragments have been identified . once the disc herniation has been identified , a determination is made as to whether a further annulotomy is needed for improved access . if so , an annulotomy may be performed as described above . the herniated disc tissue is then removed according to known techniques , such as using pituitary rongeurs and / or curettes . laminar distraction and / or flexion of the hips can be used to aid in exposure of the hernia site . in addition , distraction of the affected disc may be desired to improve the stability of the disc . this distraction may be accomplished using any of the techniques described above . if sufficient disc tissue has been removed around the herniation site , a distraction balloon may be used , provided that the balloon is removed once the desired distraction has been achieved . the balloon distraction may also be supplemented in a two stage distraction technique described as follows . after a total or partial nucleotomy has been performed , in the first stage , a distraction balloon is inserted into the intradiscal space . the balloon is then inflated to gain distraction of the anterior column of the disc space . in the second stage , a secondary distraction instrument is introduced to act on any posterior bony structures at the particular intervertebral level in accordance with known surgical techniques . the secondary instrument is used to obtain distraction of the posterior column at an appropriate amount decided by the surgeon . the nature and amount of this second stage distraction may increase the overall amount of distraction of the total space , change the lordotic angle at the intervertebral level or cause no appreciable increase in the overall distraction of the space . once the appropriate amount and type of secondary distraction has been obtained , the first stage distraction balloon is removed , while the secondary instrument remains in place to prevent any loss of distraction that may occur . with the distraction balloon removed , the injectable nucleus may be injected as described above . after suitable distraction has been achieved , a saline solution as described above with respect to the ddd procedure may be injected through a vented needle into the intradiscal space to check the integrity of the annulus and to determine that there are no other leakage paths , as well as to estimate the volume of the intradiscal space to be filled . while this annulus integrity test is described as being conducted after distraction , it may also be done after removal of nucleus and prior to distraction . when the nuclear cavity has been prepared , the surgeon mixes the injectable nucleus constituents , as described above , to prepare the injectable nucleus material for injection . an injection needle ( which is not required to be a vented and sealed needle ) is introduced through the opening in the annulus until the needle tip reaches the far side of the cavity . as the injectable nucleus material is injected , the needle is preferably angled side - to - side and gradually withdrawn toward the annulus to ensure a complete fill of the space . when the injectable nucleus material is detected at the inner border of the annulus opening , the injection is stopped and the needle is removed from the site . alternatively , a vented needle 40 with a seal 46 may be used , such as where the rent through the annulus is relatively small and not too irregular . with a vented needle 40 , the injection is stopped when the injectable nucleus material is seen at the vent . it is contemplated that the injectable nucleus material will be injected under pressure , typically on the order of 25 - 40 psi , to ensure complete fill of the cavity , with the seal 46 of the vented needle 40 being pressed against the annulus during injectable nucleus injection . another procedure for percutaneous direct injection of a curable biomaterial for treatment of degenerative disc disease is indicated where the disc annulus is generally intact , but the nucleus pulposus has been compromised , either by dehydration or the creation of fissures and the patient suffers from significant pain . in some ddd procedures , for example , as described hereinabove , some or all of the nucleus is removed to create an intradiscal space for injection of curable biomaterial . the defective or degenerated nucleus is not removed , but is instead augmented by a curable biomaterial or injectable nucleus material in a percutaneous procedure . in a percutaneous procedure , access to the spinal disc is achieved simply by introduction of a relatively small and sharp cannulated device , which may include a needle , through the skin and body tissue down to the surgical site under fluoroscopy or by using other conventional surgical navigation techniques . no incision is made nor is any body tissue retracted . further , injection is continued by insertion of the cannulated device through the annulus into the nucleus pulposus , preferably without additional dilators and without removing any of the annulus tissue . as such , a percutaneous procedure provides a minimally invasive approach to treating ddd conditions . in accordance with the percutaneous procedure , the injectable nucleus material is prepared in the same manner described above , with the loaded mixing assembly and crosslinker syringes made available on a sterile instrument table until the appropriate time for injection of the injectable nucleus material . in particular , an injection assembly 70 shown in fig3 may be used to accomplish the injection step . details of the injection assembly may be obtained from previously incorporated co - pending application ser . no . 11 / 170 , 657 with particular attention to fig1 - 20 thereof , the disclosure of which is incorporated herein by reference . the assembly 70 includes a sharp cannulated device , such as a thin - walled docking cannula 72 with an integral mating hub 76 . in this particular construction , the cannula 72 has a relatively smooth outer surface and substantially constant outer and inner diameters along its length . an injection needle 74 ( fig4 ) is slidably disposed within the docking cannula in a relatively close dimensional fit . the needle 74 is integral with a hub 78 that may be configured to mate with the hub 76 of the cannula . a stopcock valve 80 is fluidly connected to the hub 78 , and the injection syringe 82 is configured to engage the stopcock valve in any known manner effective to create a fluid tight connection . the patient is preferably placed in a prone position on an appropriate conventional andrews frame or equivalent table , in the proper lordotic posture with the hips flexed to aid in the exposure of the posterior disc . the docking cannula 72 is introduced to the disc in an extraforaminal location using a typical posterolateral discography approach . a guide stylet may extend through and be disposed in the cannula to assist in passing the cannula through the body tissue to the disc annulus a . once the docking cannula is properly docked within the annulus , it forms a substantially fluid - tight interface with the disc annulus . since the procedure does not require an annulotomy , the elasticity of the annulus and other tissues surrounding the disc cause those tissues to compress around the cannula 72 to create a seal . once the cannula 72 has been docked within the annular wall the injectable nucleus may be prepared and injected under pressure into the nucleus pulposus to fill all voids , interstices and fissures that may exist in the existing nucleus . when the polymer cures in situ , it adheres to the existing natural disc material for essentially seamless integration with the existing disc nucleus , thereby substantially restoring the normal disc function . once the desired amount of injectable nucleus material has been injected , the stopcock valve 80 is closed to maintain the fluid pressure . the injection assembly 70 is preferably held in place during the minimum cure time , which is about five minutes in the specific embodiment . after the initial cure period , the injection needle is removed . the natural disc and augmenting injectable nucleus material will collapse to fill the minimal channel left by removal of the injection needle 74 . while the injection assembly 70 has been described herein as including the docking cannula 72 and a separate injection needle 74 , it should be understood that other injection alternatives are contemplated . for example , in certain situations where perhaps the surgeon has more time to inject a curable material than the particular embodiments described , the needle 74 itself may be directly injected without use of the docking cannula 72 . in an alternative approach depicted in fig5 - 6 , a docking cannula 90 may be provided that includes a threaded tip 92 . the threads are configured to pierce the annulus as the docking cannula 90 is rotated . with this alternative , the hub may be modified from the hub 76 of the cannula 72 to provide a gripping surface suitable for manual threading of the cannula 90 into the disc annulus . thus , the threaded cannula 90 may provide a more positive anchoring of the cannula 90 to the annulus . in addition , a seal may be provided between the threaded tip 92 and the wall of the annulus since the cannula 90 is threaded into the annulus without an annulotomy being performed . as such , it is considered that such a threaded cannula 90 would allow injection of curable biomaterial at pressures greater than 160 psi and potentially up to as high as 200 psi . in a modification of the threaded docking cannula 90 , a flange 95 may be defined on the cannula , as depicted in phantom lines in fig6 . this flange 95 may act as a stop to control the amount of insertion of the threaded tip 92 into the disc annulus . the flange may also assist in providing and maintaining a fluid - tight seal at the opening formed in the annulus . the flange may also include a fitting , such as a luer lock fitting , to mate with the hub 78 of the injection needle . in this case , the fitting is preferably sized so that the fitting is accessible outside the percutaneous wound in the patient . such a flanged cannula may have particular application in the open ddd and / or amd surgical procedures described hereinabove . in a further modification , a threaded docking cannula 100 , depicted in fig7 - 8 , includes an expandable flange 106 . the cannula includes a cannula body 102 terminating in threads 104 for engagement within the disc annulus , as with the embodiments described above . the expandable flange 106 is interposed between a fixed collar 108 and a sleeve 110 that is slidably disposed about the cannula body 102 . the expandable flange is configured to have an un - expanded condition 106 , as shown in fig7 and then to move to an expanded condition 106 ′, shown in fig8 , upon pressure from the sleeve 110 . in a specific embodiment , the flange 106 is formed of a resilient material that deforms when pressed by the sleeve but returns substantially to its un - expanded condition ( fig7 ) when the pressure is removed . in its un - expanded condition , the flange 106 has a small enough outer profile or diameter to be used percutaneously . in the previous embodiments , the sealing element of the injectable nucleus injection device is fixed relative to the injection tube or cannula . these devices are therefore limited to a particular needle length . variations in needle length may allow a surgeon to introduce the injectable nucleus at a desired location within the disc . moreover , different needle lengths may be necessary to account for variations in patient anatomy . similarly , the devices described above include a certain seal geometry . however , in some procedures , the anatomy of the disc , and particularly the disc annulus , may require a more specialized seal configuration to effectively seal around the disc access opening . for instance , in an open ddd procedure , an annulotomy is used to form a controlled access opening in the annulus . on the other hand , in an amd procedure , access to the disc nucleus may be through an irregular opening in the annulus that may be the result of a tear or rupture . the injection seal that is suitable for the ddd procedure may not be sufficient for the amd procedure . other variations in disc anatomy may dictate or restrict the geometry of the seal that is acceptable . thus , the present invention contemplates a modular injection needle and seal apparatus . in particular , a modular injection apparatus 200 shown in fig9 ( g ) includes an injection needle 210 with a modular seal 220 mounted thereon . the needle 210 may be configured like the needle 40 described above , namely including a primary cannula 212 through which the injectable nucleus may be injected and a secondary vent cannula 214 . as shown in fig1 ( a )-( b ), the primary cannula may terminate in a fitting 213 for engagement to a source of injectable nucleus fluent material . similarly , the vent cannula 214 may also terminate in a fitting 215 for engagement to a reservoir for receiving fluid venting through the cannula . it should be understood , however , that in some applications the injection needle 210 may be used only with a primary cannula 212 without the vent cannula 214 . as further shown in fig1 ( a )-( b ), the injection needle 210 includes a stop 217 connected to the needle offset from the distal end 211 of the needle . the stop 217 is positioned at a distance l ( fig9 ( g )) from the distal end . this distance varies among a selection of injection needles 210 from a base location ( 0 mm ) to a farthest upstream position ( 15 mm in the illustrated example ). the selection of injection needles may have the stop 217 located at 5 mm increments from this base location . thus , in the illustrated example , the selection of injection needles 210 will have the stop 217 located at 0 mm , 5 mm , 10 mm and 15 mm . the base location ( 0 mm ) is preferably established so that the distal end 211 extends just inside the interior surface of the disc annulus a ( fig1 ) when the seal 220 is engaged to the outer surface of the annulus . the base location is preferably indexed to a minimum expected thickness for the disc annulus . the alternative stop positions may thus account for variations in annulus geometry or may position the distal end 211 at variable incursions into the interior of the disc space . as shown in the detail views of fig1 ( a )-( d ), the stop 217 includes a contoured surface 218 which is preferably defined at a spherical radius . this contoured surface engages the seal , as described herein . the stop further defines an opening or bore 219 therethrough that is configured to conform to the outer surface geometry of the injection needle 210 . thus , the bore 219 includes a larger portion 219 a that is sized to snugly receive the primary cannula 212 and a smaller portion 219 b that is sized to snugly receive the secondary vent cannula 214 . the stop 217 is connected to the injection needle 210 in a manner so that the stop cannot slip along the needle when the seal 220 is pressed between the stop and the disc annulus . moreover , it is preferable that the stop be connected to the needle in a fluid - tight manner so that no fluid ( or no appreciable amount of fluid ) may leak between the stop and needle . thus , in a preferred embodiment the stop 217 is affixed in a conventional manner , such as by welding or bonding . other forms of connection are contemplated provided that the stop cannot slip proximally along the needle and provided that a fluid - tight connection is ensured . returning to fig9 ( a )-( f ), various seal configurations are shown for use in the needle assembly 200 . the configuration of the seals may vary to accommodate different surgical procedures and different disc anatomies . for example , three seals 221 , 222 and 223 in fig9 ( a ), 9 ( b ) and 9 ( c ), respectively , including corresponding sealing surfaces 221 a , 222 a and 223 a that are optimally configured for use in amd procedures . as explained above , in a typical amd procedure , the disc access is obtained through an existing tear or rupture in the disc annulus . in this case , the irregularity of the opening in the annulus requires a greater coverage area for the seal . thus , the sealing surface 221 a of the seal 221 provides a circular coverage area at a relatively large diameter , about 9 . 5 mm in the illustrated embodiment , as shown in the detail views of fig1 ( a )-( b ). likewise , the cup - shaped sealing surface 222 a of the seal 222 may be provided in the same diameter , as shown in fig1 ( a )-( b ). for cases in which the opening in the annulus is in the nature of a tear , an elliptical sealing surface 223 a of the seal 223 in fig1 ( a )-( c ), may be provided . the elliptical shape of sealing surface 223 a also allows for greater potential angulation of the injection needle 210 while still sealably covering an irregular opening in the annulus . as described above , the typical ddd procedure involves providing a prepared access opening through the annulus . thus , the opening may be more readily controlled and sized to receive the injection needle 210 . in certain cases , the controlled opening may have a diameter of about 2 . 5 mm , or less than about 5 . 0 mm . this controlled access opening size permits the use of a smaller seal , such as the circular seal 225 shown in fig1 - 18 . this seal may have an outer diameter of about 6 . 5 mm . alternatively , since the prepared opening in the annulus in a ddd may be made circular ( as opposed to the irregular openings encountered in an amd ), the seal may be conical , like the seals 226 and 227 of fig9 ( e )-( f ). as shown in the detail view of fig1 ( a )-( b ), the sealing surfaces 226 a , 227 a and 228 a of these seals may taper from a diameter of 3 mm to a diameter of 6 . 5 mm . the taper may be at a 30 ° or a 45 ° angle , for example , with commensurate adjustments in the overall length of the seal . in certain embodiments , the interface between any of the seals 220 - 227 and the stop 217 may be fixed — i . e ., the seal is pressed onto the needle 212 and against the stop 217 in a manner that does not permit any relative angulation or articulation . in these embodiments , the surface 218 of the stop 217 may be generally flat to bear against an interior surface of the seal , such as surface 230 of the seal 221 shown in fig1 ( b ). however , it is preferable that the interface between the seal and the needle accommodate some articulation since some manipulation of the injection needle within the disc may be desirable . for instance , movement of the distal end 211 of the needle 210 may be desirable to direct the fluent material , or injectable nucleus material , throughout the disc space . in this case it is important that the seal 220 maintain fluid - tight contact with the disc annulus . thus , in certain embodiments a bearing element 240 , as shown in fig1 ( b ) and 18 , may be disposed in the body of the selected seal in which the bearing element includes a complementary contoured surface 246 adapted for articulating contact with the surface 218 of the stop 217 ( fig1 ) . thus , for the spherical contoured surface 218 , the complementary contoured surface 246 of the bearing element is preferable a spherical convex surface , as illustrated in fig1 . the bearing element 240 includes a circumferential flange 242 and a cylindrical portion 244 in which the convex surface is defined . a tapered exit surface 248 is defined in the flange 242 , as shown in fig1 ( b ), to provide clearance for the needle 210 as it moves through a spherical angle . in the illustrated embodiment , the exit surface may be tapered at a 60 ° spherical radius . the body of the seal , such as seal 225 shown in fig9 ( d ) and 17 , is configured to receive the flange 242 . thus , in the illustrated embodiment , the seal defines an internal groove 231 at the mating surface 230 . the internal groove is sized to receive the flange 242 in fluid - tight engagement . similarly , the seal 225 defines a cylindrical bore 234 for fluid - tight engagement around the cylindrical portion 244 of the bearing element 240 . the central bore 232 extends through the seal to receive the needle 210 , as described above . the body of the seals 221 - 227 may be similarly configured to receive a corresponding bearing element 240 . the elliptical seal 223 may incorporate a modified bearing element 240 ′, as shown in fig1 , to interface with the elliptical interior features 230 ′, 231 ′ and 234 ′ of the seal 223 illustrated in fig1 . however , the bearing element 240 ′ includes the same spherical convex interior surface 246 for articulating engagement with the surface 218 of the stop 217 . since the seals 221 - 227 are intended for fluid - tight engagement to the disc annulus the seals are preferably formed of a resilient conformable or compliant biocompatible material . most particularly for the seals 221 , 222 , 223 and 225 , the seal material must be compliant enough to conform to the surface of the annulus under manual pressure . thus , in one embodiment , the seals are formed of a resilient polymer , such as silicone . in one specific embodiment , the seal is formed of dow corning mdx4 - 4210 silicone . it can be appreciated that the conical seals 226 and 227 may also be formed of the same compliant and resilient material ; however , since the body of the conical seals is intended to be engaged within the opening in the annulus the need for the seal to conform to the annulus is less critical . thus , for the conical seals 226 and 227 , the body of the seal may be formed of a more rigid biocompatible material , such as a high density plastic or resin , or a metal such as stainless steel . since the stop 217 and bearing element 240 are intended to articulate in bearing contact , these components are preferably formed of a bearing material , such as 304 stainless steel . alternatively , these elements may be formed of a high density plastic or resin suitable for bearing contact , such as delrin ® acetal resin . in accordance with one aspect of the invention , a kit of modular needle components may be provided . in particular , several needles 210 having different stop locations may be provided in the kit . likewise , a selection of seals may be provided in the kit , including the seals 221 - 227 and variations thereof . the kit allows the surgeon to defer the selection of the injection needle assembly until the nature of the injectable nucleus injection procedure is ascertained . in other words , the surgeon may determine whether an amd or a ddd procedure is indicated and evaluate the disc anatomy to determine what combination of needle and seal is appropriate . once the selection is made , the seal 220 is easily slid onto the distal end 211 of the needle 210 until the seal contacts the stop 217 . in use , the surgeon may maintain manual pressure on the needle assembly 200 to press the seal against the disc annulus . referring to fig2 - 21 , an articulating modular seal 250 is provided that permits a wider range of angulation between the seal and the cannula . the seal assembly 250 includes a substantially spherical ball 252 that is affixed to the injection needle 210 that operates as the stop . in one embodiment , the ball 252 is formed of a bearing material , such as 304 stainless steel , and is suitably affixed in sealed engagement to the injection cannula 212 and the vent cannula 214 . the ball may define bores 253 through which the injection needle 210 is inserted and welded in position . it is understood that the ball 252 operates as a stop , similar to the stop 220 affixed to the injection needle shown in fig9 - 10 as described above . in this embodiment , the modular seal 250 incorporates a snap - fit or press - fit engagement between the seal and the ball / stop . thus , the modular seal may include a seal 254 that incorporates a cap or collar 256 configured to be fixed in bearing contact with the ball 252 . the cap 256 may thus include a spherical cavity 257 a that terminates in an upper lip 257 b . the cavity and lip are configured to capture the ball therein in a snap - fit or press - fit engagement . thus , the lip 257 b is configured so that over half of the ball 256 is captured within the spherical cavity 257 a . the cap 256 may be provided with slits 258 that separate as the ball is pressed past the lip 257 b into the cavity 257 a . the seal 254 further includes a seal body 260 that may be configured like any of the seals 221 - 225 illustrated in fig9 . the body 260 preferably defines a cavity 262 as shown in fig2 ( a ) that is positioned over the opening in the disc annulus . the cavity further includes an angled wall 264 that provides clearance for the injection needle 210 as the seal and needle are pivoted relative to each other . thus , in one specific embodiment , the injection needles 210 may be manipulated through a 20 ° spherical angle as the injectable nucleus material is introduced through the cannula 212 . of course , as with the prior embodiments , the modularity of the modular seal 250 contemplates a selection of seals 254 and a selection of injection needles 210 with different positions for the ball stop 252 , as described above . in an alternative embodiment , the seal may incorporate self - anchoring features — i . e ., features that temporarily anchor the seal to the disc annulus in a fluid - tight connection . one such seal is the seal 270 shown in fig2 . this seal may be a modification of the seal 226 or 227 shown in fig9 and 19 . in particular , the seal 270 includes a conical body 272 that is adapted to be pressed into the prepared opening through the disc annulus , as might arise in an amd procedure . threads 274 are provided on the conical body for threaded engagement within the annulus to anchor the seal as well as the injection needle to the disc . in practice , the needle , with the seal mounted thereon , is introduced through the opening in the annulus until the threads of the seal contact the opening . the seal 270 may then be manually rotated to engage the opening and advance the seal farther into the annulus . while the invention has been illustrated and described in detail in the drawings and foregoing description , the same should be considered as illustrative and not restrictive in character . it is understood that only the preferred embodiments have been presented and that all changes , modifications and further applications that come within the spirit of the invention are desired to be protected .

a kit for injecting a biomaterial into an intradiscal space accessed through an opening in the disc annulus comprises a plurality of needles , each sized for introduction through the annulus opening with a passageway for injecting the biomaterial therethrough , and each including a distal end to be disposed within the intradiscal space when the needle extends through the annulus opening . each needle includes a stop affixed thereto at different pre - determined distances from the distal end to define the location of the distal end within the intradiscal space when the needle extends through the opening in the annulus . the kit further includes a plurality of seals defining a bore for sliding engagement with a needle , each of the plurality of seals including a sealing face for engaging the annulus around the needle . each sealing face defines a differently configured area of contact , such as circular , elliptical , tapered and threaded .

fig1 shows schematically an osteosynthesis device for fastening two bone parts 2 a , 2 b to a fixing plate 4 . the fixing plate 4 has holes for pins 6 a , 6 b , 6 c , 6 d , to pass through , on at least part of which is a thread 8 a , 8 b , 8 c , 8 d for screwing the pin into one of the bone parts . the osteosynthesis device has two pins per bone part but it will be understood that it could have only one pin per bone part in certain cases . it will be noticed that the pins can be screwed in a direction perpendicular to that of the plane of the fixing plate 4 . pin 8 b is an example of this . they can also be screwed at an angle to this perpendicular direction . pins 8 a , 8 c and 8 d are examples of this . lock rings 10 a , 10 b , 10 c , 10 d are placed in the holes of the fixing plate 4 to fasten the pins to this fixing plate . embodiments of a lock ring according to the invention will now be described with reference to fig2 - 6 . fig2 illustrates part of an osteosynthesis device comprising a ring in a first embodiment of the invention . this figure shows only one pin , but it will be understood that an osteosynthesis device preferably comprises at least two pins in order to unite two bone parts . in fig2 , a fixing plate 12 is placed over a bone part 14 . the fixing plate comprises a hole 16 to receive a pin 18 and a lock ring 20 . according to the invention the lock ring 20 comprises a first part 22 which has an axial bore 24 for the passage of the pin 18 , which bore may or may not be threaded , the periphery of the first part 22 of the lock ring comprising a thread 26 to enable it to be screwed into the hole in the fixing plate , and a second part 28 , continuing on from the first part 22 . in preferred embodiments , the second part is more readily deformed than the first part . in an embodiment , the second part of the lock ring is thinner than the first part . in an embodiment , the second part has a sufficiently thinner wall than the first part that the second part is more easily deformed than the first part . in an embodiment , the first and second parts have substantially similar external diameters , but the wall of the second part is thinner than the wall of the first part . in an embodiment , the second part has an axial bore 30 similar to that of the first part . in an embodiment , the axial bore of the second part has a diameter which is substantially the same as the diameter of the axial bore of the first part . in an embodiment , the second part is thinner than the first part and has an axial bore similar to that of the first part . in an embodiment , the end of the first part proximal to the second part ( the distal end ) is adapted to engage a screwdriver , wrench or other tool suitable for removal of the pin by the practitioner . preferably , the first part comprises an external driving feature adjacent to the second part . in one embodiment , the external driving feature has an external diameter or dimension which is greater than that of the remainder of the first part . the external driving feature can be a polygonal casing , such as a square or hexagonal casing , for engaging a tool , such as a screwdriver or wrench . the external driving feature can also comprise two or more notches or slots in the periphery of the distal end of first part . in one embodiment , the distal end of the first part comprises three notches separated by 120 °. in another embodiment , the external driving feature comprises more than three notches , for example , four , five or six notches . the notches are preferably evenly spaced ; that is , for n notches , adjacent notches are preferably separated by 360 / n degrees . the thickness of the second part 28 is selected to suit the material of which the ring 20 is made , so that when the pin and the second part are sheared , the remaining part of the second part deforms and is pushed down against the top of the remaining pin , thus locking the pin relative to the fixing plate . in an embodiment , the second part is made of 316l surgical steel and has a wall thickness of about 0 . 05 mm to about 1 . 5 mm , more preferably between about 0 . 1 mm and about 0 . 6 mm . in one embodiment , the second part is made of 316l surgical steel and has a wall thickness of about 1 mm . in an embodiment , the lock ring is made of titanium , titanium alloy , or steel , preferably surgical steel , such as 316l surgical steel . in an embodiment , the lock ring is made of a biodegradable material , such as polylactide ( pla ) or another biodegradable polymer . the osteosynthesis device is installed in the following manner . the practitioner provides or selects a plate comprising at least two holes sufficient for affixing the plate to the bone parts . alternatively , the practitioner drills holes in the fixing plate at least two points selected to enable it to be fixed to the bone parts . he then drills each bone part , using a drill bit guided perpendicular to the fixing plate . he next pre - positions the lock ring 20 by screwing it part of the way into the hole 16 . he can also screw the lock ring 20 all the way into the hole 16 , if for example the axial bore of the first part 22 of the lock ring is not threaded . the pin 18 , whose bottom part comprises a thread 32 , is then screwed into the bone part to the desired length , the lock ring 20 , or at any rate its second part , now having a secondary sighting function for guiding the pin as it is screwed in . if the lock ring 20 has merely been pre - positioned , it is now screwed fully into the hole 16 . the practitioner then shears off the pin 18 and the ring 20 approximately at the base of the second part 28 — that is , at the junction between the first part 22 and the second part 28 . a mark such as a slight groove can be provided at the periphery of the ring in order precisely to define the position of the shearing tool . the remaining part 34 of the second part 28 of the lock ring 22 is deformed toward the pin 18 by the shearing action . the pin 18 is thus locked relative to the lock ring 22 , and hence relative to the fixing plate 12 , by a crimping action . consequently , when the practitioner shears the pin 18 and the ring 20 at the junction between the first part 22 and second part 28 , using suitable pliers , the jaws of the pliers initially tend to squeeze the lock ring 20 . as the jaws come together , they deform it and finally cut off both the lock ring 20 and the pin 18 . a sheared free edge of the second part is thus formed , making a remaining part 34 attached to the first part . two diametrically opposite portions of this free edge are now pushed toward each other by the shearing action and roughly cover the sheared free end of the pin 18 . thus deformed tightly around the pin 18 , the remaining part 34 of the second part 28 of the lock ring 22 locks the pin 18 relative to the lock ring 22 by a crimping action . the situation now is that shown in fig3 , where elements identical to those in fig2 are given the same references . the lock ring according to the invention is particularly advantageous in that it offers excellent locking efficiency for small - diameter pins , with diameters of for example from 0 . 8 to 1 . 8 mm , which corresponds to the type of pin used on bone parts in the wrist , hand and face . thus , experiments have demonstrated a resistance to tension of more than 200 kg on a testing machine able to measure no more than 200 kg with a 4 mm diameter pin and a ring made of 316l surgical steel in which the second part has a thickness of 1 mm . in this test , the ring had no internal thread . it will be appreciated that the resistance to tension would be greatly increased with an internally threaded ring . this would provide in particular excellent resistance to tension , even with small - diameter pins . clearly , the lock ring according to the invention is also usable and effective with larger - diameter pins . fig4 shows a cross section through part of an osteosynthesis device that has a lock ring in accordance with a second embodiment of the invention , and fig5 is a top view along a direction d parallel to the direction of the pin axis . the lock ring 36 comprises a threaded ( thread 40 ) frustoconical first part 38 provided with an axial bore 42 and a second part 44 , continuing on from the first part , comprising an axial bore 46 similar to that of the first part 38 . according to the invention the thickness of the second part is chosen to suit the material used so that this second part is deformable and thus locks the pin , by deformation , when sheared off . the second embodiment of the invention differs from the first embodiment essentially in that the lock ring is mounted on a collar 48 whose orientation in the orifice 50 of the fixing plate can be adjusted . for this purpose the collar has a convex edge 52 and the hole in the fixing plate 12 has a corresponding concave edge 54 . preferably , the collar has a radial slot 50 . the pin is installed in the same way as in the device described with reference to fig2 and 3 . in one embodiment , the practitioner first selects a plate with at least two holes positioned to be attached to the two bone parts . preferably the holes have concave edges . in another embodiment , the practitioner introduces the holes into the plate by drilling the plate at least two points . he next forms the concave edge of the hole to permit the subsequent insertion of the collar . he then drills the bone part at the chosen angle using a drill bit . the collar 48 is next placed in the hole in the fixing plate , its insertion being facilitated by the radial slot 50 in the collar 48 . the lock ring 36 is screwed at least part of the way onto the collar 48 to immobilize its orientation and thus guide the pin 18 . when the pin has been screwed in to the desired length , and the lock ring has been screwed fully down onto the collar 48 , the practitioner shears off the lock ring 36 and the pin 18 at the lower part of the second part 44 of the lock ring 36 , thus deforming the residual part of this second part and thereby locking the pin 18 . the pin ( 18 ) is preferably provided as a headless pin . as can be seen in fig5 , shearing of the pin and the second part forms a screw head comprising the remaining end of the pin , the remaining part of the second part and the external driving feature , shown in the figure as three notches ( 56 ). the practitioner thus cuts the pin to the required length upon installation of the device . thus , the invention eliminates the need for a stock of pins of varied lengths . another embodiment of the lock ring of the invention is illustrated in fig6 a - c . fig6 a presents an external view of the lock ring , which comprises first part 22 and second part 28 . first part 22 comprises external driving feature 31 , represented in the figure by an hexagonal casing of which three faces are visible in the figure . first part 22 further comprises external threading 26 , which is intended to engage with the threading of a hole in a fixing plate . fig6 b is a longitudinal cross - section of the lock ring of fig6 a . the lock ring comprises inner bore 30 of second part 28 and inner bore 24 of first part 22 . inner bore 30 and inner bore 24 are cylindrical . first part 22 comprises internal threading 33 . it is to be understood that in fig6 a and 6b , the first part includes external driving feature 31 , external threaded region 26 and the region , if any , between external driving feature 31 and external threaded region 2 . second part 28 is cylindrical . the portions of first part 22 other than external driving feature 31 are cylindrical . fig6 c is a view along axis a as shown in fig6 a and shows cylindrical second part 28 , inner bore 30 and the hexagonal external driving feature 31 . the plates , lock rings and pins used in the devices of the invention can be provided in a range of sizes . for example , the plates can have a range of thicknesses such as is typical for osteosynthesis plates . for example , in certain embodiments the plates are from about 1 mm to about 2 mm thick . moreover , the plates can have a range of lengths . in certain embodiments , the plates range from about 5 cm to about 15 cm in length and from about 2 . 5 cm to about 8 cm in width . in certain embodiments , the width of the plate varies along its length , in certain embodiments having a width from about 2 . 5 cm to about 3 . 5 cm near a hole and from about 5 cm to about 7 cm between two holes . the pins can have diameters which are typical for pins used in osteosynthesis devices . in certain embodiments , the pin has a diameter from about 1 mm to about 3 mm , preferably a diameter of from about 2 mm to about 2 . 5 mm . in certain embodiments , the lock ring has a diameter ranging from about 2 cm to about 5 cm . in certain embodiments , the lock ring has a diameter of about 3 cm . those of skill in the art can readily select the appropriate plate , lock ring and pin size for the bone parts to be joined . the osteosynthesis device of the invention preferably comprises a plate with at least two holes configured to join two bone parts , two lock rings as described herein and two pins . however , in certain embodiments , the osteosynthesis device comprises a plate comprising a first means of attachment to a bone part comprising at least one hole , at least one lock ring as described herein and at least one pin . in this embodiment , the device further comprises a second means of attachment to a bone part which is different from the first means . in one embodiment , the second means does not include the lock ring of the invention . the second means can be any means known in the art for attaching a fixing plate to a bone part , for example , a prior art lock ring and pin , a staple , or a pin which is directly screwed into the bone through the plate . in an embodiment , the invention provides a method of attaching a fixing plate ( 12 ) to a bone part ( 14 ) in a subject in need of osteosynthesis . the method comprises the steps of : ( a ) providing : ( i ) a fixing plate ( 12 ) comprising a hole ( 16 ); ( ii ) a threaded fixing pin ( 18 ) designed to be screwed into the bone part ; and ( iii ) a lock ring ( 20 , 36 ) comprising a first part ( 22 , 38 ) having an axial bore ( 24 , 42 ) to receive the fixing pin ( 18 ), and the periphery of said first part being threaded to engage with a hole of the fixing plate ; said ring being characterized in that it further comprises , continuing on from said first part , a deformable second part ( 28 , 44 ); ( b ) positioning the fixing plate ( 12 ) over the bone part ( 14 ) such that the at least one hole ( 16 ) of the plate ( 12 ) overlays the bone part ( 14 ); ( c ) drilling a hole in the bone part ( 14 ), wherein the hole in the bone part ( 14 ) is aligned with the hole in the fixing plate ( 12 ) of step ( c ); ( d ) partially or completely screwing the lock ring ( 20 , 36 ) into the hole of the fixing plate ( 12 ); ( e ) inserting the fixing pin ( 18 ) through the axial bore ( 24 , 42 ) of the lock ring ( 20 , 36 ) and screwing the fixing pin ( 18 ) into the hole in the bone part ( 14 ) to a depth sufficient to secure the pin in the bone part ; ( f ) if the lock ring ( 20 ) was only partially screwed into the fixing plate ( 12 ) in step ( e ), screwing the lock ring ( 20 ) completely into the hole of the fixing plate ( 12 ); and ( g ) shearing the fixing pin ( 18 ) and the second part ( 28 , 44 ) of the lock ring ( 20 , 36 ), thereby deforming a remaining part ( 34 ) of the second part ( 28 , 44 ) toward the fixing pin ( 18 ) and locking the fixing pin ( 18 ) relative to the fixing plate ( 12 ); thereby affixing the fixing plate ( 12 ) to the bone part ( 14 ). preferably , in step ( g ), the pin ( 18 ) and the second part of the lock ring ( 28 , 44 ) are sheared simultaneously . in an embodiment , the process comprises the steps of identifying first and second bone parts in the subject in need of osteosynthesis . in this embodiment , the fixing plate comprises at least two holes , each hole being configured for attachment to one of the bone parts . in this embodiment , steps ( a )-( g ) are conducted for attachment of the plate to each of the bone parts , thereby fixing and joining the ends of the bone parts . the plate can be affixed to the two bone parts serially or in parallel . in certain embodiments , the plate comprises more than two holes , and the plate is attached to at least one of the bone parts by installation of two or more lock rings and pins according to steps ( a )-( g ). in one embodiment , the hole in the fixing plate has a concave edge and is modified prior to step ( d ) by insertion of a collar as described above , where the collar is oriented within the hole at the desired angle . the patent and scientific literature referred to herein establishes the knowledge that is available to those with skill in the art . all united states patents and published or unpublished united states patent applications cited herein are incorporated by reference . all published foreign patents and patent applications cited herein are hereby incorporated by reference . all other published references , documents , manuscripts and scientific literature cited herein are hereby incorporated by reference . while this invention has been particularly shown and described with references to preferred embodiments thereof , it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims .

the invention relates to a locking ring for a threaded holding pin to be screwed into a part of a bone , said ring including a first portion having an axial bore for receiving said holding pin , the periphery of said first portion being threaded so as to interact with a holding plate , wherein said ring in characterized in that the same further comprises , as an extension to said first portion , a second portion , said second portion being deformable and thus capable of blocking said ring on said pin by deformation .

according to the invention , isolated β - glucans from plants such as oats , barley , and mushrooms can be metabolized to support the growth , of the probiotic lactobacillus rhamnosus strain gg ( lgg ). β - glucans admixed with lgg can increase the intestinal colonization and numbers of lgg in the bowel when administered orally in the form of foods such as drinks , cheeses , dairy products , baby formulas , and baby cereals , and medicaments in the forms of capsules or tablets . accordingly , the effectiveness of lgg in preventing or treating medical conditions and improving well - being is enhanced . the combination of the probiotic lgg with a prebiotic β - glucan designed to enhance the growth of lgg in the gastrointestinal tract and at other mucosal surfaces such as the respiratory tract , genital tract , nasal cavity , oral cavity , rectum , urethra , or lungs provides an effective combination to improve the efficacy and uses of the probiotic organism lgg . the necessary daily ingestion of β - glucan to exert a prebiotic effect and increase the numbers of lgg is between 2 to 8 grams / day . this level of β - glucan cannot be attained by ingestion of the native food stuffs such as oats or barley . bulk β - glucan can be obtained from , e . g ., ahd international , nurture ®, inc ., and quaker ® oats company . the numbers of lgg required to attain a probiotic health benefit is between 10 7 and 10 10 bacteria ingested daily . therefore an effective amount of a food product that would result in an enhanced probiotic health effect includes about 10 to 100 ml or 10 to 100 grams of a yogurt , drink , food , cheese , or baby formula which contains between about 10 6 and 10 8 lgg bacteria per ml or between about 10 6 and 10 8 lgg bacteria per gram , or a capsule , tablet or suppository containing about 10 mg to 100 mg lypholized lgg powder containing 10 9 to 10 11 lgg per gram , or an ointment that contains about 10 mg to 100 mg of lypholized lgg powder containing about 10 9 to 10 11 lgg per gram . any of these compositions will also include about 0 . 5 to 8 grams of β - glucan isolated from a natural source . for adult consumers of the foods of the invention , the amount of β - glucan can be at least about 2 grams per 100 g of a food product . preferably , the amount of β - glucan in food products for adult consumers is between about 2 to 8 grams per 100 g of a food product . for infant consumers , the amount of β - glucan can be at least about 0 . 5 grams per 100 g of a food product . preferably , the amount of β - glucan in food products for infant consumers is between about 0 . 5 to 3 grams per 100 g of a food product . for example , a food product can contain , per 50 ml or per 50 g of the food product , at least 10 6 probiotic organisms ( e . g ., lgg bacteria ) and at least 0 . 5 grams of β - glucan isolated from a natural source . any of the preparations described herein may be administered once daily . alternatively , preparations may be administered twice daily , three times daily , or up to five times daily . an example of an appropriate capsule is a 250 mg gelatin capsule containing about 10 to 100 mg of lgg lyophilized powder ( 10 8 to 10 9 bacteria ), 160 mg microcrystalline cellulose , 77 . 5 mg gelatin , and 2 . 5 mg magnesium saturate along with about 0 . 5 to 8 grams of partially purified β - glucan isolated from an oat or barley source . in another embodiment , a suppository cartridge could contain about 10 to 100 mg of pure lgg powder mixed with about 0 . 5 to 8 grams of β - glucan . in order to prevent a reaction between lgg and β - glucan the individual suppository would be dry ( less than 0 . 1 % moisture ). an ointment of the invention can contain , in an amount of ointment normally used for treatment ( e . g ., in an amount between 1 g and 100 g ), about 10 to 100 mg of lgg lyophilized powder ( 10 6 to 10 9 bacteria ) and about 0 . 5 to 8 grams of β - glucan . also envisioned is a packaged food product that includes at least a first and a second compartment isolated from each other by an intermediate partition or seal that prevents mixing of the contents of the compartments . the first compartment can include a composition containing a probiotic and the second compartment can include a composition containing an isolated β - glucan ( in the amounts discussed above ). the package is constructed to permit mixing of the two compositions in the package , e . g ., by a consumer prior to consumption of the mixed food product . the package can include a tube with at least two compartments that are separated by a seal that is more readily broken than the seal forming the periphery of the package , i . e ., a “ burst ” seal . after purchase by the consumer , the consumer applies sufficient pressure to the tube to burst the seal separating the two compartments . once the seal is broken , the two compositions in the separate compartments can be mixed by the consumer . preferably , the β - glucan - containing composition is maintained in a dry state , such as in powder form , and the probiotic - containing composition is a liquid or semi - solid food , such as a dairy or non - dairy food ( e . g ., yogurt , butter , cheese , infant formula , or ice cream ). the packaged food product can be prepared according to techniques known in the art , such as those described in u . s . patent application publication no . 20020150658 and u . s . pat . no . 4 , 874 , 618 , each of which is incorporated by reference . all publications , patents , and patent applications mentioned in this specification are incorporated herein by reference to the same extent as if each independent publication or patent application was specifically and individually indicated to be incorporated by reference . while the invention has been described in connection with specific embodiments thereof , it will be understood that it is capable of further modifications and this application is intended to cover any variations , uses , or adaptations of the invention following , in general , the principles of the invention and including such departures from the present disclosure that come within known or customary practice within the art to which the invention pertains and may be applied to the essential features hereinbefore set forth , and follows in the scope of the claims .

the invention features a food product containing a probiotic and β - glucan isolated from a natural source , methods of treating a disease or disorder by administering the food product , and a package containing separated components of the food product .

preferred active compounds for the new agents for combating pests are carbamates , p esters ( including the ester - amides and the thiono , thiol and thiono - thiol derivatives ) and pyrethroids which are usually employed as agents for combating soil pests ( compare chemistry of pesticides , edited by k . h . buchel , john wiley & amp ; sons , new york , 1983 , farm chemicals handbook , meister publishing co ., wolloughby , 1983 , u . s . pat . no . 4 , 127 , 652 and european patent application 84 105 133 . 7 and corresponding u . s . patent application no . 06 / 606 , 106 ). the active compounds described below which are preferred are the p esters , carbamates and pyrethroids ( r 1 , r 2 and r 3 are not used in this text ): ( a ) p esters of the general formula ( ii ) ## str2 ## in which q represents oxygen or sulphur , u , v and w are identical or different and represent oxygen or sulphur , it moreover also being possible for one of the radicals u , v and w to denote a direct bond or the -- nh -- group , r 4 and r 5 are identical or different and represent c 1 - c 4 - alkyl ( preferably c 1 - c 3 - alkyl ) and r 6 represents c 1 - c 5 - alkyl ( preferably c 1 - c 2 - alkyl ), which can be substituted by c 1 - c 4 - alkylthio ( preferably c 1 - c 2 - alkylthio ) and / or halogen ( preferably chlorine ), or represents c 2 - c 4 - alkenyl , which can be substituted by halogen ( preferably chlorine ) and / or halogenophenyl ( preferably chlorophenyl ) or represents phenyl , which can be substituted by halogen ( preferably chlorine and / or bromine ), c 1 - c 4 - alkyl ( preferably methyl ), c 1 - c 4 - alkylthio ( preferably methylthio ), c 1 - c 4 - alkylsulphinyl ( preferably methylsulphinyl ) and / or c 1 - c 4 - alkoxycarbonyl ( preferably propoxycarbonyl ), or represents pyridyl , which can be substituted by halogen ( preferably chlorine ) or represents pyrimidinyl , which can be substituted by c 1 - c 4 - alkyl , c 3 - c 6 - cycloalkyl and / or phenyl , or represents the radical 5 - chloro - 1 -( 1 - methylethyl )- 1h - 1 , 2 , 4 - triazol - 3 - yl , or represents the group -- n ═ cr 7 ( cn ), r 7 denotes phenyl which is optionally substituted by halogen ( preferably chlorine ). in formula ii , r 4 and r 5 preferably represent methyl , ethyl or n - or i - propyl . r 6 preferably represents chloromethyl , propyl , ethylthiomethyl , ethylthioethyl , t - butylthiomethyl , 1 -( 2 , 4 - dichlorophenyl )- 2 - chloro - ethen - 1 - yl , phenyl , 3 - methyl - 4 - methylthio - phenyl , 4 - methylsulphinyl - phenyl , 2 - i - propoxycarbonylphenyl , 2 , 4 - dichlorophenyl , 2 , 4 , 5 - trichlorophenyl , 2 , 5 - dichloro - 4 - bromophenyl , 3 , 5 , 6 - trichloro - 2 - pyridyl , the radical -- n =( cn ) ( phenyl ) or the radical 5 - chloro - 1 -( 1 - methylethyl )- 1 - h - 1 , 2 , 4 - triazol - 3 - yl . the following p esters may be mentioned as examples ( common name or chemical name ): disulfoton , femamiphos , isofenfos , trichloronat , fensulfothion , protiofos , phoxim , chlorfenvinfos , bromophos , terbutos , chlorpyrifos , chlormephos , fenfos , isazophos , ethoprofos , phorate , o - ethyl o - i - propyl o -( 2 - t - butyl - pyrimidin - 5 - yl ) thionophosphate and o , o - diethyl o -( 2 - t - butyl - pyrimidin - 5 - yl ) thionophosphate . preferred esters which may be mentioned are : terbufos , chlorpyrifos , fenofos , isofenfos , fenaminphos , phorate , o - ethyl o - i - propyl o -( 2 - t - butyl - pyrimidin - 5 - yl ) thionophosphate and o , o - diethyl o -( 2 - t - butyl - pyrimidin - 5 - yl ) thionophosphate . ( b ) carbamates of the general formula ( iii ) ## str3 ## in which r 8 represents phenyl , which can be substituted by c 1 - c 4 - alkylthio - c 1 - c 4 - alkyl ( preferably ethylthiomethyl ) c 1 - c 4 - alkyl ( preferably methyl ), c 1 - c 4 - alkoxy and / or c 1 - c 4 - alkylthio ( preferably methylthio ), or represents the radical 2 , 3 - dihydro - 2 , 2 - di - methyl - 7 - benzofuranyl , or represents the radical -- n ═ cr 9 r 10 , r 9 denotes c 1 - c 4 - alkyl ( preferably propyl ), which can be substituted by c 1 - c 4 - alkylthio ( preferably con ( ch 3 ) 2 ) and r 10 denotes hydrogen or c 1 - c 4 - alkylthio ( preferably methylthio ), r 11 represents c 1 - c 4 - alkyl ( preferably methyl ) and r 12 denotes hydrogen or the radical -- s -- nr 13 r 14 , r 14 denotes cooc 1 - c 4 - alkyl ( preferably n - butyl ) or c 1 - c 4 - alkyl , which can be substituted by coo - c 1 - c 4 - alkyl ( preferably cooc 2 h 5 ), r 8 preferably represents 3 , 4 , 5 - trimethylphenyl , 2 - ethylthiomethylphenyl , 3 , 5 - dimethyl - 4 - methyl - thiophenyl , 2 , 3 - dihydro - 2 , 2 - dimethyl - 7 - benzofuranyl , -- n ═ ch -- c ( ch 3 ) 2 ( sch 3 ), -- n ═ c ( sch 3 )( con ( ch 3 ) 2 ) or 2 - i - propoxyphenyl , r 12 preferably represents hydrogen , -- s -- n ( ch 3 )( cooc 4 h 9 n ), -- s -- n ( c 4 h 9 n ) 2 or -- s -- n ( ic 3 h 7 )( ch 2 ch 2 cooc 2 h 5 ). the following carbamates may be mentioned as examples ( common name or chemical name ): ethiofencarb , carbofuran , methiocarb , furatiocarb , carbosulfan , aminosulfuram , aldicarb , oxamyl and 3 , 4 , 5 - trimethylphenyl carbamate . carbamates which may be mentioned as preferred are : carbofuran , furatiocarb , carbosulfan , aminosulfuram and aldicarb . ( c ) pyrethroids of the general formula ( iv ) ## str4 ## in which r 15 represents the group ## str5 ## in which r 18 denotes halogen ( preferably chlorine or bromine ) or c 1 - c 4 - alkyl ( preferably methyl ) and r 19 denotes halogen ( preferably chlorine or bromine ). c 1 - c 4 - alkyl ( preferably methyl ) or phenyl , which can be substituted by halogen ( preferably chlorine ) or r 15 represents the group ## str6 ## in which r 20 denotes phenyl , which can be substituted by halogen ( preferably chlorine ), c 1 - c 4 - halogenoalkyl ( halogen is preferably chlorine or fluorine ), c 1 - c 4 - halogenoalkoxy ( halogen is preferably chlorine or fluorine ) and / or c 1 - c 4 - alkoxy , r 17 represents phenyl , which can be substituted by halogen ( preferably fluorine or chlorine ) and / or phenoxy . r 18 and r 19 in the groups r 15 preferably represent chlorine , bromine or methyl , or r 18 represents chlorine and r 19 represents 4 - chlorophenyl . r 20 preferably represents 4 - chlorophenyl or 2 - chloro - 4 - trifluoromethylphenyl . examples of pyrethroids which may be mentioned are ( common name ): phenothrin , permethrin , deltamethrin , fenvalerat , fluvalinate , cyfluthrine and fenfluthrin . the present invention thus relates to the new use of the carboximides of the general formula ( i ) as agents for prolonging the action of nematicidal and insecticidal carbamates , p esters and pyrethroids , agents for combating pests containing at least one compound of the formula ( i ) and at least one nematicidal or insecticidal active compound from the series comprising the carbamates p esters and pyrethroids , and the use of these agents for combating soil pests , preferably nematodes and insects . for simplicity , the term insects will in each case also include the less important arthropods which occur as soil pests , for example , ants , springtails , millepedes , termites , woodlice and root mites . the compounds of the formula ( i ) are known by their common name captan ( r is ccl 3 ) and captafol ( r is ccl 2 -- chcl 2 ), c . f . e . g . k . h . buechel , chemistry of pesticides , john wiley & amp ; sons , new york , 1983 , pages 284 and 285 . the new mixtures of the active compounds and the extender can be employed against a large number of nematodes and insects , typical soil pests being the focus , but is also being possible to affect all the other important arthropods which usually occur , or occur only purely accidentally at times , in the soil or close to the soil . from the order of the isopoda , for example , oniscus asellus , armadillidium vulgare and porcellio scaber . from the order of the diplopoda , for example , blaniulus guttulatus . from the order of the chilopoda , for example , geophilus carpophagus and scutigera spec . from the order of the symphyla , for example , scutigerella immaculata . from the order of the thysanura , for example , lepisma saccharina . from the order of the collembola , for example , onychiurus armatus . from the order of the orthoptera , for example , blatta orientalis , periplaneta americana , leucophaea maderae , blattella germanica , acheta domesticus , gryllotalpa spp ., locusta migratoria migratorioides , melanoplus differentialis and schistocerca gregaria . from the order of the dermaptera , for example , forficula auricularia . from the order of the isoptera , for example , reticulitermes spp . from the order of the anoplura , for example , phylloxera vastatrix , pemphigus spp ., pediculus humanus corporis , haematopinus spp . and linognathus spp . from the order of the mallophaga , for example , trichodectes spp . and damalinea spp . from the order of the thysanoptera , for example , hercinothrips femoralis and thrips tabaci . from the order of the heteroptera , for example , eurygaster spp ., dysdercus intermedius , piesma quadrata , cimex lectularius , rhodnius prolixus and triatoma spp . from the order of the homoptera , for example , aleurodes brassicae , b . aisia tabaci , trialeurodes vaporariorum , aphis gossypii , brevicoryne brassicae , cryptomyzus ribis , doralis fabae , doralis pomi , eriosoma lanigerum , hyalopterus arundinis , macrosiphum avenae , myzus spp ., phorodon humuli , rhopalosiphum padi , empoasca spp ., euscelis bilobatus , nephotettix cincticeps , lecanium corni , saissetia oleae , laodelphax striatellus , nilaparvata lugens , aonidiella aurantii , aspidiotus hederae , pseudococcus spp . and psylla spp . from the order of the lepidoptera , for example , pectinophora gossypiella , bupalus piniarius , cheimatobia brumata , lithocolletis blancardella , hyponomeuta padella , plutella maculipennis , malacosoma neustria , euproctis chrysorrhoea , lymantria spp ., bucculatrix thurberiella , phyllocnistis citrella , agrotis spp ., euxoa spp ., feltia spp ., earias insulana , heliothis spp ., laphygma exigua , mamestra brassicae , panolis flammea , prodenia litura , spodoptera spp ., trichoplusia ni , carpocapsa pomonella , pieris spp ., chilo spp ., pyrausta nubilalis , ephestia kuehniella , galleria mellonella , tineola bisselliella , tinea pellionella , hofmannophila pseudopretella , cacoecia podana , capua reticulana , choristoneura fumiferana , clysia ambiguella , homona magnanima and tortrix viridana . from the order of the coleoptera , for example , anobium punctatum , rhizopertha dominica , bruchidius obtectus , acanthoscelides obtectus , hylotrupes bajulus , agelastica alni , leptinotarsa decemlineta , phaedon cochleariae , diabrotica spp ., psylliodes chrysocephala , epilachna varivestis , atomaria spp ., oryzaephilus surinamensis , anthonomus spp ., sitophilus spp ., otiorrhynchus sulcatus , cosmopolites sordidus , ceuthorrhynchus assimilis , hypera postica , dermestes spp ., trogoderma spp ., anthrenus spp ., attagenus spp ., lyctus spp ., meligethes aeneus , ptinus spp ., niptus hololeucus , gibbium psylloides , tribolium spp ., tenebrio molitor , agriotes spp ., conoderus spp ., melolontha melolontha , amphimallon solstitialis and costelytra zealandica . from the order of the hymenoptera , for example , diprion spp ., hoplocampa spp ., lasius spp ., monomorium pharaonis and vespa spp . from the order of the diptera , for example , aedes spp ., anopheles spp ., culex spp ., drosophila melanogaster , musca spp ., fannia spp ., calliphora erythrocephala , lucilia spp ., chrysomyia spp ., cuterebra spp ., gastrophilus spp ., hyppobosca spp ., stomoxys spp ., oestrus spp ., hypoderma spp ., tabanus spp ., tannia spp ., bibio hortulanus , oscinella frit , phorbia spp ., pegomyia hyoscyami , ceratitis capitata , dacus oleae and tipula paludosa . from the order of the siphonatera , for example , xenopsylia cheopis and ceratophyllus spp . the phytoparasitic nematodes include , for example , pratylenchus spp ., radopholus similis , ditylenchus dipsaci , tylenchulus semipenetrans , heterodera spp ., meloidogyne spp ., aphelenchoides spp ., longidorus spp ., xiphinema spp . and trichodorus spp . the new agents for combating pests are particularly preferably employed against the above mentioned nematodes . moreover , they are preferably employed against pests from the group of the &# 34 ; corn rootworms &# 34 ; of the genera diabrotica , such as diabrotica virgifera , diabrotica balteata and diabrotica longicornis . the mixtures of active compounds and extenders can be converted to the customary formulations , such as solutions , emulsions , suspensions , powders , granules , natural and synthetic materials impregnated with active compound and very fine capsules in polymeric substances and in coating compositions for seed . these formulations are produced in known manner , for example by mixing the active compounds with diluents , that is , liquid solvents and / or solid carriers , optionally with the use of surface - active agents , that is , emulsifying agents and / or dispersing agents , and / or foam - forming agents . in the case of the use of water as a diluent , organic solvents can , for example , also be used as auxiliary solvents . as liquid solvents , there are suitable in the main : aromatics , such as xylene , toluene or alkyl naphthalenes , chlorinated aromatics or chlorinated aliphatic hydrocarbons , such as chlorobenzenes , chloroethylenes or methylene chloride , aliphatic hydrocarbons , such as cyclohexane or paraffins , for example mineral oil fractions , alcohols , such as butanol or glycol as well as their ethers and esters , ketones , such as acetone , methyl ethyl ketone , methyl isobutyl ketone or cyclohexanone , strongly polar solvents , such as dimethylformamide and dimethylsulphoxide , as well as water . as solid carriers there are suitable for example ground natural minerals , such as kaolins , clays , talc , chalk , quartz , attapulgite , montmorillonite or diatomaceous earth ; and ground synthetic minerals , such as highly dispersed silicic acid , alumina and silicates . as solid carriers for granules there are suitable for example crushed and fractionated natural rocks , such as calcite , marble , pumice , sepiolite , dolomite and brick gravel ; as well as synthetic granules of inorganic and organic meals , and granules of organic material such as sawdust , coconut shells , corn cobs and tobacco stalks . as emulsifying and / or foam - forming agents there are suitable for example nonionic and anionic emulsifiers , such as polyoxyethylene - fatty acid esters , polyoxyethylene - fatty alcohol ethers , alkylaryl polyglycol ethers , alkyl sulphonates , alkyl sulphates , aryl sulphonates as well as albumen hydrolysis products . as dispersing agents there are suitable : for example lignin - sulphite waste liquors and methylcellulose . adhesives such as carboxymethylcellulose and natural and synthetic polymers in the form of powders , granules or lattices , such as gum arabic , polyvinyl alcohol and polyvinyl acetate , as well as natural phospholipids , such as cephalins and lecithins , and synthetic phospholipids , can be used in the formulations . further additives can be mineral and vegetable oils . it is possible to use colorants such as inorganic pigments , for example iron oxide , titanium oxide and prussian blue , and organic dyestuffs , such as alizarin dyestuffs , azo dyestuffs and metal phthalocyanine dyestuffs , and trace nutrients such as salts of iron , manganese , boron , copper , cobalt , molybdenum and zinc . preferred formulation forms are granules , emulsifiable concentrates , suspension concentrates and water - dispersible powders , and particularly preferred are granules . the formulations in general contain between 0 . 1 and 95 % by weight of the mixture of active compound and extender , preferably between 0 . 5 and 90 %. it is also possible to formulate the active compounds and extenders separately and to mix the formulated products , or to apply the formulated products separately in their formulations . the mixtures according to the invention can be present in their commercially available formulations and in the use forms , prepared from these formulations , as a mixture with other active compounds , such as other insecticides , baits , sterilizing agents , acaricides , nematicides , fungicides or growth - regulating substances . the other insecticides , include , for example , phosphates , carbamates , carboxylates , chlorinated hydrocarbons , phenylureas , pyrethroids , substances produced by microorganisms , and others . the active compounds according to the invention can furthermore be present in their commercially available formulations and in the use forms , prepared from these formulations , as a mixture with synergistic agents . synergistic agents are compounds which increase the action of the active compounds , without it being necessary for the synergistic agent added to be active itself . the mixtures are employed in a customary manner appropriate for the use forms . as already indicated above , it is also possible to use the active compounds and extenders in ( optionally different ) separate formulations in mixtures of the formulations or as separate formulations . the active compound content of the use forms prepared from the commercially available formulations can vary within wide limits . the active compound concentration of the use forms can be from 0 . 0000001 to 95 % by weight of active compound , preferably between 0 . 0001 and 20 % by weight . the proportions of active compound to extender in the formulations can vary within wide limits , depending on the chosen extender and the relative activity of the particular active compound used and the active compound content in the formulation , without the prolonging in action being lost . the ratios ( weight ratios ) of active compounds / extender are preferably between the ranges of 1 : 50 and 50 : 1 , particularly preferably between 1 : 20 and 20 : 1 and very particularly preferably between 1 : 10 and 10 : 1 . the new mixtures of active compounds and extenders are preferably employed in amounts of between 0 . 1 and 10 kg / ha , preferably between 0 . 5 and 5 kg / ha , and particularly preferably between 0 . 8 and 2 kg / ha ( based on the non - formulated substances ). the expert can easily determine the most advantageous formulations , compositions and use amounts for solving the particular problems with the aid of his expert knowledge or with the aid of simple orientating experiments . the prolonged duration of action of the new mixtures according to the invention may be illustrated by the following examples . in order rapidly to achieve advantageous results in the discovery and development of suitable extenders under laboratory and greenhouse conditions , model soils suitable for the investigations were developed and the tests were carried out at relatively high soil temperatures of 20 °- 25 ° c . the particularly preferred active compounds employed in examples a and b can be illustrated by the following formulae : for the investigations , in each case 4 mg of active compound by itself or a mixture of in each case 4 mg of active compound and 4 mg of the extenders listed were mixed with in each case 1 l of the model soil , so that the individual substances were in each case present in concentrations of 4 ppm . after storage of the soils thus pretreated , after 1 week 1 / 2 l of soil and after 4 weeks the remaining one - half were infested with 20 seven day - old larvae of diabrotica balteata . on the day of infestation pre - swollen corn seeds were placed on the bottom of each container so that , upon germination into seedlings , they served as food for the larvae . in each case 6 days after the infestation with the test larvae , the degree of action of the active compound by itself and of the mixture of active compound and extender were determined in % by counting the dead and living larvae . the degree of action is 100 % if all the test larvae have been destroyed , and is 0 % if just as many test larvae survive as in the case of the untreated control . the active compound , extender , amounts applied and results can be seen from the following tables : ______________________________________ % destruction extender of theactive compound ( r is ccl . sub . 2 -- chcl . sub . 2 ) diabrotica larvaeconcentration concentration afterin ppm in ppm 1 week 4 weeks______________________________________5 0 100 00 10 0 05 10 100 100______________________________________ ______________________________________ extender ( r is ccl . sub . 3 or % destructionactive compound ccl . sub . 2 -- chcl . sub . 2 ) of the diabroticaconcentration concentration larvae afterin ppm in ppm 1 week 4 weeks______________________________________5 0 100 00 10 0 05 10 100 100______________________________________ the extenders by themselves had no destructive action in the concentrations used . the foregoing experiments , which involved illustrative concentrations , show that the mixtures of active compounds and the extender exhibit high activity significantly longer than the active compounds themselves . model soil and test procedure correspond to example a . however , musca domestica larvae were used as test larvae . fenamiphos was used as active ingredient ( active compound 3 ). ______________________________________ extenderactive compound r is ccl . sub . 3 % destruction of theconcentration concentration musca larvae afterin ppm in ppm 2 weeks 6 weeks______________________________________5 0 100 00 10 0 05 10 100 100______________________________________ it will be understood that the specification and examples are illustrative but not limitative of the present invention and that other embodiments within the spirit and scope of the invention will suggest themselves to those skilled in the art .

the foregoing invention relates to new soil pest combating agents which can be used in plant protection for combating nematodes and arthropods , especially insects , and which contain at least one conventional active agent , especially a carbamate , p ester or pyrethroid and at least captan and / or captofol .

the present invention provides an improved method and apparatus for facilitating release of powder . in a preferred embodiment , the powder is contained in a receptacle . as used herein , the term “ receptacle ” includes but is not limited to , for example , a capsule , blister , film covered container well , chamber , and other suitable means of storing a powder known to those skilled in the art . the present invention will be described below in the context of a method and apparatus for dispensing dry powder medicaments for inhalation by a patient . however , it should be apparent to one skilled in the art that the invention is not limited to such an exemplary embodiment , and could be used for other purposes . as will be described in more detail below , an apparatus of the present invention is an inhaler that includes a chamber . in one embodiment , the chamber is configured to receive the receptacle containing the medicament . to improve the emptying of the receptacle and provide a higher reproducible emitted dose , the chamber includes a ring circumferentially coupled to an inner surface of the chamber . the ring is preferably disposed at approximately a midpoint of the chamber , or alternatively , adjacent the proximal end of the chamber . in proper use , air will exit the inhaler carrying a full dose of medicament in the form of a fine , dry powder . the inhaler of the present invention is preferably configured with a means for puncturing the receptacle that improves puncturing performance , particularly with brittle receptacle material . the means for puncturing the receptacle of the present invention is preferably configured as a substantially u - shaped staple with two prongs , each prong having a sharp point and two cutting edges . in one embodiment of the present invention , each prong has a square cross - section , with the staple material being bent around a face so that the innermost part of the u - shaped staple is flat . in another embodiment of the present invention , the staple material is rotated 45 degrees so that it is bent around an edge so that the innermost part of the u - shaped staple is an edge . in such an embodiment , the end surface of each prong is an angled diamond - shaped surface . the methods of the present invention use an inhaler to dispense powder by inhalation . as will be discussed in greater detail below , a user operates the device to puncture the receptacle to disperse powder in the chamber , and inhales the powder through the inhalation portion . a front view of one embodiment of an inhalation device 100 of the present invention is shown in fig1 . the rear view of device 100 is substantially identical to the front view . device 100 includes a first or lower casing portion 120 and a second or upper casing portion 130 removably coupled to first casing portion 120 . upper casing portion 130 and lower casing portion 120 include a flattened region 132 and 122 , respectively , for ease of gripping the casing for use by a patient . lower casing portion 120 preferably includes an outer casing 126 and an inner casing 124 movably received within outer casing 126 . a removable cap 110 is provided at the user or inhalation end of the device . preferred materials for device 100 include food and drug administration ( fda ) approved , usp tested plastics . preferably , device 100 is manufactured using an injection molding process , the details of which would be readily apparent to one skilled in the art . fig2 is a cross - section of device 100 shown in fig1 along line 2 — 2 . as shown in fig2 device 100 includes an inhalation or emitter portion 220 . inhalation portion 220 comprises a hemispheric region 222 that defines a plurality of apertures 224 . it should be understood that the present invention is not limited to a particular number of apertures 224 , and can be configured such that at least one aperture 224 is provided . an inhalation piece 226 is provided to allow for inhalation of the medicament by a user . inhalation piece 226 can be configured as a mouth piece for inhalation through a user &# 39 ; s mouth . alternatively , inhalation piece 226 can be configured as a nose piece for inhalation through a user &# 39 ; s nose . device 100 includes a cylindrical chamber 210 that is defined by a straight wall 212 of circular cross - section . chamber 210 has a proximal end 214 and a distal end 216 . a plurality of slits 218 are defined by wall 212 , and are configured for introducing air into chamber 210 to disperse powder released from a capsule 219 . it should be understood that the present invention is not limited to a particular number of slits 218 , and can be configured such that at least one slit 218 is provided . powder released from capsule 219 is dispersed in chamber 210 and inhaled through apertures 224 and inhalation piece 226 by the user . in other embodiments of the invention , receptacles other than capsules are used , such as blisters and film covered container wells as is known in the art . in one embodiment , the volume of the receptacle is at least about 0 . 37 cm 3 . in another embodiment , the volume of the receptacle is at least about 0 . 48 cm 3 . in yet another embodiment , the receptacles have a volume of at least about 0 . 67 cm 3 or 0 . 95 cm 3 . in one embodiment of the invention , the receptacle is a capsule designated with a capsule size 2 , 1 , 0 , 00 , or 000 . suitable capsules can be obtained , for example , from shionogi ( rockville , md .). blisters can be obtained , for example , from hueck foils , ( wall , n . j .). the receptacle encloses or stores particles , also referred to herein as powders . the receptacle is filled with particles in a manner known to one skilled in the art . for example , vacuum filling or tamping technologies may be used . generally , filling the receptacle with powder can be carried out by methods known in the art . in one embodiment of the invention , the particle or powder enclosed or stored in the receptacle have a mass of about 5 milligrams ( mg ). preferably the mass of the particles stored or enclosed in the receptacle is at least about 10 mg . in one embodiment of the present invention , particles used with the device have a tap density of less than about 0 . 4 g / cm 3 . particles having a tap density of less than about 0 . 4 g / cm 3 are referred to herein as “ aerodynamically light ”. in a preferred embodiment , the particles have a tap density of near to or less than about 0 . 1 g / cm 3 . tap density is a measure of the envelope mass density characterizing a particle . the envelope mass density of particles of a statistically isotropic shape is defined as the mass of the particle divided by the minimum sphere envelope volume within which it can be enclosed . features that can contribute to low tap density include irregular surface texture and hollow or porous structure . particularly preferred particles and powders are described in u . s . pat . nos . 6 , 136 , 295 , 5 , 985 , 309 , 5 , 874 , 064 , and 5 , 855 , 913 , and u . s . patent application ser . no . 09 / 591 , 307 , filed jun . 9 , 2000 entitled “ high efficient delivery of a large therapeutic mass aerosol ”, the entirety of each of the foregoing patents and patent applications is hereby incorporated herein by reference . device 100 includes a means for puncturing 230 that is used to puncture capsule 219 to release powder contained therein into chamber 210 . in the embodiment shown in fig1 means for puncturing 230 is configured as a substantially u - shaped staple having two prongs 232 . in this embodiment , each of prongs 232 is configured with a square cross - section 234 , thereby providing a sharp point and two cutting edges . this will be discussed in more detail below with respect to fig9 a and 9b . as discussed in more detail below , device 100 could alternatively be configured with the puncturing implement shown in fig7 a through 7d . as can be readily appreciated by one skilled in the art , the present invention is not limited to use of a substantially u - shaped staple as the means for puncturing the capsule . alternatively , one , or a plurality of , straight needle - like implements could be used . preferably , the puncturing implement is configured to puncture at least two holes in the capsule . means for puncturing 230 is preferably configured to be movable between a non - puncturing position ( as depicted in fig1 ) and a puncturing position . in the puncturing position , prongs 232 pierce or puncture capsule 219 to make holes therein . in a preferred embodiment , a means for biasing is provided that biases the means for puncturing 230 in the non - puncturing position . in the embodiment shown in fig2 the means for biasing is configured as a spring 242 that biases the substantially u - shaped staple in the non - puncturing position . as noted with respect to fig1 device 100 includes inner casing 124 and outer casing 126 . as shown in fig2 a spring 244 is disposed in lower casing portion 120 that biases inner casing 124 in an outward position . upon compression of spring 244 , inner casing 124 moves from the outward position to an inward position , thereby drawing lower casing portion 120 toward upper casing portion 130 . compression of spring 244 also causes compression of spring 242 , thereby causing means for puncturing 230 to move to the puncturing position . upon release of compression , springs 242 and 244 return to their biased state , thereby returning means for puncturing 230 to its non - puncturing position , and inner casing 124 to its outward position . a pair of flanges 252 is disposed on first casing portion 120 . a pair of grooves 254 is disposed on second casing portion 130 so that flanges 252 can be received within grooves 254 to thereby couple the first and second casing portions . preferably , the first and second casing portions are coupled with a friction - fit engagement . a friction - fit engagement can be achieved using the groove and flange arrangement depicted in fig2 . other alternative configurations for a friction - fit engagement would be readily apparent to one skilled in the art . fig3 is an enlarged partial cross - section of one embodiment of chamber 210 . in the embodiment shown in fig3 chamber 210 does not contain a ring disposed on an inner surface , and an inner diameter of chamber 210 is depicted as “ x ”. such a configuration may be referred to herein as a “ straight ” chamber configuration . fig4 is an enlarged partial cross - section of another embodiment of chamber 210 . in the embodiment shown in fig4 a ring 400 is circumferentially coupled to an inner surface of chamber 210 . an inner diameter of ring 400 is depicted as “ y ”, and is less than inner diameter x of chamber 210 . in the embodiment shown in fig4 ring 400 is disposed at approximately a midpoint of chamber 210 . such a configuration may be referred to herein as a “ low ” ring position or “ low ” chamber configuration . as shown in fig4 in the low ring position , ring 400 is disposed adjacent slits 218 . the ring position is measured by the distance from the top of hemispheric region 222 to the bottom edge of ring 400 . this distance is depicted as “ z ”. the following dimensions are provided as exemplary dimensions of a device of the present invention . it should be understood by one skilled in the art that the present invention is not limited to the dimensions provided herein , or to any particular dimensions . in one embodiment of the chamber 210 shown in fig4 diameter x is 0 . 47 in ., diameter y is 0 . 38 in ., and distance z is 0 . 49 in . fig6 is an enlarged partial cross - section of another embodiment of chamber 210 . in the embodiment shown in fig6 ring 400 is circumferentially coupled to an inner surface of chamber 210 . an inner diameter of ring 400 is depicted as “ y ”, and is less than inner diameter x of chamber 210 . in the embodiment shown in fig6 ring 400 is disposed adjacent the proximal end of chamber 210 . such a configuration may be referred to herein as a “ high ” ring position or a “ high ” chamber configuration . the ring position is measured by the distance from the top of hemispheric region 222 to the bottom edge of ring 400 . this distance is depicted as “ z ”. the following dimensions are provided as exemplary dimensions of a device of the present invention . it should be understood by one skilled in the art that the present invention is not limited to the dimensions provided herein , or to any particular dimensions . in one embodiment of the chamber 210 shown in fig6 diameter x is 0 . 47 in ., diameter y is 0 . 38 in ., and distance z is 0 . 29 in . fig5 is an enlarged partial cross - section of another embodiment of chamber 210 . in the embodiment shown in fig5 ring 400 is circumferentially coupled to an inner surface of chamber 210 . an inner diameter of ring 400 is depicted as “ y ”, and is less than inner diameter x of chamber 210 . in the embodiment shown in fig5 ring 400 is disposed between the low ring position of fig4 and the high ring position of fig6 . such a configuration may be referred to herein as a “ mid ” ring position or “ mid ” chamber configuration . the ring position is measured by the distance from the top of hemispheric region 222 to the bottom edge of ring 400 . this distance is depicted as “ z ”. the following dimensions are provided as exemplary dimensions of a device of the present invention . it should be understood by one skilled in the art that the present invention is not limited to the dimensions provided herein , or to any particular dimensions . in one embodiment of the chamber 210 shown in fig5 diameter x is 0 . 47 in ., diameter y is 0 . 38 in ., and distance z is 0 . 39 in . in one embodiment of the present invention , ring 400 is integral with chamber 210 . in such an embodiment , ring 400 and chamber 210 are formed as a unit , such as through an injection molding , extrusion or a casting process . in another embodiment of the present invention , ring 400 is attached to the inner surface of chamber 210 in a manner known to those skilled in the art , such as through the use of glue or other type of adhesive , or by using an attaching device such as a pin or screw , etc . preferably , the casing of device 100 is made from a material that can be injection molded , such as a plastic material ( preferably fda approved , usp tested ). as would be readily apparent to one skilled in the art , the material is preferably durable , easy to clean , and non - reactive with powder medicaments . an exploded cross - sectional view of an alternate embodiment of a device 1500 of the present invention is shown in fig1 . device 1500 includes a first or lower casing portion 1540 and a second or upper casing portion 1550 removably coupled to first casing portion 1540 . first and second casing portions 1540 and 1550 are coupled through the use of a flange 1552 and a groove 1554 . preferred materials for device 1500 include food and drug administration ( fda ) approved , usp tested plastics . preferably , device 1500 is manufactured using an injection molding process , the details of which would be readily apparent to one skilled in the art . device 1500 includes an inhalation or emitter portion 1520 . inhalation portion 1520 comprises a hemispheric region 1522 that defines a plurality of apertures 1524 . it should be understood that the present invention is not limited to a particular number of apertures 1524 , and can be configured such that at least one aperture 1524 is provided . an inhalation piece 1526 is provided to allow for inhalation of the medicament by a user . inhalation piece 1526 can be configured as a mouth piece for inhalation through a user &# 39 ; s mouth . alternatively , inhalation piece 1526 can be configured as a nose piece for inhalation through a user &# 39 ; s nose . device 1500 includes a cylindrical chamber 1510 that is defined by a straight wall 1512 of circular cross - section . a plurality of slits 1518 are defined by wall 1512 , and are configured for introducing air into chamber 1510 to disperse powder released from , for example , capsule 219 as illustrated in fig2 . it should be understood that the present invention is not limited to a particular number of slits 1518 , and can be configured such that at least one slit 1518 is provided . powder released from capsule 219 is dispersed in chamber 1510 and inhaled through apertures 1524 and inhalation piece 1526 by the user . as would be readily apparent to one skilled in the art , device 1500 can be configured with means for puncturing and means for biasing in a manner similar to that described above with respect to the embodiment shown in fig1 and 2 . means for puncturing are described in more detail below with respect to fig7 a through 7d , 8 , 9 a , and 9 b . moreover , device 1500 can be configured with the chamber designs described above with respect to fig3 - 6 . fig1 is a bar graph illustrating emitted dose at flow rates of 20 l / min ( left bar ), 40 l / min ( center bar ), and 60 l / min ( right bar ) for a total volume of 2l for four dispersion chamber configurations ( standard deviations shown ; sample size n = 3 ). the flow rates were measured with a flow meter . the emitted dose measurement involved placing a capsule into four embodiments of the inhaler of the present invention for actuation into an emitted dose ( ed ) measurement apparatus . the ed apparatus included a powder filter and a filter holder . the powder collected by the ed apparatus was quantified by fluorescence spectrophotometry . the straight configuration is shown in fig3 ; the low configuration is shown in fig4 ; the mid configuration is shown in fig5 ; and the high configuration is shown in fig6 . as can be seen from fig1 , each of the low , mid , and high configurations demonstrated a higher emitted dose at each of the three flow rates than the straight ( no ring ) configuration . thus , the ring configuration of the present invention provides an improvement over conventional chamber designs without a ring , such as those shown in the &# 39 ; 819 and &# 39 ; 385 patents . at each of the flow rates shown in fig1 , the low configuration produced a higher emitted dose and a lower standard deviation than the mid and high configurations . fig1 is a bar graph illustrating emitted dose at low flow rates for devices with varying numbers of slits 218 . a flow rate of less than about 15 l / min will be referred to herein as a “ low flow rate .” the measurements were taken at a flow rate of 5 l / min , with a volume of 67 cc and a 15 mg dosage . as show in fig1 , by decreasing the number of slits 218 , the emitted dose increases so that the device of the present invention successfully delivers a high emitted dose at low flow rate over multiple ( ten ) actuations . thus , the device of the present invention achieves a high emitted dose at low flow rates that is consistently reproducible with low standard deviation . experiments were conducted to evaluate the emitted dose as a function of air volume drawn through the inhaler . the inhaler was operated at a constant flow rate of 30 l / min for a 5 mg dose . the volume of air through the inhaler was varied by varying the actuation time . volumes of 0 . 5 , 1 . 0 , 1 . 5 , 2 . 0 and 3 . 0 l were investigated . fig1 shows the percentage emitted dose as a function of air volume ( n = 3 , standard deviations shown ). the emitted dose remained constant across the range of volumes and was consistently reproducible with low standard deviation . in the embodiments having the inner diameter x of chamber 210 of 0 . 47 in . and the inner diameter y of ring 400 of 0 . 38 in ., the ratio of the inner diameter of the ring to the inner diameter of the chamber is about 0 . 8 . by modifying the inner diameters of the ring and the chamber , it is possible to optimize the emitted dose at varying flow rates . as reported in annals of the icrp , human respiratory tract model for radiological protection , 24 ( 1 - 3 ), elsevier science , inc ., new york , 1994 , the flow rate for a tidal breathing seated adult male is 300 ml / s ( 18 l / min ) for a volume of 750 ml . in one embodiment of a device of the present invention optimized for low flow rates ( less than about 15 l / min ), inner diameter x of chamber 210 is 0 . 33 in . and inner diameter y of ring 400 is 0 . 30 in . in such an embodiment , the ratio of the inner diameter of the ring to the inner diameter of the chamber is about 0 . 9 . preferably , the ratio of the inner diameter of the ring to the inner diameter of the chamber is about 0 . 9 or less . the device of the present invention can also be optimized for varying dosage ranges . one way to do so is to vary the dimensions of chamber 210 to accommodate varying sizes of capsules . for example , a chamber having an inner diameter x of 0 . 33 in ., inner diameter y of 0 . 30 in ., and distance z of 0 . 57 in . can be used with size 2 and size 00 capsules . it should be readily apparent to one skilled in the art that chamber 210 can be scaled to accommodate varying capsule sizes , and to accommodate those capsule sizes at varying flow rates . the device of the present invention can be used with varying dosage ranges . a highly dispersible powder was prepared and loaded into capsules to obtain a large pre - metered dose ( 50 mg ) and a smaller pre - metered dose ( 6 mg ). the particle size characteristics of the powder were as follows : dg = 10 . 6 μm ; ρ = 0 . 11 g / cc ; and da = 3 . 5 μm , where dg is the mean geometric diameter , ρ is the powder density , and da is the mean aerodynamic diameter . the aerodynamic particle size distributions were characterized using a multistage liquid impinger that extracted air at 60 l / min after actuating the inhaler device ( d ). as shown in fig1 , the mass fraction was measured at d , the induction port ( ip ) of the impactor , stages s 1 - s 4 , and the filter cutoff ( sf ). size 2 capsules were used for the 6 mg dose and size 000 capsules were used for the 50 mg dose . fig1 shows the results comparing the two particle size distributions obtained for the 6 mg ( left bar ) and 50 mg ( right bar ) doses . “ ed ” used on the graph refers to emitted dose , and fpm used on the graph refers to fine particle mass ( estimate of the mass that would deposit in the lungs ). the fine particle fraction & lt ; 6 . 8 μm relative to the total dose ( fpf td & lt ; 6 . 8 μm ) for the 6 and 50 mg doses were 74 . 4 % and 75 . 0 %, respectively . similar aerodynamic particle size distributions were obtained for both doses . fig1 is a graph showing glucose ( mg / dl ) in beagle dogs after administration of human insulin using an aerosol generator and a device of the present invention with the low ring configuration substantially as shown in fig4 . the generator is a device with proven ability for forming a respirable aerosol that results in deposition of powder in dog lungs . metered powder is presented to a chamber where the powder is dispersed by a high velocity jet of air . the dispersed powder is directed toward a baffle to separate large agglomerates before inhalation by the dog . the pharmakodynamic profile shown in fig1 confirms that the device of the present invention produces a pattern of powder deposition similar to the aerosol generator . the dogs were anesthetized for the dosing procedure . a forced maneuver was used with dogs being ventilated at 75 % of their vital capacity ( approximately 100 cc / s or 6 l / min for a duration of 1 second ). a 4 second breath - hold was applied at the end of each inhalation . a physically smaller device was used with the low ring configuration to facilitate administration . the device performed well at the low flow rate with the anesthetized dogs using the forced maneuver . based on these results , such a device could be used with a sleeping person or a person having breathing problems , such as from chronic obstructive pulmonary disease ( copd ). as can be seen from the description above , the device of the present invention relies upon the breath of the user to drive the inhalation process , yet the device is configured to work successfully at low flow rates . as such , the device of the present invention has particular suitability for use with individuals who cannot breath hard , such as a child , an individual with respiratory disease , or individuals who are sleeping or in a coma . turning now to fig7 a through 7d , a preferred embodiment of a staple suitable for use in the present invention is shown . the staple preferably comprises a rectangular length of material that has four planar side surfaces 730 . each planar side surface intersects with two other planar side surfaces to create a total of four non - planar edges 736 . the staple is preferably bent into a substantially u - shaped configuration , thereby having a rounded portion and two prongs 732 . the prongs 732 terminate at two end surfaces 731 . as best seen in fig7 a , 7 c and 7 d , end surfaces 731 are diamond - shaped . the diamond - shaped end surfaces are created by bending the material about a non - planar edge . this configuration is best shown in fig7 b and 7d . as can be seen , each prong 732 has an inner surface 738 that comprises one of the non - planar edges and an outer surface 740 that comprises the opposite non - planar edge . the inner surface 738 of each prong 732 terminates at the uppermost portion 737 of the diamond - shaped end surface , thereby creating a cutting edge for the prong . the outer surface 740 of the prong 732 terminates at the lowermost portion 735 of the diamond - shaped end surface . fig9 a and 9b depict another embodiment of a staple suitable for use in the present invention . this staple preferably comprises a rectangular length of material that has four planar side surfaces . each planar side surface intersects with two other planar side surfaces to create a total of four non - planar edges . the staple is preferably bent into a substantially u - shaped configuration , thereby having a rounded portion and two prongs . the prongs terminate at two end surfaces that have a square shape . the square - shaped end surfaces are created by bending the material about a planar side surface . as shown in fig9 a , each prong has an inner surface that comprises one of the planar side surfaces and an outer surface that comprises the opposite planar side surface . the inner surface of each prong terminates at the uppermost portion of the square - shaped end surface , thereby creating a cutting edge for the prong . the outer surface of the prong terminates at the lowermost portion of the square - shaped end surface . fig9 b illustrates a puncture obtained from using the staple depicted in fig9 a . as shown , the holes formed by this staple have the appearance of being cut with a sharp edge . in addition , the material removed to create the hole is peeled back and remains well attached to the capsule ; thereby preventing the capsule material from being inhaled by the user when the powder medicament is being dispensed . fig8 illustrates a puncture obtained from using the staple depicted in fig7 a - 7d . the holes formed by the staple appear to be cut with a sharp edge , and the excess material is peeled back . in testing , the effort required to puncture the capsule is lower than circular section staples , and approximately the same as a square section staple . however , during testing , no instances were noted of crushed or otherwise mispunctured capsules . these staples are extremely inexpensive to produce , approximately one - third the cost of square section staples such as those depicted in fig9 a . in addition to improved puncturing performance , drug delivery from capsules punctured with the staple depicted in fig7 a - 7d is greatly improved . the emitted dose ( ed ) and fine particle fraction ( fpf ) of a test powder was measured at both 20 and 60 liters per minute ( lpm ). in all cases , the aerosol emitted from capsules punctured with the diamond section staple of fig7 a - 7d was improved over a conventional circular stock staple . most significantly , the fpf of powder delivered at 20 liters per minute was improved almost to the level of the fpf at 60 liters per minute . the present invention also relates to a method for dispensing powder medicaments to a user through the various embodiments of the disclosed inhalation device . in such a method , a receptacle containing the powder medicament , e . g ., a capsule 219 , is placed or formed into cylindrical chamber 210 . when the user compresses the inhalation device , staple 230 is moved toward capsule 219 thereby puncturing capsule 219 to cause the release of powder into chamber 210 . after release into the chamber , the powder is then inhaled by the user through apertures 224 and inhalation piece 226 . as noted , inhalation piece 226 , can be configured as either a mouth piece or a nose piece . for subsequent uses , the user merely replaces emptied capsule 219 with another capsule 219 that contains a new supply of power medicament . alternatively , powder medicament is injected into a permanent receptacle that is formed into chamber 210 . while various embodiments of the present invention have been described above , it should be understood that they have been presented by way of example only , and not limitation . for example , the present invention is not limited to the physical arrangements or dimensions illustrated or described . nor is the present invention limited to any particular design or materials of construction . as such , the breadth and scope of the present invention should not be limited to any of the above - described exemplary embodiments , but should be defined only in accordance with the following claims and their equivalents .

inhalation device and associated method for facilitating inhalation by a patient of powder medicaments contained in a receptacle . the inhalation device has a chamber for receiving the receptacle . a ring is circumferentially coupled to an inner surface of the chamber to achieve a higher reproducible emitted dose of medicament from the receptacle . the inhalation device also includes an improved implement for puncturing the receptacle , requiring less force and experiencing fewer failures .

the present invention relates to medical articles comprising synergistic combinations of chlorhexidine and triclosan . chlorhexidine may be provided by way of any form , salt or derivative thereof , including but not limited to chlorhexidine free base and chlorhexidine salts such as chlorhexidine diphosphanilate , chlorhexidine digluconate , chlorhexidine diacetate , chlorhexidine dihydrochloride , chlorhexidine dichloride , chlorhexidine dihydroiodide , chlorhexidine diperchlorate , chlorhexidine dinitrate , chlorhexidine sulfate , chlorhexidine sulfite , chlorhexidine thiosulfate , chlorhexidine di - acid phosphate , chlorhexidine difluoro - phosphate , chlorhexidine diformate , chlorhexidine dipropionate , chlorhexidine di - iodobutyrate , chlorhexidine di - n - valerate , chlorhexidine dicaproate , chlorhexidine malonate , chlorhexidine succinate , chlorhexidine malate , chlorhexidine tartrate , chlorhexidine dimonoglycolate , chlorhexidine monodiglycolate , chlorhexidine dilactate , chlorhexidine di - α - hydroxyisobutyrate , chlorhexidine diglucoheptonate , chlorhexidine di - isothionate , chlorhexidine dibenzoate , chlorhexidine dicinnamate , chlorhexidine dimandelate , chlorhexidine di - isophthalate , chlorhexidine di - 2 - hydroxynaphthoate , and chlorhexidine embonate . the term “ chlorhexidine ”, as used herein , may refer to any of such forms , derivatives , or salts , unless specified otherwise . chlorhexidine salts may be solubilized using polyethylene glycol or propylene glycol , or other solvents known in the art . the term triclosan refers to a compound also known as 2 , 4 , 4 ′- trichloro - 2 ′- hydroxydiphenyl ether . medical articles that may be treated according to the invention are either fabricated from or coated or treated with biomedical polymer and include , but are not limited to , catheters including urinary catheters and vascular catheters ( e . g ., peripheral and central vascular catheters ), wound drainage tubes , arterial grafts , soft tissue patches , gloves , shunts , stents , tracheal catheters , wound dressings , sutures , guide wires and prosthetic devices ( e . g ., heart valves and lvads ). vascular catheters which may be prepared according to the present invention include , but are not limited to , single and multiple lumen central venous catheters , peripherally inserted central venous catheters , emergency infusion catheters , percutaneous sheath introducer systems and thermodilution catheters , including the hubs and ports of such vascular catheters . the present invention may be further applied to medical articles that have been prepared according to u . s . pat . no . 5 , 019 , 096 by fox , jr . et al . the present invention provides , in various alternative non - limiting embodiments , for : ( 1 ) compositions which provide a local concentration of chlorhexidine of between 100 and 2000 μg / ml and a local concentration of triclosan of between 250 and 2000 μg / ml ; ( 2 ) treatment solutions of a polymer comprising between 1 and 5 percent , and preferably between 1 . 5 and 2 . 25 percent , of chlorhexidine ; and between 0 . 5 and 5 percent , and preferably between 0 . 5 and 2 percent , of triclosan , wherein a medical article may be dipped or soaked in the polymer solution ; ( 3 ) medical articles treated with a treatment solution as set forth in ( 2 ) above , and articles physically equivalent thereto ( that is to say , articles prepared by a different method but having essentially the same elements in the same proportions ); ( 4 ) treatment solutions of a polymer comprising between 1 and 5 percent , and preferably between 1 . 5 and 2 . 25 percent , of chlorhexidine ; between 0 . 5 and 5 percent , and preferably between 0 . 5 and 2 percent , of triclosan ; and between 0 . 5 and 1 percent ( preferably 0 . 75 percent ) of silver sulfadiazine , wherein a medical article may be dipped or soaked in the polymer solution ; and ( 5 ) medical articles treated with a treatment solution set forth in ( 4 ) above , and articles physically equivalent thereto ( that is to say , articles prepared by a different method but having essentially the same elements in the same proportions ). percentages recited herein refer to percent by weight , except as indicated otherwise . in preferred embodiments , the ratio , by weight , of the total amount of anti - infective agent to polymer in the treatment solution is less than 1 . 5 . in one particular non - limiting embodiment , the present invention provides for a hydrophilic polymeric medical article ( i . e ., a medical article fabricated from a hydrophilic polymer ) treated by dipping or soaking the article in a treatment solution of a hydrophilic polymer comprising chlorhexidine and triclosan wherein the chlorhexidine and triclosan are present in amounts such that their combination , in the treated article , has effective antimicrobial activity . the terms “ treat ”, “ treated ”, etc ., as used herein , refer to coating , impregnating , or coating and impregnating a medical article with polymer / anti - infective agent . the term “ hydrophilic polymer ”, as used herein , refers to polymers which have a water absorption greater than 0 . 6 percent by weight ( and , in preferred embodiments , less than 2 percent by weight ; as measured by a 24 hour immersion in distilled water , as described in astm designation d570 - 81 ) including , but not limited to biomedical polyurethanes ( e . g ., ether - based polyurethanes and ester - based polyurethanes , as set forth in baker , 1987 , in controlled release of biologically active agents , john wiley and sons , pp . 175 - 177 and lelah and cooper , 1986 , polyurethanes in medicine , crc press , inc ., fla . pp . 57 - 67 ; polyurethanes comprising substantially aliphatic backbones such as tecoflex ™ 93a ; polyurethanes comprising substantially aromatic backbones such as tecothane ™; and pellethane ™), polylactic acid , polyglycolic acid , natural rubber latex , and gauze or water - absorbent fabric , including cotton gauze and silk suture material . in a specific , non - limiting embodiment , the hydrophilic medical article is a polyurethane catheter which has been treated with ( i . e ., dipped or soaked in ) a treatment solution comprising ( i ) between about 1 and 10 percent , preferably between about 2 and 6 percent , and more preferably about 3 percent , of a biomedical polyurethane ; ( ii ) between 1 and 5 percent , and preferably between 1 . 5 and 2 . 25 percent , of chlorhexidine ; and ( iii ) between 0 . 5 and 5 percent , and preferably between 0 . 5 and 2 percent , of triclosan . in related non - limiting embodiments of the invention , the treatment solution may further comprise silver sulfadiazine , preferably in a concentration of between 0 . 5 and 1 percent ( more preferably 0 . 75 percent ). section 6 , below , presents working examples of embodiments set forth in this paragraph . in another particular non - limiting embodiment , the present invention provides for a hydrophilic polymeric medical article treated by dipping or soaking the article in a treatment solution of a hydrophobic polymer comprising chlorhexidine and triclosan , wherein the chlorhexidine and triclosan are present in amounts such that their combination , in the treated article , has effective antimicrobial activity . the term “ hydrophobic polymer ”, as used herein , refers to a polymer which has a water absorption of less than 0 . 6 percent and includes , but is not limited to , silicone polymers such as biomedical silicones ( e . g ., silastic type a ) or elastomers ( e . g ., as set forth in baker , 1987 , in controlled release of biologically active agents , john wiley and sons , pp . 156 - 162 ), dacron , polytetrafluoroethylene ( ptfe , also “ teflon ”), polyvinyl chloride , cellulose acetate , polycarbonate , and copolymers such as silicone - polyurethane copolymers ( e . g ., ptue 203 and ptue 205 polyurethane - silicone interpenetrating polymer ). in a specific , non - limiting embodiment , the medical article is a polyurethane catheter which has been dipped or soaked in a treatment solution comprising ( i ) between about 1 and 10 percent , preferably between about 2 and 6 percent , and more preferably about 3 percent , of a polyurethane — silicone copolymer ; ( ii ) between 1 and 5 percent , and preferably between 1 . 5 and 2 . 25 percent , of chlorhexidine ; and ( iii ) between 0 . 5 and 5 percent , and preferably between 0 . 5 and 2 percent , of triclosan . in related non - limiting embodiments of the invention , the treatment solution may further comprise silver sulfadiazine , preferably in a concentration of between 0 . 5 and 1 percent ( more preferably 0 . 75 percent ). section 7 , below , presents working examples of embodiments set forth in this paragraph . in another particular non - limiting embodiment , the present invention provides for a hydrophobic polymeric medical article treated by dipping or soaking the article in a treatment solution of hydrophobic polymer comprising chlorhexidine and triclosan , wherein the chlorhexidine and triclosan are present in amounts such that their combination , in the treated article , has effective antimicrobial activity . in a specific , non - limiting embodiment , the medical article is a silicone catheter or a polyvinylchloride catheter which has been dipped or soaked in a treatment solution comprising ( i ) between about 1 and 10 percent , and preferably about 5 percent , of a silicone polymer ; ( ii ) between 1 and 5 percent , and preferably between 1 . 5 and 2 . 25 percent , of chlorhexidine ; and ( iii ) between 0 . 5 and 5 percent , and preferably between 0 . 5 and 2 percent , of triclosan . in related non - limiting embodiments of the invention , the treatment solution may further comprise silver sulfadiazine , preferably in a concentration of between 0 . 5 and 1 percent ( more preferably 0 . 75 percent ). in still other related embodiments , a coating of a hydrophobic polymer may be applied over the treated article . section 8 , below , presents working examples of embodiments set forth in this paragraph . in another particular non - limiting embodiment , the present invention provides for a hydrophobic polymeric medical article treated by dipping or soaking the article in a treatment solution of hydrophilic polymer comprising chlorhexidine and triclosan , wherein the chlorhexidine and triclosan are present in amounts such that their combination , in the treated article , has effective antimicrobial activity . in a specific , non - limiting embodiment , the medical article is a silicone catheter or teflon graft which has been dipped or soaked in a treatment solution comprising ( i ) between about 1 and 10 percent , preferably between about 2 and 6 percent , and more preferably about 3 percent , of a biomedical polyurethane polymer ; ( ii ) between 1 and 5 percent , and preferably between 1 . 5 and 2 . 25 percent , of chlorhexidine ; and ( iii ) between 0 . 5 and 5 percent , and preferably between 0 . 5 and 2 percent , of triclosan . in related non - limiting embodiments of the invention , the treatment solution may further comprise silver sulfadiazine , preferably in a concentration of between 0 . 5 and 1 percent ( more preferably 0 . 75 percent ). medical articles prepared according to the invention may be treated on their external surface , internal surface , or both . for example , and not by way of limitation , where the medical article is a catheter , the internal surface and / or external surface of the catheter may be treated according to the invention . for example , where it is desired to treat both internal and external surfaces , an open - ended catheter may be placed in a treatment solution such that the treatment solution fills the catheter lumen . if only the external surface is to come in contact with treatment solution , the ends of the catheter may be sealed before it is placed in the treatment solution . if only the internal surface is to come in contact with treatment solution , the solution may be allowed to pass through and fill the lumen but the catheter is not immersed in the treatment solution . successful treatment of a medical article with a polymer comprising an anti - infective agent may be problematic , particularly where the medical article has a hydrophobic surface . the adherence of the polymer may depend upon ( 1 ) the polymeric matrix in which the anti - infective agent is suspended ; ( 2 ) compatibility ( or lack thereof ) between the agent - polymeric matrix and the surface of the article ; ( 3 ) the solvent system ; and ( 4 ) the thickness of polymer / anti - infective agent desirably applied . furthermore , the rates of release of various anti - infective agents from diverse polymers may differ . for example , the rate of release of chlorhexidine from a silicone matrix is faster than the rate of release of silver sulfadiazine from the same matrix . in order to compensate for this difference , one potential solution would be to increase the amounts of chlorhexidine and silver sulfadiazine in the matrix . unfortunately , polymers comprising high levels of chlorhexidine and silver sulfadiazine have been found to adhere poorly to silicone catheters . in order to provide an alternative solution to the problem , two different methods for treating medical articles have been developed : a one - step method , and a two - step method , both of which are set forth below . according to the one - step method of the invention , a polymeric medical article may be treated with a solution comprising one or more anti - infective agents , and optionally containing a biomedical polymer , dissolved in one or more solvent ( s ), wherein the solvent ( s ) selected are capable of swelling the polymeric medical article to be treated ; such a solution is referred to herein as an “ impregnating solution ”, and the process by which the article is treated with anti - infective agent is referred to as “ impregnation ”. suitable solvents include , but are not limited to , tetrahydrofuran (“ thf ”), dichloromethane , carbon tetrachloride , methanol , ethanol , methyl ethyl ketone , heptane , and hexane , and mixtures thereof . the biomedical polymer may be hydrophilic or hydrophobic , and includes the various polymers set forth above . if a hydrophilic polymeric medical article is to be impregnated with chlorhexidine and triclosan , the impregnating solution may , in specific non - limiting embodiments , comprise the following ( percentages of solvents in this paragraph being volume / volume ): ( 1 ) 95 % ethanol ; ( 2 ) 70 % ethanol / 30 % water ; ( 3 ) 50 % ethanol / 50 % water ; ( 4 ) 30 % reagent alcohol / 70 % thf containing 2 - 3 % of a biomedical polyurethane ; ( 5 ) 90 % reagent alcohol / 10 % thf ; or ( 6 ) 100 % reagent alcohol . preferred soaking times vary between 5 minutes and 1 hour . in specific , non - limiting embodiments of the invention , a hydrophilic medical article such as a polyurethane catheter may be impregnated using a solvent mixture of 70 - 90 % ethanol and 10 - 30 % water and chlorhexidine and triclosan for between 10 and 60 minutes . the article may then be dried for 24 - 48 hours . if a hydrophobic polymeric medical article is to be impregnated with chlorhexidine and triclosan , the impregnating solution may , in specific non - limiting embodiments , comprise the following percentages of solvents in this paragraph being volume / volume ): ( 1 ) 10 % methanol / 90 % thf ; ( 2 ) 10 % ethanol / 90 % thf ; ( 3 ) 30 % methanol / 70 % thf ; ( 4 ) 30 % ethanol / 70 % thf ; ( 5 ) 1 - 5 percent silicone polymer in 10 % methanol / 90 % thf ; ( 6 ) 1 - 5 percent silicone polymer in 10 % ethanol / 90 % thf ; ( 7 ) 1 - 2 percent polylactic acid in 10 % methanol / 90 % thf ; ( 8 ) 1 - 2 percent polylactic acid in 10 % ethanol / 90 % the ; ( 9 ) 1 - 5 percent silicone polymer in 30 % methanol / 70 % thf ; ( 10 ) 1 - 5 percent silicone polymer in 30 % ethanol / 70 % thf ; ( 11 ) 1 - 2 percent polylactic acid in 30 % methanol / 70 % thf ; ( 12 ) 1 - 2 percent polylactic acid in 30 % ethanol / 70 % thf ; ( 13 ) 1 - 5 percent silicone polymer in 100 % methyl ethyl ketone ; and ( 14 ) 1 - 2 percent polyurethane in 30 % ethanol / 70 % thf . for specific examples , see section 15 , below . in specific embodiments , the impregnating solution comprises between 0 . 2 and 10 percent anti - infective agent and between 0 . 5 and 4 percent biomedical polymer . the medical article , or a portion thereof , may be immersed in the impregnating solution to swell , after which the article may be removed and dried at room temperature until all solvent has evaporated and the article is no longer swollen . during the swelling process , anti - infective agent ( and small amounts of polymer when present in the impregnating solution ) may be distributed within the polymeric substrate of the article ; during drying , the anti - infective agent and biomedical polymer ( where present ) may migrate somewhat toward the surface of the article . after drying , the article may be rinsed in either water or alcohol and wiped to remove any excess anti - infective agent and / or polymer at the surface . this may leave a sufficient amount of anti - infective agent just below the surface of the article , thereby permitting sustained release of the agent over a prolonged period of time . anti - infective agents which may be incorporated by this process include but are not limited to chlorhexidine , triclosan , silver sulfadiazine , parachlorometaxylene , benzalkonium chloride , bacitracin , polymyxin , miconasole and rifampicin , as well as combinations thereof . in preferred , non - limiting embodiments of the invention , synergistic combinations of chlorhexidine and triclosan may be dissolved in a mixture of methanol and tetrahydrofuran to produce an impregnating solution that may be used to render a silicone catheter anti - infective . in one specific , non - limiting example , the amount of chlorhexidine may be between 1 and 5 percent and preferably between 1 . 5 and 2 . 25 percent of the impregnating solution , and the amount of triclosan may be between 0 . 5 and 5 percent , and preferably between 0 . 5 and 2 percent . the resulting impregnating solution may further contain between 1 and 10 percent and preferably between 2 and 4 percent of a biomedical polymer such as a silicone polymer ( e . g ., silastic type a ), polyurethane , or polycaprolactone . specific examples of the one - step method are provided in section 12 below . according to the two - step method of the invention , the one - step method may be used to impregnate a medical article with anti - infective agent , and then the medical article may be dipped into a polymeric solution and dried . this method forms a polymeric coating on the article and further controls the rate of release of anti - infective agent . when the two - step method is practiced , the biomedical polymer may be omitted from the first soaking step . optionally , an anti - infective agent may further be comprised in the polymeric coating . in a specific , non - limiting example , a silicone catheter may be dipped in a mixture of methanol and tetrahydrofuran containing between about 1 and 5 percent , and preferably between 1 . 5 and 2 . 25 percent , of chlorhexidine ; between 0 . 5 and 5 percent and preferably between 0 . 5 and 2 percent of triclosan ; and between 1 and 10 percent , and preferably between 2 and 4 percent , of a biomedical polymer ( preferably a silicone polymer such as silastic type a ) for about 30 minutes , dried , and then dipped in a higher concentration ( but less than 10 percent ) of biomedical polymer dissolved in a suitable solvent . for example , but not by way of limitation , a coating may be applied using a solution of 30 % ethanol / 70 % thf containing 2 - 3 percent of a biomedical polyurethane , or a solution of 1 - 5 percent of silastic type a . alternatively , a hydrophilic medical article , such as a polyurethane catheter , may be impregnated with one or more antimicrobial agents and then coated with a polymer . examples of the two - step method are set forth in sections 8 , 16 and 17 below . as set forth in section 17 , below , it has further been discovered that when medical articles were treated with mixtures of chlorhexidine free base and triclosan , uptake of chlorhexidine and triclosan was enhanced , and the antimicrobial activity of such articles was improved . while not desiring to be bound to any particular theory , it is believed that chlorhexidine free base and triclosan form a complex with improved solubility . the foregoing effect was observed when chlorhexidine free base and triclosan were combined in a respective molar ratio of 1 : 2 ; according to the invention , chlorhexidine free base and triclosan maybe dissolved in a solvent or solvent system at chlorhexidine free base : triclosan molar ratios of 1 : 1 to 1 : 3 . the total weight percent of chlorhexidine free base plus triclosan is between 1 and 10 percent . the chlorhexidine free base and triclosan may be dissolved in a solvent system comprising water , alcohol , or tetrahydrofuran , and mixtures thereof , to produce an impregnating solution . in one specific , non - limiting example of the invention , a 1 : 2 ratio of chlorhexidine free base and triclosan may be dissolved in a solvent system which is 70 percent tetrahydrofuran and 30 percent reagent alcohol . a medical article , for example , a polyurethane article , may be impregnated with chlorhexidine free base / triclosan by immersing the article in such an impregnating solution so that the medical article swells without losing substantial structural integrity . after impregnation , the article may be dried , and then optionally coated with a polymeric solution , according to the two - step method set forth above . anti - infective medical articles prepared by other methods ( e . g ., extrusion , casting ) but being otherwise substantially the same as articles produced by dipping or soaking , are within the scope of the claimed invention . 5 . example : combinations of chlorhexidine and triclosan exhibit synergistic activity in bacterial cultures various concentrations of chlorhexidine diacetate (“ cha ”) and / or triclosan (“ tc ”) were dispensed in 1 . 0 ml trypticase soy broth (“ tsb ”) containing 20 percent bovine calf serum (“ bcs ”) and inoculated with 10 7 colony - forming units (“ cfu ”) of staphylococcus aureus . after one minute , the cultures were diluted with drug - inactivating medium ( 1 : 100 dilution in ltsb drug inactivating medium , which is 5 % tween 80 , 2 % lecithin , 0 . 6 % sodium oleate , 0 . 5 % sodium thiosulfate , 0 . 1 % protease peptone and 0 . 1 % tryptone ) and 0 . 2 ml of the diluted culture was subcultured on a trypticase soy agar plate for the determination of colony counts . the results , shown in table i , demonstrate the synergistic activity of combinations of chlorhexidine and triclosan . for example , whereas 500 micrograms per milliliter of cha causes an approximately 17 - fold decrease in cfu , and 500 micrograms per milliliter of triclosan causes an approximately 2400 - fold decrease , the combination of these agents is associated with zero cfu , an at least 1 × 10 7 - fold decrease . 6 . example : combinations of chlorhexidine and triclosan are more effective than combinations of chlorhexidine and silver sulfadiazine when applied to hydrophilic catheters polyurethane central venous catheters fabricated of tecoflex 93 - a polyurethane were dipped in solutions containing 3 percent of a biomedical poly - urethane ( tecoflex 93 - a ; “ pu ”) and cha , tc and / or silver sulfadiazine (“ agsd ”) dissolved in 30 percent ethanol and 70 percent tetrahydrofuran (“ thf ”) ( v / v ) and air - dried . bacterial adherence on these catheters was measured as follows . a 2 cm segment of dipped catheter was suspended in 3 ml tsb containing 10 percent bcs and incubated in a water bath shaker at 37 ° c . the media was changed daily . after 2 days the catheter segments were removed and transferred to fresh media containing 10 6 cfu / ml of staphylococcus aureus and incubated for 24 hours . the segments were removed , rinsed with saline , and then suspended in ltsb drug - inactivating medium and sonicated for 20 minutes to remove the adherent bacteria . aliquots from the ltsb extract were then subcultured on trypticase soy agar plates to determine colony counts . the results are presented in table ii , and demonstrate that combinations of cha and tc are superior in preventing bacterial adherence when compared with cha alone or in combination with agsd . in additional experiments , additional segments of the same type of polyurethane catheters coated with cha , tc and / or agsd were tested for the ability to produce zones of inhibition in trypticase soy agar plates seeded with 0 . 3 ml of 106 cfu of staphylococcus aureus , enterobacter cloacae , candida albicans , and pseudomonas aeruginosa . the coated catheter segments were placed vertically on the seeded plates , which were then incubated for 24 hours at 37 ° c . before the zones of inhibition were measured . the results , shown in table iii , demonstrate the superior effectiveness of mixtures of chlorhexidine and triclosan . 7 . example : hydrophilic catheters coated with hydrophobic polymer comprising chlorhexidine and triclosan have antimicrobial activity the antimicrobial effectiveness of polyurethane central venous catheters ( fabricated from tecoflex 93 - a polyurethane ) coated with chlorhexidine diacetate and either triclosan or silver sulfadiazine in two polymeric coatings of differing water absorption were tested . the polymeric coatings , applied as set forth in section 6 above , comprised either polyurethane 93a (“ pu 93a ”), a hydrophilic polyurethane having a water absorption of about 1 - 2 percent or polyurethane - silicone interpenetrating polymer (“ ptue 205 ”), a hydro - phobic silicone - polyurethane copolymer having a water absorption of only 0 . 4 %. antibacterial activity was measured by zones of inhibition , using methods as set forth in section 6 , above . the results , as regards antibacterial activity toward staphylococcus aureus , enterobacter cloacae , and candida albicans at days 1 and 3 of culture , are shown in tables iv , v , and vi , respectively , and demonstrate that combinations of chlorhexidine diacetate and triclosan were effective when comprised in hydrophilic ( pu 93a ) as well as hydrophobic ( ptue 205 ) coatings . 8 . example : hydrophobic catheters treated with hydrophobic polymer comprising chlorhexidine and triclosan have antimicrobial activity silicone central venous catheters fabricated from dow coming q7 - 4765a silicone polymer or q7 - 4765b silicone polymer were used to determine the effectiveness of impregnation with hydrophobic polymers comprising chlorhexidine diacetate and triclosan on hydrophobic substrates . the silicone catheters were soaked for about 30 minutes in a solution of 5 percent methanol and 95 percent thf ( v / v ) comprising ( i ) 2 percent medical adhesive silastic type a and ( ii ) chlorhexidine diacetate and either triclosan or silver sulfadiazine . the dipped catheters were dried and then dipped in a solution of 5 percent methanol and 95 percent thf ( v / v ) containing 5 percent silastic type a (“ si1a ”), and dried again . the catheter segments were then tested for the production of zones of inhibition on trypticase soy agar plates inoculated with s . aureus or e . cloacae . the results are presented in table vii . silicone central venous catheters fabricated from dow coming q7 - 4765a silicone polymer or q7 - 4765b silicone polymer were treated as set forth in section 8 , above , and then , immediately after drying , were extracted in dichloromethane / methanol / water ( 50 %/ 25 %/ 25 %, v / v ) in order to determine the amount of agent contained in the catheter segment tested ( i . e ., the uptake ). to determine the rate of drug release , catheter segments were suspended in saline and incubated at 37 ° c . for up to seven days ; the saline was collected and replaced with fresh saline on the first day and every 48 hours thereafter , and the amount of drug present in the collected saline was measured . the results are presented in table viii . silicone catheters impregnated with silastic type a comprising either 2 % triclosan or 2 % chlorhexidine diacetate were then tested for the ability to produce zones of inhibition on trypticase soy agar plates inoculated with s . aureus , e . cloacae , c . albicans , or p . aeruginosa . the results of these experiments are shown in table ix , and demonstrate that when higher concentrations of triclosan or chlorhexidine diacetate alone were used , triclosan - treated catheters were found to be equally or more effective than cha - treated catheters . arterial grafts fabricated from polytetrafluoroethylene (“ ptfe ”) were cut into segments and impregnated with silastic type a comprising chlorhexidine diacetate or triclosan in 30 % methanol / 70 % thf ( v / v ), in proportions set forth below . the treated grafts were then extracted with dichloromethane / methanol / water ( 50 %/ 25 %/ 25 %, v / v ), and the amounts of solubilized anti - infective agents were determined . table x shows the uptake of agent by the treated grafts . 11 . example : antimicrobial effectiveness of medical articles fabricated from teflon , dacron or natural rubber latex and impregnated with combinations of chlorhexidine and triclosan chlorhexidine diacetate and either triclosan or silver sulfadiazine , in proportions set forth below , were dissolved in 5 % methanol / 95 % thf ( v / v ). segments of dacron grafts , ptfe grafts , and natural rubber latex urinary catheters were then soaked in the resulting solutions for 15 minutes to impregnate the segments with anti - infective agents . this procedure allows the polymer substrates of the devices to incorporate anti - infective agent . the segments were then removed from the soaking solution , dried , rinsed with water , and wiped . the ability of the treated segments to produce zones of inhibition on trypticase soy agar plates inoculated with s . aureus and e . cloacae was then tested . the results , shown in tables xi - xiii , demonstrate that the combination of chlorhexidine and triclosan produced superior antimicrobial results compared to the combination of chlorhexidine and silver sulfadiazine . 12 . example : antimicrobial effectiveness of silicone catheters prepared by a one - step impregnation method silicone catheters , as used in example 8 , were prepared by a one - step impregnation method as follows . segments of the silicone catheters were soaked for about 30 minutes in impregnating solutions of 90 % thf / 10 % methanol ( v / v ) containing 2 % silastic type a , chlorhexidine , and either silver sulfadiazine or triclosan . the segments were then dried , and tested for their ability to produce zones of inhibition ( at one and three days ) in trypticase soy agar plates inoculated with s . aureus , e . cloacae , c . albicans , and p . aeruginosa . the results , presented in table xiv , demonstrate the effectiveness of chlorhexidine and triclosan - impregnated catheters . additional formulations of impregnating solutions were tested for their ability to render the same type of silicone catheter segments anti - infective against c . albicans , the microorganism which appeared to be inhibited only by relatively high amounts of anti - infective agent . the following impregnating solutions comprised chlorhexidine , triclosan and either silastic type a , polycaprolactone , or no polymer in a 5 % methanol / 95 % thf solvent . table xv shows that when both polymer and anti - infective agent were comprised in the impregnating solution , higher anti - infective activity was achieved . 13 . example : diffusion of anti - infective agents from medical articles treated with impregnating solutions with and without polymer the following impregnating solutions , “ a ” and “ b ”, were used to impregnate segments of dacron and ptfe grafts . the treated grafts were then rinsed with saline , and the amounts of anti - infective agent incorporated into the grafts were determined , before and after rinsing , by extraction of anti - infective agent with dichloromethane / methanol / water ( 50 %/ 25 %/ 25 %, v / v ). the results , set forth in table xvi , demonstrate that the addition of a polymer to the impregnating solution produces a treated medical article which exhibits greater retention of anti - infective agent . 14 . example : drug uptake and release by hydrophilic catheters impregnated with chlorhexidine or triclosan polyurethane central venous catheter segments fabricated of tecoflex 93 - a polyurethane were impregnated with solutions “ c ”, “ d ”, “ e ”, “ f ” and “ g ” set forth below by soaking the catheter segments for about two minutes followed by drying and rinsing with water . drug uptake was measured by extracting the impregnated catheter segments with dichloromethane / methanol / water ( 50 %/ 25 %/ 25 % v / v ). drug release was measured over a period of six days by suspending the catheter segments in saline ( one 2 cm segment in 2 ml saline ), and agitated in a heated water bath at 37 ° c . ; the saline was changed daily and drug release was measured as described above . the results are shown in table xvii . polyurethane , as set forth below , is tecoflex 93 - a polyurethane . 15 . example : release of chlorhexidine and triclosan from impregnated silicone catheter segments segments of silicone central venous catheters fabricated from dow corning q7 - 4765a silicone polymer or q7 - 4765b silicone polymer were impregnated with either solution h or i by soaking for 30 minutes , and then the release of drug was measured daily by methods set forth above . the results of these measurements are presented in table xviii . 16 . method of rendering polyurethane catheters infection - resistant by impregnation with a synergistic combination of chlorhexidine and triclosan a one - step method (“ method 1 ”) and a two - step method (“ method 2 ”) were used to treat polyurethane catheters . method 1 : an entire polyurethane central venous catheter assembly including the hub , extension line and catheter body may be soaked in an alcoholic solution containing chlorhexidine and triclosan for a specific time period sufficient to impregnate these elements with chlorhexidine and triclosan without altering the integrity of the polyurethane substrate . the following solvent systems and soaking times are suitable . the concentrations of chlorhexidine and triclosan range from 0 . 5 - 5 %. selection of the solvent mixture depends on the type of polyurethane substrate and antimicrobials used for impregnation . after soaking , the catheter is rinsed in water for 24 to 48 hours to allow the catheter to regain its original integrity and size . method 2 . a catheter impregnated with chlorhexidine and triclosan according to method 1 is then dipped in 70 % thf / 30 % reagent alcohol / 1 - 3 % polyurethane / 1 - 3 % chlorhexidine / 1 - 3 % triclosan . catheters prepared by method 1 provide a relatively slow and steady release rate from the luminal surface and outer surface for a prolonged period of time . this pattern of drug release results from the relatively lower ratio of drug to polyurethane matrix ( 0 . 015 ). catheters prepared by method 2 exhibit biphasic drug release . the higher ratio of drug to polyurethane in the outer coating ( 1 . 3 ) permits an initial release of large amounts of drugs ( which may inactivate bacteria entering through the skin at the time of insertion ) followed by slow and steady release of drug impregnated in the catheter by method 1 . the outer polyurethane coating acts as a barrier and permits the controlled release of drug over a prolonged period of time . as specific examples , tecoflex polyurethane catheters were prepared using the following method and then tested for antimicrobial efficacy in their luminal and outer surfaces : i ) catheters were soaked in 2 % chlorhexidine dissolved in 100 % reagent grade alcohol for 1 hour , rinsed in water , and dried for 24 - 48 hours (“ catheter c ”); ii ) catheters were soaked in 2 % chlorhexidine + 2 % triclosan dissolved in 100 % reagent grade alcohol for 15 minutes , rinsed in water , and dried for 24 - 48 hours (“ catheter tc ”); iii ) catheters were soaked in 2 % triclosan in 70 % reagent alcohol / 30 % water for 2 minutes , rinsed in water , and dried for 24 - 48 hours (“ catheter t ”); iv ) catheter c ( above ) was dipped in 3 % polyurethane + 2 % chlorhexidine dissolved in 70 % thf / 30 % reagent alcohol (“ catheter c — c ”); v ) catheter c ( above ) was dipped in 3 % polyurethane + 2 % chlorhexidine + 0 . 75 % agsd dissolved in 70 % thf / 30 % reagent alcohol (“ catheter c - a ”); vi ) catheter t ( above ) was dipped in 2 % chlorhexidine + 2 % triclosan dissolved in 70 % thf / 30 % reagent alcohol (“ catheter t - r ”); vii ) catheter tc ( above ) was dipped in 2 % chlorhexidine + 2 % triclosan dissolved in 70 % thf / 30 % reagent alcohol (“ catheter tc - r ”); and viii ) catheter tc ( above ) was dipped in 2 % chlorhexidine + 0 . 75 % agsd dissolved in 70 % thf / 30 % reagent alcohol . trypticase soy agar plates were seeded with 10 5 cfu staphylococcus aureus / ml and 0 . 5 cm segments of catheter were embedded vertically . the plates were then incubated for 24 hours at 37 ° c . and zones of inhibition were measured . the results are shown in table xx . 17 . method of rendering polyurethane catheters infection - resistant by impregnation with a synergistic combination of chlorhexidine free base and triclosan it was further discovered that when catheters were coated using insoluble chlorhexidine free base and triclosan , a soluble chlorhexidine / triclosan complex was formed which improved the drug uptake and , therefore , the efficacy of the catheter . method 3 : catheters prepared by method 1 ( see section 16 ) were dried for 24 - 72 hours and then their outer surfaces were dipped in a polyurethane solution ( 1 - 3 % polyurethane dissolved in thf / alcohol ). catheters prepared by this method exhibited a large amount of drug release initially followed by a small but synergistically effective amount of drug release for a prolonged period of time . method 4 : followed the same procedure as method 1 , except that insoluble chlorhexidine free base ( chx ) was solubilized with triclosan ( 1 molar chx : 2 molar triclosan ratio ), which forms a complex with chx . after soaking for 5 - 10 minutes the catheters were dried for 1 - 3 days and then the outer surface was dipped in either a polyurethane solution alone ( 1 - 3 % polyurethane ) or a solution of polyurethane containing chx and triclosan ( tc ). when relatively soluble chlorhexidine salts such as chlorhexidine acetate ( cha ) were used to impregnate catheters , the release was undesirably rapid . we investigated the use of chx as a substitute for cha . chx is not soluble is water or alcohol but , surprisingly , we found that when it was combined in a 1 : 2 molar ratio with triclosan , an alcohol soluble complex formed . the uptake of chlorhexidine from a solution containing chx - tc complex was greater than that obtained from a cha - tc solution despite a higher cha concentration in the soaking solution . due to higher chlorhexidine levels and higher rate of chlorhexidine release from the substrate resulting from impregnation with chx - tc complex , the infection resistance of the catheters was greater than those containing only cha . method 5 : same as method 4 but the soaking and outer coating solutions also contained soluble chlorhexidine acetate . as specific examples , the following experiments were performed using tecoflex catheters : ( 1 ) catheters were prepared according to method 3 . specifically , catheters were soaked in 5 % cha + 1 % tc dissolved in reagent alcohol for 10 minutes , dried for three days , and then the outer surface was dipped in 2 . 7 % tecoflex polyurethane dissolved in thf / reagent alcohol ( 70 %/ 30 %); the resulting catheters are referred to as type 1 , and the polyurethane / thf / reagent alcohol solution is referred to as solution j . ( 2 ) a second group of catheters was prepared as in ( 1 ), but instead of using solution j for the outer coating , another solution was used : 0 . 5 % chx + 0 . 5 % tc + 2 . 7 % polyurethane dissolved in 70 % thf / 30 % reagent alcohol (“ solution k ”). the resulting catheters are referred to as type 2 . ( 3 ) catheters were prepared using method 5 . specifically , catheters were soaked in a solution containing 2 % chx + 2 % cha + 2 % tc dissolved in reagent alcohol for 10 minutes , dried for 3 days and their outer surfaces were dipped in solution j . the resulting catheters are referred to as type 3 . ( 4 ) catheters were prepared as in ( 3 ) but were dipped in solution k to produce an outer coating . the resulting catheters are referred to as type 4 . ( 5 ) catheters were prepared according to method 4 . specifically , catheters were soaked for 10 minutes in 3 % chx + 3 % tc in reagent alcohol , dried for 3 days , and outer surface coated in solution j . the resulting catheters are referred to as type 5 . ( 6 ) catheters were prepared as in ( 5 ) but outer surface coated with solution k . the resulting catheters are referred to as type 6 . ( 7 ) catheters were prepared according to method 3 . specifically , catheters were soaked in a solution containing 5 % cha + 1 % tc in reagent alcohol for 10 minutes , dried for 3 days and then outer surface coated using solution j . the resulting catheters are referred to as type 7 . ( 8 ) catheters were prepared as in ( 7 ), except were outer surface coated with 2 . 7 % polyurethane + 3 % cha in 70 % thf / 30 % reagent alcohol . the resulting catheters are referred to as type 8 . segments of catheter types 1 - 8 were placed vertically in inoculated trypticase soy agar plates inoculated with 108 cfu of staphylococcus aureus per plate , and incubated for 24 hours . after measuring the zones of inhibition , the catheters were transferred daily to fresh culture plates ( shown in table xxi ). the amount of drug uptake per cm / catheter in catheters prepared using various soaking solutions was measured as set forth above . the luminal adherence of bacteria was quantified in catheters impregnated with antimicrobials and then coated with a solution of 2 . 7 percent tecoflex 93a and various antimicrobial agents . bacterial adherence was measured as follows . 12 cm segments of test and control 7fr catheters were each connected to an individual channel of a peristaltic pump via an extension line , hub , and injection cap . the hubs were inoculated initially and after 24 hours with 10 6 cfu of s . aureus which causes the extension line to become colonized thus acting as a continuous source of bacteria for seeding lumens . the lumens were continuously perfused at a rate of 20 ml / hour with trypticase soy broth ( tsb ) diluted 1 : 10 with physiological saline over the course of 7 days . at the end of one week the catheter segments were disconnected and their outer surfaces disinfected with 70 % ethanol . each lumen was flushed with sterile tsb to remove non - adherent bacteria . each catheter was then cut into 2 cm segments each of which is further divided into 2 mm subsegments and placed in tubes containing 4 ml of antiseptic inactivating broth ( ltsb ). the tubes were sonicated for 20 minutes at 4 ° c . to remove bacteria adhering to the lumens . to quantify the adherence , a 0 . 5 ml aliquot of the ltsb extract was subcultured on trypticase soy agar plates . the results are shown in table xxiii . various publications are cited herein , which are hereby incorporated by reference in their entireties .

the present invention relates to polymeric medical articles comprising the anti - infective agents chlorhexidine and triclosan . it is based , at least in part , on the discovery that the synergistic relationship between these compounds permits the use of relatively low levels of both agents , and on the discovery that effective antimicrobial activity may be achieved when these compounds are comprised in either hydrophilic or hydrophobic polymers . it is also based on the discovery that chlorhexidine free base and triclosan , used together , are incorporated into polymeric medical articles more efficiently . medical articles prepared according to the invention offer the advantage of preventing or inhibiting infection while avoiding undesirably high release of anti - infective agent , for example into the bloodstream of a subject .

the novel and inventive features of the apparatus of this invention are best appreciated by reference to the attached drawings . the general nature and utility of this invention may be understood by reference to fig1 and 2 . this apparatus is especially useful for one hitting golf balls from a practice tee where 25 - 50 golf balls will be hit , one - by - one , from a tee ( which elevates the ball above ground level about one - half to one inch ) over a relatively short time , e . g . , about 15 minutes . the apparatus is used to pick up a golf ball from the ground as shown in fig1 and place it on a tee as shown in fig2 . the apparatus comprises two telescopically slidable tubular members in the form of tubes or pipes 20 and 21 . inside tube 20 fits loosely , but not wobbly , inside of outside tube 21 such that there is a common longitudinal axis 46 for both tubes 20 and 21 . tubes 20 and 21 are shown to be round in cross - section , but may be square , triangular or other regular shape . tubes 20 and 21 are generally coextensive , i . e . they have generally the same length between their respective ends but inside tube 20 is made longer so that its upper end 22 and its lower end 23 extend outwardly of respective ends 22 &# 39 ; and 23 &# 39 ; of outside tube 21 . the total length is that which is convenient for a person to use , and , therefore , may vary depending on the height of the person , although generally the overall length will be about 28 - 36 inches . the tubes 20 and 21 may be made of any convenient material , although plastic or metal are preferred . pvc pipe material is an especially convenient material from which this apparatus may be constructed . at lower end 23 &# 39 ; of outer pipe 21 there is a golf ball gripping means , shown here as a combination of three equally spaced wire fingers 25 bent to conform to the spherical shape of a golf ball and made from spring wire so that each finger 25 can expand outwardly , and when at rest , will contract inwardly in a radial direction to engage the golf ball . it is easily understood , therefore , that by pressing the wire fingers 25 downwardly over a golf ball 26 resting on the ground , the fingers 25 will spread outwardly to slide over the golf ball 26 and then contract around the golf ball 26 allowing the golf ball 26 to be picked up while it is being held by the fingers against the lower end 23 of inner tube 20 . a collar 35 is shown around lower end 23 &# 39 ; of outer tube 21 which holds fingers 25 in position and also serves as a seat against which the collar stop 34 of inner tube 20 rests . the apparatus can then be moved around or rested on its legs 24 ( as in fig1 ) and the ball 26 will remain in the grip of fingers 25 . in use it is preferable after dispensing a ball , to regrip another ball with fingers 25 before resting on legs 24 so that it supports the apparatus ( with legs 24 ) thereby protecting fingers 25 from engagement with the ground or the like . inner tube 20 in the position shown in fig1 has its lower end 23 outwardly of the lower end 23 &# 39 ; of outer tube 21 . when it is desired to dispense a golf ball 26 onto a tee 27 as shown in fig2 inner tube 20 is pushed downwardly and slid longitudinally so as to protract its lower end 23 further outside of outer tube 21 and push the golf ball 26 out of the grip of fingers 25 . this is accomplished by pushing downward on the cap 32 of upper end 22 of inner tube 20 . the tee 27 is shown to be a short rubber tube set into a mat 28 as is typically used at public golf practice tees . the ball 26 in fig2 can be placed , instead , on the familiar wooden tee , if desired . a spring means 29 is provided internally of outer tube 21 which connects tube 20 to tube 21 and is biased to automatically and sufficiently retract lower end 23 of inner tube 20 inwardly of outer tube 21 when no pressure is applied to further protract inner tube 20 through fingers 25 to release a golf ball 26 therefrom . in order to prevent inner tube 20 from being protracted too far out lower end 23 of outer tube 21 there is a cap 32 attached to upper end 22 of inner tube 20 . this functions as a stop means to prevent further downward movement of inner tube 20 with respect to outer tube 21 . collar 33 is shown on outer tube 21 to provide a cooperating surface for cap 32 . it is not essential to include collar 33 , but it does provide a convenient finger grip for the person operating the apparatus with a thumb on cap 32 . if desired an enlarged knob of a convenient shape may be added to the upper end to fit in the palm of the hand of the user or any other type or shape handle can be used in place of cap 32 . outer tube 21 has an enlarged portion 30 on the outside of tube 21 and another enlarged portion 35 adjacent the lower end 23 &# 39 ; of tube 21 , the distance between the two portions 30 and 35 depending on the size and shape of legs 24 . here legs 24 are two in number and are made of heavy wire to form with lower end 23 of inner tube 21 ( with golf ball 26 gripped by fingers 25 ) a tripod to allow the apparatus to stand in generally vertical position , tipped to an angle of about 10 °- 20 ° from the vertical . enlarged portion 30 has a pair of spaced grooves 42 in it to seat the upper extremities of the legs 24 . the grooves 42 are longitudinal to receive straight portions 43 therein and curved upper end portions which extend laterally so as to keep legs 24 from twisting or otherwise coming loose when the sleeve cover 31 is slid lengthwise snugly over the outside of enlarged portion 30 after legs 24 are nested in grooves 42 , as explained more fully hereinafter . this arrangement locks legs 24 securely at the desired angle and provides stability for the apparatus . fig3 and 4 show inner tube 20 including lower collar 34 , upper collar 32 , and spring means 29 . spring means 29 is shown as a long coil spring having a hook 40 at its upper end and a hook connection 39 at its lower end through an opening 39 &# 39 ; in tube 20 fixed in place by collar 34 . a slot 37 extends upwardly from lower end 23 sufficiently to allow spring to be positioned within the inner tube 20 and slot 37 and thereby to reduce any scraping noise which may be caused by the spring and not to obstruct the sliding movement of inner tube 20 inside of outer tube 21 . hook 40 is attached to outer tube 21 as by screw 41 ( see fig7 ), such that as tube 20 is pushed downwardly so as to protract further out of lower end 23 &# 39 ; of outer tube 21 ( see fig2 ) spring 29 will be stretched ; and when downward forces on the upper cap 32 of inner tube 20 are released the spring 29 will return to its normal length causing inner tube 20 to retract upwardly into outer tube 21 until collar 34 engages the lower end 23 &# 39 ; of outer tube 21 . fig7 shows a cross - section along the length of spring 29 and depicts hook 40 as attached to a rivet or screw 41 in the wall of outer tube 21 . spring 29 is generally housed in slot 37 and / or within inner tube 20 and does not interfere with the telescopic movement of inner tube 20 inside of outer tube 21 . outer tube 21 is shown in fig5 and 6 including collar 33 , enlarged portion 30 , sleeve cover 31 , lower enlarged portion or collar 35 , fingers 25 , and anchor portions 36 for holding fingers 25 in place . the upper ends 36 of fingers 25 are bent in a u - shape and are anchored to the collar 35 and / or the outer tube 21 by glue or the like . legs 24 are shown in fig8 and 10 as being heavy wire with an elongated lower straight portion 24 , an angled straight portion 43 , and a curved portion 44 which partially encircle outer tube 21 , as seen in fig9 . caps 47 are shown on the bottom end of legs 24 to prevent legs 24 from sinking into the earth or other soft surfaces upon which the apparatus might rest . the shape and conformation of portions 43 and 44 may be varied as desired in order to be easily attachable and detachable from outer tube 21 . in the preferred embodiment shown in the attached drawings , particularly fig8 and 9 , an enlarged portion 30 is positioned on the lower portion of outer tube 21 with spaced and longitudinal grooves 42 to fit leg portions 43 . in this instance grooves 42 receive angled portion 43 , such grooves being generally parallel to longitudinal axis 46 of outer tube 21 . a circumferential ledge 45 is formed around the upper end of enlarged portion 30 to receive curved portion 44 of each leg 24 . when portions 43 and 44 of two legs 24 are nested into grooves 42 and engage ledge 45 of enlarged portion 30 , sleeve cover 31 is slid over the outside of enlarged portion 30 as shown in fig5 . the fit between cover 31 and enlarged portion 30 is snug so that legs 24 are firmly releasably attached to outer tube 21 . it is , of course , entirely within the scope of this invention to employ other types of legs , whether permanently attached or detachably connected . the primary advantage to using detachable legs is to allow for easy packaging or storage of this apparatus . the use of two legs 24 permits the legs 24 to be substantially inserted into the hollow of the lower end 23 of inner tube 20 with the curve ends 44 being within the confines of the spaced fingers 25 . it may be desirable to have the ends 44 joined so that the legs 24 are unitary in other arrangements . the materials of construction of the apparatus of this invention may be metal , plastic , or other suitable material . spring metal wire may be desirably employed for fingers 25 , legs 24 and spring 29 , whereas pvc , as aforesaid , is preferable for the remainder of the apparatus . another embodiment of the invention is depicted in fig1 - 13 where like numerals depict substantially identical elements . the spring 29 has an upper end 39 hooked into an opening 39 &# 39 ; passing laterally through inner tube 20 . the lower end 40 of spring 29 is connected to outer tube 21 by screw or rivet 41 . slot 37 is provided as set forth in the embodiment shown in fig1 - 10 . whether the spring 29 is adjacent the upper ends 22 , 22 &# 39 ; or lower ends 22 , 23 &# 39 ; is immaterial . cap 32 engages the upper end of collar 33 to stop the protraction of the lower end extension pin 50 which extends through opening 51 in resilient cup member 52 attached to the lower end 23 &# 39 ; of outer tube 21 . extension pin 50 is attached generally centrally of plug 53 which in turn is affixed to inner tube 20 as by glue or the like . likewise , cup member 52 includes a sleeve 54 which fits over , and may be secured to , the lower end 23 &# 39 ;, as by glue or any other appropriate manner , so that it may be replaced when the same has been damaged as by cracking or tearing or the like . resilient cup member 52 in and of itself is known in the prior art being sold to be attached to the upper end of the handle of a putter so that one may use such cup member to retrieve a golf ball after the same has been putted into the cup of a golf green . the cup member 52 expands when the cup member 52 is forced onto a golf ball 26 and is slightly larger than hemispherical so that the cup member contracts to frictionally grip and retain the golf ball until a releasing force pushes or pulls the golf ball 26 therefrom . this is accomplished herein by pin 50 pushing golf ball 26 out of the grip of cup member 52 by depression of the inner tube 20 by a manual force on cap 32 about one quarter of the diameter of a golf ball whereby tube 20 moves downwardly with respect to outer tube 21 whereby the ball 26 is dispensed from the frictional engagement with cup member 52 . the screw 41 has a shank 41 &# 39 ; which passes through a slot 55 of a predetermined axial length which not only prevents relative rotation between inner tube 20 and outer tube 21 , but acts as stops for the axial protraction of inner tube 20 with respect to outer tube 21 . of course , cap 32 engaging the upper end 22 &# 39 ; of outer tube 21 may actually limit the protraction of inner tube 20 rather than screw shank 41 &# 39 ; engaging the upper portion of slot 55 . while the invention has been described with respect to certain specific embodiments , it will be appreciated that many modifications and changes may be made by those skilled in the art without departing from the spirit of the invention . it is intended , therefore , by the appended claims to cover all such modifications and changes as fall within the true spirit and scope of the invention .

an apparatus for picking up one golf ball and placing it on a tee includes two telescoping tubular members , and spring biased fingers at the lower end to grip a golf ball . the inner tubular member is movable outwardly to push the golf ball out of the grip of the fingers , and a spring biased inner tubular member is in retracted position further inside the outer tubular member until ready to dispense the golf ball from the grip of the fingers . a pair of removable legs engage the outer tubular member to allow the apparatus to stand generally upright . another embodiment employs a resilient cup member in lieu of the spring biased fingers at the lower end , such cup member frictionally gripping a golf ball and releasing same by a selective dispensing force exerted on the golf ball by the inner tubular member .

although the following detailed description contains many specifics for the purposes of illustration , anyone of ordinary skill in the art will readily appreciate that many variations and alterations to the following exemplary details are within the scope of the invention . accordingly , the following preferred embodiment of the invention is set forth without any loss of generality to , and without imposing limitations upon , the claimed invention . the present invention is an electro - adhesive tissue manipulator that is able to attach to a tissue on demand and release it on demand . the electro - adhesive tissue manipulator could be used to manipulate any kind of biological tissue layer during , for instance , surgical procedures , tissue implants , interventions ( including drug , agent or antibiotic interventions ), or the like . as it will be clear by reading the description , the electro - adhesive tissue manipulator will make it possible to manipulate tissue by accessing the tissue from only one side . this is in contract to the use of tweezers or forceps since these will require access of a tissue from two sides , i . e . pinch or grip the tissue . fig1 shows an electro - adhesive tissue manipulator 100 according to the present invention . electro - adhesive tissue manipulator 100 is composed of an insulated probe 120 with a protruding conductive element 110 . conductive element 110 serves as an active electrode and could be made out of a metal wire , a tungsten filament , or any type of material that has conductive properties . a second electrode is used as a return electrode . the return electrode is typically much larger than the active electrode and its location in the operation field is not critical . in the example of fig1 , the second electrode could be a needle , which hosts insulator 120 and conductive element 110 . in one embodiment the following parameters were used : a 20 gauge needle ( about 0 . 92 mm ), an insulator ( e . g . glass or plastic ; about 0 . 64 mm in diameter ) and a wire of about 50 micrometers in diameter and 1 mm long . however , the invention is not limited to these dimensions . the conductive could range from about 10 micrometers to about 10 millimeters in diameter . electro - adhesive tissue manipulator 100 is activated by an electrical means ( e . g . a pulse generator ) capable of providing a first ( electrical ) pulse and a second ( electrical ) pulse between conducting element 110 and the return electrode 130 . preferably the manipulator has a control means in communication with e . g . buttons on the manipulator , a foot - pedal connected to the manipulator or even a voice recognition means to control the generation of the pulses . once conducting element is placed in contact with a tissue layer 150 and first pulse is generated on demand , the state of adhesiveness of tissue layer 150 is changed as a result . the adhesiveness of tissue is created by partial denaturation of proteins in the proximity to the conductive element . this effect is induced either by high electric field and / or heating . this change in adhesiveness creates an adhesive bonding 160 between conductive element 110 and tissue layer 150 through which electro - adhesive tissue manipulator 100 is capable of manipulating tissue layer 150 . tissue layer 150 could be elevated from an underlying tissue layer 170 . in one example a cavity 180 between tissue layer 150 and underlying tissue layer 170 is created . cavity 180 could be useful for implantation , intervention or delivery of an agent , a drug or an antibiotic . the adhesive bonding is remarkably strong and allows one to move a tissue layer in any direction as well as to elevate it away from underlying tissue layer ( s ). there are no pulses required after the adhesion is achieved ; tissue can be kept to the conducting element as long as the second pulse is not applied . fig2 shows a membrane 220 that is elevated by electro - adhesive tissue manipulator 200 when attached to conducting element 210 . fig2 shows an illumination probe 220 to highlight the elevated membrane . to establish electro - adhesion , pulse duration of the first pulse 310 ( see fig3 ) can vary between about 10 microseconds to about 10 milliseconds . more specifically the duration of the first pulse varies from about 1 microsecond to about 0 . 5 milliseconds . pulse duration is limited on a long side by heat diffusion ; i . e . to avoid thermal damage beyond 100 μm the pulse duration should preferably not exceed 10 ms . pulse energy should be below the threshold energy required for formation of a complete vapor cavity around the conducting element . a complete vapor cavity will disconnect the conducting element from the tissue and prevent adhesion . in fact , the effect of vapor cavity is used to disconnect the attached tissue from the conducting element ( see below ). the first pulse could be a single pulse 410 or a burst of shorter pulses 420 with a frequency that could vary between about 0 . 1 khz to 10 mhz . the first pulse could be a unipolar or a charge - balanced or voltage - balanced bipolar burst of pulses . application of such pulse or a few pulses when the probe is held in contact with a tissue layer induces adhesion of the tissue to the metal surface , and so the tissue can be lifted and manipulated . in one embodiment pulse parameters are 200v with a 100 microsecond pulse duration . voltage should be above 50 v , but below 500 v , since threshold of plasma formation is somewhere between 200 to 400 v , depending on pulse parameters and electrode configuration . to minimize the tissue damage induced by electroporation a voltage - balanced train of pulses could be applied . at optimal settings the damage does not exceed one or two layers of cells 510 adjacent to the probe 520 , as shown in fig5 . to detach the tissue layer from the conducting element a stronger ( in terms of energy ) second pulse 320 needs to be applied , such that it creates a complete vapor cavity around the probe thus detaching the tissue from conducting element . the second pulse could also be a single pulse 410 or a burst of shorter pulses 420 with a frequency that could vary between about 0 . 1 khz to 10 mhz . the duration of the second pulse could be between about 10 microseconds to about 10 milliseconds . more specifically the duration of the second pulse varies from about 1 microsecond to about 0 . 5 milliseconds . the second pulse could also be a unipolar or a charge - balanced or voltage - balanced bipolar burst of pulses . to minimize the tissue damage induced by electroporation a voltage - balanced train of pulses can be applied . to establish successful adhesion of conducting element to a tissue layer , it is important to maintain the surface of the conducting element clean of biological debris . if the conducting element does get contaminated , i . e . coated with a layer of coagulated proteins and other materials the conducting element can easily be cleaned without withdrawal from the surgical field . this can for instance be accomplished by application of few pulses in the plasma - mediated cutting regime . these pulses remove all the debris from the conducting element . to avoid tissue damage during this procedure the conducting element should be withdrawn from tissue by a certain distance . in one embodiment the conducting element was withdrawn at least 0 . 1 mm ; distance larger than the width of the typical damage zone in cutting regime . the present invention has now been described in accordance with several exemplary embodiments , which are intended to be illustrative in all aspects , rather than restrictive . thus , the present invention is capable of many variations in detailed implementation , which may be derived from the description contained herein by a person of ordinary skill in the art . for instance , the conducting element could take any type of shape , but is preferably dull . fig6 shows some examples of different shapes of conductive elements such as a hooked shape 610 , a ball - shape 620 , or a rectangular shape 630 , which should all be regarded as illustrative rather than limiting to the scope of the invention . conventional medical instruments could be combined with electro - adhesive tissue manipulation features as embodied in the present invention by coating them with isolating material and exposing a part that will be used as an active electrode . fig7 shows electro - adhesive tissue manipulator 700 combined with a needle 710 for injection of a liquid , agent , drug of antibiotic under an elevated tissue layer to enhance tissue separation . all the surface of the needle may be exposed and used as an active conductive element ( electrode ), or alternatively , a part of its surface might be coated and part be exposed . fig8 shows a conventional forceps 800 that can be coated with insulating material and a strip of the arm ( e . g . at location 810 or 820 ) can be exposed to use it as a conducting element ( electrode ) to develop an electrical forceps embodying the features of the present invention . to increase the mechanical force , a second ( conventional ) arm of the forceps may be used for mechanical grasp of the tissue as soon as it is detached from the underlying tissue . the second arm 830 of forceps 800 can also be made as an active conducting element ( electrode ). this combination can be used , for example , for cutting of tissue attached to the first arm . since tissue is approached from only one side a device embodying the features of the present invention does not have to have a sharp - pointed end , as conventional micro - forceps typically do . lack of the sharp apex makes it safer with respect to occasional or unintended piercing of tissue . in addition to the types of applications discussed herein the electro - adhesive tissue manipulator could further be used for peeling or lifting thin membranes , for example in vitreoretinal surgery . another application of the electro - adhesive tissue manipulator could be attaching a lens holder to a surface of an eye for posterior pole surgery ( replacing a current suturing procedure ). for this application , the lens holder should have an active electrode or an array of active electrodes on its periphery , which will induce adhesion to sclera outside cornea ( in order to avoid potential damage to corneal surface ). yet another application could include attaching an implant to tissue for anchoring or attaching temporary patches to tissue surface during operation . still another application could include attaching tissue to the scaffold or reconnecting two ends of a cut blood vessel using a conductive stent . all such variations are considered to be within the scope and spirit of the present invention as defined by the following claims and their legal equivalents .

an electro - adhesive tissue manipulator capable of manipulating tissue with a single conducting element is provided . the manipulator includes a conducting element , an electrical means and a control means capable of generating a first and a second pulse on demand . the first pulse generates an adhesive state between the conducting element and the tissue layer strong enough to manipulate the tissue layer . the second pulse , which has higher pulse energy than the first pulse , generates a non - adhesive state to detach the adhered tissue layer from the conducting element . the electro - adhesive device could be combined with a medical instrument to enhance the capabilities of the medical instrument so that it can manipulate tissue . the advantage of the present invention , in contrast to mechanical tools , is that tissue can be manipulated with a single tip of a conducting element , without folding and piercing of the tissue , thus avoiding damage to the tissue .

the present invention provides novel cyclic molecules and methods of preparing and potential therapeutic uses of these novel compounds . the inventive compounds may be useful in the treatment of b cell lymphoma , leukemia and autoimmune disorders . the present invention provides compounds of any of formula ( a ), which are useful as btk inhibitors . in one aspect are compounds of formula ( a ), pharmaceutically acceptable salts , pharmaceutically active metabolites , pharmaceutically acceptable prodrugs , and pharmaceutically acceptable solvates thereof . r a is h , halogen , l 1 -( substituted or unsubstituted c 1 - c 3 alkyl ), l 1 -( substituted or unsubstituted c 2 - c 3 alkenyl ), l 1 -( substituted or unsubstituted heteroaryl ), or l 1 -( substituted or unsubstituted aryl ), wherein l 1 is a bond , o , s , — s (═ o ), s (═ o ) 2 , s (═ o ) 2 — nh , nh , c ( o ), — nhc ( o ) o , — oc ( o ) nh , — nhc ( o ), or — c ( o ) nh ; r 1 is h , l 2 -( substituted or unsubstituted alkyl ), l 2 -( substituted or unsubstituted cycloalkyl ), l 2 -( substituted or unsubstituted alkenyl ), l 2 -( substituted or unsubstituted cycloalkenyl ), l 2 -( substituted or unsubstituted heterocycle ), l 2 -( substituted or unsubstituted heteroaryl ), or l 2 -( substituted or unsubstituted aryl ), l 2 -( substituted or unsubstituted aryl )- l 2 -( substituted or unsubstituted aryl ), l 2 -( substituted or unsubstituted aryl )- l 2 -( substituted or unsubstituted heteroaryl ), l 2 -( substituted or unsubstituted heteroaryl )- l 2 -( substituted or unsubstituted aryl ), l 2 -( substituted or unsubstituted heteroaryl )- l 2 -( substituted or unsubstituted heteroaryl ), wherein l 2 is a bond , o , s , — s (═ o ), — s (═ o ) 2 , c (═ o ), -( substituted or unsubstituted c 1 - c 5 alkyl ), or -( substituted or unsubstituted c 2 - c 5 alkenyl ); r 2 and r 3 are independently selected from h , c 1 - c 8 alkyl and substituted c 1 - c 8 alkyl ; ring a is a 3 to 12 membered carbocyclic ring ; or ring a is a 3 to 12 membered carbocyclic ring in which one or more carbon ring atoms are replaced with one or more o , s , — c ( o )—, — c ( s )—, nr c , or ring a is a 3 to 12 membered carbocyclic ring which unsubstituted or substituted with one or more r c ; or ring a is a 3 to 12 membered carbocyclic ring in which one carbon ring atoms is replaced with a nitrogen atom and the nitrogen atom in ring a is connected with j when j is a carbon atom ; r c is independently chosen from halogen , c 1 - 12 alkyl , c 2 - 12 alkenyl , c 2 - 12 alkynyl , c 3 - 12 cycloalkyl , c 6 - 12 aryl , a 3 - 12 membered heteroalicyclic ring , a 5 - 12 membered heteroaryl ring , — nh 2 , — cn , — oh , — o —( ch 2 ) n c 3 - 12 cycloalkyl , — o —( ch 2 ) n c 6 - 12 aryl , — o —( ch 2 ) n ( 3 - 12 membered heteroalicyclic ring ) or — o —( ch 2 ) n ( 5 - 12 membered heteroaryl ring ), with the proviso that when r c is halogen , — cn , — oh , — o — c 1 - 12 alkyl , — o —( ch 2 ) n c 3 - 12 cycloalkyl , — o —( ch 2 ) n c 6 - 12 aryl , — o —( ch 2 ) n ( 3 - 12 membered heteroalicyclic ring ) or — o —( ch 2 ) n ( 5 - 12 membered heteroaryl ring ), r c is connected to an atom different than nitrogen , ring b is a 3 to 12 membered carbocyclic ring ; or ring b is a 3 to 12 membered carbocyclic ring in which one or more carbon ring atoms is replaced with one or more o , s , s ( o ), s ( o ) 2 , c ( o ), c ( s ), n — x ; or ring b is a 3 to 12 membered carbocyclic ring which is unsubstituted or substituted by x , — nr d — x or c 1 - c 6 alkyl - nr d x ; r d is h , c 1 - 6 alkyl , c 3 - 6 cycloalkyl , aryl or heteroaryl ; r 5 , r 4 and r 6 are independently selected from among h , c 1 - 12 alkyl , c 1 - 12 heteroalkyl , c 1 - 12 heterocycloalkyl , c 2 - 12 alkenyl , c 2 - 12 alkynyl , c 3 - 12 cycloalkyl ; in another embodiment , the invention provides a compound of formula ( b ) the following structure : r 5 , r 4 and r 6 are independently selected from among h , c 1 - 12 heteroalkyl , c 1 - 12 heterocycloalkyl , c 2 - 12 alkenyl , c 2 - 12 alkynyl , c 3 - 12 cycloalkyl ; l 3 is ch 2 , o , s , nr d , r d is h , c 1 - 6 alkyl , c 3 - 6 cycloalkyl , aryl or heteroaryl ; ar is an aryl or heteroaryl which is optionally substituted with one or more r e ; r e is independently halogen , c 1 - 12 alkyl , c 2 - 12 alkenyl , c 2 - 12 alkynyl , c 3 - 12 cycloalkyl , c 6 - 12 aryl , a 3 - 12 membered heteroalicyclic ring , a 5 - 12 membered heteroaryl ring , — s ( o ) m r d , — s ( o ) 2 nr d r d , — s ( o ) 2 or d , sf 5 , — cn , — no 2 , — nr d r d , —( cr 6 r 7 ) n or d , — cn , — c ( o ) r d , — oc ( o ) r d , — o ( cr d r d ) n r d , — nr d c ( o ) r d , —( cr d r d ) n c ( o ) or 4 , —( cr d r d ) n or 4 , —( cr d r d ) n c ( o ) nr d r d , —( cr d r d ) n ncr d r d , — c (═ nr d ) nr d r d , — nr d c ( o ) nr d r d , — nr d s ( o ) 2 r d or — c ( o ) nr d r d , each hydrogen in r d is optionally substituted by r f ; two r d on the same atom can be connected to form a carbocyclic ring in which one or more carbon ring atoms are optionally replaced with one or more o , s , s ( o ), s ( o ) 2 , c ( o ), c ( s ) and nr d ; r f is independently halogen , c 1 - 12 alkyl , c 2 - 12 alkenyl , c 2 - 12 alkynyl , c 3 - 12 cycloalkyl , c 6 - 12 aryl , a 3 - 12 membered heteroalicyclic ring , a 5 - 12 membered heteroaryl ring , — nh 2 , — cn , — oh , — o — c 1 - 12 alkyl , — o —( ch 2 ) n c 3 - 12 cycloalkyl , — o —( ch 2 ) n c 6 - 12 aryl , — o —( ch 2 ) n ( 3 - 12 membered heteroalicyclic ring ) or — o —( ch 2 ) n ( 5 - 12 membered heteroaryl ring ); two r e on adjacent atoms are unconnected or connected to form a c 6 - 12 aryl , a 5 - 12 membered heteroaryl ring , c 5 - 20 cycloalkyl or a 5 - 20 membered heteroalicyclic ring which may contain one or more heteroatom ( s ) such as o , nr d , s ; in another embodiment , the invention provides stable isotope - labeled compounds of formula ( a ). in another embodiment , the invention provides prodrugs of the compounds of formula ( a ). in another embodiment , the invention provides the compounds having the following structures in table 1 and table 2 : the present invention will be more readily understood by referring to the following examples which are given to illustrate the invention rather than to limit its scope . to a mixture of 3 - iodo - 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 4 - amine ( 1 . 044 g , 4 mmol ), ( 4 - phenoxyphenyl ) boronic acid ( 0 . 94 g , 4 . 4 mmol , 1 . 1 eq ), pdcl 2 ( dppf ) ( 0 . 29 g , 0 . 4 mmol , 0 . 1 eq ) and na 2 co 3 ( 0 . 89 g , 8 . 4 mmol , 2 . 1 eq ) in a 40 ml reaction vial under vacuum , 25 ml of h 2 o / thf ( 1 : 4 ) is added via a syringe . the mixture is refilled with n 2 and heated to 110 ° c . overnight . tlc showed that the reaction is almost completed . then solvent is evaporated and the residue is suspended in 200 ml ( 15 % thf / etoac ) and washed with water , brine , dried over na 2 so 4 , filtered , and evaporated . the residue is purified with a 50 g silica gel cartridge by combi - flash ( 0 - 10 % gradient of methanol in dcm to afford 513 mg of 3 -( 4 - phenoxyphenyl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 4 - amine . 1 hnmr ( 300 mhz , dmso - d 6 ): δ 8 . 22 ( s , 1h ), 7 . 66 ( d , 2h ), 7 . 43 ( t , 2h ), 7 . 10 - 7 . 23 ( m , 5h ). to a mixture of 3 -( 4 - phenoxyphenyl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 4 - amine ( 100 mg , 0 . 33 mmol ), tert - butyl 6 - hydroxy - 2 - azaspiro [ 3 . 3 ] heptane - 2 - carboxylate ( 141 mg , 0 . 66 mmol , 2 eq ), triphenylphosphine ( 173 mg , 0 . 66 mmol , 2 eq ) in a 40 ml reaction vial under vacuum , 5 ml of thf is added via a syringe . the mixture is refilled with n 2 and diad ( 0 . 13 ml , 0 . 66 mmol , 2 eq ) is added dropwise at rt . the mixture is then stirred at rt overnight . tlc showed that the reaction is almost completed . then solvent is evaporated and the residue is purified with a 24 g silica gel cartridge by combi - flash ( 0 - 10 % gradient of methanol in dcm to afford 78 mg of tert - butyl 6 -( 4 - amino - 3 -( 4 - phenoxyphenyl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 1 - yl )- 2 - azaspiro [ 3 . 3 ] heptane - 2 - carboxylate . 1 hnmr ( 300 mhz , acetone - d 6 ): δ 8 . 26 ( s , 1h ), 7 . 78 ( d , 2h ), 7 . 46 ( t , 2h ), 7 . 10 - 7 . 23 ( m , 5h ), 5 . 30 - 5 . 45 ( m , 1h ), 4 . 11 ( s , 2h ), 4 . 05 ( s , 2h ), 2 . 71 - 3 . 0 ( m , 4h ), 1 . 44 ( s , 9h ). a solution of tert - butyl 6 -( 4 - amino - 3 -( 4 - phenoxyphenyl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 1 - yl )- 2 - azaspiro [ 3 . 3 ] heptane - 2 - carboxylate ( 89 mg , 0 . 18 mmol in a 3 . 6 ml of formic acid ( 85 %) is sonicated at rt for 1 . 5 hr ( bath temperature raised to 45 - 50 ° c .). the solvent is evaporated and the residue is purified with a 50 g silica gel cartridge by combi - flash ( 0 - 100 % gradient of solvent b / dcm , while solvent b is prepared by mixing 400 ml of dcm with 100 ml of 20 % ammonia in methanol ) to afford 47 mg of 3 -( 4 - phenoxyphenyl )- 1 -( 2 - azaspiro [ 3 . 3 ] heptan - 6 - yl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 4 - amine . 1 hnmr ( 300 mhz , cdc 3 ): δ 8 . 33 ( s , 1h ), 7 . 67 ( d , 2h ), 7 . 39 ( t , 2h ), 7 . 05 - 7 . 21 ( m , 5h ), 5 . 25 - 5 . 35 ( m , 1h ), 3 . 86 ( s , 2h ), 3 . 78 ( s , 2h ), 2 . 90 - 3 . 02 ( m , 2h ), 2 . 68 - 2 . 84 ( m , 2h ). to a solution of 3 -( 4 - phenoxyphenyl )- 1 -( 2 - azaspiro [ 3 . 3 ] heptan - 6 - yl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 4 - amine ( 48 mg , 0 . 12 mmol ) and 0 . 05 ml of triethylamine ( 3 eq ) in 2 . 4 ml of dcm stirred at − 78 ° c . is added acryloyl chloride ( 1 . 29 m , 0 . 093 ml , 0 . 12 mmol , 1 eq ) dropwise . the reaction is warmed up to rt and stirred for 2 hr . the reaction is worked up by the addition of saturated sodium bicarbonate solution . the organic layer is separated and the aqueous phase is extracted with dcm , dried over na 2 so 4 , filtered , and evaporated . the residue is purified with a 24 g silica gel cartridge by combi - flash ( 0 - 100 % gradient of solvent b / dcm , while solvent b is 10 % methanol / acetate ) to afford 25 mg of 1 -( 6 -( 4 - amino - 3 -( 4 - phenoxyphenyl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 1 - yl )- 2 - azaspiro [ 3 . 3 ] heptan - 2 - yl ) prop - 2 - en - 1 - one . 1 hnmr ( 300 mhz , dmso - d 6 ): δ 8 . 24 ( s , 1h ), 7 . 67 ( d , 2h ), 7 . 44 ( t , 2h ), 7 . 05 - 7 . 23 ( m , 5h ), 6 . 20 - 6 . 40 ( m , 1h ), 6 . 09 ( d , 1h ), 5 . 41 - 5 . 51 ( m , 1h ), 5 . 21 - 5 . 36 ( m , 1h ), 4 . 39 ( s , 1h ), 4 . 29 ( s , 1h ), 4 . 10 ( s , 1h ), 4 . 00 ( s , 1h ), 2 . 65 - 2 . 95 ( m , 4h ). to a suspension of 3 -( 4 - phenoxyphenyl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 4 - amine ( 210 mg , 0 . 692 mmol , 1 . 0 equiv ), tert - butyl 2 - hydroxy - 7 - azaspiro [ 3 . 5 ] nonane - 7 - carboxylate ( 334 mg , 1 . 385 mmol , 2 . 0 equiv ) and ph 3 p ( 363 mg , 1 . 385 mmol , 2 . 0 equiv ) in thf ( dry , 5 ml ) is added diad ( 0 . 273 ml , 1 . 385 mmol , 2 . 0 equiv ) by syringe dropwise at 0 ° c . under n 2 . after addition , the reaction solution is allowed to warm to room temperature slowly and stirred at room temperature overnight . the mixture is concentrated by evaporator in vacuo to give a residue which is purified by combiflash [ 25 g silicagel column , ( etoac / meoh = 10 / 1 )/ hexane : 0 - 100 %] to give tert - butyl 2 -( 4 - amino - 3 -( 4 - phenoxyphenyl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 1 - yl )- 7 - azaspiro [ 3 . 5 ] nonane - 7 - carboxylate , which is submitted for next reaction without further purification . to a solution of tert - butyl 2 -( 4 - amino - 3 -( 4 - phenoxyphenyl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 1 - yl )- 7 - azaspiro [ 3 . 5 ] nonane - 7 - carboxylate ( 360 mg , 0 . 684 mmol , 1 . 0 equiv ) in dcm ( 10 ml ) is added a solution of hcl in dioxane ( 4 . 0 n , 3 ml ). the reaction mixture is stirred at room temperature for 1 h . tlc indicated that starting material is consumed . the reaction mixture is concentrated by evaporator in vacuo to give a residue which is purified by combiflash [ 25 g silicagel column , {[( meoh / nh 4 oh = 4 / 1 )/ dcm ]= 4 / 1 }/ dcm : 0 - 60 %] to give 25 mg ( yield 8 . 6 %) of 3 -( 4 - phenoxyphenyl )- 1 -( 7 - azaspiro [ 3 . 5 ] nonan - 2 - yl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 4 - amine as a white solid . to a solution of 3 -( 4 - phenoxyphenyl )- 1 -( 7 - azaspiro [ 3 . 5 ] nonan - 2 - yl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 4 - amine ( 25 mg , 0 . 059 mmol , 1 . 0 equiv ) and triethylamine ( 25 μl , 0 . 176 mmol , 3 . 0 eqiuv ) in dcm ( 2 ml ) is added a solution of acryloyl chloride in dcm ( 1 . 29 m , 45 μl , 0 . 059 mmol , 1 . 0 equiv ) at − 78 ° c . under nitrogen . it is allowed to warm to room temperature slowly and stirred at room temperature overnight . the reaction solution is concentrated by evaporator in vacuo to give a solid which is purified by combiflash [ 12 g silicagel column , [( etoac / meoh = 10 / 1 )/ hexane : 0 - 100 %] to give 7 . 4 mg ( 26 %) of 1 -( 2 -( 4 - amino - 3 -( 4 - phenoxyphenyl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 1 - yl )- 7 - azaspiro [ 3 . 5 ] nonan - 7 - yl ) prop - 2 - en - 1 - one as a white solid . 1 h nmr ( acetone - d6 , 500 mhz ): δ 8 . 25 ( s , 1h ), 7 . 78 ( d , 2h ), 7 . 46 ( t , 2h ), 7 . 17 ( m , 5h ), 6 . 81 ( m , 1h ), 6 . 16 ( dd , 1h ), 5 . 63 ( dd , 1h ), 5 . 49 ( m , 1h ), 3 . 66 ( m , 2h ), 3 . 56 ( m , 2h ), 2 . 61 ( m , 2h ), 2 . 50 ( m , 2h ), 1 . 78 ( m , 4h ). to a suspension of 3 -( 4 - phenoxyphenyl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 4 - amine ( 135 mg , 0 . 445 mmol , 1 . 0 equiv ), tert - butyl 7 - hydroxy - 2 - azaspiro [ 3 . 5 ] nonane - 2 - carboxylate ( 215 mg , 0 . 89 mmol , 2 . 0 equiv ) and ph 3 p ( 233 mg , 0 . 89 mmol , 2 . 0 equiv ) in thf ( dry , 5 ml ) is added diad ( 175 μl , 0 . 89 mmol , 2 . 0 equiv ) by syringe dropwise at 0 ° c . under n 2 . after addition , the reaction solution is allowed to warm to room temperature slowly and stirred at room temperature overnight . the mixture is concentrated by evaporator in vacuo to give a residue which is purified by combiflash [ 25 g silicagel column , ( etoac / meoh = 10 / 1 )/ hexane : 0 - 100 %] to give tert - butyl 7 -( 4 - amino - 3 -( 4 - phenoxyphenyl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 1 - yl )- 2 - azaspiro [ 3 . 5 ] nonane - 2 - carboxylate , which is used directly for next reaction without further purification . a solution of tert - butyl 7 -( 4 - amino - 3 -( 4 - phenoxyphenyl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 1 - yl )- 2 - azaspiro [ 3 . 5 ] nonane - 2 - carboxylate ( 230 mg , 0 . 437 mmol , 1 . 0 equiv ) in formic acid ( 6 ml ) is sonicated for 1 . 5 hrs . tlc indicated that starting material is consumed . the mixture is concentrated by evaporator in vacuo to give a brown residue which is purified by combiflash ( 25 g silicagel column , {[( meoh / nh 4 oh = 4 / 1 )/ dcm ]= 4 / 1 }/ dcm : 0 - 60 %) to afford 110 mg ( 59 %) of 3 -( 4 - phenoxyphenyl )- 1 -( 2 - azaspiro [ 3 . 5 ] nonan - 7 - yl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 4 - amine as a pale yellow solid . to a solution of 3 -( 4 - phenoxyphenyl )- 1 -( 2 - azaspiro [ 3 . 5 ] nonan - 7 - yl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 4 - amine ( 110 mg , 0 . 258 mmol , 1 . 0 equiv ) and triethylamine ( 108 μl , 0 . 774 mmol , 3 . 0 equiv ) in dcm ( 5 ml ) is added a solution of acryloyl chloride in dcm ( 1 . 29 m , 200 μl , 0 . 258 mmol , 1 . 0 equiv ) at − 78 ° c . under nitrogen . it is allowed to warm to room temperature slowly and stirred at room temperature overnight . it is concentrated by evaporator in vacuo to give a yellow solid which is purified by combiflash [ 25 g silicagel column , [( etoac / meoh = 10 / 1 )/ hexane : 0 - 100 %] to give 63 mg ( yield 51 %) of 1 -( 7 -( 4 - amino - 3 -( 4 - phenoxyphenyl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 1 - yl )- 2 - azaspiro [ 3 . 5 ] nonan - 2 - yl ) prop - 2 - en - 1 - one as a white solid . 1 h nmr ( acetone - d 6 , 400 mhz ): δ 8 . 25 ( s , 1h ), 7 . 75 ( d , 2h ), 7 . 44 ( t , 2h ), 7 . 16 ( m , 5h ), 6 . 36 ( m , 1h ), 6 . 20 ( m , 1h ), 5 . 61 ( d , 1h ), 4 . 78 ( m , 1h ), 4 . 11 ( s , 1h ), 3 . 97 ( s , 1h ), 3 . 81 ( s , 1h ), 3 . 67 ( s , 1h ), 1 . 98 ( m , 8h ). to a suspension of 3 -( 4 - phenoxyphenyl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 4 - amine ( 285 mg , 0 . 94 mmol , 1 . 0 equiv ), benzyl 2 - hydroxy - 6 - azaspiro [ 3 . 5 ] nonane - 6 - carboxylate ( 517 mg , 1 . 88 mmol , 2 . 0 equiv ) and ph 3 p ( 493 mg , 1 . 88 mmol , 2 . 0 equiv ) in thf ( dry , 5 ml ) is added diad ( 370 μl , 1 . 88 mmol , 2 . 0 equiv ) by syringe dropwise at 0 ° c . under n 2 . after addition , the reaction solution is allowed to warm to room temperature slowly and stirred at room temperature overnight . the mixture is concentrated by evaporator in vacuo to give the residue which is purified by combiflash [ 25 g silicagel column , ( etoac / meoh = 10 / 1 )/ hexane : 0 - 100 %] to give crude benzyl 2 -( 4 - amino - 3 -( 4 - phenoxyphenyl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 1 - yl )- 6 - azaspiro [ 3 . 5 ] nonane - 6 - carboxylate , which is employed directly for next reaction without further purification . to a solution of crude benzyl 2 -( 4 - amino - 3 -( 4 - phenoxyphenyl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 1 - yl )- 6 - azaspiro [ 3 . 5 ] nonane - 6 - carboxylate ( 530 mg , 0 . 945 mmol , 1 . 0 equiv ) in thf / meoh ( 5 / 5 ml ) is added with pd ( oh ) 2 ( 80 mg , 20 wt % ( dry basis ) on carbon ) in one portion . the mixture is stirred at room temperature under h 2 balloon for 18 hrs . pd ( oh ) 2 ( 60 mg ) and acetic acid ( 4 ml ) are added . the mixture is stirred at room temperature under h 2 balloon for 30 hrs . the mixture is passed through a pad of celite , eluted with meoh ( 30 ml ). the combined filtrate is concentrated by evaporator in vacuo to give a residue which is purified by combiflash ( 25 g silicagel column , {[( meoh / nh 4 oh = 4 / 1 )/ dcm ]= 4 / 1 }/ dcm : 0 - 60 %) to afford 77 mg ( 59 %) of 3 -( 4 - phenoxyphenyl )- 1 -( 6 - azaspiro [ 3 . 5 ] nonan - 2 - yl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 4 - amine as a pale yellow solid . to a solution of 3 -( 4 - phenoxyphenyl )- 1 -( 6 - azaspiro [ 3 . 5 ] nonan - 2 - yl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 4 - amine ( 77 mg , 0 . 181 mmol , 1 . 0 equiv ) and triethylamine ( 108 μl , 0 . 774 mmol , 3 . 0 equiv ) in dmf / dcm ( dry , 3 / 1 ml ) is added a solution of acryloyl chloride in dcm ( 1 . 29 m , 200 μl , 0 . 258 mmol , 1 . 4 equiv ) at − 78 ° c . under nitrogen . after addition , the solution is allowed to warm to room temperature slowly , and then stirred at room temperature overnight . it is concentrated by evaporator in vacuo to give a yellow solid which is purified by combiflash [ 10 g silicagel column , [( etoac / meoh = 10 / 1 )/ hexane : 0 - 100 %] to give 18 mg of example 4a , a pure diasteromer ( cis or trans unidentified ) of 1 -( 7 -( 4 - amino - 3 -( 4 - phenoxyphenyl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 1 - yl )- 2 - azaspiro [ 3 . 5 ] nonan - 2 - yl ) prop - 2 - en - 1 - one as a white solid [ lc - ms : 481 . 3 ( m + + h , esi )], followed by 2 . 4 mg of example 4b , a mixture of diasteromers ( cis / trans ≈ 1 / 1 ) of 1 -( 7 -( 4 - amino - 3 -( 4 - phenoxyphenyl )- 1h - pyrazolo [ 3 , 4 - d ] pyrimidin - 1 - yl )- 2 - azaspiro [ 3 . 5 ] nonan - 2 - yl ) prop - 2 - en - 1 - one as a white solid . lc - ms : 481 . 3 ( m + + h , esi ). the btk inhibitory activities of compounds of formula a are assayed at reaction biology corporation , one great valley parkway , malvern , pa ., usa . human btk enzyme is used and the substrate is a peptide substrate , [ kvekigegtygvvyk ] at 20 μm . the atp concentration for the assay is 10 μm and staurosporine is used as a standard with an ic 50 of 3 . 94 nm . while preferred embodiments have been described above and illustrated in the accompanying drawings , it will be evident to those skilled in the art that modifications may be made without departing from this disclosure . such modifications are considered as possible variants comprised in the scope of the disclosure .

the present document describes novel molecules having protein tyrosine kinase inhibitory activity , and methods of synthesizing and using such compounds . more specifically , the present document describes compound of formula : ) or a pharmaceutically acceptable salt , hydrate or solvate thereof , and methods of synthesizing and using such compounds .

the techniques described herein are believed to be applicable to a wide variety of chickens ( gallus domesticus ), and in particular to high production , commercially prevalent species thereof such as the white leghorn ( preferably the single comb white leghorn ) and the new hampshire . crosses between these species are also useable . the invention should also have applicability to low cholesterol mutant forms such as that reported in a . quershi , et al . 34 nutritional reports international 457 - 464 ( 1986 ). in the united states , eggs are graded by weight based on the number of ounces ( shell included ) per dozen . a &# 34 ; small &# 34 ; egg is 18 to 20 . 99 ounces per dozen . a &# 34 ; medium &# 34 ; egg is 21 to 23 . 99 ounces per dozen . a &# 34 ; large &# 34 ; egg is 24 to 26 . 99 ounces per dozen . an &# 34 ; extra large &# 34 ; egg is 27 to 29 . 99 ounces per dozen . a &# 34 ; jumbo &# 34 ; egg is 30 or above ounces per dozen . the experiments described below were performed with large eggs . it should be appreciated that the same techniques can be applied to other sizes of eggs . the large egg is preferred as persons who are on a diet are reluctant to select &# 34 ; extra large &# 34 ; or &# 34 ; jumbo &# 34 ; eggs . also , medium and small eggs are too small for many consumers to feel that the product has value . eggs are first sorted by weight to divide them into the various sizes of small , medium , large , extra large and jumbo . in accordance with the present invention , there is then a further selection in which only those eggs in the lower third of the weight size range ( preferably those in the lower sixth of the range ) are selected ( e . g . for large , below 2 . 083 ounces per egg ). in addition to the above type of selection , one can candle ( illuminate ) the egg in order to determine the area of the shadow that the egg yolk throws . conventional candling equipment currently used for spotting cracks or fertilized eggs can be used to project the shadow in the usual fashion . however , in accordance with the invention , the candling can project the shadow on a wall that has a bull &# 39 ; s eye target type pattern . when the yolk shadow exceeds a selected area , the egg can be selected out . for example , this shadow can be compared to a selected norm ( e . g . one that only selects on average the smallest 1 / 3 or 1 / 6th yolk shadow area for the grade ). in this regard , almost all of the cholesterol in an egg is in its yolk . therefore , while selection by overall weight is helpful , a further desirable step involves the selection by yolk size after the initial weight selection . in the alternative , the shadow can be projected onto computer imaging equipment , and a computer can then calculate even more accurately the overall yolk shadow area . eggs collected shortly after a chicken reaches maturity for egg laying typically have the lowest concentration of cholesterol per gram of yolk . the cholesterol concentration in the yolk typically increases over time until the first molt . thereafter , it drops somewhat ( but generally not all the way back to the beginning levels ). it then increases again . thus , the total cholesterol concentration in the yolk zig - zags upwardly with chicken age , with the lowest cholesterol level being in the youngest chickens . to assist in achieving the results of the present invention it is preferred to select eggs from chickens that are between initial maturity and 38 weeks old . if extremely low levels need to be achieved , the selection could be skewed to the early part of the range ( e . g . 80 % or more 18 weeks old ). the egg in a chicken is believed to be the excess cholesterol deposit site for the chicken . typically , the more eggs that the chicken lays , the lower the concentration of cholesterol found in the average yolk . as such , it is preferred to select eggs from only flocks averaging over 80 % production per day ( 80 % of the chickens lay an egg that day ). a clutch is the period of consecutive days in which a hen lays an egg . if a hen lays an egg on eight consecutive days , it would have a clutch size of eight . it has been learned that those eggs which appear later in a clutch typically have the lowest concentration of cholesterol . thus , it is preferred to select eggs from clutch sizes of five or more , with eggs from days 5 or later being selected . it has been learned that high levels of stress can increase the level of cholesterol in the egg . under extremely low stress conditions , the cholesterol concentration in the chicken &# 39 ; s egg is typically slightly reduced . techniques that have proved to be of assistance in connection with lowering the level of cholesterol are housing the chickens in indirect light with high fresh air circulation ; keeping the chickens caged and not crowded ( not on the floor ); keeping the cage areas very clean ; and periodically providing soothing and relatively quiet music ( e . g . classical music ) for the chickens . when one provides a low fat , high fiber diet to the chicken , cholesterol levels will decrease . a preferred feed contains about twenty to twenty - five pounds per day , per 100 birds , of the following feed : 50 - 75 % corn , 10 - 30 % soy bean meal , grit , standard vitamin , and calcium mix , 2 - 10 % alfalfa , 20 - 100 gms / ton of niacin , 2 pounds / ton of yea - sacc 1026 or 1036 yeast ( available from all - tech ). applicants housed 5 , 600 single comb white leghorns in a barn , and used the following selection process for the unfertilized eggs . they selected eggs only from chickens of 30 weeks or younger , and only eggs between 2 ounces and 2 . 083 ounces . a flock having over 80 % productivity at the time of selection was used . the standard environment for the chickens was 65 °- 75 ° f ., with 14 - 17 hours of light per day . ( at week 18 of a chicken &# 39 ; s life the light was 14 hours per day , with the light gradually being increased to 17 hours by the 28th week ). this &# 34 ; pseudo - spring &# 34 ; further increases production . the birds were caged with an average of at least 54 square inches per bird . the feed for the birds was 20 gms / ton niacin ; 80 pounds / ton dehydrated alfalfa meal ; 2 pounds / ton yea - sacc yeast ; about 398 pounds / ton soy bean meal ; 120 pounds / ton calcium ; 1390 pounds / ton corn ; and 10 pounds / ton grit and conventional nutritional requirements for the chicken (&# 34 ; n . r . c &# 34 ;: standard vitamins and minerals ). eggs selected using the above procedures were then assayed for total egg cholesterol . the average ( over twelve selected large eggs ) was 165 milligrams cholesterol per 51 . 22 g of egg white and yolk ( which equals roughly 161 mg on a 50 g basis ). in another separate test , a sample of eggs averaged 159 . 7 mg cholesterol per 50 g egg white and yolk . it should be appreciated that the above experiments were primarily intended to achieve the minimum government labelling requirements . even further reductions in cholesterol content may be desirable . in this regard , the candling selection step can be added so as to further reduce the average cholesterol content . for various health and regulatory reasons ( e . g . 21 c . f . r . § 101 . 9 ( 1993 )) it is also desirable to reduce total fat and saturated fat levels in foods . surprisingly , the methods of the present invention also provide eggs with reduced levels of total and saturated fat . for purposes of the claims , total fat is determined by the ether extraction method . see e . g . official methods of analysis , 15th edition , 925 . 32 aoac , ( 1990 ). typical levels of total fat for prior art chicken eggs average as follows : small ˜ 3 . 8 gm / egg ; medium ˜ 4 . 2 gm / egg ; large ˜ 4 . 6 gm / egg ; extra large ˜ 5 . 8 gm / egg ; jumbo ˜ 6 . 2 gm / egg . in one test of the present invention , a sample of large eggs achieved an average total fat content of 3 . 8 grams fat per egg ( compared with the normal ˜ 4 . 6 gm / egg ), with the saturated fat portion reduced by more than 10 %. it should be appreciated that only the preferred embodiments have been described above . the following claims should therefore be looked to in order to judge the full scope of the invention .

reduced cholesterol , low fat eggs are obtained . at least a twenty - five percent reduction in cholesterol is achieved over normal levels for the grade size . the reduction can be achieved by weight monitoring of the egg , size monitoring of the yolk through candling , and selecting eggs from high producing , young , and high clutch chickens .

referring to fig1 a cannula introducer is shown generally at 20 and has a gun - like handle 21 , which , as seen in fig1 is a plan view ( in section ) in its normal operative position . the handle 21 has a cavity portion 22 enclosed on the bottom by a bottom wall 23 , which wall is surrounded about substantially its entire periphery by an upstanding flange 24 . the flange 24 extends upwardly for more than one - half of the thickness of the handle so that a cross sectional view as seen in fig1 goes through the flange 24 . as seen in fig1 the left side of the indroducer 20 is the proximal direction in relation to the operator while the right side is the distal direction with respect to the operator and will hereinafter be so referred . as seen in fig2 a cover plate 25 is adapted to overlie and be secured on the handle 22 , supported peripherally by the flange 24 ; the cover plate having three projections 26 , 27 and 28 extending into the cavity portion 22 and adapted to be secured to the bottom wall 23 about the openings 29 , 30 and 31 , respectively , as by screws ( not shown ) extending conventionally from the underside of the handle ( not shown ) through the openings 29 - 31 in the bottom wall 23 and into the projections 26 - 28 respectively . the flange 24 at the distal end of the handle 21 is enlarged internally to form a shoulder as shown at 32 and is enlarged externally of the flange 24 to form a truncated conical boss externally of the handle as shown at 33 ; the enlarged base of the conical boss is formed integral with the flange 24 of the handle and the distal end of the boss is the portion thereof which is truncated . an elongated cannula 34 has a medial straight portion 35 , a formed distal portion 36 , to be more clearly hereinafter described , and a conically shaped proximal portion 37 . the internal surface of the cannula &# 39 ; s proximal portion 37 is a mating fit on the conical boss 33 ; by mating fit is meant it is a sliding interference fit which securely yet releasably holds the cannula on the conical boss . the handle 21 adjacent the conical boss 33 is thick enough and the position of the boss 33 is selected so that the cannula does not project beyond the handle . a central bore 38 is formed in the boss 33 , which bore extends inwardly from the outer end of the boss 33 and into the enlarged shoulder 32 , but terminates slightly distally of the proximal end of the shoulder . suitably secured in the bore 38 , as by gluing , is a hollow rod housing 39 which is cylindrical for its entire length , except for the distal end 40 thereof as more fully described hereinafter . the rod housing 39 extends distally from the boss 33 , and lies within and supports the cannula 34 in a sliding fit for its full length , except for the proximal conical portion 37 of the cannula which is spaced from the rod housing 39 . to the left of the bore 38 in the boss 33 is a slightly smaller bore 41 which is approximately equal in size to the bore 42 in the rod housing 39 . telescopically received within the bore 41 of the shoulder 32 and the bore 42 of the rod housing 39 is a blade rod or stylet 43 ( which stylet except for its distal and proximal ends is cylindrical ); the stylet 43 terminating at its distal end 44 in a cutting blade more fully described hereinafter . the cannula 34 is open at its distal end 36 as shown at e in fig1 and 10 and the rod housing 39 is also open at its distal end as shown at f in fig1 and 8 . these openings allow the distal end 44 of the stylet 43 to project out of the rod housing and cannula during certain stages of operation of the device 20 . the stylet 43 extends proximally of the shoulder 32 to terminate at its proximal end in a square ( in cross section ) proximal projection 45 . for the purpose of clearly describing the first and second triggers , the reverse hammer and the spring - loaded stop , since fig1 is a plan view and the handle 20 is at the distal end of the device , in fig1 and 13 , the direction indicated by the arrow g will be identified as the left and the direction indicated by the arrow h will be identified as the right . a stylet operating or first trigger 46 is provided for actuating the stylet 43 . as seen in fig4 the trigger has a pair of pivot pins 48 and 47 extending respectively upwardly and downwardly therefrom . referring to fig1 the pivot pin 47 ( which cannot be seen in this view ) extends downwardly into and is pivotally mounted in a hole ( not shown ) in the bottom wall 23 of the handle 21 , while the pin 48 extends upwardly and into and is pivotally mounted in a hole ( not shown ) in the handle cover plate 25 . a finger engageable portion 49 of the trigger 46 extends to the right out of the handle 21 through a slot 50 formed in the right side flange 24 of the handle , which slot is located just distally of the graspable portion 51 of the handle 21 . as seen in fig1 the left end 52 of the trigger 46 is disposed within the handle 21 and the distal end of the left end of the trigger has a curved cam shape shown at 53 , which cam appears to look like a parrot &# 39 ; s beak . as seen in fig4 the curved cam is thinner in the up and down direction than the wider portions of the trigger 46 , while the lower side 54 and upper side 55 of the trigger adjacent the pins 47 and 48 respectively are wider than the cam 53 and are bearing surfaces which slideably engage the lower wall 23 and the wall of the cover 25 to laterally support the trigger . an eye 56 is formed in the distal side of the trigger 46 and proximally of the eye 56 and slightly to the left thereof , a post 57 is secured to and projects upwardly from the bottom wall 23 of the handle 21 . a tension coil trigger return spring 58 has its distal end secured to the post 57 and its proximal end secured to the eye 56 and constantly biases the trigger 46 in a counterclockwise direction to the cocked position as seen in fig1 so that the finger portion 49 of the trigger 46 is constantly biased distally . a reverse hammer or cam follower 59 is disposed in the cavity portion 22 of the handle 21 distally and to the left of the trigger 46 . more particularly , the hammer 59 is angularly elongated as sen in fig1 and intermediate its ends is an upper pivot pin 60 seen in fig1 and a lower pivot pin shown in phantom at 61 in fig3 ; the pin 61 extending downwardly into and is pivotally mounted in a hole ( not shown ) in the bottom wall 23 of the handle 21 , while the pin 60 extends upwardly and into and is pivotally mounted in a hole ( not shown ) in the handle cover plate 25 . the upper and lower surfaces of the reverse hammer 59 slidingly engage the bottom wall 23 and the wall in the cover plate 25 to laterally stabilize the hammer 59 . as seen in the cocked position of fig1 the lower distal surface 62 of the hammer 59 is a cam surface adapted to cooperate with the cam surface 53 of the trigger 46 . more particularly , the cam surfaces 53 and 62 abut each other in the cocked position of fig1 . just to the left of the cam surface 62 is a proximally extending slot 63 which extends inwardly of the hammer 59 adjacent the cam 62 . as seen in fig3 the slot 63 extends completely through the hammer 59 , and is bounded by an upper surface 64 ( as seen in fig1 ) and a lower surface 65 ( seen in fig3 ), so that the cam end 62 of the cam follower 59 is connected to the remainder of the cam follower around the slot 63 . the space between upper 64 and lower 65 surfaces as well as the right to left sides of the slot 63 is large enough to receive the distal end 53 of the trigger which has the curved cam shape like a parrot &# 39 ; s beak . adjacent the right end 63a of the hammer 59 is an opening 72 which receives the distal end of a coiled compression spring 73 compressed between the latter and the proximal flange 24 of the handle 21 . the spring biases the hammer counterclockwise to a stylet withdrawal position . the left end of the hammer 59 projects through a slot 66 formed in the flange 24 , which is formed therein at the junction of the left and proximal portions of the wall ; slot 66 extending distally sufficient to allow the hammer to rotate clockwise , as seen in fig1 to its uncocked position . adjacent the left outer end of the hammer 59 is an axially extending slot 67 ( clearly seen in fig3 ) which slot receives the proximal end of the square proximal portion 45 of the stylet 43 . the cam follower or reverse hammer 59 has aligned upper and lower openings 68 and 69 ( opening 68 is seen in fig1 while opening 69 is seen in fig3 ), which openings pivotally receive a pivot pin 70 seen in fig1 and 5 . as seen in fig5 the pivot pin 70 has a square opening 71 therein which receives the left proximal end of the square proximal projection 46 on the stylet 43 . a set screw 74 is threaded into the pivot pin 70 from the left upper surface thereof to secure the stylet projection 45 therein . the upper and lower ends 75 and 76 , respectively , of the pivot pin 70 slide upon the bottom wall 23 of the handle and the inner wall ( not shown ) of the cover plate 25 . the set screw 74 may be loosened to adjust the axial position of the stylet 43 relative to the cannula 34 and the rod housing during pivotal movement of the hammer 59 . the pivot pin 70 travels a slightly arcuate path , and the square proximal portion of the stylet 45 is sufficiently flexible to allow for this arcuate movement to take place without breaking of the stylet 43 . upon the operator moving the finger portion 49 of the trigger 46 distally , it will engage a spring loaded stop 78 to inform the operator that this position has been reached . concurrently with reaching the spring loaded stop , the right distal tip of the cam surface 53 on the trigger 46 will have reached a position just to the right of the slot 63 and the reverse hammer 59 . the spring loaded stop 78 provides a resistance against further counterclockwise rotation of the trigger 46 upon the latter &# 39 ; s engagement therewith , so that the operator knows that the stylet is at the maximum distal position . the stop 78 has a tapered surface 79 on the distal left corner thereof which is cammingly engaged by the tapered surface 77 on the trigger 46 . the stop 78 , as seen in fig6 has upper and lower shoulders 80 and 81 respectively , formed along the proximal edge thereof . these shoulders can be seen in fig6 but only upper shoulder 80 can be seen in fig1 . upper shoulder 80 slides in a slot ( not shown ) formed in the cover plate 25 while the lower shoulder 81 slides in a slot 82 formed in the handle 21 just proximally of the flange 24 at the distal side of the graspable portion 51 of the handle 21 ; the main body of the stop , distal of the shoulders 80 and 81 , projecting distally through a slot 84 formed in the flange 24 . the slot 82 in the handle 21 to the right side of the stop 78 , and the registering slot ( not shown ) in the cover plate 25 extend to the right of the stop 78 and compressed between the lower end thereof and the bottom of the slot 82 is a coiled compression spring 85 which biases the stop 78 to the left . upon the trigger 46 being moved past the stop 78 , the latter is biased to the right and the curved cam 53 on the trigger 46 enters the slot 63 in the hammer 59 and the spring 73 quickly fires the hammer 59 ; by firing is meant quickly rotates the same counterclockwise so that the stylet is in its withdrawn or proximal position . since the cam 53 is in the slot 63 the trigger is no longer operative to move the stylet 43 . further , the spring loaded stop 78 will be biased to the left against the bottom of the trigger to help hold the trigger in the fired position . to re - cock the reverse hammer 59 , the left end thereof extending out of the slot 66 is forced distally by the operator while the cam 53 on the trigger 46 is withdrawn from the slot 63 ; the trigger 46 being moved counterclockwise to its position shown in fig1 while the stop 78 is held to the right , to allow movement of the trigger . while the trigger is held in its counterclockwise position , the hammer is allowed to move counterclockwise so that the cam 53 on the trigger 46 once more engages the cam 62 on the reverse hammer or cam follower 59 . as seen in fig1 the rod housing 39 is disposed within the cannula 34 and terminates just proximally of the end of the cannula 34 . fig9 and 10 show that the distal end 36 of the cannula is formed with a lower beak - like configuration so that it may easily be moved into the opening formed in the blood vessel by advancing the entire cannula introducer 20 with the cannula thereon in the direction of the blood vessel . once the distal end 36 of the cannula 34 is in the blood vessel the desired extent , the operator slips the proximal portion 37 of the cannula off of the conical boss 33 and withdraws the rod housing from within the cannula . the remaining manipulation and use of this cannula is well known in the art . as seen in fig1 and 8 , the distal end 40 of the rod housing 39 is cut open at f like a lower beak ; the curvature of the distal end being such that the housing can closely fit to the inner surface of the lower beak shaped end 36 of the cannula 34 . as seen in fig1 and 12 , the distal end 44 of the stylet 43 is formed with a suitable cutting end 86 ; it being understood that cutting ends of different configurations may be utilized . as seen in fig1 , the bottom of the cutting end 86 is formed on the center line off the stylet 43 so that it can move past the distal end 40 of the rod housing 39 and distal end 36 of the cannula 34 without interference or damage to the cannula or rod housing . when the distal end 44 of the stylet is in its cocked or withdrawn position , the cutting end 86 will lie within the confines of the distal end 40 of the rod housing 39 and thereby whether or not the cannula 34 is present , the cutting end 86 will not be in a position to cause inadvertent cutting . referring now to fig1 and 14 , wherein a second embodiment is shown , and structures will have the same number as like structures of the embodiment of fig1 - 12 , a second trigger or cannula separating means 87 is provided . a trigger 87 has a rightwardly extending finger engaging portion 88 which , as seen in fig1 , projects to the right from a pivot pin 89 carried by the housing and pivotally mounting the trigger to the housing at a location intermediate the left and right ends of the trigger . the pivot pin 89 has an enlarged head 90 to prevent the trigger from coming off of the pin 89 . to the left of the pivot pin 88 , the trigger has an opening 91 substantially axially aligned with a post 92 carried by the cover plate 25 . a coiled tension spring 93 has its opposed ends secured in the opening 91 and to the post 92 to bias the second trigger in a counterclockwise direction . the second trigger 87 has a portion thereof extending to the left of the pivot pin 89 and the left end thereof extends somewhat past the center line of the modified cannula 94 ; the cannula 94 being mounted on a conical boss 33 ( not seen in fig1 ). a cannula ejector 95 is mounted to the left portion of the trigger 87 . more particularly , as seen in fig1 , the ejector , when viewed from the left , is &# 34 ; l &# 34 ;- shaped in cross section . as seen in fig1 and 14 , the ejector 95 extends distally from a pivot pin 96 which pivotally secures the ejector to the second trigger 87 . a pair of spaced posts 97 and 98 , the post 97 being to the left and the post 98 being to the right of the ejector 95 to substantially limit movement of the ejector in a proximal - distal direction ; the fit not being so tight as to prevent some lateral rocking of the ejector as it moves proximally and distally since the pivotal connection at the trigger will move slightly arcuately . the leg 99 of the &# 34 ; l &# 34 ;- shaped ejector 95 extends downwardly ( downwardly as seen in fig1 ) into a registering slot 100 formed in the proximal end of the cannula 94 . to operate the second trigger 87 ; after the distal end of the cannula 94 has been introduced into the blood vessel , the finger engaging portion of the second trigger is moved proximally by the operator to force the cannula 94 off of the boss 33 . this is accompanied by proximal movement of the handle 21 to withdraw the guide rod from within the cannula . it will thus be seen that the objects set forth above , and those made apparent by the foregoing description , are efficiently attained , and since certain changes may be made in the above construction without departing from the scope of the invention , it is intended that all matters contained in the foregoing description , or shown in the accompanying drawings , shall be interpreted as illustrative and not in a limiting sense . it is also to be understood that the following claims are intended to cover all of the generic and specific features of the invention herein described , and all statements of the scope of the invention which , as a matter of language , might be said to fall therebetween .

a cannula introducer device for providing a cut in a blood vessel wall and inserting a cannula into such cut . the device includes a rod housing carried by a pistol - shaped handle . telescoped within the rod housing is a blade rod terminating at its distal end in a knife blade and extending from the proximal end of the rod housing to be secured to a reverse hammer - cam follower which is biased in a direction to move the blade rod proximately into the rod housing . surrounding the rod housing and releasably carried by the handle is a cannula , the distal end being substantially co - extensive with the rod housing . a first trigger in the handle engages the reverse hammer and upon proximal movement of the trigger moves the blade out of the distal end of the rod housing and cannula where the operator can use the blade to cut an opening in the blood vessel . a spring loaded stop engages the trigger at its blade extended position . further proximal movement of the trigger overcomes the stop and allows the reverse hammer to be biased to move the blade rod proximally into the confines of the rod housing . the entire device is then advanced distally to insert the distal end of the cannula in the cut in the vessel wall , and the cannula is then withdrawn from the handle and supporting blade housing . in a second embodiment , a second trigger is mounted on the handle and is spring loaded so that its upper end moves proximally . a rod pivotally secured to the upper end of the trigger extends distally into a notch at the proximal end of the cannula . upon activation of the second trigger the rod pushes the cannula in a distal direction relative to the handle .

before describing the present invention in detail , it is to be understood that this invention is not limited to particularly exemplified systems or process parameters as such may , of course , vary . it is also to be understood that the terminology used herein is for the purpose of describing particular embodiments of the invention only , and is not intended to limit the scope of the invention in any manner . all publications , patents and patent applications cited herein , whether supra or infra , are hereby incorporated by reference in their entirety to the same extent as if each individual publication , patent or patent application was specifically and individually indicated to be incorporated by reference . it must be noted that , as used in this specification and the appended claims , the singular forms “ a ,” “ an ” and “ the ” include plural referents unless the content clearly dictates otherwise . thus , for example , reference to a “ fragrance bead ” includes two or more such beads . unless defined otherwise , all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains . although a number of methods and materials similar or equivalent to those described herein can be used in the practice of the present invention , the preferred materials and methods are described herein . the following description includes embodiments presently contemplated for carrying out the present invention . this description is made for the purpose of illustrating the general principles of the present invention and is not meant to limit the inventive concepts claimed herein . as used herein the term “ dirty ” when used to describe air refers to malodor - laden air that contains odors associated with animal dross . as used herein the term “ clean ” when used to describe air refers to malodor - laden air , i . e ., dirty air that has been passed through an odor absorbing filter , e . g ., an activated carbon filter . as used herein the term “ activated carbon ” means absorbent carbon - based materials , including activated and reactivated carbon - based absorbents . activated carbon , including the material commonly called activated charcoal , is an amorphous form of carbon characterized by high adsorptivity for many gases , vapors and colloidal solids . carbon is generally obtained by the destructive distillation of coal , wood , nut - shells , animal bones or other carbonaceous materials , including coconuts . the carbon is typically “ activated ” or reactivated by heating to about 800 - 900 ° c ., with steam or carbon dioxide , which results in a porous internal structure . disclosed herein is an air treatment device for a litter box that will absorb , remove and / or contain the malodors emanating from deposited waste , especially those odors emanating from freshly deposited fecal waste that has not yet been buried by the animal . in addition , the device will expel a pleasant fragrance and / or sanitize the exiting air ( as well as the air immediately surrounding the litter box ). an embodiment of a compact and portable air treatment device that is capable of attachment to the side of a litter box is shown in fig1 . the device includes a housing assembly 10 and an interior cavity ( not shown ). housing assembly 10 includes a front cover 12 and a back cover 14 . when assembled the housing also includes a top 16 and a bottom 18 . front cover 12 includes an air inlet 20 having downward facing slats 22 which keep the animal litter from entering the interior of the housing . back cover 14 includes an air outlet 24 . fig1 a shows the interior of the front cover and fig1 b shows the interior of the back cover . referring again to fig1 , the device may contain a sensor 25 to detect the presence of an animal and turn the fan on when an animal is detected . additionally , the device may contain a timer ( not shown ) to automatically turn the fan off after a predetermined period of time , e . g . 1 - 30 minutes after the sensor detects that the animal is no longer present in the box . sensor 25 may detect motion , sound , light reflection , weight or heat and should be limited in sensitivity to that corresponding to a small animal , e . g ., a cat . fig2 shows the interior cavity of the device . an odor absorbing material 26 , e . g ., activated carbon , zeolite , silica gel , activated alumina , baking soda or a combination thereof is positioned between air inlet 20 and a fan 28 or alternatively between the fan and a secondary treatment material . the odor absorbing material may be in a secondary housing , e . g ., a filter cartridge , or may be in a form where secondary containment is unnecessary . a battery 30 , e . g ., a standard 9 volt , is used to power the fan and may also be used to power sensor 25 and timer 27 . positioned between fan 28 and air outlet 24 can be a reservoir ( not shown ) to place a secondary treatment material such as a fragrance source to mask the odor , an air sanitizing material to sanitize the air exiting the device or an odor canceling material to neutralize the odor , e . g ., a chemical ( s ) that reacts with an odiferous constituent contained in the waste such that any remaining odor is neutralized . area 32 in fig1 b shows a possible location for the reservoir . a preferred fragrance source comprises fragrance beads such as those supplied by commercial fragrance houses such as iff and firmenich . other fragrance sources include natural materials that emit their native scents . odor absorbing materials in addition to activated carbon include baking soda ; zeolites ; activated alumina ; silicas ; silicates , such as diatomaceous earth metals ; filter agents , such as celatom ; and aluminosilicates , such as fuller &# 39 ; s earth , montmorillonite or bentonite , or a combination thereof . examples of air sanitizing and / or odor canceling materials include : acid / base effervescents ; antimicrobial - impregnated polymers ; sodium bicarbonate ( baking soda ); sodium carbonate ; iron in solid or salt form ; hypochlorite or hypochlorite salts , peroxide or peroxide salts , chlorous acid or chlorous acid salts , chlorine dioxide , and / or glycols . device 10 can be attached to the litter box in any way feasible . for example , velcro , a clip , a clamp , a suction cup , a cloth strap with a buckle , a rubber belt , a groove ( s ), a slot ( s ) or ridge ( s ) compatible with a matching groove ( s ), slot ( s ) or ridge ( s ) on the litter box . in one embodiment , air treatment device 10 can have multiple air inlet ports . fig3 shows a litter box 50 with an embodiment of the air treatment device 10 of the present invention attached . device 10 can be attached on either the interior or the exterior of the box although the interior is preferred . in this embodiment , device 10 includes several additional inlets 52 that are strategically spaced around the perimeter of the litter box , preferably on the inside of the box just below the edge of the litter box rim . inlets 52 are in communication with the air inlet 20 of device 10 by some form of air transport mechanism , such as tubing 54 . this embodiment enables malodor - laden air from in and around the litter box to be vacuumed into air treatment device 10 . the activated carbon can be in the form of a removable / replaceable cartridge . one form of carbon is carbon foam manufactured by foamex international , inc ., which is a polyurethane foam coated with activated carbon and a binder . substrates other than polyurethane are available such as polyester , or other similar polymers . although activated carbon is a preferred odor absorbing material for the foam , other possible odor adsorbents could also be used . the fragrance source and / or sanitizing material can also be in the form of a removable / replaceable cartridge or otherwise be designed to be easily removable / replaceable so that the end user can , for example , easily switch between fragrance choices and / or alternate between air sanitizing / odor canceling materials . for example , fragrance beads can be contained in packets . depending on the type of air sanitizing / odor canceling material used , it can either be contained in packets or in a removable / replaceable cartridge . the secondary treatment material cartridge could be similar to the one shown in fig4 a and described below . depending on the properties of the secondary treatment material , it may be incorporated onto a foam substrate in a manner similar to the activated carbon , i . e ., a polyurethane or other suitable polymeric material can be coated with the treatment material and a binder . however , the secondary treatment material could be in any appropriate form ( e . g ., liquid , solid , granular , block , etc .) within the cartridge . referring to fig4 a , one embodiment of an activated carbon cartridge is shown . in this embodiment the air flow is designed to follow a convoluted , high surface area , tortuous path so that the contact time between the dirty air and the surface area of the activated carbon is maximized . the activated carbon 46 is coated with a binder onto polyurethane ( i . e ., “ carbon foam ”) and is filled along dividers 48 which protrude the top 60 of the cartridge . referring to fig4 b , cartridge 40 is designed to snap into either front cover 12 or rear cover 14 and be encompassed by dividers 47 contained on either the front or rear cover to form a sealed tortuous air flow path ( front cover is shown ). the front cover 12 or rear cover 14 has an air inlet 42 and an air outlet 44 which is in communication with the fan ( not shown ) of the device or the air inlet of the device ( not shown ) to force the air flow in the direction shown by the arrows . fig4 a and 4b depict 5 dividers , but any number of dividers could be utilized with the understanding that the greater the number of dividers the more tortuous the ensuing air path and the greater the contact time between the dirty air and the surface area of the activated carbon . thus , the carbon filter can effectively utilize a very small physical area if used together with a highly tortuous air flow path . filter cartridge 40 can be plastic and can be manufactured using well known plastics fabrication techniques , such as injection molding and thermoforming . it should be designed to “ snap fit ” securely into either the front or rear cover of the housing assembly . without departing from the spirit and scope of this invention , one of ordinary skill can make various changes and modifications to the invention to adapt it to various usages and conditions . as such , these changes and modifications are properly , equitably , and intended to be , within the full range of equivalence of the following claims .

disclosed herein is a portable deodorizing air treatment device adaptable for use in a litter box . the device is activated by the presence of the animal in the litter box . after the animal uses the box , the device intakes dirty air , treats it with odor - absorbing activated carbon and optionally fragrance , expelling clean unscented or scented air .

fig1 shows a disposable cassette 10 that can be retained in a correspondingly designed cassette compartment or mount of a dialysis machine ( e . g ., a peritoneal dialysis machine ) 100 ( shown in fig2 ). referring to fig1 and 2 , the reference numerals 2 , 4 , 6 characterize connection elements for the connection of solution bags , of lines leading to the patient and to the dialysis machine , and of drainage lines . two fixedly attached hoses or lines 104 and 106 are arranged at the connectors 4 and 6 , with one of the hoses representing the patient hose and the other representing the drainage hose . the connection elements 2 allow the operator to connect the solution bags or other medication containers to the cassette 10 . referring again to fig1 , the cassette 10 includes a base body 12 that is made of plastic and can be manufactured using injection molding technology or deep - drawing technology . cut - outs as well as passages extend in the base body 12 . the base body 12 partly forms the walls of two pump chambers 20 , 22 arranged next to one another as well as liquid passageways 30 , 40 , 50 , 60 extending within the cassette 10 . liquid passageways 80 and 90 are likewise partly formed by the base body 12 between the pump chambers 20 and 22 . the liquid passageway 50 is serpentine shaped and is provided within a heating region 52 of the cassette 10 . one end of the passageway 50 is connected to the passageway 30 , and the other end of the passageway 50 is connected to the passageway 40 . the cassette 10 , as discussed above , is configured to be retained in a cassette compartment of the dialysis machine 100 . referring briefly to fig3 , the dialysis machine 100 includes a heating device 108 . when the cassette 10 is positioned within the cassette compartment of the dialysis machine 100 , as shown in fig2 , the heating device 108 is positioned adjacent the heating region 52 of the cassette 10 through which the passageway 50 extends . as a result of this arrangement , the dialysis liquid ( e . g ., dialysate ) flowing through the passageway 50 is heated when the cassette 10 is positioned within the cassette compartment of the dialysis machine 100 and the beating device 108 is activated . as shown in fig3 , in addition to the heating device 108 , the dialysis machine 100 includes two pumps 110 , 112 and multiple valve tappets t 1 , t 2 , t 3 , t 4 , t 5 , t 6 , t 7 , t 8 , t 9 , t 10 , t 11 , t 12 , t 13 , t 14 , t 15 , and t 16 . the pumps 110 , 112 cooperate with the pump chambers 20 , 22 to pump liquid through the various passages of the cassette 10 . the valve tappets t 1 , t 2 , t 3 , t 4 , t 5 , t 6 , t 7 , t 8 , t 9 , t 10 , t 11 , t 12 , t 13 , t 14 , t 15 , and t 16 cooperate with corresponding valves v 1 , v 2 , v 3 , v 4 , v 5 , v 6 , v 7 , v 8 , v 9 , v 10 , v 11 , v 12 , v 13 , v 14 , v 15 and v 16 of the cassette 10 to direct the conveyed liquid through the cassette 10 in a desired manner . the valve tappets t 1 , t 2 , t 3 , t 4 , t 5 , t 6 , t 7 , t 8 , t 9 , t 10 , t 11 , t 12 , t 13 , t 14 , t 15 , and t 16 can be pneumatically , hydraulically and / or mechanically controlled . other details regarding the cassette and its function substantially correspond to those details and functions described in ep 0 956 876 b1 , which is incorporated by reference herein . during normal function of the cassette 10 and the dialysis machine 100 , liquid ( e . g ., dialysate ) is conveyed from the pump chamber 22 through the heating region 52 of the cassette 10 in the direction of the patient line that carries the liquid to the patient and that is connected to the connector 4 . the liquid thus flows from the pump chamber 22 via the passageway 80 after the opening of the valve v 4 through the passageway 50 adjacent the heater 108 of the dialysis machine 100 and via the opened valve v 5 as well as the opened valve v 6 . as the liquid flows through the passageway 50 adjacent the heater 108 , heat emitted from the heater 108 increases the temperature of the liquid . thus , the heater 108 and the heating region 52 of the cassette 10 together act as a continuous - flow heating mechanism . at the same time that liquid is forced out of the pump chamber 22 and through the passageway 50 , the pump chamber 20 is supplied with fresh liquid . the fresh liquid can , for example , be supplied to the pump chamber 20 via the opened valves v 11 and v 1 , while the valves v 7 , v 3 and v 2 as well as v 9 are simultaneously closed . if problems arise in the patient line ( e . g ., if the patient line 104 connected to the connector 4 becomes occluded ), the liquid present in the passageway 50 can be overheated due to an overshooting of the heating regulator . the overheated liquid can typically not be infused into the peritoneum due to its elevated temperature . when overheating of the liquid in the passageway 50 occurs , the valve v 6 is closed and the heating power in the heater 108 of the dialysis machine 100 is reduced via a control unit that is arranged in the dialysis machine 100 . at the same time , the valve v 11 is closed to prevent any additional fresh solution from being delivered to the pump chamber 20 . after turning off the heater 108 and closing valves v 6 and v 11 , the overheated solution is pumped via the pump chamber 22 through the passageway 50 adjacent the continuous - flow heater and into the pump chamber 20 . to do this , the valve v 4 , the valve v 5 , the valve v 7 , and the valve v 1 are opened . the pump stroke of the pump chamber 22 is ended when the pump chamber 20 is filled or the pump chamber 22 is emptied . two possibilities now generally result for the cooling of the liquid in dependence on the ratio of the liquid contained in the pump chamber 20 to the warm liquid conveyed into the pump chamber 20 . if a high proportion of cool liquid ( i . e ., liquid that has not passed through the passageway 50 adjacent the heater 108 ) is present in the pump chamber 20 , the resulting mixed liquid , which is comparatively cooler than the overheated liquid due to the mixing of the liquids , is conveyed via the passageway 50 adjacent the heater 108 into the pump chamber 22 in reverse operation . in particular , the liquid is pumped back into the pump chamber 22 via the opened valve v 1 , the opened valve v 7 , the opened valve v 5 , and the opened valve v 4 . the partially overheated heating region 52 of the cassette 10 is also cooled by the comparatively cooler liquid . if , after delivering the overheated liquid to the pump chamber 20 , a high proportion of overheated liquid is present in the pump chamber 20 , the mixture of liquid ( i . e ., the mixture of the overheated liquid and any cool liquid that was present in the pump chamber 20 when the overheated liquid was delivered to the pump chamber 20 ) is conveyed in forward operation via the passageway 50 adjacent the heater 108 into the pump chamber 22 . starting from the pump chamber 20 , the liquid is conducted into the pump chamber 22 via the opened valve v 2 , the opened valve v 5 , the opened valve v 7 , and the opened valve v 3 . in this variant , the excess heat of the overheated liquid is distributed in the cassette so that the temperature of the overheated liquid can be lowered to the desired temperature . while the heater 108 has been described as being part of the dialysis machine 100 and positioned adjacent to the passageway 50 of the cassette 10 when the cassette 10 is positioned in the cassette compartment of the dialysis machine 100 , in certain implementations , the cassette itself includes a heater or part of a heater . the heating region of the cassette can , for example , be equipped with a heating coil . in such cases , the heating coil can be connected to a power supply of the dialysis machine when the cassette is inserted into the cassette compartment in order to provide the coil with power that generates heat . while the control unit has been described as being part of the dialysis machine 100 , the control unit can alternatively be located at any of various other locations outside of the cassette 10 .

a method that includes conveying overheated dialysate through a cassette in a manner to reduce the temperature of the overheated dialysate , and a dialysis system including a control unit configured to cause overheated dialysate to be conveyed through a cassette in a manner to reduce the temperature of the overheated dialysate .

pioneer brand hybrid 3310 is a single cross , yellow endosperm , dent maize hybrid which is high yielding and demonstrates very strong early growth and very good staygreen . for a relatively early crm hybrid , hybrid 3310 demonstrates good resistance to the southeastern virus complex , a dual infection of both maize dwarf mosaic virus and maize chlorotic dwarf virus . hybrid 3310 demonstrates good resistance to gray leaf spot and demonstrates good silage appearance . this hybrid demonstrates very good test weight and very good grain appearance . hybrid 3310 combines several important characteristics that are needed for areas of high risk for disease and no - till acreage . hybrid 3310 demonstrates strong early growth , excellent overall disease resistance and high yield . hybrid 3310 demonstrates the unique combination of good mdm / mcdv resistance and high yield . hybrid 3310 exhibits this high yield and mdm / mcdv resistance in a maturity that is earlier than most other hybrids resistant to mdm / mcdv . hybrid 3310 is approximately 113 relative maturity based on the comparative relative maturity rating system for harvest moisture grain . this hybrid has the following characteristics based on the data collected primarily at johnston , iowa . table 1__________________________________________________________________________variety description informationvariety = 3310__________________________________________________________________________ type : ( describe intermediate types in comments section ): 2 1 = sweet 2 = dent 3 = flint 4 = flour 5 = pop 6 = ornamental maturity : days heat units65 1 , 407 from emergence to 50 % of plants in silk66 1 , 420 from emergence to 50 % of plants in pollen5 114 from 10 % to 90 % pollen shed69 1 , 422 from 50 % silk to harvest at 25 % moisture standard sample plant : deviation size292 . 0 cm plant height ( to tassel tip ) 16 . 97 2130 . 0 cm ear height ( to base of top ear node ) 14 . 14 219 . 5 cm length of top ear internode 1 . 84 101 average number of tillers 0 . 00 21 . 0 average number of ears per stalk 0 . 00 21 . 0 anthocyanin of brace roots : 1 = absent 2 = faint 3 = moderate 4 = dark standard sample leaf : deviation size 11 . 5 cm width of ear node leaf 0 . 14 10 84 . 7 cm length of ear node leaf 0 . 42 10 6 . 0 cm number of leaves above top ear 0 . 28 10 15 . 5 degrees leaf angle ( measure from 2nd leaf 6 . 36 2 above ear at anthesis to stalk above leaf ) 3 leaf color dark green ( munsell code ) 5gy341 . 0 leaf sheath pubescence ( rate on scale from 1 = none to 9 = like peach fuzz ) 7 . 5 marginal waves ( rate on scale from 1 = none to 9 = many ) 8 . 5 longitudinal creases ( rate on scale from 1 = none to 9 = many ) standard sample tassel : deviation size8 . 4 number of primary lateral branches 0 . 28 1045 . 0 branch angle from central spike 0 . 00 26 . 5 pollen shed ( rate on scale from 0 = male sterile to 9 = heavy shed ) 7 anther yellow ( munsell code ) 2 . 5yr541 glume color light green ( munsell code ) 5gy461 . 0 bar glumes ( glume bands ): 1 = absent 2 = present6a . ear ( unhusked data ): 11 silk color ( 3 days after emergence ) pink ( munsell code ) 7 . 5yr661 fresh husk color ( 25 days after 50 % silking ) light green ( munsell code ) 5gy5621 dry husk color ( 65 days after 50 % silking ) buff ( munsell code ) 2 . 5y8 . 41 position of ear at dry husk stage : 1 = upright 2 = horizontal 3 = pendant upright5 . 5 husk tightness ( rate of scale from 1 = very loose to 9 = very tight ) 2 husk extension ( at harvest ): 1 = short ( ears exposed ) 2 = medium (& lt ; 8 cm ) 3 = long ( 8 - 10 cm beyond ear tip ) 4 = very long (& gt ; 10 medium standard sample6b . ear ( husked ear data ): deviation size19 . 6 cm ear length 0 . 5656 1048 . 3 mm ear diameter at mid - point 1 . 2727 10217 . gm ear weight 25 . 031 1015 . 2 number of kernel rows 1 . 1313 102 kernel rows : 1 = indistinct 2 = distinct distinct1 row alignment : 1 = straight 2 = slightly curved 3 straight13 . 8 cm shank length 1 . 4142 10 average2 ear taper : 1 = slight 2 = average 3 = extreme standard sample kernel ( dried ): deviation size12 . 3 mm kernel length 0 . 1414 108 . 9 mm kernel width 0 . 1414 104 mm kernel thickness 0 108 . 62 % round kernels ( shape grade ) 1 . 5163 21 aleurone color pattern : 1 = homozygous 2 = segregating homozygous7 aluerone color yellow ( munsell code ) 2 . 5y8147 hard endosperm color yellow ( munsell code ) 2 . 5y8 . 163 endosperm type : normal starch 1 = sweet ( su1 ) 2 = extra sweet ( sh2 ) 3 = normal starch 4 = high amylose starch 5 = waxy starch 6 = high protein 7 = high lysine 8 = supersweet ( se ) 9 = high oil 10 = other . sub .-- 33 gm weight per 100 kernels ( unsized sample ) 1 . 4142 2 standard sample cob : deviation size 25 . 4 mm cob diameter at mid - point 2 . 8410 1014 cob color red ( munsell code ) 10r3102 cob strength 1 = weak 2 = strong disease resistance ( rate from 1 ( most susceptible ) to 9 ( most resistant ); leave blank if not tested ; leave race or strain options blank if polygenic : a . leaf blights , wilts , and local infection diseases anthracnose leaf blight ( colletotrichum graminicola ) 6 common rust ( puccinia sorghi ) common smut ( ustilago maydis ) 6 eyespot ( kabatiella zeae ) 8 goss &# 39 ; s wilt ( clavibacter michiganense spp . nebraskense ) 6 gray leaf spot ( cercospora zeae - maydis ) helminthosporium leaf spot ( bipolaris zeicola ) 5 northern leaf blight ( exserohilum turcicum ) 5 southern leaf blight ( bipolaris maydis ) 6 southern rust ( puccinia polysora ) 8 stewart &# 39 ; s wilt ( erwinia stewartii ) other ( specify ) -- b . systemic diseases7 corn lethal necrosis ( mcmv and mdmv ) 9 head smut ( sphacelotheca reiliana ) maize chlorotic dwarf virus ( mdv ) maize chlorotic mottle virus ( mcmv ) 5 maize dwarf mosaic virus ( mdmv ) sorghum downy mildew of corn ( peronosclerospora sorghi ) other ( specify ) -- c . stalk rots4 anthracnose stalk rot ( colletotrichum graminicola ) diplodia stalk rot ( stenocarpella maydis ) fusarium stalk rot ( fusarium moniliforme ) gibberella stalk rot ( gibberella zeae ) other ( specify ) -- d . ear and kernel rots aspergillus ear and kernel rot ( aspergillus flavus ) diplodia ear rot ( stenocarpella maydis ) 3 fusarium ear and kernel rot ( fusarium moniliforme ) 6 gibberella ear rot ( gibberella zeae ) other ( specify ) -- 10 . insect resistance ( rate from 1 ( most susceptible ) to 9 ( most resistant ); ( leave blank if not tested ) banks grass mite ( oligonychus pratensis ) corn worm ( helicoverpa zea ) leaf feeding silk feeding mg larval wt . ear damage corn leaf aphid ( rhopalosiphum maidis ) corn sap beetle ( carpophilus dimidiatus ) european corn borer ( ostrinia nubilalis ) 3 1st generation ( typically whorl leaf feeding ) 5 2nd generation ( typically leaf sheath - collar feeding ) stalk tunneling 2 . 4 cm tunneled / plant fall armyworm ( spodoptera fruqiperda ) leaf feeding silk feeding mg larval wt . maize weevil ( sitophilus zeamaize ) northern rootworm ( diabrotica barberi ) southern rootworm ( diabrotica undecimpunctata ) southwestern corn borer ( diatreaea grandiosella ) leaf feeding stalk tunneling cm tunneled / plant two - spotted spider mite ( tetranychus urticae ) western rootworm ( diabrotica virgifrea virgifera ) other ( specify ) -- agronomic traits : 8 staygreen ( at 65 days after anthesis ) ( rate on a scale from 1 = worst to excellent ) 0 . 7 % dropped ears ( at 65 days after anthesis ) % pre - anthesis brittle snapping % pre - anthesis root lodging13 . 4 post - anthesis root lodging ( at 65 days after anthesis ) 10 , 550 kg / ha yield ( at 12 - 13 % grain moisture ) __________________________________________________________________________ comparisons of characteristics for pioneer brand hybrid 3310 were made against pioneer brand hybrids 3223 , 3245 and 3293 . table 2a compares pioneer hybrid 3310 and pioneer hybrid 3223 . the results show that while hybrid 3223 is higher yielding than hybrid 3310 , both hybrids are above average yielding and hybrid 3310 demonstrates significantly lower harvest moisture and significantly better test weight than hybrid 3223 . hybrid 3310 also demonstrates significantly better seedling vigor than hybrid 3223 . hybrid 3310 demonstrates above average staygreen and significantly better resistance to gray leaf spot , southern leaf blight , stewart &# 39 ; s wilt and southern rust than hybrid 3223 . in addition , hybrid 3310 exhibits greater resistance to goss &# 39 ; s wilt , corn lethal necrosis and mdm complex than hybrid 3223 . table 2b compares pioneer hybrid 3310 and pioneer hybrid 3245 . the results show that both hybrids are above average yielding . hybrid 3310 demonstrates significantly better seedling vigor , and significantly better staygreen than hybrid 3245 . hybrid 3310 demonstrates significantly better resistance to gray leaf spot , common rust , southern rust , northern leaf blight , corn lethal necrosis and maize dwarf mosaic complex hybrid 3245 . hybrid 3310 demonstrates very good resistance to goss &# 39 ; s wilt , anthracnose stalk rot , and stewart &# 39 ; s wilt . table 2c compares pioneer hybrid 3310 and pioneer hybrid 3293 . the results show that hybrid 3310 is higher yielding and demonstrates significantly higher test weight than hybrid 3293 . hybrid 3310 also demonstrates above average staygreen and significantly better staygreen and significantly better resistance to gray leaf spot than hybrid 3293 . hybrid 3310 demonstrates better resistance o both maize dwarf mosaic complex and corn lethal necrosis than hybrid 3293 . hybrid 3310 also demonstrates better resistance to southern rust than hybrid 3293 . in addition , 3310 exhibits very good resistance to goss &# 39 ; s wilt , stewart &# 39 ; s wilt and common rust . table 2a__________________________________________________________________________variety # 1 = 3310variety # 2 = 3223__________________________________________________________________________ prm bu bu tst sdg est gdu prm shd acr acr mnst wt vgr cnt shd abs abs abs % mn % mn abs % mn % mn % mn__________________________________________________________________________total sum 1 114 114 164 . 4 101 100 58 . 6 113 100 101 2 115 118 171 . 0 105 107 56 . 5 93 103 106 locs 26 36 129 129 136 87 88 63 54 reps 26 36 170 170 181 105 142 87 85 diff 2 4 6 . 6 3 6 2 . 1 20 3 5 pr & gt ; t . 000 # . 000 # . 005 # . 026 + . 000 # . 000 # . 000 # . 060 * . 000 # __________________________________________________________________________ gdu stk plt ear rt sta stk brt grn slk cnt ht ht ldg grn ldg stk app % mn % mn % mn % mn % mn % mn % mn % mn % mn__________________________________________________________________________total sum 1 100 100 104 102 96 121 102 85 103 2 105 102 103 111 106 123 97 95 96 locs 47 173 81 81 58 72 85 10 23 reps 74 262 124 124 97 96 96 12 23 diff 5 2 1 8 10 1 5 10 7 pr & gt ; t . 000 # . 000 # . 033 + . 000 # . 024 + . 745 . 063 * . 265 . 374__________________________________________________________________________ drp glf nlf slf gos stw ant hd ear spt blt blt wlt wlt rot smt cln % mn abs abs abs abs abs abs abs abs__________________________________________________________________________total sum 1 98 5 . 6 5 . 3 5 . 5 8 . 0 8 . 0 3 . 8 100 . 0 7 . 5 2 102 3 . 2 5 . 5 3 . 5 7 . 3 7 . 0 3 . 1 100 . 0 3 . 0 locs 19 13 4 18 2 2 4 1 1 reps 20 19 7 48 4 2 8 2 2 diff 5 2 . 3 0 . 3 2 . 0 0 . 8 1 . 0 0 . 6 0 . 0 4 . 5 pr & gt ; t . 259 . 000 # . 844 . 000 # . 500 . 000 # . 368__________________________________________________________________________ mdm fus eye com sou ecb ecb ecb cpx ers spt rst rst dpe 1lf 2sc abs abs abs abs abs abs abs abs__________________________________________________________________________total sum 1 5 . 0 3 . 7 6 . 0 6 . 0 5 . 5 97 . 1 4 . 3 6 . 1 2 4 . 3 4 . 09 3 . 0 3 . 5 4 . 5 100 . 0 3 . 5 5 . 9 locs 3 5 1 2 2 2 2 8 reps 8 7 1 3 4 2 4 9 diff 0 . 7 1 . 2 3 . 0 2 . 5 1 . 0 2 . 9 0 . 8 0 . 2 pr & gt ; t . 184 . 255 1 . 26 . 000 # . 500 . 500 . 728__________________________________________________________________________ *= 10 % sig += 5 % sig #= 1 % sig table 2b__________________________________________________________________________variety # 1 = 3310variety # 2 = 3245__________________________________________________________________________ prm bu bu tst sdg est gdu prm shd acr acr mnst wt vgr cnt shd abs abs abs % mn % mn abs % mn % mn % mn__________________________________________________________________________total sum 1 113 114 168 . 2 102 100 58 . 1 112 101 102 2 114 114 168 . 6 102 101 58 . 3 101 101 101 locs 39 42 184 184 194 118 99 97 56 reps 39 42 239 239 252 141 133 125 64 diff 0 0 0 . 5 0 1 0 . 2 11 0 0 pr & gt ; t . 999 . 999 . 772 . 999 . 095 * . 092 * . 000 # . 999 . 999__________________________________________________________________________ gdu stk plt ear rt sta stk brt grn slk cnt ht ht ldg grn ldg stk app % mn % mn % mn % mn % mn % mn % mn % mn % mn__________________________________________________________________________total sum 1 102 101 104 103 97 124 100 87 106 2 103 101 100 96 103 103 99 103 104 locs 38 234 96 96 73 104 134 15 48 reps 40 325 120 120 100 135 162 20 52 diff 1 0 4 7 6 21 1 16 1 pr & gt ; t . 002 # . 999 . 000 # . 000 # . 104 . 000 # . 435 . 009 # . 677__________________________________________________________________________ drp glf nlf slf gos stw ant hd ear spt blt blt wlt wlt rot smt cln % mn abs abs abs abs abs abs abs abs__________________________________________________________________________total sum 1 99 5 . 4 4 . 8 4 . 8 8 . 0 8 . 0 4 . 6 99 . 3 7 . 3 2 101 4 . 2 2 . 7 4 . 5 8 . 0 4 . 5 2 . 9 94 . 4 4 . 8 locs 38 37 8 6 2 2 8 3 2 reps 46 38 15 11 4 2 17 6 4 diff 2 1 . 2 2 . 1 0 . 3 0 . 0 3 . 5 1 . 7 4 . 9 2 . 5 pr & gt ; t . 185 . 000 # . 003 # . 501 . 999 . 090 * . 018 + . 061 * . 000 # __________________________________________________________________________ mdm fus gib eye com sou ecb ecb ecb cpx ers ers spt rst rst dpe 1lf 2sc abs abs abs abs abs abs abs abs abs__________________________________________________________________________total sum 1 5 . 0 3 . 7 5 . 6 6 . 0 6 . 0 5 . 5 98 . 1 3 . 4 5 . 7 2 2 . 9 5 . 7 6 . 0 6 . 0 4 . 0 2 . 5 98 . 0 3 . 5 4 . 8 locs 4 7 2 1 2 2 3 4 22 reps 11 11 5 1 3 4 5 9 29 diff 2 . 1 2 . 0 0 . 4 0 . 0 2 . 0 3 . 0 0 . 1 0 . 1 0 . 9 pr & gt ; t . 004 # . 021 # . 728 . 000 # . 000 # . 941 . 391 . 097 * __________________________________________________________________________ ecb 2it abs__________________________________________________________________________ total sum 1 2 . 4 2 1 . 8 locs 1 reps 3 diff 0 . 6 pr & gt ; t__________________________________________________________________________ *= 10 % sig += 5 % sig #= 1 % sig table 2c__________________________________________________________________________variety # 1 = 3310variety # 2 = 3293__________________________________________________________________________ prm bu bu tst sdg est gdu prm shd acr acr mnst wt vgr cnt shd abs abs abs % mn % mn abs % mn % mn % mn__________________________________________________________________________total sum 1 113 114 171 . 3 104 102 57 . 9 115 101 102 2 113 111 167 . 1 101 101 56 . 2 111 100 98 locs 18 20 95 95 98 76 45 44 29 reps 18 20 110 110 116 89 59 56 31 diff 0 3 4 . 1 2 1 1 . 7 3 2 3 pr & gt ; t . 999 . 000 # . 035 + . 047 + . 280 . 000 # . 399 . 228 . 000 # __________________________________________________________________________ gdu stk plt ear rt sta stk brt grn slk cnt ht ht ldg grn ldg stk app % mn % mn % mn % mn % mn % mn % mn % mn % mn__________________________________________________________________________total sum 1 102 101 105 104 91 133 98 74 101 2 98 100 99 101 88 101 101 88 104 locs 22 121 42 42 31 56 67 5 30 reps 22 161 47 47 36 70 80 7 34 diff 4 1 6 3 3 32 3 14 4 pr & gt ; t . 000 # . 348 . 000 # . 006 # . 467 . 000 # . 110 . 074 * . 249__________________________________________________________________________ drp glf nlf slf gos stw ant hd ear spt blt blt wlt wlt rot smt cln % mn abs abs abs abs abs abs abs abs__________________________________________________________________________total sum 1 99 5 . 5 4 . 6 5 . 0 8 . 0 8 . 0 4 . 6 99 . 3 7 . 3 2 98 3 . 7 5 . 4 5 . 5 8 . 3 6 . 5 4 . 8 100 . 0 3 . 8 locs 26 26 6 5 2 2 8 3 2 reps 33 36 12 10 4 2 17 6 4 diff 0 1 . 8 0 . 8 0 . 5 0 . 3 1 . 5 0 . 1 0 . 7 3 . 5 pr & gt ; t . 999 . 011 + . 351 . 500 . 205 . 869 . 423 . 090 * __________________________________________________________________________ mdm fus gib com sou ecb ecb ecb ecb cpx ers ers rst rst dpe 1lf 2sc 2it abs abs abs abs abs abs abs abs abs__________________________________________________________________________total sum 1 5 . 3 3 . 4 8 . 6 6 . 0 5 . 5 100 . 0 3 . 4 5 . 1 2 . 4 2 2 . 4 4 . 2 7 . 2 6 . 0 2 . 5 96 . 7 3 . 1 4 . 6 3 . 0 locs 2 6 2 1 2 1 4 2 1 reps 7 9 5 2 4 3 9 5 3 diff 2 . 8 0 . 8 1 . 6 0 . 0 3 . 0 3 . 3 0 . 3 0 . 5 0 . 6 pr & gt ; t . 037 + . 370 . 382 . 000 # . 391 . 500__________________________________________________________________________ *= 10 % sig += 5 % sig #= 13 % sig comparison data was collected from strip tests that were grown by farmers . each hybrid was grown in strips of 4 , 6 , 8 , 12 , etc . rows in fields depending on the size of the planter used . the data was collected from strip tests that had the hybrids in the same area and weighed . the moisture percentage was determined and bushels per acre was adjusted to 15 . 5 percent moisture . the number of comparisons represent the number of locations or replications for the two hybrids that were grown in the same field in close proximity and compared . comparison strip testing was done between pioneer brand hybrid 3310 and pioneer brand hybrids 3293 , 3245 and 3223 . the comparisons come from all the hybrid &# 39 ; s adapted growing areas in the u . s . these results are presented in table 3 . hybrid 3310 has a 9 . 0 bushel per acre yield advantage and a $ 22 . 96 per acre income advantage over hybrid 3293 . hybrid 3310 has a 1 . 9 pound per bushel test weight advantage and a 0 . 5 percentage point moisture advantage over hybrid 3293 . hybrid 3310 has a 1 . 7 pound per bushel test weight advantage and a 0 . 9 percentage point moisture advantage over hybrid 3223 . hybrid 3310 also has a weighted average 0 . 5 percentage point moisture advantage over the other hybrids and a weighted average 1 . 2 pound per bushel test weight advantage over the other hybrids . table 3__________________________________________________________________________1995 performance comparison report for corn1 year summary of all standard test types . income / pop stand roots testpioneer 3310 151 . 8 21 . 3 361 . 50 24 . 3 90 97 57 . 2pioneer 3293 142 . 8 21 . 8 338 . 54 24 . 8 92 95 55 . 3advantage 9 . 0 0 . 5 22 . 96 0 . 5 - 2 2 1 . 9number of comparisons 71 71 71 40 28 23 59percent wins 74 73 76 47 39 30 89probability of difference 99 99 99 78 76 97 99pioneer 3310 146 . 7 17 . 5 360 . 42 23 . 4 95 100 58 . 8pioneer 3245 150 . 2 17 . 4 369 . 04 22 . 7 98 100 59 . 0advantage - 3 . 5 - 0 . 1 - 8 . 62 0 . 7 - 3 0 - 0 . 2number of comparisons 119 119 119 77 74 45 100percent wins 41 45 41 63 16 6 30probability of difference 98 68 98 98 99 8 82pioneer 3310 147 . 0 18 . 9 357 . 06 24 . 0 95 100 58 . 3pioneer 3223 147 . 2 19 . 8 355 . 19 24 . 1 94 100 56 . 6advantage - 0 . 2 0 . 9 1 . 87 - 0 . 1 1 0 1 . 7number of comparisons 203 203 203 112 98 67 173percent wins 51 809 53 41 24 7 85probability of difference 12 99 53 41 16 21 99pioneer 3310 147 . 8 18 . 9 358 . 88 24 . 0 94 99 58 . 3weighted avg 147 . 3 19 . 4 356 . 38 23 . 8 95 99 57 . 1advantage 0 . 5 0 . 5 2 . 50 0 . 2 - 1 0 1 . 2number of comparisons 393 393 393 229 200 135 332percent wins 52 68 53 49 23 11 69probability of difference 47 99 80 86 89 85 99__________________________________________________________________________ note : the probability values are useful in analyzing if there is a &# 34 ; real &# 34 ; difference in the genetic potential of the products involved . high values are desirable , with 95 % considered significant for real differences . characteristics of pioneer hybrid 3310 are compared to pioneer hybrids 3293 , 3245 and 3223 in table 4 . the values given for most of the traits are on a 1 - 9 basis . in these cases 9 would be outstanding , while 1 would be poor for the given characteristics . these values are based on performance of a given hybrid relative to other pioneer commercial , precommercial and competitive hybrids that are grown in research strip test trials . these performance based values are determined utilizing several factors such as research data , experience the trained corn researchers had in the field , and the sales experience with the hybrids in strip tests in the field . these values reflect the hybrid &# 39 ; s relative performance to other hybrids for the characteristics listed . table 4 shows hybrid 3310 demonstrates very good early growth and staygreen when compared to other hybrids . in addition , the results show hybrid 3310 demonstrates above average scores for a combination of characteristics including yield , dry down , resistance to stalk lodging , staygreen , drought tolerance , early growth and protein / yield ratio . table 4__________________________________________________________________________hybrid patent comparisons - characteristicspioneer hybrid 3310 vs . pioneer hybrids 3293 , 3245 and 3223__________________________________________________________________________ silk phy gdu gdu h / l / varietycrm crm crm silk phy yld pop pop d / d s / l r / l__________________________________________________________________________3310 113 114 114 1420 2770 8 8 7 6 6 43293 114 111 112 1390 2720 7 8 9 4 8 43245 115 115 114 1440 2770 8 7 8 6 5 43223 116 117 116 1460 2830 9 9 8 6 5 7__________________________________________________________________________sta tst plt ear brtvarietygrn d / t wt e / g ht ht d / e stk pro p / y__________________________________________________________________________3310 8 7 7 8 7 7 2 5 83293 7 7 5 8 5 6 4 3 6 83245 5 5 8 5 6 4 5 6 6 93223 7 8 5 6 8 9 5 3 4 8__________________________________________________________________________ this invention includes hybrid maize seed of 3310 and the hybrid maize plant produced therefrom . the foregoing was set forth by way of example and is not intended to limit the scope of the invention . as used herein , the term plant includes plant cells , plant protoplasts , plant cell tissue cultures from which maize plants can be regenerated , plant calli , plant clumps , and plant cells that are intact in plants , or parts of plants , such as embryos , pollen , ovules , flowers , kernels , ears , cobs , leaves , seeds , husks , stalks , roots , root tips , anthers , silk and the like . duncan , williams , zehr , and widholm , plante , ( 1985 ) 165 : 322 - 332 reflects that 97 % of the plants cultured which produced callus were capable of plant regeneration . subsequent experiments with both inbreds and hybrids produced 91 % regenerable callus which produced plants . in a further study in 1988 , songstad , duncan & amp ; widholm in plant cell reports ( 1988 ), 7 : 262 - 265 reports several media additions which enhance regenerability of callus of two inbred lines . other published reports also indicated that &# 34 ; nontraditional &# 34 ; tissues are capable of producing somatic embryogenesis and plant regeneration . k . p . rao , et al ., maize genetics cooperation newsletter , 60 : 64 - 65 ( 1986 ), refers to somatic embryogenesis from glume callus cultures and b . v . conger , et al ., plant cell reports , 6 : 345 - 347 ( 1987 ) indicates somatic embryogenesis from the tissue cultures of maize leaf segments . thus , it is clear from the literature that the state of the art is such that these methods of obtaining plants are , and were , &# 34 ; conventional &# 34 ; in the sense that they are routinely used and have a very high rate of success . tissue culture of maize is described in european patent application , publication 160 , 390 , incorporated herein by reference . maize tissue culture procedures are also described in green and rhodes , &# 34 ; plant regeneration in tissue culture of maize ,&# 34 ; maize for biological research ( plant molecular biology association , charlottesville , va . 1982 , at 367 - 372 ) and in duncan , et al ., &# 34 ; the production of callus capable of plant regeneration from immature embryos of numerous zea mays geneotypes ,&# 34 ; 165 plante 322 - 332 ( 1985 ). thus , another aspect of this invention is to provide cells which upon growth and differentiation produce maize plants having the genotype of 3310 . maize is used as human food , livestock feed , and as raw material in industry . the food uses of maize , in addition to human consumption of maize kernels , include both products of dry - and wet - milling industries . maize , including both grain and non - grain portions of the plant , is also used extensively as livestock feed , primarily for beef cattle , dairy cattle , hogs , and poultry . industrial uses of maize include production of ethanol , maize starch in the wet - milling industry and maize flour in the dry - milling industry . the industrial applications of maize starch and flour are based on functional properties , such as viscosity , film formation , adhesive properties , and ability to suspend particles . the maize starch and flour have application in the paper and textile industries . other industrial uses include applications in adhesives , building materials , foundry binders , laundry starches , explosives , oil - well muds , and other mining applications . plant parts other than the grain of maize are also used in industry . stalks and husks are made into paper and wallboard and cobs are used for fuel and to make charcoal . the seed of the hybrid maize plant and various parts of the hybrid maize plant can be utilized for human food , livestock feed , and as a raw material in industry . although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity and understanding , it will be obvious that certain changes and modifications may be practiced within the scope of the invention , as limited only by the scope of the appended claims . applicants have made a deposit of at least 2500 seeds of hybrid maize line 3310 with the american type culture collection ( atcc ), rockville , md . 20852 u . s . a ., atcc deposit no . 209335 . the seeds deposited with the atcc on oct . 6 , 1997 were taken from the deposit maintained by pioneer hi - bred international , inc ., 700 capital square , 400 locust street , des moines , iowa 50809 - 2340 since prior to the filing data of this application . this deposit of the hybrid maize line 3310 will be maintained in the atcc depositor , which is a public depository , for a period of 30 years , or 5 years after the most recent request , or for the enforceable life of the patent , whichever is longer , and will be replaced if it becomes nonviable during that period . additionally , applicant has satisfied all the requirements of 37 c . f . r . §§ 1 . 801 - 1 . 809 , including providing an indiction of the viability of the sample . applicant imposes no restrictions on the availability of the deposited material from the atcc ; however , applicant has no autherity to waive any restrictions imposed by law on the transfer of biological material or its transportation in commerce . applicant does not waive any infringement of its rights granted under this patent .

according to the invention , there is provided a hybrid maize plant , designated as 3310 , produced by crossing two pioneer hi - bred international , inc . proprietary inbred maize lines . this invention relates to the hybrid seed 3310 , the hybrid plant produced from the seed , and variants , routants , and trivial modifications of hybrid 3310 .

preliminarily , it should be noted that terms such as &# 34 ; right &# 34 ; and &# 34 ; left &# 34 ; are made with reference to an observer standing behind the machine and looking in the direction of forward travel . also , various components are described as occurring in pairs while only one of the pair is shown , it to be understood that the unshown component is the same as , or a mirror image of , the one shown . referring now to fig1 there is shown a self - propelled windrower 10 including a main frame 12 comprising a pair of fore - and - aft extending , rearwardly converging , side beams 14 having forward portions joined together by a front cross beam 15 and being joined to right and left , downwardly extending support structures 16 to which are respectively mounted a pair of transversely spaced front drive wheels 18 . a pair of rear support caster wheels 20 are mounted to opposite ends of an axle 22 mounted to a cross member 24 , joining the rear of the side beams 14 , for oscillating about a fore - and - aft pivot axis located centrally between opposite ends of the axle 22 . mounted to and supported above a forward end portion of the main frame 12 at a location inboard of the drive wheels 18 is an operator &# 39 ; s cab 26 containing well - known items ( not shown ) such as a seat , steering wheel , and various switches and control levers for remotely controlling various functions of the windrower . a header or platform 30 is connected , as by a suspension 32 to a forward end of the main frame 12 . the header or platform 30 includes a frame defined in part by an upper rear structural member in the form of a tubular cross beam 34 extending between and having opposite ends fixed to opposite side walls 36 , and in part by a cutterbar support structure 38 also extending transversely between and having opposite ends fixed to lower , middle locations of the side walls 36 . a plurality of skid shoes 39 are positioned along and are fixed to the support structure 38 . the suspension 32 includes a pair of parallel header lift arms 40 having their respective rear ends pivotally attached , as at 42 , to lower locations of the windrower frame support structures 16 , and having their respective forward ends pivotally attached , as at 44 , to the cutterbar support structure 38 . a central stabilizer link 46 has its forward end pivotally attached , as at 48 , to the upper end of a bracket 50 projecting upwardly and slightly rearwardly from a central location along the cross beam 34 of the header frame , and has its rearward end pivotally attached , as at 52 , to the forward end of a bracket 54 fixed to a central location along and projecting forwardly from the windrower main frame front cross beam 15 . a rockshaft 56 extends across the front of and is pivotally mounted to the cross beam 15 . a single - acting lift cylinder 58 has its cylinder end pivotally anchored , as at 60 , to the windrower main frame 12 and has its rod end pivotally attached , as at 62 , to an upper end of a rockshaft input arm 64 fixed to and projecting upwardly from the rockshaft 56 . a pair of rockshaft output arms 66 project forwardly from and are fixed to the rockshaft 56 at respective locations placing the arms 66 in coplanar relationship to the pair of header lift arms 40 . a pair of lift links 68 have respective upper ends pivotally attached , as at 70 , to one of the output arms 66 , and respective lower ends pivotally attached , as at 72 , to a location approximately midway along the length of one of the lift arms 40 . each lift link 68 includes a slot 74 at its pivotal connection 70 which permits the lift arms 40 , and hence , the header or platform 30 , to float vertically when the header has been lowered for mowing operation . provided for counterbalancing or supporting a major portion of the weight of the header or platform 30 , when the latter is in its lowered operating condition , so that only enough weight is supported by the skid shoes 39 to keep the platform on the ground are right - and left - hand suspension float cylinders 76 and 78 ( see fig2 ) having upper ends respectively pivotally attached , as at 80 , to the pair of windrower frame structures 16 , and having lower ends respectively pivotally attached to the header lift arms 40 by the pivotal connections 72 . referring now to fig2 there is shown an electrohydraulic control system 82 for controlling the operation of the header lift cylinder 58 and header suspension float cylinders 76 and 78 and for warning an operator of unacceptably low pressure in a float pressure circuit containing the float cylinders when the header 30 is lowered for cutting operation . specifically , provided for controlling the flow of pressure fluid to a rod end port 86 of the single - acting lift cylinder 58 so as to cause the cylinder to contract and lift the platform 30 is a solenoid - operated , two - position lift valve 88 ; and provided for controlling the exhaust of fluid from the cylinder 58 so as to permit the platform 30 to gravitate to its working position is a solenoid - operated , two - position lower valve 90 . pressure fluid is supplied by an engine - driven pump 92 having an inlet coupled to a sump 94 and an outlet coupled , as by a branched conduit 96 , to an inlet port of the lift valve 88 , an outlet port of the valve 88 being connected to the cylinder port 86 by a branched conduit 98 . the branched conduit 98 also connects the cylinder port 86 to an inlet port of the lower valve 90 , the valve 90 having an outlet port connected to the sump 94 by a branched return conduit 99 . the lift valve 88 includes a spring 100 which acts to bias the valve to an &# 34 ; off &# 34 ; position wherein a check valve 102 blocks the flow of pressure fluid from the pump 92 to the lift cylinder 58 , as shown . the valve 88 occupies its &# 34 ; off &# 34 ; position anytime that a solenoid 104 of the valve is de - energized , energization of the solenoid 104 causing the valve to be shifted to its &# 34 ; lift &# 34 ; position wherein it couples the pump 92 to the cylinder 58 . the lower valve 90 is somewhat similar to the lift valve 88 in that it includes a spring 106 biasing the valve to an &# 34 ; off &# 34 ; position , as shown , wherein a check valve 108 blocks the exhaust of fluid from the lift cylinder 58 to the sump 94 . the lower valve 90 occupies its &# 34 ; off &# 34 ; position anytime a solenoid 110 of the valve is de - energized , energization of the solenoid 110 causing the valve to be shifted to its &# 34 ; lower &# 34 ; position wherein it couples the lift cylinder 58 to the sump 94 . when the output of the pump 92 is not required for operating any of the functions illustrated in the control circuit 82 , a standby condition of the pump 92 is established wherein the output of the pump is connected to the sump 94 . specifically , a two - position , solenoid operated valve 111 has an inlet port connected to the branched supply line 96 and an outlet port connected to the branched return line 99 with the valve being biased , by a spring 112 , to a normal &# 34 ; off &# 34 ; position wherein it establishes the standby condition of the pump 92 by interconnecting the inlet and outlet ports . the valve 111 includes a solenoid 113 which , when energized , shifts the valve to an &# 34 ; on &# 34 ; position where it blocks communication between its inlet and outlet ports and hence establishes a working condition of the pump . energization of the solenoids 104 and 110 respectively of the lift and lower valves 88 and 90 is controlled by a lift cylinder control switch 114 , preferably in the form of a rocker switch , having a switching element 115 connected , as by a power lead 116 , to a source of electrical power here shown as a battery 118 . the switching element 114 normally occupies an &# 34 ; off &# 34 ; position , as shown , where it is centered between a &# 34 ; lift &# 34 ; contact 120 connected to the solenoid 104 of the lift valve 88 by a &# 34 ; lift &# 34 ; lead 122 , and a &# 34 ; lower &# 34 ; contact 124 connected to the solenoid 110 of the lower valve 90 by a &# 34 ; lower &# 34 ; lead 126 . a lead 127 is connected between the &# 34 ; lift &# 34 ; lead 122 and the solenoid 113 thereby energizing the latter to shift the valve 111 to its &# 34 ; on &# 34 ; position so as to place the pump 92 in its working condition whenever the switching element 115 of lift cylinder control switch 114 is rocked into engagement with the &# 34 ; lift &# 34 ; contact 120 . when the header 30 is lowered for mowing operation , it is necessary for the solenoid 110 of the lower valve 90 to remain energized , and hence , for the valve 90 to remain in its &# 34 ; lower &# 34 ; position so that a fluid path is established for letting fluid to escape from and enter the cylinder 58 as the header 30 moves up and down in response to the skid shoes 39 passing over undulations of the terrain . to free the operator from the need to keep the switch 114 rocked to engage the element 115 with the &# 34 ; lower &# 34 ; contact 124 , a latching relay switch 128 is provided which has a relay coil 130 coupled to the &# 34 ; lower &# 34 ; lead 126 by a coil lead 132 , and has a normally &# 34 ; off &# 34 ; switching element 134 which is moved to engage a &# 34 ; latch &# 34 ; contact 136 when the coil 130 is energized . the switching element 134 is connected to the power lead 116 by way of an unlatching relay switch 138 having a switching element 140 coupled , by a lead 141 , to the power lead 116 and normally engaged with a power contact 142 that is connected , as by a lead 144 , to the switching element 134 of the latching relay switch 128 . the unlatching relay switch 138 includes a coil 146 connected to the &# 34 ; lift &# 34 ; lead 122 by a coil lead 148 containing a diode 150 for permitting current flow in the direction of the coil 146 from the &# 34 ; lift &# 34 ; lead 122 . thus , it will be seen that once the operator momentarily actuates the lift cylinder control switch 114 so as to energize the &# 34 ; lower &# 34 ; lead 126 , the latching relay switch 128 will act to establish an alternate current path to the lead 126 and this path will remain completed until such time that the operator momentarily actuates the lift cylinder control switch 114 to energize the &# 34 ; lift &# 34 ; lead 122 thereby energizing the unlatching relay switch coil 146 resulting in the switching element 140 moving to its &# 34 ; open &# 34 ; position to open the circuit leading to the latching switch relay coil 130 so that the latching relay switching element 134 is released to move to its &# 34 ; off &# 34 ; position . a safety interlock is provided for preventing the header 30 from being inadvertently lowered when the windrower 10 is traveling on a road . specifically , a &# 34 ; road &# 34 ;/&# 34 ; field &# 34 ; condition relay switch 151 has a switching element 152 connected to the power lead 116 by a lead 153 and normally engaged with a contact 154 to which a branched lead 155 is connected . connected in parallel with each other and to the lead 155 are a &# 34 ; road &# 34 ; condition indicator light 156 and the coil 146 of the unlatching relay switch 138 , with a diode 157 being located in the lead 155 for preventing current from flowing from the lead 148 in the direction of the light 156 . thus , the safety interlock is normally in a default condition wherein the light 156 and coil 146 are energized resulting in the light being lit and the circuit through the relay switch 138 to the switching element 134 of the latching relay 128 being open . momentary actuation of the lift control switch 114 to energize the &# 34 ; lower &# 34 ; lead 126 will only momentarily energize solenoid 110 of the &# 34 ; lower &# 34 ; valve 90 resulting in very little lowering of the platform 30 . the relay switch 151 further includes a relay coil 158 having one end connected to a switching element 159 of a manually operated &# 34 ; road &# 34 ;/&# 34 ; field &# 34 ; condition selection switch 160 , the switching element 159 being movable between a &# 34 ; road &# 34 ; contact 159 , which opens the circuit containing the relay coil 158 , and a &# 34 ; field &# 34 ; contact 161 which establishes a ground connection for the circuit containing the relay coil 158 . connected between the power lead 116 and the coil 158 for providing a source of current for energizing the coil is a &# 34 ; neutral &# 34 ; signal lead 162 containing a &# 34 ; neutral &# 34 ; switch 163 having a normally open switching element 164 that is moved to a closed position when the speed / direction control lever ( not shown ) for the windrower hydrostatic transmission is shifted to &# 34 ; neutral &# 34 ;. thus , energization of the coil 158 to permit normal field operation requires the switching element 159 to be moved into engagement with the &# 34 ; field &# 34 ; contact 161 and the hydrostatic transmission control lever to be placed in its &# 34 ; neutral &# 34 ; position . energization of the coil 158 causes the switching element 152 to be moved into engagement with a contact connected to a ground speed control valve lead 165 that is connected to the coil 158 to cause it to latch the switching element 152 in place so as to ensure that the coil 158 remains energized even though the transmission control lever is moved from its &# 34 ; neutral &# 34 ; position resulting in the opening of the switch 163 . diodes 166 and 167 , respectively , are provided in the leads 162 and 165 for preventing current from flowing from the lead 165 to the lead 162 and vice - versa . a supply of fluid pressure for the float cylinders 76 and 78 is provided by a gas - over - oil accumulator 168 having its fluid reservoir coupled , as by a branched conduit 169 , to rod end ports 170 and 171 , respectively , of the cylinders 76 and 78 , the float cylinders 76 and 78 , the accumulator 168 and the branched conduit 169 cooperating to define a closed float pressure circuit . pressure in the float pressure circuit may be adjusted in order to enhance float characteristics for different crop or terrain conditions , for headers or platforms of different weights and / or for making up for leakage or inadvertent discharge of fluid from the circuit . used in adjusting the pressure are two - position , solenoid - operated , float pressure increase and decrease valves 172 and 173 , respectively . the valve 172 has pump and sump ports 174 and 175 , respectively , coupled to the pump 92 and sump 94 by the branched conduits 96 and 99 , and has a connecting port 176 coupled in fluid communication with a connecting port 177 of the float pressure decrease valve 173 by a connecting conduit 178 . the float pressure decrease valve 173 has a control port 179 coupled to the branched conduit 169 so as to be in fluid communication with the accumulator 168 . the float pressure increase and decrease valves 172 and 173 are illustrated in respective &# 34 ; off &# 34 ; positions , as shown , to which they are biased by their respective springs 180 and 181 in the absence of power being connected to their respective solenoids 182 and 183 . when in their respective &# 34 ; off &# 34 ; positions , pressure fluid delivered by the pump 92 is blocked at the pump port 174 of the float pressure increase valve 172 while pressure fluid , as established by the accumulator 168 , is prevented from flowing to the sump 94 by a check valve 184 contained in the float pressure decrease valve 173 . energization of the solenoid 182 of the float pressure increase valve 172 results in the valve shifting to its &# 34 ; increase &# 34 ; position wherein the pump 92 is connected to the connecting conduit 178 , by way of the pump port 174 and connecting port 176 , with fluid pressure in the connecting conduit 178 unseating the check valve 184 so as to permit fluid to flow to the accumulator 168 by way of the branched conduit 169 . on the other hand , energization of the solenoid 183 of the float pressure decrease valve 173 will result in the valve 173 shifting to its &# 34 ; decrease &# 34 ; position wherein it connects the accumulator 168 to the sump 94 by way of the branched conduit 169 , connecting conduit 178 and branched return conduit 99 . a float pressure control switch 186 , preferably in the form of a rocker switch , is provided for selectively actuating the solenoids of the float pressure increase and decrease valves 172 and 173 , respectively , and for that purpose includes a switching element 188 connected to the power lead 116 and normally located in an &# 34 ; off &# 34 ; position between an &# 34 ; increase &# 34 ; contact 190 , connected , as by an &# 34 ; increase &# 34 ; lead 192 , to the solenoid 182 of the float pressure increase valve 172 , and a &# 34 ; decrease &# 34 ; contact 194 connected , as by a &# 34 ; decrease &# 34 ; lead 196 , to the solenoid 183 of the float pressure decrease valve 173 . because the pump 92 supplies the pressure fluid for increasing the float pressure , a lead 197 is connected between the &# 34 ; increase &# 34 ; lead 192 and the lead 127 connected between the &# 34 ; lift &# 34 ; lead 122 and the solenoid 113 of the valve 111 . thus , when the &# 34 ; increase &# 34 ; lead 192 is energized , the solenoid 113 is energized to shift the valve 111 to establish the working condition in the pump 92 . diodes 198 and 199 , respectively , are provided in the leads 127 and 197 for preventing current from flowing from the &# 34 ; increase &# 34 ; lead 192 to the &# 34 ; lift &# 34 ; lead 122 and vice - versa . an operator is kept informed of the fluid pressure contained in the float circuit by a pressure monitoring and display circuit . specifically , a pressure transducer 200 is coupled to the branched conduit 169 , the transducer 200 being of any known type which produces an electrical output representative of the sensed pressure . a programmable microprocessor 201 , preferably contained in a tachometer of a known design having capabilities for monitoring various vehicle and equipment functions , has an input port 202 connected , as by a lead 204 to receive the electrical output signal from the pressure transducer 200 . this signal is processed by the microprocessor and a visual indication of the sensed pressure is displayed at a control panel located in the vehicle cab 26 . operating the windrower 10 when the float pressure is too low to adequately counterbalance the weight of the header or platform 30 can result in premature wear on the skid shoes 39 and / or in mechanical damage to the header or to the suspension components linking the header to the traction unit . accordingly , it is desirable to warn the operator of the presence of such an unacceptably low - pressure condition so that the operator can actuate the float pressure control switch 186 to increase the float pressure or to have the pressure automatically increased with or without warning the operator of the existence of the condition . the disclosed control system both warns the operator and automatically increases the pressure to a desired amount if an undesirable low pressure condition exists . specifically , the microprocessor 201 is preferably embodied in a tachometer of a known design adapted to be programmed , from the face of a display panel at the operator &# 39 ; s station , to contain a minimum pressure setting reflective of the weight of the particular header or platform being used . a branched warning device lead 206 is connected between the power lead 116 and a coil 207 and a switching element 208 of a pressure - increase relay switch 209 , the switching element 208 normally being in an &# 34 ; off &# 34 ; position , as illustrated , and being moved , upon energization of the coil 207 , into engagement with a contact 210 coupled , as by a lead 212 , to the pressure increase lead 192 . connected in the lead 206 in parallel with an input end of the coil 207 and in parallel with each other are an audible warning device 213 , which may be a horn or buzzer , and a light 214 , the lead 206 and output end of the coil 207 ending at an input port 215 of the microprocessor 201 . internally of the microprocessor 201 , the port 215 is connected to a normally open electronic switch 216 , which in turn is connected to a grounded output port 217 . the electronic switch 216 is actuated to complete a circuit to ground in response to receiving a signal indicative of a situation where the sensed float pressure is below the preset minimum pressure . in order to suppress this signal in situations where the sensed pressure falls below the preset minimum pressure as a result of the platform being supported free of the ground by the lift cylinder 58 , a &# 34 ; lower &# 34 ; sensing lead 218 is connected between the &# 34 ; lower &# 34 ; lead 126 and a &# 34 ; lower &# 34 ; signal input port 220 of the microprocessor 201 , the port 220 being connected internally of the microprocessor 201 to a timer 222 that , in turn , is coupled to the electronic switch 216 . when the &# 34 ; lower &# 34 ; signal lead 126 is energized and the sensed float pressure is below the preset minimum pressure , the timer 222 is started , the latter being selected so as to time out in about ten seconds . this time delay has been found adequate to allow the platform 30 to reach the ground ( less than two seconds with the disclosed float suspension linkage ) and the pressure to stabilize after the lift control switch 114 has been actuated to connect the switching element 115 to the &# 34 ; lower &# 34 ; signal lead 126 . a further benefit of the time delay is that , during field operation , sensed pressures of short duration are ignored . if the monitored conditions are unchanged at the end of the timed cycle , a signal is emitted closing the electronic switch 216 , thus completing a circuit through the lead 206 and causing the audible warning device 213 to sound and the light 214 to be lit . it will be appreciated that at the same time that the circuit is completed through the warning devices 213 and 214 , the coil 207 of the relay 209 will be energized to close the switching element 208 so as to establish a current path to the solenoid 182 of the &# 34 ; increase &# 34 ; valve 172 and to the solenoid 113 of the valve 111 . this then results in the pump 92 supplying pressure fluid to the float circuit by way of the valve 172 . when the pressure in the float pressure circuit increases to a value equal to or above the preset minimum pressure programmed into the microprocessor 201 , the signal received by the microprocessor 201 from the transducer 200 will reflect this fact and result in the electronic switch 216 opening to effect the shutting off of the audible warning device 213 and light 216 and the de - energization of the coil 207 so that the switching element 208 of the relay switch 209 returns to its &# 34 ; off &# 34 ; position . the solenoid - operated pump output control valve 111 and float pressure increase valve 172 will then be de - energized , resulting in the output of the pump 92 being directed to the sump 94 to establish the standby condition in the pump simultaneously with the output of the pump being blocked from fluid communication with the float pressure circuit . for various reasons it may not be desired that pressure be increased automatically . for example , it may be preferred that an operator be given the opportunity to check the float circuit for defects , such as leaks , once a low pressure warning is received before routing fluid to increase the pressure . the circuit 82 can be modified to permit such operation by merely removing the relay switch 209 from the circuit . the operator would then manually operate the pressure control switch 186 to add pressure if desired . further , if desired , the timer 222 and &# 34 ; lower &# 34 ; signal sensing lead 218 could be omitted with sensing of the header condition being done with a normally open header position sensing switch 224 ( see fig3 ) located in the warning device power lead 206 that is connected to the input port 215 of the microprocessor 201 . the switch 224 has a switching element 226 located for being engaged and moved to its closed position by a component of the suspension linkage , here shown as the rockshaft input arm 64 , at a position in its movement corresponding to the header 30 being located in a working position . the microprocessor 201 would then operate to compare the sensed float pressure with the minimum pressure setting pre - programmed into the microprocessor and to close the electronic switch 216 only in the event the sensed pressure is below the programmed minimum pressure setting and the header position - sensing switch 226 is closed , the warning devices 213 and 214 then , and only then , being energized . in any event , completion of the circuit through the lead 206 establishes , by way of the relay switch 209 , an alternate route for current to pass to the &# 34 ; increase &# 34 ; signal lead 192 resulting in the energization of the solenoid 182 of the increase valve 172 causing the latter to shift to connect the pump 92 to the float pressure circuit conduit 169 . the pressure in the float circuit will then increase until such time that the pressure sensed by the transducer 200 results in a signal being sent to the microprocessor which is representative of a pressure equal to or greater than the preselected minimum pressure setting programmed into the microprocessor 201 . the electronic switch 216 will then be caused to open in response to this new pressure so as to discontinue the flow of electrical current through the lead 206 and , hence , to the &# 34 ; increase &# 34 ; signal lead 192 by way of the relay switch 209 . this being the case , the &# 34 ; increase &# 34 ; valve solenoid 182 will become de - energized resulting in the valve 172 shifting back to its &# 34 ; off &# 34 ; position . if desired , the relay switch 209 could be omitted , in which case , the operator , having noticed the energization of the warning devices 213 and 214 , would operate the float pressure control switch 186 to effect actuation of the &# 34 ; increase &# 34 ; valve solenoid 182 , the operator holding the switch 186 in place until the warning devices 213 and 214 are no longer energized which indicates that the float pressure has been increased to a value equal to or greater than the preset minimum value .

an agricultural implement includes a header or platform suspended from a main frame by a suspension permitting movement of the header between a lowered working position and a raised transport position . the suspension includes single - acting float cylinders and a single - acting lift cylinder controlled by an electrohydraulic control system including a programmable microprocessor in which a signal representative of a minimum acceptable float pressure may be set . the microprocessor contains an electronic switch that couples a warning device lead to ground to effect energization of the warning device in response to the microprocessor receiving an electronic signal representative of a float circuit pressure below the minimum acceptable float pressure . in one embodiment , the microprocessor contains a timing device which is triggered whenever a control switch is connected to energize a &# 34 ; lower &# 34 ; signal lead the timing device being set to time out when sufficient time has elapsed to ensure that the header has reached its working position . the timing device works to suppress the signal representative of the float circuit pressure so that a premature energization of the warning device does not occur when a low float pressure is due to the header being elevated from the ground . in another embodiment , a normally open mechanical switch is connected in series with the electronic switch and is closed only when the header reaches its working position . replenishing of float pressure to a desirable level may be done either manually or automatically once the low pressure warning device has been energized .

accordingly , the present invention relates to the use of laminin peptides for the treatment of systemic lupus erythematosus . the present invention is based on the observation that the r38 peptide , which is a peptide derived from the c - terminal region of the mouse laminin ∝ chain , is recognized by pathogenic lupus antibodies and may therefore possess therapeutic potential in the treatment of sle by competing in the binding to the lupus antibodies . furthermore , the present invention relates to the use of a mixture of at least two or more different peptides derived from laminin for the treatment of systemic lupus erythematosus . in a preferred embodiment , at least one of the peptide is r38 or an analog thererof . the present invention also provides methods of treating a subject having sle by the extracorporeal removal of lupus antibodies ( anti - r38 and derivatives thereof ) from a subject &# 39 ; s plasma and returning the plasma to the subject . in one embodiment , the antibodies are removed by column chromatography wherein at least one type of peptide is adsorbed to the column . in a further embodiment , the column is adsorbed with two or more types of peptides . in another embodiment , the peptide is selected from the group consisting of seq . id . no . 1 - 22 . in a further embodiment , the peptide has seq . id . no . 1 . in yet another embodiment , the peptide has seq . id . no . 10 . in one embodiment , the column is a nhs - activated sepharose ™ high performance column . the invention also relates to a method of monitoring disease activity of patients suffering from sle , comprising detecting the ability of the antibodies in the urine to bind to the r38 component of the laminin . this binding can have a direct correlation to disease activity evaluated by a combination of various laboratory parameters . an increase in the amount of antibodies binding to r38 may indicate an approaching active phase of sle and a declining level of antibodies may indicate an approaching remission . therefore , this method provides an assay for detecting changes in the level of laminin - specific antibodies and may enable the initiation of therapy prior to the onset of an active phase of the disease . this method also provides an easy assay that can be used by the patients themselves as it is performed using urine and does not require venipuncture . it may be used as a diagnostic assay , a routine assay for evaluation of sle disease activity , for early identification of disease exacerbation and for early therapeutic intervention in lupus nephritis . the r38 peptide or analogs , fragment or derivatives thereof may be used in such an assay using the methods described in ep 670 , 495 . thus , the r38 peptide may be bound to a solid phase and incubated with the urine from a patient . if the patient is suspected of suffering from sle , suffering from sle or is approaching an active phase of the disease , the level of r38 - binding antibodies in the urine will increase . detection of r38 - binding antibodies maybe undertaken by any method known by one skilled in the art . examples of such methods of detection include elisa and variations thereon , chemiluminescent techniques , etc . the actual method of detection is not crucial to the success of the assay . the level of r38 - binding antibodies observed may then be compared to values observed in a control group . the control group may consist of healthy volunteers , or the patient may act as an internal control i . e ., the observed value is compared to an earlier value from the same patient . in this manner , a profile of the patient &# 39 ; s disease state may be complied and uses as an indicator of further active phases or remission states of the disease . pharmaceutically acceptable salts of the r38 peptide include both salts of the carboxy groups and the acid addition salts of the amino groups of the peptide molecule . salts of the carboxy groups may be formed by methods known in the art and include inorganic salts such as sodium , calcium , ammonium , ferric or zinc salts and the like and salts with organic bases such as those formed with amines such as triethanolamine , arginine or lysine , piperidine , procaine and the like . acid addition salts include salts with mineral acids such as hydrochloric acid and sulphuric acid and salts of organic acids such as acetic acid and oxalic acid . the pharmaceutical composition may contain laminin peptides such as the r38 peptide as unique peptides or in polymerized or conjugated forms attached to macromolecular carriers or polymers . the composition may optionally contain pharmaceutically acceptable excipients . in an alternative embodiment , the composition may contain the r38 peptide alone . the route of administration may include oral , intra - venous , intra - peritoneal , intra - muscular , subcutaneous , intra - articular , intra - nasal , intra - thecal , intra - dermal , trans - dermal or by inhalation . an effective dose of the r38 peptide or derivatives thereof for use in treating sle may be from about 1 μg / kg to 100 mg / kg body weight , per single administration , which may be easily determined by one skilled in the art . the dosage may depend upon the age , sex , health and weight of the recipient , kind of concurrent therapy , if any , and frequent of treatment . peptides r26 , r28 , r30 , r31 , r35 , r37 , and r38 ( also referred hereinafter as “ 5100 ” and “ tv 5100 ”) derived from the c - terminal of mouse laminin ∝ chain , and the r18 peptide derived from the n - terminal of mouse laminin ∝ chain were tested . the peptides are 17 - 22 - mer synthetic peptides , and were prepared by the f - moc technique ( carpino , l . a . & amp ; han , g . y . ( 1972 ), j . org . chem ., 37 , 3404 ). these peptides could also be produced by methods well known to one skilled in the art of biotechnology . for example , using a nucleic acid selected from the group including dna , rna , cdna , genomic dna , synthetic dna , mrna , total rna , hnrna , synthetic rna , the desired peptides may be produced in live cell cultures and harvested . the sequences of the peptides are presented in the table 1 . other laminin peptides used for comparative purposes in the examples include as31 ( comprising the residues yigsr ), ac15 and f9 ( other laminin peptides ) and r27 a peptide from the 4th loop of the globular region of the laminin α chain . additional peptides which are fragments of , or analogs closely derived from r38 have been constructed and are presented in table 2 hereinbelow . peptides 5200 and 5101 - 5111 disclosed in table 2 were prepared in the same manner as the peptides of table 1 hereinabove . the table 2 peptides comprise r38 ( 5100 ), human r38 ( 5300 ), fragments of r38 , a fragment 5111 derived from 5300 or analogs of r38 wherein one or more point substitutions were made according to techniques which are well known to one skilled in the art . these peptides were constructed to investigate , among other things , the effect on anti - dna antibody binding activity caused by changing the net charge of the r38 peptide . the c72 murine anti - dna antibody has been derived from ( nzb × nzw ) f1 lupus mice by the hybridoma technique as described in eilat d . et al j . immunol . ( 1991 ) 147 361 - 368 . the monoclonal anti - dna antibodies dil6 and b3 were derived from lupus patients by hybridoma technique as described in ehrenstein m . r . et al j . clin . invest . ( 1994 ) 93 1787 - 1799 and ehrenstein m . r . et al kidney inter . ( 1995 ) 48 705 - 711 . it should be understood that the following description contemplates use of antibodies specific to the laminins and to the peptides disclosed herein . methods for producing peptides specific to the laminin peptides and to r38 and its analogs and derivatives are well known to one skilled in the art . in this regard , specific reference may be had to the text “ antibodies , a laboratory manual ,” ed harlow and david lane , cold spring harbor publishing 1988 , the contents of which are incorporated herein by reference . this reference discloses methods which may be used for obtaining monospecific antibodies , i . e ., monoclonal antibodies and polyclonal antibodies directed against laminin peptides . wells were coated with 10 μg / ml of the peptides , blocked with 1 % bsa ( bovine serum albumin ) in pbs ( ph 7 , 4 ), reacted with appropriately diluted serum or urine samples or monoclonal antibodies , incubated with anti - human or anti - mouse immunoglobulin enzyme conjugated to alkaline phosphatase and detected by addition of substrate ( sigma 100 phosphatase substrate tablets ) and color development using an organon teknika microwell system spectrometer at wavelength of 405 nm . in competitive inhibition assays , the antibodies were incubated with various concentrations of the inhibitor ( for example : peptide , dna , heparin ) or with dnase for 45 minutes at room temperature and the remaining binding was then evaluated by elisa as described heretofore . % inhibition was computed as : o . d .  binding   without   inhibitor - o . d .  binding   with   inhibitor o . d .  binding   without   inhibitor × 100 = %   inhibition a : murine sle antibodies bind to c terminal peptides of laminin α chain . the interaction of the c72 murine anti - dna antibody with laminin peptides was analyzed by elisa as described above . the c72 conditioned medium was diluted in pbs in various dilutions . the results are summarized in fig1 which shows the binding of c72 murine anti - dna antibody to the 5200 , r37 , and r30 peptides , but not to r28 or r18 peptides of the laminin α chain . control murine antibody , the anti - hel hy5 did not bind to the 5200 peptide ( data not shown ). b : inhibition of the binding of c72 to 5200 is inhibited by dna and heparin the binding of c72 to 5200 was tested before and after incubation with 5200 , r38 , r18 , heparin , dna and dnase . the results are summarized in fig2 which shows the inhibition of the binding of c72 to 5200 by the r38 or 5200 peptides of the present invention , by dna and by heparin , but not by a control peptide or treatment with dnase . the percent inhibition is the percent reduction of the o . d . after incubation with the inhibiting agent . analysis of the interaction of mrl / lpr / lpr urine antibodies with the 5200 peptide by a direct binding elisa revealed specific binding . thus , pooled urine from at least 5 mice ( either mrl / lpr / lpr or control mice , e . g . balb / c ) was added to wells coated with r38 ′ ( 5200 ), r18 or dna as described above and bound 5200 assayed by elisa . antigen mice dna 5200 r18 balb / c u . d . u . d . u . d . mrl / lpr / lpr u . d . 0 . 26 (*) u . d . the human monoclonal anti - dna antibodies dil 6 and b3 were derived from lupus patients by the hybridoma technique . as shown in fig3 and 4 these antibodies were found to bind to the 5200 peptide but not to other laminin peptides tested . in fig3 and 4 , the peptides are referred to as denoted above or as follows ; as30 is r27 , as19 is r35 as35 is r26 , as17 is r28 and as6 is r18 . effect of r38 ( 5100 ) & amp ; r38 ′ on the clinical course of murine sle to test whether r38 peptides can affect the course of sle we have tested their effect on mrl / lpr / lpr mice disease . 60 μg of 5200 ( r38 ′ alone or in peptide combinations , 30 μg of each ) in 0 . 1 ml pbs , was injected i . p . to 6 week old female mlr / lpr / lpr mice once a week for 16 week and the mice were evaluated for survival ( fig8 ), and for renal histology . 50 μg of 5100 ( r38 ) or 5300 ( human r38 ) in 0 . 1 ml pbs , was injected i . p . to 6 week old mrl / lpr / lpr mice three times a week and the mice were evaluated for survival ( fig9 ), and for renal histology . control mice received 0 . 1 ml phosphate buffer solution . each test and control group contained 12 - 15 mice . the survival of mrl / lpr / lpr mice treated with 100 , 5200 or 5300 was compared to that of pbs treated mice . as shown in fig8 and 9 , the survival of mice treated with 5100 or 5200 was significantly higher than that of control mice . in fig8 and 9 the time in days shown on the x axis relates to the age of the mice . two mice in each group were sacrificed after 5 months and their kidneys evaluated by light microscopy the kidneys from the control mice showed severe diffuse proliferative glomerulonephritis with crescents and sclerosis whereas the 5100 or 5200 treated mice showed mild proliferative changes with no crescents and no sclerosis . urine from lupus patients with and without renal disease in active and inactive state were collected repeatedly and tested for presence of anti - r38 antibodies by elisa . activity of the disease was evaluated also by accepted clinical and serological parameters ( lockshin m . d . et al am . j . med . ( 1984 ) 77 893 - 898 ) and their correlation with anti - r38 levels was compared . 103 urine samples of 37 sle patients were tested for anti - r38 activity by elisa as described above . 23 of the samples were from patients without renal disease and 80 samples from patients with renal disease . a further 12 samples from patients with renal disease not relates to sle were also included sle present present absent renal disease absent present present no . samples 23 80 12 urine anti - r38 0 . 035 ± 0 . 003 0 . 229 ± 0 . 03 * 0 . 07 ± 0 . 01 o . d . ( mean + s . e .) positivity of the samples in those patients with renal disease usually correlated with active disease according to an activity score that includes 19 clinical and laboratory parameters ( lockshin m . d . et al supra ). these parameters included assessment of the presence / absence / condition of the following clinical criteria alopecia , rash , fever , serositis , athralgia / arthritis , mucosal ulcers , neurological events , malaise , fundi changes , nodes , spleen and the following blood tests including esr ( erytrocyte sedimentation rate ), anti dna antibodies , complement ( u / ml ), creatinine , haemoglobin ( g / dl ), plt platelets (/ mm 2 ) or urinalysis . the assessment of these parameters is measured as described in lockshin supra . the overall percentage given reflects only the assessed parameters . in some patients urine samples were tested in more than one occasion and a good correlation between the clinical activity and the level of anti r38 binding were observed . three representative examples from three different lupus patients are shown in fig5 and 7 where the x - axis shows the no . of the hospital visit and the y - axis , the observed binding ( od at 405 nm ) or percentage of the activity score described above . as can be seen from these figures , the assay using the r38 peptide provides a reliable method of monitoring disease activity . analysis of the correlation between anti - 5200 ( r38 ′) antibodies and disease activity in an additional experiment , 178 urine samples from lupus patients , 24 with and 22 without disease in active and inactive state were collected and tested for presence of anti - 5200 antibodies by elisa as described above . the following results were obtained : renal disease absent present no . samples 46 132 urine anti - 5200 0 . 05 ± 0 . 005 0 . 335 ± 0 . 035 * o . d . ( mean + s . e .) analysis of the correlation between anti - 5100 ( r38 ) antibodies and disease activity 45 urine samples from 21 lupus patients , some with and some without renal disease in active and inactive state were collected and tested for presence of anti - 5100 antibodies by direct elisa as described above . renal disease absent present no . samples 6 39 urine anti - 5100 0 . 058 ± 0 . 006 0 . 376 ± 0 . 05 * o . d . ( mean + s . e .) analysis of the correlation between anti - 5200 ( r38 ′) antibodies and disease activity 52 urine samples from 21 lupus patients , with and without renal disease in active and inactive state were collected and tested for presence of anti - 5200 antibodies by elisa as described above . renal disease absent present no . samples 6 46 urine anti - 5200 0 . 052 ± 0 . 03 0 . 431 ± 0 . 09 o . d . ( mean + s . e .) analysis of the correlation between anti - 5108 , 5101 , 5109 and 5110 — antibodies and disease activity 24 urine samples from some of the lupus patients of examples 7 and 8 , 2 with and 22 without renal disease in active and inactive state were collected and tested for binding to 5108 peptides by elisa as described above . renal disease absent present no . samples 2 22 urine anti - 5108 0 . 064 ± 0 . 05 0 . 672 ± 0 . 1 o . d . ( mean + s . e .) similar results were observed for binding of peptides 5101 , 5109 and 5110 . the peptides of the present invention were tested for their ability to bind directly with c72 murine anti - dna antibodies and b3 human anti - dna antibodies according to the method described hereinabove . the results of the direct binding study are reported in table 3 : a competitive inhibition study compared how each of the peptides competes with r38 ( 5100 ) for binding to the c72 anti - dna antibody . conducted according to the methods described hereinabove , the results of the study are disclosed in table 4 below and are further elucidated by reference to fig1 . the r38 peptide was dissolved in the coupling buffer ( 0 . 2m nahco 3 , 0 . 5m nacl , ph 8 . 3 ) in a concentration of 1 mg / ml in 5 ml coupling buffer . a 5 ml n - hydroxysuccinimide ( nhs )- activated sepharose ™ high performance column ( pharmacia 17 - 0717 - 01 ) is used . the isopropanol in the column was washed out from the column with 30 ml of cold ( 4 ° c .) 1 mm hcl and 5 ml of the peptide solution was then injected onto the column with a syringe ( 2 . 5 ml / minute ). the column was sealed and stood for 30 minutes at room temperature . the column was then washed with 30 ml buffer a ( 0 . 5 m ethanolamine , 0 . 5 m nacl , ph 8 . 3 ) and 30 ml buffer b ( 0 . 5 m acetate , 0 . 5 m nacl , ph 4 ) consecutively three times , and then with neutral ph buffer ( 0 . 05 m na 2 hp0 4 and 0 . 1 % nan 3 ). the column was washed with 15 ml pbs ( phosphate buffered saline ), followed by 15 ml elution buffer ( 0 . 1 m glycine hcl ) and then 50 ml pbs . the c72 antibody or the patients &# 39 ; plasma samples were filtered through a 0 . 45 microm filter . the samples were applied onto the column by a fitted syringe at a rate of 2 . 5 ml / min . the column was then washed with 5 ml pbs and the flow - through was applied to the column again . the binding of the samples ( original and flow - through ) to r38 was tested by the anti - r38 elisa test . in the instant example , the mouse c72 and the sle patients &# 39 ; plasma were applied to the r38 column . their anti - r38 binding was evaluated by elisa in the original samples and in the flow - through of the column . as shown in table 5 , affinity absorption on the column removed 99 % of the anti - r38 activity of the mouse monoclonal c72 and between 30 %- 60 % of the antibodies in the human sle patients &# 39 ; plasma . it should be understood that the foregoing description and examples are merely illustrative and that many modifications and variations may be made thereto by one skilled in art without departing from the scope and spirit of the invention as claimed hereinbelow .

a method is disclosed for treating systemic lupus erythematosus in a mammalian subject , comprising administering to said subject an effective dose of at least one laminin peptide , or an analog or a derivative thereof . in one exemplary embodiment , the laminin peptide is selected from the group consisting of r38 , and claimed r38 analogs and derivatives thereof including 5200 , 5104 , 5105 , 5106 , 5107 , 5108 , 5109 , 5110 . the laminin peptides of the present invention may be prepared by known chemical synthetic methods or by biotechnological methods . the invention also provides assays useful for the diagnosis of and following pathological activity course of systemic lupus erythematosus in patients suffering therefrom . in addition , the subject invention concerns a method of treating systemic lupus erythematosus in a subject comprising the extracorporeal removal of lupus antibodies from the subject &# 39 ; s plasma and returning the plasma to the subject .

to identify the enzyme responsible for activation of latent pdgf - dd , upa was cloned into an expression vector , co - transfected with another expression vector encoding full - length pdgf - d , and determined that released growth factor domain of pdgf - dd migrating as a 21 kda species was found only when latent pdgf - dd and upa were co expressed . cloning of urokinase plasminogen activator ( upa ): total cellular rna from ag1523 fibroblastic cells was prepared using the guanidinium thiocyanate / acid phenol method . single - stranded cdna was synthesized using amv reverse transcriptase ( amersham ) and oligo - dt to prime the reaction . oligonucleotides flanking the 1293 bp coding sequence of upa were used under standard pcr reactions with cdna from the fibroblastic cell line ag1523 cells as template . hindiii / xhoi digested product was cloned into the eukaryotic expression vector pcdna3 . 1 / zeo (+) ( invitrogen ) and the construct was verified by nucleotide sequencing . all primers used were purchased from invitrogen . forward primer ( including a hindiii site for in - frame cloning ) was 5 ′- gta gaa gct tga cct cgc cac cat gag ag ( seq id no : 1 ) and reverse primer was 5 ′- gta got cga gtt aca gat cct ctt ctg aga tga gtt ttt gtt cga ggg cca ggc cat tct ctt c ( seq id no : 2 ) ( including an xhoiii site for in - frame cloning and a myc - tag for detection ). in vitro processing of pdgf - dd . to explore the proteolytic activity of upa on full - length pdgf - dd , the expression vector for upa was cotransfected ( lipofectamine plus , invitrogen ) with an expression vector encoding full - length pdgf - d in cos - 1 cells as previously outlined for the analysis of tpa - mediated activation of pdgf - cc . following the incubation in serum free medium , aliquots were subjected to tca - precipitation , and precipitated proteins were analyzed by sds - page under reducing conditions . immunoblotting with rabbit polyclonal antibodies against human pdgf - d was used to detect pdgf - d species ( fredriksson , l ., li , ii ., fieber , c ., li , x ., and eriksson , u . ( 2004 ) embo j . 23 , 3793 - 3802 ; see also bergeten et al ., 2001 , supra ). donkey anti - rabbit igg - hrp linked whole antibody ( amersham biosciences ) was used as secondary antibody . the membranes were subsequently stripped and reprobed with goat anti - human upa igg ( american diagnostica inc .) in order to confirm the presence of upa . donkey anti - goat igg - hrp ( sc - 2020 , santa cruz biotechnology ) was used as secondary antibody . it is known that tpa activates latent pdgf - cc ( fredriksson et al . ( 2004 ) embo j . 23 , 3793 - 3802 ). pdgf - cc and pdgf - dd share structural similarities , and upa also has certain structural similarities to tpa ( fig1 ). the ability of upa to activate latent pdgf - dd was investigated using a co - transfection assay similar to the assay previously developed to explore the activation of pdgf - cc using tpa ( see e . g . u . s . patent application ser . no . 10 / 971 , 705 ). sds - page analysis of pdgf - dd , co - expressed with upa , revealed that a significant portion of the factor was activated since the released growth factor domain was observed as a distinct 21 kda species ( fig2 ). in supernatants from cells expressing latent pdgf - dd , but not co - expressing upa , a released 21 kda growth factor domain of pdgf - dd was not present . these data show that upa is able to activate latent pdgf - dd . given the similar domain structures of the two substrates ( pdgf - cc and pdgf - dd ) and the two proteases , respectively , the mechanisms of activation of pdgf - cc and pdgf - dd may be very similar . this suggestion was verified using several chimeric pdgf - c / pdgf - d molecules . for the details of how these chimeric factors were generated , see attachment 1 ( fredriksson et al 2005 , j . bio . chem .). the results showed that upa required both the cub domain and the growth factor domains from pdgf - d to efficiently cleave the substrate ( fig2 ). upa is found to be specific for pdgf - dd while tpa is specific for pdgf - cc . the foregoing description and examples have been set forth merely to illustrate the invention and are not intended to be limiting . since modifications of the disclosed embodiments incorporating the spirit and substance of the invention may occur to persons skilled in the art , the invention should be construed broadly to include all variations falling within the scope of the appended claims and equivalents thereof . all references cited hereinabove and / or listed below are hereby expressly incorporated by reference . aase k , abramsson a , karlsson l , betsholtz c , eriksson u ( 2002 ) expression analysis of pdgf - 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( 1998 ) tissue plasminogen activator ( tpa ) increases neuronal damage after focal cerebral ischemia in wild - type and tpa - deficient mice . nat med , 4 , 228 - 231 . wu y p , siao c j , lu w , sung t c , frohman m a , milev p , bugge t h , degen j l , levine j m , margolis r u , tsirka s e ( 2000 ) the tissue plasminogen activator ( tpa )/ plasmin extracellular proteolytic system regulates seizure - induced hippocampal mossy fiber outgrowth through a proteoglycan substrate . j cell biol 148 : 1295 - 1304 . yepes m , sandkvist m , coleman t a , moore e , wu j y , mitola d , bugge t h , lawrence d a ( 2002 ) regulation of seizure spreading by neuroserpin and tissue - type plasminogen activator is plasminogen - independent . j clin invest 109 : 1571 - 1578 . yepes m , sandkvist m , moore e g , bugge t h , strickland d k , lawrence d a ( 2003 ) tissue - type plasminogen activator induces opening of the blood - brain barrier via the ldl receptor - related protein . j clin invest 112 : 1533 - 1540 . zwerner j p , may w a ( 2001 ) pdgf - c is an ews / fli induced transforming growth factor in ewing family tumors . oncogene 20 : 626 - 633 .

methods for inhibiting angiogenesis comprising administering urokinase plasminogen activator inhibitors , and pharmaceutical compositions suitable for the methods comprising the upa inhibitors . also provided are methods for stimulating angiogenesis comprising administering upa or an agonist thereof to a patient in need thereof , and pharmaceutical compositions comprising an effective amount of upa or an agonist thereof for the methods of stimulation . the present invention discloses that upa is a specific pdgf - d activatin rotease .

the present invention relates generally to improvements in blood flow detection due to the improved contact and possibility of improved contact between the various detection sensors and the living tissue mucosa under investigation . referring to the drawings , like numbers indicate like parts throughout the views as used in the description herein , the meaning of “ a ” “ an ,” and “ the ” includes plural reference unless the context clearly dictates otherwise . also , as used in the description herein , the meaning of “ in ” includes both “ in ” and “ on ” unless the context clearly dictates otherwise . also , as used in the description herein , the meanings of “ and ” and “ or ” include both the conjunctive and disjunctive and may be used interchangeably unless the context clearly dictates otherwise . fig1 depicts a schematic diagram of blood detection system 100 containing three detection sensors . however , as will be appreciated by those skilled in the art , the number of detection sensors or windows is not limited to three . light source 1 is in contact with single fiber rod 2 . the light emanating from light source 1 is focused on the end face of single fiber rod 2 . due to the internal configuration of single fiber rod 2 , the beams of light are repeatedly reflected off the inner walls of the single fiber &# 39 ; s core resulting in a light source of uniform intensity , i . e ., collimated light . single fiber rod 2 is further in contact with fiber bundle 3 . fiber bundle 3 is made up of the independent illumination fibers 3 a , 3 b , 3 c , . . . 3 n . the transmitted light is communicated on the respective illumination fibers 3 a to 3 n to measurement units 12 a to 12 n . in each measurement unit 12 a to 12 n , the transmitted light passes through a series of polarizers , lenses and prisms before exiting . the exiting light illuminates the areas of living tissue under examination . interacted light from the illuminated tissue mucosa is correspondingly detected by the measuring units 12 a to 12 n . in each measurement unit 12 a to 12 n , received interacted light passes through the measurement unit prism , lens , and polarizer as seen in fig3 and is transmitted via collectors 7 a and 7 b back to spectroscope 9 for analysis . fig2 depicts a block diagram of an exemplary configuration of the system 100 of fig1 . referring to fig2 , the exemplary system seen in fig2 contains light source 1 for generating light of sufficient intensity and frequency to illuminate the tissue under investigation so as to ascertain the blood content within the illuminated tissue mucosa . single fiber rod 2 may be , for example , a fiber optic conductor containing a optical core or similarly designed to equalize and collimate the light emitted from light source 1 to ensure uniform intensity and frequency of the light entering the illumination fibers . illuminator fibers 3 a - 3 n are individual optical transmission lines that convey the light from single fiber rod 2 to the measurement units 12 a - 12 n . light source 1 may be , for example , a xenon lamp , a halogen , lamp , an led , or any other light source capable of providing a light of adequate intensity and frequency . in addition to light source 1 , measurement units 12 a - 12 n further includes polarizer 4 , lens 5 , prism 6 and measurement window 15 . polarizer 4 is a linear polarizer designed to ensue that the transmitted light waves are aligned in a linear fashion , i . e ., horizontally or vertically . lens 5 is an optical lens that conveys light waves in a parallel orientation . light waves exit lens 5 in a generally parallel direction and strike the surface of prism 6 . prism 6 is a optical prism with a coated reflective surface . light waves striking the surface of prism 6 are orthogonally reflected through measurement window 15 into the underlying living tissue . measurement window 15 is an optical window typically , glass or other transmissive material in the detection wavelength range , that does not adversely interact with or attenuate transmitted or reflected light waves . light that interacts with or is reflected off of the underlying tissue is conveyed through window 15 back through prism 6 , lens 5 and polarizer 4 onto collectors 7 a and 7 b . optical fibers 7 a and 7 b each convey the reflected light back to spectroscope processing unit ( spectroscope ) 9 . it should be noted that as a result of the placement of optical collectors 7 a and 7 b with respect to polarizer 4 , optical fibers 7 a and 7 b convey either horizontally or vertically polarized light waves back to spectroscope 9 . fibers 7 a and 7 b enter spectroscope 9 at slot 8 and convey there respective blood content data to the data receiver located in spectroscope 9 . an exemplary detailed operation of the system 100 is now described with respect to a single measurement unit 12 a with regard to fig1 and 2 . however , it shall be understood that this operation may be carried out simultaneously or otherwise by the measurement units 12 a - 12 n depicted in fig1 . referring to fig2 , light emitted from light source 1 passes through single fiber rod 2 to reach the individual optical fibers 3 . as light emanating from light source 1 passes through single fiber rod 2 , the rod 2 equalizes and collimates the intensity and wavelength of the light emitted from light source 1 and guides the equalized and collimated light into the individual illuminator fibers 3 a to 3 n . once the collimated light enters a single fiber 3 a to 3 n it is communicated to the individual measurement units 12 a to 12 n . each measurement unit 12 a to 12 n is comprised of a illuminator fiber , a polarizer unit 4 , a lens 5 , a prism 6 , and window 15 . the transmitted light exits the measurement unit 12 a via window 15 and illuminates a region of tissue within the living body . certain light interacted with the illuminated tissue is reflected back and collected by the corresponding measurement unit 12 a to 12 n through its corresponding window 15 and passes back through prism 6 , lens 5 , and polarizer unit 4 to the collector fibers 7 a and 7 b . each measurement unit 12 a to 12 n has two optical receiving or collector fibers 7 a and 7 b that direct the received or collected interacted light to pass - through slit 8 in spectroscope 9 for analysis . as an alternative to the receiving fibers 7 a and 7 b of measurement units 12 a to 12 n , directly entering spectroscope processing unit 9 via a slit 8 , a lens may be provided between receiving fibers 7 a and 7 b and the slit 8 for an improved and more efficient light transmission . an exemplary configuration for such a lens is cylindrical . however , alternative shapes or other configurations may be employed in accordance with the invention . as depicted in and later described with respect to fig1 , individual fibers 3 a to 3 n may have a diameter as small as , for example , 100 μm , resulting in a fiber bundle 3 in fig1 as small as 1 mm . in this example , the diameter of a single fiber should likewise be of sufficient size to receive light emitted from light source 1 to produce light emitted from the various windows of a desired intensity . in order to maintain each fiber bundle 3 a - 3 n of sufficiently small size , each individual fiber end may have a tapered shape and the area of the core at the end face close to the light source is greater than that of the other end face close to the respective single measurement unit 12 a - 12 n . fig3 depicts an exemplary configuration of measurement unit 12 a . other measurement units 12 b to 12 n may contain similar optical configurations . referring to fig3 , measurement unit 12 a contains illumination fibers , and collector fibers , linear polarizer 41 and 42 , lens 5 , prism 6 , and measurement window 15 . in operation of the measurement unit of fig3 , light emitted from light source 1 ( shown in fig1 and 2 ) travels through illumination fiber 3 and passes through linear polarizer 4 . polarizer 4 is comprised of two linear polarizers 41 and 42 . linear polarizer 41 may be oriented for polarization in a horizontal direction and linear polarizer 42 may be oriented for polarization in a perpendicular direction relative to the linear polarization produced by polarizer 41 . the transmitted linear polarized light beams 301 pass through linear polarizer 41 and enter lens 5 . due to the shape of lens 5 , the light beams 301 exit the lens parallel to each other before being refracted by prism 6 . the light is reflected off prism surface 21 and is conveyed through window 15 and illuminates the target tissue mucosa 17 . prism surface 21 may contain , for example , a vapor - deposited coating of silver , aluminum , or other material in order to produce the preferred reflectivity . in the instance when window 15 is in contact with the target tissue mucosa 17 , the transmitted light is interacted with by the tissue mucosa 17 . portions of the interacted light 302 and 303 reenter prism 6 and again refracted off of the prism surface 21 and back through lens 5 . the interacted light 302 and 303 passes through lens 5 and into polarizer unit 4 , passing through either linear polarizer 41 or linear polarizer 42 . after passing through the respective polarizer 41 or 42 , the light 302 and 303 enters the respective collector fibers 7 a or 7 b depending on which linear polarizer 41 or 42 , the light has passed through . because of this lens , prism , and polarizer unit configuration , only light that interacts with tissue mucosa 17 at specific angles enters the collectors or receiving fibers 7 a and 7 b . more specifically , light entering collector or receiving fiber 7 a is oriented at the same polarization direction as the transmitted light , since both transmitted and reflected light are passing though linear polarizer 41 . in contrast , the light entering collector or receiving fiber 7 b is always perpendicular to the transmitted light since it passes through linear polarizer 42 which is oriented in a perpendicular direction relative to that of liner polarizer 41 . fig4 depicts an alternative embodiment of the polarizer , lens , prism combination of measurement unit 12 of fig3 . in fig4 , the lens 5 and the prism 6 of fig3 are integrated into a single lens prism unit 19 . the integration of the two components decreases the number of sides the individual lens and prism combination has , thereby reducing the amount of stray light generated by reflection on the sides and accordingly , the stray light that reaches the light receiving fibers . a further advantage of utilizing a single lens prism combination may be realized due to the reduced number of optical components required , the reduced cost in manufacturing and assembly . in another embodiment , the flat reflection surface 21 of the prism may be spherical or ellipsoidal so as to achieve the same effect as the lens itself , thereby further reducing the number of components and manufacturing costs . in operation , the measurement unit of fig4 operates in a similar manner to that described with respect to fig3 . light emitted from light source 1 travels through illuminator fiber 3 and passes through linear polarizer 41 . linear polarizer 41 may be oriented for polarization in a horizontal direction and linear polarizer 42 may be oriented for polarization in a perpendicular direction relative to the linear polarization produced by polarizer 41 . the transmitted linear polarized light beams 301 pass through linear polarizer 41 and enter lens prism unit 19 . due to the shape of the lens portion of lens prism unit 19 , light beams 301 are oriented parallel to each other before being refracted by surface 21 of lens prism unit 19 . the light is reflected off surface 21 and is conveyed through window 15 and illuminates the target tissue mucosa 17 . prism surface 21 may contain , for example , a vapor - deposited coating of silver , aluminum , or other material in order to produce the preferred reflectivity . in the instance when window 15 is in contact with the target tissue mucosa 17 , the transmitted light interacts with the tissue mucosa 17 . portions of the interacted light 302 and 303 reenter lens prism unit 19 and are again refracted off of surface 21 and back through the lens portion of lens prism unit 19 . the light 302 and 303 pass through lens prism unit 19 and into either linear polarizer 41 or linear polarizer 42 . after passing through the respective polarizer 41 or 42 , the light enters the respective collectors or receiving fibers 7 a or 7 b , accordingly . because of the configuration of lens prism unit 19 and polarizer units 41 and 42 only light that interacts with tissue mucosa 17 at specific angles enters the collectors or receiving fibers 7 a and 7 b . more specifically , light entering receiving fiber 7 a is oriented at the same polarization direction as the transmitted light , since both transmitted and reflected light are passing though linear polarizer 41 . in contrast , the light entering receiving fiber 7 b is always perpendicular to the transmitted light since it passes through linear polarizer 42 which is oriented in a perpendicular direction relative to that of liner polarizer 41 . fig5 depicts an exemplary configuration of the linear polarizer unit 4 of fig2 - 4 . fig5 illustrates that the linear polarizers 41 and 42 of fig2 through 4 may be composed of a glass substrate 51 with a polymer material 52 bonded to a first side and an aluminum wire vapor - deposited on an opposite , second side 53 . the polarizing surfaces i . e ., polymer side or aluminum - wire side , may preferably be bonded on the surface of the light receiving fibers . due to the thermostability of the polarizing surface , the surface is preferably formed from an aluminum wire , such as , for example , the aluminum - wire grid polarizing filter manufactured by edmunds optics inc . of barnington , n . j . in the present invention , calculations are computed based on the detection of interacted light received by each individual measurement unit . fig6 shows a schematic diagram of an exemplary spectroscope 9 . in fig6 , the spectroscope 9 includes a data receiver 620 , a data preprocessor 621 , a blood content estimator 622 ( or blood content calculator ), a data validator 623 , a power supply 624 , an optional display or indicator 625 and a data comparator 626 . data receiver 620 receives information from the receiving fibers 7 a and 7 b . in operation , the data received by the data receiver 620 of the spectroscope 9 in fig6 is provided to a data preprocessor 621 . the data preprocessor 621 executes , for example , a data correction algorithm , such as white correction represented in the following equation ( 1 ). where the symbols π and ⊥ used in the numerator and denominator of equation ( 1 ) represent the spectrum of horizontally polarized light and the spectrum of vertically polarized light , respectively . in equation ( 1 ), λ represents wavelength , δi ( λ ) indicates the measured difference polarization spectrum , δiw ( λ ) is the spectrum measured using a standard white plate and is calculated by summing the white horizontal polarization spectrum iw π ( λ ) and the white perpendicular polarization spectrum iw ⊥ ( λ ), as shown in the denominator of equation ( 1 ). in the numerator of equation ( 1 ), the difference between the horizontal polarization spectrum i π ( λ ) and the perpendicular polarization spectrum i ⊥ ( λ ) is calculated and a signal indicative of δi ( λ ). based on the generated results of the data processor 621 , the blood content estimator 622 calculates the blood content by using equation ( 2 ) below , which is shown in , for example , m . p . siegel et al . assessment of blood supply in superficial tissue by polarization - gated elastic light - scattering spectroscopy , applied optics , vol . 45 , issue 2 , pp . 335 - 342 ( 2006 ), which is incorporated by reference herein . the blood content estimator 622 calculates the blood quantity by using a model equation , such as equation ( 2 ), and may provide a corresponding blood content value to optional display 625 . alternatively , the blood content estimator 622 may also provide the blood content value to data validator 623 as a check on the integrity of the collected data . further , blood content estimator 622 may provide the results from the various detection units to comparator unit 626 to determine the validity of a measurement and to improve the accuracy of detection based on the numerous measurement units . various configurations of exemplary endoscopes with multiple measurement units in accordance with the invention are depicted in fig7 to 13 . more specifically , fig7 depicts an endoscope tip 71 with multiple measurement units . endoscope tip 71 is generally concave in shape with the multiple measuring units 72 deployed along the concave surface of the tip . in operation , by pressing an endoscope tip 71 into living tissue , the tissue is drawn into , or aspirated into contact with the multiple measuring units 72 . the placement of numerous measurement units on the concave surface ensures contact by one or more of the measurement units . contact with multiple measurement units would tend to provide a more accurate reading than a probe with a single measurement unit . in additional , greater accuracy in blood content detection is achievable by comparing the data obtained from the multiple measuring units 72 . in the configuration of fig8 multiple measurement units 84 are employed with a traditional flexible endoscope 8 . endoscope 8 contains a rigid tip 81 , a connecting portion 82 , angled portion 83 , and measurement units 84 in accordance with the invention . by placing the measurement units 84 on the outer circumference of the insertion portion of the flexible endoscope , the detection windows are advantageously more likely to contact the tissue mucosa upon insertion and removal of the device . fig9 depicts a variation of the configuration of the invention shown in fig8 . a second ring of detection units 184 is longitudinally located on the circumference of the connecting portion 82 . by utilizing a second ring of measurement units 184 on the circumference of the flexible endoscope , a user is able to obtain measurement results at two different locations along the longitudinal access of the endoscope . by analyzing the data from the two different regions on the living tissue , an operator can more accurately determine the proximity of the abnormal lesion by utilizing the differences between the two areas of measurement . fig1 depicts an alternative embodiment to those disclosed in fig8 and 9 . as seen in fig1 , the measurement units 184 may be arranged in a substantially helical arrangement about the circumference of the insertion portion of a flexible endoscope . such an arrangement significantly increases the coverage area of the multiple detection windows . fig1 depicts an embodiment of the present invention wherein the connecting portion of the endoscope has a thread - like or helical protruded portion 112 . in this embodiment , the multiple measurement units 111 are placed in the outer circumference of the helical protrusion 112 . in operation of this configuration , the multiple measurement units 111 tend to serially come into contact with the same areas of tissue mucosa as the insertion portion is rotated upon insertion or extraction . fig1 depicts an endoscope 122 covered by a sheath 121 with measurement units 123 disposed therein . sheath 121 is essentially a tube into which , for example , an endoscope 122 , such as a conventional endoscope is inserted . multiple measurement units 123 are arranged along the circumference of sheath 121 and contact living tissue mucosa 124 . this type of sheath configuration allows the user to employ a conventional endoscope while at the same time advantageously utilizing blood content detection methods for guiding the endoscope to abnormal tissue . it will be appreciated by one skilled in the art that sheath 121 may also be configured with the thread - like protrusions 112 and the multiple measurement units 123 may likewise be configured in a spiral configuration along the circumference of the thread - like shape . fig1 depicts an embodiment with sheath 131 , endoscope 132 , and balloon 133 having multiple measurement units 134 disposed therein . sheath 131 is typically a hollow tube through which , for example , a endoscope 132 will be inserted . balloon 133 is attached to or formed integral with the sheath 131 and is inflated by either air or water pressure . upon placement of sheath 131 , balloon 133 is inflated to contact the target tissue mucosa 135 . the inflation of balloon 133 ensures contact between the multiple measurement units 134 and tissue mucosa 135 . further , a sensor 136 may be employed to start the blood detection process based on inflation of balloon 133 . as will be appreciated by those skilled in the art , sensor 136 may be located internally or externally to the sheath 131 or balloon 133 . for example a sensor could be located on the surface of balloon 136 or within sheath 131 and may sense the back pressure exerted by the balloon 133 when it inflates and contacts living tissue 135 . in an alternative embodiment , two or more balloons may be utilized , each with its own set of measurement units 134 . by utilizing multiple balloons 133 , the multiple measurement units 134 can be spread out along sheath 131 . in the manner , the blood content detection data can be analyzed to determine which of the balloons 133 is closest to an area of interest . such information will aid in isolating and detecting potential areas of interest . in another exemplary embodiment of the present invention , blood data collection is triggered upon the sensing of contact between balloon 133 and tissue mucosa 135 . such sensing of contact may be the result of back pressure sensed in the balloon inflation mechanism or as a result of surface sensors 136 located in balloon 133 . while the foregoing description and drawings represent the preferred embodiments of the present invention , it will be understood that various changes and modifications may be made without departing from the spirit and scope of the present invention . for example , although the improved method and apparatus described herein as part of or in conjunction with an endoscope , it is also possible to use the invention with a stand alone probe or other medical device .

light scattering and absorption techniques for the detection of possible abnormal living tissue . apparatus and methods for utilizing multiple blood content detection sensors and / or contact sensors for beneficially providing data to better guide an endoscope or colonoscope to locate abnormal tissue , tumors , or tissues that precede the development of such lesions or tumors .

fig1 illustrates an embolic coil retrieval system 10 which includes a sheath 12 , an actuator wire 14 , and an embolic coil retriever 16 . the sheath 12 is approximately 60 inches in length and is preferably formed of a polymer material with a durometer in the range of about 50d and 80d . the outside diameter of the sheath 12 is about 0 . 038 inches while the lumen 18 of the sheath 12 has a diameter of approximately 0 . 021 inches . the actuator wire 14 is approximately 70 inches in length and is preferably made from a metallic material . the diameter of the actuator wire 14 is less than the diameter of the lumen 18 of the sheath 12 so that the actuator wire 14 may slide within the lumen 18 of the sheath 12 . the embolic coil retriever 16 is laser cut from a nickel - titanium alloy tube and is attached to the distal end 20 of the actuator wire 14 . fig2 illustrates the embolic coil retriever 16 in a normally open configuration . the embolic coil retriever 16 includes a cylindrical member 22 with a lumen 24 ( not shown ), a proximal section 26 , and distal section 28 . the cylindrical member 22 is approximately 0 . 040 inches in length and is preferably formed from a nickel - titanium alloy . the outside diameter of the cylindrical member 22 is about 0 . 018 inches while the diameter of the lumen 24 is approximately 0 . 012 inches . there are attachment holes 30 in the wall 32 of the cylindrical member 22 which allow the distal end 20 of the actuator wire 14 to be attached within the lumen 24 of the cylindrical member 22 . attached to the distal section 28 of the cylindrical member 22 is an elongated tubular member 34 which is approximately 0 . 12 inches in length and is also preferably made from a nickel - titanium alloy . the outside diameter of the elongated tubular member 34 and the diameter of the lumen 36 ( not shown ) of the tubular member 34 are generally the same as the cylindrical member 22 . a jaw member 38 is formed from the elongated tubular member 24 . preferably , the jaw member 38 is laser cut from the elongated tubular member 34 . the jaw member 38 includes a first jaw 40 , a second jaw 42 , and a third jaw 44 where each jaw 40 , 42 , and 44 takes the form of a longitudinal portion of the elongated tubular member 34 . each jaw 40 , 42 , and 44 has a distal end 48 , a proximal end 50 , a first longitudinal edge 52 , and a second longitudinal edge 54 . the distal ends 48 of the jaws 40 , 42 , and 44 are biased outwardly such that the distal ends 48 are approximately 0 . 008 inches from the longitudinal axis of the elongated tubular member 34 . the first jaw 40 , second jaw 42 , and third jaw 44 include longitudinal legs 56 having a proximal end 58 and a distal end 60 . the proximal ends 58 of the longitudinal legs 56 are attached to the distal ends 48 of the jaws 40 , 42 , and 44 . the longitudinal legs 56 are approximately 0 . 002 inches in length and may include a radiopaque marker 62 for use during fluoroscopic visualization . preferably , the longitudinal legs 56 are laser cut from the elongated tubular member 34 . attached to the first longitudinal edges 52 and second longitudinal edges 54 of the jaws 40 , 42 , and 44 are teeth 66 . these teeth 66 are described in more detail in the description of fig4 . fig3 illustrates the embolic coil retriever 16 in a closed configuration . the overall length of the embolic coil retriever 16 in the closed position is approximately 0 . 16 inches . the cylindrical member 22 includes attachment holes 30 ( one shown ) for the actuator wire 14 . the elongated tubular member 34 which takes the form of a jaw member 38 is attached to the distal section 28 of the cylindrical member 22 . the jaw member 38 includes a first jaw 40 , a second jaw 42 , and a third jaw 44 . as can be appreciated , each jaw 40 , 42 , and 44 takes the form of a longitudinal portion of the elongated tubular member 34 . at the distal ends 48 of the jaws 40 , 42 , and 44 , longitudinal legs 56 are attached which may include radiopaque markers 62 . each jaw 40 , 42 , and 44 of the jaw member 38 includes teeth 66 attached to the first longitudinal edge 52 and second longitudinal edge 54 . this configuration of the teeth 66 is described below . fig4 illustrates the teeth 66 of the embolic coil retriever 16 . the teeth 66 generally take the form of triangular members each having a base 68 attached to a longitudinal edge 52 and 54 of a jaw 40 , 42 , and 44 . preferably , the teeth 66 are laser cut from the elongated tubular member 34 . the teeth 66 may take the form of major teeth 70 which are generally obtuse triangular members having an obtuse angle 74 and a base 76 . the base 76 of each major tooth 70 has a proximal end 78 and a distal end 80 . the obtuse angle 74 of each major tooth 70 is located at the proximal end 78 of the base 76 . the teeth 66 may also take the form of minor teeth 82 which are generally acute triangular members having a base 86 . the base 86 of each minor tooth 82 is attached to a longitudinal edge 52 and 54 of a jaw 40 , 42 , and 44 . the configuration of the teeth 66 shown in fig4 includes a combination of major teeth 70 and minor teeth 82 . there is a pattern of alternating major teeth 70 and minor teeth 82 along the longitudinal edges 52 and 54 of each jaw 40 , 42 , and 44 . in addition , each major tooth 70 is generally aligned with a minor tooth 82 on an adjacent longitudinal edge 52 and 54 of an adjacent jaw 40 , 42 , and 44 , and each minor tooth 82 is generally aligned with a major tooth 70 on an adjacent longitudinal edge 52 and 54 of an adjacent jaw 40 , 42 , and 44 . this pattern forms a plurality of pockets 88 which are gaps between the major teeth 70 and the minor teeth 82 on the longitudinal edges 52 and 54 of the jaws 40 , 42 , and 44 . each pocket 88 is approximately 0 . 015 inches wide and 0 . 015 inches tall . however , the size of the pocket 88 may be varied so as to generally match the size of the pockets 88 with the size of the embolic coil 90 being retrieved . fig5 through 8 illustrate a preferred method of using the embolic coil retrieval system 10 to capture an embolic coil 90 . in fig5 , the embolic coil retrieval system 10 is inserted into the vasculature 92 of the human body . the embolic coil retriever 16 is attached to the actuator wire 14 and is disposed within the lumen 18 of the sheath 12 . the embolic coil retrieval system 10 is moved distally towards the embolic coil 90 to be retrieved . fig6 shows the actuator wire 14 being moved distally causing the embolic coil retriever 16 to exit the lumen 18 of the sheath 12 thereby causing the jaws 40 , 42 , and 44 of the jaw member 38 of the embolic coil retriever 16 to assume a normally open position . the jaw member 38 in the open position is aligned with the embolic coil 90 to be retrieved . in fig7 , the sheath 12 is moved distally causing the jaws 40 , 42 , and 44 of the embolic coil retriever 16 to assume a closed position around the embolic coil 90 . the embolic coil 90 is captured within the pockets 88 formed by the gaps between the alternating major teeth 70 and minor teeth 82 on the jaws 40 , 42 , and 44 . fig8 illustrates the embolic coil retrieval system 10 and the embolic coil 90 being removed from the vasculature of the body . as the embolic coil retrieval system 10 is moved proximally , the embolic coil 90 is held within the pockets 88 and is wedged behind major teeth 70 thereby preventing the embolic coil 90 from falling out of the jaw member 38 . a novel system has been disclosed in which an embolic coil retrieval system is introduced into the vasculature of the human body for retrieval of an embolic coil . although a preferred embodiment of the invention has been described , it is to be understood that various modifications may be made by those skilled in the art without departing from the scope of the present invention . for example , there may be variations to the jaw member of the embolic coil retriever . the jaw member may include four or more jaws formed from an elongated tubular member . each jaw may be a longitudinal portion of the elongated tubular member . in another alternative construction , the embolic coil retriever may be covered with a high density metallic coating , like gold . this coating may provide enhanced reflection during fluoroscopic visualization . in still another alternative construction , the pockets formed by the major teeth and minor teeth along the longitudinal edges of the jaws may vary in size . for example , at the distal end of the jaw member the pockets may be small for capturing small embolic coils , but pockets may gradually become larger towards the proximal end of the jaw member for capturing larger embolic coils . this construction would allow physicians to use one jaw member configuration for capturing various sized embolic coils . finally , the embolic coil retriever may be used for capturing other medical devices such as dilation balloons or stents . these and other modifications would be apparent to those having ordinary skill in the art to which this invention relates and are intended to be within the scope of the claims which follow .

an embolic coil retrieval system for retrieving or repositioning an embolic coil within the vasculature of the human body which is comprised of a very small embolic coil retriever having a jaw member with major and minor teeth which form pockets for grasping an embolic coil when the jaw member is closed .

referring first to fig1 through 6 of the accompanying drawings , a first embodiment of a below - the - rod double - bearing type fishing reel constructed in accordance with the present invention will be described . as seen in fig1 a reel body 1 includes two opposed end plates 2a and 2b , fixedly supported and spaced apart by supporting rods 3 . a shank 4 extends above the end plates 2a and 2b , and flares into a mounting foot 4a for attachment to the rod ( not shown ). covers 5 and 5 &# 39 ; cover the outer sides of the end plates 2a and 2b and define spaces in which the operating mechanism of the reel is contained . a fishing line spool 6 is rotatably mounted between the end plates 2a and 2b via a spool shaft 7 . as seen in fig5 the shaft 8 of a winding handle is rotatably mounted to the cover 5 . in the space defined between the cover 5 and the end plates 2a , a clutch mechanism , as shown in fig1 is provided for selectively rotatably coupling the shaft 8 to the shaft 7 of the spool 6 . a conventional drag mechanism may be provided between the shafts 7 and 8 . further , a reverse rotation preventing mechanism may be provided within the space defined between the cover 5 and the end plate 2a . an operating lever 12 is fixed to a shaft 10 , and the shaft 10 is rotatably mounted between the end plates 2a and 2b . a spring 11 is provided for rotatably biasing the operating lever 12 opposite to the direction a indicated in fig1 . the operating lever 12 is movable in the direction a by the operator . a first clutch lever is fixedly mounted to one end of the shaft 10 inside of the space defined between the cover 5 and the end plate 2a . the clutch lever 13 has on one side thereof a cam portion 14 . the clutch lever 13 also includes an arm portion 15a . at the end of the arm portion 15a opposite the shaft 10 is attached a pin 15 , the latter extending parallel to the shaft 10 . a brake lever 17 is rotatably mounted on a shaft 16 , as is a second clutch lever 18 . the shaft 16 is fixed to the end plate 2a . the brake lever 17 is urged in the direction opposite the direction b indicated in fig1 by a coil - type brake spring 19 . the brake spring 19 is connected between a pin 17a , fixed to approximately the center portion of the brake lever 17 , and the shaft 10 . the brake spring 19 thus urges one side of the brake lever 17 into engagement with the cam portion 14 of the first clutch lever 13 with the shaft 16 acting as the fulcrum . one end of a dead - point spring 20 is engaged with the free end of the second clutch lever 18 , while the other end of the dead - point spring 20 is engaged with the end plate 2a . the spring 20 thus urges the second clutch lever 18 into abutment with the pin 15 . accordingly , movement of the operating lever 12 in the direction a causes the brake lever 17 and second clutch lever 18 to move in the directions b and c against the forces of the springs 19 and 20 , respectively . a brake shoe 21 is provided at the movable end of the brake lever 17 , positioned so as to contact with a flange 6a of the spool 6 to brake the spool 6 . the brake shoe 21 is fixedly mounted , as shown in fig3 with a washer 24 to an inner end of a shaft 17b which is fixed to the movable end of the brake lever 17 . the shaft 17b passes through an elongated hole 2a &# 39 ; formed in the end plate 2a . as shown in fig1 the clutch mechanism 9 includes an operating plate 26 and a clutch plate 27 . the operating plate 26 is journaled on the spool shaft 7 . the operating plate 26 is slidably engaged at opposite ends with fixed shafts 25 , and a spring ( not shown ) for biasing the operating plate 26 inwardly as viewed in fig1 is engaged with the shafts 25 . the clutch plate 27 is provided with two cam portions 26 which , when the clutch plate 27 is rotated counterclockwise as viewed in fig1 engage with the operating plate 26 to move it against the force of the spring engaged with the shafts 25 . a pin 22 , fixed to one end of the second clutch lever 18 , is engaged with an arm of the clutch plate 27 via an elongated hole 23 formed in the arm . the operating plate 26 is slidable axially to engage a gear of a drag mechanism ( not shown ) with a pinion ( not shown ). the operating plate 26 is moved axially by the cam portions 27a when the clutch plate 27 is rotated couterclockwise by operation of the second clutch lever 18 upon the operator pulling the operating lever 12 in the direction a . this action releases the interconnection between the spool shaft 7 and the handle shaft 8 . on the other hand , when the operating lever 12 is released , the reverse movement of the clutch plate 27 causes the operating plate 26 to move in the opposite direction , thereby rotatably linking the spool shaft 7 and the handle shaft 8 . more specifically , when the operating lever 12 is at the position indicated by a solid line in fig1 the levers 13 , 17 and 18 are at positions also indicated by solid lines due to the biasing actions of the springs 19 and 20 . in this state , the brake shoe 21 is held separated from the flange 6a of the spool 6 and the clutch mechanism 9 is in the engaged state . then , when the lever 12 is pulled in the direction a , the first clutch lever 13 is rotated in the clockwise direction , thereby rotating the brake lever 17 and the clutch 18 counterclockwise and clockwise , respectively , with the shaft 16 acting as a fulcrum . this action simultaneously releases the clutch mechanism 9 and causes the brake shoe 21 to move into contact with the flange 6a of the spool 6 , thereby halting the rotation of the spool 6 . when the operator releases his finger from the lever 12 , allowing lever 12 to return to the position indicated by the solid line , the first clutch lever 13 is restored to the position indicated by the solid line , thereby restoring the brake lever 17 due to the force of the spring 19 . also , the brake shoe 21 is separated from the flange 6a of the spool 6 , releasing the braking state and allowing the spool 6 to rotate to allow the fishing line to be played out . it is of course possible to brake the spool by operating the lever 12 in the direction a during the casting operation to prevent backlash of the line . the construction of the below - the - rod double - bearing type reel of the first embodiment described above is advantageous over the prior art construction with respect to the clutch releasing and braking mechanism . specifically , in the above - described embodiment , the construction of the operating lever is simpler than that employed in the conventional reel since all elements other than the lever 12 and brake shoe 21 are received inside of the case of the reel . the overall size of the reel is made more compact , and backlash of the fishing line during the casting operation can easily be prevented . referring now to fig7 through 9 , a second embodiment of the invention will now be described . in fig7 through 9 , components identical or similar to corresponding components in the embodiment of fig1 through 6 are identified by like reference numerals , and further detailed descriptions thereof are omitted . as shown in fig7 a reel body 1 is connected to the shank 4 with screws 47 . as in the first - described embodiment , the shank 4 flares into a mounting foot 4a used to attach the reel to a rod 30 . in this embodiment , the operating lever 12 is mounted upon a shaft 10 &# 39 ; extending between leg portions 4b and 4c provided in the lower portion of the shank 4 . the operating lever 12 is rotationally biased counterclockwise in fig7 by a spring 11 wound around the shaft 10 &# 39 ;. a clutch pin 41 is provided at an end of a portion of the lever 12 which protrudes rearwardly from the juncture point with the shaft 10 &# 39 ;. the pin 41 is slidably inserted into an elongated hole 42 provided in the end plate 2b of a side frame 2 &# 39 ;. a cam portion 14 &# 39 ; is formed integrally with a central portion 43 of the operating lever 12 . a brake shoe 21 &# 39 ; is disposed below the central portion 43 of the operating lever 12 , between the bottom of the cam portion 14 &# 39 ; and the flange 6a of the spool 6 . the brake shoe 21 is movable in the vertical direction of fig7 and is urged upwardly by a spring 19 &# 39 ;. the cam 14 &# 39 ; is in the position shown in fig7 when the operating lever 12 is in the illustrated released state . however , when the operating lever 12 is pulled upwardly ( rotated in the clockwise direction in fig7 ), the cam portion 14 is rotated so as to depress the brake shoe 21 &# 39 ; against the force of the spring 19 &# 39 ;, thereby moving the brake shoe 21 &# 39 ; into abutment with the flange 6a of the spool 6 , and thereby braking rotational movement of the spool 6 . the braking mode is illustrated in fig9 . if desired , the cam 14 &# 39 ; can be formed integrally with the operating lever 12 by deforming a part of the central portion 43 of the operating lever 12 , or it may be formed by uniting a second member to the operating lever . any desired construction of the cam portion 14 &# 39 ; may be employed so long as the cam portion 14 &# 39 ; is rotatable together with the operating lever 12 . the brake shoe 21 &# 39 ;, which has a generally rectangular configuration , has an elongated through - hole 45a at the center thereof as shown in fig8 . a guide piece 48 is provided at the inner surface of the leg portion 4c and fitted into the elongated hole 45a to guide the movement of the brake shoe 21 &# 39 ; in the vertical direction . the spring 19a is disposed between a top end 45b of the elongated hole 45a . the guide piece 48 is prevented from disengaging from the elongated hole 45 by a holding plate 49 , the latter being attached to the leg portion 4c by pins 50 . the bottom end of the brake shoe 21 &# 39 ; passes through a recess 51 provided in a flange portion 2c of the end plate 2b . the pin 41 performs the function of the pin 15 in the first - described embodiment . therefore , the arm portion 15a of the lever 13 employed in the first - described embodiment can be omitted . otherwise , the clutch mechanism in this second embodiment may be the same as in the first - described embodiment . of course , there is no need to provide the brake lever 17 , etc ., used to perform the braking function in the first - described embodiment . in operation , when the operating lever 12 is pulled upwardly ( turned counterclockwise in the drawing ) by the finger f of the operator , the rotation of the operating lever 12 causes the clutch pin 41 at the rear end of the operating lever 12 to move downwardly along the elongated hole 42 , thereby releasing the clutch mechanism . simultaneously , the cam portion 14 &# 39 ; rotates to push the brake shoe 21 &# 39 ; downwardly by the top portion 14a &# 39 ; of the cam portion 14 &# 39 ;. this action forces the brake shoe 21 &# 39 ; into engagement with the periphery 6a of the spool 6 , thereby braking the rotational movement of the spool 6 . when the operating lever 12 is released , the operating lever 12 turns in the counterclockwise direction in fig7 thereby moving the clutch pin 41 outwardly and thus engaging the clutch . also , rotation of the cam portion 14 &# 39 ; causes the brake shoe 21 &# 39 ; to disengage from the periphery 6a of the spool 6 . accordingly , the mode illustrated in fig7 is restored . in the second preferred embodiment described above , because the brake shoe 21 &# 39 ; is provided at a position under the pivoted central portion of the operating lever 12 while the clutch pin 41 is provided at the end of a rearward extension from the central portion of the operating lever 12 , there is no danger whatsoever of any interference between the two operating members . also , the brake shoe 21 &# 39 ; will always be pushed down smoothly and surely by the rotation of the cam portion 14 &# 39 ; so that the braking and clutch operating movements are always performed smoothly . this completes the description of the preferred embodiments of the invention . although preferred embodiments have been described , it is believed that numerous modifications and alterations thereto would be apparent to one of ordinary skill in the art without departing from the spirit and scope of the invention .

a clutch releasing and braking mechanism for a below - the - rod double - bearing type fishing reel having a simplified and compact construction . an operating lever of the reel is pivotally mounted on a frame member of the reel , and a cam portion , rotatable with the operating lever , is provided at the pivot point of the operating lever . the cam portion engages with and operates a braking mechanism . a clutch operating lever , which may be formed as a separate lever and connected to the operating lever via a rotary shaft or as a rearward extension of the operating lever , has a clutch - operating pin at its outward end . the clutch - operating pin engages a second clutch lever , the latter having a pin which directly operates the clutch mechanism .

sweet mixes or danish mixes in accordance with the present invention include substantial quantities of wheat flour . wheat flour usually makes up at least about 60 weight percent of the dry mix . a typical range is between about 60 and about 75 weight percent , based upon the total weight of the mix , preferably between about 62 and about 68 weight percent , based upon the total weight of the mix . it is preferred that this wheat flour be of the type which is generally known as hard wheat . so - called hard varieties of wheat have a relatively high protein content . the protein content of a hard wheat is typically approximately 12 weight percent , usually tightly ranging between 11 . 5 % and 12 . 5 %. so - called soft wheats have a protein content on the order of about 8 weight percent . examples of suitable hard wheat components according to the invention include ellison hard flour , morebread hard flour , and the like . often , these flours are bleached and enriched with enriching components such as niacin , reduced iron , thiamine mononitrate , riboflavin , folic acid , and the like . moisture contents of these types of hard wheat flours typically range between about 12 . 5 and 14 weight percent . maximum ash contents are usually about 0 . 5 %. being a sweet dough dry mix , substantial quantities of one or more sweetening components are included . the sweetening components typically will comprise at least about 10 weight percent of the total weight of the dry mix . in a typical application , the sweetening component includes both granulated sugar and more natural sugars such as dextrose , glucose and the like . generally , the sweetening component content within the dry mix will be between about 5 weight percent and about 20 weight percent , based upon the total weight of the dry mix . so - called granulated sugars are freeflowing , bright light granules which typically are approximately 99 . 9 % sucrose in the form of free - flowing granular solids . dextrose or corn sugar can be preferably combined with the use of granular sugar . an especially suitable dextrose is a highly purified crystalline product resulting from complete hydrolysis of corn starch . such dextroses can be produced by the enzyme conversion of corn starch , followed by refining by ion - exchange demineralization . such dextrose components are bland and sweet and are typically white , dry and crystalline . in an important aspect of the invention , carboxymethyl cellulose ( cmc ) is added to the sweet dry mix . typical sodium carboxymethyl cellulose is classified as a gum and is in the form of white granules , and the cmc is incorporated directly into the sweet mix in its dry form . it is preferred that the cmc be added as a non - hydrated component and without dispersing the cmc into any carrier , such as water . the cmc component first encounters water at the bowl level when subsequently combined with the other dough components during the dough making and baking operations . such non - hydrated carboxymethyl cellulose is added dry to the dry sweet mix so as to attain a level of cmc within the dry mix of between about 0 . 1 and about 1 . 5 weight percent , typically between about 0 . 1 and about 0 . 8 weight percent , preferably between about 0 . 15 and about 0 . 5 weight percent , most preferably between about 0 . 2 and about 0 . 4 weight percent based upon the total weight of wheat flour . a typical sodium carboxymethyl cellulose is prepared by treating alkali cellulose with sodium chloroacetate . while carboxymethyl cellulose components are available in various viscosities , it has been found to be especially advantageous to incorporate high viscosity cmc directly into the sweet mix . especially preferred is a cmc component which has a viscosity of between about 1500 and about 3000 centipoise , measured by a brookfield viscometer when in a one percent solution at 250 ° c . thus , the preferred cmc component is especially thixotropic . it is also somewhat less hydroscopic than other cmc components of lower viscosities . an especially preferred high viscosity cmc is available from hercules company under the designation 7 hf . especially when this high viscosity cmc is used , it can be important to avoid the higher levels of use noted herein . for example , conventional current large - scale dough - working equipment may have difficulty in handling doughs incorporating cmc contents much above 0 . 5 weight percent , based on the wheat flour . although not bound by any particular theory , it is currently believed that this cmc component interacts in an especially advantageous manner with the protein , such as flour protein or gluten , of the hard wheat flour . according to this belief , ionic charge coupling occurs between the wheat protein molecules and the cmc molecules . water , which is subsequently added when the sweet mix is used to make up the sweet dough formulation , is believed to facilitate this ionic charge coupling . the cmc is believed to react in what is understood to be an ionic manner with the water soluble protein of the wheat flour . in this regard , it is preferred that the cmc be present at between about 0 . 3 and about 0 . 7 weight percent , based upon the total weight of the wheat flour . this attachment of cmc molecules to the wheat protein is believed to improve the workability of the flour by interacting with it while also modifying properties of the protein in order to modify its interaction with other components within the dough , even after the dough is baked into a finished product . whatever mechanism is in operation , the ultimate result is overall improvement in the handling attributes of the sweet dough prior to baking , as well as important improvements in the baked products themselves . more specifically , the inclusion of cmc relaxes the dough incorporating the mix and provides a better conditioned dough which is more easily machined out or rolled out . for example , when operated on by rollers of commercial - scale dough processing equipment , the dough does not shrink back , which is characteristic of doughs having substantial elasticity . instead , doughs incorporating the mix according to the invention remain rolled out once thus flattened or thinned by rolling equipment or the like . because of the inclusion of the cmc component in the dough , the finally baked sweet dough products are judged to be more tender , more flavorful to eat , and exhibit a more pleasing mouth feel . baked products according to the invention also have a noticeable improvement in height or volume . in addition , the baked products are structurally more even , particularly with respect to the air cells present in the baked product . the cell structure is generally more even throughout . with the invention , individual cells are less likely to break open during the baking process and thus combine with other broken small cells in order to form less desirable larger air cells . this is believed to be due at least in part to a stronger cell wall structure allowing the cells to expand more readily . often , such air cell formation is initiated by the action of leavening agents such as yeast , typically while the dough is within the proof box . the inclusion of the cmc in accordance with the present invention is also instrumental in retarding staling of the baked products . an element of the staling process is having wheat granules move back toward their dry state . this process can be generally described as recrystallizing of starch granules . this effect is retarded when the present invention is practiced . it is believed that the cmc interferes with the tendency of the starch to recrystallize . this phenomena is illustrated by textural analysis data . due in part to the high viscosity characteristics of the carboxymethyl cellulose component according to the present invention , it is important to avoid excessive cmc addition . if this highly viscous cmc is added at too great a level , the workability of the subsequently formulated dough would be extremely difficult because the dough itself would become very viscous and difficult to reshape to the extent needed in making the baked product , particularly when using large - scale dough processing equipment . it will be appreciated that this is somewhat dependent upon the capabilities of the dough processing equipment . other components may be included within the sweet dry mix , these being generally appreciated in the art . a milk protein source will typically be included , such as nonfat dry milk , for example at a level of between about 4 and 6 weight percent based upon the total weight of the mix . typical non - fat dry milk solids have a moisture level of about 4 %. another typical component is an edible oil , which can be present at levels of up to about 10 weight percent , based upon the total weight of the sweet dry mix , often at least about 5 weight percent . a bulk vegetable shortening which is suitable in this regard is partially hydrogenated vegetable oil , such as partially hydrogenated soybean oil . a typical iodine value is between about 75 and about 85 . a typical solids fat index ( sfi ) profile for such hydrogenated soybean oils exhibits 22 to 26 units at 50 ° f ., 12 to 15 units at 70 ° f ., 1 to 2 . 5 units at 92 ° f ., and less than 1 unit at 104 ° f . a further possible added component is defatted soy flour . such a product can have a protein level of about 50 to 52 % and a moisture level of about 6 %. other typical ingredients included within the sweet dry mix include mono - and diglycerides of fat - forming fatty acids . these are generally characterized as emulsifiers , and when included will be at a level of about 2 weight percent , based upon the weight of the sweet dry mix . salt in the form of sodium chloride also typically will be included , such being at a level of between about 1 and about 1 . 5 weight percent , based upon the weight of the sweet dry mix . another preferred and typical ingredient is sodium acid pyrophosphate , usually at a level of not greater than about 0 . 5 weight percent , based upon the weight of sweet dry mix . this is a baking powder component having leavening attributes . a similar typical component is sodium bicarbonate or baking soda , which can be present at levels of about 0 . 25 weight percent , based upon the weight of the sweet dry mix . coloring components can also be added at the relatively low weight percent levels associated with these types of products . thus , the total of chemical leavening and coloring agents will be between about 0 . 5 and about 1 weight percent , based upon the total weight of the sweet dry mix . in preparing the sweet dry mix , the flour and sugar bulk ingredients , typically with the non - fat dry milk component , are blown into the ribbon blender . thereafter , the lower quantity or trace ingredients , most notably including the carboxymethyl cellulose component , are then blown into the ribbon blender . the liquefying components such as the emulsifier and bulk vegetable oil are then drawn into the ribbon blender and blended for at least five minutes , to a temperature maximum of about 80 ° f . ( 26 . 7 ° c .). formulation of the mix is completed by running the flow from the ribbon blender through a disintegration mill having a screen sized at about 0 . 25 inch . such a mix formulation has a total moisture content which is typically lower than 10 % by weight and a ph of about 6 . 0 to about 7 . 0 . the resulting dry danish mix is suitable for bagging and making into a sweet dough when desired . this danish mix is the majority component of the sweet dough , typically making up between about 60 and 70 weight percent , based upon the total weight of the dough formulation . another typical component is an egg source , such as between about 3 and 8 weight percent whole eggs , based upon the total weight of the dough formulation . a cream yeast , which is an active wet yeast , is incorporated at a level of about 2 to 7 weight percent , based upon the total weight of the dough formulation . water is also incorporated into the dough formulation , often in separate stages , to achieve a total water content of about 20 to 30 weight percent , based upon the total weight of the dough formulation . these components are added to commercial dough mixing equipment in accordance with generally known procedures . in preparing the baked sweet dough products , the mixed dough is subjected to commercial - scale baking operations . usually this includes a substantial time in one or more retard chambers , for several hours at between about 35 and about 42 ° f . ( between about 1 . 5 and 5 . 60 ° c . ), such being in accordance with generally appreciated procedures . lamination with a roll - in composition can follow , after which additional retard chamber time can be carried out . after passage through reducing rollers , the dough is subjected to proof box conditions at high humidity , followed by oven baking and cooling . the following examples are illustrative of some of the aspects of the present invention . a danish dry mix was prepared to include 2659 pounds of morebread hard flour having a protein level of about 12 . 1 weight percent ; 300 pounds of ellison hard flour having a protein level of 12 . 2 weight percent ; 90 pounds defatted soy flour ; 500 pound granulated sugar ; 200 pounds dextrose ; 430 pounds partially hydrogenated soybean oil having a iodine value of about 80 ; 200 pounds nonfat dry milk solids ; 90 pounds mono - and diglycerides of fat - forming fatty acids prepared from edible vegetable fat ; 50 pounds sodium chloride ; 17 pounds sodium acid pyrophosphate baking powder ; 13 pounds sodium bicarbonate baking soda ; 1 . 4 pounds yellow color ; and 7 . 5 pounds high viscosity carboxymethyl cellulose ( hercules 7 hf ). of these , the flour and sugar bulk components were combined and they were then blended together with the bulk vegetable oil , and the trace components were added thereafter . the latter included the carboxymethyl cellulose , which was added in its dry gum state without dissolving or dispersing in water or any other solvent . such cmc was added at a level of about 0 . 25 weight percent of the wheat flour . the sweet flour dry mix in accordance with example 1 was combined with whole eggs , cream yeast and water in customary proportions . without adding any roll - in component , the dough was shaped as a danish pastry , proofed , cut to 56 grams , and baked at 375 ° f . ( 190 . 6 ° c .) for 12 minutes . a total of 30 tests were performed on the thus baked pastries , using current and conventional commercial - scale equipment . the dough was readily processed by this equipment , including without experiencing shrink back after rolling . for these 30 tests , the average height was 1 . 5 cm , the average width was 12 . 00 cm , and the average volume was 330 cc . this represented a substantial height and volume increase over prior art baked pastries of about the same weight and which excluded cmc from the dry mix but which were otherwise similarly prepared . such prior art pastries have a height of about 1 . 0 cm , a width of about 8 . 5 cm , and a volume of not more than about 300 cc . a danish dry mix having ingredients and proportions in accordance with example 1 was used to make up a danish sweet dough . 1600 grams of the danish mix were blended with 140 grams of whole egg , 36 grams of cream yeast , and 712 grams of water . more specifically , the danish mix was first blended with the yeast for one minute within a model a120t hobart mixer . the water and liquid whole egg components were next added and mixed for about one minute until the dough was formed . the water temperature was 39 ° f . ( 3 . 9 ° c .) and the dough temperature was 82 ° f . ( 27 . 8 ° c .) the danish dough was placed on a floured sheet pan , a bag was placed around the pan , and this was subjected to a cool environment of 40 ° f . ( 4 . 4 ° c .) over night . the dough was worked and given a 3 -- 3 fold with a commercial roll - in formulation . 622 grams of roll - in were used with 2488 grams of dough . this was allowed to rest in a cooler at 40 ° f . ( 4 . 4 ° c .) for at least two hours . a danish roll was made up to a diameter of 2 . 5 inches , with a water wash and sugar . pieces cut to 2 ounces ( 56 . 7 grams ) were placed on a paper lined sheet pan and proofed at 90 ° f . ( 32 . 2 ° c .) and 90 % humidity for about one hour . thereafter , the danish rolls were baked at 370 - 3750 ° f . ( 187 . 8 - 190 . 6 ° c .) for 12 minutes . the baked danish rolls were judged to have good volume and texture . another dough formulation was made up from 3544 . 5 pounds of the example 1 dry mix , 310 pounds of whole egg , 248 pounds of cream yeast , 1231 . 5 pounds of water added in a first mixing stage and 177 . 2 pounds of water added in a second mixing stage . this danish mix had been modified to include 9 pounds of 7 hf cmc . this represented a cmc content of 0 . 39 weight percent , based upon the weight of wheat flour in the sweet dough dry mix . this danish sweet dough was processed and baked in accordance with example 2 . resulting danish products were judged to have excellent results . good volume and good texture were evident . example 4 was essentially repeated , except a higher level of cmc was used . in this case , 17 . 7 pounds of cmc were included within the danish mix , such being approximately 0 . 77 weight percent , based upon the weight of the wheat flour . the dough was judged to be too stiff for optimum use within older conventional commercial - scale dough handling equipment , but it was successfully processed manually . the resulting danish rolls nevertheless exhibited good volume and good texture . example 4 was substantially repeated , except the level of cmc was substantially higher , the danish mix including 35 . 4 grams of cmc , which indicates 1 . 54 weight percent cmc , based upon the weight of wheat flour . the dough was very tough and stiff and less satisfactory for use within currently used commercial production scale dough handling equipment , although the resulting baked danish rolls had good volume and texture when processed manually . a dough formulation generally in accordance with example 3 was made up with 0 . 5 weight percent cmc , based on the weight of wheat flour present in the formulation . this formulation was in accordance with the invention . a control formulation was also made up to be virtually the same , except no cmc was added . each dough formulation was baked into an unlaminated danish product to which no roll - in had been added . both types of baked products were subjected to textural analysis testing using instron equipment , specifically stable micro systems texture expert equipment . this equipment was fitted with a plexiglass cylindrical probe which was one inch in diameter . each baked danish product was cut to a height of 25 mm and was compressed to approximately 50 % of that height . the probe was directed to the freshly severed side of the danish product and the puncture test was carried out . the puncture test inserted the probe to approximately one - half of the compressed danish product . the probe encountered only internal crumb and no crust . double compression testing was carried out through a grid system to ensure the second insertion was in registration with the location within the baked product of the first insertion . the first insertion provided a relative indication of softness , texture and starch granule recrystallization to give an objective indication of staleness . the probe was fully retracted after about 4 seconds . after waiting about 8 seconds , the second compression was carried out for evaluation of springiness , with withdrawal being completed in about 3 seconds . the baked products in accordance with the invention registered 300 grams force for the first insertion and 260 grams force for the second insertion . the control products registered 400 grams force for the first insertion and 350 grams force for the second insertion . from these data , it is observed that the control required 100 grams of additional force in order to penetrate the same distance when compared with the force required for the first insertion into the products according to the invention . thus , the control required one - third more force during the first insertion , thereby indicating significant staleness when compared with the baked product made by the formulation according to the invention . it will be understood that the embodiments of the present invention which have been described are illustrative of some of the applications of the principles of the present invention . various modifications may be made by those skilled in the art without departing from the true spirit and scope of the invention .

a sweet dough dry mix is provided which incorporates highly viscous carboxymethyl cellulose in combination with hard wheat flour . when used to make up a sweet dough , the resulting dough exhibits enhanced handling when compared with similar formulations which do not incorporate the combination . also provided are products baked from the sweet dough . these products have noticeably enhanced height and structured evenness , and they better retard staling when compared with other doughs omitting the carboxymethyl cellulose .

referring now to fig1 it will be seen that the main structural component of the back saver 1 is a chest platform 2 . the depicted shape of which is rectangular , but any desired shape may be utilized so long as the platform area adequately supports the chest / abdomen portion of a weightlifter . chest platform 2 normally has padded surface 15 affixed to and disposed on the top surface of the chest platform 2 . strapping means 16 , which is connected to the side ( or bottom ) of chest platform 2 , firmly secure padded surface 15 of the back saver against the chest / abdomen portion of a weightlifter . firmly affixed to the bottom side of chest platform 2 , adequately spaced apart , in the vicinity of the corners , are hinge mechanisms 11 , 12 , 13 and 14 . the hinge mechanisms provide attachment means for the other back saver components to the bottom side of the chest platform 2 . a left thigh support 3 is pivotally attached , at one end thereof , to the hinge mechanism 13 while the second end thereof is connected , by a pin hinge means 10 , to an outer leg 8 of a telescoping adjustment unit 5 . the second end of telescoping adjustment unit 5 , the far end of inner leg 7 , is pivotably attached to the hinge mechanism 12 . the right thigh support 4 is similarly attached being pivotably connected to chest platform 2 by hinge mechanism 14 , at one end thereof , and having its second end pivotably connected by a pin hinge means 9 to an outer leg 8 of a telescoping adjustment unit 6 , while the second end of telescoping adjustment unit 6 , the far end of inner leg 7 , is pivotably connected by a hinge mechanism 11 to the bottom side of chest platform 2 . both outer telescoping legs 8 , at the end surrounding the inner telescoping leg 7 , are split tube tapered ends 27 which have a threaded portion to allow a locking hub 26 to be screwed toward the tapered end thus causing the split tube tapered end to frictionally engage with the inner tube . thigh support 3 additionally has a thigh platform 19 firmly affixed in the vicinity of the pin hinge means 10 connection , but on the opposite side thereof . thigh platform 19 has a padded surface 20 , which cushions and protects the left thigh of a weightlifter , affixed to the surface of the thigh platform projecting away from the pin hinge means 10 connection . a strapping means 17 is attached to the lower part of the left thigh support 3 and , when connected , securely restrains the left thigh of the weightlifter against padded surface 20 . right thigh support 4 has a similar arrangement whereby a thigh platform 20 is firmly affixed thereto in the vicinity of the pin hinge means 9 connection , but on the opposite side thereof . a padded surface 22 is affixed to the surface of the thigh platform projecting away from the pin hinge means 9 connection . a strapping means 18 securely restrains the right thigh of the weightlifter against padded surface 22 . although the drawings show that the left and right thigh supports are separate units , it is possible to have them connected together to form one structural unit such as a &# 34 ; tee &# 34 ; shaped configuration . referring now to fig2 and 3 , it can be seen that a weightlifter 23 will initially have to position the padded surface 15 of the back saver 1 against his or her chest / abdomen portion . the weightlifter then connects strap means 16 to secure the back saver apparatus to the weightlifter &# 39 ; s chest / abdomen area . the weightlifter 23 is then ready to adjust the position of the thigh supports relative to the chest platform 2 . the weightlifter rotates both locking means 25 counter clockwise which gradually releases the locking arrangement and enables both inner legs 7 to telescope in or out of both outer legs 8 . when the desired adjustment is achieved , both locking means 25 are rotated clockwise thereby locking the desired adjustment . the weightlifter then secures strapping means 17 and 18 to lock the left and right thighs against padded surfaces 22 and 22 of the thigh supports 3 and 4 , respectively . while a screw - type locking means is provided in the embodiment shown , other types of locking means may be also utilized . the important thing is that locking means are provided to lock the thigh supports in a desired arrangement relative to the chest platform . once the back saver has been adjusted and strapping means secured , the weightlifter 23 is then ready to commence his weightlifting exercises with a barbell 24 , or other similar weightlifting device . when the weightlifter has completed his exercise routine , or desires a break , he can remove the back saver by releasing strapping means 16 , 17 and 18 . fig2 and 3 show the position of a weightlifter relative to the back saver at two different adjustments . fig2 shows the position at a 90 degree angle of the thigh supports relative to the chest platform , while fig3 shows a 50 degree angle of the thigh supports relative to the chest platform 2 . the inventor has found that a range from 50 to 90 degrees between these two components is most beneficial . nevertheless , a greater range of adjustment may be provided without departing from the scope and content of the present invention . while the fundamental and novel features of the invention have been shown and described , as applied to the preferred embodiment , it will be understood that various omissions , substitutions and changes of the form and details of the device illustrated and in its operation may be made by those skilled in the art , without departing from the spirit and scope of this invention . the embodiment of the invention in which exclusive property and privilege is claimed is defined as follows .

a weight - lifting apparatus , for reducing the amount of back injuries , having a chest platform to which thigh supports and telescoping adjustment and locking devices are pivotally connected . the unconnected ends of the thigh supports and the telescoping adjustment and locking devices being connected to one another enabling the thigh supports to pivot relative to the platform and lock the thigh support adjustment at any desired location . the apparatus is further provided with a strapping member to secure the apparatus to the chest / abdomen portion of a weightlifter .

the use of functionalized nanoparticles to develop antiviral agents that act by interfering with viral infection , in particular attachment and entry is gaining wide popularity ( tallury et al ., 2010 ; bowman et al ., 2008 ; lara et al ., 2010 ; vig et al ., 2008 ). these particles generally exhibit high surface to volume ratios , leading to entirely new properties as compared to the bulk form of the substance . for example , gold nanoparticles were shown to inhibit cell - to - cell spread of hsv ( baram - pinto et al ., 2010 ). zno has long been known for its antibacterial and antifungal properties including the recent report for selective destruction of tumor cells by zno nanoparticles and its potential in the development of anti - cancer agents ( rasmussen et al ., 2010 ). in addition , the use of zno nanoparticles in sunscreens is one of the most common uses of nanotechnology in consumer products ( beasley and meyer , 2010 ). recently the use of zno nanostructures has been suggested in nonresonant nonlinear optical microscopy in biology and medicine ( kachynski et al ., 2008 ). wo 2007 / 093808 a1 is directed to the use of nanoparticles of metals and / or metal compounds , including zno in the prevention of viral infection . there is a need in the art for efficient , well - tolerated and inexpensive agents for the treatment and / or prevention of conditions caused by viral infections . provided are specific applications of particles or particle agglomerates with semiconductor surfaces ( semiconductor particles , scps ) with polar defect sites that can be used as a viral particle binding substrate . the particles described herein have an average surface to volume ratio larger than 7 for a unit volume and have a preferred largest cross sectional length in a range of from about 100 nm to about 30 μm . a significantly enlarged average surface to volume ratio for a unit volume ( compared for example to less elaborate structures mainly with planar surfaces or to spherical particles ), as described herein , offers an advantageous potentially large binding interface between scps and the viral particles . the scps may be of similar size to or of smaller or larger size than any given target viral particle . scps with semiconductor surfaces comprising different metals ( e . g . zn , sn , fe , bi , al , in , zr , ti , ni ), metal - oxides ( e . g . zno , sno 2 , tio 2 , in 2 o 3 , fe 2 o 3 , bi 2 o 3 , al 2 o 3 zro 2 ), metal - sulphides , metal - nitrides and metal - carbides may be used for binding viral particles . various combinations from the above mentioned metals such as for example zn — fe , in — zn , sn — zn , in — zn — sn , in — sn , bi — zn , bi — sn , fe — bi , zn — ti , sn — ti , in — ti , etc . may also be used for binding viral particles . the particles or particle agglomerates may also comprise a mixture of at least two semiconductor compounds with polar defect sites . mass production of free standing scps using suitable synthesis techniques is one of the main requirements for their use in antiviral applications . one suitable method for the production of these scps is flame synthesis , described in wo 2011 / 116751 a2 . this method enables the production of large amounts ( kilograms ) of metal , metal - oxide , metal - sulphide , metal - nitride or metal - carbide scps in a cost - effective manner . the scps with an average surface to volume ratio larger than 7 for a unit volume may be of the snowflake type , having for example the shape of tetrapods , interconnected hexagonal rods , or sea urchins capped with nanoscopic filopodia - like structures . such forms exhibit high surface to volume ratios for a unit volume as compared to their bulk counterparts , leading to advantageous functional properties such as efficient viral particle binding . the largest cross sectional length of such scps should be between about 100 nm and about 30 μm . a general scp form may be a core - spike / filopodia - type structure , i . e . a structure consisting of a core covered by spikes . such a structure may have for example a metal or metal oxide core surrounded by spikes of metal oxide . the average diameter of the scp core may vary in the range of 100 nm to 10 μm , depending on the powder characteristics initially used for synthesis . the dimensions of the spikes may also be controlled by varying synthesis conditions ( mainly temperature and time ). the diameter of the spikes may range from 20 nm to 4 μm , whereas their length may vary from 25 nm to 20 μm . scps with these characteristics have the advantage of being self - supported , i . e . they do not require a substrate , and they can easily be handled for application . the viral binding activity of the scps not only depends on their surface polarity but is also strongly influenced by the existing polar defects , both intrinsic defects ( like grain boundaries , twin boundaries , vacancies / interstitials etc .) and extrinsic defects ( external doping elements ). the particles or particle agglomerates may thus be doped to generate polar defect sites . hence , metal , metal - oxide , metal - sulphide , metal - nitride , metal - carbide and / or mixed composition scps may be functionalized by suitable physical or chemical treatments to generate polar defect sites leading to the desired viral particle binding . metal - oxide ( for example zno , tio 2 , etc .) and / or metal - sulphide scps may be illuminated with ultraviolet ( uv ) light to generate polar defect sites . uv illumination results in the creation of electron - hole pairs ( depending on the bandgap ) which results in changes in surface polarities by creating oxygen vacancies in metal - oxide scps . in particular , zno - scps may be doped to generate polar defect sites for example by uv - treatment or by heating under h 2 - atmosphere . aging effects should be considered in this context : if the uv - treated metal - oxide scps remain in the dark for some time ( for example a few days ), oxygen in the atmosphere starts occupying the oxygen vacancies , thus neutralizing the polar defect sites . the doping may therefore occur directly before the use of the scps as a viral particle binding substrate , but it may also occur at another time before the use , taking these aging effects into account . common commercially available uv lamps may be used for scp illumination . however , since the penetration depth of uv radiation is not very large ( less than a few mm ), the illumination conditions should be chosen so as to enable an efficient generation of polar defect sites . scps according may be used to bind enveloped viral particles . these viral particles may be herpes simplex or human immunodeficiency viral particles or any other enveloped viral particles that bind to scps . these viral particles may thus for example be from the following groups : scps may be part of a pharmaceutical composition for the treatment and / or prevention of conditions caused by viral infection . such pharmaceutical compositions may contain particles or particle agglomerates in physiologically effective doses in a pharmaceutically acceptable carrier . in particular , zno - scps are effective at low concentrations ( 0 . 1 - 10 μg / ml ) and only exhibit cytotoxic effects at higher concentrations ( above 500 μg / ml ). such scps may thus be used in the preparation of a medicament for the treatment and / or prophylaxis of conditions caused by viral infection . this medicament may be used topically in form of suspensions , ointments , creams , lotions and / or lipsticks . the binding ( and removal ) of viral particles present in a liquid may be achieved by applying to the viral particle containing liquid a composition comprising the disclosed particles or particle agglomerates . the scps with bound viral particles may then be removed from the liquid by any method known in the art such as filtration , centrifugation , etc . moreover , viral particles present on a surface may be bound ( and removed from the surface ) by applying to a liquid a composition comprising particles or particle agglomerates as viral particle binding substrate , and putting that liquid in contact with the viral particle contaminated surface . such scp containing liquids may thus be used to wash surfaces and objects that should be freed from viral particles . also provided are methods for binding viral particles , wherein a composition comprising scps is applied to a surface , and this substrate surface is put contact with viral particles to enable binding . scps used in this method may suitably be formulated for application in an appropriate carrier , coating or solvent . scps may thus also for example be applied on conventional clinical tapes used for dressing wounds and lesions caused by viral infection . binding characteristics of scps further enable the generation of filters to trap viral particles . such filters may consist of a free - standing interconnected stable network of scps or alternatively of a filter scaffold onto which the scps are applied . hence , also provided is a method for binding viral particles by applying to a filter a composition comprising scps , and putting the filter in contact with viral particles . such a filter may be used to bind viral particles present in fluids as for example in viral particle contaminated water , in solutions , in culture media or in body fluids such as blood or also in the air . decontamination procedures or viral research may thus be additional uses of scps . also provided is a device for binding viral particles contained in fluids . such a device includes an scp - based filter for viral particles with the possibility to treat the scps so as to generate polar defect sites , as well as a pump mechanism to enable fluid circulation through the filter and the device in general . the large quantities ( several 100 grams ) of snowflake type zno - scps ( tetrapods , interconnected hexagonal rods , sea urchins capped with nanoscopic filopodia - like structures ) were synthesized by flame transport synthesis . the synthesized snowflake type zno powder stored in a glass tube is shown in fig1 a . compared to standard powder ( fig1 b a ), the synthesized zno powder shows a higher order of tetrapod structures and a snowflake - like symmetry ( fig1 b b ). scanning electron microscopy ( sem ) ( fig1 c ) shows the geometric orientation and morphology of the semiconductor particles powder . a typical cluster of zno - scps can form a well - ordered array of sea urchin - like structures with filopodia - type nanospikes ( fig1 d ). further analysis of the latter by sem revealed that lengths of the spikes are in the range of a few microns ( 2 to 8 μm ), with thicknesses ranging from 100 to 200 nm ( fig1 e ). cell toxicity of the zno - scps was determined using human dermal fibroblasts ( nhdf ; promocell , c - 12300 ). in terms of fibroblast viability , there is a clear concentration dependency of zno - scps toxicity ( fig2 a ). concentrations up to 500 μg / ml do not significantly impair cell viability . the concentration - effect curve for zno - scps treated with uv - light is slightly shifted to the right . the ec50 value derived from the curves increases approximately twofold after uv - light treatment from about 1 . 3 to 3 mg / ml zno . though this shift was statistically not significant , the results show that the toxicity of zno - scp is not increased by uv treatment . upon zno - scp treatment , there is only a slight concentration - dependent decrease in total protein in cell cultures ( fig2 b ). this could be explained by the fact that , especially at higher concentrations , a layer of zno structures covers the cell monolayer , and this might have prevented in part the detachment of dead cells upon washing . the concentration of zno - scps was kept below the toxic levels throughout the following experiments . zno - scps significantly block hsv - 1 entry into glycoprotein d ( gd ) receptor expressing cho - k1 cells the effect of zno - scps on hsv - 1 entry into the target cells was determined by using β - galactosidase expressing hsv - 1 reporter virus ( gl86 ) into wild type chinese hamster ovary ( cho - k1 ) cells expressing gd receptor nectin - 1 . as shown in fig3 a , hsv - 1 pre - incubation with zno - scps significantly blocks viral entry in a dose dependent manner in cho - k1 cells expressing gd receptors . the positive control cells treated with 1 × pbs ( untreated ) showed hsv - 1 entry . the blocking activity of zno - scps was pronounced even at low concentrations ( 0 . 1 μg / ml or 100 μg / ml ). human corneal fibroblasts ( cf ), a natural target for hsv - 1 infection , were used to further confirm the blocking activity of zno - scps on hsv - 1 entry . cf express hvem and 3 - ost - 3 as gd receptors ( tiwari et al ., 2006 ). as shown in fig3 ( b ), treatment with zno - scps ( 0 . 1 μg / ml or 100 μg / ml ) leads to a significant blocking of hsv - 1 entry . similar results were obtained with hela cells that express all the known gd - receptors ( data not shown ). in all cases , the mock treated cells used as positive control showed hsv - 1 entry . the results obtained with cf and hela cells are thus consistent with the results from nectin - 1 expressing cho - k1 cells : in all three in vitro systems , zno - scps at concentrations at least as low as 0 . 1 μg / ml significantly inhibit hsv - 1 entry . assuming that viral entry inhibition properties of zno - scps are due to their partial negatively charged oxygen vacancies , zno - scps were exposed to uv illumination ( raytech uv - lamp model r5 - fls - 2 ; midtown , conn ., usa ) for 30 min , which is known to generate additional oxygen vacancies and hence additional negative charge centers on the atomic scale at the surface ( wu and chen , 2011 ; kong et al ., 2008 ). in order to visualize the effect of uv illumination of zno - scps on viral binding , the scps were stained red via phalloidin staining ( fig4 a ). the uv treated red zno - scps were mixed with green fluorescent protein ( gfp )- tagged hsv - 1 ( vp26 ). as shown in fig4 c , uv - exposed zno - scps ( 0 . 1 mg / ml ) showed a significant viral trapping as evident by strong yellow co - localization signal as compared to uv - untreated red zno - scps ( fig4 b ). enhanced viral trapping by uv - exposed zno - scps also translates into enhanced viral inhibition : hsv - 1 ( kos ) virions were pre - incubated with either uv - treated zno - scps or uv - untreated zno - scps before infecting target cells . clearly , the uv - exposed particles were more efficient in blocking hsv - 1 entry ( fig4 d ). this result underlines the significance of negative charged molecules in hsv - 1 entry . zno - scp treatment inhibits hsv - 1 glycoprotein mediated cell - to - cell fusion and polykaryocyte formation finally , the effect of zno - scps during hsv - 1 glycoproteins mediated cell to cell fusion was investigated . the main emphasis of cell to cell fusion was to demonstrate the viral and cellular requirements during virus - cell interactions and also as means of testing viral spread . the goal was to determine whether zno - scps interaction with hsv - 1 envelope glycoproteins , essential for viral entry , affects cell to cell fusion . surprisingly , zno - scps treatment ( 0 . 1 mg / ml ) of effector cells expressing hsv - 1 glycoproteins impaired cell to cell fusion in cho - k1 cells expressing gd receptor nectin - 1 ( fig5 ). in parallel , the control untreated effector cells co - cultured with target cells showed the expected fusion ( fig5 ; black bars in panel a ). this response was further confirmed when polykaryocytes formation was visualized . zno - scps treated effector cells failed to form polykaryons when co - cultured with target cells ( fig5 b ; panel c ). the control untreated effector cells efficiently showed larger polykaryons ( fig5 b ; panel b ), while no polykaryons were observed in absence of hsv - 1 glycoprotein ( negative control , fig5 b ; panel a ). these results indicate that the presence of zno - scps significantly reduce viral penetration . zno - scps may therefore possibly disrupt the viral envelope glycoproteins binding to cell surface hs , thereby preventing the virus attachment , surfing , and fusion processes . to evaluate the broader significance of uv - treated zno - scps as an anti - hsv agent , the ability of scps to block viral entry for different clinically - relevant strains of hsv ( f , g , and mp ) ( dean et al ., 1994 ) was tested . here , nectin - 1 expressing cho ig8 cells that express β - galactosidase upon viral entry ( montgomery et al ., 1996 ) were used . the virulent strains were pre - incubated with scps , and then used for infecting the cells . the results from this experiment again showed that scps blocked entry of additional hsv strains as evident by onpg assay ( fig6 ; panel a ). finally , the in vivo significance of scps in an animal model was addressed . for this zebrafish embryos were chosen , since these provide a quick and easy model for testing hsv - 1 infection in vivo ( burgos et al ., 2008 ). as shown in fig6 , panel b , the scps were able to prophylactically block infection of the zebrafish embryos as well . this result underlines the promising character of scps for the development of effective anti - hsv prophylactic agents . the initial quantitative viral entry assay revealed that pre - treatment of hsv - 1 with zno - scps significantly affected the viral entry at non - toxic concentrations ( fig3 ). uv - irradiated zno - scps were even more potent in blocking hsv - 1 entry and spread . fluorescent imaging experiments further confirmed the quantitative viral entry data that uv - treated zno - scps neutralized the viral infectivity by “ viral - trapping ” or “ virostatic activity ”, which was evident from the enhanced accumulation of gfp - tagged virus around scps ( fig4 ). the viral trapping activity of scps can be explained as uv - exposure of zno spikes enhances the distribution of negative charge by oxygen vacancies , thereby allowing more viruses to bind . the major advantage of zno - scps is their effectiveness at lower concentrations ( μg ), the low cost of their synthesis , molecular specificity to viral envelope protein without affecting the expression of native heparan sulfate chains , and ease in designing particle capsules coated with additional anti - hsv - 1 agents including envelop glycoprotein b ( gb ) and d ( gd ) based peptides to block hsv - 1 entry receptors while keeping the hsv - 1 virions trapped to scps . zno is an integral component of skin , face and lip creams where hsv - 1 infection or reactivation leads to painful blisters . therefore zno - scps exhibit strong potentials to develop anti - hsv medication for cold sore in the form of a protective gel or cream , which may be further activated by uv - light , also by the uv portion of sun light . in addition , such scps will become the bench tool to create additional antiviral agents against many other viruses with the conjugation of peptides against specific virus envelope glycoproteins . furthermore , they can also be used to deliver antiviral peptides with minimal pharmacokinetic problems together with enhanced activity of drug for the treatment of hsv infection . taken together the findings of the inventors support the model by which partially negatively charged zno - scps trap hsv - 1 to prevent virus - cell interaction ( fig7 ), which are key steps for successful viral infection of the host cells and , therefore , scps - based compounds present a useful therapeutic approach . this is further supported by the observation that scps also block infection in vivo , in a zebra - fish model of hsv - 1 infection ( fig6 b ). the following examples are intended to illustrate the present invention but not to limit the scope thereof . the snowflake type free standing complex network of interconnected zinc oxide semiconductor particles ( thickness in the range of 100 to 500 nm and length in the range of 1 to 5 μm ) which consists of hexagonal nanorods , tetrapods , nanocombs and nano - sea - urchin - like structures , were synthesized by a simple flame transport synthesis approach using a sacrificial polymer ( polyvinyl butyrol ) as the local host . commercial zn powder ( particle diameter ˜ 3 to 5 μm ; goodfellows , uk ) and polyvinyl butyrol powder ( pvb ; kuraray europe gmbh , germany ). the zn and pvb powders were mixed in particular ratio with the help of ethanol and then heated in a simple furnace at 900 ° c . for 1 hour . the process for semiconductor particle formation was used as previously described ( wo 2011 / 116751 a2 ). the microstructural evolution of different semiconductor particles inside snowflake type free standing powdery material was investigated by scanning electron microscopy ( sem ) using a philips xl - 30 microscope equipped with lab6 filament and energy dispersive x - ray diffraction analysis ( edax ) detector . sem images of different structures were recorded at 6 kv electron beam acceleration voltage with 20 μa beam current . a large quantity of snowflake type zno semiconductor particle powder was synthesized under identical conditions and used for different biomedical tests , as described in the next examples . the cytotoxicity of the zno - scps after 24 h of treatment was determined by mtt assay ( mosmann , 1983 ; röhl and sievers , 2005 ) and protein measurement ( lowry et al ., 1951 ). after two days in culture , when confluence was reached , human fibroblasts ( nhdf ; promocell , c - 12300 ) were treated with zno - scps . these were either first irradiated with uv light at 254 nm for one hour distributed in a thin layer in a plastic petri dish or they were directly brought into suspension with culture medium at a concentration of 5 mg / ml . this stock solution was used to prepare the samples . for the treatment culture medium was completely removed and cells were treated with 0 , 0 . 1 , 0 . 2 , 0 . 5 , 1 . 0 , 2 . 0 , and 5 . 0 mg / ml zno - scps (−/+ uv ) for 24 h . cells were washed carefully one time with the culture medium before using mtt assay or three times with phosphate - buffered saline ( pbs ) before the protein measurement . using the mtt assay , the portion of viable cells in treated cultures was estimated on the basis of the formation of formazan by viable cells . formazan and protein suspensions were transferred to new plates before colorimetrical measurements performed at 570 nm for the mtt test and at 630 nm for the protein determination ( universal microplate reader elx800uv ; bio - tek instruments inc .). hela and cultured human corneal fibroblasts ( cf ) cells were grown in dulbecco &# 39 ; s modified eagles medium ( dmem ; invitrogen corp .) supplemented with 10 % fetal bovine serum ( fbs ), while wild - type cho - k1 cells expressing gd receptors ( nectin - 1 and 3 - ost - 3 ) were grown in ham &# 39 ; s f - 12 medium ( gibco / brl ) supplemented with 10 % fbs , and penicillin and streptomycin ( gibco / brl ). normal human dermal fibroblasts ( nhdf ; promocell , c - 12300 ) were cultured in quantum 333 medium ( paa , u15 - 813 ) supplemented with 1 % ( v / v ) penicillin / streptomycin . subcultured fibroblasts ( maximum until passage 9 ) were seeded into 96 - well microtiter plates at a seeding density of 100 , 000 cells / cm 2 in 310 μl / cm 2 medium . cells were kept at 37 ° c . and 5 % co 2 . the β - galactosidase expressing recombinant hsv - 1 ( kos ) gl86 ( shukla et al ., 1999 ) and gfp - expressing hsv - 1 ( k26gfp ) were provided by p . g . spear ( northwestern university , chicago ) and p . desai ( johns hopkins university ) ( desai and person , 1998 ). the plasmids expressing nectin - 1 ( pbg38 ) was kindly provided by dr . spear ( northwestern university , chicago ). viral entry assays were based on quantitation of β - galactosidase expressed from the viral genome in which β - galactosidase expression is inducible by hsv infection . cells were transiently transfected in 6 - well tissue culture dishes with plasmids expressing hsv - 1 entry receptors ( necitn - 1 expression plasmids ) using lipofectamine 2000 at 1 . 5 μg dna per well in 1 ml . at 24 h post - transfection , cells were re - plated in 96 - well tissue culture dishes ( 2 × 10 4 cells per well ) at least 16 h prior to infection . cells were washed and exposed to serially diluted pre - incubated virus with zno - scps or 1 × pbs at two fold dilutions in 50 μl pbs containing 0 . 1 % glucose and 1 % heat inactivated cs ( pbs - gcs ) for 6 h at 37 ° c . before solubilization in 100 μl pbs containing 0 . 5 % np - 40 and the β - galactosidase substrate , o - nitro - phenyl - β - d - galactopyranoside ( onpg ; immunopure , pierce , rockford , ill . ; 3 mg / ml ). the enzymatic activity was monitored at 410 nm by spectrophotometry ( biotek instruments inc . elx808 absorbance microplate reader , vt , usa ). the free standing zno - scps ( sea urchin and tetrapod shaped particles containing long filopodia - type of spikes ) from snowflake type powder were distributed in a thin layer in a plastic petri dish followed by irradiation with uv light at 254 nm for 30 min at room temperature . in this experiment zno - scps were stained with 10 nm rhodamine conjugated phalloidin ( invitrogen ) followed by mixing with gfp - tagged hsv - 1 or with 1 × pbs . images of fluorescent labeled zno - scps ( either pre - treated with uv , uv +, or untreated , uv −) mixed with gfp - tagged hsv - 1 were acquired using a confocal microscope ( nikon d - eclipse - c1 ) with the software ez - c1 . in this experiment , the cho - k1 cells ( grown in f - 12 ham , invitrogen ) designated as “ effector ” cells were co - transfected with plasmids expressing four hsv - 1 ( kos ) glycoproteins , ppep98 ( gb ), ppep99 ( gd ), ppep100 ( gh ) and ppep101 ( gl ), along with the plasmid pt7emcluc that expresses firefly luciferase gene under the t7 promoter ( tiwari et al ., 2004 ). wild - type cho - k1 cells express cell surface hs but lack functional gd receptors , therefore they have been transiently transfected with hsv - 1 entry receptors . wild type cho - k1 cultured cells expressing hsv - 1 entry receptor nectin - 1 considered as “ target ” cells were co - transfected with pcagt7 that expresses t7 rna polymerase using chicken actin promoter and cmv enhancer . the untreated effector cells expressing pt7emcluc and hsv - 1 essential glycoproteins and the target cells expressing gd receptors , transfected with t7 rna polymerase , were used as the positive control , while the effector cells pre - treated with the zno - scps were used for the test . for fusion , at 18 h post transfection , the target and the effector cells were mixed together ( 1 : 1 ratio ) and cocultivated in 24 well - dishes . the activation of the reporter luciferase gene as a measure of cell fusion was examined using reporter lysis assay ( promega ) at 24 h post mixing . clinical strains of hsv ( f , g , and mp at 25 pfu / cell ) were either pre - incubated with 1 × pbs (−) or with zno - scps (+) at 10 μg / ml for 90 min at room temperature . after 90 min of incubation the two pools of viruses were incubated on cho ig8 cells that express β - galactosidase upon viral entry . the viral entry blocking was measured by the onpg ( ortho - nitrophenyl - β - d - galactopyranoside ) assay . β - galactosidase expressing hsv - 1 ( kos ) gl86 reporter virus at 2 × 10 8 pfu were pre - incubated with 1 × pbs (−) or with 100 μg / ml scps (+) for 2 hours before infecting zebrafish embryos for 12 h . hsv - 1 entry in both the groups of embryos was measured by the onpg assay . akhtar , j ., shukla , d ., 2009 . viral entry mechanisms : cellular and viral mediators of herpes simplex virus entry . febs j . 276 , 7228 - 7236 . 454 baram - pinto , d ., shukla , s ., gedanken , a ., sarid , r ., 2010 . inhibition of hsv - 1 attachment , entry , and cell - to - cell spread by functionalized multivalent gold nanoparticles . small 6 ( 9 ), 1044 - 1050 . beasley , d . g ., meyer , t . a ., 2010 . characterization of the uva protection provided by avobenzone , zinc oxide , and titanium dioxide in broad - spectrum sunscreen products . am j clin dermatol . 11 , 413 - 421 . bowman , m . c ., ballard , t . e ., ackerson , c . j ., feldheim , d . l ., margolis , d . m ., melander , c ., 2008 . inhibition of hiv fusion with multivalent gold nanoparticles . j am chem soc . 130 ( 22 ), 6896 - 6897 . burgos , j . s ., ripoll - gomez , j ., alfaro , j . m ., sastre , i ., valdivieso , f ., 2008 . zebrafish as a new model for herpes simplex virus type - 1 infection . zebrafish 5 , 323 - 333 . corey , l ., spear , p . g ., 1986 . infections with herpes simplex viruses . n . eng . j . med . 314 , 686 - 691 . dambrosi , s ., martin , m ., yim , k ., miles , b ., canas , j ., sergerie , y ., boivin , g ., 2010 . neurovirulence and latency of drug - resistant clinical herpes simplex viruses in animal models . j . med . virol . 82 , 1000 - 1010 . dean , h . j ., terhune , s ., shieh , m . t ., susmarski , n ., spear , p . g ., 1994 . single amino acid substitutions in gd of herpes simplex virus 1 confer resistant to gd - mediated interference and cause cell type - dependent alterations in infectivity . virology 199 , 67 - 80 . 474 desai , p ., person , s ., 1998 . incorporation of the green fluorescent protein into the herpes simplex virus type 1 capsid . j . virol . 72 , 7563 - 7568 . hill , j . m ., ball , m . j ., neumann , d . m ., azcuv , a . m ., bhattacharjee , p . s ., bouhanik , s ., clement , c ., lukiw , w . j ., foster , t . p ., kumar , m ., kafman , h . e ., thompson , h . w ., 2008 . the high prevalence of herpes simplex virus type 1 dna in human trigeminal ganglia is not a function of age or gender . j . virol . 85 , 8230 - 8234 . kachynski , a . v ., kuzmin , a . n ., nyk , m ., roy , i ., prasad , p . n ., 2008 . zinc oxide nanocrystals for non - resonant nonlinear optical microscopy in biology and medicine . j phys chem c nanomater interfaces . 112 , 10721 - 10724 . kaye , s . b ., baker , k ., bonshek , r ., maseruka , h ., grinfeld , e ., tullo , a ., easty , d . l ., hart , c . a ., 2000 . human herpesviruses in the cornea . br . j . opthalmol . 84 , 563 - 571 . kong , j ., chu , s ., olmedo , m ., li , l ., yang , z ., liu , j ., 2008 . dominant ultraviolet light emissions in packed zno columnar homojunction diodes appl . phys . lett . 93 , 132113 . lara , h . h ., ayala - nuñez , n . v ., ixtepan - turrent , l ., rodriguez - padilla , c . 2010 . mode of antiviral action of silver nanoparticles against hiv - 1 . j . nanobiotechnology . 20 ; 8 : 1 . liesegang , t . j ., 2001 . herpes simplex virus epidemiology and ocular importance . cornea 20 , 1 - 13 . liesegang , t . j ., 2001 . herpes simplex virus epidemiology and ocular importance . cornea 20 , 1 - 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( 1951 ) j . biol . chem . 193 , 265 - 275 . montgomery rebecca i ., warner morgyn s ., lum brian j ., spear patricia g . herpes simplex virus - 1 entry into cells mediated by a novel member of the tnf / ngf receptor family . cell . 1996 ; 87 ( 3 ): 427 - 436 . mosmann , t ., 1983 . rapid colorimetric assay for cellular growth and survival : application to proliferation and cytotoxicity assays . j . immunological methods 65 , 55 - 63 . rasmussen , j . w ., martinez , e ., louka , p ., wingett , d . g ., 2010 . zinc oxide nanoparticles for selective destruction of tumor cells and potential for drug delivery applications . expert opin drug deliv . 9 , 1063 - 1077 . roehl , c ., sievers , j ., 2005 . microglia is activated by astrocytes in trimethyltin intoxication . toxicology and applied pharmacology 204 , 36 - 45 . schulte , e . c ., sauerbrei , a ., hoffmann , d ., zimmer , c ., hemmer , b ., mühlau , m ., 2010 . acyclovir resistance in herpes simplex encephalitis . ann neurol . 67 , 830 - 833 . shukla , d ., liu , j ., blaiklock , p ., shworak , n . w ., bai , x ., esko , j . d ., cohen , g . h ., eisenberg , r . j ., rosenberg , r . d ., spear , p . g ., 1999 . a novel role for 3 - o - sulfated heparan sulfate in herpes simplex virus 1 entry . cell 99 , 13 - 22 . superti , f ., ammendolia , m . g ., marchetti , m ., 2008 . new advances in anti - hsv chemotherapy . curr med chem . 15 , 900 - 911 . tallury , p ., malhotra , a ., byrne , l . m ., santra , s ., 2010 . nanobioimaging and sensing of infectious diseases . adv drug deliv rev . 62 ( 4 - 5 ): 424 - 37 . tiwari , v ., clement , c ., duncan , m . b ., chen , j ., liu , j ., shukla , d ., 2004 . a role for 3 -° sulfated heparin sulfate in cell fusion induced by herpes simplex virus type 1 . j . gen . virol . 85 , 805 - 809 . tiwari , v ., clement , c ., xu , d ., valyi - nagy , t ., yue , b . y ., liu , j ., shukla , d ., 2006 . role for 3 - o - sulfated heparan sulfate as the receptor for herpes simplex virus type 1 entry into primary human corneal fibroblasts . j . virol . 80 , 8970 - 8980 . travan , a ., marsich , e ., donati , i ., benincasa , m ., giazzon , m ., felisari , l ., paoletti , s ., 2010 . silver - polysaccharide nanocomposite antimicrobial coatings for methacrylic thermosets . acta biomater . [ epub ahead of print ] vig , k ., boyoglu , s ., rangari , v ., sun , l ., singh , a ., pillai , s ., singh , s . r ., 2008 . use of nanoparticles as therapy for respiratory syncytial virus inhibition . nanotechnology 2008 : life sciences , medicine & amp ; bio materials — technical proceedings of the 2008 nsti nanotechnology conference and trade show , volume 2 : 543 - 546 . whitley , r . j ., kimberlin , d . w ., roizman , b ., 1998 . herpes simplex viruses . clin . infect . dis . 26 , 541 - 553 . wu , j . m ., chen , yi - r ., 2011 . ultraviolet - light - assisted formation of znonanowires in ambient air : comparison of photoresponsive and photocatalytic activities in zinc hydroxide . the journal of physical chemistry 115 ( 5 ), pp 2235 - 2243 .

specific applications of particles and particle agglomerates with semiconductor surfaces are provided . the particles and particle agglomerates display a high affinity for viral particles , and may be used therapeutically and / or prophylactically to treat or prevent viral infections . the particles and particle agglomerates may also be used to remove viral particles from a surface or fluid , e . g ., as an absorbent in a filter , applied to surfaces to render them virostatic , and as tool to handle viral particles , e . g ., for research , diagnostic , or decontamination purposes .

the acoustic impedance of body tissue is generally estimated to be about 1 . 58 megrayls , and since most materials that are otherwise satisfactory for the diaphragm have a higher acoustic impedance , the first alternative mentioned above would normally be used so that the acoustic impedance of the liquid would have to exceed that of the diaphragm . for various reasons set forth below , polyethylene having an acoustic impedance of 1 . 8 megrayls was chosen for the diaphragm so that it was necessary to find a liquid having an acoustic impedance of close to 2 . 05 . this was difficult to do and is essentially satisfied by a preferred mixture for this particular application that has the following proportions by weight : of these constituents , cesium chloride has been found to be the most critical because it has the high density necessary to increase the acoustic impedance of a liquid in which it is dissolved . the percentages of the other constituents can be varied more than the percentage of cesium chloride without appreciably changing the acoustic impedance of the mixture . in fact , other liquids may be substituted for the other three constituents if the proportions are changed . it should be kept in mind that a selection of a diaphragm material having a greater acoustic impedance than 1 . 8 megrayls would require a greater proportion of cesium chloride and , conversely , that selection of a diaphragm material having a lesser acoustic impedance than 1 . 8 megrayls but larger than 1 . 6 megrayls would require a smaller proportion of cesium chloride . furthermore , if the diaphragm significantly attenuates the acoustic waves passing through it , the waves reflected from the diaphragm / body interface will have an amplitude less than the amplitude of the acoustic waves reflected from the liquid / diaphragm interface so that complete cancellation of the waves in the central portions of the reflected pulses does not occur . in this event , the acoustic impedance of the liquid can be decreased by use of a lesser portion of cesium chloride so as to reduce the amplitude of the waves reflected at the liquid / diaphragm interface to that of the waves reflected from the diaphragm / body interface and produce perfect cancellation of the central portions of the reflected pulses . in addition to having an appropriate acoustic impedance , the liquid should have an acoustic velocity very close to the velocity of 1 . 6 of the soft tissue as this will make the interpretation of the image easier . it should also have as low a viscosity as possible so as to minimize the attenuation of the acoustic pulses passing through it . an attenuation of about 1 db / cm at 5 mhz would be satisfactory . fig1 illustrates an ultrasound system having a stand - off device 2 interposed between a body b being examined and a transducer 4 . a transceiver 6 is coupled to the transducer 4 so as to cause it to transmit ultrasonic waves . the transceiver 6 also receives the electrical signals produced by the transducer 4 in response to the impingement thereon of reflections of the transmitted waves and produces signals from which an image can be formed . these signals are coupled via a band - pass filter 8 to a cathode ray tube 10 or other image - forming means . the stand - off device 2 is a chamber containing liquid that causes the transducer 4 to stand off from the body b so that certain portions of the body b are in a region of better focus . if the system is of the sector - scanning type , the stand - off device 2 also causes those structures near the surface of the body b to be well within the sector where they are surrounded by enough other structures to simplify identification . reference is now made to fig2 a for a description of the construction of one embodiment of a stand - off device that may incorporate the invention . this embodiment is similar to that which is the subject of a joint invention of myself and thaddeus g . minior , the patent application for which is filed concurrently herewith . in order to simplify the drawing , all parts of the device are shown as being transparent , but certain parts could just as well be opaque . the chamber of the stand - off device is formed in part by a diaphragm d that is made of pliant material such as polyethylene in the form of a hollow rectangular box 12 with one side open . the inner edge of this open side is adhered , as indicated at 14 , to the outer edge of an open side of a hollow rectangular box 16 that is made of rigid material . the bottom 17 of the box 16 , which is opposite its open side , is provided with an opening 18 and a filling port 20 through which liquid can be introduced into the interior of the chamber formed by the hollow boxes 12 and 16 . a clip c that is mounted on the outside of the bottom 17 has an opening in its top 22 that is in registration with the opening 18 in the bottom 17 of the box 16 . when a transducer is mounted within the clip c so as to fill the opening 18 , the chamber is completely enclosed . resilient fingers 24 , 26 and 28 that are longitudinal portions of an annulus and perpendicular to the bottom 17 of the box 16 are respectively provided with inwardly extending curved ridges 24 &# 39 ;, 26 &# 39 ; and 28 &# 39 ;. the fingers 24 , 26 and 28 are centered 90 degrees apart so that there is a fourth finger , not visible in this view , that is opposite the finger 26 . fig2 b shows the exterior of a cylindrical transducer 30 having an array 32 of parallel crystals protruding from one end and covered by a lens 33 . the outer diameter of the transducer 30 is such that it can be axially inserted within the resilient fingers 24 , 26 and 28 so as to position the array 32 in the opening 18 in the bottom 17 of the box 16 . an annular step 34 on the outside of the transducer 30 is positioned so as to exert radially outward forces on the ridges 24 &# 39 ;, 26 &# 39 ; and 28 &# 39 ; respectively at the inner ends of the fingers 24 , 26 and 28 so as to push the fingers outwardly as the transducer 30 is being inserted . when the transducer 30 reaches its final position , the step 34 slides above the ridges 24 &# 39 ;, 26 &# 39 ; and 28 &# 39 ; and the fingers move inwardly so as to hold the transducer 30 firmly in place . if the top 22 of the clip c is sealed to the bottom 17 of the box 16 , liquid can be introduced into the interior of the boxes 12 and 16 that form the chamber via the filling port 20 , in which event the liquid is coupled to the array 32 by contact with the lens 33 . instead of coupling the liquid to the transducer 30 in this manner , a membrane ( not shown in fig2 a ) could be sealed to the bottom 17 of the box 16 so as to be in contact with the lens 33 when the transducer 30 is mounted in the clip c . such a membrane could be made of pliant material having an acoustic impedance similar to the transducer lens 33 or the liquid . fig3 which is a cross - section aa of fig2 a , further illustrates the structure just described and has , in addition , a membrane 36 that is sealed to the outside of the bottom 17 of the box 16 so as to cover the opening 18 therein . although not shown in fig3 the filling port 20 would extend through the membrane 36 . most importantly , fig3 shows the liquid l that is introduced into the chamber formed within the boxes 12 and 16 via the filling port 20 . as best seen in fig3 the diaphragm / body interface is at i b and the liquid / diaphragm interface is indicated at i l . the characteristics of a number of liquid mixtures are set forth in the table below . the percentages of each component refers to its relative weight . as can be seen , the preferred liquid indicated by an asterisk (*) has an acoustic impedance of 2 . 02 megrayls that is very near to what is required to make the amplitude reflection coefficients at the diaphragm / body and liquid / diaphragm interfaces the same when the body is considered to have an impedance of 1 . 58 megrayls and the portion of the chamber wall of the diaphragm d that is adjacent the body is made of light density polyethylene having an impedance of 1 . 8 megrayls . as previously noted , however , a liquid having a different acoustic impedance would be preferable if the body tissue and / or the diaphragm had different impedances than those just indicated . it should also be noted that substances other than one or more of glycerin , ethylene glycol and propylene glycol could be used , but in accordance with this invention a liquid having an acoustic impedance sufficiently greater than that of any practicable diaphragm so as to reflect acoustic waves at the liquid / diaphragm interface that exhibit any significant degree of cancellation with the acoustic waves reflected at the diaphragm / body interface will have to contain cesium chloride or the solution of some high density salt . thallous format or iodoform may be used in place of cesium chloride but their toxicity makes them less desirable for stand - off devices that are to be in contact with the human body . another salt that may be used is cesium sulfate . __________________________________________________________________________fluid mixturescesium ethylene propylene characteristicschlorideglycerin glycol glycol density velocity impedance attenuation__________________________________________________________________________ * 15 . 0 % 20 . 6 % 41 . 2 % 23 . 2 % 1 . 23 1 . 63 2 . 02 low ˜ 1db / cm for 5mhz15 . 8 % 15 . 2 % 41 . 6 % 27 . 3 % 1 . 22 1 . 61 1 . 9611 . 8 % 16 . 0 % 43 . 6 % 28 . 6 % 1 . 18 1 . 61 1 . 8914 . 5 % 19 . 6 % 53 . 6 % 12 . 2 % 1 . 21 1 . 63 1 . 9713 . 1 % 17 . 3 % 47 . 2 % 22 . 8 % 1 . 20 1 . 63 1 . 9657 . 0 % 28 . 5 % 14 . 5 % -- 1 . 22 1 . 67 2 . 04 high20 . 0 % 27 . 0 % 53 . 0 % -- 1 . 30 1 . 64 2 . 13 high16 . 5 % 22 . 3 % 61 . 0 % -- 1 . 26 1 . 66 2 . 09 high -- 50 . 0 % -- 50 . 0 % 1 . 14 1 . 65 1 . 88 high__________________________________________________________________________ * preferred fluid the reasons for using the four ingredients noted above so as to produce a fluid having a high acoustic impedance are as follows . as previously stated , acoustic impedance is the product of density and acoustic velocity so that a fluid having a high acoustic impedance could be formed with components that have either a high density or a high velocity or both , but the velocity should be kept near the velocity of sound in soft body tissue in order to avoid refraction of the acoustic waves at the diaphragm / body interface . furthermore , the attenuation of sound waves should be a minimum and the vapor pressures of the various ingredients should be low so that the fluid will retain its initial characteristics . the table below sets forth the pertinent characteristics of a number of materials that might be used for the diaphragm . ______________________________________ required acoustic liquiddiaphragm im - im - material pedance pedance remarks______________________________________natural 1 . 74 1 . 92 a . high vapor leakage raterubber b . attacked by fluids used as coupling , e . g ., mineral oil c . difficult to form sufficiently thin diaphragmneoprene -- -- poly - 1 . 73 1 . 89 if sufficiently flexible , notbutadine strong enoughpoly - 1 . 68 1 . 79 less flexiblemethyl - pentanepoly - 2 . 0 2 . 50urathinedimethyl - 1 . 8 2 . 05pentene * poly - 1 . 8 2 . 05 a . easily formedethylene b . low vapor leakage c . very flexible and pliable d . slow crack propagation rate______________________________________ * preferred a . it has an acoustic impedance that is close to that of body tissue . c . it has low vapor leaking rate and low gas leaking rate compared to many other organic materials . e . it has good tear strength and also has a slow crack propagation rate . in order for the waves respectively reflected at the diaphragm / body and liquid / diaphragm interfaces to be precisely 180 degrees out of phase , the thickness of the diaphragm should be an odd number of quarter - wavelengths of the carrier frequency in the material from which the diaphragm is made . in the preferred material , polyethylene , a quarter - wavelength of a carrier frequency of 5 mhz is 4 . 0 mils . this thickness was used because it is sufficiently durable and yet flexible enough to conform to the contours of the patient &# 39 ; s body as desired . in actual practice , it will be found that the sheet material from the factory varies in thickness and further changes in thickness can result when the box 12 is formed by vacuum - forming or other methods . omitting the effect of attenuation , which is generally negligible , the variation in thickness in percent of one quarter - wavelength has the effect on the uncancelled energy relative to the energy cancelled for an ideal thickness as indicated in the following table . ______________________________________thickness variation uncancelled energy______________________________________ + 50 % of quarter - wavelength 6 dbquarter - wavelength 0 db - 20 % of quarter - wavelength 6 db - 50 % of quarter - wavelength 13 db______________________________________ if the carrier frequency were 10 mhz , the ideal thickness of a diaphragm would be 2 mils , but as this may be too fragile , thicknesses of 6 mils could be used . with the information set forth herein , one skilled in the art could formulate a liquid having the acoustic impedance required for obtaining highly advantageous cancellation of the acoustic waves reflected from the diaphragm / body and liquid / diaphragm interfaces , low attenuation and the desired acoustic velocity . as one departs from the ideal relationships , the degree of cancellation of the reflected waves is reduced , but more than 6 db reduction in reflected pressure wave amplitude is considered desirable .

a stand - off device for use with acoustic transducers is described in which a chamber having a diaphragm portion contains liquid , the ratio of the acoustic impedance of said diaphragm to the acoustic impedance of soft body tissue and the ratio of the acoustic impedance of said liquid to the acoustic impedance of said diaphragm being whole numbers or fractions , and said diaphragm being of such thickness that reflections from its diaphragm / body interface , when it is held against the body of a patient , and its liquid / diaphragm interface tends to cancel each other .

fig1 is a schematic view of a milking device 1 according to the invention that operates in this embodiment on compressed air and is provided for this purpose with a compressor 2 which is provided with a pressure vessel 3 . the pressure vessel 3 is connected to a compressed air conduit 5 which in this case is provided with a pressure meter 4 comprising a regulator and filter unit . the pressure conduit or compressed air conduit 5 is shown schematically connected to various milking points 6 , each milking position or milking point for a single cow in this embodiment . in fig1 one of the milking points 6 is again represented schematically in greater detail and comprises the following components . a milking set is in this case provided with four teat cups 7 ( also known as teat holders ), by means of short milk conduits 26 connected to a milk claw 27 . the milk claw 27 is connected to a milk conduit 28 which discharges the milk to an air separator 9 and which is provided with a valve 17 which can be operated , for example , by means of compressed air or electrically . the compressed air conduit 5 has a branch to each milking point 6 from which one branch leads to a valve block 10 which splits the branch into teat cup compressed air conduits 11 which are each connected to a teat cup . each teat cup 7 has in this case a teat cup compressed air conduit 11 . the milk is discharged by means of the milk conduit 13 out of the air separator 9 to a collecting tank ( not shown ). the air separator 9 is provided with a valve 14 in the milk conduit 13 which is operable by means of compressed air or electronically . the air separator 9 can be introduced into the space above the milk at overpressure . for this purpose , the air separator 9 is connected to a branch of the compressed air conduit 5 . this branch can in this case be closed by means of a valve 15 operated by compressed air or electrically . the air separator 9 is further provided with a vacuum generator 12 , in a preferred embodiment of the same type as the vacuum generator described hereinafter of the teat cups 7 . this vacuum generator is driven by means of air under overpressure or compressed air which originates via branches from the compressed air conduit 5 . the milking device 1 further comprises a control unit 38 which is operatively connected to a sensor 37 for the measuring of the flow of milk ( flow rate ), and optionally other milk properties such as colour , conductivity , temperature and the like . furthermore , the control unit is in this case operatively connected to the vacuum generator 12 , to the valves 14 , 15 , 16 and 17 , and to the valve block 10 . fig2 is a cross section of one of the teat cups 7 . the teat cup 7 has a peripheral teat cup wall 20 having therein a teat liner 21 comprising a teat space 40 , and between the peripheral teat cup wall 20 and teat liner 21 the teat cup space 24 . the teat liner may be of a type known per se . the teat cup 7 is in this case provided with an ejector - type vacuum generator 23 . an ejector 23 of the si02 - 2 coax technology type , as sold by piab sa , can be used as the ejector 23 . this allows the ( reduced ) pressure in the teat cup space 24 to be adapted very rapidly . in addition , it has been found to be possible to produce during milking a taut pressure curve , i . e . a pulsation cycle having a smooth course . an ejector 23 of this type comprises an inlet 41 , a flow channel and in the flow channel an outflow opening 43 having a sectional surface area which is smaller than the sectional surface area of the inlet 41 . the outflow opening 43 opens into the flow channel in a flow chamber having a sectional surface area which is larger than the sectional surface area of the outflow opening 43 . the flow chamber is connected to an outlet 22 and via said outlet to a space outside the ejector . the venturi effect increases the speed , and thus reduces the pressure , of air flowing through the outflow opening 43 . the arrangement in series of a plurality of outflow openings , each having a larger sectional surface area , provides a larger vacuum capacity and an improved output . an arrangement of this type is also referred to as a “ multistage ejector ”. an embodiment comprising an adaptable outflow opening in order locally to set a specific reduced pressure is conceivable . an ejector is also referred to as an aspirator or mini - eductor . in fact , an ejector may be regarded as a device which generates a reduced pressure by means of application of the venturi effect , for example by means of a fluid having a flow speed or a difference in pressure before and after a restriction . the ejector 23 is received in a receiving space in the peripheral wall , as a result of which the inlet 41 and the outlet 22 emerge outside of the teat cup space 24 and the flow channel is fluidically connected to the teat cup space 24 . in the illustrated embodiment the outlet 22 in the ejector is directed toward the udder . it is also conceivable , possibly in order to prevent disturbance to a cow as a result of the air which is blown out , to reverse the ejector , i . e . for example to point the outlet 22 in the ejector away from the udder or teat during use . it may also be conceivable to connect the outlet 22 to a return conduit , for example if use is made of a fluid other than air . in the situation illustrated in fig2 a reduced pressure is applied to the milk conduit 26 and no overpressure is placed on the inlet in the ejector 23 . as a result , an atmospheric pressure prevails in the teat cup space 24 , and when a teat 30 is introduced into the teat space 40 the teat liner is closed as a result of the difference in pressure between the teat cup space 24 and the teat space 40 . for rapid response of the milking device , it is preferable if the teat cup space 24 is as small as possible . in one embodiment this teat cup space 24 is smaller than approximately 50 ml , and even smaller than 25 ml has been found to be possible . a lower limit for that volume is approximately 5 ml . such small volumes can be achieved by , for example , at least locally thickening the inside of the teat cup wall 20 , or at least locally thickening the wall of the teat liner 21 . a combination of these measures is also conceivable . use may also successfully be made of an unround teat liner , such as a teat liner having a triangular or square cross section instead of the teat space in the teat liner 21 . fig3 shows the milk cup or teat cup 7 from fig2 in the milking position . in this situation , compressed air is supplied and thus a vacuum / reduced pressure generated by the ejector 23 in the teat cup space 24 between the teat cup wall 20 and the teat liner 21 . as a result , the teat liner is drawn open and the reduced pressure of the milk conduit 26 reaches the milk opening in the teat and the milk m is able to be expelled . fig4 shows the teat cup 7 from fig2 in a condition in which the outlet 22 in the ejector 23 is closed off by hand and an overpressure is thus produced in the teat cup space 24 . as a result , the teat space 40 is closed and the milk conduit 26 is almost impervious to external influences , and hardly any air is drawn in . fig5 a shows the milk cup 7 in the same situation as fig4 , the opening being in this case provided with an electronically regulatable valve 32 , in this case in the closed position . the overpressure in the teat cup space 24 closes the teat space 40 . fig5 b shows the milk cup 7 from fig5 with the valve 32 in the open position . a reduced pressure is again produced in the teat cup space 24 and the teat space opens . fig6 a - 6d show a milk cup 7 having a 2 - valve 33 , 34 operation and a shut - off valve in the form of a ball valve 35 instead of the valve 32 . in the condition shown in fig6 a , the valve 34 is open and the valve 33 closed . a reduced pressure is produced in the teat cup space 24 and the ball 35 is in its top position as a result of the fact that air blows out of the ejector . in fig6 b the valve 34 is closed , the valve 33 is closed and as a result of gravity the ball 35 will block the outlet in the ejector . a relatively stable reduced pressure prevails in the teat cup space 24 . milk m flows . in fig6 c the valve 33 is opened and air under atmospheric pressure flows toward the teat cup space 24 . because a reduced pressure still prevails in the teat space 40 , the teat space 40 will be closed . this final situation is shown in fig6 d . fig7 a - 7d are various views of a milk cup 7 provided with a teat cup space filler 46 . the teat space filler 46 has a hollow cylindrical shape . the outer circumference of the teat cup space filler 46 adjoins the teat cup wall 20 . the inner circumference of the teat cup space filler 46 is provided with peripheral thickenings . these thickenings are attached to the upper edge and the lower edge of the teat cup space filler 46 which is provided between the teat cup wall 20 and the teat liner 21 to reduce the size of the teat cup space 24 in order to shorten the response times of the milking device . in one embodiment this teat cup space 24 is smaller than approximately 50 ml , and even smaller than 25 ml has been found to be possible . a lower limit for that volume is approximately 5 ml . also conceivable is a peripheral thickening which covers a portion of the inner circumference of the teat cup space filler 46 . in this way , the teat liner 21 is locally compressed somewhat by the thickening . it is thus possible to determine in advance the location of the folded seam of the teat liner when the teat liner 21 is closed as a result of the difference in pressure between the teat cup space 24 and the teat space 40 . fig7 b is a cross section along line b in fig7 a . it will be clear that the teat cup space filler 46 reduces the size of the teat cup space 24 . the teat liner 21 is not closed and rests against the teat cup space filler 46 . it is possible for the teat liner 21 to be in this case pressed in somewhat in order to determine in advance the location of the folded seam of the teat liner when the teat liner 21 is closed as a result of the difference in pressure between the teat cup space 24 and the teat space 40 . fig7 c is a cross section along line c in fig7 d . the teat liner 21 is in this case compressed as a result of the difference in pressure between the teat cup space 24 and the teat space 40 . fig8 is a perspective sectional view of the teat cup space filler 46 from fig7 a - 7d . in this embodiment the teat cup space filler 46 is not rotationally symmetrical . fig9 - 9b show an embodiment of the teat cup 7 according to the invention . all alterations to the embodiment in fig2 - 4 will be described . in this embodiment the teat cup wall 20 is thickened in order to preform the teat liner 21 . accordingly , the teat cup space 40 is smaller when the teat liner 21 is closed as a result of the difference in pressure between the teat cup space 24 and the teat space 40 . furthermore , the preformed teat liner 21 allows it to be determined in advance about which folding line the teat liner 21 is closed . in this embodiment the ejector 23 is received within the cylindrical circumference of the milk cup 7 . the ejector 23 is fluidically connected to the teat cup space 24 by means of connections 43 . the outlet 22 in the ejector 23 is directed radially away from the teat 30 . this milk cup 7 can be handled by the integrally received ejector 23 and by the outlet 22 which the operator can easily seal using his finger . in one embodiment two ejectors are placed directly above in the air separator , whereas the teat cups are further connected to a reduced pressure conduit . this is done to eliminate a number of disadvantageous effects and to use the ejectors as effectively as possible . the ejectors are in this case , for example , 2 - stage ejectors , for example the si32 - 2 from piab . an advantage of this is that the vacuum level can be controlled / regulated rapidly and directly in the event of faults occurring in the vacuum level . a vacuum is thus generated in the air separator . the air separator is connected to the milk hose and can thus draw in air through the milk hose and in this way there is produced via the collector and the milk hose a vacuum in the teat space , as a result of which milk flows out of the teat and is drawn via the receiving piece and milk hose to the air separator . as milk has a greater specific weight than air , the milk is not drawn into the ejector but rather the milk drops into the milk / air separator . one ejector is operated by a directly controlled 2 / 2 proportional valve . this 2 / 2 proportional valve is activated by the plc and is operated continuously throughout the milking process in order to be able to obtain the vacuum level of from 10 - 50 kpa . the other ejector is also operated by a directly controlled 2 / 2 proportional valve and operated by the plc . however , the difference from the activation of the other ejector consists in the fact that this ejector is not activated continuously . this ejector is positioned in order to maintain the vacuum level at the desired level to eliminate faults . these faults are produced for the most part by the pulsation strokes of the pulsator . by then activating the ejector , for example , 0 . 1 sec earlier than the pulsation stroke , the fault in the vacuum level can be eliminated and removed by the use of the second ejector . in order during start - up of the installation to reach the desired vacuum level within a short time , the operator may choose simultaneously to activate the two ejectors for a short time . this allows the desired vacuum level to be reached within a very short time and also the buffer vessel to be brought to the desired pressure . the advantage which can be obtained from this embodiment is that the flow of milk can be milked in a controlled manner . this means that the milk vacuum for each cow can be regulated electronically and the vacuum can thus be adapted to the amount of milk which the cow produces . as a result , teat point loading during milking is limited as far as possible and irritated teats are prevented . in this case too , the air separator is directly connected to the buffer vessel . the ejectors thus also ensure that the buffer vessel is pressurized and kept under pressure . the buffer vessel is positioned in order to be able to intercept any faults . the pulsator is also placed directly above the buffer vessel and also then obtains the pulsation vacuum therefrom . the advantage of the use of the ejector is that the ejector does not have to be activated continuously , but only during the milking process . this has the advantage that it is to a certain degree (± 30 %) more energy - efficient than current technologies in which the vacuum pump is operated continuously throughout the milking process . in another embodiment the buffer vessel is not coupled directly to the air separator . however , there is placed in the buffer vessel an ejector which keeps the buffer vessel at a higher vacuum than that required in the air separator . the vacuum level in the air separator is then regulated by means of a vacuum regulator which regulates the vacuum level back to the desired vacuum level , for example 40 kpa . the air separator is thus connected to the buffer vessel via the vacuum regulator . the advantage of this embodiment is that the fluctuations in pressure which are produced by faults of , for example , the pulsator can be eliminated substantially directly by means of this buffer vessel . fig1 is a schematic view of an embodiment of a milking device 1 according to the above - described embodiment according to the invention . this embodiment operates , again , based on compressed air and , again , includes a compressor 2 which is provided with a pressure vessel 3 . the pressure vessel 3 is connected to the compressed air conduit 5 which is in this case provided with a pressure meter 4 comprising a regulator and filter unit . the pressure conduit or compressed air conduit 5 is shown schematically connected to various milking points 48 , each milking position or milking point for a single cow in this embodiment . in fig1 one of the milking points 48 is represented schematically in greater detail . the milking point 48 comprises the following components . the milking point 48 is in this case provided with four teat cups 49 ( also referred to as teat holders ). the teat cups are in this case of a more traditional embodiment in which each is connected via a reduced pressure conduit or vacuum conduit 50 to an in this case common pulsator 55 . each teat cup 49 is in this case further connected to a milk claw 27 by means of a short milk conduit 26 . the milk claw 27 is in turn connected to a milk conduit 28 which discharges the milk to an air separator 51 . the air separator 51 is brought to a reduced pressure . for this purpose , the air separator 51 is in this case operatively connected to the vacuum generator 54 . also , the air separator 51 is in this case openly connected to a buffer vessel 53 . the compressed air conduit 5 has , as stated hereinbefore , a branch to each milking point 48 from which one branch leads to the vacuum generator 54 . before the conduit reaches the vacuum generator 54 , said vacuum generator is split in order to be able to activate by means of the proportional 2 / 2 valve 57 and 58 two ejectors of the vacuum generator 54 . the milking device 48 further comprises a control unit 56 which is operatively connected to sensors 63 and 62 for the measuring of the level of the milk in the air separator 51 and the level of the milk in the pressure chamber 52 . furthermore , the control unit is in this case operatively connected to the reduced pressure generator or vacuum generator 54 , to the valves 59 , 60 , 57 , 58 , and to the pulsator 55 which is positioned above the buffer vessel 53 . the pulsation stroke is transmitted by means of the reduced pressure conduits 50 to the teat cup space of each of the teat cups 49 . the mode of operation of the outlined embodiment from fig1 is as follows . milk is discharged by means of the air separator 51 via the valve 59 to the pressure chamber 52 . this pressure chamber 52 has a specific content , allowing the milking speed and amount to be measured by means of the sensor 62 . when the level of the milk reaches the sensor 62 , the valve 59 will close and the milk will be pressed away by means of an overpressure which is introduced through the compressed air conduit via the valve 60 into the pressure chamber 52 . the milk is then discharged via the milk conduit 13 to a collecting tank ( not shown ). the valve 61 will be closed again once the level has dropped to / below the sensor 62 , after which the valve 59 will open again and the pressure chamber 52 will be brought back to a reduced pressure . the cycle can proceed again . fig1 shows schematically in greater detail an embodiment of , inter alia , an air separator 51 from fig1 . as far as possible , the reference numerals correspond to fig1 . the proportional 2 / 2 valve 57 and 58 ( both of which include a coil ) controls the required amount of fluid under overpressure by means of the inlet 41 in the vacuum generator through a flow channel of the vacuum generator 54 , in this case a 2 - stage ejector , as a result of which a reduced pressure is produced in the air separator 51 . the fluid under overpressure leaves the vacuum generator 54 by means of the outflow opening 43 and is discharged by means of a muffler 64 . the reduced pressure which is generated by the vacuum generator 54 provides via the vessel of the air separator 51 a reduced pressure in the milk conduit 28 . as a result of this reduced pressure , the milk is drawn out of the teats . the milk is discharged via the milk conduit 28 to the air separator 51 . the ( pneumatically activated ) valve 59 is opened in the illustration . this allows the milk to flow also into the pressure chamber 52 . when the level of the milk reaches the sensor 63 , the control unit ( not shown ) will allow the valve 59 to be closed by means of the operation of the cylinder 70 . when the valve 59 is closed , a fluid under overpressure , in this case compressed air which will be introduced into the pressure chamber by means of the valve 60 , will press the milk away along the non - return valve 61 through the milk discharge conduit 13 by means of the main conduit 69 to the milk storage tank ( not shown ). when the level of the milk reaches below the bottom sensor 62 , the 3 / 2 valve 60 will cease to press the milk away and said valve will also deaerate the pressure chamber 52 : the overpressure is also , again , discharged by means of this 3 / 2 valve 60 . once in the pressure chamber 52 the overpressure has been reduced again , the valve 59 can be opened again and , as soon as the overpressure on the pressure chamber has been removed , the non - return valve 61 will be closed again , after which the process recommences . during the opening of the valve 59 the cylinder 70 will fall . as a result of the fact that the valve 59 is designed with a certain degree of play around the piston rod of the cylinder 70 , this valve 59 will not also fall in the same way ; this is due to the fact that there still prevails in the pressure chamber 52 an atmospheric pressure and in the air separator 51 a reduced pressure , as a result of which this valve 59 is still pressed into the seat of the connecting tube 66 . this atmospheric pressure will be discharged only via the space between the valve 59 and the piston rod of the cylinder 70 by means of the ejector 54 , as a result of which there is produced in the pressure chamber 52 a reduced pressure and the weight of the milk and the reduced pressure push the valve 59 downward onto the cap nut at the end of the piston rod of the cylinder 70 . the advantage of opening the valve 59 in this way is that this will produce no air swirls in the milk located in the air separator . fig1 shows a number of graphs with the pressure course in a milking point 48 from fig1 . the top graph shows the reduced pressure of the pulsation cycle which is caused by the pulsator . this pulsation cycle lasts for one second , after which it recommences . this pulsation stroke produces faults in the vacuum level . these faults have to be eliminated . this is done by starting to use one of the ejectors for this purpose . by activating this ejector 0 . 1 second earlier than the pulsation cycle commences , a fault in the vacuum level can be corrected . in this graph the activation of the ejector is represented by the middle graph in which the overpressure on the ejector is indicated as a function of time . the ejector is in this case activated by giving it a short pulse . as a result , the ejector creates in turn vary rapidly a reduced pressure . the activating of the ejector creates a very stable vacuum level which is represented in the bottom graph . finally , fig1 shows a detail from the illustration of fig1 . in fact , this to a large extent integrates the reduced pressure generator 54 with the air separator 51 . the upper lid 65 of the air separator 51 has a head space which is openly connected to the vessel of the air separator 51 . an ejector is received in the head space . the ejector has an inlet 41 for fluid under overpressure and an outlet 43 for the fluid . the inlets for air are indicated by the oblique arrows . the flow of the fluid under overpressure from the inlet 41 to the inlet 43 produces a reduced pressure , as a result of which air is drawn in by means of the side inlets . in this design this allows air to be drawn directly out of the vessel of the air separator 51 . the present description of the mode of operation relates to fig1 . a compressor 2 is placed centrally in the milking device using the pressure vessel 3 . compressed air is passed by means of conduits 4 to the locations in the milking device where a vacuum has locally to be created such as teat cups 7 and the air separator 9 . the peripheral teat cup wall 20 contains the teat liner 21 including the teat 30 . the teat cup 7 has a teat cup space 24 between the teat cup 20 and the teat liner 21 , where there is located the ejector 23 through which compressed air is blown . this produces a vacuum around the teat liner 21 , as a result of which the teat 30 is opened and the milk is able to flow . the air flow leaves the teat cup through the opening 22 . as a result of the supplied compressed air , the ejector 12 generates in the air separator 9 a vacuum , as a result of which air is drawn in through the long milk hose 28 , the milk collector 27 and the short milk hoses 26 . this produces the milk vacuum in the teat spaces 40 , as a result of which milk m is drawn out of the teat and is discharged through the milk hoses and to the milk receptacle , in this case the air separator 9 . as a result of the milk vacuum , the milk m is drawn out of the opened teat 30 . the valve block 10 subsequently interrupts the flow of compressed air in a pulsating manner , and the air inlet replaces the air outlet as the opening . this produces normal atmospheric pressure in the teat cup space 24 , causing the teat to close . subsequently , the high - pressure air flow is allowed again and the cycle recommences . when the outlet / inlet 22 is closed off by hand , as shown in fig4 , or electronically by means of a valve , as represented in fig5 a - 5b , an overpressure will be produced in the teat cup space 24 as a result of the fact that the compressed air no longer has an exit . as a result , the teat liner 21 will close and the milk cup 7 can easily be placed around the teat . the control unit 38 activates the valve block 10 ; as a result , the milk vacuum is regulated in such a way that the teat point 31 is loaded as little as possible during milking . when the teat holder 7 is in operation , vacuum and the pressure of the outside air prevail alternately in the pulsation space ( teat cup space 24 ). vacuum ( reduced pressure ) prevails in the teat space 40 during milking . when the pressure inside and outside the teat liner is identical , the liner is in an opened — normal — position . because in this situation milk flows out of the teat , this period is referred to as the suction stroke or b phase . after some time the pulsator breaks off the connection of the pulsation space to the vacuum conduit and then allows outside air to flow into the pulsation space . there is now produced between the inside and outside of the teat liner wall a difference in pressure which causes the wall of the teat liner under the teat to collapse and the teat liner to close . this situation is referred to as the rest stroke or d phase . no milk then flows out of the teat . subsequently , the pulsator again allows a vacuum in the pulsation space , as a result of which the cycle of movement of the teat liner is repeated . a vacuum and outside air pressure or atmospheric pressure prevail in the pulsation space of the teat holders alternately . the drawing - off of air and the allowing of air to flow take up a certain amount of time . these periods form the transition phases . the pressure course during the alternation of vacuum and outside air can be represented in a curve . a complete alternation is referred to as the pulsation cycle . the pulsation cycle consists of four components ( see also fig1 , top graph ), also referred to as phases : in order to analyze the pulsation curve , the curve is provided with measurement lines . the bottom measurement line is placed 4 kpa above the base line , the top measurement line 4 kpa beneath the top of the curve . the various phases start and end at the intersections of the measurement lines and the pulsation curve . the duration of a phase can be represented both in milliseconds and in percentages of the pulsation cycle . generally , the phases are given in percentages of the cycle time . the suction stroke consists of the a and b phase , the rest stroke of the c and d phase . the suction / rest stroke ratio is represented as a + b : c + d . p / min , the number of pulsations , is usually from 50 to 65 pulsations per minute . the suction / rest ratio is usually from 50 : 50 to 70 : 30 . a high s : r ratio of 65 : 35 / 70 : 30 is often combined with approximately 60 p / min . the a phase must preferably be no longer than 20 percent of the cycle time and at most 200 ms . the b phase must , under iso recommendations , be at least 30 percent or 300 ms of the cycle time . it is assumed that 55 percent ( 550 ms ) can be used as the maximum value . the c phase causes what are known as cyclic vacuum variations . there are no specific standards for these . generally , the c phase is from 10 to 15 percent . c phases of shorter than 10 % would appear to be less desirable . the d phase may be no shorter than 15 percent of the cycle time or 150 ms . an upper limit of 300 ms would appear to be the maximum . in the case of flow of milk - controlled pressure exchange systems , the number of pulsations and the design of the pulsation curve are not constant ; instead , these are controlled by the flow of milk . a cow which produces a large amount of milk is in this case milked with a higher s : r ratio than a cow which produces a small amount of milk . in many cases , the number of pulsations / minute is also adapted . the reduced pressure will usually be about 50 kpa , in particular from approximately 38 - 45 kpa . it has been found that the use of the ejector as described allows a very beneficial pulsation curve to be achieved . it is even possible to adapt or to adjust the pulsation curve for each teat ( for example in a cow ). in addition , the reaction time of the ejector can be made very short . it will be understood that the foregoing description is intended to illustrate the mode of operation of preferred embodiments of the invention , and not to limit the scope of the invention . starting from the foregoing discussion , a person skilled in the art will immediately think of a large number of variations which fall under the spirit and the scope of the present invention .

the invention relates to a milking device for milking animals , the required vacuum being , for example , generated by generating compressed air using a compressor and passing said compressed air through the system , the compressed air creating a vacuum at all required locations by means of the venturi system . because this vacuum differs at the various locations , the reduced pressure can be regulated precisely and adapted as required .

the present invention has significant benefits across a broad spectrum of endeavors . it is the applicant &# 39 ; s intent that this specification and the claims appended hereto be accorded a breadth in keeping with the scope and spirit of the invention being disclosed despite what might appear to be limiting language imposed by the requirements of referring to the specific examples disclosed . to acquaint persons skilled in the pertinent arts most closely related to the present invention , a preferred embodiment that illustrates the best mode now contemplated for putting the invention into practice is described herein by , and with reference to , the annexed drawings that form a part of the specification . the exemplary embodiment is described in detail without attempting to describe all of the various forms and modifications in which the invention might be embodied . as such , the embodiments described herein are illustrative , and as will become apparent to those skilled in the arts , may be modified in numerous ways within the scope and spirit of the invention . although the following text sets forth a detailed description of numerous different embodiments , it should be understood that the detailed description is to be construed as exemplary only and does not describe every possible embodiment since describing every possible embodiment would be impractical , if not impossible . numerous alternative embodiments could be implemented , using either current technology or technology developed after the filing date of this patent , which would still fall within the scope of the claims . to the extent that any term recited in the claims at the end of this patent is referred to in this patent in a manner consistent with a single meaning , that is done for sake of clarity only so as to not confuse the reader , and it is not intended that such claim term by limited , by implication or otherwise , to that single meaning . further , terms such as “ pivoting portion ” and “ rear portion ” and other terms may be used interchangeably in some instances . a walker 100 with an adjustable strap 132 is shown in fig1 . the walker 100 in this particular embodiment comprises four portions disposed around the perimeter of the walker 100 . a right portion 108 is rigidly connected to a front portion 112 , which is rigidly connected to a left portion 104 . the connection between the left portion 104 and a rear portion 116 is a hinged connection 140 such that the rear portion 116 is rotatable about the hinged connection 140 relative to the remaining portions 104 , 108 , 112 . one skilled in the art will appreciate further embodiments where the connections between the portions 104 , 108 , 112 are not rigid . rather , in alternative embodiments the connections may be hinged or otherwise mobile to allow for articulation between the portions 104 , 108 , 112 . similarly , one skilled in the art will appreciate embodiments where the portions 104 , 108 , 112 are a single continuous portion . when the walker 100 is in a closed position , the rear portion 116 rotates about the hinged connection 140 and a distal end of the rear portion 116 contacts a first end of the right portion 108 . the distal end of the rear portion 116 and the first end of the right portion 108 may selectively connect to define a user region and secure and fully enclose the user within the walker 100 . this selective connection may include , but is not limited to , a latch - and - eyelet connection , a magnetic connection , a velcro ® connection , a snap fastener connection , a button connection , connections where a protrusion on the rear portion 116 is held in place in a channel or depression on the right portion 108 with a moveable lever or arm , and any other connection that selectively connects the distal end of the rear portion 116 and the first end of the right portion 108 . one skilled in the art will appreciate that the selective connection and hinged connection 140 in fig1 are merely exemplary in nature , and these connections may be positioned between any portions of the walker 100 in any combination . fig1 shows an adjustable strap 132 disposed between the front portion 112 and the rear portion 116 of the walker 100 . in this embodiment , the adjustable strap 132 is connected to the front portion 112 , and the adjustable strap 132 is operatively connected to a retraction device 128 , which is connected to the rear portion 116 . the adjustable strap 132 is generally centered on the front portion 112 , and the retraction device 128 is generally centered on the rear portion 116 . in other embodiments , the retraction strap 132 may include a retraction device 128 at both ends , and in yet further embodiments , the retraction strap 132 may have more than two ends disposed on one or more portions of the walker 100 . the retraction device 128 may be any device that retracts or extends an end of the adjustable strap 132 . examples of possible retraction devices 128 include , but are not limited to , a snubbing winch , a wakeskate winch , a glider winch , an air winch , a hoist , a pulley , and a winch puller . in addition , the possible sources of power for the retraction device 128 include , but are not limited to , an ac motor , a dc motor , hydraulic power , pneumatic power , solar power , an internal combustion engine , and a hand crank . embodiments of the retraction device 128 may include a ratchet and pawl system to prevent the adjustable strap 132 from inadvertently extending unless the pawl is retracted . again , one skilled in the art will appreciate embodiment of the present invention where the adjustable strap 132 has two or more ends , and more than one retraction device 128 is employed to retract or extend the two or more ends of the adjustable strap 132 . a seat 136 is optionally disposed on the adjustable strap 132 in the embodiment depicted in fig1 . the seat 136 may be connected or selectively connected at any point along the adjustable strap 132 . the seat 136 may be a conventional seat like a bicycle seat or a seat cushion . the seat 136 may also be an unconventional seat such as a bar or ball . in some embodiments , the seat 136 is a modular design . a receiving portion may be disposed on any point along the adjustable strap 132 . then a seat portion may be selectively connected to the receiving portion to provide a seat 136 on the adjustable strap 132 . with this two - piece configuration , a given walker 100 may accommodate any user and his or her personal seat . in some embodiments , the seat 136 and / or adjustable strap 132 may include lights such as leds or glow - in - the - dark materials or paints to illuminate the seat 136 and / or adjustable strap 132 in dimly - lit conditions . the walker 100 in fig1 comprises a left leg set and a right leg set . the right leg set comprises a fore leg 120 and an aft leg 124 . in this embodiment , the legs 120 , 124 each comprise a proximate end positioned on the right portion 108 and a distal end positioned near the ground . the proximate ends of the legs 120 , 124 are each disposed in a channel on the underside of the right side 108 . thus , the proximate ends of the legs 120 , 124 are allowed to translate positions along a longitudinal axis of the right side 108 . next , the fore leg 120 and the aft leg 124 are hingedly connected to one another at a midpoint of the fore leg 120 and a midpoint of the aft leg 124 or any other point along the fore leg 120 or aft leg 124 . therefore , as the proximate ends of the legs 120 , 124 translate positions in their respective channels , the legs 120 , 124 move about each other in a scissor - like fashion . the legs 120 , 124 may selectively lock in place in their respective channels when the legs 120 , 124 are in a collapsed position , when the legs 120 , 124 are in an extended position , or any position in between . the collapsibility of the leg sets allow for a compact reduction in size of the walker 100 . as mentioned above , the connections between the portions 104 , 108 , 112 , 116 may all be hinged or otherwise movable relative to one another . therefore , during operation the leg sets may be collapsed and the portions 104 , 108 , 112 , 116 may be folded against one another to form a fully collapsed walker 100 that may fit into a brief case or small location . in a further embodiment , hydraulic devices may be disposed on either side of the hinged connection between the fore leg 120 and the aft leg 124 such that extension and retraction of a hydraulic piston moves the legs 120 , 124 in a scissor - like fashion . one skilled in the art will appreciate other location to dispose the hydraulic pump such as in the above - mentioned channels among other locations . in addition , instead of having the portions 104 , 108 , 112 , 116 , some embodiments of the present invention may comprise only a single , continuous portion . in this embodiment , the scissor - like actuation of the legs 120 , 124 allows the walker 100 to collapse to the ground , then a user may position themselves over the adjustable strap , and the scissor - like movement of the legs 120 , 124 may raise the single , continuous portion upwards to enclose the user . the left leg set in fig1 is generally identical to the right leg set ; the left leg set comprise a fore leg and an aft leg . one skilled in the art will appreciate embodiments where the left leg set is not generally identical to the right leg set . further , one skilled in the art will appreciate embodiments of the present invention that have one leg set , no leg sets , or more than two leg sets . one skilled in the art will appreciate a variety of dimensions of the walker 100 . for example , in some embodiments , the left portion 100 is between approximately 42 ″ and 48 ″ in length , wherein “ approximately ” implies variation of +/− 10 %. in various embodiments , the left portion 100 is between approximately 30 ″ and 60 ″ in length . the right portion 108 may be identical in length to the left portion 104 in some embodiments . in alternative embodiments , the right portion 108 may comprise two pieces wherein the selective connection to define the user region exists between the two right portion 108 pieces and not between the right portion 108 and the rear portion 116 . in this embodiment , a fore piece of the right portion 108 is between approximately 32 ″ and 40 ″. in a preferred embodiment , the right portion 108 is 36 ″. an aft piece of the right portion 108 is between approximately 6 ″ and 12 ″. in a preferred embodiment , the aft piece of the right portion 108 is approximately 8 ″. fig2 shows a top plan view of a walker 100 with an adjustable strap 132 . from this view , the open and closed positions of the rear portion 116 are shown . in the closed position , a distal end of the rear portion 116 contacts a first end of the right portion 108 to define a user region and form a perimeter around the user . when the rear portion 116 is in an open position , the rear portion 116 is coaxial with the left portion 104 , and in other embodiments the rear portion 116 is not coaxial with the left portion 104 . in some embodiments , the rear portion 116 may lock into this open position . for example , a deflectable protrusion may be disposed on the proximate end of the rear portion 116 that deflects as the rear portion 116 is opening then extends or “ pops ” into place into a depression in a first end of the left portion 104 . a mechanically - linked or electronically - linked connection may depress the protrusion and allow the rear portion 116 to close . this protrusion - depression combination may be located anywhere on the walker 100 . fig3 shows a side elevation view of a walker 100 with an adjustable strep 132 . as in other embodiments described herein , four portions form a square or rectangle around a user , wherein an adjustable strap is disposed between a rear portion 116 and a front portion 112 . in the embodiment illustrated in fig3 , the walker 100 has four legs 144 that descend downwardly from the four connections between the four portions . the four legs 144 provide a way to adjust the height of the walker 100 . the legs 144 are telescoping in nature . that is , in this embodiment , a lower portion of a leg 144 is at least partially disposed in an upper portion of the leg 144 . the lower portion of the leg 144 is selectively positioned at various longitudinal lengths within the upper portion of the leg 144 . in one embodiment , a plurality of apertures is disposed on the outer surface of the upper portion of the leg 144 . the lower portion of the leg 144 comprises a deflectable protrusion that deflects , extends , or “ pops ” into place in one of the apertures of the upper portion . to adjust the position of the lower portion of the leg 144 , and thus the height of the walker 100 , a user may depress the protrusion on the lower portion of the leg 144 while simultaneously pushing or pulling the lower portion of the leg 144 to a different longitudinal position relative to the upper portion of the leg 144 . one skilled in the art will appreciate variations of the telescoping legs 144 . first , one skilled in the art will appreciate positions adjustment mechanisms beyond the aperture - protrusion combination . for example , the upper and lower portions of the leg 144 may slide freely relative to each other . a clamp disposed on the upper portion of the leg 144 may selectively press into the side of the lower portion of the leg 144 such that the longitudinal position of the lower portion is fixed relative to the upper portion of the leg 144 . in some embodiments , the upper portion of the leg 144 may be disposed within the lower portion of the leg 144 . in various embodiments , the telescoping leg 144 may comprise more than two portions . fig4 shows a front elevation view of the walker 100 with an adjustable strap 132 . similar to previous embodiments , the walker 100 in fig4 has four portions that form a rectangle or square around a user where an adjustable strap is connected to a rear portion 116 and a front portion 112 . the legs 144 are telescoping in nature , and the position of a lower portion of the legs 144 may be adjusted relative to the position of an upper portion of the legs 144 to adjust the height of the walker 100 . also shown in fig4 is a seat 136 positioned on the adjustable strap 132 . embodiments of the seat 136 as a two - piece design are discussed elsewhere herein , but one skilled in the art will appreciate further seat 136 designs . for example , in one embodiment the seat 136 is not secured to the adjustable strap 132 , and the position of the seat 136 is not fixed . in some embodiments , the seat 136 may comprise protrusions that contact the adjustable strap 132 to provide friction between the seat 136 and the adjustable strap 132 . thus , the seat 136 may translate positions along the adjustable strap 132 if a large enough force is applied to the seat 136 , but the seat 136 may remain in place relative to the adjustable strap 132 if the threshold force is not applied . in yet other various embodiments , the plurality of snap fasteners may be used to locate the seat 136 relative to the adjustable strap . the seat 136 may include a first portion of a snap fastener , and the adjustable strap 132 may include a plurality of second snap fastener portions . thus , the seat 136 may snap into a discrete number of locations along the adjustable strap 132 . fig5 depicts an alternative embodiment of the walker 100 with an adjustable strap 132 . in this embodiment , there are only two portions : the front portion 112 and the rear portion 116 . the front portion 112 has a segment with a radius at one end of the walker 100 . at the ends of the segment , the front portion 112 extends into two tubular sections that are a parallel to each other . the rear portion 116 is symmetric to the front portion 112 in this embodiment , and the two tubular sections from the front portion 112 meet the two tubular sections of the rear portion 116 at a hinged connection 140 and a selective connection . these connections may be any type of connections discussed elsewhere herein or otherwise commonly known in the art . four legs 144 are disposed at different locations on the walker 100 . in the embodiment illustrated in fig5 , two legs 144 are disposed on the rear portion 116 , and two legs 144 are disposed on the front portion 112 . the two legs 144 on the rear portion 116 are positioned symmetric to the two legs 144 on the front portion 112 about a lateral plane through the walker 100 . the two legs 144 on the right side of the walker 100 are positioned symmetric to the two legs 144 on the left side of the walker 100 about a longitudinal plane through the walker 100 . one skilled in the art will appreciate other embodiments that are not symmetric about one or both of these planes . fig6 depicts an embodiment of the walker 100 with an adjustable strap 132 wherein the front portion 112 and the rear portion 116 have segments comprising a radius . this embodiment further comprises a lower front portion 148 and a lower rear portion 152 that are shaped like the front portion 112 and rear portion 116 , respectively . however , the lower portions 148 , 152 are disposed closer to the ground surface and add rigidity and sturdiness to the overall walker 100 . the relative spacing between the portions 112 , 116 and the lower portions 148 , 152 can take many forms . for example , in the embodiment depicted in fig6 , the lower portions 148 , 152 are connected to the legs 144 , which in turn extend downward and contact the ground either directly or via another component such as wheels , without or without spring dampeners . in alternative embodiments , the legs 144 terminate at the lower portions 148 , 152 . then , wheels , skis , treads , etc . may be connected to the lower portions 148 , 152 . thus , in some embodiments , the lower portions 148 , 152 are disposed between approximately 0 ″ and 12 ″ from the ground . in various embodiments , the lower portions 148 , 152 are disposed between approximately 3 ″ and 8 ″ from the ground . the lower portions 148 , 152 may also be disposed more proximate to the front portion 112 and the rear portion 116 . in one embodiment , the lower portions 148 , 152 are disposed adjacent to the portions 112 , 116 to provide added rigidity and sturdiness to the overall walker 100 . in some embodiments , the lower portions 148 , 152 are spaced between approximately 0 ″ and 12 ″ below the portions 112 , 116 . in various embodiments , the lower portions 148 , 152 are spaced between approximately 3 ″ and 8 ″ below the portions 112 , 116 . one skilled in the art will appreciate that the lower portions 112 , 116 may be disposed at any point along the legs 144 , including the midpoint of the legs 144 . in addition , one skilled in the art will appreciate a variety of lower portion 148 , 152 combinations that add rigidity and sturdiness to the overall walker 100 . for example , the walker 100 may comprise more than one set of lower portions 148 , 152 . in some embodiments , there may be more than one lower portions that correspond to more than one portions as noted in above embodiments that comprise four portions arranged in a square or rectangle . in the embodiment depicted in fig6 , the lower portions 148 , 152 , are made of a tubular shaped material . in alternative embodiments , the lower portions 148 , 152 may be solid tubular portions or solid portions of another shape such as hexagonal . further yet , the lower portions 148 , 152 may be straps , ropes , cords , wires , magnetic couplings , etc . one skilled in the art will appreciate a variety of dimensions of the walker 100 in fig6 . for example , the overall longitudinal length of the front portion 112 is between approximately 12 ″ and 24 ″. in a preferred embodiment , the overall longitudinal length of the front portion 112 is approximately 18 ″. the overall longitudinal length of the rear portion 116 is between approximately 2 ″ and 16 ″. in a preferred embodiment , the overall longitudinal length of the rear portion 116 is approximately 6 ″. the height of the legs 144 is between approximately 20 ″ and 40 ″. in a preferred embodiment , the height of the legs 144 is approximately 30 ″. fig7 depicts an isometric view of a walker 100 that comprises an adjustable strap 132 and a plurality of planar support portions 156 and angled support portions 160 . the planar support portions 156 extend rearward of the left portion 104 and the right portion 108 . then , the rear portion 116 is disposed between the planar support portions 156 . from the point where the rear portion 116 and a planar support portion 156 meet , an angled support portion 160 descends downwardly at an angle from a generally horizontal plane . in this embodiment , the angled support portion 160 extends toward a leg 144 descending from the right portion 108 . similarly and symmetrically , an angled support portion 160 descends downwardly from a rear portion 116 - planar support portion 156 connection at an angle from a generally horizontal plane , and the angled support portion 160 extends toward a leg 144 descending from the left portion 104 . in the embodiment depicted in fig7 , the planar support portion 156 and the angled support portion 160 that are proximate to the left portion 104 are hingedly connected to the left portion 104 and the leg 144 that descends from the left portion 104 , respectively . this hinged connection allows the rear portion 116 , planar support portions 156 , and angled support portions 160 to fully enclose the user within a user region of the walker 100 . the hinged connection may be any hinged - type connection discussed elsewhere herein or otherwise commonly known in the art . in various embodiments of the invention , each of the planar support portion 156 and the angled support portion 160 proximate to the left portion 104 comprise a hinged connection to the left portion 104 and the leg 144 that descend from the left portion 104 , respectively . in alternative embodiments , an intermediate portion may extend between the distal ends of the planar and angled support portions 156 , 160 , and the intermediate portion is hingedly connected to the left portion 104 or the leg 144 descending from the left portion 104 . the planar support portion 156 and the angled support portion 160 that are proximate to the right portion 108 selectively connect to the right portion 108 and the leg 144 that descends from the right portion 108 , respectively . this selective connection allows a the combination of the rear portion 116 , the planar support portions 156 , and the angled support portions 160 to latch into place and define a user region and fully enclose the user . the selective connection may be any device or method discussed elsewhere herein or otherwise commonly known in the art . in various embodiments of the invention , an intermediate portion may extend between the distal ends of the planar and angled support portions 156 , 160 proximate to the right portion 108 , and the intermediate portion is selectively connected to the right portion 108 or the leg 144 descending from the right portion 108 . one skilled in the art will appreciate a variety of dimensions of the walker 100 in fig7 . in some embodiments , the width of the front portion 112 is between approximately 18 ″ and 26 ″. in a preferred embodiment , the width of the front portion 112 is approximately 20 ″. in various embodiments , the length of the planar support portions 156 is between approximately 2 ″ and 12 ″. in a preferred embodiment , the length of the planar support portions 156 is approximately 6 ″. the height of the legs 144 is between approximately 20 ″ and 40 ″. in a preferred embodiment , the height of the legs 144 is approximately 30 ″. fig8 depicts a walker 100 that has an upper frame and a lower frame wherein the frame have different dimensions . the upper frame &# 39 ; s length 164 represents the largest dimension of the upper frame &# 39 ; s ovoid shape . in some embodiments , the upper frame &# 39 ; s length 164 is between approximately 20 ″ and 40 ″. in other embodiments , the upper frame &# 39 ; s length 164 is between approximately 25 ″ and 35 ″. in one embodiment , the upper frame &# 39 ; s length 164 is 30 ″. a lower frame &# 39 ; s length 168 is the largest dimension of the lower frame &# 39 ; s ovoid shape . in some embodiments , the lower frame &# 39 ; s length 168 is between approximately 26 ″ and 46 ″. in other embodiments , the lower frame &# 39 ; s length 168 is between approximately 31 ″ and 41 ″. in one embodiment , the lower frame &# 39 ; s length 168 is 36 ″. in this embodiment , the lower frame is larger in size than the upper frame , but it will be appreciated that the lower frame may also be equal or smaller in size than the upper frame . the walker in fig8 also has an upper frame width 172 and a lower frame width 176 . in some embodiments , the upper frame &# 39 ; s width 172 is between approximately 12 ″ and 32 ″. in other embodiments , the upper frame &# 39 ; s width 172 is between approximately 17 ″ and 27 ″. in one embodiment , the upper frame &# 39 ; s width 172 is 22 ″. in some embodiments , the lower frame &# 39 ; s width 176 is between approximately 17 ″ and 37 ″. in other embodiments , the lower frame &# 39 ; s width 176 is between approximately 22 ″ and 32 ″. in one embodiment , the lower frame &# 39 ; s width 176 is 27 ″. in this embodiment , the lower frame is larger in size than the upper frame , but it will be appreciated that the lower frame may also be equal or smaller in size than the upper frame . the upper frame and the lower frame of the walker 100 are separated by a predetermined distance known as the frame distance 180 . in some embodiments , the frame distance 180 is between approximately 20 ″ and 40 ″. in other embodiments , the frame distance 180 is between approximately 25 ″ and 35 ″. in one embodiment , the frame distance 180 is 30 ″. the walker 100 depicted in fig8 also has a number of components . a control 184 allows a user to operate the retractable or adjustable strap among other functions discussed elsewhere herein . the outlet plug 188 communicates electrical energy from an outlet to the walker 100 . it will be appreciated that the outlet plug is not the only way to energize the walker 100 . the walker 100 may be battery - powered , or powered by any other source of energy described elsewhere herein . the seat 136 in this embodiment comprises a seat belt , which may be used to secure a user to the seat 136 and prevent the user from slipping off of the seat 136 . the legs 144 in fig8 are spring - loaded , meaning that the legs 144 comprise a spring disposed at a lower end of the legs 144 to provide a dampening effect as the walker 100 is used and moved . the walker 100 also comprises a banner 192 disposed under the upper frame . the banner 192 can display messages for walker &# 39 ; s 100 user . for example , the banner 192 may indicate what medications the user is taking or other medical signals . further , the banner 192 may include messages about the user such as “ i am a vietnam veteran ”, the user &# 39 ; s church information , holiday slogans , or other identifying information about the user , the user &# 39 ; s location , or the user &# 39 ; s environment . the banner 192 in this embodiment is interconnected underneath the top frame . however , it will be appreciated that the banner 192 may be interconnected to any component of the walker , including , but not limited to , the lower frame , the seat , the strap , the power source , the legs , the wheels , the controls , and any positions on these components . for example , on the front section of the upper frame or the rear section of the upper frame , facing inward or outward . the banner may be interconnected to the walker 100 using any means commonly known in the art . this may include glue , screws , velcro ®, hook - and - loop fasteners , etc . the exemplary devices and methods of this disclosure have been described in relation to a walker with an adjustable strap and associated devices . however , to avoid unnecessarily obscuring the present disclosure , the preceding description omits a number of known structures and devices . this omission is not to be construed as a limitation of the scopes of the claims . specific details are set forth to provide an understanding of the present disclosure . it should however be appreciated that the present disclosure may be practiced in a variety of ways beyond the specific detail set forth herein . a number of variations and modifications of the disclosure can be used . it would be possible to provide for some features of the disclosure without providing others . although the present disclosure describes components and functions implemented in the aspects , embodiments , and / or configurations with reference to particular standards and protocols , the aspects , embodiments , and / or configurations are not limited to such standards and protocols . other similar standards and protocols not mentioned herein are in existence and are considered to be included in the present disclosure . moreover , the standards and protocols mentioned herein and other similar standards and protocols not mentioned herein are periodically superseded by faster or more effective equivalents having essentially the same functions . such replacement standards and protocols having the same functions are considered equivalents included in the present disclosure . the present disclosure , in various aspects , embodiments , and / or configurations , includes components , methods , processes , systems and / or apparatus substantially as depicted and described herein , including various aspects , embodiments , configurations embodiments , subcombinations , and / or subsets thereof . those of skill in the art will understand how to make and use the disclosed aspects , embodiments , and / or configurations after understanding the present disclosure . the present disclosure , in various aspects , embodiments , and / or configurations , includes providing devices and processes in the absence of items not depicted and / or described herein or in various aspects , embodiments , and / or configurations hereof , including in the absence of such items as may have been used in previous devices or processes , e . g ., for improving performance , achieving ease and / or reducing cost of implementation . the foregoing discussion has been presented for purposes of illustration and description . the foregoing is not intended to limit the disclosure to the form or forms disclosed herein . in the foregoing detailed description for example , various features of the disclosure are grouped together in one or more aspects , embodiments , and / or configurations for the purpose of streamlining the disclosure . the features of the aspects , embodiments , and / or configurations of the disclosure may be combined in alternate aspects , embodiments , and / or configurations other than those discussed above . this method of disclosure is not to be interpreted as reflecting an intention that the claims require more features than are expressly recited in each claim . rather , as the following claims reflect , inventive aspects lie in less than all features of a single foregoing disclosed aspect , embodiment , and / or configuration . thus , the following claims are hereby incorporated into this detailed description , with each claim standing on its own as a separate preferred embodiment of the disclosure . moreover , though the description has included description of one or more aspects , embodiments , and / or configurations and certain variations and modifications , other variations , combinations , and modifications are within the scope of the disclosure , e . g ., as may be within the skill and knowledge of those in the art , after understanding the present disclosure . it is intended to obtain rights which include alternative aspects , embodiments , and / or configurations to the extent permitted , including alternate , interchangeable and / or equivalent structures , functions , ranges or steps to those claimed , whether or not such alternate , interchangeable and / or equivalent structures , functions , ranges or steps are disclosed herein , and without intending to publicly dedicate any patentable subject matter .

a walker for assisting persons with varying degrees of physical ability is provided with an adjustable strap . a user opens a portion of the walker and enters the walker , and then the user closes the portion of the walker to enclose himself or herself in the walker . the user is positioned over an adjustable strap , and the adjustable strap is in an extended position . the adjustable strap may then be retracted such that a seat disposed on the adjustable strap rises and contacts the user to bear at least a portion of the user &# 39 ; s weight .

in a first embodiment ( 1 ), both with regard to the first and second aspect of the invention , formula ( i ) r b denotes a hydrogen atom or a c 1 - 4 - alkyl group , r c denotes a cyclopropylmethoxy , cyclobutyloxy , cyclopentyloxy , tetrahydrofuran - 3 - yl - oxy , tetrahydrofuran - 2 - yl - methoxy , tetrahydrofuran - 3 - yl - methoxy , tetrahydropyran - 4 - yl - oxy or tetrahydropyran - 4 - yl - methoxy group , r d denotes a dimethylamino , n - cyclopropyl - n - methyl - amino , n - cyclopropylmethyl - n - methyl - amino , n - ethyl - n - methyl - amino , n , n - diethylamino , n - isopropyl - n - methyl - amino , n -( 2 - methoxyethyl )- n - methyl - amino , n -( 1 - methoxy - 2 - propyl )- n - methyl - amino , n -( 3 - methoxypropyl )- n - methyl - amino , pyrrolidino , 2 - methylpyrrolidino , 2 -( methoxymethyl )- pyrrolidino , morpholino , ( 1s , 4s )- 2 - oxa - 5 - aza - bicyclo [ 2 . 2 . 1 ] hept - 5 - yl , ( 1r , 4r )- 2 - oxa - 5 - aza - bicyclo [ 2 . 2 . 1 ] hept - 5 - yl , n - cyclopropyl - n - methyl - amino -, n - methyl - n -( tetrahydrofuran - 3 - yl )- amino , n - methyl - n -( tetrahydrofuran - 2 - ylmethyl )- amino , n - methyl - n -( tetrahydrofuran - 3 - yl - methyl )- amino , n - methyl - n ( tetrahydropyran - 4 - yl )- amino or n - methyl - n -( tetrahydropyran - 4 - yl - methyl )- amino group , or a group of formula ( ii ) wherein r e and r f , which may be identical or different , in each case denote a hydrogen atom or a c 1 - 3 - alkyl group , optionally in form of its tautomers , racemates , enantiomers , diastereomers and the mixtures thereof and optionally in form of the pharmacologically acceptable acid addition salts , solvates , hydrates , polymorphs , physiologically functional derivatives or prodrugs thereof . in a second embodiment ( 2 ), both with regard to the first and second aspect of the invention , formula ( i ) r c denotes a cyclopropylmethoxy , cyclobutyloxy , cyclopentyloxy , tetrahydrofuran - 3 - yl - oxy , tetrahydrofuran - 2 - yl - methoxy , tetrahydrofuran - 3 - yl - methoxy , tetrahydropyran - 4 - yl - oxy or tetrahydropyran - 4 - yl - methoxy group , r d denotes a dimethylamino , n - cyclopropyl - n - methyl - amino , n - cyclopropylmethyl - n - methyl - amino , n - ethyl - n - methyl - amino , n , n - diethylamino , n - isopropyl - n - methyl - amino , n -( 2 - methoxyethyl )- n - methyl - amino , n -( 1 - methoxy - 2 - propyl )- n - methyl - amino , n -( 3 - methoxypropyl )- n - methyl - amino , pyrrolidino , 2 - methylpyrrolidino , 2 -( methoxymethyl )- pyrrolidino , morpholino , ( 1s , 4s )- 2 - oxa - 5 - aza - bicyclo [ 2 . 2 . 1 ] hept - 5 - yl , ( 1r , 4r )- 2 - oxa - 5 - aza - bicyclo [ 2 . 2 . 1 ] hept - 5 - yl , n - methyl - n -( tetrahydrofuran - 3 - yl )- amino , n - methyl - n -( tetrahydrofuran - 2 - yl - methyl )- amino , n - methyl - n -( tetrahydrofuran - 3 - yl - methyl )- amino , n - methyl - n -( tetrahydropyran - 4 - yl )- amino or n - methyl - n -( tetrahydropyran - 4 - yl - methyl )- amino group , or a group of formula ( ii ) in a third embodiment ( 3 ), both with regard to the first and second aspect of the invention , formula ( i ) r c denotes a tetrahydrofuran - 3 - yl - oxy , tetrahydrofuran - 2 - yl - methoxy , tetrahydrofuran - 3 - yl - methoxy , tetrahydropyran - 4 - yl - oxy or tetrahydropyran - 4 - yl - methoxy group , r d denotes a dimethylamino , n - cyclopropyl - n - methyl , n - ethyl - n - methyl - amino , n , n - diethylamino , n - isopropyl - n - methyl - amino , morpholino , ( 1s , 4s )- 2 - oxa - 5 - aza - bicyclo -[ 2 . 2 . 1 ] hept - 5 - yl or ( 1r , 4r )- 2 - oxa - 5 - aza - bicyclo [ 2 . 2 . 1 ] hept - 5 - yl , group , or a group of formula ( ii ) in a fourth embodiment ( 4 ), both with regard to the first and second aspect of the invention , formula ( i ) r d denotes a dimethylamino group or a group of formula ( ii ) wherein r e and r f , denote a hydrogen atom . in a fifth embodiment ( 5 ), both with regard to the first and second aspect of the invention , formula ( i ) is defined to encompass the compounds selected from the group consisting of ( a ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 - cyclobutyloxy - quinazoline , ( b ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 - cyclopentyloxy - quinazoline , ( c ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -(( r )- tetrahydrofuran - 3 - yloxy )- quinazoline , ( d ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -(( s )- tetrahydrofuran - 3 - yloxy )- quinazoline , ( e ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -( tetrahydropyran - 4 - yloxy )- quinazoline , ( f ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( tetrahydrofuran - 2 - yl ) methoxy ]- quinazoline , ( g ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( tetrahydrofuran - 3 - yl ) methoxy ]- quinazoline , ( h ) 4 -[( r )-( 1 - phenyl - ethyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 - cyclopropylmethoxy - quinazoline , ( i ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( morpholin - 4 - yl )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( tetrahydrofuran - 2 - yl ) methoxy ]- quinazoline , ( j ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( s )-( tetrahydrofuran - 2 - yl ) methoxy ]- quinazoline , ( k ) 4 -[( 3 - chloro - 4 - fluoro - phenyl ) amino ]- 6 -{[ 4 -( homomorpholin - 4 - yl )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( s )-( tetrahydrofuran - 3 - yl ) oxy ]- quinazoline , ( l ) 4 -[( 3 - chloro - 4 - fluoro - phenyl ) amino ]- 6 -{[ 4 -( n - ethyl - n - methyl - amino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( s )-( tetrahydrofuran - 3 - yl ) oxy ]- quinazoline , ( m ) 4 -[( 3 - chloro - 4 - fluoro - phenyl ) amino ]- 6 -{[ 4 -( n - isopropyl - n - methyl - amino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( s )-( tetrahydrofuran - 3 - yl ) oxy ]- quinazoline , ( n ) 4 -[( 3 - chloro - 4 - fluoro - phenyl ) amino ]- 6 -{[ 4 -( n - cyclopropyl - n - methyl - amino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 - cyclopentyloxy - quinazoline , ( o ) 4 -[( 3 - chloro - 4 - fluoro - phenyl ) amino ]- 6 -{[ 4 -( n , n - diethyl - amino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 - cyclopropylmethoxy - quinazoline , ( p ) 4 -[( 3 - chloro - 4 - fluoro - phenyl ) amino ]- 6 -{[ 4 -(( 1s , 4s )- 2 - oxa - 5 - aza - bicyclo [ 2 . 2 . 1 ]- hept - 5 - yl )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( s )-( tetrahydrofuran - 3 - yl ) oxy ]- quinazoline , ( q ) 4 -[( 3 - chloro - 4 - fluoro - phenyl ) amino ]- 6 -{[ 4 -(( 1r , 4r )- 2 - oxa - 5 - aza - bicyclo [ 2 . 2 . 1 ]- hept - 5 - yl )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( s )-( tetrahydrofuran - 3 - yl ) oxy ]- quinazoline and ( r ) 4 -[( 3 - chloro - 4 - fluoro - phenyl ) amino ]- 6 -{[ 4 -( dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 - cyclopropylmethoxy - quinazoline . in a sixth embodiment ( 6 ), both with regard to the first and second aspect of the invention , the compounds of formula ( i ) are selected from the group consisting of in a preferred embodiment the invention relates to the use of a compound of formula ( i ) according to the invention , wherein the disease is cancer selected from the group consisting of carcinomas , sarcomas , melanomas , myelomas , hematological neoplasias , lymphomas and childhood cancers . examples of carcinomas within the scope of the invention include but are not limited to adenocarcinoma ( ac ), squamous cell carcinoma ( scc ) and mixed or undifferentiated carcinomas . carcinomas within the scope of the invention include but are not limited to the following histologies : head and neck tumours : scc , ac , transitional cell cancers , mucoepidermoid cancers , undifferentiated carcinomas ; central nervous system tumours : astrocytoma , glioblastoma , meningeoma , neurinoma , schwannoma , ependymoma , hypophysoma , oligodendroglioma , medulloblastoma ; bronchial and mediastinal tumours : small cell lung cancers ( sclc ): oat - cell lung cancer , intermediate cell cancer , combined oat - cell lung cancer ; non - small cell lung cancers ( nsclc ): scc , spindle cell carcinoma , ac , bronchioalveolar carcinoma , large cell nsclc , clear cell nsclc ; oesophageal cancers : scc , ac , anaplastic , carcinoid , sarcoma ; gastric cancers : ac , adenosquamous , anaplastic ; colorectal cancers : ac , including hereditary forms of ac , carcinoid , sarcoma ; anal cancers : scc , transitional epithelial cancer , ac , basal cell carcinoma ; pancreatic cancers : ac , including ductal and acinary cancers , papillary , adenosquamous , undifferentiated , tumours of the endocrine pancreas ; hepatocellular carcinoma , cholangiocarcinoma , angiosarcoma , hepatoblastoma ; biliary carcinomas : ac , scc , small cell , undifferentiated ; gastrointestinal stroma tumours ( gist ); breast cancers : ac , including invasive ductal , lobular and medullary cancers , tubular , mucinous cancers , paget - carcinoma , inflammatory carcinoma , ductal and lobular carcinoma in situ ; ovarian cancers : epithelial tumours , stroma tumours , germ cell tumours , undifferentiated tumours ; cervical cancers : scc , ac , mixed and undifferentiated tumours ; endometrial cancers : ac , scc , mixed , undifferentiated tumours ; vulvar cancers : scc , ac ; vaginal cancers : scc , ac ; testicular cancers : seminoma ; non - seminomatous germ cell tumours : teratoma , embryonal cell carcinoma , choriocarcinoma , yolk sac tumour , mixed , sertoli and leydig - cell tumours ; extragonadal germ cell tumours ; prostate cancers : ac , small cell , scc ; renal cell cancers : ac , including clear cell , papillary and chromophobous carcinomas , hereditary forms ( e . g . von - hippel - lindau syndrome ), nephroblastoma ; urinary bladder cancers : transitional cell ( urothelial ) cancers , scc , ac ; urethral cancers : scc , transitional cell cancers , ac ; penile cancers : scc ; thyroid cancers : papillary , follicular , anaplastic , medullary carcinomas , including men syndrome ; tumours of the endocrine pancreas ; carcinoids ; pheochromocytoma . examples of sarcomas within the scope of the invention include but are not limited to ewing - sarcoma , osteosarcoma or osteogenic sarcoma , chondrosarcoma , synovial sarcoma , leiomyosarcoma , rhabdomyosarcoma , mesothelial sarcoma or mesothelioma , fibrosarcoma , angiosarcoma or hemangioendothelioma , liposarcoma , glioma or astrocytoma , myxosarcoma , malignant fibrous histiocytoma , mesenchymous or mixed mesodermal tumour , neuroblastoma and clear cell sarcoma . examples of melanomas within the scope of the invention include but are not limited to superficial spreading melanoma , nodular and lentigo - maligna melanoma . examples of myelomas within the scope of the invention include but are not limited to immunocytoma , plasmocytoma and multiple myeloma . in another preferred embodiment the invention relates to the use according to the invention , wherein the hematological neoplasia is leukemia . further examples of hematologic neoplasias within the scope of the invention include but are not limited to acute or chronic leukemias of myeloid , erythroid or lymphatic origin , myelodysplastic syndromes ( mds ) and myeloproliferative syndromes ( mps , such as chronic myelogeneous leukemia , osteomyelofibrosis , polycythemia vera or essential thrombocythemia ). examples of lymphomas within the scope of the invention include but are not limited to : low and intermediate grade : chronic lymphocytic leukemia ( cll ), prolymphocytic leukemia ( pll ), small lymphocytic lymphoma , hairy cell leukemia , plasmacytoid lymphoma , mantle cell lymphoma , follicular lymphoma , marginal zone lymphoma including malt - lymphoma ; high grade : diffuse large b - cell lymphoma ( dlbcl including immunoblastic and centroblastic variants ), lymphoblastic , burkitt &# 39 ; s lymphoma ; low grade : t - cll , t - pll , mycosis fungoides , sezary - syndrome ; high grade : anaplastic large cell , t - immunoblastic and lymphoblastic . in another preferred embodiment the invention relates to the use according to the invention , wherein the disease is cancer selected from the group consisting of mixed tumours , undifferentiated tumours and metastases thereof . examples of mixed tumours within the scope of the invention include but are not limited to adenosquamous carcinomas , mixed mesodermal tumours , carcinosarcomas and teratocarcinomas . examples of undifferentiated , other tumours or metastases thereof within the scope of the invention include but are not limited to undifferentiated tumours , carcinomas of unknown primary ( cup ), metastases of unknown primary ( mup ) and pheochromocytoma , carcinoids . additionally the following tumour diseases which can be treated with a compound of formula ( i ) in accordance with the invention are summarized : acral lentiginous melanoma , actinic keratoses , adenoid cycstic carcinoma , adenomas , adenosarcoma , adrenocortical carcinoma , aids - related lymphoma , bartholin gland carcinoma , brain stem glioma , capillary carcinoma , central nervous system lymphoma , chondosarcoma , choriod plexus papilloma / carcinoma , cystadenoma , endodermal sinus tumor , endometrial hyperplasia , endometrial stromal sarcoma , endometrioid adenocarcinoma , epitheloid , focal nodular hyperplasia , gastrinoma , gestational trophoblastic tumor , glucagonoma , hepatic adenoma , hepatic adenomatosis , hypopharyngeal cancer , hypothalamic and visual pathway glioma , insulinoma , intraepithelial neoplasia , interepithelial squamous cell neoplasia , intraocular invasive squamous cell carcinoma , large cell carcinoma , islet cell carcinoma , kaposi &# 39 ; s sarcoma , laryngeal cancer , leukemia - related disorders , lip and oral cavity cancer , malignant mesothelial tumors , malignant thymoma , medulloepithelioma , merkel cell carcinoma , mucoepidermoid carcinoma , multiple myeloma / plasma cell neoplasm , mycosis fungoides , myelodysplastic syndrome , myeloproliferative disorders , nasal cavity and paranasal sinus cancer , nasopharyngeal cancer , neuroepithelial adenocarcinoma , nodular melanoma , oat cell carcinoma , oligodendroglial , oral cancer , oropharyngeal cancer , pineal cell , pituitary tumors , pseudosarcoma , pulmonary blastoma , parathyroid cancer , pineal and supratentorial primitive neuroectodermal tumors , pituitary tumor , plasma cell neoplasm , pleuropulmonary blastoma , retinoblastoma , serous carcinoma , small intestine cancer , soft tissue carcinomas , somatostatin - secreting tumor , supratentorial primitive neuroectodermal tumors , uveal melanoma , verrucous carcinoma , vipoma , waldenstrom &# 39 ; s macroglobulinemia , well differentiated carcinoma , and wilm &# 39 ; s tumor . in a further preferred embodiment ( 7 ), both with regard to the first and second aspect of the invention , the compounds of formula ( i ) are selected from the group consisting of ( a ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 - cyclobutyloxy - quinazoline , ( b ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 - cyclopentyloxy - quinazoline , ( c ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -(( r )- tetrahydrofuran - 3 - yloxy )- quinazoline , ( d ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -(( s )- tetrahydrofuran - 3 - yloxy )- quinazoline ( bibw2992 ), ( e ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -( tetrahydropyran - 4 - yloxy )- quinazoline , ( f ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( tetrahydrofuran - 2 - yl ) methoxy ]- quinazoline , ( g ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( tetrahydrofuran - 3 - yl ) methoxy ]- quinazoline , ( h ) 4 -[( r )-( 1 - phenyl - ethyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 - cyclopropylmethoxy - quinazoline , ( i ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( morpholin - 4 - yl )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( tetrahydrofuran - 2 - yl ) methoxy ]- quinazoline , ( j ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( s )-( tetrahydrofuran - 2 - yl ) methoxy ]- quinazoline , ( k ) 4 -[( 3 - chloro - 4 - fluoro - phenyl ) amino ]- 6 -{[ 4 -( homomorpholin - 4 - yl )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( s )-( tetrahydrofuran - 3 - yl ) oxy ]- quinazoline , and ( r ) 4 -[( 3 - chloro - 4 - fluoro - phenyl ) amino ]- 6 -{[ 4 -( dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 - cyclopropylmethoxy - quinazoline , and the cancer indication to be treated by administration of a compound of formula ( i ) is selected from the group consisting of head and neck tumours : scc , ac , transitional cell cancers , mucoepidermoid cancers , undifferentiated carcinomas ; central nervous system tumours : astrocytoma , glioblastoma , meningeoma , neurinoma , schwannoma , ependymoma , hypophysoma , oligodendroglioma , medulloblastoma ; bronchial and mediastinal tumours : non - small cell lung cancers ( nsclc ): scc , spindle cell carcinoma , ac , bronchioalveolar carcinoma , large cell nsclc , clear cell nsclc ; oesophageal cancers : scc , ac , anaplastic ; gastric cancers : ac , adenosquamous , anaplastic ; colorectal cancers : ac , including hereditary forms of ac , carcinoid , sarcoma ; pancreatic cancers : ac , including ductal and acinary cancers , papillary , adenosquamous , undifferentiated , tumours of the endocrine pancreas ; hepatocellular cancers , cholangiocarcinoma breast cancers : ac , including invasive ductal , lobular and medullary cancers , tubular , mucinous cancers , paget - carcinoma , inflammatory carcinoma , ductal and lobular carcinoma in situ ; ovarian cancers : epithelial tumours , stroma tumours , germ cell tumours , undifferentiated tumours ; prostate cancers : ac , small cell , scc ; renal cell cancers : ac , including clear cell , papillary and chromophobous carcinomas , hereditary forms ( e . g . von - hippel - lindau syndrome ), wilm &# 39 ; s tumor , nephroblastoma ; urinary bladder cancers : transitional cell ( urothelial ) cancers , scc , ac . examples of sarcomas within the scope of the invention include but are not limited to ewing - sarcoma , osteosarcoma or osteogenic sarcoma , chondrosarcoma , synovial sarcoma , leiomyosarcoma , rhabdomyosarcoma , mesothelial sarcoma or mesothelioma , fibrosarcoma , angiosarcoma or hemangioendothelioma , liposarcoma , glioma or astrocytoma , myxosarcoma , malignant fibrous histiocytoma , mesenchymous or mixed mesodermal tumour , neuroblastoma and clear cell sarcoma . in a very preferred embodiment ( 8 ), both with regard to the first and second aspect of the invention , the compounds of formula ( i ) are selected from the group consisting of and the cancer indication to be treated by administration of a compound of formula ( i ) is selected from the group consisting of head and neck tumours : scc , ac , transitional cell cancers , mucoepidermoid cancers , undifferentiated carcinomas ; colorectal cancers , metastatic or non - metastatic : ac , including hereditary forms of ac , carcinoid , sarcoma ; pancreatic cancers : ac , including ductal and acinary cancers , papillary , adenosquamous , undifferentiated , tumours of the endocrine pancreas ; breast cancers , metastatic or non - metastatic : ac , including invasive ductal , lobular and medullary cancers , tubular , mucinous cancers , paget - carcinoma , inflammatory carcinoma , ductal and lobular carcinoma in situ ; prostate cancers : ac , small cell , scc ; gastric cancers : ac , adenosquamous , anaplastic ; ovarian cancer ; non - small cell lung cancers ( nsclc ): scc , spindle cell carcinoma , ac , bronchioalveolar carcinoma , large cell nsclc , clear cell nsclc . it is known that cancer patients carrying activating egfr mutations in their tumors , i . e . within the tyrosine kinase domain of the egf receptor , may show increased sensitivity to treatment with egfr inhibitors . analogously , cancer patients carrying activating her2 mutations , e . g . m774_a775insayvm , in their tumors may show increased sensitivity to treatment with her2 inhibitors . both groups of patients as well as a subgroup carrying both activating egfr and her2 mutations may show increased sensitivity to treatment with dual inhibitors of erbb1 receptor ( egfr ) and erbb2 ( her2 / neu ). the presence of specific gain - of - function mutations within the tyrosine kinase domain of the egf receptor in a subgroup of nsclc patients has been associated with increased sensitivity to treatment with gefitinib and erlotinib ( lynch , new england journal medicine 350 , 2129 ( 2004 ); paez , science 304 , 1497 ( 2004 ); pao , proceedings of the national academy of science of the united states 101 , 13306 ( 2004 )). in particular , the l858r point mutation ( exon 21 ) as well as deletion / insertion mutations in the elrea sequence ( exon 19 ) account for the majority of gefitinib responders . a secondary point mutation in exon 20 , t790m , is associated with acquired resistance to gefitinib or erlotinib . this mutation is analogous to the t315i mutation identified in cml patients who relapse under imatinib treatment ( imatinib resistant patients ). irreversible inhibitors ( e . g ., hki - 272 or cl 387 , 785 ), in contrast to reversible inhibitors ( e . g ., gefitinib ), are able to inhibit proliferation and egf - induced egfr phosphorylation in cell lines expressing double mutant egf receptors ( kwak , proceedings of the national academy of science of the united states 102 , 7665 ( 2005 ) and kobayashi , new england journal medicine 352 , 786 ( 2005 )). any aspect of the present invention therefore includes , as a sub - aspect , optional pre - selection of cancer patients for an egfr mutation in the tyrosine kinase domain of the egf receptor as well as pre - selection of cancer patients for an her2 mutation . the egfr mutations preferably relevant in in this context are selected from the group consisting of the l858r and l861 point mutations in the activation loop ( exon 21 ), in - frame deletion / insertion mutations in the elrea sequence ( exon 19 ), substitutions in g719 situated in the nucleotide binding loop ( exon 18 ), activating mutations in the extracellular domain of the egf receptor such as egfr viii displaying exon 2 - 7 deletions , the t790m point mutation in exon 20 , exon 20 insertions such as d770_n771insnpg , and double mutants such as the combined l858r / t790m mutation and the exon - 19 - del / t790m . the her2 mutation preferably relevant in in this context is the m774_a775insayvm mutation . methods for detecting mutations in the tyrosine kinase domain of the egf receptor are known in the art , several corresponding diagnostic tools are approved by the fda and commercially available , e . g . an assay for the detection of epidermal growth factor receptor mutations in patients with non - small cell lung cancer ( genzyme corp . ; see also journal of clinical oncology , 2006 asco annual meeting proceedings ( post - meeting edition ). vol 24 , no 18s ( june 20 supplement ), 2006 : abstract 10060 ). any of the embodiments of the invention mentioned hereinbefore defining compounds of formula ( i ) and cancer indications applies accordingly to the optional sub - aspect of pre - selection of cancer patients for an activating egfr mutation in the tyrosine kinase domain of the egf receptor and / or pre - selection of cancer patients for an activating her2 mutation . treatment of egfr mutant cancer patients with the compounds of formula ( i ) may allow a response in cancer patients with acquired or persistent resistance to gefitinib or erlotinib treatment . treatment of cancer patients carrying an activating her2 mutant in their tumors with the compounds of formula ( i ) may allow a responce in cancer patients with acquired or persistent resistance to certain chemotherapeutics such as e . g . lapatinib or herceptin . most preferred cancer indications with egfr or her2 mutations relevant in connection with the sub - aspect of patient pre - selection for mutations are selected from the group consisting of head and neck tumours : scc , ac , transitional cell cancers , mucoepidermoid cancers , undifferentiated carcinomas ; colorectal cancers , metastatic or non - metastatic : ac , including hereditary forms of ac , carcinoid , sarcoma ; pancreatic cancers : ac , including ductal and acinary cancers , papillary , adenosquamous , undifferentiated , tumours of the endocrine pancreas ; breast cancers , metastatic or non - metastatic : ac , including invasive ductal , lobular and medullary cancers , tubular , mucinous cancers , paget - carcinoma , inflammatory carcinoma , ductal and lobular carcinoma in situ ; prostate cancers : ac , small cell , scc ; gastric cancers : ac , adenosquamous , anaplastic ; ovarian cancer ; non - small cell lung cancers ( nsclc ): scc , spindle cell carcinoma , ac , bronchioalveolar carcinoma , large cell nsclc , clear cell nsclc , non - small cell lung cancers ( nsclc ): scc , spindle cell carcinoma , ac , bronchioalveolar carcinoma , large cell nsclc , clear cell nsclc , especially metastatic , second line patients who have failed at least one prior chemotherapy regimen or 3rd / 4th line patients who have received tarceva or iressa for at least 12 weeks and then failed , preferably to be treated by administration of a compound of formula ( i ) selected from the group consisting of : ( a ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 - cyclobutyloxy - quinazoline , ( b ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 - cyclopentyloxy - quinazoline , ( c ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -(( r )- tetrahydrofuran - 3 - yloxy )- quinazoline , ( d ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -(( s )- tetrahydrofuran - 3 - yloxy )- quinazoline ( bibw2992 ), ( e ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -( tetrahydropyran - 4 - yloxy )- quinazoline , ( f ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( tetrahydrofuran - 2 - yl ) methoxy ]- quinazoline , ( g ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( tetrahydrofuran - 3 - yl ) methoxy ]- quinazoline , ( h ) 4 -[( r )-( 1 - phenyl - ethyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 - cyclopropylmethoxy - quinazoline , ( i ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( morpholin - 4 - yl )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( tetrahydrofuran - 2 - yl ) methoxy ]- quinazoline , ( j ) 4 -[( 3 - chloro - 4 - fluorophenyl ) amino ]- 6 -{[ 4 -( n , n - dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( s )-( tetrahydrofuran - 2 - yl ) methoxy ]- quinazoline , ( k ) 4 -[( 3 - chloro - 4 - fluoro - phenyl ) amino ]- 6 -{[ 4 -( homomorpholin - 4 - yl )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 -[( s )-( tetrahydrofuran - 3 - yl ) oxy ]- quinazoline , and ( r ) 4 -[( 3 - chloro - 4 - fluoro - phenyl ) amino ]- 6 -{[ 4 -( dimethylamino )- 1 - oxo - 2 - buten - 1 - yl ] amino }- 7 - cyclopropylmethoxy - quinazoline , the first aspect of the present invention therefore includes , as a sub - aspect ( a ), a method of treating cancer comprising pre - selection of cancer patients for egfr and / or her2 mutations and administering a therapeutically effective amount of a compound of formula ( i ) to a pre - selected cancer patient shown to carry an egfr mutation in the tyrosine kinase domain of the egf receptor and / or with a tumor harboring an activating her2 mutation , optionally in combination with radiotherapy , radio - immunotherapy and / or tumour resection by surgery . accordingly , the second aspect of the present invention includes , as a sub - aspect ( b ), the use of a compound of formula ( i ) for the manufacture of a medicament for the treatment of cancer in a pre - selected cancer patient shown to carry an egfr mutation in the tyrosine kinase domain of the egf receptor and / or with a tumor harboring an activating her2 mutation . the method of treatment according to the invention comprises administration of a therapeutically effective amount of a compound of formula ( i ), optionally in form of its tautomers , racemates , enantiomers , diastereomers and the mixtures thereof and optionally in form of the pharmacologically acceptable acid addition salts , solvates , hydrates , polymorphs or physiologically functional derivatives thereof , to a patient in need thereof , wherein the active ingredient is administered orally , enterically , transdermally , intravenously , peritoneally or by injection , preferably orally . the patient preferably is a human patient . the compounds of formula ( i ) may be administered to the human patient in a daily dose of 0 . 01 - 4 mg / kg of body weight ( bw ), preferably 0 . 1 - 2 mg / kg , particularly preferred in a dose of 0 . 2 - 1 . 3 mg / kg bw . for oral treatment the compounds of formula ( i ) may be administered daily in a total dose of 10 , 20 , 30 , 40 , 50 , 60 , 70 , 100 , 200 , or 300 mg , optionally divided into multiple doses , e . g . 1 to 3 doses to be administered through the day . preferably the oral daily dose is administered only once a time . these doses can be applied with any of the compounds of formula ( i ), e . g . with bibw2992 or an equivalent dose of bibw2992ma 2 containing respective amounts of the active base component . especially for higher doses periods of treatment should alternate with periods of recovery , without administering the active of formula ( i ). for instance , treatment could follow a “ 7 day on - 7 day off ”, a “ 14 day on - 14 day off ”, a “ 21 day on 7 day off ” or a continuous dosing schedule . “ on - off ” time periods can be chosen shorter , especially if higher doses are administered , or individually adapted to the needs of the patient . the dosage for intravenous use of a compound of formula ( i ), e . g . of bibw2992ma 2 may be 1 - 1000 mg , preferably 5 - 300 mg , particularly preferred 10 - 100 mg ( dosages refer to the base form bibw2992 ), either given as a bolus or , especially if higher doses are applied , as a slow intravenous infusion over several hours , e . g . over about 1 , 2 , 4 , 6 , 10 , 12 or 24 hours . in one embodiment the invention relates to the method of treatment described above , characterised in that a compound of formula ( i ), or its polymorph , metabolite , hydrate , solvate , an individual optical isomer , mixtures of the individual enantiomers or racemates thereof , or a pharmaceutically acceptable salt thereof , is administered intermittent or in a daily dosage such that the plasma level of the active substance preferably lies between 10 and 5000 nm for at least 12 hours of the dosing interval . however , it may optionally be necessary to deviate from the amounts specified , depending on the body weight or method of administration , the individual response to the medication , the nature of the formulation used and the time or interval over which it is administered . thus , in some cases , it may be sufficient to use less than the minimum quantity specified above , while in other cases the upper limit specified will have to be exceeded . when large amounts are administered it may be advisable to spread them over the day in a number of single doses . a compound of formula ( i ), its tautomers , the racemates , the enantiomers , the diastereomers and the mixtures thereof , and optionally the pharmacologically acceptable acid addition salts , solvates , hydrates , polymorphs , physiologically functional derivatives or prodrugs thereof , may be used in monotherapy or combined with other active substances according to the invention , optionally also in conjunction with other pharmacologically active substances . suitable pharmaceutical preparations for the use in accordance with the invention include , for example , tablets , capsules , suppositories , solutions , and particularly solutions for injection ( s . c ., i . v ., i . m .) and infusion , syrups , emulsions or dispersible powders . the amount of pharmaceutically active compound in each case should be in the range from 0 . 1 - 90 wt . %, preferably 0 . 5 - 50 wt . % of the total composition , i . e . in amounts which are sufficient to achieve the dosage range given below . the doses specified may , if necessary , be given several times a day . suitable tablets may be obtained , for example , by mixing the active substance ( s ) with known excipients , for example inert diluents such as calcium carbonate , calcium phosphate or lactose , disintegrants such as corn starch or alginic acid , binders such as starch or gelatine , lubricants such as magnesium stearate or talc and / or agents for delaying release , such as carboxymethyl cellulose , cellulose acetate phthalate , or polyvinyl acetate . the tablets may also comprise several layers . coated tablets may be prepared accordingly by coating cores produced analogously to the tablets with substances normally used for tablet coatings , for example collidone or shellac , gum arabic , talc , titanium dioxide or sugar . to achieve delayed release or prevent incompatibilities the core may also consist of a number of layers . similarly the tablet coating may consist of a number of layers to achieve delayed release , possibly using the excipients mentioned above for the tablets . syrups or elixirs containing the active substances or combinations thereof according to the invention may additionally contain a sweetener such as saccharin , cyclamate , glycerol or sugar and a flavour enhancer , e . g . a flavouring such as vanillin or orange extract . they may also contain suspension adjuvants or thickeners such as sodium carboxymethyl cellulose , wetting agents such as , for example , condensation products of fatty alcohols with ethylene oxide , or preservatives such as p - hydroxybenzoates . solutions for injection and infusion are prepared in the usual way , e . g . with the addition of preservatives such as p - hydroxybenzoates , or stabilisers such as alkali metal salts of ethylenediamine tetraacetic acid , optionally using emulsifiers and / or dispersants , while if water is used as the diluent organic solvents may optionally be used as solubilisers or auxiliary solvents , and transferred into injection vials or ampoules or infusion bottles . capsules containing one or more active substances or combinations of active substances may for example be prepared by mixing the active substances with inert carriers such as lactose or sorbitol and packing them into gelatine capsules . suitable suppositories may be made for example by mixing with carriers provided for this purpose , such as neutral fats or polyethyleneglycol or the derivatives thereof . suitable excipients may be , for example , water , pharmaceutically acceptable organic solvents , such as paraffins ( e . g . petroleum fractions ), oils of vegetable origin ( e . g . groundnut or sesame oil ), mono - or polyfunctional alcohols ( e . g . ethanol or glycerol ), carriers such as e . g . natural mineral powders ( e . g . kaolin , clays , talc , chalk ), synthetic mineral powders ( e . g . highly dispersed silica and silicates ), sugar ( e . g . glucose , lactose and dextrose ), emulsifiers ( e . g . lignin , spent sulphite liquors , methylcellulose , starch and polyvinylpyrrolidone ) and lubricants ( e . g . magnesium stearate , talc , stearic acid and sodium lauryl sulphate ). the preparations are administered in the usual way , preferably by oral or transdermal route , particularly preferably by oral route . when administered orally the tablets may , of course , contain additives , such as e . g . sodium citrate , calcium carbonate and dicalcium phosphate together with various additives , such as starch , preferably potato starch , gelatine and the like , in addition to the abovementioned carriers . lubricants such as magnesium stearate , sodium laurylsulphate and talc may also be used to form tablets . in the case of aqueous suspensions the active substances may be combined with various flavour enhancers or colourings in addition to the abovementioned excipients . for parenteral use , solutions of the active substances may be prepared using suitable liquid carrier materials . the following examples serve to illustrate the invention without restricting it : molecular potency and selectivity of bibw 2992 compared to prior art compounds the data summarized in table 1 were obtained using standard in - solution kinase assays performed at saturating atp concentrations measuring incorporation of phosphate into poly ( glutyr ). the same conditions were used for the different compounds in any kinase assay for direct comparison . ic50 values were generated from 12 - point dose - response curves run in triplicates . ec50 values were generated from 12 - point dose - response curves . for receptor phosphorylation assays cells were pre - incubated for 1 h with test compound . cells were then either stimulated with egf ( 100 ng / ml for 20 min ) or directly harvested and tested for pegfr or pher2 by elisa . propidium iodide based assays were used to assess the proliferation of bt - 474 cells in vitro . the compounds were tested under conditions allowing direct direct comparison . nci - n87 gastric cancer cells were treated in vitro with 250 nm bibw 2992 . at indicated time points cells were harvested and samples were analyzed for free nucleosomes ( apoptosis hallmark ) using the cell death elisa kit # 1774425 from roche diagnostics . results are shown in fig1 ( appendix ). the following examples show that once daily dosing of bibw 2992 significantly inhibits , in a dose dependent manner , the growth of a variety of human tumor xenografts in nude mice : effect of bibw 2992 on the growth of preexisting hnscc fadu xenografts mice carrying established tumors ( 50 - 100 mm3 ) were treated orally , once daily at indicated doses . on the last day of treatment plasma samples were collected and analyzed for compound levels . results are shown in fig2 ( appendix ). effect of bibw 2992 on the growth of mda - mb - 453 and skov - 3 xenografts mice carrying established tumors ( 50 - 100 mm3 ) were treated orally , once daily at indicated doses with the respective compounds . on the last day of treatment plasma samples were collected and analyzed for compound levels . results are shown in fig3 ( appendix ). mice carrying established tumors ( panel a : 50 - 100 mm3 ; panel b : 450 mm3 ) were treated once daily p . o . with bibw 2992 or once weekly i . v . with herceptin at indicated doses . daily oral treatment with bibw 2992 induces regression of nci - n87 xenografts . results are shown in fig4 ( appendix ). mice carrying established tumors ( 50 - 100 mm 3 ), were treated orally , once daily at indicated doses with the respective compounds . on the last day of treatment plasma samples were collected and analyzed for compound levels . daily oral treatment with bibw 2992 at a dose of 20 mg / kg results in full anti - tumor activity in various xenograft models . results are summarized in table 3 . median value in the treated group in relation to median value of tumor size in the control group ( usually n = 10 ) at the end of the experiment , set to 100 % ( e . g . : a median value in the treated group of 200 mm 3 in relation to a median value in the control group of 1000 mm 3 results a t / c value of 20 %). ( a ) one female patient with metastatic adenocarcinoma of the lung ( nsclc ) treated with bibw2992 ma2 at 10 mg daily ( dose refers to the base form ; continuous administration schedule ) had a confirmed partial response after two months of treatment . the pulmonary lesions have clearly shrunk by & gt ; 35 %, confirmed with a repeat ct scan in 4 weeks . ct scans done in regular intervals confirm the continuation of the partial response . the patient treated developed brain metastases on treatment and increasing the dose of bibw2992 to 40 mg daily has led to a response in her cerebral disease . this patient remains on treatment 23 months after starting bibw 2992 . this patient &# 39 ; s tumour cells have a complex heterozygous egfr mutation including a deletion and missense mutations of 4 - amino acids in the kinase domain , but a wildtype her2 domain . ( b ) another female patient with non - small cell lung cancer , pleural tumours and mediastinal lymph nodes treated with bibw2992 ma2 also treated in a continuous dosing schedule at 40 mg daily did develop a partial response as measured by a ct scan after two months of treatment . five target lesions had been identified ; the sum thereof has gone down from 7 . 3 to 2 . 6 cm , a decrease of 65 %. the patient remains in partial response 14 months after starting treatment with bibw 2992 . an in - frame deletion of 5 amino acids in the same region of the kinase domain has been detected in this patient . ( c ) using a 14 day on 14 day off schedule 2 patients with parotid tumors , one patient with esophageal cancer , one patient with colorectal cancer , one patient with breast cancer , one patient with thyroid cancer and one patient with other endocrine cancer have had stable disease for at least 6 months and have been treated for more than 6 months . ( d ) in a continuous dosing schedule and in addition to the above mentioned non - small cell lung cancer patients with partial remissions , a patient with thymic cancer ( 40 mg daily ) and a patient with ovarian cancer ( 20 mg daily ) have had stable disease for at least six months . ( e ) in a combined treatment schedule with docetaxel ( given every 3 weeks ) and bibw 2992 given for 3 days after the administration of docetaxel one patient had a complete response ( breast cancer ) and one had partial response ( oesophageal ). ( f ) in a combined treatment schedule with docetaxel ( given every 3 weeks ) and bibw 2992 given for 20 or 13 days after the administration of docetaxel , two patients had a partial responses ( ovarian and non - small cell lung cancer ). coated immediate - release tablets containing 75 mg of active substance by dry - granulation process active substance 75 . 0 mg calcium phosphate anhydrous 108 . 0 mg corn starch 35 . 5 mg polyvinylpyrrolidone 10 . 0 mg magnesium stearate 1 . 5 mg hydroxypropylmethylcellulose 7 . 5 mg polyethylene glycol 1 . 0 mg polydextrose 5 . 0 mg talc 1 . 0 mg pigments 0 . 5 mg water ( volatile ) 245 . 0 mg the active substance is mixed with calcium phosphate , corn starch , polyvinylpyrrolidone , hydroxypropylmethylcellulose and half the specified amount of magnesium stearate . ribbons are produced in a roller - compactor and these are then rubbed through a screen with a mesh size of 1 . 5 mm using a suitable machine and mixed with the rest of the magnesium stearate . this granulate is compressed in a tablet - making machine to form tablets of the desired shape . the tablet cores are subsequently coated with an aqueous film - coat consisting essentially of hydroxypropylmethylcellulose , polyethylene glycol , polydextrose , talc and pigments . extended - release tablets containing 100 mg of active substance by organic granulation granulation process the active substance , lactose and hydroxypropylmethylcellulose are mixed together and uniformly moistened with solution of the polyvinylpyrrolidone in ethanol . after the moist composition has been screened ( 2 . 0 mm mesh size ) and dried in a rack - type drier at 50 ° c . it is screened again ( 1 . 5 mm mesh size ) and the lubricant is added . the final blend is compressed to form tablets . weight of tablet : 220 mg tablet shape : 10 mm , flat - faced , with bevelled edges . tablets containing 150 mg of active substance by aqueous granulation process the active substance mixed with lactose , corn starch is moistened with a 20 % aqueous polyvinylpyrrolidone solution and passed through a screen with a mesh size of 1 . 5 mm . the granules , dried at 45 ° c ., are passed through the same screen again and mixed with the specified amount of magnesium stearate and colloidal silica . tablets are pressed from thefinal blend . the active substance is mixed with the excipients in a high - shear mixer , passed through a screen with a mesh size of 0 . 75 mm and homogeneously mixed using a suitable apparatus . the finished mixture is packed into size 1 hard gelatin capsules . hard capsules containing 150 mg of active substance as a liquid fill the active substance is dissolved in the excipient inside a homogenizer and the colloidal silica is added for adjustment of viscosity . the finished mixture is filled into size 1 hard gelatin capsules . after the suppository mass has been melted the active substance is homogeneously suspended therein and the melt is poured into chilled moulds . the distilled water is heated to 70 ° c . the methyl and propyl p - hydroxybenzoates together with the glycerol and sodium salt of carboxymethylcellulose are dissolved therein with stirring . the solution is cooled to ambient temperature and the active substance is added and homogeneously dispersed therein with stilling . after the sugar , the sorbitol solution and the flavouring have been added and dissolved , the suspension is evacuated with stirring to eliminate air . the active substance is dissolved in the requisite amount of 0 . 01 n hcl , made isotonic with sodium chloride , filtered sterile and transferred into 2 ml ampoules with subsequent steam sterilization . the active substance is dissolved in the necessary amount of 0 . 01 n hcl , made isotonic with sodium chloride , filtered sterile and transferred into 10 ml ampoules with subsequent steam sterilization . the active substance is mixed with lactose for inhalation . the mixture is packed into capsules in a capsule - making machine ( weight of the empty capsule approx . 50 mg ). weight of capsule : 70 . 0 mg size of capsule 3 the active substance and benzalkonium chloride are dissolved in ethanol / water ( 50 / 50 ). the ph of the solution is adjusted with 1n hydrochloric acid . the resulting solution is filtered sterile and transferred into suitable containers for use in hand - held nebulisers ( cartridges ).

the present invention relates to the use of quinazolines of formula , wherein the groups r a to r d have the meanings given in the claims and specification , in cancer therapy .

fig1 and 2 illustrate a conventional duran ring construction . like the cosgrove band illustrated in fig6 e - g , the duran ring 10 has a lumen 11 containing a generally rectangular inner core 12 of radio - opaque silicone rubber which is radially completely flexible . the radiopacity of the core 12 allows the presence and functioning of the implant to be monitored after completion of the implant sugery . the core 12 is completely enclosed by a sheath 14 of biocompatible cloth . the sheath 14 is made by folding a cloth sheet around the core 12 and sewing the folded ends together at 13 . the combination of the core 12 and sheath 14 result in a ring which is completely flexible yet essentially nonextensible . this property allows the annuloplasty ring or band , when implanted in the heart , to prevent the valve annulus from becoming distended , without significantly impeding the natural motion of the annulus . the ring 10 has three trigone markers 15 sewn thereon at 120 ° intervals to assist the surgeon in the placement of sutures . one of the disadvantages of the fully flexible ring 10 is that it needs to be supported in its proper shape during the implantation procedure . this is typically accomplished by mounting the ring 10 on a holder such as that shown in u . s . pat . no . 5 , 011 , 481 , which is removed once the implant sutures are in place . such holders , however , do not prevent the ring 10 from bunching or pleating when the implant sutures are tied off , if the sutures are not precisely placed . in accordance with the present invention , the need for a holder is obviated by temporarily stiffening the annuloplasty ring or band itself during the implant procedure , and then removing the integral stiffening element after the sutures have been tied off . fig3 - 7 illustrate the present invention using a removable stiffener 28 . in fig4 and 5 , it will be seen that the interior of the inventive ring or band 30 is preferably divided by an inner cloth wall 32 into a stiffener lumen 34 and a radiopaque core lumen 36 . the core lumen 36 contains the silicone rubber core 38 and receives the implant sutures therethrough as does the ring 10 of fig1 and 2 . the folds of the cloth 14 and the ends of the cloth wall 32 are sewn together at 37 . the stiffener lumen 34 of the inventive ring or band 30 contains the stiffener 28 . the position of stiffener 28 beside the core 38 and separated therefrom assures that the stiffener 28 will not interfere with the placement of sutures through the core 38 , and that conversely , the sutures will not interfere with the eventual removal of the stiffener 28 . the stiffener 28 extends substantially around the entire circumference or extent of the ring or band 30 and terminates in a grasping portion 39 which protrudes through the cloth sheath 14 . the grasping portion 39 may take the form of a loop or hook , or any other form that lends itself to being grasped by a tool or by the surgeon &# 39 ; s hand , and which prevents the grasping portion 39 from being pushed into the ring or band 30 as explained below in connection with fig7 . the stiffener 28 must satisfy several criteria . for one , it must be fully insertable into the ring or band 30 through an opening 40 ( fig7 ) without snagging or tearing the cloth sheath 14 or inner wall 32 . secondly , it must be withdrawable with a minimum of stress on the ring or band 30 to prevent damage to the sutures 42 which secure the ring or band 30 to the annulus 44 ( fig5 ) when the surgery is complete . thirdly , it must be stiff enough to maintain the ring or band 30 in a flat plane during implantation but flexible enough to allow the deformation inherent in withdrawal . in a preferred embodiment , these objectives are achieved by using for the stiffener 28 a length of haynes alloy # 25 wire . this wire has a thickness of about 750 μm and would have a length of about 10 cm for a 29 mm duran ring . the end or ends 46 of the stiffener wire 28 opposite the grasping portion 39 are preferably formed into a generally bulbous shape to prevent the wire 28 from snagging the cloth 12 when it is threaded through the lumen 34 during manufacture of the ring or band 30 . the stiffener wire 28 itself is preferably polished to a very smooth surface , so that it will easily slide in the lumen 34 during insertion and withdrawal . fig6 a - g illustrate various preferred ways in which a stiffener 28 can be placed in a ring ( fig6 a - d ) or band ( fig6 e - g ). the stiffener 28 may have a single leg 54 which extends from the grasping portion 39 although the entire length of the ring 50 or band 30 ( fig6 a , 6c , 6e and 6f ). alternatively , the stiffener 28 may have a pair of legs 56 , 58 extending in opposite directions from a centrally located grasping portion 39 ( fig6 b , 6d and 6g ). the grasping portion may be located in the upper or lower center of the ring or the center of the band ( fig6 b , 6d and 6g ); on the right side or end of the ring or band 30 ( fig6 a and 6f ); on their left side or end ( fig6 c and 6e ); or in the generally 1 o &# 39 ; clock position shown in fig3 and 4 . typically , because the legs 56 , 58 of the two - leg embodiments are shorter , these embodiments tend to place less stress on the ring or band 30 during removal of the stiffener 28 . fig7 details the preferred arrangment of the opening 40 which receives the stiffener 28 . in order to prevent snagging or tearing of the cloth 12 during insertion or removal of the stiffener 28 , a reinforcement or trim 60 is added to the cloth 14 around the circumference of the opening 40 . in addition , a security suture 62 is preferably placed through the grasping portion 39 and core 38 to prevent premature removal of the stiffener 28 . the suture 62 is so attached to the grasping portion 39 that all of the suture 62 will come out with the stiffener 28 when the suture 62 is cut at 64 and the stiffener 28 is withdrawn from the ring or band 30 . because surgeons unfamiliar with the construction of the inventive ring or band 30 may accidentally try to suture the ring or band 30 through the stiffener lumen 34 , it is desirable to provide indicia to delineate the core lumen 36 through which the sutures should be made . the indicia can be any of a variety of visual features , for example , an additional suture may be placed lengthwise of the ring or band 30 at 70 in fig5 ( the suture at 37 is already visible ). a preferred method , however , is to apply a distinctive color to the portion of the sheath 14 which surrounds the core lumen 36 , i . e . the right half 72 of the sheath 14 in fig5 . it will be seen that the present invention provides an effective way of temporarily stiffening a duran ring during the implantation process , and then restoring its full flexibility once the implantation is completed . it should be understood that the exemplary annuloplasty ring with removable stiffener described herein and shown in the drawings represents only a presently preferred embodiment of the invention . indeed , various modifications and additions may be made to such embodiment without departing from the spirit and scope of the invention . thus , other modifications and additions may be obvious to those skilled in the art and may be implemented to adapt the present invention for use in a variety of different applications .

a fully flexible annuloplasty ring is temporarily stiffened during implantation by inserting a withdrawable stiffening wire into a lumen of the ring . the annuloplasty ring has a lumen which is able to hold the stiffener prior to and during insertion . the stiffener includes a portion extending out of the lumen which can be pulled to withdraw the stiffener once the implant has been implanted .

referring now to fig1 and 2 , there is seen apparatus for light curing of a relatively large size restorative object such as a denture . a denture , designated d , is shown positioned on a rotatable table 52 . the denture is made of a suitable base material such as disclosed in co - pending u . s . application ser . no . 486 , 688 , titled &# 34 ; organic amine salt of an acid , manufacture and use as accelerator &# 34 ;, assigned to the same assignee . while the drawings illustrate a denture as the object being cured , it is to be understood that the invention relates broadly to the curing of medical objects of any sort , including particularly prostheses , portions of medical devices that must be custom shaped or contoured , and medical assist devices such as custom - formed shoe inserts . positioned to direct beams of collimated light at the table 52 , and thus at a denture d placed thereon , is a collimated light source means comprising one or more lamps , or light sources . in the preferred embodiment of this invention , four such lamps are used . in fig1 lamps 30 , 31 and 32 are shown positioned relative to the table 52 . fig2 illustrates four lamp surfaces 35 , positioned at approximately 90 ° intervals around the center axis of table 52 . the lamp outputs are directed through surfaces , or faces 35 , which in the preferred embodiment are about 23 / 8 inches in diameter . the light output from each lamp is collimated , and thus casts a light beam of about 23 / 8 inches diameter onto the table 52 . the lamps are tilted such that the axis of each light beam is at an angle within the range of about 20 °- 45 ° from the horizontal surface of table 52 . the preferred angle is about 30 °. further , the lamps are directed so that all portions of the table 52 , or denture d resting thereon , are irradiated , the light beams having overlaping portions . by this means , wherever the denture is positioned on the table , during the course of each rotation light will be incident on the denture so as to penetrate to all portions thereof . as seen in detail in fig3 each light means has a parabolic reflector 40 , and a bulb or lamp 43 positioned at the center thereof . the lamp is preferably a tungsten halogen bulb , but other types of bulbs may be used . in the preferred embodiment , the lamp is driven by a transformerless regulated power supply 48 , which also contains suitable timing means for timing the length of turn on of each lamp . the lamps are designed for rated power of 200 watts and 41 volt operation , and preferably are operated at about - 20 % of rated voltage , or 32 . 8 volts . at this voltage , each lamp delivers about 54 . 7 mw / cm 2 of light in the 400 - 500 bandwidth , at a distance of about 10 cm , i . e . the distance from the center of the light surface 35 to the center of the table . each light means also contains a bandpass filter 37 , having a heat reflecting film 38 on the bulb side thereof , and a heat absorbing filter 39 . as seen in fig1 leads 45 , 46 and 47 , from the three light sources illustrated , are connected through the top of housing 50 to the power supply 48 . a like lead is provided to the fourth lamp , and if five or more lamps are utilized they are powered in the same manner . the table 52 is rotated by a motor 54 which drives shaft 55 which is connected through to the table . in practice , the speed of rotation of the table is not believed critical , but it has been found that a range of about 0 . 5 to 50 rpm is suitable and about 2 rpm is a preferred speed . further means 58 are employed to raise or lower the table 52 , which may be necessary to accommodate dentures of mounted on models of different sizes . it has been found that a 4 inch diameter table is suitable to accommodate any anticipated denture size . for other applications involving curing of prosthetic objects , a larger table is used . depending upon the height of the table , the lamps , which are fixed in position , may be within a range of 5 to 13 cm from the surface of the denture or object of similar size , and on the average the distance from the rim of each light source to the center of the table is about 10 cm . for larger medical or medical - related objects , a greater average distance is utilized . while the preferred embodiment of a rotatable table is disclosed , the invention embraces any means for moving the object to be cured relative to the light source means , e . g . the lights may be moved , or the table can be moved through a different cycle , which may include raising and lowering as well as rotating . still referring to fig1 and 2 , there is shown an enclosure 60 , preferably made of sheet metal , which encloses an upper chamber 64 within the overall housing 50 . the table 52 and denture d are in a region 65 , which is accessible through a door 72 . the enclosure wall 60 has circular openings into which the faces 35 of the light sources are positioned . the lamps are connected to the sheet metal 60 with suitable mounting and connecting means , so as to provide a substantially air tight separation between spaces 64 and 65 . as illustrated in fig2 a fan or other air circulating means 68 is provided , along with one or more vents 70 , to provide positive or negative pressure for air cooling of the light sources . the enclosure 60 provides that the air circulation , which is necessary for cooling , does not affect the environment where the denture is , thereby keeping it free of circulating dust particles or other elements which could be detrimental to proper curing and formation of the denture . the curing unit of the present invention also may incorporate a housing 50 having walls or doors 72 that are visually transparent to allow inspection during operation of the unit in a closed operating mode . it is important for maintenance purposes that an operator be able to observe whether the lamps are operating . the transparent door , wall or wall portions may form one of the safety filters for protection of the operator &# 39 ; s eyes while allowing a clear view of the unit &# 39 ; s exact operation for precision of operation , particularly where a remake is involved caused by an operation caused flaw . the filtering arrangement also eliminates the emission of dangerous light waves such as uv waves . in practice , whenever the denture or medical object has been formed of the light curable material , the operator opens door 72 in the housing 50 , and places the denture on the table 52 . the operator then sets a timer , which is part of the apparatus in the box designated 48 , and energizes the system for the programmed time of curing . in the preferred embodiment , the transformerless power supply 48 is as shown in co - pending application , titled power control apparatus with optical isolation feedback means , d - 154 , u . s . ser . no . 492 , 285 , assigned to the same assignee and incorporated herein by reference . a soft start of power supplied to the lamps is provided , i . e . the voltage is ramped up to the designated power . by operating at about 20 % less than rated value , a relatively long lifetime of about 600 hours can be obtained for the lamps used in the preferred embodiment . in practice , the lamps may have a rating in the range of 30 - 60 volts , and may be operated at 10 to 25 % reduction of rated voltage . depending upon the size of the object to be cured , the operator adjusts the level of table 52 appropriately . as the object is rotated , light from each of the four light sources is incident thereon at continuously different angles , such that all portions of the object are irradiated . by holding the lamps within about 10 cm from the object surface , and providing collimated beams with a diameter of at least about 2 inches and a beam power of at least about 50 mw / cm 2 at the denture , there is more than sufficient light power to thoroughly penetrate and cure all portions of the object . as used in this specification and the claims hereto , the term &# 34 ; object &# 34 ; or &# 34 ; medical object &# 34 ; means any object which is shaped and then light cured for use in a medical or medically related application , or any portion of such an object , or any portion of a device used in any medical or medically related application . also , it is to be understood that the phrase collimated light refers to a beam of light having light flux lines which are substantially parallel , it being understood that it is physically impossible to generate a precisely and totally collimated beam . the simple parabolic reflector as used in the apparatus of this invention provides a beam which is sufficiently collimated that there is relatively little loss of light flux from the light source face 35 to the position of the denture , i . e . there is relatively little loss over the beam distance of 5 - 13 cm . further , while the lamp which is preferred for use in the apparatus of this invention has a rated voltage of 41 volts , and a rated power of about 200 watts , and these parameters have been found to provide excellent results , the lamps can be designed for different power and voltage ratings within the scope of this invention . likewise the power supply can be a conventional power supply utilizing a transformer or other design . however , it is noted that the combination of all of the design parameters as has been set forth herein contribute to an overall system and method which has been found to be unusually efficient for the stated purpose of curing dentures and like objects , and the parameters as disclosed and claimed are preferred for the practice of this invention . in carrying out the method of this invention , the object is placed under the light for a time of about 1 / 2 to 15 minutes , during which the object is moved cyclically relative to the lamp or lamps . collimated light is directed onto the object at the preferred angle , from a distance of about 10 cm and with a power at the object surface of at least about 50 mw / cm 2 . based on visual observations of a denture undergoing light curing , improved direct light penetration is achieved . also , visual observation has revealed that there is light curing of shaded areas , i . e . areas shaded by opaque material . this is believed to result from scattering of light rays that , due to the collimated light , have penetrated deeply into the translucent denture material . in some embodiments , it may be desirable to equip the curing chamber 65 with air circulating means in the general manner disclosed with respect to chamber 64 , or the two chambers may be interconnected . from all of the above , it will be understood that a method is provided for curing medical objects having light curable material as their composition or a portion of their composition . the object is engaged with a support and the light curable material is positioned for curing by projecting collimated light on it . it is preferred to project the light onto the curable material from a plurality of light sources positioned at different degree settings of an imaginary 360 ° circle . as shown in fig2 the lamps 30 , 31 , 32 and 33 are positioned one in each of the four 90 ° quadrants of an imaginary 360 ° circle around the object d . the circle is envisioned as extending around the object in a horizontal plane . the light sources or lamps are preferably positioned in at least three of the quadrants and prefrably positioned so that all quadrants of the imaginary 360 ° circle are simultaneously projected with light at the periphery of the light curable material . the light sources are preferably aimed with the center of the projected light from each light source approximately crossing an imaginary line corresponding with the average vertical height or the outer peripheral massive positions of the light curable material . by massive portions , it is meant to eliminate distortions in position due to small thin projecting portions which , in general , would not be expected to exhibit severe curing problems . the projected light is preferably projected at an angle of 20 ° to 45 ° from an imaginary horizontal plane taken at the lowermost portion of light curable material which corresponds to the top surface of the table 52 in fig1 . preferably the light curable materal is positioned for curing by adjusting the height of the support or table 52 . the table is preferably rotated as previously discussed . to achieve the depth of penetration providing the best results in thick objects , the light should be of high intensity in the activation wavelength region . high intensity light is further important to compensate for the loss of cure efficiency on the cured object surface by oblique incident light . while a source of high intensity light in the activation band is indicated , the adverse heating effects normally associated with such a source should be avoided on the article being cured to avoid damage in the usual instance . by adverse heating effects , it is meant quantitites of radiant heat that cause the article being cured to change shape due to heat induced flow or thermal expansion . the present invention avoids these adverse heating effects by heat absorption and reflection filters without substantial loss of light in the activation band . the removal of red and infrared light rays in the wave length range between 700 nm and 2400 nm is important to limit because of heating that demonstrates an adverse effect on light sensitive materials if not properly filtered . if excess infrared energy is permitted in the collimated light beam , excessive temperature rise in the material may result , causing rapid changes in the material to reduce viscosity or if sufficiently high , results in decomposition of the material . because of an excessive high temperature rise problem in material , optical filtering is important to reduce the red and infrared wave lengths between 700 nm and 2400 nm . for example , a 41 volt , 200 watt tungsten halogen lamp operated at - 20 % of its rated voltage or at 32 . 8 voltage having a 50 mm diameter parabolic reflector delivers a total of 35 watts at 6 cm distance from the reflector rim . in a preferred application of the invention , such as shown in fig2 where four ( 4 ) lamps are used , the material receives about 140 watts of optical power from wave lengths that are present in the light beam between 700 nm and 2400 nm . a heat - reflecting filter placed in the optical beam path can be made to reflect or virtually remove wave lengths between 700 nm and 1100 nm . this reduces the power delivered from the parabolic reflector to 17 . 5 watts per lamp or a total of 70 watts delivered to the material using four ( 4 ) lamps . this is a 50 % reduction in heating rays of the light beam . the addition of a second heat - absorbing filter is capable of removing wave lengths between 700 nm and 2400 nm and further reducing the red and infrared rays from the beam when used in conjunction with the heat reflecting filter to 1 . 4 watts or a total of 5 . 6 watts , using the four ( 4 ) lamps in the preferred application . this is a net reduction of 96 % of the heating rays in the light beam delivered to the material . the addition of a heat - absorbing filter only that is capable of removing wave lengths between 700 and 2400 nm reduces the red and infrared rays from the beam to 2 . 8 watts , or a total of 11 . 2 watts using four ( 4 ) lamps in the preferred application . this is a net reduction of 92 % of the heating rays in the light beam delivered to the materials . in special instances , some of the parameters previously delineated can be varied to advantage in preferred ranges . for example , the table may be rotated at from 0 . 5 to 50 rpm and the lamps or light source faces may be 1 to 15 cam , or more for large objects , from their closest approach to the surface to be cured . it is an important aspect of the apparatus of the present invention that it is adapted for use in hospitals and other medical uses where special needs exist , as contrasted to industrial equipment . the use of collimated light enables operation with a minimum of heat , which provides for safer operation in medical applications . the apparatus and method further provide a greater amount of cure power with the least amount of infrared generation , and with a minimum amount of input power required . a further feature that enables operation at low power is the fact that with collimated light there is less scattering of the light , resulting in a higher efficiency utilization . thus , the curing apparatus of this invention enables a compact light weight construction and operates at a relatively cool temperature , which is a substantial advantage in medical applications . also , due to the minimized power requirements it can be operated from a standard 110 volt line .

apparatus and method for providing light curing of prostheses and other medical object materials , the object being prefabricated of a material which is hardened , or polymerized when exposed to visible light . an array of light sources is provided relative to a rotatable platform on which the object is placed , each light source providing a substantially collimated light beam and directed to optimally intercept the rotating object . there are preferably four such light sources , each having a visible light bandpass characteristic and directed at an angle within 25 °- 45 ° of the platform surface , the light beams being directed at the platform surface in overlapping fashion so as to provide continuous incident light on the object during each cycle of rotation .

the earth has a natural magnetic field formed by the rotation of the earth . this rotation creates electrical currents in the molten iron found within the earth &# 39 ; s core , thereby producing a magnetic field . in addition to this magnetic field , the earth &# 39 ; s core also produces a range of electromagnetic radiation . one type of electromagnetic radiation produced is an ultra - high frequency radiation typically referred to as geopathic radiation . geopathic radiation filters out from the core of the earth and occurs in varying intensities at the surface of the earth . these varying intensities are caused by disturbances under the surface of the earth . these disturbances ( including geological faults , underground ore masses , underground water , and mineral deposits , among others ) reflect , refract , and / or diffuse the geopathic radiation as it travels through the earth and thereby concentrate the geopathic radiation at certain areas on the surface of the earth . studies have shown that the presence of geopathic radiation , especially in a location where a person spends a significant amount of time , produces illnesses and maladies including arthritis , cancer , and sleep disturbances . geopathic radiation can contribute to a vast array of other illnesses by interfering with the immune system and the production of growth hormones which rebuild the body during sleep . these studies , several of which have been funded by european governments , attest to the existence of geopathic radiation and document evidence of the illnesses that this radiation induces . these studies also evidence immediate relief from symptoms of certain illnesses when the patient is removed from the area of radiation . because of the observed detrimental effects of geopathic radiation , certain municipalities in europe require a determination of the intensity of the geopathic radiation at a location before a building permit is issued . one study has found that these detrimental effects may be due to the effect of geopathic radiation on the surface tension of water . geopathic radiation has been shown to change this surface tension , and since humans are over 70 % water , this change in surface tension greatly effects the operation of the human body ( for example , the membrane process of creating seratonin , which regulates sleep ). the effect of geopathic radiation on the human body is discussed in further detail in geopathic stress : how earth energies affect our lives , by jane thurnell - read , element books ( rockport , mass . ), copyright 1995 , which is incorporated herein by reference . while one method of avoiding the detrimental effects of geopathic radiation is to avoid the radiation altogether , this is often impossible due to the fact that one or more zones of geopathic radiation may be pervasive throughout an existing building or other occupied areas . furthermore , geopathic radiation zones may shift over time , making it difficult to move away from the radiation . embodiments of the present invention solve this problem by providing geopathic radiation shields that may be positioned between a source of geopathic radiation and an area to be protected or shielded ( hereinafter referred to as the “ shielded area ”). in order to protect a shielded area from geopathic radiation , embodiments of the present invention employ mica , which has been discovered to prevent the transmission of geopathic radiation , in a number of different forms . [ 0017 ] fig1 illustrates several embodiments of the present invention employed in a room 10 of a building to prevent or partially prevent geopathic radiation from being transmitted to certain shielded areas of room 10 . in the illustrated embodiment , sheets 20 of mica ( or material loaded or doped with mica ) are used to block geopathic radiation . for example , a mica - loaded electrical insulation mat may be used as sheet 20 . in addition , any other sheets , mats or other layers of any material that include mica may also be used as sheets 20 . in general , as the thickness of the layer of mica ( or the amount of mica loaded in a particular material ) in sheet 20 increases , the amount of geopathic radiation blocked by sheet 20 also increases . although any thickness or amount of mica may be used according to the present invention , it has been observed that thicknesses of mica less than 0 . 015 inches will deteriorate within about three to four months and may need to be replaced . as illustrated in fig1 sheets 20 may be employed to block geopathic radiation in room 10 in a variety of ways . for example , sheet 20 a is positioned under a bed 30 to prevent geopathic radiation originating from under bed 30 from reaching an occupant of bed 30 . likewise , sheet 20 b is placed under a chair 32 to prevent geopathic radiation originating from under chair 32 from reaching an occupant of chair 32 . although it may be more economical to only place sheets 20 under areas that are occupied for significant periods of time , such as bed 30 and chair 32 , a sheet 20 may also be placed over the entire floor 36 of room 10 ( thus making the entire room 10 a shielded area ). such a sheet 20 may be hidden under carpeting or placed under the surface of floor 36 during the construction of the building . due to reflection and refraction below the earth &# 39 ; s surface , geopathic radiation may also propagate in a direction other than the direction that is perpendicular to the earth &# 39 ; s surface . such reflected or refracted radiation may travel through walls 34 of room 10 in addition to traveling through floor 36 . to protect an occupant against such radiation , a sheet 20 c may be hung on wall 34 to prevent geopathic radiation from traveling through wall 34 . in addition , a sheet 20 d may be incorporated inside wall 34 during construction and / or may be incorporated in existing thermal insulation materials . as illustrated in fig2 sheets 20 may include one or more layers 40 of material , in addition to a layer of mica 42 , that are operable to block other types of electromagnetic radiation . for example , a layer 40 of lead may be employed to block x - ray or gamma ray radiation . in addition , although not required , all of the sheets 20 described above may be fabricated such that no materials toxic to humans are included . [ 0021 ] fig2 illustrates a building 50 having a foundation 52 that is operable to block geopathic radiation . building 50 may be a house , apartment , hospital , office building or any other structure that may be supported by a foundation . in this embodiment , a quantity of mica is mixed into the concrete ( or other material used to create the foundation 52 ) such that foundation 52 at least partially prevents geopathic radiation 54 from being transmitted from below surface 56 to building 50 . as is illustrated in fig2 the mica in foundation 52 may absorb , diffuse , reflect , refract , or transmit geopathic radiation . preferably , geopathic radiation is either absorbed , diffused , reflected , or refracted away from building 50 . however , acceptable amounts of geopathic radiation may still be transmitted through foundation 52 to building 50 . to construct foundation 52 , the concrete or other appropriate foundation material is mixed as is typical in the construction industry . at any point in this mixing process ( or even when the dry concrete mix is made ), a quantity of mica is mixed in the concrete or other material . this mica may be in any form , including mica powder and mica flakes . for example , but not by way of limitation , a fifty pound bag of powdered mica or mica flakes may be added to each cubic yard of concrete , or other material . the mica may be mixed into the concrete or other material in any manner such that the mica is sufficiently distributed throughout the concrete or other material . any suitable amount of mica may be added to the concrete or other foundation material according to the present invention . however , it has been observed that the greater the quantity of mica added to the foundation , the greater amount of geopathic radiation that is blocked . in an alternate embodiment , mica powder is added to paint during or after the paint manufacturing process . this mica powder is mixed into the paint such that the mica is suspended in the paint and at least partially prevents the transmission of geopathic radiation through the paint . the paint into which the mica is mixed may include any type of paint , including primer . the mica may be added during the manufacturing process by the paint manufacturer , during the mixing process by the paint retailer , by an end user before applying the paint , or at any other appropriate time . as described above , the greater the amount of mica used , the greater the amount of geopathic radiation that is blocked . therefore , multiple coats of the paint may be applied to a surface to increase the amount of geopathic radiation blocked by the paint . as illustrated in fig1 the mica - paint mix 60 may be applied to walls 34 or floor 36 to at least partially prevent the transmission of geopathic radiation through these surfaces . mica may also be included in numerous other building materials to block the transmission of geopathic radiation into the building into which they are incorporated . for example , mica may be incorporated into or added as a layer on shingles used to roof a building , siding used to cover the sides of a building , tiles used to tile the floor of a building , linoleum flooring used to cover the floors of a building , and insulation used in the walls , floors , and ceiling of a building . any other appropriate use of mica to block the transmission of geopathic radiation is also encompassed within the scope of the present invention . although the present invention has been described with several embodiments , a myriad of changes , variations , alterations , transformations , and modifications may be suggested to one skilled in the art , and it is intended that the present invention encompass such changes , variations , alterations , transformations , and modifications as fall within the spirit and scope of the appended claims .

a method of blocking geopathic radiation is provided that includes identifying a location at which the blocking of geopathic radiation is desired . the method further includes positioning a layer of material including mica between a source of the geopathic radiation and the identified location , such that the geopathic radiation is at least partially prevented from being transmitted to the identified location .

detailed descriptions of the preferred embodiment are provided herein . it is to be understood , however , that the present invention may be embodied in various forms . therefore , specific details disclosed herein are not to be interpreted as limiting , but rather as a basis for the claims and as a representative basis for teaching one skilled in the art to employ the present invention in virtually any appropriately detailed system , structure or manner . in accordance with the present invention , fig1 a shows the position of angular adjustment mechanism for snowboard bindings 10 in an exploded position relative to both boot binding 20 and section of snowboard 40 . those portions of the invention which mate rigidly to either the snowboard 40 or the boot binding 20 are shown in fig1 b . referencing both fig1 a and 1 b , upper plate 11 and upper gear coupling 12 are shown with a bolt hole pattern matching that of boot binding 20 and , when incorporated , would mate rigidly to same . lower retainer 16 and lower gear coupling 15 are shown with a bolt hole pattern matching that of snowboard 40 and , when incorporated , would mate rigidly to same . the components shown in use in angular adjustment mechanism for snowboard bindings 10 in all figures are shown substantially thicker than necessary for purposes of clarity of illustration and can therefore be reduced in size for manufacturing . fig2 a shows an exploded view of the angular adjustment mechanism for snowboard bindings 10 . upper plate 11 and upper gear coupling 12 both mount rigidly to boot binding using bolts or similar fasteners ( not shown ). lower retainer 16 and lower gear coupling 15 , both mount rigidly to snowboard using bolts or similar fasteners ( not shown ). the upper retainer 13 features a lip at its top with bolt holes for affixing to upper plate 11 using bolts or similar fasteners ( not shown ). inside the upper retainer 13 , at its bottom is a lip extending inwards . the lower retainer 16 features a lip at its top extending outwards . when assembled , the lower lip of upper retainer 13 is below the upper lip of lower retainer 16 which prevents a detachment of upper retainer 13 and lower retainer 16 and provides an annular cavity between these two features . within this cavity is positioned wave washer 14 . wave washer 14 provides a tension force that drives the combination of upper gear coupling 12 and lower gear coupling 15 together which locks the mechanism from rotating when external forces are absent . wave washer 14 is an undulating ring of spring steel that provides a resistive opposition to compression forces . washers of differing stiffness or a plurality of washers could be made available to fit the user &# 39 ; s preferences . alternative components might include belleville washers , compression springs , or elastomers . upper plate 11 and upper gear coupling 12 are shown as separate items but can be constructed as one piece . furthermore , lower retainer 16 and and lower gear coupling 15 are shown as separate items but can be constructed as one piece . upper gear coupling 12 and lower gear coupling 15 are plates with one side comprised of radially - extending raised teeth . when upper gear coupling 12 and lower gear coupling 15 are engaged ( teeth of one extended into the recesses of the other ), radial forces from the rider can be transmitted to the snowboard . upper gear coupling 12 and lower gear coupling 15 are shown with a coarse tooth spacing for clarity of illustration , but more closely - spaced teeth would provide for a wider selection of boot angular orientation . fig2 b shows a side view of the mechanism fully assembled . as shown , there is upper retainer 13 fastened to upper plate 11 . also visible is lower retainer 16 . to illustrate the principles of operation , there is shown in fig3 a and 3 b cross - sectional side views of the assembled mechanism . upper plate 11 and upper gear coupling 12 are both mounted rigidly to the boot binding . lower retainer 16 and lower gear coupling 15 are both mounted rigidly to snowboard . upper retainer 13 would be positioned as shown surrounding lower retainer 16 . the lower lip of upper retainer 13 is a slip fit over the vertical side walls of lower retainer 16 such that relative vertical motion is allowed , but snow and grime will not pass the touching surfaces to get inside . wave washer 14 is positioned within the cavity formed by the lower inside lip of upper retainer 13 and the upper outside lip of lower retainer 16 . while there are no external forces on the mechanism shown in fig3 a , the wave washer 14 exerts pressure upward against lower retainer 16 and simultaneously downward against upper retainer 13 . this forces the upper part of the assembly ( upper plate 11 , upper gear coupling 12 , and upper retainer 13 ) down against the lower part of the assembly ( lower gear coupling 15 and lower retainer 16 ), thereby forcing together into a mating relationship upper gear coupling 12 and lower gear coupling 15 , which prevents any angular rotation of the top portion with respect to the lower portion . fig3 b illustrates the mechanism when it is disengaged . when the upper portion of the assembly ( upper plate 11 , upper gear coupling 12 , and upper retainer 13 ) which is attached rigidly to the boot binding is forced upward while simultaneously the lower portion of the assembly ( lower gear coupling 15 and lower retainer 16 ) which is attached to the snowboard is forced downward , the resistance to compression of the wave washer 14 is overcome . the wave washer 14 then becomes substantially flattened as the upper and lower portions of the assembly are forced apart . when the separation of the upper and lower portions of the assembly become sufficiently great , the upper gear coupling 12 and lower gear coupling 15 become disengaged and the upper portion of the assembly is free to swivel in an angular direction with respect to the lower portion . in accordance with the present invention , fig4 a and 4 b illustrate a typical application . in these figures , the present invention angular adjustment mechanism for snowboard bindings is mounted between the underside of boot binding 20 and the upper surface of snowboard 40 and is therefore concealed from view . in a static circumstance ( no external forces applied ), the angular adjustment mechanism for snowboard bindings is locked and no angular motion is possible . to initiate intended angular repositioning , in fig4 a , the snowboard rider puts his or her weight on one boot 30 ( indicated in the figure by the “ down ” arrow ). simultaneously , the rider lifts up on the other boot ( indicated in the figure by the “ up ” arrow ) which disengages the locking feature of the angular adjustment mechanism for snowboard bindings which permits the angular rotation of the boot 30 in any orientation desirable ( fig4 b ). relieving the opposing forces on the angular adjustment mechanism for snowboard bindings re - engages the locking mechanism prohibiting further angular motion . the preceding steps may be repeated in the opposite order to adjust the other boot &# 39 ; s angular orientation . while the invention has been described in connection with a preferred embodiment , it is not intended to limit the scope of the invention to the particular form set forth , but on the contrary , it is intended to cover such alternatives , modifications , and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims .

the angular adjustment mechanism for snowboard bindings positioned between the snowboard and boot bindings allows angular adjustment between the snowboard rider &# 39 ; s boot bindings and the snowboard without the need for any tools or levers . the user can make adjustments at any time by weighting the board with either foot and lifting and rotating the opposite foot . a lifting action releases the mechanism allowing for the adjustment of angular orientation . removal of the lifting force engages the locking mechanism preventing further angular movement .

the invention is a portable exercise device 10 comprising a first bar 12 , a second bar 14 , a third bar 16 , a first arm 18 and a second arm 20 . each of the bars 12 , 14 and 16 and each of the arms 18 and 20 has a proximal end 12a - 20a 128 and a distal end 12b - 20b . each of the bars 12 , 14 and 16 and each of the arms 18 and 20 can be constructed of any suitably rigid material . preferably , for ease of manufacture and for good strength - to - weight ratio , each of the bars 12 , 14 and 16 and each of the arms 18 and 20 is constructed of a metal , such as aluminum or steel . each of the bars 12 , 14 and 16 is preferably padded with a durable foam material or other suitable padding material 22 . the padding material 22 markedly increases the comfort to the user when using the device 10 . the device 10 can be constructed in an e - shape or in an s - shape . in either case , the proximal end of the first arm 18 is attached to the proximal end of the first bar 12 , such that the first bar 12 and the first arm 18 are disposed at right angles . in the embodiment shown in the drawings , the first arm 18 is rigidly attached to the first bar 12 , although this is not necessary . so long as the movement of the first arm 18 with respect to the first bar 12 is controlled , the first arm 18 can be swivably attached to the first bar 12 . the proximal end of the second arm 20 is swivably attached to one end of the first bar 12 , such that the first bar 12 and the second arm 20 are disposed substantially at right angles . when the second arm 20 is attached to the proximal end of the first bar 12 , the resulting shape of the device 10 is e - shaped , as shown in fig1 - 3 . when the second arm 20 is attached to the distal end of the first bar 12 , the resulting shape of the device 10 is s - shaped , as shown in fig1 . the proximal end of the second bar 14 is attached to the distal end of the first arm 18 , such that the second bar 14 is disposed at substantially right angles to the first arm 18 and such that the second bar 14 is disposed substantially parallel with the first bar 12 . the proximal end of the third bar 16 is attached to the distal end of the second arm 20 , such that the third bar 16 is disposed at substantially right angles to the second arm 20 and such that the third bar 16 is disposed substantially parallel with the first and second bars 12 and 14 . the first bar 12 , the second bar 14 and the third bar are retained in spaced - apart , parallel relationship with one another solely by the first arm 18 and the second arm 20 . in other words , each of the bars 12 , 14 and 16 is attached at one end to one of the arms 18 or 20 , and the other end of each of the bars 12 , 14 and 16 is unattached to any structure . this allows the user to position his or her body between the bars 12 , 14 and 16 as illustrated in fig1 . preferably , the length of the arms 18 and 20 are adjustable to allow a greater or lesser distance between the three bars 12 , 14 and 16 . as shown in the drawings , the arms 18 and 20 can each be comprised of telescoping moieties 23a and 23b . this makes the arms 18 and 20 telescopically adjustable between predetermined matching notches 24 , and held within a specified notch 24 by some form of pins 26 . such pins 26 can be spring steel prongs such as shown in fig2 and 3 , or thumb screws such as shown in fig1 . alternatively , a u - shaped bracket 28 , such as illustrated in fig9 can be affixed within the arms 18 and 20 and adapted to snap in and out of the notches 24 by detent - type pins 26 disposed within the two ends of the bracket 28 . the device 10 further incorporates torsion means for resisting the swiveling action of the second arm 20 with respect to the first bar 12 . in those devices where the first arm 18 is free to swivel about the first bar 12 , additional torsion means ( not shown ) are provided for resisting the swiveling of the first arm 18 with respect to the first bar 12 . as shown in the drawings , the torsion means can comprise a coil spring 30 or a torsion bar 32 . other torsion means can also be used . a coil spring torsion means 30 is illustrated in fig2 and 4a . the coil spring 30 is disposed within the first bar 12 . a first end 34 of the coil spring 30 is affixed to the first bar 12 . a second end 36 of the coil spring 30 is affixed to a pivotable pin 38 which is linked to the second arm 20 via a pair of rachet washers 40 . a torsion bar torsion means 32 is illustrated in fig3 and 7 . the torsion bar 32 is disposed within the first bar 12 . the torsion bar 32 has a first end 42 which is affixed to the first bar 12 . the torsion bar 32 has a second end 44 which is affixed to the second arm 20 via rachet washers 40 . preferably , the torsion means are adjustable . as shown in fig4 a , a coil spring torsion means 30 can be made adjustable by use of an adjustment bolt 48 which is affixed to the first end 34 of the coil spring 30 . loosening the adjustment bolt 48 provides less tension to the coil spring 30 . tightening the adjustment bolt 48 increases tension . as shown in fig5 where the torsion means is a torsion bar 32 , the torsion means can be made adjustable by means of a ring 50 which can be slid axially along the torsion bar 32 . the ring 50 has a dog 52 which is received and retained within one of several notches 54 disposed within the first bar 12 . the ring 50 is selected so that it can be slid axially along the torsion bar 32 , but it does not slip when the torsion bar 32 is turned radially . a set screw 56 can be disposed within the dog 52 to firmly affix the ring 50 to the torsion bar 32 at the predetermined location . in another embodiment , the torsion means is readily interchangeable with similar torsion means of a different strength . this allows the device 10 to be used for a wide variety of exercises requiring widely different torsion resistance strengths . accordingly , the invention 10 is also a kit comprising the device 10 of the invention plus one or more interchangeable torsion means of differing strength . the rachet washers 40 allow for the &# 34 ; at - rest &# 34 ; disposition of the second bar 14 with respect to the third bar 16 to be ; adjustably set at a predetermined distance by loosening the rachet washer attachment nut 58 , allowing the arms 18 and 20 to pivot with respect to one another to a predetermined position , and then tightening down on the rachet attachment nut 58 . the invention 10 provides an inexpensive and easily maintained multiple - muscle exercise device which can be easily stored and transported by a user within a suitcase or other convenient travel means . fig1 illustrates a number of ways that the device 10 can be used to exercise different muscles . fig1 a illustrates how the device 10 can be used to strengthen stomach muscles . the first bar 12 is placed to the rear of the user and the second and third bars 14 and 16 are placed in front of the user . the user then squeezes the second and third bars 14 and 16 toward each other using his or her chest and legs . fig1 b illustrates how the device 10 can be used to strengthen triceps muscles . the user places the first bar 12 against his or her back . the user then squeezes the second and third bars 14 and 16 toward each other by pressing downward on the upper - most arm with the user &# 39 ; s hands . fig1 c illustrates how the device 10 can be used to strengthen biceps muscles . again , the user places the first bar 12 against his or her back . in this case , however , the user squeezes the second and third bars 14 and 16 toward each other by pressing upward on the bower - most arm with the user &# 39 ; s hands . fig1 d illustrates how the device 10 can be used to strengthen the chest muscles of the user . the first bar 12 is positioned against the chest of the user and the second and third bars 14 and 16 are squeezed toward each other with the user &# 39 ; s arms . fig1 e illustrates how the device 10 can be used to strengthen the user &# 39 ; s thigh muscles . the first bar 12 is placed between the user &# 39 ; s legs and the second and third bars 14 and 16 are squeezed toward each other by use of the user &# 39 ; s legs . fig1 f illustrates how the device 10 can be used to strengthen other leg muscles . the user lies on his or her back with the first bar 12 resting on the floor . the user then squeezes the second and third bars 14 and 16 toward each other using his or her legs . fig1 g illustrates how the device 10 can be used to strengthen triceps and shoulder muscles . the user sits upon the first bar 12 with the second and third bars 14 and 16 disposed behind the user . the user then presses downwardly on the upper - most ( second 14 or third 16 ) bar using his or her hands placed behind the back . fig1 h illustrates how the device 10 can be used to strengthen chest , shoulder and triceps muscles . the device 10 is placed on a flat surface with the first bar 12 disposed away from the user . the user then squeezes the second and third bars 14 and 16 together by pressing down on the upper - most bar with his or her arms . fig1 i illustrates how the device 10 can be used to strengthen other leg muscles . the first bar 12 is placed beneath the user &# 39 ; s knees . one of the other bars 14 and 16 is placed in front of the user &# 39 ; s lower legs and the remaining bar is placed to the front of the user &# 39 ; s upper legs . the user then squeezes the second and third bars 14 and 16 together by lifting his or her legs . fig1 j illustrates an alternative procedure for strengthening leg muscles . in this procedure , the user sits upon the first bar 12 and one of the other bars 14 or 16 . the user then lifts the remaining bar 14 or 16 with his or her legs . fig1 k illustrates how the device 10 can be used to strengthen back muscles . the user sits on the second or third bar 14 or 16 with the first bar 12 positioned behind the user and the remaining bar 14 or 16 disposed along the user &# 39 ; s back . the user then thrusts the bar 14 or 16 disposed along his or her back in a rearward fashion by sitting up straight . having thus described the invention , it should be apparent that numerous structural modifications and adaptations may be resorted to without departing from the scope and fair meaning of the instant invention as set forth hereinabove and as described hereinbelow by the claims .

a portable exercise device is provided which is inexpensive and easy to maintain while being capable of providing exercise to a wide variety of human muscles . the device has three padded parallel bars disposed in fixed relationship by a pair of arms . although the two arms can be disposed in a single line , generally they are disposed to form a v - shape . a torsion device is provided to resist the swiveling of one arm with respect to the other .

refer to fig1 . the permeable aerodam ( dam ) 10 is utilized to prevent turbulence along the side of the rider &# 39 ; s head by placing it behind the cheekbone - eyebone area 12 and in front of the ear canal 14 . the dam is conveniently fitted onto a front strap 16 of bicycle helmet 18 by a friction clip 20 which is glued to the bottom surface of base 36 as shown in fig2 . the front strap 16 is held in place by a strap buckle 22 which also connects a rear helmet strap 24 and lower chin strap 26 . in fig1 and 2 a headwind 28 approaches the side of the rider &# 39 ; s head . the air flow closest to the head passes through the dam by first passing through a containment screen or netting 30 and then by tortuous path through a fiber filter or labyrinth 32 . refer to fig2 and 3a . the filter 32 is held in position by a matrix 52 comprising a containment 30 , a series of triangular foam abutments 34 , and a base 36 . the abutments , which are 2 milimeters thick are glued to the upper surface of the base 36 which is 3 mm thick . the containment is a netting woven with a 0 . 05 mm polyester monofilament thread thus forming a very light weight highly permeable tulle . the netting 30 covers the part of the dam above the base and is glued to the front edge 38 of all abutments as well as to the front edge 40 and rear edge 42 of the base . the front surface of the filter 32 is lightly glued to the rear edge 44 of abutment 34 and the rear surface 46 of filter 32 is lightly glued to the containment 30 . the bottom 48 of the filter is glued to the top of the base 36 and the edge tip 50 or upper edge of filter 32 terminates at the tip 51 of the abutment 34 . thus , the filter is held firmly in position against wind pressure and rough handling . the most effective , readily available and inexpensive flow impedance material which i have found is a polyester batting comprised of monofilaments 0 . 0125 mm to 0 . 025 mm in diameter and about 2 . 5 cm long each , and which are collectively woven and layered randomly into a fiber mass . hundreds of fibers per cubic centimeter are loosely intermixed together resulting in a fiber density of 2 % to 7 %. thus , there is a considerable amount of void volume for the air to flow through . the commercial name of the combed fiber is trademarked mountain mist glazene , type 203 and is manufactured by the stearns technical textile company ( sttc ), cincinnatti , ohio , 45215 . the type 203 is anisotropic in character , that is the fibers are combed so that a majority of them are caused to lay in one direction . there are uses for the uncombed isotropic type as well , such as type 605 which will be discussed in the variations . fig2 shows the anisotropic character of a type 203 fiber filter 32 . the fibers are generally oriented so that they span the distance between adjacent abutments . this is done to increase the fabrication strength and to decrease the migration of the individual fibers . although the fibers mentioned above are very useful and appropriate for cycle apparel , other fibers such as cotton , stainless steel wool , etc can be used to achieve the same result as will be discussed in the operation section . refer to fig3 b . the fiber filter does not require anisotropic or combed fiber direction provided the containment 30 is in contact with the filter on all sides . the isotropic filter such as type 605 can be used as an alternative . the containment is glued to edge 44 of abutment 34 and the bottom of the filter 33 is glued to the upper surface of base 36 . refer to fig3 c . there is no containment in this variation . anisotropic fiber is glued to base 36 and the ends of the fibers are butt glued to the abutment surface 55 . the outer extensions of the fibers are trimmed to the dimensional limits of the edges 38 and 44 of abutments 34 . the lengths of the fibers are exposed to handling , but the elimination of the containment 30 decreases the flow impedance through the dam for quietest operation . refer to fig3 d . this design is similar to fig3 c except that the matrix 52 consists of wires 70 which replace the abutments . the wires are fastened to the base at points 54 . the wires 70 form an arch which has a highest point at apex 56 . the advantages are that the filter surrounds the matrix for a better lateral control of the velocity profile as will be discussed in the operation section . refer to fig3 e . anisotropic fibers 32 are glued to the surface of a series of screens 58 which are bent and glued to base 36 at points 60 . advantages of this construct is that the screens can be bent at will to alter the three dimensional shape of the dam 10 while operating in the field under experimental or quick adjust purposes . refer to fig3 f . this variation addresses the problem of product liability . the methods of attachment by clip 20 can be altered to a foam rubber flap 62 . a fabric hinge 64 attaches flap 62 to the edge 40 of base 36 . a velcro loop strip 66 and a velcro hook strip 68 are attached to the opening edges of base 36 and flap 62 respectively . this arrangement allows easy fastening to strap 16 of the helmet and all materials are flexible to prevent injury in case of a crash . refer to fig3 g . this variation proposes a quiet matrix and tip edge combination . the same construction of filter 32 is used as in fig3 a . however , the front edge 38 of abutment 34 is cut back to edge 72 to accomodate a thin strip of isotropic fibers 33 in order to act as a buffering leading edge on the abutment 34 . this prevents the leading edge from whistling at high incident speeds . the containment 30 is lightly glued to the outer surface of fibers 33 . included in this design is a tip 73 which is formed by doubling back or pleating the containment netting 30 and lightly gluing the rear fold 74 of tip 73 to the front fold 75 . this construct orients the tip of the containment 73 to be perpendicular to the overflow 90 at the tip 50 of the filter 32 . this minimizes the flow impedance at the tip . another feature of fig3 g is that the bottom of the base 36 has no clip or hinge flap , but instead relies on a contact cement 76 to adhere the aerodam to a pre - existing surface such as the dome of a helmet , or to any surface that requires turbulence control . refer to fig4 . end plates 78 composed of foam sheeting are cemented to the rear edge 44 of the outer abutments 34 . the end plates delay the end flow or wake 80 from encroaching inward toward the ear canal 14 . end plates reduce the three dimensional effects on the wake 82 which is caused by the limited span of the dam . end plates also reduce the end - flow 80 when the rider &# 39 ; s head is tilted too far up or down . there are three regions in and around the aerodam which are responsible for the stable flow in an otherwise turbulent environment . the first is a pressure zone in front of the dam , the second is the molar viscosity within the fiber filter and the third is the laminar wake and its maintainance behind the dam and around the ear canal . the three zones will be discussed in order . refer to fig5 . the schematic diagram shows the fiber filter 32 having a median line m which is forward leaning . the forward leaning area between the filter 32 and the base 36 is occupied by a high pressure zone 94 just aft the cheekbone area 12 and up to a height y from the wearer &# 39 ; s temple area . the high pressure is caused by the filter impedance . a circulation or bubble with an axis parallel to the width of the dam and perpendicular to the incoming air flow 28 is trapped in front of the filter and is stationary . without the filter , the bubble would turn with its axis parallel to the flow 28 and induce turbulence around the temple area ( kristiansen , et . al ., fig6 ). the high pressure zone 94 stabilizes the headwind 28 so that induced turbulence is prevented . the consequence of forward stabilization is that the aerodam wake must also be stabilized . thus , the kinetic energy developed in the pre flow will be partially consumed in pressurizing flow through the flow impedance or filter 32 . the flow through the dam must be silent if it is going to be successfully used as an aeroacoustic filter on a bicycle helmet . for this , the gauge of the fiber for filter 32 must be properly sized . if the fiber is relatively large in diameter an unstable wake will occur which can create a whistling sound called streuhall radiation , which will have a lowest frequency of f = sv / d , where v is the speed of the air flowing around the fiber , d is either the diameter of the fiber or the distance between fibers , whichever is larger , and s is a constant . to prevent instability the diameter d must be made as small as possible so that the damping viscosity becomes the dominant force surrounding the fiber . indeed , taylor found that the amount of time t it takes to damp a vortex generated behind a small fiber of diameter d to one nth its original vorticity strength is πd 2 / 8ν ( n 2 / 3 - 1 ), where ν is the kinematic viscosity which for air is 0 . 14 cm 2 / sec -( dryden , et . al , chapter 3 . 4 ). for a fiber diameter of 0 . 0025 cm ( 0 . 001 inch ) and n = 10 , the decay time is 64 microseconds . if the flow speed past the fiber is 48 . 4 km / hr ( 30 mph ) then the 1 / 10th decay distance is 0 . 86 mm ( 0 . 034 inch ), which is well within the separation between the helmet strap 16 and the ear canal 14 . the fiber dimensions of the type 203 or 605 sttc are ideally suited for the application of the taylor damping function . generally , the fiber density k to be used at the tip 50 of the filter is too dense and must be lofted to 1 % or 2 % fiber density by the use of a small vacuum or mechanical plucking process . refer again to fig5 . the cross section of the filter 32 comprising type 203 sttc fibers is tapered to form a wedge having a width w at a height y above the base 48 of the filter . the wedge provides a low impedance gradient or wake stabilizer where the fast overflow 90 around the wedge is prevented from breaking into turbulence by a slightly slower injection or effusion velocity 82 just below it within the height of tip 50 . that injection is stabilized by yet a lower and slower velocity , etc . all the way to the base in a continuous diminuation of injection speeds so that the injection process defines the velocity profile 92 . roll - up 84 is formed downstream and is caused by wake circulation . like a rotating wheel , the fast overflow passes and rolls down over the slower effusion wake , in a slow , low shear stress laminar flow . when the overflow meets the surface the shear stress is suddenly increased and pre - turbulence may again commence . between this point and the wedge 32 is called the null zone 86 , because the flow is so quiet near the surface . calculations were done which fit well with field trials , such as roll - up distance as a function of y , fiber distribution , and height as a function of camber line m . the distance from the wedge to the beginning of roll - up was observed to be about four inches behind the aerodam for one of the designs of fig3 . noise attenuation was observed to be 20 to 30 decibels in still air using the type of test described in u . s . pat . no . 5086789 ( tichy ). the noise attenuation was so complete that in a road bike test at 30 miles per hour , it was difficult to assess the accuracy of decibel drop due to the noise of the bicycle wheels on the pavement . so slight was the head wind noise that i could hear a car door shut , a small dog bark , a bird sing , and some children playing in a yard as i coasted downhill . without turbulence abatement none of those sounds could have been heard . the aerodam is considerably successful with many types of wedge designs . but in windy conditions where there is turbulence , soft pulsing may be felt in some designs because of the induced variations in the roll - up distance or by variations in the overflow envelope induced by bernoulli fluctuations of the overflow . this is a universal problem for sound sensitive devices such as submarine hydrophones travelling through a turbulent sea ( strasberg ), or microphones in windy conditions . the parameters mentioned above can be adjusted to minimize these non acoustic effects . in addition end plates can be quite effective at stabilizing pulses . see fig4 . end plates reduce the three dimensional effects of flow by increasing the length of the injection wake 82 before roll - up 84 where stationary circulation commences , fig5 . the effect of end plates is to extend the null zone 86 rearward to help isolate the ear canal from the overflow 90 . the present invention is useful in reducing turbulence caused noise past a sound sensitive device or system without physically covering the system . by now it should be evident to one skilled in the art that the permeable aerodam concept achieves a stable injection velocity profile at any flow speed over a sound sensitive system without having to physically cover the system . the advantages over the deflection art include the lack of fabric noise over the system ; an optically visible system which satisfies style requirements or optical monitoring or ventilation ; easy access to the system ; simplicity ; ease of operation ; and flexibility in design . uses in air include hearing protection , hearing aid protection , architectural gust abatement , automotive flow control , and drag control . filter methods can be redesigned to render use in any fluid medium other than air , such as water , blood or explosive liquids and gasses where flow separation at a critical point may be prevented . the methods of base mounting are not limited to those mentioned in the embodiments , but can cover welded , bolted , sewn , glued , or magnetic strip attachments as well . methods of filter support may cover integrated matrix and filter or a discrete matrix labyrinth with filter . although the present invention is useful in the control of fluid flow , many other varied embodiments that incorporate the teachings of the present invention may be easily constructed by those skilled in the art . high speed flow separates from a convex surface which ultimately causes turbulence downstream . to calm the flow an aerodam comprising a tilt - up filter is strategically placed so that the flow impedance of the filter causes a forward pressure zone at the point of separation . the filter impedes the near - surface flow by an in - situ process , causing a design shaped wake velocity profile . the profile wake injects stabilized flow beneath the overflow so that a local laminar flow regime is created . a null zone is created downstream providing a quiet flow environment . ambient sounds are simply not affected . since the aerodam is forward positioned , the null zone falls in the same position as the ear canal . the null zone is also a good place to put a microphone or a hydrophone for underwater use . the success of the filter depends on its tilt angle , fiber density , fiber diameter and the height of the aerodam . d . smith , march 1993 bicycling , &# 34 ; questions and answers , wind noise &# 34 ;, pp 43 - 44 . u . r . kristiansen , o . k . pettersen , 1978 journal of sound and vibration , &# 34 ; experiments on the noise heard by human beings when exposed to atmospheric winds &# 34 ;, 58 ( 2 ), 285 - 291 . w . k . van moorheim , et . al ., 1981 journal of sound and vibration , &# 34 ; the effects of motorcycle helmets on hearing and the detection of learning signals &# 34 ;, 77 ( 1 ), 39 - 49 . hugh l . dryden , et . al ., 1956 hydrodynamics , dover publications , inc ., new york , chapter 3 . 4 &# 34 ; the growth and decay of vortex motion &# 34 ;, pp212 - 222 . jacob bear , 1972 dynamics of fluids in porous media , dover publications , inc ., new york . m . strasberg , 1979 j . acoust . soc . am ., &# 34 ; nonacoustic noise interference on measurements of infrasonic ambient noise &# 34 ;, 65 ( 5 ) nov . pp 1487 - 1493 .

a permeable aerodam 10 is fastened to a front helmet strap 16 of a bicycle rider &# 39 ; s helmet 18 . the aerodam includes a shaped fiber filter 32 which is mounted on a base 36 and is designed to impede , but not arrest the motion of air flowing through it . the aerodam also includes a matrix 52 which includes the base and which shapes , supports , and locates the filter next to the temple area . a headwind experienced by the rider flows around the side of the head and partially through the aerodam such that an impedance gradient caused by the shaped filter will cause a quiet retrolaminar flow velocity profile 92 alonside the rider &# 39 ; s ear canal . the effect eliminates the onset of noisy turbulence heard by the rider while allowing unobstructed ambient sounds and ventilation to be enjoyed .

the following description is provided , alongside all chapters of the present invention , so as to enable any person skilled in the art to make use of said invention and sets forth the best modes contemplated by the inventor of carrying out this invention . various modifications , however , will remain apparent to those skilled in the art , since the generic principles of the present invention have been defined specifically to provide means and method of treating hernia by means of helically deploying a mesh rolled in an applicator . the term ‘ mesh ’ refers hereinafter in anon - limiting manner to a flexible member characterized by a plane body portion and an elastic rim ( collar ). the plane body portion is either a two - dimensional sheet - like member or a three - dimensional inflatable bladder - like member . the mesh is preferably characterized by either complete or incomplete circular , oval , and / or polygonal contour . according to one embodiment of the present invention , the mesh , as well as other ingredients of the device hereto defined and described , is selected in anon limiting manner fro biocompatible compositions selected from polymeric compositions ; glassware ; titanium containing , stainless steel , nitinol , and or other metal ware ; composite materials ; cardboard , natural fiber , silicone , rubber or rubber - like compositions or any mixture thereof . the present invention provides a novel method of repairing hernia by means of implanting at least one collapsible mesh rolled in an elongate open - bored applicator . this applicator is characterized by an anterior portion terminated outside the body and by posterior portion located inside the body . this method comprising inter alia the following : ( a ) inserting the posterior end of the applicator throughout the hernia into the wall of the abdominal cavity ; ( b ) releasing said mesh into said cavity while helically deploying the same such that said mesh is laying in parallel to said wall ; and finally ( c ) ejecting said applicator . it is according to one embodiment of the present invention wherein the applicator comprising at least one posterior and at least one anterior collapsible meshes . those two or more meshes are interconnected in their central portion by means of a connector lying inside the hernia . thus , the aforesaid method comprising inter alia the following : ( a ) inserting said applicator throughout the hernia into the wall of the abdominal cavity ; ( b ) releasing said posterior mesh into said cavity while helically deploying the same such that said mesh is laying in parallel to the posterior portion of said wall ; ( c ) at least partially ejecting said applicator to an anterior into mesh anterior said deploying ( d ) and , location ; predetermined said cavity such that it is laying in parallel to the anterior portion of said wall . it is according to yet another embodiment of the present invention wherein the balloon ( and / or the posterior mesh ) is in connection with least one elongated stripe extended outside the anterior end of the applicator . moreover , the method potentially additionally comprising steps of deflating the balloon and pulling said stripe and thus thrusting the balloon towards the posterior abdominal wall while or after ejecting said applicator . the role of the stripe is hence to ensure complete deflation of the balloon thus enabling its easy ejection throughout the applicator . it is acknowledged in this respect that the inflating tube may provide an effective means for ejecting the balloon . it is according to another embodiment of the present invention wherein the method defined in any of the above comprising inter alia immobilizing the rim of the posterior mesh to the posterior abdominal wall utilizing a plurality of anchoring means . it is according to another embodiment of the present invention wherein the method further comprising utilizing of at least one inflatable balloon thus providing a driving force for helically deploying the posterior mesh . this method comprising inter alia the following : ( a ) inserting said applicator throughout the hernia into the wall of the abdominal cavity ; ( b ) releasing at least one mesh into said cavity while helically deploying the same , such that said mesh is laying in parallel to said wall ; ( c ) inflating said balloon to a predetermined size , hence thrusting said mesh towards the posterior abdominal wall ; ( d ) deflating said balloon and evacuating it throughout said applicator ; and then ( e ), removing said applicator . steps b and c are provided simultaneously , step b before c and vice versa . it is according to another embodiment of the present invention wherein the method additionally comprising coordinating the steps of helically deploying the posterior mesh and inflating the balloon by means of utilizing a sleeve that is adapted to reversibly yet effectively envelop the posterior mesh . thus , a coordinated method may comprise the following : enveloping the posterior mesh and at least the anterior portion of the balloon with a sleeve ; helically deploying said mesh while inflating a balloon such that the sleeve is sliding forwardly ( anteriorly ) and then ejecting said sleeve outside the abdominal cavity . it is another object of the present invention to disclose a cost effective and novel implantable means for treating hernia . this therapeutic assembly comprising inter alia the following ingredients : ( a ) an elongate open - bored applicator having an anterior portion which is terminated outside the body , and a posterior portion , which is terminated with an orifice . this orifice or the same with a detachable member is adapted to be inserted via the hernia into the abdominal cavity . ( b ) at least one collapsible mesh rolled in the applicator . the mesh is adapted to be deployed helically when injected outside the applicator ( i . e ., posterior mesh ). ( c ) injecting means adapted to push the mesh throughout the open bore of the applicator via the said posterior orifice . the injecting means are comprised of a maneuverable pistol and a handle operating the same . it is another embodiment of the present invention wherein inflating means adapted to inflate a 3d mesh , e . g ., inflatable bladder - like mesh are provided ( not shown in the figures ). those inflating means are continuing through the applicator outside the abdominal cavity , and utilized to inflate said mesh to a predetermined volume or shape . it is another embodiment of the present invention wherein the perimeter of the collar is shorter than the perimeter of the mesh , such that a portion of the mesh &# 39 ; s plane body is free of enveloping collar . it is another embodiment of the present invention wherein the device is comprised of posterior and anterior collapsible meshes interconnected in their central portion by means of a connector . the connector may comprise an aperture reversibly covered by a plurality of overlapping wings . it is another embodiment of the present invention wherein the mesh as defined in any of the above is in connection with least one stripe , extended outside the anterior end of the applicator such that by pulling said stripe , said mesh is effectively thrusted towards the posterior abdominal wall . the stripe is preferably yet not exclusively extended outside the anterior throughout an aperture of the connector and ensuring the deflation of the balloon after use . it is another embodiment of the present invention wherein the device defined in any of the above is additionally comprised of at least one inflatable balloon located at the posterior end of the applicator . this balloon is providing an extra driving force for thrusting the helically deployed posterior mesh towards the posterior abdominal wall . the balloon is preferably in connection with inflating means comprising fluid injector and fluid tubing , interconnecting said injector to said balloon . the tubing is located inside the open bore of the applicator , and penetrated the mesh via its connector . it is another embodiment of the present invention wherein the posterior mesh and the balloon are enveloped by a means of a sleeve , adapted to coordinate the helically deploying of the mesh with the balloon inflation . preferably , this sleeve is ejected outside the body cavity by ejecting means located inside the open bore of the applicator . it is another embodiment of the present invention wherein the mesh additionally comprising fastening means adapted to immobilize the posterior mesh to the posterior abdominal wall , the anterior mesh to the anterior abdominal wall or the connector to the hernia . at least a portion of the fastening means may be located in a site or sites selected from the plane body portion facing the posterior abdominal wall , the connector , the elastic rim ( collar ) or any combination thereof . it is another embodiment of the present invention wherein fastening means are selected from hooks , clips , catches , fasteners ; wherein the fastening means are connected with said mesh directly or indirectly ; and / or wherein the fastening means are connected with said mesh by means of a flexible or strainable strips . reference is made now to fig1 a , schematically illustrating a perspective view of an implantable means for treating hernia according to one embodiment of the present invention ( 1 ) comprising two parallel thin meshes , interconnected by means of a radial connection . connector ( 14 ) connects anterior mesh ( 12 ) and posterior mesh ( 10 ). device ( 1 ) comprises an elastic , spring - like collar ( 16 ), not entirely enveloping the plane body of mesh ( 10 ). fig1 b presenting the same from a top view , demonstrating respectively small - diameter anterior mesh ( 12 ) and larger posterior mesh ( 10 ), wherein the ratio of their diameter may widely vary , e . g ., from about 10 : 1 to 1 : 10 . it is acknowledged in this respect that the shape of either of the meshes may be determined and adjusted before implanting the same . fig1 c schematically presenting a lateral cross section of the same , wherein fig1 d illustrates the same , wherein the rim of anterior mesh ( 12 ) is erected upwardly such that the two meshes are connected by means of connector ( 14 ). reference is made now to fig2 a and 2 b , schematically illustrating lateral cross sections of the same , wherein mesh ( 10 ) is located between biological tissues b and c , and mesh ( 12 ) clasps between tissues ( a ) and ( b ). the hernia ( 9 ) between layers a and b is sealed by means of the novel two meshes infrastructure . it is acknowledged in this respect that the width and thickness of the biological tissues ( a - c ) and the hernia diameter may vary without significantly decreasing the effectiveness of the device ( 1 ). either posterior or anterior meshes are flexible , and tolerate a wide scope of hernia systems , such as the case demonstrated in fig2 b . reference is made now to fig3 a and 3 d , schematically illustrating top view of the implantable means for treating hernia according to another embodiment of the present invention . collar ( 16 ) is presented in various modes . the portion of mesh ( 10 ) which is not enveloped is determined by various parameters , such as meshes flexibility , size etc . collar ( 16 ) may be utilized as single thin member ( fig3 a ), layered member ( fig3 b - c ), double layered member ( fig3 d ) etc . reference is made now to fig4 a to 4 d , schematically illustrating perspective view of the implantable means for treating hernia according to another embodiment of the present invention , wherein collar ( 16 ) is rolled in a manner it deployed helically . those examples are provided with few possible mechanisms to construct 3d cone - like mesh member from 2d flattened mesh . various collapsing techniques are hence demonstrated , wherein other are also possible . fig5 also presenting a schematic view of a helix - like rolled mesh , adapted to expend in a manner is perimeter is enlarged while it rotates , thus enabling the effective , smooth and rapid thrust of the mesh towards the posterior abdominal wall . reference is made now to fig6 a and 6 b , schematically illustrating a perspective view of the implantable means having two interconnected mesh layers according to another embodiment of the present invention . the posterior mesh ( 10 ) is loosely folded ( fig6 a ) such that flexible helix is directed to the posterior side of the hernia , wherein the anterior mesh ( 12 ) is folded in an opposite direction . connection ( 14 ) interconnects the same . right scheme , i . e ., fig6 b presents the same in a helix - like tight rolling configuration such that the external diameter of the rolled mesh is significantly smaller than its diameter in its terminal open configuration . reference is made now to fig7 a to 7 c , schematically illustrating a perspective and lateral cross sections of sterilizeable implantable means comprising an elongated applicator ( 2 ) with an open bore , wherein two interconnected mesh layers are rolled according to another embodiment of the present invention . this syringe - like applicator is comprised of injecting means comprising a handle ( 3 ) adapted for one hand use ( 24 ) wherein the piston axle ( 22 ) penetrates the applicator - rounded envelope ( 20 ) via opening ( 26 ). aperture 21 is especially provided for feeding fluids , chemicals , lubricants , glues , biocides etc into or onto the hernia . the two meshes may by assembled by a means of joint or connector ( 28 ). reference is made now to fig8 a and 8 f , schematically illustrating a perspective view and lateral cross sections of a method of treating hernia by means of implantable applicator comprising two interconnected mesh layers according to another embodiment of the present invention . the applicator is initially inserted into the hernia ( fig8 a ) such that its posterior orifice is located between two predetermined tissues ( a and c ). the posterior mesh is helically deployed ( fig8 b - 8 f ) such that it protruded in the body along the layers , and situated itself tightly between layers b and c . reference is made now to fig9 a and 9 c , schematically illustrating a perspective views of the implantable means according to another embodiment of the present invention . the role of the anterior mesh is hereby presented , wherein maneuvering the pistol of the applicator backwardly ; the anterior mesh is ejected , lying parallel to the abdominal wall , sealing hermetically the hernia opening . reference is made now to fig1 a and 10 h schematically illustrating one method of utilizing a balloon as a driving force for helically deploying the posterior mesh according to another embodiment of the present invention . the balloon comprising an inflatable portion ( 40 ), fluid tubing ( 42 ) and a liquid anterior orifice ( 44 ). this method is comprising the step of applying at least one stripe ( 45 ), said stripe is immobilized to the balloon inner portion and loose free at the anterior end of the applicator ( 44 ), such that by pulling the stripe deflated balloon is ejected outside the applicator in a collapsed manner . the proportions of the two meshes ( 10 , 12 ), collar ( 16 ) and balloon may widely vary ; especially their external diameter may be of various ratios . views 10 e to 10 g present one possible mode of the sealed connector , adapted to comprise inflation tube ( 42 ), by comprising overlapping wings of both upper and lower meshes . view 10 h presents a perspective illustration of the same . the balloon is shown to provide an effective foundation and driving force for thrusting the posterior mesh forwardly . reference is made now to fig1 , schematically illustrating a perspective view of the implantable assembly according to another embodiment of the present invention . this assembly comprises the applicator ( 1 - 4 ) as defined in any of the above , a balloon inflating tubing ( 42 ), and inflating means comprising inter alia a syringe ( 5 ) and tubing connector ( 44 ). reference is made now to fig1 a - 12 c , schematically illustrating a perspective views and a cross section of the implantable assembly according to another embodiment of the present invention . those schemes present the folding - deployment mechanism of balloon 40 in respect to the helically rolled posterior mesh . the inner diameter of the pistol handle ( 3 ) and the inner diameter of balloon &# 39 ; s inflating tubing 42 is adapted to be wide enough that the deflated balloon can be collapsed and ejected outside the applicator via the pistol handle . reference is made now to fig1 a - 13 c , schematically illustrating lateral cross sections of the implantable assembly according to another embodiment of the present invention . those schemes demonstrate the incorporated mechanism of the implant assembly , specifically presenting the inflation of the balloon and then the helical deployment of posterior mesh . reference is made now to fig1 a to 14 d , schematically illustrating cross sections of the implantable assembly according to another embodiment of the present invention . those schemes show that after inflating the balloon and deploying the two meshes ( 10 , 12 ), applicator ( 2 , 3 ) is removed . this assembly thus comprise a non - return valve ( 44 ) retaining the inflating fluid inside the balloon and its tubing ( 42 ). reference is made now to fig1 a to 15 c , schematically illustrating fastening means ( 18 , 19 , 19 a ) e . g ., nail - like , tooth - like , screw - like fasteners according to another embodiment of the present invention . those fastening means are of various sizes , shapes and fastening mechanisms . usually yet not exclusively the fastening means are located on the collar portion ( 16 ) of the device . those fastening means may be directly or indirectly ( 19 b ) immobilize to the collar . reference is made now to fig1 a to 16 d , schematically illustrating coordinating sleeve ( 50 ) according to another embodiment of the present invention . hence , for example , sleeve 40 is enveloping balloon 50 such that the steps deployment of mesh 10 and inflation of balloon 40 are coordinated at time . reference is made to fig1 a to 17 c , presenting the method of coordinating or sustaining either the deployment of mesh 10 , and / or balloon 40 by means of sleeve 50 located in the applicator shall ( 2 ). lastly , reference is made to fig1 a to 18 d showing the same method and coordinating / sustaining means and the various implementing process .

a method and device for treating hernia by implanting at least one collapsible hernia repair patch , such as a planar mesh body at least partially enveloped by one or more elastic collars . a posterior end of an applicator carrying the repair patch may be inserted through a hernia and into the wall of the abdominal cavity , and the patch may be released into the cavity , e . g ., so as to helically deploy the patch such that the patch lies in parallel to the abdominal wall . a balloon , which is removably attached to the patch , may be inflated to help move the patch to a deployed configuration , and thereafter the balloon removed from the hernia site .

referring to fig1 to 8 , the system according to the invention comprises , in the first embodiment , an elongate connection rod 2 of circular cross section and several connector sub - assemblies 4 which can be fixed to the latter . each of these sub - assemblies , of which two can be seen in fig1 and of which one can be seen in fig2 , comprises a connector 6 , a first vertebral screw or main screw 8 , a clamping screw 10 , a second vertebral screw or secondary screw 12 , and a ring 13 . referring to fig3 and 4 , the connector 6 includes two branches 16 extending opposite to and at a distance from each other , giving the connector a general u - shaped profile . the connector 6 includes a plane of symmetry s perpendicular to the width of the branches 16 and parallel to their length . referring to fig6 , at the point of origin of the branches 16 the connector has two cylindrical and coaxial inner faces 18 , 20 with axis 22 perpendicular to the plane s and with different radii , the face 20 of greater radius being in two distinct parts and extending on either side of the face 18 of lesser radius , which is traversed by the plane s . at their junctions , the two faces 18 , 20 form two circular edges 24 with axis 22 . the ring 13 has a cylindrical inner face 26 and a spherical outer face 28 which are coaxial . the cylindrical inner face 26 has a radius about equal to that of the rod 2 in such a way that the ring 13 , slotted on one side along its axis , can be received as a sliding fit on the rod . moreover , the ring 13 can be lodged between the branches 16 opposite the cylindrical faces 18 , 20 . the spherical outer face 28 of the ring has a radius which is adapted such that in this position the edges 24 of the connector 6 are in linear contact with the spherical outer face 28 of the ring 13 and serve as bearings for it . in this position , before clamping of the branches 16 , the angular position of the rod 2 engaged in the ring 13 can be controlled in two mutually perpendicular planes over an amplitude of , for example , 15 ° on either side of a mean position of the rod in which the rod is perpendicular to the plane s . the branches 16 have two respective smooth cylindrical openings which , in this case , are through - orifices 30 extending coaxially opposite each other . the main screw 8 is a bicortical vertebral screw and has a threaded body for this purpose , in a manner known per se . it has a head 32 having a smooth cylindrical outer face 34 . at the junction between the head and the body , the screw includes an annular flange 36 having a plane lower face perpendicular to a longitudinal axis of the screw and a frustoconical upper face 38 with the narrowest cross section of the frustum situated towards the head 32 of the screw . the head 32 has a threaded orifice 39 coaxial to the body of the screw and , formed in the threaded face of the orifice 39 , a noncircular shape such as a hexagon socket . the clamping screw 10 includes a threaded body 42 which is able to form a screw - nut connection with this orifice 39 , and a screw head 44 in which a hexagon socket is formed . the head 44 has a spherical and convex lower outer face 46 whose narrowest cross section is situated towards the point of the screw . one of the branches 16 , which for the sake of clarity we will here call the lower branch , has an extension 50 extending in the direction away from the cylindrical faces 18 , 20 of the connector . this is the branch intended to be adjacent to the vertebra . the two branches 16 are able to be engaged simultaneously on the head 32 of the main screw 8 introduced starting from the lower branch against which the upper face 38 of the flange 36 comes into abutment . the clamping screw 10 is then introduced into the head 32 of the main screw 8 starting from the upper branch 16 . the tightening of the screw 10 in the head 32 of the main screw 8 causes the branches 16 to close towards each other and causes frictional blocking of the rod 2 in the chosen position relative to the connector 6 . the orifice 30 of the lower branch 16 has a lower edge , remote from the upper branch and intended to be towards the vertebra , having a concave spherical recess 40 intended to come into contact with the upper face 38 of the flange 36 in order to effect , by friction , rotational blocking of the connector 6 relative to the axis of the main screw 8 . the orifice 30 of the upper branch 16 has an upper edge , remote from the lower branch and intended to be remote from the vertebra , having a concave spherical recess 40 intended to come into contact with the convex and spherical lower face 46 of the head 44 of the clamping screw 10 and making it possible to fix the latter and the main screw 8 by controlling the angular orientation of the main screw 8 relative to the connector . the extension 50 has an opening in the form of a through - orifice s 2 . the lower branch 16 is curved in the area of the extension 50 in a direction away from the upper branch 16 in such a way that the axes of its orifices 30 and s 2 are not quite parallel . the secondary screw 12 is a vertebral screw , here a monocortical screw , having a threaded body and a head 56 with a spherical and convex lower face 58 whose narrowest cross section is situated towards the body . its head has a hexagon socket . the orifice 52 of the extension has an upper edge , oriented towards the other branch 16 and intended to be remote from the vertebra , having a spherical and concave recess 60 intended to come into contact with the spherical and convex lower face 58 of the head 56 of the secondary screw 12 , making it possible to control the angular orientation of this screw relative to the connector 6 . certain characteristics of the connector 6 which have not been expanded on in detail here will be found in the abovementioned related documents fr - 2 , 731 , 344 and wo - 96 / 2730 . the lower branch 16 can be bent in order to accentuate or reduce its curvature for better adaptation to the shape of the anterior part of the vertebra for which it is intended . once bent , this branch 16 is no longer stressed in flexion since it is fixed to the vertebra by two screws 8 , 12 along its length . the two screws , namely the main screw 8 and the secondary screw 12 , are self - tapping and include bone threads . in an alternative embodiment , the main screw 8 does not have a hexagon socket in its threaded orifice 39 , and instead the flange 36 has a hexagonal shape or has two parallel and diametrically opposite flats which can cooperate with a tightening wrench for rotating this screw 8 relative to the connector 6 . in the present example , the connector 6 is made in one piece . the different parts of the system are made of biocompatible metal . such a device is fitted in the following manner , with reference to fig8 . after exposing the affected vertebra 70 and the two adjacent vertebrae 72 , a vertebrectomy is performed while preserving , if possible , the respective plates of these vertebrae . for each subassembly , a pilot hole is made on the lateral side of the associated vertebra 72 at an equal distance from the upper and lower plates , and at the limit of the most posterior quarter of the vertebral body . the main screw 8 is then inserted into this pilot hole as far as the limit flange 36 . the connector 6 is then positioned on the said main screw 8 , blocked in translation by the conical face 38 of the said main screw 8 matching the recess 40 of the connector 6 . the fit of the connector 6 on the vertebra is then checked and can be adjusted by withdrawing the said connector in order to bend the lower branch 16 which is its most anterior part . the secondary screw 12 is then screwed relative 15 to the main screw 8 into the second orifice 52 of the lower branch 16 until the spherical seat 60 of the extension , provided for this purpose , comes into contact with the spherical part 58 of the said secondary screw 12 . it is desirable to position the connector 6 as parallel as possible to the plates . after the two adjacent vertebrae 72 have been thus equipped , the rod 2 is positioned in the rings of the connectors 6 and its angular position on each subassembly is controlled . final clamping is effected by virtue of the clamping screw 10 which is inserted into the main screw 8 and thereby compresses the connector 6 in order to clamp the rod . in the second embodiment illustrated in fig9 to 13 , the system is very similar to that of the first embodiment . however , it is distinguished by the presence of a second elongate connection rod 3 or secondary rod of circular cross section , and by the adaptation of the connector 6 for receiving this second rod . the ring 13 is received on the first rod or main rod 2 . the two connection rods 2 , 3 each have a profiled rectilinear shape , the profile here being circular . the secondary rod 3 has a cross section , transverse to its longitudinal axis , having a diameter smaller than that of the main rod 2 . the main rod 2 will , for example , have a diameter of 6 mm . the diameter of the secondary rod 3 will , for example , be between 30 % and 80 % of the diameter of the main rod 2 . this small diameter allows the surgeon to choose the curvature of the secondary rod 3 corresponding to that of the level of the spine which is being operated on . by contrast , since the rings 13 allow relative angular positioning of the two connectors 6 , the main rod 2 does not have to be bent . it can thus have a substantial diameter in order to be very robust . the branches 16 of the connector have respective cylindrical recesses or jaws 74 formed in the faces of the branches opposite each other . the recesses 74 extend opposite each other and have axes parallel to each other and perpendicular to the plane of symmetry s . on the upper branch 16 , the recess 74 extends at a free end of the branch such that the orifice 30 is interposed between the faces 18 , 20 , on the one hand , and the recess 74 on the other . on the lower branch 16 , the recess 74 extends between the two orifices 30 and 52 , at the origin of the extension 50 . it is contiguous with the orifice 52 so that it engages on its edge 60 . the secondary rod 3 is intended to be received in the recess 74 of the lower branch 16 in a unique angular position relative to the connector , perpendicular to the plane of symmetry s . when the two branches 16 are clamped in the direction of each other , the recess 74 of the upper branch comes into contact with the secondary rod 3 which is thus in surface contact with each of the two recesses , which effect frictional blocking of the secondary rod 3 relative to the connector 6 , which are thereby rigidly fixed to each other . the secondary rod 3 is placed in the recess 74 of the lower branch after the secondary screw 12 has been introduced into the orifice 52 . the position of the recess 74 of the lower branch is such that the secondary rod 3 then extends in the trajectory of the head of the secondary screw 12 for its disengagement from the connector and its exit from the orifice 52 . consequently , once the secondary rod 3 has been fixed to the connector , the secondary screw 12 can no longer be separated from the connector . the upper branch 16 of the connector has at its free end a notch 76 which engages on the recess 74 with which it is contiguous and facilitates manoeuvring of the secondary screw 12 by means of a tool despite the space occupied by the upper branch . the system according to the second embodiment is fitted in a similar way to the system of the first embodiment . the placement of the main screw 8 and of the secondary screw 12 remains unchanged . after the two adjacent vertebrae 72 have been equipped , the main rod 2 is positioned in the rings 13 of the connectors 6 and the angular position of each sub - assembly 4 relative to this rod 2 is controlled . the secondary rod 3 is then introduced into the recesses 74 of the connectors 6 after it has first been bent manually to obtain the curvature required for the corresponding level of the spine . in the event of an error , this rod 3 can be removed in order to correct its curvature and then put back in place . fig9 shows the system before the clamping of the branches . final clamping is effected by virtue of the clamping screw 10 which is inserted into the main screw 8 and thereby compresses the connector 6 in order to clamp its two branches 16 towards each other . during this clamping , the clamping force is directed first on the main rod 2 via the ring 13 , until the recess 74 of the upper branch comes into contact with the secondary rod 3 . thereafter , the clamping force is distributed on the two rods 2 , 3 . thus , the reaction at the level of the pairing of main screw 8 and clamping screw 10 is substantially coaxial to these . when the system is in place , the connectors 6 , of which there are at least two , are each rigidly and simultaneously fixed to the same main rod and secondary rod . the characteristics relating to the association of first screw 8 with the clamping screw 10 will be able to implemented independently of the presence of the extension and of the second screw 12 . although less advantageous , the extended branch can the one which is intended to be farthest from the vertebra . the characteristics relating to the presence of the vertebral screws on the connector will be able to be implemented independently of those relating to the presence of main and secondary rods , and vice versa .

the invention concerns a backbone osteosynthesis system comprising an elongated element , a vertebral screw , and a connecting element comprising two branches for clamping between them the linking element , at least one first branch being capable of being engaged onto the screw . the system comprises a second vertebral screw , the first branch having an extension capable of being engaged onto the second screw . the system may comprise a second elongated linking element .

fig1 illustrates an in - sink dishwasher 10 mounted in a traditional cabinet fixture 12 having doors 14 providing access to the cabinet interior where the lower portion of the in - sink dishwasher 10 is located . the in - sink dishwasher 10 is illustrated in the environment of a double - bowl sink 16 comprising a first bowl 18 and a second bowl 20 . the first bowl 18 performs the function of a traditional sink bowl and includes a drain opening 21 . the second bowl 20 performs the dual function of a traditional sink bowl while also forming a portion of the housing for the in - sink dishwasher . the first and second bowls 18 , 20 are spaced from each other to define an intervening flange portion 22 that intersects a peripheral flange 24 surrounding both of the bowls 18 , 20 . preferably , the double - bowl sink is made from stainless steel . a traditional water faucet 28 is located in the peripheral flange 24 of the double - bowl sink and provides water to either of the first and second bowls 18 , 20 . referring to fig2 specifically and fig1 generally , the in - sink dishwasher 10 comprises a wash chamber 30 that is defined by the second bowl 20 , which has an open top . a lid 32 is hingedly mounted to the peripheral flange 24 of the double - bowl sink 16 and is movable between opened and closed positions to cover the open top of the second bowl 18 as shown in fig1 . the second bowl 20 is formed by a peripheral wall 34 and a bottom wall 36 . the peripheral wall 34 extends upwardly and away from the bottom wall 36 . a drain 38 is provided in the bottom wall 36 . a self - aligning poppet valve 40 also is located in the bottom wall 36 . preferably , the self - aligning poppet valve 40 is centered in the bottom wall since the poppet valve 40 forms one part of a liquid coupling for supplying liquid to the wash chamber 30 when the second bowl 20 is used as an in - sink dishwasher . referring to fig2 - 4 , several removable components are provided for the in - sink dishwasher 10 and include a bottom screen 42 , drain filter 44 , drain plug 46 , spray arm 48 , and dish basket 50 . the bottom screen 42 is preferably formed of a thin metal material , such as stainless steel , in which is formed a series of perforations or holes 54 . a downwardly extending annular flange 56 is provided in the bottom screen 42 and defines a drain opening 58 , which aligns with the drain 38 when the bottom screen 42 is mounted to the bottom wall 36 . a recess 60 is formed on one side of the bottom screen 42 and is sized to receive the poppet valve 40 when the bottom screen 42 is positioned against the bottom wall 36 . as best seen in fig3 and 4 , the bottom wall includes a well 52 having an annular flange 53 . the shape of the well 52 corresponds to the shape of the bottom screen 42 thereby permitting the bottom screen 42 to nest within the well 52 to mount the bottom screen 42 to the bottom wall 36 . the annular flange 53 defines an opening 55 in which the drain 38 and the poppet valve 40 are located . when the bottom screen 42 is positioned within the well 52 , the upper surface of the bottom screen 42 effectively performs the function of , and is in alignment with , the upper surface of the bottom wall 36 surrounding the bottom screen 42 . in other words , the bottom screen 42 effectively forms a portion of the upper surface of the bottom wall 36 when the bottom screen 42 is used . referring to fig2 - 4 , the drain filter 44 has a generally cylindrical shape with an open top and an open bottom . the drain filter 44 comprises a skeletal frame 62 , preferably made from plastic , comprising top , middle , and bottom rings 64 , 66 , 68 , each of which includes a corresponding shoulder 70 , 72 , 74 . the bottom ring 68 includes locking lugs 76 forming part of a bayonet mount for securing the drain filter 44 within the drain 38 . the rings 64 , 66 , 68 are connected by spaced rails 78 to thereby define a series of windows 80 . a screen 82 , preferably in the form of a fine wire mesh , is mounted to and is carried by the skeletal frame 62 such that the screen 82 overlies the windows 80 located between the middle and bottom rings 66 , 68 . the screen 82 functions as a filter for the drain 38 . the plug 46 also has a generally cylindrical shape with an open top and a closed bottom , with an outer periphery small enough to be received within the interior of the drain filter 44 . the plug 46 comprises a skeletal frame 88 , preferably made from plastic , and comprising a top annular ring 90 and a bottom wall 92 , which are connected by rails 94 . a series of intermediate annular ribs 96 are integrally formed with the rails 94 . as best seen in fig3 , when the drain filter 44 and plug 46 are received within the drain 38 , the top ring 64 of the drain filter 44 is positioned above the bottom wall 36 and bottom screen 42 and the middle ring 66 is adjacent to or in contact with the bottom screen 42 . the top ring 90 of the plug 46 is in contact with the middle ring 66 of the drain filter 44 . therefore , liquid can pass through the windows 80 between the top rings 64 and the middle ring 62 and flow into the interior of the plug 46 , where the liquid will then pass through the skeletal frame 88 of the plug 46 , through the screen 82 of the drain filter 44 , and into the drain 38 , to filter particulates from the liquid . the top annular ring 90 also includes a shoulder 98 . multiple feet 100 extend downwardly from the bottom wall 92 . a stopper support 102 extends downwardly from the bottom wall 92 and carries a stopper 104 , preferably made from a suitable rubber or plastic . the stopper support 102 terminates in a key 106 , which cooperates with the drain 38 to fix the position of the plug 46 in the drain 38 . a knob 108 extends upwardly into the interior of the skeletal frame 88 from the bottom wall 92 . the knob 108 aids in rotating the plug 46 . referring to fig2 and 5 , the spray arm assembly 48 comprises a hollow spray arm 114 , preferably made from stainless steel , with a liquid inlet 116 formed in a lower surface and spray outlets 117 formed on an upper surface . a mounting bracket 118 is secured to the upper surface of the spray arm 114 and includes resilient hooks 120 for snap - fitting with the basket 50 and a rotatable coupling 122 that rotatably mounts the spray arm 114 to the resilient hooks 120 . thus , the mounting bracket 118 provides for the snap - fit mounting of the spray arm 114 to the basket along with permitting the spray arm 114 to rotate relative to the basket 50 . a deflector 126 is mounted to the lower surface of the spray arm 114 and circumscribes the liquid inlet 116 . the deflector 126 comprises an annular collar 128 from which extends an angled surface 130 , terminating in an annular lip 132 . the annular collar 128 and angled surface 130 form a funnel - type structure leading to the liquid inlet 116 . the diameter of the angled surface 130 is greater than the diameter of the liquid inlet 116 . the deflector 126 forms part of a coupling that automatically aligns the liquid inlet 116 with the poppet valve 40 . referring to fig2 and 5 , the basket 50 is made from multiple coated wires in a well - known manner and will not be described in great detail . the basket includes multiple peripheral wires 136 , forming the outer periphery of the basket side wall , and multiple u - shaped wires 138 laterally spanning the peripheral wires 136 to form the basic basket shape . feet 140 are formed by wires extending from the side of the basket . the feet 140 are preferably l - shaped and extend below the bottom of the basket so that the bottom of the basket will be spaced from the bottom wall of the sink when the feet touch the bottom wall . referring to fig3 - 7 , the drain 38 is shown in greater detail . the drain 38 is preferably made from plastic and includes a top wall 146 and in which is formed a sump 148 . the top wall 146 mounts to the annular flange 53 of the sink bottom wall 36 . an annular platform or shoulder 150 is formed within the interior of the sump 148 and provides a support on which are mounted a temperature sensor 152 , preferably in the form of a thermistor , and a liquid level sensor 154 , preferably in the form of a dome - type pressure sensor . spaced mounting lugs 156 extend radially inwardly from a side wall 157 of a reduced diameter portion of the sump 148 , which terminates in a second shoulder 159 . the lugs 156 are located axially beneath the shoulder 150 . the mounting lugs 156 cooperate with the lugs 76 on the skeletal frame 62 of the filter 44 to permit the bayonet mounting of the filter 44 to the sump by rotation of the skeletal frame 62 . a key hole 158 is located in the center of a waste drain portion 160 of the sump 148 and below the lugs 156 . an annular angled sealing surface 162 provides the transition from the second shoulder 159 to the waste drain 160 . the key hole 158 cooperates with the key 106 on the end of the stopper support 102 of the plug 46 for securing the plug to the sump 148 . when the drain filter 44 is received within the sump 148 and secured by the interacting lugs 76 and 156 , the shoulder 74 of the bottom ring 222 will bear against the platform 150 and / or the side wall 157 to effect a seal between the filter 44 and the sump 148 . when the plug 46 is secured to sump 148 by the cooperation between the key 106 and the keyhole 158 , the stopper 104 is compressed against the annular sealing surface 162 to close off the waste drain 160 . a recirculation inlet 170 is formed in the side wall 157 of the sump 148 below the lugs 156 and above the annular sealing surface 162 . a recirculation inlet 170 is connected to the poppet valve 40 by a liquid conduit 172 , which is shown schematically in fig5 - 7 . the recirculation inlet 170 permits liquid flow in the sump 148 to be directed through the conduit 172 to the poppet valve 40 and into the spray arm 48 , when the basket 50 is seated within the second bowl 20 to establish a recirculation loop where liquid can be continuously recirculated from the sump and onto the dishes contained in the basket 50 . the recirculation inlet 170 of the sump 148 is positioned above the annular sealing surface 162 so that when the stopper 104 of the plug 46 closes the waste drain 160 , liquid can still be drawn into the recirculation loop through the recirculation inlet 170 . the recirculated liquid will be drawn through the drain filter to ensure that particulates in the liquid are not recirculated back onto the dishes . a recirculation drain 174 is fluidly connected to the waste drain 160 below the keyhole 158 . the recirculation drain 174 is also fluidly connected to the conduit 172 . the fluid connection of the recirculation drain 74 between the waste drain 160 and the liquid conduit 172 permits the draining of the liquid in the recirculation loop even when the drain plug 46 has closed off the waste drain 160 . shown schematically in fig5 - 7 , an in - line liquid heater 176 and a recirculation pump 178 are fluidly connected to the liquid conduit 172 and form part of the recirculation loop . the in - line water heater 176 is used to receive liquid passing through the conduit 172 and the recirculation pump 178 pumps liquid through the recirculation loop . a drain pump 180 is also fluidly connected to the liquid conduit 172 as well as to the recirculation drain 174 . the drain pump 180 permits the liquid in the recirculation loop to be drained from the wash chamber through the sump when the drain plug 46 has closed the waste drain 160 . the recirculation pump 178 and drain pump 180 act both as a valve and a pump since when the pumps are turned off , water cannot pass through the pump . therefore , both pumps can be coupled to the liquid conduit 172 without interfering with the flow of liquid through the recirculation loop or the draining of liquid from the recirculation loop . it is possible for a single pump to be used in place of separate recirculation in drain pumps . referring to fig5 - 8 , the poppet valve 40 is shown in greater detail . the poppet valve 40 comprises a housing 190 that is mounted to the top wall 146 and defines a chamber 192 therebetween that is fluidly connected to the liquid conduit 172 by an inlet 194 formed in the top wall 146 . a liquid outlet opening 196 is formed in the housing 190 . the chamber 192 can be thought of as essentially a continuation of the conduit 172 and the liquid outlet opening 196 can be thought of as an outlet for the liquid conduit 172 . a poppet assembly comprising a feed tube 198 and a poppet 200 extend from the poppet chamber 192 through the liquid outlet opening 196 . the feed tube 198 comprises a nozzle 202 extending from a base 204 . the nozzle 202 defines a hollow interior and has a proximal end that connects to the base 204 and a distal end that terminates in a radially extending annular rib 206 . the interior of the nozzle comprises a shoulder 208 that functions as a stop for the poppet 200 . the poppet comprises cap 210 from which depend resilient legs 212 , which terminates in radially extending feet 214 . the resilient legs 212 are located along the cap 210 such that they can be received through the hollow interior of the nozzle 202 . the feet 214 extend a sufficient radial distance so that they will bear against the shoulder 208 of the nozzle 202 to limit the axial movement of the poppet 200 relative to the nozzle 202 . the resilient nature of the legs 212 permits the poppet 200 to be assembled to the nozzle 202 by deflecting the legs 212 radially inwardly until they can pass through the opening to the hollow interior of the nozzle defined by the annular rib 206 . as the legs 212 are inserted into the hollow interior of the nozzle 202 , they will spring radially outwardly once the feet 214 clear the shoulder 208 . the operation of the poppet valve 40 is dependent on whether or not there is pressurized liquid being directed through the liquid conduit 172 . when there is no pressurized liquid acting on the poppet valve 40 , the poppet valve is as it appears in fig5 and 5a . in such an unpressurized condition , the base 204 is spaced from the liquid outlet opening 196 of the housing 190 and rests on the top wall 146 circumscribing and enclosing the poppet chamber inlet 194 . the cap 210 of the poppet 200 rests on the annular rib 206 of the nozzle 202 to close off the hollow interior of the nozzle 202 . when there is pressurized liquid acting on the poppet 40 , the poppet valve 40 takes the position as illustrated in fig6 and 6a . in such a pressurized condition , the pressurized liquid forces the feed tube 198 upwardly until the base 204 contacts the housing 190 to seal the liquid outlet opening 196 . the pressurized liquid must then pass through the hollow interior of the nozzle 202 where it contacts the cap 210 of the poppet to raise the cap above the annular rim 206 of the nozzle 212 and permits fluid flow through the nozzle 200 to and between the cap 210 and the annular rib 206 . in the pressurized condition , the cap 210 forms a spray head for the poppet valve 40 and forms outlet openings defined by the gaps between the cap 210 , annular rib 206 , and legs 212 . since the cap 210 and annular rib 206 are radially extending , the defined outlet openings are inherently laterally extending , resulting in any liquid passing through the poppet valve 40 to be directed laterally toward the peripheral wall 34 of the bowl 20 . in other words , the axial flow of the pressurized liquid through the nozzle 202 is laterally deflected when it contacts the cap 210 to direct the pressurized liquid laterally toward the peripheral wall 34 of the bowl 20 . the seating of the basket 50 within the second bowl 20 and the corresponding alignment of the poppet valve 40 with the liquid inlet 116 of the spray arm 114 is best seen by comparing fig5 - 7a . fig5 and 5a illustrate the poppet valve 40 aligned with the liquid inlet 116 of the spray arm 114 , but before the basket 50 is completely seated within the second bowl 20 . for the preferred embodiment disclosed in the specification , the basket 50 is seated when the feet 140 of the basket 50 rest on the bottom wall 36 of the second bowl 20 . fig6 illustrates the poppet valve 40 aligned with the liquid inlet 116 of the spray arm 114 when the basket 50 is seated in the second bowl 20 . the seating of the basket 50 and the alignment of the liquid inlet 116 with the poppet valve 40 will correspond to fig5 - 6a when the nozzle 202 is axially aligned with the liquid inlet 116 as the basket 50 is inserted into the second bowl 20 and the axial alignment is maintained through the seating of the basket 50 in the second bowl 20 . in such a seated and aligned condition , when pressurized liquid flows through the liquid conduit 172 , the cap 210 of the poppet 200 will lie substantially at the midpoint of the hollow interior of the spray arm 114 as shown in fig6 and 6a . in such a position , the pressurized liquid exiting the nozzle 202 is directed laterally by the cap 210 of the poppet 200 and will naturally flow laterally and fill the hollow interior of the spray arm 114 where the liquid exits the spray openings 117 to spray the dishes retained in the basket above . it is anticipated that the user will not ensure that the nozzle 202 and the poppet 40 are manually aligned with the liquid inlet 116 of the spray arm 114 when the user seats the basket 50 within the second bowl 20 , especially since the outer periphery of the basket 50 is smaller than the area defined by the peripheral wall 34 . the difference in the dimensions between the outer periphery of the basket 50 and the area defined by the peripheral wall 34 results in some “ play ” between the basket 50 and the peripheral wall 34 . the play between the basket 50 and the peripheral wall 34 can be quantified as the range of movement of the basket within the bowl 20 assuming nothing other than contact between the basket 50 and the peripheral wall 34 limits their relative movement . the play between the basket 50 and the peripheral wall 34 can result in the misalignment of the nozzle 202 with the liquid inlet 116 when the basket is being seated unless some action is taken to keep or force the alignment . the nozzle 202 , in combination with the deflector 126 , forms a self - aligning coupling for fluidly coupling the liquid conduit 172 to the liquid inlet 116 . the angled surface 130 of the deflector 126 will contact the annular rib 206 of the nozzle 202 when the nozzle 202 is not axially aligned with the liquid inlet 116 as the basket 50 is being seated . such a condition is shown in fig7 . once the angled surface 130 contacts the annular rib 206 , further insertion by the user of the basket 50 to complete the seating of the basket 50 within the second bowl 20 moves the nozzle 202 laterally relative to the second bowl peripheral wall 34 and into alignment with the liquid inlet 116 . the nozzle 202 is free to laterally move until the nozzle 202 contacts the liquid outlet opening 196 . to ensure that the nozzle 202 can laterally move a sufficient distance to align the nozzle 202 with the liquid inlet 116 , the range of lateral movement of the nozzle 202 and the liquid outlet opening 196 is preferably greater than the range of lateral movement of the basket 50 relative to the second bowl 20 . the deflector 126 can reduce or eliminate the need for the range of motion of the nozzle 202 relative to the liquid outlet opening 196 to be greater than the range of motion of the basket 50 relative to the peripheral wall 34 of the second bowl 20 . with the deflector 126 , alignment between the nozzle 202 and the liquid inlet 116 can be ensured as long as the deflector is sized such that the greatest diameter of the angled surface 130 will make contact with the nozzle 202 . it is preferred that the greatest diameter of the angled surface 130 is sized such that the nozzle 202 always lies entirely within the deflector 126 for the entire range of movement of the basket 50 relative to the peripheral wall 34 of the second bowl 20 . it should be noted that the invention will still work if for some reason the entire nozzle 202 does not lie within the deflector 126 . under such circumstances , contact between the nozzle 202 and the deflector 126 will provided the user with tactile feedback in positioning the nozzle 202 within the deflector 126 . fig9 schematically illustrates a controller 220 , preferably a microprocessor - based controller , used to control the operation of the in - sink dishwasher and the electrical coupling of the controller to the in - line heater 176 , recirculation pump 178 , drain pump 180 , inlet valve 224 , liquid level sensor 154 , and temperature sensor 152 to control their respective operations . the controller 200 controls the operation of a wash cycle and preferably has multiple pre - programmed wash cycles stored within the memory of the controller . there are many well - known wash cycles such as regular wash , high temperature or sanitizing wash , china wash , wash with pre - soak , and pots and pans wash , to name a few . the wash cycles typically comprise multiple steps , the building blocks of which include introducing and recirculating a charge of water into the wash chamber . some steps can include the addition of a detergent . other steps might include heating the water . the exact cycles and steps are not germane to the current invention other than the controller 200 for the in - sink dish washer is capable of performing one or more wash cycles . to perform a wash cycle , the controller 200 operates the in - line heater 176 , recirculation pump 178 , drain pump 180 , and inlet valve 224 , along with data from the water level sensor 154 and the temperature sensor 152 . the controller generally includes an internal clock that handles timing functions and internal counters for any cycle functions . a user interface 222 is located adjacent the second bowl 20 and is electronically coupled to the controller 200 . the user interface 222 permits the user to select the desired wash cycle from the multiple wash cycles stored in the memory of the controller 200 and enter any necessary or optional operating data or parameters for the wash cycles . the user interface preferably includes one or more visual or audible indicators used to display information to the user . for example , lights , preferably light - emitting diodes (“ leds ”), can be illuminated adjacent descriptive text or symbol on the user interface to indicate an associated status . a common use of the visual or audible indicators is to signal an error in the wash cycle , or the completion of one or more steps in the wash cycle or the entire wash cycle . all of the wash cycles traditionally used in an automatic dishwasher or an in - sink dishwasher require the recirculation of liquid , with or without detergent , through the wash chamber to perform one step of the wash cycle . for example , during a rinse step of the overall cycle , water is introduced into the wash chamber and subsequently recirculated for a predetermined time . during a wash step , detergent is mixed with the water introduced into the wash chamber . the recirculation of the water with the detergent forms a wash liquid that is then recirculated through the wash chamber to clean the additions . to effect such a recirculation of liquid , the controller 220 ensures that the drain pump 180 is shut off , which prevents liquid from leaving the liquid conduit 172 and draining through the recirculation drain 174 . the controller 220 energizes the recirculation pump 178 to recirculate the liquid from the sump 148 , through the spray arm 114 , onto the dishes in the basket 50 , and the liquid subsequently flows back into the sump 148 where it is recirculated . to drain the liquid from the wash chamber when the sink is operated as an in - sink dishwasher 10 , meaning that the plug 46 is in place and closing the waste drain 160 , the controller 220 ensures that the recirculation pump 178 is turned off to prevent the recirculation of the liquid within the liquid conduit 172 . the controller 220 energizes the drain pump 180 which pumps the liquid from the sump 148 through the liquid conduit 172 and into the recirculation drain 174 , which flows into the waste drain 160 to thereby drain the liquid from the sump . if the liquid must be heated for a particular step of the wash cycle , the controller 220 will energize the in - line water heater 176 and heat the liquid passing therethrough . one advantageous benefit of the in - sink dishwasher 10 is that the poppet valve 40 can be used to provide a self - cleaning function for the bowl 20 . to accomplish this function , the user merely removes the basket 50 from the second bowl 20 . the user then selects the self - cleaning function from the user interface 222 . the controller 200 will introduce water into the wash chamber by opening the inlet valve 224 and recirculate the liquid as previously described . since the combination of the poppet 200 and nozzle 202 results in the recirculated liquid being directed laterally toward the peripheral wall 34 , the recirculated liquid will impact the peripheral wall and naturally clean the peripheral wall and flush any particles from the sink and into the sump 148 . once the recirculation of the liquid is completed , the controller 200 will drain the liquid from the sump as previously described . the self - cleaning sink cycle can include additional steps . for example , it is possible to heat the recirculated liquid to better remove encrusted particles on the peripheral wall 34 or bottom wall 36 . the self - cleaning sink cycle can include multiple sequences of a recirculation step followed by a drain step as previously described . the recirculation step could include the addition of detergent . the self - cleaning sink cycle can be limited to operation only when the lid is closed . under such circumstances , the controller can be linked to a latch securing the lid in the closed position to provide feedback to the controller that the lid is closed . the implementation of a lid - close sensor and data feedback to a controller is well known in the art and will not be described in detail . while the invention has been specifically described in connection with certain specific embodiments thereof , it is to be understood that this is by way of illustration and not of limitation , and the scope of the appended claims should be construed as broadly as the prior art will permit .

a method for cleaning a dish - cleaning appliance having a removable basket that carries a spray arm . the method comprises : uncoupling the liquid supply from the sprayer , spraying liquid against the peripheral side wall from the liquid supply , and draining the sprayed liquid from the wash chamber .

embodiments of the present invention are directed to devices , methods and systems for therapeutic delivery that employ multiple therapeutic delivery heads . in some embodiments , a device , system or method may be used for delivering therapeutic and other agents or fluids to a target site of a patient &# 39 ; s body . the device , system or method may include a rotating multi - headed delivery body where one or more therapeutic delivery heads may be able to dispense therapeutic therefrom . the dispensing end of each head may be in fluid communication with a therapeutic supply , which may be within the head and elsewhere . the ) device may be used to deliver therapeutic to a target site during or subsequent to the spinning or rotation of the delivery body . these heads may pierce into the target site , may simply deposit the therapeutic and may have other defining features . these as well as other aspects of the invention are provided herein . fig1 is a plan view of the proximal end of a catheter 100 that may be employed in accord with the present invention . this catheter 100 may include a housing gauge 150 , a first lumen 112 , a second lumen 122 with a luer fitting 130 , indices 152 , and pointer 140 . the pointer 140 may indicate to a practitioner the distance that the second lumen 122 has slid within the first lumen . this may indicate how far the second lumen is extending from the first lumen if the second lumen is long enough to extend from the end of the first lumen . the various embodiments of the present invention may use this catheter 100 as a supply line to the rotatable delivery bodies described herein . other sources of therapeutic may be used as well . the shaft 110 of the catheter 100 may have a reinforcement member therein . this member may include a co - braided polymer tube , a co - extruded tube with two or more polymers , one or more rigid polymer or metallic wires and rods embedded in a polymer tube . it may also include two coaxial tubes , one being of a rigid nature , mechanically joined by , for example , a heat shrink tube over a polymer tube . the first lumen 112 and the second lumen 122 may be made of various metallic and non - metallic materials . these materials may include , but are not limited to , stainless steel and nickel - titanium alloy . regardless of which materials are used for first the first lumen 112 and the second lumen 122 , it is preferred that the materials be chosen such that they have compatible physical properties in order to be able move in a one to one relationship as the catheter 100 is snaked through a patient . this one to one relationship increases the likelihood that the movement of the second lumen within the first lumen can be accurately measured by gauge 150 . fig2 shows a catheter 100 within the vascular system 220 of patient 200 . also shown in fig2 are the heart 210 , blood vessels 230 and 232 , access sheath 240 , and leg 250 of patient 200 . as is shown , a distal end of catheter 100 may be disposed within heart 210 . specifically , a distal end of catheter 100 may be disposed against tissue of a wall of heart 210 . once positioned there , the multi - head delivery body of the present invention may be used to deliver therapeutic to the heart or other target site . fig3 is a side view of a multi - head delivery device 300 in accord with an embodiment of the present invention . this device 300 as well as other devices of the present invention may be used with the catheter system 100 described above as well as with other positioning and control systems . it is preferred that these systems be steerable or otherwise controllable such that a practitioner may direct their location and position during a medical procedure . the device 300 in fig3 , has a first elongate shaft 310 , a distal end 311 , and a lumen 312 . distal end 311 may be rotably coupled to an axle 316 , the axle defining a lumen 317 and co - axially aligned with the multi - head delivery body 320 . axle 316 may also be in fluid communication with lumen 312 and inner cavity 321 of the multi - head delivery body 320 . multi - head - delivery body 320 may include a first circular side 322 , a second circular side ( not shown ), and a circular wall portion 323 extending between outer diameter edges of first circular side 322 and second circular side , the circular sides defining inner cavity 321 . multi - head delivery body 320 may also include multiple injection heads 324 , which may be evenly spaced around an exterior surface of circular wall portion 323 . embodiments of the present invention are contemplated in which multi - head delivery body 320 may have a total diameter including multiple injection heads 324 that fit within a 9 french or larger catheter . multiple embodiments of the present invention are contemplated including the single row of injection heads 324 around circular wall portion 323 as shown in fig3 , multiple rows of injection heads 324 with aligned columns , and multiple rows of injection heads 324 with heads in every other row being aligned with each other . other orientations are also plausible . each injection head 324 may include an upwardly and inwardly extending conical wall portion 325 , which may define a base opening 326 in wall portion 323 and a port 327 with a lumen 328 extending there between . lumen 328 may have a conical shape similar to conical wall portion 325 defined by an inner surface of conical wall portion 325 , with an embodiment of the present invention . alternative embodiments of lumen 328 are also contemplated to include , for example , a cylindrical lumen , as well as various other shaped lumens . moreover , first elongate shaft 310 may be straight and run along one side of multi - head delivery body 320 , first elongate shaft 310 may also be angled near distal end 311 . in accord with embodiments of the present invention , each injection head 324 may include a substantially circular hinged base opening cover 330 coupled to a plunger 332 . the proximal end 333 of the plunger may be coupled to substantially circular hinged base opening cover 330 and a distal end 334 , extending out through port 327 . cover 330 may be biased against an inner surface of circular wall portion 323 to close off opening 326 by , for example , a spring loaded hinge . although , for reasons of clarity and ease of illustration , only one injection head 324 is illustrated with cover 330 and plunger 332 , each injection head 324 may also be so configured . moreover , proximal end 333 may also be coupled to cover 330 at a substantially 90 ° angle while distal end 334 may include a rounded tip 335 that may extend out past port 327 . also , regardless of the shape of lumen 328 , hinged based cover 330 may be sized to provide a liquid - tight seal , thereby preferably ensuring no fluid from inner cavity 321 may escape when hinged base opening cover 330 is covering opening 326 . in fig3 , rounded tip 335 may have a diameter smaller than a diameter of port 327 . this allows rounded tip 335 to retract through port 327 . this allows rounded tip 335 to retract through port 327 and back into lumen 328 to open opening 326 when urged in the proximal direction . this may occur when rounded tip 335 is pressed against a target site . rounded tip 335 may extend out past port 327 when not pressed against the target tissue site . cover 330 may be biased toward the inner surface of circular wall portion 323 . in general , rounded tip 335 will be sized to permit fluid within inner cavity 321 to escape through lumen 328 in injection tip 324 when rounded tip 335 is pushed back within lumen 328 . similarly , when rounded tip 335 is extended past port 327 , hinged base opening cover 330 may seal substantially circular base opening 326 to prevent fluid within inner cavity 321 from escaping through lumen 328 . in some embodiments the therapeutic may be under pressure from the delivery head and / or a lumen in communication with the delivery head . fig4 is a top view of a portion of the multi - head delivery device of fig3 , in accord with an alternate embodiment of the present invention . in fig4 , a first elongate shaft 410 may have a proximal end ( not shown ) and a distal end 411 with a lumen 412 extending there between . distal end 411 may be rotably coupled to axle 316 defining lumen 317 , which may be coupled to and co - axially aligned with multi - head delivery body 320 . axle 316 may be in fluid communication with lumen 412 and inner cavity 321 within multi - head delivery body 320 . in the embodiment in fig4 , first elongate shaft 412 may be radially aligned with multi - head delivery body 320 and may have an end section 413 including a substantially perpendicular section 415 proximal of multi - head delivery body 320 . as shown in the embodiment in fig4 , multi - head delivery body 320 may have a single row of injection heads 324 . there may be other configurations and alignments as described herein as well . first elongate shaft 410 may have a symmetrical end section 413 ′ ( shown in phantom line ). this may include a substantially perpendicular section 415 ′, that may extend past second circular surface 422 of multi - head delivery body 320 and be coupled to a final distal section 417 ′ of first elongate shaft 410 . this distal section 417 ′ may also substantially perpendicular to substantially perpendicular section 415 ′ and substantially parallel to first circular surface 322 of multi - head delivery body 320 . distal end 411 ′ may be rotably coupled to and co - axially aligned with another axle 416 , which may be co - axially aligned with axle 316 . symmetrical end section 413 ′ may also be in fluid communication with inner cavity 321 . first elongate shaft may take other configurations as well . fig5 is an enlarged partial cross - sectional view of an injection head in accord with an embodiment of the present invention . in fig5 , base cover 330 covers base opening 326 of injection head 324 . hinged base cover 330 may include a hinge 510 that may be coupled to a substantially circular plate 520 and an inner surface of circular wall portion 323 adjacent to substantially circular base opening 326 . hinge 510 may bias substantially circular plate 520 against the inner surface of circular wall portion 323 by , for example , a spring 511 . in general , spring 511 may be arranged in a similar fashion to a spring in a standard mousetrap that urges the arm of the mousetrap against the base . the force of spring 511 may be sufficient to prevent substantially circular plate 520 from unsealing from the inner surface of circular wall portion 323 when multi - head delivery body 320 is rotated . in addition , substantially circular plate 520 may include a material that may form a tight liquid seal when biased against the inner surface of circular wall portion 323 . for example , substantially circular plate 520 may be comprised of the material and / or include the material only on the side facing the inner surface of circular wall portion 323 , where the material may include natural rubber , isoprene , urethane , latex , acrylonitrile / butadiene , cyanoacrylate , fibrin , collagen and / or silicone . fig6 is an enlarged partial cross - sectional side view of a portion of a head in an open position , in accord with an embodiment of the present invention . in fig6 , substantially circular plate 520 may be displaced from the inner surface of circular wall portion 323 as the plunger 332 is urged in the proximal direction . this will force rounded end 335 into port 327 . displacing substantially circular plate 520 away from the inner surface of circular wall portion 323 may create a vent 610 for the fluid in inner cavity 321 to enter lumen 328 through substantially circular base opening 326 and exit through port 327 . in the open position , spring 511 may be compressed so that it may exert a bias against substantially circular plate 520 to return to the closed position shown and described in fig5 . fig2 is an enlarged view of another head 2102 that may be employed by one or more of the rotatable bodies of the present invention . like the other heads , they may be spaced and positioned in various locations and may be employed with other types of heads on the same system or device . a plunger 2103 , flap 2104 , biasing element 2105 , and multi - head rotatable body 2101 , may all be seen in this figure . the biasing element 2105 may act to keep the plunger 2103 in a closed position until the plunger is depressed . fig7 is a side view of a portion of a distal end of another multi - head delivery device in accord with the present invention . in fig7 , a multi - head delivery device 700 may include an elongated shaft 710 having a proximal end ( not shown ), a distal end 711 , and a lumen 712 there between . multi - head delivery device 700 may be disposed in a catheter 705 having a proximal end , a distal end , and a lumen extending there between . elongated shaft 710 may be rigidly coupled to and coaxially aligned with an axle 716 having a lumen 717 that may be coupled to a multi - head delivery body 720 to permit lumen 712 to be in fluid communication with an inner cavity 721 through an opening in a first side surface 722 in multi - head body 720 . multi - head body 720 may include an outer tread 723 having multiple injection heads 724 and an inner portion 729 defining inner cavity 721 . outer tread 723 may be adapted to rotate around inner portion 729 and to receive and hold fluid to be ejected from each injection head 724 either from within outer tread 723 or inner cavity 721 . for example , outer tread 723 , as in other embodiments , may be adapted to receive and hold fluid separate and apart from inner cavity 721 , which may , itself , be inflatable to press against an inner surface of outer tread 723 . in so doing , inner cavity 721 may either increase or put the fluid in outer tread 723 under pressure , which may aid in the ejection of the fluid from each injection head 724 . inner portion 729 may include an inner bladder that may be deflated to permit easy movement of multi - head body 720 through catheter 705 to a target tissue site once positioned , multi - head body 720 may be extended out of catheter 705 and inner portion 729 may be inflated / expanded to permit outer tread surface 723 to rotate around inner portion 729 and eject fluid through multiple injection heads 724 . the injections head 724 may also be configured and operate in other fashions , such as those described above for fig3 , and 21 . the heads 724 may be sized to fit within a 9 french or larger catheter . conversely , the multi - head delivery body 720 may also have a height and width greater than a 9 french when it is inflated . inner portion 729 having a constant size and shape . fig8 is a top view of multi - head delivery device of fig7 . as can be seen , elongate shaft 710 may be longitudinally aligned with multi - head delivery body 720 and may have a symmetrical end section 713 , the end section including substantially perpendicular sections 715 , 815 . sections 715 and 815 may extend past first side surface 722 and second side surface 822 and may be coupled to final distal sections 717 , 817 . as also shown in fig8 , multi - head delivery body 720 may have multiple rows of offset injection heads 724 . however , the injection heads shown elsewhere may also be used in this and other embodiments . as shown in fig8 , elongate shaft 710 may be asymmetrical , similar to fig4 , and may only include end section 713 . distal end 711 may be rigidly coupled to and co - axially aligned with axle 716 , which may be co - axially aligned with axle 316 . asymmetrical end section 713 may also be in fluid communication with inner cavity 721 . fig9 is a cross - sectional side view of a portion of the distal end of a catheter in accord with an embodiment of the present invention . in fig9 , a catheter 905 having a proximal end 906 , a distal end 907 and a lumen 908 extending there between , is shown disposed within lumen 908 of multi - head delivery device 900 . multi - head delivery device 900 may include an elongate shaft 910 having a proximal end , a distal end , and a lumen extending there between . a multi - head delivery body 920 may have an inner cavity 921 similar to delivery body 320 from fig3 . it may also have multiple injection heads 924 in fluid communication with inner cavity 921 . multi - head delivers device 900 may also include a control mechanism 930 to spread and close multiple injection heads 924 of multi - head delivery body 920 . for example , control mechanism 930 may include push and pull wires and / or a mechanism similar to an umbrella to permit closing the multiple injection heads 924 and to permit the transport of the multi - head delivery device 900 through lumen 908 . as in fig3 , in fig9 , the lumen of elongate shaft 910 may be rotably coupled to and , co - axially aligned with inner cavity 921 in multi - head delivery body 920 . fig1 is a cross - sectional side view of the distal end of the catheter and multi - head delivery device of fig9 . in fig1 , the multi - head delivery body extends past the distal end of the catheter and is shown fully open . as can be seen , the multi - head delivery body 920 may be extended past distal end 907 of catheter 905 and multiple thin injection heads 924 may be extended using control mechanism 930 . moreover , multi - head delivery body 920 may rotate around distal end 911 of elongate shaft 910 and may receive fluid from inner cavity 921 . this fluid may be ejected out a distal end of each injection head 924 . fig1 is a cross - sectional side view of a portion of the distal end of the catheter and the multi - head delivery device from fig9 . in fig1 the multi - head delivery body is retracted back into the distal end of the catheter so that it may move toward the proximal end of the catheter . in fig1 , multi - head delivery body 920 may be retracted back into distal end 907 of catheter 905 and multiple thin injection heads 924 may be collapsed in the opposite direction of fig9 , which is similar to an umbrella that has been opened past the desired normal open position . multiple injection heads 924 may be designed to permit movement in this opposite direction to ease movement of the multi - head delivery body 920 back into distal end 907 . in another embodiment of the present invention , control mechanism 930 may also permit closing the 924 back into the configuration shown in fig9 . however , bringing multi - head delivery body 920 back into distal end 907 of catheter 905 in this position may be more difficult than in the configuration shown in fig1 . fig1 is a perspective view of a distal end of a multi - head delivery device in accord with an embodiment of the present invention . in fig1 , a multi - head delivery device 1200 along with an elongate shaft 1210 , a distal end 1211 , a lumen 1212 , a multi - part delivery body 1220 , an inner cavity 1221 , injection heads 1224 , and exterior surface 1223 may all be seen . multiple injection heads 1224 may be configured similarly to those described in fig3 - 6 and 21 . distal end 1211 may include a semi - rigid and / or rigid symmetrical forked section 1213 that may be rotably coupled to and co - axially aligned with an axis of multi - head delivery body 1220 . embodiments of multi - head delivery body 1220 are also contemplated in which the outer diameter of multi - head delivery body 1220 may fit within a 9 french or larger catheter and the length of multi - head delivery body 1220 may be approximately 1 cm . embodiments of multi - head delivery body 1220 are also contemplated in which multi - head delivery body 1220 may be moved longitudinally through a catheter . for example , multi - head delivery body 1220 may need to be enclosed in a sheath ( not shown ) to help hold multi - head delivery body 1220 and forked section 1213 in a contracted position . the sheath may help to prevent the injection heads 1224 from catching on and damaging a lumen of the catheter through which multi - head delivery body 1220 may be moved . upon extending multi - head delivery body 1220 past a distal end of the catheter , the sheath may be removed , and forked section 1213 may unfold as shown in fig1 . once multi - head delivery body 1220 has been positioned over a target tissue site , it may be rolled across the target tissue site to deliver therapeutic through injection heads 1224 . after delivering the therapeutic , multi - head delivery body 1220 may be retracted back into a distal end of the catheter . the multi - head delivery body 1220 may also be retracted back into a distal end of the sheath so that multi - head delivery body 1220 may be removed from a patient within or outside of the catheter . in fig1 , the multi - head delivery device 1300 may include an elongate shaft 1310 , a distal end 1311 , a lumen 1312 , a multi - head delivery body 1320 , an inner cavity 1321 , and multiple injection heads 1324 spaced in a substantially even pattern around an exterior surface 1323 of multi - head delivery device 1320 . multiple injection heads 1324 may be configured and operate similar to those described in fig3 - 6 and 21 . in the present embodiment , elongate shaft 1310 may be rotably coupled to and co - axially aligned with multi - head delivery body 1320 . embodiments of multi - head delivery body 1320 may include a multi - head delivery body that may be moved longitudinally through a catheter . for example , multi - head delivery body 1320 may need to be enclosed in a sheath ( not shown ) to prevent multiple injection heads 1324 from catching on and damaging a lumen of the catheter through which multi - head delivery body 1320 may be moved . upon extending multi - head delivery body 1320 past a distal end of the catheter , the sheath may be removed , if present , and multi - head delivery body 1320 may be positioned over a target tissue site and rolled across the target tissue site to deliver a therapeutic through multiple injection heads 1324 that may be provided by lumen 1312 of elongate shaft 1310 . after delivering the therapeutic , multi - head delivery body 1320 may be retracted back into a distal end of the catheter using , for example , elongate shaft 1310 to pull multi - head delivery body 1320 back into the catheter and then remove the catheter and multi - head delivery body 1320 together . in the sheath embodiment , the multi - head delivery body 1320 may also be retracted back into a distal end of the sheath so that multi - head delivery body 1320 may be removed with or without the catheter . fig1 is a side view of a portion of a distal end of a catheter with an alternative multi - head delivery body . in fig1 , expandable multi - head delivery device 1800 may include an elongated shaft 1810 having a proximal end , a distal end 1811 and a lumen 1812 extending there between . it may also include a symmetrical , collapsible multi - head delivery body 1815 having a first arm 1820 and a second arm 1830 . lumen 1812 may be in fluid communication with the proximal end of elongated shaft 1810 . first arm 1820 may include a distal arm section 1821 having a distal end 1822 and a proximal end 1823 . first arm distal end 1822 may be pivotally coupled to elongated shaft distal end 1811 . first arm 1820 may also include a proximal arm section 1825 having a distal end 1826 pivotally coupled to distal arm section proximal end 1823 to form a side needle 1828 and a proximal end 1827 slidingly coupled to a section 1816 of elongated shaft 1810 . first arm 1820 may also include a lumen 1829 extending between first arm distal end 1822 and second arm proximal end 1827 , the lumen in fluid communication with elongated shaft lumen 1812 . second arm 1830 may include a distal arm section 1831 having a distal end 1832 and a proximal end 1833 . second arm distal end 1832 may be pivotally coupled to elongated shaft distal end 1811 to form a distal needle 1850 . second arm 1830 may also include a proximal arm section 1835 having a distal end 1836 pivotally coupled to distal arm section proximal end 1833 to form a side needle 1838 . second arm may also have a proximal end 1837 slidingly coupled to a section 1817 of elongated shaft 1810 near elongated shaft distal end 1811 . second arm 1830 may also include a lumen 1839 extending between first arm distal end 1832 and second arm proximal end 1837 in fluid communication with elongated shaft lumen 1812 . as can be seen in fig1 elongated shaft 1810 may be disposed within a catheter 1860 to permit elongated shaft 1810 to be moved to a target tissue site within catheter 1860 thus preventing needles 1828 , 1838 , and 1850 from substantially injuring tissue in a patient before the distal end of elongated shaft 1810 can be positioned near the target tissue site . as seen in fig1 , the distal end of elongated shaft 1810 including collapsible multi - head delivery body 1815 is extended out past catheter 1860 distal end 1861 and illustrates collapsible multi - head delivery body 1815 in a partially open position . movement lines indicate the collapsible multi - needle structure 1815 is being closed . in the closed position , collapsible multi - head delivery body 1815 may abut an exterior surface of elongated shaft 1810 to permit easy movement of elongated shaft 1810 through catheter lumen 1862 . in the closed position elongated shaft lumen 1812 may remain in fluid communication with first arm lumen 1829 and second arm lumen 1839 . this may be done , for example , via proximal end 1827 and / or proximal end 1837 and distal end 1822 and / or distal end 1832 . alternatively , elongated shaft lumen 1812 may not remain in fluid communication with first arm lumen 1829 and second arm lumen 1839 in the closed position . in accord an embodiment of the present invention a control mechanism may be implemented similar to an umbrella opening and closing mechanism that may be actuated from the proximal end of elongated shaft 1810 to control the opening and closing of collapsible multi - head delivery body 1815 . for example , one or more push / pull wires may be attached to collapsible multi - head delivery body 1815 to permit the opening and closing of collapsible multi - head delivery body 1815 by pushing / pulling one or more of the push / pull wires . alternatively , collapsible multi - head delivery body 1815 may be biased toward the open position by , for example , a spring - loaded umbrella mechanism that may be opened by a control mechanism 1870 to permit collapsible multi - head delivery body 1815 to open . similarly , collapsible multi - head delivery body 1815 may open upon being extended past the distal end of catheter 1860 a predetermined distance . similarly , collapsible multi - needle structure 1815 may also be closed by control mechanism 1870 . opening may be accomplished by releasing the spring - loaded mechanism and closing may be accomplished by pulling a proximal end of push / pull wire 1870 at the proximal end of catheter 1860 in the proximal direction . alternatively , fluid pressure ( positive or negative ) may be used to open or close the device . although the embodiment shown in fig1 may only show two arms 1820 , 1830 , other embodiments are contemplated in which three or more arms , may be implemented . fig1 is a side view of the portion of the distal end of the catheter of fig1 with the expandable multi - tip injection structure in an expanded position . in fig1 , the extended position collapsible multi - head delivery body 1815 may be urged distally to inject a target tissue site with needle 1850 . likewise , collapsible multi - head delivery body 1815 may be urged laterally in one or both directions to inject tissue sites with needle 1828 and / or needle 1838 . fig2 is a flow diagram illustrating a method in accordance with an embodiment of the present invention . in fig2 , the method may include inserting ( 2010 ) a multi - head delivery device into a catheter and moving the multi - head delivery device to a distal end of the catheter . the method may also include positioning ( 2020 ) the distal end of the catheter substantially adjacent to a target tissue site within a patient and extending ( 2030 ) the multi - head delivery device past the distal end of the catheter . the method may further include engaging ( 2040 ) the target tissue site with the multi - head delivery device heads of the multi - head delivery device into the target tissue site , and moving ( 2050 ) the multi - head delivery device over the target tissue site to deliver a therapeutic to the target tissue site . the method may also further include retracting ( 2060 ) the multi - head delivery device back into the distal end of the catheter and removing ( 2070 ) the distal end of the catheter from the target tissue site . although the method of fig3 described above may appear to indicate an exact order of execution of the elements of the method , it is not intended as such . for example , in an embodiment of the present invention , the operation of multi - head delivery body 320 of fig3 may include inserting ( 2010 ) multi - head delivery body 320 into lumen 116 at the proximal end of catheter 100 of fig1 , and moving multi - head delivery body 320 to a distal end of catheter 100 . the method may also include positioning ( 2020 ) the distal end of catheter 100 substantially adjacent to a target tissue site within a patient and extending ( 2030 ) multi - head delivery body 320 past the distal end of catheter 100 . the method may further include engaging ( 2040 ) the target tissue site with multi - head delivery body 320 , for example inserting some number of multiple injection heads 324 of multi - head delivery body 320 into the target tissue site , and moving ( i . e ., rolling ) ( 2050 ) multi - head delivery body 320 over the target tissue site to deliver a therapeutic to the target tissue site . this may include rolling ( 2050 ) multi - head delivery body 320 across the target tissue site once as well multiple times to provide the coverage deemed necessary by the practitioner . the method may still further include retracting ( 2060 ) multi - head delivery body 320 back into the distal end of catheter 100 and removing ( 2070 ) the distal end of catheter 100 from the target tissue site . in the present embodiment , the therapeutic may be introduced into lumen 312 of elongated shaft 310 either prior to or after inserting ( 2010 ) multi - head delivery body 320 into catheter 100 , extending ( 2030 ) multi - head delivery body 320 past the end of catheter 100 or engaging ( 2030 ) the target tissue site . fig2 is another alternative embodiment of the present invention . in this embodiment the multi - head delivery device 2200 includes an outer disc 2204 and an inner disc 2202 ; the inner disc having a port 2203 and the outer disc having several delivery heads 2205 . both the inner disc and the outer disc may rotate about the support 2201 . when the port 2203 of the inner disc aligns with a delivery head 2205 , therapeutic within the inner disc may be released through the port 2203 and the head 2205 . this therapeutic may be stored within the disc as well as be supplied to the inner disc through the support 2201 . a detailed description of embodiments of catheter assemblies that may be used in embodiments of the present invention may be found in co - pending u . s . patent application ser . no . 09 / 635 , 083 , filed by the same assignee on aug . 8 , 2000 , and entitled “ catheter shaft assembly .” the term “ therapeutic agent ” as used herein may include one or more “ therapeutic agents ” or “ drugs .” the terms “ therapeutic agents ” and “ drugs ” are used interchangeably herein and may include pharmaceutically active compounds , nucleic acids with and without carrier vectors such as lipids , compacting agents ( such as histones ), virus ( such as adenovirus , andenoassociated virus , retrovirus , lentivirus and α - virus ), polymers , hyaluronic acid , proteins , cells and the like , with or without targeting sequences . the therapeutic agent may be any pharmaceutically acceptable agent such as a non - genetic therapeutic agent , a biomolecule , a small molecule , or cells . exemplary non - genetic therapeutic agents include anti - thrombogenic agents such heparin , heparin derivatives , prostaglandin ( including micellar prostaglandin e1 ), urokinase , and ppack ( dextrophenylalanine proline arginine chloromethylketone ); anti - proliferative agents such as enoxaprin , angiopeptin , sirolimus ( rapamycin ), tacrolimus , everolimus , monoclonal antibodies capable of blocking smooth muscle cell proliferation , hirudin , and acetylsalicylic acid ; anti - inflammatory agents such as dexamethasone , rosiglitazone , prednisolone , corticosterone , budesonide , estrogen , estrodiol , sulfasalazine , acetylsalicylic acid , mycophenolic acid , and mesalamine ; anti - neoplastic / anti - proliferative / anti - mitotic agents such as paclitaxel , epothilone , cladribine , 5 - fluorouracil , methotrexate , doxorubicin , daunorubicin , cyclosporine , cisplatin , vinblastine , vincristine , epothilones , endostatin , trapidil , halofuginone , and angiostatin ; anti - cancer agents such as antisense inhibitors of c - myc oncogene ; anti - microbial agents such as triclosan , cephalosporins , aminoglycosides , nitrofurantoin , silver ions , compounds , or salts ; biofilm synthesis inhibitors such as non - steroidal anti - inflammatory agents and chelating agents such as ethylenediaminetetraacetic acid , o , o ′- bis ( 2 - aminoethyl ) ethyleneglycol - n , n , n ′, n ′- tetraacetic acid and mixtures thereof ; antibiotics such as gentamycin , rifampin , minocyclin , and ciprofolxacin ; antibodies including chimeric antibodies and antibody fragments ; anesthetic agents such as lidocaine , bupivacaine , and ropivacaine ; nitric oxide ; nitric oxide ( no ) donors such as lisidomine , molsidomine , l - arginine , no - carbohydrate adducts , polymeric or oligomeric no adducts ; anti - coagulants such as d - phe - pro - arg chloromethyl ketone , an rgd peptide - containing compound , heparin , antithrombin compounds , platelet receptor antagonists , anti - thrombin antibodies , anti - platelet receptor antibodies , enoxaparin , hirudin , warfarin sodium , dicumarol , aspirin , prostaglandin inhibitors , platelet aggregation inhibitors such as cilostazol and tick antiplatelet factors ; vascular cell growth promotors such as growth factors , transcriptional activators , and translational promotors ; vascular cell growth inhibitors such as growth factor inhibitors , growth factor receptor antagonists , transcriptional repressors , translational repressors , replication inhibitors , inhibitory antibodies , antibodies directed against growth factors , bifunctional molecules consisting of a growth factor and a cytotoxin , bifunctional molecules consisting of an antibody and a cytotoxin ; cholesterol - lowering agents ; vasodilating agents ; agents which interfere with endogeneus vascoactive mechanisms ; inhibitors of heat shock proteins such as geldanamycin ; and any combinations and prodrugs of the above include statins , β - blockers , and ace inhibitors . exemplary biomolecules include peptides , polypeptides and proteins ; oligonucleotides ; nucleic acids such as double or single stranded dna ( including naked and cdna ), rna , antisense nucleic acids such as antisense dna and rna , small interfering rna ( sirna ), and ribozymes ; genes ; carbohydrates ; angiogenic factors including growth factors ; cell cycle inhibitors ; and anti - restenosis agents . nucleic acids may be incorporated into delivery systems such as , for example , vectors ( including viral vectors ), plasmids or liposomes . non - limiting examples of proteins include monocyte chemoattractant proteins (“ mcp - 1 ) and bone morphogenic proteins (“ bmps ”), such as , for example , bmp - 2 , bmp - 3 , bmp - 4 , bmp - 5 , bmp - 6 ( vgr - 1 ), bmp - 7 ( op - 1 ), bmp - 8 , bmp - 9 , bmp - 10 , bmp - 11 , bmp - 12 , bmp - 13 , bmp - 14 , bmp - 15 . preferred bmps are any of bmp - 2 , bmp - 3 , bmp - 4 , bmp - 5 , bmp - 6 , and bmp - 7 . these bmps can be provided as homdimers , heterodimers or combinations thereof , alone or together with other molecules . alternatively , or in addition , molecules capable of inducing an upstream or downstream effect of a bmp can be provided . such molecules include any of the “ hedghog ” proteins , or the dna &# 39 ; s encoding them . non - limiting examples of genes include survival genes that protect against cell death , such as anti - apoptotic bcl - 2 family factors and akt kinase and combinations thereof . non - limiting examples of angiogenic factors include acidic and basic fibroblast growth factors , vascular endothelial growth factor , epidermal growth factor , transforming growth factor α and β , platelet - derived endothelial growth factor , platelet - derived growth factor , tumor necrosis factor α , hepatocyte growth factor , and insulin like growth factor . a non - limiting example of a cell cycle inhibitor is a cathespin d ( cd ) inhibitor . non - limiting examples of anti - restenosis agents include p15 , p16 , p18 , p19 , p21 , p27 , p53 , p57 , rb , nfkb and e2f decoys , thymidine kinase (“ tk ”) and combinations thereof and other agents useful for interfering with cell proliferation . exemplary small molecules include hormones , nucleotides , amino acids , sugars , and lipids and compounds have a molecular weight of less than 100 kd . exemplary cells include stem cells , progenitor cells , endothelial cells , adult cardiomyocytes , and smooth muscle cells . cells can be of human origin ( autologous or allogenic ) or from an animal source ( xenogenic ), or genetically engineered . any of the therapeutic agents may be combined to the extent such combination is biologically compatible . any of the above mentioned therapeutic agents may be incorporated into a polymeric coating on the medical device or in the medical device . the polymers may be biodegradable or non - biodegradable . non - limiting examples of suitable non - biodegradable polymers include polyvinylpyrrolidone including cross - linked polyvinylpyrrolidone ; polyvinyl alcohols , copolymers of vinyl monomers such as eva ; polyvinyl ethers ; polyvinyl aromatics ; polyethylene oxides ; polyesters including polyethylene terephthalate ; polyamides ; polyacrylamides ; polyethers including polyether sulfone ; polyalkylenes including polypropylene , polyethylene and high molecular weight polyethylene ; polyurethanes ; polycarbonates , silicones ; siloxane polymers ; cellulosic polymers such as cellulose acetate ; polymer dispersions such as polyurethane dispersions ( bayhdrol ®); squalene emulsions ; and mixtures and copolymers of any of the foregoing . non - limiting examples of suitable biodegradable polymers include polycarboxylic acid , polyanhydrides including maleic anhydride polymers ; polyisobutylene copolymers and styrene - isobutylene - styrene block copolymers such as styrene - isobutylene - styrene tert - block copolymers ( sibs ); polyorthoesters ; poly - amino acids ; polyethylene oxide ; polyphosphazenes ; polylactic acid , polyglycolic acid and copolymers and mixtures thereof such as poly ( l - lactic acid ) ( plla ), poly ( d , l ,- lactide ), poly ( lactic acid - co - glycolic acid ), 50 / 50 ( dl - lactide - co - glycolide ); polydioxanone ; polypropylene fumarate ; polydepsipeptides ; polycaprolactone and co - polymers and mixtures thereof such as poly ( d , l - lactide - co - caprolactone ) and polycaprolactone co - butylacrylate ; polyhydroxybutyrate valerate and blends ; polycarbonates such as tyrosine - derived polycarbonates and arylates , polyiminocarbonates , and polydimethyltrimethylcarbonates ; cyanoacrylate ; calcium phosphates ; polyglycosaminoglycans ; macromolecules such as polysaccharides ( including hyaluronic acid ; cellulose , and hydroxypropylmethyl cellulose ; gelatin ; starches ; dextrans ; alginates and derivatives thereof ), proteins and polypeptides ; and mixtures and copolymers of any of the foregoing . the biodegradable polymer may also be a surface erodable polymer such as polyhydroxybutyrate and its copolymers , polycaprolactone , polyanhydrides ( both crystalline and amorphous ), maleic anhydride copolymers , and zinc - calcium phosphate . in a preferred embodiment , the polymer is polyacrylic acid available as hydroplus ® ( boston scientific corporation , natick , mass . ), and described in u . s . pat . no . 5 , 091 , 205 , the disclosure of which is incorporated by reference herein . in a more preferred embodiment , the polymer is a co - polymer of polylactic acid and polycaprolactone . such coatings used with the present invention may be formed by any method known to one in the art . for example , an initial polymer / solvent mixture can be formed and then the therapeutic agent added to the polymer / solvent mixture . alternatively , the polymer , solvent , and therapeutic agent can be added simultaneously to form the mixture . the polymer / solvent mixture may be a dispersion , suspension or a solution . the therapeutic agent may also be mixed with the polymer in the absence of a solvent . the therapeutic agent may be dissolved in the polymer / solvent mixture or in the polymer to be in a true solution with the mixture or polymer , dispersed into fine or micronized particles in the mixture or polymer , suspended in the mixture or polymer based on its solubility profile , or combined with micelle - forming compounds such as surfactants or adsorbed onto small carrier particles to create a suspension in the mixture or polymer . the coating may comprise multiple polymers and / or multiple therapeutic agents . the coating can be applied to the medical device by any known method in the art including dipping , spraying , rolling , brushing , electrostatic plating or spinning , vapor deposition , air spraying including atomized spray coating , and spray coating using an ultrasonic nozzle . the coating on the medical device is typically from about 1 to about 50 microns thick . in the case of balloon catheters , the thickness is preferably from about 1 to about 10 microns , and more preferably from about 2 to about 5 microns . very thin polymer coatings , such as about 0 . 2 - 0 . 3 microns and much thicker coatings , such as more than 10 microns , are also possible . it is also within the scope of the present invention to apply multiple layers of polymer coatings onto the medical device . such multiple layers may contain the same or different therapeutic agents and / or the same or different polymers . methods of choosing the type , thickness and other properties of the polymer and / or therapeutic agent to create different release kinetics are well known to one in the art . the medical device may also contain a radio - opacifying agent within its structure to facilitate viewing the medical device during insertion and at any point while the device is implanted . non - limiting examples of radio - opacifying agents are bismuth subcarbonate , bismuth oxychloride , bismuth trioxide , barium sulfate , tungsten , and mixtures thereof . the present invention may include designs that use catheters manufactured by boston scientific of natick , mass . including the stiletto catheter . likewise , embodiments of the present invention may also use catheters with and without hoods , with and without an electrode sensor tip , and with combinations of the above - described features in catheters with and without deflectable tips . still further , the present invention may include a body with multiple heads spaced over an exterior surface of the body . the multiple heads may be spaced evenly , randomly and / or in a specific pattern over on exterior surface of the body . for example , the multi - head delivery device may include a cylindrically shaped body with the multiple heads being arranged in evenly spaced longitudinal rows and evenly spaced circumferentially arranged columns or the multiple heads may be arranged in evenly spaced and offset longitudinal rows so that heads in every other row may be aligned with each other . the multiple heads may provide for the injection or other delivery of therapeutic from within the multi - head delivery device as well as be made of a solid therapeutic that may break off as each head is inserted into a target area . the multi - head delivery device may permit the rapid deployment of therapeutic agents over a tissue area by rolling , for example , the device across the area . this may be especially useful when a large area of tissue needs to be dosed with the therapeutic agent while the multi - head device is positioned inside a patient &# 39 ; s body . this can reduce procedural time and costs due to the large tissue area that may be quickly treated with embodiments of the present invention . although the present invention has been disclosed in detail , it should be understood that various changes , substitutions , and alterations may be made herein , the present invention is intended to cover various modifications of each embodiment as well as between embodiments . other examples are readily ascertainable from the above description and may be made without departing from the spirit and scope of the present invention .

a therapeutic delivery device is provided wherein a delivery body is supported by an elongate member such that the body may rotate as it delivers therapeutic to a target site . therapeutic may be delivered by deploying delivery heads into a target site as well as by dispensing therapeutic from the delivery head . the delivery body may be cylindrically shaped , spherically shaped or shaped in various other configurations . in one embodiment the delivery body contains tracks that may roll back and forth over a target site to dispense therapeutic . in another embodiment , the delivery heads of the delivery body have internal valves that open and close in order to dispense therapeutic .

methods , systems and devices according to embodiments of this invention seek to provide improved trialing during complete and partial joint replacement and repair . a trial fixation device of this invention may include a device that engages and secures a trial in a bone canal , such as a device including a body adapted to be received in a resected bone and a fixation portion attached to the body for engaging a trial stem . in one embodiment of this invention , the fixation portion comprises a first capture member attached to the body , a second capture member , and a first fastener adapted to move the second capture member towards the first capture member to engage the trial stem . the first capture member has a first aperture , the second capture member has a second threaded aperture , and the first fastener is a first tension bolt adapted to extend through the first aperture and thread through the second aperture so that when the first tension bolt is tightened , the second capture member moves toward the first capture member . the first capture member has a third threaded aperture and the second capture member has a fourth aperture and the device further includes a second tension bolt adapted to extend through the fourth aperture and thread through the third aperture so that when the second tension bolt is tightened the second capture member moves toward the first capture member to engage the trial stem . consider one example of a device according to one embodiment of this invention . fig1 and 2 illustrate an exploded view of an intramedullary trial fixation device 10 according to one embodiment of the present invention . fig3 and 4 illustrate perspective views of the trial fixation device 10 . the trial fixation device 10 includes a fixation portion 12 and a body 14 . the fixation portion 12 includes a first fastener 16 , a first bias 18 , a first capture member 20 , a second fastener 22 , a second bias 24 , and a second capture member 26 . the first capture member 20 has two apertures — an inner , smooth aperture 28 and an outer , threaded aperture 30 . the second capture member 26 has two apertures — an inner , threaded aperture 32 and an outer , smooth aperture 34 . the capture members 20 , 26 have opposite fingers 36 , 38 at the inner end of each capture member . the first capture member is attached to a collar 40 on the body 14 . the second capture member 26 is not attached to the body 14 and its position is determined by the fasteners 16 , 22 . the fasteners 16 , 22 in the embodiment shown in fig1 - 4 are tension bolts . in other embodiments , any suitable fastener may be used . as shown in fig3 and 4 , the first fastener 16 extends through the inner , smooth aperture 28 and is threaded in the inner , threaded aperture 32 . the second fastener 22 extends through the outer , smooth aperture 34 and is threaded in the outer , threaded aperture 30 . tightening either fastener moves the second capture member 26 toward the first capture member 20 and loosening either fastener moves the second capture member 26 away from the first capture member 20 . as the first fastener 16 is tightened or loosened , the second fastener 22 slides through the outer , smooth aperture 34 . as the second fastener 22 is tightened or loosened , the first fastener 16 slides through the inner , smooth aperture 28 . for example , when the first fastener 16 is tightened the outer , smooth aperture 34 of the second capture member 26 slides over the second fastener 22 allowing the second capture member 22 to move closer to the first capture member 20 . the first bias 18 and second bias 24 are placed around the fasteners 16 , 22 between the capture members 20 , 26 and serve to keep the second capture member 26 from becoming loose and sliding back and forth . in the embodiment of fig1 - 4 , the biases 18 , 24 are compression springs . in other embodiments , any suitable biasing element may be used . while above described embodiment of the fixation portion 12 uses two fasteners , one of skill in the art understands that one fastener could be used . fig1 and 11 illustrate an embodiment of a fixation device 100 using one fastener 101 , in the illustrated embodiment , a tension bolt . as shown in fig1 and 11 a capture member connector 102 is attached to the first capture member 104 and slidably extends through an outer aperture on the second capture member 106 . the capture member connector 102 adds stability to the fixation portion . the fixation portion illustrated in the figures is designed to work with the neer 3 and modular neer 3 trial stems from smith & amp ; nephew , inc . one of skill in the art understands that the fixation portion could be configured a variety of different ways to secure a neer 3 or modular neer 3 trial stem and different trial stems to the fixation device . for example , a radially compressing semi - circular clamp fitting within the collar at the top of the device could close around the diameter of the implant , thereby providing fixation . also , a tight fitting but compressible liner could be used in the distal portion of the device to control height , rather than a clamping mechanism . also , a clamping mechanism devised to attach to the medial fixation fin rather than the lateral fixation fin could be used to attach the device to the trial stem . as shown in fig1 - 4 , the body includes a collar 40 around the proximal end to which the fixation portion 12 is connected . two rotation prevention fins 42 extend from the collar 40 down the sides of the body 14 . the proximal section of the body 14 includes a medial trial fin slot 44 and a lateral trial fin slot 46 . the distal end of the body includes a trial stem sleeve 48 . in one embodiment , a friction liner 50 is affixed to the interior surface of the trial stem sleeve 48 . in one embodiment , the friction liner 50 is made of plastic , but in other embodiments may be made of any suitable material . one of skill in the art understands that the body can be configured a variety of different ways to accommodate a neer 3 trial stem or different trial stems . the preferred method of manufacturing the fixation device is machining . although other methods , such as casting , could be used . fig5 illustrates an exemplary intramedullary humeral trial stem 52 that can be used with the intramedullary trial fixation device . the trial stem 52 includes a humeral trial head plateau 54 with a humeral trial head attachment post 56 affixed on the proximal side of the plateau . a humeral trial head ( not shown ) is attached to the humeral trial head attachment post 56 for modular trial stems . monoblock trial stems have an attached humeral trial head . a stem 58 is formed on or affixed to the distal side of the humeral head plateau 54 . the proximal end of the stem 58 may have graduated laser markings 60 to allow for stem positioning in the humerus . a medial fin 62 extends from the distal side of the humeral head plateau 54 to the stem 58 . two lateral fins 64 are included on the stem opposite the medial fin 62 . the lateral fins 64 and the medial fin 62 replicate the fixation fins on a humeral prosthetic implant . fig6 and 7 illustrate an embodiment of the fixation device 10 engaging the trial stem 52 . the trial is secured in the fixation device 10 by locking the fixation portion 12 on the trial stem 52 . in the embodiment shown in fig6 and 7 , the trial is inserted into the fixation device 10 through the trial stem sleeve 48 so that the fingers 36 , 38 of the capture members 20 , 26 engage the lateral fins 64 of the trial stem 52 and the friction liner 50 engages the stem 58 . the lateral fins 64 of the trial stem 52 fit in the lateral trial fin slot 46 and the medial fin 62 of the trial stem 52 fit in the medial trial fin slot 44 . the friction liner 50 keeps the height of the trial stem 52 constant until the fixation portion 12 engages the trial stem 52 . the position of the trial stem 52 is adjusted by unlocking the fixation portion 12 , moving the trial stem 52 , and locking the fixation portion 12 to re - engage the trial stem 52 . fig9 illustrates an exemplary humeral prosthetic implant 70 . the prosthesis has a humeral head 72 and a stem 74 extending from the head . the prosthetic implant 70 could be modular or monoblock . a medial fixation fin 76 extends from the humeral head to the stem and includes a fixation hole 78 . two lateral fixation fins 80 are formed on the proximal part of the stem 74 . the lateral fixation fins are in a sixty degree angle to each other positioned in a way that they align with the bicipital groove , giving the correct retroversion for the prosthesis . the lateral fixation fins each have four holes 82 allowing for the anatomical fixation of the tuberosities with sutures . in cases of three or four part fractures of the proximal humerus or severe osteoarthritis , a humeral prosthetic implant like the one illustrated in fig9 and described above is used to repair the shoulder . initially , during surgery the humerus is prepared according to established surgical technique , which may include resecting the proximal portion and may include reaming the medullary canal . an appropriate trial stem is placed into the fixation device . the fixation portion of the fixation device is locked onto the trial stem . as shown in fig8 the fixation device 10 and attached trial stem 52 are introduced into the medullary canal until the collar of the fixation device is flush , or as close as possible , to the bony surface of the humerus 90 . a trial fixation device driver can be used to lock the fixation device to the trial stem . fig1 illustrates an embodiment of a trial fixation device driver . the fixation portion 12 of the fixation device 10 is unlocked and the height of the trial stem 52 is adjusted to the desired position based on the use of x - rays and x - ray templates before surgery . once the trial stem 52 is adjusted to the desired position , the fixation portion 12 is locked onto the trial stem 52 . the fixation device 10 illustrated in fig1 - 7 has two fasteners 16 , 22 to allow easy access to the fasteners for use in left and right shoulder procedures . a trial head is placed on the trial stem and the range of motion of the shoulder is evaluated . if the range of motion is satisfactory , the position of trial height is noted by observing the marks 60 on the trial stem in relation to the device or the surface of the humerus . if desired , the trial stem 52 is marked with a pen at the appropriate position . if the range of motion is not satisfactory , the fixation portion 12 is unlocked and the height of the trial stem 52 adjusted until an acceptable position is reached . the trial stem 52 and fixation device 10 are then removed . if the device 10 does not come out with the trial stem 52 , a trial fixation device extractor can be used to lever the device out of the humerus . fig1 illustrates an embodiment of the trial fixation device extractor . the humeral prosthesis is marked at the same position as the trial stem in order to indicate the correct offset for the prosthetic implant . cement may be inserted medullary canal . the prosthetic implant 70 is placed in the canal at the marked height . the tuberosities and other soft tissue are then connected to the prosthetic implant . the disclosure of devices and processes as recited above is not intended to limit the scope of the present invention . a person of skill in the art understands that various fixation portions can be used with different intramedullary fixation device body structures to accommodate different stem geometries . a person of skill in the art understands that , while the embodiments of the fixation device are described in terms of a prosthetic implant for a humerus , the fixation device could be used with other prosthetic devices .

an intramedullary fixation device for use in securing a trial in the medullary canal of a bone to determine the offset and orientation of a prosthetic implant for replacement of a joint articulating surface of the bone is disclosed . the fixation device comprises a body for receiving a trial and a fixation portion for engaging the trial . a system for use in surgical repair of a joint comprising a selection of prosthetic implants of various sizes , a selection of trials of various sizes corresponding to the sizes of the implants , a selection of fixation devices of various sizes corresponding to the sizes of the trials , a trial fixation device driver for inserting the fixation device and attached trial into the canal of a bone , and a trial device extractor for removing the fixation device from the resected bone is disclosed . methods of using the fixation device and system of the invention are disclosed .

the present invention is directed to a placement device for flat doppler probes to aid in transmitting and receiving doppler signals . the present invention also discloses a method of using the placement device to obtain a doppler spectrum . it should be noted that this is an exemplary embodiment and use of the present invention . the apparatus and method may be used outside the treatment and diagnosis of humans . for example it may be used on animals . furthermore , there may be other variations of the placement device that will be appreciated by one skilled in the art that relate to flat doppler probes or other ultrasound devices . fig1 is a side view of an exemplary embodiment of the flat doppler probe placement device 10 in accordance with the invention . the placement device 10 includes bottom 12 and top 13 surfaces and distal 24 and proximal 26 ends . the bottom surface 12 contacts a surface 1 of a patient , such as the skin . the bottom surface 12 , or the patient contacting surface , may comprise a material suitable for transmitting and receiving doppler signals . in one embodiment , the material may be a hydrophilic material that is optimized to conduct ultrasound signals thus eliminating the need for using ultrasound gel . the hydrophilic material should be capable of transmitting a frequency in the range of 5 to 8 mhz . those of skill in the art will appreciate that suitable materials include hydrophilic materials having low tear strength such as hema : vp ( hydroxyethyl methacrylate vinyl pyrrolidone ) or mma : vp ( methyl methacrylate vinyl pyrrolidone )), as well as hydrophilic materials having relatively high tear strength such as an : vp ( acrylonitrile vinyl pyrrolidone ), hema : mma ( hydroxyethyl methacrylate methyl methacrylate ) or polyamide vinyl pyrrolidone . the material may also be of optimal thinness and durometer to minimize interference with doppler transmitting and receiving signals . the top surface 13 of the flat doppler probe placement device 10 in accordance with the invention opposes the bottom surface and is securedly coupled thereto . those of skill in the art will appreciate that the two surfaces 12 , 13 may be secured by thermal bonding , adhesive , or the like . the top surface may comprise the same material as the patient contacting surface 12 or alternatively may comprise a material that is non - transmissive or in other words not suitable for transmitting and receiving doppler signals . ideally , the top and bottom surfaces are made from clear film to allow the clinician to view the placement of the doppler probe . in an alternative embodiment ( not shown ), the placement device 10 may include two bottom surfaces that are thermally or adhesively bonded together and enclose an optimal volume of ultrasound gel . one bottom surface is the patient contacting surface while the “ inner ” bottom surface bonds with the top surface . in this way , ultrasound gel is used but is conveniently contained within the placement device 10 . the flat doppler probe placement device 10 in accordance with the invention may be treated with an adhesive coating 14 on the patient contacting surface or around the perimeter of patient contacting surface 12 . preferably , the adhesive is placed around the perimeter of the patient contacting surface 12 to ensure that there is no interference with the doppler signals . the adhesive coating 14 may include any repositionable , pressure sensitive adhesive that does not interrupt physiological parameter monitoring . the adhesive coating is an inherently tacky , elastomeric , solvent - dispersible , solvent - insoluble pressure sensitive adhesive . in one embodiment , the adhesive coating is a monomer or polymer blend selected from the group consisting of alkyl acrylate , alkyl methacrylate ester , acrylic acid , methacrylic acid , itaconic acid , crotonic acid , maleic acid , fumaric acid , sulfoethyl methacrylate , and ionic monomers such as sodium methacryate , ammonium acrylate , sodium acrylate , trimethylamine p - vinyl benzimide , 4 , 4 , 9 - trimethyl - 4 - azonia - 7 - oxo - 8 - oxa - dec - 9 - ene - 1 - sulphonate , n , n - dimethyl - n -(. beta .- methacryloxyethyloxy - ethyl ) ammonium propionate betaine , trimethylamine methacrylimide , and 1 , 1 - dimethyl - 1 -( 2 , 3 - dihydroxypropyl ) amine methacrylimide . in another embodiment , the adhesive coating may include microspheres selected from the group consisting of acrylate , alkylacrylate and alkylacrylate ester monomers alone or in combination with vinyl monomers . the adhesive coating may be covered with a removable paper or other type of film used to maintain the tackiness of the adhesive coating during storage , transportation and other non - use situations . as best seen in fig2 , the removable cover may also include tab portions 18 that extend past the perimeter of the placement device 10 , allowing the user to easily remove cover 16 to expose the adhesive 14 . when the placement device is adhesively placed in position on the patient , it allows the “ hands - free ” operation of the doppler probe by the clinician or technician . those of skill in the art will appreciate that the size and shape of the placement device 10 can be varied depending on the size and shape of the flat doppler probe with which it is used . referring now to fig2 , a plan view of the flat doppler probe placement device 10 is shown . proximal end 26 of the placement device 10 includes receiving opening 20 while distal end 24 is secured to top and bottom surfaces as previously described . first , second and third sidewalls 30 , 32 , 34 define a probe receiving chamber 28 therewithin . as depicted , receiving opening 20 is arcuate shaped . however , those of ordinary skill in the art will appreciate the receiving opening 20 may be sized or shaped to receive any size or shape of flat doppler probe . flat doppler probe 22 is inserted through receiving opening 20 and positioned within receiving chamber 28 of the probe placement device 10 . the removable cover may optionally include tab portions 18 that extend past the perimeter of the placement device 10 , allowing the user to easily remove cover 16 to expose the adhesive 14 . in operation , a clinician or technician positions the placement device 10 through arcuate receiving opening 20 and determines the correct placement of the device on a surface of a patient . the clinician views the placement of the device through the clear top and bottom surfaces and slides the flat doppler probe within the placement device 10 over the skin surface . when the ideal surface is located , the clinician or technician grasps tab portions 18 and easily removes cover 16 , exposing the adhesive 14 . the placement device 10 containing the flat doppler probe is then pressed on the skin causing the adhesive to secure the placement device 10 to the patient . the flat doppler probe 22 then transmits and receives reflected doppler signals , which are then processed by computer means to obtain a doppler spectrum . although the description of the preferred embodiment has been presented , it is contemplated that various changes , including those mentioned above , could be made without deviating from the spirit of the present invention . it is therefore desired that the present embodiment be considered in all respects as illustrative , not restrictive , and that reference be made to the appended claims rather than to the foregoing description to indicate the scope of the invention .

the present invention is directed towards a placement device for a flat doppler probe and a method of use that allows for hands - free use of a flat doppler probe . the device replaces gel for transmitting and receiving ultrasound signals or alternatively encapsulates the gel . the placement device includes a hydrophilic surface that contacts a patient and allows for the transmission and receiving of ultrasound signals . the placement device eliminates the use of gel for easier clean up and optimizes the transmission of ultrasound signals . the placement device includes an adhesive on the patient contacting surface that allows the placement device to adhere to a surface on a patient .

the current disclosure utilizes commercially available products in a novel combination that achieves optimal results . the specific products utilized are 20 fluid ounces ( two 10 fl oz bottles ) of citrate magnesia ( laxative ), between 50 and 66 grams of p - glycol powder , and a standardized saline enema product such as a fleet ® enema . these are commonly available without a prescription as over the counter medications . this disclosure teaches combining these products in specific amounts and administering them in a specific order to be used for cleansing of the colon for preparation for colonoscopy . the novel mixture must be administered in conjunction with specific foods , both to eat and avoid . the mixture replaces other currently employed preparation medications or use of the citrate or p - glycol powder alone . the novel mixture combined with the protocol disclosed herein allows patients to achieve adequate cleansing without the drawbacks noted above . the following description , for purposes of explanation , specific numbers , materials and configurations are set forth in order to provide a thorough understanding of the present invention . however , it will be apparent to one skilled in the art that the present invention may be practiced without the specific details . in other instances , well known features are omitted or simplified in order not to obscure the present invention . furthermore , for ease of understanding , certain method steps are delineated as separate steps , however , these separately delineated steps should not be construed as necessarily order dependent in their performance . in the preferred method begins the day prior to the diagnostic or surgical procedure . the patient must consume clear fluids in abundance , preferably at least 64 fluid ounces . conventional precautions associated with colonoscopy preparation are observed , including but not limited to avoidance of red or purple fluids ( e . g ., grape juice ) which may be mistaken for blood . the patient must refrain from consuming all solid foods , with the sole exception of this method of consuming potatoes , potato constituents or potato substitutes . in particular , patients should consume two to three medium boiled potatoes , preferably peeled with butter and a little salt as desired , for breakfast the day prior to the procedure . the method requires that no further solid food be consumed following the potatoes . starch ( amylum - amylose : amylopectin in ratio of 1 : 13 ) including carbohydrates , insoluble , and sugars ( sucrose , glucose , fructose ) approximately 5 % to 35 %; protein , approximately 1 % to 10 %; ash including inorganic minerals / materials ( miscellaneous ) such as nitrogen , phosphorus , potassium , magnesium , amino acids , approximately 1 % to 5 %; fat , approximately 0 . 01 % to 1 %; pulpy pectoses ( protopectin ), approximately 1 % to 8 %; pectin , approximately 0 . 1 % to 1 %; crude fiber , approximately 0 . 2 % to 5 %; cellulose , approximately 0 . 1 % to 1 %; and water , approximately 60 % to 85 %. as an alternative to medium boiled potatoes , the patient may instead consume a mixture of potato constituents in the foregoing proportions . the best mode of potato constituents for purposes of the method is : 20 % starch ( amylum - amylose : amylopectin in ratio of 1 : 13 ) including carbohydrates , insoluble , and sugars ( sucrose , glucose , fructose ); 2½ % protein ; 1 % ash including inorganic minerals / materials ( miscellaneous ); 0 . 1 % fat ; 4 % pulpy pectoses ; 0 . 4 % pectin ; 0 . 6 % crude fiber ; ½ % cellulose ; and the remainder being approximately 71 % water . as more convenient alternatives to medium boiled potatoes or potato constituents , the patient may instead consume any one of the following potato - substitutes instead : ( a ) eight ounces of instant mashed potatoes together with one cup of water ; or ( b ) eight ounces of potato chips ( also termed potato crisps ) together with one cup of water ; or ( c ) eight ounces of ready - to - eat cereals : wheat , shredded , plain , sugar - and salt - free together with a half cup of water . the method requires that no further solid food be consumed following one of the potato - substitutes or constituents . between 1 p . m . and 5 p . m . the same day , the patient must perform the following protocol . first , drink approximately 10 fl . oz . of magnesium citrate while continuing to drink clear fluids . second , approximately two hours later , the patient drinks one dosage of between 25 and 33 grams of p - glycol . this may be mixed with a clear beverage of the patient &# 39 ; s preference , such as tea or gatorade . third , about ten minutes following the consumption of the p - glycol dose in the second step , the patient consumes a full glass ( approx . 8 fl . oz .) of water or other clear fluid . fourth , two or three hours following the consumption of the water or fluid of the third step , the patient drinks a second , approximate 10 fl . oz . dose of magnesium citrate . s better than existing because it results in better cleansing and is less costly to the patient . fifth , the patient continues drinking clear fluids throughout the day , as desired by the patient sixth , if the procedure is to be performed the following morning , the patient drinks another 25 to 33 grams of p - glycol between approximately 9 p . m . and 11 p . m . alternatively , for an afternoon procedure the following day , the patient drinks the second 25 to 33 grams of p - glycol at approximately 8 a . m . of the day of the afternoon procedure . seventh , starting at approximately four hours before the diagnostic or surgical procedure , the patient must refrain from consuming all fluids . the sole exception is a sip of water sufficient to ingest any medications .

a method is disclosed for cleansing bowels prior to a colonic procedure utilizing conventional preparations along with potatoes or potato - constituents or potato - substitutes .

fig1 , has a part a wherein the rider is shown using the prior art knee scooter of u . s . pat . no . 8 , 348 , 788 , wherein the right leg is the injured leg and as such is shown disposed on the kneepad 115 of the scooter 100 . in fig1 b , it is just the opposite , the injured leg is the left leg and it shown disposed on the kneepad 115 of knee scooter 100 . fig2 is a view unrelated to the invention , showing an injured foot in what is called a protective walking boot — also a prior art item — resting on the kneepad 115 of a prior art scooter 100 . the purpose of this view is to illustrate the appliance worn by one of the applicants of this application that necessitated the use of the prior art knee scooter that led to the invention of this patent application due to limited mobility fig3 is a perspective view of a typical prior art knee scooter , namely the one of u . s . pat . no . 7 , 780 , 180 . the text of that us issued patent is incorporated herein by reference . thus only a brief discussion will be set out of the construction of such a knee walker . the apparatus is seen to have spaced front wheels on an axle , forming a front wheel assembly 106 , attached to a steering mechanism 107 in fig4 that allows the front wheels to turn left and right like those of an automobile . the rear wheels are on a fixed axle ( rear wheel assembly 102 ) and move only in a straight line . steering is manually controlled from the handle bar and the steering mount 108 , whose movement directionally is mimicked by the front wheels . a vertical height adjustable shaft 105 seen also in fig5 is disposed between the frame members 101 and is connected to the handle bars and other elements for steering the scooter . the frame comprises a pair of inverted u - shaped parallel tubular members , 101 a and 101 b which are disposed on one end to a front frame cross member that extends laterally outwardly from the frame and on the other end to a rear frame member and wheel assembly 102 that also extends laterally outwardly therefrom . a knee cushion 115 , is adjustably upwardly supported on the upper side of said frame . reference is also made to fig4 a closeup view which also shows some of these elements as ell as fig5 . elements 108 and 109 will be discussed infra . for the invention at hand the reader only needs to be concerned about the frame , the knee cushion and vertical tube 105 . in fig5 , the relative positioning of the apparatus of this invention is seen when mounted for use on the scooter 100 , relative to the knee pillow 115 . other elements of the scooter have been discussed supra . in fig6 we see the first embodiment of this invention . the apparatus 10 , is generally rectangular in cross section , and is about 13 inches wide and about 11 inches long from front to rear . length is intended to mean the dimension of the inventive unit between the front and back wheels of the scooter , while width is the transverse dimension across the frame of the scooter . the height of the unit is preferably about 1 . 75 inches , measured at the circumferential raised rim 13 which is raised up about 0 . 5 inches above the top surface 12 . thus general elevation of the main body 15 , is about one inch from bottom to top surface . apparatus 10 is seen to have a series of defined recesses on its upper surface and a raised rim 13 along the entire periphery of the storage platform of this invention . the left front corner has a first recess 29 , formed in the shape of a chamfered square , about 4 . 25 × 4 . 25 inches in cross section of 4 normally disposed strips of wood , 28 or molded as a unitary member 0 . 625 inches wide and about 0 . 5 inch down from the top surface 12 of the apparatus . this first recess 29 is sized to hold a ½ gallon carton of milk or juice within the recess on the surface of the strips . a second concentric square recess 30 is sized about 3 . 0 inches × 3 . 0 inches and is disposed at a lower second level from the top surface 12 . square 30 is formed from the vertical edges of the strips 28 or molding and is intended due to its size , either a one quart cardboard container or a ½ pint cream size container . since there are small vertical surfaces between the different recess depths , the properly sized containers will stay within the confines of their recess for transportation from refrigerator to table and back . on the right side of the first embodiment there are two concentric circular recesses . circular recess 31 is formed of an approximately 0 . 375 ″ circular strip about 0 . 25 inch deep , and is about 3 . 50 inches in cross section and designated 32 ; while the lower surface concentric circle therein is about 2 . 625 inches in diameter . these are sized to receive common household jars and cups and coffee mugs . it is within the scope of this invention to have a third concentric circle of an even smaller diameter , at a third level down from top surface 12 , such as to hold an espresso cup or a jar from such products as instant coffee . likewise a third concentric square recess of even smaller diameter is also envisioned at a third level down . a preferably diagonally disposed trough 33 , about 0 . 75 inches to 1 . 0 inches in the small dimension and about 7 inches long by about 0 . 25 to 0 . 75 inches deep is intended to hold a pen or pencil or a single piece of flatware such as a butter knife or steak knife . if made smaller than 7 inches in length , the trough 33 could also be disposed parallel to the front wall 13 f of the rim 13 . rear recess 36 is disposed downwardly to the second level and may have chamfered corners for its rectangular shape . this recess is about ⅜ ths inch deep and measures between 8 inches and 10 inches in width parallel to front wall 13 f , and about 3 . 0 to 3 . 5 inches in length . this large well 36 is intended for reception of a land line or cell phone , or several items of flat ware , or even the base of a small plate such as a saucer . it is within the skill of the art to determine what other items one might want to carry in this large well 36 / as mentioned earlier the rim 13 is raised up above the top level 12 . this is done to permit large items , both flat and non flat , to lie on the top surface 12 and be transported without fear of falling off . the raised edge of 13 acts like a guard to retain items on the surface 12 . mounted on the left side wall 16 and on the right side wall — but not visible in fig6 are a pair of hook and loop closure straps , 22 and 24 . these are each retained on one end , at about the midpoint of the sidewall 16 by a one or more screws 25 , as is seen in fig8 . the other end of each strap is matingly engaged to a tab 26 of the opposite gender self adhesive hook and loop material , of which velcro ® is the most well known brand , attached to the front wall 20 . usually the tab is the hook portion and the loop portion of the strap is the end having the loop connections capability . note how the platform 10 of this invention is disposed beneath and forwardly of the pillow 115 such that all items placed on the storage platform 10 can be easily accessed . in fig7 , a top slightly perspective view thereof , the depth 11 which is the difference in elevation between the top of the rim 13 and the upper or top surface 12 can be readily seen . fig8 is a bottom perspective view wherein strap 22 the left strap is seen on the right side of the figure . a series of 4 medium size grip clips 39 a , 39 b , 39 c , and 39 d marketed under the crawford brand by lehigh consumer products llc of macungie , penna and available at ace and other hardware stores , are seen to be attached to the underside of the apparatus 10 . note that the r and l are for the convenience of the reader and set out the side of the unit when viewed from the top . the four clips are mounted such that 39 c the left side forward clip is disposed rearwardly of right front clip 39 a , while the two rear clips 39 b and 39 d are in alignment parallel to the rear wall 21 of the apparatus . the reason for the disposition configuration is that by placing 39 c rearwardly , yet aligned with 39 d to ensure mountability to left tube 101 , the screw used to hold 39 c is able to be driven into an area where there are no troughs or recesses , thus ensuring a good grasping hold for the mounting screw . clips 39 a and 39 b are in a line and evenly spaced apart laterally from 39 c and 39 d to ensure that all 4 clips will fit onto the two parallel tubes 101 a — right and 101 b — left of the frame of the scooter . while 4 clips is preferred , 2 clips , one per tube will work also . it is believed that there are other manufacturers of similar clips in the marketplace . fig9 is a bottom front perspective view of this apparatus . the two straps 24 and 22 are both seen to be removingly attached to front tab 26 on wall 19 b of the rim 13 , such as to be out of the way when not in use over the top of the apparatus , thus ensuring that they do not interfere with forward movement of the scooter should they be left dangling down . fig1 is a bottom right side perspective view showing right strap 24 retained by screw 25 on the side wall 19 b of the rim 13 . the disposition of the clips has already been discussed . note however that the positioning of the clips is not critical , in that they need not be at any specific location along the mounting line that permits mounting on the two frame tubes of the scooter . the only critical dimension is the lateral spacing to ensure the mating engagement with the frame tubes . fig1 is a view similar to fig1 but taken on the opposite side of the apparatus and as such strap 22 the left strap is seen attached by screw 25 . however here , the strap has been moved forwardly to connect to the tab 26 as discussed supra . fig1 - 17 inclusive are all present to illustrate how various types of everyday goods may be carried on this apparatus by the scooter user . in fig1 , a calculator 70 is seen partially disposed in square recess 30 below the rim 13 , while a land line phone is resting neatly within rear trough 36 . whereas in fig1 , a % gallon milk jug is seen resting in the larger square recess 28 on strip 29 , while the water bottle 73 rests in the smaller circular recess 34 below the strip 32 that defines the upper larger circular recess . in fig1 , a small ½ pint of half and half is seen disposed in the smaller square recess 30 with strip 28 which defines the to recesses acting as a retainer barrier . in fig1 a large ( 12 inch ) dinner plate and accompanying flatware 75 are seen resting on top surface 12 and over the edge of the rim 13 . even so disposed , the plate can be safely transported to the dinner table without fear of spillage , should it be filled with food . fig1 shows today &# 39 ; s assorted mail articles resting on the top surface 12 of the apparatus , while in fig1 a conventional ball pen 77 is resting in the deep angled trough 38 . again the land line phone 71 or equally well a cell phone could be , disposed in the elongated rear trough 36 . fig1 is a top plan view of a second embodiment of this apparatus 110 . this embodiment is laid out differently from the first embodiment . here at the forward end of the apparatus 121 on the left is a large square recess 129 and to the right thereof in this top plan view a second smaller square recess is seen , 130 . each of these have only a single level recess , and can be used for carrying the same items discussed for the square recesses of the first embodiment . in the center is a dual level round recess of concentric circles duplication the elements 31 , 32 and 34 but in the 100 series , wherein similar numbers refer to like parts . these concentric circular recesses can be used to transport , jelly jars , water bottles , among other consumables , and even cups or mugs that fit within either of the two recesses . in the rear right hand corner of the platform 110 is a different retainer means not discussed previously , designated 130 . this retainer has a metal or plastic plate 131 disposed over a flexible strap 132 . the plate is screwed down or other wise attached to the surface of the top surface 112 , and the flexible strap of any length is fixedly disposed under the plate as by screws or glue . the portion of the flexible strap 132 not under the plate has an unseen male portion of a snap connector that can releasably matingly engage a fixed female portion of a snap connector disposed at a location on surface 12 where engagement can transpire . being flexible , such as of a polymeric material or fabric , strap 132 can retain all types of small items tightly against the surface 12 . among such items are pill bottles , pens , pencils , the handle of a magnifying glass , a glasses case and many other useful objects . since a rim is optional it is shown only in part on the left front to rear edge of the platform 121 . if present the rim would be similar to rim 13 of the first embodiment and would be raised above the top surface 112 . while quite a few modes of attachment of the main body to the tubes of a knee scooter will be shown , other modes of attachment available in the marketplace are contemplated well . also , since certain brands of prior art scooters only have a single body tube , only 1 set of front and rear mounting means would be required for such scooters . though front retainers as discussed infra may be employed for added stability to prevent pivoting of the device . the main body as in the exploded view of fig1 of the apparatus may be made of various layers of wood , glued , screwed or nailed together , which body would be strong and not easily dislodge . in addition , the body could be made by injection molding of various thermo plastics , as well as by roll molding . reference is made to fig1 , which illustrates how 3 separate layers , “ a ”, “ b ”, & amp ; “ c ”. of wood or hard plastic can be glued or screwed together to create the first embodiment of the invention . the method is equally applicable to the second embodiment . in this method , of construction , there are three layers or segments ; namely a , b , and c , which are shown apart prior to gluing or screwing of one to the other with b in between a & amp ; c . the assembly by screwing is deemed conventional with a set of screws passing from beneath segment c through b and into a , or in reverse , from a , through b into c ; or a set of countersunk screws going through from the bottom of b segment into a segment and a second set of screws going from the bottom of b into segment a . segment a is comprised of upper platform 50 with its cutouts and trough as described supra , connected to the rim here designated 51 . this rim is the same rim as designated 13 in other figures . platform 50 may be abutted to the surface of rim 50 , or a slot , 53 , may be routed out such as is shown in rim section 52 in the same figure , into which slot 53 , segment 50 may be inset for greater strength . of course it is to be recognized that for ease and convenience of the reader and illustration , two sections of the rim 51 are not shown attached . thus the renumbering of the rim . segment 52 is seen to be a platform with 3 openings there through , segment b is sized the same as segment a if segment a is butt fitted , if not it is slightly smaller so as be butt fitted within the confines of the rim 51 . of course the sections of the rim not shown in a can be added after a and b are fastened together . platform c which is segment 53 can also be sized to fit within the confines of the rim , or the rim can only retain platforms a and b with segment c overlying both platform b and the underside of the rim . thus there are various permutations of how to assemble the invention of this application , all of which are deemed conventional and within the scope of this invention . the main body could also be made by molding polyurethane elastomer or some other filled polymer into the desired shape in one piece or the rim could be attached to a sandwich of platforms a , b , and c , as may prove most cost effective in manufacture . while the spring clips mentioned above are the primary mode of attachment to the tubes of the commercial knee scooter , other modes of attachment are also contemplated . fig2 is an exploded perspective view showing two segments , “ b ” & amp ; “ c ” of the main body of the apparatus and illustrates the use of boltable plates to act as clamp devices mounted to the under side of the main body 15 . in the version of embodiment # 1 shown here , the upper layer as seen in fig2 , is not shown for ease of understanding . also only 1 such clamping means 49 is shown . clamping means 49 consists of passing through segment “ c ” a pair of spaced flathead machine screws 55 that are placed through screw apertures 56 , prior to attachment of segment b to segment c , which screws 55 when placed through apertures 57 a in plate 57 and then tightened rest against the tubes 101 a and 101 b by wing nuts 58 tightly retain the platform to the two tubes . it should also be noted that it is contemplated that machine screws 55 could be placed through a pre - made sandwich of segments ‘ a ”, “ b ” & amp ; “ c ’ at suitable locations as well . use of this clamping means 49 instead of the spring clips will provide a more permanent , yet removable , mounting of the apparatus to the two parallel tubes 101 a & amp ; b . indeed , the clamping means shown in fig2 , can be used alone singly with one pair of grip clips — not seen in fig2 , or two spaced clamping means 49 may be employed or clamping means 49 may be employed a supplement to the two pairs of grip clips 39 . fig2 is a rear view showing the clamp means 49 mounted to a two tube knee scooter &# 39 ; s tubes . here however , an optional sheet of rubber 59 is shown glued or other wise secured to the underside of segment “ c ” and interposed against the two tubes . the rubber sheet may be 1 / 16 to ⅛th inch thick and serves to add friction to help prevent movement of the device relative to the tubes . fig2 is related to fig2 but shows a prior art single tube scooter &# 39 ; s tube retained in like manner as in fig2 . referring back to fig3 , element 109 is a lower steering tube , and element 108 is an upright retention means , which when loosened , allows steering column 105 to tilt downwardly toward the knee pad 115 for compact storage in a vehicle . turning now to fig2 and 24 , two modes of preventing pivoting of the mounted device , particularly on single tube scooters are shown . in both of these figures all but one of the grip clips have been omitted for ease of illustration as have two straps 22 , 24 . in fig2 , a first anti - rotational means , namely a broom clip such as one sold under the crawford brand by leheigh consumer products llc or any other conventional broom clip 61 , can be attached as by screws 62 , through suitable bores to the front wall 20 of device 10 to snap around lower steering tube , so as to still permit the tube to rotate as in some model scooters , while providing an anti - torque means to prevent pivoting of the removably mounted device . fig2 illustrates another anti - torque means , 64 . this second anti - torque means employs a bored block of metal or plastic 65 which is mounted by screws 65 to the bottom of device 10 and which has a threaded u - bolt 66 passing through the bores unseen . this u - bolt may be loosely tightened around lower steering tube 109 — per fig3 — by wing nuts 67 to provide an anti rotational force on device 10 to keep it in a true horizontal plane . either of these anti - rotational means can be employed with either the clamping mode of attachment or the grip clip mode of attachment to both single and double tube knee scooters . when applicant jacobs had a fractured ankle he used the two tube scooter made by essential medical supply as illustrated in the drawings of this application . drive medical of port washington n . y . sells a prior art knees cooter , model 790 that has two arcuate tubes . see fig2 . therefore to permit either embodiment of the platform of this invention to be employed with that scooter it is necessary to interpose a suitably sized sizing block , 41 between the underside of the device and the front set of grip clips . see fig1 . sizing block 41 would be screwed or otherwise attached to the underside of the platform and the grip clips would be mounted thereon . it is within the skill of the art to determine the dimensions of the sizing block 41 for this or any other arcuate tube knee scooter . it is seen that we have a devised a series of storage platforms that can be mounted both removably and semi - permanently upon knee scooters ( knee walkers ) made by various manufacturers . a variety of mount means have been set forth such that the devices of this invention will appeal to the users of a variety of the knee scooters that are available in the marketplace today . while a specific brand of gripping clips has been set forth , it is to be understood that any similar arcuate shaped metal or plastic clip that can releasably grip metal tubing can be employed .

an apparatus that mounts in a horizontal disposition on the frame member of a knee scooter for the transportation of goods between locations . the apparatus is a generally rectangular main body member having recesses in the top surface thereof of various shapes for the lodging of articles in the recesses for the retention thereof during the operation of the knee scooter . straps are provided for the retention of articles that are not disposed in the recesses , but instead will rest on the top surface of the apparatus , such as books or a newspaper for carrying same from place # 1 to place # 2 . the apparatus is removably mounted to the frame member of the scooter by medium size spring type grip clips or a clamp formed form a bar held by machine screws . anti - torque attachments mountable facing forward are also shown .

a preferred embodiment of the invention is shown in longitudinal cross - section in fig1 . fig1 shows a fishing rod holder 10 mounted to a structural panel 12 , such as a gunwhale , of a marine vessel . fishing rod holder 10 comprises a hollow , cylindrical tube 14 having an open upper end , or mouth 15 , and a lower end 18 . tube 14 may be formed of plastic or any suitable material but is preferably formed of metal of a type resistant to corrosion or plated or coated to be resistant to corrosion such as stainless steel or chrome plated steel . optionally , lower end 18 of tube 14 may include a drain opening 27 through which water may freely drain from the interior of rod holder 10 . if desired , drain opening 27 may include internal pipe threads for receiving a nipple to which a length of plastic tubing ( not shown ) may optionally be connected in order to direct drain water to a desired drain location . in order to protect the surface finish of fishing rods as well as to provide an attractive internal appearance , the interior of tube 14 is optionally provided with a tubular liner 31 of plastic or other suitable material sized to fit snugly but removably within the interior of tube 14 as shown in fig1 . the open upper end 15 of hollow tube 14 is surrounded by an annular mounting bezel 35 which may suitably be formed of plastic or any desired material but which is preferably formed of aluminum , stainless steel or other corrosion resistant material . mounting bezel 35 and hollow tube 14 are inseparable from one another and comprise a unitary member . hollow tube 14 and said mounting bezel 13 may be inseparably connected to one another by a weld . bezel 35 includes an upper surface 39 which may be provided with a desired surface finish and which , in accordance with the invention and as illustrated in fig1 and 3 , shows no visible signs of any fasteners when rod holder 10 is installed . the surface finish of the upper surface 39 of the mounting surface is preferably one which exhibits an aesthetically pleasing appearance such as a brightly polished , or brushed metal finish or any suitable clear or colored surface coating such as an anodized finish , a powder - coated finish or the like . to this end , according to one preferred embodiment of the invention , the lower surface 42 of mounting bezel 35 is provided with at least one , and preferably several , blind holes 40 for receiving a fastener 44 , such as a cap screw , used for securing fishing rod holder 10 to panel 12 . if mounting bezel 35 is sufficiently thick and strong , blind holes 40 may simply be formed entirely within the main portion of the body of mounting bezel 35 . otherwise , if additional strength is needed , mounting bezel 35 can be provided with one or more hollow or partially hollow projections or bosses 46 through which pass at least a portion of the depth of blind holes 40 as shown in fig1 . blind holes 40 may suitably be provided with internal threads in order to receive a correspondingly threaded fastener 44 . alternatively , fastener 44 may be of a self - tapping or self - threading type so that blind holes 40 need not be internally pre - threaded . in the embodiment shown in fig1 , tube 14 happens to project from the underside 42 of mounting bezel 35 at an angle of sixty degrees ( 60 °) but the angle is not critical to the invention . other angles including without limitation ninety degree ( 90 ), forty - five degree ( 45 ), and thirty degree ( 30 ), or other angles are of course within the scope of the present invention . to provide enhanced structural integrity , rod holder 10 is preferably mounted with the aid of an optional backing plate 50 which may suitably be formed of a flat stock material having a central opening 54 through which tube 14 may freely pass . backing plate 50 is particularly useful in cases where the panel 12 in which rod holder 10 is mounted is thin or lacks structural integrity . backing plate 50 is provided with a series of openings 55 through which bodies , but not heads , of fasteners 44 may pass . preferably , openings 55 are elongated and backing plate 50 has an open ended shape , such as the open - ended “ u ” shape shown in fig4 . the elongation of fastener openings 55 and the open end 59 of opening 54 within backing plate 50 allow an angled rod holder 10 to be installed in panels 12 having a range of thicknesses and allow a single configuration of backing plate 50 to accommodate a variety of rod holders whose tubes 14 depend at a differing angle from their mounting bezel 35 . as shown in fig1 , the bottom portion of tube 14 may contain a support member in the form of a disc shaped base 69 , the circumferential surface of which is not flush with tube 14 both in order to account for the insertion of a tubular liner 31 and to allow the space for disc shaped base 69 to rotate about its central axis once tubular liner 31 is inserted . as fig1 shows , a threaded shaft 71 engages disc shaped base 69 by way of an internally threaded blind hole 73 such that a rod engaging member 72 in the form of a pin 72 ′, extends transversely across a portion of the diameter of the upper surface 88 of disc shaped base 69 . rod engaging member 72 / 72 ′ is mechanically coupled to an adjustable brake 83 . a lower surface 87 of disc shaped base 69 rests atop a first plastic washer 70 such that the lower surface 87 of disc shaped base 69 does not directly touch the bottom portion of tube 14 . the top surface of a second plastic washer 74 abuts the exterior underside of tube 14 and the underside of second plastic washer 74 abuts the top surface of a stainless steel washer 75 . threaded shaft 71 passes through stainless steel washer 75 , second plastic washer 74 , the bottom of tube 14 and first plastic washer 70 and is securely threaded into an internally threaded blind hole 73 formed in the underside of disc shaped base 69 . a hex nut of stainless steel 76 is affixed to the threaded shaft of stainless steel 71 and the top surface of hex nut of stainless steel 76 makes contact with the underside of stainless steel washer 75 . as shown in fig1 and 5 , the bottom portion of tube 14 contains a support member in the form of a disc shaped base 69 having an exterior wall 81 which projects upwardly in fig1 to form a cup 79 . as fig1 shows , exterior wall 81 abuts an interior surface 32 of tubular liner 31 , but preferably not such as to significantly impede the rotation of cup 79 . in this embodiment , rod engaging member 72 takes the form of pin 72 ′ whose ends are attached to the cup 79 by way of rivets ( not shown ). pin 72 ′ extends across the diameter of the cup 79 . thus , the portion of pin 72 ′ not affixed to cup 79 , a freestanding portion spanning the open inside diameter of cup 79 , can engage one of the aforementioned grooves in the butt of a fishing rod . threaded shaft 71 engages cup 79 by way of internally threaded blind hole 73 and passes through , in descending order , first plastic washer 70 , the bottom surface of tube 14 , second plastic washer 74 , stainless steel washer 75 , and , finally , a hex nut of stainless steel 76 . fig5 shows a top view of the swivel mechanism along line 5 - 5 in fig1 . rod holder 10 is installed by drilling , or otherwise forming a hole through a gunwhale , or other panel 12 of a marine vessel , of sufficient diameter to accommodate tube 14 and a mounting bezel 35 . smaller holes for accommodating fasteners 44 are then drilled , or otherwise formed , in locations corresponding to the locations of blind holes 40 of mounting bezel 35 . the lower end 18 of rod holder 10 is then passed through hole 55 and rod holder 10 is lowered until the underside 42 of mounting bezel 35 rests flush on the upper surface of panel 12 . fasteners 44 are then passed upwardly through backing plate 12 and panel 12 and are fastened inside blind holes 40 to securely fasten rod holder 10 to vessel panel 12 . the fasteners 44 are not visible on an upper surface 39 of mounting bezel 35 and thus neither detract from the finished appearance of the upper surface 39 of mounting bezel 35 nor accumulate contaminants or moisture capable of fostering deterioration or corrosion of surface 39 . in use , the butt end of a fishing rod may be inserted into the tube 14 of fishing rod holder 10 to support the rod for storage or while the rod is in use with the vessel either stationary or in motion , as when drifting or trolling a lure or other bait . the grooves in the butt of the rod engage rod engaging member in the form of a pin 72 ′. furthermore , in each embodiment described herein , hex nut 76 may be tightened or loosened in relationship to stainless steel washer 75 on threaded shaft 71 in order to adjust the resistance of rod engaging member 72 or rod engaging member in the form of a pin 72 ′ to pull in a given direction . the potential resistance of rod engaging member 72 ′ to pivoting motion thus ranges from zero to substantially locked against pivoting . threaded shaft of stainless steel 71 , hex nut of stainless steel 76 , stainless steel washer 75 , second plastic washer 74 , the bottom wall 19 of tube 14 , and first stainless steel washer 70 comprise an adjustable brake 83 which is mechanically coupled to rod engaging member 72 ′ and which may be set or adjusted by tightening or loosening hex nut 71 to set or adjust the resistance to pivoting of the rod . brake 83 is substantially infinitely adjustable over a range which extends from substantially zero resistance to rotation to a resistance to rotation at which said rod engaging member is substantially locked against rotation . while the invention has been described with reference to preferred embodiments , it should be understood by those skilled in the art that various changes may be made and equivalents substituted for elements thereof without departing from the scope of the invention . in addition , many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof . therefore , it is intended that the invention not be limited to the particular embodiments disclosed as the best mode contemplated for carrying out this invention , but that the invention will include all embodiments falling within the scope of the appended claims and all legal equivalents .

this invention is directed to a fishing rod holder having a generally annular mounting bezel which generally surrounds the mouth of a tube for receiving the butt of a fishing rod . the underside of the mounting bezel includes at least one blind hole or projecting mounting stud for receiving a fastener for mounting the rod holder without penetrating the exposed surface of the mounting bezel , providing an aesthetically pleasing appearance . a rod engaging member or pin engages grooves in the butt of a rod , allowing it to swivel . the amount of resistance of the rod engaging member or pin to swivel motion can be adjusted .

as shown in fig1 , the point of impact has a first surface ( 10 ), a second surface ( 20 ) and attachment means ( 30 ). a first surface ( 10 ) has a static or ionized charge such that pet hair and other debris will be attracted and will remain in contact with first surface ( 10 ) if a pet should rub against first surface ( 10 ) or get up and push off from first surface ( 10 ). thus , a cat lying down on first surface ( 10 ) would drop cat hair and other debris , which would remain on first surface ( 10 ) because of first surface ( 10 )&# 39 ; s ionic static properties . the ionic and static properties of first surface ( 10 ) would be as conventionally known , such that first surface ( 10 ) could be made of any conventionally known material that has static cling or an ionized attraction . second surface ( 20 ) is attached to the back side of first surface ( 10 ) via any conventional means . second surface ( 20 ) needs to be a moisture barrier of any conventional substance because it is not enough to prevent pet hair and other debris from penetrating the present invention , but moreover , the present invention must prevent moisture from reaching a chair or other surface protected by the present invention . for example , when a pet lies in a pet bed and sleeps for an hour or more , the moisture and heat that is created from the pet needs to be prevented from reaching the actual pet bed that is being covered by the present invention . should sweat and other moisture reach the pet bed covered by the present invention , undesirable smells would result in the pet bed becoming dirty and requiring cleaning — and the present invention prevents such from occurring . moreover , second surface ( 20 ), being a moisture barrier , would be important when a dog is taken to a lake or to the beach . the dog typically will climb into the back of a car or a truck , and the moisture that will drip off of the dog needs to be contained . the present invention would contain the drippings from the dog because the present invention would be laid out in the back of the car or laid out in the back of the truck , so that as the dog climbs in , any water or sweat or a combination thereof , would not drip into the car and cause a musty , stale odor in the car long after the dog has departed , but the present invention would prevent the moisture and sweat from reaching any of the surfaces underneath the dog . an intermediate layer ( 25 ) is preferably provide in the present invention . intermediate layer ( 25 ) is made of any conventionally absorbent material , so that when moisture from the pet comes into contact with the present invention , intermediate layer ( 25 ) will try to absorb the moisture , so that if a lot of moisture is dripping from the pet , such as dripping from a dog that has just been in the water at the lake , rather than just prevent the water from coming into contact with the car , the present invention will actually absorb it as well . thus , in operation , should a dog get into the back of a car that has been equipped with the present invention , the dog would stand or lie on first surface ( 10 ), which would not only attract loose dog hair and other debris that might be on the dog , but water dripping from the dog would pass through first surface ( 10 ), be absorbed by intermediate surface ( 25 ) and then be prevented from seeping through the present invention by second surface ( 20 ). because the present invention is intended to be fully disposable , it would not matter that pet hair and other debris , as well as moisture , sweat , and any other liquid material is retained in the present invention . the present invention is also preferably biodegradable , such that all materials used in the present invention are inexpensive , so that they are disposable , but are biodegradable . the present invention can be secured to any surface . preferably , the present invention has attachment means ( 30 ), which are conventional hook and loop type fasteners of various shapes and sizes . so , for example , the present invention via attachment means ( 30 ), could be secured to a loveseat in the living room , or it could be secured to a blanket on top of a bed . similarly though , the present invention could use any conventional means of attachment so that it can be secured and prevented from moving when a pet gets up or runs across it . for example , conventional drawstring ties , elastic bands or adhesive surfaces could be provided as part of the present invention , much like attachment means ( 30 ), so that the present invention remains in one spot when the pet is on top of it . the attachment means would need to be temporary though , because while the present invention needs to remain intact and in position during use , a person would want to be able to simply and quickly remove the present invention , so that the protected surface underneath the present invention could be quickly shown or viewed or used , if necessary . the present invention is made in a variety of colors , as well as a relatively transparent or translucent color . it is contemplated that while some users of the present invention would want to show the true color of a blanket or furniture or other item being protected under the present invention , other users of the present invention might want to change the color of the actual surface being protected . for example , one user might want to preserve the color and the look of the tablecloth on the kitchen table , and knowing that a cat tends to sit on top of a kitchen table , or lie on top of the kitchen table , the user would use the present invention made of materials that are relatively transparent and / or translucent , so that you can actually see through the present invention and appreciate the color or pattern of the tablecloth . on the other hand , other users of the present invention might desire to completely cover a pet bed that is being protected underneath the present invention . in such case , the user might want to provide a green pet bed or a red pet bed or a blue pet bed , depending on the time of day , the season or a holiday . thus , for example , the present invention could be used to make a bed look appropriate for the 4 th of july , where the pet bed could be colored red or white or blue , and even more particularly , first surface ( 10 ) of the present invention would have a pattern , such as stars and stripes . it should be understood that the first surface ( 10 ) could have conventional adhesive properties that augment and / or replace the static or ionized charge aforementioned .

a cover that attracts pet hair and other debris , while covering a table , chair , pet bed , or other item . the cover prevents moisture from penetrating completely through it , as it has a second surface to ensure that whatever it covers remains dry . conventional means of attachment ensures that the present invention , which is biodegradable , can be held securely during use but can be easily attached and removed when desired .

the hockey skill improvement device of this invention is indicated generally at 10 in fig1 . the device is here shown in the shape of an elongated rectangle and this is the shape it is currently contemplated will be most useful , but variations therefrom can undoubtedly be made within the spirit and scope of the invention . the device is equally adaptable for right handed or left handed stick handlers in the position of fig1 it being 5 understood that the right end of the device as viewed in fig1 is the start or at rest position which is assumed prior to contact of the puck means by a hockey stick . the device , in this embodiment , has a framework consisting of top 11 , front end 12 , left side 13 , right side 14 ( see fig2 - 4 ) and rear end 15 ( see fig2 - 4 ). the top , front , rear and sides form a support structure for a striker puck to be hereinafter described . an elongated slot 16 positioned parallel to the sides 12 and 14 and extending much of the length of the top is seen in its entirety in fig1 the slot consisting of left side 17 and right side 18 as viewed from the rear end ( see fig4 ). a striker puck , which may be , and preferably is , a modified regulation hockey puck , is indicated generally at 20 . the puck is rotatably secured to a puck mounting assembly which , when struck by a hockey stick , slides along slot 16 and then automatically returns to the at rest or starting position of fig1 as will be described hereinafter . a plurality of indicia are indicated at 21 alongside slot 16 whose purpose is to disclose the power applied to the striker puck by the user according to a convenient scale . here a series of decade members have been shown but it will be understood that letters or any other readily understandable indicia , such as logos or animals ( i . e . : chicken to elephant ) could be used . non - skid , slightly compressible support buttons are indicated at 22 , the compressibility of the buttons 22 serving to help maintain the top 11 in a level horizontal plane when the device is placed on a slightly irregular surface . referring now to fig2 and 3 particularly the puck mounting assembly is indicated generally at 24 . puck mounting assembly 24 includes a slider , indicated generally at 25 , 5 which is held to the striker puck 20 by any suitable fastener , here a carriage bolt 26 . the top center of striker puck 20 is recessed , as at 27 ( see fig4 ), to a depth sufficient to receive the head 28 and a washer 29 so that the head 28 projects only very slightly , if any , above the top surface of striker puck 20 . a nut 30 which is snugged up against the bottom surface of slider 25 secures the striker puck 20 to the slider . a clearance between the bores in the striker puck 20 and slider 25 are provided so that precise manufacturing tolerances are not required between the interfitting parts and the striker puck retains more of the “ feel ” of a regulation hockey puck . slider 25 is maintained in the position of fig1 between strikings by an extensible and retractable return spring member indicated at 32 . the front end of spring member 32 is secured by any suitable means to any one of , here five , anchors 33 , 34 , 35 , 36 or 37 which project inwardly from the inside surface of left wall 13 ( see fig2 ). here conventional eye screws have been shown with one eye screw located in vertical relationship with each of indicia 10 , 20 , 30 , 40 and 50 . the other end of spring member 32 passes around a rotatable pulley 40 , see fig2 and 3 , and its rear end is secured by any suitable means to an anchor 41 , here a conventional shook , ( see fig2 and 3 ). from fig4 particularly it will be noted that nut 30 maintains anchor 41 fixed with respect to slider 25 . pulley 40 rotates , preferably freely , around mounting pin 42 which projects downwardly from an inverted generally u - shaped mounting strap 43 . the outwardly extending feet of the mounting strap are secured to a pair of mounting blocks 46 , 47 which extend between the inside surfaces of walls 13 and 14 . obviously a single piece may take the place of the two mounting blocks 46 , 47 . a pair of generally l - shaped rails which are secured to the underside of top 11 are indicated generally at 49 , 50 , see particularly fig4 . the horizontal bar of each rail faces toward the center axis 51 ( see fig1 ), to form indented elongated slots 52 , 53 , one on either side of the central axis and parallel to it . the slots 52 , 53 receive left and right wings 54 and 55 which extend outwardly from the mid - portion of slider 25 into sliding relationship with slots 52 , 53 , respectively . spring member 32 is formed from any material which has the ability to extend under impetus of a striking blow by a hockey stick against striker puck 20 , and retract when the momentum provided by the hockey stick is overcome by the increasing return tension inherent in the spring member 32 . the return travel of the striker puck 20 will of course be limited when the slider 25 butts against the rear end 56 of slot 16 . preferably the spring member has the characteristics with respect to extension and retraction of rubber . although many suitable cross sections may be employed in the spring member , the simple round tube is illustrated at 57 in fig4 has been found to give excellent results . the use and operation of the invention is believed to be apparent from the foregoing description . starting from the position of fig1 a user strikes the striker puck 20 with his or her hockey stick swinging in a direction moving toward the highest numbered indicia on the top 11 of the device , here the numeral “ 50 ”. the momentum imparted to the puck 20 by the hockey stick will keep the puck moving toward indicia “ 50 ” until the increasing tension on the slider 25 which is exerted in the opposite direction by the extension of spring member 32 equals the momentum of the puck 20 at which time forward movement of the puck will stop for an instant and then the slider will reverse direction under the pull or tension of the contracting spring member 32 to complete a cycle . as a hockey user acquires increased skill and strength , the tension in spring member 32 may be increased by securing the forward end of spring member 32 to anchors successively more remote from anchor 33 , thereby requiring more striking power by the user to move the striker puck the same distance from the rear end 56 of slot 16 . in addition , the device provides physiological memory training at all skill levels of the user which is largely derivable from the tension of spring member 32 . thus , as the user hits striker puck 20 repeatedly both his mind and his body are physiologically conditioned to expect resistance to the impact of his stick against the striker puck , as a consequence , when the user puts on his / her skates and takes to the ice , the loose puck on the ice will be struck with more power and emphasis due to the prior conditioning of the user &# 39 ; s mind and body to expect resistance to contact with the stick on ice shooting skill is thereby increased to a markedly higher level , or at least the power aspect of it , than can be attributed to known devices which lack the resistance , and increasing resistance , characteristics of the device of this invention . it is not possible to specify an exact number of strikes which will result in the desired physiological memory training of a hockey participant because the factors of age , coordination , physical strength and training susceptibility will vary from individual to individual . indeed , such factors as alertness and fatigue , and the length of time lapse between the last practice strike of the puck and the first on - ice swing will all enter into the equation . suffice it to say that it is always desirable to strike the puck off - ice a sufficient number of times starting from an at rest position to physiologically condition the mind and body of the user to the existence of a resistance to a striking of the puck prior to the first on - ice strike of the puck . the device may be of any convenient length , though about five feet has been found to be entirely satisfactory , and it need be only about 2 ″ in height . as a result the device may be used in a very small space , such as the open floor space in a conventional sized bedroom , easily transported and its position adjusted by young hockey players . the weight of the device will vary with the type of materials used and their thickness . preferably the top 11 , slider 25 and the rails 49 , 50 are formed from plastic , or at least include a plastic surface , but the construction details may vary widely . although it is intended that the above description be taken as a representation of the invention in a broad sense along with a description of a specific embodiment , it will be understood that the scope of the invention should not be limited by the foregoing description but rather solely by the appended claims when interpreted in view of the relevant prior art .

a hockey practice device which provides physiological memory training to the user includes a low , short open bottom housing having a variable resistance striker puck which slides in a slot in the top of the housing , the puck being secured to a slider beneath the top which is secured to a variable tension extensible and retractable spring member having one end fixed to the housing and the other end to the slider , the entire assembly being only about five feet long or less so as to be usable indoors or outdoors in a minimal space .

fig3 shows an implantable port device for establishing direct or indirect access to a blood vessel of a patient . the device is implanted beneath the patient &# 39 ; s skin surface 325 and includes a tapered seat ( fig4 - 5 ) configured to receive a tip of an access tube ( i . e . needle 301 or trocar 302 ), the seat has a proximal portion , a distal portion , and a conical surface disposed between the proximal portion and the distal portion . the access tube ( i . e . needle 301 or trocar 302 ) is inserted in the center of the flat surface 363 and into the tapered seat . the flat surface 363 is generally parallel with the skin surface when subcutaneously implanted . the device provides a low profile to facilitate relatively shallow subcutaneous placement . unlike the domed geometry of some prior art devices such as fig1 , the flat ( plateau - like ) surface eases skin tension to prevent stretching and / or tearing of the skin . insertion of the access tube into the tapered seat opens the conduit to physiological pressure and continuous blood flow through the conduit . an opening 305 to the proximal portion is shown in fig3 . a guide 307 is configured to engage the tip of the access tube and to assist in directing the tip of the access tube toward the seat opening 305 . the interface surface is configured to engage a tubular structure 631 ( e . g . a native blood vessel , a vascular access catheter or a synthetic tube grafted to a blood vessel ). the interface surface has an aperture in fluid communication with the distal end of the seat . the conical surface includes a taper angle having a value within a range from about 0 . 5 degrees to about 4 . 0 degrees ( fig4 - 5 ). the proximal portion of the seat is configured to receive the tip of the access tube therethrough . in this embodiment , the device includes a hinge on one side and an opening on the opposite site so that the device is able to open in a manner similar to the way a clam shell opens and closes to surround the outside of the blood vessel or synthetic tube in the closed position as shown in fig3 . a latch , clip , snap or other similar securing apparatus 304 located opposite the hinge may be used to attach the device around the outside of the vessel wall . extrinsic pressure maintains hemostasis . the device shown in fig3 does not require a valve but may optionally include a valve mechanism , such as a silicon valve 510 as shown in fig5 for example . if no valve is present , the device is sealed at the conclusion of treatment using the healing characteristics of the vessel wall . regardless of the presence or absence of the optional valve mechanism , the port devices shown in fig3 and 5 fit snugly around the external diameter of the native vessel or synthetic tube to compress the vessel and provide extrinsic pressure to maintain hemostasis . the vessel wall tension acts as a tamponade to close or block the wound left from the access tube after the tube is withdrawn . the tamponade promotes natural blood clotting and encourages intrinsic coagulation at the puncture site on the skin where the access tube penetrated . this prevents bleeding and promotes healing . alternatively , the vessel may be secured as shown in fig5 . in this embodiment , the device 564 has a stabilizer base 564 b reversibly attached to the device to increase the footprint of the device when implanted . two or more clips 508 a , 508 b may be used to fasten the top portion of the device 564 a to the bottom stabilizer base 564 b to securely fasten the device around a blood vessel 531 . the bottom stabilizer base 564 b may include one or more suture rings 509 to attach the subcutaneously implanted device in the patient &# 39 ; s body . by fastening the device in this manner , the flat surface 563 of the device is maintained in an orientation essentially parallel with the skin when subcutaneously implanted . attaching the device with sutures may also prevent movement , migration , or wobble when the access tube is inserted into the device . fig4 a and 4b illustrate the taper of the tapered seat . the shape of the access tube and the tapered seat allow for a wide range of flow rates . the opening of the tapered seat 405 has a proximal portion 401 that is wider than the distal portion 402 . the taper angle 403 of the conical surface between the proximal 401 and distal 402 portions is about 0 . 5 degrees to 4 . 0 degrees . preferably , the taper angle 403 has a value within a range from about 2 . 5 degrees to about 3 . 5 degrees . these ranges can conveniently accommodate anything from a parallel - walled needle 421 b with a very high gripping ceiling area fit to a leur tip connector which is about 4 degrees . most preferably , the taper angle 403 is 3 . 3 degrees from the proximal 401 to the distal 402 portion . the distance 404 between the proximal portion 401 and the distal portion 402 is between about 1 . 0 mm and 5 . 0 mm . preferably , the distance between the proximal 401 and distal 402 portions is between about 1 . 5 mm and 2 . 5 mm as this has been found to provide maximum dependability and functionality while minimizing the height of the device . the tapered seat creates a mismatch fit with a diameter of an access tube when tapered seat receives the access tube ( fig4 b ). the tapered seat creates a mismatch fit with a diameter of the access tube when the tapered seat receives the access tube . the mismatch fit is particularly conducive to performing procedures requiring relatively high pressure flow rates ( e . g . flow rates greater than or above normal physiologic pressures ) including the injection of contrast dyes or performing dialysis procedures , for example . one advantage of the larger taper angle is that it allows a health care professional to begin to layer ( i . e . flare ) the needle more quickly . the flow rates received through the access tube depend ( at least ) on its internal liminal diameter or radius . optimum flow rates are generally realized with a steeper taper . unlike the connections between an iv tube and a catheter or needle , a matching fit between an access tube ( i . e . needle , trocar , removable cannula ) and a port is novel ( fig4 a ). creating a match fit ( fig4 a ) between the tapered seat and a diameter of the access tube is particularly conducive to performing procedures requiring relatively low pressure flow rates ( e . g . flow rates less than or below normal physiologic pressures ) including the administration of intravenous fluids , for example . a matching or mismatching fit could be accomplished using an adaptor ; however , changing the outside diameter of the access tube 421 a , 421 b placed into the taper seat would accomplish similar goals . it is contemplated that the access tube may be disposable ( i . e . single use ). fig6 shows an embodiment of a single molded graft - port device 660 implanted below the skin surface 625 . a connecting line 623 is attached to an access tube 621 ( i . e . needle or trocar ), with a swivel mechanism 624 . the swivel mechanism 624 prevents the connecting line 623 from kinking or binding when the patient moves or otherwise changes position . in addition to allowing patient mobility , the swivel also prevents accidental decannulation . the access tube 621 is inserted in the center of the flat surface 663 a and into the tapered seat . the flat surface 663 a is generally parallel with the skin surface when subcutaneously implanted . insertion of the access tube 621 into the tapered seat opens the conduit to physiological pressure and continuous blood flow through the conduit . the port 664 includes a nozzle 670 with an outlet opening 665 which is attached to a catheter 620 . the catheter may contain pores 668 and / or a central opening 669 . the catheter 620 interfaces with the blood vessel 631 or other body space filled with ( or potentially filled with ) a fluid ( i . e . blood , urine , cerebral - spinal fluid ). it is contemplated that the device can be used for various therapies beyond hemodialysis with little or no modification . some other therapeutic uses may include peritoneal dialysis , urinary tract drainage , pleural effusion and cerebral - spinal fluid drainage . the port may be used to administer insulin or even inflate a penile prosthetic , for example . fig7 a is an exploded view of the needle 701 which fits inside an opening 703 in the trocar 702 . the tip 702 a of the trocar is non - coring and non - lacerating for added patient comfort . the trocar 702 fits inside the tapered seat of the port 664 . the nozzle 770 connects to the catheter ( not shown ). an area 706 provides a space for excursion of the optional valve assembly . the port may be configured to attach a stabilizer wire at grooves 765 a , 765 b on each side of the port 764 . fig7 b show a top view of the port body 764 including the opening on the tapered seat 705 and guide 707 . the guide 707 may include a ridge elevated from the flat surface 763 a to guide the access tube into the opening 705 after the access tube has pierced the skin . the ridge may be rounded or flat on top . other elevated configurations are contemplated to catch the tip of the access tube in the vicinity of the opening 705 and guide the access tube toward the opening 705 along the intersection of the flat surface and beginning of the ridge elevation . alternatively , the device 764 ( or at least the flat surface 763 a ) may include a transparent material and the guide may include led lights 708 a , 708 b ( alone or in combination with the ridge embodiment ) and a receiver coil for receiving an electrical current . the lights may be arranged in many configurations including a ring arrangement , a linear 708 a arrangement ( pointing toward the opening 705 ) or a triangular 70 b arrangement ( surrounding the opening 705 ), for example . the led lights may include ruby , sapphire or other durable , radiant material visible through the skin of the patient and the lights may be arranged in a ring configuration raised above the flat surface 763 a to engage the access needle , for example . the lights are configured to illuminate when an electromagnetic induction chip 709 is placed external to the patient and substantially above the subcutaneously implanted device . the induction chip producing a voltage in the receiver coil , the voltage powering the lights so that a location of the subcutaneously implanted device is visually revealed to the health care professional . fig7 c a bottom view of the port device 764 according to an embodiment of the invention including the underside 763 b of the flat surface 763 a . fig7 d is an end view showing the area 706 that provides a space for excursion of the optional valve assembly . fig7 d is an end view of the area 706 that provides a space for excursion of the optional pressure competent valve assembly . the opposite end of the device 764 from fig . d is shown in fig7 e . fig7 e includes the catheter attachment area ( i . e . nozzle ) 770 and outlet opening 765 which is attached to a catheter ( not shown ). an optional stabilizer wire may be attached at grooves 765 a , 765 b on each side of the port 764 . fig7 f is a side view of the port device 764 an alternative manufacturing method to the single molded port 664 shown in fig6 , is a two piece press - fit configuration depecited in port 764 shown in fig7 c - 7f and catheter connection 800 shown in fig8 . the cyndrical end 801 of the catheter connection 800 can be inserted into the body 764 of the device at outlet opening 765 shown in fig7 f . machining technology ensures a snug fit between the port 764 and catheter connection 800 . when inserted , the nozzle 870 and nozzle opening 865 protrude from the outlet opening 765 to facilitate connecting the nozzle 870 to a catheter . the press - fit configuration may allow better fit with the ball seating , for example . fig9 a - 9i are examples of ridge and / or light pattern guide configurations according to certain embodiments of the invention as viewed from the top of the flat surface 963 a . the guide 907 a may extend from the centrally - located tapered seat opening 905 to the edge 963 c of the flat surface 963 a ( as shown in fig9 a ) or the guide 907 b may extend from the opening 905 to a distance 901 short of reaching the edged 963 c of the flat surface 963 a ( as shown in fig9 f ), for example . the guide configurations may include a combination of distances from the opening 905 as depicted in fig9 b and 9g , for example . the guide ( s ) can be straight ( i . e . fig9 a , 9b , ( e , 9 f , 9 g , and 9 i ) or the guide may be curved ( fig9 c , 9d and 9h ). fig9 i is a preferred embodiment with is also generally shown in fig1 c , 16d , 17c , 17d also . in some embodiments , the guide forms a target - like shape where the lights and / or ridges do not extend from the tapered seat opening 905 as shown in fig9 d and 9e , for example . of course , many other configurations are possible and the present invention is not limited to the examples provided herewith . one purpose of the guide is to assist the health care professional in accessing the opening to the tapered seat . the device can be palpated when it is implanted just under the skin . while it is possible to pierce the skin with the access tube and directly insert it into the tapered seat , a more likely scenario is to palpate the subcutaneously implanted device and feel the circular edges of the flat surface ( which is about the diameter of a dime ). the diameter may be about 14 mm but is scalable for alternative applications . after the location of the flat surface has been felt , the access tube punctures the skin in the vicinity of the opening of the tapered seat . the tip of the access tube engages ( e . g . bumps into ) the ridge and the access tube is moved along the guide ridge until if finds the opening . fig1 a is a side view of a slit valve mechanism according to an embodiment of the invention . the port device is implanted under the skin surface 1025 . the tapered seat 1003 has an opening 1005 that is centrally - located on the flat surface 1063 of the port device . the distance 1004 of the tapered seat 1003 is between about 1 . 0 mm and 5 . 0 mm . preferably , the distance is between about 1 . 5 mm and 2 . 5 mm as this has been found to provide maximum dependability and functionality while minimizing the height of the device . a semi - rigid silicon disc 1001 a includes a centally - located slit 1002 a that is generally aligned with the center of the tapered seat 1003 . a plate 1001 b sits on top of silicon disc 1001 a . the plate 1001 b may be made of metal , plastic , or other hardened material . a top view of the plate 1001 b is shown in fig1 b . slits 1008 a , 1008 b , 1008 c form multiple pie shaped wedges that spread downward into the silicon disc 1001 a when an access device travels down the tapered seat 1003 and contacts the centrally - located intersection of the slits 1009 . as the slits 1008 a , 1008 b , 1008 c spread apart and downward into the silicon 1001 a , slit 1002 a opens to allow the access tube passage through the silicon to open the conduit . of course , many other mechanisms that are capable of spreading the slit 1002 a apart could also be used to open the valve . upon removal of the access tube at the conclusion of a treatment , the silicone rebounds to close the slit 1002 a , the slits 1008 a , 1008 b , 1008 c also rebound to seal the valve closed . the plate 1001 b serves to protect the relatively softer silicon 1001 a from cuts and abrasions from the access tube . the access tube does not directly contact the silicon to open slit 1001 a . rather the plate opens slit 1001 a . this prevents damage to the silicon 1001 a from the access tube and lengthen the live of the valve , for example . fig1 c is a top view of the closed slit valve of fig1 a with the plate 1001 b removed . fig1 d shows the oval shape of the silicon disc 1001 a before the disc is positioned in the device and thus constrained by the device in direction 1006 to form an essentially circular shape per fig1 c with the valve loaded in an initial closed position . fig1 a - 11g show various views and types of over molds 1101 , 1102 that may be attached from the underside 1110 of the device to assist in stabilizing and / or anchoring the device . one embodiment of an over mold 1101 is shown in fig1 a and includes suture rings 1106 a , 1106 b on each side of wing - like protrusions 1104 a , 1104 b extending from the over mold central body 1103 a . the over mold 1101 . 1102 may be attached to the device on the side opposite the smooth surface with guides so that access to the tapered seat is not occluded by the over mold . the over mold can be a single molded configuration and separate from the port device or the over mold and port can be integrated or even fused together . a single molded configuration may be machined or molded and has no seams or parts than require adhesive or fastening , for example . an alternative embodiment of an over mold 1102 is depicted in fig1 b where three wing - like extensions serve to widen the base of the device so that the implanted device is not prone to move , wobble or tilt when the access tube is inserted during use . in this embodiment , horizontally flattened wings extend from the over mold body 1103 b to each of opposite sides 1104 c , 1104 d along a horizontal plane . additionally , a vertically flattened wing 1104 e may extend in from the port body 1103 b in the same general plane as the wings 1104 c , 1104 d and at about 90 degrees from wings 1104 c and 1104 d . one example of how the over mold is attached to the port device is shown in various perspectives at fig1 c - 11g , for example . the wings prevent or minimize linear and / or rotational motion of the device . the wing 1104 e minimizes yaw movement 11 y in a similar way a rudder prevents yaw movement in an airplane during flight . wings 1104 c and 1104 d minimize roll movement 11 r ( and to some extent also limit pitch movement 11 p ) when the device is implanted . the nozzle 1170 is located at the opposite end of the device ( 180 degrees ) from wing 1104 e . fig1 h - 11i show another embodiment of an over mold made of a bioresorbable , bioabsorbable or a biodegradable material 1103 e . the material 1103 e may include polylactide ( pla ), polycaprolactone ( pcl ), polydioxanone ( pdx ), poly ( l - glutamate ), poly ( l - lysine ), or poly ( l - leucine ), for example . the over mold resorbs or degrades over time ultimately leaving the port device implanted . the over mold may promote or at least support tissue integration to secure the implanted device and limit movement of the device . the over mold may include suture rings 1106 c , 1106 d on each side of wing - like protrusions 1104 f , 1104 g that extend from the over mold . the suture rings may be resorbed or degraded over essentially the same time period as the over mold resorbs absorbs or degrades into the surrounding tissues of the patient &# 39 ; s body . fig1 k is a perspective view of a port device with a stabilizer wire 1103 attached . the wires may be made of any rigid metallic material although a magnesium wire with a diameter of about 2 mm is preferred . one advantage in using magnesium wire is that is safely and gradually degrades to form magnesium hydroxide in the presence of human body fluids ( and other electrolytic solutions ), when implanted . magnesium hydroxide is not known to have any adverse side effect on the human body . as seen in fig1 k and 11l , the deployed wire attached to the device at grooves 765 a , 765 b ( fig7 ) take on a cruciate configuration ( i . e . cross shape ). the wings 1104 h , 1104 i , 1104 j are intended to prevent or minimize movement in various directions along various planes ( i . e . up / down 11 u , left / right 11 d , yaw 11 y , pitch 11 p , backward / forward 11 b ) in a similar manner as previously described regarding other stabilizer embodiments . additional stabilization may be realized from the open ends of the wire 1104 k , 1104 l near the nozzle opening 1165 of the port device especially in movements 11 b , 11 d . fig1 j shows the wire stabilizer before deployment and before attachment to the port . after the port is subcutaneously implanted in the patient , the wire stabilizer is grasped ( preferably ) by the thumb and index finger of a health care professional at locations 1120 and 1121 , respectively , and leading tip of the stabilizer wire 1104 j is inserted ( e . g . gently pushed ) into a small incision in the patient &# 39 ; s skin near the location of the implanted port . this technique avoids the step of surgically creating a tissue pocket to receive the stabilizer wire . pre - deployed wings 1104 h , 1104 i follow as the wire in pushed through the incision opening and beneath the skin . when all or most of the wire stabilizer is implanted under the skin , the stabilizer is deployed to an open position by gently compressing the wires in directions 1125 a and 1126 . the wire 1103 and port device 764 are then be positioned by palpating the wire and port under the skin to engage the wire 1103 in the grooves 765 a , 765 b . the device is centered at the apex of the wire crossing 1122 and center the device in the opened wires . it should be noted that the apex 1122 is the only location where the wires are cross in the pre - deployment configuration and require deformation to uncross the wires at apex 1122 by applying direction forces 1125 and 1126 . the configuration of this wire stabilizer is both elegant in its simplicity while also allowing a lot of mechanical advantages . once the wire is released from positions 1120 and 1121 , the wire rebounds slightly with a spring or memory force to apply tension to the device holding the wire in the grooves 765 a , 765 b . each wing 1104 h , 1104 i , 1104 j provides a low profile blunt end stabilizer without tearing the skin . the ends 1121 and / or 1120 may be shortened by trimming them with a wire cutter if needed and the incision can be closed with sutures , for example . now turning to fig1 a - 12b , a vortex clamp 1201 may be removably attached to the outside of a blood vessel or synthtic tube which , in turn , is attached to the port device . the unique shape of the clamp modifies the vascular blood flow path 1207 and reduces fluid turbulence through the vessel 1208 when the valve is open and the vortex clamp is positioned around a blood vessel . the vortex clamp includes a side 1202 that is essentially a semi - circular shape and another side 1203 that includes an indented portion 1206 . side 1202 is connected by hinge mechanisms 1205 to the opposite side 1203 in a clam shell configuration to allow the vortex clamp to surround and close around the outside of the vessel and fasten securely with a latch mechanism 1204 . fig1 b shows a side view illustration of a vortex clamp in a flow path according to an embodiment of the invention . the vortex clamp changes the vessel shape from an essentiall cylindrical shape to a helical shape which changes the flow through the vessel from a laminar to a vortical flow . fig1 a is a front perspective view of a double port configuration according to another embodiment of the invention . this configuration is essentially two ports 664 ( as shown in fig6 ) fused together into a single implantable double port device 1364 . the double port 1364 has separate flat surfaces 1363 c , 1363 d , guides 1307 a , 1307 b , openings to the tapered seat 1305 a , 1305 b , conduits , valves , and nozzles . the areas 1306 a , 1306 b , shown in fig1 b , provide spaces for excursion of the optional valve assembly . the nozzles 1370 a , 1370 b can be connected to a catheter ( not shown ). one double - lumen catheter or two single - lumen catheters can be used to establish access to the patient &# 39 ; s blood vessel via outlet openings 1365 a , 1365 b . fig1 c depicts an insertion sequence of two access tubes , each tube opening a separate associated port in the double port device . it is contemplated that the double port device can be used to deliver two different therapies simultaneously ( e . g . each therapy through one access tube ). alternatively , the double port can be used to deliver a double dose of the same therapy ( e . g . one therapy through each access tube ) which may reduce the time of the procedure by about 50 % or more in some cases . some of the many therapeutic uses of the double port may include hemodialysis , peritoneal dialysis , urinary tract drainage , pleural effusion and cerebral - spinal fluid drainage or combinations thereof , for example . each of the two tapered seats may fit with a diameter of each of two access tubes to include any combination of mismatched or matched configurations ( as described with respect to fig4 a and 4b ) to create a combination of therapeutic procedures requiring relatively high pressure flow rates and / or requiring relatively low pressure flow rates . high pressure flow rates are considered to be flow rates greater than or above normal physiologic pressures and flow rates less than or below normal physiologic pressures are considered low pressure flow rates . therefore , it is possible to administer dialysis ( high flow rate ) and intravenous fluids ( low flow rate ) simultaneously using the double port , for example . referring to fig1 c 1 , the double port device 1364 is implanted under the patient &# 39 ; s skin 1325 . an access tube 1321 a ( i . e . trocar ) may include a swivel attachment 1324 to attach a connecting line 1323 . the swivel mechanism 1324 is capable of rotating 360 degrees in a clockwise or counter - clockwise direction 1398 to prevent the connecting line 1323 from binding if the patient moves . an access tube 1321 a is inserted through the skin 1325 and contacts the flat surface 1363 a . the tip of the access tube 1321 a engages a guide 1307 and the access tube is moved along the guide to find the centrally - located opening of the tapered seat 1305 a . the access tube is inserted into the tapered seat ( fig1 c 2 ). a pressure competent valve is opened via percutaneous insertion of the access tube into the tapered seat . the valve may include a polymer spring ( fig1 ), silicon disc ( fig5 a - 10d ), a sphere ( fig1 a - 14g ) or other valve configuration . a needle 1301 a is removed 1397 from a lumen of the access tube ( fig1 c 3 ). the needle may be a single use needle . a clear container space 1399 , located between the access tube and the swivel attachment , can be used to confirm the valve is open to continuous blood flow ( or other body fluid ) by viewing the blood ( or other body fluid ) in the clear container space 1399 . the valve allows continued vascular blood flow through the conduit and the flow unobstructed by the access tube . the access tube may be rotated 1396 about 45 degrees to lock in place ( fig1 c 4 ) and / or a snap - fit or other similar configuration ensures the access tube is securely inserted into the tapered seat . this process is repeated by inserting a second access tube 1321 b through the skin 1325 ( fig1 c 5 ) to contact the flat surface 1363 b . the tip of the access tube 1321 b engages a guide 1307 and the access tube is moved along the guide to find the centrally - located opening of the tapered seat 1305 b . the access tube is inserted into the tapered seat ( fig1 c 6 ). a second valve is opened via percutaneous insertion of the access tube into the tapered seat . a needle 1301 b is removed from a lumen of the access tube ( fig1 c 6 ). a clear container space 1399 , located between the access tube and the swivel attachment , can be used to confirm the valve is open to continuous blood flow . the access tube may be rotated 1396 about 45 degrees to lock in place ( fig1 c 6 ) and / or a snap - fit or other similar configuration ensures the access tube is securely inserted into the tapered seat . in this manner , two access tubes are used to each open separate valves to continuous blood flow ( or other body fluid ) via a catheter ( not shown ) attached to the outlet openings 1365 a , 1365 b . fig1 d shows one of many examples of how the implanted device may access a blood flow . in this example , a t - catheter is attached to the device and used to access a vessel . the outside walls of the t - catheter are proximate the inside walls of the blood vessel so that the catheter takes up most or all of the space of the vessel lumen . in this way , all or the majority of the blood flow path flows through the conduit of the catheter . this configuration provide a more efficient therapy and also reduces blood flow turbulence , clotting , and other hemodynamic consequences . the valve is closed upon removal of the access tube from the tapered seat at a treatment conclusion . fig1 e is a perspective view of a triple port configuration according to an embodiment of the invention . this embodiment illustrates , in part , that the flat surfaces may be scalable for alternative applications . flat surface 1363 e is relatively smaller diameter than flat surfaces 1363 c or 1365 d , for example . in a manner similar to the double port configuration described above and with respect to fig1 a - 13d , the triple port can be used to deliver three different therapies simultaneously ( e . g . each therapy through one access tube ). alternatively , the triple port can be used to deliver a triple dose of the same therapy ( e . g . one therapy through each access tube ). also , in a manner similar to the insertion sequence described above and with reference to fig1 c , the triple port follows a similar sequence using three access tubes . it is contemplated and is understood by those of ordinary skill in the art that additional fused port configurations in excess of three ports can also be used in a similar manner as disclosed and described herewith . fig1 a is a cut - a - way side view illustration of a ball valve in a closed position according to an embodiment of the invention . a nozzle 1463 connects to a catheter ( not shown ) which ultimately taps into a blood flow path ( i . e . a blood vessel ). the opening of the tapered seat 1405 is closed to blood flow when the conduit is occluded by a spherical element 1499 a ( i . e . ball ). when the access tube 1421 tracks down a guide 1463 on the flat surface 1407 , the ball 1499 a is laterally displaced by the access tube 1421 as the tube is inserted into the tapered seat . fig1 b shows the ball 1499 a displaced in this manner to open the valve . an area 1406 provides a space for excursion of the ball 1499 a . the ball 1499 a is generally displaced the difference in the distances between distance 1497 ( fig1 a ) and distance 1996 ( fig1 b ). the flow path between the tip of the access tube 1421 and the out flow through the nozzle 1463 is thus opened to allow flow unobstructed by the access tube in use . the area 1406 may include an elastomeric spring 1498 ( fig1 c ) or silicone ring 1598 ( fig1 ), for example , in order to accommodate the displaced ball 1499 a . of course , other materials that add a resistant force against a displaced sphere may be used in area 1406 . fig1 d 1 - 14 d 4 are perspective views of a first spherical element 1449 c portion of a valve mechanism according to an embodiment of the invention . fig1 d 1 and 14 d 2 are left and right side views respectively . fig1 d 3 and fig1 d 4 are top and bottom views respectively . both spherical elements 1449 c , 1449 d may be balls made of stainless steal , synthetic saffire or other hard material that is hard and lubricious . fig1 d 1 shows the locational relationship between the slot 1411 b and recess 1410 . the slot 1411 b runs along a diameter located substantially opposite the recessed area 1410 . fig1 e 1 is a side cut - a - way view of the slotted ball of fig1 d 1 - 14 d 4 positioned in an implantable port device 1464 according to an embodiment of the invention . this embodiment of a valve mechanism comprises a spring element 1415 , a conical piston 1416 , a washer 1421 , a cup element 1422 , a first spherical element 1449 c and a second spherical element 1449 d . the second spherical element 1449 d has a smaller diameter than the first spherical element 1449 c and the first spherical element has a recessed area 1410 configured to receive a portion of the second spherical element 1449 c . when a needle is percutaneouly inserted into the tapered seat 1405 of the device , the needle contacts the slot 1411 b in a substantially horizontal position and rotates the ball in direction 1425 ( about 90 degrees along an axis ) to open the valve in a substantially vertical position . the second spherical element 1449 d simultaneously rotates within the recessed portion 1410 as the first spherical element 1449 c is rotated . the second spherical element 1449 d transmits a compression force toward the conical portion 1416 when the valve is open . fig1 e 2 and 14 e 3 are top and bottom views of conical portion 1416 , respectively . fig1 e 4 and 14 e 5 are left and right views , respectively . as seen in various perspective views including fig1 e 3 and 14 e 4 , the cup element 1422 has a slot 1417 and a groove 1418 located on one end of the slot 1417 . the groove may be about 1 . 5 mm in diameter , for example . when element 1449 d rotates , it migrates into groove 1418 thus creating a cam effect . the second spherical element 1449 d transmits a compression force toward the conical portion when the valve is open . the force is translated from element 1449 d to the conical piston and washer 1421 . the washer 1421 ( i . e . o - ring ) is compressed into the cup element 1422 when the valve is open to seal the valve and prevent leakage . the tip 1420 of the conical portion 1416 closes a space 1423 between the spring 1415 and tip 1421 . this , in turn , provides a resistant force against the needle when the valve is open . removal of the needle relieves the force and the first spherical element 1449 c rotatatably rebounds to the first position to close the valve . fig1 e 6 is a top view of a spring 1415 of the valve mechanism according to an embodiment of the invention . area 1421 extends to the outer diameter of the spring to allow easy insertion of the spring near the tip 1420 of the conical piston 1416 during assembly . the spring 1415 may be made of metal , nitinol or similar material . turning now to fig1 f , a side view of a value mechanism of fig1 d 1 - 14 e 6 is disclosed . this embodiment is advantageous in that it provides a durable device that minimizes wear and tear while increasing valve longevity because the first spherical element travels a very short distance 1424 ( e . g . between about 1 . 0 mm and 1 . 7 mm ) and the spring distance is also reduced . additionally , the valve components ( i . e . spring element 1415 , conical piston 1416 , washer 1421 , cup element 1422 , first spherical element 1449 c and second spherical element 1449 d ) relax when the valve is closed which allows a lock solution to bathe the components between uses . fig1 g 1 - 14 g 3 show an alternative valve mechanism using a slotted ball 1499 b to open and close the valve . a single ball 1449 b resides in the tube connecting the opening for the access tube 1405 with the conduit . the ball may be secured at a location in the tube by a circular area 1407 b in a similar manner as described with respect to fig1 f . note that unlike fig1 f , the slotted ball valve embodiment includes a single ball and the valve is no a pinch clamp valve mechanism . the ball 1499 b has a slot 1411 a running generally along half of the diameter of the ball . fig1 g 1 and 14 g 2 show the examples of the orientation of the ball when the valve is in the closed position . the access tube 1421 is inserted into the opening 1405 in the direction 1412 until it contacts the slotted ball 1499 b . the contact rotates the ball 1499 b in an axial direction 1413 , allowing the access tube 1421 to track along the slot 1411 a as the tube is inserted deeper into the tube to open the valve and tap into a blood flow path in the conduit . when the access tube 1499 b is removed ( e . g . retracted in the opposite direction of 1412 ) from the tube at the conclusion of treatment , the ball rotates back into the position shown in fig1 g 1 to close the valve . fig1 is a cross sectional view of a silicon bumper spring configuration . this is basically another way to receiving a ball 1599 in addition to the elastomeric spring 1498 embodiment shown in fig1 c . fig1 shows the silicon bumper spring resting against the ball 1599 ( or other spherical element ) when the valve is closed . the ball is displaced by the access tube ( not shown ) during tube insertion through the opening 1505 and the ball pushes into the silicone . area 1506 includes a layer of relatively soft silicone 1507 and an area of relatively hard silicone 1508 which is located furthest from the nozzle 1563 at the opposite end of the port device 1564 . a metal spring 1598 is embedded in ( and surrounds ) the soft silicone portion 1507 . the soft silicone 1507 provides the spring force and excursion of the ball 1599 . the soft 1507 and hard 1508 silicone are fused together and the hard silicone 1508 is compressed to hold the silicone in place . in this manner , the spring does not extrude out the end 1510 but simply compresses the soft silicone 1507 . when the ball 1599 is displaced and pushes further into the center of the soft silicon 1507 bumper in the direction 1511 , the silicone is moved from the center to the outside . the metal spring 1598 adds rigidity to retain the leading edge of the silicone material as it compresses against the ball 1599 and moves outward from the center of the silicone . other materials that add a resistant force against a displaced sphere may be used in area 1506 . although silicone is convenient to use in the human body , however , many polymeric or other materials may be used in combination . fig1 a is a cut - a - way side view illustration of a port housing with a ball bed and an axial flow connector according to an embodiment of the invention . in this embodiment , the angle 1698 of the tube / tapered seat and outlet opening 1665 ( which ultimately attaches to a catheter ) is about 90 degrees . fig1 b is a bottom view illustration of a port housing with a ball bed and an axial flow connector according to an embodiment of the invention . fig1 c is a perspective view of the port device of 16 a and 16 b that includes suture rings 1609 a , 1609 b to stabilize the port when subcutaneously implanted . fig1 d is a top view illustration of a port housing with an axial connector according to an embodiment of the invention showing the flat surface 1663 and ridges 1607 that engage and guide the access tube into the opening 1605 of the tapered seat . fig1 a is a cut - a - way side view illustration of a port housing with a ball bed of 40 degrees boring and an axial flow connector according to an embodiment of the invention . it has been found that an angled ball bed ( i . e . the resting area of the ball when the valve is closed to flow ) of less than 90 degrees positions the ball so the access tube , when inserted through the opening 1705 , engages the ball more eccentrically than an angle of 90 degrees . an angle 1798 of about 40 degrees is shown in fig1 a . this positions the ball so the access tube strikes the ball closer to the open end 1765 . by engaging the ball at a location other than at its geometrical center , the health care professional need not supply as much force when the access tube is inserted into the tube . the ball more easily moves into the polymeric spring , silicone bumper spring or other similar structure . the point at which the ball contacts the access tube should be at least less than 90 degrees . an angle of between about 40 and 90 degrees between the tube ( first vector ) and the opening connecting the catheter ( second vector ) is preferred to easily move the ball and open the valve . fig1 b is a bottom view illustration of a port housing with a ball bed of 40 degrees with associated bore 1797 . the bore 1797 is an example of a manufacturing technique that allows the ball to engage as described above . the bore 1797 is plugged closed after maching . the opening 1765 of the outflow tube is about 90 degrees relative to the opening 1705 of the tapered seat . fig1 c is a perspective view of the port device of 17 a and 17 b including an outlet opening 1765 which is attached to a catheter ( not shown ). referring now fig1 a - 18c , locking of a subcutaneously implanted catheter 1820 used for hemodialysis access will be described . the catheter 1820 is implanted under the skin between a target blood vessel 1824 , typically a vein , and an implanted port 1822 . during hemodialysis , blood 1831 may be withdrawn in a direction 1827 through the catheter 1820 , through the port 1822 and externally through an access tube 1821 and connecting line 1823 used to percutaneously access the port 1822 ( fig1 a ). alternatively , the port and catheter could be used to return treated blood to the patient . when it is desired to end a hemodialysis ( or hemofiltration ) treatment , a flushing solution 1828 will be introduced in a direction 1829 through the access tube 1821 ( typically from a syringe which is attached to the connecting line 1823 ) to flush the lumen , as depicted in fig1 b . after the flush is complete , a container such as syringe 1826 containing the hydrophobic antimicrobial lock solution of mid - chain fatty acid ( s ) and tocopherol / ricinoleic acid mixture is injected through the line 1823 / port 1822 in a direction 1830 into the lumen of catheter 1820 to displace the flushing solution and lock the catheter ( fig1 c ). the lock solution will remain in place within the catheter 1820 . the methods of the present invention may also be used to lock non - vascular catheters , such as peritoneal dialysis catheters 1930 , as shown in fig1 a - 19c . after a peritoneal dialysis treatment , the used dialysate 1931 will be withdrawn from the catheter 1930 in a direction 1932 as shown in fig1 a . after the dialysate has been sufficiently removed , the dialysis catheter 1930 may optionally be flushed in a direction 1929 with a flushing solution 1928 , as shown in fig1 b . after flushing , the lock solution 1933 of mid - chain fatty acid ( s ) and tocopherol / ricinoleic acid mixture is introduced to the peritoneal dialysis catheter 1930 in direction 1934 as shown in fig1 c , so that it fills the lumen of the catheter , as described previously with the vascular catheters . the use of the aforementioned lock solution for peritoneal dialysis catheters is particularly advantageous in inhibiting or eliminating infections . referring now to fig2 , the use of a lock solution containing mid - chain fatty acid ( s ) and tocopherol and a mixture possessing desirable antimicrobial and anticoagulant properties for locking a catheter can be enhanced by utilizing an implanted catheter which is formed at least partially from a porous or semi - permeable material . when the lumen 2040 of the porous catheter body 2042 is filled with a hydrophobic antimicrobial lock solution of mid - chain fatty acid ( s ) and tocopherol mixture 2043 , the solution will be able to slowly penetrate ( i . e . seep or permeate ) into the catheter body and preferably outwardly ( as shown in direction 2044 ) into the tissue 2041 surrounding the catheter , as shown by the arrows in fig2 . thus , the antimicrobial properties of the lock solution will not be entirely limited to the interior lumen 2040 of the catheter , but will also be effective on the surface of the catheter 2045 and in the tissue 2041 immediately surrounding the catheter body . the solution provides anti - thrombotic ( catheter lock ) and pro - thrombotic ( needle site ) qualities . particularly suitable materials and porosity properties for the catheter bodies have been set forth above . the ability of ricinoleic acid to remove toxins from the blood may be particularly beneficial in peritoneal treatments . in addition , the solution serves to lubricate the implanted device including internal structures and valves . although embodiments of the invention have been described in considerable detail with reference to certain preferred versions thereof , other embodiments are possible . therefore , the spirit and scope of the appended claims should not be limited to the descriptions of the embodiments above .

the present invention relates to subcutaneously implanted graft - port systems , devices and methods for establishing access to the vascular system of a patient requiring multiple blood treatments over an extended period of time . the systems , devices and methods disclosed herein reduce miscannulation , promote intra - session hemostasis , and decrease the incidence of bacteremia and sepsis among other improvements and advantages . the devices include a port with a flattened plateau - like surface for receiving an access tube . the flat surface may include a tactile or visual guide to assist with placement of the access tube into the tapered seat . optional valve mechanisms reduce the size and form factor of the implantable graft - port device and seals the conduit of the port closed to physiologic pressures until the valve is opened upon percutaneous insertion of the access tube . the access tube does not pass into the conduit . a mismatch fit between the access tube and tapered seat causes a decrease in the cross - sectional sealing area , a reduction in the overall device size , and an increase in blood flow during treatment . lock solutions to prevent fowling and infection are also disclosed .

referring now to fig1 there is shown a seat , designated generally by the numeral 11 , which for purposes of illustration is in the form of a chair . it should be kept in mind that the seat 11 also could be in the form of other seating structures and arrangements , such as sofas , benches , or any other seating structure designed to accommodate one or more persons . the seat 11 includes a sling , designated generally by the numeral 12 , which is supported between a pair of frame members , designated generally by the numerals 13 -- 13 . the sling 12 is made of a fabric , such as canvas , vinyl or the like , and serves to receive and support a person sitting in the seat . in order to support the sling 12 between the frames 13 -- 13 , the sling is secured to front top and rear cross rungs 14 , 15 and 16 , respectively , which extend between the frame members 13 -- 13 . in the illustrated embodiment , the sling 12 is divided into a front segment 17 , a back segment 18 and a rear segment 19 . as best seen in fig5 the front , back and rear segments 17 , 18 and 19 radiate from a seam 21 with the front segment having its free end 22 attached to the front cross rung 14 , the back segment having its free end 23 attached to the top cross rung 15 , and the rear segment 19 having its free end 24 attached to the rear cross rung 16 . the front segment 17 serves to support the buttocks and thighs of the person sitting in the seat 11 , while the back segment 18 supports the back of the person sitting in the seat 11 . in order to help define a comfortable seating contour , the rear segment 19 , limits forward movement of the seam 21 by limiting the distance from the rear cross rung 16 , so that the seam can move when a person sits in the seat 11 . the specific structure for securing the web 12 on the rungs 14 , 15 and 16 will be discussed in detail hereinafter . as seen in fig2 and 3 , the seat 11 is collapsible from the erect condition shown in fig1 to the collapsed folded condition shown in fig3 . this is accomplished by making the frame members 13 -- 13 foldable . as generally shown in the drawings , the frame members 13 - 13 each include an arm member 31 , a front leg 32 and a rear leg 33 . as seen in fig2 and 3 , the front legs 32 - 32 are joined to the arm members 31 - 31 by links 34 - 34 , while the rear legs 33 - 33 are joined to the arm members by hinges 36 - 36 which form fixed pivots . in order to fold the chairs , the rear legs 33 - 33 are pivoted about the hinges 36 - 36 in order to extend flush against the arms 31 - 31 . the front legs 32 - 32 are then pivoted over the rear legs 33 - 33 , so as to overlie the rear legs , as shown in fig3 . this is accomplished by pivotally mounting the links 34 - 34 on pins 46 - 46 . after the chair is folded to the collapsed configuration of fig3 it may be stood on end as shown in fig6 . as is perhaps best known in fig4 the links 34 are rigidly secured to the front legs 32 - 32 by inserting the links in slots 40 formed in the top ends 41 of the legs . the links 34 may be secured in the slots 40 by a suitable adhesive binder and pins 42 are preferably inserted through holes 43 and 44 in the legs and links , respectively , in order to form a firm mechanical connection . in the illustrated embodiment , the links 34 project normally to the extent of the legs 32 . each link 34 has a slot 45 extending therein , which receives a pin 46 inserted into the associated arm 31 . the pins 46 are positioned in slots 47 extending back from the ends 48 of the arms . the links 34 are received in the slots 47 , while the pins 46 register with the slots 45 extending in the links to form sliding pivots . as best seen in fig5 and 8 , each link 34 has two positions . in the first position shown in fig8 the link 34 is able to pivot about the pin 46 , whereas in the second position shown in fig5 the link 34 is not able to pivot about the pin 46 . as seen in fig5 the link 34 extends back into the slot 47 , so that the top surface 50 of the link engages the top surface 51 of the slot 47 . this engagement blocks the rotation of the legs 32 , so that they remain fixed relative to the arms 31 , thereby rigidly holding the chair 11 in its erect condition . by pulling the legs 32 , so that the links 34 slide out of the slots 47 until the ends of the slots 45 in the links engage the pins 46 , it becomes possible to rotate the legs 32 relative to the arms 31 . this is because top surfaces 50 of the links 34 no longer engage the surfaces 51 of the slots 47 . in addition , the links 34 now extend a sufficient distance from the arms 31 , so as to accommodate the widths of the rear legs 33 . in the preferred embodiment , the ends 41 of the legs 32 and the ends 48 of the arms 31 are at 45 ° with respect to the extent of the legs and arms , so that the ends abut one another along a plain which is at 45 ° with respect to the horizontal . with this particular configuration , the legs 32 extend normally with respect to the arms 31 . if it is desired to have the legs 32 extend at , for example , an obtuse angle with the arms 31 , then the ends may be cut at a different angle . in any event , the engagement between the ends 40 and 48 provides a rigid support for the chair 11 , when combined with the interaction of the links 34 and slots 47 as described above . as seen in the drawings , the front rung 14 extends between the front legs 32 - 32 , the rear rung 16 extends between the legs 33 - 33 and the top rung 15 extends between projecting portions 60 - 60 of the rear legs 33 - 33 . as best seen in fig4 and 5 , the sections 17 , 18 and 19 of the sling 12 are secured to the rungs 14 , 15 and 16 by rods 63 , 64 and 65 attached to the sections and received in grooves 66 , 67 and 68 cut in the rungs . the rods 63 are preferably positioned in pockets 70 formed or sewn in the ends of the sections 17 , 18 and 19 . in order to provide for adjustment , several pockets 70 may be provided at the end of each section . as seen in fig5 the end of the sling section 17 is secured in the slot 66 by the rod 63 , and then extended counterclockwise around the rung 14 , so that it extends over the rod 63 . the end of the sling section 19 is retained in the slot 68 by the rod 65 and extended around the rung 16 in the clockwise direction and over the rod 65 . finally , the end of the sling section 18 is held in the slot 67 by the rod 64 and extended around the rung 15 in the clockwise direction , so as to extend over the rod 64 . when a person sits in the sling 12 , the various sections 17 , 18 and 19 are pulled taut and the portions of the sections overlying the rods 63 , 64 and 65 hold the rods in their respective slots 66 , 67 and 68 . again , as seen in fig5 when a person is sitting in the sling 12 , he rests in the section 17 with his back against the section 18 . this causes tension on the section 18 , which tends to rotate the legs 33 - 33 in the clockwise direction into abutment with the ends 73 of the arms 31 . the force is greater than the tensional force along the web section 19 , so that the legs 33 will not tend to rotate in the counterclockwise direction about the pivots 36 and collapse . in order to insure safety , a positive retaining means , such as a hook 74 may be used to hold the legs 33 in engagement with the arms 31 . the tensional force along section 17 of the sling 12 tends to hold the ends 41 and 48 of the front legs 32 and arms 31 in engagement , and also tends to hold the link 34 within the slot 47 in the afore - mentioned second position , so that the front legs 32 cannot pivot relative to the arms 31 . in order to provide additional convenience , the rungs 14 , 15 and 16 are attached to the front legs 32 and rear legs 33 , respectively , by brackets 75 ( see fig7 ) which allow the rungs to be readily detached . as shown in fig7 each bracket 75 has a pair of keyhole slots 76 and 77 therein . each rung has a pair of headed members , such as screws 78 and 79 which register with the keyhole slots 76 and 77 , respectively . during assembly , the headed members 78 and 79 are slid into the wide portions of the slots 76 and 77 , and then moved to the narrow portions of the slots , so that they will not slip out of the slots . as seen in fig6 when the seat 11 is folded , its center of gravity is located at point 80 , which is between the points 81 and 82 of the arms 31 and legs 32 upon which the seat rests . consequently , the chair 11 may be stored in a vertical position without falling over . as seen , specifically , in fig5 the rear legs 33 deviate from the vertical by an angle of about 12 ° in order to enhance the stability of the chair , when it is in its erect condition and not being sat in . the rear ends 73 of the arms 31 are also angled at 12 °, so that the legs 33 will fit flushed there against . while the instant invention has been illustrated by way of the foregoing drawings and embodiment , which are for the purpose of illustration only , the invention is limited only by the following appended claims .

a folding seat includes a pair of side frame members joined by detachable rungs . each side frame member has an arm , a front leg and a back leg . one of the legs is pivoted directly to the arm , while the other leg is pivoted to the arm with a sliding link which locks with the arm when the seat is erected . a web is slung between the rungs to support a person sitting in the seat and is detachably held in place by rods which register with slots in the rungs .

referring to the figures , the light emitting safety wrap 1 generally comprises a flexible sleeve portion 2 , a wrap side - fastener 3 , and a light emitting source 4 . the wrap side - fastener 3 is affixed to said flexible sleeve portion 2 as is the light emitting source 4 . in use , the light emitting source 4 is enabled to emit light and enhance the visibility of the user , and the flexible sleeve portion 2 is wrapped round a strap or a tubular structure ( e . g . a backpack strap , dog collar , or bike frame tube ) that will accompany a user during times of decreased visibility or low light levels . the preferred flexible sleeve portion 2 “ is substantially rectangular ,” further comprises a front side 21 and a backside 22 , and is constructed from a fabric such as nylon . other materials of similar strength may which may be reflective or a combination of reflective and non - reflective material may also be used for the flexible sleeve portion 2 . moreover , the rectangular piece of substantially flexible nylon has dimensions sufficient to enable constructing a wrap 1 of adequate size . what constitutes an adequately sized wrap 1 will depend largely on the application and the dimensions of said strap or said tubular structure upon which the wrap 1 is used . for example , a rectangular piece of nylon that is 13 ″ by 5 . 5 ″ will suffice for most applications of the wrap 1 . the front side 21 of the wrap 1 faces away from the strap or tubular structure , and the backside 22 of the wrap 1 will faces towards and touches the strap or tubular structure , when the wrap 1 is releasably attached to said strap or tubular structure sewn , but capable of being otherwise affixed , to the flexible sleeve portion 2 is the wrap side - fastener 3 that is included in the preferred embodiment . the wrap side - fastener 3 is affixed to the edges of the longer dimension of the rectangular piece of flexible material that makes up the flexible sleeve portion 2 . the wrap side - fastener 3 enables securing the flexible sleeve portion 2 about itself or around said strap or said tubular structure . in the preferred embodiment , the wrap side - fastener 3 is comprised of two strips of hook - and - loop fastener material . alternatively , other fasteners such as buttons and snaps are capable of securing the flexible sleeve portion 2 and are also contemplated as useful sleeve fasteners 3 . the preferred light emitting source 4 further comprises a programmable microchip 41 , circuit board 46 , an energy source 42 , an on / off switch 43 , a wiring harness 45 , and at least one light emitting diode (“ led ”) 44 . the preferred energy source 42 is a small pen light or flashlight dry cell battery and the on / off switch 43 a single - pole / single - throw type . said wiring harness 45 may be either wire , ribbon cable or flexible printed circuit board and connects together the components of the electrical circuit 4 . although other types of light emitting devices , including tiny incandescent bulbs , can also be used . leds 44 are preferred because they use little power , have a relatively long life , and are made of durable material . the leds 44 will ordinarily a have hard plastic encapsulate lens and are equidistantly affixed along the wiring harness 45 . said hard plastic encapsulate lenses of the led &# 39 ; s 44 protrude through apertures in the flexible sleeve portion 2 to the front side 21 of the flexible sleeve portion 2 . the programmable microchip 41 is preferably programmed to cause each led 44 to cycle on and off repeatedly . the programming of the microchip 41 is considered to be within the knowledge of an ordinarily skilled practitioner . optionally , a remote control on / off switch 48 can be used in place of the ordinary on / off switch 43 . as a second option , an audible alarm 47 may be employed in the electrical circuit 4 to alert when the led &# 39 ; s 44 are enabled to emit light . for military purposes , infrared (“ ir ”) lights 49 may be employed in place of the visible light leds 44 and the electrical circuit 4 connections waterproofed with silicon or epoxy . for added durability , strength , and protection for the electrical circuit 4 , a thin nylon or polypropylene strapping 23 is affixed to the backside 22 of the flexible sleeve portion 2 over the wiring harness 45 thereby “ sandwiching ” all of the components of the light emitting source 4 except the leds 44 lens portions that protrude through the front side of the flexible sleeve portion 2 . an end of this strapping 24 ( approximately 2 ″) is unattached to the flexible sleeve portion 2 and serves as an easy access cover for the circuit board 46 energy source and on / off switch 43 . this portion of the strapping 23 closes using hook - and - loop fastener , with one portion of the hook - and - loop fastener material , either the hook or loop portion , attached to the sleeve portion 2 , and the other portion of the hook - and - loop fastener , either the loop or hook portion attached to the strapping 23 . so that the wrap 1 may also be wrapped circumferencially around and fastened about a user &# 39 ; s wrist , head , or other structures , a sleeve end - fastener 5 is affixed to the rectangular flexible sleeve portion 2 . said sleeve end - fastener 5 preferably comprises strips of hook and loop fastener and a buckle 6 attached to the rectangular flexible sleeve portion 2 as shown in the figures . the preferred embodiment of the invention is described above in the drawings and description of preferred embodiments . while these descriptions directly describe the above embodiments , it is understood that those skilled in the art may conceive modifications and / or variations to the specific embodiments shown and described herein . any such modifications or variations that fall within the purview of this description are intended to be included therein as well . unless specifically noted , it is the intention of the inventor that the words and phrases in the specification and claims be given the ordinary and accustomed meanings to those of ordinary skill in the applicable art ( s ). the foregoing description of a preferred embodiment and best mode of the invention known to the applicant at the time of filing the application has been presented and is intended for the purposes of illustration and description . it is not intended to be exhaustive or to limit the invention to the precise form disclosed , and many modifications and variations are possible in the light of the above teachings . the embodiment was chosen and described in order to best explain the principles of the invention and its practical application and to enable others skilled in the art to best utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated .

a light emitting safety wrap or sleeve worn by people and / or pets engaged in activities , or attached to objects during periods of limited visibility with flashing or blinking lights so as to be visible in darkness ; powered by direct current ; having three optional capabilities : remote on - off switch and / or digital voice / sound message and / or infared signaling lights .

the present invention provides a liquid composition for use as a pan - release agent in bakeries , method of preparing same , and a method of de - panning baked goods which comprises spraying onto the surfaces of a baking pan a liquid composition comprising a liquid emulsifier containing monoglycerides and diglycerides as derived from animal fats or vegetable oil or both and a polysorbate compound , and at least about 80 % water by weight . unbleached liquid lecithin as derived from soya oils may also be added to the liquid composition of the present invention in order to aid its adherence to the walls of a baking pan . the liquid emulsifier used in the spraying composition is a mixture of monoglycerides , diglycerides , a polysorbate and a limited amount of water , and has the following general characteristics and specifications : ______________________________________classification food emulsifierform at or about 77 ° f . clear , golden liquidmelting point approx . 45 ° f . iodine value approx . 39 ° f . flash point above 300 ° fire point above 300 ° f . total monoglycerides approx . 32 % hydrophile - lipophile balance 8 . 1ratingmonoglyceride content 28 . 0 min . ( alpha form , %) free glycerin , % 1 . 1 max . free fatty acid 1 . 0 max . ( as oleic , %) ______________________________________ the liquid emulsifier is known to be soluble at low levels in vegetable oils as well as being dispersible in water . the monoglyceride and diglyceride components of the liquid emulsifier used in the liquid composition of the present invention are derived from animal fats and / or vegetable oils . the polysorbate component is preferably derived from the reaction of ethylene oxide and the sorbitan ester of stearic acid , e . g ., polyoxyethylene ( 20 ) sorbitan monostearate . this particular polysorbate is commercially known as polysorbate 60 . the monoglycerides and diglycerides preferably comprise from about 3 . 5 percent to about 9 . 0 percent by weight of the liquid composition while the polysorbate preferably comprises from about 2 . 5 percent to about 6 . 5 percent by weight of the liquid composition . preferably , the ratio of the mono - and diglyceride components to the polysorbate component is less than 1 . 5 but more than 1 . 4 . the only commercially available liquid emulsifier currently known in the art is produced by ici americas , inc ., specialty chemicals division , wilmington , del . 19897 , under the name of tandem ® 552 . these blends contain a ratio of approximately 60 percent by weight of the mono - and diglycerides portion to approximately 40 percent by weight of the polysorbate component . as currently manufactured , tandem ® 552 contains approximately 53 percent by weight mono - and diglycerides , 36 percent by weight polysorbate ( 60 ), and 11 percent by weight water . however , tandem ® 552 cannot be applied directly to the surface of the dough without causing streaking or spotting in the color of the dough as it bakes . as previously mentioned , this unappetizing effect is unacceptable to the baking industry . in addition , hydraulic or air pressure spray equipment commonly used in bakeries cannot be used to spray tandem ® 552 due to its viscosity . to ensure that the liquid compositions of the present invention do not discolor the dough as it bakes , the compositions comprise a major portion of water by weight , specifically at least about 80 percent water by weight , and preferably between 83 percent and 93 percent water by weight as shown by the following examples . when a commercial liquid emulsifier which contains a limited amount of water is used , such as tandem ® 552 , the amount of water added thereto is preferably within the range of five to fourteen times by weight of the liquid emulsifier component , resulting in a liquid composition having at least 80 percent water by weight as in the examples which follow . thus , they can be used to adhere a topping material to the dough surface as well as be sprayed directly onto the pan surfaces to provide good product release . it should be noted , however , that if excessive ( and economically wasteful ) amounts are sprayed directly onto the dough , some discoloring may occur . as previously mentioned , unbleached liquid lecithin as derived from soya oils may also be added to the liquid composition in order to aid its adherence to high - walled baking pans , such as a bread pan . lecithin also adds to the stability of the liquid composition . the lecithin comprises less than 4 . 0 percent by weight of the liquid composition and preferably about 2 . 0 percent in those liquid compositions used with high - walled pans . to form a composition having a shelf life of more than a few days , certain preservatives should be added to the liquid composition . in particular , it has been found that the addition of potassium sorbate in an amount ranging from about 0 . 1 to about 0 . 2 percent by weight of the water and liquid emulsifier components , together with citric acid in an amount ranging from about 0 . 015 to about 0 . 3 percent by weight of the water and liquid emulsifier components provides a stable solution having a shelf life of at least two to three weeks when kept at a temperature between about 33 ° f . and about 110 ° f . for storage . preferably , the liquid composition is stored and used at room temperature to prolong its shelf life . the stabilization of the liquid composition is also aided by preferably maintaining its ph between about 3 . 75 and 4 . 0 . in particular , the potassium sorbate is not as effective at a ph greater than about 5 . 0 while a more acidic ph than about 3 . 75 results in a sharp odor emanating from the liquid composition . a preferred method of preparing the liquid compositions of the present invention is to first place the water component under rapid agitation using a high - shear mixer , such as a turbon high - speed , high - shear mixer having a speed of about 3450 rpm ( available from tobert industries , inc ., in south bridge , mass .). if the speed of the high - shear mixer is much greater than 3450 rpm , the liquid composition will become foamy due to the presence of too much air . however , mixer speeds which are much less than 3450 rpm have been found not to thoroughly mix the liquid composition . in addition , if a high - shear mixer is not used , the liquid composition has a tendency to separate into its different components after a few days . the water may be at ambient temperatures , ranging from about 56 ° f . to about 90 ° f . if potassium sorbate and citric acid are used as preservatives , they are slowly added to the agitating water component until the solution is thoroughly mixed , usually about 3 to 5 minutes . the liquid emulsifier component is then slowly added thereto while the agitation continues , and the resulting mixture is then thoroughly agitated for approximately 5 minutes to ensure a homogeneous solution . the liquid emulsifier is added to the water to prevent the formation of lumps which have a tendency to form when water is added to the liquid emulsifier . if lecithin is to be added to the liquid composition of the present invention , the lecithin and the liquid emulsifier are first pre - mixed at ambient temperatures using a high - shear mixer , usually for about 3 to 5 minutes , until these components are thoroughly mixed and form a stable solution . this mixture is then added to the water component as stated above . should the lecithin be introduced into the water rather than the liquid emulsifier , a lumpy mixture may result with much of the lecithin eventually separating out and floating to the top of the mixture . the resulting liquid composition which incorporates lecithin has a creamy color and a viscosity such that it may be sprayed using standard pressure spray apparatus , such as hydraulic or air pressure spray equipment . the resulting liquid composition without lecithin may be similarly sprayed but is a milky white opaque solution which is slightly less stable than those compositions incorporating lecithin . however , liquid compositions without lecithin are particularly useful with bun pans or the like which do not have the deep pan walls found in a bread pan , as well as in adhering a topping material to the dough surface . the preferred liquid composition used in the method of the present invention for the release of baked breads from a bread pan is set forth in example 1 below . this liquid composition has an approximate ratio of 6 parts water to 1 part liquid emulsifier , with the liquid emulsifier comprising about 12 . 4 percent by weight of the composition , and about 2 . 0 percent by weight lecithin is added . potassium sorbate and citric acid may also be added to the liquid composition as preservatives . this liquid composition is particularly effective with baking pans having deep or high walls such as a bread pan . the liquid composition is generally sprayed directly onto the empty pan until complete coverage of all the surfaces of the pan which the dough will contact is obtained . when the liquid compositions disclosed in the method of the present invention are used for the release of buns or the like from their baking pans , the lecithin component is not necessary . however , the presence of lecithin does aid the stability of the liquid composition . thus , a preferred liquid composition for this use may be obtained by diluting the liquid composition of example 1 with equal parts water to produce a liquid composition having an approximate ratio of about 12 to 13 parts water to each part liquid emulsifier . such a preferred composition is disclosed in example 2 . this liquid composition is also preferred where a topping material is to be adhered to the dough surface before , during , and after the baking process . the liquid compositions of the present invention are either sprayed onto the pan before the dough is placed in it , or sprayed onto the dough in the pan before the dough is fully proofed , i . e ., risen . it has been found that if the dough has been fully proofed , the areas of the pan where the sticking of the dough primarily occurs are already covered by the dough . consequently , the spray cannot reach and coat these areas . however , where a topping material is to be adhered to the dough , the liquid composition need not be sprayed onto the pans before the dough is placed therein . rather , it has been found that spraying the liquid composition only after the dough is in the pan so that it covers the remaining surfaces of the pan which the dough will contact as it rises , as well as covering the surface of the dough itself , provides satisfactory release of the baked dough from the pan . although not necessary , if desired , the pan may also be sprayed before the dough is placed therein to provide complete coverage of all the pan surfaces . as previously noted , however , it is important that an excessive amount of the liquid composition not be sprayed directly onto the dough in order to avoid the possibility of any discoloration of the baked dough . the liquid composition is sprayed onto the baking pans by means of spray heads or nozzles known in the art , e . g ., those used when water is used as the means for adhering the topping material onto the dough . the spray nozzles are connected to a hydraulic or air pump or a mechanical centrifugal pump which can provide a constant fluid pressure of about 40 lbs . to about 100 lbs . suitable hydraulic pumps are well known in the baking industry under the trade names &# 34 ; graco &# 34 ; and &# 34 ; alemite &# 34 ;. the pumps draw the liquid composition directly from the steel drums in which it is stored . the following nonlimiting examples of the liquid compositions of the present invention are provided for illustration only in order to further describe the liquid compositions of this invention . ______________________________________composition : weight percent blend : ______________________________________liquid emulsifiermono - and diglycerides 7 . 4polysorbates 5 . 0 * water 85 . 6lecithin 2 . 0______________________________________ * includes water incorporated with the liquid emulsifier . ______________________________________composition : weight percent blend : ______________________________________liquid emulsifiermono - and diglycerides 4 . 0polysorbates 2 . 7 * water 92 . 3lecithin 1 . 0______________________________________ * includes water incorporated with the liquid emulsifier . ______________________________________composition : weight percent blend : ______________________________________liquid emulsifiermono - and diglycerides 7 . 5polysorbates 5 . 1 * water 86 . 9lecithin 0 . 5______________________________________ * includes water incorporated with the liquid emulsifier . ______________________________________composition : weight percent blend : ______________________________________liquid emulsifiermono - and diglycerides 5 . 8polysorbates 4 . 0 * water 89 . 2lecithin 1 . 0______________________________________ * includes water incorporated with the liquid emulsifier . ______________________________________composition : weight percent blend : ______________________________________liquid emulsifiermono - and diglycerides 8 . 8polysorbates 6 . 0 * water 85 . 2______________________________________ * includes water incorporated with the liquid emulsifier . ______________________________________composition : weight percent blend : ______________________________________liquid emulsifiermono - and diglycerides 7 . 3polysorbates 5 . 0 * water 84 . 7lecithin 3 . 0______________________________________ * includes water incorporated with the liquid emulsifier . ______________________________________composition : weight percent blend : ______________________________________liquid emulsifiermono - and diglycerides 4 . 4polysorbates 3 . 0 * water 92 . 6______________________________________ * includes water incorporated with the liquid emulsifier . ______________________________________composition : weight percent blend : ______________________________________liquid emulsifiermono - and diglycerides 4 . 7polysorbates 3 . 2 * water 90 . 1lecithin 2 . 0______________________________________ * includes water incorporated with the liquid emulsifier . ______________________________________composition : weight percent blend : ______________________________________liquid emulsifiermono - and diglycerides 6 . 5polysorbates 4 . 4 * water 87 . 1lecithin 2 . 0______________________________________ * includes water incorporated with the liquid emulsifier . in each of the above examples , the amount of water referred to is the total water in the liquid composition . however , when tandem ® 552 is used as the liquid emulsifier , it already contains between about 10 percent to about 11 percent weight water . accordingly , the above stated percentages of water include 11 percent for the water contained in the tandem ® 552 . while the preferred application of this invention has been shown and described , it would be apparent to those skilled in the art that many more modifications in the specific formulas of the liquid compositions are possible without department from the inventive concept herein described . the invention , therefore , is to be limited only by the lawful scope of the claims which follows .

a liquid composition for use as a pan - release agent in bakeries and a method of preparing such composition and de - panning baked goods which comprises spraying onto a pan in which dough is to be baked a liquid composition comprising a liquid emulsifier containing monoglycerides , diglycerides , and polysorbate , and a major portion of water . lecithin may also be added to the liquid composition , as well as certain preservatives . the present invention enables bakery products , particularly yeast - raised bakery products , to be easily released from the pans at the conclusion of the baking process and minimizes the build - up of carbon residue on the surfaces of the baking pans . the liquid composition does not affect the color of the baked dough and has a viscosity suitable for spraying through hydraulic or air pressure spray equipment . the liquid composition disclosed in the present invention can also be used to adhere a topping material , such as sesame seeds , onto yeast - raised bakery products without interfering with the release of the baked goods from the baking pans or adding to a build - up of carbon residue .

with reference to the figures attached hereto and briefly referred to above , several preferred embodiments are now described in detail . the invention described herein ( fig1 ) is an endoluminal introducer ( 100 ) that can be used in conjunction with a laparoscope ( 150 ) for endoluminal examination following lar surgery . the introducer acts as a conduit for introducing the laparoscope into the rectum and enables the viewing of the endoluminal surface and surgical margin or anastomosis with the same hd endoscope that is used for intra - peritoneal viewing during surgery . the introducer incorporates all of the features required for examination of the endoluminal surface with a surgical endoscope . these features may include channels for the introduction of insufflation air ( or co2 ) to expand the endoluminal space and for the washing and aspiration of liquids so as to provide for the complete examination of the surgical anastomosis . furthermore , if the hd laparoscope is capable of near infrared illumination and imaging , the anastomosis may be viewed using an icg imaging agent to highlight the perfusion of tissue at and around the area of the surgery . one such laparoscope is the pinpoint ® system ( novadaq technologies inc ., canada ) that provides for simultaneous white - light and near infra - red illumination and imaging . this allows for enhanced visualization and assessment of the anastomosis and surgical margin over that which can be achieved with conventional white - light endoscopes . in one embodiment , ( fig2 ), the introducer ( 100 ) is composed of a rigid plastic formed into a tube structure by molding , extrusion or other appropriate plastic manufacturing process . the plastic may be selected from a medical plastic , polypropylene , polycarbonate , polyethylene , polystyrene , k - resin , or any other appropriate rigid plastic . the tube structure may be transparent or opaque . the introducer may contain a single main channel or a main channel with one or more ancillary channels ( 102 )— the laparoscope being inserted into a main channel and the other channels being utilized for insufflation , washing and aspiration of fluids from the endoluminal surface . if the introducer has a single main channel that is open to the endoluminal space , then the space between the laparoscope and the tube wall may be utilized for insufflation , washing and aspiration of fluids from the endoluminal surface . in many embodiments , the introducer is approximately the length of the laparoscope , such that when the laparoscope is inserted into the introducer , the tip of the endoscope reaches , but does not protrude from the end of the introducer . the main channel ( 103 ) of the introducer may be sealed at the distal end with a transparent window ( 104 ) and , if sealed , the main channel window may be transparent to uv , visible or near infra - red light . the tip of the laparoscope is sufficiently close to the end of the main channel of the introducer , so that the introducer does not enter the field of view seen through the laparoscope or block the illumination emitted by laparoscope . the tip ( 105 ) of the introducer may be angled at 30 °, 45 °, or 90 ° to accommodate angle viewing laparoscopes . ancillary channels for washing and aspiration are appropriately directed to terminate in the same direction as the viewing angle . a separate ancillary channel may be terminated to direct a spray of wash water across the window of the main channel . the tip ( 105 ) of the introducer may be composed of a softer more compliant plastic than the remainder of the shaft of the introducer , ( e . g . teflon or a similar material ) or may have rounded edges so as not to scrape the endoluminal surface when inserted . the introducer may have markings ( 106 ) on the exterior surface to indicate the depth of insertion . the proximal end of the introducer may have a feature ( 110 ) that seats the laparoscope light guide stem and maintains it in position such that the introducer and laparoscope will move together if rotated . this is especially useful in instances when side - viewing laparoscopes are used . the proximal end of the introducer may have a connection point for the insufflation , aspiration and / or washing channel ( s ) such as a luer connection or a hose barb . an insufflation bulb ( 201 ) can be connected to the insufflation connection point . alternatively , other insufflation sources ( such as pumps , plumbed pressurized gas , etc ) may be connected to the insufflation connection point . this allows for greater flexibility in choice of insufflation apparatus and also allows for replacement of the insufflation apparatus without necessitating replacement of the entire introducer . in another embodiment , the proximal end of the introducer may contain a number of valves ( 112 ) for controlling the insufflation , aspiration , and wash functions of the introducer . one possible arrangement of separate channels and valves for this purpose , but in no way intended to be limiting , is shown in fig3 . insufflation air and wash water may be supplied by an air pump and water bottle built into the endoscopic illuminator or as standalone components . alternatively plumbed - in air or co2 , water and vacuum lines in the operating room may be used . aspiration may be provided by a vacuum pump or similar vacuum source . the proximal end of the introducer may also have a flange or tabs or handle ( 111 ) that facilitate easier handling of the laparoscope and introducer assembly . this handle may also contain a number of valves for controlling the insufflation , suction and wash functions of the introducer . the valves may be deployed in any arrangement that allows for separate and reliable control of the insufflation , wash and aspiration functions . the handle may be positioned at an angle to the main structure of the introducer so that it can be manipulated and operated in a gun fashion . an alternative embodiment may have all of the features of the aforementioned embodiments , except that the main channel at the distal end of the introducer does not have a window that seals and separates the endoscope from the endoluminal space ( fig4 ). in this embodiment , the laparoscope tip is exposed to the endoluminal surface and the introducer contains a circumferential seal ( 108 ) between the exterior of the laparoscope and the interior surface of the main channel of the introducer so as to contain the insufflation air within the endoluminal cavity . the seal may be located anywhere along the length of the introducer main channel containing the laparoscope shaft . the seal may be composed of rubber , silicon or other compliant and sufficiently impermeable material . the seal may be in the form of a valve , a wiping seal , 2 - stage seal ( e . g . a cross slit valve and backup seal ) or compliant compression seal ( e . g . an o - ring ). such an embodiment may also integrate the insufflation and main channels of the introducer into a single channel . such an embodiment may also integrate one or more separate ancillary channels to direct a spray of wash water across the tip of the laparoscope or ancillary channels for the irrigation and aspiration of fluids . in another embodiment , shown in fig5 , the introducer may feature a connection mechanism ( 113 ) midway between the distal and proximal ends such that the device may be assembled prior to insertion of the laparoscope . the connection may be in the form of a threaded connection , snap - fit , twist & amp ; lock or compression connection and shall prevent leaking of insufflation gas and the transfer of any fluids in ancillary channels . the connection may feature a seal of any type described herein ( fig6 , 114 ) so as to maintain insufflation pressure in the connection . in another embodiment the introducer may feature a removable handle extending at any non - parallel angle in relation to the tube axis . this handle may also contain the valves used to control insufflation , wash / irrigation and aspiration functions . such an embodiment is shown in fig7 . in this embodiment the handle ( 115 ) may be a reusable component that attaches to a single - use tube ( 116 ) that would be inserted inside the patient . the reusable handle may contain reusable or single - use valves ( 117 ) and fluid channels ( 118 ) that connect to the main and / or ancillary lumens . the handle may be positioned at an angle to the main structure of the introducer so that it can be manipulated and operated in a gun fashion . while the invention has been described in the context of examination of an anastomosis or surgical margin in the rectum of a patient following lar surgery , it will be readily apparent to those of skill in the art that the introducer of the present invention could be used in other contexts . for example , alternate embodiments of the introducer could be deployed in other proximal regions of the bowel or in other body orifices where it would be advantageous to have an introducer that provides multiple channels for imaging and other functionalities ( such as irrigation and aspiration ) and that provides protection for the surrounding tissue from the surfaces of the laparoscope . as has been described herein in the context of lar surgery , the alternate embodiments of the introducer could be used in conjunction with a conventional , white - light laparoscope or with an endoscope capable of near infra - red fluorescence illumination and imaging . while the endoluminal introducer has been illustrated and described in connection with preferred embodiments shown and described in detail , it is not intended to be limited to the details shown since various modifications and structural changes may be made without departing in any way from the scope of the present invention . the embodiments chosen and described explain the principles of the invention and its practical application and do thereby enable a person of skill in the art to best utilize the invention and its various embodiments

an introducer for use during endoscopic procedures provides insufflation , washing , and aspiration functions , and provides for the protection of the endoluminal surface during laparoscopic examination of an anastomosis or suture line following low anterior resection of the bowel . the introducer may be designed for the insertion of an endoscope capable of white light and / or near infra - red fluorescence imaging into the rectum for analysis of an anastomosis following low anterior resection of the bowel .

an eyemask of a first embodiment of the present invention is shown in fig1 , where 100 is the eyemask itself , and 101 illustrates an area light emitter combined with a lightguide and which is substantially larger than light exit windows 102 designed to illuminate the eyes . the mask can be attached , for example , by a strap 103 to the wearer &# 39 ; s head . in a second embodiment of the invention , one or more area light sources such as 101 a and 101 b may be used as shown in fig2 . fig3 illustrates a third embodiment of the invention in which the emitter and lightguide 101 might take up substantially the entire area of the light mask to maximize the light output or to reduce the luminance required from the source . there are several important benefits with this approach . first , heat dissipation becomes negligible and no area of the mask feels warm to the wearer . second , the invention enables the use of low intensity light sources or to operate light sources at extremely low luminance . the mask can utilize a number of light sources , for example oled ( organic light emitting diodes ), electroluminescent films , chemiluminescent layers , phosphorescent layers or even bioluminescent materials . in one embodiment , oled is used as the light source . the oled source is ideally 2 - 1000 times larger than the emissive area required for the eyes . for example , the emissive oled face can be 20 × 5 cm while the area illuminating the eyes can be 1 × 1 cm for each eye . the oled area can take up substantially the whole area of the eye mask . correspondingly , the oled device is run at lower luminance . the device can be operated at reduced voltages and current density , which increases the lifetime of the oled source . reduced voltage operation is highly desirable for portable devices . in many oled sources the power efficiency is improved at low luminance . thus the invention also enables such devices to be run in a regime where they are more efficient . in another embodiment long decay phosphorescent materials are used as the light source . the phosphorescent source is ideally 2 - 1000 times larger than the emissive area required for the eyes . for example , the emissive phosphorescent layer can be 20 × 5 cm while the area illuminating the eyes can be 1 × 1 cm for each eye . the phosphorescent layer can take up substantially the whole area of the eye mask . in turn the light output of the phosphorescent layer is amplified to higher intensity by the light guide . the invention therefore enables very low intensity afterglow materials to be used , yet provides sufficient light levels for the treatment of the eye . in yet another embodiment , chemiluminescent or bioluminescent materials are used as the light source . the chemiluminescent source is ideally 2 - 1000 times larger than the emissive area required for the eyes . for example , the emissive chemiluminescent surface can be 20 × 5 cm while the area illuminating the eyes can be 1 × 1 cm for each eye . the chemiluminescent layer can take up substantially the whole area of the eye mask . in turn the light output of the chemiluminescent layer is amplified to higher intensity by the light guide . the invention therefore enables very low intensity chemiluminescent materials to be used , yet provides sufficient light levels for the treatment of the eye . the light guide used in the mask can propagate light towards the eye using adjacent layers of low optical index materials or reflective layers . the light guide in the mask may optionally comprise at least one luminescent dye to effectively capture the light emitted by the area source . the dye may be used to define the spectra of the light emitted into the eye . in order to compensate for variations of light intensity with time , the mask may comprise one or more photochromic layers . for example , phosphorescent or chemiluminescent sources exhibit decaying luminance with time . by including a photochromic member , it is possible to reduce the initial brightness and make the output illumination more even with time . as the luminance of the area source decays the photochromic layer becomes gradually more transparent , effectively providing a simple compensation mechanism . fig4 is a crossection view of an area of the mask 20 with an area emitter with the eye region 6 emitting light into the eyes or onto the eyelids of the patient . the device comprises a lightguide 1 optionally doped with a luminescent dye . layers 2 and 3 are low index materials designed to ensure total internal reflection of the light entering layer 1 . an emissive layer 8 is provided , with an area substantially larger than the eye region 6 . light emitted by emissive layer 8 is absorbed by the dye 5 and is reemitted into layer 1 . the path of light 7 is then guided via internal reflection to the eye region 6 . the mask may further comprise optionally a reflective layer 9 and a protective layer 10 . the eye region 6 comprises a light outcoupling feature such as embossed or moulded features . this region may also contain pigment particles to scatter light for efficient outcoupling . any suitable outcoupling technique can be used . fig5 illustrates a technique for charging the mask when the emissive layer 8 comprises long afterglow phosphorescent materials . the layer 8 can be charged by external incident light 4 , which can be ambient light or any suitable light source . in this embodiment the device might be charged by a dedicated light charger unit . the charger may be an enclosure containing one or more illuminating sources such as leds or incandescent bulbs . the charger may also be in the form of an illuminator sheet with which the mask is brought into contact . fig6 is a crossection view of a mask 20 with an area emitter 8 and the eye region 6 emitting light into the eyes or onto the eyelids of the patient . the device comprises a lightguide 1 optionally doped with a luminescent dye . layers 2 and 3 a are low index materials designed to ensure total internal reflection of the light entering layer 1 . layer 3 a may optionally be a reflective layer such as metal . the light emitting layer 8 has an area substantially larger than the eye region 6 . light emitted by 8 is absorbed by the dye 5 and is reemitted into layer 1 . the path of light 7 is then guided via internal reflection to the eye region 6 . the mask may further comprise a protective layer 10 . fig7 is a crossection view of a mask 30 with area emitters 8 and 8 a on both sides of the lightguide 1 in order to further increase the area of the source . an optional reflective layer 9 a is provided to prevent escape of the light from the surface of the mask . in this embodiment the total light output can be further increased or the luminance of the source reduced . the eye region 6 emits light into the eyes or onto the eyelids of the patient . the device comprises a lightguide 1 optionally doped with a luminescent dye . layers 2 and 3 a are low index materials designed to ensure total internal reflection of the light entering layer 1 . the light emitting layers 8 and 8 a together have an area substantially larger than the eye region 6 . light emitted by light emitting layers 8 and 8 a is absorbed by the dye 5 and is reemitted into layer 1 . the path of light 7 is then guided via internal reflection to the eye region 6 . the mask may further comprise protective layers 10 and 10 a . fig8 illustrates a mask having a foldable structure with two sets of area emitters comprising segments 20 a and 20 b . in one embodiment , the emitters comprise long afterglow phosphorescent layers in each segment . this mask can be conveniently charged in the open state as shown in fig8 ( i ). external light 4 from the ambient or from a light charger unit excites the phosphorescent material causing it to glow following excitation . the mask can be folded as shown in fig8 ( ii ). the mask 35 is shown in its closed state in fig8 ( iii ). light irradiated from either side is captured in the lightguide and propagated toward the eye via internal reflection . in this embodiment the emissive area is significantly larger than the area to illuminate the eyes . for example , the total emissive area can be as large as 400 cm 2 , while each of the areas illuminating the eye can be 1 cm 2 . fig9 further illustrates a foldable eyemask 35 with two parts 20 a and 20 b having absorbing / emitting layers . preferably the part 20 a shining light on the eye is folded inwards to secure it to the head when strapped . fig1 illustrates a preferred embodiment of the mask 40 in which the lightguide 1 is tapered or narrowed towards the edge of the mask . this reduces the number of reflections for the light emitted at the edge due to the gradually increasing angle of reflection from the low index layer 2 and / or reflective layer 9 . the edge of the lightguide might also be rounded to reduce outcoupling and loss of light at the edge . in this embodiment light emitted from the area source 8 is coupled into the lightguide material 1 . the lightguide may optionally be doped with a dye . outcoupling is effected via regions 6 a and 6 b . fig1 is further embodiment where an additional region is disposed within the lightguide . region 12 is doped with a dye 5 to effect conversion or correction of the emitted wavelength of the light 7 . fig1 illustrates another embodiment , in which the eyemask comprises a further optical element 13 to couple light in close proximity to the eye or eyelid . element 13 may be a polymer optionally shaped into a lens . this portion may also comprise a gel material to make soft contact with the eyelids . the gel may have additional functionality of cooling , for example , by placing it in a refrigerator prior to use . fig1 . illustrates a further embodiment with a light controlling layer 14 . this layer may comprise a photochromic material , which attenuates the light at high intensities while staying substantially transparent at low intensities . such an element is an effective method to control light intensity variations from the source and is especially useful when the light source is phosphorescent or chemiluminescent . the invention may utilize any area source , for example oled , bioluminescent , phosphorescent coatings , e . g . luminophore , or chemiluminescent emitters . the mask might comprise one or more area sources , for example two sources on each side of the mask with the lightguide positioned in the middle . the two sides may form a foldable structure . to benefit from sources of low luminance the area of the source is at least twice the area of the outcoupling region provided to illuminate the eyes . preferably the source is between 2 to 1000 times than the outcoupling region . more preferably , the source is between 4 to 200 times larger than the outcoupling region . even more preferably the source is between 10 to 100 times the size of the area illuminating the eye . the area illuminating the eyes or eyelids is preferably between 1 mm 2 to 20 cm 2 . more preferably , the area illuminating the eyes or eyelids is between 0 . 1 cm 2 to 10 cm 2 . even more preferably , the area illuminating the eyes or eyelids is between 1 cm 2 to 5 cm 2 . the source should be structured in a manner that improves light coupling into the waveguide or on to the wavelength conversion materials . such structuring may include the formation of 2d or 3d photonic crystals to direct the light emission or larger scale structures formed by , for example , deposition onto non - planar surfaces such as microprisms , or moulding into non - planar shapes . oled sources might include luminescent or phosphorescent emitters . oled films can be manufactured by any suitable technique , for example evaporation , solution coating techniques or printing . the source might comprise small molecule or polymeric materials . the emission colour can be defined by the choice of oled materials . the oled source comprises at least one emitting surface coupling to the lightguide . optionally inorganic thin film luminescent or electroluminescent layers might be used . these may include inorganic quantum dots or inorganic luminescent or transport materials instead or in addition to oled materials . the oled source can be provided on a rigid substrate such as glass . ideally the oled source is provided on a flexible substrate such as polyester ( pet ) or polyethylene naphthalene ( pen ). any suitable polymeric substrate and barrier material can be used . since the invention enables running the oled at lower luminance , less perfect encapsulation is acceptable . it is estimated that in an optimized mask configuration , the luminance of the oled source can be reduced by a factor of 2 - 100 . when oled area sources are used the mask comprises a power source such as a battery . low voltage (& lt ; 10v ) operation is preferred for safety reasons as well as for reducing the size and complexity of the power source . ideally the power source is less than 6 v , more preferably less than 3 v . importantly , the invention enables running oled at low voltages and current densities . in one embodiment the area light source comprises phosphorescent or luminescent materials that exhibit long glow after excitation . for example , following a light exposure they glow for minutes or hours . such materials make it possible to provide battery free phototherapy devices with the capability to recharge the device for prolonged light emission . materials with delayed phosphorescence excited by any electromagnetic radiation can be considered , for example infrared light or heat . such materials can be formed into a film , sheet or coating to provide an area , light source . the sheet or coating may comprise substantially the entire area of the mask , coupling light into the lightguide described in the present invention . materials particularly relevant to the invention are long decay luminophore materials where the re - emitted light is slowly released over a period of time after initial excitation . suitable materials include , but are not limited to , those described in u . s . pat . no . 5 , 424 , 006 and u . s . pat . no . 5 , 686 , 022 . suitable materials include those manufactured by nemoto & amp ; company , tokyo and are available under the brand name luminova having the general formula mal 2 o 4 , where m is one or more metals selected from strontium ( sr ), calcium ( ca ), barium ( ba ), magnesium ( mg ) activated by europium ( eu ) and at least one co - activator selected from lanthanum ( la ), cerium ( ce ), praseodymium ( pr ), neodymium ( nd ), samarium ( sm ), gadolinium ( gd ), dysprosium ( dy ), holmium ( ho ), erbium ( er ), terbium ( tb ), thulium ( tm ), ytterbium ( yb ), lutetium ( lu ), tin ( sn ), manganese ( mn ) and bismuth ( bi ). chemical compositions of exemplary materials for use in the invention include , but are not limited to : sral 2 o 4 : eu ; sral 2 o 4 : eu , dy ; sral 2 o 4 : eu , nd ; sr 4 al 14 o 25 : eu ; sr 0 . 5 ca 0 . 5 al 2 o 4 : eu , dy ; baal 2 o 4 : eu , nd ; baal 2 o 4 : eu , sn ; zns : cu ; zns : cu , co ; zns : mn ; zns : ag ; bamgal 10 o 17 : eu ; bamgal 10 o 17 : mn , eu ; sr 2 p 2 o 7 : eu ; cawo 4 ; cawo 4 : pb ; srga 2 s 4 : eu ; cepo 4 : tb ; mgwo4 ; y 2 o 3 : eu ; y 3 al 5 o 12 : ce ; ( ba 1 - x sr x ) 5 ( po 4 ) 3 ( f , cl ): eu ; ( y 1 - x - y gd x lu y ) 3 ( al 1 - y ga y ) 5 o 12 : ce ; ( y 1 - x gd x ) 2 o 3 : bi , eu ; ( y 1 - x p x ) 2 o 4 : eu ; yvo 4 : eu ; y 2 o 2 s : eu . chemiluminescent sources may also be provided as the area light emitter . such light sources exploit the light emission associated with the product of the chemical reaction between at least two reactants . a common example of such light source is the so - called glow stick where a fluorescent dye is excited by the decomposition of the product of the reaction between hydrogen peroxide and oxalate ester . particularly attractive to the invention in the case of a single use phototherapy device is a system where one of the reactants is contained in a vessel which is broken by application of pressure ( or folding ) to allow the reactants to mix and initiate the chemical reaction responsible for light emission . the reactants may be included in a sheet comprising a gel . the sheet may take up substantially the entire area of the mask , coupling light into the lightguide described in the present application . the lightguide may comprise substantially the whole area of the eye mask . preferably the lightguide comprises between 5 % to 100 % of the mask area . more preferably the lightguide comprises between 10 % to 95 % of the mask area . the lightguide is the same size or larger than the light source . suitable lightguide constructions include a polymer core with a high index material and surrounding low index polymer layer ( s ), which may extend to both sides of the lightguide . where required , for example in the case where the refractive index of the light source ( i . e . oled source ) is substantially higher than the low index layer or even the higher index core , an additional high index coupling layer such as narrow angle high gain grin diffusers ( for example those offered by microsharp ltd ) can be placed in between the source and waveguide . where a wavelength conversion layer is used , an appropriate position would be between the low index cladding and high index core , in order to take advantage of supercritical angle fluorescence ( saf ) which allows the preferential injection of converted light into waveguided modes of the high index core . appropriate materials for the waveguide should have a high degree of transparency in the spectral region of interest , and where required should be flexible and appropriate for the particular method of manufacture . low index materials therefore may include my - 132 ( my polymers ltd ), with refractive index 1 . 32 . a high index core could include material such as polysiloxanes ( wo / 2003 / 011944 ) with refractive index of up to 1 . 581 . this combination of materials would have a critical angle of 58 degrees , and saf emission from the interface would couple up to approximately 70 % of light directly into the waveguided modes . these may include polystyrenes , poly ( ethylene terephthalate ), a transparent polyolefin , in particular a clarified polyolefin , for example clarified polypropylene , poly ( methyl methacrylate ) ( pmma ), transparent polyamide or polycarbonate and perfluorinated polymers such as polyperfluorobutenylvinylether , polysulphones , polyether sulphones and polyacrylates . pmma and polycarbonate are two transparent thermoplastics of choice because of their ease of processing , their availability on the market , their high transparency in the visible range and refractive index in the visible range . other materials which are recommended for use with fluorescent dyes include styrene - butadiene . for the low index cladding , polymers such as teflon fep , pctfe ( polychlorotrifluoro - ethylene ) or pvdf as well as uv curable low index polymers such as the opti clad ( manufactured by ovation polymers ) series , may be chosen , which have refractive indices as low as 1 . 33 . further examples of polymers can be found in “ encyclopedia of polymer science and engineering ”, 2nd edition , j wiley and sons and “ polymer handbook ”, 4th ed . ; john wiley & amp ; sons , 1999 . the lightguides may be further surrounded by reflectors , as described in a later section in order to recycle non - waveguided light , both allowing light from the initial light source to be down converted on later passes and also recycle non - saf emitted light . in general , structures constructed so that the majority of the light is waveguided by total internal reflection ( tir ) will have better device performance . additionally the high index core of the lightguide may be doped with light accumulation or wavelength converting chemical . the ends of the lightguides may be squared and mirrored , or they may be tapered to a point or curved edge such as a parabola such that waveguided light may be turned and reflected towards the centre of the guide again with minimal reflections from metallic surfaces . the lightguide may also be a gel material within a polymer shell . the lightguide may comprise wavelength conversion materials such as dyes . such materials can aid coupling of light into the lightguide . wavelength conversion is also an approach to adjust the wavelength emitted into the eyes . by using such materials it is possible to convert less effective wavelength light into an effective spectrum . suitable materials or mixtures of materials are those which absorb light at a first wavelength and subsequently emit light at a second wavelength which is different from the first wavelength . the emitted light might be result of fluorescence and / or phosphorescence depending on the type of material or mixture of materials . in addition the nature of the material or mixture of materials and associated energy conversion mechanisms will dictate if the wavelength emitted is larger or smaller than that of the absorbed light . light can be absorbed by one species and re - emitted by a second species following non - radiative energy transfer . suitable wavelength conversion materials may be of any type including but not limited to coumarins ; perylenes ; xanthenes ; thioxanthenes ; fluoresceins ; rhodamines ; azlactones ; methines ; oxazines ; thiazines ; phtalocyanines ; stilbenes ; distilbenes ; distyrenes ; azomethines ; phenanthrenes ; rubrene ; quinacridones ; naphtalimides ; methines ; pyrazolones ; quinophthalones ; perinones ; anthraquinones . materials particularly relevant to the invention are those which can be efficiently doped into light guide materials without compromising their optical function and which exhibit a high quantum yield . of particular interest are fluorescent dyes manufactured by basf and available under the brand name lumogen f dyes . other commercial materials of interest include those available under the following brand names macrolex ( bayer ), hostasol ( clariant ), thermoplast ( basf ), solvaperm ( clariant ), sandoplast ( clariant ), amaplast ( color - chem ). quantum dot materials may also be used to adjust the emission characteristics of the mask . suitable quantum dots materials include but are not limited to cdse , cdte , zns , znte , znse , cds , hgs , hgse , hgte , cdtese , cdtes , znsse , zntese , znste , cdznse , cdznte , cdzns , gaas , gap , gasb , gan , inn , inp , inas , insb , ingap , ingaas , ingan , alingan , alingap , alingaas , si , ge . the above wavelength conversion materials may also be used as part of the area light source or the outcoupling region . the mask comprises at least one outcoupling region as an exit window to shine light onto the eye . outcoupling from this region may be achieved through the use of scattering , embedded nanoparticles and / or quantum dots which may be doped or undoped , of various shapes and orientations such as rods , triangles or spheres , optical interference structures such as diffraction gratings or holographic structures , photonic crystals which may be either 2d or 3d , macroscopic shaped structures such as , but not limited to , micropyramids and microprisms , microlenses , lens arrays , grin structures , fiber optics for either scattering or redirection of light through waveguiding or other coupling methods through variation of refractive index . the outcoupling region may either be directly on the side of the escape window area forming part of the window , it may be an external component attached to the window , or it may be on the opposite side of the waveguide to the window ( i . e . diffractive components ) additionally bulk components such as scattering particles , nanoparticles and lumophores may be present in the waveguide near the window for outcoupling , or they may form part of external components . concave or convex outcoupling schemes may be employed . reflectors will have two primary purposes . the first is to ensure that light that is not wavelength converted and will be substantially reflected through the wavelength conversion region so that a significant proportion of light will be converted on later passes as opposed to being absorbed and lost . the second is to provide supplementary waveguiding to light intended for emission that has not been injected into supercritical waveguided modes in the waveguide core . in the case of the saf layer above , this would make up around 30 % of the light . the reflectors may consist of periodic or aperiodic dielectric multilayers which may be either isotropic or anisotropic in nature , with the particular arrangements of refractive indices , thicknesses and index ellipsoid orientations chosen to optimise reflections of light which is not captured within the waveguide to either ensure its passage to the outcoupling region or to increase the chances of absorption and re - emission at the wavelength conversion layers . such materials may either be custom arrangements of layers which may be extruded or laminated onto the core or commercially available films . the choice of materials may also be chosen to allow their dual use as barrier layers to lengthen the lifetime of the devices . in the event that no practical arrangements can be found , it would also be possible to used metallic or metallised layers as a reflector . however for large numbers of reflections , the efficiencies of metallic layers are significantly poorer . the mask may optionally comprise one or more optically variable layers for modulation of the light coupling . this may for example be a photochromic light absorber ( such as silver chloride ) or may change refractive index such that index matching between layers ( 3 ) or ( 5 ) and ( 9 ) increases and decreases according to the desired conditions . such layers that change properties based on conditions including but not limited to , ph and chemicals ( chemochromic ), humidity ( hydrochromic ), temperature ( thermochromic ) and pressure may also be used . the optically variable layer may be between the light source and waveguide , in the waveguide outcoupling area , or in the additional pad ( 13 ). the layer may consist of pure photochromic chemical , a doped material such as polymer , or be dispersed in a solution . the range of suitable materials is large and includes inorganic materials such as zinc halides and silver chloride , as well as organic materials such as spirooxazines which have fast switching in gels and spiropyrans which can be cross linked with other molecules . such organic molecules as these may be tuned to specific wavelength switching requirements . the eyemask is ideally flexible or conformal . the mask may be provided for both eyes or for one eye or as a patch . the form factor and bend angles of the waveguide should remain small with respect to the thickness of the waveguide in order to ensure an acceptable level of total internal reflection is maintained . the lightguide may comprise a soft material such as a gel . the gel may provide an additional cooling function to soothe the eyes . the external surface of the mask may be covered with a fabric material or other soft layer or layers such as a foam . these layers can have the function to provide vapour transmission . the eyemask can be manufactured by a variety of techniques . the lightguide is preferably manufactured by moulding , lamination , stretching , forming of the lightguide as well as emissive components . the outcoupling features can be formed in a single moulding step when forming the mask or defined in a second step by embossing or coating further layers . the area light source such as oled or phosphorescent source may be laminated or attached to the lightguide using an adhesive . the source may also be directly coated onto the lightguide by solution coating techniques such as screen -, flexo -, gravure -, or inkjet printing , spray coating or dip coating . the source may also be deposited on the lightguide by evaporation . in patent application gb2410903a , arden describes an eye mask device using inorganic led light sources to illuminate the eyes of patients suffering from retinal diseases during their sleep . because the treatment is carried out during sleep a phototherapy device with minimum discomfort for the user is advantageous . because of the low light intensity required and the long illumination time available a passive phototherapy device using luminophore for slow release of light is particularly suitable . this example describes such device . a light guide sheet element ( less than 2 mm thick in thickness ) could be moulded in the shape of an eye mask as to cover the eye of a patient as shown in fig1 . the element is formed by injection moulding silicone resin containing 0 . 1 % of lumogen f green 850 ( basf ). the light guide is coated on both sides with a 5 microns thick lower index polymer such as polychlorotrifluoro - ethylene . a blue light emitting oled is formed on top of the lightguide using 4 , 4 ′- bis ( 2 , 2 ′ diphenilvinyl )- 1 , 1 ′- biphenyl ( dpvbi ) as the emitter , for example by using a device structure described by othman et al in proc . ieee of icse , 2004 . the blue emission centered at 483 nm is then absorbed by the lightguide and transmitted to the emitting surface . on the opposite side of the oled , two light delivery areas are defined to coincide with the eye of the patient so that the light emitted by the phototherapy device can illuminate the eye lids of the patient . these areas assist outcoupling by surface structuring to the attachment of a soft sac containing mineral oil or silicone gel of an equal or higher refractive index to the core . this allows light to be coupled directly from the lightguide core into a non - waveguiding structure directly over the eye , and allowing light into the eye . the use of a gel further assists comfort and coupling between the lightguide mask and eye . a large proportion of the light emitted by the oled enters the lightguide , where it is absorbed by the fluorescent die and re - emitted as light with peak wavelength around 500 nm . the 500 nm light is emitted through the emitting surface is adequate for absorption rod cells . it will be appreciated by persons skilled in the art that the above embodiments have been described by way of example only and not in any limitative sense , and that various alterations and modifications are possible without departure from the scope of the invention as defined by the appended claims .

an apparatus for directing electromagnetic radiation into a respective pupil of at least one eye of a user is disclosed . the apparatus comprises first radiation emitting means comprising at least one radiation emitting layer adapted to emit electromagnetic radiation and second radiation emitting means adapted to direct electromagnetic radiation into at least one eye and / or onto at least one eyelid of a user . a light guide is adapted to receive radiation emitted by the first radiation emitting means and to direct at least part of the radiation to the second radiation emitting means , wherein a total surface area of the first emitting radiation means from which radiation is emitted is larger than a total cross sectional area of a beam of radiation entering the or each pupil of the user in use , in a direction transverse to an optical axis of the beam .

fig1 shows a typical wearer wearing the safety device of the present invention . in the embodiment as shown in fig1 , the device comprises eyeglasses having a left eye lens 2 and a right eye lens 4 connected by a bridge 6 . a support member 8 fits over the bridge of the nose . a first side support member 10 extends from the left eye lens as shown in fig1 . a second side support member 12 extends from the right lens and along the side of the wearer &# 39 ; s head . the side support members in one embodiment extend in a generally horizontal manner along each side of the wearer &# 39 ; s head , and then extend downwardly and generally vertically , and then again extend generally horizontally into the ear of the wearer . each of the left eye lens and right eye lens are made of appropriate impact resistant materials that will resist the impact of debris or projectiles and are made to standards that are required and / or are common for safety glasses . the lenses may be formed of safety glass , or may be formed of impact resistant plastic or other impact resistant materials that are commonly used for safety glasses . the lenses may be transparent , or may be tinted as desired , or required , by the particular application . as demonstrated by fig3 , the safety device of the present invention has a pad or earplug 14 that is mounted at or near the end of each of the side support members . the pad or plug is formed of a resilient material that is both comfortable to the wearer when the pads or plugs are inserted into the ear , and further , the resilient nature of the plug helps to seal the ear canal and helps to absorb sound which would enter the ear canal . the plugs are formed of generally tapered , or otherwise have a reduced dimension , on the end that is inserted into the ear , with a relatively larger dimension where the plugs attach to the side support members . as demonstrated in fig3 , the plugs are mounted to the lower generally horizontal portion 16 of the side support members by a structure that allows the plugs to swivel , pivot and / or rotate . in the embodiment shown in fig3 , a ball and socket 18 relationship between the mounting point for the earplug and the side support member allows the earplugs to rotate relative to the side support members . this structure is one ( 1 ) feature which allows the device to be worn by a large number of users , irrespective of the dimensional relationships of the wearer &# 39 ; s respective heads , eyes , ears and ear canals . as demonstrated in fig4 , the side support members each telescope relative to the lens . this telescoping feature allows the relative length of the side support members to be extended or retracted , so that the distance of the earplugs to the bridge between the lenses can be lengthened or shortened . this is another feature which allows the glasses to be worn by a relatively large percentage of the adult population . in one embodiment , the telescoping feature comprises a slidable member 20 that engages the side support 10 locks by a series of detents 22 and a pin 24 that engages the detents . the pin may be spring biased and mounted to the slidable member 20 . the pin may be pressed inwardly to remove it from the relatively large opening provided by the detents , and moved to another detent having a relatively large opening . as shown , there are three ( 3 ) detents in each side support member . other known methods and devices for telescoping may be used . in another embodiment , the member 26 that adjoins the side support member and extends generally vertically downward from the side support members may be rotated relative to the side support member . this further allows adjustment of the device for more universal use by the population . it is important that , if this generally vertical member 26 rotates relative to the slidable portion 20 of horizontal side support member , that it be capable of locking or fixing in place , so that an inward pressure of the side support members pushing the earplugs into the ears of the user can be maintained . it is important that the earplugs are retained within the ears . the fit of the earplugs within the ear should be such that that the earplugs contact the outer portion of the ear canal , and compress slightly . however , the earplugs should not be uncomfortable to the wearer , or present a risk of injury to the wearer . as shown in fig2 , the side support members 10 , 12 provide inward pressure on the earplugs . it is preferred that the side members are in a spring biased relationship with each other , such that each of the side members provides inward pressure , as demonstrated in fig2 . the dark lines of fig2 demonstrate the position of the side support members in their normal state , with the phantom lines demonstrating the side support members being pushed outwardly as they are placed on the user &# 39 ; s head and the earplugs are placed within the out ear canal of the wear . spring biasing will urge the side support members toward the head of the user and push and hold the ear pads into the ear canals of the user . spring biasing pressure may be provided by the frame of the eyeglasses , such as at the bridge 6 of the eyeglasses , due to the materials used . many plastic materials will provide sufficient inward pressure as required by the invention , so that the side support members may move relative to each other as demonstrated by fig2 . alternatively , spring biasing may be provided in the optional hinge 28 where the side support members join the lenses , or spring biasing may be provided in the frame that supports the lenses of the eyeglasses . the bridge of the eyeglasses should also be comfortable for the wearer , and accommodate wearers in a substantially universal manner , so that a large percentage of workers can wear the device . the removable nose pad 30 may also assist in meeting this goal of the invention . the bridge 6 of the eyeglass frame is provided with a pad support , having a relatively wide opening . removable pads of various sizes may be used to size the eyeglasses for comfort for the wearer , and also to better retain the glasses on the wearer . by using a pad that compresses , a large number of wearers can use the glasses , while at the same time , a compressible material such closed cell foam will help retain the glasses in place on the wearer &# 39 ; s head .

protective eyeglasses provide hearing protection from elevated noise levels . the protective eyeglasses have safety lenses for protection of each of the eyes . support members extend from the lenses of the eyeglasses to the ears , and have earplugs or protectors thereon which are inserted into the ears . the side support members are spring biased towards each other so that the side members provide pressure to hold the plugs in the ears of the wearer . ear plugs are mounted so as to swivel relative to the side support members . the side support members are telescoping and are adjustable in length .

the present invention refers to a medicinal , local composition comprising spermidine for the treatment of a gynecologic disorder with prevailing inflammatory and neurogenic signs named vulvar vestibulitis syndrome ( vvs ). the active ingredient of the present invention is spermidine , a substance of structure nh 2 ( ch 2 ) 3 nh ( ch 2 ) 4 nh 2 , and formula c 7 h 19 n 3 . spermidine is easily incorporated as salt or complex in water - based gynecologic compositions ; or as pure amine in water - free or emulsified gynecologic compositions . example of salt form are formed by spermidine with inorganic acid such as hcl , h 2 so 4 , h 3 bo 3 , h 3 po 4 , etc ., o with organic acid such as acetic , methylsulfonic , ascorbic , lauric , glycolic , lactic , pyruvic , succinic , and citric acid , and the like . in case of use of spermidine pure amine , partial or full anion exchange may take place in situ in contact with acidic substances in composition . analogously , a simple salt such as spermidine 3hcl may undergo acid - base exchange within the composition medium . in a further embodiment , the composition of invention will comprise a supramolecular complex with spermidine for the sustained release thereof . the expression “ supramolecular complex ” as used herein includes polyacid complex formed by polyanionic polymer ( s ) and spermidine as well as the inclusion complex of spermidine into cyclodextrins . technical and operative details are enclosed in co - pending applications wo12 / 017288 and wo12 / 017290 . the main inventive object is a topical medicinal composition for treating vvs , wherein “ medicinal composition ” include drugs , medical devices , and lenitive cosmetics intended for the specific curative purpose . the inventive composition will comprise spermidine in concentration from about 1 % to 0 . 0001 % w / v , more preferably from about 0 . 1 % to 0 . 001 % w / v , even more preferably around 0 . 01 % w / v of the composition . in the inventive composition , the unitary dose of spermidine will be comprised between 1 mmoles and 1 nmoles / unit dose , preferably between 100 μmoles e 10 nmoles / unit dose , even more preferably around 10 μmoles and 100 nmoles / unit dosea . the compositions according to the invention , which are administered vaginally , will be presented in semi - fluid forms such as of gel , cream , ointment , etc ., or in solid form such as tablets , capsule , pessaries , ovules , etc . for the release of around 1 μmole of spermidine . excipients and auxiliary active ingredients to produce a formulation with proper safety , efficacy , patient compliance , aesthetics , acceptability to regulatory authorities , and cost requires are known . e . g ., garg s et al . in compendium of pharmaceutical excipients for vaginal formulations pharmaceutical technology , drug delivery 2001 , 14 - 24 ; listed vaginal excipients , the functional classification , allowed concentrations ( when available ), and regulatory status . the inventive composition may be packaged in ordinary al or plastic tubes for hand application ; or as spray , mousse and other means for the application onto female external genitalia without a direct contact with hand , or other device . in general , no vaginal applicator is needed , unless burdens were widely spread out into the vaginal tract . in another embodiment , compositions of invention comprise spermidine in combination or in conjunction with an anethetic agent to deliver a fast relief from vvs pain . exemplary anesthetic agents include ester - type like benzocaine , chlorprocaine , cocaine , procaine , tetracaine ; and amide - type like lidocaine , prilocaine , mepivacaine , bupivacaine , ropivacaine . for use in combination , spermidine and anesthetic agent may be presented in ratio consistent with the desired effect . in particular , the molar ratio of spermidine to anesthetic agent will suitably be approximately 1 to 300 . preferably , this ratio will be between 0 . 001 to 3 and 1 to 3 , and especially from 0 . 01 : 3 to 0 . 1 : 3 . in another embodiment , compositions of invention comprise spermidine in combination or in conjunction with an estrogenic substance to further improve the therapeutic ratio . exemplary estrogenic substances include estrone , estrone esters , estriol esters , estriol , equilin , equilin esters , estradiene , equilenin , ethinyl estradiol , 17β - estradiol , 17β - estradiol esters ( i . e . benzoate , cypionate , dienanthate , valerate , etc . ), 17α - dihydroequilenin , 17β - dihydroequilenin , 17α - dihydroequilin , 17p - dihydroequilin , 17α - ethynylestradiol , 17α - ethynylestradiol esters , dienestrol , mestranol , mestranol esters , des , phytoestrogen ( s ), tibolone , ethynediol and conjugated estrogens . conjugated estrogens refer to estrogenic steroidal substances in which one or more functional groups ( typically the oh groups ) on the steroid exists as a conjugate ( typically a sulfate or glucuronide ). the conjugated estrogens may be a single conjugated estrogen , or may consist of mixtures of various conjugated estrogens . for administration in combination , spermidine and the estrogenic substance may be presented in a ratio consistent with the desired effect . in particular , the molar ratio of spermidine to estrogenic substance will suitably be approximately 1 to 1 . preferably , this ratio will be between 0 . 01 to 1 and 100 to 1 , and especially from 0 . 1 : 1 to 10 : 1 . the inventive composition may include other additional active ingredients . examples include , but not limited to , anti - infective agent such as antibiotics , anti - fungals , antivirals , biocides ; calcium antagonists such as nifedipine ; heparins such as enoxaparin ; botulin ; gabaergics such as pregabalin , and gabapentin anti - inflammatories ; immuno - suppressant ; plant or algal extracts ; antihistamines ; antioxidants ; and a variety of other ingredients such as astringents , fragrances , dyes , vitamins , sunscreens , deodorants , preservatives , and other customary ingredients . in another embodiment , spermidine is fully or partially replaced by the pa spermine , a substance of structure nh 2 ( ch 2 ) 3 nh ( ch 2 ) 4 nh ( ch 2 ) 3 nh 2 and formula c 10 h 26 n 4 . other inventive compositions may similarly contain a variety of complementary ingredients as those skilled in the art can select using conventional criteria . an investigational device ( id ) for local use was prepared in form of gel having ingredients as set forth below . the resulting transparent gel was packaged in 30 ml al tube in a gmp / glp facility . the general design of clinical protocol is illustrated herein after , with a summary of the key protocol chapter given in brief . change in physical signs of vestibulitis on physical exam after 4 + 4 weeks of treatment by gynaecology visit ranked with a vulvovaginal health index ( vvhi ), whose 1 - to - 5 score is illustrated in table i . change in self - reported , subjective symptoms ( ss ) of vvs from baseline to 4 + 4 weeks by weekly questionnaire , whose 0 - to - 3 score is illustrated in table ii . 1 = light ( tolerable symptoms in few , short episode during 24 hours ); 2 = moderate ( tolerable symptoms for most 24 hours , with limited impairment of daily tasks ); 3 = severe ( hardly tolerable symptoms for most 24 hours , with relevant impairment of daily tasks ). tolerability , scored from excellent to poor , is included on patient &# 39 ; s questionnaire . safety was monitored from the adverse events ( ae ) report , that were recorded at all visits from subject experience or by physician controlled , to be reported and described in full length referring to date of beginning , intensity and duration . signature of the informed consensus ; women complaining a typical vvs , thereby confirmed by a local gynaecologic visit ; collaborative subjects who are able to follow instruction and protocol schedule . presence di cancer or chronic disease with less - then 2 year of life expectancy ; subjects unable to follow the protocol or comprehend scopes and effects ; visit 1 ( v1 , week 0 ): enrolment with baseline assessment , id delivery and instruction to start treatment by 3 applications per week ; visit 2 ( v2 , week 4 ): after 4 weeks of treatment , objective assessment and next id delivery for a new cycle with indication of two applications per week ; visit 3 ( v3 , week 8 ): end of 4 + 4 weeks of treatment with final objective assessment and delivery of the questionnaire . ip was delivered at v1 and v2 with instruction to apply on vulvar area by hand 3 times per week during the first 4 weeks ; followed by 3 times per week during next 4 weeks . a caucasian woman aged 38 presented to the ambulatory asking medication for recalcitrant vvs . beside that , health conditions were good , with no sign of allergy , sensitization , nor immuno - reactivity . she was primipara with regular menstrual cycles . history vulvodynia started 5 years before . past attempts to treat vvs were various with no significant results . she furthermore reported recurrent vulvovaginitis from candidosis . patient performed a pap test within past 6 month with negative response . she accepted to enter the pilot study after signing the informed consensus . first visit ( v1 ) upon external exploration , vulva displayed reddish vulvar vestibulus as well as redness on inner labia minora . by inserting speculum , patient experienced strong pain and contracted perineum muscles . instead , inner vaginal mucosa appeared normal . on ss , patient scored a fair vaginal burning , moderate itching and severe dyspareunia . second visit ( v2 ) after 4 weeks of treatment by 3 weekly applications the patient referred about the increase of itching and burning by week 6 , then treated with local anti - fungal . mucosa looked pink with reduced reddish areas . speculum insert provoked less pain . patient avoided sexual intercourses , hence dyspareunia was scored as unchanged . third visit ( v3 ) after second cycle of 4 weeks by 2 weekly applications , examination revealed an almost normalized vulvar mucosa . patient did not complain nor perceive pain at speculum insertion . during this period an episode of candidosis were medicated with local antibiotic therapy . dyspareunia was scored as moderate . conclusion clinical remission was finally attained , as denoted by objective scores ( ss ) and objective scores ( os ) trends , which are plotted in fig1 and fig2 , respectively . interestingly , the improvement already found at visit 2 ( v2 ) by objective examination did not correspond to the perceived symptoms , which persist or even worsened ( beside the transient burdens due to candidosis in w4 - w5 ) until a sudden improvement noticed from w6 on . nonetheless , the two scores converged at the end of the treatment . an emulsion was prepared by mixing under turbo - emulsifier the oily phase melted at around 70 ° c . with the water - soluble warmed at the same temperature , which end up with a cream having ingredients as set forth below . the resulting cream was packaged in 30 ml al tube under gmp / glp provisions . it provides an immediate pain relief from the very beginning of the spermidine therapy . the emulsion obtained in example 1 was modified by adding 10 mg g of b - estradiol instead of 2 g of lidocaine . the innovation entails the local use of spermidine to treat vvs . it should be understood that the foregoing relates only to preferred embodiments and to applicative examples of the present invention and that numerous modifications or alterations may be made therein without departing from the spirit and the scope of the invention as set forth in the appended claims .

a gynecologic composition contains spermidine to treat vulvar vestibulitis syndrome . in this therapeutic context , spermidine is effective at around one micromole per applied dose in the form of a simple salt or complex , alone or in combination or in conjunction with auxiliary actives such as anaesthetics and estrogens .

referring to fig1 a flexible utility stretcher 11 is disclosed . the stretcher comprises a generally rectangular shaped , light weight , generally tubular aluminum frame 13 . four folding wheel and caster assemblies 15 are disposed adjacent to the four corners of the frame and are held in place by clamps 16 . a fifth folding wheel and caster assembly 17 is disposed such that the wheel and caster assembly , when down and in an operating position , pivots substantially at the center of the stretcher . a top plate 19 extending from slightly past the mid - point of the stretcher , through the mid - point to a point approximately half the distance to one end ( the head end ) of the stretcher , is coupled to the frame 13 and disposed on a top side thereof , that is , on the side opposite the wheel and caster assemblies 15 and 17 . a bottom plate 23 having approximately the same extent as the top plate 19 is coupled to the bottom side of frame 13 , that is , on the opposite side thereof from the top plate 19 . a middle plate 21 , partially interleaved between top plate 19 and bottom plate 23 , extends from a point slightly past the mid - point of the stretcher , through the mid - point , a distance approximately half way to the other end ( the foot end ) of the stretcher opposite plates 19 and 23 . the plates 19 , 21 and 23 are coupled to frame 13 by welds , suitable clamps or other means for securely connecting the plates to the frame . for reasons to be discussed below , plate 21 preferably is in two pieces coupled at hinge 22 extending the width of the plate . inasmuch as weight is an important factor , plates 19 , 21 and 23 should be made of aluminum or other strong , but lightweight material . as noted above , the middle plate 21 is interleaved between top plate 19 and bottom plate 23 at approximately the mid - point of the stretcher 11 . a king pin 29 is disposed at approximately the mid - point of the stretcher and passes through plates 19 , 21 and 23 . frame 13 comprises telescoping mid - portions 25 which can be retracted such that the frame is split into two portions separated from each other at approximately the middle of the stretcher . when the telescoping mid - portions 25 are retracted , the two portions of the stretcher are connected only at the king pin 29 pivot point . accordingly , the end portions of the stretcher may be freely pivoted around the king pin 2 when telescoping mid - portions 25 are retracted . the interleaved plates 19 , 21 and 23 are slightly separated from each other to allow a free pivoting motion when the telescoping mid - portions 25 are retracted . as best seen in fig5 in the area adjacent king pin 29 , thrust bearing surfaces 42 separate plates 19 , 21 and 23 . frame 13 further comprises telescoping end portions 27 . when telescoping end portions 27 are retracted , the overall length of the stretcher is decreased allowing the stretcher to fit into elevators and other relatively small spaces in which the full length stretcher is unable to fit . when telescoping end portions 27 are extended , the stretcher is at its full length . the stretcher further comprises , as shown is fig3 and 4 , a two piece cover 34 on top of the stretcher . a two piece mattress 35 lies on top of cover 34 . the portion of the cover 34 adjacent the foot end of the stretcher includes three hinges 36 , 38 and 40 extending the width of the cover and disposed adjacent telescoping end portions 27 . when the telescoping end portions 27 are in an extended position , cover 34 lies flat on top of the stretcher . when the telescoping end portions 27 are in a retracted position , the foot end portion of the cover flexes at hinges 36 , 38 and 40 forming an upside down v - shaped section . the upside down v - shaped section enables the knees to be maintained in a flexed position . alternatively , by rotating a patient 180 °, the upside down v - shaped section is used as a back rest for a patient enabling the patient to maintain his upper torso in a raised position . the mattress 35 includes hinges 36 &# 39 ;, 38 &# 39 ; and 40 &# 39 ; corresponding to hinges 36 , 38 , and 40 of cover 34 which cause the foot end portion of the mattress to form a corresponding upside down v - shaped section when the telescoping end portions 27 are in a retracted position . referring again to fig1 the invented stretcher further comprises a monorail assembly 31 coupling the wheel and caster assembly 17 to king pin 29 . the monorail assembly 31 allows the wheel and caster assembly 17 to be placed in a retracted position when necessary to store the stretcher in an emergency vehicle and , when the stretcher is in use , to be moved into a down and operating position such that the caster and wheel assembly pivots about the mid - point of the stretcher at king pin 29 . unlike the four corner wheel and caster assemblies 15 , the wheel and caster assembly 17 cannot be clamped or otherwise connected to the frame 13 of the stretcher . thus , the monorail assembly 31 provides the structural integrity needed at the pivoting king pin 29 , while allowing the wheel and caster assembly 17 to be retracted to reduce space when the stretcher is stored . in an alternate embodiment , instead of monorail assembly 31 and wheel and caster assembly 17 , four wheel and caster assemblies can be coupled to the ends 26 ( see fig3 ) of frame 13 adjacent king pin 29 to provide the necessary integrity at the king pin . the stretcher further comprises tubular cross - members 44 , 46 , 48 and 50 extending the width of frame 13 . two of the cross - members 44 and 46 are disposed approximately equally spaced through the head end half of the stretcher while the other two cross - members 48 and 50 are disposed approximately equally spaced through the foot end half of the stretcher . the cross - members are welded , clamped or otherwise attached to the frame and provide structural support therefor as well as support for cover 34 . in a preferred embodiment , the cross - members are held in place by clip rings 105 . the cover 34 is connected to the cross - members 44 , 46 , 48 and 50 with , for example , machine screws which extend through the cover into threaded engagement with the cross - members . additionally , a tubular member 52 , disposed at the longitudinal axis of the stretcher extends from the head end of the stretcher through cross - member 44 , to cross - member 46 . cabling 54 , necessary for a release mechanism to be described below , passes through members 52 and 46 . details of the monorail assembly 31 will now be described with reference to fig6 and 8 . the monorail assembly is attached to bottom plate 23 by four bolts 55 or other suitable means for insuring that the assembly is securely attached to the bottom plate 23 . the assembly is generally rectangular in shape with one end formed into an angle of approximately 90 ° in the direction of the top surface of the stretcher . the assembly 31 includes tracks 57 disposed at its sides , only one of which may be seen in fig6 . a depression 60 extends the length of the assembly . wheel and caster assembly 17 slidingly engages monorail assembly 31 with portions 58 extending into tracks 57 in a sliding relationship as best seen in fig8 . wheel and caster assembly 17 includes a pin 68 which extends longitudinally through the axis of the assembly . when the wheel and caster assembly 17 is in a retracted position , pin 68 extends through bore 65 in the monorail assembly . by pulling the wheel of wheel and caster assembly 17 to pull pin 68 out of bore 65 , the assembly is free to slide the length of tracks 57 such that pin 68 engages bore 63 in the monorail assembly thereby locking wheel and caster assembly 17 into its operating position . similarly , if it is desired to move wheel and caster assembly 17 back into its retracted position , the wheel is pulled so as to disengage pin 68 from bore 63 and the assembly is slid back along tracks 57 until pin 68 engages bore 65 thereby locking the assembly in its retracted position . expansion biasing spring 70 disposed on pin 68 is used to hold pin 68 in bore 63 or 65 until a pulling force is applied to wheel and caster assembly 17 to disengage pin 68 from the bore . the details of wheel and caster assemblies 15 will now be described with reference to fig9 through 12 . it is to be noted that each of the four wheel and caster assemblies 15 have an identical structure . thus , the following description applies to all four wheel and caster assemblies 15 . the wheel and caster assembly 15 includes a collar 71 having two ends with circular openings through which the frame 13 of the stretcher passes . clamp 16 is disposed between the two ends of rotating collar 71 . the clamp forms a cylindrical sleeve through which frame 13 passes . the clamp is secured to the frame by set screws ( not shown ) or other suitable means which bear against the frame . the clamp 16 includes a bore 73 and a bore 75 approximately perpendicular to each other . wheel caster assembly 15 includes a pin 77 and expansion biasing spring 79 held in place by lock washer 78 . by pulling on the wheel of wheel and caster assembly 15 , collar 71 is free to rotate around frame 13 such that the entire wheel and caster assembly 15 rotates . if it is desired that the wheel be in an operating position , the assembly is rotated until pin 77 engages bore 73 . similarly , when it is desired that the wheel be in a retracted position , the assembly is rotated until pin 77 engages bore 75 . preferably , clamp 16 includes flanges 80 and 80 &# 39 ; to limit the rotation of wheel and caster assembly 15 to the approximately 90 ° necessary for proper operation . that is , when collar 71 engages flange 80 or 80 &# 39 ; the wheel and caster assembly is released and the force exerted by biasing spring 79 will cause the pin 77 to engage bore 75 or 73 , as appropriate . the details of telescoping mid - portions 25 and their associated locking mechanism will now be described with reference to fig1 and 14 . telescoping mid - portions 25 are comprised of two identical assemblies , one disposed within the head end half of frame 13 at one side thereof , and the other disposed in the head end half of frame 13 at the other side thereof . the two telescoping members 25 are identical as are the corresponding release mechanisms 102 . therefore , the following description applies to both telescoping mid - portions and release mechanisms . each telescoping mid - portion 25 comprises a tube 81 with a check rod 84 disposed within the tube . the check rod includes a pull spring 86 which bears against bushing 95 at one end of tube 81 and bumper 96 at one end of check rod 84 when tube 81 is in an extended position . the check rod 84 also includes a push spring 88 which bears against bushing 97 , at the other end of the check rod 84 and the end of tube 81 at bushing 95 when tube 81 is in a retracted position as shown in fig1 . bushing 97 is coupled to frame 13 and check rod 84 by a pin 101 through the bushing and frame , or other suitable means . after check rod 84 is inserted into tube 81 , bushing 95 is coupled to tube 81 by a set screw ( not shown ) or other suitable means , nearest the head end of the stretcher . the other end of tube 81 has coupled thereto a rubber bumper 98 . tube 81 includes three grooves 90 equally spaced around the circumference of the tube and extending slightly more than half the length of the tube . ball bearings 92 are inserted through openings 93 in frame 13 and held in place by clip - ring 105 . the ball bearings are sized such that tube 81 is free to slide within frame 13 along grooves 90 while maintaining the tube in a relatively stable position within the frame . bushings 95 and 97 and bumpers 96 and 98 limit the length of travel of tube 81 along check rod 84 in a manner to be described below . as best seen in fig1 , release mechanism 102 comprises a pin 108 which is coupled to connecting member 110 which in turn passes thru guide sleeve 112 . expansion biasing spring 114 is disposed on connecting member 110 separating pin 108 from guides sleeve 112 . release mechanism 102 is disposed within cross - member 46 such that guide sleeve 112 is held stationary within cross - member 46 by set screws ( not shown ) threadedly engaging the cross - member and guide sleeve . in this manner , connecting member 110 and pin 108 are free to slide within cross - member 46 with the travel being limited at one end by guide sleeve 112 and at the other end by frame 13 . connecting member 110 extends through guide sleeve 112 and at the end thereof opposite pin 108 is coupled to cable 54 . the cable is coupled to the connecting member by an eyelet 116 or other suitable means . pin 108 includes a protrusion 118 which extends into a first bore 119 or a second bore 125 through frame 13 and tube 81 as described below . the cable 54 extends from eyelet 116 through cross - member 46 , around guide wheel 123 ( see fig1 ) at approximately the mid - point of cross - member 46 through tubular member 52 to the head end of the stretcher terminating at handle 121 . by squeezing on handle 121 , pin 108 and protrusion 118 is removed from bore 119 ( or bore 125 ). when the handle is released , expansion biasing spring 114 forces the protrusion 118 back into bore 119 ( or bore 125 ). when pin 108 is in its retracted position , tube 81 is free to slide along the length of check rod 84 . when bore 119 is engaged by pin 108 , telescoping portion 25 is in an extended position . when it is decided that the telescoping portion be locked in its retracted position , handle 121 is squeezed so as to release pin from bore 119 , the telescoping portion is then moved into its retracted position , the handle is released and pin 108 engages a second bore 125 in tube 81 . the details of telescoping end portions 27 and their associated locking mechanisms will now be described with reference to fig1 and 15 . telescoping end portions 27 are comprised of two identical assemblies , each assembly comprising a tube 130 whose outside diameter is slightly less than the inside diameter of tube 132 such that when tube 130 is inserted into tube 132 they are engaged in a sliding relationship . disposed within each tube 130 is a locking mechanism 134 . as best seen in fig1 , the locking mechanism 134 is comprised of two main assemblies 136 and 138 . the two assemblies 136 and 138 are connected to tube 130 with set screws ( not shown ) in threaded engagement with tube 130 and assemblies 136 and 138 respectively or other suitable means . with respect to assembly 136 , the set screws or other suitable means engage pin boss 140 , at one end thereof , while assembly 138 is attached to tube 130 by set screws which threadedly engage tube 130 and guide sleeve 142 . it should be noted that assembly 138 is substantially identical to locking assembly 102 with pin 108 of the locking assembly 102 corresponding to beveled engaging member 144 of assembly 138 . thus , expansion biasing spring 146 corresponds to expansion biasing spring 114 and connecting member 110 corresponds to connecting member 148 and eyelet 116 correspond to eyelet 150 . assembly 136 further comprises protrusion 158 and beveled surface 152 with expansion biasing spring 154 inserted in bore 156 . normally , engaging member 144 bears against beveled surface 152 forcing the compression of spring 154 . when handles 160 at the foot end of the stretcher are squeezed , cables 164 are pulled . the ends of cables 164 opposite the handle 160 pass through frame 13 around guide wheels 166 and are coupled to each eyelet 150 such that when the cables are pulled , each connecting member 148 is pulled through sleeve 142 which in turn disengages engaging member 144 from beveled surface 152 . at such time , the force exerted by spring 154 causes assembly 136 to pivot within tube 130 at pivot point 162 . tube 132 includes two bores 168 and 170 through one of which protrusion 158 extends , depending on whether the end portions 27 are retracted or extended . by pulling on handles 160 thereby releasing protrusion 158 from one of the bores 168 or 170 , tubes 130 are free to slide within tubes 132 . when the handles 160 are released , the tubes 130 will continue to slide until protrusion 158 engages one of bores 168 or 170 at which time the force exerted by engaging member 144 on beveled surface 152 will force protrusion 158 through one of said bores thereby locking telescoping end portions 27 in either a retracted or extended position . protrusions 158 extend through bores 168 when the telescoping end portions are in a retracted position , and through bores 170 when the telescoping end portions are in an extended position . the operation of the stretcher will now be described . referring first to fig2 once telescoping mid - portions 25 are retracted , the stretcher is divided into two sections connected at approximately the mid - point thereof at king pin 29 . as best seen in fig5 king pin 29 retains plates 19 , 21 and 23 , passing through each plate such that the plates are free to rotate about the pin and the stretcher can be easily maneuvered through tight quarters . if necessary , cardiopulmonary resuscitation can be carried our while the stretcher is being moved because the disclosed king pin 29 and wheel caster assembly 17 provide adequate support even when telescoping mid - portions 25 are retracted . while the plates are free to rotate , the range of rotation is limited by the obstruction created by frame 13 when the stretcher is flexed as shown in fig2 . while this range of rotation may be increased by decreasing the length of telescoping mid - portions 25 , as a practical matter , there is no need to allow for rotation of greater than approximately 30 ° inasmuch as a torso of a patient on the stretcher would ordinarily not flex more than the capability of the stretcher . after the stretcher has been maneuvered through tight quarters and the flexing capability of the stretcher is no longer needed , by squeezing handle 121 , each tube 81 is free to slide along its corresponding check rod 84 within frame 13 . at such time , force exerted by each expansion spring 88 causes tubes 81 to slide towards the foot end of the stretcher . by lining up the foot end and head end of the stretcher such that the side rails of frame 13 are aligned , tubes 81 may be pulled towards the foot end of the stretcher until protrusion 118 of locking pin 108 engages bore 119 thereby locking the telescoping mid - portions in an extended portion . when the length of the stretcher must be shortened to fit into a small space , or the knees of the patient must be flexed , or the head of the patient must be in a raised position , telescoping end portions 27 may be retracted as follows . firstly , telescoping mid - portions 25 should be locked in their retracted positions so that each tube 130 is free to slide the entire length of tube 132 . at such time , handles 160 are squeezed thereby releasing protrusion 158 from bore 170 as above - described . tubes 130 are then free to slide within tubes 132 and the foot end of the stretcher may be moved towards the head end of the stretcher . by continuing to move the foot end of the stretcher towards the head end of the stretcher , protrusions 158 will engage bores 168 and the telescoping end portions 27 will be locked in a retracted position . when it is desired that the stretcher again be extended to its full length , handles 160 are squeezed thereby releasing protrusion 158 from bores 168 and the foot end of the stretcher is pulled away from the head end of the stretcher until protrusions 158 engage bores 170 . as noted above , when telescoping end portions 27 are retracted , hinged cover 34 flexes at hinges 36 , 38 and 40 to thereby form an inverted v - shaped portion which supports the patient &# 39 ; s knees when knee flexion is desired or necessary , or the upper torso of the patient when desired or necessary . it should be noted that when telescoping mid - portions are retracted and the foot end and head end of the stretcher are connected only at king pin 29 , if the head end or foot end of the stretcher is lifted , a large force will be applied to king pin 29 as well as plates 19 , 21 and 23 . accordingly , a hinge 22 extends the width of metal plate 21 such that if either end of the stretcher is raised when telescoping mid - portions 25 are retracted , the stretcher will flex at hinge 22 , and no undue force will be exerted on king pin 29 or plates 19 , 21 or 23 . generally , when the stretcher is to be stored in the emergency vehicle , telescoping mid - portions 25 and telescoping portions 27 are in their extended positions . wheel and caster assemblies 15 and 17 are in their retracted positions in order to minimize the space taken up by the utility stretcher in the emergency vehicle . thus , the flexible utility stretcher has been described . although numerous details have been set forth regarding materials used and means for implementing the various mechanical linkages and other such requirements , those skilled in the art will recognize that other materials may be used and different means may be employed for implementing the various mechanical linkages and the like of the stretcher without departing from the spirit and scope of the invention as set forth in the claims appended hereto .

a flexible utility stretcher is disclosed for use by paramedics , ambulance operators and other emergency vehicle personnel whose duties include the use of utility stretchers to transport patients to an emergency vehicle . the stretcher comprising the subject invention generally corresponds to the size and shape of utility stretchers presently employed by paramedics and other emergency personnel who use emergency vehicles in connection with their duties . the main features which distinguish the subject invention from prior art utility stretchers are telescoping side frame members and a pivot point at approximately the center of the stretcher separating one portion or head end of the stretcher from the other portion or foot end of the stretcher . either half may be pivoted through an angle of up to approximately 30 °. this pivoting capability allows the stretcher to be maneuvered around sharp turns which would be impossible to accomplish using a stretcher without such pivoting capability . the telescoping side frame members allow the stretcher to be shortened so that it will fit in an elevator or other relatively short space . another important feature is that uninterrupted cardiopulmonary resuscitation can be performed on a victim being transported in the prone position with the stretcher in both the flex mode and in the shortened mode .

a retinal stimulation system , disclosed in u . s . application ser . no . 11 / 207 , 644 , filed aug . 19 , 2005 for “ flexible circuit electrode array ” by robert j . greenberg , et , al . incorporated herein by reference , is intended for use in subjects with retinitis pigmentosa . fig1 and fig2 show a retinal stimulation system ( 1 ) wherein a patient / subject is implanted with a visual prosthesis . reference can also be made to fig1 - 5 of u . s . application ser . no . 11 / 796 , 425 , filed apr . 27 , 2007 for “ visual prosthesis fitting ”, also incorporated herein by reference in its entirety . the retinal stimulation system ( 1 ) is an implantable electronic device containing electrode array ( 2 ) that is electrically coupled by a cable ( 3 ) that pierces sclera of the subject &# 39 ; s eye and is electrically coupled to an electronics package ( 4 ), external to the sclera . the retinal stimulation system ( 1 ) is designed to elicit visual percepts in blind subjects with retinitis pigmentosa . referring to fig3 , a fitting system ( fs ) may be used to configure and optimize the visual prosthesis ( 3 ) of the retinal stimulation system ( 1 ). the fitting system may comprise custom software with a graphical user interface ( gui ) running on a dedicated laptop computer ( 10 ). within the fitting system are modules for performing diagnostic checks of the implant , loading and executing video configuration files , viewing electrode voltage waveforms , and aiding in conducting psychophysical experiments . a video module can be used to download a video configuration file to a video processing unit ( vpu ) ( 20 ) and store it in non - volatile memory to control various aspects of video configuration , e . g . the spatial relationship between the video input and the electrodes , which is one of the main aspects of the present disclosure . the software can also load a previously used video configuration file from the vpu ( 20 ) for adjustment . the fitting system can be connected to the psychophysical test system ( pts ), located for example on a dedicated laptop ( 30 ), in order to run psychophysical experiments . in psychophysics mode , the fitting system enables individual electrode control , permitting clinicians to construct test stimuli with control over current amplitude , pulse - width , and frequency of the stimulation . in addition , the psychophysics module allows the clinician to record subject responses . the pts may include a collection of standard psychophysics experiments developed using for example matlab ( mathworks ) software and other tools to allow the clinicians to develop customized psychophysics experiment scripts . any time stimulation is sent to the vpu ( 20 ), the stimulation parameters are checked to ensure that maximum charge per phase limits , charge balance , and power limitations are met before the test stimuli are sent to the vpu ( 20 ) to make certain that stimulation is safe . using the psychophysics module , important perceptual parameters such as perceptual threshold , maximum comfort level , and spatial location of percepts may be reliably measured . based on these perceptual parameters , the fitting software enables custom configuration of the transformation between video image and spatio - temporal electrode stimulation parameters in an effort to optimize the effectiveness of the retinal prosthesis for each subject . the fitting system laptop ( 10 ) is connected to the vpu ( 20 ) using an optically isolated serial connection adapter ( 40 ). because it is optically isolated , the serial connection adapter ( 40 ) assures that no electric leakage current can flow from the fitting system laptop ( 10 ). as shown in fig3 , the following components may be used with the fitting system according to the present disclosure . a video processing unit ( vpu ) ( 20 ) for the subject being tested , a charged battery ( 25 ) for vpu ( 20 ), glasses ( 5 ), a fitting system ( fs ) laptop ( 10 ), a psychophysical test system ( pts ) laptop ( 30 ), a pts cd ( not shown ), a communication adapter ( ca ) ( 40 ), a usb drive ( security ) ( not shown ), a usb drive ( transfer ) ( not shown ), a usb drive ( video settings ) ( not shown ), a patient input device ( rf tablet ) ( 50 ), a further patient input device ( jog dial ) ( 55 ), glasses cable ( 15 ), ca - vpu cable ( 70 ), cfs - ca cable ( 45 ), cfs - pts cable ( 46 ), four ( 4 ) port usb hub ( 47 ), mouse ( 60 ), led test array ( 80 ), archival usb drive ( 49 ), an isolation transformer ( not shown ), adapter cables ( not shown ), and an external monitor ( not shown ). the external components of a fitting system may be configured as follows . the battery ( 25 ) is connected with the vpu ( 20 ). the pts laptop ( 30 ) is connected to fs laptop ( 10 ) using the cfs - pts cable ( 46 ). the pts laptop ( 30 ) and fs laptop ( 10 ) are plugged into the isolation transformer ( not shown ) using the adapter cables ( not shown ). the isolation transformer is plugged into the wall outlet . the four ( 4 ) port usb hub ( 47 ) is connected to the fs laptop ( 10 ) at the usb port . the mouse ( 60 ) and the two patient input devices ( 50 ) and ( 55 ) are connected to four ( 4 ) port usb hubs ( 47 ). the fs laptop ( 10 ) is connected to the communication adapter ( ca ) ( 40 ) using the cfs - ca cable ( 45 ). the ca ( 40 ) is connected to the vpu ( 20 ) using the ca - vpu cable ( 70 ). the glasses ( 5 ) are connected to the vpu ( 20 ) using the glasses cable ( 15 ). in a visual prosthesis , every electrode in the implanted array of electrodes produces a spot of light ( phosphene ) in the visual field . a transformation needs to be specified to map the stimulation of individual electrodes in the stimulating array to specific locations , or regions , in the acquired video image . this transformation is specified in a look - up table referred to as the spatial map . in other words , spatial mapping is the relationship of a pixel , or pixels , in the camera &# 39 ; s view to an electrode on the retina . due to the optics of the eye , the retina is laid out reverse of the real world and proportional . the scale depends on the distance of the object . as shown in the prior art embodiment of fig4 , usually a one - to - one spatial mapping is used . in this mapping , the locations of the individual electrodes in the retinal stimulating array are projected into the visual field . the corresponding locations of the input video image ( pixels ) are then mapped to the corresponding single electrode in the array . fig4 shows a 4 × 4 prior art electrode array embodiment , where pixel ( 80 ) is mapped to electrode l 6 , pixel ( 90 ) is mapped to electrode l 7 , pixel ( 100 ) is mapped to electrode m 4 , pixel ( 110 ) is mapped to electrode m 1 , and so on , so that each pixel corresponds to a single electrode and vice versa . in other words , the corresponding locations of the input video image ( pixels ) are mapped to the corresponding single electrode in the array . however , in certain cases there is a need to use a different mapping . for example , a regular spacing of stimulating electrodes may result in a distorted spatial pattern of phosphenes . because the ganglion cell axons are stretched away from their foveal cones , a regular pattern of stimulating electrodes may result in a pattern of phosphenes that is compressed to the center of the visual field . in order to address this case , applicants have altered the spatial map to undo the perceptual distortion . in particular , in cases where the patient cannot resolve the spatial information in the fine resolution of the spacing between electrodes , a group of electrodes are associated with a correspondingly large area in the video image . this is useful for cases in which areas in the array don &# 39 ; t yield a bright percept up to the maximum allowed current . when neighboring electrodes are stimulated simultaneously , due to current summation , the percept is brighter . grouping electrodes create “ virtually ” one electrode with a larger area , which enable to increase the maximum allowed current . as shown in fig5 , a plurality of electrodes , e . g . four electrodes , are mapped to an average of a plurality of pixels , where the number of the electrodes in the group corresponds to the number of pixels the average of which is taken . therefore , each electrode of group ( 120 ) is mapped to a first average ( 130 ) of four pixels , each electrode of group ( 140 ) is mapped to a second average ( 150 ) of four pixels , and so on . fig6 shows a further embodiment of the present disclosure , where random mapping is performed . for example , pixel ( 160 ), instead of being mapped to electrode l 6 , is being mapped to electrode l 7 ( 170 ). similarly , pixel ( 180 ), instead of being mapped to electrode l 2 , is being mapped to electrode m 8 ( 190 ). random mapping can be used in order to test whether a specific subject is benefitting from spatial modulation in the array . flexible spatial mapping can also solve wiring mistakes in the implant that are found after the implantation surgery . a third embodiment can also be provided , which is a combination of the first two embodiments . in other words , a plurality of electrodes is randomly mapped to an average of a plurality of pixels . the embodiments of fig5 and 6 have been shown with reference to a 4 × 4 electrode arrangement for the sake of simplicity . current electrode arrangements are in a 6 × 10 array ( e . g ., electrodes a 1 through f 10 ), and the 6 × 10 electrode array represents the best mode of the present disclosure . the person skilled in the art will note that the embodiments of fig5 and 6 can be easily adapted to a 6 × 10 electrode array environment . therefore , in accordance with some of the embodiments of the present disclosure , an improved method of operating a visual prosthesis is disclosed . the method uses spatial maps to control neural stimulation for correcting distortions from the foveal pit , correcting wiring mistakes in the implant , bypassing broken electrodes , testing the resolution limit , testing the benefit the patient receives from correct spatial mapping , and solving orientation problems . accordingly , what has been shown are methods and systems for providing stimulation inputs to a visual prosthesis implant . while these methods and systems have been described by means of specific embodiments and applications thereof , it is understood that numerous modifications and variations could be made thereto by those skilled in the art without departing from the spirit and scope of the disclosure . it is therefore to be understood that within the scope of the claims , the disclosure may be practiced otherwise than as specifically described herein .

a visual prosthesis and a method of operating a visual prosthesis are disclosed . neural stimulation through electrodes is controlled by spatial maps , where a grouped or random association is established between the data points of the acquired data and the electrodes . in this way distortions from the foveal pit and wiring mistakes in the implant can be corrected . moreover , broken electrodes can be bypassed and a resolution limit can be tested , together with testing the benefit the patient receives from correct spatial mapping .

with initial reference to fig1 a bed knife blade constructed in accordance with the teachings of an embodiment of the present invention is generally identified at reference numeral 10 . the bed knife blade 10 is shown operatively associated with an exemplary mower 12 having a cutting reel 14 rotatably mounted to a frame 16 . a backing plate 18 is also coupled to the frame 16 for receiving and mounting the bed knife blade assembly 10 thereto . an adjustment mechanism 20 cooperates with the frame 16 and the backing plate 18 for positioning the bed knife blade assembly 10 relative to the cutting reel 14 . one skilled in the art will appreciate that proper cutting or shearing of grass blades is accomplished by maintaining a minimal clearance between the rotating cutting reel 14 and the bed knife blade assembly 10 . specifically , the cutting reel 14 includes a plurality of helical blades providing individual shear interfaces along the entire length of bed knife blade assembly 10 . as mentioned earlier , proper function of the mower 12 also depends on maintaining the sharpness of the helical blades and the bed knife blade 10 . the longevity of blade sharpness depends on a variety of factors including cutting edge hardness and mower usage . as is commonly known , the carbon content of steel alloys may be increased for hardenability purposes . however , a trade - off generally exists whereby an increase in material hardenability results in a decrease in material toughness . however , certain steel alloys exist which exhibit high hardenability and adequate toughness . unfortunately , these materials are expensive and difficult to machine in their annealed state , let alone after hardening . based on the aforementioned limitations , a standard bed knife blade is created by first hot forming a blank . subsequently , the blank is rough machined . finish machining occurs by drilling and counter - sinking holes in a portion of the blank . at least a portion of the blank is heat treated and subsequently ground to form a cutting edge . with continued reference to fig1 the bed knife blade assembly 10 of the present invention incorporates a multi - piece design including a blade insert 24 and a clamp plate 26 . the clamp plate 26 functions to couple the blade insert 24 to the backing plate 18 of the mower 12 but performs no cutting function . accordingly , the clamp plate 26 is preferably constructed from a low cost , easily machined material exhibiting impact resistance and toughness . on the other hand , because the blade insert 24 cuts the grass and does not provide a mounting function , it is preferably constructed from a high carbon steel capable of achieving high hardness when heat treated . the hardened portion of the blade insert 24 is subsequently ground to a knife edge for cutting the blades of grass . with reference to fig2 the clamp plate 26 is an elongate structure having a body 28 and a flange 30 extending a distance “ x ” therefrom . the body 28 includes a mounting surface 32 for engagement with the backing plate 18 . the body 28 also includes a plurality of apertures 34 for receipt of fasteners such as threaded bolts or screws . in the preferred embodiment , the apertures 34 include a counter sink 36 thereby allowing the installed fastener to rest flush with a bottom surface 38 . the flange 30 extends substantially along the entire length of the body 28 and includes a end face 40 and a locking surface 42 for engagement with the blade insert 24 . the locking surface 42 is positioned at an angle relative to the mounting surface 32 to effectively couple the blade insert 24 to the clamp plate 26 after assembly to the backing plate 18 . in the preferred embodiment , the locking surface 42 forms a small acute angle 43 with the mounting surface 32 in the range of 3 - 10 degrees . one skilled in the art will appreciate that the simple geometry of the clamp plate 26 may be created using a variety of cost effective manufacturing methods including roll forming , forging and casting . referring to fig1 and 3 , the blade insert 24 functions to provide a cutting edge 44 in close relation to the helical blades 22 of the cutting reel 14 for cutting grass blades . the blade insert 24 includes a knife end 46 and a tab 48 extending a distance “ y ” therefrom . the tab 48 includes a first clamping surface 50 and a second clamping surface 52 extending along the length of the tab 48 . it should be appreciated that the first clamping surface 50 and the second clamping surface 52 form an acute angle 53 preferably in the range of 2 - 9 degrees . additionally , it should be appreciated that the angle 53 formed by the first clamping surface and the second clamping surface is preferably one degree less than the angle 43 formed between the locking surface 42 and the mounting surface 32 as will be described in greater detail hereinafter . the second clamping surface 52 terminates at a stop face 54 . preferably , the second clamping surface 52 transitions to stop face 54 through a generous radius 56 . the knife end 46 of the blade insert 24 also includes a bottom surface 58 and a relief 60 formed along the entire length of the blade insert 24 . in the preferred embodiment , each of the surfaces defining the tab 48 and the body 46 are roll formed to their net shape shown . accordingly , costly rough machining is eliminated . the body 46 also includes a first machined surface 62 intersecting a second machined surface 64 at the cutting edge 44 . each of the first and second machine surfaces are ground after heat treatment of the blade insert 24 to produce a sharp cutting edge 44 . referring to fig1 and 4 , the bed knife blade assembly 10 is assembled to the mower 12 by placing the tab 48 of the blade insert 24 in contact with the flange 30 of the clamp plate 26 . specifically , the flange 30 extends the distance x from the body 28 while the tab 48 extends the lesser distance y from the first end 46 of the blade insert 24 . accordingly , the end face 40 abuts the stop face 54 once the bed knife blade assembly 10 is coupled to the backing plate 18 . one skilled in the art will appreciate that the abutment of end face 40 with stop face 54 assists in maintaining the position of the blade insert 24 relative to the backing plate 18 during operation . with specific reference to fig1 and 4a it should also be appreciated that the locking surface 42 is positioned such that an interference zone 66 ( shown in phantom line ) is created when the first clamping surface 50 of the blade insert 24 is aligned with the mounting surface 32 of the clamp plate 26 as when clamped against the backing plate 18 . the tapered shape of the interference zone 66 in addition to the back angles 43 and 53 tend to bias the blade insert 24 towards the clamp plate 26 thereby closing the gap between the end face 40 and the stop face 54 . the clamp plate 26 is coupled to the backing plate 18 with a plurality of fasteners 68 ( fig1 ) disposed within the apertures 34 . as the fasteners 68 begin to exert clamping force , each of the tab 48 and the flange 30 compress in an attempt to account for the interference zone 66 . in addition , the flange 30 deflects to biasingly load the tab 48 against the backing plate 18 . therefore , once the fasteners 68 have seated the mounting surface 32 against the backing plate 18 , the blade insert 24 is fixed in relation to the clamp plate 26 . referring to fig5 a second embodiment of the bed knife of the present invention is depicted at 110 . it should be appreciated that the second embodiment of the bed knife 110 includes similar components and performs essentially the same function as the first embodiment 10 . accordingly , like elements will be identified with like reference numerals . with reference to fig6 the clamp plate 126 includes a body 128 having a flange 130 extending a distance “ x ” therefrom . the flange 130 includes a first key 170 extending a distance 171 from the bottom surface 138 of the claim plate 126 . a first recess 172 is configured to interlock with a second key 174 and a second recess 176 of the blade insert 124 . with reference to fig7 a blade insert 124 includes a knife end 146 and a tab 148 extending a distance “ y ” therefrom . as mentioned earlier , the tab 148 includes the second key 174 for disposition within the first recess 172 and the second recess 176 for acceptance of the first key 170 . it should be appreciated that the second recess 176 is positioned a distance 180 from the first clamping surface 150 of the blade insert 124 . in order to provide the clamping retention feature of the blade insert 124 within the clamp plate 126 the sum of the distances 171 and 180 is greater than the total thickness of the clamp plate 182 ( fig6 ). in this manner , the flange 130 will be biasingly loaded against the tab 148 in similar fashion to the first embodiment . therefore , it should be appreciated that the configuration and operation of the bed knife blade assembly 10 provides a variety of advantages over the prior art . specifically , the two - piece construction of the present invention reduces the cost of manufacturing by eliminating several rough machining steps and reducing the quantity of costly high carbon alloy steel . additionally , a novel interlocking attachment method is used to couple the blade insert to the clamp plate . the foregoing discussion discloses and describes merely exemplary embodiments of the present invention . one skilled in the art will readily recognize from such discussion , and from the accompanying drawings and claims , that various changes , modifications and variations may be made therein without departing from the spirit and scope of the invention as defined in the following claims .

a method of constructing a bed knife blade assembly for a reel - type lawn mower having a frame rotatably supporting a cutting reel . the bed knife blade assembly comprises a clamp plate having a flange with a locking surface , and a blade insert having a tab cooperating with the locking surface to restrict movement of the blade insert relative to the clamp plate . the clamp plate is adapted to be coupled to the frame such that the flange biasedly engages the tab to further restrict movement of the blade insert relative to the clamp plate .

as shown in fig4 and 5 , a flat insole 10 of the present invention is made of a foam material not molded under heat and pressure and is composed of a toe portion 11 , a sole portion 12 , a heel portion 13 , and an arch 121 extending from the sole portion 12 . the flat insole 10 has two longitudinal side walls which slant from two upperside edges 101 such that the two longitudinal side walls form respectively angles α and β with an underside of the insole 10 . the α angle and the β angle are greater than 90 degrees . as a result , the flat insole 10 has an upperside and an underside which is smaller in width than the upperside . the toe portion has the smallest machining angle . the heel portion 13 has the intermediate machining angle . the arch 121 of the sole portion 12 has the greatest machining angle . the slanted longitudinal side walls of the flat insole 10 have arcuate edges . as shown in fig6 the flat insole 10 is kept in place in a shoe 70 such that no void is formed between the heel portion 13 and the inner wall 72 of the shoe 70 , and that the upperside edges 101 of the flat insole 10 are in an intimate contact with the inner wall of the shoe 70 , thereby preventing the upperside edges 101 from warping to press against the sole of a foot wearing the shoe 70 . in light of the flat insole 10 of the present invention being provided with the arch 121 , the flat insole 10 is capable of covering the foot sole 100 . as shown in fig7 the arch 121 is in contact with the inner wall 72 of the shoe to prevent the formation of a large void . the flat insole 10 of the present invention is securely kept in place in the shoe such that the flat insole 10 is in an intimate contact with the inner wall 72 of the shoe , so as to prevent the flat insole 10 from displacing or twisting . the flat insole of the present invention affords a good support to the foot wearing the shoe , thanks to the arch 121 of the flat insole 10 . the arch 121 is in contact with the inner wall 72 of the shoe such that only small void 8 is formed . the flat insole 10 makes an intimate contact with the inner wall 72 and has a wider upperside to cover the foot sole 100 without pressing against the foot sole . the flat insole 10 of the present invention is free of the drawbacks of the conventional flat insole which is prone to warp to press against the foot sole . the present invention affords its wearer comfort . unlike the conventional flat insole and the conventional molded insole , the flat insole 10 of the present invention has a greater allowance for error . as a result , the flat insole 10 of the present invention fits better into the shoe sole 71 . the flat insole 10 of the present invention is cost - effective in all respects .

an insole has an upperside and an underside narrower than the upperside , so as to give an added support , wearing stability , and comfort to the foot .

in order to describe the structure and the technical solution of the present invention , the following description will be made in detail with reference to the accompanying drawings . the cited examples are for the purpose of explaining the present invention and are not intended to limit the scope of the utility model . heart rate is an important indicator of health . each person &# 39 ; s heart rate is different , with normal adult normal heart rate ranging around 60 to 100 times per minute . normal heart rhythm is affected by many factors , when the movement of the heartbeat will speed up , rest or sleep when the heartbeat will slow down , exhaled heartbeat slower , fever , tension , excessive pressure , pain , etc ., will also affect the heart rate . heart rate is affected by breathing speed , under normal circumstances , women heart rate faster than men , normal adults breathing about 16 - 20 times per minute , and the heart rate is 1 : 4 , that is , every breath , heart beat four times . heart beat blood flows through the contraction of the heart into the aorta , and is then passed to the systemic arteries . when the blood enters into the blood vessels of the head , the pulse will make the whole face fluctuate slightly . the amplitude of these fluctuations is quite subtle , under normal circumstances the human eye cannot directly detect these subtle changes , but through the high - speed camera shooting slowed down , any slight fluctuations can be accurately captured . the present invention mainly utilizes the fluctuation of the facial area of the body when the heartbeat occurs , and then forms a fine displacement in the image . by recognizing the small displacement of the facial area in the image frame , the heartbeat can be judged and then the heartbeat rate is counted and calculated . in addition , as the heart beats , facial blood vessels will be followed by congestion , facial color will have a small change , through the capture and analysis of the camera , you can change the frequency of face color to get heart rate . respiratory frequency measurement principle and the principle of the heart rate measurement similar to the lung and the air exchange , when the lungs inhalation of air will make the chest ups and downs , by capturing the image of the chest between the site changes to identify the occurrence of breathing , and then analyze the respiratory rate . the foregoing is an explanation of the principles of the present invention , which will be further described below with reference to examples . in order to realize the purpose of remote accurate measurement of human heart rate , respiratory rate and body temperature , as well as realizing sharing of cloud data transmission , the utility model sets an 8 million pixel high - definition camera 1 , multi - point infrared temperature sensor 5 , micro - microphone 4 , buzzer 2 , and an adjustable direction pillar 3 and a reset switch 6 . the utility model uses a high - definition camera 1 to continuously shoot the measured object to obtain a series of video images , and then analyzes the video images to obtain the heart rate and the respiratory rate . in one of these methods , a series of images were taken with 1080p at 30 frames per second using an 8 - megapixel wide - angle lens . the image is extracted by multi - frame image processing , 1080p image resolution of 1920 × 1080 about two million frames , through the face recognition program to lock the face position of each image , using the face recognition algorithm to locate the face in each image . the faces of each image are located by the face recognition algorithm , and the position of the face in the image is determined by the upper left corner and the lower right corner of the frame . the image is illustrated with 30 frames per second for example . the coordinates of the upper left corner and lower right corner of the region are as follows : as can be seen from the above data , the measured object in the inertial oscillation direction is slightly to the top right ( to the observer &# 39 ; s point of view ), from the beginning of the first 12 to 19 images for the emergence of a fluctuation , which represents a when a heartbeat occurs . followed by analysis of the follow - up video frame , this can produce a count of the number of heartbeats that occur per minute , and thus the heart rate . breathing frequency measurement and heart rate measurement are similar . extracted from the image of multi - frame image , face detection algorithm is used to determine the location of the face in each image ; according to the location of the face , determine the location of the thoracic position ; detect the chest region , a region located 1 . 5 to 2 . 0 face lengths below the upper edge of the face ; near the location of the chest , identify the generation of breathing , respiratory ups and downs when an event is captured on behalf of a breathing occurs ; according to the number of changes in chest location per minute , the respiratory rate can be obtained . the measured human heart rate and respiratory rate can also be set up in real time and uploaded to the cloud server in the region . the user can bind the device account login and connect to the server for real - time view of the measured heart rate and respiration . preferably , the invention further comprises a face recognition unit which records the historical heart rate and the respiratory rate data of each measured object . when it is found that the heart rate or the respiratory rate measured by the same subject has large differences from the historical measured data , this may suggest that physical condition of the measured object may be abnormal , which can be detected via remote monitoring and can trigger alerts to the users . normal body temperature is generally 36 . 1 ° c .˜ 37 ° c ., lower than the oral temperature by about 0 . 2 ° c .˜ 0 . 4 ° c ., according to the level of fever ( oral temperature ), can be divided into : low heat : 37 . 4 ° c .˜ 38 ° c . ; 39 ° c . to 41 ° c . ; ultra - high heat : 41 ° c . or higher ; and in the present invention , the effective temperature range of the human body is set to 35 ° c . to 42 ° c ., and points are only considered when the collected temperature falls within the above - mentioned effective temperature range . otherwise , it means that the corresponding sampling points do not belong to the human body area or the human body area is blocked by other objects , resulting in abnormal temperature . by eliminating the above abnormal temperature , the average temperature of the sample obtained can produce more accurate body temperature data , avoiding the errors of single point measurement due to the impact of environmental interference . the above is an explanation of the principle of the present invention , and the following description will be given by way of example . in the camera on the side set up a high - precision infrared temperature sensor 5 , the infrared temperature sensor can simultaneously collect the temperature of 64 sampling points , the effective temperature acquisition distance of 1 . 5 meters or more , 64 sampling points in matrix distribution , as shown in fig4 ; 64 sampling points are distributed in the whole imaging area . when the human body is detected in the camera shooting area , the infrared temperature sensor is triggered to carry out the temperature sampling , and the temperature corresponding to the 64 sampling points is obtained . only some of the sampling points fall within the effective region of the human body . because some of the sampling points are not covered by the human body , or because of object occlusion and other reasons , some of the sampling points of the temperature significantly deviate from the human body temperature range . in calculating the body temperature , abnormal points are removed from the sampling points . if the temperature of the sampling point is not within the effective temperature range of the human body , it is considered that the temperature is not the effective temperature and is not taken into account in the calculation ; if the sampling point has temperature 35 ° c .˜ 42 ° c ., then it is within the effective temperature rate . the temperatures of sampling points which belong to the effective temperature range are averaged , and the average temperature obtained is the measured body temperature . the measured temperature data will be uploaded to the local cloud server in real time . therefore , no matter where the user is , the user can simply open the browser to the specified page or login account through app to view real - time camera image and body temperature data , remote body temperature measurement , and monitoring . preferably , the invention further comprises a face recognition unit which records the historical temperature data of each measured object and when it is found that the body temperature measured by the same subject has a greater difference than the body temperature measured recently by the history , it will note that there may be physical anomalies and will be timely to alert the user about the noted temperature difference . the above is only a few embodiments of the utility model , and is not intended to limit the scope of the utility model . any modifications , equivalent replacements , improvements , and the like within the spirit and principle of the utility model shall be included in the protection scope of the utility model is within the scope .

the utility model relates to a device for measuring the heartbeat , respiration , and body temperature of a human body , comprising of a shell and a base , wherein a pcb board , a buzzer , and a multi - point infrared temperature sensor and a camera are arranged in the shell . the infrared temperature sensor is used for temperature sampling of m × n sampling points , where m ≧ 3 , n ≧ 3 , and the camera is used for acquiring the video image of the measured object .

referring now to fig1 there is shown a forage harvester header 10 having a frame 12 on which eight intake and mowing arrangements 14 are arranged side - by - side to each other . the intake and mowing arrangements 14 each consist , in a manner known in itself , of conveyor disks arranged coaxially over associated mowing disks having a plurality of pocket - shaped recesses distributed over their circumference . the conveyor disks grasp and transport the stalk - like harvested crop that was cut from the surface of the field by means of the mowing disks . the number of intake and mowing arrangements 14 of the header 10 can be chosen freely , hence more or fewer than eight intake and mowing arrangements 14 can be employed . on the rear side of the intake and mowing arrangements 14 , the harvested crop is taken out of the conveyor disks by removal devices ( not shown in the drawing for the sake of clarity ), that are configured as rotating disks or stationary elements , and conveyed sideways toward the center of the header 10 by transversely spaced conveyor drums 16 that interact with the intake and mowing arrangements 14 , and that are equipped with projecting driver teeth which penetrate corresponding slots in a rear wall of the frame 12 . at the center of the rear of the header 10 , a discharge channel 18 of the header 10 is arranged . the harvested crop is conveyed into the discharge channel 18 in the center of the header 10 by a pair of slope conveyor drums 20 , that are also equipped with toothed drivers . the conveyor drums 20 are arranged on opposite sides of and ahead of the discharge channel 18 . the axes of rotation of the slope conveyor drums 20 are inclined toward the front . the intake and mowing arrangements 14 are driven about approximately vertical axes of rotation , or axes that are inclined slightly forward . the transverse conveyor drums 16 and the slope conveyor drums 20 are coupled to a drive so that they may be put into rotation . the header 10 is that for a self - propelled forage harvester and the power for driving the various drives is provided by an engine of the machine , which also powers drive wheels for moving the harvester over a field in the forward direction of travel . the header 10 includes a carrier frame 28 located centrally behind the discharge channel 18 which is fastened , so that it can be removed , to the forward end of the self - propelled forage harvester . the directions of rotation of the intake and mowing arrangements are opposite on the opposite sides of a vertical longitudinal center plane of the header 10 , where each of the three inner intake and mowing arrangements 14 rotate in an opposite direction than does the outermost intake and mowing arrangement 14 . if the header 10 is moved over a field , standing plants 24 are pushed to the side , if necessary by means of stalk dividers 22 , and grasped by the intake and mowing arrangements 14 , which operate independent of rows , and cut from the ground . then the plants 24 are transported transverse to the forward direction of operation to the center of the header 10 in the transverse conveying channel 26 , that is defined between the rear wall of the header 10 and the transverse conveyor drums 16 , on the one hand , and the intake and mowing arrangements 14 , on the other hand . there they are conveyed by the slope conveyor drums 20 into the discharge channel 18 . it should be noted that the configuration of the transverse conveying channel 26 can be selected freely within the scope of the invention . fig1 through 3 are concerned with a channel formed between the rear wall of the header 10 and the intake and mowing arrangements 14 arranged ahead of it through which the harvested crop is transported by the intake and mowing arrangements 14 interacting with the transverse conveyor drums 16 arranged behind them or with driven removal disks or transverse conveying bands ( de 195 27 607 a ; de 195 31 918 a and de 198 56 444 a ). a transport of the harvested crop in the transverse conveying channel 26 independent of the intake and mowing arrangements 14 is also conceivable , which can be accomplished by separate conveyors , for example , in the form of a conveyor band or screw conveyors ( gb 2 012 154 a ). in case only an outer intake and mowing arrangement 14 is supplied with harvested crop , it is conceivable , in particular , that individual plants cannot be retained securely in the transverse conveying channel 26 by the other intake and mowing arrangements 14 due to an insufficient supply of harvested crop . these plants 24 may fall over , as is the plant identified in fig1 with the number call - out 24 ′, as a result of its relatively high center of gravity , and slide out of the transverse conveying channel 26 with its lower end . in such a case , it is possible that the plant comes to rest on a plate - shaped center table 30 arranged between the two central intake and mowing arrangements 14 . in known headers 10 for mowing of the stalks of crop such as corn , the operator must stop the engine of the forage harvester , climb out of the operator &# 39 ; s cab and manually remove the plants 24 ′ from the center table 30 . in order to avoid this disadvantage , a conveying arrangement 32 , in the form of a star - shaped conveyor disk equipped with drivers 38 , is arranged at the center of the upper surface of the center table 30 so that the disk lies in a vertical plane that is parallel to the forward operating direction . the conveying arrangement 32 penetrates an opening in the center table 30 . it is connected , so as to be driven , with an intake and mowing arrangement 14 by a shaft 36 and a gear box 34 . it is driven about a horizontal axis extending transverse to the forward direction of operation of the forage harvester , where the shaft 36 and the axis of rotation of the conveying arrangement 32 are located underneath the center table 30 . the conveying arrangement 32 conveys plants 24 ′, that have slid out of the transverse conveying channel 26 , automatically again into the transverse conveying channel 26 , since its upper side rotates in the direction towards the discharge channel 18 in normal harvesting operation . there the plants are conveyed by the slope conveyor drums 20 into the discharge channel 18 . since the conveying arrangement 32 is coupled so as to drive the intake and mowing arrangements 14 , the conveying arrangement 32 is driven in the reverse direction when the header is operated in the reverse direction . it supports the depositing on the center table 30 of the harvested crop thrown out of the discharge channel 18 during the reverse operation . if , after the reverse operation , the normal harvesting operation is again resumed , it conveys the harvested crop that was deposited on the center table 30 again into the transverse conveying channel 26 , from which it reaches the discharge channel 18 . referring now to fig2 only the center four intake and mowing arrangements 14 are pictured . this embodiment differs from that shown in fig1 in that instead of a single conveying arrangement 32 , two conveying arrangements 32 are shown arranged on the table 30 for rotation about parallel axes , with one arrangement 32 being located directly ahead of the other . the two conveying arrangements 32 are driven so as to rotate in the same direction and make it possible for plants deposited over the entire fore - and - aft dimension of the center table 30 to be conveyed back into the transverse conveying channel 26 and from there into the discharge channel 18 . in its remaining configuration , the header 10 is identical to that shown in fig1 where corresponding components are identified by the same number call - outs . fig3 shows a third embodiment of the invention . in this embodiment , the forage harvester header 10 is equipped with a conveying arrangement 40 in the form of a fore - and - aft extending belt conveyor located in the center of the table 30 and including transverse ribs 42 . a rear roller supporting the conveyor belt of the conveying arrangement 40 is driven by the gear box 34 of the intake and mowing arrangement 14 immediately to the left of the conveying arrangement 40 , the direction of driving being such that the upper side of the conveyor belt , which is located above the center table 30 , moves in the direction towards the discharge channel 18 during the normal harvesting operation . any plants that have possibly emerged from the transverse conveying channel 26 are again conveyed automatically into the transverse conveying channel 26 in this way and reach the discharge channel 18 from there . otherwise , the header 10 shown in fig3 corresponds to the headers shown in fig1 and 2 . the operation of the header 10 of each of the embodiments is thought to be apparent from the foregoing description , suffice it to say that the conveying arrangements at the center of the headers act to intercept crop stalks which have emerged from the transverse channel 26 and deliver them back to the channel 26 .

a forage harvester header includes a plurality of intake and mowing arrangements disposed side - by - side across the width of the header and adapted for being driven about respective upright axes . located behind the intake and mowing arrangements and leading to a centrally located discharge channel is a transverse conveying channel having upright conveying drums associated therewith to aid in moving the harvested crop stalks toward the discharge channel . a table is provided across the top of the center two intake and mowing arrangements and mounted centrally in the table is a conveyor arrangement which operates to gather and deliver rearwardly any crop stalks which emerge from the transverse conveying channel and go across the table in the vicinity of the conveyor arrangement .

hereinafter , a safety belt for a vehicle according to the present invention will be described in detail with reference to the attached drawings . fig2 is a perspective view illustrating the safety belt for a vehicle , according to an embodiment of the present invention . fig3 is a front view illustrating the safety belt according to the present invention . fig4 a is an exploded perspective view showing the installation of retractors according to the present invention . fig4 b is a sectional view showing the installation of the retractor according to the present invention . fig5 a and 5b are views showing a control unit installed in the retractor according to the present invention . fig6 a and 6b are views showing a belt guide member according to the present invention . fig7 is an exploded perspective view illustrating a fastening unit according to the present invention . fig8 is a plan view illustrating the fastening unit according to the present invention . as shown in fig2 through 8 , the safety belt 100 according to the present invention includes a pair of retractors 110 which are installed in a rear surface of a seat back 102 . each retractor 110 has the same structure as that of a typical retractor which is used for vehicle safety belts . the structure of the retractor 110 will be briefly explained below . the retractor 110 includes a body 112 to which a drum 114 is coupled . the drum 114 has ratchet teeth 114 a on a predetermined portion thereof . a belt 210 , 210 a is wound around the drum 114 . a ball 116 is disposed in the body 112 at a predetermined position below the ratchet teeth 114 a . a control shaft 116 a is coupled in the vertical direction to the ball 116 in such a way that upper and lower ends of the control shaft 116 a protrude upwards and downwards from the ball 116 . the retractor 110 further includes a ball housing 118 into which the lower end of the control shaft 116 a is inserted , and onto which the ball 116 is seated . the refractor 110 further includes an operating lever 119 which has a pawl 119 a at a predetermined position thereof . the pawl 1119 a is locked to or removed from the ratchet teeth 114 a when the ball 116 is moved by vertical movement of the control shaft 116 a . to install the retractors 110 each of which has the above - mentioned structure in the seat back 102 , an installation depression 104 is formed in the rear surface of the seat back 102 to a predetermined depth . the two retractors 110 are installed in the installation depression 104 at positions spaced apart from each other by a predetermined distance . in detail , a hinge shaft 106 is provided at an upper position in the installation depression 104 . the retractors 110 are rotatably coupled to the hinge shaft 106 . in an embodiment , a mounting bracket 120 is provided on an upper end of the body 112 of each retractor 110 and has a mounting hole 122 into which the hinge shaft 106 is inserted . thus , the retractor 110 is rotatably coupled to the hinge shaft 106 in such a way that the hinge shaft 106 is inserted into the mounting hole 122 of the mounting bracket 120 . furthermore , stoppers 108 are fastened to the hinge shaft 106 on opposite sides of the mounting bracket 102 to prevent the retractor 110 from undesirably moving along the hinge shaft 106 to the left or the right . in the present invention , although the angle at which the seat back 102 is inclined is changed , the retractor 110 can be maintained in a vertical state because it is rotatable around the hinge shaft 106 . further , a control unit 130 is provided in the body 112 of each retractor 110 to control unwinding of the belt 210 , 210 a . the control unit 130 includes a motor 132 which is fastened to the body 112 of the retractor 110 at a position corresponding to the direction in which the ratchet teeth 114 a are formed . a rotary member 134 is provided on a motor shaft of the motor 132 and is rotated by the operation of the motor 132 . the rotary member 134 is disposed under the ball housing 118 and has thereon a contact protrusion 136 which comes into contact with the lower end of the control shaft 116 a that protrudes downwards from the ball housing 118 , so that the control shaft 116 a is vertically moved by the contact protrusion 136 . in the present invention , a control box 140 is provided to operate the motor 132 of the control unit 130 . in detail , a predetermined speed is set by a user and stored in the control box 140 . when the vehicle reaches the preset speed , the motor 132 is automatically operated so that the contact protrusion 136 of the rotary member 134 moves the control shaft 116 a upwards . then , the pawl 119 a of the operating lever 119 is disposed at an upper position to be locked to the ratchet teeth 114 a , thus preventing the belt 210 , 210 a from being unwound from the retractor 110 . on the contrary , when the speed of the vehicle becomes lower than the preset speed , the control box 140 senses this and automatically operates the motor 132 so that the contact protrusion 136 of the rotary member 134 moves away from the control shaft 116 a . then , the control shaft 116 a moves downwards to a lower position , thus allowing for the user to extract the belt 210 , 210 a from the retractor 110 . as such , when the speed of the vehicle reaches the preset speed , the control unit 130 receives this information from the control box 140 to operate the motor 132 . then , the rotary member 134 is rotated by the operation of the motor 132 . due to the rotation of the rotary member 134 , the contact protrusion 136 pushes the control shaft 116 a upwards . the control shaft 116 a that moves upwards pushes the pawl 119 a of the operating lever 119 upwards so that the pawl 119 a engages with the ratchet teeth 114 a , thus preventing the belt 210 , 210 a from being unwound . meanwhile , a switch 142 is provided on the control box 140 to allow the locking of the control unit 130 to be released by the demand of the user , who is wearing the safety belt 100 , even when the speed of the vehicle exceeds the preset speed and the pawl 119 a of the operating lever 119 has been locked to the ratchet teeth 114 a . therefore , even when the pawl 119 a of the operating lever 119 has been locked to the ratchet teeth 114 a under the control of the control unit 130 , as necessary , the pawl 119 a of the operating lever 119 is released from the ratchet teeth 114 a for a predetermined time . after the predetermined time has passed , the motor 132 is operated by the control of the control box 140 so that the pawl 119 a of the operating lever 119 is locked to the ratchet teeth 114 a again . furthermore , two guide depressions 109 are formed in the rear surface of the seat back 102 and extend from the installation depression 104 upwards . the guide depressions 109 function to guide the corresponding belts 210 and 210 a extracted from the retractors 110 . the rear surface of the seat back 102 is covered with a cover plate 107 . that is , the cover plate 107 is fastened to the seat back 102 by bolts or the like to cover the installation depression 104 and the guide depressions 109 . meanwhile , the belts 210 and 210 a are extracted from the two retractors 110 , pass over the upper end of the seat back 102 , and are disposed on opposite sides of a front surface of the seat back 102 . ends of the belts 210 and 210 a are respectively fastened to anchors 212 which are fixed to opposite sidewalls of a lower end of the seat back 102 . in other words , the belts 210 and 210 a are extracted from the retractors 110 and are disposed on opposite sides of the front surface on the seat back 102 in the shape of suspenders . therefore , the belts 210 and 210 a that are disposed on the opposite sides of the front surface of the seat back 102 support the shoulders of the user in a manner similar to wearing suspenders , thus preventing the belts 210 and 210 a from compressing the chest and abdomen of the user . therefore , the user can not only sit on the seat in a comfortable position but can also comfortably drive the vehicle . in this embodiment , belt guide members 220 which guide the corresponding belts 210 and 210 a are provided on the upper end of the seat back 102 at both sides corresponding to the respective guide depressions 109 . each belt guide member 220 includes a casing 222 which is fastened to a predetermined portion of the upper end of the seat back 102 by a fastening means and has a hole 224 therein . a guide shaft 226 which guides the belt 210 , 210 a is provided in the hole 224 of the casing 222 . due to the belt guide members 220 , the belts 210 and 210 a which are extracted from the retractor 110 can always move based on the constant positions on the seat back . furthermore , a fastening unit 310 is provided on the belts 210 and 210 a and fastens the belts 210 and 210 a to each other to support a user who is sitting on the seat . the fastening unit 310 includes a tongue plate 320 which is provided on one ( for example , 210 ) of the belts 210 and 210 a , and a buckle 330 which is provided on the other belt ( 210 a ). the tongue plate 320 is removably fastened into the buckle 330 . one end of the tongue plate 320 has a hook 322 which is removably locked to the buckle 330 . a first insert slot 324 into which the belt 210 is inserted is formed in the tongue plate 320 at a side opposite to the hook 322 . a first twist prevention slot 326 into which the belt 210 is also inserted is formed in the tongue plate 320 at a position adjacent to the first insert slot 324 and is slanted at an angle with respect to the first insert slot 324 to prevent the belt 210 from being twisted . the belt 210 is successively inserted into the first insert slot 324 and the first twist prevention slot 326 . thus , the user can easily adjust the position at which the tongue plate 320 is disposed . in addition , when the belt 210 is not in use , the tongue plate 320 can be maintained in a state of being in close contact with the seat back 102 . the buckle 330 has in a first end thereof a fastening hole 332 into which the hook 322 of the tongue plate 320 is inserted . a connection member 350 to which the belt 210 a is coupled is provided on a second end of the buckle 330 that is opposite the fastening hole 332 . the buckle 330 includes a button 334 which is used to unlock the tongue plate 320 from the buckle 330 . an open recess 336 is formed in the second end of the buckle 330 that is opposite to the button 334 . seating depressions 336 a corresponding to each other are formed in respective inner sidewalls of the open recess 336 . a through hole 336 b is formed in each seating depression 336 a in the lateral direction of the buckle 310 . a cover member 338 which covers seating depressions 336 a is provided on the buckle 330 in such a way that a first end of the cover member 338 is rotatably coupled to the buckle 330 by a hinge 338 a . a coupling hole 338 b is formed in a lower portion of a second end of the cover member 338 . further , a release pin 340 is inserted into the through holes 336 b of the open recess 336 via the through hole 336 b of the cover member 338 . in detail , a handle 342 is provided on a first end of the release pin 340 that protrudes outwards from the buckle 330 . a locking ball 344 which prevents the release pin 340 from being undesirably removed from the buckle 330 is provided in a second end of the release pin 340 that protrudes outwards from the buckle 330 in the direction opposite to the direction in which the handle 342 protrudes outwards . in detail , an installation hole 344 a is formed through the second end of the release pin 340 in the lateral direction of the release pin 340 . the locking ball 344 is inserted into the installation hole 344 a . an elastic member 344 b which elastically supports the locking ball 344 is provided in the installation hole 344 a . a bolt 344 c is threaded into the installation hole 344 a to hold the elastic member 344 b in the installation hole 344 a . furthermore , the connection member 350 is inserted into the open recess 336 of the buckle 330 . in an embodiment , an insert part 352 is provided on the corresponding end of the connection member 350 . seating protrusions 352 a protrude outwards from the insert part 352 in opposite directions . the seating protrusions 352 a are movably inserted into the corresponding seating depressions 336 a so that the connection member 350 is movably coupled to the buckle 330 . here , the seating protrusions 352 a of the insert part 352 are inserted into the corresponding seating depressions 336 a of the buckle 330 in such a way that the insert part 352 is disposed below the release pin 340 . furthermore , a second insert slot 354 into which the belt 210 a is inserted is formed in the connection member 350 at a side opposite the insert part 352 . a second twist prevention slot 356 is formed in the connection member 350 at a position adjacent to the second insert slot 354 and slants with respect to the second insert slot 354 to prevent the belt 210 a from being twisted . a method of coupling the belt 210 a to the connection member 350 is the same as the method of coupling the belt 210 to the tongue plate 320 through the first insert slot 324 and the first twist prevention slot 326 . in addition , the buckle 330 is movably coupled to the connection member 350 . therefore , when the belts 210 and 210 a are not in use , the buckle 330 is rotated around the junction between the buckle 330 and the connection member 350 and is folded onto the connection member 350 to be brought into contact with the connection member 350 . thus , the buckle 330 can be stably maintained in a state of being in close contact with the seat back 102 . meanwhile , when the user who is wearing the safety belt 100 is involved in a vehicle collision , the fastening unit 310 of the safety belt 100 may not be unlocked . at this time , the user holds the handle 342 of the release pin 340 and strongly pulls it . then , the release pin 340 is removed from the buckle 330 so that the cover member 338 can be open . thereby , the connection member 350 coupled to the belt 210 a can be easily removed from the buckle 330 , thus allowing the user to move away from the accident vehicle . preferably , each of the tongue plate 320 and the connection member 350 has an arc shape that is concave on its surface which comes into contact with the body of the user . as such , the tongue plate 320 and the connection member 350 have arc shapes corresponding to the body of the user that are designed to make contact with the body of the user . the buckle 330 has a shape corresponding to the arc shape of the connection member 350 , that is , a convex surface corresponding to the arc shape of the connection member 350 is formed on the buckle 330 so that after the buckle 330 is folded onto the connection member 350 to make contact with it , the buckle 330 is reliably maintained in a state of close contact with the connection member 350 . therefore , when the user wears the safety belt 100 , the tongue plate 320 and the connection member 350 that have arc shapes can reliably come into close contact with the body of the user . in the case where the safety belt 100 is not in use , after the buckle 330 and the connection member 350 are folded around the junction therebetween , the buckle 330 can be reliably maintained in a state of close contact with the connection member 350 . the operation of the safety belt according to the present invention having the above - mentioned construction will be described with reference to an example of the case of a driver &# 39 ; s seat . fig9 is a view showing the user who is wearing the safety belt to illustrate the operation of the safety belt according to the present invention . fig1 is a view showing the safety belt which is not in use , illustrating the operation of the safety belt according to the present invention . fig1 is a view showing the operation of the safety belt according to the present invention , illustrating the buckle being forcibly unlocked . as shown in the drawings , in the safety belt 100 according to the present invention , a driver sits on the seat and puts the belts 210 and 210 a on his / her shoulders . subsequently , the driver fastens the tongue plate 320 of the fastening unit 310 to the buckle 330 , thus completing the wearing of the safety belt 100 . in the present invention , the belts 210 and 210 a support the shoulders of the driver in a manner similar to wearing suspenders , thus allowing the driver to freely move . further , the belts 210 and 210 a do not compress the chest or abdomen of the driver , thus making it possible for the driver to drive the vehicle in a comfortable position . if the vehicle is involved in a collision after the driver has fastened the safety belt 100 , the belts 210 and 210 a supports the shoulders of the driver so that an impact caused by the collision is dispersed over the entire body of the driver rather than being concentrated on one spot , thus preventing the driver from suffering from enterorrhexis , fracture of spine , etc . meanwhile , when the angle at which the seat back 102 is inclined is adjusted , for example , when the seat back 102 is inclined backwards , each retractor 110 rotates around the hinge shaft 106 due to its on weight such that the retractor 110 is always in the vertical state . thereby , the belt 210 , 210 a can be reliably extracted from or retracted into the retractor 110 . furthermore , when the speed of the vehicle which is in motion reaches the preset speed , the motor 132 of the control unit 130 is operated to rotate the rotary member 134 . because of the rotation of the rotary member 134 , the contact protrusion 136 pushes the control shaft 116 a upwards . when the control shaft 116 a that is pushed by the contact protrusion 136 upwards reaches the uppermost position , the motor 132 stops . as such , when the contact protrusion 136 of the rotary member 134 pushes the control shaft 116 a upwards , the control shaft 116 a moves the pawl 119 a of the operating lever 119 to engage the pawl 119 a with the ratchet teeth 114 a of the drum 114 so that the belt 210 , 210 a can no longer be extracted from the retractor 110 . thereby , the driver can be maintained in a state of being held by the belts 210 and 210 a and so be in close contact with the seat back 102 . meanwhile , in the present invention , the first and second twist prevention slots 326 and 236 are respectively formed in the tongue plate 320 and the connection member 350 of the buckle 330 . therefore , when the safety belt 100 is not in use or the belts 210 and 210 a are fastened to each other so that the safety belt 100 can be worn , the belts 210 and 210 a are prevented from being twisted . furthermore , the belt 210 is coupled to the tongue plate 320 by the first insert slot 324 and the first twist prevention slot 326 . thus , when the safety belt 100 is not in use , the tongue plate 320 can maintain a state of close contact with the seat back 102 . also , the belt 210 a is coupled to the connection member 250 of the buckle 330 in the same manner as the method of coupling the belt 210 to the first insert slot 324 and the first twist prevention slot 326 of the tongue plate 320 . thus , the belt 210 a is prevented from being twisted . when the safety belt 100 is not in use , the buckle 330 rotates around the connection junction between the buckle 330 and the connection member 350 . thereby , the buckle 330 is brought into close contact with the upper portion of the connection member 350 so that the buckle 330 can be reliably maintained in a state of being in close contact with the seat back 102 . meanwhile , when the vehicle which is in motion is involved in a collision , the tongue plate 320 and the buckle 330 of the safety belt 100 may be damaged and thus not be separated from each other . at this time , the user who is wearing the safety belt 100 holds the handle 342 of the release pin 340 which has been locked to the buckle 330 and strongly pulls it . then , the release pin 340 is removed from the buckle 330 so that the cover member 338 can open . thereafter , the connection member 350 is separated from the buckle 330 , thus allowing the user to be easily released from the safety belt 100 . as a result , the user can easily unfasten the safety belt 100 to safely escape from the vehicle which has been in an accident . as described above , in a safety belt for a vehicle according to the present invention , belts which are configured in a shape similar to that of suspenders support the shoulders of a user , for example , a driver , who is sitting on a seat . thus , when the vehicle is in motion , pressure is prevented from being concentrated on portion of the body of the driver . therefore , the present invention makes it possible for the driver to drive the vehicle in a comfortable position . furthermore , because the belts support the shoulders of the driver , impact caused by a vehicle collision can be evenly dispersed to the entire upper body of the driver , thus more effectively preventing the driver from being injured . in addition , each of a buckle and a tongue plate has an insert slot to which the corresponding belt is coupled , and a twist prevention slot which prevents the belt from being twisted . because the belt is double - coupled to the insert slot and the twist prevention slot , the belt can be reliably prevented from being twisted . further , retractors are received in a rear surface of a seat back . the upper end of each retractor is rotatably supported by a hinge . thus , even when the driver adjusts the angle at which the seat back is inclined depending on the body type of the driver , the retractors can always be maintained in the vertical state , thus preventing the retractors from malfunctioning . moreover , the retractors that are received in the rear surface of the seat back are covered with a cover plate . hence , repair or maintenance of the retractors can be facilitated . also , each retractor is provided with a control unit so that when the speed of the vehicle which is in motion reaches a preset degree , the belt is automatically restricted from being unwound from the retractor . thus , the present invention can stably support the driver on the seat back and protect the driver from safety accidents which may occur while the vehicle is in motion . furthermore , belt guide members which guide the corresponding belts are provided on the upper end of the seat back . thus , the belts are guided by the belt guide members so that the belts pass over the same portions of both sides of the body of the driver . therefore , when a vehicle collision occurs , the present invention prevents the driver from suffering from enterorrhexis , fracture of spine , etc . in addition , a release pin is provided in the buckle to allow the driver to forcibly unfasten the safety belt . thus , even if the safety belt cannot be unfastened when a vehicle collision occurs , the driver can use the release pin to forcibly unfasten the safety belt and safely escape from the vehicle which has been in an accident . although the preferred embodiment of the safety belt for vehicles according to the present invention has been disclosed for illustrative purposes , the present invention is not limited to this embodiment and can be applied to typical retractors or buckles which are installed in vehicles . furthermore , those skilled in the art will appreciate that various modifications , additions and substitutions are possible , without departing from the scope and spirit of the invention as disclosed in the accompanying claims .

a safety belt for a vehicle which can be worn in a manner of wearing suspenders to prevent a concentration of pressure to a part of the body of a seat occupant , and to uniformly distribute impact to thereby safely protect the seat occupant even upon the occurrence of an emergency during travel . to accomplish the above - described object , the safety belt for a vehicle according to the present invention comprises a pair of belts spaced apart from each other in a vertical direction on the front surface of a seatback and a connection unit for interconnecting the pair of belts .

referring to the drawings more particularly by reference numbers , fig1 shows a toy set 10 of the present invention . the toy set 10 includes a vehicle 12 that is remotely controlled by an end user through a transmitter unit 14 . the transmitter unit 14 has a lever and / or buttons 16 which can be manipulated by the end user to transmit control signals to the vehicle 12 . fig2 shows a control system for the toy set 10 . the system includes a transmitter 18 located within the unit 14 . the transmitter 18 sends signals to a receiver 20 located within the vehicle 12 . the signals may be modulated electrical signals operating in a radio frequency range . alternatively , the transmitted signals may be in the infrared frequency range . the receiver 20 is coupled to a motor controller 22 which controls the speed of a motor 24 that powers the vehicle 12 . the receiver 20 is also coupled to an actuator 26 . the actuator 26 may be a solenoid which moves a plunger 28 to an extended position . the transmitter 18 may have a lever button ( s ) which transmits a first signal to control the motor 24 , and a separate lever or button that transmits a second signal which energizes the actuator 26 . the first and second command signals are typically provided on separate communication channels . although a plunger 28 is shown and described , it is to be understood that the vehicle 12 may have other mechanisms which can mechanically engage an external device . referring to fig1 the vehicle 12 may be constructed as a toy train that moves about a circular track 30 . the vehicle 12 and track 30 may have elements that guide the train 12 around the track 30 as is known in the art . the track 30 may be constructed as individual pieces which are assembled by the end user onto a playing surface . the train set may have a loading station 32 and an unloading station 34 . as shown in fig3 a , the loading station 32 includes an action accessory 35 . the accessory 35 has a plurality of individual toy barrels 36 located on a ramp 38 . the barrels 36 are held in place by a lever mechanism 40 . the lever mechanism 40 is coupled to a trigger 42 located within the track 30 . the lever 40 is moved into a downward direction when the trigger 42 is depressed . as shown in fig3 b , the end user manipulates the transmitter to move the train 12 in front of the loading station 32 . when the plunger 28 is aligned with the trigger 42 , the end user transmits a command signal to energize the actuator 26 . energizing the actuator 26 extends the plunger 28 into the trigger 42 . the depression of the trigger 42 lowers the lever 40 and allows the toy barrels 36 to fall into a container compartment 44 of the train 12 . when the command signal is terminated , the plunger 28 disengages from the trigger 42 and returns to the original position . the actuator 26 typically has a spring return that moves the plunger 28 to the original position when power is terminated to the solenoid . fig4 a shows an unload lever 46 and a latch button 48 that are located on the track 30 and adjacent to the unloading station 34 shown in fig1 . depressing the button 48 moves the lever 46 into an upward loaded position . as shown in fig4 b when the train 12 moves into the unloading station 34 , the lever 46 engages a cam mechanism ( not shown ) which tilts the container compartment 44 of the train and rolls the toy barrels 36 into a bin 50 . the engagement of the vehicle with the unload lever 46 moves the lever 46 down into a lower position . the lever 46 may be reset by depressing the button 48 . as shown in fig5 a - c the loading station 32 may further include a flexible alignment tab 52 that aligns the plunger 28 of the train 12 with the trigger 42 . the train 12 may have a locator 54 which moves over the flexible tab 52 when moving in a first direction . when the direction of the train 12 is reversed , the locator 54 engages the tab 52 and prevents further train motion , so that the plunger 28 is located above the trigger 42 . the locator 54 and tab 52 allows the end user to more readily align the plunger 28 with the trigger 42 and load the toy barrels 36 into the container compartment 44 of the train . fig6 shows an alternate embodiment of the toy set . the toy set includes a remotely controlled vehicle 100 which has a plunger 102 that can depress a trigger 104 of an action accessory 106 . the action accessory 106 contains a plurality of toy missiles 108 which are ejected from a toy launcher 110 when the plunger 102 depresses the trigger 104 . the launcher 110 may contain a mechanical or electrical selector which sequentially fires the missiles after each depression of the trigger 104 . the toy set can be operated through a remote transmitter unit 112 held and manipulated by the end user . the transmitter 112 sends signals to a receiver located within the vehicle 100 . the transmitted signals control the speed and direction of the vehicle . additionally , the transmitted signals can activate the plunger 102 and depress the trigger 104 . the vehicle 100 may contain an action figure 114 that moves to an up position when the plunger 102 is activated by the transmitter 112 . the transmitter 112 may contain three separate channels that control the vehicle speed , vehicle direction , and the plunger , respectively . there may be a v - shaped guide channel 116 located along the bottom of the vehicle 100 . the guide channel 116 cooperates with an outer annular rim 118 of the trigger 104 to guide the vehicle 100 and align the plunger 102 with the trigger 104 . fig7 shows an alternate embodiment of an action accessory 120 which has a toy missile launcher 122 that can be rotated about a base 124 . when the vehicle 100 moves adjacent to the accessory 120 , the guide channel 116 exerts a force on the outer trigger rim 126 and rotates the missile launcher 122 relative to the base 124 . the launcher 122 ejects a toy missile 128 when the trigger 130 is depressed by the plunger 102 of the vehicle 100 . fig8 shows an another action accessory 140 which emits a stream of fluid when the trigger 142 is depressed by the plunger 102 of the vehicle 100 . the accessory 140 may be molded as a toy cannon which contains a reservoir that can be filled with water . fig9 a and 9b show an alternate action accessory 150 which has a platform mechanism 152 that projects a plurality of toy cargo containers 154 when the trigger 156 is depressed by the plunger 102 of a vehicle 100 . the action accessory 150 provides the appearance of blowing up the containers 154 when the vehicle 100 is in alignment with the accessory 150 . fig1 a and 10b show an alternate action accessory 160 similar to the accessory 150 shown in fig9 a and 9b . the accessory 160 contains a platform mechanism 162 that lifts a number of action figures 164 when the trigger 166 is depressed by the plunger 102 of the vehicle 100 . fig1 a and 11b show an alternate action accessory 170 which contains a toy bunker 172 mounted to a cardboard mat 174 . the bunker 172 contains an action figure 176 that is lifted past a rotating lid 178 when the plunger 102 of the vehicle 100 depresses the trigger 180 of the accessory 170 . fig1 a and 12b show an alternate action accessory 190 which has a number of walls 192 that pivot about a base 194 . the walls 192 have interlocking roof sections 196 which allow the walls 192 to become detached and rotated to a downward position when the trigger 198 is depressed by the plunger 102 of the vehicle 100 . the action accessory 190 provides the appearance of a building that is blowing up as the vehicle is in alignment with the accessory 190 . fig1 shows another action accessory 200 which projects a toy airplane 202 from a spring - loaded launcher 204 when the plunger 102 of the vehicle 100 depresses the trigger 206 . the toy airplane 202 may be constructed from a light foam material that can be projected a relatively long distance . fig1 shows an alternate action accessory 210 which ejects a rotating ring 212 from a launcher 214 when the trigger 216 is depressed by the plunger 102 of the vehicle 100 . the action accessory 210 may provide the appearance of a helicopter taking off from a launching pad . the present invention provides a remote controlled vehicle that mechanically actuates a number of action accessories . each toy set may have a plurality of action accessories that can be actuated through a relatively inexpensive two or three channel transmitter . while certain exemplary embodiments have been described and shown in the accompanying drawings , it is to be understood that such embodiments are merely illustrative of and not restrictive on the broad invention , and that this invention not be limited to the specific constructions and arrangements shown and described , since various other modifications may occur to those ordinarily skilled in the art .

a remotely controlled vehicle that mechanically activates an action accessory . the vehicle contains a remotely controlled plunger that engages a trigger of the action accessory . engaging the trigger activates a mechanism within the action accessory . activation of the mechanism induces a mechanical action such as ejecting a projectile or loading items onto the vehicle . the plunger and vehicle are remotely controlled by a transmitter which emits command signals to a receiver located within the vehicle . in operation , the end user skillfully manipulates the vehicle over the trigger and then transmits a command to extend the plunger and activate the mechanism of the action accessory .

in carrying out our invention we show in fig1 a front elevation of the dishwasher . the wash and rinse compartment a , is enclosed in the housing and is illustrated schematically in fig7 . the housing has a front door 1 which may be opened and closed by handles 2 . within the compartment a , we show a dish rack b for containing the dishes to be washed and rinsed . upper and lower spray arms c , are positioned in the wash / rinse compartment a and are shown schematically in fig7 . a water receiving tank d underlies the wash / rinse compartment and receives water therefrom . schematic fig7 illustrates a motor e for driving an impeller pump f , and this pump receives water from the tank d through a pipe 3 and forces this water through a pipe 4 to the lower spray arm c . a branch pipe 5 connects the pipe 4 to the upper spray arm c so that when the impeller pump f , is operated by the motor e , it will force hot water through the pipes 4 and 5 and out through the two spray arms . the hot water returns to the tank d by gravity and is rady to be used again . the dishwasher is designed to operate through a dishwashing cycle followed by a combined dish rinsing and sterilizing cycle so that the rinse water can be at a temperature of 140 ° f ., rather than the 180 ° f ., which would be required if no sanitizing agent such as chlorine were used . in fig8 we graphically show the two timing cycles one for washing the dishes and the other for rinsing and sterilizing the dishes . we also indicate when the detergent is added to the wash water and when the sanitizing agent and rinsing aid are added to the rinse water . before describing the timing cycles in detail it is best to set forth how the detergent is delivered to the wash water and how the sanitizing agent and rinse aid are simultaneously delivered to the rinse water . in fig2 and 7 we show a container g for the liquid detergent , a container h , for the sanitizing agent , such as chlorine , and a container j for the liquid rinse aid . a tube 6 leads from the detergent container g to a solenoid controlled valve k mounted in a housing l , see fig3 and 4 . in like manner , another tube 7 leads from the sanitizing agent container h to a solenoid controlled valve m positioned in the housing l , and a tube 8 leads from the rinse aid container j to a solenoid controlled valve n . all three solenoid valves are identical to each other except that the solenoid valve n has a fine adjustment mechanism for controlling the flow of the rinse aid in the tube 8 which the other two solenoid valves k and m , do not need . therefore the solenoid valve n will be described in detail and this will suffice for the other two solenoid valves . fig5 and 6 illustrate the solenoid valve n , in detail . the tube 8 is shown lying between a block 9 and a tube compressing member 10 . the solenoid 11 when energized by an electric current will lift a spring biased rod 12 and raise the tube compressing member 10 so as not to compress the tube 8 as is shown in fig5 . when the solenoid coil 11 is de - energized , a spring 13 will force the rod 12 to cause the member 10 to compress the tube 8 and stop any fluid flow therethrough . in addition to the closing and opening of the tube 8 , we show a fine adjustment mechanism for varying the size of the passage in the tube 8 when the tube compressing member is raised and frees the tube . the block 9 has a recess 14 therein , see fig6 in which an adjustable plunger 15 is mounted . a set screw 16 is threaded into a bore in the block 9 and the screw may be adjusted for slightly compressing the tube 8 even when the tube compressing member 10 is in raised position as shown in fig5 . a lock nut 17 on the set screw 16 secures the plunger 15 in adjusted position . in the present invention the solenoid valves k , and m do not need the fine adjustment plunger 15 and set screw 16 and are therefore not shown in fig4 . one vital and novel feature of our invention lies in the manner of removing the liquid detergent from the container g , and for removing the liquid sanitizing agent from the container h , and the liquid rinse aid from the container j . reference to fig2 and 7 shows the three tubes 6 , 7 and 8 after being controlled by the solenoid valves k , m , and n , in a manner hereinafter described , communicate with a common tube 18 and the end of this tube is positioned adjacent to the greatest suction created by the impeller of the pump f , see especially fig7 . we have found that this suction created at the open end of the tube 18 is sufficient to entrain fluid through the common tube 18 and the separate tubes 6 , 7 and 8 to remove liquid from the containers g , h , and j , this depending on which of the three tubes 6 , 7 and 8 are not closed by the solenoid valves k , m , and l . this will be described more in detail hereinafter . the suction at the open end of the tube 18 is sufficient to draw a liquid detergent from the container g during the washing cycle and is sufficient to draw a liquid sanitizing agent from the container h , and a liquid rinse aid from the container j during the rinse and sanitizing cycle . this is a very important feature of our invention . a solid state electric control series of circuits are shown in fig4 and these control the various timing cycles shown in fig8 where it will be seen that the wash cycle is on for 45 seconds , then off for 10 seconds while the wash water is drained to the sewer and then the rinse cycle is on for 35 seconds after which the dishwasher automatically stops . these two cycles cover a period of 90 seconds which includes the 10 second time period for draining the wash water between the wash and rinse cycles . we do not wish to be confined to the exact timing of the wash and rinse cycles as indicated because the solid state electronic circuits shown in fig4 have adjustable time delays shown at p , q , and r . the time delay p controls the solenoid valve k for the detergent carrying tube 6 and the knob 19 can be adjusted to open the tube 6 for only 5 seconds at the start of the wash cycle to admit the liquid detergent into the wash water . in fig8 the detergent line 20 is shown in open position only during the first five seconds of the washing cycle . the tank d , see fig7 has previously been filled with hot wash water at 140 ° f . the spring 13 in the solenoid k will keep the detergent carrying tube 6 closed except for this 5 second period when it is open . since the knob 19 is set for this 5 second opening of the detergent line 6 , there is no need for using the fine adjustment set screw 16 and the plunger 15 and these therefore are not shown for the solenoid valve k . the graph line 21 in fig8 represents the duration that the electric power is on during the wash and rinse cycles and this is shown for a period of 90 seconds after which the power is automatically cut off . the next lower graph line 22 is the wash cycle and the rinse cycle line and the electric current to the motor e is on for the first 45 seconds for the wash cycle , then off for 10 seconds while the wash water is drained and then on for 35 seconds during the rinse cycle . the foruth graph line 23 is for the drain valve 24 , shown diagrammatically in fig7 . a solenoid 25 is energized after 45 seconds of the wash cycle and lifts a rod 26 to open the valve 24 and drain the wash water into the sewer for a period of 10 seconds , after which the solenoid is de - energized and the drain valve closes . the bottom graph line 27 in fig8 represents the sanitizing agent ( chlorine ) and the rinse aid both of which are simultaneously introduced into the rinse water for a five second period . the adjustable timer q controls the solenoid valve m for opening the chlorine carrying tube 7 , see fig4 for a period of five seconds during the rinsing cycle . at the same time the adjustable timer r , controls the solenoid valve n for opening the rinse aid carrying tube 9 for delivering the rinse aid into the rinse water . very little rinse aid is required and that is why we use the set screw 16 for moving the plunger 15 for partially collapsing the tube 8 against the raised compressing member 10 so that a predetermined volume of rinse aid will flow through the tube during the five second interval while the solenoid valve n , is held open as indicated in graph line 27 of fig8 . the electronic circuits shown in fig4 are regulated to function in the following manner . the knob 19 on the adjustable timer p causes the detergent valve k to open the tube 6 for five seconds at the start of the wash cycle as shown by the graph line 20 in fig8 . the suction created by the impeller pump f , is sufficient to draw liquid detergent from the container g , shown in fig7 and deliver it into the wash water that flows through the pipe 4 and the spray arms c . after the wash cycle , the electronic circuit will energize the solenoid 25 in fig7 to raise the rod 26 and open the drain valve 24 for emptying the tank d of its wash water , see the graph line 23 in fig8 . during this time , the motor e and the impeller pump f do not function . then the rinse cycle starts and functions and the graph line 22 in fig8 shows the rinse cycle extending from the 55 second position on the chart and terminating at 90 second position at which point the rinse cycle terminates . any means may be used for delivering fresh rinse water at 140 ° f ., into the tank d , in fig7 and we have shown schematically a fresh rinse hot water pipe 28 controlled by a valve 29 for delivering fresh rinse water into the tank starting at the 55 second position on the graph line 22 . a predetermined volume of hot rinse water is delivered into the tank d , and then the valve 29 automatically closes by the electronic timing circuit . the hot rinse water at 140 ° f ., will be delivered to the impeller pump f which starts again at the 55 second position on the graph line 22 in fig8 . then the electronic solid state circuits of fig4 will cause the solenoid valves m , and n , both to open for five seconds , see the graph line 27 in fig8 . the solid state &# 34 ; on &# 34 ; timer q can be adjusted y the knob 30 and the &# 34 ; off &# 34 ; timer r can be adjusted by the knob 31 so that the solenoid valves m and n , will open for the five second interval during the rinse cycle . the hot rinse water at 140 ° f ., is sufficient to sterilize the dishes during the rinse cycle because the sanitizing agent , chlorine , has been added . the sterilizing agent is removed from the container h by the suction created by the impeller pump f , and this suction will create an entraining action in the common tube 18 sufficient to deliver the strerilizing agent into the rinse water . the same holds true for removing a predetermined volume of rinse aid from the container j when the solenoid valve n is opened . again , the suction created by the impeller pump f will entrain the rinse aid from the common tube 18 and the rinse aid tube 8 that has its inlet end submerged in the rinse aid liquid in the container j .

a commercial dishwasher having a wash / rinse compartment for receiving dishes and a tank below the compartment for receiving wash or rinse water after a motor driven impeller has circulated the water from the tank and has forced it through spray arms in the compartment employs the suction created by the impeller for removing a detergent from a container in timed sequence by an entraining action during the wash cycle and mixing the detergent with the wash water during the dishwashing cycle . this same suction created by the impeller is employed for simultaneously removing a sanitizing liquid from a container and a rinse aid liquid from another container and mixing these two liquids with a rinse water during the rinsing and sterilizing cycle in timed sequence .

fig1 illustrates a microfluidic delivery system 10 in accordance with one embodiment of the disclosure . the microfluidic delivery system 10 includes a housing 12 having an upper surface 14 , a lower surface 16 , and a body portion 18 between the upper and lower surfaces . the upper surface of the housing 12 includes a first hole 20 that places an environment external to the housing 12 in fluid communication with an interior portion 22 of the housing 12 . the interior portion 22 of the housing 12 includes a holder member 24 that holds a removable microfluidic refill cartridge 26 . as will be explained below , the microfluidic delivery system 10 is configured to use thermal energy to deliver fluid from within the microfluidic refill cartridge 26 to an environment external to the housing 12 . access to the interior portion 22 of the housing is provided by an opening 28 in the body portion 18 of the housing 12 . the opening 28 is accessible by a cover or door 30 of the housing 12 . in the illustrated embodiment , the door 30 rotates to provide access to the opening 28 . although the opening and door are located on the body portion of the housing , it is to be appreciated that the opening and door may also be located on the upper surface and the lower surface of the housing . furthermore , it is to be appreciated that in other embodiments , the housing has two or more separable parts for providing access to the interior portion . the holder member 24 includes an upper surface 32 and a lower surface 34 that are coupled together by one or more sidewalls 36 and has an open side 38 through which the microfluidic refill cartridge 26 can slide in and out . the upper surface 32 of the holder member includes an opening 40 that is aligned with the first hole 20 of the housing 12 . the holder member 24 holds the microfluidic refill cartridge 26 in position when located therein . in one embodiment , the holder member 24 elastically deforms , thereby gripping the microfluidic refill cartridge 26 in place when located in the holder member . in another embodiment , the holder member 24 includes a locking system ( not shown ) for holding the microfluidic refill cartridge in place . in one embodiment , the locking system includes a rotatable bar that extends across the open side of the holder member to hold the microfluidic refill cartridge in place . the housing 12 includes conductive elements ( not shown ) that couple electrical components throughout the system as is well known in the art . the housing 12 may further include connection elements for coupling to an external or internal power source . the connection elements may be a plug configured to be plugged into an electrical outlet or battery terminals . the housing 12 may include a power switch 42 on a front of the housing 12 . fig2 a shows the microfluidic refill cartridge 26 in the holder member 24 without the housing 12 , and fig2 b shows the microfluidic refill cartridge 26 removed from the holder member 24 . a circuit board 44 is coupled to the upper surface 32 of the holder member by a screw 46 . as will be explained in more detail below , the circuit board 44 includes electrical contacts 48 ( fig3 ) that electrically couple to contacts of the microfluidic refill cartridge 26 when the cartridge is placed in the holder member . the electrical contacts 48 of the circuit board 44 are in electrical communication with the conductive elements . fig3 is a cross - section view of the microfluidic refill cartridge 26 in the holder member 24 along the line 3 - 3 shown in fig2 a . with reference to fig2 b and fig3 , the microfluidic refill cartridge 26 includes a reservoir 50 for holding a fluid 52 . the reservoir 50 may be any shape , size , or material configured to hold any number of different types of fluid . the fluid held in the reservoir may be any liquid composition . in one embodiment , the fluid is an oil , such as a scented oil . in another embodiment , the fluid is water . it may also be alcohol , a perfume , a biological material , a polymer for 3 - d printing , or other fluid . a lid 54 , having an inner surface 56 and an outer surface 58 , is secured to an upper portion 60 of the reservoir 50 to cover the reservoir 50 . the lid 54 may be secured to the reservoir in a variety of ways known in the art . in some embodiments , the lid 54 is releasably secured to the reservoir 50 . for instance , the lid 54 and the upper portion 60 of the reservoir 50 may have corresponding threads , or the lid 54 may snap onto the upper portion 60 of the reservoir 54 . between the lid 54 and the reservoir 50 there may be an o - ring 62 for forming a seal therebetween . the seal may prevent fluid from flowing therethrough as well as prevent evaporation of the fluid to an external environment . a microfluidic delivery member 64 is secured to an upper surface 66 of the lid 54 of the microfluidic refill cartridge 26 as is best shown in fig2 b . the microfluidic delivery member 64 includes an upper surface 68 and a lower surface 70 ( see also fig4 ). a first end 72 of the upper surface 68 includes electrical contacts 74 for coupling with the electrical contacts 48 of the circuit board 44 when placed in the holder member 24 . as will be explained in more detail below , a second end 76 of the microfluidic delivery member 64 includes a fluid path for delivering fluid therethrough . in reference to fig3 , inside the reservoir 50 is a fluid transport member 80 that has a first end 82 in the fluid 52 in the reservoir and a second end 84 that is above the fluid 52 . the fluid 52 travels from the first end 82 of the fluid transport member 80 to the second end 84 by capillary action . in that regard , the fluid transport member 80 includes one or more porous materials that allow the fluid to flow by capillary action . the construction of the fluid transport member 80 permits fluid to travel through the fluid transport member 80 against gravity . fluid can travel by wicking , diffusion , suction , siphon , vacuum , or other mechanism . the second end 84 of the transport member is located below the microfluidic delivery member 64 . the fluid transport member 80 delivers fluid 52 from the reservoir 50 toward the microfluidic delivery member 64 . as best shown in fig4 , the second end 84 of the fluid transport member 80 is surrounded by a transport cover 86 that extends from the inner surface of the lid 54 . the second end 84 of the fluid transport member 80 and the transport cover 86 form a chamber 88 . the chamber 88 may be substantially sealed between the transport cover 86 and the second end 84 of the fluid transport member 80 to prevent air from the reservoir 50 from entering the chamber 88 . above the chamber 88 is a first through hole 90 in the lid 54 that fluidly couples the chamber 88 above the second end 84 of the fluid transport member 80 to a second through hole 78 of the microfluidic delivery member 64 . the microfluidic delivery member 64 is secured to the lid 54 above the first through hole 90 of the lid 54 and receives fluid therefrom . in some embodiments , the fluid transport member 80 includes a polymer ; non - limiting examples include polyethylene ( pe ), including ultra - high molecular weight polyethylene ( uhmw ), polyethylene terephthalate ( pet ), polypropylene ( pp ), nylon 6 ( n6 ), polyester fibers , ethyl vinyl acetate , polyvinylidene fluoride ( pvdf ), and polyethersulfone ( pes ), polytetrafluroethylene ( ptfe ). the fluid transport member 80 may be in the form of woven fibers or sintered beads . it is also to be appreciated that the fluid transport member of the present disclosure is of smaller size than is typically used for fluid transport members for refillable cartridges . as shown in fig4 , the fluid transport member 80 may include an outer sleeve 85 that surrounds radial surfaces of the fluid transport member 80 along at least a portion of its length while keeping the first and second ends 82 , 84 of the fluid transport members 80 exposed . the sleeve 85 may be made from a non - porous material or a material that is less porous than the fluid transport member 80 . in that regard , the sleeve 85 may prevent or at least reduce air in the reservoir from entering the fluid transport member 80 by radial flow . the outer sleeve 85 may be a material that is wrapped around the fluid transport member 80 . in other embodiments , the material 85 is formed on the fluid transport member 80 in an initial liquid state that dries or sets on the fluid transport member . for instance , the material may be sprayed on the fluid transport member or the fluid transport member may be dipped into a liquid material that dries . the outer sleeve may be a polymer sheet , a teflon tape , a thin plastic layer , or the like . teflon tape has particular benefits since it provides a fluid - tight seal , is flexible to wrap , is strong , and also makes it easy to slip member 80 into place . the fluid transport member 80 may be any shape that is able to deliver fluid 52 from the reservoir 50 to the microfluidic delivery member 64 . although the fluid transport member 80 of the illustrated embodiment has a width dimension , such as diameter , that is significantly smaller than the reservoir , it is to be appreciated that the diameter of the fluid transport member 80 may be larger and in one embodiment substantially fills the reservoir 50 . fig5 a and 5b , respectively , are top and bottom views of the microfluidic delivery member 64 in accordance with one embodiment . fig5 c illustrates the microfluidic delivery member 64 in exploded view . the microfluidic delivery member 64 includes a rigid planar circuit board , which can be a printed circuit board ( pcb ) 106 having the upper and lower surfaces 68 , 70 . the pcb 106 includes one or more layers of insulative and conductive materials as is well known in the art . in one embodiment , the circuit board includes fr4 , a composite material composed of woven fiberglass cloth with an epoxy resin binder that is flame resistant . in other embodiments , the circuit board includes ceramic , glass or plastic . the upper surface 68 of the second end 76 of the printed circuit board 106 includes a semiconductor die 92 above the second through hole 78 and leads 112 located proximate the die 92 . electrical contacts 74 at the first end 72 of the microfluidic delivery member 64 are coupled to one or more of the leads 112 at the second end 76 by electrical traces ( not shown ). the upper and lower surfaces 68 , 70 of the pcb 106 may be covered with a solder mask 124 as shown in the cross - section view of fig4 . openings in the solder mask 124 may be provided where the leads 112 are positioned on the circuit board or at the first end 72 where the electrical contacts 74 are formed . the solder mask 124 may be used as a protective layer to cover electrical traces . the die 92 is secured to the upper surface 68 of the printed circuit board 106 by any adhesive material 104 configured to hold the semiconductor die to the pcb . the adhesive material may be an adhesive material that does not readily dissolve by the fluid in the reservoir . in some embodiments , the adhesive material is activated by heat or uv . in some embodiments , a mechanical support ( not shown ) may be provided between a bottom surface 108 of the die 92 and the upper surface 68 of the printed circuit board 106 . as best shown in fig6 , the die 92 includes a plurality of bond pads 109 that are electrically coupled to one or more of the leads 112 by conductive wires 110 . that is , a first end of the conductive wires 110 is coupled to a respective bond pad 109 of the die 92 and a second end of the conductive wires 110 is coupled to a respective lead 112 . thus , the bond pads 109 of the die 92 are in electrical communication with the electrical contacts 74 of the microfluidic delivery member 64 . a molding compound or encapsulation material 116 may be provided over the conductive wires 110 , bond pads 109 , and leads 112 , while leaving a central portion 114 of the die 92 exposed . as best shown in fig4 , the die 92 includes an inlet path 94 in fluid communication with the second through hole 78 on the second end 76 of the delivery member 64 . with reference also to fig7 and 8 , which illustrate corresponding cross sections of the die of fig6 , the inlet path 94 of the die 92 is in fluid communication with a channel 126 that is in fluid communication with individual chambers 128 and nozzles 130 , forming a fluid path through the die 92 . above the chambers 128 is a nozzle plate 132 that includes the plurality of nozzles 130 . in a first embodiment , each nozzle 130 is located above a respective one of the chambers 128 and is an opening in the nozzle plate 132 that is in fluid communication with an environment outside of the microfluidic refill cartridge 26 . the die 92 may have any number of chambers 128 and nozzles 130 , including one chamber and nozzle . in the illustrated embodiment , the die 92 includes 18 chambers 128 and 18 nozzles 130 , each chamber associated with a respective nozzle . alternatively , it can have 10 nozzles and 2 chambers , one chamber providing fluid for a bank of five nozzles . it is not necessary to have a one - to - one correspondence between the chambers and nozzles . in one embodiment , the nozzle plate 132 is 12 microns thick . in some embodiments , in some embodiments , the nozzle 130 has a diameter between 20 - 30 microns . as is best shown in fig8 b , proximate each chamber 128 is a heating element 134 that is electrically coupled to and activated by an electrical signal being provided by a bond pad of the die 92 . in use , when the fluid in each of the chambers 128 is heated by the heating element 134 , the fluid vaporizes to create a bubble . the expansion that creates the bubble causes a droplet to form and eject from the nozzle 130 . other ejection elements may be used for causing fluid to be ejected from the nozzle 130 . for instance , piezoelectric elements or ultrasonic fluid ejection elements may be used to cause fluid to be ejected through the nozzles 130 as is well known in the art . each nozzle 130 is in fluid communication with the fluid in the reservoir by a fluid path that includes the first end 82 of the fluid transport member 80 , through the transport member to the second end 84 , the chamber 88 above the second end 84 of the transport member , the first through hole 90 of the lid , the second through hole 78 of the pcb , through the inlet path 94 of the die , through the channel 126 , to the chamber 128 , and out of the nozzle 130 of the die 92 . in reference again to fig4 , a filter 96 may be positioned between the chamber 88 and inlet path 94 of the die 92 . the filter 96 is configured to prevent at least some particles from passing therethrough , thereby preventing and / or reducing blockage in the fluid path , most particularly in the nozzles 130 of the die 92 . in some embodiments , the filter 96 is configured to block particles that are greater than one third of the diameter of the nozzles . the filter 96 may be any material that blocks particles from flowing therethrough and does not break apart when exposed to the fluid , which could create further particles to block the fluid path . in one embodiment , the filter 96 is a stainless steel mesh . in other embodiments , the filter 96 is a randomly weaved mesh and may comprise polypropylene or silicon . referring now to fig1 , there is provided a close up view of a portion of a microfluidic refill cartridge 26 illustrating a flow path with a filter 96 between the second end 84 of the fluid transport member 80 and the die 92 in accordance with one embodiment . the filter 96 is separated from the lower surface 70 of the microfluidic delivery member 64 proximate the second through hole 78 by a first mechanical spacer 98 . the first mechanical spacer 98 creates a gap 99 between the bottom surface 70 of the microfluidic delivery member 64 and the filter 96 proximate the through hole 78 . in that regard , the outlet of the filter 96 is greater than the diameter of the second through hole 78 and is offset therefrom so that a greater surface area of the filter 96 can filter fluid than would be provided if the filter was attached directly to the bottom surface 70 of the microfluidic delivery member 98 without the mechanical spacer 98 . it is to be appreciated that the mechanical spacer 98 allows suitable flow rates through the filter . that is , as the filter clogs up with particles , the filter will not slow down the fluid flowing therethrough . in one embodiment , the outlet of the filter is 4 mm 2 or larger and the standoff is 700 microns thick . the first mechanical spacer 98 may be a separate rigid support , a protrusion formed on the lower surface 70 of the microfluidic delivery member 64 , such as the solder mask , or adhesive material that conforms to a shape that provides an adequate distance between the filter 96 and the lower surface 70 of the microfluidic delivery member 64 . the adhesive material may be an adhesive material that does not readily dissolve by the fluid in the reservoir . in some embodiments , the adhesive material is activated by heat or uv . the adhesive material may be the same or different from the adhesive material used to secure the die to the microfluidic delivery member . it is to be appreciated that in some embodiments , the fluid transport member 80 is made from one or more materials that do not react with the fluid . thus , the fluid transport member 80 does not introduce contaminants into the fluid that could block fluid flow through the microfluidic delivery member 64 . in one embodiment , the fluid transport member 80 may replace the filter , so that a separate filter 96 is not needed . as shown in fig1 , the second through hole 78 of the microfluidic delivery member 80 may include a liner 100 that covers exposed sidewalls 102 of the pcb 106 . the liner 100 may be any material configured to protect the pcb from breaking apart , such as to prevent fibers of the pcb from separating . in that regard , the liner 100 may protect against particles from the pcb 106 entering into the fluid path and blocking the nozzles 130 . for instance , the second through hole 78 may be lined with a material that is less reactive to the fluid in the reservoir than the material of the pcb . in that regard , the pcb may be protected as the fluid passes therethrough . in one embodiment , the through hole is coated with a metal material , such as gold . prior to use , the microfluidic refill cartridge 26 may be primed to remove air from the fluid path . during priming , air in the fluid path is replaced with fluid from the reservoir 50 . in particular , fluid may be pulled up from the fluid transport member 80 to fill the chamber 88 , the first through hole 90 of the lid 54 , the second through hole 78 of the microfluidic delivery member 64 , the inlet path 94 of the die 92 , the channel 126 , and the chamber 128 . priming may be performed by applying a vacuum force through the nozzles 130 . the vacuum force is typically performed with the microfluidic refill cartridge in an upright position for a few seconds . in some embodiments , a vacuum force is applied for 30 to 60 seconds . the microfluidic refill cartridge 26 may also be primed by applying air pressure through a hole 140 ( fig9 ) in the lid 54 of the cartridge that is in fluid communication with the reservoir 50 to increase the air pressure on the fluid in the reservoir 50 , thereby pushing fluid up the fluid transport member 80 through the fluid path . it is to be appreciated that the hole is sealed with a cover 120 ( see fig2 b ), such as elastic material that fits into at least a portion of the hole , after priming . once primed , the nozzles 130 may be sealed to prevent de - priming of the fluid path . de - priming may occur when air enters the fluid path . in that regard , a cover ( not shown ) may be placed over the nozzles 130 to prevent air from outside of the microfluidic refill cartridge 26 from entering the fluid path . it is to be appreciated that in some embodiments , the outer sleeve 85 of the fluid transport member 80 may prevent de - priming of the fluid transport member 80 . that is , the sleeve 85 prevents air from entering the fluid transport member 80 along its radial surface . once primed , during use , when fluid exits the nozzle 130 , fluid from the reservoir 50 is pulled up through the fluid path by capillary action . in that regard , as fluid exits the chamber 128 , fluid automatically refills the chamber 128 by being pulled through the fluid path by capillary action . as indicated above , the transport cover 86 in combination with the second end 84 of the fluid transport member 80 form a seal that fluidly isolates the chamber 88 from the reservoir 50 to assist in keeping the microfluidic refill cartridge 26 primed . it is to be appreciated that the chamber 88 may be at a different pressure than the reservoir 50 . it is to be appreciated that in many embodiments , the fluid transport member 80 is configured to self - prime . that is , fluid may travel from the first end 82 of the fluid transport member 80 to the second end 84 without the aid of a vacuum force or air pressure as discussed above . the microfluidic refill cartridge 26 includes a vent path that places the reservoir in fluid communication with the external environment of the microfluidic refill cartridge 26 . the vent path equalizes the air pressure in the reservoir 50 with the air pressure of the external environment . that is , as fluid exits the microfluidic refill cartridge 26 through the nozzles 130 , air from the external environment fills the space in the reservoir 50 that is made by the removed fluid . in that regard , the air pressure above the fluid in the reservoir remains at atmosphere . this allows the microfluidic refill cartridge to remain primed and prevents or at least reduces back pressure in the fluid path . that is , by equalizing the pressure in the reservoir , the reservoir does not create a vacuum that pulls the fluid from the fluid path back into the reservoir . referring now to fig9 , the vent path includes a first vent hole 142 in the lid 54 of the microfluidic refill cartridge and a second vent hole 144 in the microfluidic delivery member 64 ( see fig5 a and 5b ). the first and second vent holes 142 , 144 are not aligned with each other but are in fluid communication with each other by a channel 146 formed in the upper surface 66 of the lid 54 . it is to be appreciated that in another embodiment , the lower surface 70 of the microfluidic delivery member 64 could alternatively or additionally include a channel that places the first vent hole 142 in fluid communication with the second vent hole 144 . it is to be appreciated that separating the first vent hole 142 from the second vent hole 144 by the channel 146 reduces the evaporation rate of the fluid in the reservoir 50 through the vent path . upon depletion of the fluid in the reservoir 50 , the microfluidic refill cartridge 26 may be removed from the housing 10 and replaced with another microfluidic refill cartridge 26 . alternatively , the microfluidic refill cartridge 26 may be refilled through the hole 140 in the lid 54 as best shown in fig9 . the various embodiments described above can be combined to provide further embodiments . all of the u . s . patents , u . s . patent application publications , u . s . patent applications , foreign patents , foreign patent applications and non - patent publications referred to in this specification and / or listed in the application data sheet are incorporated herein by reference , in their entirety . aspects of the embodiments can be modified , if necessary to employ concepts of the various patents , applications and publications to provide yet further embodiments . these and other changes can be made to the embodiments in light of the above - detailed description . in general , in the following claims , the terms used should not be construed to limit the claims to the specific embodiments disclosed in the specification and the claims , but should be construed to include all possible embodiments along with the full scope of equivalents to which such claims are entitled . accordingly , the claims are not limited by the disclosure .

one or more embodiments are directed to a microfluidic delivery system that dispenses a fluid in a direction that , at least in part , opposes gravity . in one embodiment , the microfluidic delivery system includes a microfluidic refill cartridge that is configured to be placed in a housing . the microfluidic refill cartridge includes at least one nozzle that faces upward or off to a side . the microfluidic refill cartridge includes a fluid transport member that allows fluid to travel upward from a fluid reservoir in opposition to gravity . a fluid path is located above the fluid transport member placing an end of the fluid transport member in fluid communication with a chamber and a nozzle . in response to the microfluidic delivery system receiving an electrical signal , an ejection element is configured to cause fluid in the chamber to be expelled through the nozzle . in response to the fluid being expelled from the nozzle , fluid may be pulled up through the fluid transport member and through the fluid path to refill the chamber .

illustrated in fig1 - 8 ( o ) is a preferred embodiment for a method for playing a game on the subject matter of death and taxes . referring to fig1 ( a ), a board is illustrated . a randomizer ( pair of dice ) is indicated in fig1 ( b ). a device for recording game information is included at fig1 ( c ), and player indicators are indicated at fig1 ( d ). in one embodiment , the randomizer is two six - sided die in which the side indicating the integer “ one ” has been replaced with a depiction of a skull and crossbones . the device for recording game information indicated in fig1 ( c ) is a pad of paper with “ death & amp ; taxes status pad ” embossed on it and a writing instrument such as a pencil . the player indicators shown in fig1 ( d ) may be wooden game pieces . although the embodiment disclosed herein contemplates a standard board game , the method could be practiced by electronic display of the board in fig1 ( a ), use of a computer program to output a random integer within a selected range , electronic display of player indicators , and electronic display and storage of game information . this would not alter the rules or procedure of the game . referring to fig2 , a plurality of game spaces corresponding to predetermined operations are depicted . a plurality of spaces comprises a path on which game play progresses , forming a level of play . the plurality of levels each has a start space on which players promoted or demoted to that level begin , and each level corresponds to a predetermined range of net worth . net worth is defined as the value of scrip money recorded as being owned by the individual players in the game . each player records his / her net worth on a status pad , such as shown in fig1 ( c ). in one embodiment , the start of the initial level is depicted at level 1 , space 1 , and corresponds to a predetermined range of net worth less than $ 40 , 000 . in one embodiment , there are four levels ; level 2 corresponds to the net worth range greater than $ 40 , 000 to $ 99 , 999 ; level 3 corresponds to the net worth range greater than $ 100 , 000 to $ 499 , 999 ; and level 4 corresponds to a net worth greater than $ 500 , 000 . the number of levels is in the range of two to ten . a preferred number is four . in one embodiment , having four levels , the list of game spaces is as follows : level 1 , space 1 : start level 1 level 1 , space 2 : disaster level 1 , space 3 : swindler level 1 , space 4 : roll again level 1 , space 5 : tragedy level 1 , space 6 : swindler level 1 , space 7 : unemployment level 1 , space 8 : swindler level 1 , space 9 : revive ! level 1 , space 10 : lottery level 1 , space 11 : informer level 1 , space 12 : welfare level 1 , space 13 : swindler level 1 , space 14 : bonus level 1 , space 15 : you &# 39 ; re fired ! level 1 , space 16 : welfare level 1 , space 17 : swindler level 1 , space 18 : unemployment level 1 , space 19 : bonus level 1 , space 20 : occupation level 2 , space 1 : start level 2 level 2 , space 2 : swindler level 2 , space 3 : bonus level 2 , space 4 : informer level 2 , space 5 : lottery level 2 , space 6 : tragedy level 2 , space 7 : welfare level 2 , space 8 : you &# 39 ; re fired level 2 , space 9 : occupation level 2 , space 10 : refund level 2 , space 11 : swindler level 2 , space 12 : death level 2 , space 13 : informer level 2 , space 14 : revive ! level 2 , space 15 : lottery level 2 , space 16 : audit , 10 % taxes level 2 , space 17 : swindler level 2 , space 18 : occupation level 2 , space 19 : roll again level 2 , space 20 : swindler level 2 , space 21 : you &# 39 ; re fired level 2 , space 22 : welfare level 2 , space 23 : swindler level 2 , space 24 : unemployment level 2 , space 25 : swindler level 2 , space 26 : bonus level 2 , space 27 : roll again level 2 , space 28 : disaster level 3 , space 1 : start level 3 level 3 , space 2 : refund level 3 , space 3 : roll again level 3 , space 4 : you &# 39 ; re fired ! level 3 , space 5 : bonus level 3 , space 6 : swindler level 3 , space 7 : disaster level 3 , space 8 : lottery level 3 , space 9 : swindler level 3 , space 10 : tragedy level 3 , space 11 : occupation level 3 , space 12 : informer level 3 , space 13 : you &# 39 ; re fired ! level 3 , space 14 : refund level 3 , space 15 : disaster level 3 , space 16 : revive ! level 3 , space 17 : occupation level 3 , space 18 : welfare level 3 , space 19 : swindler level 3 , space 20 : unemployment level 3 , space 21 : lottery level 3 , space 22 : audit , 30 % taxes level 3 , space 23 : swindler level 3 , space 24 : death level 3 , space 25 : roll again level 3 , space 26 : bonus level 3 , space 27 : informer level 3 , space 28 : swindler level 3 , space 29 : disaster level 3 , space 30 : bonus level 3 , space 31 : roll again level 3 , space 32 : tragedy level 3 , space 33 : occupation level 3 , space 34 : informer level 4 , space 1 : start level 4 level 4 , space 2 : revive ! level 4 , space 3 : you &# 39 ; re fired ! level 4 , space 4 : swindler level 4 , space 5 : lottery level 4 , space 6 : death level 4 , space 7 : refund level 4 , space 8 : disaster level 4 , space 9 : roll again level 4 , space 10 : tragedy level 4 , space 11 : occupation level 4 , space 12 : informer level 4 , space 13 : audit , 50 % taxes level 4 , space 14 : disaster level 4 , space 15 : refund level 4 , space 16 : bonus level 4 , space 17 : roll again level 4 , space 18 : swindler level 4 , space 19 : death level 4 , space 20 : unemployment level 4 , space 21 : disaster level 4 , space 22 : informer level 4 , space 23 : tragedy level 4 , space 24 : lottery level 4 , space 25 : roll again level 4 , space 26 : audit , 50 % taxes level 4 , space 27 : swindler level 4 , space 28 : tragedy level 4 , space 29 : informer level 4 , space 30 : you &# 39 ; re fired level 4 , space 31 : swindler level 4 , space 32 : roll again level 4 , space 33 : death level 4 , space 34 : occupation level 4 , space 35 : bonus level 4 , space 36 : informer . the list may be amended in order of frequency of repetition of each space on any level without changing the operation or method of the game . referring to fig3 ( a ), cards depicting game information are illustrated by a template . an exemplar game information card is shown in fig3 ( b ). in one embodiment , the cards shown in fig3 ( a ) are occupation cards . occupation cards contain job titles and salary information denoted in dollars per round . the occupation cards illustrated at fig3 ( b ) correspond to the level 3 , with a job title of investment broker , and a salary of $ 24 , 000 per round . this dollar amount is added to net worth of a player holding the card at the end of each round . in one embodiment , there are four levels with fifteen occupations cards per level , with the following game information , for example : level 1 , fast food cook , $ 200 per round ; level 1 , worker at sav - mart , $ 250 per round ; level 1 , convenience store clerk , $ 275 per round ; level 1 , security guard , $ 300 per round ; level 1 , hair dresser , $ 350 per round ; level 1 , pizza delivery driver , $ 375 per round ; level 1 , warehouse manager , $ 400 per round ; level 1 , dental assistant , $ 450 per round ; level 1 , circus clown , $ 475 per round ; level 1 , police academy student , $ 475 per round ; level 1 , auto mechanic , $ 600 per round ; level 1 , florist , $ 700 per round ; level 1 , disk jockey , $ 800 per round ; level 1 , photographer , $ 900 per round ; level 1 , telemarketer , $ 1 , 000 per round ; level 2 , farmer , $ 1 , 100 per round ; level 2 , carpenter , $ 1 , 200 per round ; level 2 , plumber , $ 1 , 300 per round ; level 2 , ranch hand , $ 1 , 500 per round ; level 2 , volunteer fireman , $ 1 , 500 per round ; level 2 , social worker , $ 2 , 100 per round ; level 2 , forest ranger , $ 2 , 200 per round ; level 2 , airline steward ( ess ), $ 2 , 300 per round ; level 2 , secretary , $ 2 , 500 per round ; level 2 , real estate agent , $ 2 , 600 per round ; level 2 , accountant , $ 2 , 700 per round ; level 2 , policeman , $ 2 , 800 per round ; level 2 , inventor , $ 2 , 900 per round ; level 2 , registered nurse , $ 3 , 000 per round ; level 3 , chef , $ 4 , 300 per round ; level 3 , private investigator , $ 4 , 400 per round ; level 3 , college professor , $ 4 , 600 per round ; level 3 , bio - chemist , $ 4 , 800 per round ; level 3 , para - legal , $ 5 , 000 per round ; level 3 , dentist , $ 5 , 200 per round ; level 3 , county sheriff , $ 5 , 400 per round ; level 3 , doctor , $ 5 , 600 per round ; level 3 , pro sports mascot , $ 5 , 800 per round ; level 3 , lawyer , $ 6 , 000 per round ; level 3 , architect , $ 15 , 000 per round ; level 3 , cattleman , $ 18 , 000 per round ; level 3 , movie star , $ 20 , 000 per round ; level 3 , engineer , $ 21 , 000 per round ; level 3 , investment broker , $ 24 , 000 per round ; level 4 , hollywood producer , $ 27 , 000 per round ; level 4 , t . v . evangelist , $ 30 , 000 per round ; level 4 , scientist , $ 33 , 000 per round ; level 4 , astronaut , $ 36 , 000 per round ; level 4 , vice - chairman , $ 38 , 000 per round ; level 4 , best selling author , $ 41 , 000 per round ; level 4 , high fashion designer , $ 42 , 000 per round ; level 4 , lieutenant governor , $ 43 , 000 per round ; level 4 , pro sports agent , $ 44 , 000 per round ; level 4 , open heart surgeon , $ 45 , 000 per round ; level 4 , governor , $ 46 , 000 per round ; level 4 , company president , $ 49 , 000 per round ; level 4 , chairman of the board , $ 50 , 000 per round . the occupations and compensation per round may vary without changing the operation or method of the game . referring to fig4 , cards depicting game information are illustrated in a template at fig4 ( a ), and an exemplar of a card depicting game information is depicted at fig4 ( b ). in one embodiment , the cards in fig4 are sweepstakes cards . sweepstakes cards are distributed randomly with the occupation cards illustrated in fig4 ( a ) and fig4 ( b ). in one embodiment , sweepstakes cards are numbered in pairs , 1 - 5 . if a player draws a sweepstakes card , and matches a pair , he adds a predetermined amount to his net worth . in one embodiment , this predetermined amount is $ 1 , 000 , 000 . the game logic will now be discussed . flowcharts illustrated in fig5 - 8 ( o ) map the game logic and operation . the following flowchart convention is used in the diagrams : terminator : the start or end of a process process : an action performed in the operation decision : asks a question , answer determines operation flow ◯ connector : connects two or more parts of flowchart together { circle around (+)} or : connects two alternate steps off page connector : connects parts of flowcharts on separate pages manual operation : player performs a manual operation stored data : data written to storage medium → arrows : indicate flow referring to fig5 , a flowchart of the initial setup of game play is depicted . the starting player is selected . the players operate the randomizer illustrated at fig1 ( b ). the player with the highest resulting value begins game play , and play continues clockwise with players seated around playing field or board illustrated at fig1 ( a ). if the result is a tie , the randomizer is operated until a highest result is obtained . all players are given a predetermined amount of scrip as a starting net worth , which is recorded on the status pad at fig1 ( c ). players place player indictors illustrated at fig1 ( d ) on level one start , illustrated at fig2 , level 1 , and space 1 . this is the start of the initial player &# 39 ; s turn , and also the start of the round . the player &# 39 ; s turn will end when he has operated the randomizer , moved that player &# 39 ; s player indicator , landed on a space , and performed the operation of the space . a round ends when all players have had their turn . in one embodiment , players roll a six - sided die to determine who goes first . referring to fig6 , a flowchart of the beginning of a turn is depicted . in the initial round of play , each player will start on level one illustrated at fig2 , level 1 , space 1 , and will draw a level one occupation card illustrated in fig3 ( a ) in turn . in one embodiment , the player will operate the randomizer by rolling two six - sided dice as shown in fig1 ( b ). if the player rolls “ cross - bones ”, that player is declared legally dead and is temporarily suspended from game play . “ cross - bones ” is defined as rolling a value of 2 in the range of 2 - 12 possible with two six - sided dice . recall that the dice illustrated in fig1 ( b ) have drawings of skull and crossbones in place of the integer “ one .” alternately , “ cross - bones ” can be the number one on a regular die , or any design emblazoned on the die . if the roll is not “ cross - bones ,” the player advances the player &# 39 ; s indicator at illustrated in . fig1 ( d ) around the game board shown in fig1 ( a ), and lands on a space illustrated in fig2 , level 1 , and space 3 - 13 . the possible effects of landing on a space are further defined in fig8 , and the operations associated with each space are illustrated in fig8 ( a )- 8 ( o ). the successive players then repeat the process until the last player has completed that player &# 39 ; s turn , signaling the end of the round . in successive turns of play , players within a predetermined range of net worth begin the corresponding level by moving the player indicator to the start space of that level . referring to fig7 , a flowchart of the end of a round is depicted . after all players have completed their turn , each player collects the salary as indicated on that player &# 39 ; s occupation card . if any player is on unemployment , they add a predetermined amount to their net worth . if any player is a swindler they perform the operation depicted in fig8 ( k ). if any player is on welfare that player collects a predetermined amount from all the other players . players then calculate their net worth . if the value of net worth is sufficient to move a player to a new level , that player &# 39 ; s player indicator is moved to the start space of the corresponding level , the player discards the player &# 39 ; s occupation card , and draws an occupation card corresponding to that level . if any player has a net worth exceeding a predetermined amount , that player is declared the winner . otherwise , a new round begins by next live player clockwise from beginning player operating randomizer . if all but one player is declared legally dead before a player reaches the predetermined amount to be declared the winner , the game ends in a stalemate . in one embodiment , a player on unemployment will collect $ 2000 each round and a player on welfare will take $ 200 from the other players each round . an example from one embodiment : a player has $ 38 , 000 at the end of a round , during the player &# 39 ; s turn the player collects $ 3 , 000 , and calculates the player &# 39 ; s net worth at the end of the next round at $ 41 , 000 . because the player &# 39 ; s net worth is in the range of $ 40 , 000 - 100 , 000 , the player would move to level 2 start illustrated in fig2 level 2 , space 1 , discard the player &# 39 ; s level 1 occupation card , and draw a level 2 occupation card . referring to fig8 ( a ), a flowchart of the operations associated with landing on an audit space is depicted . if the player either lands on or is moved to audit , the player must pay taxes at a predetermined rate indicated in the space . if the player has been taxed in that round the player does not pay taxes again , and game play continues . referring to fig8 ( b ), a flowchart of the operations associated with landing on a bonus space is depicted . if the player has an occupation card , the player receives 50 % of the salary indicated , immediately added to the player &# 39 ; s net worth . if not , the space is treated as blank , and game play continues . referring to fig8 ( c ), a flowchart of the operations associated with landing on a death space is depicted . if the player lands on death the player is declared legally dead , must discard the player &# 39 ; s occupation card , and the player &# 39 ; s net worth is reduced to zero . if two remaining players are tied for lowest net worth , the dead player &# 39 ; s net worth is divided among all remaining players . if not , the player with the lowest net worth receives the dead player &# 39 ; s net worth . referring to fig8 ( d ), a flowchart of the operations associated with landing on a disaster space is depicted . if a player lands on disaster , all players forfeit salary , unemployment , and welfare for that round . referring to fig8 ( e ), a flowchart of the operations associated with landing on an informer space is depicted . if there is an audit space on any level a player is currently playing on , the player landing on informer may move that player to audit , and perform the operation of fig8 ( a ). referring to fig8 ( f ), a flowchart of the operations associated with landing on a lottery space is depicted . if a player lands on lottery , the player chooses 3 numbers in sequence in a predetermined range . the player then operates the randomizer 3 times to obtain a sequence of three numbers . if the player correctly guessed the numbers obtained by operating the randomizer in sequence , the player wins a predetermined amount of scrip immediately added to the player &# 39 ; s net worth . if the player correctly guessed the numbers obtained by operating the randomizer in any sequence , the player wins a predetermined amount of scrip immediately added to the player &# 39 ; s net worth . if the player correctly guessed 2 of 3 numbers obtained by operating the randomizer in any sequence , the player wins a predetermined amount of scrip immediately added to the player &# 39 ; s net worth . in one embodiment , a player correctly guessing 3 of 3 rolled numbers in sequence would win $ 1 , 000 , 000 , a player correctly guessing 3 of 3 rolled numbers in any sequence would win $ 500 , 000 , and a player correctly guessing 2 of 3 rolled numbers in any sequence would win $ 10 , 000 . referring to fig8 ( g ), a flowchart of the operations associated with landing on an occupation space is depicted . if a player lands on occupation , that player may discard the player &# 39 ; s occupation card , if any , and draw an occupation card corresponding to the player &# 39 ; s level . if the player draws a sweepstakes card illustrated in fig4 ( a ) and fig4 ( b ), the player may redraw until the player receives an occupation card . referring to fig8 ( h ), a flowchart of the operations associated with landing on a refund space is depicted . if a player lands on refund , the player is awarded 20 % of the player &# 39 ; s net worth . referring to fig8 ( i ), a flowchart of the operations associated with landing on a revive space is depicted . if a player lands on revive , all dead players return to the game at beginning of next round . referring to fig8 ( j ), a flowchart of the operations associated with landing on a roll again space is depicted . if a player lands on roll again , the player operates the randomizer and moves the player &# 39 ; s player indicator as indicated on the randomizer . referring to fig8 ( k ), a flowchart of the operations associated with landing on a swindler space is depicted . if a player lands on swindler , the player receives all other players salary or unemployment payments at the end of the round . if there are multiple swindlers they all receive other players &# 39 ; salary and unemployment payments and divide it equally among the swindlers . if all players land on swindler , payments are made in usual fashion . referring to fig8 ( l ), a flowchart of the operations associated with landing on a tragedy space is depicted . if a player lands on tragedy , the player loses all salary , unemployment , and welfare for the round . referring to fig8 ( m ), a flowchart of the operations associated with landing on an unemployment space is depicted . if a player does not have an occupation or welfare benefits , the player can elect to receive a predetermined amount per round . referring to fig8 ( n ), a flowchart of the operations associated with landing on a welfare space is depicted . if a player lands on welfare , and does not have an occupation or unemployment benefits , the player can elect to take a predetermined amount of money from each player each round . referring to fig8 ( o ), a flowchart of the operations associated with landing on a you &# 39 ; re fired ! space is depicted . if a player lands on you &# 39 ; re fired ! the player must discard the player &# 39 ; s occupation card , and is not eligible to receive a salary until the player &# 39 ; s status is changed . although the present invention has been described with respect to specific details , it is not intended that such details should be regarded as limitations on the scope of the invention , except to the extent that they are included in the accompanying claims .

a board game is provided having the theme death and taxes . multiple levels of paths of spaces are indicated on a board , each level having differing rules affecting the amount of scrip currency that a player receives or loses in playing . players &# 39 ; pieces are moved to differing levels dependent on the amount of currency assigned to that player .

this invention relates to irrigation systems optimized for the efficient use of water that incorporate line source water emitters , such as porous pipe , to distribute water directly to the base of plants , or point source water emitters that operate similarly . more particularly , a combination is disclosed in which both line source and point source emitters can be combined in a single irrigation system so as to take advantage of the best characteristics of both emitters . as water becomes an increasingly valuable resource , it is ever more necessary to conserve its use . evaporation and surface runoff can waste water that should be delivered directly to plants . two prior art systems have evolved to provide controlled irrigation to plants . each has certain advantages in different circumstances . the first and older system uses impervious tubing , usually polyethylene , to distribute water throughout a yard or field that is to be watered . in the specific locations where water is needed , a variety of different type point source emitters may be attached to the tubing by inserting a barbed connector into a hole in the tube so as to extract water from the tube . for the purposes of this specification , point source emitters may include drip type emitters , spray heads , jet sprays , or any other low volume sprinkler head . the connector feeds water to the point source emitter which in turn drips or sprays water on the plants . the advantage of this type of emitter is that an emitter design can be selected at each location that is ideal for the specific plant or watering task at hand . for example , some emitters simply allow a controlled drip onto the ground at the base of the plant which quickly sinks in with little loss to evaporation or surface runoff . other emitter designs offer spray patterns of various shapes and sizes that are more appropriate for other kinds of plants or arrangements of plants . point source emitters can have different flow rates if desired , more for large plants or trees , or less for smaller plants . thus , an irrigation system based on point source concepts may be very flexible and can be tailored with ease to the mixture of different plants in a garden . the second system in use in the art uses porous pipe to distribute water throughout a field or garden . water slowly leaks from the entire length of the pipe so that a line source emitter is provided that delivers an even distribution of water directly to the ground at the base of the plants with minimal loss to evaporation and runoff . the porous pipe can be formed from fabric , thermoplastic resins such as nylon or vinyl . the preferred porous pipe is made by extruding a mixture of granulated rubber and a thermoplastic binder resin such as polyethylene as disclosed in u . s . pat . no . 4 , 616 , 055 . other thermoplastic binder resins such as vinyl can also be utilized . the advantages of line source emitters are that they are simpler to assemble and maintain . they are durable and flexible and can even be buried underground to feed water to plant roots directly so as to totally eliminate losses to evaporation and runoff . they do not cause erosion , will not freeze , and can be fitted to follow unusual shapes . since they do not spray , other objects are protected and splash transmitted plant diseases are prevented . porous pipe cannot be used to irrigate plants efficiently since the water that leaks onto or into the ground between plants is wasted . the most desirable irrigation system would have all of the advantages and none of the disadvantages of both the point and line source emitter designs . the present invention provides such a system . briefly , the present invention includes the combination of porous pipe and impervious pipe in a single integrated irrigation system . any combination of emitters may be used depending on the exact requirements of the watering task . drip type point emitters may be used where spot requirements are high or spray heads employed where surface broadcasting of water is appropriate . for areas that need even surface watering , a porous pipe may be connected to the same water circuit . if a plant that grows in the middle of an otherwise even watering area needs extra water , the instant invention even allows a point source emitter to be inserted into a porous pipe line source emitter . such combinations have not been previously possible due to the fundamentally different hydrodynamic requirements of point and line source systems and it was not known if point source emitters could be punched through porous pipe . the pores in the preferred porous pipe are formed by incomplete wetting or attachment of the polyethylene resin to the rubber particles forming serpentine - like paths through the wall of the pipe . it was not known if point source emitters could be punched - through the wall of porous pipe without cracking and / or weakening the wall of the porous pipe . point source emitters generally operate at pressures around 20 - 30 psi to insure that the emitters have predictable design flow rates and do not clog up over time with water impurities . these higher pressures are , however , incompatible with the proper operation of porous pipe , or as it is commonly called , soaker hose . soaker hose normally operates at 5 - 10 psi so as to avoid uneven leakage rates along its length . at the higher pressures of 20 - 30 psi , the flow rate of prior art soaker hose is too great to be operated in the same water circuit with point source emitters . this invention provides a soaker hose incorporating a smaller pore size to allow operation at the higher pressures needed to assure proper functioning of the various types of point source emitters . the details of this construction along with further advantages and benefits will become apparent from the following explanation and drawings . fig1 shows a typical irrigation system with a wide variety of watering tasks schematically diagrammed , each task individually addressed by the selectable emitter system available through the combined point and line sources of the present invention ; fig2 is an enlarged cross - section taken along line 2 -- 2 of fig1 ; and fig3 is an enlarged cross - section taken along line 3 -- 3 of fig1 . in the drawing a source of water 10 is shown coming perhaps from the side of a building 12 . a length of distribution tubing 14 is connected thereto in a conventional manner and also connected to a soaker hose 16 by means of a connector 18 . for a grouping of plants 20 that are relatively close together , porous soaker hose 16 is an ideal solution since it can be threaded through the plantings and allowed to wet the earth over an extended area . another excellent use for soaker hose is to connect a short length 22 so as to wrap about a single large plant such as a tree 24 . still another segment of porous hose 26 is shown in a regular garden 28 . hose 26 may be buried underground as at 30 so as to effectively water just the roots of a row of plants 32 . some watering tasks are , however , better solved with point source emitters . for more widely distributed plants , such as plants 34 , one may use point source spray heads connected to a tube 38 . heads 36 spray water in a selected pattern as shown by exemplary arrows 40 . for mixed requirements , one may even utilize both a soaker hose 42 and point source emitters 44 and 46 . emitter 44 , for example , could be of the drip type that wraps around hose 42 as shown at 45 in the enlarged detail . a barbed tap 45a conveys water through a drip controller 45b . or emitter 46 could be of the spray head type shown in the other enlarged detail where water is conveyed through a tap 46a to a spray head 46b . these point source emitters are well known to those skilled in the art but have always been useable only on high pressure tubing due to the inherently different hydrodynamic characteristics . with the instant invention it becomes possible to use point source emitters connected directly to the soaker hose itself . the important design consideration is that the soaker hose be flow balanced to the chosen point source emitter flow rates . this should take into consideration the selected operating pressures of the point emitters . if the water flow in the porous hose is balanced to the flow in the point emitters , a combined point and line source system is possible . with respect to the above referenced u . s . pat . no . 4 , 616 , 055 , a higher pressure porous hose may be constructed in accordance with the principles of that patent by changing some of the parameters taught therein . smaller pore size , allowing higher operating pressure , may be obtained by using a greater proportion of polyethylene , or a finer mesh of rubber , or a slower rate of extrusion . alternatively , a combination of two or three of these techniques may be employed to achieve the balanced water flow through the porous hose and the point source emitters . an additional benefit of the generally higher operating pressures of this combined irrigation system is a reduced sensitivity to level changes in the porous soaker hose . for example , in the drawing an elevated planting box 50 is illustrated . a porous soaker hose 52 in box 50 is connected to the main system by a tube 54 and a tee connection 56 . higher pressures permit this arrangement to work well whereas in the prior art it was unwise to have too severe a height change with a soaker hose system . many variations within the spirit and scope of the invention are possible , hence , we intend limitation only in accordance with the appended claims .

an irrigation system that uses porous and non - porous pipe in combination , the porous pipe having a porosity such that the flow of water therethrough is balanced to the flow of water through point source emitters connected to both the porous and non - porous pipes so that simultaneous point source and line source watering is possible .

as used herein , “ creatine compound ” refers to creatine , pharmaceutically acceptable creatine analogs , precursors , and pro - drugs which metabolize to creatine , and biologically active salts thereof . in particular , a creatine compound can be creatine monohydrate , creatine phosphate , the creatine analog cyclocreatine , the creatine precursor guanidoacetic acid , and hydrosoluble organic salts of creatine as described in u . s . pat . no . 5 , 973 , 199 of negrisoli et al ., which is hereby incorporated by reference . preferably , the creatine compound is creatine monohydrate . the term “ treating ” refers to all types of control such as prophylaxis , cure , relief of symptoms , attenuation of symptoms and arrest of advance . in particular , treating refers to counteracting muscle loss associated with liver , kidney and other diseases and conditions . the present inventor has realized that weight loss associated with kidney and liver diseases is a consequence of a failure to synthesize creatine . the present inventor has further realized that a diseased kidney or liver cannot produce normal levels of creatine . without creatine , kidney and liver patients cannot synthesize muscle protein . any amino acids liberated by breakdown of protein are consumed for synthesis of glucose and energy rather than for building muscle . thus , patients with liver and kidney disease lose weight . the present inventor believes this is the first reported proposal of a connection between weight loss accompanying liver and kidney diseases and failure to synthesize sufficient creatine . the danger of muscle loss is well known , and attempts are made to feed a high protein intake to patients with liver or kidney disease . however , liver patients have difficulty disposing of the toxic ammonia produced by metabolism of amino acids since a damaged liver cannot dispose of ammonia as easily as it can non - toxic urea . thus , patients with chronic liver disease have difficulty adhering to high protein diets . further , the present inventor believes that a high protein diet alone is an inadequate therapy for liver and kidney patients so long as such patients lack adequate levels of creatine . both the liver and kidney are normally required not only to produce necessary creatine , but also to detoxify and excrete toxic by - products of the consumption of amino acids . loss of muscle and death frequently results from disease of either organ , due to the cachexia of severe muscle loss and the toxicity of the by - products ( e . g . ammonia ) of excessive use of body protein for brain glucose . renal dialysis and peritoneal dialysis are used regularly in renal disease to remove the toxic breakdown products , and creatine can be included as a regular component of dialysis fluids . creatine has been used clinically as a nutritional supplement to improve the strength , speed and size of athletes &# 39 ; muscles . however , the key positive role proposed for creatine phosphate in muscle protein synthesis has been overlooked by all who have studied or discussed the use of creatine in supporting energy enhancement , particularly in the field of athletics . even though possible growth of muscle has been observed in some cases , it has been discounted as the collection of water due to the osmotic effect of creatine accumulation in the muscle tissue , rather than actual tissue protein growth . this conclusion cannot be supported by osmotic calculations based on the minimal information available , but it is a general assumption . the failure of the athletic use of creatine to reveal a direct effect of creatine phosphate on muscle protein synthesis is likely due to the use of creatine in well - muscled athletes whose relative increase in creatine - stimulated muscle mass would go unnoticed . in accordance with this invention , a patient suffering muscle loss from reduced production of endogenous creatine is administered a creatine compound to treat the muscle loss . the creatine compound can be administered through routes well known in the art such as oral , intravenous , or dialysis . when provided orally , the creatine compound can be in the form of a pill , tablet , capsule , powder , solution , suspension and the like . whatever the route , the compound can be mixed with additional components such as buffers , salts , adjuvants , solubilizers , carriers , flavoring agents , sugars , minerals , and vitamins . in some cases , adequate levels of creatine cannot be attained orally . in such cases , creatine can be administered by dialysis to achieve higher levels . either hemodialysis or peritoneal dialysis can be performed . in hemodialysis , the patient &# 39 ; s blood is passed through an artificial kidney having a membrane that acts to clean the blood . in peritoneal dialysis , a dialysis solution is introduced into the patient &# 39 ; s peritoneal cavity where the peritoneum can act as a semi - permeable membrane for exchanging solutes between the dialysis solution and the patient &# 39 ; s blood . another advantage of creatine administration by dialysis is the higher blood levels of creatine achieved during dialysis compare with oral administration . higher blood levels could result in rapidly rising intracellular concentrations of creatine . a further advantage of dialysis is that undesirable guanidine analogs or creatine precursors can be dialyzed out during dialysis , reducing their levels in comparison with heavy oral creatine therapy . in a preferred embodiment , creatine in the form of creatine monohydrate can be added to a dialysis solution at concentrations up to about 1 . 5 grams / 100 ml of solution , the solubility limit of creatine monohydrate in aqueous solutions . preferably , the concentration of creatine monohydrate is about 1 . 5 grams / 100 ml of solution , or the maximum solubility attainable in a particular dialysis solution , which depends in part upon the other components of the solution . as is readily understood by those working in the field , a creatine fortified dialysis solution can include other solutes such as sodium , potassium , glucose , bicarbonate , magnesium , calcium and chloride . the concentrations of these other solutes can be adjusted to assure proper plasma levels in the patient . creatine administration , and particularly creatine fortified dialysis , can be beneficial for counteracting muscle loss in patients suffering from kidney and liver diseases . many kidney patients regularly undergo dialysis , and creatine can be added as a regular component of dialysis fluids . for patients with severe liver disease , creatine fortified dialysis may be a way of preserving failing physiology until transplant . other types of muscle loss that can be amenable to the beneficial effects of creatine administration , and particularly parenteral administration , are anorexia nervosa , chronic gastrointestinal disease , and severe wounds that interfere with oral intake of food . there is a large group of patients who must be fed parenterally and who may benefit by obviating the need for complete dependence on endogenous creatine synthesis . creatine may also be of value in the chronic parenteral feeding of vegetarians with mild liver or kidney ailments or other causes of severe weight loss . “ failure to thrive ” defines infants who delay for months before a normal growth rate takes place . these children may also benefit from creatine administration . although the subjects described herein are human subjects , the invention can be extended to animal subjects with diseases or conditions associated with muscle loss . an effective amount of a creatine compound is any amount that achieves the goal of therapy . for example , an effective amount for prophylaxis is any amount necessary to maintain muscle mass . alternatively , an effective amount for counteracting muscle loss is any amount that leads to increased muscle mass . as would be apparent to those working in the field , an effective amount in any given case depends upon the particular formulation employed , the route of administration , the site and rate of administration , the clinical tolerance of the patient involved , the age and health of the patient , the pathological condition afflicting the patient and the like . the patient &# 39 ; s condition can be monitored and the dosages varied accordingly . to measure muscle mass , excretion of the compound creatinine can be monitored . creatinine , which is formed from creatine by irreversible loss of a molecule of water , has no known function . it is excreted by the normal human in almost exact proportion to the muscle mass of the individual . its daily excretion is equivalent to about 2 grams of creatine . as would be expected , the daily excretion of creatinine by the female , also proportional to muscle mass , is smaller than the male . it has been suggested that creatinine is formed by muscle contraction , but the number of molecules of creatinine excreted represents only a small fraction of the molecules of creatine phosphorylated and dephosphorylated per day . no enzymatic process has been found for the formation of creatinine . about 100 grams of creatine are present in the normal body , and if all of the creatine were converted to creatinine , about 57 grams would form . if synthesis of creatine stops , muscle loss occurs and the excretion of creatinine diminishes proportionately . although details concerning creatinine function and synthesis remain to be determined , creatinine has been found to be a good measure of muscle mass . as currently envisioned , the need for , and effectiveness of , creatine treatment can be determined by measuring the twenty - four hour urinary output of creatinine , a standard laboratory test . this measurement will give a baseline value for initiating creatine administration . a normal male excretes about 1 . 50 grams of creatinine per day . if excretion of creatinine is below the normal amount relative to a patient &# 39 ; s weight , supplemental creatine can be administered until the excretion of creatinine is approximately normal . increase in muscle mass would be shown by increase in creatinine excretion . other ways of monitoring changes in muscle mass include measuring 40 k , a natural isotope of potassium that is present primarily in muscle tissue and that requires a special counting apparatus , and examination by magnetic resonance imaging , which can give additional information on localization and density of muscle tissue . 1 . bessman , s . p . and fonyo , a . the possible role of the mitochondria bound creatine kinase in regulation of mitochondrial respiration . biochem . biophys . res . comm . 22 , 597 - 602 ( 1966 ). 2 . bessman , s . p . hexokinase — acceptor theory of insulin action . new evidence . israel j . med . sci . 8 , 344 ( 1972 ). 3 . carpenter , c . l ., mohan , c . and bessman , s . p . inhibition of protein and lipid synthesis in muscle by 2 , 4 - dinitrofluorobenzene , an inhibitor of creatine phosphokinase . biochem . biophys . res . comm . 111 , 884 - 889 ( 1983 ). 4 . savabi , f ., carpenter , c . l ., mohan , c . and bessman , s . p . the polysome as a terminal for the creatine phosphate energy shuttle . biochem . med . metab . biol . 40 , 291 - 298 ( 1988 ). 5 . ingwall , j . s ., morales , m . f . and stockdale , f . e . creatine and the control of myosin synthesis in differentiating skeletal muscle . proc . natl . acad . sci . usa . 69 , 2250 - 2253 ( 1972 ). 6 . stockler , s ., hanefeld , f . and frahm , j . creatine replacement therapy in guanidinoacetate methyltransferase deficiency , a novel inborn error of metabolism . lancet 348 , 789 - 790 ( 1996 ). 7 . stockier , s ., marescau , b ., de deyn , p . p ., trijbels , j . m . f . and hanefeld , f . guanidino compounds in guanidinoacetate methyltransferase deficiency , a new inborn error of creatine synthesis . metabolism 46 , 1189 - 1193 ( 1997 ).

a method of using a creatine compound to treat muscle loss associated with liver and kidney diseases . in preferred embodiments , creatine monohydrate is administered by dialysis . the method can be extended to other diseases or conditions associated with muscle loss . also provided is a composition comprising a dialysis fluid containing a creatine compound .

as seen in fig1 - 7 wherein similar parts are identified by like reference numerals and may be found in one or more of the drawings , a platform 12 is engaged to an underlying substantially rigid platform support 13 . this engagement can be seen in fig3 - 4 and also in fig7 which shows the exploded view of the various components of the preferred mode of the device 10 . as depicted in fig1 and 5 , a platform 12 is held in an elevated position adjacent to the upper end of a sidewall formed of an upper tubular member 14 and lower tubular member 16 . both tubular members have sealed interior cavities 26 formed by surrounding sidewalls formed of elastic material such as rubber , polypropylene , polyethylene , or other polymers adapted to the task . the tubular members are inflated ( using a valve stem , not shown ) and the flexible and compressible nature of the inflated tubular members 14 and 16 having elastic walls , renders the platform 12 unstable for both lateral and vertical movement by a user moving in a position on top of the platform 12 . as can be discerned from the sliced views of fig3 the two tubular members 14 and 16 formed of elastic material , combine to form a sidewall supporting the platform 12 , which is flexible when filled with air yielding a resilience to the sidewall . the sidewall so formed will collapse a bit under the user &# 39 ; s weight , especially when that weight is imparted to the platform 12 off balance and will also tend to slide horizontally due to motions by the user . both the vertical and horizontal movement are impacted by the resilience of the formed sidewall formed by the tubular members 14 and 16 . changing the air pressure inside the interior cavities 26 of either or both tubular members 14 and 16 provides a means to change the resilience of the sidewall and thus a means to change the reactive horizontal and vertical movement of the attached platform 12 relative to the user movement thereon . the platform 12 being supported across its planar surface by the underlying platform support 13 may also be substantially rigid or may be a compressible material for cushioning if so desired . this two component surface is preferred because the platform 12 may be replaced or of a different material than the platform support 13 however the device would simply employ a unitary or single piece platform 12 having the components of the aforementioned two parts in a single unit . as shown in fig3 - 4 , a novel means for engagement of the platform support 13 to upper tubular member 14 is provided by a flexible annular member 15 connected to or formed as part of the upper tubular member 14 about its inside circumference . the annular member 15 is connected in a sandwiched engagement between the bottom surface of the platform support 13 and a ring 17 . this engagement is shown in fig4 where the ring 17 is shown with a slot formed therein to engage the annular member 15 . the ring 17 is connected to the platform support 13 with a snap - in engagement 21 or other means of engagement of the ring 17 to the platform support 13 such as a bolt . the annular ring 15 being formed integral with the wall of the upper tubular member 14 provides a very secure mount for the platform support 13 and platform 12 to keep it from dismounting during vertical or sideways motions which would otherwise dismount the rigid support . the annular member 15 also allows for flex since it is elastic or resilient like the upper tubular member 14 . this resilience allows the platform support 13 and platform 12 of the device 10 to sway and vertically translate during use without impacting that motion since the annular member 15 will stretch to accommodate the rigid platform support 13 during such movement which is why is employed in the preferred mode of the device 10 . another means of engagement of the planar support surface provided by the platform support 13 and platform 12 to the upper tubular member 14 is shown in fig4 a . in this mode , projection 19 extending from the exterior perimeter of the platform support 13 engages with a recess 20 on the top surface of the upper tubular member 14 in the pair of engaged tubular members forming the sidewall of the device 10 . this mode of the device also allows for the platform to be easily engaged in a very secure mount and avoids the inherent problems of lacing and conventional means for engaging such platforms . in a preferred embodiment of the device 10 the lower tubular member 16 is of a slightly larger diameter than the upper tubular member 14 as shown in fig1 , 3 , and 5 . this as noted allows for lateral movement as well as vertical movement of the platform 12 on which the user stands during use . with the lower tubular member 16 larger when the user compresses the sidewall formed of the two tubular members 14 and 16 , the vertical movement tends to rotate the upper tubular member 14 toward the center axis of the device 10 thereby providing means for stability . the larger diameter lower tubular member 16 also provides a larger footprint on the floor or support surface to as noted earlier prevent slippage . this is enhanced with means for frictional engagement to the support surface by a plurality of ridges 24 extending from the bottom surface of the lower tubular member 16 helping maintain engagement on the floor or support surface , even if wet . both the tubular members forming a sidewall for the elevated platform 12 , have interior cavities 26 which are sealed and may be air - filled to maintain their shape and to provide resilience to the formed sidewall . the employment of two such tubular members allows for inflation of each at different inflation levels and thus different resilience levels which provides a means to adjust the resilience of the formed sidewall to adjust the horizontal and vertical stability of the platform 12 . also shown in fig4 is a view of the means of engagement of a top surface of the lower tubular member 16 to a bottom surface of the upper tubular member 14 . currently , a preferred means of such engagement is tongue and groove 27 engagement between the upper and lower tubular members since it allows for removable engagement of the two and transport of the device in component pieces . however because the two tubular members 14 and 16 are collapsible if their interior cavities 26 are de - pressurized , the two tubular members might be extruded as a single unit with a permanent connection or employ other means for permanent connection between the two . also in a preferred mode of the device 10 there is shown fig5 and fig1 , a plurality of mounts 28 for elastic or resistance band exercise device devices . the mount 28 has a gap underneath to allow for the resistance band to encircle the mount 28 such that a user may stand on the platform 12 and use the resistance band exerciser and concurrently receive the benefits from the device 10 of shock absorption while concurrently enhancing the exercise with proprioception exercise since the platform 12 will move both vertically and horizontally relative to the actions of the user . adjacent to the mount 28 are air vents 30 which are positioned below the outside edge of the platform support 13 to direct air vented from the interior of the device 10 downward and away from the user to avoid chilling the user or blowing dust or particulate into their eyes which might be on the floor . also on the top are shown handles 32 . a second means to alter the stability of the platform 12 is provided by the pressurized air or gas employed to fill the tubular members 16 and 14 . since the tubular members 14 and 16 will be either harder or softer depending on internal pressure , they will react with different compression rates and roll rates toward the center axis of the device 10 when the user shifts their weight , depending on the internal pressure . by inflating one tubular member more than the other , unique unstable configurations can be achieved for balance practice . as noted , the device 10 may be employed as a step exercise platform or a balance exercise platform for proprioception enhancement . when employed as a step exercise platform , a reduction in height may be desirable of the platform 12 and such can be achieved by employing only the upper tubular member 14 engaged with the platform 12 . however the most cushioning and utility is provided when the sidewall supporting the platform 12 is formed by a plurality of tubular members 14 and 26 engaged along a seam therebetween . the device 10 may also be employed as a game , by placing a plurality of the devices 10 similarly configured , adjacent to each other . adjacent players supported by adjacent devices 10 would thereafter try and dislodge their fellow game players from their respective platforms 12 using hands or padded members and other instruments to prod adjacent players . while all of the fundamental characteristics and features of the balance and exercise device have been disclosed and described , with reference to particular embodiments thereof , a latitude of modification , various changes and substitutions are intended in the foregoing disclosure and it will be apparent that in some instance , some features of the invention will be employed without a corresponding use of other features without departing from the scope of the invention as set forth . it should be understood that such substitutions , modifications , and variations may be made by those skilled in the art without departing from the spirit or scope of the invention . consequently , all such modifications and variations are included within the scope of the invention as defined herein .

an exercise for step aerobics , games , and proprioceptive input training . the device features a rigid platform supported by a resilient inflated tubular sidewall . the sidewall may be of a single tube or a plurality of tubular members engaged on top of each other . inflation pressure of said sidewall provides an adjustment of the resilience thereby adjusting instability of the platform in the horizontal and vertical directions . instability in the vertical direction provides a cushioning to users in a step aerobics exercise while instability in both direction provides a manner for a user moving or exercising on the platform to obtain proprioceptive input training .

the present invention will be described in terms of the various preferred embodiments . in fig1 a helmet 1 has a strapping system according to the present invention . the strapping system includes two rear straps 2 and two front straps 3 that are connected by strap assembly clips 5 . extending from the two strap assembly clips 5 are chin straps 4 and mateable clip elements 6 . the rear strap stabilizer clip 10 joins the rear straps 2 at a position along the straps that is distal from the point of attachment at the back portion of the helmet 1 . the rear strap stabilizer 10 can be positioned by the wearer so as to provide a comfortable and stable fit on the wearer &# 39 ; s head . an enlarged view of the rear strap stabilizer clip 10 is shown in fig2 . the rear strap stabilizer clip 10 has a base plate member 11 and an upper cover member 12 , which has hinged and free ends . the base plate member 11 has a generally inverted y - shape . the rear strap stabilizer clip 10 has slots 25 and 26 that are formed by the base plate member 11 and the upper cover member 12 for placement of the rear helmet straps . the slots 25 and 26 orient the straps in a generally parallel position with each other . as shown in fig3 the rear strap stabilizer clip 10 can be opened by disengaging a locking means ( not shown ) and swinging upper cover member 12 by hinge 14 to an open position . the base plate member 11 has upper surfaces 21 and 22 and lower surfaces 23 and 24 upon which the rear straps will lie . the rear straps are held in slots 25 and 26 formed by the sidewalls 13 , 15 , 20 and 27 and inverted y - shape center guidewalls 18 and 19 . the slots of the rear strap stabilizer clip are sized to accommodate most standard helmet straps . the hinge 14 can also be placed between sidewalls 13 and 20 . projections 16 located on the inner surface of the upper cover member 12 and projections 17 on the base plate member 11 act to prevent the rear strap stabilizer clip 10 from accidentally sliding on the rear straps after the clip 10 is positioned . it is preferred that projections 16 and 17 be conically shaped , although other suitable shapes may be used . alternately , the inner surfaces of the rear strap stabilizer clip 10 can be textured to provide friction , whereby the movement of the rear straps can also be prevented . the projections 16 and 17 grip the rear straps holding them in place once the wearer determines the ideal location for the rear strap stabilizer clip &# 39 ; s placement . various locking means for locking the stabilizer clip 10 may be used with the invention , such as a clasp , snap , latch , etc . it is within the skill of the ordinary artisan to choose an appropriate locking means and determine its placement , depending on the shape of the rear stabilizer chip . it is also within the scope of the invention to vary the number of locking means used in the design of the rear strap stabilizer clip . in the embodiment shown in fig3 the locking means may be placed on sidewalls 13 and 20 and / or center guidewalls 18 and 19 . an alternative embodiment of the present invention is shown in fig4 and 5 . rear strap stabilizer clip 29 has a base plate member 30 and upper cover member 31 that are generally circular . the upper cover member 31 is connected to the base plate member 30 by a extension member 43 and a hinge 44 . the rear straps 32 and 33 are positioned in slots 34 and 35 in the base plate member 30 . the slots 34 and 35 are recessed channels formed in base plate member 30 . a center guidewall 36 separates the two rear straps 32 and 33 . in this embodiment , the slots 34 and 35 are further apart at the bottom of the clip and the hinge 44 is placed between the slots . the base plate member 30 has a recessed portion 45 that allows the upper cover member 31 to fit in mateable engagement , as shown in fig5 . the upper cover member has a pair of projecting locking elements 39 and 40 that engage a pair of recessed locking elements 37 and 38 . as shown in fig4 the inner surface 41 of upper cover member 31 has projections 42 , which act to hold straps 32 and 33 in place . the slots 34 and 35 may also have similar projections for preventing the straps from sliding . fig6 is an alternative embodiment of the present invention . the rear strap stabilizer clip 50 is a generally flat plate that has slots 51 , 52 , 53 and 54 . slots 51 and 53 are horizontal and on the same level , while slots 52 and 54 are diagonal and form a v - shape . rear strap 56 is shown inserted through slot 52 from the back - side of clip 50 and through slot from the front - side . rear strap 55 is also shown inserted in slots 53 and 54 . naturally , the straps may be inserted into slots 51 and 53 from the front . the rear straps 55 and 56 are shown connected to the back portion of a helmet 57 . the rear strap stabilizer clip 50 has slots that allow the straps to form an inverted y - shape in a natural manner so as to provide an additional anchoring point in the strapping system of the helmet . this embodiment eliminates the need for a cover . however , this embodiment does not permit the ease of adjustment which is available in the embodiments that have a moveable upper cover member . the modified design shown in fig7 and 8 is generally similar to that of fig2 and 3 . the rear strap stabilizer clip 60 has base plate member 62 and upper cover member 61 that form slots 65 and 66 . in this embodiment , the center guidewall 63 on upper cover member 61 and the center guidewall 64 on base plate member 62 have a linear construction . in addition , it is within the scope of the invention to provide a concave surface on the back of the base plate member in each of the aforementioned embodiments . the curved surface permits the rear strap stabilizer clip to fit better and feel more comfortable . according to the present invention , the rear strap stabilizer clip can be easily and inexpensively fabricated in one piece by , for example , injection molding . in the embodiment shown in fig6 the clip can either be die - cut or formed by injection molding since it does not have a movable upper cover . the rear strap stabilizer clip may be fabricated from a suitable polymeric material , such as polypropylene . finally , since numerous modifications and changes will readily occur to those skilled in the art , it is not desired to limit the invention to the exact constructions and operations shown and described , and accordingly all suitable modifications and equivalents may fall within the scope of the invention .

a movable rear strap stabilizer clip for use with a helmet &# 39 ; s strapping system . the stabilizer clip provides a bridge between the rear straps at a location distal from the back portion of the helmet . the stabilizer clip provides an additional support point in the helmet &# 39 ; s strapping system for greater conformability with the user &# 39 ; s head .

according to the present invention , optical tomographic imaging of objects in a highly scattered turbid media is provided using an optical imaging ( opt ) technique and an independent component analysis ( ica ) technique to provide a technique known as optica which can provide for the optical tomographic imaging of objects in a highly scattering turbid medium . according to the present invention , an object located in a highly scattered turbid medium , such as a tumor in a human breast tissue , can be determined with an accuracy of 1 mm . the optica technique can use a multiple - source illumination and multiple detector data acquisition scheme as will be explained below . according to the present invention , a multi - source illumination is used to scan a sample in the xy plane across the incident beam propagating in the z - direction and multiple detectors , for example a charge - coupled device ( ccd ) camera wherein each pixel of the ccd may be viewed as a detector , are used to locate the objects . the resulting spatial diversity and multiple angular observations provide robust data for extracting three - dimensional location information about the embedded targets ( i . e ., inhomogeneities ) in the medium with a millimeter scale accuracy . the data can be analyzed using an independent component analysis ( ica ) of information theory . ica of the light intensity distribution at the detection plane identifies the major components ( which represent the embedded targets ) contributing to the intensity distribution data . using this scheme , every target may be looked upon as a secondary light emitter . a salient feature of optica is that ica provides independent components due to the targets , with minimal processing of the data and the ica does not have to resort to any specific light propagation model for obtaining this information . specific light propagation models are necessary only in a later stage to determine location ( of the targets ) by curve fitting of green &# 39 ; s functions as will be described below . optica is also not model specific , since any appropriate model for light propagation including a diffusion approximation or a radiative transfer equation may be used . another advantage is that optica can be used with light scattering and / or absorbing targets , as well as with fluorescent targets where the fluorophore may be extrinsic or intrinsic . an advantage of the optica method is that it can be used with data acquired from objects of different types of geometric shapes , such as , slabs , cylinders , spheres , and / or arbitrary shaped boundaries . the optica approach as taught by the present invention is fast , and amenable to near real - time detection and localization of objects in a turbid medium , which is a key consideration for in vivo medical imaging . the approach disclosed herein is remarkably sensitive , and can detect a 5 - mm diameter and a 5 - mm long cylindrical target , at least one of having a reduced scattering coefficient , which is only 10 % higher than the surrounding medium , in a 166 - mm long , 82 - mm wide , and 55 - mm thick slab made of materials having a reduced scattering coefficient μ s , ˜ 0 . 9 mm − 1 ( transport length , l t ˜ 1 . 1 mm ), and an absorption coefficient , μ a ˜ 0006 mm − 1 . conventionally , such objects were considered improbable to be detected ( e . g ., see j . hall et al ., “ imaging very - low - contrast objects in breastlike scattering media with a time - resolved method ”, appl . opt ., vol . 36 , pp . 7270 - 7276 , 1997 )). optica is suitable for imaging small targets . for example , optica can be used to detect small objects ( e . g ., objects with a size of ˜ 1 mm ) in a highly scattering medium . given its ability to identify low - contrast small objects , the present invention is suitable for imaging and detecting early , as well as later , - stage tumors in living tissue and body organs , which can be especially beneficial when dealing with cancerous tumors . theoretical formalisms and algorithms of optica taught by the present invention will now be provided . optica is an information theory approach to detect and locate objects within a turbid medium . for the sake of clarity a detailed description of well known principles will not be given , when it may obscure the present invention . an exploded perspective view block diagram illustrating an optica scanning system including a sample according to the present invention is shown in fig1 . optica uses a multi - source illumination and multi - detector signal acquisition scheme providing a variety of spatial and angular views essential for three - dimensional ( 3 - d ) object localization . the multi - source illumination can be realized by scanning an input surface ( or , a source plane ) 110 across an incident beam 170 in a two - dimensional ( 2 - d ) array of points ( e . g ., x s k , y s k ; k = 1 , 2 , . . . , n ). alternatively , the input surface may be kept fixed , and a beam of light may be scanned . corresponding to illumination of the k - th grid point on the source plane 110 , a charge - coupled device ( ccd ) camera 120 records the spatial intensity distribution , i k ( x d , y d ), on the exit surface ( or , detector plane ) 130 . thus , every pixel of the ccd camera 120 can function as a detector implementing the multi - detector measurement arrangement . the difference between the above - mentioned spatial intensity distribution , i k ( x d , y d ) and an estimated background ( for example , an averaged intensity distribution obtained from different source scanning positions ) provides the perturbation in the spatial intensity distribution in the detector plane for illumination at the k - th grid point , δi k ( x d , y d ). the different source and scanning positions can be created using a light emitting diode ( led ) laser array ( not shown ). additionally , one or more lasers 180 , can be used with steering optics to guide an incident beam 170 to predetermined locations . a fiber optic guide 175 can also be used to channel the incident beam 170 . a localization algorithm is based on the premise that each object ( or , target 160 ) within the turbid medium 150 alters the propagation of light through the turbid medium 150 . consequently , the spatial distribution of the light intensity at a detector plane of the turbid medium 150 is different with embedded targets or objects ( e . g ., target 160 ) than that without them . the influence of an object on the light intensity distribution δi k ( x d , y d ) involves propagation of light from the source to the object , and from the object to the detector , and can be described in terms of two green &# 39 ; s functions ( propagators ): the first g ( r , r s ) describing light propagation from a source r s to an object r ; and the second g ( r d , r ) from the object r to the detector at r d . in order to correlate perturbations in the light intensity distributions δi k ( x d , y d ), with the objects embedded in the turbid medium , these objects illuminated by the incident wave are assumed to be “ virtual sources ”, and light intensity distribution δi k ( x d , y d ) assumed to be a weighted mixture of signals arriving from the virtual sources to the detector plane . ica assumes these “ virtual sources ” to be independent , and based on this assumption provides the independent components of the virtual sources . the number of leading independent components is the same as the number of the embedded objects . the effective contributions of the independent components to the light intensity distribution on the source and detector planes are proportional to the projection of the green &# 39 ; s functions g ( r , r s ) and g ( r d , r ), on the source and detector planes , respectively . the location and characteristics of the objects are obtained from fitting either or both of the projections of the green &# 39 ; s functions to those of the model green &# 39 ; s function in a background medium . in a linearized scheme of inversion , the perturbation of the detected light intensities on the boundaries of the medium , the scattered wave field , due to absorptive and scattering objects ( i . e ., inhomogeneities ) can be defined by a diffusion approximation ( da ) shown in equation 1 below . diffusion approximations are further defined in xu , m . lax and r . r . alfano , “ time - resolved fourier optical diffuse tomography ,” j . opt . soc . am . a , vol . 18 , no . 7 , pp . 1535 - 1542 , ( 2001 ), the contents of which are incorporated herein by reference . φ sca ( r d , r s )=−∫ d 3 rg ( r d , r ) δμ a ( r ) cg ( r , r s )−∫ d 3 rδd ( r ) c ∇ r g ( r d , r )·∇ r g ( r , r s ) ( 1 ) when illuminated by a unit point source , where r s , r , and r d are the positions of the source , the inhomogeneity or object , and the detector , respectively , δμ a =( μ a , obj − μ a ) and δd =( d obj − d ) are the differences in an absorption coefficient and a diffusion coefficient , respectively , between the inhomogeneity and the background , c is the speed of light in the medium , and g ( r , r ′) is a green &# 39 ; s function describing light propagation from r ′ to r inside the background turbid medium of absorption coefficient μ a and diffusion coefficient d . it is noted that the explicit dependence on the modulation frequency of the incident wave in the frequency domain in equation 1 has been omitted for the sake of clarity . the following formalism can be applied to continuous wave , frequency - domain and time - domain measurements . the time domain measurement is first fourier transformed over time to obtain data over many different frequencies . although equation 1 includes a da , it should be emphasized that the invention is not limited to a da , but can be used with other models of light propagation in a turbid media , such as , a cumulant approximation ( e . g ., see w . cai , m . lax and r . r . alfano , “ analytical solution of the elastic boltzmann transport equation in an infinite uniform medium using cumulant expansion ,” j . phys . chem . b , vol . 104 , no . 16 , pp . 3996 - 4000 , ( 2000 ); and m . xu , w . cai , m . lax and r . r . alfano , “ a photon transport forward model for imaging in turbid media ,” opt . lett ., vol . 26 , no . 14 , pp . 1066 - 1068 , ( 2001 )), a random walk model ( e . g ., see h . gandjbakhche et . al ., “ photon path - length distributions for transmission through optically turbid slabs ,” phys . rev . b , vol . 48 , no . 2 , pp . 810 - 818 , ( 1993 , the contents of each of which are incorporated herein by reference ) and linearized radiative transfer models . the green &# 39 ; s function g for a slab geometry in the diffusion approximation is given by for an incident amplitude - modulated wave of modulation frequency ω , where k = 0 , ± 1 , ± 2 , . . . , is the distance between the two points r =( x , y , z ) and r ′=( x ′, y ′, z ′) projected onto the xy plane , chosen to have a nonnegative real part , and extrapolated boundaries of the slab are located at z = 0 and z = d = l z + 2z e , respectively , where l z is a physical thickness of the slab and an extrapolation length z e should be determined from a boundary condition of the slab ( e . g ., see lax et . al ., “ classical diffusion photon transport in a slab , in laser optics of condensed matter ,” plenum , new york , pp . 229 - 237 , ( 1987 ); and r . c . haskell , et al ., “ boundary conditions for the diffusion equation in radiative transfer ,” j . opt . soc . am . a , vol . 11 , no . 10 , pp . 2727 - 2741 , ( 1994 ) the contents of each of which are incorporated herein by reference ). equation 2 serves as the model of green &# 39 ; s function in the uniform background medium of a slab geometry . the modulation frequency ω = 0 for a continuous wave light . the green &# 39 ; s function for the slab in time domain is the inverse fourier transform of equation 2 in a frequency domain . in practice , the projections of the green &# 39 ; s function on the source and detector planes , are determined from the measured perturbations in the light intensity distribution using ica according to the present invention . the comparison to the prototype green &# 39 ; s function is then used to locate and characterize the inhomogeneities . the formalism given is for absorptive , scattering and fluorescent targets are detailed in the following subsections . under the assumption that absorptive targets are localized , the jth one is contained in volume v j centered at r j ( where l j j ), the scattered wave field φ sca ( r d , r s ) of equation 1 can be rewritten as : where q j = δμ a ( r j ) cv j is the absorption strength of the jth target , and r j is the position of the jth target . the scattered wave may be interpreted as an instantaneous linear mixture ( e . g ., see j . f . cardoso , “ blind signal separation : statistical principles ,” proceedings of the ieee , vol . 9 , no . 10 , pp . 2009 - 2025 , ( 1998 ) the contents of which is incorporated herein by reference ). in equation 4 separated virtual sources s ( r s )=( q 1 g ( r l , r s ), . . . , q j g ( r j , r s )) t represents the j virtual sources , i . e ., the j targets illuminated by the incident wave . a is a mixing matrix given by equation 5 . whose jth column ( which is a mixing vector ) provides weight factors for the contributions from the jth absorbtive target to the detectors , and a multi - source multi - detector set x ( r s )=(( φ sca ( r d 1 , r s ), . . . , − φ sca ( r d m , r s )) t ) is an observed light intensity change where the superscript “ t ” denotes a transposition . the observation is made over m positions r d 1 , . . . , r d m . the incident light source scans a total of n positions r s 1 , . . . , r s n , sequentially , which can be regarded as “ temporal ” sampling points in the instantaneous linear mixture model of equation 4 . the multi - source multi - detector data set x ( r ) thus describes signals observed in m channels ( i . e ., m detectors ) from j virtual sources ( or j absorbtive targets ) simultaneously over n discrete “ temporal ” points ( n spatial scanning points ). a single absorptive target is represented by a single virtual source q j g ( r j , r s ). the virtual source q j g ( r j , r s ) represents the individual absorbtive target illuminated by the incident wave and is similar to the concept of the secondary source in huygen &# 39 ; s principle ( e . g ., see m . v . klein , “ optics ,” john wiley & amp ; sons , ( 1970 )). the role of detectors and sources can be interchanged due to the reciprocal property of light propagation . the principal assumption of the above - stated formalism is that the jth absorptive target ( treated as virtual source q j g ( r j , r s )) is independent of the virtual sources at other locations . under this assumption , ica can be used with the observations from the light source scanned at n & gt ;& gt ; j positions to separate out both virtual sources s ( r s ) and the mixing matrix a ( e . g ., see p . comon , “ independent component analysis — a new concept ?”, signal processing , vol . 36 , pp . 287 - 314 ( 1994 ); and j . f . cardoso , “ blind signal separation : statistical principles ”, proceedings of the ieee , vol . 9 , no . 10 , pp . 2009 - 2025 , ( 1998 ), the contents of each of which is incorporated herein by reference ). ica is a statistical approach to separate independent sources from linear instantaneous or convolutive mixtures of independent signals without relying on any specific knowledge of the sources except that they are independent . the sources are recovered by a minimization of a measure of dependence , such as mutual information ( e . g ., see p . comon , “ independent component analysis — a new concept ?”, signal processing , vol . 36 , pp . 287 - 314 ( 1994 ); and a . j . bell , “ information theory , independent component analysis , and applications ”, in unsupervised adaptive filtering , vol . 1 , wiley , pp . 237 - 264 , ( 2000 ), the contents of each of which is incorporated herein by reference ) between the reconstructed sources ( e . g ., see j . f . cardoso , “ blind signal separation : statistical principles ”, proceedings of the ieee , vol . 9 , no . 10 , pp . 2009 - 2025 , ( 1998 ), the contents of which are incorporated herein by reference ). the recovered virtual sources and mixing vectors from ica are unique up to permutation and scaling . the two green &# 39 ; s functions of light propagating from the source to the target ( i . e ., g ( r , r s )) and from the target to the detector ( i . e ., g ( r , r d )) are retrieved from the separated virtual sources s ( r s ) and the mixing matrix a . the jth element s j ( r s ) of the virtual source array and the jth column a j ( mixing vector ) of the mixing matrix a provide scaled projections of the green &# 39 ; s function on the source and detector planes , g ( r j , r s ) and g ( r d , r j ), respectively . s j ( r s ) and a j can be defined as : s j ( r s )= α j g ( r j , r e ); and where α j and β j are scaling constants for the jth target . both the location and strength of the jth target can be computed by a simple fitting procedure using equation 6 . for example , a least square fitting procedure given by equation ( 7 ) can be used . the fitting procedure yields the location r j of , and the two scaling constants α j and β j for , the jth absorptive target whose absorption strength is then given by q j = α j β j . for scattering targets , under the assumption that the targets are localized in a few regions , an analysis which is similar to the analysis of absorptive targets can be used . up to three virtual sources may appear for a single scattering target corresponding to the x , y , and z components in the dot product ∇ r g ( r d , r )·∇ r g ( r , r s )= x g ( r d , r ) x g ( r , r s )+ y g ( r d , r ) y g ( r , r s )+ z g ( r d , r ) z g ( r , r s ) shown in equation 1 . by introducing two auxiliary functions as shown in equations 8 and 9 below , the scattered wave due to scattering targets can be rewritten as : φ sca ( r d , r s )=− d 3 rδd ( r ) c {[( x − x d )( x − x s )+( y − y d )( y − x 5 )] g ( r , r d ) g ( r , r s )+ g z ( r , r d ) g z ( r , r s )}. ( 10 ) by denoting the scattering targets as q j ′= δd ( r j ) cv j ′ where c is the speed of light in the medium , an v j ′ is the volume of the jth scattering target , the scattered wave field can be transformed to : and θ d and θ s are the azimuth angles of r d − r j and r s − r j , respectively . this scattered wave can be regarded as a mixture of contributions from ( 3j ′) virtual sources : q j ′ g z ( r j , r s ), q j ′ ρ sj cos θ s g ( r j , r s ), and , q j ′ ρ sj sin θ s g ( r j , r s ), ( 12 g z ( r j , r d ), ρ dj cos θ d g ( r j , r d ), and , ρ dj sin θ d g ( r j , r d ), ( 13 ) where 1 & lt ; j & lt ; j . generally , there are three virtual sources of specific patterns ( e . g ., one centrosymmetric pattern and two dumbbell shaped patterns ) associated with a single scattering target , whereas only one centrosymmetric virtual source is associated with a single absorptive target . this difference may be used to discriminate absorptive and scattering targets . however , for scattering target deep within a turbid media , only the q j ′ g z ( r j , r s ) virtual source remains significant and the other two virtual sources ( i . e ., q j ′ ρ sj cos θ s g ( r j , r s ), and , q j ′ ρ sj sin θ s g ( r j , r s )) are substantially attenuated . in such a situation , other corroborative evidences such as multi - wavelength measurements are required to determine the nature of targets . both the location and strength of the jth scattering object are computed by fitting the retrieved virtual sources and mixing vectors to equations 12 and 13 , respectively . the light propagation in a highly scattering medium with embedded fluorescent targets ( e . g ., intrinsic and / or exogenous contrast agents ) excited by an external light source can be described by coupled diffusion equations at the excitation and emission wavelengths ( e . g ., see m . s . patterson and b . w . pogue , “ mathematical model for time - resolved and frequency - domain fluorescence spectroscopy in biological tssues ”, appl . opt ., vol . 33 , no . 10 , pp . 1963 - 1974 , ( 1994 ); and adam b . milstein et . al . “ fluorescence optical diffusion tomography ”, appl . opt ., vol . 42 , no . 16 , pp . 3081 - 3094 , ( 2003 ), the contents of each of which are incorporated herein by reference ). a fluorescence signal u m ( r d , r s ω ) can be expressed in terms of the two green &# 39 ; s functions g x ( r , r s ω ) and g m ( r d , r , ω ) describing the light propagation from the source r s to a fluorophore at r at an excitation wavelength λ x and the light propagation from the fluorophore to the detector at r d at a transmission wavelength λ m , respectively where ω is the angular modulation frequency of the light as shown in equation 14 below ( e . g ., see x . d . li et . al ., “ fluorescent diffuse photon density waves in homogeneous and heterogeneous turbid media : analytic solutions and applications ”, appl . opt ., vol . 35 , no . 19 , pp . 3746 - 3758 , ( 1996 ) the contents of which are incorporated herein by reference ). assuming a unit point illumination source located at r s and a single exponent decay model of fluorescence with a lifetime of τ ( r ). the subscripts x and m denote the quantities associated with the excitation and emission wavelengths , respectively , and c is the speed of light in the medium . a fluorescent yield y ( r )= ημ af ( r ) is a product of the fluorophore &# 39 ; s quantum efficiency η ( which depends upon the type of the fluorophore and chemical environment ) and the flororphore &# 39 ; s absorption coefficient μ af ( r )= η ( r ) σ a , where η ( r ) is the fluorophore concentration and σ a is the known fluorophore absorption cross section at the excitation wavelength . the nonlinear effect due to multiple passages of light through fluorophores can be incorporated into equation 14 using a nonlinear correction factor if necessary . in the case of multiple fluorescent targets within the medium , it is preferable to rewrite equation 14 as a summation shown in equation 15 below . where the fluorescence strength q f ( ω )= γ ( r i ) cv i /( 1 − jωt ( r i )) and r i is the location of the ith fluorescent target of volume v i . equation 15 casts again the fluorescence signal to a mixture of contributions from virtual sources where the virtual source is proportional to q i g x ( r i , r s , ω ) and the mixing matrix is proportional to g x ( r d , r i , ω ). the virtual sources are statistically independent . by seeking the maximal mutual independence , the virtual sources can be separated with independent component analysis of observations made from a multi - detector array outside the medium produced by an external scanning point source . both the location and strength of the fluorophores can be obtained by comparing the virtual source and mixing matrix to the respective green &# 39 ; s functions , in the exactly same procedure outlined for absorptive targets . an exemplary fluorescent target will now be used to illustrate how the size and shape of a target can be estimated according to an embodiment of the present invention . once one fluorescent target is located and centered at r i the fluorescent target &# 39 ; s contribution to the fluorescence signal is given by : where the integration is performed within an ith fluorescent target assuming uniform fluorescent yield γ j and lifetime r i . to estimate the shape of the fluorescent target , the volume v i is further projected in the longitudinal direction to its transverse cross section s i and thickness of the fluorophore δz i ( ρ ) is introduced . accordingly , equation 16 can be rewritten as shown in equation 17 below . where ρ d , ρ , and ρ s , are transverse coordinates of a detector , the fluorescent target , and the source , respectively . the weighted convolution of equation 17 in ρ can be further simplified as shown in equation 18 below . in the fourier space where q d , q , and q s are conjugate variables of ρ d , ρ , and ρ s , respectively , and “*” denotes a complex conjugate . this yields a solution for δz i ( q ) shown in equation 19 below . please note , q s was chosen to be equal to 0 , because usually there are much fewer sources than detectors ( e . g ., in the present embodiment where a ccd camera is used to detect the light emission at the surface illuminated by a single laser source 120 as shown in fig1 ). an inverse fourier transform of ( δz i ( q ) yields a thickness profile of the fluorescent target in the z direction . the fwhm ( full width at half maximum value ) and the contour of the thickness profile provide an estimation of size and shape of the ith target , respectively . according to the present invention using optica , virtual sources are assumed to be mutually independent and a specific light propagation model is not assumed . appropriate light propagation models including the diffusion approximation , the cumulant approximation ( e . g ., see w . cai , m . lax and r . r . alfano , “ analytical solution of the elastic boltzmann transport equation in an infinite uniform medium using cumulant expansion ,” j . phys . chem . b , vol . 104 , no . 16 , pp . 3996 - 4000 , ( 2000 ); and m . xu , w . cai , m . lax and r . r . alfano , “ a photon transport forward model for imaging in turbid media ,” opt . lett ., vol . 26 , no . 14 , pp . 1066 - 1068 , ( 2001 ), the contents of which are incorporated herein by reference ), the random walk model ( e . g ., see a . h . gandjbakhche et . al ., “ photon path - length distributions for transmission through optically turbid slabs ,” phys . rev . e , vol . 48 , no . 2 , pp . 810 - 818 , ( 1993 ) the contents of which are incorporated herein by reference ), and radiative transfer can also be used with the optica method according to the present invention . the number of targets within a medium is determined by the number of the independent components presented in a multi - source multi - detector data set contained within a turbid medium . analysis of retrieved independent components from ica then localizes and characterizes absorptive and / or scattering targets inside the turbid medium where an appropriate model of the light propagator is adopted . when a noise level is high and / or systematic errors are present , extra independent components may appear in readings . only the leading independent components according to the respective contribution need to be analyzed to detect and characterize targets of interest and other components can be discarded . provided herein are several experiments which illustrate actual embodiments of the present invention in which optica enables the detection and location of targets whose light absorption , scattering , or emission characteristic are different from that of a surrounding turbid medium . absorptive , scattering , or fluorescent targets embedded in turbid media were used for experimental demonstration . a description of samples ( e . g ., specimens ) used in the demonstration , experimental arrangement and procedures as well as experimental results will now be provided below . three tissue - simulating phantoms with absorption and scattering coefficients within the reported range of values emulating healthy human breast tissues and a fourth sample of ( ex vivo ) human breast tissue was used for following experiments ( e . g ., see h . heusmarin et . al ., “ characterization of female breasts in vivo by time resolved and spectroscopic measurements in near infrared spectroscopy ”, j . biomed . opt ., vol . 1 , pp . 425 - 434 , ( 1996 ), the contents of which are incorporated herein by reference ). a diagram of illustrating a first specimen including an intralipid - 10 % suspension in water with two cylindrical absorbing objects having an absorption coefficient of 0 . 23 mm − 1 is shown in fig2 . the first specimen 200 includes a 250 mm × 250 mm × 50 mm transparent plastic container ( for forming a slab ) 210 ( which is similar to the sample 410 shown in fig1 ) filled with intralipid - 10 % suspension in water ( not shown ) with two absorbing targets 220 and 230 , respectively , embedded in the container 210 . the concentration of intralipid - 10 % was adjusted ( e . g ., see hugo j . van staveren et . al ., “ light scattering in intralipid - 10 % in the wavelength range of 400 - 1100 nm ”, app . opt ., vol . 30 , no . 31 , pp . 4507 - 4514 , ( 1991 ), the contents of which are incorporated herein by reference ) to provide a transport length l t ˜ 1 mm at 785 nm . the absorbing targets 220 and 230 each include an 8 - mm diameter 250 - mm long cylindrical glass tube filled with a intralipid - 10 % suspension ( to provide the same scattering coefficient as the intralipid - 10 % suspension ) and an absorbing - ink solution for changing the absorption coefficient to 0 . 23 mm − 1 . the absorbing targets 220 and 230 were placed at different depths along the 50 mm path length ( i . e ., the depth corresponding to the z - axis ) of the plastic container 210 . a diagram illustrating a second specimen including a plurality of cylindrical scattering objects is shown in fig3 . the second specimen 300 includes a 166 - mm long , 82 - mm wide , and 55 - mm thick slab 310 formed from materials having a reduced scattering coefficient μ ′ s ˜ 0 . 9 mm − 1 ( transport length , l t ˜ 1 . 1 mm ), and an absorption coefficient , μ ′ a ˜ 0 . 006 mm − 1 . the slab 300 includes four 5 - mm diameter by 5 - mm long cylindrical scattering targets 320 , 330 , 340 , and 350 . the center of each cylindrical scattering object ( i . e ., 320 , 330 , 340 , and 350 ) is located in a plane 360 which is located halfway between a front side 310 f and a back side 310 f of the slab 310 . the absorption coefficient of each cylindrical scattering object 320 , 330 , 340 , and 350 , is 0 . 006 mm − 1 , which is the same as that of the material of the slab 310 , but the scattering coefficient of each cylindrical scattering object 320 , 330 , 340 , and 350 is respectively 1 . 5 , 2 . 0 , 4 . 0 , and 1 . 1 times greater than the scattering coefficient of the slab 310 . the first and the third cylinders , and the second and the fourth cylinders are on two horizontal lines about 22 mm apart . the distance between neighboring cylinders is 11 mm . further details about similar slabs may be obtained in d . j . hall , et al . “ imaging very - low - contrast objects in breastlike scattering media with a time - resolved method ”, appl . opt ., vol . 36 , pp . 7270 - 7276 , ( 1997 ), the contents of which are incorporated herein by reference . a perspective view diagram illustrating a third specimen is shown in fig3 . the third specimen is also shown in fig1 the third specimen 400 includes a spherical fluorescent target 420 placed inside a slab 410 measuring 250 mm × 250 mm × 50 mm , which is similar to the size and the composition of the slab 210 and 310 shown in the first and second specimens , respectively . the slab 410 is filled with an intralipid - 10 % aqueous suspension . the fluorescent target 400 includes a 9 . 0 mm diameter sphere filled with a solution in water and indocyanine green ( icg ) dye that can be ex cited in the 650 nm - 800 nm spectral range . a fourth specimen ( not shown ) includes a spherical fluorescent target placed inside an ex vivo human breast tissue sample . the tissue sample was assembled as a 26 mm thick , 50 mm long and 50 mm wide slab slightly compressed between two glass plates . the fluorescent target was a 4 . 0 mm - diameter glass sphere filled with icg solution in water . the experimental setup is the similar to the setup used by the third specimen and will not be further discussed for the sake of clarity . referring back to fig1 , an experimental setup for analyzing a slab ( e . g ., the third specimen 400 ) will now be discussed in further detail . an optical source ( e . g ., a laser ) provides incident light beams having a wavelength of λ x = 785 nm . two ( optional ) long wavelength pass absorption filters 150 - 1 and 150 - 2 were placed between the fluorescent target 410 and the ccd camera unit 120 to block the excitation wavelength and allow fluorescence light to pass . the wavelength of the peak fluorescence light adjusted by the filtering and the ccd camera 120 response efficiency is about λ m = 870 nm . the intralipid - 10 % suspension is diluted with pure water such that the transport mean free paths and absorption coefficients are l t x = 1 . 01 mm and μ a x = 0 . 0022 mm − 1 at the excitation wavelength , and l t m = 1 . 14 mm and μ a m = 0 . 0054 mm − 1 at the emission wavelength , respectively . sample targets 180 are shown for illustration purposes only and are not included with the third sample slab 400 in actual embodiments . the experimental arrangement shown in fig1 can be used for imaging of specimens , including the first to fourth specimens , etc . for cw measurements a 200 - μm fiber 170 delivers a beam of 784 - nm light from a diode laser 180 ( e . g ., an ocean optics r - 2000 ) illuminates an input surface ( or source plane ) 110 of the specimen 410 . a cooled ccd camera 120 set to an acquisition time of 150 - ms records two - dimensional ( 2 - d ) intensity patterns of the light transmitted through the opposite side of the slab specimen 410 ( i . e ., the side adjacent to a detector plane 190 ). for time - resolved measurements a 1 - mm diameter collimated beam of 785 - nm , 150 - fs , 1 - khz repetition rate light pulses from a ti : sapphire laser and amplifier system ( e . g ., see q . fu et . al . “ high - average - power kilohertz - repetition - rate sub - 100 - fs ti - sapphire amplifier system ”, opt . lett , vol . 22 , pp . 712 - 714 , ( 1997 )) can be used to illuminate the sample ( e . g ., fluorescent sample 410 ). an ultrafast gated intensified camera system ( ugics ) that provides an fwhm gate width variable from 80 ps to 6 ns can be used to record 2 - d intensity patterns of the light transmitted through the opposite side of the slab . computer controlled xy translation stages were used for scanning the specimens in an array of points in the xy plane as displayed in fig3 . the computer controlled xy translation stages is adjusted according to variables which can include the number of expected targets and the size , shape , and type of expected targets . for example , for the long cylindrical absorbing targets included in the first specimen , a line scan of 16 points with a step size of 2 . 5 mm along x - axis is used to obtain ( x , z ) locations of the absorbing cylinders . using the second specimen , an array of 20 × 18 points with a step size of 2 . 5 mm across the lateral positions of the 4 scattering targets was used for scanning to obtain the locations of the 4 scattering targets . using the third specimen , point source scans over a 10 × 10 grid system with spacing of 2 . 5 mm between consecutive grids , was used to establish the position the fluorescent target . using the previously described methods and targets , temporal profiles of the transmitted pulses were generated using the ugics in the scan mode with an 80 - ps gate width . average optical properties of the turbid medium were estimated by fitting the temporal profiles to the diffusion approximation of the radiative transfer equation ( rte ). ica of the perturbations in the spatial intensity distributions provided corresponding independent intensity distributions on the source and detector planes . ica generated independent intensity distributions on the source and detector planes are shown in diagrams ( a ) and ( b ) of fig4 respectively , for the two absorbing cylinders of the first specimen . locations of the absorbing cylinders are obtained by fitting independent component intensity distributions to those of the diffusion approximation in a slab using equation 6 . in actual experiments , the first cylinder was determined to be located at x = 24 mm , 29 mm away from the source plane and 21 mm away from the detector plane , and the location was determined to be second cylinder at x = 47 mm , 33 mm away from the source plane and 17 mm away from the detector plane . the experimentally obtained ( x and z ) coordinates of both of the cylinders are within 0 . 5 mm of their actual known positions . independent intensity distributions at the detector plane corresponding to the four scattering targets of the second specimen are displayed in diagrams ( a )-( d ) of fig5 . these independent intensity distribution components are then used to obtain projections of a target - detector green &# 39 ; s function , g ( r d , r j ), with j = 1 , 2 , 3 , 4 , on the detector plane for the four small cylindrical scattering targets embedded in the second specimen . locations of the targets are determined by fitting the projections to those of the model green &# 39 ; s function e . g ., see diagrams ( e )-( h ) of fig5 . locations of all four targets were then experimentally determined . even the weakest scatterer , with a scattering coefficient just 11 . 1 times the background and hence considered to be rather unlikely to be found e . g ., see davie j . hall et . al ., “ imaging very - low - contrast objects in breastlike scattering media with a time - resolved method ”, appl . opt ., vol . 36 , pp . 7270 - 7276 , 1997 ), were detected . the known and optica estimated positions of the four objects are presented in table 1 below . as shown in table 1 , positions along z - axis ( depth ) of the cylinders were experimentally determined to be located at 28 . 13 mm , 27 . 87 mm , 27 . 08 mm and 32 . 6 mm . except for the experimental results for the last cylinder , the depth of other cylinders agree within 1 mm of their known center positions of 27 . 5 mm . the opica - estimated lateral positions of each of the other targets was within 2 - 3 mm of the actual lateral positions of each respective target . independent intensity distributions at the detector plane and the source plane obtained by ica for the third specimen 3 is shown in fig6 . the fluorescent target is found to be z = 33 mm away from the input window by fitting independent intensity distributions at the detector plane and the source plane to the respective green &# 39 ; s functions ( e . g ., see diagrams ( a ) and ( b ) of fig7 ). this agrees with the input value z = 32 mm away from the input window . the thickness map is obtained using equation 19 and presented in diagram ( c ) of fig7 while the horizontal and vertical thickness profile of δ z / z max are also plotted in diagram ( d ) of fig7 . the target is found to be centered at ( x = 11 , z = 9 ) mm and have a circular shape . the fwhm of the peak found to be d = 11 . 5 mm . this value should be compared to the diameter of the fluorophore 9 mm . the fluorescent target in the fourth sample is found to be z = 11 mm away from the input window by fitting independent intensity distributions at the detector plane and the source plane to the respective green &# 39 ; s functions ( see diagrams ( a ) and ( b ) of fig8 ). this agrees well with the input value z ˜ 10 mm away from the input window . the thickness map is obtained using equation 19 and presented in diagram ( c ) of fig8 while the horizontal and vertical thickness profile of δ z / zmax are also plotted in diagram ( d ) of fig8 . the target is found to be centered at ( 21 , 33 ) mm and have a circular shape . the fwhm of the peak is found to be d = 7 . 1 mm . this value should be compared to the diameter of the fluorophore 4 mm . the experimental results demonstrate that the present invention using optica , can successfully detect and obtain the location of absorbing , scattering , and / or fluorescent targets embedded inside a turbid medium . 4 mm targets located deep within a thick human breast tissue have been shown to be successfully located within an error of several millimeters and characterized in experiments . accordingly , the present invention using optica can be used to detect and obtain the location of absorbing , scattering , and / or fluorescent targets of 1 mm size embedded inside a turbid medium . graphs illustrating normalized independent spatial intensity distributions as a function of the lateral position x at the input ( or source ) plane ( first row ) and the exit ( or detector ) plane ( the second row ) generated by ica and a horizontal profile of intensity distributions on the source plane ( illustrating diamonds ) and on the detector plane ( illustrating using circles ) are displayed on the third row for the two absorbing cylinders of the first specimen is shown in diagrams ( a )-( f ) of fig4 . solid lines illustrate the respective green &# 39 ; s function fit used for obtaining locations of objects . graphs illustrating independent spatial intensity distributions at the exit ( or detector ) plane generated by ica corresponding to objects with scattering coefficients : ( a ) 4 times , ( b ) 2 times , ( c ) 1 . 5 times , and ( d ) 1 . 1 times of that of the material of the slab in the second specimen are shown in diagrams ( a )-( h ) of fig5 . horizontal profiles of intensity distributions shown in diagrams ( a )-( d ) of fig5 are illustrated by circles in diagrams ( e ) and ( f ) of fig5 , respectively , with solid lines representing the green &# 39 ; s function fit used for extracting object locations . graphs illustrating independent intensity distributions of the fluorescence from the target generated by ica at the detector plane and the source plane , are illustrated in diagrams ( a )-( b ) of fig6 , respectively . graphs illustrating fitting of the independent intensity distribution of fluorescence from a sphere of diameter 9 mm embedded in intralipid - 10 % solution to the model green &# 39 ; s function are shown in diagrams ( a )-( c ) of fig7 . the independent intensity distribution of fluorescence from a sphere of diameter 9 mm embedded in intralipid - 10 % solution to the model green &# 39 ; s function are at the detector plane and at the source plane are illustrated in diagrams ( a ) and ( b ) of fig7 , respectively . the thickness map of the target centered at ( 11 , 9 ) mm and the thickness profiles along x and y directions , are illustrated in diagrams ( c ) and ( d ) of fig7 , respectively . graphs illustrating fitting of the independent intensity distribution of fluorescence from a sphere of diameter 4 mm embedded in human breast tissue to the model green &# 39 ; s function is illustrated in diagrams ( a )-( c ) of fig8 . the independent intensity distribution of fluorescence from a sphere of diameter 4 mm embedded in human breast tissue to the model green &# 39 ; s function at the detector plane and at the source plane , are illustrated in diagrams ( a ) and ( b ) of fig8 , respectively . a thickness map of the target centered at ( 21 , 33 ) mm , and a thickness profiles along x and y directions , are shown in diagrams ( c ) and ( d ) of fig8 , respectively . fig9 is a block diagram illustrating a control system for controlling the experimental arrangement shown in fig1 according to an embodiment of the present invention . the system 900 includes a controller 930 , a ccd control unit 940 , a ccd camera 950 , an display unit 960 , an input / output device 970 , an optical control unit 980 , a light source unit 990 , an source control unit 922 , and a memory unit ( e . g ., ram , rom , flash , etc .) 920 . the controller 930 controls the overall operation of the system 900 and stores data and retrieves necessary data ( e . g ., operating instructions , data generated during use , etc .) in the memory unit 920 . the ccd control unit 940 interacts with the controller 930 and controls the operation of the ccd camera 950 . the display 960 receives data from the controller ( and / or other device such as a ccd camera , etc .) and displays the data . the input / output unit 970 can include a mouse , a keyboard , a touch - screen , etc . ( not shown ) for entering commands from a user , and other devices ( e . g ., a network connection for communicating with a lan / wan , the internet , etc ., and an optional external memory ) for controlling the operation of the system 900 . the optical control unit 980 is controls the location of incident light relative to a source plane . for example , optical control unit 980 can be used to focus and / or locate incoming ( incident ) light as desired using lenses and mirrors , respectively , which are controlled by stepper motors , etc . the source control unit 922 is operated by the controller 930 and controls the light source 990 . the light source 990 can include a laser or other suitable device for producing a desired incident beam and can preferably produce an incident beam having a given wavelength and duration . the controller 930 ( and / or other devices shown in fig9 can be included within a personal computer ( pc ) 190 shown in fig1 . in other embodiments , optical sources and detectors can be remotely located and operated by one or more controllers . in yet other embodiments , a plurality of light sources ( e . g ., a plurality of light - emitting - diode ( led ) lasers can be used in which case the source an optical control system for locating an incident beam may not be necessary . fig1 is a flow chart illustrating the operation of an embodiment of the present invention for locating a target location . in step 1000 a sample is illuminated by the light source . in step 1020 , a camera ( e . g ., a ccd camera ) captures an image of the illuminated sample . in step 1030 resulting special diversity and multiple angle observations are obtained . in step 1040 a target located within the sample is located and characterized using a comparison to a prototype greens function . in step 1050 generated data is displayed on a display . while the invention has been shown and described with reference to certain preferred embodiments thereof , it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims .

disclosed is a system and a method for detecting the presence of one or more objects in a turbid medium , the method including : illuminating at least a portion of the turbid medium with incident light having at least one wavelength which interacts with the one or more objects contained in the turbid medium differently than the incident light interacts with the turbid medium ; measuring light that emerges from the turbid medium ; and detecting and locating the one or more objects using independent component analysis of the emergent light from the turbid medium . the present invention is useful for medical applications , such as for finding and locating , a tumor in body organs , or excised tissues . moreover , the present invention can be used to locate objects in obscuring medium , such as , mines in shallow coastal water , a plane in fog , military targets under fog , smoke or cloud cover .

one drug delivery system is shown in fig1 . the intravenous bag 1 is connected to a drug delivery bag 5 by means of a y - connector 20 . the y - connector 20 combines the solutions into an injection line 25 that is subsequently introduced to the hand 30 or any other body part . the drug delivery bag 5 holds pre - formed concentrated solution , which is diluted for iv injection by fluid from the diluent bag 1 . as noted in the background section , this arrangement has certain disadvantages . with reference to fig2 a drug delivery pack 35 is shown in - line with an intravenous solution bag 1 . the solution bag 1 is part of the intravenous delivery system 36 . the iv line 3 leads from the intravenous delivery system 36 to the drug delivery pack 35 via luer locks 4 , and then to an injection site 30 , which in this example is at a human hand . those skilled in the art will realize that other injection sites include but are not limited to the arm , neck and leg . now referring to fig3 a housing 37 of the drug delivery pack 35 is preferably composed of a clear material , such as plastic polymer or glass . an inlet 40 in the housing top 45 provides a connection between an input line ( not shown ), such as an iv line , and the body of the housing 37 . the inlet 40 includes a collar 42 terminating at one end with a connection fitting 55 to connect to the diluent source . the housing 37 also contains an air vent ( not shown ) and a terminal outlet 160 at the axial terminus of the housing 37 opposite to the inlet 40 . the air vent is preferably sealed against fluid flow by an air permeable / fluid impermeable barrier or a mechanical valve . immediately adjacent to the inlet 40 is a distribution chamber 60 , defined between an inlet frit 80 and the housing top 45 , which are separated by radial fins 65 protruding from the housing top 45 . referring to fig4 the radial fins 65 are shown in a cross - section , stopping short of a central opening . referring again to fig3 the inlet frit 80 is a porous material , which can be hydrophilic but is preferably hydrophobic . the porosity of the frit 80 can range from about 5 to about 100 microns , with the preferred range in porosity between about 5 and about 50 microns , and more preferably between about 10 and about 20 microns . exemplary materials are porous polymers and cellulose filters . an open bore 90 is located below the inlet frit 80 , which is just below the distribution chamber 60 . also below the inlet frit 80 is an upstream compression component 85 . the illustrated compression component 85 takes the form of a cylinder surrounding the open central bore 90 . the compression component 85 is composed of open celled polymeric material , which upon compression exerts a pressure as a result of memory of the material . this pressure is measured as a compression deflection ( cd ) or an indentation load deflection ( ild ). in other arrangements , the compression component can comprise a polymer or metal spring . the bore 90 is filled with a core 105 of porous material . the core 105 can be tailored as needed , but preferably has a greater porosity in pores per inch ( ppi ) than the compression component 85 . below the compression component 85 is an upper reagent restraint 95 . in the illustrated embodiment , the upper reagent restraint 95 is a disk of material with a central hole 100 accommodating the core 105 . the upper reagent restraint 95 can be porous or nonporous polymeric or cellulosic material . the upper reagent restraint is preferably hydrophilic . below the upper reagent restraint 95 is a reagent bed 110 . it consists of a fluid soluble material suitable for administering to a patient via dissolution and iv drip . the core 105 also extends through the reagent bed . below the reagent bed 110 is a lower reagent restraint 115 . the lower reagent restraint 115 comprises a pliable or rigid disk . the restraint can be similar to the upper restraint 95 , and is illustrated with a lower reagent central hole 120 . if pliable , the lower reagent restraint 115 is preferably backed by a rigid disk 125 , as shown . the lower reagent restraint 115 is preferably hydrophobic . the bore 90 thus extends through the compression component 85 , the upper reagent restraint 95 , the reagent bed 110 , the lower reagent restraint 115 and ( if present ) the rigid backing 125 . below the lower reagent restraint 115 and the rigid backing 125 , is a collection area 135 . the collection area 135 is defined by the housing body 37 , the lower reagent restraint 115 or the rigid backing 125 . below the collection area 135 is a terminal frit 140 . the terminal frit 140 consists of porous polymeric material that may have either a hydrophobic or hydrophilic nature . preferably , the terminal frit 140 is hydrophobic , such that it generates sufficient back - pressure to accumulate fluid in the overlying collection area 135 before passing the fluid . a collection chamber 145 is located below the terminal frit 140 . the collection chamber 145 is defined by the terminal frit 140 , the bottom of the housing 150 , and the bottom radial fins 175 located adjacent to the housing outlet 160 . the outlet end of the pack 35 is thus similar to the inlet end . the housing outlet 160 forms a tube connecting the housing collection chamber 145 to the exterior of the housing 37 . the exterior terminus of the outlet 160 includes a fitting to enable a sterile , closed connection to the downstream portion of the diluent flow . both the inlet 40 and outlet 160 can be covered by port covers ( not shown ), if desired , to maintain sterility prior to use . in operation , with reference to fig2 the drug delivery pack 35 is attached in - line to an intravenous administration set 36 including an upstream reservoir 1 of intravenous fluid connected to a tube 3 linking the reservoir to the patient . attachment of the drug delivery pack 35 is accomplished by in - line luer connectors 4 at the inlet and outlet of the drug delivery pack 35 . more specifically , on a preexisting iv line , flow is stopped by closing clips ( not shown ). the intra - line connections are opened and the drug delivery pack 35 is inserted and locked with luer locks . next , the closing clips on the fluid line are opened and diluent flow is reestablished . it will be readily apparent to those skilled in the art that a variety of other techniques may be used to connect the drug delivery pack 35 in - line along an iv line . such techniques include but are not limited to having an iv bag spike at the inlet of the drug delivery pack 35 and / or an iv spike receptacle at the outlet associated with a drip chamber . referring now to fig3 diluent from the upstream reservoir 1 ( fig2 ) enters the housing 37 via the inlet 40 and first encounters the inlet radial fins 65 . the inlet radial fins 65 cooperate with back - pressure from the inlet frit 80 promote a uniform distribution of diluent across the entire cross - section of the drug delivery pack 35 . the downstream fins 65 similarly cooperate with the outlet frit 140 to form a downstream manifold distribution chambers for the solution . the hydrophobic nature of the inlet frit 80 forces the diluent to the periphery within the distribution chamber 60 prior to penetration of the frit 80 . thus , an initially uniform pattern of diluent flow through the upstream portions of the drug delivery pack 35 is established . it will be readily apparent to one skilled in the art that other arrangements can also achieve uniform distribution . furthermore , the drug pack 35 would also entail advantages without an initial uniform distribution . the uniform face of diluent enters and passes through the upper compression component 85 . after passing through the upper compression component 85 , the diluent encounters the preferred upper reagent restraint 95 upstream from the reagent bed 110 . the hydrophilic nature of the preferred upper reagent restraint 95 thoroughly “ wets ” the restraint uniformly by capillary action . this serves to provide a wetting of the entire reagent bed 110 . this is particularly advantageous for dissolution of hydrophobic reagents . a portion of the diluent bypasses the reagent bed 110 by traveling down the porous central core 105 within the bore 90 . this diluent accumulates in the collection area 135 above the hydrophobic terminal frit 140 . the diameter of the bore 90 holding the core 105 , together with the relative porosity and hydrophobocity of the compression component 85 , restraint 95 , reagent bed 110 , and restraint 115 , determines the portion of diluent entering the reagent bed 110 , as compared to that bypassing the bed 110 . partitioning the amount of diluent that enters the reagent bed 110 effectively regulates the rate of dissolution of that reagent . desirably , the hydrophobic nature of the preferred lower reagent restraint 115 retains diluent with the reagent bed 110 , enhancing the wetting of the reagent bed 110 . also , a rigid material may be furnished to provide support for the reagent restraint 115 . such material may include but is not limited to sintered plastics . the solution prepared from the dissolving reagent passes through the reagent bed 110 and exits into the central core 105 and / or through the lower restraint 115 . in the upper collection area 135 , the portion of the diluent which bypassed the reagent bed 110 is mixed with the solution formed from diluent passing through the reagent bed 110 . the solution is thus diluted within the area 135 . dissolved reagents have time to diffuse to even out concentration in the preferred embodiment . this is due to the fact that enough solution must gather in the collection area 135 to create , preserve and overcome the hydrophobicity of the preferred terminal frit 140 . when sufficient solution enters the collection area 155 to create sufficient head pressure to overcome the hydrophobicity of the terminal frit 140 , solution terminal frit 140 and into the lower collection chamber 145 and into the housing outlet 160 . an additional hydrophobic barrier of varied porosity may also be placed before the outlet . the collection area 135 can also be created by the use of a spring , rather than the rigid and welded elements 115 or 125 , as will be apparent to those skilled in the art . as will be apparent to the skilled artisan in view of the discussion above , the various elements in the drug pack 35 can be arranged to vary the relative diluent flow through the core component 105 , as compared to diluent flow through the reagent bed 110 . varying the relative flows thus varies the concentration of drug solution exiting the pack 35 . for example , for a given set of materials , the diameter of the bore 90 and core element 105 therein can be varied as desired . alternatively , for a given bore 90 size , the relative porosity of the core element 105 as compared to that of the upper reagent restraint 95 can be changed . varying materials to accomplish different levels of hydrophobicity can also influence the relative flow rates . for a given application , accordingly , the skilled artisan can determine an appropriate set of materials and relative dimensions to achieve a desirable solution concentration . thus , no separate diluent line needs to be employed , and the overall iv administration system is much simplified . the skilled artisan will readily appreciate , in view of the disclosure herein , numerous other manners of varying the relative flow of diluents through the reagent bed as compared to a bypassing flow . for example , in contrast to the illustrated central core 90 and core element 105 housed therein , a peripheral gap between the reagent bed 110 and the housing 337 can be created by surrounding the bed with a frit having a smaller diameter than the housing 37 , spaced therefrom by periodic spacers or ribs , for example . in yet another arrangement , the central core 105 need not extend through each of the elements 85 , 95 , 110 , 115 and 125 . note that the inlet frit can also be made hydrophilic to bias fluid flow coming through the inlet 40 , through the central core 105 , rather than encouraging a uniform flow distribution at the inlet end . such an arrangement would produce a more dilute solution than use of a hydrophobic inlet frit 80 . in the preferred embodiment , the inlet frit 80 is polypropylene . the compression component 85 is made of an open cell foam . the central core 105 is also made of an open cell foam . the terminal frit 140 is cellulose . the lower reagent restraint 115 is hydrophobic and made of porous polypropylene , to retain diluent within the reagent bed . the collection area 135 is maintained by a polymer spring with greater force deflection than the upper compression component 85 , thus spacing the upper components above the terminal frit 140 . the terminal frit 140 is hydrophobic to form the collection area 135 within the housing 37 upstream of the housing outlet . an example of a device for delivery of a typical antibiotic ( for example a cephalosporin like cefazolin ™) with a drug bed 110 of 1000 mg utilizes a housing 37 0 . 75 inches in internal diameter and a height of 1 . 25 inches . the internal volume of this housing 37 is roughly 9 milliliters . for appropriate delivery this drug is administered over a period of 40 minutes , forming a total of 60 milliliters of solution at concentration between 10 and 40 milligrams / milliliter . the interior of the housing 37 is divided into two chambers . the upper chamber contains the compression component 85 , the core and the reagent . for exemplary 1000 mg dose of drug , the dry volume is 3 . 0 milliliters . the preferred compression component has a height of 0 . 875 inches . the central cavity 90 within this component 85 has an interior diameter of 0 . 25 inches to accommodate the core 105 . the preferred component 85 has a preferred porosity of about 60 to 90 pores per inch ( ppi ), more preferably 75 ppi , and a preferred compression load deflection ( cld ) of about 0 . 4 to 0 . 6 psi at 25 % compression , more preferably 0 . 5 psi at this compression . at 65 % compression the cld is preferably about 0 . 5 to 0 . 8 psi , more preferably 0 . 65 psi . these cld were determined by measurement of deflection 50 square inches of material . it is compressed within the housing to fill the area upstream of the reagent bed . the exemplary core 105 has a height of 0 . 675 inches and an outer diameter of 0 . 225 inches . the prosity of this material is preferably 90 to 110 ppi , more preferably 100 . the reagent bed restraints 95 , 115 have a preferred range in pore size of 5 to 25 microns , more preferably about 10 microns . the support for the reagent bed restraints 95 , 115 preferably has pores of 20 to 80 microns , more preferably 40 to 60 microns . the diameter of the hole in the reagent restraints and the support is about 0 . 215 inches to accommodate the core 105 . the lower chamber 135 is open with a frit 140 at the distal end of the housing 37 , adjacent to the outlet 160 . the frit 140 between the open chamber 135 and the outlet 160 preferably has pores of between 5 and 25 microns , more preferably about 10 microns . the frit 140 is preferably hydrophobic , comprising polypropylene . it has a preferred thickness of between 0 . 25 and 0 . 75 inches , more preferably 0 . 5 inches . other variations will be apparent for those skilled in the art . for instance , an increased diameter of the housing 37 could be employed with an increased core 105 diameter for hydrophilic reagents to decrease the efficiency of dissolution of the reagent .

an in - line drug delivery pack that connects in - line with an intravenous line and allows for the mixing of diluent with a drug reagent to be delivered to the patient . an internal drug bed bypass mechanism is tailored to apportion diluent flow between the bypass and the drug bed . the apportionment is selected to achieve a solution concentration suitable for iv administration as the dried reagent is dissolved . thus , both dissolution and precisely tailored dilution are performed in the same simple device .

the dispenser 1 is a vertically stacked single unit and dual purpose personal - portable and or homebound - institutional medication dispenser . it is capable of safely dispensing an almost infinite number of medication filled dispensing wheels to the most comprehensive , diversified , and specialized groups of medical and psychiatrically diagnosed patients . this dispenser is the most technologically advanced and sophisticated automatic medication dispenser of this twenty first century . no other single medication dispenser can service both the personal - portable and home - institutional medication dispensing needs of patients . the dispenser will provide novel , innovative , and breakthrough dispensing and treatment services for the numerous unresolved medical and psychiatric dispensing problems of the past twentieth century . other objects , advantages , and novel features of the invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings . in the drawings , of the caregiver automatic medication dispenser , closely related figures have the same number but different alphabetic suffixes . like characters represent like or corresponding parts throughout the several views , one sees in fig1 a , 1 b and 1 c are a view of the preferred embodiment of an expandable caregiver personal - portable and homebound - institutional automatic medication dispenser or device 1 . the dispenser delivers individual v shaped medication containers 111 containing all of the medication needed at the time delivered . the dimensions of its housing 12 are ( approximately 12 cm in diameter × 6 cm in height ). this panel is a structural cross member ( 0 . 100 thick aluminum plate with a plastic facade ) screwed and or riveted onto the outer wall of the dispenser . it is attached to the lower half and outside wall of the dispenser &# 39 ; s housing and next to the dispensing draw . the device 1 has a liquid crystal display ( lcd ) 16 ( approximately 2 cm . long × 0 . 5 cm wide × 0 . 2 cm thick ) and located in the upper most part of the display panel . it will electronically display the day of the week , time of the day , and the date . the front panel 15 houses a red circular push button compliance button 17 . this button is located in the center of the display panel and under the electronic lcd 16 . the circular red flashing - push button light 18 ( approximately 0 . 7 cm in diameter and 0 . 3 cm × depth ) flashes when the patient &# 39 ; s medication has been dispensed . after the patient takes their medication they will push this flashing red circular compliance button 17 . located directly under the circular red flashing compliance button is a rectangular shaped yellow indicator light led 19 ( 2 cm in length × 0 . 5 cm in width × 0 . 2 cm thick ) that activates if a malfunction occurs in its sequencing pattern . the yellow light displays the message danger get help . if it lights up the patient will call a family member and or caregiver for assistance . fig2 is a pictorial view of the integrated modular dispensing wheel system of the caregiver personal - portable and homebound - institutional automatic medication of fig1 . fig1 c is a top view of a dispensing wheel 18 . fig3 is a detailed view of the first integrated modular dispensing wheel 21 ( approximately 11 . 8 cm in diameter × 1 to 1 . 5 cm in height ). it is the drive wheel for all of the vertically stacked dispensing wheels 21 above . it consists of the following parts : a magnetic probe , a groove for the magnetic probe to travels in , and an entrapment room located in this groove . the entrapment room is composed of a door and a magnetic wall . the flat magnetic probe 38 ( approximately 0 . 2 cm width × 0 . 4 cm height × 0 . 2 cm thick ) is attached to the top and outside wall of the first dispensing wheel 23 , and at the proximal wall of its first dispensing unit is a cut out groove that encircles the base of the second dispensing wheel above . the magnetic probe 38 from the top of the first dispensing wheel 23 travels around and through this cut out groove . the dimensions of the cut out groove in the preferred embodiment are approximately 0 . 4 cm in width × 0 . 5 cm in depth ). the width of the base and outside wall is approximately 1 cm . the groove is cut into this base . in this example , the magnetic probe 38 on the top of the first dispensing wheel will travel through the cut out groove at the base of the second dispensing wheel above fig3 located within this cut out groove is an entrapment room . the entrapment room 36 is located at the base of dispensing wheel number two . the entrapment room is located just before and below the distal wall of the first medication filled dispensing unit 1 of dispensing wheel number two above . the entrapment room has a door 41 and a magnetic plate 39 . the magnetic plate 39 is directly under the distal or proximal wall of the first dispensing unit of dispensing wheel number two above . the entrapment door 25 extends laterally across and near the top of the entrapment room 36 . the entrapment door 25 will extend laterally ( approximately ¾ quarter ) of the way across the entrapment room 39 from either the outside wall - in or the inside wall - out . the entrapment door 25 is a thin , flexible , and rectangular shaped object made out of metal . the metallic magnetic probe on top of the first dispensing wheel will pass through the door of the entrapment room 36 and become attached to its the magnetic wall . fig4 is a pictorial and detailed view of the v shaped cut 122 out dispensing unit 32 on the first dispensing floor 23 , a triangular v shape medication container 111 ( smaller than the v shaped cut out dispensing unit on the dispensing floor ), a dispensing draw or * shallow semicircular medication cup 111 at the base of the dispenser 1 . as the first dispensing wheel turns one preprogrammed dispensing unit 32 the triangular medication container 111 ( and the medications contained within it ), will fall through the v shaped cut out dispensing unit on the first dispensing floor and down a clear vertical 16 pathway into either a dispensing draw or a shallow semicircular dispensing cup at the base of the dispenser 1 . fig5 is a frontal and pictorial view of the over sized door to the medication dispensing draw inside the housing of the dispenser , a spring loaded hinge or hinges for the dispenser &# 39 ; s medication dispensing door , an over sized medication draw inside the housing of the dispenser , is a shallow semicircular medication dispensing cup , an enclosed inclined slide that &# 39 ; s attached to the top 29 and back wall of the containment room for the medication draw . the top wall of the containment room is attached to the bottom of the parts attachment floor above . in the preferred embodiment , there is a key and lock for the medication dispensing door . the spring loaded hinges or hinges will snap the door to the medication draw shut . the medication draw is located behind the dispenser &# 39 ; s door and inside the housing 12 of the dispenser 1 . the door is located next to the operating - display panel . the medication draw is located behind this door and inside the dispenser 1 . the shallow semicircular dispensing cup is an extension of the base of the dispenser 1 . when a v shaped medication container 111 is dispensed it will slide down the inclined chute 277 and into the semicircular cup at the base of the dispenser . the chute 277 has a vertical wall on each of its sides . this will prevent the medication container from falling off the inclined slide 27 . the top end of this slide 27 is connected to the top of the back wall 28 of the containment room for the medication draw . the top of the containment room will be secured to the bottom of the parts attachment floor . the medication draw will slide in and out of the dispenser 1 . it will slides in and out on the floor of the dispenser ( the base of the dispenser 1 ). the thickness of the base allows the door and draw to be slightly elevated from the bottom of the base . the door will have an indented handle . the medication draw will have protruding horizontal handle . fig6 shows the flat metallic dispensing bar 31 and its attached * thin flexible metallic probes 32 or miniature solenoids 48 . the flat metallic bar is attached to the u shaped structure on top of the bottom half of the dispenser 1 . the flat metallic bar is [*]( approximately * 4 cm . in length × 1 cm wide × 0 . 2 cm thick .). the flat metallic bar extends down ( approximately * 1 cm .) from this u shaped structure . fig7 is a pictorial and detailed view of the integrated modular dispensing wheel system of drawing fig2 with two thin metallic rods 35 extending vertically down from the center and inside wall of the top half of the dispenser &# 39 ; s housing 12 and its two corresponding vertical receiving holes located at the top and center of each vertically stacked modular dispensing wheel . the rods extend vertically down to the top of the first dispensing wheel ; but they don &# 39 ; t make contact with the top of the first dispensing wheel . this specific structure will hold the modular dispensing wheels and their cut out v shaped dispensing units in a specific and fixed 17 position . the v shaped cut out on the top and bottom of each vertically stacked modular dispensing wheel , a dispensed and vertically aligned dispensing unit , the v shaped cut dispensing unit on the first dispensing floor , and the medication draw or the slide to the shallow semicircular dispensing cup at the base of the dispenser will be vertically aligned with one another . referring to the drawings , wherein like characters represent like or corresponding parts throughout the several views , one sees in fig1 . a a view of the caregiver automatic medication dispenser and its interrelated parts . in an embodiment of the invention there could be an optional miniature television camera 38 that maybe mounted on the top and middle of the dispenser &# 39 ; s top . the invention could have miniature or small rectangular shaped stepper motor 15 with a square vertical male geared shaft that extends up vertically into a slightly larger square geared female receptor in the center of the first dispensing wheel . this geared female receptor extends through the center of the first dispensing wheel . the first dispensing wheel is the drive wheel . it will turn all of the vertically stacked dispensing wheels above . there is another means to interconnect the shaft of the steeper motor with the first ( drive ) dispensing wheel above . the top part of this shaft will have two and or four vertical interlocking and protruding male ridges that fits into the corresponding two and or four female vertical grooves at the bottom and center of the first dispensing wheel . the female grooves extend up into the center of the first dispensing wheel . there is the first dispensing floor that &# 39 ; s shaped like an upside down cake baking pan . the outer wall of this first dispensing floor will be attached to the lower part of the flat metallic dispensing bar 31 . a parts attachment floor is a right side up like cake backing pan with a diameter slightly less than the upside down dispensing floor . the difference in size enables the wall of the parts attachment floor to fit tightly inside the wall of the first dispensing floor . this will enable the space between the first and second floor to be adjustable . the space between the two floors can be either increased and or decreased . the distance between the two floors will be adjusted to accommodate the stepper motor 15 . after the steeper motor 15 is in place , the first the two floors will be secured together and then secured to the lower part of the flat vertical dispensing bar 31 . the common wall between the first dispensing floor and the parts attachment floor will be attached to one another and then attached to the flat metallic dispensing bar 31 . they can be attached at any given or required point on the lower part of the flat metallic dispensing bar 31 . they can be attached and secure together with nuts , bolts , and lock washers or any other attachment means . the bottom of the parts attachment floor 47 can be used to attach some of the electronic components . the first medication dispensing floor will have a very small circular cut out hole in its exact center . the shaft of the stepper motor 15 will protrude through this small cut out circle . the shaft of the stepper motor 15 will be connecting to the first dispensing wheel above . the stepper motor 15 will have two side extensions with vertical attachment holes on its housing . the attachment floor will have two corresponding attachment holes . the holes in the housing of the two extensions of the stepper motor and the holes on the attachment floor will be aligned with one another and then will be bolted together . the timing mechanism is a microprocessor with the watch dog timer 59 . fig3 is a dispensing wheel with its magnetic probe with a connector for a plug in co - axial cable for an online compliance computer . there are the bolts , lock washers , nuts or rivets that secure the first dispensing floor and the parts attachment floor to the flat vertical dispensing bar 31 . fig6 is the flat metallic dispensing bar 31 ( approximately 4 cm × height , 1 cm × width , 0 . 2 × thick ) with a series of vertically attached thin metallic probes 32 or small - miniature solenoids 33 . the thin flexible metallic probes 31 or miniature solenoids 33 are vertically aligned and equidistant apart on the flat metallic dispensing bar 31 of fig6 . the thin flexible metallic probe or arm from the solenoid will extend into a vertical cut out groove o the outside wall of each vertically stacked medication dispensing wheel . the probes or solenoids will enter at a point that is about three quarters of the way up the vertical cut out groove of each dispensing wheel . the flat metallic bar 31 with its attached probes or solenoid arms is attached to the inside wall of the inside part of the u shaped top of the bottom half of the dispenser 1 . the flat metallic bar 31 is attached at a point on the u shaped top one dispensing unit behind or before the dispensing draw or shallow semicircular cup at the base of the dispenser 1 . the probes and arms will hold the individual dispensing wheels in a specific and fixed position until they are automatically dispensed one dispensing wheel at a time . fig3 shows the first medication dispensing wheel . in the preferred embodiment , the dispensing wheel is ( approximately 12 cm in diameter ×[ 1 to 1 . 5 ] in height ) with sixteen individual v shaped dispensing units with fourteen dispensing units . the medication dispensing wheel can be custom designed . the number and size of the dispensing units a can be custom designed to fulfill the dispensing needs of healthcare institutions and individual patients . each v shaped dispensing unit of a sixteen unit dispensing wheel ( 12 cm diameter × 1 . 5 or 1 cm in height ) has the following measurements : the sides of each of the v shaped dispensing units are ( approximately 5 . 8 cm . in length , 1 or 1 . 5 cm in height and a width of about 1 cm ) across its rounded outer wall ( circumference ); and a small square vertical shaft through the center of the first or drive dispensing wheel . the base of each dispensing unit is approximately 1 cm . in width . the individual dispensing units for the fourteen unit dispensing wheel will be larger than the dispensing unit for the sixteen unit dispensing wheel . a magnetic probe is located on the top outer wall of the dispensing wheel . it is located at the * proximal or distal wall of the number one dispensing unit of the vertically stacked dispensing wheels . fig2 shows the fixed in place horizontal and sideway u shaped modular dispensing wheel . the modular dispensing wheel houses the medication dispensing wheel fig3 ( a wheel within a wheel ). the top ceiling and bottom dispensing floor 23 of the horizontal u shaped modular dispensing wheel extends out toward the outside wall of the dispenser 1 . the diameter of the top ceiling and bottom floor of the modular wheel is ( approximately 1 cm ) less that the diameter of the medication dispensing wheel . each modular side way or horizontal u shaped dispensing wheel has a cut out v shaped dispensing unit on its top ceiling and bottom floor . the v shaped cut outs of all of the vertically stacked modular dispensing wheels are vertically aligned with one another . the vertical alignment of the v shaped cut out unit of these vertically stacked modular dispensing wheels will form a clear vertical pathway to the medication dispensing draw or the shallow semicircular dispensing cup at the base of the dispenser . when a v shaped dispensing unit of a dispensing wheel , and ( the smaller v shaped medication container 111 within this v shaped dispensing unit ) moves a distance of one preprogrammed dispensing unit and over top of a v shaped cut out on the floor of a vertically stacked modular dispensing wheel , the smaller v shaped medication container will fall out of the v shaped dispensing unit and down a clear pathway to the medication dispensing draw or the slide to the shallow semicircular dispensing cup at the base of the dispenser . the modular dispensing wheels ( not the medication dispensing wheels ) are being held in a specific , fixed , position within the dispenser by two vertical rods 35 attached to the top and center of the inside wall of the dispenser &# 39 ; s top or cover . these two thin vertical rods will pass through two vertical holes in the top and center of each vertically stacked modular dispensing wheel . these two vertical rods are attached to the inside wall of the top half of the dispenser &# 39 ; s housing . the two vertical holes on top of each vertically stacked modular dispensing wheel will be precisely positioned and cut out . the specific positioning of the vertical cut out holes in the center of the stacked modular dispensing wheels will automatically align the vertical v shaped cut out dispensing units on the top and bottom of the modular dispensing wheels directly over top of the medication dispensing draw at the base of the dispenser 1 . the dispenser has an emergency yellow light that flashes when there is a dispenser malfunction . the dispenser 1 has an electric chord receptor . fig1 b displays a microprocessor or watch dog timer battery that will activate the back up batteries when there is a power failure or malfunction . the back up batteries will activate the emergency response phone calls via modem etc . a microchip or the internal microprocessor will automatically and sequentially count each unit of medication dispensed . after the patient takes their medication they will push the flashing red compliance button . when the patient pushes the flashing red compliance button the microprocessor or the sequential counting chip will record the patient &# 39 ; s compliance response . if the patient fails to push the compliance button on two consecutive scheduled dispensing times the microprocessor will signal the modem 67 to make preprogrammed emergency phone calls to family members or a caregiver . there is an emergency red panic button 117 . when the panic button 117 is pushed a signal will be sent directly to the microprocessor . the microprocessor will automatically initiate the pre - programmed emergency phone calls . fig1 shows the two halves of the circular and cylindrical housing of the dispenser 1 . the dispenser has a flat base with an attached rubber mat . the flat base is circular with a diameter of ( approximately 10 cm ). the bottom half of the dispenser &# 39 ; s housing has a u shaped rim on top . a locking mechanism will be located on the inner part of the outer wall of the u shaped rim of the dispenser . the following is an operational description of the preferred embodiment of the dispenser . a lap top computer will program the microprocessor . the computer will be connected to the medication dispenser at a plug in receptor on the lower half of the medication dispenser . the lap top computer will enter preprogrammed dispensing directions into the microprocessor . when the start button 68 is pushed the timed dispensing program of the microprocessor will be activated . a timer or timing mechanism will activate the programmed timing directions of the microprocessor . the microprocessor will coordinate and execute the various operating systems . the timing program of the microprocessor will activate the battery . the battery will activate the stepper motor and its gear shaft . the geared shaft 1 of the stepper motor will turn the interconnecting gear of the first dispensing wheel one programmed dispensing unit at a time . for example , when a preprogrammed dispensing signal activates the steeper motor of a sixteen unit dispensing wheel , it will turn the dispensing wheel twenty two point five degrees or one dispensing unit . when a programmed dispensing signal activates the steeper motor of a fourteen unit dispensing wheel , it will turn the dispensing wheel a distance of twenty five point four degrees or one dispensing unit . when the medication wheel is turned one programmed dispensing unit the medication contained in the first dispensing unit or the triangular dispensing container in the first v shaped dispensing unit of the first dispensing wheel fig3 will be moved one v shaped dispensing unit over top of the v shaped cut out dispensing unit on the first dispensing floor . the triangular medication container in the first dispensing unit will fall through the clear vertical pathway of the vertically stacked modular dispensing wheel system , and into the medication dispensing draw ; or on to the enclosed slide of the shallow semicircular medication cup , directly below and at the base of the dispenser . in the preferred embodiment , as the medication is being dispensed the microprocessor as shown in fig1 b the dispenser 1 will initiate a variety of dispensing signals from a variety of signaling devices located at the bottom half of the dispenser : 1 . ( a ) speaker 44 and voice chip 45 , buzzer 70 , a flashing red light - compliance button 17 and or a signaling device worn by the patient . the signaling process will be persistent and continuous . the voice chip will deliver a dispensing message to the speaker 44 . the message will say “ your medication has been dispensed , please take your medication ; and then push the flashing red compliance button ”. the voice message of the dispenser and the remote signaling device worn by the patient continue for thirty to forty five minutes . the signaling will be repeated every minute for five minutes . then every five minutes for the remaining time for this cycle . when the patient receives the dispensing signals they will go over to their dispenser and open the dispenser &# 39 ; s door , take out the medication draw , consume their medication , put the draw back into the dispenser 1 , close the door , and then push the red flashing compliance button 17 . when the patient pushes the red flashing compliance button the voice chip will say , “ thank you ; now please put the medication draw back into the dispenser , and close the door ”. when the patient pushes the red flash compliance button a signal will be sent to the microprocessor or sequential counting chip . they will keep a running count and record of the number of medication doses dispensed . if the patient fails to respond to the signaling process within forty five minutes , the signaling will stop ; but the timed dispensing process will continue . if the patient fails to push the flashing red compliance button after two consecutive medication deliveries , the sequential counting program of the microprocessor will send a signal to the modem and the programmed emergency telephone calls will be initiated . when a family member receives an emergency response signal they will go over to the patient &# 39 ; s residence and investigate for a possible patient emergency . after attending to the patient the caregiver will go over to the medication dispenser 1 and push the flashing red medication compliance button . when the caregiver pushes this button the emergency response system will be deactivated and then automatically reactivated . if no one responds to the emergency phone calls , and the flashing red compliance button isn &# 39 ; t pushed within thirty to forty five minutes , the microprocessor will signal the modem to call the 911 emergency telephone number . the microprocessor will activate the voice chip and a prerecorded message will be played . the programming of the microprocessor will continue to initiate the programmed dispensing directions until all of the medication filled dispensing units of the first dispensing wheel are dispensed . as the first dispensing wheel is in the process of dispensing its last unit dose of medication , its magnetic probe 49 will pass through the entrapment door 36 of the second dispensing wheel above . as the magnetic probe 49 moves into the entrapment room 36 the entrapment door will snap shut and entrap the magnetic probe 49 . the forward momentum of the first dispensing wheel , and the magnetic attraction of the probe from the top of the first dispensing wheel and the magnetic attraction of the magnetic wall of the entrapment room at the base of the number two dispensing wheel above , will entrap the magnetic probe 49 in the entrapment room 36 . the entrapment of the magnetic probe will interconnect or enjoin the first and second dispensing wheel . the enjoined dispensing wheels will now move as a single and combined dispensing wheel . on the next scheduled dispensing time the enjoined dispensing wheel will be moved forward one dispensing unit by the forward movement of the probe of the first or drive dispensing wheel . the forward movement of the drive or first dispensing wheel and its interconnecting probe is related to the forward movement of the interconnected and geared male shaft of the stepper motor and the female receiving gear of the first or drive dispensing wheel . as they begin to move forward one dispensing unit the thin flexible metallic probe 32 , extending into the vertical groove on the outside wall of the second dispensing wheel , will bend over and release the second dispensing wheel . or , if the probe of a miniature solenoid is holding the second dispensing wheel in place , it will be pulled out of the vertical groove on the outside wall of the second dispensing wheel . when the probe is pulled out of the vertical groove on the second dispensing wheel the single and combined dispensing wheel will move forward one dispensing unit . when they move forward one dispensing unit the v shaped medication container 111 in the first dispensing unit of the second dispensing wheel will move forward and over top of the v shaped cut 112 out dispensing unit on the floor of the second dispensing floor , the v shaped medication container 111 will fall through and down a clear vertical pathway and into a medication dispensing draw at the base of the dispenser directly below ; and or the v shaped medication container 111 will slide down an inclined and diagonal planed floor at the bottom of this vertical pathway , and into the shallow semicircular medication dispensing cup at the base of the dispenser 1 . this programmed dispensing process will continue autonomously and automatically until all of the vertically stacked modular dispensing wheels are dispensed . when the top and last vertically stacked dispensing wheel dispenses all but six of its remaining dispensing units , the programming of the microprocessor will activate a * voice chip . the voice chip will tell the patient t “ your dispenser has only six more doses of medication , please refill your medication dispenser now !”. the patient will either refill the dispenser 1 themselves or have a family member fill it , and or have their pharmacist refill it . a pharmacist &# 39 ; s assistant can make a home visit and refill the dispenser . the design of the integrated modular dispensing wheel will simplify the refilling process . the patient , family member , caregiver and or the pharmacist will unlock the dispenser and lift off the top half of the dispenser &# 39 ; s housing . then they will lift the first integrated modular dispensing wheel system as shown in fig3 out of the dispenser &# 39 ; s housing , turn if upside down , and then align the vertical center hole of the integrated modular wheel with the vertical shaft of a refilling device . the diameter of the base of the refilling device will be slightly smaller than the diameter of the modular dispensing wheel . the height of the base of the refilling device will be high enough for the magnetic probe of the dispensing wheel to clear the dispensing table &# 39 ; s floor . now , the patient will lower the system down on to the floor of the refilling device . the patient will rotate the body of the dispensing system until it is stopped by the smaller raised v shaped dispensing unit on the floor of the loading device . the v shaped dispensing unit of the modular dispensing wheel will interconnect and interlock with the smaller v shaped dispensing unit of the floor of the loading device . the height of this v shaped raised unit will be tall enough to stop the modular dispensing wheel &# 39 ; s housing from moving . the dispensing wheel of the modular dispensing wheel will be free to turn . the patient and or caregiver will be grasp the magnetic probe and turn the dispensing wheel as they refill the medication dispensing wheel . to start loading process the patient and or caregiver will move the probe from the dispensing wheel to the proximal wall of the v shaped cut out of the modular dispensing wheel . then place the first medication filled v shaped medication container 111 into the first dispensing unit of the first dispensing wheel : the morning dose to be dispensed between 8 : 30 to 9 : 30 . the patient will turn the dispensing wheel one v shaped dispensing unit and place the second v shaped container and its prescribed medication mix into the second dispensing unit : the afternoon dose between 1 : 30 and 2 : 30 . the patient will turn the dispensing wheel one v shaped dispensing unit and place the third v shaped medication container and its prescribed medication mix into the third dispensing unit : the evening dose of medication between 5 : 30 and 6 : 30 . the first day &# 39 ; s medication has been loaded into the integrated modular dispensing wheel system . the patient , family member or pharmacist will continue to fill the dispenser one dispensing unit at a time , and one dispensing wheel at a time , and until all of the prescribed doses of medication have been loaded into the dispenser . the unique capability to vertically stack , hold in place , and then to dispense numerous vertically stacked integrated modular dispensing wheels will enable a nearly unlimited supply of prescribed medications to be dispensed for a nearly unlimited period of time . after the dispenser has been refilled the top will put back on and locked . referring now to the computer programs flow chart of the caregiver dual purpose automatic medication dispenser , the programmed delivery sequence is shown . assume that all times and alarms have been initialized . 1 — at the correct dosing times shown on the display the main program commences making various decisions the micro - processor 215 . various testing alarms are tested and set - off if needed acoustic signaling including the human voice 240 . also , the sensors are checked for discrepancies . 2 — if the sound is ignored by the patient minute up to a programmed interval 30 to 60 minutes the volume of the sound is increased every five minutes . 3 — simultaneously , the red flashing compliance button 17 and stepper motor are activated and ready for use . 4 — the microprocessor 215 and / or timing device will signal the steeper motor 15 . to turn the dispensing wheel one dispensing unit and the v shaped medication container 111 will fall into the medication draw or shallow semicircular dispensing cup at the base of the dispenser . 5 . after the v shaped container is automatically dispensed the number and verbal dispensing signaling will commence for the medication pick up . 8 . the automated steeper motor 15 . is de - energized and the cycle is restarted for the next delivery . 9 . if the patient doesn &# 39 ; t push the compliance button after one hour family members or a caregiver can be alerted through the rs - 232 telephone modem 39 . 10 — also , container on the top of the dispenser is a small video camera to view the patient taking their medication . it can be used to assist patient who have difficulty complying with their medication schedule . most of the structures and operations of the second embodiment of the dispenser 1 are the same . the only difference between the first embodiment and the second embodiment as shown in fig8 are the means whereby one vertically stacked dispensing wheel automatically becomes interconnect and interlocked with another vertically stacked dispensing wheel . this single version of the dispenser 1 has two means whereby one vertically stacked dispensing wheel can be automatically interconnected and interlocked with another vertically stacked dispensing wheel either above or below . in the first version , the spring loaded interconnecting probe located on the outside wall at the base of the top or second dispensing wheel will snap down into a vertical interconnecting entrapment hole at the top outside wall of the first dispensing wheel below . in the second version , the spring loaded interconnecting probe located on the top of the outside wall of the first dispensing wheel will pop up into a vertical interconnecting entrapment hole on the bottom outside wall and base of dispensing wheel number two above . the spring loaded probe is housed within a shallow containment hole . the spring is attached to bottom of the shallow containment hole . the probe is protruding out from the top of the containment hole . when a dispensing wheel is place on top , and then the dispenser is close and locked , the spring from the probe will be compressed . the compressed statue of the spring will create the potential energy to snap or propel the attached probe from the top of the first dispensing wheel up and into the entrapment hole at the base of the second dispensing wheel above or the potential energy of the entrapment probe from the base of the second dispensing wheel will pop the spring loaded probe down and into the entrapment hole on the top of the first dispensing wheel below . the probe has a ball bearing 72 that will enable it to turn as it moves through a shallow groove that encircles either the top out side wall at the base of the second dispensing wheel or the shallow groove on the top outside wall of the first dispensing wheel below . the tension on the spring loaded probe will pop the probe into a corresponding vertical entrapment hole as it moves over top of the entrapment hole . there will be a ball bearing 72 at the end of the pop up or pop down spring loaded probe . the ball bearing 72 will enable the probe to move across the surface either the top outer wall or the bottom outer wall of the dispensing wheel that is dispensing the medication . when the dispensing wheel that has just dispensed its last medication filled dispensing unit passes over top of the entrapment hole of the next vertically stacked dispensing wheel either the spring loaded probe at the base of dispensing wheel above will snap down or the spring loaded probe on the top of dispensing wheel number one will pop up and into the dispensing hole . this will automatically interconnected and interlock the two dispensing wheels together . on the next dispensing time the two interconnected and interlocked dispensing wheel will move together as a single and combined dispensing wheel . as they move forward the distance of one preprogrammed dispensing unit the medication contained within the first dispensing unit of the dispensing wheel above will be dispensed . the v shaped medication container 111 will fall through the v shaped cut dispensing unit on the dispensing floor and down a clear vertical pathway to the dispensing draw or shallow semicircular medication cup at the base of the dispenser . from this point forward the static and operational description of the second version is the same as the preferred embodiment . the third embodiment basically involves the same static and operational features and components as the first and second embodiment of the dispenser . the main differences are the components in the upper half of the dispenser are connect to a dispensing rod that suspends down from the center and inside wall of the dispenser &# 39 ; s top , and the first dispensing floor that is connected to the outside of the inside wall of the u shaped top of the bottom half of the dispenser &# 39 ; s housing . the parts right side up dispensing parts attachment floor &# 39 ; s diameter is slightly smaller than the upside down cake pan like first dispensing floor . therefore , the space between the two floors can be adjusted to accommodate the size of the stepper motor . t he dispensing parts that are connected to and or revolve around the dispensing rod are : 1 ) the dispensing floors that are attached to the rod 2 ) the medications wheels that turn on the dispensing floors 3 ) and the thin flexible dispensing rods 35 that hold the dispensing wheels in a fixed and specific position within the dispenser . a cover for the first dispensing wheel is a part of the dispensing rod . the cover is located at the bottom of the dispensing rod and covers the first dispensing wheel . the covers for all of the vertically stacked dispensing wheels are the dispensing floor of the dispensing floor immediately above . there is a cover for the top dispensing wheel . from this point forward the static and operational features and parts are basically the same as the first or second version of the dispenser 1 . there are numerous variations for the physical structure and position for the groove that the magnetic probe passes through . the dispensing wheel has a number of v shaped dispensing units that fan out from its small inner circle and or vertical holes at the center of the dispensing wheel . each of the single v shaped dispensing units fan out from the center of the dispensing wheel . the two walls that fan out from the center of the dispensing wheel form - dispensing unit . a small portion of the base and or top will have a cut out vertical valley or groove . the magnetic probe will move around and through this cut out groove . a cut out groove can be cut through the v shaped walls of the dispensing units concentrically . also , a number of cut out valleys can be concentrically cut out from the center of the dispensing wheel inner to the outer circumference of the dispensing wheel . subsequently , the magnetic probe , entrapment door , and the magnetic wall can be placed in one of these concentric valleys . there is still another new embodiment of this invention . it is a do it yourself and or self - assembly automatic dispenser kit . this do it yourself kit also introduces another new fastener invention . the caregiver automatic medication dispenser is the only single and dual purpose and combined personal portable and homebound - institutional dispensing system is the only single dual purpose single medication dispenser capable of dispensing medication to the broadest - diversified and most comprehensive groups of medical , psychiatric and special needs patients . as a homebound - institutional and bedside - table top dispenser it will dispenses medication to the homebound patient , patients in hospitals , assisted living facilities , nursing homes and in all other kinds of health related facilities . as a personal - portable dispenser it can be inconspicuously and conveniently carried by a patient while they are working , participating in their community , traveling , vacationing , and visiting friends and or family . the dispenser can be made the size of a compact disc player and or smaller . it can also be expanded to any sized desired by the patient and or prescribed by the physician . the dispenser can be easily modified to service the specialized dispensing needs of patients suffering from alcohol and or substance abuse , visual and or hearing impairments , emotional , neurological , and or memory impaired . in addition , the dispenser can be used as the main part of an automated and integrated networking system that interconnects and communicates with the private physician , pharmacist , and patients in the community . it can also be used by the private physicians , institutional physicians , pharmacists , and nurses in hospitals , nursing homes and all other health related facilities . the physician , pharmacist , and nurse will be able to communicate and exchange information related to the dispensing and monitoring needs of their patients . this dispensing and monitoring system will eliminate medication mistakes , cut costs , and increase productivity . by automating the present manual and labor intensive medication dispensing process healthcare providers will be able to successfully manage an historic and precedent setting healthcare crisis that will unfold over the next fifty plus years . for the first time in history the vast majority of the world &# 39 ; s population will be senior citizens that are over the age of sixty five . recent changes in corporate policy and government regulations mandates that this aging workforce will have to work for at least an additional ten plus years . this aging work force will have to work longer and harder ; and therefore will experience a substantial increase in emotional , physical , and economic stress . therefore , workers will have to rely on a substantial and sustained increase use of medication and healthcare services . the caregiver automatic personnel - portable automatic medication dispenser will enable this aging work force to successfully manage their healthcare needs . they will be to carry their personal and portable medication dispenser while they are at work , participating in their community , traveling , vacationing , and visiting their friends and family . the dispenser will actively assist the patient to actively manage their health problems , and illnesses related to the aging process . the dispenser will enable physicians to resolve many of the unresolved medication and medical treatment problems of the past twentieth century . and the caregiver will continue to meet these medical dispensing challenges in this twenty - first century . from the description above , a number of advantages the personal portable and homebound - institutional dispenser becomes evident : ( a ) the automatic medication dispenser and its dispensing system will eliminate medication mistakes made in hospitals , assisted living facilities , nursing homes , alcohol and substance abuse treatment facilities , specialized group homes for exceptional and special needs residents , residential treatment centers , and out patient clinics . it will prevent medication mistakes made by individual patients , family members , and caregivers that fill the medication dispenser . medication mistakes will eventually be eliminated by the use of the dispenser 1 , and its related inventions , and by the “ one and only one pair of professionally trained hands ”; the hands of a professionally trained pharmacist . hospital and other healthcare related facilities can eliminate medication mistakes by having all medications dispensed in a central location within the dispensary . the professionally trained pharmacist would receive the physician &# 39 ; s prescription , select the medications , fill the medication dispensing wheels , lock and label the dispenser and then have a pharmacist assistant deliver the filled dispenser to the patient . the assistant would check the identifying information on the patient &# 39 ; s wrist band with the information on the dispenser . then plug the dispenser in and connect it to a co - axial cable . the programmed dispensers will automatically dispense the patient &# 39 ; s medications on a timely basis . the nurse will be able to monitor and assist the patient with the compliance computer and their personal communication system . a recent article published in the “ the wall street journal , friday , jul . 26 , 2002 ,” by laura landro staff reporter ; reported that the fda held a conference relate to exploring the use of technology to help “ curb medication errors ” and mistakes . and to consider requiring hospitals to affix a bar code to drugs and the patient &# 39 ; s id in order to track prescriptions and dosages . some hospitals and pharmaceutical companies have embraced the concept as a way to prevent potential “ deadly medication mistakes ” that lead to thousands of deaths a year . the institute of medicine said that preventable medical errors cause between 44 , 000 and 98 , 000 deaths a year . jane englebright , a vice president for quality at the federal american hospitals — hac inc ., with over one hundred and eight three hospitals , believes that a more integrated approach is needed . susan delbance of the leapfrog group stated , “ eventually we will see the entire process automated .” the systems that were presented are good at preventing errors in the ordering phase but they can &# 39 ; t control mistakes further along the patient - care chain . the automatic medication dispensing system is the only medication dispensing system that protects the patient throughout the entire patient - care chain . it integrates and safeguards all of the of the separate processes and or steps involved in the patient - care chain for dispensing medication . in addition , there are two related and supportive inventions that will reinforce and strengthen the mistake free operation of the caregiver dispensing system . a combination of these three dispensing and monitoring devices will eliminate medication mistakes . it would eliminate the manual and labor intensive process of dispensing a patient &# 39 ; s medication . ( b ) the dispenser will safely dispense medication to alcohol and substance abuse patients . for the first time , physician &# 39 ; s will be able to safely medicate and treat alcohol and substance abuse patient for the underlying symptoms that initiated and presently maintains their substance abuse . this invention provides one of the missing links required for a real and sustainable “ cure ” for the substance abuse and alcoholism . the dispenser is made out of stainless steel , can be locked , and will be serviced and dispensed by a pharmacist . the pharmacist will keep the key for the dispenser in a locked safe . this invention will provide a real and sustainable “ cure ” for alcohol and substance abuse . according to an article in the newspaper usa today , monday sep . 30 . 2002 three - fourths ( 75 %) of the $ 5 billion a “ year ” spent imprisoning drug convicts goes to confine people who &# 39 ; ve never committed a violent crime . in the past ten years the prison population for substance abusers has surged from 40 , 000 to over 453 , 000 . based on the justice department ( news — web sites ) records and surveys the sentencing project finds that : * 74 % of these prisoners no convictions for violence , * 27 % have been convicted on simple possession charges “ not selling ” or intending to sell , * 58 % have no history of violence or high - levels of drug dealing . non violent offenders are serving 15 years or more . to build one cell a minimum charge of $ 50 , 000 and $ 20 , 000 to house one inmate . new york &# 39 ; s law is equivalent to criminals who commit rape and manslaughter ; 15 years and more . california &# 39 ; s voters approved the release of non - violent offenders into treatment programs . they have already helped thousands and realized a cost savings of over $ 6 . 7 million dollars ; every 1 dollar spent on treatment has saved 7 dollars in reduced crime and health costs . the state of arizona is obtaining similar results . these programs plus “ drug courts ” have cut repeat offenders by 50 to 90 %. public support for these programs is 71 % but vote sensitive politicians have not supported these changes . ( c ) the dispenser can be used as main part of a three part integrated and comprehensive system that will enable the world &# 39 ; s criminal justice systems and correctional facilities to pardon and release over one million alcohol and substance abuse inmates . inmates that successfully complete this in house and short term treatment and evaluation program can earn and an early release and pardon . there are approximately one 450 , 000 alcohol and substance abuse prisoners in the united states . twenty four thousand australians die from alcohol and substance abuse each year . it has become the predominate killer of young englishman . in germany it is the leading cause of fatal motor vehicle accidents . the economic cost to the world &# 39 ; s economy is hundreds of billions of dollars a year . ( d ) the invention can be used safely , and without medication mistakes , automate the present manual , repetitive and labor intensive medication dispensing systems used in hospitals and all other health related facilities . each patient will have their own bedside automatic medication dispenser . the dispenser will be filled by a pharmacist in the dispensary . ( e ) this invention can provide personal and individual patient monitoring services within a healthcare facilities and at home . a miniaturized television camera can be mounted on top of the bed side and or home bound automatic medication dispenser . home bound patients can also be monitored and assisted by the video camera mounted on top of their medication dispenser . ( f ) the dispenser will provide a multi - systems approach to alert the patient , family members and or a caregiver when there is an emergency , dispenser malfunction , and or compliance problem . ( g ) it will provide a fail safe system of last resort . if there is no response from the patient and or family members to an emergency and or malfunction signals the caregiver will automatically call the emergency response system of 911 and deliver a pre - recorded emergency response message . ( h ) the dispenser can send dispensing signal to at patient when they are at a remote location from their dispenser . ( i ) the dispenser will provide a special dispensing signal for sensory impaired patients and for patients with exceptional and special needs : ( j ) the dispenser will provide an automatic medications dispenser kit that can be purchased and easily assembled by the patient . the parts for the dispenser will be able to be easily assembled and automatically snapped into place . although many features , functions , and advantages of the present invention have been described in this specification , together with details of the structure of specific embodiments thereof , the description as a whole is illustrative only , and substitutions may be made in detail , especially in matters of shape , dimension and arrangement of elements within the principles of the invention to the full extent indicated by the broad , general meaning of the terms in which the claims are expressed . therefore , the point and scope of the appended claims should not be limited to the description of the preferred versions contained herein .

this invention is a fault tolerant computer controlled automatic medication dispenser with a unique dispensing system . this dispensing system enables a large number of detachable medication filled dispensing wheels to be vertically stacked and held in a fixed position ; and then be automatically dispensed one dispensing wheel . the patient &# 39 ; s medication can be dispensed for a few days , weeks , and or many months without a refill . these medication filled dispensing wheels are stored and held in a fixed position within the dispenser .

while the ensuing description is primarily and illustratively directed to the use of lcrf as a peptide component in various compositions and formulations of the invention , it will be appreciated that the utility of the invention is not thus limited , but rather extends to any peptide species which are covalently or associatively conjugatable in the manner of the invention , including , but not limited to , the following peptide species : calcitonin , acth , glucagon , somatostain , somatotropin , somatomedin , parathyroid hormone , erythropoietin , hypothalmic releasing factors , prolactin , thyroid stimulating hormone , endorphins , antibodies , hemoglobin , soluble cd - 4 , clotting factors , tissue plasminogen activator , enkephalins , vasopressin , non - naturally occurring opioids , superoxide dismutase , interferon , asparaginase , arginase , arginine deaminease , adenosine deaminase ribonuclease , trypsn , chemotrypsin , and papain , alkaline phosphatase , and other suitable enzymes , hormones , proteins , polypeptides , enzyme - protein conjugates , antibody - hapten conjugates , viral epitopes , etc . the disclosures of the following u . s . patent applications are incorporated herein by reference : ser . nos . 08 / 059 , 701 ; 08 / 276 , 890 ; 08 / 509 , 422 ; 08 / 958 , 383 ; 09 / 134 , 803 ; 09 / 336 , 548 ; 09 / 429 , 798 ; 60 / 153 , 579 ; 60 / 153 , 649 ; 60 / 160 , 412 ; 60 / 161 , 864 ; 60 / 161 , 884 . the disclosure of international patent application no . pct / us99 / 18248 is incorporated herein by reference . one objective of the present invention is to provide suitable polymers for conjugation with peptides so as to obtain the desirable characteristics enumerated above . another objective is to utilize such modified peptides for sustained in vivo delivery of the peptide . yet another objective is to use the technology to deliver peptides orally in their active form . a further objective is to employ associatively conjugated peptides for use in immunoassay , diagnostic , and other non - therapeutic ( e . g ., in vitro ) applications . still another objective of the present invention is to provide stabilizingly conjugated peptide compositions , including covalently bonded compositions variously suitable for in vivo as well as non - in vivo applications , and to alternatively provide non - covalent , associatively conjugated peptide compositions variously suitable for in vivo as well as non - in vivo applications . within the broad scope of the present invention , a single polymer molecule may be employed for conjugation with a plurality of peptide species , and it may also be advantageous in the broad practice of the invention to utilize a variety of polymers as conjugating agents for a given peptide ; combinations of such approaches may also be employed . further , stabilizingly conjugated peptide compositions may find utility in both in vivo as well as non - in vivo applications . additionally , it will be recognized that the conjugating polymer ( s ) may utilize any other groups , moieties , or other conjugated species , as appropriate to the end use application . by way of example , it may be useful in some applications to covalently bond to the polymer a functional moiety imparting uv - degradation resistance , or antioxidation , or other properties or characteristics to the polymer . as a further example , it may be advantageous in some applications to functionalize the polymer to render same reactive or cross - linkable in character , to enhance various properties or characteristics of the overall conjugated material . accordingly , the polymer may contain any functionality , repeating groups , linkages , or other constitutent structures which do not preclude the efficacy of the conjugated composition for its intended purpose . other objectives and advantages of the present invention will be more fully apparent from the ensuing disclosure and appended claims . illustrative polymers that may usefully be employed achieve these desirable characteristics are described herein below in an exemplary reaction scheme . in covalently bonded peptide applications , the polymers may be functionalized and then coupled to free amino acid ( s ) of the peptide ( s ) to form labile bonds which permit retention of activity with the labile bonds intact . removal of the bond by chemical hydrolysis and proteolysis then enhances the peptidal activity . the polymers utilized in the invention may suitably incorporate in their molecules constituents such as edible fatty acids ( lipophilic end ), polyethylene glycol ( water soluble end ), acceptable sugar moieties ( receptor interacting end ), and spacers for peptide attachment . among the polymers of choice , polysorbates are particularly preferred and are chosen to illustrate various embodiments of the invention in the ensuing discussion herein . the scope of this invention is of course not limited to polysorbates , and various other polymers incorporating above - described moieties may usefully be employed in the broad practice of this invention . sometimes it may be desirable to eliminate one of such moieties and to retain others in the polymer structure , without loss of objectives . when it is desirable to do so , the preferred moieties to eliminate without losing the objectives and benefits of the invention are the sugar and / or the spacer moieties . it is preferred to operate with polymers whose molecular weights fall between 100 and 10 , 000 daltons . in the practice of the present invention , polyalkylene glycol residues of c 2 - c 4 alkyl polyalkylene glycols , preferably polyethylene glycol ( peg ), are advantageously incorporated in the polymer systems of interest . the presence of these peg residues will impart hydrophilic properties to the polymer and to the corresponding polymer - peptide conjugates . certain glycolipids are known to stabilize proteins and peptides . the mechanism of this stabilization probably involves association of the glycolipid fatty acid moieties with the hydrophobic domain of the peptide or protein ; aggregation of the protein or peptide is thus prevented . it also is known that aggregated peptides are poorly absorbed in the small intestine compared to native peptides . the invention therefore contemplates polymer - peptides products in which the peptides , e . g ., lcrf , is conjugated with either the hydrophilic or hydrophobic residue of the polymer . the fatty acid portion of the polymer is provided to associate with the hydrophobic domain of the peptide and thus prevent aggregation in solution . the resulting polymer - peptide conjugates thus will be : stabilized ( to chemical and enzymatic hydrolysis ); water - soluble , due to the peg residue ; and , by virtue of the fatty acid - hydrophobic domain interactions , not prone to aggregation . polyalkylene glycol derivatization has a number of advantageous properties in the formulation of polymer - peptide conjugates in the practice of the present invention , as associated with the following properties of polyalkylene glycol derivatives : improvement of aqueous solubility , while at the same time eliciting no antigenic or immunogenic response ; high degrees of biocompatibility ; absence of in vivo biodegradation of the polyalkylene glycol derivatives ; and ease of excretion by living organisms . the polymers employed in the practice of the present invention thus comprise lipophilic and hydrophilic moieties , rendering the resulting polymer - peptide conjugate highly effective ( bioactive ) in oral as well as parenteral and other modes of physiological administration , and highly effective in non - physiological applications . set out below as illustrative examples of polymer - peptide conjugates of the present invention are the formulae of covalently bonded conjugates denoted for ease of subsequent reference as conjugate 1 , conjugate 2 , and conjugate 3 , and specific values of m , n , w , x , and y will be described in the ensuing discussion . conjugate 1 features commercially available polysorbate monooleate at the center of the polymeric system , a sugar derivative used in many pharmaceutical applications . lipophilic and absorption enhancing properties are imparted by the oleic acid chain , while the polyethylene glycol ( peg ) residues provide a hydrophilic ( hydrogen bonding accepting ) environment . lcrf is attached through a carbamate linkage adjacent to the peg region of the polymer . in conjugate 2 the sugar residue is excluded , but lcrf is once again attached to the polymer through a carbamate bond adjacent to the hydrophilic peg region of the polymer . the lipophilic fatty acid region of the polymer is thus some distance from the point of attachment to lcrf . the arrangement described above for conjugate 2 is reversed in the case of conjugate 3 . once more the sugar residue is excluded , but in this structure the lipophilic fatty acid residue is closest to the point of attachment to lcrf and the hydrophilic peg region is distant from the point of attachment , which is again through a carbamate bond . in the general practice of the invention , various methods of coupling the polymers to the peptide are available and are discussed more fully hereinafter . in working with proteins and polypeptides , it should be realized that certain residue groups in the peptide are important in their overall biological integrity . it is important to choose a suitable coupling agent that does not unduly interfere with such residues . in some instances , it may be difficult to avoid coupling and therefore masking the activity of these important residues , but some activity may be traded for increased stability while maintaining the endowed beneficial properties . in in vivo applications , for example , frequency of dosing may thus be reduced , resulting in reduced costs and increased patient compliance . the polymers utilized in protein / peptide conjugation in accordance with the invention are designed to incorporate good physical characteristics that enable them to achieve the desired objectives . absorption enhancers , while enabling penetration of peptides through the cell membrane , do not improve the stability characteristics of the peptides , and in vivo applications may therefore utilize the polymer - peptide conjugates of the invention in formulations devoid of such penetration enhancers . one aspect of the present invention therefore relates to the incorporation of fatty acid derivatives within the polymer , to mimic penetration enhancers . in the covalently conjugated polymer - peptide conjugates of the present invention , the peptide may be covalently attached to the water - soluble polymer by means of a labile chemical bond . this covalent bond between the peptide and the polymer may be cleaved by chemical or enzymatic reaction . the polymer - peptide product retains an acceptable amount of activity ; full activity of the component peptide is realized when the polymer is completely cleaved from the peptide . concurrently , portions of polyethylene glycol are present in the conjugating polymer to endow the polymer - peptide with high aqueous solubility and prolonged blood circulation capability . glycolipids are usefully associated with the polymer in such a way that their fatty acid moieties occupy the hydrophobic domain of the peptide and thus prevent aggregation . aggregation of peptides results in their being poorly absorbed in the small intestine . unaggregated peptides are more easily absorbed by the small intestine . the incorporation of glycolipids into the conjugating polymer thus serves the purposes of improving stability and preventing peptide aggregation after conjugation . the modifications described above confer improved solubility , stability , and membrane affinity properties on the peptide . as a result of these improved characteristics the invention contemplates parenteral and oral delivery of both the active polymer - peptide species and , following hydrolytic cleavage , bioavailability of the peptide per se , in vivo applications . the polymers used in the embodiment described below can be classified as polyethylene glycol modified glycolipids and plyethylene glycol modified fatty acids . among preferred conjugating polymers may be mentioned polysorbates comprising monopalmitate , dipalmitate , tripalmitate , monolaurate , dilaurate , trialaurate , monooleate , dioleate , trioleate , monostearate , distearate , and tristearate . the number average molecular weight of polymer resulting from each combination is preferred to be in the range of from about 500 to about 10 , 000 daltons . alternative polymers of preference for this embodiment are polyethylene glycol ethers or esters of fatty acids , such fatty acids being lauric , palmitic , oleic , and stearic acids , and the polymers ranging from 500 to 10 , 000 daltons in number average molecular weight . it is preferred to have a derivatizable group in the polymer , where such group can be at the end terminating with polyethylene glycol or at the end terminating with fatty acid . the derivatizable group may also be situated within the polymer and thus may serve as a spacer between the peptide and the polymer . several methods of modifying fatty acid sorbitan to achieve the desired polymer will be discussed in further detail with structural illustrations . polysorbates are esters of sorbitols and their anhydrides , which are copolymerized with approximately twenty moles of ethylene oxide for each mole of sorbitol and sorbitol anhydrides . shown below is the structure of a representative polymer . the sum of w , x , y , z is 20 and r 1 , r 2 and r 3 are each independently selected from the group consisting of lauric , oleic , palmitic and stearic acid radicals , or r 1 and r 2 are each hydroxyl while r 3 is lauric , palmitic , oleic or stearic acid radical . these polymers are commercially available and are used in pharmaceutical formulations . where a higher molecular weight polymer is desired , it may be synthesized from glycolipids such as sorbitan monolaurate , sorbitan monooleate , sorbitan monopalmitate or sorbitan monostearate , and an appropriate polyethylene glycol . structures of glycolipids which may be used as starting reagents are depicted below . in the synthesis of glycolipid polymers substituted in three positions with polyethylene glycol , a desired plyethylene glycol having two free hydroxyls at the termini is protected at one terminus with a trityl group in pyridine using one mole of trityl chloride . the remaining free hydroxyl group of the polyethylene glycol is converted to either tosylate or bromide . the desired glycolipid is dissolved in a suitable inert solvent and treated with sodium hydride . the tosylate or bromide of the protected polyethylene glycol is dissolved in inert solvent and added in excess to the solution of glycolipid . the product is treated with a solution of para - toluenesulfonic acid in anhydrous inert solvent at room temperature and purified by column chromatography . the structures of the transformation are depicted below . by adjusting the molar equivalent of reagents and using the appropriate molecular weight range of polyethylene glycol , mono or disubstituted glycolipids of the desired molecular weight range can be obtained by following the above procedures . wherein each n and m may vary independently , and have any suitable value appropriate to the specific peptide being stabilized , e . g ., from 1 to 16 . the sugar portion of the glycolipid described above can be substituted with glycerol or aminoglycerol whose structural formulae are shown below . in this modification , the primary alcohol is first etherified or esterified with a fatty acid moiety such as lauric , oleic , palmitic or stearic ; the amino group is derivatized with fatty acids to form amides or secondary amino groups , as shown below . wherein m may have any suitable value , e . g ., from 10 to 16 . the remaining primary alcohol group is protected with a trityl group while the secondary alcohol group is converted with polyethylene glycol to a desired polymer . usually , the polyethylene glycol bears a leaving group at one terminal and a methoxy group at the other terminal . the polyethylene glycol is dissolved in inert solvent and added to a solution containing glycolipid and sodium hydride . the product is deprotected in para - toluenesulfonic acid at room temperature to give the desired polymer as depicted . sometimes it is desirable to incorporate fatty acid derivatives in different parts of the polyethylene glycol chain to achieve certain physicochemical properties similar to polysorbates that have been substituted with two / three molecules of fatty acids , e . g ., polysorbates trioleate . structures representing the polymers are shown in the reaction scheme below as the open chain of the polysorbate . in the synthesis of polymer a , it is desirable to protect the hydroxyl moieties on the first and second carbon of glycerol , e . g . solketal . the remaining hydroxyl group is converted to the sodium salt in an inert solvent and reacted with halogenated or tosylated polyethylene glycol in which one end of the polyethylene glycol has been protected as an ester . the glycerol protection is removed and the resulting two free hydroxyl groups are converted to the corresponding sodium salts . these salts are reacted in inert solvent with polyethylene glycol which has been partially derivatized with fatty acids . reaction takes place after the free hydroxyl is converted to the tosylate or bromide . polymer g is synthesized in the same manner except that the protected glycol is first reacted with esters of fatty acids which have been halogenated at the terminal carbon of the acid . in the synthesis of polymer c , it is preferable to start with 1 , 3 - dihalo - 2 - propanol . the dihalo compound is dissolved in inert solvent and treated with the sodium salt of two moles of polyethylene glycol which has been previously derivatized with one mole of a fatty acid moiety . the product is purified by chromatography or dialysis . the resulting dry product is treated , in inert solvent , with sodium hydride . the sodium salt thus formed is reacted with a halo derivative of partially protected polyethylene glycol . sometimes it may be desired to omit the sugar portion of the polymer . the resulting polymer still contains a polyethylene glycol fragment . the membrane affinity properties of the fatty acid moiety may be retained by substituting a fatty acid proper with a lipophilic long chain alkane ; biocompatibility is thus preserved . in one instance of this embodiment the polyethylene glycol with two terminal free hydroxyl groups is treated with sodium hydride in inert solvent . one equivalent weight of a primary bromide derivative of a fatty acid - like moiety is added to the polyethylene glycol solvent mixture . the desired product is extracted in inert solvent and purified by column chromatography if necessary . where it is desired to form an ester linkage between the fatty acid and the polyethylene glycol , the acid chloride of the acid is treated with excess of desired polyethylene glycol in suitable inert solvent . the polymer is extracted in inert solvent and further purified by chromatography if necessary . in some modifications of peptides , it is desired to conjugate the fatty acid moiety directly to the peptide . in this case the polymer is synthesized with the derivatizable function placed on the fatty acid moiety . a solution of mono - methoxypolyethylene glycol of appropriate molecular weight in inert solvent is treated with sodium hydride followed by the addition of solution containing the ethyl ester of a fatty acid bearing a leaving group at the terminal carbon of the acid . the product is purified after solvent extraction and if necessary , by column chromatography . the ester protection is removed by treating with dilute acid or base . where it is desired to form a carbamate bond with the polypeptide , the carboxyl or ester is converted to a hydroxyl group by a chemical reduction method known in the art . the functional groups that are used in polypeptide conjugation are usually at a terminal end of the polymer , but in some cases , it is preferred that the functional group is positioned within the polymer . in this situation , the derivatizing groups serve as spacers . in one instance of this embodiment , a fatty acid moiety may be brominated at the carbon alpha to the carboxylic group and the acid moiety is esterified . the experimental procedure for such type of compound is similar to the one outlined above , resulting in the product shown below . when an extended spacer is desired , a polyethylene glycol monoether may be converted to an amino group and treated with succinic anhydride that has been derivatized with a fatty acid moiety . a desired polyethylene glycol bearing primary amine is dissolved in sodium phosphate buffer at ph 8 . 8 and treated with a substituted succinic anhydride fatty acid moiety as shown in the scheme below . the product is isolated by solvent extraction and purified by column chromatography if necessary . it is to be understood that the above reaction schemes are provided for the purposes of illustration only and are not to be limitingly construed in respect of the reactions and structures which may be beneficially utilized in the modification of peptides in the broad practice of the present invention , e . g ., to achieve solubility , stabilization , and cell membrane affinity for parenteral and oral administration . the present invention provides conjugates of biocompatible polymers with as biologically active macromolecules , diagnostic reagents , etc ., which may for example consist of peptides , proteins , enzymes , growth hormones , growth factors and the like . such macromolecular compounds may be built with alpha - amino acids joined in an amide linkage to form peptide oligomers and polymers . depending on the functions of these substances , the peptide components can be proteins , enzymes , growth hormones , etc . for the purpose of brevity , these substances are collectively referred to here as peptides and are designated as pr . in all cases , biologically active peptides contain free amino or carboxyl groups . linkage between the polymer and peptides is generally effected through free amino or carboxyl groups . the peptides chosen for the purposes of illustration herein are of particular interest in the fields of medicine , agriculture , science , and domestic , as well as industrial applications . they may be enzymes utilized in replacement therapy ; hormones for promoting growth in animals , or cell growth in cell culture ; or active proteinaceous substances used in various applications , e . g ., biotechnology and biological and medical diagnostics . among the enzymes that can be mentioned are superoxide dismutase , interferon , asparaginease , glutamase , arginase , arginine deaminase , adenosine deaminase ribonuclease , trypsin , chromotrypsin , and papin . among the peptide hormones that can be mentioned are insulin , calcitonin , acth , glucagon , somatosin , somatropin , somatomedin , parathyroid hormone , erthyropoietin , hypothalamic releasing factors , prolactin , thyroid stimulating hormones , endorphins , enkephalins , and vasopressin . the reaction of the polymer with the peptide to obtain covalently conjugated products is readily carried out . for the purpose of brevity in discussion herein , the polymer is referred to as ( p ). where the polymer contains a hydroxyl group , it is first converted to an active carbonate derivative such as para - nitrophenyl carbonate . the activated derivative then is reacted with the peptide in a short period of time under mild conditions producing carbamate derivatives with preserved biological activity . the above reaction and reagent only serve as illustration and are not exclusive ; other activating reagents resulting in formation of urethane , or other , linkages can be employed . the hydroxyl group can be converted to an amino group using reagents known in art . subsequent coupling with peptides through their carboxyl groups results in amide formation . where the polymer contains a carboxyl group , it can be converted to a mixed anhydride and reacted with the amino group of the peptide to create a conjugate containing an amide bond . in another procedure , the carboxyl group can be treated with water - soluble carbodiimide and reacted with the peptide to produce conjugates containing amide bonds . the activity and stability of the peptide conjugates can be varied in several ways , such as changing the molecular ratios of polymer to peptide and by using a polymer of different molecular size . solubilities of the conjugates can be varied by changing the proportion and size of the polyethylene glycol fragment incorporated in the polymer composition . hydrophilic and hydrophobic characteristics can be balanced by careful combination of fatty acid and polyethylene glycol moieties . set out below are some illustrative modification reactions for polymer - peptide conjugates of the present invention . in the above reaction scheme involving species i , j and k , routes are demonstrated for modifying the hydrophilicity / lipophilicity balance of the conjugating polymer . ester groups in the conjugating polymer are susceptible to hydrolysis by esterases ; the conjugating polymer containing ester groups therefore may be modified to convert the ester groups to ether groups which are more hydrolysis - resistant in character . the reaction scheme involving l and m species illustrates the conversion of hydroxyl groups to carboxylate groups . in this respect , the carboxyl groups will provide carboxylate anion , which is a better stabilizing functionality ( forming ionic coordinated complexes ) than hydroxyl , which does not form such complexes . other suitable anion source functional groups for the formation of coordinate ionic complexes involving the polymer species of the present invention include sulfate and phosphate groups . in general , various techniques may be advantageously employed to improve the stability characteristics of the polymer - peptide conjugates of the present invention , including : the functionalization of the polymer with groups of superior hydrolysis resistance , e . g ., the previously illustrated conversion of ester groups to ether groups ; modifying the lipophilic / hydrophilic balance of the conjugating polymer , as appropriate to the peptide being stabilized by the polymer ; and tailoring the molecular weight of the polymer to the appropriate level for the molecular weight of the peptide being stabilized by the polymer . the unique property of polyalkylene glycol - derived polymers of value for therapeutic applications of the present invention is general biocompatibility . the polymers have various water solubility properties and are not toxic . they are non - antigenic , non - immunogenic and do not interfere with biological activities of enzymes . they have long circulation in the blood and are easily excreted from living organisms . the products of the present invention have been found useful in sustaining the biological activity of peptides and may for example be prepared for therapeutic administration by dissolving in water or acceptable liquid medium . administration is by either the parenteral or oral route . fine colloidal suspensions may be prepared for parenteral administration to produce a depot effect , or by the oral route . in the dry , lyophilized state , the peptide - polymer conjugates of the present invention have good storage stability ; solution formulations of the conjugates of the present invention are likewise characterized by good storage stability . the therapeutic polymer - peptide conjugates of the present invention may be utilized for the prophylaxis or treatment of any condition or disease state for which the peptide constituent is efficacious . in addition , the polymer - peptide conjugates of the present invention may be utilized in diagnosis of constituents , conditions , or disease states in biological systems or specimens , as well as for diagnosis purposes in non - physiological systems . further , the polymer - peptide conjugates of the invention may have application in prophylaxis or treatment of condition ( s ) or disease state ( s ) in plant systems . by way of example , the peptide component of the conjugate may have insecticidal , herbicidal , fungicidal , and / or pesticidal efficacy amenable to usage in various plant systems . still further , the peptide component of the conjugates of the present invention may be antibodies or alteratively antigenic in character , for diagnostic , immunological , and / or assay purposes . in therapeutic usage , the present invention contemplates a method of treating an animal subject having or latently susceptible to such condition ( s ) or disease state ( s ) and in need of such treatment , comprising administering to such animal an effective amount of a polymer - peptide conjugate of the present invention which is therapeutically effective for said condition or disease state . subjects to be treated by the polymer - peptide conjugates of the present invention include both human and non - human animal ( e . g ., bird , dog , cat , cow , horse ) subjects , and preferably are mammalian subjects , and most preferably human subjects . depending on the specific condition or disease state to be combatted , animal subjects may be administered polymer - peptide conjugates of the present invention at any suitable therapeutically effective and safe dosage , as may readily be determined within the skill of the art , and without undue experimentation . in general , suitable doses of the formula ( 1 ) compounds for achievement of therapeutic benefit , will be in the range of 1 microgram ( μg ) to 100 milligrams ( mg ) per kilogram body weight of the recipient per day , preferably in the range of 10 μg to 50 mg per kilogram body weight per day and most preferably in the range of 10 μg to 50 mg per kilogram body weight per day . the desired dose is preferably presented as two , three , four , five , six , or more sub - doses administered at appropriate intervals throughout the day . these sub - doses may be administered in unit dosage forms , for example , containing from 10 μg to 1000 mg , preferably from 50 μg to 500 mg , and most preferably from 50 μg to 250 mg of active ingredient per unit dosage form . alternatively , if the condition of the recipient so requires , the doses may be administered as a continuous infusion . the mode of administration and dosage forms will of course affect the therapeutic amounts of the compounds which are desirable and efficacious for the given treatment application . for example , orally administered dosages are typically at least twice , e . g ., 2 - 10 times , the dosage levels used in parenteral administration methods , for the same active ingredient . the polymer - peptide conjugates of the invention may be administered per se as well as in the form of pharmaceutically acceptable esters , salts , and other physiologically functional derivatives thereof . the present invention also contemplates pharmaceutical formulations , both for veterinary and for human medical use , which comprise as the active agent one or more polymer - peptide conjugate ( s ) of the invention . in such pharmaceutical and medicament formulations , the active agent preferably is utilized together with one or more pharmaceutically acceptable carrier ( s ) therefor and optionally any other therapeutic ingredients . the carrier ( s ) must be pharmaceutically acceptable in the sense of being compatible with the other ingredients of the formulation and not unduly deleterious to the recipient thereof . the active agent is provided in an amount effective to achieve the desired pharmacological effect , as described above , and in a quantity appropriate to achieve the desired daily dose . the formulations include those suitable for parenteral as well as non - parenteral administration , and specific administration modalities include oral , rectal , buccal , topical , nasal , ophthalmic , subcutaneous , intramuscular , intravenous , transdermal , intrathecal , intra - articular , intra - arterial , sub - arachnoid , bronchial , lymphatic , vaginal , and intra - uterine administration . formulations suitable for oral and parenteral administration are preferred . when the active agent is utilized in a formulation comprising a liquid solution , the formulation advantageously may be administered orally or parenterally . when the active agent is employed in a liquid suspension formulation or as a powder in a biocompatible carrier formulation , the formulation may be advantageously administered orally , rectally , or bronchially . when the active agent is utilized directly in the form of a powdered solid , the active agent may advantageously be administered orally . alternatively , it may be administered bronchially , via nebulization of the powder in a carrier gas , to form a gaseous dispersion of the powder which is inspired by the patient from a breathing circuit comprising a suitable nebulizer device . the formulations comprising the active agent of the present invention may conveniently be presented in unit dosage forms and may be prepared by any of the methods well known in the art of pharmacy . such methods generally include the step of bringing the active compound ( s ) into association with a carrier which constitutes one or more accessory ingredients . typically , the formulations are prepared by uniformly and intimately bringing the active compound ( s ) into association with a liquid carrier , a finely divided solid carrier , or both , and then , if necessary , shaping the product into dosage forms of the desired formulation . formulations of the present invention suitable for oral administration may be presented as discrete units such as capsules , cachets , tablets , or lozenges , each containing a predetermined amount of the active ingredient as a powder or granules ; or a suspension in an aqueous liquor or a non - aqueous liquid , such as a syrup , an elixer , an emulsion , or a draught . a tablet may be made by compression or molding , optionally with one or more accessory ingredients . compressed tablets may be prepared by compressing in a suitable machine , with the active compound being in a free - flowing form such as a powder or granules which optionally is mixed with a binder , disintegrant , lubricant , inert diluent , surface active agent , or discharging agent . molded tablets comprises of a mixture of the powdered active compound with a suitable carrier may be made by molding in a suitable machine . a syrup may be made by adding the active compound to a concentrated aqueous solution of a sugar , for example sucrose , to which may also be added any accessory ingredient ( s ). such accessory ingredient ( s ) may include flavorings , suitable preservative , agents to retard crystallization of the sugar , and agents to increase the solubility of any other ingredient , such as a polyhydroxy alcohol , for example glycerol or sorbitol . formulations suitable for parenteral administration conveniently comprise a sterile aqueous preparation of the active compound , which preferably is isotonic with the blood of the recipient ( e . g ., physiological saline solution ). such formulations may include suspending agents and thickening agents or other microparticulate systems which are designed to target the compound to blood components or one or more organs . the formulations may be presented in unit - dose or multi - dose form . nasal spray formulations comprise purified aqueous solutions of the active compounds with preservative agents and isotonic agents . such formulations are preferably adjusted to a ph and isotonic state compatible with the nasal mucus membranes . formulations for rectal administration may be presented as a suppository with a suitable carrier such as cocoa butter , hydrogenated fats , or hydrogenated fatty carboxylic acid . ophthalmic formulations are prepared by a similar method to the nasal spray , except that the ph and isotonic factors are preferably adjusted to match that of the eye . topical formulations comprise the active compound dissolved or suspended in one or more media , such as mineral oil , petroleum , polyhydroxy alcohols , or other bases used for topical pharmaceutical formulations . in addition to the aforementioned ingredients , the formulations of this invention may further include one or more accessory ingredient ( s ) selected from diluents , buffers , flavoring agents , disintegrants , surface active agents , thickeners , lubricants , preservatives ( including antioxidants ), and the like . in non - therapeutic applications of the present invention , the polymer - peptide conjugate may utilize a covalently bonded or alternatively non - covalent bonding relation between the peptide and polymer components . in addition , associatively related peptide and polymer components may be utilized in administration of therapeutic peptide agents , by appropriate administration methods such as those illustratively described hereinabove in connection with illustratively discussion of covalently bonded polymer - peptide conjugates of the invention . in such non - therapeutic , associatively related peptide - polymer compositions , the peptide and polymer components may be initially formulated together to provide an enhanced stability and degradation resistance , alternatively , these components may for example be separate parts of a multipart composition which is mixed at time of use , and which in the absence of associative bonding between the polymer and peptide in the resulting mixture would be susceptible to quick decay or other degradative modality . regardless of the form of the associatively related peptide and polymer composition , the present invention contemplates a relational association which enhances some characteristic or aspect of the peptide or otherwise enhances the utility of same , relatively to the peptide component in the absence of such associative polymer . accordingly , the present invention contemplates the provision of suitable polymers for in vitro stabilization of peptides in solution , as a preferred illustrative application of non - therapeutic application . the polymers may be employed for example to increase the thermal stability and enzymic degradation resistance of the peptide . enhancement of the thermal stability characteristic of the peptide via conjugation in the manner of the present invention provides a means of improving shelf life , room temperature stability , and robustness of diagnostic and research reagents and kits , e . g ., immunoassay kits . by way of specific example , alkaline phosphatase may be covalently or associatively coupled to a suitable polymer in accordance with the invention , to impart stability to such phosphatase when used as a reagent in kits for colorimetric detection of antibody or antigen in biological fluids . the following examples are provided to illustrate the present invention , and should not be construed as limiting thereof . lcrf - amphiphilic polymer conjugate can be synthesized and tested for cck - releasing activity . the lcrf conjugate can then be evaluated for resistance to proteolysis . physiological and behavioral effects can be confirmed by in vivo animal studies . by using amphiphilic oligomers or polymers of different size and chemical composition , the peptide conjugate absorption and partitioning properties can be altered . it is preferred that the polymers that will be coupled to the lcrf peptide must not interfere with receptor binding . the precise nature of the interaction between lcrf and its receptor is not known , but two observations concerning the interaction have been made : residues 11 - 25 are crucial for the interaction , and cleavage between residues 19 and 20 destroys binding activity . therefore , we will use a hydrolyzable linker at k19 to protect the peptide from trypsin proteolysis . the conjugates of the invention have two components ( peg and alkyl chain ) that will endow the lcrf with two useful properties . first , using a larger , branched oligomer at the n - terminus prevents uptake into the bloodstream from the gut . we will add a 5 - 10 kda oligomer to the n - terminus for this purpose , since molecules with a molecular weight of greater that 4 kda do not cross the gut wall into the bloodstream , but are retained in the lumen . ( parlesak , a ., bode , j . c ., bode , c . “ parallel determination of gut permeability in man with m ( r ) 400 , m ( r ) 1500 , m ( r ) 4000 and m ( r ) 10 , 000 polyethylene glycol ,” eur . j . clin . chem . & amp ; clin . biochem ., 32 : 813 - 820 ( 1994 ) ( the disclosure of which is incorporated herein in its entirety )). second , the hydrophobic alkyl chain will be able to integrate into cell membranes of the gut epithelium , bringing the peptide in close proximity to its target receptor on the epithelial cell surface . it is preferable to attach the peg / alkyl conjugate at the n - terminus , far from residues implicated in receptor binding . the first 35 residues of lcrf iii can be synthesized by solid phase methods and obtained from commercial suppliers . the lcrf conjugation techniques will follow three basic designs , summarized in fig2 . lcrf contains two reactive amino groups that can be used for linking the conjugate — the amino terminus and a lysine sidechain . a first conjugate ( conjugate 1 ) can utilize a branched oligomer having a total average molecular weight of 4 - 10 kda attached to the n - terminus of lcrf using a non - hydrolyzable linker . there are three key features of this conjugate . first , the oligomers at the n - terminus are positioned distal to the known receptor - binding domain of lcrf and are thus unlikely to impair its biological potency . second , the branched oligomer on the n - terminus will provide steric hindrance to aminopeptidases that would otherwise digest the peptide . third , the branched oligomers provide both extreme water solubility and greatly increased size of the lcrf conjugate , which prevents passage of the peptide through the epithelial wall of the small intestine . conjugate 2 can utilize the n - terminal conjugate described for conjugate 1 and a second , linear conjugate attached to the epsilon amino group of k19 . this linear oligomer can be attached with a hydrolyzable bond so that , over time , the oligomer will be hydrolyzed off to permit the lcrf to bind its receptor . k19 is in the approximate center of the putative receptor - binding sequence . the key features of conjugate 2 , in addition to those described for conjugate 1 , are the addition of a hydrolyzable oligomer at k19 that will protect against trypsin hydrolysis . second , the hydrolyzable linkage of the oligomer should enable appropriate receptor binding . third , the slow hydrolysis of the oligomer at k19 ( expected t ½ of 30 - 60 min ) may provide an extended time of action of the lcrf . design 3 will have a conjugate added at the c - terminus , n - terminus , and at k19 . the c - terminal residue ( tyrosine ) is changed to lysine , thus providing a third site for conjugation . this mutation is not expected to alter receptor binding , as the binding domain is at least 10 residues from residue 35 . the balance of amphiphilicity is achieved using three linear polymers instead of a branched oligomer . the addition of a hydrolyzable oligomer at the c - terminus will provide resistance to degradation by carboxypeptidases . the removal of all the oligomers by hydrolysis will regenerate the active lcrf for full biological activity . hydrolysis ( expected t ½ of 30 - 60 min ) of the oligomers may provide extended action of the lcrf . the synthetic chemistry for lcrf conjugate synthesis is shown in fig3 . oligomeric carboxylic alkanols are activated with bromine and esterified . oligomeric peg is then coupled to the activated alkane oligomers . coupling of the peg / alkane carboxylic acid to the free amino group of the peptide , is achieved with n - hydroxysuccinamide in aqueous solution at a ph where the amino group is nucleophilic . previously synthesized and purified oligomers are activated and coupled to lcrf in variable reaction conditions that permit the attachment of oligomers at certain sites ( n - terminus , c - terminus or k19 ). a sequence of conjugation reactions and product purifications can also be used to achieve specific conjugation patterns . selectivity of the n - terminal amino group over the lysine side chain will be achieved by choosing the ph of the reaction medium . coupling to the n - terminus ( pka ˜ 8 ) is carried out a ph ˜ 9 where the epsilon amino group ( pka ˜ 10 . 6 ) is still protonated . by varying the relative length of the alkane ( hydrophobic ) and peg ( hydrophilic ) components , the amphiphilicity and solution structure of the conjugate can be optimized . the reaction mixture is purified on a preparative hplc column ( c - 18 ) with a solvent gradient system made of isopropanol / water ( 0 . 1 % trifluoroacetic acid ). the solvent is evaporated under reduced pressure and temperature below 20 ° c . to give dry products . purity of the product is analyzed by reverse phase hplc and mass spectrometry . cell - based assays provide a rapid means of confirming the biological activity ( e . g ., the ability of the conjugates to elicit cck release from cck - releasing cells ) of the lcrf conjugates . cell based assays can be used to compare the effect of treatment with out conjugates to treatment with vehicle . native lcrf elicits about a 300 % increase in cck secretion . our objective is to elicit at least a 200 % increase in cck secretion with our conjugates . six assays per experiment are expected to provide statistically significant results . native cck cells can be prepared as follows : intestinal mucosal cells are prepared from 200 - 225 g male and female sprague - dawley rats . after sacrifice , the proximal 10 cm of small intestine , beginning 2 cm distal to the pylorus , are quickly removed and immediately placed in saline and washed . the intestine is cut into short lengths , everted , and placed in phosphate buffered saline ( pbs ). the mucosal surface is rinsed twice with pbs and placed in trypsin - free dissociation media at 37 ° c . with gentle agitation for 2 minutes . the solution is removed and replaced with fresh dissociation media and incubated for 10 more minutes with gentle agitation . the remaining suspension is filtered ( 450 μm ) and the effluent centrifuged ( 1000 rpm , 3 minutes ). the pellet is resuspended in hank &# 39 ; s balanced salt solution with hepes ( 10 mm ; ph 7 . 4 )( hhbss ) and centrifuged as above . the pellet is resuspended in 5 ml hhbss and divided into aliquots for testing . activity of conjugates can be confirmed as follows : cck cells are incubated with test compounds ( or vehicle ) for between 5 and 40 minutes . the incubation is stopped by placing the cells in ice , centrifuging the cells , and removing supernatant . for conjugates containing hydrolyzable linkers , incubations will be stopped at 5 , 10 , 15 , 20 , 30 and 40 minutes . for conjugates without a hydrolyzable linker , only one time point ( 15 minutes ) need be used . supernatant is used for the ria measurement of cck described below . 50 μl of the supernatant is assayed by hplc and maldi - tof mass spectrometry to measure the amounts of lcrf conjugates remaining . a radioimmunoassay ( ria ) can be used for measuring cck secretion . ( mangel , a . w ., prpic , v ., wong , h ., et al . “ phenylalanine - stimulated secretion of cholecystokinin is calcium dependent ,” a . j . physiol ., 268 : g90 - 94 ( 1995 ) ( the disclosure of which is incorporated herein in its entirety )). secretion is measured from cck - releasing cells plated in 24 - well microtitre plates . cells are incubated at 37 ° c . and washed with hhbss containing hepes ( 10 mm , ph 7 . 4 ). 0 . 5 ml of buffer is added with or without test agents to cells for times ranging from 5 to 40 minutes . 350 μl are removed , centrifuged and placed on ice or frozen . 300 μl of the sample will be used for the ria . the ria is performed in pbs containing hepes ( 10 mm , ph 7 . 5 ), 0 . 1 % gamma globulin , with 0 . 01 % nan 3 . 50 μl of sample are added to 200 μl of the ria buffer and 100 μl of a 1 : 80 , 000 dilution of a rabbit cck antibody ( oal - 656 ). 100 μl of 125 i - cck - 8 ( 3 , 000 - 4 , 000 cpm ) are then added to the tubes at 4 ° c . for 12 hours . samples are treated with goat anti - rabbit igg sepharose cl4b beads for one hour with gentle agitation . the sepharose beads are then pelleted by brief centrifugation and the pellet is aspirated . the pellet is re - suspended in 0 . 5 ml of hepes buffered saline , and the beads are pelleted once again . then the beads are removed and washed , and the pellet is counted on a gamma counter for 5 minutes . unconjugated lcrf causes about a 300 % increase in cck secretion from native cck and stc - 1 cells , and will be used as a positive control for cell assays . in the case of test compounds with hydrolyzable conjugates , cck release ( ria ) can be correlated with conjugate hydrolysis ( hplc - ms ). the precise nature of the conjugate can be optimized to provide desired properties . the n - and c - terminal conjugation approach will be tested to see whether n - or c - terminal conjugation , or both , provides the best protection and biological activity . when lcrf is infused into the duodenum of rats , a biphasic dose - response of curve of pancreatic protein output is observed , with higher doses of lcrf leading to decreased pancreatic protein output . suitable conjugate concentrations can be determined by those of skill in the art in view of the instant disclosure and may range from 1 to 1000 nm . cck secretion is thought to be regulated by negative feedback inhibition . lcrf is produced constitutively in the duodenum in rats , and in response to nutrients in humans . when food is absent , lcrf is degraded by proteases in the duodenum . since duodenal infusion of trypsin inhibitors is sufficient to cause an increase in cck release in rats , we propose that protection from trypsin cleavage will be sufficient to protect the lcrf conjugation from proteolytic digestion . ( green , g . m ., taguchi , s ., friestman , j ., chey , w . y ., liddle , r . a . “ plasma secretin , cck , and pancreatic secretion in response to dietary fat in the rat ,” am . j . physiol ., 256 : g1016 - 1021 ( 1989 )). we have used our conjugation technique successfully to protect calcitonin and insulin from proteolysis . the stability of conjugated lcrf in intestinal environments can be determined by examining the stability of the peptides to the proteolytic enzymes trypsin , pancreatic elastase , and chymotrypsin over 40 minutes , a typical gut transition time . conjugated lcrf solutions are incubated at 37 ° c . ( 0 . 1 % tween 20 [ w / v ], 10 mm nahpo 4 , ph 7 . 4 ) and proteases are added . tween ( 0 . 1 %) will be added to solubilize the peptides if required . the proteolysis is stopped by adjusting ph to 2 - 3 . the resultant samples are separated by hplc using a 5 μm , c - 18 column ; and eluted for 25 minutes at 0 . 5 ml / min with a linear gradient of 90 % h 2 o / 0 . 1 % trifluoroacetic acid and 10 % 2 - propanol increasing to 60 % 2 - propanol . the stability of conjugated lcrf in stomach can be determined by examining the stability of the peptides to pepsin . pepsin degradation of conjugated lcrf is determined in simulated gastric fluid ( 33 mm nacl , ph 1 . 2 ). peptide solutions are incubated at 37 ° c . and pepsin is added . proteolysis is stopped by raising ph to 7 . 0 - 7 . 5 . hplc can be used to monitor the proteolysis . area under absorbance peaks ( 280 nm ) is integrated to follow the rate of proteolysis over time . decrease in the integrated area of the peak arising from the uncleaved lcrf conjugate will be used to monitor the rate of hydrolysis . hplc separation will be done as described above in specific aim 1 for conjugated lcrf purification . chymotryptic cleavage sites exists at residues y17 and y20 . if chymotrypsin rapidly cleaves the peptide , we will add a protecting peg group to the tyrosine hydroxyl group with a linkage that slowly hydrolyses at ph 7 . 4 . elastase cleavage sites exist at residues 5 , 10 , 29 , 30 and 31 . these residues are outside the region ( 11 - 25 ) identified as crucial for receptor binding . if required , protection from gastric fluid will be provided by enteric coating , a well - established technology in the pharmaceutical industry . in a preferred aspect of the invention , the conjugates provide an increase over basal secretion of at least 200 % in cck release upon treatment with conjugated lcrf , as measured by ria . native lcrf causes about a 300 % increase in cck secretion from native cck cells and will be used as a positive control for these studies . moreover , it is preferred that the conjugates experience less than 70 % proteolysis of the lcrf conjugate , upon exposure to serine proteases ( ph 7 . 4 ) for 40 minutes . it is also preferred that the conjugates experience less than 10 % proteolysis of the enteric - coated lcrf conjugate , upon exposure to simulated gastric fluid for 40 minutes . those of skill in the art can , with the aid of the present disclosure , confirm the physiological and behavioral consequences related to feeding and obesity in animal models and human subjects . rat intestine is used as the source of tissue for purification of mucosal cck cells . rats are sacrificed for the sole purpose of collecting intestinal tissue . following sacrifice , the intestine is surgically removed and washed and intestinal cells are prepared by collagenase and edta dispersion . male and female sprague - dawley rats , 2 . 5 - 3 months old weighing 250 - 300 g will be the source of the cck cells . approximately 48 rats will be required for the proposed study to yield meaningful results . considerable work has been done on the regulation of cck secretion in rats . each rat should provide enough cck cells for one experiment . rats are sacrificed for the collection of intestinal tissue . the method of euthanasia is preferably co 2 narcosis , for which rats are placed into an air - tight cage containing co 2 . this method is consistent with the recommendations of the panel on euthanasia of the american veterinary medical association . ser thr phe trp ala tyr gln pro asp gly asp asn asp pro thr asp

proteins and / or peptides , such as luminal cholecystokinin releasing factor , are conjugated with amphiphilic oligomers and polymers . such conjugates may modulate the pharmacokinetic profile and / or peptides ; thereby improving their clinical utility . such conjugates may also stabilize and deliver the proteins and / or peptides , such as lcrf , to receptors in the gut without absorption into the bloodstream .

as used herein ‘ fixedly attached ’ refers to permanent attachment of one object to another . objects may be fixedly attached by means of glue , thread , staples , rivet fasteners , and other fastening means which permanently attach one object to another . as used herein ‘ removably attached ’ refers to temporary attachment of one object to another . removable attachment may be achieved through the use of button type fasteners , snap fasteners , hook and loop type fasteners ( such as velcro ®), nut and bolt fasteners , pin and clip fasteners , and other fastening means which temporarily attach one object to another . as used herein ‘ height ’ or ‘ ornament height ’ or ‘ ornamental height ’ refers to the height of an ornament . the body of a necktie is typically two dimensional defining a plane which , when the necktie is worn , is substantially parallel to the chest of the wearer . the ‘ height ’ or ‘ ornament height ’ or ‘ ornamental height ’ is the maximum perpendicular distance from the front surface of the body of the necktie to the most distant portion of the ornament exterior . as used herein ‘ front surface ’ refers to the surface of the body of a necktie that faces away from the body of the wearer . the ‘ front surface ’ is the necktie surface that the wearer displays to viewers . as used herein ‘ substantially three - dimensional ’ refers to objects , such as ornaments , which possess a height which is substantially greater than the thickness of the necktie . embodiments of the invention have an ornament height of at least one centimeter . preferably the ornament height is between one centimeter and ten centimeters . most preferably the ornament height is between one centimeter and five centimeters . embodiments of the invention will now be described with reference to the drawings . the specific embodiments described herein exemplify , but do not limit , the invention . as will be readily apparent to those skilled in the art other specific embodiments of the invention may be readily envisioned . embodiments of the invention are neckties comprising an upper portion configured to attach the necktie to a wearer , a body portion configured to hang vertically downward from the upper portion and at least one ornament , which imparts a substantially three - dimensional appearance to the necktie , attached to the body portion of the necktie . an embodiment of the invention , a golf ball necktie , is shown in fig1 . comprising the necktie are and upper portion ( not shown ), the tie body ( 1 ) and golf ball ornament ( 2 ). the upper portion may comprise a length of fabric or other material comprising the body of the tie , as in a four - in - hand tie , or the upper portion may comprise a decorative knot to which a clip ( fig4 ) or strap ( s ) ( fig5 ) is attached . the clip or strap ( s ) may be used to attach the necktie to the wearer , typically about the wearer &# 39 ; s neck or about the collar of the wearer &# 39 ; s shirt . the strap ( s ) may be secured to one another by any convenient means such as button and buttonhole , snaps , hook and eye fastener , hook and loop fasteners ( velcro ®), by knotting the straps together , or other conventional means . the golf - ball tie comprises an ornament that resembles a golf ball and has a height that is substantially greater than the thickness of the necktie ( fig2 ) thereby imparting a substantially three - dimensional appearance to the necktie . the surface of the tie body ( 1 ) may optionally be decorated . shown in fig1 is an optional decoration displaying a golf club ( putter ), golf cup and golf flag as might be seen on a golf putting green . the optional decorations may be painted , or dyed , or otherwise applied to the surface of the necktie , or the decorations may be formed from fabric patterns , or they may be formed through embroidery , or the optional decorations may comprise additional ornaments , such as conventional ornaments which do not impart a three - dimensional appearance to the necktie . an alternative embodiment of the invention is shown in fig3 . in this embodiment the ornament resembling the golf ball is only a partial sphere , instead of a complete sphere . the height of the ornament in fig3 is great enough to impart a substantially three - dimensional appearance to the necktie . an alternative embodiment of the invention is a necktie comprising an upper portion configured to attach the tie to a wearer , a body portion configured to hang vertically downward from the upper portion and at least two ornaments which impart a substantially three - dimensional appearance attached to the body portion of the necktie . in the case of the golf ball tie the second ornament may resemble a golf flag , the flag also imparting a substantially three - dimensional appearance to the necktie . other embodiments of the invention include neckties comprising ornaments resembling such things as trees , animals , automobiles , trucks , trains , machinery , such as construction machinery , farm machinery , or mining machinery , boats , aircraft , political mascots , buildings , bridges , mountains , famous landmarks , architectural landmarks , scenic landmarks , balls , ribbons , such as yellow ribbons for remembrance , planets , sports mascots , fruit , logos , or flowers . the preceding list is not meant to be exhaustive . other possible ornaments falling within the scope of the invention will be evident to those of ordinary skill in the art . the body of the necktie may comprise fabric , plastic , wood , metal , or a combination thereof . most preferably the body of the necktie is comprised of fabric , such as wool , cotton , silk , nylon , rayon , or other fabrics or blends of fabrics . ornaments may be comprised of fabric , plastic , wood , leather , rubber , metal , or a combination thereof . a fabric ornament may comprise an outer fabric surface and an interior fill material such as cotton , wool , leather , rubber , cloth , styrofoam , or other filler material to fill the hollow interior of a fabric ornament . ornaments made of wood , plastic , rubber , leather , or metal may be solid or hollow . the surface of the ornaments may be decorated . for example , the surface of an ornament may be decorated so that the ornament resembles a ball such as a football , golf ball , basketball , baseball , soccer ball , volley ball , tennis ball or other ball . the ornaments may comprise miniature versions of the balls that they resemble , comprising not only the shape and surface , but also the materials used in the manufacture of the full - sized counter parts . an ornament of the invention may be shaped and / or decorated to resemble a hockey puck , an animal or a corporate logo . embodiments of the invention may optionally comprise a second ornament imparting a substantially three - dimensional appearance to the necktie . for example , a second ornament may resemble a basketball hoop , a volleyball net , a baseball backstop , a hockey net , a football goalpost , a soccer net , or a golf flag . the ornaments may be fixedly attached to the body of the necktie by conventional means such as sewing , riveting , gluing , stapling , or other means of fixedly attaching the ornament to the body of the necktie . the ornaments may be removably attached to the body of the necktie by conventional means such as snap fasteners , hook and loop fasteners ( such as velcro ®), pin and clip fasteners , nut and bolt fasteners , buttonhole - button type fasteners , or other conventional fastening means . the base of the ornament may comprise the button body of a button - type fastener and the body of the necktie may comprise a buttonhole into which the ornament button body may fit . neckties of the invention may optionally comprise a pocket , or multiple pockets , located on front surface of the necktie . such pockets may be used to removably attach ornaments to a necktie of the invention . for example , a wearer may wish to display an ornament resembling a flower , such as a rose . the wearer would insert the stem of the floral ornament into a pocket on the front surface of a necktie of the invention . the floral ornament would then be prominently displayed for others to view . multiple three dimensional ornaments could be inserted into a plurality of pockets to create a bouquet effect . the body of the necktie may optionally comprise a rigid or semi - rigid reinforcing member , such as wood , plastic , metal , or cardboard which imparts stiffness to the necktie body . the rigid or semi rigid reinforcing member is covered by the material , such as fabric , comprising the body of the necktie . the rigid or semi rigid reinforcing member will therefore add stiffness to the necktie while remaining unseen by people looking at the necktie body . adding rigid or semi - rigid reinforcing member to the body of the necktie may prevent the necktie from folding due to the weight of an ornament ( s ), light system , sound system or motion system . neckties of the invention may optionally comprise a light system . such a light system comprises a battery , switch , incandescent light bulbs or light emitting diodes ( led ), and optional circuitry for controlling the light bulbs or leds . the elements comprising the light system are electrically connected . u . s . pat . nos . 6 , 753 , 068 , 6 , 336 , 730 , 5 , 493 , 731 , 5 , 836 , 670 , and 4 , 283 , 797 describe light systems that may be adapted for use in neckties of the invention . light systems may be used to spell out a message , highlight a portion of a design , provide supplementary lighting for the wearer of the necktie , and draw attention to the necktie wearer . a light system may be attached directly to the body of a necktie of the invention or the light system may be attached to a reinforcing member within the body of the necktie , or a combination of both methods of attachment may be used . neckties of the invention may optionally comprise a sound system . such a sound system may be used to produce sounds such as chants , songs , greetings , spoken messages , or other sounds . a sound system for use with neckties of the invention may comprise a battery , a switch , sound production circuitry , and a sound producing element , such as a piezoelectric element . the elements of the sound system are electrically connected . u . s . pat . no . 5 , 761 , 836 , 5 , 275 , 285 , 5 , 245 , 171 , and 5 , 063 , 698 describe sound systems that may be adapted for use with a necktie of the invention . a sound system may be placed within the body of a necktie of the invention , between the front and back surfaces . the sound system may be attached directly to the fabric or other material comprising the body of the tie , or the sound system may be attached to a reinforcing member comprising the interior of the necktie . the sound system switch is located on the rear surface of the necktie so as to be hidden . the switch is preferably a push - button type switch which , when activated , initiates the playback of a short sound sequence , such as a song , greeting , chant , spoken message , or other sound . neckties of the invention may optionally comprise a motion system . a motion system may be powered electrically , for example with a battery , or mechanically , for example with a wind up spring . a electrically powered motion system may comprise a battery , switch , motor , and optional control circuitry . the elements comprising the motion system are electrically connected . a mechanically powered motion system may comprise a miniature wind - up motor and a wind - up means . a motion system may be located behind the front surface of a necktie of the invention . such a motor system may be used to move an ornament or a plurality of ornaments of a necktie of the invention . for example , an ornament resembling an automobile may be connected to a motion system and the front surface of the necktie may be decorated to resemble a race track . when the motion system is activated the automobile ornament may be moved , the motion simulating the motion of a automobile about a race track . a motion system may be connected to reinforcing member within the body of a necktie of the invention . the body of the motion system is placed behind the front of the necktie so as to hide the motion system from viewers . the motor shaft perpendicularly penetrates the front surface of a necktie and ornaments are attached directly or indirectly to the shaft of the motor . the motion system is activated by a switch located on the rear surface of the necktie . u . s . pat . nos . 6 , 679 , 753 , 6 , 402 , 584 , 5 , 816 , 910 , 5 , 310 , 375 , 5 , 139 , 454 , and 5 , 087 , 852 describe systems that may be adapted for use with a necktie of the invention . for example , the flapping heart device of u . s . pat . no . 6 , 402 , 584 may be attached to reinforcing member of a necktie of the invention so that the motion mechanism is supported by the reinforcing member . the flapping portions of the device are positioned in front of the front surface of the necktie and the central support means , and linkage means penetrate the front surface of the necktie , connecting the flapping portions with the rest of the motion mechanism . the necktie may worn by the wearer by tying the necktie in a convention knot , such as a windsor knot . other embodiments of the invention may be attached to the wearer through the use of a clip as in conventional clip on ties ( fig4 ). still other embodiments of the invention are attached to the wearer through the use of straps ( fig5 ) which surround the neck and clip together using conventional fasteners such as snaps , buttons , or hook and loop fasteners velcro ®), or other conventional fastening means .

embodiments of the invention are neckties comprising ornaments that impart a substantially three - dimensional appearance to the necktie . such neckties may be decorated with colors and logos indicating sports team affiliation , corporate affiliation , favorite pet , political affiliation , tourist attraction , favorite automobile , or may indicate some other interest of the wearer .

the embodiments of the present invention will now be described in the following with reference to fig1 to 5 . fig1 is a general schematic of the optical system arrangement of the three - dimensional shape measurement apparatus according to the present invention . in fig1 reference numeral 1 denotes a laser light source of helium - neon ( he - ne ) or argon ( ar + ), for example . a laser beam 2 produced by the laser light source 1 is expanded to a specific size by a beam expander 3 and is then reflected by a mirror 4 to impinge on a lens 5 . the lens 5 is for shaping the laser beam for the rectangular aperture of a following acousto - optical deflector ( aod ) 6 , and incorporates a multiplicity of cylindrical lenses . the aod 6 is bracketed by a pair of prisms 7 and 8 which compensate for the wavelength dependency of the angle of incidence and angle of emergence of the laser beam with respect to the aod 6 . the laser beam deflected in one dimension ( horizontally ) by the aod 6 is reformed from the rectangular ( elliptical ) shape to its original circular shape by a lens 9 which is constituted analogously to the lens 5 , following which the beam passes through a lens 10 and a slit 11 . the slit 11 is for blocking zero - order light ( not shown ) from the aod 6 so as to utilize only first - order diffraction light . first - order diffraction light 12 from the slit 11 is scanned one - dimensionally with the central portion of a mirror 15 disposed at a position optically conjugate with the pupil of the eye 14 being examined as the pivot point of deflection . a laser beam scanning frequency of 15 . 75 khz corresponding to the ordinary ntsc standard television horizontal scan rate is selected for the aod 6 . the prisms 7 and 8 may not be required if only a laser beam of one wavelength is used . the laser beam reflected by the mirror 15 is reflected onto a mirror 17 by a concave mirror 16 which possesses the function of a lens . the mirror 17 is attached to a galvanometer 18 for vertical scanning of the laser beam , and is referred to as an oscillating mirror or a galvanometer mirror . the laser beam scanned two - dimensionally by the mirror 17 is passed through an objective lens 19 and is thereby projected onto the eye fundus via the central portion of the pupil of the eye 14 being examined . the light reflected from the fundus , which in fig1 is indicated by a dashed line , is guided via the objective lens 19 to be reflected again by the mirror 17 and the concave mirror 16 . the light reflected from the eye fundus is in a two - dimensionally scanned state , but after being directed onto the concave mirror 16 by the mirror 17 it is fixed in a vertical scanning state by the deflective action of the mirror 17 ; i . e ., it becomes reflected light that is scanned only one - dimensionally . a vertical scanning frequency of 60 hz corresponding to the ordinary television vertical scanning frequency is selected for the oscillating mirror 17 . light reflected from the eye fundus and then reflected by the concave mirror 16 passes around the periphery of the mirror 15 , which is the point at which it is separated from the projected laser light . this one - dimensionally scanned reflected light from the fundus that passes around the periphery of the mirror 15 passes through a lens 20 . half of this reflected light is then reflected by a half mirror 21 , passes through a detection slit 22 and a lens 23 and is detected by a photosensor 24 . disposed in front of the photosensor 24 is a filter 25 which corresponds to the wavelength of the laser beam . also , between the lens 20 and the half mirror 21 is a black spot 26 for eliminating the effect of light reflecting from the surface of the objective lens 19 . the other half of the light reflected from the eye fundus is transmitted by the half mirror 21 and , similarly to the reflected half , passes through a detection slit 27 , a lens 28 and a filter 29 to a photosensor 30 . the filter 29 has the same characteristics as the filter 25 , corresponding to the wavelength of the laser beam . as is apparent from fig1 each of the detection slits 22 and 27 has been situated slightly away from the respective positions 22a and 27a that are optical conjugates of the fundus of the eye 14 . in addition , viewed along the optical axis in the direction of the eye 14 , one of the detection slits is situated slightly to the front , and the other slightly to the rear , of the positions that are the optical conjugates of the fundus of the eye 14 . fig2 illustrates part of the optical system of fig1 particularly the portion for guiding the light reflected from the fundus , in a configuration that is closer to an actual arrangement . in fig2 the laser beam 12 ( first - order diffraction light ) deflected one - dimensionally ( in the horizontal direction ) by the aod 6 is guided via the lens 13 to be scanned with the mirror 15 as the pivot point of deflection , said mirror 15 being disposed at a position that is optically conjugate with the pupil of the eye being examined . in fig2 the scanning direction of the first - order diffraction light 12 is perpendicular to the drawing sheet , so the laser beam is therefore depicted as following the central axis of the optical system . the laser beam reflected by the mirror 15 and scanned in the horizontal direction ( vertically with reference to the fig2 drawing sheet ) is reflected by the concave mirror 16 , is again reflected by the oscillating mirror 17 attached to the galvanometer 18 and is also scanned vertically ( horizontally with respect to the drawing sheet ). the laser beam scanned two - dimensionally ( horizontally and vertically ) by the oscillating mirror 17 is projected onto the fundus of the eye 14 by the objective lens 19 , and the light reflected from the eye fundus , depicted by a dashed line in fig2 is returned through the same optical system elements 19 , 17 and 16 as the incident beam . the light reflected from the eye fundus that has been separated from the incident beam at the mirror 15 passes through the lens 20 and impinges on the half mirror 21 which splits the optical path by reflecting one half of the light and transmitting the other half . the light reflected by the mirror 21 passes through the detection slit 22 , lens 23 and filter 25 and is detected by the photosensor 24 . the portion of the light transmitted by the mirror 21 passes through the detection slit 27 , lens 28 and filter 29 and is detected by the photosensor 30 . in fig2 the reflected light from the eye fundus , represented by the dashed lines from the oscillating mirror 17 to the photosensors 24 and 30 , is only being scanned horizontally ( vertically with reference to the fig2 drawing sheet ). this being the case , the laser beam is depicted as following the central axis of the optical system as if it is not being scanned . as is apparent from the drawing , the two detection slits are oriented so that the reflected light is scanned in a direction that is parallel to the slits , and in a direction that is perpendicular to the slits the scanning is stationary , in addition to which they are oriented along the optical axis toward the eye so that one is displaced slightly to the front , and the other slightly to the rear , of the positions 27a and 22a that are the optical conjugates of the fundus . the electrical signal obtained as a result of detection and optoelectronic conversion by the photosensors 24 and 30 reflects the reflection characteristics of the fundus of the eye 14 . also , as the frequencies of the horizontal and vertical scanning of the laser beam by the aod 6 and the oscillating mirror 17 correspond to the scanning rates of an ordinary television , by appropriately amplifying the output signals from the photosensors 24 and 30 for feeding to a television monitor , two - dimensional images of the fundus can be displayed on the screen . the image shown on the monitor will mirror the optical reflection characteristics of the layer of fundus tissue corresponding to the wavelength of the laser beam . however , because in this case the detection slits 22 and 27 are slightly displaced from the position that is optically conjugate with the fundus , the output signals from the two photosensors that detect the reflected light from the fundus that passes through the two detection slits will differ in intensity depending on the state of the optical conjugate relations between the detection slits and the fundus . that is , assuming the two slits are equal , when the positions that are optically conjugate with the fundus , i . e ., the positions of the focal points of the fundus , are an equal distance from the detection slits 22 and 27 the output signals from the two photosensors will be about equal in intensity . however , unevenness in the fundus will cause a slight displacement in the said conjugate positions , giving rise to a difference in intensity between the signals output by the two photosensors . fig3 shows a typical characteristic waveform of the signal output by the two photosensors 24 and 30 . the horizontal axis represents a distance in the direction along an optical axis z perpendicular to both the horizontal x and vertical y directions in which the laser beam is scanned , and the vertical axis represents the intensity i of the photosensor output signals . the two waveforms i 1 , i 2 show the changes in the respective output signals of the photosensors 24 and 30 , such as when a depression , for example , in the fundus causes the location of the position of optical conjugate with the fundus to shift along the optical axis z . as is apparent from fig2 when the position 22a that is an optical conjugate of the fundus coincides with the position of the detection slit 22 ( indicated in fig3 by a ) the intensity i l of the output signal of the photosensor 24 is at its peak , and on each side thereof there is a smooth fall - off in signal intensity i 1 . on the other hand , when the position 27a that is an optical conjugate of the fundus coincides with the position of the detection slit 27 ( indicated in fig3 by b ) the intensity i 2 of the output signal of the photosensor 30 is at its peak , falling off to each side thereof in the same way as i 1 . what has to be noted here is that the signal intensity is completely dependent on the reflectivity of fundus . this means that when the laser beam is scanning a part of the fundus that exhibits high reflectivity the waveform of fig3 shows a proportional increase in size and , conversely , decreases in size when reflectivity is lower . fig4 shows a typical waveform characteristic obtained by computing the output signals of the photosensors 24 and 30 having the type of characteristic shown in fig3 . the horizontal axis represents a distance along an optical axis z and the vertical axis represents the signal intensity i &# 39 ; obtained by computation . the two waveforms were obtained by calculating i l - i 2 and i 2 / i 1 , respectively . the i l - i 2 type of differential characteristic is featured by the intensity value having a zero point and being partially proportional to z , and because of this it is used in video - disc systems for detection of the position of the focal point in the z direction . however , as is clear from the above explanation , because i l - i 2 depends entirely on the reflectivity of the fundus , unless the intensity of the reflected light from the fundus is known , the z - direction value cannot be determined from the value i l - i 2 . regarding i 2 / i 1 , even if the intensity of i l and i 2 depend on the reflectivity of the fundus , each can cancel out the other by denominator and numerator to make them independent of the fundus reflectivity , and thus making it possible to determine the value in the z direction from i 2 / i 1 . expressed mathematically , if i 0 ( x , y ) is the intensity of the reflected light from the fundus , when as i 2 / i 1 = f 2 ( z )/ f 1 ( z ), i 2 / i 1 becomes a prescribed function that depends only on the value of z , not on the reflectivity , so it is clear that the z value can be obtained from i 2 / i 1 . as such , by finding the value of i 2 / i l by calculation it is possible to quantify the degree of unevenness three - dimensionally , the amount of displacement in the location of the optically conjugate position along the optical axis z , i . e ., the displacement in the z direction of each location in the fundus as it is scanned by the laser beam in the x and y directions . the range of values that can be set along z , based on such characteristics , becomes a constant measurement range that falls inside the points a and b shown in fig4 . also , as the value of i 2 / i l is not proportional to the z value but is instead rather non - linear , when it used with an actual measurement apparatus a means of correcting this non - linearity is required . moreover , it is , for example , also possible to combine the addition , subtraction , and division to cancel the intensity of the reflected light according to the following equation . ## equ1 ## in this case , the calculated value possesses the different non - linearity from that obtained using the value i 2 / i 1 . fig5 is a block diagram illustrating the electrical configuration of the three - dimensional shape measurement apparatus according to the present invention . the laser beam produced by the laser light source 1 is deflected horizontally and vertically by means of the aod 6 and the oscillating mirror 17 , and is beamed at the eye 14 being examined . a driver 31 is connected to the aod 6 , the driver 31 being controlled by a sawtooth signal generated by a sawtooth waveform generator 32 . connected to the galvanometer 18 which drives the mirror 17 is a driver 33 which is controlled by a sawtooth signal generated by a sawtooth waveform generator 34 . the light reflected from the eye 14 is detected by the photosensors 24 and 30 , and the output signals therefrom are amplified to the required level by amplifiers 35 and 36 . the output signals i l and i 2 from the amplifiers are input to a divider 37 , the divisional operation i 2 / i l is performed , and the result is input to a function generator 38 . as was explained above , the calculated outputs of photosensors 24 and 30 have the type of intensity characteristics shown in fig4 . the purpose of the function generator 38 is to cancel the nonlinearity of the value i 2 / i l seen in fig4 . the intensity of the output signal of the function generator is proportional to the displacement of the fundus in the direction of the optical axis z , i . e ., to the degree of unevenness of the fundus . the divider 37 and the function generator 38 may be constituted entirely of analog integrated circuitry , or it may be comprised of a / d , d / a converters and digital operation circuitry . after the output signals of the function generator 38 and of the amplifiers 35 and 36 are input to a signal processor 39 , the information is selected and the prescribed processing carried out , an output device 40 such as a display monitor is used to display the output image . when the signal selected is from the amplifier 35 or 36 , the image output is an ordinary two - dimensional depiction of the reflection characteristics of the fundus , while when the function generator 38 signal is selected the image displays unevenness of the fundus surface with different shade levels or colors . also , microprocessors and software provided in the signal processor 39 can be used to create three - dimensional graphic patterns based on the output signals of the function generator 38 , enabling , for example , an observation of the fundus taken at an angle to be displayed on the output device 40 as a three - dimensional bird &# 39 ; s - eye view . the control system of the two - dimensional scanning of the laser beam and the output system that detects and processes the reflected light from the fundus are synchronized by a horizontal synchronizing signal 41a and vertical synchronizing signal 41b from a synchronizing signal generator 41 , thereby enabling time - based control of the overall system . moreover , although in this embodiment the scanning is fixed ( stationary ) in the vertical direction at the photosensors , the light reflected from the object ( fundus ) being scanned by the oscillating mirror only , and two detection slits are therefore used to detect displacement of the focal point of the reflected light , a rotating multi - faced mirror , for example , could of course be used as the horizontal deflector for scanning the reflected light , and when the horizontal scanning is also fixed the detection slit could be replaced by a round aperture . that is , the present invention encompasses use of two deflectors , and the reflected light from the object is scanned with respect to one direction and the scanning is stationary in at least direction . also encompassed is the arrangement in which the scanning of the reflected light is performed with respect to both directions and the scanning is completely stationary in both directions at the detection aperture , if the arrangement is one that performs detection of information related to shape characteristics of the object in the direction of an optical axis perpendicular to the direction of scanning by the two deflectors , based on the displacement of the focal point of the light reflected from the object . while the invention has been described with reference to a preferred embodiment in which the object is an eye fundus , it will be understood that the invention is not limited thereto but may be utilized to ascertain three - dimensional shapes such as the features of integrated circuit patterns , or of microorganisms , cells and the like by applying this to , for example , a laser scanning microscope . as can be seen from the above description , the three - dimensional shape measurement apparatus according to the present invention is new and eminently practical , applicable as it is to objects , such as the fundus of the human eye , which exhibit abrupt changes in reflectivity and where it is impossible to obtain the type of large angular difference needed by the triangulation method . it can also be used to carry out measurements on a television monitor at a resolution as high as the screen resolution ; and it has good accuracy and reproducibility . in addition to this , the time required for processing the measurements can be shortened : by using different shades to represent the unevenness in the contours of the object , it is possible to conduct the measurements on a fully real - time basis and at the same time obtain ordinary two - dimensional information relating to the reflection characteristics of an object .

a three - dimensional shape measurement apparatus uses a laser beam to illuminate an object . the light reflected from the object is processed to obtain information about the shape of the object in three dimensions . as the beam moves over contour features of the object , there is a corresponding displacement of the focal point of the light reflected back from the object which is calculated to convert it to depth - wise shape information . the apparatus includes a laser light source ; deflectors for scanning the laser beam at a set frequency ; an optical system for projecting the laser beam scanned by the optical deflectors at the object ; detection slits arranged parallel to the direction in which the reflected light is scanned and facing the object along on an optical axis that is perpendicular to the direction of the scanning by the optical deflectors , the slits being placed a certain distance from a point that is optionally conjugate with the object ; photosensors for detecting light passing through the detection slits ; and a signal processor to eliminate the effect of the reflection characteristics of the object .

fig1 shows a first embodiment of a forehead support 10 according to the present invention . the forehead support 10 includes a generally t - shaped cushion frame 12 pivotally mounted to a joining member 14 . the joining member 14 is connected to a nasal respiratory mask 16 used to supply breathable gas to a wearer &# 39 ; s airways . the mask 16 includes a mask shell 17 and a mask cushion 19 . the mask shell 17 also includes an angled connector 18 which has a distal end 20 for connection to a gas supply conduit ( not shown ) and a proximal end 22 for connection to the mask 16 . the connector 18 communicates the supplied gas from the gas supply conduit to the interior of the mask 16 . the mask shell 17 also includes a pair of slotted connectors 24 to which are respectively connected ends of a lower head strap ( not shown ) for securing the nasal mask to the wearer &# 39 ; s head . the joining member 14 is connected on top of the mask shell 17 generally adjacent and above the wearer &# 39 ; s nose . it will be appreciated that the nasal mask 16 shown is just one example of a respiratory mask that could be supported by the forehead support 10 . for example , the forehead support also finds application in supporting full - face ( ie . nose and mouth ) masks . forehead supports according to the invention can also be used with facial masks in which the gas supply connector 18 is incorporated into the mask in the general position of the joining member 14 . in this type of mask , the supplied gas flows through or past the forehead support 10 . the t - shaped cushion frame 12 includes a pair of forehead cushions 25 mounted at each end of the upper portion of the t on the wearer contacting side . examples of cushions 25 include open or closed cell foam , silicone , dual durometer foams , single pads or multiple pads joined together . the forehead cushions 25 can be integrally moulded with the frame 12 or attached thereto by clips or adhesives or the like . the frame 12 also includes a slotted connector 26 adjacent each of the forehead cushions 25 to which are respectively connected ends of an upper head strap ( not shown ) for securing the cushion frame 12 to the wearer &# 39 ; s head . the t - shaped cushion frame 12 also includes a pair of shafts 27 ( only one shown ) on the lower portion of the t which are each respectively received in part circular openings 28 ( only one shown ) provided on the joining member 14 . the shafts 27 can pivot or rotate in their respective openings 28 to provide for pivotal or rotational movement between the cushion frame 12 and the joining member 14 about axis 30 in the direction of double - headed arrow 31 . the curved shape of the cushions 25 allows them to effectively “ roll ” over the wearer &# 39 ; s forehead during angular adjustment between the cushion frame 12 and the joining member 14 . as best shown in fig2 and 3 , the cushion frame 12 also includes a flexible member 32 which has two side by side spaced apart tongues 34 and a middle protruding button 36 on its distal end . the joining member 14 also includes two generally arcuate shaped portions 38 that each have a pair of four grooves 40 . it will be appreciated that the pair of four grooves is merely preferable and that only two or more grooves are required . it will also be appreciated that the flexible member 32 can be on the joining member 14 and the grooves 40 can be on the cushion frame 12 . the tongue 34 and the grooves 40 extend in a direction substantially parallel to a line extending radially from the axis 30 . the cushion frame 12 is constructed from a plastics material , such as polypropylene or polycarbonate , which allows the member 32 to be flexed relative to the cushion frame 12 upon which is mounted when pressure is applied to the button 36 in the direction of arrow 42 . the corresponding movement of the tongues 34 releases them from engagement with one of the pairs of grooves 40 ( as shown in fig3 ) to allow angular adjustment between the cushion frame 12 and the joining member 14 about the axis 30 . releasing the button 36 allows the tongue 34 to resiliently flex back towards the grooves 40 . when the tongues 34 and one of the pairs of grooves 40 are aligned ( as shown in fig2 and 4 to 7 ) the tongues 34 engage one of the pair of grooves 40 . when the tongues 34 are engaged with one of the pair of grooves , the cushion frame 12 and joining member 14 are locked against pivotal movement therebetween at a predetermined angle . fig4 to 7 respectively show forehead support 10 adjacent the heads of different wearers with the tongues 34 engaged in the first , second , third and fourth of the four pairs of grooves 40 . as fig4 to 7 show , the angle between the cushion frame 12 and the joining member 14 adjacent the wearer &# 39 ; s forehead can be increased to suit wearer &# 39 ; s with relatively high nasal regions and relatively low foreheads ( fig4 and 5 ) and decreased to suit wearers with relatively low nasal regions and relatively high foreheads ( fig6 and 7 ). in this way the forehead support 10 advantageously allows the mask 16 to be positioned to comfortably suit the particular topography of the wearer &# 39 ; s face to ensure the mask cushion 19 is positioned ideally relative to the wearer &# 39 ; s face . as examples , the relative position of the cushion frame 12 and the joining member 14 in fig4 would be more suitable for use with a wearer having a shallow forehead or protruding cheeks or nose whilst the position of the cushion frame and joining member 14 in fig7 would be more suitable for use with a wearers having a protruding or bulbous forehead . fig8 shows a second embodiment of a forehead support 50 according to the present invention . like reference numerals to those used in describing the first embodiment will be used to denote like features in relation to the second embodiment . in the second embodiment , their are two buttons 36 . pressing the buttons together in the direction of arrows 52 flexes the tongues 34 towards each other to disengage them from the grooves 40 and allow angular adjustment between the cushion frame 12 and the joining member 14 . releasing the buttons 36 allows the tongues 34 to resiliently flex towards , and into engagement with , the grooves 40 to lock the cushion frame 12 and the joining member 14 against relative pivotal movement . fig9 to 14 show a third embodiment of a forehead support 60 according to the present invention . like reference to those used in describing the first embodiment will also be used to denote like features in relation to the third embodiment . in the third embodiment , the cushion frame 12 is integrally moulded with the joining member 14 and joined by an integral hinge 62 ( sometimes known as a natural or living hinge ). the cushion frame 12 and the joining member 14 can be pivotted relative to each other about the hinge 62 . the forehead support 60 is moulded in a substantially ‘ flat ’ configuration , as shown in fig9 . the cushion frame 12 is then pivotted through approximately 180 ° relative to the joining member 14 until the tongue 34 engages one of the four grooves 40 . as with the earlier embodiments , pressing the button 36 in the direction of arrow 42 frees the tongue 34 from engagement with the grooves to allow adjustment of the angle between the cushion frame 12 and the joining member 14 . the button 36 and the tongue 34 are inherently biased to a position engaging one of the grooves 40 , again consistent with earlier embodiments . in the preferred form shown , the mask shell 17 is also integrally formed with the joining member 14 . this simplifies manufacturing and assembly and reduces production costs . the forehead support 60 is preferably manufactured from polypropylene due to its ability to mould integral hinges . fig1 and 16 show a fourth embodiment of a forehead support 100 according to the invention . like reference to those used in describing the first embodiment will also be used to denote like features in relation to the fourth embodiment . the fourth embodiment is almost identical to the first embodiment except the tongue 34 and the grooves 40 are angled with respect to a line extending radially from the axis 30 to the tongue 34 or the grooves 40 . this angled arrangement reduces the likelihood that the tongue 34 will inadvertently release from engagement with one of the grooves 40 if the front of the mask 16 is subjected to a force in the direction of the wearer &# 39 ; s face . although the invention has been described with reference to a specific example , it will be appreciated by those skilled in the art that the invention may be embodied in many other forms . as an example , the forehead support can include means to resiliently bias the cushion frame and the joining member relative to one another such that they increase or decrease their angle relative to one another when the tongues are disengaged from one of the pairs of slots .

a respiratory mask assembly includes a respiratory mask and a forehead support secured to the mask via a joining member . the forehead support includes a cushion frame pivotably mounted to the joining member so as to be pivotably movable relative to the mask when the cushion frame is secured to the mask . at least one cushion is mounted on the cushion frame . a finger - operated adjustment control member is provided to the cushion frame . the finger - operated adjustment control member is manually manipulable to adjust a position of the cushion frame relative to the joining member along a predetermined path generally towards and away from the patient &# 39 ; s forehead .

this invention relates in general to games , and more particularly to an astrological - astronomical conquest game . while it is to be appreciated from the outset that the format of this game is set forth to correspond to the solar system , the principles set forth with respect to this game can carry over to a variety of different representative game boards as long as the basic interrelationships among the movement paths for the player &# 39 ; s pieces are maintained . broadly , the game equipment comprises : a game board , two types of player position markers , two types of dice , and two types of player instruction cards . specifically , game board 10 is shown complete in fig1 and is comprised of the superposition of the partial depictions of the game board 10a and 10b shown respectively in fig2 a and 2b . as is shown in fig2 a , the game board 10a has a rectangular configuration and is inscribed in any convenient manner with a central circular area 12 and a series of nine concentric orbits or circles 14 - 22 surrounding the common center 12 . twelve lines 23 radiate outwardly from circular area 12 to divide the game board 10 into twelve sectors 24 - 35 . each of concentric circles 14 - 22 are formed as a broken line to indicate movement steps , such as movement steps 36 shown with respect to circle 22 . none of these steps are intersected by lines 23 , and it should be appreciated with respect to fig2 a that circle 14 has one step in each of sectors 24 - 35 while circles 15 and 16 have two such movement steps in sectors 24 - 35 . circles 17 and 18 have three such movement steps in sectors 24 - 35 and circles 19 , 20 , and 21 have four such movement steps in each of sectors 24 - 35 . finally , circle 22 has five movement steps in each of sectors 24 - 35 . each of circles 14 - 22 define circular paths or orbits about the common center with this center being representative of the sun . accordingly , each of circular orbits 14 - 22 represents the nine paths of the planets about the sun , and these planets are designated on game board 10 and 10a as colonization points 38 - 40 and base locations 41 - 46 . fig2 b shows partial game board 10b having the common elements of the circular center 12 , lines 23 and sectors 24 - 35 as described with repect to fig2 a . it should be appreciated that game board 10 is formed by the superpositioning of partial game board 10b on partial game board 10a . additional movement paths or orbits 48 - 53 are inscribed on board 10b as broken ellipses surrounding common center 12 . orbits 48 - 51 have common center 12 located at a central portion thereof while orbits 52 and 53 have common center 12 located at one extreme end thereof . elliptical orbits 48 - 53 are provided with base points 60 - 71 with a single base point being located in each of sectors 24 - 35 . additionally , exit points 72 - 75 are provided and correspond to selected one of base points 60 - 71 , as described below . when partial game board 10b is superpositioned on partial game board 10a , the complete game board 10 is formed as is shown in fig1 . intersections of elliptical orbits 48 - 53 with circular orbits 14 - 22 thus occur , and are indicated on game board 10 by a plurality of solid dots , such as dots 37 . these intersections occur at preselected locations along movement steps for each orbit , and players may change orbits , if desired , when encountering an intersection . as may be noted with reference to fig1 the broken lines forming concentric circular orbits 14 - 22 and elliptical orbits 48 - 53 intersect at a variety of locations . as discussed below in more detail , each player has playing pieces which are confined for movement in a counter - clockwise direction around a common center 12 and are constrained to move in a specific orbital until a intersection point is reached . at an intersection , the player may elect to move in a counter - clockwise direction along any such intersecting orbital . each exit point 72 - 75 corresponds to an entry point which , in the preferred embodiment is also a base point which is designated as a &# 34 ; star &# 34 ;. for example , exit point 72 corresponds to base point 66 , exit point 73 corresponds to base point 60 , exit point 74 corresponds to base point 61 and exit point 75 corresponds to base point 63 . these respective pairs form pairs of jump points allowing a player to directly move from a respective exit points 72 - 75 to its corresponding base point in a single move without the necessity of moving in a complete orbital path thereto . fig3 and 4 show perspective views of representative playing pieces for the preferred embodiment of this game , although it should be appreciated that any suitable configuration of the playing pieces may be used . it is important , however , that carrier piece 80 shown in fig3 be able to transport physically a plurality of unit pieces 82 shown in fig4 . to this end , carrier piece 80 includes an upright stand 84 which supports an upwardly turned hemispherical shell 86 with support post 84 extending through shell 86 to terminate in an upwardly positioned gripping nub 88 which facilitates movement of carrier piece 80 . unit piece 82 is a single value piece of any convenient configuration , although in the preferred embodiment it is shown as a generally triangularly shaped piece having rounded ends 90 at each vertex of the triangle . carrier piece 80 is designated as a &# 34 ; star ship &# 34 ; and should be constructed to receive approximately forty unitary pieces 82 designated as a &# 34 ; fighter &# 34 ;. a carrier piece 80 has a value which is larger than unit piece 82 , for example , in the preferred embodiment carrier piece 80 has a value fifteen times that of unit piece 82 . fig5 is a representative sample of an instruction card , namely , destiny card 94 . each destiny card 94 contains an instruction controlling or influencing events either specifically directed at the player who draws such a destiny card or which effect conditions for all players in a specific sector 24 - 35 . by way of example only , the preferred embodiment of the present invention has a set of destiny cards having forty - eight individual cards , 24 of which relate to the player &# 39 ; s roll of the movement dice discussed below . destiny card 94 , for example , reduces the number of dice which the player may roll . twelve of the destiny cards influence conditions to create positive effects in a selected one of sectors 24 - 35 , for example , by increasing the number of playing pieces for each player having pieces in that sector . twelve destiny cards 94 relate to negative events and thus negatively influence conditions on corresponding sector 24 - 35 , such as , the removal of all playing pieces in that sector . fig6 shows a representative command card 96 , with the set of command cards comprising forty - eight command cards having values thereon from one to ten . a command card is drawn by a player after a successful attack on an opponent &# 39 ; s pieces and must be used immediately . the value of the command card awards the player additional unit pieces corresponding to the number on the command card and , when the command cards are turned in , these pieces are entered onto the game board in the manner described below . it is an objective for each player in the game to attempt to eliminate all of his opponents , and the winner of the game is , accordingly , the last player to remain . the removal of opposing player pieces is accomplished by means of movement dice 98 , shown in fig7 and attack dice 100 shown in fig8 . while it should be appreciated that movement dice 98 and a set of attack dice 100 are preferred for this invention , any suitable chance means known in the art may be utilized both to move the player &# 39 ; s pieces and to determine the outcome of an attack . by way of example , then , a player moves groups of his pieces according to the values rolled by casting dice 98 along the movement steps of orbits 14 - 22 and 48 - 58 with each dash or movement steps such as movement step 36 , having a unit value . a player having the roll shown in fig8 would be entitled to move 17 steps . an attack is effected by the movement of the moving player &# 39 ; s forces or groups of playing pieces behind and adjacent an opposing player &# 39 ; s piece or group of playing pieces . one such a juxtaposition occurs , the moving player rolls the attack dice until either his own group of playing pieces is eliminated from the board or until the opposing player &# 39 ; s playing pieces are removed from the board . accordingly , attack dice 100 must determine a ratio of relative losses for each player to determine how many unit pieces 82 that the attacking player and the defending player must each remove from the board . in the preferred embodiment of the present invention , a set of attack dice 100 having individual die members 101 are each cubic with one side color coded to correspond to each of the six colors used for playing pieces 80 and 82 . in fig8 these colors are labeled as letters a - f for representation purposes . when dice 100 are cast , only the exposed colors corresponding to the attacking player and the defending player have any effect . for example , fig8 shows the cast of dice 100 for an attack by player a on player b . since two exposed or upturned faces of dice 100 have an &# 34 ; a &# 34 ; color and one of the dice 100 has an exposed &# 34 ; b &# 34 ; color , player a would be required to remove two unit playing pieces and player b would be required to remove one playing piece . players c - f would not be affected . of course , any suitable means for determining relative removal of pieces is within the scope of this invention . while it should be appreciated , from the above discussion , that any interrelated pattern and shape of movement paths may be utilized without departing from the scope of this invention , the game board as described above represents the solar system . specifically , the common center 12 represents the sun while colonization points 38 - 40 represent the planets mercury , venus and earth . base locations 41 - 46 respectively represent the planets mars , jupiter , saturn , uranus , neptune and pluto . concentric circles 14 - 22 thus represent the orbit of these planets about the sun . the sectors 24 - 35 correspond to each of the twelve astrological or zodiac signs such that the destiny cards 94 which relate to events within each sector thus correspond to positive and negative astrological fates , hence introducing an element of astrological fate to the astonomical configuration of the planet orbitals . base points 60 - 71 correspond to stars or star regions with elliptical orbits 48 - 53 corresponding to interstellar travel paths between the sun and the stars . exit points 72 - 75 represent black holes whereby player &# 39 ; s pieces may exit the board and enter through a corresponding star or base point 60 - 71 as set forth above . however , to complete the understanding of the preferred embodiment of this conquest game , it is helpful to have a further understanding of the relationships of the various game components . specifically , the preferred embodiment of the present invention is designed for use by two to six players a - f , as discussed above , who arbitrarily decide the order of turns to be taken . each player begins the game with a specified number of fighters and one star ship . preferably orbits 17 - 22 are color coded to correspond to colored playing pieces representing each distinct player . prior to the start of the game , it is preferred that each player have twenty - five fighters and one starship which has a value of fifteen fighters . these pieces are then placed anywhere on a player &# 39 ; s color coded home orbit 17 - 22 . the deck of command cards 96 and the deck of destiny cards 94 are each shuffled and conveniently placed anywhere on the board , and the destiny card deck is cut in half so that , when half of the deck is used the entire deck is reshuffled . at the start of each player &# 39 ; s turn , the respective player draws a destiny card which is immediately revealed and the resultant instruction followed which may affect all or none of the players . any additions or removal or movement of pieces , forming playing forces , takes place immediately according to the destiny card . if the destiny card indicates that a specific event cause two or more players occupy a common space , the player who drew the card occupies that space and the next player occupies the next empty space ahead of the first player and so on for the other players . after the instructions of the destiny card have been followed , the first player rolls the movement dice 98 . normally four such dice are rolled , however , a destiny card may require a player roll less than the complete set of movement dice . playing pieces are moved as groups or forces and the fighters must move in groups of five or less unless accompanied by a starship which may contain or carry as many fighters as it can hold . thus , a large force must be moved by a starship . only one force may be moved at a time and all movement must be in a counter - clockwise direction around the center 12 up to the amount of steps indicated by the throw of the dice . while moving , a player may jump his own forces or playing pieces , but no opposing forces may be jumped by a player . if , upon movement of his pieces , a player confronts an opposing player &# 39 ; s pieces by moving his force adjacent the opponent &# 39 ; s pieces , the player may elect to attack those forces . attack is accomplished by means of rolling the attack dice 100 which yields a ratio which requires that each player remove a corresponding number of pieces from the attacking and defending groups . for example , as described above , the attack dice may be color coded , so that the attacking player must remove a number of fighters corresponding to the number of upturned faces corresponding to his color after rolling the attack dice and the defending player must remove the number of fighters corresponding to the number of upturned faces corresponding to his color . for those players who are neither attacking nor defending , there is no effect if their color lies face up after casting the attack dice . if the defender successfully defends by defeating the attacking force , the attacking player &# 39 ; s turn ends . if the attacking player eliminates the defending player &# 39 ; s forces , the attacking player draws a command card and is awarded additional fighters corresponding to the value thereon . these fighters must be brought into the game immediately on the player &# 39 ; s home planet in the home orbital 17 - 22 . if the player elects to continue his turn , another destiny card is drawn , and , after its instructions are followed , the player then rolls the movement dice again and play proceeds as before . the turn ends when a player is not in a position for attack or chooses not to continue his turn ; the next player then begins his turn . additional rules govern the turn , as follows . the attacking position must be immediately adjacent an opponents force in a space immediately behind that force and this positioning may be accomplished through destiny cards , an opponent &# 39 ; s movements , or a player &# 39 ; s movements by way of the movement dice . no force may be attacked in its home orbit except at an intersection unless that player &# 39 ; s forces are found only in its home orbit . an attack must continue until the defender or the attacker wins once an attack is declared . upon completion of the attack , the attacking force occupies the space formerly held by the defender . during movement , any number of fighters may be picked up or left off on any given orbital movement as long as the rule regarding the starships is followed . the use of the pairs of jump points comprising exit points 72 - 75 and their corresponding base points permit &# 34 ; instantaneous leaps &# 34 ; from the exit point to its corresponding base point . exit points 72 - 75 are designated as &# 34 ; black holes &# 34 ; and four are present in the preferred embodiment of the present invention . a player may decide to pass over a black hole or enter it , but the player may not stop on it except to attack . if a player enters a black hole , the forces thereon are transported to the indicated entry point which is a corresponding star and forms one of the base points 60 - 71 . upon such transportation , the player may either continue with the remainder of the roll or stop . also , when passing over a black hole , it is permissible for the player to dispatch any portion of the force to the indicated star . if the designated entry point or star is occupied however by an opposing force , the transported force must attack immediately . additional fighters are awarded at the start of a turn for colonization of the stars base points 60 - 71 or base locations 41 - 46 or colonizations points 38 - 40 according to an arbitrary value assigned thereto . these additional fighters are assigned at the start of the player &# 39 ; s turn if that player presently occupies those positions and must be brought immediately onto the game on the player &# 39 ; s home planet . the additional fighters awarded for colonization , as well as fighters awarded by command cards , cannot be entered onto the board and are thus forfeited if that player &# 39 ; s home planet is occupied by an opponent . although the present invention has been described with a certain degree of particularity , it is understood that the present disclosure has been made by way of example and that changes in details of the structure may be made without departing from the spirit thereof .

a solar system conquest game has a game board including a plurality of movement paths that form a first set of concentric circular orbits and a second set of orbits intersecting the circular orbits at pre - selected locations with these orbits defining movement paths for playing pieces corresponding to each player . the intersections define exchange points where pieces may change orbits . a set of cards determines additional pieces to be entered onto the board by a player , and dice determine the number of movement steps to be traversed by a player during his turn , and a second set of dice controls the outcome of a confrontation between playing pieces . the game board may further be divided into a number of sectors , and a set of instruction cards influence events in a particular sector for all players having pieces located therein . base points may be located on selected orbits , and pairs of jump points may also be located on selected orbits and defined by exit points and entry points whereby a player may move directly from an exit point to an entry point . playing pieces are of two types , a unit piece and a carrier piece having a larger value than the unit piece and configured to physically receive said unit pieces for transport therewith . additional chance cards may be provided to influence game conditions .

the present invention , in a broad sense , relates to an rf activated aimd telemetry transceiver which includes ( 1 ) a telemetry transceiver associated with an aimd , having an active telemetry mode wherein the telemetry transceiver is powered by the aimd , and a sleep mode ; ( 2 ) a passive rf tag associated with the telemetry transceiver ; and ( 3 ) a telemetry wake - up circuit electrically disposed between the telemetry transceiver and the passive rf tag . the telemetry wake - up circuit is responsive to a signal from the rf tag to place the telemetry transceiver in the active telemetry mode . in a preferred embodiment , the aimd transceiver has a timer wherein it returns to its sleep mode after a predetermined amount of time . as an alternative , a remote aimd programmer may send a signal to the aimd telemetry antenna and associated transceiver telling it to turn off and return to its sleep mode . in a preferred embodiment , the remote aimd programmer can incorporate a low frequency ( lf ) rf transmitter or rfid reader / interrogator operating in the 50 to 135 khz frequency range which would transmit a signal sufficient to penetrate right through the titanium housing of an aimd and activate an embedded passive rf chip . the circuitry of the rf chip would be connected to telemetry circuits contained within the aimd . for example , in the case of a pacemaker , the remote pacemaker programmer would send the rf signal as a wake - up call to turn on the aimd telemetry receiving circuits so that the pacemaker could communicate with the remote aimd programmer . in a preferred embodiment , the rf chip is a four terminal rfid chip . rfid is widely used for inventory and article tracking . rfid operational protocols and frequencies have evolved worldwide . there are epc and iso standards , and also ansi standards that cover the frequency band , forms of modulation , etc . in particular , the iso 18 , 000 standards are particularly applicable to the present invention . for example , low frequency rfid systems operating below 135 khz are governed by iso 18 , 000 - 2 . there are also standards governed by the standard body known as epc global which defines various uhf and hf rfid protocols . for example , epc hf class 1 covers 13 . 56 mhz . 13 . 56 mhz is also known as the rfid hf band and is covered by iso 18 , 000 - 3 . the use of a passive four terminal rfid tag for the present invention is preferred because the frequency allocations and other protocols have been worked out over the last couple of decades and have resolved themselves into these international standards . the passive rfid tag draws no current at all from the aimd battery . a passive rfid tag is entirely powered from the external reader / interrogator . this is what makes it possible to achieve such very low levels of current drop when the telemetry circuit is in its sleep mode . the only part of the aimd transceiver or receiver that would be active at all is the electronic switch that is coupled to the rfid chip . in the case where this is a field effect transistor ( fet ) switch , the current draw would be exceedingly low . it is only when the rfid tag itself receives energy from an external source such as an rfid reader / interrogator , that it sends a pulse to activate the transceiver electronic switch , thereby waking up the entire aimd telemetry transceiver circuitry . the prior art zarlink chip shortens a pacemaker battery life by over one month . the present invention would , in contrast , shorten a pacemaker battery life by only a portion of a single day . there is another significant advantage to using a passive rfid tag to wake up the aimd telemetry circuit . the rfid tag can be multifunctional . that is , when it receives a wake - up encoded pulse from an external reader / interrogator , it can act as the described telemetry wake - up trigger . however , by sending it an interrogation pulse , it can also be used to identify the make , model number , and / or identify mri compatible features of the aimd . fig3 is a cross - sectional view taken generally along section 3 - 3 from fig2 . shown is a circuit board or substrate 110 which contains many electronic components and microelectronic chips which enable the aimd 100 c to function . also shown is an rf or rfid tag 112 which includes an antenna 114 and a four terminal rf or rfid chip 116 . two of the leadwires that are routed to the rfid chip 116 are connected to the antenna 114 . there are also leadwires 118 , 120 that are connected from the rfid chip 116 to aimd telemetry transceiver circuitry 122 as shown . in a typical application , energy is received from a remote rfid reader / interrogator 124 ( fig6 ) and coupled to the rfid tag 112 antenna 114 . a resonant circuit is formed between this antenna 114 and the rfid chip 116 . normally , a capacitor 126 ( fig7 ) would be placed in parallel with the antenna 114 to store energy . once the rfid chip 116 receives the proper encoded signal from the reader / interrogator 124 ( fig7 ), it is activated and transmits a wake - up signal via leadwires 118 , 120 to the aimd telemetry transceiver 122 . this wake - up pulse puts the telemetry transceiver 122 into its active mode so that it may communicate with its external / remote programmer 128 ( fig6 ). the remote programmer 128 may be the older style close - wanded telemetry low frequency magnetic coupling - type ( fig9 ) or it may be the newer rf distance telemetry - type ( fig8 ). referring once again to fig3 , the rfid tag 112 and its associated component antenna 114 and rfid chip 116 need not be biocompatible or hermetic . this is because they are disposed inside the overall electromagnetically shielded and hermetically sealed housing 102 of the aimd 100 c . there are advantages and disadvantages to this placement . the obvious advantage is the rfid tag 112 and all its associated components are in an environmentally inert environment and are never exposed to body tissue or body fluids . a disadvantage is the fact that the antenna 114 is disposed inside of the electromagnetically shielded housing 102 of the aimd . this means , the antenna 114 can only effectively pick up low frequency rfid signals . these signals would typically be in the 50 to 135 khz frequency range . the antenna 114 would be completely ineffective in picking up signals from an external rfid reader / interrogator 124 at hf ( 13 . 56 mhz ) or higher frequencies . this is because the housing 102 of the aimd would effectively shield such signals . fig4 illustrates a cardiac pacemaker 100 c having an rfid tag 112 which is mounted in the aimd plastic header block 104 . in this application , the rfid antenna 114 would be more efficient because it is outside of the generally electromagnetically shielded housing 102 of the aimd . since the antenna 114 that is associated with the rfid tag 112 is now displaced within the plastic header block 104 , it can more effectively pick up signals from the rfid reader / interrogator 124 . in this case , the rfid frequency could still be in the low frequency range ( lf ) generally from 50 to 135 khz , but it could also be in the hf ( 13 . 56 mhz ) frequency range or even the uhf frequency bands . when the rfid tag 112 and its associated chip 116 and antenna 114 are placed in the header block 104 , it is important that these components be resistant to body fluids . over time , body fluids can penetrate through bulk permeability through the header block 104 plastic material . accordingly , the antenna 114 of the rfid tag 112 must be made of biocompatible material , such as platinum , palladium , niobium and the like . in addition , the rfid chip 116 itself must be either biocompatible or placed within a hermetic package so it is also resistant to body fluids . see u . s . patent application ser . no . 12 / 566 , 233 , which is incorporated herein by reference . leadwires 118 and 120 should also be biocompatible up to the point where they are connected to the hermetic seal 130 . it will be apparent to those skilled in the art that the hermetic seal 130 for the rfid tag 112 could be incorporated within the overall hermetic seal 132 which is coupled to the is - 1 connectors 106 , 108 and internal electronic circuits . leadwires 118 and 120 are routed to leadwires 118 ′ and 120 ′ within the aimd housing 102 and are connected to the telemetry transceiver 122 which is disposed on a circuit board 110 . fig5 shows that the rfid tag 112 of fig4 consists of antenna structure 114 and a hermetically sealed package 132 in which the rfid chip 116 is disposed . terminals 134 and 136 are connected to the rfid tag &# 39 ; s antenna 114 . leadwires 118 and 120 are routed to the telemetry transceiver 122 which is located inside of the electromagnetically shielded and hermetically sealed aimd housing 102 . referring once again to fig4 , one can see that the antenna 114 of the rfid tag 112 is disposed outside of the hermetic and electromagnetically sealed housing 102 of the aimd 100 c . in an alternative embodiment , the rfid chip 116 could be disposed inside of the housing 102 of the aimd , for example , placed on the circuit board 110 adjacent to transceiver chip 122 . in this embodiment , the antenna 114 of the rfid tag 112 would still be disposed outside of the aimd shielded housing 102 wherein its associated rfid chip and energy storage capacitor 126 are disposed inside the hermetically sealed housing 102 . fig6 is a diagrammatic view illustrating how the rfid activated aimd telemetry transceiver of the present invention would operate . shown is an rfid reader / interrogator 124 . it may be a standalone unit , such as a hand - held rfid reader ( fig8 - 10 ) or it could be incorporated within or adjacent to the aimd remote programmer 128 ( fig1 ). a signal or pulse 138 is produced when the rfid reader / interrogator 124 is activated which couples energy to tuned antenna 114 of the rfid tag 112 . this couples energy to terminals 134 and 136 of the rfid chip 116 which activates the rfid chip . the rfid chip 116 stores this energy in a capacitor ( not shown ) which then transmits a wake - up pulse via terminals 140 and 142 to the telemetry wake - up circuit 144 . the telemetry wake - up circuit 144 then turns power to the aimd telemetry transceiver 122 placing it into an active telemetry mode . also shown is an optional timer 146 which will turn off the telemetry transceiver 122 and put it back into its sleep mode after a predetermined amount of time . an alternative to the timer 146 is that a second activation of the rfid reader / interrogator 124 would cause the rfid chip 116 to once again be activated so that it sent a toggle pulse back to the telemetry wake - up circuit 144 . this would unlatch or turn off the telemetry transceiver 122 and put it back into its sleep mode . there is a third method of putting the telemetry transceiver 122 back into its sleep mode and that would be by sending a special pulse 148 from the remote programmer 128 which would instruct the telemetry transceiver 122 to go back into its sleep mode . fig7 is an electrical schematic diagram of the system of fig6 , illustrating the components of the telemetry wake - up circuit 144 . shown , in this case , is a bipolar junction transistor ( bjt ) which is also known as a n - p - n transceiver switch 150 . the transistor 150 base 152 receives a signal from the rfid chip 116 from terminals 140 and 142 through leadwires 118 and 120 . this results in a very low voltage drop between the transistor 150 collector c and the emitter e . this effectively connects the telemetry transceiver 122 to voltage source v s and to the ground reference voltage 0v . this activates the telemetry transceiver 122 which is shown connected to its antenna 148 so that it can receive and transmit information from the aimd remote programmer 128 ( fig6 ). the voltage source v s is normally supplied from the aimd internal battery 154 ( fig3 ). the n - p - n transceiver switch 150 is illustrative of any type of microelectronic switch . these can include a bipolar junction transistor ( bjt ), a field effect transistor ( fet ), a metal oxide substrate field effect transistor ( mosfet ), a microelectronic mechanical switch ( mems ), a unijunction transistor switch , a silicon - controlled rectifier ( scr ) switch , a pin diode , a p - n junction transistor switch , a p - n - p transistor switch , or any type of n - p - n transistor switch . in general , the rfid chip 116 of the present invention contains at least four terminals . two of these terminals 134 , 136 are reserved for connection to the antenna 114 and its associated resonating capacitor 126 . the other two or more terminals 140 , 142 are for connection to aimd telemetry transceiver circuits 118 , 120 in order to provide both wake - up and go back to sleep pulses . fig8 illustrates the operation of the present invention . shown is a human patient 156 who has an aimd 100 . in its normal operating mode , the aimd &# 39 ; s telemetry transceiver circuits would be in a sleep or quiescent low battery drain mode . a signal 138 is transmitted by an rfid reader / interrogator 124 . this pulse 138 is coupled to the rfid tag 112 that is associated with the aimd 100 . the rfid signal 138 then wakes up the aimd &# 39 ; s telemetry transceiver 122 . it is at this point that the remote programmer 128 can form a two - way communication link between the aimd 100 and the programmer 128 . in the case shown in fig8 , the remote programmer 128 has an antenna 158 , which is an rf antenna . this forms a so - called distance telemetry link between the remote programmer 128 and the aimd 100 . this typically operates at high frequency . one popular set of frequencies is the mics band operating in the 402 to 405 mhz frequency range . as previously described , the telemetry transceiver of the aimd 100 can be put back into its wake - up mode in a number of ways , including an internal timer circuit 146 , receipt of a second type of rfid pulse 138 ′ which will instruct the rfid chip 116 to unlatch the telemetry wake - up circuit thereby putting the telemetry transceiver back into its sleep mode , or even by transmission of a special pulse sequence 160 from the remote programmer 128 which instructs the transceiver 122 to go back into its sleep mode . fig9 is very similar to fig8 , except that an older style of remote programmer 128 is shown which includes a wand 162 which is placed over the patient &# 39 ; s aimd 100 . the wand 162 is generally connected through leads 164 to the remote programmer 128 . this type of wanded telemetry involves a close coupled low frequency magnetic link between an antenna in the wand 162 and an associated multi - turn loop antenna associated with the aimd 100 . generally , the wand 162 would be placed either very close to or directly on the patient &# 39 ; s chest directly over the aimd 100 . this is the case for a cardiac pacemaker 100 c . of course , the aimd 100 could be located anywhere within the human body in which case the wand 162 would have to be placed over it . the system of fig9 operates in all ways as previously described in connection with fig8 . fig1 and 11 are similar to fig8 and 9 , however in this case , the rfid reader 124 , which is illustrated in fig1 , can be incorporated either within or connected to the aimd remote programmer 128 . this eliminates the need to have an external portable rfid reader 124 , which would be about the size of a garage door opener . the problem with a small reader around a hospital or operating theater is it is easily misplaced or lost . accordingly , it is a feature of the present invention that the rfid reader 124 that activates the rfid tag 112 may be built inside of or connected to via leads 166 of the aimd remote programmer 128 . from the foregoing , it will be appreciated that the present invention relates to an rf - activated aimd telemetry transceiver which includes a telemetry transceiver associated with the aimd , an rf tag associated with the telemetry transceiver , and a telemetry wake - up circuit electrically disposed between the telemetry transceiver and the rf tag . the rf tag comprises a passive rf chip and an antenna . preferably , the antenna is biocompatible and the rf chip is disposed within a hermetic package . the telemetry transceiver has an active telemetry mode wherein a telemetry transceiver is powered by the aimd , and a sleep mode . the telemetry wake - up circuit is responsive to a signal from the rf tag to place the telemetry transceiver into the active telemetry mode . although several embodiments of the invention have been described in some detail for purposes of illustration , various modifications may be made without departing from the spirit and scope of the invention . accordingly , the invention is not to be limited , except as by the appended claims .

a telemetry wake - up circuit is electrically disposed between a telemetry transceiver associated with an aimd , and an rf tag . the rf tag may be remotely interrogated to generate a signal to which the telemetry wake - up circuit is responsive to switch the telemetry transceiver from a sleep mode to an active telemetry mode . in the sleep mode , the telemetry transceiver draws less than 25 , 000 nanoamperes from the aimd , and preferably less than 500 nanoamperes .

fig1 is a schematic diagram illustrating an implantable stimulation system 10 for alleviation of urinary incontinence . as shown in fig1 , system 10 may include an implantable pressure sensor 12 , implantable stimulator 14 and external programmer 16 shown in conjunction with a patient 18 . pressure sensor 12 senses a pressure level exerted by urinary sphincter 22 on urethra 20 proximate the neck 23 of bladder 24 , and transmits pressure information based on the sensed pressure level to at least one of stimulator 14 and programmer 16 by wireless telemetry . stimulator 14 or programmer 16 may record the information , generate adjustments to electrical stimulation parameters applied by the stimulator , or both . in some embodiments , pressure sensor 12 may support purely diagnostic purposes , such as urodynamic study , e . g ., by transmission of information to external programmer 16 . in other embodiments , pressure sensors 12 may form part of a closed loop feedback system for stimulator 14 . fig2 is an enlarged schematic diagram illustrating implantable pressure sensor 12 as shown in fig1 and 2 , pressure sensor 12 includes a sensor housing 26 and a flexible tube 28 that extends from the housing . flexible tube 28 contains a volume of fluid 30 , and includes a closed end 32 and an open end ( not shown in fig1 ). sensor housing 26 contains a sensing element ( not shown in fig1 ) adjacent the open end of flexible tube 28 . the sensing element senses pressure level within flexible tube 28 . sensor housing 26 further contains electronics to generate pressure information , and telemetry circuitry for transmission of the information . as further shown in fig1 and 2 , sensor housing 26 may reside within bladder 24 . sensor housing 26 may be temporarily or permanently attached to an inner wall 27 of bladder 24 , such as the mucosal lining , as will be described . alternatively , housing 26 may be implanted sub - mucosally . flexible tube 28 extends away from sensor housing 26 and through an inner lumen defined by the bladder neck proximate urinary sphincter 22 . in this manner , flexible tube 28 is positioned to directly sense the pressure level exerted by urinary sphincter 22 . yet , flexible tube 28 may be sufficiently thin to avoid significant obstruction of urethra 20 or disruption of the function of urinary sphincter . as a further alternative , housing 26 may reside outside bladder 24 , in which case flexible tubes 28 , 29 may extend into bladder 24 and through urinary sphincter 22 through a hole formed in the bladder . in this case , housing 26 may be surgically or laparoscopically implanted within the abdomen . tube 28 may be surgically or laparoscopically guided through a hole in the wall of bladder 24 . a cystoscope may be used to grab tube 28 and pull it downward through urinary sphincter 22 and urethra 20 . in some embodiments , housing 26 and its contents may be integrated with stimulator 14 , in which case flexible tube 28 extends from the stimulator housing and into bladder 24 , much like leads carrying stimulation or sense electrodes . with further reference to fig1 , implantable stimulator 14 includes an electrical lead 15 ( partially shown in fig1 ) carrying one or more electrodes that are placed at a nerve site within the pelvic floor . for example , the electrodes may be positioned to stimulate the sacral nerve and thereby innervate urinary sphincter 22 . in particular , electrical stimulation may be applied to cause urinary sphincter 22 to increase closing pressure to avoid involuntary leakage from bladder 24 . alternatively , if voluntary voiding is desired by patient 18 , electrical stimulation can be suspended or reduced to reduce the closing pressure exerted by urinary sphincter 22 on urethra 20 at the bladder neck . for spinal cord injury patients who cannot perceive a sensation of bladder fullness , sphincter pressure sensed by pressure sensor 12 may be transmitted to external programmer 16 , with or without an accompanying stimulator 14 , to advise the patient when urinary sphincter pressure is high , indicating bladder fullness . in this case , the advice may be in the form of a audible , visual or vibratory stimulus . in response to the advice , the spinal cord injury patient is able to catheterize the urethra 20 and bladder 24 to voluntarily relieve urine . implantable stimulator 14 delivers stimulation therapy to the sacral nerve in order to keep the sphincter 22 constricted and keep contents of bladder 24 from leaking out through urethra 20 . at predetermined times , or at patient controlled instances , the external programmer 16 may program stimulator 14 to interrupt the stimulation to allow the sphincter to relax , thus permitting voiding of bladder 24 . upon completion of the voiding event , external programmer 16 may program stimulator 14 to resume stimulation therapy and thereby maintain closure of urinary sphincter 22 . in this manner , implantable stimulator 14 delivers stimulation therapy to the sacral nerve in order to keep the sphincter 22 constricted and keep contents of bladder 24 from leaking out through urethra 20 . at predetermined times or at patient controlled instances , the external programmer 16 may program stimulator 14 to interrupt the stimulation to allow the sphincter to relax , thus permitting voiding of bladder 24 . upon completion of the voiding event , external programmer 16 may program stimulator 14 to resume stimulation therapy and thereby maintain closure of urinary sphincter 22 . in addition , adjustment of stimulation parameters may be responsive to pressure information transmitted by implantable pressure sensor 12 . for example , external programmer 16 or implantable stimulator 14 may adjust stimulation parameters , such as amplitude , pulse width , and pulse rate , based on pressure information received from implantable sensor 12 . in this manner , implantable stimulator 14 adjusts stimulation to either increase or reduce urinary sphincter pressure based on the actual pressure level exerted by urinary sphincter 22 . pressure sensor 12 may transmit pressure information periodically , e . g ., every few seconds , minutes or hours . in some embodiments , pressure sensor 12 may transmit pressure information when there is an abrupt change in sphincter pressure , e . g ., a pressure change that exceeds a predetermined threshold . in addition to parameter adjustments , or alternatively , adjustment may involve on and off cycling of the stimulation in response to pressure levels indicative of a particular bladder fill stage . for example , stimulation may be turned off until the pressure level exceeds a threshold indicative of a particular fill stage of the bladder , at which time stimulation is turned on . then , stimulation parameters may be further adjusted as the sensed pressure level changes . external programmer 16 may be a small , battery - powered , portable device that accompanies the patient 18 throughout a daily routine . programmer 16 may have a simple user interface , such as a button or keypad , and a display or lights . patient 18 may initiate a voiding event , i . e ., a voluntary voiding of bladder 24 , via the user interface . in some embodiments , the length of time for a voiding event may be determined by pressing and holding down a button for the duration of a voiding event , pressing a button a first time to initiate voiding and a second time when voiding is complete , or by a predetermined length of time permitted by programmer 16 or implantable stimulator 14 . in each case , programmer 16 causes implantable stimulator 14 to temporarily terminate stimulation so that voluntary voiding is possible . in some embodiments , stimulator 14 may immediately recommence stimulation upon completion of a voiding event , and thereafter adjust stimulation parameters based on pressure information generated by implantable sensor 12 . alternatively , stimulator 14 may terminate stimulation upon initiation of a voiding event , and recommence stimulation only after implantable pressure sensor 12 measures a decrease of pressure in the urethra 20 that corresponds to bladder 24 being empty . as a further alternative , following completion of the voiding event , stimulator 14 may wait to recommence stimulation until pressure sensor 12 detects generation of an inadequate pressure level by urinary sphincter 22 , which could result in involuntary leakage . in this case , stimulator 14 recommences stimulation to enhance urinary sphincter pressure . implantable stimulator 14 may be constructed with a biocompatible housing , such as titanium or stainless steel , or a polymeric material such as silicone or polyurethane , and surgically implanted at a site in patient 18 near the pelvis . the implantation site may be a subcutaneous location in the side of the lower abdomen or the side of the lower back . one or more electrical stimulation leads 15 are connected to implantable stimulator 14 and surgically or percutaneously tunneled to place one or more electrodes carried by a distal end of the lead at a desired nerve site , such as a sacral nerve site within the sacrum . in the example of fig1 and 2 , sensor housing 26 of implantable pressure sensor 12 is attached to the inner wall 27 of bladder 24 near bladder neck 23 . however , the attachment site for sensor housing 26 could be anywhere with access to urinary sphincter 22 . with a relatively long flexible tube 28 , for example , sensor housing 26 could be positioned at a greater distance from bladder neck 23 . also , in some embodiments , sensor housing 26 could be attached within urethra 20 , e . g ., downstream from urinary sphincter 22 , although attachment of the sensor housing within bladder 24 may be desirable to avoid possible obstruction of the urethra . fig3 is an enlarged , cross - sectional side view of the implantable pressure sensor 12 of fig1 and 2 . fig3 is a conceptual illustration . as shown in fig3 , sensor housing 26 receives an open end 34 of flexible tube 28 . a sensing element 36 is mounted within sensor housing 26 , at open end 34 , to sense a pressure level within fluid tube 28 . sensing element 34 may be coupled to a circuit board 38 within sensor housing 26 . in some embodiments , sensing element 34 may be implemented as a conventional strain gauge sensor . the strain gauge sensor may be formed by thin film deposition on a flexible membrane . circuit board 38 may include processing electronics to process signals generated by sensing element 34 , and generate pressure information based on the signals . in addition , circuit board 38 may include telemetry circuitry for wireless telemetry with stimulator 14 , external programmer 16 , or both . sensor housing 26 may be made from a biocompatible material such as titanium , stainless steel or nitinol , or a polymeric material such as silicone or polyurethane . another material for fabrication of sensor housing 26 is a two - part epoxy . an example of a suitable epoxy is a two - part medical implant epoxy manufactured by epoxy technology , inc ., mixed in a ratio of 10 grams of resin to one gram of activator . in general , sensor housing 26 contains no external openings , with the exception of the opening to receive flexible tube 28 , thereby protecting sensing element 26 and circuit board 38 from the environment within bladder 24 . the proximal , open end 34 of flexible tube 28 resides within sensor housing 26 while the distal , closed end 32 resides outside of the sensor housing . the opening in sensor housing 26 that receives open end 34 of flexible tube 28 may be sealed to prevent exposure of interior components . flexible tube 28 may be formed from a variety of flexible materials , including polyurethane or silicone . the flexibility of tube 28 permits it to conform to contours within bladder neck 23 , and deform in response to pressure exerted urethra 20 by urinary sphincter 22 at bladder neck 23 . in particular , urinary sphincter 22 exerts pressure inward against the outer wall of urethra 20 . in turn , the inner wall of urethra 20 exerts pressure inward against the outer wall of flexible tube 28 , causing the wall of the tube to deform and compress inward . in some embodiments , flexible tube 28 may be coated to avoid calcification . inward deformation of flexible tube 28 causes an elevation in the internal pressure of the tube . sensing element 36 senses the elevation in pressure at open end 34 of flexible tube 28 , and generates a pressure signal that represents the pressure level . although end 34 is referred to as “ open ,” it is sealed by sensing element 34 . consequently , deformation of flexible tube 28 causes volumetric changes in the tube , and hence pressure changes in the fluid 30 within the tube . electronics on circuit board 38 generate pressure information based on the pressure signal . the pressure information can be used to evaluate the pressure level exerted by urinary sphincter 22 . the fluid 30 contained within flexible tube 28 may be a liquid or gas , or a combination of liquid and gas . for example , flexible tube 28 could be filled with saline , distilled water , oxygen , air , or any other biocompatible fluid . preferably , the fluid 30 within flexible tube 28 is generally non - compressible . fluid 30 tends to exhibit an elevation in pressure as the wall of tube 28 is deformed during constriction of urinary sphincter 22 . conversely , fluid 30 exhibits a reduction in pressure as urinary sphincter 22 relaxes . in each case , the pressure level is transduced by sensing element 36 . flexible tube 28 may be provided with different dimensions selected for patients having different anatomical dimensions . in particular , implantable pressure sensor 12 may be constructed with a flexible tube 28 having different lengths of diameters . different tube lengths may be necessary given the distance between the attachment site of sensor housing 26 and urinary sphincter 22 , either to ensure that flexible tube 28 reaches the sphincter or does not extend too far down urethra 20 . multiple diameters may also be necessary to allow a dysfunctional sphincter 22 to close completely or to allow fluid - filled tube 28 to be placed into a narrow urethra 20 . the dimensions may be fixed for a given pressure sensor 12 , as a complete assembly . alternatively , fluid tubes of different sizes may be attached to a pressure sensor housing 26 by a physician prior to implantation . in general , for male patients , flexible tube 28 may have a length of less than approximately 9 cm and more preferably less than approximately 7 cm . for female patients , flexible tube 28 may have a length of less than approximately 7 cm and more preferably less than approximately 5 cm . in some embodiments , flexible tube 28 may have a length of approximately 0 . 5 cm to 3 cm . the length of tube 28 may vary according to the anatomy of the patient , and may vary between male , female and pediatric patients . in addition , tube 28 may have an outer diameter in a range of approximately 1 to 3 mm . the wall of tube 28 may be relatively thin to ensure sufficient deformation and conformability , yet thick enough to ensure structural integrity . as an example , the thickness of the wall of tube 28 may be in a range of approximately 0 . 1 mm to 0 . 3 mm . sensing element 36 , in some embodiments , may be constructed as a membrane that carries a resistive strain gauge or piezoelectric element selected to be effective as a pressure transducer . upon deformation of the membrane , in response to pressure levels within flexible tube 28 , sensing element 36 produces an electrical signal . when sphincter 22 closes , the flexible tube 28 deforms and the pressure inside the tube increases . the higher pressure forces membrane in sensing element 36 to deform , thus producing an electrical signal change and enabling implanted pressure sensor 12 to measure sphincter closing pressure . attaching implantable pressure sensor 12 to the mucosal lining of bladder 24 may be accomplished in a variety of ways , but preferably is completed in a manner that will not excessively injure bladder 24 or otherwise cause excessive trauma during implantation . preferably , attachment should cause limited inflammation and substantially no adverse physiological modification , such as tissue infection or a loss in structural integrity of bladder 24 . however , it is desirable that implantable pressure sensor 12 also be attached securely to the attachment site in order to provide an extended period of measurement without prematurely loosening or detaching from the intended location . as an example , sensor housing 26 may contain a vacuum cavity 39 that permits a vacuum to be drawn by a vacuum channel 40 . the vacuum is created by a deployment device having a vacuum line in communication with vacuum channel 40 . the vacuum draws a portion 42 of the mucosal lining 44 of bladder 24 into vacuum cavity 39 . once the portion 42 of mucosal lining 44 is captured within vacuum cavity 39 , a fastening pin 46 is driven into the captured tissue to attach sensor housing 26 within bladder 24 . fastening pin 46 may be made from , for example , stainless steel , titanium , nitinol , or a high density polymer . the shaft of pin 46 may be smooth or rough , and the tip may be a sharp point to allow for easy penetration into tissue . fastening pin 46 may be driven into housing 26 and the portion 42 of mucosal lining 44 under pressure , or upon actuation by a push rod , administered by a deployment device . in some embodiments , fastening pin 46 may be manufactured from a degradable material that the breaks down over time , e . g . in the presence of urine , to release implantable pressure sensor 12 within a desired time period after attachment . in still another embodiment , implantable pressure sensor 12 may be attached without the use of a penetrating rod but with a spring - loaded clip to pinch trapped mucosal lining 44 within cavity 39 . a variety of other attachment mechanisms , such as pins , clips , barbs , sutures , helical screws , surgical adhesives , and the like may be used to attach sensor housing 26 to mucosal lining 44 of bladder 24 . fig4 is a schematic diagram illustrating placement of an implantable pressure sensor 12 with a flexible tube 28 extending through the urinary sphincter 22 of a patient 18 . in the example of fig4 , flexible tube 28 leaves bladder 24 through bladder neck 23 and passes through internal urinary sphincter 22 as it enters urethra 20 . in general , sphincter 22 is an annulus shaped muscle that surrounds the portion of urethra 20 below bladder neck 23 and constricts to make the urethral walls meet and thereby close urethra 20 to prevent involuntary urine leakage from bladder 24 . upon constriction of sphincter 22 , the walls of urethra 20 close onto flexible tube 28 to increase the internal pressure of the tube , which provides a direct measurement of the closing pressure of sphincter 22 . because tube 28 has a circular cross - section and a small diameter , a closed sphincter 22 will still be able to substantially seal urethra 20 around tube 122 . when sphincter 22 is relaxed , in some embodiments , implantable pressure sensor 12 may be used to measure the pressure of fluid in urethra 20 . the open sphincter 22 allows urine to be passed out of the urethra and patient 18 . flexible tube 28 is under the same pressure as the urethra and can allow implantable pressure sensor 12 to measure this urethral pressure . this may allow monitoring of urinary dysfunctions due to pressure during voiding events and may also be used by implantable stimulator 14 to detect the end of a voiding event by measuring decrease of urethral pressure as an indication of reduced urine flow . as shown in fig4 , the placement of tube 28 does not significantly interfere with normal bladder function . bladder function is unimpaired and fluid flow to urethra 20 can occur normally , as tube 28 allows enough room for urine to pass and exit bladder 24 via urethra 20 . due to varying sizes and shapes of patient anatomy , tube 28 may be manufactured in a variety of lengths and diameters . fig5 is functional block diagram illustrating various components of an exemplary implantable pressure sensor 12 . in the example of fig5 , implantable pressure sensor 12 includes a sensing element 36 , processor 48 , memory 50 , telemetry interface 52 , and power source 54 . sensor 36 transforms mechanical deformation from tube 28 into electrical signals representative of closing pressure of urinary sphincter 22 . the electrical signals may be amplified , filtered , and otherwise processed as appropriate by electronics within sensor 12 , or circuitry associated with the sensor . in some embodiments , the signals may be converted to digital values and processed by processor 48 before being saved to memory 50 or sent to implantable stimulator 14 as pressure information via telemetry interface 52 . memory 50 stores instructions for execution by processor 48 and pressure information generated by sensing element 36 . pressure data may then be sent to implantable stimulator 14 or external programmer 16 for long - term storage and retrieval by a user . memory 50 may include separate memories for storing instructions and pressure information . in addition , processor 48 and memory 50 may implement loop recorder functionality in which processor 48 overwrites the oldest contents within the memory with new data as storage limits are met , thereby conserving data storage resources within pressure sensor 12 . processor 48 controls telemetry interface 52 to send pressure information to implantable stimulator 14 or programmer 16 on a continuous basis , at periodic intervals , or upon request from the implantable stimulator or programmer . wireless telemetry may be accomplished by radio frequency ( rf ) communication or proximal inductive interaction of pressure sensor 12 with programmer 16 . power source 54 delivers operating power to the components of implantable pressure sensor 12 . power source 54 may include a battery and a power generation circuit to produce the operating power . in some embodiments , the battery may be rechargeable to allow extended operation recharging may be accomplished through proximal inductive interaction between an external charger and an inductive charging coil within sensor 12 . in some embodiments , power requirements may be small enough to allow sensor 12 to utilize patient motion and implement a kinetic energy - scavenging device to trickle charge a rechargeable battery . in other embodiments , traditional batteries may be used for a limited period of time . as a further alternative , an external inductive power supply could transcutaneously power sensor 12 whenever pressure measurements are needed or desired . fig6 is a functional block diagram illustrating various components of an implantable stimulator 14 . in the example of fig6 , stimulator 14 includes a processor 56 , memory 58 , stimulation pulse generator 60 , telemetry interface 62 , and power source 64 . memory 58 stores instructions for execution by processor 56 , stimulation therapy data , and pressure information received from pressure sensor 12 via telemetry interface . pressure information is received from pressure sensor 12 and may be recorded for long - term storage and retrieval by a user , or adjustment of stimulation parameters , such as amplitude , pulse width or pulse rate . memory 58 may include separate memories for storing instructions , stimulation parameter sets , and pressure information . processor 56 controls stimulation pulse generator 60 to deliver electrical stimulation therapy and telemetry interface 62 to send and receive information . an exemplary range of neurostimulation stimulation pulse parameters likely to be effective in treating incontinence , e . g ., when applied to the sacral or pudendal nerves , are as follows : 1 . frequency : between approximately 0 . 5 hz and 500 hz , more preferably between approximately 5 hz and 250 hz , and still more preferably between approximately 10 hz and 50 hz . 2 . amplitude : between approximately 0 . 1 volts and 50 volts , more preferably between approximately 0 . 5 volts and 20 volts , and still more preferably between approximately 1 volt and 10 volts . 3 . pulse width : between about 10 microseconds and 5000 microseconds , more preferably between approximately 100 microseconds and 1000 microseconds , and still more preferably between approximately 180 microseconds and 450 microseconds . based on pressure information received from sensor 12 , processor 56 interprets the information and determines whether any therapy parameter adjustments should be made . for example , processor 56 may compare the pressure level to one or more thresholds , and then take action to adjust stimulation parameters based on the pressure level . information may be received from sensor 12 on a continuous basis , at periodic intervals , or upon request from stimulator 14 or external programmer 16 . alternatively , or additionally , pressure sensor 12 may transmit pressure information when there is an abrupt change in the pressure level , e . g ., at the onset of involuntary leakage . processor 56 modifies parameter values stored in memory 58 in response to pressure information from sensor 12 , either independently or in response to programming changes from external programmer 16 . stimulation pulse generator 60 provides electrical stimulation according to the stored parameter values via a lead 15 implanted proximate to a nerve , such as a sacral nerve . processor 56 determines any parameter adjustments based on the pressure information obtained form sensor 12 , and loads the adjustments into memory 58 for use in delivery of stimulation . as an example , if the pressure information indicates an inadequate sphincter closing pressure , processor 56 may increase the amplitude , pulse width or pulse rate of the electrical stimulation applied by stimulation pulse generator 60 to increase stimulation intensity , and thereby increase sphincter closing pressure . if sphincter closing pressure is adequate , processor 56 may implement a cycle of downward adjustments in stimulation intensity until sphincter closing pressure becomes inadequate , and then incrementally increase the stimulation upward until closing pressure is again adequate . in this way , processor 56 converges toward an optimum level of stimulation . although processor 56 is described in this example as adjusting stimulation parameters , it is noted that the adjustments alternatively may be generated by external programmer 16 and transmitted to stimulator 14 as parameter or program changes . the adequacy of closing pressure is determined by reference to the pressure information obtained from sensor 12 . sphincter pressure may change due to a variety of factors , such as an activity type , activity level or posture of the patient 18 . hence , for a given set of stimulation parameters , the efficacy of stimulation may vary in terms of sphincter pressure , due to changes in the physiological condition of the patient . for this reason , the continuous or periodic availability of pressure information from implantable sensor 12 is highly desirable . with this pressure information , stimulator 14 is able to respond to changes in sphincter pressure with dynamic adjustments in the stimulation parameters delivered to the patient 18 . in particular , processor 56 is able to adjust parameters in order to cause constriction of sphincter 22 and thereby avoid involuntary leakage . in some cases , the adjustment may be nearly instantaneous , yet prevent leakage . as an example , if patient 18 laughs , coughs , or bends over , the resulting force on bladder 24 could overcome the closing pressure of urinary sphincter 22 . if pressure sensor 12 indicates an abrupt change in sphincter pressure , however , stimulator 14 can quickly respond by more vigorously stimulating the sacral nerves to increase sphincter closing pressure . in general , if sphincter 22 is not constricting enough to effectively close urethra 20 , processor 56 may dynamically increase the level of therapy to be delivered . conversely , if sphincter 22 is consistently achieving effective constriction , processor 56 may incrementally reduce stimulation , e . g ., to conserve power resources . as in the case of sensor 12 , wireless telemetry in stimulator 14 may be accomplished by radio frequency ( rf ) communication or proximal inductive interaction of pressure stimulator 14 with implantable pressure sensor 12 or external programmer 16 . accordingly , telemetry interface 62 may be similar to telemetry interface 52 . also , power source 64 of stimulator 14 may be constructed somewhat similarly to power source 54 . for example , power source 64 may be a rechargeable or non - rechargeable battery , or alternatively take the form of a transcutaneous inductive power interface . fig7 is a schematic diagram illustrating cystoscopic deployment of an implantable pressure sensor 12 via the urethra 20 using a deployment device 66 . pressure sensor 12 may be surgically implanted . however , cystoscopic implantation via urethra is generally more desirable in terms of patient trauma , recovery time , and infection risk . pressure sensors 12 may be implanted in a variety of ways , using a variety of different deployment and attachment structures . accordingly , the embodiment depicted in fig7 is exemplary and not limiting of the invention as broadly embodied herein . in the example of fig7 , deployment device 66 includes a distal head 68 , a delivery sheath 69 and a control handle 70 . deployment device 66 may be manufactured from disposable materials for single use applications or more durable materials for multiple applications capable of withstanding sterilization between patients . as shown in fig7 , distal head 68 includes a cavity that retains sensor housing 26 of implantable pressure sensor 12 for delivery to a desired attachment site within bladder 24 . sensor housing 26 may be held within cavity 72 by a friction fit , vacuum pressure , or a mechanical attachment . in each case , once distal head 68 reaches the attachment site , sensor housing 26 may be detached . sheath 69 is attached to distal head 68 and is steerable to navigate urethra 20 and guide the distal head into position . in some embodiments , sheath 69 and distal head 68 may include cystoscopic viewing components to permit visualization of the attachment site . in other cases , external visualization techniques such as ultrasound may be used . sheath 68 may include one or more steering mechanisms , such as wires , shape memory components , or the like , to permit the distal region adjacent distal head 68 to turn abruptly for access to the mucosal lining of bladder 24 . a control handle 70 is attached to sheath 69 to aid the physician in manually maneuvering deployment device 66 throughout urethra 20 and bladder 24 . control handle 70 may have a one or more controls that enable the physician to contort sheath 69 and allow for deployment device 66 to attach pressure sensor housing 26 to the mucosal lining of bladder 24 and then release the sensor housing to complete implantation . in other embodiments , pressure sensor housing 26 may be attached sub - mucosally to the muscle wall of bladder 24 for more secure attachment . a vacuum source 74 supplies negative pressure to a vacuum line within sheath 69 to draw tissue into the vacuum cavity defined by sensor housing 66 . a positive pressure source 76 supplies positive pressure to a drive a fastening pin into the tissue captured in the vacuum cavity . deployment device 66 enters patient urethra 20 to deliver pressure sensor 12 and implant it within bladder 24 . first , the physician must guide distal head 68 through the opening of urethra 20 in patient 18 . second , distal head 68 continues to glide up urethra 20 and past the relaxed internal sphincter 22 . distal head 300 is then pushed through bladder neck 23 and into bladder 24 , for access to an appropriate site to attach pressure sensor 12 . using actuators built into control handle 70 , sheath 69 is bent to angle distal head 68 into position . again , sheath 69 may be steered using control wires , shape memory alloys or the like . as pressure sensor 12 is guided into place against the mucosal wall 44 of bladder 24 , a physician actuates control handle 70 to attach sensor 12 to mucosal wall 44 and then release the attached sensor . upon attachment , pressure sensor 12 is implanted within bladder 24 of patient 18 and deployment device 66 is free to exit the bladder . exemplary methods for attachment and release of sensor 12 , including the use of both vacuum pressure and positive pressure , will be described in greater detail below . although fig7 depicts cystoscopic deployment of pressure sensor 12 , surgical or laparoscopic implantation techniques alternatively may be used . fig8 is a schematic diagram illustrating retraction of deployment device 66 upon fixation of pressure sensor 12 within the urinary tract of patient 18 . once the sensor 12 is released , flexible tube 28 remains attached to sensor housing 26 . during removal of deployment device 66 , tube 28 maintains its position within bladder neck 23 adjacent sphincter 22 . as deployment device 66 is removed , tube 28 passes through a guide channel formed in the deployment device . the guide channel ensures that flexible tube 28 remains pinned between distal head 68 and the wall of bladder 24 . as distal head 68 slides through sphincter 22 and urethra 20 , however , flexible tube 28 releases from deployment device 66 and is left in place within the urethra in the region proximate urinary sphincter 22 . deployment device 66 may then be completely withdrawn past the external urinary sphincter and out of the remainder of urethra 20 . in the example of fig8 , flexible tube 28 is suspended by device housing 26 , which is attached to mucosal wall 44 , and is held in place by pressure exerted against the urethral wall by urinary sphincter 22 . in other embodiments , tube 28 may be kept in place using other techniques such as actively fixing tube 28 to the side of urethra 20 , e . g ., with sutures or other anchor mechanisms . in one embodiment , sheath 69 and distal head 68 may be disposable . disposable devices that come into contact with patient 18 tissues and fluids greatly decrease the possibility of infection in implantable devices . control handle 70 does not come into contact with body fluids of patient 18 and may be used for multiple patients . in another embodiment , the entire deployment device 66 may be manufactured out of robust materials intended for multiple uses . the device would then need to be sterilizable between uses . in still a further embodiment , the features of distal head 68 may be incorporated into pressure sensor 12 . in this configuration , pressure sensor 12 may be larger in size but would include the necessary elements for attachment within the device . after attachment , the entire sensor would detach from sheath 69 , making removal of deployment device 66 easier on patient 18 . after the useful life of implantable pressure sensor 12 is complete or it is no longer needed within patient 18 , it can be removed from patient 18 in some manner . as an example , deployment device 66 may be reinserted into patient 18 , navigated into bladder 24 , and reattached to pressure sensor 12 . deployment device 66 may then be withdrawn from the bladder 24 and urethra 20 , explanting sensor 12 , including housing 26 and flexible tube 28 , from patient 18 . in another embodiment , as mentioned with respect to fig3 , the attachment method of pressure sensor 12 to bladder 24 may involve degradable materials , such as a biodegradable fixation pin . after a certain period of time exposed to urine in the bladder 24 , the fixation material may structurally degrade and allow pressure sensor 12 to be released from the mucosal wall 44 of bladder 24 . in some embodiments , sensor 12 may be sized sufficiently small to follow urine out of the bladder , urethra , and body during a voiding event . in other embodiments , sensor housing 26 or tube 28 may carry a suture - like loop that can be hooked by a catheter with a hooking element to withdraw the entire assembly from patient 18 via urethra 20 . in still further embodiments , such a loop may be long enough to extend out of the urethra , so that the loop can be grabbed with an external device or the human hand to pull the sensor 12 out of the patient . fig9 is a cross - sectional side view of distal head 68 of deployment device 66 during deployment and fixation of pressure sensor 12 . in the example of fig9 , distal head 68 receives a vacuum line 78 and a positive pressure line 80 . vacuum line 78 is coupled to vacuum source 74 via a tube or lumen extending along the length of sheath 69 . similarly , positive pressure line 80 is coupled to positive pressure source 76 via a tube or lumen extending along the length of sheath 69 . vacuum line 78 is in fluid communication with vacuum cavity 39 , and permits the physician to draw a vacuum and thereby capture a portion 42 of mucosal lining 44 within the vacuum cavity . positive pressure line 80 permits the physician to apply a pulse of high pressure fluid , such as a liquid or a gas , to drive fixation pin 46 into sensor housing 26 and through the portion 42 of mucosal lining 44 . pin 46 thereby fixes sensor housing 26 to mucosal lining 44 . in some embodiments , a membrane mounted over an opening of positive pressure line 80 may be punctured by pin 46 . flexible tube 28 resides within a channel of sheath 69 prior to detachment or sensor 12 from distal head 68 . once fixation pin 46 attaches sensor 12 to bladder 24 , vacuum line 78 is no longer needed . however , in some embodiments , vacuum line 78 may be used to detach pressure sensor 12 from distal head 68 of deployment device 66 . by terminating vacuum pressure , or briefly applying positive pressure through vacuum line 78 , for example , head 68 may separate from sensor 12 due to the force of the air pressure . in this manner , vacuum line 78 may aid in detachment of sensor 12 prior to withdrawal of deployment device 66 . as described previously in fig3 , fixation pin 46 punctures mucosal lining 44 for fixation of sensor 12 . while the force of this fixation may vary with patient 18 , deployment device 66 provides adequate force for delivery of pin 46 . in an exemplary embodiment , positive pressure line 80 is completely sealed and filled with a biocompatible fluid ( such as water , saline solution or air ). sealing the end of positive pressure line 80 is a head 82 on fixation pin 46 . head 82 is generally able to move within positive pressure line 80 much like a piston . force to push fixation pin 46 through the portion 42 of mucosal lining 44 captured in vacuum cavity 39 is created by application of a pulse of increased fluid pressure within positive pressure line 80 . for example , the physician may control positive pressure source 76 via control handle 70 . this simple delivery method may provide high levels of force , allow multiple curves and bends in sheath 69 , and enable a positive pressure line 80 of many shapes and sizes . in an alternative embodiment , a flexible , but generally incompressible , wire may be placed within positive pressure line 80 and used as a push rod to force fixation pin 46 through the captured portion 42 of mucosal lining 44 . this wire presents compressive force from control handle 70 directly to the head 82 of fixation nail 46 . this method may eliminate any safety risk of pressurized fluids entering patient 18 or , in some embodiments , permit refraction of pin 46 after an unsuccessful fixation attempt . the flexible wire may be attached to pin 46 and pulled back to remove the pin from capture mucosal tissue 42 . the flexible wire may be sheared from fixation nail 46 for detachment purposes as distal head 68 releases sensor 12 . this detachment may be facilitated by a shearing element or low shear stress of the wire . in fig9 , deployment device 66 illustrates flexible tube 28 on the same end of housing 26 as sheath 69 , while the fixation structures are located in the opposite , or distal end of distal head 68 . in some embodiments , it may be necessary for pressure sensor 12 to be deployed with tube 28 located at the distal end of head 68 and the fixation structures located near sheath 69 . in still other embodiments , the fixation structures and tube 28 may be located on the same end of pressure sensor 12 . in some embodiments , deployment device 66 may include a small endoscopic camera in the distal head 68 . the camera may enable the physician to better guide deployment device 66 through urethra 20 , past sphincter 22 , and to a desired attachment location of bladder 24 in less time with more accuracy . images may be displayed using video fed to a display monitor . fig1 is a cross - sectional bottom view of the deployment device 66 of fig1 before attachment of pressure sensor 12 . as shown in fig1 , distal head 68 includes proximal tube channel 84 to accommodate flexible tube 28 during placement of sensor 12 and distal tube channel 86 to accommodate the flexible tube during retraction of deployment device 66 . in addition , sheath 69 includes a sheath channel 88 to accommodate flexible tube 28 . channels 84 , 86 , 88 serve to retain tube 28 during delivery of sensor 12 to an attachment site . distal head 68 is rounded on both sides at the distal end to permit easier entry of deployment device into areas of patient 18 . head 68 may also be lubricated before delivery to facilitate ease of navigation . on the proximal end of head 68 , proximal tube channel 84 runs through the head for unimpeded removal of tube 28 during detachment of pressure sensor 12 . this channel may be u - shaped , e . g ., closed on 3 sides . in some embodiments , proximal tube channel 84 may be an enclosed hole in which tube 28 resides and glides through upon deployment device 30 removal . sheath channel 88 is formed within sheath 69 to allow tube 28 to stay in place during delivery of pressure sensor 12 . in this embodiment , tube 28 is only partially retained within channel 88 . in some embodiments , sheath channel 88 may be deeper to allow tube 28 to lie completely within sheath 69 , whereas others may include a completely enclosed channel that tube 28 must glide out of after attachment . distal channel 86 in distal end of head housing 68 is not used by tube 28 before attachment . the purpose of this open channel is to allow tube 28 to glide through it while head 68 is removed from bladder 24 . as head 68 slides back past pressure sensor 12 , tube 28 will slide through channel 86 and head housing 68 will keep tube 28 between the wall of bladder 24 and head 68 until head 68 has been removed beyond sphincter 22 . tube 28 may then be ensured correct placemnet through sphincter 22 . some embodiments of tube 28 include multiple length and diameter combinations which would lead to modifications in channels 84 , 86 and 88 . the channels herein may be of different diameters or lengths to properly house tube 28 . one embodiment may include flexible housing channels to accommodate a wide variety of tube 28 dimensions . further embodiments of deployment device 30 may contain modified channel locations in head housing 68 . these locations may be needed to place tube 28 in different locations , particularly at different sphincter sites as in some embodiments . fig1 is a flow chart illustrating a technique for delivery of stimulation therapy based on closed loop feedback from an implantable pressure sensor . in the example of fig1 , implantable stimulator 14 requires information from implantable pressure sensor 12 and external programmer 16 . the flow of events begins with implantable stimulator 14 communicating with implantable pressure sensor 12 and sending a command to sense the pressure of sphincter 22 ( 90 ). in other embodiments , pressure sensor 12 may voluntarily sense pressure on a periodic basis . the pressure sensor 12 subsequently acquires a pressure measurement and delivers the data to implantable stimulator 14 ( 92 ), e . g ., by wireless telemetry . alternatively , the sense data may be transmitted from sensor 12 to external programmer 16 . upon receiving the pressure data , implantable stimulator 14 calibrates the data and compares it to a determined minimum pressure threshold ( 94 ). if the measured pressure is higher than the threshold , the loop begins again . if the pressure is lower than the threshold , the flow continues to the next step of stimulation . stimulator 14 and programmer 16 may receive sense data from sensor 12 in some embodiments . for example , stimulator 14 may react to instantaneous changes in pressure level , while programmer 16 may react to changes in pressure level over a period of time , e . g ., trend data . alternatively , either stimulator 14 or programmer 16 may be configured to react to instantaneous and trending pressure level changes . in some embodiments , implantable stimulator 14 may communicate with external programmer 16 to check if patient 18 has desired to void the contents of bladder 24 ( 96 ). if patient 18 has signaled a voiding event , stimulation is skipped and the process begins again . in the case of no voiding event desired , sphincter 22 is not providing adequate closing pressure and needs to be stimulated . implantable stimulator 14 next performs the necessary tasks to adjust the level of stimulation from stimulation pulse generator 60 ( 98 ), and thereby increase sphincter closing pressure . stimulator 14 concludes the loop by delivering electric stimulation therapy to the nerve that innervates sphincter 22 ( 100 ). after stimulation therapy has commenced , the loop begins again to continue appropriate therapy to patient 18 . in some embodiments , pressure sensor 12 may be used exclusively for monitoring pressure without providing feedback for stimulation therapy . in this case , the process represented in fig1 would be much simpler and only include collecting data and sending it to an external programmer ( 90 and 92 ). pressure may be measured continuously , intermittently or at the request of external programmer 16 . these embodiments may be used for disease diagnosis or condition monitoring and may provide a patient to avoid frequent clinic visits and uncomfortable procedures . in some embodiments , the pressure measurements may form part of an automated voiding diary that records voluntary voiding events , involuntary voiding events , and urinary sphincter and urethral pressure levels prior to , contemporaneous with , of after such an event . although the invention may be especially applicable to sensing urinary sphincter pressure , the invention alternatively may be applied more generally to other sphincters within the patient , such as the lower esophageal sphincter ( les ) or pyloric sphincter . in addition , in those instances , the invention may be adapted to support electrical stimulation of other body organs , such as the stomach or intestines , e . g ., for treatment of obesity or gastric mobility disorders . not only may stimulation of certain nerves allow for the proper closure of a sphincter , but nerve stimulation may be able to modify stomach contractions or intestinal contractions based upon pressure measurements at those sites . pressure feedback from the implantable pressure sensor may provide the most effective therapy for some patients , e . g ., in the form of biofeedback that aids the patient in self - regulating bladder control . also , the invention need not be limited to neurostimulation , and may be applied to stimulate other tissue , including muscle tissue . various embodiments of the described invention may include processors that are realized by microprocessors , application - specific integrated circuits ( asic ), field - programmable gate arrays ( fpga ), or other equivalent integrated or discrete logic circuitry . the processor may also utilize several different types of data storage media to store computer - readable instructions for device operation . these memory and storage media types may include any form of computer - readable media such as magnetic or optical tape or disks , solid state volatile or non - voltatile memory , including random access memory ( ram ), read only memory ( rom ), electronically programmable memory ( eprom or eeprom ), or flash memory . each storage option may be chosen depending on the embodiment of the invention . while the implantable stimulator and implantable pressure sensor ordinarily will contain permanent memory , a patient or clinician programmer may contain a more portable removable memory type to enable easy data transfer for offline data analysis . many embodiments of the invention have been described . various modifications may be made without departing from the scope of the claims . for example , although the invention has been generally described in conjunction with implantable neurostimulation devices , a flexible tube sensor may also be used with other implantable medical devices , such as electrical muscle stimulation devices , functional electrical stimulation ( fes ) devices , and implantable drug delivery devices , each of which may be configured to treat incontinence or other conditions or disorders . these and other embodiments are within the scope of the following claims .

the disclosure describes a therapeutic sphincter control system with a fluid tube pressure sensor . the system senses sphincter pressure and sends the information to a stimulator that is capable of stimulation therapy to control sphincter contractility , thus reducing unwanted urinary incontinence . measuring sphincter pressure is accomplished through the use of a fluid - filled tube placed through the sphincter and attached to a module implanted within the bladder . pressure within the tube is transduced to generate an electrical signal that is sent wirelessly to an implanted stimulator connected to a lead positioned near pelvic floor nerves . an external device may be used to wirelessly send information to the implanted stimulator and inhibit stimulation in order for the patient to empty the bladder . pressure information and stimulation information may be recorded and reviewed for continued patient monitoring . in addition , the system may only include the pressure sensor to monitor patient pressure information .

while the present invention is susceptible of embodiments of various forms , there is shown in the drawings , and will hereinafter be described some exemplary and non - limiting embodiments , with the understanding that the present disclosure is to be considered an exemplification of the invention . it is not intended to limit the invention to the specific embodiments listed . as can be seen in fig1 - 7 , in one embodiment of the present invention , a fixator 10 comprises a rail 12 , at least one clamp system 14 , and a pin 16 . generally , the clamp system 14 is configured to attach to both the rail 12 and the pin 16 , which is connected to the bone 40 for fixation and stabilization . the fixator 10 may further include compression and distraction nuts 18 functionally connected to the fixator 10 to allow for additional manipulation of bone healing and growth . the clamp systems 14 can be splined to receive and hold rails 12 and pins 16 . the rails 12 may be any size or shape , and persons of skill in the art will recognize that different application require rails 12 of many differing sizes or shapes , all of which are contemplated herein . the rails 12 may , for example , have a circular , oblong , square , rectangular , or other - shaped cross section . typically , however , the rails 12 have a round or circular cross - section and are sized in a manner suitable for fixation of small bones 41 , such as those of the foot or hand . the rails 12 may be composed of many materials including , for example , carbon fiber or high density plastic , which allows the rod to be radiolucent . optionally , the rails 12 may also be threaded to allow for attachment of clamp systems 14 , distraction / compression nuts 18 , or other components of a fixator 10 . in one embodiment of the present invention , the rail 12 has a “ negative ” thread pattern , in which the threads 22 are grooves in the surface of the rail 12 rather than protrusions . in this specification , reference to a threaded component will be a disclosure of both a positive and negative thread . the negative thread pattern allows , for example , the clamp system 14 to easily slide up and down the rail 12 , while still allowing for the attachment of compression nuts 18 or other components which could be threaded onto the rail 12 . in such situations , the corresponding component , such as a compression nut 18 , will have a positive thread pattern . in a preferred embodiment , the rail 12 has a thread pitch of approx 1 mm so one revolution of around the threaded rail 12 produces 1 mm of linear movement . in another embodiment , the rail 12 can be geared . in such an embodiment , the rail has a rack and pinion design 20 that allows for compression or distraction . this geared version can have a scale 24 indicating the amount of compression or distraction . as can be seen more specifically in fig6 and 7 , in a preferred embodiment , the clamp system 14 comprises a first clamp area 32 and a second clamp area 42 . preferably , the first clamp area 32 comprises a pin clamp 34 while the second clamp area 42 comprises a rail or bar clamp 44 . preferably , the first clamp area 32 is functionally connected to the second clamp area 42 such that the object held by the different clamp areas , either pins 16 or rails 12 , can lie in different planes . preferably , the first clamp area 32 is a pin clamp 34 that can comprise a pin clamp top 36 , a pin clamp bottom 38 and a first clamp bolt 40 . the pin clamp top 36 and bottom 38 are each configured to allow the first clamp bolt 40 to pass through them . in one embodiment , the first clamp bolt 40 is threaded , and the pin clamp top 36 and pin clamp bottom 38 have internal , threaded holes configured to receive the threaded first clamp bolt 40 . when held by the first clamp bolt 40 , the pin clamp top 36 and bottom 38 can be thought of as a set that together define at least one pin passage 33 capable of receiving the pin 16 . preferably , the pin clamp top and bottom 36 , 38 each have inner surfaces 35 that together define two distinct pin passages 33 each capable of receiving the pin 16 . it is preferred that the inner surfaces 35 of the pin passages 33 be textured to allow for more secure engagement of the pin 16 . for example , the inner surfaces 35 may have a 2 × diamond face with grooves 90 degrees to each other . in addition to the inner surfaces 35 being textured , other surfaces of the pin clamp top and bottom 36 , 38 may be textured where a more secure engagement is desired . in one embodiment , the two distinct pin passages 33 are configured to receive the same size pin 16 . in another embodiment , one pin passage 33 is configured to receive one size pin 16 , for example a half pin , while the other pin passage 33 is configured to receive a second size pin 16 , for example a transfixing pin . it is contemplated that the pin passage 33 will extend in a direction substantially perpendicular to the first clamp bolt 40 . in one embodiment , the pin clamp top and bottom 36 , 38 can be rotated around the first clamp bolt 40 such that the pins 16 can be orientated in any direction in the plane perpendicular to the first clamp bolt 40 . in a preferred embodiment , the first clamp area 32 further comprises another pin clamp 34 or a rail clamp 44 . an example of a first clamp area 32 with at least two pin clamps can be found in fig7 . as can be seen in fig7 , two sets of pin clamp top and bottom clamps 36 , 38 can be arranged proximate each other on the pin clamp bolt 40 . in such a set up , four distinct pin passages 33 , each capable of receiving a pin 16 , can be defined by the pin clamp top and bottoms 36 , 38 . in a preferred embodiment , the first clamp area 32 further comprises springs 46 which are functionally attached to the first clamp area 32 and that exert pressure on some of the pin clamp tops and bottoms 36 , 38 . in such a configuration , the pin clamps 34 can be “ snap in .” that is , one can exert force on the pin clamp top and / or bottom 36 , 38 . when so doing , the pin clamp top and / or bottom 36 , 38 will push against the springs 46 and thereby be in a position that defines an opening 48 leading into the pin passage 33 capable of allowing the pin 16 to be pressed into that pin passage 33 . when the force is released , the springs 46 again exert full pressure on the pin clamp top and / or bottom 36 , 38 , causing the pin clamp top and bottom 36 , 38 set to clamp on the pin 16 and hold it in a fixed position . in addition , a nut 52 can then be tightened to more securely hold the rail 12 or pin 16 in place . in another embodiment , the first clamp area further comprises a rail clamp 44 . the rail clamp 44 comprises a rail clamp top 46 , a rail clamp bottom 47 and a rail clamp bolt 49 . the rail clamp top and bottom 46 , 47 are each configured to allow the rail clamp bolt 49 to pass through them . in one embodiment , the rail clamp bolt 49 is threaded , and the rail clamp top and rail clamp bottom 46 , 47 have internal , threaded holes configured to receive the threaded rail clamp bolt 49 . when held by the rail clamp bolt 49 , the rail clamp top and bottom 46 , 47 can be thought of as a set that together define at least one rail passage 54 capable of receiving the rail 12 . it is contemplated that the inner surfaces 56 of the rail passage 54 can be textured to allow for more secure engagement of the rail 12 . for example , the inner surfaces 56 may have a 2 . times . diamond face with grooves 90 degrees to each other . in addition to the inner surfaces 56 being textured , other surfaces of the rail clamp top and bottom 46 , 47 may be textured where a more secure engagement is desired . as seen in fig5 , the first clamp area 32 can comprise a rail clamp 44 and a pin clamp 34 . in such cases , the rail passage 54 can be in a different plane than the pin passage 33 . the first clamp area 32 can be configured to allow for the rail 12 in the rail passage 54 to be disposed in a different direction than the pin 16 in the pin passage 33 . for example , the pin 16 may extend at an angle generally perpendicular to the bone or bones 41 to be fixed so that it can be anchored in the bone 41 while the rail 12 may extend at an angle generally parallel to the bone or bones 41 to be fixed . in one embodiment , a hinge 60 is attached to the first clamp bolt 40 proximate to either a pin or rail clamp bottom 38 , 47 . in a preferred embodiment , the hinge 60 has a male element 62 and a female element 64 . the use of the terms male and female elements 62 , 64 is not meant to suggest a certain structure , but only to disclose that the two elements are configured to work together to provide a hinged connection . the male element 62 has a first section 66 and a second section 68 that are connected to each other . the first section and the second section 66 , 68 can be disposed at about a 90 degree angle in relation to each other . preferably , the first section 66 is configured to receive the first clamp bolt 40 by having a hole therethrough . the hole may be threaded . it is also preferred that the surface 69 of the first section 66 proximate the pin clamp 34 be textured . for example , the surface may have a 2 × diamond face with grooves 90 degrees to each other . preferably , the second section 28 is configured to receive a hinge bolt 70 by having a hole therethrough . the hole may be threaded . the female element 64 can have a first section 72 that is connected to a second section 74 , preferably at about a 90 degree angle in relation to each other . the first section 72 of the female element 64 is preferably configured to receive a rail clamp bolt 49 by having a hole therethrough . the second section 74 of the female element 64 can have a hole therethrough that is able to accommodate the hinge bolt 70 . the female element 64 is hingedly connected to the male element 62 . in a preferred embodiment , both the female element 64 and the male element 62 are disposed on the hinge bolt 70 , and are held thereon by a hinge retaining washer or nut 76 . when the hinge bolt 70 and retaining washer or not 76 are loose , the female element 64 can be rotated in relation to the male element 62 , and vice versa . to stabilize the connection , the hinge bolt 70 is tightened , thus holding the male element 62 against the female element 64 . the surfaces 78 of the female and male elements 62 , 64 that come into contact with each other may be textured to increase friction and create a more stable connection . in addition , washers 80 may be employed to ensure a stable connection . in a preferred embodiment , the first clamp area 32 is connected via the hinge 60 to the second clamp area 42 . the second clamp area 42 can comprise a pin clamp 34 , a rail clamp 44 , or a combination of pin and rail clamps , 32 , 44 . preferably , each clamp system 14 allows for multi - planar attachment of rails 12 and pins 16 . in another embodiment , the clamp system 14 comprises one clamp area . in such a system , the one or more pin clamps 32 and one or more rail clamps 34 can be linearly attached to the same bolt 82 . for example , as can be seen in fig3 , such a clamp system comprises one or more pin clamp tops 36 held in spaced relation to one or more corresponding pin clamp bottoms 38 . together , the pin clamp top and bottom 36 , 38 define a pin passage 33 that can accept a pin 16 . the pin clamp tops and bottoms 36 , 38 are configured with a hole therethrough that accepts a pin clamp bolt 82 . the pin clamp tops and bottoms 36 , 38 can be loosened and tightened to accept a pin 16 and then securely attach to that pin 16 . this embodiment of a clamp system 14 further comprises a clamp body 84 that preferably is configured with a hole therethrough that can accept the pin clamp bolt 82 . the clamp body 84 can further define a rail passage 86 that is capable of accepting a rail 12 . the clamp body 84 can further comprises a device , such as a bar clamp bolt 88 , that is capable of being screwed into the rail passage 86 to secure the rail 12 . the pins 16 can be half pins or transfixing pins . in practice , one part of the pin 90 is set into a patient &# 39 ; s bones while a second part of the pin 92 is attached to a clamp area 32 , 42 . the configuration of the fixator 10 allows for such pins 16 to be placed prior to , during , or after assembly of the other parts of the fixator 10 without comprising the accuracy of the fixation . as can be seen in fig1 , 2 , 4 , and 5 , it is contemplated that the fixator 10 comprise more than one clamp system 14 . a first clamp system 14 is preferably attached to a bone 41 at a first location . a second clamp system 14 is preferably attached to a bone 41 , either the same bone , or a different bone , at a second location . the two clamp systems 14 are connected by a rail 12 , to which both clamps systems 14 are attached via the rail clamp 44 . more than one clamp system 14 and more than one rail 12 can be utilized . in one embodiment , a first clamp system 14 has a rail clamp 44 attached to a first rail 12 and a pin clamp 34 attached to two pins 16 . the pins 16 are attached to a bone 41 at a first location . a second clamp system 14 has a rail clamp 44 attached to the first rail 12 , and a pin clamp 34 attached to two different pins 16 , which are attached to a bone 41 at a second location . the second clamp system 14 also has a second rail clamp 44 attached to a second rail 12 . a third clamp system 14 has a rail clamp 44 attached to the second rail 12 and a pin clamp 34 attached to two pins 16 . these two pins 16 are attached to either the same bone 41 , or a different bone . as can be seen , the fixator 10 described herein , with each clamp system 14 capable of being comprised of one or more adjustable rail or pin clamps 44 , 34 , allows for a wide range of fixator 10 configurations that allow for effective treatment of a number of injuries . the clamps systems 14 are adjustable with respect to the rail 12 in that each clamp system 14 can slide up or down the rail 12 and also rotate around the rail 12 freely . once the optimum position for each clamp system 14 is obtained , the clamp system 12 may then be fixed securely in place by simply tightening the rail clamp 44 . moreover , additional clamp systems 14 may be added to or removed from the fixator 10 easily , both prior to fixation and stabilization and at any point during the healing process , and any number of rail or pin clamps 44 , 34 may be used , depending upon the number of rails or pins 12 , 16 necessary for a given treatment . the pins 16 can be placed independently of the fixator 10 because of the snap - in functionality of the clamp systems 14 and the ability of the fixator 10 to correct in all planes due to the multi - planar movement of the clamp systems 14 . in a further embodiment of the present invention , compression nuts and distraction nuts 18 can attached to the rails 12 and used in conjunction with the clamp systems 14 to further adjust bone healing and growth . the nuts 18 may be used to move the clamp systems 14 incrementally along the rail 12 without moving the pins 16 or other components of the fixator 10 , thus providing additional correction on a minute scale during the healing or growth process . the compression nuts 18 are preferably attached on the rail 12 such that , when moved , they will force two clamp systems 14 to move closer to each other . the distraction nuts 18 are preferably attached on a rail 12 between two clamp systems 14 such that when the distraction nut 18 is moved , it will force one clamp system 14 away from the other . preferably , more than one compression and or distraction nuts 18 can be attached to the same rail 12 to allow for compression or distraction , i . e ., the movement of one or more than one clamp systems 14 in either direction along the rail 12 . optionally , the compression and distraction nuts 18 may have built in washers . further , the compression and distraction nuts 18 may have a positive thread and can be used in conjunction with a round rail 12 having a negative thread , as described previously . in a further embodiment of the present invention , the fixator 10 may be easily modified in many ways , such as for example to accommodate pins 16 of multiple diameters and lengths . additionally , many various sizes and shapes of clamps systems 14 , rails 12 , and / or compression / distraction devices may be employed without detracting from the spirit of the invention . clamp systems 14 , pins 16 , and rails 12 can be easily reproduced , for example , for medium and large applications as well , such as for use on long bones of the leg or arm . because of the exceptional adjustability of the fixator 10 , the fixator described herein can be connected to various parts of the foot or other body parts without being limited by the configuration of the device . further , the clamp systems 14 also have the mechanical ability to interconnect with other rails and fixation systems , allowing for multiple - rail systems or more complex applications . in further embodiments of the present invention , for example , the fixator can be used in conjunction with foot plate (“ u ring ”) attachments , wires , ilizarov fixators , or any other compatible external fixator device ( none of which are shown ) through the use of pins , wires ( not shown ), and / or transfixing pins . the fixator 10 can be comprised of a wide variety of materials . in a preferred embodiment , the components of the fixator 10 are composed of anodized aluminum , stainless steel , or composite polymer . specifically , the pins 16 can be manufactured from 316l stainless steel and are preferably 2 mm , 2 . 5 mm , or 3 mm in length .

a fixator for use in the reconstruction of acute , chronic and traumatic injuries to the upper and lower extremities . the fixator has a unique clamping system that allows for the snapping in of pins and rails , and for multi - planar fixation of bones . the claim system includes a hinge , a first clamp , and a second clamp .

in fig1 - 6 there is depicted a toilet brush ( generally 10 ) having a disposable brush head 11 and a multi - part wand / handle ( generally 12 ). fig2 and 4 depict that the wand 12 can be assembled from an extension 14 , and upper and lower clam shell housing parts 15 and 16 . the extension 14 is preferably largely hollow to reduce weight , and is formed with a hole 17 for assisting in hanging up the wand 12 ( or the wand 12 with an unused brush head 11 connected thereto ) between uses ( for example on a nail or a hook ). near the opposite end of the extension 14 are radially extending holes 19 and 20 that are suitable to receive corresponding snap parts 21 and 22 of the housing parts 15 and 16 . the housing part 15 has a radial slot 24 on one surface and an arcuate inner channel along its opposite surface . the housing part 16 has a corresponding arcuate inner channel along its upper surface extending to a rear depressed area 26 . when the housing parts 15 and 16 are assembled together , they form a somewhat clam shell - like housing with a hollow internal cavity communicating with the slot 24 and a mouth outlet 25 at a lower end . prior to assembling the housing parts 15 and 16 , an actuator ( generally 29 ) is positioned there between . as shown in fig2 , the actuator 29 has a radially outward projecting section 34 , a lower flexible spring 35 , a series of catch teeth 36 , a rod 37 ( which is preferably of a cross - shaped cross section to reduce weight and friction ), and a flexible jaw 38 having one or more abutment ears 39 . the projection 34 extends through the slot 24 , with the spring 35 then abutting housing part 16 . from fig5 it can be seen that corresponding teeth 40 are formed on an internal surface of housing part 15 . once the parts 15 and 16 have sandwiched the actuator 29 , that subassembly can be snap fit into the extension 14 via the interaction of the parts 19 , 20 , 21 and 22 . this creates a secure and rigid wand structure . when the projection 34 is in the fig5 position , teeth 36 are interfit with the teeth 40 such that downward movement of the connecting rod 37 is inhibited . in this position the upper and lower jaws 30 have been driven by the mouth 25 firmly against the rearward portion of the brush 11 of the present invention . in this configuration the jaws firmly hold the brush head 11 , and the control rod 37 is inhibited from accidentally moving in a way that would permit release of the brush head . however , when a consumer pushes radially inward on the projection 34 ( compare fig5 and 6 ) against the opposing spring pressure , the teeth 36 and 40 will clear each other ( see fig6 ) such that a consumer can then readily push the projection 34 axially towards the handle mouth . subsequent release of the projection permits the teeth to re - engage . the actuator 29 is preferably molded from a plastic such as polypropylene which holds a position bias . the jaw portion thereof can be molded with a rest position that is more open than shown in fig6 . when the jaws are dragged into the wand mouth 25 , they will tend to move towards each other as shown in fig5 . however , even a slight release of the wand holding pressure , as shown in fig6 , will allow the jaw to flex open , thereby releasing the brush head . it is expected that the brush head will then be able to easily fall out of the jaw into the toilet bowl for flushing disposal . however , if the brush head tends to hold in place , one can lightly shake the brush head to dislodge it . when it is desired to reclose the jaw to clamp a replacement brush head , simple axial movement of the projection 34 ( without any depressing of it ) will achieve this due to the particular sloping of the teeth . thus , a unidirectional movement of the projection is sufficient to catch a new brush head , while a bidirectional movement is required to create a release . this helps avoid accidental release of the brush head , while making insertion of the replacement brush head easy and intuitive . wand parts 14 - 16 are preferably made of plastic . it is especially preferred that a more flexible plastic be used for actuator 29 than for the outer parts 14 - 16 . while parts 14 - 16 are shown as being linked together by a snap fit connection of a type conventional with vacuum cleaner hose parts , a variety of other mechanical means for securing the parts together are possible . for example , there may be some benefits to the use of a bayonet type connection , rather than a simple axial snap connection . alternatively , the parts 14 - 16 could be reconfigured as a two - part clam shell , albeit this would be less preferred due to it taking up extra shelf and shipping space prior to purchase by the consumer . also , while teeth 36 / 40 are angled to render clamping of the brush head easier to achieve than release , the teeth could be otherwise angled . for example , rendering them normal to the wand would make it equally difficult to move the connecting rod 33 in either direction , and require radial motion for both to proceed . particularly now with respect to fig7 and 8 , the brush head 11 is a stack of layers ( 50 , 51 , etc .) of water - degradable material . the layers may be folded back on each other once , and then stacked . the stack has a series of undulations 53 at its rearward end 54 on both the top 73 and bottom 74 of the brush head . as will be described in more detail below , the undulations can be formed by a compression roller , with the pressure bonding the layers together in a manner similar to mechanical quilting . where there are the undulations , the compression of the stack sufficiently bonds the layers of the stack together , while permitting the forward end 58 to flower outward . fig9 shows a slightly modified jaw structure 60 , with a mouth 61 defined by a series of generally parallel , longitudinal , two - part , almost cylindrical , openings 62 separated by narrowed linking openings 63 . as best seen in fig1 , the presenting face of the jaw mouth thus acts to provide a corresponding reception area for the undulations 53 . the undulations 53 and parallel cylindrical openings 62 provide an alignment device , while also controlling the type of refill used with the wand . as the jaw tightens , it bites into the corresponding undulations . this provides an even more secure connection . fig1 depicts a consumer beginning to attempt to insert the brush head 11 into the jaw 30 . fig1 shows a modified brush head 80 that is similar in all respects to the brush head 11 , except that the undulations 81 do not extend all the way to the rear 82 of the brush head , and a slightly compressed , but not undulating , region 83 can be left at the rear of the brush head 80 . again , parallel slits 85 can be provided to create an array of bristles 86 . fig1 shows the relative degree of compression of the respective sections , with region 83 preferably being at an intermediate level of compression relative to the most compressed area 81 and the non - compressed area of the bristles 86 . fig1 shows that the parts could be configured so that the brush head 80 could similarly be longitudinally inserted into jaw 90 ( in a manner analogous to how the parts can be assembled with respect to the fig1 embodiment ). however , it is preferable for this embodiment that the length of the connecting rod be such that even when the jaw is at its maximum open position , it won &# 39 ; t open enough for the end 83 to pass longitudinally into the jaw . instead , in this configuration , one would need to slide the end 83 into side cheek holes 91 , from the side , as indicated by the arrow a . after doing this , the head 80 cannot be simply moved longitudinally out the jaw 90 . the jaw can then be clamped tightly against the head 83 to prevent removal out the side cheek opening . this has several advantages . first , it insures that the brush head will always be inserted a sufficient distance so that it will be securely clamped . further , it insures that brush heads not having this type of cross section , and of sufficient thickness , cannot be easily used with the brush wand 93 . the brush head 80 can be manufactured in accordance with the method depicted schematically in fig1 and 16 . one can take an elongated continuous stack of sheets 94 and then roll its top with a compression roller 95 . at the same time , a roller 96 can roll its bottom . each roller has two wavy regions 97 sandwiching a non - wavy region 98 . the rollers create two regions of highly compressed undulations 81 adjacent a middle slightly compressed continuous region 83 . outside regions 99 are not compressed . one may then cut the material along transverse cut lines 101 , 102 , 103 , etc ., followed by a further cut 104 , to thereby create a plurality of brush heads 60 . while specific embodiments of the invention have been described , additional embodiments are possible without departing from the spirit or scope of the invention . for example , the term “ undulation ” is not limited to just a smoothly contoured set of waves of uniform dimension . rather , the undulations could be a series of pointed or more complex projections separated by recesses . similarly , the cross section of the openings in the jaw need not be purely cylindrical . as such , one skilled in the art will readily appreciate that still other alternative embodiments fall within the scope and breadth of the invention . the claims should be looked to in order to understand the full scope of the invention , and the claims are not to be limited to just the preferred embodiments shown . an improved toilet brush is provided with an undulating brush head that is disposable and replaceable , in a wand having a complementary jaw .

disclosed are brushes for cleaning toilet bowls and the like . the brushes have a permanent handle and can be used with a replaceable / disposable brush head that is flushable after use . the brush is a stack of sheets of water - dissolvable material . the sheets are compressed to both bind them together into a stack and create axial / longitudinal undulations . a wand provides a remote system for clamping and unclamping the brush head . the wand has a jaw whose mouth has corresponding undulating configurations . a side opening in the jaw may also be provided to facilitate assembly , as may a rear catch portion on the brush head .

as can be seen in fig1 and 2 , a particulate spreader indicated generally at 20 comprises a chamber or metering block 22 with a pressurized gas entrance conduit 24 and an exit conduit 26 connected thereto . a material hopper 28 is located generally above the metering block 22 and includes a passage 30 that runs from the bottom of the material hopper 28 to the top of the metering block 22 . preferably , the passage 30 is gravity - fed with particulate material from the material hopper 28 . in one embodiment of the invention , the channel 30 includes a valve 32 for adjusting the amount of particulate or particulate material that enters the metering block 22 . in a most preferred embodiment of the invention , the valve 32 on the channel 30 is a standard ball valve . referring to fig3 , the air entrance conduit 24 includes an air nozzle 54 which protrudes through a first wall 34 of the metering block 22 by a predetermined distance d . in a preferred embodiment of the invention , the nozzle 54 has an exit diameter 55 of about one - eighth of an inch . as shown in fig4 , the pressurized gas entrance conduit 24 runs from the metering block 22 back to an air tank 36 . in the illustrated embodiment of the invention , the pressurized gas entrance conduit 24 is in the form of an air hose and has a diameter of about three - eighths of an inch . the air inside the air tank 36 and the pressurized gas entrance conduit 24 is compressed by a compressor 38 which is connected to the air tank 36 by an air supply line 40 . also connecting the compressor 38 to the air tank 36 is a second pressure line 98 . communicating with the air tank 36 on the entrance conduit 24 is a regulator 42 , which is connected to the air tank 36 via an intermediary conduit 96 . communicating between the compressor 38 and the air tank 36 is an unloader 92 . a pressure gauge 94 is also attached to the air tank 36 so that a user can visually monitor the air pressure inside the air tank 36 . the unloader 92 is preset for a standard operating range . the compressor 38 is connected by a transmission link 43 to a prime mover such as a motor or a preferably gasoline - driven internal combustion engine 44 . the engine 44 can be the same as the engine used by a vehicle upon which the spreader 20 is mounted ( fig1 ), or the engine 44 can be dedicated to supply power to the spreader 20 alone . a throttle 46 is coupled to the engine 44 . the compressor 38 and the engine 44 are connected to each other by a first pressure line 70 and by the transmission link 43 which is used by the engine 44 to supply power to the compressor 38 . the power transmission link drive train 43 can take the form of a drive shaft , belt , a hydraulic line , gearing , or a more complicated transmission . referring to fig2 and 3 , the exit conduit 26 is in the form of a flexible hose 48 . the hose 48 is connected to the metering block 22 by a hose disconnect 50 at a second wall 52 of the chamber . the hose 48 can be any of several lengths and preferably has a diameter of about one inch . the length of hose 48 is selected to be long enough for a user on foot to use it comfortably , supposing that the spreader 20 is mounted on a vehicle , but not so long that significant reductions of pressure and velocity result . the user can also employ the flexible hose while riding in or driving the vehicle . a wand 58 terminates the hose 48 , and can be pointed in virtually any direction by the user in order to precisely direct the flow of particulate materials to the areas where they are wanted . a handle 60 is mounted on the hose 48 near its end and includes an electrical switch 62 for adjusting the air flow in the spreader 20 . as seen in fig4 the switch 62 is electrically connected to an electrically - actuated valve 64 which is coupled to the entrance conduit 24 . the switch 62 is capable of being placed in at least two positions . in the illustrated embodiment of the invention , the electrically - actuated valve 64 is in the form of a solenoid valve which can either completely open or close the entrance conduit 24 , either permitting or restricting the movement of air to the metering block 22 . in an alternative embodiment of the invention , the electrically - actuated valve can have three or more positions such that when the position of the switch 62 is adjusted , a signal is sent to the electrically - actuated valve 64 , which in turn adjusts its position to either permit more or less air to pass through the entrance conduit 24 . the switch 62 selectively connects the electrically - actuated valve 64 to a battery 68 . in a preferred embodiment of the invention , the battery 68 is capable of producing a current of about three amperes at twelve volts dc . the air flow to the metering block 22 can also be manually controlled by adjusting a ball valve 25 ( fig2 and 4 ) located along the pressurized gas entrance conduit 24 . in one embodiment of the invention , the ball valve 25 acts as an emergency shut - off for the spreader 20 . the operation of the spreader is as follows . the engine 44 is used to power the compressor 38 . the compressor 38 works to compress the air inside the air tank 36 . in order to adequately operate the electrically - actuated valve 64 ( when , as preferred , it is a solenoid valve ), the compressor 38 should compress the air in the air entrance conduit 24 to about fifty pounds per square inch . in a preferred embodiment of the invention , the pressure in the air entrance conduit 24 is regulated to be in the range of sixty to ninety pounds per square inch . in order to maintain the appropriate pressure in the air entrance conduit 24 at this range , the pressure generated in the air tank should remain in the range of about 100 to 115 pounds per square inch . to maintain the pressure in this range , the pressure gauge 56 and the unloader 92 monitor the air pressure . when the pressure exceeds about 115 pounds per square inch in the pressure gauge 56 , the unloader 92 closes the first pressure line 70 running between the compressor 38 and the engine 44 . the closure of the first pressure line 70 results in a closing of the throttle 46 . the closing of the throttle 46 powers down the engine 44 , in one embodiment of the invention , preventing the compressor 38 from forcing additional air into the air tank 36 . similarly , when the pressure in the air tank falls below about 80 pounds per square inch , in one embodiment of the invention , this will be sensed by the pressure gauge 56 , giving the user a visual indication of the pressure . the unloader 92 opens the first pressure line 70 running between the compressor 38 and the engine 44 . this also opens the throttle 46 ( fig2 ), which powers up the engine 44 . additional power is then applied to the compressor 38 in order to increase the pressure in the air tank 36 . referring in particular to fig2 and 3 , when the air inside the air tank 36 is under the appropriate pressure and the ball valve 25 is at least partially open , compressed air is forced into the metering block 22 . by opening the valve 32 between the material hopper 28 and the metering block 22 , particulate material is permitted to fall into the metering block 22 . in preferred embodiment of this invention , the particulate material can be salt , sand , fertilizer , pesticide , herbicide , urea , or grass or other seed , although other materials are possible so long as the materials are not so thick or sticky as to clog up the inside of the channel 30 or the metering block 22 . one advantage of the invention is that the air pressure and particulate feed flow can be adjusted for different particulate or particulate materials . the density and therefore the fluid - entrainment characteristics will vary greatly among these various kinds of solid particulates ; less air mass is needed to push grass seed than , for example , quartzite sand . as the particulate material falls into the metering block 22 , it carried by the air stream flowing out of the nozzle 54 into the exit conduit 26 . in order to ensure to that substantially all of the particulate material is transported into the exit conduit 26 , the location of the end of the nozzle 54 relative to the second wall 52 is important . preferably , the open end of the nozzle 54 should be positioned at a distance d which is between one - half and three - fourths of the width w , taken between the first wall 34 and the second wall 52 . in a most preferred embodiment of the invention , the end of the nozzle 54 is positioned about five - eighths of the way across the metering block 22 to the second wall 52 . in one preferred embodiment of the invention , the distance from the first wall 34 to the second wall 52 is about 2 . 2 inches . the end of the nozzle 54 is substantially coaxial with the exit conduit 26 . as the particulate or granular materials interact with the air stream coming from the nozzle 54 , they are transported through the hose 48 to the wand 58 . the user holds the wand 58 by the handle 60 and points the wand 58 in the desired direction . when the switch 62 is in a position in which at least some air is flowing through the entrance conduit 24 , the particulate materials will be forced out of the wand 58 and the particulate materials will be spread in the desired direction . in a preferred embodiment of the invention where fertilizer is used as the particulate material , between about six and a half and seventeen pounds of material should be spread per minute , although this amount can be easily adjusted by adjusting the regulator 42 , the valve 32 below the material hopper , or adjusting the switch 62 on the handle 60 if the switch 62 has more than two positions . for example and in one embodiment of the invention , between about six and a half and twenty - four pounds of material would be spread per minute when using a six foot hose . the exact flow rate of particulate materials can also vary depending on the diameter of the entrance and exit conduits 24 and 26 , the size and geometry of the metering chamber 22 , and the density of the material being spread . in another embodiment of the invention , the spreader 20 can be altered so that more than one person can use it at one time . as shown in fig5 a , the compressor 38 can be used to supply compressed gas to two metering blocks 22 a , b . in one embodiment of the invention , each air line 40 is connected to its own air tank 36 , although it is also possible to have one air tank 36 supply air for two air entrance conduits 24 as shown in fig5 b . where there two air tanks 36 a and 36 b , a pressurized gas entrance conduit 24 a , b connects each air tank 36 a , b to separate metering blocks 22 a , b , with material hoppers 28 a , b located above respective metering blocks 22 a , b . each metering block 22 a , b has an exit conduit 26 a , b leading away from it towards a respective wand 58 a , b . in this manner , two users may use separate wands 58 a , b so as to be able to spread the material in different directions . in a preferred embodiment of the invention , a compressor which produces more cubic feet of gaseous material per minute would be used . in a second alternative embodiment of the invention as shown in fig6 a second material hopper 100 can be placed inside the primary material hopper 28 . the second material hopper 28 is connected to the primary hopper 28 by a hook 108 or other mechanical means that are well - known to those skilled in the art such as bolts or latches . the second hopper 100 is coupled to a flexible line 102 which runs to the bottom of the primary hopper 28 . an additional ball valve 104 is coupled to the line 102 for adjusting the flow of material from the second hopper 100 . attached to the base of the primary hopper 28 and the line 102 is a fitting 106 which allows material from both hoppers 28 and 100 to enter the passage 30 leading to the metering block 22 . depending upon the particular system requirements , the material can flow from both hoppers 28 and 100 simultaneously , or the ball valve 104 could be of the type that permits material to flow from only one of the hoppers 28 and 100 at a time . due to the smaller dimensions of the second hopper 100 and the line 102 , it is preferable that very light materials such as seed or insecticide be used in the second hopper 100 , although other materials may be possible . in yet another embodiment of the invention as shown in fig1 the spreader 20 includes all of its essential components arranged inside a frame 90 that is of proper size so as to be able to be placed in the back of a vehicle 80 such as a low - bed pickup . several such “ truckster ” vehicles , such as a john deere gator , a toro utility vehicle , a cushman utility vehicle , a kawasaki mule , or a haulmaster are all capable of having the frame 90 of the particulate spreader stored thereon . by having the hose 48 be of a sufficient length , the user is capable of directing the wand 58 to spread particulate material while still keeping the vehicle 80 in motion . additionally , it is also possible to have the particulate spreader 20 mounted on a trailer to be towed by a motorized vehicle . the user ( s ) may apply particulate material while seated in or even while driving the vehicle , or the user may stand near the vehicle while spraying the material . another embodiment of the invention is shown in fig7 in which an alternative metering assembly , shown generally at 200 , is used to meter precise quantities of material for spreading . the metering assembly 200 comprises a first section 202 , a second section 204 and a third section 206 . the first section 202 and the third section 206 are maintained in a substantially constant position relative to the passage 30 . the second section 204 , however , is movable between first and second positions . in one embodiment of the invention , an actuator 212 is coupled to the second section 204 by an actuator arm 214 . the second section 204 includes a first storage area 208 and a second storage area 210 . when the second section 204 is moved into a first position , shown in fig7 the second storage area 210 is located directly beneath the passage 30 . this positioning permits the second storage area 210 to fill with a specific amount of material to be spread . at the same time , if the first storage area 208 had previously been filled with material , then the material in the first storage area 208 falls through a first storage conduit 218 to be entrained by the stream of air emanating from the nozzle 54 , forcing the material into the exit conduit 26 . after the second storage area 210 is filled with material , the actuator 212 moves the second section to a second position ( not shown ), in which the material from the second storage area is entrained by the stream of air from the nozzle after the material passes through a second storage conduit 220 . at the same time , the first storage area 208 is positioned beneath the passage 30 so that the first storage area 208 may be filled with material . in the embodiment shown in fig7 the nozzle 54 is positioned within a nozzle chamber 222 such that the nozzle 54 extends a length w between about five - eighths to about three - quarters of the distance d from one end of the nozzle chamber to the point at which the first storage conduit 218 begins . the arrangement described in fig7 permits the user to meter a specific , controlled amount of material for application , ranging from about one quarter of a teaspoon to much larger quantities . in one preferred embodiment of the invention , the second section 204 is replaceable such that exact quantity of material to be metered can change depending upon the user &# 39 ; s particular requirements . while several preferred embodiments have been shown and described , it is understood that changes and modifications can be made to the invention without departing from the invention &# 39 ; s broader aspects . for example , instead of using two material hoppers for an apparatus that comprises two hoses for spreading the particulate materials , the apparatus could use one large hopper which is connected to both metering blocks . also , the metering block can have the shape of a cylinder , wherein the first and second walls mentioned in the specification would each represent a portion of the inner cylindrical wall of the block . additionally , it is possible to use fluids other than pressurized air to transport the particulate materials through the exit conduit . instead of relying on a dedicated engine , the prime mover of the pump could be a vehicle engine with power obtained from a belt , shaft , or hydraulic line , and a different power / pressurized air regulation scheme . finally , it is feasible that frozen materials such as very fine - grained snow or ice could be spread using this apparatus . thus , it is apparent that alternative embodiments are available to those skilled in the relevant art . therefore , the present invention is not limited to the described and illustrated embodiments but only by the scope and spirit of the appended claims .

a system for applying particulate materials comprising a supply source of pressurized gas , a chamber with first and second opposed side walls , at least one pressurized gas entrance conduit for transporting pressurized gas to the chamber , at least one material hopper for depositing particulate material into the chamber , and at least one pressurized gas exit conduit for transporting particulate material away from the chamber . the wand is flexible and is manually controlled so that the user can control the exact direction in which the particulate material is to be focused . the wand includes a switch which sends a signal to a signal - actuated valve which is coupled to the entrance conduit . upon receiving the appropriate signal , the signal - actuated valve adjusts so as to alter the flow of particulate material . the apparatus is powered by a motor source which maintains an optimum pressure range inside the entrance conduit through the use of a feedback loop operating between the motor source , the compressor , a pressure valve and a throttle . the apparatus is of the appropriate size so as to be mounted on a vehicle .

fig1 shows a human operator performing a curling exercise with the exercising device 10 of this invention . the curling exercise is usually performed with a barbell and it is the purpose of fig1 to show one example of how exercising device 10 can be substituted for a barbell in weight training . the operator simply dials the desired &# 34 ; weight &# 34 ; setting on the device and then uses the exercising device as if it were a barbell weighing the dialed amount . exercising device 10 is provided with a flexible pull cord 12 , preferably made of nylon , and a detachable hand grip 14 . various different types of hand or other grips can be attached to the end of cord 12 in order to meet the requirements of various exercise routines . examples of different grips include double grips , bar grips , loop grips , grips to fit the operator &# 39 ; s head , and grips to fit the operator &# 39 ; s feet . the exercising device of this invention is not limited to any specific type of grip attached to the end of pull cord 12 . in order to hold the exercising device 10 in a stationary position ( which is usually preferred ), the exercising device may be provided with various fittings or apertures , such as apertures 16 through which a short length of line 18 can be looped . line 18 can then be attached to a foot rest 20 , or to a wall fitting , or to a ceiling fitting , or to other fixed supports . it will be understood that a wide variety of such fittings is contemplated and this invention is not limited to any specific type or location of fitting , or any specific type or location of line , or any specific type or location of foot rest or other fixed support . referring now to fig2 and 4 , it will be seen that the exercising device 10 has a hollow two part housing 22 which is bolted together and which has a cord opening 24 through which pull cord 12 extends . the outer end of cord 12 is fitted with hand grip 14 and the inner end of cord 12 is fixed to and is wrapped several times around retractor reel 26 . retractor reel 26 is rotatably mounted in the housing on shaft 27 and is spring - powered in the clockwise or rewind direction . preferably , retractor reel 26 exerts a continuous rewind force on the cord of approximately 1 to 3 lbs . this force level can be adjusted by modifying the spring tension . thus , whenever the operator releases hand grip 14 , or exerts less than the retractor reel rewind force , cord 12 will be drawn into housing 22 through opening 24 and will be rewound on reel 26 . the size of hand grip 14 prevents the outer end of cord 12 from being drawn entirely into housing 22 through opening 24 . in order to provide a substantial force which will resist the operator &# 39 ; s outward pull on the cord , a manually adjustable variable resistance friction brake means is mounted within the housing for cooperation with the cord retractor reel 26 . the friction brake means acts through automatic locking means to brake the retractor reel when the cord is pulled out of the housing and to release the retractor reel to permit the cord to be pulled back into the housing . as clearly shown in fig3 and 4 , the friction brake means includes an annular bearing 28 which is fixed within the larger or back side of the housing ; an annular brake disk 30 which rotates within bearing 28 ; an annular brake shoe 32 which is fixed against rotation within the smaller or front side of the housing ; an annular spring 34 which is pressed against brake shoe 32 ; a circular pressure plate 36 which is pressed against spring 34 ; and a bolt 38 which has a large easily manipulated bolt head 40 on its trailing end and which has a ball bearing 42 mounted on its leading end . the bolt is screwed through the front side of housing 22 and engages against pressure plate 36 to clamp elements 28 , 30 , 32 , 34 and 36 together . in greater detail , bearing 28 is preferably made of oilless bearing material and is keyed to the back side of the housing to prevent rotation thereof . brake disk 30 , which is preferably smooth steel on all of its surfaces , has centrally extending teeth 44 which engage with the automatic locking means in a manner which will be described subsequently . brake shoe 32 has brake lining or other abrasive material affixed to its back surface which faces brake disk 30 . alternatively , brake disc 30 could have the brake lining material affixed to its front surface and brake shoe 32 could have the smooth metal back surface . brake shoe 32 is keyed to the front side of the housing to prevent its rotation . the brake lining material can be affixed to brake shoe 32 in a replaceable manner or permanently . in order to continuously press the keyed brake shoe 32 against the rotating brake disk 30 , a belleville spring 34 is positioned against the front side of brake shoe 32 . of course , other types of resilient elements could be substituted for the belleville spring . a circular pressure plate 36 is positioned to bear against the front side of spring 34 . the pressure plate preferably has a small depression 46 at its center on the front side and the plate has a reduced diameter portion on its back side which extends into the annular opening of the spring 34 . bolt 38 is screwed through threaded hole 48 in the front side of the housing and carries a poundage indicating arrow 50 which is fixed to the bolt shaft by a set screw 52 . the poundage indicating arrow 50 turns with bolt 38 across dial markings on the housing and indicates the level of resisting force being applied against the cord . the bolt mounts a ball bearing 42 at its leading end which is seated within depression 46 in pressure plate 36 . thus , it will be appreciated that the friction brake means is set up and adjusted to its desired friction brake force level by turning bolt head 40 until the poundage indicating arrow 50 is aligned with the desired force level marking on the front of the housing . this causes bolt 38 to press against pressure plate 36 which presses against spring 34 which presses against brake shoe 32 which presses against brake disk 30 which presses against bearing 28 which is seated in the back side of housing 22 . this stack of elements comprises the friction brake means . when the cord is being rewound into the housing by the retractor reel , the friction brake means is not engaged and does not move at all . however , when the cord is pulled out of the housing , the friction brake means is engaged by the automatic locking means which is mounted on the circular front side of the retractor reel 26 . specifically , the automatic locking means is a ratchet mechanism employing two identical pawl housings 54 and two radially extending spring - loaded engaging pawls 56 . the pawls ride over the brake disk teeth 44 when the reel rewinds , and the pawls engage teeth 44 when the reel is unwound . thus , when the cord is pulled out of the housing 22 , the revolving reel is locked to the brake disk 30 which revolves while in frictional contact with fixed brake shoe 32 . this frictional braking exerts drag on the cord . obviously , the more tightly brake shoe 32 is clamped against brake disk 30 the greater the braking action on the retractor reel and the greater the drag on the cord . in contrast , when the cord is rewound , the pawls , because of their shape , reciprocate in their housings 54 and do not cause brake disk 30 to revolve at all . it will be seen that this ratchet mechanism operates automatically to engage or disengage the friction brake mechanism with relation to the retractor reel 26 . an optional cord resistance force is provided by the capstan which is generally indicated as 58 . the capstan has an inoperative mode in which its freewheels in both directions and an operative mode in which it is stationary in the unwind direction and freewheels in the rewind direction . capstan 58 has a flanged shaft 60 which is fixed to an underlying flanged bearing 61 which in turn is rotatably secured in the back side of housing 22 by a retaining ring 63 . by means of engaging pawls 62 and as unshown inwardly toothed ring mounted within the lower interior of the capstan shaft 60 , the capstan can be set in its operative ratcheting mode or in its inoperative freewheeling mode . a control button 64 is mounted in the back side of the housing and is of the type which when depressed once stays depressed and which when depressed again springs back to its original position . in this optional embodiment , when control button 64 is depressed once , the ratcheting mechanism ( including pawls 62 ) is inserted into the capstan shaft interior where it aligns with the beveled toothed ring which is fixed to the interior of the capstan shaft . in this operative mode , the capstan freewheels in the rewind direction and is locked against rotation in the unwind direction . when control button 64 is depressed again , the ratcheting mechanism is retracted from within the capstan interior thereby permitting the capstan to freewheel in both directions . when the optional capstan embodiment is employed , the cord is run from the retractor reel to the capstan around which it is wrapped preferably one full turn . the cord is then run out of housing cord opening 24 which has smooth curved walls . when the optional capstan is omitted , it is either replaced by a conventional guide roller or it is omitted entirely . a guide roller facilitates somewhat smoother functioning and decreases friction on the cord . the reason that the capstan is included in the optional embodiment is that the capstan multiplies the resistance force opposing the unwinding of the cord . obviously , many factors will affect the exact multiplying ratio produced by the capstan . examples of these factors include the diameter of the capstan , the capstan surface roughness , the diameter of the cord , the cord material , the number of turns on the capstan , and numerous others . however , regardless of the exact multiplying ratio , the capstan will produce a substantial resistance force opposing the passage of the cord out of the housing . although the capstan has been described as preferably having a ratchet operative mode , it alternatively could have an entirely stationary operative mode , i . e . one in which the capstan is stationary in both the unwind and rewind directions . this is functionally possible because a capstan cannot provide significant frictional resistance against the cord unless the cord is pulled tightly around the capstan shaft from both directions . for this reason , when the operator releases the hand grip ( or ceases to pull on it ), there is no outward force on the cord . thus , the cord simply slips on the stationary capstan shaft , and the small rewind force of retractor reel 26 is sufficient to rewind the cord onto the reel . in order to use the exercising device of this invention , the operator first determines the force level to be applied against the cord by the device . if it is a relatively low force level , he sets the capstan in the inoperative mode by depressing control button 64 to retract ratcheting mechanism 62 from within capstan shaft 60 . this permits the capstan to freewheel in both directions . if it is a relatively high force level , he sets the capstan in the operative mode by depressing control button 64 to insert the ratcheting mechanism into the capstan shaft . this locks the capstan in the unwind direction and permits it to freewheel in the rewind direction . then , the operator turns bolt head 40 until indicator arrow 50 aligns with the desired figure on the calibrated housing dial . this sets the friction brake means at the tightness level needed to produce the desired braking force opposing the outward pull on the cord . preferably , the dial has two rings of concentric figures . one ring shows the resistance force levels for the capstan inoperative mode , and the other ring shows the resistance force levels for the capstan operative mode . the device is anchored to a fixed support and the handle is pulled by the operator away from the housing by using a pulling force exceeding that of the dialed internal resistance force . when the operator reduces his pulling force below that of the retractor reel , the cord smoothly rewinds back into the housing . in this fashion , the operator can exercise slowly or rapidly and can adjust the cord resistance force level quickly and easily . the above description obviously suggests many possible variations and modifications of this invention which would not depart from its spirit and scope . it should be understood , therefore , that the invention is not limited in its application to the details of structure specifically described or illustrated and that within the scope of the appended claims , it may be practiced otherwise than as specifically described or illustrated .

the exercising device has a housing which is attached to a stationary surface . a cord which has a hand grip on its free end can be pulled out of the housing against the adjustable internal resistance of the exercising device . the amount of internal resistance can be varied by means of a control knob . a spring - powered cord retractor reel rewinds the cord back into the housing when the cord is released . the internal resistance is quantitatively adjusted by a friction brake mechanism including a fixed annular brake shoe , a rotatable annular brake disk , and a mechanism for continuously clamping the brake shoe against the brake disk . an automatic mechanism is provided to lock the brake disk to the cord retractor reel as the cord is pulled out of the housing , and to unlock the brake disk from the cord retractor reel as the cord is rewound into the housing . optionally , the cord is passed around a guide roller which can be selectively immobilized as the cord is pulled out of the housing so that the guide roller acts as a capstan .

the bed shown in accompanying fig1 to 5 has the general appearance of a hospital bed of well - known type . it is constituted by a base structure 1 made up of a solid metal frame 10 having castors 11 attached thereto and defining between them an elongate rectangular shape . the frame supports equipment 12 for raising and lowering the bed proper , mainly for the purpose of making it easier for hospital staff to take action . such equipment is also provided for positioning the patient in so - called “ safe ” positions , in particular acclivous and declivous positions ( sloping up and sloping down ). naturally , the base structure can receive other mechanical and / or electronic equipment suitable for co - operating with the bed proper . this base structure also has fixed thereto vertical panels at the head and foot ends of the bed , given respective references 4 and 4 ′ in the figures . they extend transversely , defining the longitudinal ends of the bed . as can be seen , these panels present large cutouts 40 and 40 ′ which form handles and make it easier to maneuver the bed when it is desired to move it within a room or outside the room . in conventional manner , the bed proper is essentially formed by that which is referred to throughout the present application as the “ bed plane ”, i . e . a surface that coincides with or is situated immediately below the bottom face of the mattress and that is usually constituted by a hard plane made up of several portions , with at least one of these portions being movable so as to occupy positions other than horizontal . this makes it possible , in particular by tilting up one or another of these portions , to put the mattress in a position similar to that of a seat . this bed plane is not visible in fig1 to 5 . these figures show only the mattress 3 which rests thereon . as shown in fig1 to 3 , the bed is fitted in accordance with the invention with two barrier elements 5 and 5 ′ that are hinged relative to each other . they extend parallel to one of the longitudinal edges of the bed . these barrier elements are in the form of generally rectangular plates . their dimensions are substantially similar , such that when they are superposed one on the other ( fig1 and 2 ) in an “ overlapping ” position , they occupy much the same space as a single element . in the longitudinal direction , they are of a size that is no greater than half the length of the mattress . in this way , when they are deployed , they occupy practically the entire length of the mattress . in a variant embodiment , the first element could occupy substantially three - fourths of the length of the bed while the second element occupies the last fourth . in yet another embodiment , there could be three such elements , each occupying no more than one - third of the length of the bed . fig6 and 7 show a slightly different embodiment of these two elements . in an additional embodiment ( not shown ), these elements may have large open areas or glazed areas , like traditional barriers . fig6 is a side view of the bed plane 2 on which there rests the mattress 3 of the bed . this bed plane is built up by assembling bars . in the example shown , it comprises two portions 20 and 21 which are hinged relative to each other about a horizontal axis y , y ′ which is generally perpendicular to the longitudinal direction of the bed . the portion 20 is at the foot end of the bed while the portion 21 is at its head end . when the portion 21 occupies a raised position , this enables the mattress to be put into a position similar to that of a seat . with reference to fig7 , there can be seen an assembly 210 of bars constituting a fraction of the portion 21 of the bed plane . on one of the longitudinal sides of the portion 210 there is fixed a piece of equipment 50 ′ enabling the barrier elements 5 and 5 ′ to be positioned either in a vertical raised position above the bed plane ( fig1 , 3 , 6 , and 7 ), or else in a vertical position retracted below the bed plane ( fig2 ). this is a deformable parallelogram mechanism . it is not described in greater detail herein since , properly speaking , it does not form part of the invention . nevertheless , reference can be made to french patent no . 91 / 11185 in the name of the present applicant which describes in particular the operation of the linkage constituting the mechanism 50 ′. the mechanism makes it easy to move the barrier elements from the folded - up position of fig1 to the retracted position of fig2 . in fig2 , arrow h represents the upward movement of the barrier elements . the retracted position beneath the bed plane is particularly useful when hospital staff need to gain access to the bed without their own movements being impeded . naturally , the piece of equipment 50 ′ could be replaced by some other mechanical system suitable for performing the function of retracting the elements in the overlapping position . in accordance with the invention , the barrier elements 5 and 5 ′ are hinged relative to each other about an axis xx ′ which is generally perpendicular to the longitudinal axis of the bed . this hinge is constituted by a mechanism that is not visible in fig6 and comprising , for example , a cylindrical spacer , distance pieces , and a helical spring . nevertheless , any other known type of hinge mechanism may be adopted . certain embodiments of this mechanism are described below . the mechanism may merely comprise a mechanism enabling the elements to turn relative to each other without allowing them to be separated . nevertheless , this option for separating the elements , or at least for spacing them apart from each other , is preferred so as to give access for cleaning the barrier elements in full , in particular in their zones that face each other , and still more particularly , in the zone where they overlie each other . with reference to fig8 and 9 , there follows a description of a first embodiment of the hinge mechanism for the barrier elements . each of the elements 5 and 5 ′ presents a circular opening of the same diameter passing through its thickness , this opening receiving a bushing 60 . the bushing comprises a generally cylindrical body with a generally flat peripheral flange 601 at one of its ends . the flange is received in and comes into abutment against a countersink provided in the outside face of the barrier element 5 . the length of the bushing is such that the body 60 is flush with the opposite face of the element 5 ′. the axis of the bushing coincides with the hinge axis xx ′ between the elements . the inside space of the bushing receives a sleeve 61 , and more particularly the body 611 thereof . this body is longitudinally hollow and communicates via one of its ends with a generally flat head 610 of circular shape and of diameter greater than that of the body . between the bushing 60 and the head 610 of the sleeve there is interposed a compressible o - ring 63 , e . g . made of natural rubber . at the opposite end of the body there is a generally longitudinal projection 612 extending beyond the thickness of the two elements . a pivoting control handle 62 of conventional type having a cam surface 620 is hinged thereto . this hinge is about an axis 613 that is generally parallel to the planes occupied by the elements 5 and 5 ′. the sleeve 61 is engaged in the bushing 60 while the handle 62 is in alignment therewith ( see fig9 ). by folding the handle down , the sleeve is moved in translation , thereby compressing the o - ring 63 ( fig8 ). this configuration makes it possible to secure the elements 5 and 5 ′ to each other while also making it possible for one of them to turn about the axis xx ′. nevertheless , the tightness with which the handle 62 is actuated serves to brake turning of the element . when it is desired to gain access to the facing faces of the elements 5 and 5 ′, in particular for the purpose of cleaning them , it suffices to fold the handle out so that it is in alignment with the sleeve ( fig9 ) and to separate the element 5 by pulling on it . another embodiment of the hinge mechanism is described below , more particularly with reference to fig1 to 12 . in the same manner as above , each of the barrier elements presents an opening through its thickness enabling the component parts of the hinge mechanism to be inserted therein . in this case , the hinge mechanism comprises a first part referenced 70 and referred to as the inside cap . it is for mounting beside the face of the element 5 ′ that faces towards the inside of the bed . for this purpose , said face is locally recessed in order to receive said cap . the cap comprises a circular plate in the form of a disk 700 whose inside face presents projecting studs 701 at the corners of a square . they are intended to receive means for fastening to the barrier elements , in particular screw fastener means . on the same side of the plate 700 there extends from its center a generally cylindrical sleeve 702 . the length of the sleeve is such that when the cap is in place on the element 5 ′, it extends into the element 5 . this sleeve presents a set of axial slots 704 that are equidistant angularly . between them , pairs of slots define branches 703 . the cap is preferably made of a slightly deformable plastics material , such that the branches 703 are radially deformable . their free ends form respective catches 705 with chamfered faces looking outwards . the mechanism also comprises a spacer 71 suitable for being received in a recess provided for this purpose in the element 5 . it comprises a generally cylindrical body and a plane peripheral flange 710 projecting outwards . this flange presents a series of orifices 711 for fastening the spacer to the outside face of the element 5 . the body of the spacer has a first axial portion 712 which extends from the flange 710 . it communicates with another cylindrical portion of smaller diameter 714 via a shoulder - forming transition zone 713 extending parallel to the flange 710 . the inside diameter of the portion 714 is equal to the outside diameter of the sleeve 702 , ignoring clearance . the central opening of the spacer 7 receives a circular button 72 having a hollow inside and which includes in particular an axially - extending partition 720 whose function is explained below . finally , the mechanism includes an outside cap 73 essentially constituted by a flat disk 730 with a central recess 731 for passing the button 72 . the inside cap 72 and the spacer 71 are engaged in each other from opposite sides of the elements 5 and 5 ′. in so doing , the portion 714 of the spacer encounters the catches 705 of the sleeve 702 so that the sleeve tends to deform radially inwards . this enables the portion 714 to come into position against the plate 700 of the spacer . this is the position shown in fig1 . the spacer is prevented from being withdrawn by the shoulders of the catches 705 . nevertheless , it will be understood that by pressing against the button 72 in the direction of arrow a , its partition 720 comes to bear against the catches 705 , and more particularly against their chamfered flats . this causes the branches 703 to move radially by titling inwards . this enables the spacer 71 to be released and thus also the element 5 which is associated therewith . this type of hinge mechanism , like the above - described mechanism , makes it possible to pivot the elements relative to each other . merely by pressing on the button , it also makes it possible to separate them from each other , in particular for cleaning purposes . fig1 to 17 show another embodiment of the hinge mechanism between the two barrier elements . this mechanism comprises in particular an outside cap secured to the element 5 and given numerical reference 80 . this cap is received in a countersink provided in the thickness of the element . it is constituted by a generally cylindrical piece of molded plastics material having an outer circular wall 800 of small thickness . this wall has radial partitions attached thereto , there being seven such partitions referenced 801 . these branches converge towards the center of the part and they join a central ring 802 of small diameter which defines an inside space 803 . an opening 805 is provided in the thickness of the wall 800 , giving access to a housing 804 which extends diametrically and which crosses part of the inside space 803 of the central ring 802 . the mechanism further comprises a pin 81 having a head 810 in the form of a disk and an axial rod 811 . close to its free end , the rod has a peripheral groove 812 . it is positioned in such a manner that when the pin is engaged on the element 5 ′, the groove lies inside the above - mentioned housing 804 . a cap 82 covers the pin 81 and occupies a position that is flush with the element 5 ′. the outside cap 80 is suitable for receiving a blocking element 83 via the opening 805 , which blocking element is constituted by a curved resilient clip 831 analogous to a hair pin , with one end having a head 830 for grasping . when the blocking element is engaged in the opening , a zone of the clip 831 is received inside the groove 812 of the pin 81 so as to prevent it being withdrawn from the outside cap . this is the position shown in fig1 and 16 . thus , when the spring clip is in position , the elements 5 and 5 ′ can pivot relative to each other . when the clip is extracted by pulling on its head 830 , it becomes possible to disengage the pin 81 and to separate the elements 5 and 5 ′. in the embodiment of fig1 to 23 , the hinge mechanism comprises an outside cap 90 mounted on the element 5 ′. it comprises a plate 900 of circular outline with four screw - fastening orifices . this plate has a low cylindrical wall 901 in a centered position . two tabs extend from the wall so as to face each other , i . e . they are diametrically opposite . they are attached to the wall , substantially halfway up it . the tabs are l - shaped , each having a base limb 903 connected to the wall and extending parallel to the plate 900 . the axially - extending limb 902 of each l - shape projects in the same direction as the wall and is of a curved shape , which means that these two limbs occupy a cylinder centered on the axis of the part . a part referred to as an “ angular sector ” 91 is engaged in the cap . this part comprises a cylindrical body 910 of diameter corresponding to the inside diameter of the geometrical cylinder defined by the two limbs 902 , ignoring clearance . one end of this body carries a coaxial head 911 in the form of a cylinder of smaller diameter . the opposite end of the body is connected to a flat plate 912 which extends in a diametral direction . the central portion 915 of the plate is circular , and it carries lugs 913 and 914 in the form of sectors of a ring . overall this gives the plate a shape that is reminiscent of a bow tie . the angular sector is engaged in the cap 901 via the space left empty between the limbs 902 until the plate 901 comes into contact with the plate 900 . it is then possible to turn the angular sector with the plate 912 being guided and held axially by the tabs 902 . a helical spring 94 is received in the gap between the spacer 910 and the tabs 902 . the assembly is covered by a spacer 92 in the form of a cylindrical sleeve which is fixed to the element 5 ′. its base 920 bears against the plate 900 . at this level , its inside diameter is selected to be equal to the outside diameter of the wall 901 , ignoring clearance . the spacer 92 has an inside shoulder 921 which comes into abutment against the top of said wall . finally , its end remote from the base 920 is shaped like a cylindrical chimney 922 providing guidance in rotation for the sector 91 . the spring 94 bears against the spacer , immediately behind the chimney . the last part of this assembly is constituted by an inside cap 93 . it is provided with a low cylindrical wall which is received in the chimney 922 and which constitutes an abutment in sliding for the sector 91 . it is also provided with a peripheral flange 931 which presses against the spacer . as constituted in this way , the mechanism serves to hinge the two barrier elements around the part 91 . this part is constantly held inside the cap 90 under the effect of the spring 94 . nevertheless , by causing the elements to pivot in such a manner that the lugs 913 and 914 are no longer in register with the tabs 902 , it becomes possible by applying traction to the element 5 ′ to overcome the force of the spring 94 and to move the element 5 ′ temporarily away from the element 5 . this gives access to the gap between them in order to clean them locally . the hinge means are preferably selected in such a manner as to leave as little space as possible between the two elements in normal operation so as to ensure that even a child cannot slide a finger between them . this makes it possible to avoid any risk of a pinching accident , particularly when moving the elements . fig2 to 27 show a system that makes it possible when the barrier elements are in the overlapping position , whether above or below the bed plane , to avoid any involuntary movement that might bring them into a position other than the desired position . in these figures , reference 500 ′ designates the main , central arm that forms an integral portion of the above - mentioned deformable parallelogram system 50 ′. the barrier element 5 ′ is hinged to the top of this arm about an axis 501 ′, while the arm itself is hinged relative to the base structure of the bed about a parallel axis 502 ′. reference 211 designates a part that is secured to the base structure of the bed , which part comprises in two distinct zones respective openings 212 and 213 associated with respective abutments 214 and 215 . the central arm 500 ′ is hollow and a safety catch 503 ′ can slide in its end . this safety catch is connected to a cable 504 ′ represented in fig2 and 27 by dashed lines . a remote control mechanism ( not shown ) enables the cable to be pulled to actuate the safety catch . in the position of fig2 , the elements extend above the hard plane of the bed and the safety catch is engaged in the opening 212 of the part 211 . in order to unlock the elements while in this position , it is necessary to act on the cable 504 to extract the safety catch from its housing . when in the retracted position beneath the hard plane of the bed , the safety catch is received in the opening 213 , and in that case also it is necessary to act on the cable 504 ′ in order to change position . fig2 shows an additional opening 216 and an additional abutment 217 on the part 211 . they enable the elements 5 and 5 ′ to occupy an intermediate locked position between the positions described above . more precisely , this is a position in which the elements are spaced apart from the bed and extend in part above the bed plane . this position is particularly suited for enabling the patient to take hold of a handle situated beside the axis xx ′ and to pull on the handle in order to get out of bed . fig2 and 29 show the actuator means that enable traction to be applied to the cable 504 . these means comprise a control constituted by a button b that is movable in a slideway a fixed to the element 5 ′. the button receives the end of the cable 504 ′ which actuates the mechanism for retracting the barrier . the control is positioned in such a manner that it is not directly accessible for the patient , since it faces outwards . in addition , it is positioned in such a manner that the button b is accessible only when the elements are in the overlapping position , as shown in fig2 . fig7 shows a mechanism 56 which is described below and which makes it possible to unite the two barrier elements when they are in the mutually overlapping position . in this position , and as can be seen in fig1 , 2 , and 7 , the barrier elements are contiguous with each other , and they occupy substantially the same amount of space as a single element . this position is particularly preferred when the patient desires to avoid any danger of falling , while still being able to sit on the edge of the bed . indeed sitting on the edge of the bed is made easier by the patient taking hold of the barrier elements . in the embodiment shown in the accompanying figures , except in fig3 and 31 , the bed plane 2 is fitted longitudinally with a rail 6 ′ for co - operating with one of the barrier elements . it is situated longitudinally on the side of the bed , on the portion 20 of the bed plane opposite from the portion carrying the retraction equipment 50 ′. this rail is constituted by an upside - down u - shaped meal bar whose two parallel vertical limbs 60 ′ are joined to the bed plane by a respective horizontal end portions that are not visible . the bar 61 ′ uniting them thus extends longitudinally and horizontally along the bed plane . the mechanism 56 for locking together the two barrier elements can be seen more particularly in fig3 . it comprises an orifice 53 passing through the thickness of the element 5 and receiving from the outside of the bed a button 54 . this button has a rod which passes through the thickness of the element 5 and comes out the opposite side . at this level , the rod receives a catch 55 which is generally t - shaped . the upright of the t - shape co - operates with the rod of the button , while its two perpendicular cross - bar portions 551 are disposed vertically on the side of the element 5 . each cross - bar portion co - operates with the associated element 5 to leave an empty jamming space . when the two barrier elements are overlapping one on the other ( fig7 ) it is possible to lock them together by bringing the catch 55 so that one of its cross - bar portions 551 pinches the top edge of the element 5 ′. when the two elements are in the deployed position , i . e . when they occupy a parallel position substantially in line with each other ( fig3 and 6 ), it is the opposite cross - bar portion of the t - shape which co - operates with the base 60 ′ of the guide rail 6 ′. the rail performs a first function which is an abutment function in which it prevents the barrier element 5 from pivoting below the level of the bed plane . nevertheless , it also performs a second function which is to guide the element 5 ′. thus , when the head portion 21 of the bed plane is raised ( fig4 and 5 ), it moves the set of elements 5 and 5 ′ longitudinally towards the foot of the bed . as a result , when the two elements are in the deployed position ( fig5 ), the rail 6 serves not only to press against the element 5 , but also to guide it longitudinally as a function of the position of the bed plane . furthermore , when the bed plane is returned to the strictly horizontal position , the barrier element 5 can be seen to move along the rail 6 ′. it should be observed that the operation of tilting the barrier elements to go from one position to the other is very easy to perform since it suffices to take hold of the outer element 5 and cause it to pivot about the axis xx ′. the double - headed arrows in fig3 illustrate these movements . in addition , large handle - forming notches are provided in this case in the thickness of the elements , in order to make these operations even easier . in the embodiment of fig3 and 31 , the bottom portion of the element 5 comprises a longitudinally extending element of smaller thickness referenced r . the base structure of the bed includes a stand p projecting towards the outside of the bed so as to be situated vertically beneath the element 5 . its top portion constitutes a slideway g in which a handle n is hinged . the shape of the portion r of the element 5 is complementary to that of the slideway . when the element 5 is deployed , the portion r clips automatically into the slideway and in order to release the element it is pulled upwards while actuating the handle n . thus , in operation , when the various portions of the bed are moving , the element 5 implements longitudinal displacement by the portion r sliding in the slideway . the bed shown in part in fig3 and 35 has a frame c fitted at one of its ends with a bed head panel 4 . at the opposite end , a bed foot panel 4 ′ is secured to an assembly suitable for supporting the legs of a patient in different orientations . the frame c receives the hard bed plane which is constituted in this case by four distinct elements 20 , 21 , 22 , and 23 . the element 20 is secured to a torso - lifting mechanism capable of occupying various horizontal positions ( see fig3 ). the element 21 is stationary while the element 22 is hinged thereto about an axis yy ′ that is generally horizontal and extends transversely relative to the longitudinal axis of the bed . thus , it can occupy positions that are not horizontal . finally , a last element 23 is secured to the above - mentioned leg - raising assembly . a bed head barrier element 5 ′ is hinged to the bed plane element 20 . this element is secured to a retraction mechanism 50 ′ of the same type as that described above . as in the examples described above , a barrier element 5 is hinged to the element 5 ′ about an axis xx ′ that is generally perpendicular to the longitudinal axis of the bed . the element 5 is hollow and an additional barrier element 5 ″ is received inside it . by pulling on this additional element in the direction of arrow j ( fig3 ), this element is caused to rest on a locking device 230 fitted to the element 23 of the bed plane . this device is preferably fitted with a pivot and support pin 231 such that regardless of the respective orientations of the elements 20 to 23 , the barrier element 5 ″ might possibly slide , but always while being supported on the device 230 . in addition , the element 23 may be provided with an integral extension ( not shown ) e . g . having a length of 18 centimeters ( cm ). the element 5 ″ can then slide simultaneously with the element 23 being extended , thus adapting it to the length of the bed . this makes it possible to provide the patient with continuous protection , regardless of the orientations of the portions 20 , 22 , and 23 . by means of this system combining hinged and sliding barrier elements , it is possible to provide protection beside substantially the entire length of the bed , which is particularly reassuring both for the patient and for hospital staff . when the barrier elements are in the erect position , a space is released beneath the bed plane going from the element 5 ′ to the locking mechanism 230 , and this occurs regardless of the position of the bed and of its barrier elements . fig3 to 38 show a retractable support part for the element 5 , constituting a variant embodiment of the above - described foot p . this part is situated along one of the bars 20 and projects transversely relative to the bed . it is constituted by a pair 220 of stationary lugs 221 and by a flap - forming element 230 . the lugs 221 extend parallel to each other transversely and vertically relative to the bar 20 . on top and close to the bar 20 , they carry a pin 222 parallel to the longitudinal axis of the bed . further down and away from said bar , each of them is pierced by an opening for passing a locking pin 240 . this pin is constituted by a cylindrical rod 241 and by an actuator button 244 . they are separated by a cylindrical sleeve 243 which is integral with the button and of a diameter that is greater than that of the rod 241 . this rod extends between the lugs , while the button 244 and the sleeve 243 lie outside the zone between them . finally , the free outside end of the rod 241 is terminated by a tip 242 of small diameter which passes through the corresponding lug opening provided for this purpose . the rod 241 has a helical spring secured thereto ( not shown ) tending to urge said rod into the position shown in the figures , i . e . with the cylindrical sleeve 243 pressing against the first lug and the tip 242 engaged in the opening in the second lug . a flap - forming element 230 is hinged to the lugs . this element comprises two parallel branches 233 and 234 interconnected by a solid part 232 having two parallel partitions 232 ′. the branches are hinged to the lugs about the pin 222 . they are spaced apart slightly wider than the lugs . the branch 233 has a notch 235 opening out upwards . the “ bottom ” 237 of this notch is circular and its diameter is equal to the diameter of the sleeve 243 , ignoring clearance ( see fig3 ). nevertheless , the width of the notch tapers close to its bottom so as to constitute a constriction 236 whose opposite edges are spaced apart by a distance that is smaller than the diameter of the bottom 237 . finally , the solid part 232 interconnecting the branches 233 and 234 is constituted by two parallel plates 232 ′ having a space left between them for receiving the bed barrier element 5 . in the position of fig3 and 37 , the support part is suitable for receiving the element 5 which presses against that part 232 between the plates 232 ′. nevertheless , when the two elements overlap each other , the part 232 can hinder a patient attempting to get out of bed . it is then useful to be able to retract the flap 230 . for this purpose , the button 244 is grasped and traction is applied . this has the effect of moving the sleeve 243 away from the bottom 237 of the notch 235 , thus releasing the flap 230 since the constriction 236 is no longer held by the sleeve . this traction also has the effect of disengaging the tip 242 from the orifice 238 in the branch 234 . consequently , the flap can tilt about the pin 222 . as soon as traction on the button 244 is released , it returns to its initial position . in order to return the flap to the erect position , it suffices to lift it manually and to pull on the button so as to be able to lock the two branches 233 and 234 together . the retracted position can also be useful when the bed needs to be moved out from a room . when retracted in this way , the risk of the flap striking against a wall or a door frame is reduced .

a bed comprises a head end , a foot end , first and second sides and a deck which includes , a head section and a foot section . the head section is pivotable . head end and foot end barriers are positioned along one of the sides , and both barriers are adapted to move between raised and lowered positions . the head end barrier is moveable with the head section as the head section pivots . when both barriers are raised 1 ) the foot end barrier extends footwardly beyond the head end barrier , 2 ) a portion of the head end barrier and a portion of the foot end barrier overlap each other over a portion of their longitudinal extents at all pivoted positions of the head end barrier , and 3 ) the overlapped portion of the head end barrier is laterally between the deck and the overlapped portion of the foot end barrier .

in one aspect of this invention , the metabolic capacity of a living system is used to explore the impact of a stressor on that system by comparing its biochemical response to that of an un - treated control , directly and within a single sample . the method uses a specific experimental design and universally distributed isotopic incorporations to establish baseline responses for each system in a normal ( or “ control ”), and one or more experimental ( treated , or otherwise “ stressed ”) system ( s ). as used herein , a “ stressor ” can be any thing that causes or could cause a change in a living organism . exemplary stressors include a drug , hormone , temperature , ionizing and non - ionizing radiation and the like . the word “ drug ” is meant to include an externally ( exogenously ) supplied chemical substance that upon absorption into a cell , alters the function of the cell in some manner . as such , a compound such as an exogenously supplied vitamin , mineral , toxin , antagonist , or agonist can be deemed to be a “ drug ”. dietary minerals are the chemical elements required by living organisms , other than the four elements carbon , hydrogen , nitrogen , and oxygen that are present in common organic molecules . dietary minerals are often classified as “ macromineral ” or “ microminerals ” ( or “ trace minerals ”) and are usually required in greater or lesser amounts by an organism . hormones are defined as being internally ( endogenously ) supplied materials that alter the function of a cell in some manner . a hormone that is supplied to a cell from a source external to the cell is still considered a hormone herein . thus , control sample organisms are grown in a first nutrient medium containing predetermined amounts of first and second stable isotopes of a first atom within a nutrient . the experimental sample organisms are grown in a second nutrient medium substantially identical to the first nutrient medium , but containing different predetermined amounts , compared to said first nutrient medium , of the first and second stable isotopes of that first atom within the nutrient . illustratively for a system using stable isotopes of carbon [ carbon - 12 ( 12 c ) and carbon - 13 ( 13 c )], the isotopic ratios in this example specifically include a dilution of five to ten percent of one carbon isotope in another ; i . e ., one sample is grown on a carbon source ( nutrient in a medium ) that can be 95 % carbon - 12 ( 12 c ) and 5 % carbon - 13 ( 13 c ), hereinafter called “ c - 12 medium ”, and in such a situation the other sample is grown in mirrored medium that contains a nutrient that contains 95 % carbon - 13 and 5 % carbon - 12 in a medium , hereinafter called “ c - 13 medium ”. in each of these cases the biological system takes up the nutrient in the medium and grows upon it in such a way as to transform itself so that all of its parts are distinctively identifiable as to their origin . further information can sometimes be obtained by incorporating a second set of two isotopes of a second atom present at two different predetermined isotopic ratios into the nutrient compositions . as used herein , predetermined first and second stable isotope amounts are preferably present in “ inverted ratios ” of each other such as those discussed immediately above in which the number of the numerator of the first ratio is the number of the denominator of the second ratio , and the number of the denominator of the first ratio is the number of the numerator of the second ratio . taking the above ratios of 95 % and 5 %, a first ratio would be 95 / 5 12 c / 13 c in the c - 12 medium , whereas the second , inverted ratio , would be 5 / 95 12 c / 13 c in the c - 13 medium . it is to be understood that a contemplated set of preferred ratios need not be 95 / 5 and 5 / 95 and that those numbers are just used for convenience . it is preferred that neither isotopic ratio is the naturally occurring ratio . experimental variance or “ noise ” is a fact of any experimental design . because experimental variance or noise is so prevalent , experiments are often required to be performed with a large number of replicates in order to be assured that the true signal may be discriminated from artifactual ( or statistical ) noise . in the current “ design of experiments ” literature the sample population size needed to achieve a given power is specifically calculated from the amount of expected variance in the sample set . therefore , any reduction in sample variance ( or “ noise ”) reduces the number of samples required to determine a given effect . the sources of variance are the result of 1 ) uncontrollable differences in the sample ( for instance : sourcing , growth , development , handling , processing , etc . ), 2 ) uncontrolled differences in the analytical process ( for instance : materials , handling , processing , timing , etc . ), or 3 ) errors introduced during the informatic analysis ( for instance : randomness errors , algorithm errors , hardware errors , etc .). this invention reduces these sources of variance by : 1 ) removing pre - experimental , or “ source - based ”, variance by establishing all samples from a single source , and holding this source constant for the duration of the experiment ; 2 ) removing post - experimental ( analytical , or informatics - based ) variance by combining the material content of the experimental and control samples into a single composite sample . there can therefore no longer be variation introduced by sample handling because what happens to the control sample also happens to the experimental sample . in order to combine the samples , the samples are uniformly and universally labeled with appropriate isotopes . an element in which there are two stable isotopes that are not significantly distinguished by enzymes or living systems can be used . carbon ( specifically , 12 c and 13 c ) is used for purposes of illustration herein because of its universal applicability ; however , additional examples include the isotopes of nitrogen ( 14 n and 15 n ), oxygen ( 16 o , 17 o , or 18 o ), sulfur ( 32 s , 33 s , 34 s , or 36 s ), chlorine ( 35 cl and 37 cl ), magnesium ( 24 mg , 25 mg and 26 mg ), silicon ( 27 si , 28 si and 29 si ), calcium ( 40 ca , 42 ca , 43 ca , and 44 ca ), and bromine ( 79 br and 81 br ). the use of isotopes that exhibit minimal biological isotope effect is of import . for instance , the use of the isotopes of hydrogen ( d or t , which is radioactive and thus not favored ) would not be suitable because they frequently cause an observable effect on metabolism due to the fact that the deuterium isotope has a mass that is twice that of hydrogen , and thus , is known to cause a reduction in the kinetics of some enzyme mechanisms but not in others . the discussion that follows considers carbon as an illustrative element for incorporation and use in an assay . however , there are examples where other elemental combinations can provide less broad but specific insights . compounds of biological origin are unique in that they are all interrelated through the biological process . a contemplated method extends this truth by creating two populations of almost identical biological potential but requiring that each be based on differing isotopic source material . thus , each biological sample has a full biochemical complement that is made up of differing isotopic distributions . in the simplest case , two classes of samples are created , e . g . experimental and control . one of these classes , for the sake of this discussion the “ control ”, is derived from medium in which the isotopic distribution was primarily carbon twelve and the other ( the “ experimental ) is based on medium that was primarily carbon thirteen . when these two samples are mixed , intermingled or otherwise composited , the composite sample contains molecules from both the “ control ” ( that are made up of a substantial majority ; i . e ., 90 % to 95 %, of 12 c ) and the “ experimental ” ( that are made up of a substantial majority ; i . e ., 90 % to 95 %, of 13 c ). using the mass distribution for all of compounds identified from such a composite sample one can determine the relative contributions for each compound from either original sample . deviating significantly from the 90 % to 95 % ratio taught by this method reduces the potential for interpretation . consider three cases for isotopic ratios ; 1 ) the natural abundance of 12 c is approximately 98 . 9 %, whereas the natural abundance of 13 c is approximately 1 . 1 %, 2 ) nearly pure ( i . e . approaching 100 %) of each , or 3 ) controlled isotopic ratio mixtures . in case 1 , natural abundance , every compound will be a collection or mixture of isotopomers that vary in mass due the presence of 13 c impurity in the 12 c background ( see fig3 ). thus , the distribution of these isotopomers as seen in the mass spectrometer will include a number of peaks derived from ions ( also called “ daughter ”) that are shifted up to higher mass from the peak ( also called “ parent ”) of the majority ion . unfortunately , in a majority of biochemicals or metabolites these secondary peaks are quite small and often lost as they are indistinguishable from noise . if one were to create a similar “ anti - natural abundance ” for 13 c ; i . e ., 98 . 9 % 13 c and 1 . 1 % 12 c , then the sample would have the majority peak as the highest mass and show a number of peaks that are shifted down from it at lower masses , but again in the majority of cases these additional peaks will be indistinguishable from noise , ( not shown but similar to fig4 ), if they are detectable at all . in the case of nearly pure isotopic starting material ( see fig4 ) the majority peak becomes even more dominant and the other peaks are even less likely to be seen . in both of the preceding cases , in a majority of the time one cannot count on seeing anything except the majority peak for each compound . thus , in both of these cases from a composited sample , as defined above , there would be two peaks from glucose , at 180 and 186 amu , in a mass spectrum of the sample . based on the fact that this is a known compound and previously identified , these two could be distinguished , and if the “ experimental ” response caused the c - 13 glucose peak to drop below detectable limits then this could be determined . however , if the compound were not glucose , but rather an unknown compound and there was only one peak it would be impossible to determine if the identified peak originated from the “ control ” side or the “ experimental ”. this invention improves upon this situation by specifically using material that is devised to assure that the minority peaks are present in sufficient quantity that they will generally be seen ( see fig5 ). in this case , the source of every compound can be identified because , relative to the majority peak , the minority peak will be larger in mass ( and therefore derived from 12 c based cells ), or the minority peak will have a smaller mass ( and therefore be derived from the 13 c based cells ). thus , it is optimal to increase the percentage of the “ impurity ”; i . e ., 12 c in 13 c or visa versa , in carefully controlled amounts significantly above their natural abundance ( see tables 1a and 1b , below ). table 1a shows the mass profile ; i . e ., the isotopic distribution , for a c - 12 based compound with a molecular compound of mass 180 ( c 6 h 12 o 6 ) that has been diluted with various percentages of c13 . thus , a c12 - based molecule of mass 180 with 95 % c - 12 and 5 % c - 13 will have an m + 1 (@ 181 amu ) that is 31 . 95 % of the height of the parent peak at 180 amu . it will furthermore have a m + 2 that is 5 . 5 % of the parent peak . the remaining values illustrate lesser and greater dilutions of c - 12 with c - 13 . conversely to table 1a , table 1b shows the mass profile ; i . e ., the isotopic distribution , for a c - 13 based compound with a molecular compound of mass 186 ( c 6 h 12 o 6 ) that has been diluted with various percentages of c12 . thus , a c13 - based molecule of mass 186 with 95 % c - 13 and 5 % c - 12 will have an m − 1 (@ 185 amu ) that is 31 . 55 % of the height of the parent peak at 186 amu . it will furthermore have a m − 2 that is 4 . 15 % of the parent peak . note that this molecule will have very small m + 1 , etc . peaks due to isotopic contributions from other atomic species , i . e . oxygen , hydrogen , nitrogen , etc . therefore , the compounds that are contributed to the composite from the 13 c sample can be distinguished because they will have daughters that are at m − 1 ( trailing the parent ), whereas those peaks from the 12 c samples will have their daughters at m + 1 ( leading the parent ). using this rule one can easily distinguish the source of any peak as to control or experimental . the addition of 10 % impurity ( 13 c in 12 c or visa versa ) results in a daughter peak that is about 66 % of the size of the parent ( see tables 1a and 1b ). the optimal increase over natural abundance is a function of the study in question and the average size of the molecules that the study is targeted to see , but the benefit of the augmentation of the isotopic ratios in both the 13 c and 12 c media is always a benefit . the components of the composite sample are themselves typically separated prior to introduction into the mass spectrometer . that separation can be carried out using gas chromatography , high pressure liquid chromatography ( hplc ), size exclusion chromatography , electrophoresis and the like . various separation techniques can also be combined . illustrative equipment that can be used to carry out a contemplated method include the following . agilent 6520 accurate - mass q - tof lc / ms , agilent 5975 series msd , thermo - fisher ltq , thermo - fisher orbitrap ®, waters micromass ® gct premier ™, and waters lct premier ™. separation systems can be part of the ms ( as in gc ) or separate , and illustratively include : waters acquity uplc ®, agilent rapid resolution , and thermo surveyor plus systems . the two other major classes of compounds found in any sample , namely artifacts , and introduced compounds , can now be examined . in the case of artifacts , the material necessarily exhibits a natural abundance isotopic distribution . if the biological compounds derived from biological sources were developed on media containing non - natural distributions of isotopes , the ability to discriminate artifacts becomes quite easy based on the size of the daughter peaks . on the other hand , for compounds that are exogenously introduced as an experimental variable , as drugs , medicines , toxins , or the like , it is likely that they will participate to some extent in the biological processes . therefore , if they are synthesized using highly enriched 13 c , they will not have the significant daughters of the normal biological components and thus can be distinguished . even after these exogenous compounds have undergone significant biological transformation , their daughter ions will have lower than normal ratios allowing them to be identified as derivatives of the exogenously applied compounds . the above observations permit one to classify distinctive patterns that are important in the interpretation of the resulting composite spectra . because one can discriminate which portion of the study ; i . e ., 12 c or 13 c , artifact or derivative of an exogenously applied compound , every peak in the composite comes from , one can interpret the analytical results of the composite sample to an even greater extent . these expectations are easily reduced to appropriate software , and thus this process can be fully automated . ion suppression is a phenomenon that occurs during the mass spectroscopic ionization processes when the efficiency of ionization is subjected to variability due to characteristics of the compounds that are present . thus , in its most common form , the number of molecules that could be ionized is in excess of the amount of charge available . in this situation the molecules that become ionized most efficiently are those that can acquire the charge most strongly , and the remaining molecules become ionized with much lower efficiency . the variability introduced here makes the quantification of these molecules very poor . the present method side - steps this issue completely . because every compound is found in both control and experimental compositions , with each being represented by two isotopomeric equivalents , and for every compound both compounds are internal to the same sample and have nearly identical chemical properties , then both will be subject to exactly the same ion suppression inefficiencies . under this scenario the ratio of one to the other is a true reflection of their relative concentrations in the original sample irrespective of anything except 100 % ion suppression , which rarely occurs . in the vast majority of cases very valuable information has been recovered that would otherwise have been lost or of suspect quantification . a general description of the method is illustrated by a study in which : 1 . a single homogeneous collection of living organisms ( it can be a cell culture of animal , bacterial , fungal or of plant cells , and can be actively growing or in a suspended , but revivable , state , or even whole organisms ), 2 . is subjected to one or more wash / rinse cycle ( s ) using a biologically neutral buffer , 3 . is re - suspended in the same buffer and apportioned in such a way as to create a number of samples that they have an equal or approximately equal number of cells or organisms . 4 . the buffer is removed ( by centrifugation , filtration or other means ). 5 . two identical media are prepared , in one ( herein called “ c12 media ”) all carbon sources ( sugars , lipids , amino acids , proteins , etc ) contain only isotopically enriched 12 c ( i . e ., enhanced by addition of 13 c ), and in the other ( herein called “ c13 media ”), all the carbon sources are isotopically enriched 13 c enhanced with a comparable percentage of 12 c . 6 . wash ( as in step 2 ) one - half of the samples one or more times with the c12 medium and the other half of the samples should be equally treated with the c13 medium . 7 . after the final wash , dispense the cells to a vessel suitable for growth and in which the only medium available is either the c12 or c13 medium in which the cells were last washed . 8 . by performing the above steps , one should end up with two sets of identical cultures , all of which have approximately the same number of the statistically similar cells , but half of which use c12 medium for growth ( herein referred to as “ c12 samples ”) and the remainder use c13 medium for growth ( herein referred to as “ c13 samples ”). for purposes of this illustration , the c12 samples are deemed to receive the control and the c13 samples are deemed to receive the stressor , although in practice this can be reversed . what is important is that the samples be handled so that for each c13 sample there is an equivalent c12 sample . 9 . both sets of samples are permitted to grow out for a number of cell division cycles before proceeding . ( this growth will dilute any of the original isotopes that may inadvertently have been carried in at the start of this study by the original cells .) 10 . after an appropriate growth period , one of the test systems ( here arbitrarily , c13 ) should receive treatment with the stressor ( drug , toxin , physical , physiological or other ), while the other ( c12 ) gets an identical placebo or control treatment . 11 . after an appropriate period for the stressor to act , the cells / organisms are harvested and the samples are matched up . the c13 ( stressor - treated ) and the c12 ( control or placebo treated ) matched samples are combined during the harvest process to create a single composite sample . 12 . a detailed analysis ( metabolomic , proteomic , transcriptomic , or analysis for any other carbon - based class of compounds ) can be performed on the composite samples : a ) the relative c12 / c13 ratios of the analytes ( of known or unknown identity ) are determined , c ) an analyte compound that has a ratio that is a significant deviation from the average ratio indicates a point where the biochemistry was altered . for instance , if the average ratio for the all of the analytes is 1 ( 1 : 1 c12 / c13 ratio ), but some analytes have ratios of 10 ( 10 : 1 ) or 0 . 1 ( 1 : 10 ), then the analytes that are outliers to the general population are those most strongly effected by the stressor . the above method easily supersedes current methods in which individual samples representing the different populations , but not isotopically defined , are used . the benefits of this method include : 1 . the ability to prepare and label composite samples . the composite sample is statistically derived from a single homogeneous cell mass , grown , treated , and harvested under nearly identical conditions , and prepared and analyzed under identical conditions . experimentally , the major source of biological variance is the treatment with the stressor . 2 . abnormalities are seen by looking for outliers ; i . e ., deviations in the ratios of the 12 c to 13 c ratios for every desired analyte / compound within the sample . 3 . the process does not require that the identity of an analyte / compound be known to understand that its biochemical environment has been effected . 4 . a smaller number of samples are required to be analyzed in order to determine any outcome because the artifactual noise inherent in the experiment is reduced . 5 . although the method can applied to situations where the cells are actively dividing , it can also be applied to any situation in which the cells are metabolically active . 6 . artifacts can be identified as analyte compounds that are not seen as paired in either control or experimental samples , and demonstrate a “ normal ” isotopic distribution . 7 . within this method , exogenous compounds and their biochemical derivatives can be identified and tracked when they are given an isotopic distribution that is different from the media isotopic distributions . a contemplated method relies on establishing a set of relationships within a single sample that is to be analyzed . because of the predictable form these relationships take , the entire method can be reduced to a set of algorithms that can be coded in software . this software performs these functions in an automated manner , and produces a data set that details 1 ) analyte compounds found in the sample , 2 ) the 12 c / 13 c ratios for those analyte compounds , 3 ) the relevance of the compound to the response profile , 4 ) non - biological artifacts , and 5 ) derivatives of exogenously applied compounds . at its most fundamental the methods described impose patterns in the final data set that can be used in the interpretation of the data set to achieve a greater degree of precision , and accuracy than can be achieved by any other method . however , it is one thing to create these patterns , and another to use them . the software that is required in their use must be aware of the nature of the patterns created and then seek them in the final data set . in one such application , a composite sample is provided and is subjected to a separation phase , such as a gc , hplc or other chromatographic separation . the effluent of the separation is then analyzed by mass spectroscopy . the patterns are buried in the raw mass spectrometer data set as a series of scans with each scan representing a sequential time segment . the algorithm used to seek the patterns can take many forms ; however , in one instance 1 ) all of the ions seen by the mass spectrometer at a single point in time ( scan , or possibly a de - convoluted peak ) are gathered into a subset ; 2 ) the analyte ions in this subset are initially sorted by their m / z values , and then are then resorted based on their height or amplitude ; 3 ) the pattern of ions ( from top to bottom ) is examined to determine where the slope of the ion trace becomes approximately level . this point defines random noise , and all further ions are considered “ noise ”. noise ions are removed from consideration . 4 ) starting from the ions with the greatest height or amplitude , the individual ions are examined ( queried by the software ) sequentially : a ) for each ion ( that has m / z or mass of m ) i . does the m + 1 have the size compatible with its being based on a c - 12 majority molecule ; i . e ., with 3 % to 10 % c - 13 overall incorporation ? in this situation , the m + 1 will be between 18 %, 31 %, or 66 % if the molecule has a mass of approximately 180 and has 3 %, 5 %, or 10 % c - 13 content , respectively . if so , the analyte ion is identified as a c - 12 majority molecule and all associated ions ( m + 1 , m + 2 , etc . ; similarly identified ) are removed from future consideration . the next highest available analyte ion is then examined . ii . does the m − 1 have the size compatible with its being based on a c - 13 majority molecule ; i . e ., with 3 % to 10 % c - 12 overall incorporation ? in this situation , the m − 1 will be between 18 %, 31 %, or 66 %, respectively , if the molecule has a mass of approximately 180 and has 3 %, 5 %, or 10 % c - 13 content . if so , this analyte is identified as a c - 13 majority molecule and all associated ions ( m − 1 , m − 2 , etc . ; similarly identified ) are removed from future consideration . the next highest available ion is thereafter examined . iii . does the m + 2 demonstrate a pattern associated with a standard ? if so , it is identified as a standard and all associated ions ( m + 2 , etc .) are removed from future consideration . the next highest available analyte ion is thereafter examined . iv . if none of the above are true , the analyte ion is derived from an artifact and not experimentally significant . it is removed from further consideration . b ) this process is repeated until all analyte ions at this time point ( and not yet accounted for ) are analyzed . 5 ) steps 1 to 4 will be repeated for all time points . 6 ) the outcome of the above process identifies all analyte ions as either derived from a c - 12 majority molecule , a c - 13 majority molecule , a standard or removes them from consideration . a ) all analyte ions are now grouped in time to form peaks ( if this has not already been done . in other manifestations this can be done in an earlier stage .) these peak characteristics include a start time , end time , maximal time , base mass , maximal height of base ion , etc .) b ) for all c - 12 majority molecules , a matching c - 13 majority molecule is sought . this matching molecule demonstrates a similar time signature ; i . e ., similar start time , end time and maximal time . values to collect include : i . the mass difference between the c - 12 majority base mass and the c13 majority base mass represents the number of carbons in the molecule . ii . the ratio between the maximal height of the c - 12 majority molecule and the maximal height of the c13 majority molecule . c ) for all standards , their time is noted . 7 ) alignment of all pairs can be accomplished by standard methods for calculating or normalizing retention indices ( illustratively by use of the internal standards ). 8 ) the mean and standard deviation for the ratio values for all pairs is calculated . 9 ) all pairs that deviate outlier ratios are identified by evaluation of their deviation from the mean . this final step of the evaluation can vary according to experimental design and analytical conditions . there are many possible ways of rearranging the steps described here or accomplishing each of their outcome but they all will need to accomplish the majority of the above steps . a contemplated method is general in its applicability and is illustrated by the following specific examples . 1 . a bacterial cell response to a stressor that is an antibacterial drug in this instance the experimental design is set up in order to determine the effect of a drug on bacterial cultures as a function of time . in this instance , because of the nature of the question to be answered , the appropriate control is a contemporaneous culture . an actively growing culture of a escherichia coli ( bacteria ) is subjected to one or more wash / rinse cycle ( s ) using an isotonic but non - nutritional ( in ) buffer ( via centrifugation ). the resulting pellet of cells is re - suspended in the same in buffer and apportioned to create 24 samples that they have an equal or approximately equal number of bacterial cells . the in buffer is removed from these 24 samples . two identical media are prepared , in one ( herein called “ c13 medium ”) the sole carbon source is isotopically enriched 13 c - glucose ( as discussed above ), and in the other ( herein called “ c12 medium ”) the sole carbon sources is isotopically enriched 12 c - glucose ( as discussed above ). twelve of the samples are washed three times with the c12 medium and the remaining 12 samples are similarly washed with the c13 medium . after the final wash , the cells are dispensed into a vessel suitable for growth and in which the only medium available is either the c12 or c13 medium in which the cells were last washed . by performing the above steps , one prepares two sets of 12 identical cultures , each of which has approximately the same number of the statistically similar cells , but half of which use c12 medium for growth ( herein referred to as “ c12 samples ”) and the remainder use c13 medium for growth ( herein referred to as “ c13 samples ”). for purposes of this illustration , the c12 samples are deemed to receive the control and the c13 samples receive the stressor , although in practice this can be reversed . the important point is that the samples be handled so that for each c13 sample there is an equivalent c12 sample . both sets of samples are grown until they reach exponential growth and have undergone several cellular divisions . after the appropriate growth period the 12 c13 samples receive treatment with a stressor such as an antibacterial drug , whereas the c12 samples receive an identical placebo or control treatment . after an appropriate period for the stressor / drug to act , the cells / organisms are harvested and the samples are matched up . the c13 ( stressor treated ) and the c12 ( control or placebo treated ) matched samples are combined during the harvest process to create a single composite sample . in this example three composites can be created at time 0 , 1 , 4 , and 24 hours , respectively . a detailed analysis ( metabolomic , proteomic , transcriptomic , or analysis for any other carbon - based class of compounds ) is performed on the composite samples . the relative c12 / c13 ratios of the analytes of each sample ( of known or unknown identity ) are determined . the statistical variance of the ratios sample is determined . an analyte compound that has a c12 / c13 ratio that is a significant deviation ( two or more standard deviations ) from the average ratio is indicative of a point at which the biochemistry was altered . for example , if the average ratio for the analytes is 1 ( 1 : 1 c12 / c13 ratio ), but some analytes have ratios of 10 ( 10 : 1 ) or 0 . 1 ( 1 : 10 ) then the analytes that are outliers to the general population , e . g ., those with ratios of 10 and 0 . 1 , are those most strongly effected by the stressor and indicate a point of biochemical alteration . in this instance , the experimental design is set up in order to determine the effect of a drug on mammalian cell cultures as a function of time . in this instance , because of the nature of the question to be answered , the appropriate control is a contemporaneous culture . an actively growing culture of human hepatocytes is subjected to one or more wash / rinse cycle ( s ) using an isotonic but non - nutritional ( in ) buffer ( via centrifugation ). the resulting pellet of cells is re - suspended in the same in buffer and apportioned in such a way as to create 24 samples that they have an equal or approximately equal number of bacterial cells . the in buffer is removed from these 24 samples . two identical media are prepared , in one ( herein called “ c13 medium ”) the sole carbon source is isotopically enriched 13 c - glucose ( as discussed above ), and in the other ( herein called “ c12 medium ”) the sole carbon sources is isotopically enriched 12 c - glucose ( as discussed above ). ( an exemplary medium is williams medium e , a fully defined medium capable of supporting growth for extended periods of time or any other medium that can be isotopically defined .) twelve of the samples are washed three times with the c12 medium and the remaining 12 samples are similarly washed with the c13 medium . after the final wash , the cells are dispensed into a vessel suitable for growth and in which the only growth nutrient - containing medium available is either the c12 or c13 medium in which the cells were last washed . by performing the above steps , one prepares two sets of 12 identical cultures , each of which has approximately the same number of the statistically similar cells , but half of which use c12 medium for growth ( herein referred to as “ c12 samples ”) and the remainder use c13 medium for growth ( herein referred to as “ c13 samples ”). for purposes of this illustration , the c12 samples are deemed to receive the control and the c13 samples receive the stressor , although in practice this can be reversed . the important point is that the samples be handled so that there is an equivalent c12 sample for each c13 sample from which a data point is desired . both sets of samples are permitted to grow ( metabolize in situ if not dividing ) until they have attained a desired isotopic replacement . in the case of a dividing cell it can have undergone several cellular divisions . after the appropriate growth period , the 12 c13 samples receive treatment with a stressor such as a drug ( atorvastatin calcium ), drug candidate , or another compound for which the biochemical response is sought , whereas the other c12 samples receive an identical placebo or control treatment . after a further appropriate time period for the stressor to act , the cells are harvested and the samples are matched up . the c13 ( stressor treated ) and the c12 ( control or placebo treated ) matched samples are combined during the harvest process to create a single composite sample . in this example three composites may be created at time 0 , 1 , 4 , and 24 hours , respectively . a detailed analysis ( metabolomic , proteomic , transcriptomic , or analysis for any other carbon - based class of compounds ) is performed on the composite samples . the relative c12 / c13 ratios of the analytes of each sample ( of known or unknown identity ) are determined . the statistical variance of the ratios sample is determined . an analyte compound that has a c12 / c13 ratio that is a significant deviation ( two or more standard deviations ) from the average ratio indicates a point at which the biochemistry was altered , as discussed previously . for example , if the average ratio for the analytes is 1 ( 1 : 1 c12 / c13 ratio ), but some analytes have ratios of 10 ( 10 : 1 ) or 0 . 1 ( 1 : 10 ) then the analytes that are outliers to the general population , e . g ., those with ratios of 10 and 0 . 1 , are those most strongly effected by the stressor and indicate a point of biochemical alteration . in this instance , the point of comparison is time zero . in this instance the experimental design is set up in order to determine the effect of aging on cell cultures . because of the nature of the question to be answered , the appropriate control is an aliquot of the time zero culture , which here is one hour after the application of fresh medium . an actively growing culture of a mammalian primary cell line is subjected to one or more wash / rinse cycle ( s ) using an isotonic but non - nutritional ( in ) buffer ( via centrifugation ). the resulting pellet of cells is re - suspended in the same in buffer and apportioned in such a way as to create 24 samples that they have an equal or approximately equal number of cells . the in buffer is removed from these 24 samples . two identical media are prepared . in one ( herein called “ c12 medium ”), the sole carbon source is isotopically enriched ( as defined in the above ), 12 c - glucose , and an appropriate collection of equally enriched 12 c - amino acids and other nutrients . in the other ( herein called “ c13 medium ”), the sole carbon sources are similarly isotopically enriched but with 13 c compounds . twelve of the samples are washed three times with the c12 medium and the remaining 12 samples should be equally treated with the c13 medium . after the final wash , the cells are dispensed into a vessel suitable for growth and in which the only nutrient - containing medium available is either the c12 or c13 medium in which the cells were last washed . one should have two sets of 12 identical cultures , all of which have approximately the same number of the statistically similar cells , but half of which use c12 medium for growth ( herein referred to as “ c12 samples ”), and the remainder use c13 medium for growth ( herein referred to as “ c13 samples ”). for purposes of this illustration , the c12 samples are the control cultures and the c13 samples are the samples which are permitted to age , although in practice this can be reversed . the important point is that the samples be handled so that there is an equivalent c12 sample for each c13 sample from which a data point is desired . both sets of samples are permitted to grow until such time that they have diluted all pre - existing or native carbon with medium - supplied carbon isotopes . if the cells are dividing they should undergo several cellular divisions . after the appropriate growth period , the c13 samples have their medium removed and replaced with fresh c13 medium . the c12 samples are similarly treated and also be given fresh medium . this can be considered time t =− 1 hr . after a further one hour period has passed ( t = 0 ), all of the aliquots of the c12 medium cells ( designated controls ) are individually harvested and frozen . three of the c13 ( aging ) cultures are harvested at time ( t = 0 ) and added to their matched 12c harvested aliquots . additional triplicate sets of the aging cells are harvested at t = 24 , t = 48 , t = 120 hours . as these cells are harvested they are paired with their matched t = 0 samples to create composite samples . a detailed analysis ( metabolomic , proteomic , transcriptomic , or analysis for any other carbon - based class of compounds ) is performed on the composite samples . the relative c12 / c13 ratios of analytes per sample ( of known or unknown identity ) are determined . the statistical variance of the ratios sample is determined . any analyte compound that has a ratio that is a significant deviation ( two standard deviations or more ) from the average ratio will indicate a point where the biochemistry was altered . for instance , if the average ratio for the all of the analytes is 1 ( 1 : 1 c12 / c13 ratio ), but some analytes have ratios of 10 ( 10 : 1 ) or 0 . 1 ( 1 : 10 ) then the analytes that are outliers to the general population are those most strongly effected by the stressor . d . growth curves or effect of age in a multicellular eukaryotic organism in this instance , the experimental point of comparison is time zero in a whole organism . the experimental design is set up in order to determine the effect of aging on an animal , for illustration here the nematode , caenorhabditis elegans . because of the nature of the question to be answered , the appropriate control is an aliquot of the time zero organism , which in this instance is one hour after the application of second round of fresh media . the stressor and stress regimen here is aging and growth of the organism during aging . an actively growing culture of a c . elegans and its feedstock of is subjected to one or more wash / rinse cycle ( s ) using an isotonic but non - nutritional ( in ) buffer ( via centrifugation ). the resulting pellet of nematodes is re - suspended in the same in buffer and apportioned in such a way as to create 2 samples , each of which has an equal or approximately equal number of nematodes . the in buffer is removed from these 2 samples . two identical media are prepared . in one ( herein called “ c12 medium ”), the sole carbon source is isotopically enriched 12 c - glucose ( upon which the bacterial feedstock of the nematode grow ), and in the other ( herein called “ c13 medium ”) the sole carbon sources is isotopically highly enriched 13 c - glucose . one of the samples is washed three times with the c12 medium and the remaining sample is equally treated with the c13 medium . after the final wash , the nematodes are dispensed into a vessel suitable for growth and in which the only nutrient - containing medium available is either the c12 or c13 medium in which the cells were last washed . two identical c . elegans cultures , both of which have approximately the same number of organisms are thus prepared . one of the cultures uses c12 medium for growth ( herein referred to as “ c12 samples ”) and the other uses c13 medium for growth ( herein referred to as “ c13 samples ”). ( for purposes of this illustration , the c12 sample is the control culture and the c13 sample is the sample that is permitted to age , although in practice this can be reversed . the important point is that the samples be handled so that there is an equivalent c12 sample for the c13 sample . both samples should be permitted to grow until they reach exponential growth and have undergone at least 1 or 2 full generations . after the appropriate growth period , the c13 sample has its medium removed and replaced with fresh c13 medium . the c12 sample is similarly treated and also be given fresh medium . after the appropriate subsequent growth period , the c13 sample should have its medium removed and replaced with fresh c13 medium and the nematodes separated for age . only the youngest stage is permitted to proceed . the c12 sample is similarly treated and also be given fresh medium . after a one hour period has passed ( t = 0 ), the c12 culture is aliquotted to 24 equal portions and nematodes in each aliquot harvested and frozen ( as the controls ). three of the c13 ( aging ) cultures are similarly harvested at time ( t = 0 ) and the harvested nematodes added to their matched 12c harvested controls . additional triplicate sets of the aging cells are harvested at t = 24 , t = 48 , t = 120 . as these nematodes are harvested they are paired with their matched t = 0 samples to create the composite samples . a detailed analysis ( metabolomic , proteomic , transcriptomic , or analysis for any other carbon - based class of compounds ) is performed on the composite samples . the relative c12 / c13 ratios of analytes per sample ( of known or unknown identity ) are determined . the statistical variance of the ratios sample is determined . any analyte compound that has a ratio that is a significant deviation ( two or more standard deviations ) from the average ratio will indicate a point where the biochemistry was altered . for instance , if the average ratio for the all of the analytes is 1 ( 1 : 1 c12 / c13 ratio ), but some analytes have ratios of 10 ( 10 : 1 ) or 0 . 1 ( 1 : 10 ) then the analytes that are outliers to the general population are those most strongly effected by the stressor . the experimental point of comparison here is a wild type organism . in this instance , the experimental design is set up to determine the effect of genetic manipulation upon the mustard , arabidopsis thaliana . because of the nature of the question to be answered , appropriate control is an aliquot of the genetically unmodified , or wild - type plant , which may be prepared separately from the experimental samples , but which needs to be from a single homogeneous control . the genetically modified plants are preferably derived from a common and consistent wild type background . for this illustration , it is presumed that there are one or more such genetically modified plants ( arbitrarily , 5 ) genetically distinct clones , all of which were derived from the same wild type stock . all of these genetically modified plants are stored as fresh viable seed at the start of the study . a large collection of wild type seeds are grown under controlled conditions in an atmosphere of isotopically enriched 13 c - carbon dioxide ( co 2 ) as defined above . these plants are harvested in a manner appropriate to the experimental design , illustratively at maturity . sufficient control sample can be prepared at one time for more than one study ; i . e ., all of the control plants should be combined into a single homogeneous sample . the plants are harvested by direct immersion into liquid nitrogen and subsequently stored at − 80 ° c . the frozen plants are powdered while in the frozen state . the genetically modified ( gmo ) seed is grown in a manner similar to that above , but these plants are grown under identical conditions except that their carbon source is carbon dioxide having an inverted 12 c / 13 c ratio . these gmo plants are harvested according to the protocol used above , and powdered as before . in the case of the gmo samples , each sample is harvested and treated individually . equal aliquots of the control powder are added to equal aliquots of the gmo experimental powders to form the composite samples . a detailed analysis ( metabolomic , proteomic , transcriptomic , or analysis for any other carbon - based class of compounds ) is performed on the composite samples . the relative c12 / c13 ratios of analytes per sample ( of known or unknown identity ) are determined . the statistical variance of the ratios sample is determined . any analyte compound that has a ratio that is a significant deviation ( two or more standard deviations ) from the average ratio will indicate a point where the biochemistry was altered . for instance , if the average ratio for the all of the analytes is 1 ( 1 : 1 c12 / c13 ratio ), but some analytes have ratios of 10 ( 10 : 1 ) or 0 . 1 ( 1 : 10 ) then the analytes that are outliers to the general population are those most strongly effected by the stressor . higher organisms represent a special case . in this instance , the experimental point of comparison is a whole higher organism and therefore one in which the concept of the experimental and control sample becomes more complicated as the biological variance within the test population is rather large . this can necessitate the compositing of individual samples to form “ biologically averaged ” experimental and control samples . these averaged samples are then composited . in this example the experimental design is set up to determine the effect of physiological stress ( induced by fasting for 24 hours ) on an animal , for illustration here the rat , rattus norvegiensus . because of the nature of the question to be answered , the appropriate control is a composite sample of rat plasma and the experimental sample is a composite sample of rat plasma from rats that have undergone the experimental , stressing treatment , which in this example will be starvation for 24 hours . due to the nature of the experiment it is expedient that the control population is the c - 13 animal as the control need not be contemporaneous and can be a standard control that is available prior to the actual running of the experiment . because the test system has animals , the experiment has more noise due to the greater variance inherent in the source material . the use of sample compositing partially offsets this problem as it averages the inherent biological variability , thus rendering the samples more representative of the norm . this results in a simplified experimental design , although it requires more complex prior preparation . a group of rats (“ the experimental population ”) of a defined strain are placed on a defined isotopically enriched c - 12 diet from birth . meanwhile another group of rats (“ the control population ”), of the same strain ( although possibly at a different point in time ) are grown on the c - 13 equivalent diet . both groups of animals are grown under identical environmental conditions . at the age of 6 weeks , the experimental animals are subjected to the experimental condition , for illustration here fasting for 24 hours beginning at the time that the light - cycle starts . therefore the experimental samples , plasma samples , are taken at the beginning of the light cycle on the following day . all of the samples from the experimental group are similarly collected . a composite experimental sample is created by mixing equal aliquots of plasma from all experimental animals . the control samples are similarly collected and composited from animals that have been feed a c - 13 equivalent diet . by performing the above manipulations , one obtains two similar samples that contain the required information content , namely the definition of the experimental response condition and the definition of the control condition . this creates the pair of samples to be mixed to create the composite sample for analysis . a detailed analysis ( metabolomic , proteomic , transcriptomic , or analysis for any other carbon - based class of compounds ) is performed on the composite samples . the relative c12 / c13 ratios of analytes per sample ( of known or unknown identity ) are determined . the statistical variance of the ratios sample is determined . any analyte compound which has a ratio that is a significant deviation ( two or more standard deviations ) from the average ratio will indicate a point where the biochemistry was altered . for instance , if the average ratio for the all of the analytes is 1 ( 1 : 1 c12 / c13 ratio ), but some analytes have ratios of 10 ( 10 : 1 ) or 0 . 1 ( 1 : 10 ) then the analytes that are outliers to the general population are those most strongly effected by the stressor . each of the patents and articles cited herein is incorporated by reference . the use of the article “ a ” or “ an ” is intended to include one or more . the foregoing description and the examples are intended as illustrative and are not to be taken as limiting . still other variations within the spirit and scope of this invention are possible and will readily present themselves to those skilled in the art .

a method for identifying a biological analyte that is affected by a stressor is disclosed in which two substantially identical biological samples are provided , with a first sample being a control sample and a second sample being an experimental sample . the control sample is grown with a nutrient having an isotope of a first atom , whereas the experimental sample is grown with a nutrient having a second isotope of the first atom . the experimental sample is grown with a stressing agent and regimen . the samples are admixed , and the formed composite is mass spectroscopically assayed for analyte peaks . the ratio of first isotope to second isotope is determined for the peaks , as is a sample median isotopic ratio . the ratio for assayed analyte peaks is compared with the median ratio . an analyte whose isotopic ratio significantly deviates from the median ratio is an analyte affected by the stressing agent .

in the following , a first exemplary embodiment of an orbital retractor 10 will be explained first , making reference to fig1 to 3 . in this connection , fig1 and 2 show the retractor 10 in a non - activated basic position ( retraction position ), while fig3 a and 3b illustrate the retractor 10 in an activated position ( introduction position ). the retractor 10 comprises a distal handle region 12 , facing away from the eye socket , as well as a proximal head region 14 , facing the eye socket . the handle region 12 is configured in the manner of a pair of tweezers , and comprises two handle parts 16 , 18 , which are coupled with one another at their distal ends by way of a connection point 20 . the two handle parts 16 , 18 form an activation device for bringing the retractor 10 from the retraction position shown in fig1 into the introduction position shown in fig3 . the handle parts 16 , 18 as well as the connection point 20 are configured in one piece and were formed by means of bending a single sheet - metal strip having resilient properties . because of the resilient properties of the sheet - metal strip , the connection point 20 acts as a spring element , which makes a pre - tension available in the state illustrated in fig1 . this pre - tension forces the two handle parts 16 , 18 away from one another about the connection point 20 . in an alternative exemplary embodiment , the connection point 20 between the two handle parts 16 , 18 is implemented by means of an articulation ( e . g . by means of a hinge ). in this case , the pre - tension can be made available by a pressure spring disposed in the region of the articulation between the two handle parts 16 , 18 . each of the two handle parts 16 , 18 possesses a handle depression 22 , 24 in a central section . the handle depressions 22 , 24 make a transition , at their proximal ends , into fastening sections set crosswise by 90 °, in which the handle region 12 is connected with the head region 14 . the head region 14 comprises two retraction elements 26 , 28 configured in area - covering manner , made of thin sheet metal . the two retraction elements 26 , 28 are connected with one another at their proximal ends , at a common pivot point 30 , and are mounted to as to pivot or rotate about this pivot point 30 , relative to one another . furthermore , the two retraction elements are coupled , at their distal ends , with the two handle parts 16 , 18 , by way of an articulation 32 , 34 , in each instance . because of this coupling of the two retraction elements 26 , 28 with the handle region 12 , the pre - tension that acts on the handle parts 16 , 18 brings about pivoting open ( or “ fanning ”) of the two retraction elements relative to one another , about the pivot point 30 . the pre - tension therefore forces the retraction elements 26 , 28 into the retraction position illustrated in fig1 . the pivoting movement of the two retraction elements 26 , 28 relative to one another , about the pivot point 30 , is restricted by a device configured in the region of the retraction elements 26 , 28 . this device comprises a pin 36 fastened onto the retraction element 26 approximately in the center , which pin engages into a groove 38 configured in the retraction element 28 . in the retraction position illustrated in fig1 , pivoting of the two retraction elements 26 , 28 is restricted in that the pin 36 makes contact with the left end of the groove 38 . in addition to this limiting function , the interaction of the pin 36 with the groove 38 also brings about guidance of the pivoting movement of the two retraction elements 26 , 28 relative to one another about the pivot point 30 . in order to bring the retractor 10 from the basic position according to fig1 into its introduction position shown in fig3 , the two handle parts 16 , 18 must be translationally moved toward one another ( in the manner of the handle parts of a pair of tweezers ), overcoming the pre - tension , until the pin 36 comes to lie against the right end of the groove 38 in fig3 ( or the two handle depressions 22 , 24 touch one another ). as a comparison of the two fig1 and 3a shows , the surface coverage ( overlap ) a 1 of the two retraction elements 26 , 28 in the retraction position according to fig1 is smaller than the surface overlap a 2 of the two retraction elements 26 , 28 in the introduction position . in other words , the effective surface area defined by the two retraction elements 26 , 28 in the introduction position according to fig3 is smaller than in the retraction position according to fig1 . in the introduction position , introduction of the reactor 10 into the eye socket is facilitated because of the resulting smaller ( maximal ) surface area cross - section , while in the retraction position , a greater effective surface area for the intended retraction purposes is available . as illustrated in fig1 and 3a , each of the two retraction elements 26 , 28 possesses the shape of half a leaf , which runs to a point in the direction of the common pivot point 30 . in their totality , the two retraction elements 26 , 28 therefore form a leaf - shaped surface that possesses a greater surface content in the retraction position than in the introduction position . the leaf - shaped surface makes a transition , by way of lateral incisions 40 , 42 , into two narrow , post - shaped fastening sections 44 , 46 . the distal end of each fastening section 44 , 46 is coupled with the fastening section of the related handle part 16 , 18 , by way of the related articulation 32 , 34 . the maximal cross - section of the leaf - shaped surface in the introduction position can amount to approximately 1 to 3 cm ( for example approximately 1 . 5 to 2 . 5 cm ), and can become larger in the retraction position , to approximately 2 to 5 cm ( for example approximately 3 to 4 cm ). the length of the leaf - shaped surface can be selected in such a manner that the surface can be completely introduced into the eye socket in the retraction position ( i . e . it can lie between 1 . 5 and 3 . 5 cm , for example ). the length of the handle part 10 can lie in the range between approximately 8 and approximately 15 cm ( for example approximately 10 to 12 cm ). as the side view of the retractor 10 according to fig2 illustrates , the retraction elements 26 , 28 can be angled away with reference to the handle region 12 , in their fastening sections 44 , 46 . this angling away facilitates handling of the retractor 10 and , in particular , introduction of the retractor 10 into the eye socket . as fig3 b further illustrates , each of the two retraction elements 26 , 28 is angled away toward the top laterally on the outside . the retraction elements 26 , 28 therefore jointly define a concave curved surface that supports the retraction function . fig4 shows a further exemplary embodiment of an orbital retractor 10 in a perspective view . the retractor 10 according to fig4 is in a state in which it has been introduced into an eye socket 50 , and has the same functions as the orbital retractor described with reference to fig1 to 3 . for this reason , the following functional explanations also apply to the retractor described above . in a design aspect , a first deviation between the orbital retractor 10 according to fig4 and the retractor described above consists in that the retractor 10 according to fig4 is produced from a single sheet - metal part ( again bent in the manner of a pair of tweezers ). furthermore , the restriction / guidance device ( composed of pin 36 and groove 38 according to fig1 ) was left out , as was the common mounting of the retraction elements 26 , 28 on a proximal pivot point ( reference symbol 30 in fig1 ). within the scope of a surgical operation , first a small incision is made in the region of a lower section of the opening of the eye socket , which incision is just sufficient to place the retraction elements 26 , 28 , in the introduction position ( analogous to fig3 ) into the eye socket 50 . in this connection , the retraction elements 26 , 28 are dimensioned in such a manner that they can be accommodated essentially completely ( with the exception of the fastening sections 44 , 46 ) in the eye socket 50 ( cf . fig4 ). thereupon the retraction elements 26 , 28 are introduced into the eye socket 50 by way of the incision . subsequently , the force applied to the handle parts 16 , 18 by the surgeon is reduced , so that the retraction elements 26 , 28 are forced into the retraction position illustrated in fig4 , as the result of the inherent pre - tension . in this connection , the handle parts 16 , 18 perform a translational movement . as soon as the retraction elements 26 , 28 are in the retraction position , the retractor 10 can be used for its intended purpose . for example , the soft tissue filling the eye socket 10 can be pushed back to treat a fracture of the eye socket floor . additionally or alternatively , the retractor 10 can also be used to push soft tissue back in advance of the incision , in order to keep the region intended for the incision clear . the mobility of the retraction elements 26 , 28 can be selected ( for example by way of the length and position of the groove 38 according to fig1 to 3 ) in such a manner that the pre - tension is able to force the retraction elements 26 , 28 against the interior of the eye socket 50 in the retraction position ( cf . fig1 and 4 ). for this reason , a cross - section of the surface area defined by the retraction elements 26 , 28 in the retraction position is greater than a corresponding cross - section of the eye socket . this leads to jamming of the retraction elements 26 , 28 in the eye socket . depending on the dimensioning of the pre - tension , a self - holding function of the retractor 10 in the eye socket 50 can be brought about or supported with this jamming . as illustrated in fig4 , the incisions of the retraction elements 26 , 28 are disposed in the region of the opening of the eye socket 50 in the retraction position . this measure supports essentially complete accommodation of the retraction elements 26 , 28 in the eye socket 50 and facilitates access to the eye socket 50 by means of other surgical instruments . although the exemplary embodiments described possess an activation device for the retraction elements in the manner of the handle parts of a pair of tweezers , it is understood that other types of activation devices can also be used . for example , it is possible to implement the activation device by means of a handle region configured in the manner of a pair of tongs or scissors . in such an embodiment , a pressure spring or other type of spring element could be provided in an articulation region , which spring or element makes the pre - tension available for forcing the retraction elements into the retraction position . a person skilled in the art will furthermore be able , on the basis of his / her technical knowledge , to implement other types of activation devices for the retraction elements ( for example on the basis of a pushing element acted on by spring force ). as is evident from the above description of exemplary embodiments , the orbital retractor presented here is easy to operate . pre - tensioning of the retractor in the retraction position facilitates its user friendliness , because a surgeon can bring the retractor from its introduction position into the retraction position by simply reducing the activation source . the pre - tension can furthermore lead to jamming of the retraction elements within the eye socket , which stabilizes the position of the retractor . in an extreme case , it would be possible to implement a self - holding function for the retractor based on the pre - tension that is made available . furthermore , an embodiment in which the retraction elements are completely accommodated in the eye socket in the retraction position is advantageous , because in this manner , the retraction elements do not impair access to the eye socket for other types of surgical instruments . furthermore , the access to the eye socket can be kept small by means of the retractor presented here ( in other words no unnecessary widening is required ). it should also be noted that the device for guiding or limiting the movement of the retraction elements ( composed of pin 36 and groove 38 ) could also be configured in other ways . in particular , it would be possible to provide this device on the retractor in such a manner that it lies outside the eye socket in the position in which the retraction elements have been introduced into the eye socket .

a retractor for use in a surgical intervention in the area of an eye socket is described . the retractor comprises two planar retraction elements , which are movable relative to each other between an insertion position with a first surface coverage and a retraction position with a second surface coverage ai , which is smaller than the first surface coverage . a spring element provides pretensioning , which presses the retraction elements into the retraction position .

patients diagnosed with cancer usually undergo a treatment plan for curing or managing progression or symptoms of the disease . these treatment plans commonly include surgery , radiation therapy , chemotherapy , hormone therapy , immunotherapy or a combination of these therapies . while the aim of these therapies is to kill cancer cells , some healthy cells can also become damaged and killed in the treatment process . the death of healthy cells can cause various side effects such as loss of appetite , weight loss or gain , nausea and vomiting . these side effects can significantly hinder the cancer patient &# 39 ; s ability to eat and assimilate necessary nutrients . the present invention provides a means of reducing the damage to , and restoring , healthy cells through the specific provision of nutrients by means of the vegetable juice therapy . additionally , arthritis patients suffer from inflammation of the joints . the present invention helps alleviate the inflammation and mitigate the side effects of biologic and immunotherapies for arthritis . the present invention comprises a therapy that is based on a specific vegetable juice formulation and cleansing application designed to meet the nutritional needs of patients undergoing cancer treatment by traditional means such as surgery , radiation therapy , chemotherapy , hormone therapy , immuno therapy , as well as to supplement such treatment by arming the patient with the relevant nutritional weapons to support general health in a safe and simple manner . while the therapy is to be supplemented by proper dieting and exercise and meditation , the cleansing application and vegetable juice therapy are the aspects of the present invention . the cleansing application is designed to purify the body and rid same of any waste matter , so as to allow other aspects of the treatment to take their full effect . the cleansing application should be administered first thing in the morning during treatment , for the full duration , and comprises one or more and preferably all of the following : i . about 2 fluid ounces ( 59 . 1 ml ) of lemon juice diluted up to 50 % by volume with approximately body - temperature water ( 4 fluid ounces if fully diluted ); ii . about 1 . 5 - 2 fluid ounces ( 44 . 3 - 59 . 1 ml ) of lime juice diluted up to 50 % by volume with approximately body - temperature water ( 3 - 4 fluid ounces if fully diluted ); iii . about 1 fluid ounce ( 59 . 1 ml ) of blended aloe vera diluted up to 50 % by volume with approximately body - temperature water ( 2 fluid ounces if fully diluted ); iv . about 4 - 6 fluid ( 118 . 3 to 177 . 4 ml ) of cranberry juice because tap water can contain chemicals , distilled or other purified water is preferred for purposes of dilution . the vegetable juice therapy is designed to provide the right balance of nutrients to promote cell regeneration and growth and promote general health . the vegetable juice therapy also contains very powerful cleansing agents which manifest themselves during treatment . the vegetable juice therapy comprises a combination of the following , in raw form , prior to extraction : i . about 8 - 10 ounces by weight ( 226 . 8 to 283 . 5 g ) carrots ( excluding greens ) ii . about 4 - 5 ounces by weight ( 113 . 4 to 141 . 8 g ) beetroot ( excluding greens ) iii . about 4 - 5 ounces by weight ( 113 . 4 to 141 . 8 g ) cucumber iv . about 1 - 2 tsp . ( 3 . 5 to 10 ml ) of blended liquid aloe vera thus , the vegetable therapy constitutes a liquid extracted from equal parts , by weight , raw , unpeeled beetroot and cucumber , and about twice the amount ( two parts ) of carrots , by weight , with the addition of a relatively small quantity of aloe vera juice . as mentioned herein , addition of ingredients with high sugar content should be avoided . further , to avoid oxidation of the ingredients prior to ingestion and absorbtion , addition of fruits , especially citrus , and acidic vegetables , such as tomatoes , should be avoided . in order for the therapy to have maximum effect the following directions must be observed : 1 . use fresh unpeeled vegetables . 2 . scrub and wash vegetables properly . 3 . cut vegetables into suitable sizes ( the sizes may vary depending on the juice extractor used ). 4 . place vegetables into juice extractor and process 5 . add 5 - 10 ml . of the liquid aloe vera ( see below for preparation of aloe vera ) to the extracted juice . 6 . drink immediately . 7 . take twice daily . it is essential that a juice extractor rather than a blender be used as a blender does not produce the level of concentration that is required . use of a blender also causes extra exposure of the juice which can lead to oxidation and the consequent destruction of vital elements of the vegetables . by extractor is meant a device that relies primarily if not exclusively on application of pressure to the fruits and vegetables to obtain juice , rather than maceration , cutting , or grinding . as mentioned , such maceration exposes the fruits and vegetables and resulting juice to excessive oxidation , reducing the effectiveness of the treatment . exposure of the cut fruits and vegetables to air can also lead to oxidation . accordingly , both the cut vegetables and the extracted juices should be minimally exposed to air before consumption to maximize effectiveness . further to steps 4 and 5 above , the extract of all three vegetables should be combined and then the liquid aloe vera ( see below ) added to same . further to step 6 above , the vegetable extract must be consumed immediately after extraction to prevent the destruction of micro - elements by oxidation and exposure to oxygen and oxidative materials , such as acids from citrus and other fruits and vegetables should be minimized . further to step 6 above , the vegetable juice therapy , which should ultimately consist of 6 - 8 ozs of juice , should be taken twice daily . in the instance where the patient has recovered , the vegetable therapy should be continued once daily as a preventative measure . while the above - mentioned therapy can be taken first thing in the morning , it is a flexible therapy in terms of time of day that it may be taken and it can also be administered either before or after meals . as the user &# 39 ; s stomach is usually empty first thing in the morning , there is an added benefit of taking the therapy at that time in that it will have a more stimulating effect . if the cancer affects the throat and particularly where radiation is being administered , the juice extract must be further filtered , by means of a filter cloth to eliminate all traces of sediments . otherwise , remaining particles could cause extreme pain to the cancer patient when swallowed . the aloe vera represents a very powerful healing substance and should be prepared separately in the following manner : 1 . wash and cut the fresh , green aloe vera ( do not use if a colour change has begun ) into small pieces without trimming or removing the green portions or any part of the skin . 2 . add 225 grams of aloe to approximately 500 ml . of water . 3 . blend and strain the combination and then cover it in an airtight container . 4 . store the container in a refrigerator , for not more than eight ( 8 ) days , until ready for use . 5 . add 5 - 10 ml of the blended aloe to the juice extract prior to drinking . the effectiveness of the vegetable juice therapy further requires that it should be kept covered at all times and not be combined with any other substance ( including water ) containing citrus , as the citrus will destroy the delicate elements in the vegetable juice . at no point should the therapy or any other aspect of the invention be used in conjunction with any form of herbal therapy , such as the brandt grape cure therapy , as this might counteract the effectiveness of the invention . the above - mentioned therapy and cleansing application is supplemented by adherence to proper diet and exercise . the primary object of the invention is to promote general health and to significantly increase the prospects of full and rapid recovery of cancer patients who are also undergoing radiation therapy or chemotherapy , as well as arthritis patients , especially those undergoing treatment with biologics or immunotherapies . the invention does not require a rigorous or painful application but can be administered by means of a simple and effective oral procedure . as mentioned above , other treatments lead to certain side effects such as nausea or vomiting . the present invention assists in counteracting such side effects and also provides no side effects of its own . it is known that certain treatments such as radiation and chemotherapy cannot , on their own , always provide for the successful recovery of a cancer patient . the present invention is a supportive treatment that ensures the rapid recovery of the patient . the present invention is not chemically based and thus will not expose the user to any health risks . the invention also provides a cost - effective means of accessing its benefits / uses .

a dietary supplement and method of supplementation comprises a vegetable component consisting essentially of juices extracted from two parts by weight fresh , unpeeled carrots ; one part by weight fresh , unpeeled beet root ; one part by weight of fresh , unpeeled cucumber ; and a selected quantity of aloe vera juice . a cleansing component includes at least one of the following : about 2 fluid ounces of lemon juice ; about 1 . 5 - 2 fluid ounces of lime juice ; about 1 fluid ounce of aloe vera juice ; and about 4 - 6 fluid ounces of cranberry juice . the vegetable component is ingested orally twice daily and the cleansing component is ingested orally once daily .

in order that the invention may be more readily understood , certain terms are first defined here for convenience . as used herein , the term “ treating ” a disorder encompasses preventing , ameliorating , mitigating and / or managing the disorder and / or conditions that may cause the disorder . the terms “ treating ” and “ treatment ” refer to a method of alleviating or abating a disease and / or its attendant symptoms . in accordance with the present invention “ treating ” includes preventing , blocking , inhibiting , attenuating , protecting against , modulating , reversing the effects of and reducing the occurrence of e . g ., the harmful effects of a disorder . the term “ modulate ” refers to increases or decreases in the activity of a cell in response to exposure to a compound of the invention . the terms “ isolated ,” “ purified ,” or “ biologically pure ” refer to material that is substantially or essentially free from components that normally accompany it as found in its native state . purity and homogeneity are typically determined using analytical chemistry techniques such as polyacrylamide gel electrophoresis or high performance liquid chromatography . particularly , in embodiments the compound is at least 85 % pure , more preferably at least 90 % pure , more preferably at least 95 % pure , and most preferably at least 99 % pure . the terms “ polypeptide ,” “ peptide ” and “ protein ” are used interchangeably herein to refer to a polymer of amino acid residues . the terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid , as well as to naturally occurring amino acid polymers and non - naturally occurring amino acid polymer . a “ peptide ” is a sequence of at least two amino acids . peptides can consist of short as well as long amino acid sequences , including proteins . the term “ amino acid ” refers to naturally occurring and synthetic amino acids , as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids . naturally occurring amino acids are those encoded by the genetic code , as well as those amino acids that are later modified , e . g ., hydroxyproline , γ - carboxyglutamate , and o - phosphoserine . amino acid analogs refers to compounds that have the same basic chemical structure as a naturally occurring amino acid , i . e ., an a carbon that is bound to a hydrogen , a carboxyl group , an amino group , and an r group , e . g ., homoserine , norleucine , methionine sulfoxide , methionine methyl sulfonium . such analogs have modified r groups ( e . g ., norleucine ) or modified peptide backbones , but retain the same basic chemical structure as a naturally occurring amino acid . amino acid mimetics refers to chemical compounds that have a structure that is different from the general chemical structure of an amino acid , but that functions in a manner similar to a naturally occurring amino acid . the term “ protein ” refers to series of amino acid residues connected one to the other by peptide bonds between the alpha - amino and carboxy groups of adjacent residues . amino acids may be referred to herein by either their commonly known three letter symbols or by the one - letter symbols recommended by the iupac - iub biochemical nomenclature commission . as to amino acid sequences , one of skill will recognize that individual substitutions , deletions or additions to a peptide , polypeptide , or protein sequence which alters , adds or deletes a single amino acid or a small percentage of amino acids in the encoded sequence is a “ conservatively modified variant ” where the alteration results in the substitution of an amino acid with a chemically similar amino acid . conservative substitution tables providing functionally similar amino acids are well known in the art . macromolecular structures such as polypeptide structures can be described in terms of various levels of organization . for a general discussion of this organization , see , e . g ., alberts et al ., molecular biology of the cell ( 3rd ed ., 1994 ) and cantor and schimmel , biophysical chemistry part i . the conformation of biological macromolecules ( 1980 ). “ primary structure ” refers to the amino acid sequence of a particular peptide . “ secondary structure ” refers to locally ordered , three dimensional structures within a polypeptide . these structures are commonly known as domains . domains are portions of a polypeptide that form a compact unit of the polypeptide and are typically 50 to 350 amino acids long . typical domains are made up of sections of lesser organization such as stretches of β - sheet and α - helices . “ tertiary structure ” refers to the complete three dimensional structure of a polypeptide monomer . “ quaternary structure ” refers to the three dimensional structure formed by the noncovalent association of independent tertiary units . anisotropic terms are also known as energy terms . the term “ administration ” or “ administering ” includes routes of introducing the compound ( s ) to a subject to perform their intended function . examples of routes of administration which can be used include injection ( subcutaneous , intravenous , parenterally , intraperitoneally , intrathecal ), topical , oral , inhalation , rectal and transdermal . the term “ effective amount ” includes an amount effective , at dosages and for periods of time necessary , to achieve the desired result . an effective amount of compound may vary according to factors such as the disease state , age , and weight of the subject , and the ability of the compound to elicit a desired response in the subject . dosage regimens may be adjusted to provide the optimum therapeutic response . an effective amount is also one in which any toxic or detrimental effects ( e . g ., side effects ) of the elastase inhibitor compound are outweighed by the therapeutically beneficial effects . the phrases “ systemic administration ,” “ administered systemically ”, “ peripheral administration ” and “ administered peripherally ” as used herein mean the administration of a compound ( s ), drug or other material , such that it enters the patient &# 39 ; s system and , thus , is subject to metabolism and other like processes . the term “ therapeutically effective amount ” refers to that amount of the compound being administered sufficient to prevent development of or alleviate to some extent one or more of the symptoms of the condition or disorder being treated . a therapeutically effective amount of compound ( i . e ., an effective dosage ) may range from about 0 . 005 μg / kg to about 200 mg / kg , preferably about 0 . 1 mg / kg to about 200 mg / kg , more preferably about 10 mg / kg to about 100 mg / kg of body weight . in other embodiments , the therapeutically effect amount may range from about 1 . 0 pm to about 500 nm . the skilled artisan will appreciate that certain factors may influence the dosage required to effectively treat a subject , including but not limited to the severity of the disease or disorder , previous treatments , the general health and / or age of the subject , and other diseases present . moreover , treatment of a subject with a therapeutically effective amount of a compound can include a single treatment or , preferably , can include a series of treatments . in one example , a subject is treated with a compound in the range of between about 0 . 005 μg / kg to about 200 mg / kg of body weight , one time per week for between about 1 to 10 weeks , preferably between 2 to 8 weeks , more preferably between about 3 to 7 weeks , and even more preferably for about 4 , 5 , or 6 weeks . it will also be appreciated that the effective dosage of a compound used for treatment may increase or decrease over the course of a particular treatment . the term “ chiral ” refers to molecules which have the property of non - superimposability of the mirror image partner , while the term “ achiral ” refers to molecules which are superimposable on their mirror image partner . the term “ diastereomers ” refers to stereoisomers with two or more centers of dissymmetry and whose molecules are not mirror images of one another . the term “ enantiomers ” refers to two stereoisomers of a compound which are non - superimposable mirror images of one another . an equimolar mixture of two enantiomers is called a “ racemic mixture ” or a “ racemate .” the term “ isomers ” or “ stereoisomers ” refers to compounds which have identical chemical constitution , but differ with regard to the arrangement of the atoms or groups in space . the term “ prodrug ” includes compounds with moieties which can be metabolized in vivo . generally , the prodrugs are metabolized in vivo by esterases or by other mechanisms to active drugs . examples of prodrugs and their uses are well known in the art ( see , e . g ., berge et al . ( 1977 ) “ pharmaceutical salts ”, j . pharm . sci . 66 : 1 - 19 ). the prodrugs can be prepared in situ during the final isolation and purification of the compounds , or by separately reacting the purified compound in its free acid form or hydroxyl with a suitable esterifying agent . hydroxyl groups can be converted into esters via treatment with a carboxylic acid . examples of prodrug moieties include substituted and unsubstituted , branch or unbranched lower alkyl ester moieties , ( e . g ., propionoic acid esters ), lower alkenyl esters , di - lower alkyl - amino lower - alkyl esters ( e . g ., dimethylaminoethyl ester ), acylamino lower alkyl esters ( e . g ., acetyloxymethyl ester ), acyloxy lower alkyl esters ( e . g ., pivaloyloxymethyl ester ), aryl esters ( phenyl ester ), aryl - lower alkyl esters ( e . g ., benzyl ester ), substituted ( e . g ., with methyl , halo , or methoxy substituents ) aryl and aryl - lower alkyl esters , amides , lower - alkyl amides , di - lower alkyl amides , and hydroxy amides . preferred prodrug moieties are propionoic acid esters and acyl esters . prodrugs which are converted to active forms through other mechanisms in vivo are also included . in aspects , the compounds of the invention are prodrugs of any of the formulae herein . the term “ subject ” refers to animals such as mammals , including , but not limited to , primates ( e . g ., humans ), cows , sheep , goats , horses , dogs , cats , rabbits , rats , mice and the like . in certain embodiments , the subject is a human . furthermore the compounds of the invention include olefins having either geometry : “ z ” refers to what is referred to as a “ cis ” ( same side ) conformation whereas “ e ” refers to what is referred to as a “ trans ” ( opposite side ) conformation . with respect to the nomenclature of a chiral center , the terms “ d ” and “ l ” configuration are as defined by the iupac recommendations . as to the use of the terms , diastereomer , racemate , epimer and enantiomer , these will be used in their normal context to describe the stereochemistry of preparations . as used herein , the term “ alkyl ” refers to a straight - chained or branched hydrocarbon group containing 1 to 12 carbon atoms . the term “ lower alkyl ” refers to a c1 - c6 alkyl chain . examples of alkyl groups include methyl , ethyl , n - propyl , isopropyl , tert - butyl , and n - pentyl . alkyl groups may be optionally substituted with one or more substituents . the term “ alkenyl ” refers to an unsaturated hydrocarbon chain that may be a straight chain or branched chain , containing 2 to 12 carbon atoms and at least one carbon - carbon double bond . alkenyl groups may be optionally substituted with one or more substituents . the term “ alkynyl ” refers to an unsaturated hydrocarbon chain that may be a straight chain or branched chain , containing the 2 to 12 carbon atoms and at least one carbon - carbon triple bond . alkynyl groups may be optionally substituted with one or more substituents . the sp 2 or sp carbons of an alkenyl group and an alkynyl group , respectively , may optionally be the point of attachment of the alkenyl or alkynyl groups . as used herein , the term “ halogen ”, “ hal ” or “ halo ” means — f , — cl , — br or — i . the term “ cycloalkyl ” refers to a hydrocarbon 3 - 8 membered monocyclic or 7 - 14 membered bicyclic ring system having at least one saturated ring or having at least one non - aromatic ring , wherein the non - aromatic ring may have some degree of unsaturation . cycloalkyl groups may be optionally substituted with one or more substituents . in one embodiment , 0 , 1 , 2 , 3 , or 4 atoms of each ring of a cycloalkyl group may be substituted by a substituent . representative examples of cycloalkyl group include cyclopropyl , cyclopentyl , cyclohexyl , cyclobutyl , cycloheptyl , cyclopentenyl , cyclopentadienyl , cyclohexenyl , cyclohexadienyl , and the like . the term “ aryl ” refers to a hydrocarbon monocyclic , bicyclic or tricyclic aromatic ring system . aryl groups may be optionally substituted with one or more substituents . in one embodiment , 0 , 1 , 2 , 3 , 4 , 5 or 6 atoms of each ring of an aryl group may be substituted by a substituent . examples of aryl groups include phenyl , naphthyl , anthracenyl , fluorenyl , indenyl , azulenyl , and the like . the term “ heteroaryl ” refers to an aromatic 5 - 8 membered monocyclic , 8 - 12 membered bicyclic , or 11 - 14 membered tricyclic ring system having 1 - 4 ring heteroatoms if monocyclic , 1 - 6 heteroatoms if bicyclic , or 1 - 9 heteroatoms if tricyclic , said heteroatoms selected from o , n , or s , and the remainder ring atoms being carbon ( with appropriate hydrogen atoms unless otherwise indicated ). heteroaryl groups may be optionally substituted with one or more substituents . in one embodiment , 0 , 1 , 2 , 3 , or 4 atoms of each ring of a heteroaryl group may be substituted by a substituent . examples of heteroaryl groups include pyridyl , furanyl , thienyl , pyrrolyl , oxazolyl , oxadiazolyl , imidazolyl thiazolyl , isoxazolyl , quinolinyl , pyrazolyl , isothiazolyl , pyridazinyl , pyrimidinyl , pyrazinyl , triazinyl , isoquinolinyl , indazolyl , and the like . the term “ heterocycloalkyl ” refers to a nonaromatic 3 - 8 membered monocyclic , 7 - 12 membered bicyclic , or 10 - 14 membered tricyclic ring system comprising 1 - 3 heteroatoms if monocyclic , 1 - 6 heteroatoms if bicyclic , or 1 - 9 heteroatoms if tricyclic , said heteroatoms selected from o , n , s , b , p or si , wherein the nonaromatic ring system is completely saturated . heterocycloalkyl groups may be optionally substituted with one or more substituents . in one embodiment , 0 , 1 , 2 , 3 , or 4 atoms of each ring of a heterocycloalkyl group may be substituted by a substituent . representative heterocycloalkyl groups include piperidinyl , piperazinyl , tetrahydropyranyl , morpholinyl , thiomorpholinyl , 1 , 3 - dioxolane , tetrahydrofuranyl , tetrahydrothienyl , thiirenyl , and the like . the term “ alkylamino ” refers to an amino substituent which is further substituted with one or two alkyl groups . the term “ aminoalkyl ” refers to an alkyl substituent which is further substituted with one or more amino groups . the term “ hydroxyalkyl ” or “ hydroxylalkyl ” refers to an alkyl substituent which is further substituted with one or more hydroxyl groups . the alkyl or aryl portion of alkylamino , aminoalkyl , mercaptoalkyl , hydroxyalkyl , mercaptoalkoxy , sulfonylalkyl , sulfonylaryl , alkylcarbonyl , and alkylcarbonylalkyl may be optionally substituted with one or more substituents . acids and bases useful in the methods herein are known in the art . acid catalysts are any acidic chemical , which can be inorganic ( e . g ., hydrochloric , sulfuric , nitric acids , aluminum trichloride ) or organic ( e . g ., camphorsulfonic acid , p - toluenesulfonic acid , acetic acid , ytterbium triflate ) in nature . acids are useful in either catalytic or stoichiometric amounts to facilitate chemical reactions . bases are any basic chemical , which can be inorganic ( e . g ., sodium bicarbonate , potassium hydroxide ) or organic ( e . g ., triethylamine , pyridine ) in nature . bases are useful in either catalytic or stoichiometric amounts to facilitate chemical reactions . alkylating agents are any reagent that is capable of effecting the alkylation of the functional group at issue ( e . g ., oxygen atom of an alcohol , nitrogen atom of an amino group ). alkylating agents are known in the art , including in the references cited herein , and include alkyl halides ( e . g ., methyl iodide , benzyl bromide or chloride ), alkyl sulfates ( e . g ., methyl sulfate ), or other alkyl group - leaving group combinations known in the art . leaving groups are any stable species that can detach from a molecule during a reaction ( e . g ., elimination reaction , substitution reaction ) and are known in the art , including in the references cited herein , and include halides ( e . g ., i —, cl —, br —, f —), hydroxy , alkoxy ( e . g ., ome , — o - t - bu ), acyloxy anions ( e . g ., — oac , — oc ( o ) cf 3 ), sulfonates ( e . g ., mesyl , tosyl ), acetamides ( e . g ., — nhc ( o ) me ), carbamates ( e . g ., n ( me ) c ( o ) ot - bu ), phosphonates ( e . g ., op ( o )( oet ) 2 ), water or alcohols ( protic conditions ), and the like . in certain embodiments , substituents on any group ( such as , for example , alkyl , alkenyl , alkynyl , aryl , aralkyl , heteroaryl , heteroaralkyl , cycloalkyl , heterocycloalkyl ) can be at any atom of that group , wherein any group that can be substituted ( such as , for example , alkyl , alkenyl , alkynyl , aryl , aralkyl , heteroaryl , heteroaralkyl , cycloalkyl , heterocycloalkyl ) can be optionally substituted with one or more substituents ( which may be the same or different ), each replacing a hydrogen atom . examples of suitable substituents include , but are not limited to alkyl , alkenyl , alkynyl , cycloalkyl , heterocycloalkyl , aralkyl , heteroaralkyl , aryl , heteroaryl , halogen , haloalkyl , cyano , nitro , alkoxy , aryloxy , hydroxyl , hydroxylalkyl , oxo ( i . e ., carbonyl ), carboxyl , formyl , alkylcarbonyl , alkylcarbonylalkyl , alkoxycarbonyl , alkylcarbonyloxy , aryloxycarbonyl , heteroaryloxy , heteroaryloxycarbonyl , thio , mercapto , mercaptoalkyl , arylsulfonyl , amino , aminoalkyl , dialkylamino , alkylcarbonylamino , alkylaminocarbonyl , alkoxycarbonylamino , alkylamino , arylamino , diarylamino , alkylcarbonyl , or arylamino - substituted aryl ; arylalkylamino , aralkylaminocarbonyl , amido , alkylaminosulfonyl , arylaminosulfonyl , dialkylaminosulfonyl , alkylsulfonylamino , arylsulfonylamino , imino , carbamido , carbamyl , thioureido , thiocyanato , sulfoamido , sulfonylalkyl , sulfonylaryl , or mercaptoalkoxy . the term “ substituents ” refers to a group “ substituted ” on any functional group delineated herein , e . g ., alkyl , alkenyl , alkynyl , cycloalkyl , cycloalkenyl , aryl , heterocyclyl , or heteroaryl group at any atom of that group . suitable substituents include , without limitation halogen , cn , no 2 , or 15 , sr 15 , s ( o ) 2 or 15 , nr 15 r 16 , c 1 - c 2 perfluoroalkyl , c 1 - c 2 perfluoroalkoxy , 1 , 2 - methylenedioxy , c ( o ) or 15 , c ( o ) nr 15 r 16 , oc ( o ) nr 15 r 16 , nr 15 c ( o ) nr 15 r 16 , c ( nr 16 ) nr 15 r 16 , nr 15 c ( nr 16 ) nr 15 r 16 , s ( o ) 2 nr 15 r 16 , r 17 , c ( o ) r 17 , nr 15 c ( o ) r 17 , s ( o ) r 17 , s ( o ) 2 r 17 , r 16 , oxo , c ( o ) r 16 , c ( o )( ch 2 ) noh , ( ch 2 ) nor 15 , ( ch 2 ) nc ( o ) nr 15 r 16 , nr 15 s ( o ) 2 r 17 , where n is independently 0 - 6 inclusive . each r 15 is independently hydrogen , c 1 - c 4 alkyl or c 3 - c 6 cycloalkyl . each r 16 is independently hydrogen , alkenyl , alkynyl , c 3 - c 6 cycloalkyl , aryl , heterocyclyl , heteroaryl , c 1 - c 4 alkyl or c 1 - c 4 alkyl substituted with c 3 - c 6 cycloalkyl , aryl , heterocyclyl or heteroaryl . each r 17 is independently c 3 - c 6 cycloalkyl , aryl , heterocyclyl , heteroaryl , c 1 - c 4 alkyl or c 1 - c 4 alkyl substituted with c 3 - c 6 cycloalkyl , aryl , heterocyclyl or heteroaryl . each c 3 - c 6 cycloalkyl , aryl , heterocyclyl , heteroaryl and c 1 - c 4 alkyl in each r 15 , r 16 and r 17 can optionally be substituted with halogen , cn , c 1 - c 4 alkyl , oh , c 1 - c 4 alkoxy , nh 2 , c 1 - c 4 alkylamino , c 1 - c 4 dialkylamino , c 1 - c 2 perfluoroalkyl , c 1 - c 2 perfluoroalkoxy , or 1 , 2 - methylenedioxy . samples of l . confervoides were collected off grassy key . 6 the non - polar extract ( etoac / meoh 1 : 1 ) was fractionated over hp - 20 resin followed by silica chromatography and reversed - phase hplc to afford 1 {[ α ] 20 d + 76 ( c 0 . 1 , ch 2 cl 2 )}. nmr data combined with a [ m + h ] + peak at m / z 1102 . 5438 in the hresims of 1 suggested a molecular formula of c 56 h 79 n 9 o 10 s 2 ( calcd for c 56 h 80 n 9 o 10 s 2 , 1102 . 5464 ). the 1 h nmr spectrum of 1 in cdcl 3 was indicative of a peptide by displaying three secondary amide doublets ( δ h 7 . 12 , 7 . 40 , 7 . 53 ), three putative n - me tertiary amide singlets ( δ h 2 . 78 , 3 . 11 , 3 . 15 ) and several resonances characteristic for α - protons of amino acids ( δ h ˜ 4 to ˜ 5 ). considering the ir spectrum , which exhibited bands due to ester ( 1733 cm − 1 ) and amide ( 1640 cm − 1 ) carbonyl stretch vibrations , 1 appeared to be a depsipeptide . analysis of the 1 h nmr , 13 c nmr , apt , cosy , hmqc , hmbc and roesy spectra recorded in cdcl 3 revealed the presence of two regular α - amino acid units ( threonine , c6 - 9 ; proline ; c37 - 41 ), two n - methylated α - amino acids ( n - methylleucine , c10 - 16 ; n - methylvaline , c42 - 47 ), one β - amino acid ( maba , c1 - 5 ), phenyllacetic acid ( pla , c48 - 56 ), a n - methylphenylalanine - derived thiazoline carboxylic acid unit ( n - me - phe - thn - ca ; c24 - 36 ), and a thiazoline carboxylic acid moiety derived from aba ( aba - thn - ca ; c17 - 23 ) ( table 1 ). the presence of the two thiazoline rings was deduced from the chemical shifts of vicinally coupled h - 18 ( δ h 5 . 32 ) and h 2 - 19ab ( δ h 3 . 58 / 3 . 27 ) as well as h - 25 ( δ h 5 . 30 ) and h 2 - 26ab ( δ h 3 . 70 ) combined with hmbc correlations of these spin systems to putative carbonyl - derived carbons from aba [ c - 20 ( δ c 178 . 5 )] and n - me - phe [ c - 27 ( δ c 177 . 2 ), respectively . in addition , 1d selective tocsy experiments revealed homoallylic coupling in both thiazoline rings between h - 18 / h - 21 and h - 25 / h - 28 . hmbc analysis ( table 1 ) readily established the connectivity of the units as shown for 1 , which was further confirmed by interresidue roesy correlations . notably , there was an unusual four - bond correlation between h - 2 and c49 , which could have arisen because of a planar “ w ” conformation . 7 7 claridge , t . d . w . high - resolution nmr techniques in organic chemistry ; elsevier : san diego , calif ., 1999 . compound 1 was hydrolyzed with 6 n hcl ( 110 ° c ., 18 h ) and the hydrolyzate subjected to chiral hplc , revealing the presence of d - aba , n - me - d - phe , l - pro , n - me - l - val , l - pla , and d - allo - thr in the molecule , but the correct assignment for n - me - leu remained unclear . a sample of 1 was also subjected to ozonolysis prior to hydrolysis in an attempt to detect cysteic acid ( cya ), and hence deduce the configuration of the thiazoline rings . however , peaks for both l - and d - cya were detected by chiral hplc , preventing unambiguous configurational assignment . marfey &# 39 ; s analysis 8 of the hydrolyzed ozonolysis product was carried out to ascertain the configuration of the maba , 9 , 10 n - me - leu and cya units , using 1 - fluoro - 2 , 4 - dinitrophenyl - 5 - l - leucinamide ( l - fdla ) as the derivatizing agent . reversed - phase hplc of 1 derivatized with l - fdla allowed the assignment of ( 2r , 3r )- maba . 11 in addition , the presence of d - allo - thr , n - me - d - phe , 12 l - pro and n - me - l - val were confirmed , and n - me - d - leu could be unambiguously assigned . l - fdla adducts for l - or d - cya were quantified by lc - ms and found present in the ratio of 1 . 64 : 1 , indicating that either the thiazolines were of opposite configuration producing cysteic acids in different yields , or that epimerization of one or both units had occurred . however , presumably at least one thiazoline had to have r configuration because of the excess l - cya produced . 8 marfey , p . carlsberg res . commun . 1984 , 49 , 591 - 596 . 9 only the 2r , 3r and 2r , 3s standards were used . the elution times of the 2s , 3s and 2s , 3r isomers were deduced by derivatizing these standards with dl - fdla . 10 ( a ) fujii , k . ; ikai , y . ; mayumi , t . ; oka , h . ; suzuki , m . ; harada , k .- i . anal . chem . 1997 , 69 , 3346 - 3352 . ( b ) fujii , k . ; ikai , y . ; oka , h . ; suzuki , m . ; harada , k .- i . anal . chem . 1997 , 69 , 5146 - 5151 . 11 two peaks were observed corresponding to ( 2r , 3r )- and ( 2s , 3r )- maba in the approximate ratio of 2 . 5 : 1 . this is consistent with chromatograms of the standards , which were obtained from the corresponding n - benzoylated - o - methyl esters . the latter also showed some epimerization at the 2 - position during hydrolysis . 12 marfey &# 39 ; s adducts of n - me - d - phe and n - me - l - leu co - eluted ; however , the relative intensity of the corresponding peak was reduced and n - me - d - glu was generated when stringent ozonolysis conditions ( 25 ° c .) were employed . thus , a n - me - d - phe residue was present in 1 . attempts were then made to crystallize the compound . eventually a small yield of crystals was produced using a mixture of dichloromethane and methanol . 13 the resulting x - ray structure ( fig1 ) confirmed the gross 2d arrangement and all the previously assigned stereocenters . additionally , both thiazolines could be assigned as r , confirming that significant epimerization had occurred under the reaction conditions . 13 one methanol molecule was seen incorporated into the lattice . upon drying , the crystals would quickly degrade , presumably due to methanol loss . the crystal structure shows hydrogen bonds between the nh ( at n1 ) of maba to the thr n ( n2 ; 2 . 35 å ) and the pla ester o ( o1 ; 2 . 52 å ). another hydrogen bond occurs between the thr nh and the carbonyl of aba - thn - ca ( o6 ; 2 . 37 å ). at the opposite site of the macrocycle , a tight turn at n - me - phe - thn - ca is stabilized by a hydrogen bond ( 2 . 04 å ) between the pro carbonyl ( o8 ) and the nh of aba - thn - ca ( at n5 ), with the angle between the planes of the thiazoline rings at almost 90 °. analogous turns occur in patellamide d at the oxazoline rings , while the thiazoles are planar . 14 in lissoclinamide 7 , a turn is centered around the other thiazoline ( ring x ), and there is a hydrogen bond between the nh of phe and the n of the adjacent thiazoline , rather than across the turn . the angle between thiazoline planes is still close to 90 °, but one is twisted so that its plane is parallel to that of the macrocycle . 14 schmitz , f . j . ; ksebati , m . b . ; chang , j . s . ; wang , j . l . ; hossain , m . b . ; van der helm , d . ; engel , m . h . ; serban , a . ; silfer , j . a . j . org . chem . 1989 , 54 , 3463 - 3472 . several aspects of the nmr data for 1 suggested that the solution structure was similar to the x - ray structure . 15 firstly , roesy data suggested that all amide bonds were trans in solution , as they are in the solid state . secondly , three calculated φ angles from 3 j nh - αh values 16 were similar to those observed in the x - ray structure . thirdly , the planar “ w ” suggested by the four - bond hmbc between h - 2 and c49 was present in the x - ray structure . 15 for conformational analysis in solution , nmr data for 1 in dmso - d 6 was used , as the differing overlap of peaks allowed the unambiguous assignment of more correlations across units . the four - bond hmbc referred to was only observed in cdcl 3 . 16 using modified karplus equation 3 j nh - αh = 8 . 40 cos 2 φ - 1 . 36 cos φ + 0 . 33 , see võgeli , b . ; ying , j . ; grishaev , a . ; bax , a . j . am . chem . soc . 2007 , 129 , 9377 - 9385 . to investigate the solution structure , 46 distance constraints were derived from roesy spectra 15 and three dihedral angle constraints from coupling constants ( nh - αh ). using a previously established molecular modeling protocol suitable for cyclodepsipeptides , 17 ten randomly drawn structures of 1 were subjected to distance geometry , 18 followed by simulated annealing and finally restrained molecular dynamics simulation for 1 ns . the modeled structures could be divided into two distinct conformational families . six structures bore striking similarity to the x - ray structure . the other four structures had altered macrocyclic ring conformation due to a differing orientation of the pla - maba - thr region , but consistently violated the same constraint between one maba methyl ( h 3 - 5 ) and h - 11 ( n - me - leu ). additionally , this second conformational family exhibited more constraint violations in general and had higher energies . 19 thus , structures in the conformational family similar to the x - ray structure are in better agreement with the roesy data , although there were not enough constraints in the pla - maba - thr region ( due to signal overlap ) to ensure convergence of all ten random structures to the same conformation . 17 luesch , h . ; yoshida , w . y . ; moore , r . e . ; paul , v . j . ; corbett , t . h . j . am . chem . soc . 2001 , 123 , 5418 - 5423 . 18 kuntz , i . d . ; thomason , j . f . ; oshiro , c . m . methods enzymol . 1989 , 177 , 159 - 204 and references therein . 19 in the x - ray structure - like family , the average number of distance constraints over 1 å was 1 . 3 , and the average energy was 17 . 507 kcal / mol . the other family had an average number of 7 distance constraint violations over 1 å and the average energy of the structures was 30 . 052 kcal / mol . the antiproliferative activity of 1 was evaluated in four cell lines derived from human osteosarcoma ( u2os ), cervical carcinoma ( hela ), colorectal adenocarcinoma ( ht29 ), and neuroblastoma ( imr - 32 ). compound 1 showed moderate broad - spectrum activity with ic 50 values of 2 . 2 μm , 1 . 0 μm , 1 . 5 μm , and 4 . 2 μm , respectively . this data is within the range of ic 50 / gi 50 values reported for lissoclinamide 7 ( 53 . 7 nm to 21 . 5 μm ), but in different cell lines which were not tested here . 4 , 20 previously , it has been shown that the thiazolines of lissoclinamide 7 are important to its cytotoxic activity . 4 it is tempting to speculate that this motif might also be responsible for the activity of 1 , and that it might indicate a shared mechanism of action with the lissoclinamides and patellamides . 20 hawkins , c . j . ; lavin , m . f . ; marshall , k . a . ; van den brenk , a . l ; watters , d . j . j . med . chem . 1990 , 33 , 1634 - 1638 . compounds of the invention can be made by means known in the art of organic synthesis . methods for optimizing reaction conditions , if necessary minimizing competing by - products , are known in the art . reaction optimization and scale - up may advantageously utilize high - speed parallel synthesis equipment and computer - controlled microreactors ( e . g . design and optimization in organic synthesis , 2 nd edition , carlson r , ed , 2005 ; elsevier science ltd . ; jähnisch , k et al , angew . chem . int . ed . engl . 2004 43 : 406 ; and references therein ). additional reaction schemes and protocols may be determined by the skilled artesian by use of commercially available structure - searchable database software , for instance , scifinder ® ( cas division of the american chemical society ) and crossfire beilstein ® ( elsevier mdl ), or by appropriate keyword searching using an interne search engine such as google ® or keyword databases such as the us patent and trademark office text database . the compounds herein may also contain linkages ( e . g ., carbon - carbon bonds ) wherein bond rotation is restricted about that particular linkage , e . g . restriction resulting from the presence of a ring or double bond . accordingly , all cis / trans and e / z isomers are expressly included in the present invention . the compounds herein may also be represented in multiple tautomeric forms , in such instances , the invention expressly includes all tautomeric forms of the compounds described herein , even though only a single tautomeric form may be represented . all such isomeric forms of such compounds herein are expressly included in the present invention . all crystal forms and polymorphs of the compounds described herein are expressly included in the present invention . also embodied are extracts and fractions comprising compounds of the invention . the term isomers is intended to include diastereoisomers , enantiomers , regioisomers , structural isomers , rotational isomers , tautomers , and the like . for compounds which contain one or more stereogenic centers , e . g ., chiral compounds , the methods of the invention may be carried out with an enantiomerically enriched compound , a racemate , or a mixture of diastereomers . preferred enantiomerically enriched compounds have an enantiomeric excess of 50 % or more , more preferably the compound has an enantiomeric excess of 60 %, 70 %, 80 %, 90 %, 95 %, 98 %, or 99 % or more . in preferred embodiments , only one enantiomer or diastereomer of a chiral compound of the invention is administered to cells or a subject . in one aspect , the invention provides a method of modulating the proliferation activity of a cell in a subject , comprising contacting the subject with a compound of formula i , in an amount and under conditions sufficient to modulate cell proliferation activity . in another aspect , the invention provides a method of treating a subject suffering from or susceptible to a cell proliferation related disorder or disease , comprising administering to the subject an effective amount of a compound or pharmaceutical composition of formula i . in other aspects , the invention provides a method of treating a subject suffering from or susceptible to a cell proliferation related disorder or disease , wherein the subject has been identified as in need of treatment for a cell proliferation related disorder or disease , comprising administering to said subject in need thereof , an effective amount of a compound or pharmaceutical composition of formula i , such that said subject is treated for said disorder . methods delineated herein include those wherein the subject is identified as in need of a particular stated treatment . identifying a subject in need of such treatment can be in the judgment of a subject or a health care professional and can be subjective ( e . g . opinion ) or objective ( e . g . measurable by a test or diagnostic method ). in certain embodiments , the invention provides a method as described above , wherein the compound of formula i is grassypeptolide . in certain embodiments , the invention provides a method of treating a disorder , wherein the disorder is cancer ( e . g ., breast , colon ) or solid tumor . in certain embodiments , the subject is a mammal , preferably a primate or human . in another embodiment , the invention provides a method as described above , wherein the effective amount of the compound of formula i ranges from about 0 . 005 μg / kg to about 200 mg / kg . in certain embodiments , the effective amount of the compound of formula i ranges from about 0 . 1 mg / kg to about 200 mg / kg . in a further embodiment , the effective amount of compound of formula i ranges from about 10 mg / kg to 100 mg / kg . in other embodiments , the invention provides a method as described above wherein the effective amount of the compound of formula i ranges from about 1 . 0 pm to about 50 μm . in certain embodiments , the effective amount ranges from about 10 . 0 pm to about 5 μm . in another embodiment , the effective amount ranges from about 1 . 0 nm to about 10 nm . in another embodiment , the invention provides a method as described above , wherein the compound of formula i is administered intravenously , intramuscularly , subcutaneously , intracerebroventricularly , orally or topically . in other embodiments , the invention provides a method as described above , wherein the compound of formula i is administered alone or in combination with one or more other therapeutics . in a further embodiment , the additional therapeutic agent is an anti - cancer agent , chemotherapeutic agent , an anti - angiogenesis agent , cytotoxic agent , or an anti - proliferation agent . examples of such chemotherapeutic agents include but are not limited to daunorubicin , daunomycin , dactinomycin , doxorubicin , epirubicin , idarubicin , esorubicin , bleomycin , mafosfamide , ifosfamide , cytosine arabinoside , bis - chloroethylnitrosurea , busulfan , mitomycin c , actinomycin d , mithramycin , prednisone , hydroxyprogesterone , testosterone , tamoxifen , dacarbazine , procarbazine , hexamethylmelamine , pentamethylmelamine , mitoxantrone , amsacrine , chlorambucil , methylcyclohexylnitrosurea , nitrogen mustards , melphalan , cyclophosphamide , 6 - mercaptopurine , 6 - thioguanine , cytarabine ( ca ), 5 - azacytidine , hydroxyurea , deoxycoformycin , 4 - hydroxyperoxycyclophosphoramide , 5 - fluorouracil ( 5 - fu ), 5 - fluorodeoxyuridine ( 5 - fudr ), methotrexate ( mtx ), colchicine , vincristine , vinblastine , etoposide , trimetrexate , teniposide , cisplatin and diethylstilbestrol ( des ). see , generally , the merck manual of diagnosis and therapy , 15th ed ., pp . 1206 - 1228 , berkow et al ., eds ., rahay , n . j ., 1987 ). another object of the present invention is the use of a compound as described herein ( e . g ., of any formulae herein ) in the manufacture of a medicament for use in the treatment of a cell proliferation disorder or disease . another object of the present invention is the use of a compound as described herein ( e . g ., of any formulae herein ) for use in the treatment of a cell proliferation disorder or disease . in one aspect , the invention provides a pharmaceutical composition comprising the compound of formula i and a pharmaceutically acceptable carrier . in one embodiment , the invention provides a pharmaceutical composition wherein the compound of formula i is grassypeptolide , and a pharmaceutically acceptable carrier . in another embodiment , the invention provides a pharmaceutical composition further comprising an additional therapeutic agent . in a further embodiment , the additional therapeutic agent is an anti - cancer agent , chemotherapeutic agent , an anti - angiogenesis agent , cytotoxic agent , or an anti - proliferation agent . in one aspect , the invention provides a kit comprising an effective amount of a compound of formula i , in unit dosage form , together with instructions for administering the compound to a subject suffering from or susceptible to a cell proliferation disease or disorder , including cancer , solid tumor , angiogenesis , etc . the term “ pharmaceutically acceptable salts ” or “ pharmaceutically acceptable carrier ” is meant to include salts of the active compounds which are prepared with relatively nontoxic acids or bases , depending on the particular substituents found on the compounds described herein . when compounds of the present invention contain relatively acidic functionalities , base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base , either neat or in a suitable inert solvent . examples of pharmaceutically acceptable base addition salts include sodium , potassium , calcium , ammonium , organic amino , or magnesium salt , or a similar salt . when compounds of the present invention contain relatively basic functionalities , acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid , either neat or in a suitable inert solvent . examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids like hydrochloric , hydrobromic , nitric , carbonic , monohydrogencarbonic , phosphoric , monohydrogenphosphoric , dihydrogenphosphoric , sulfuric , monohydrogensulfuric , hydriodic , or phosphorous acids and the like , as well as the salts derived from relatively nontoxic organic acids like acetic , propionic , isobutyric , maleic , malonic , benzoic , succinic , suberic , fumaric , lactic , mandelic , phthalic , benzenesulfonic , p - tolylsulfonic , citric , tartaric , methanesulfonic , and the like . also included are salts of amino acids such as arginate and the like , and salts of organic acids like glucuronic or galactunoric acids and the like ( see , e . g ., berge et al ., journal of pharmaceutical science 66 : 1 - 19 ( 1977 )). certain specific compounds of the present invention contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts . other pharmaceutically acceptable carriers known to those of skill in the art are suitable for the present invention . the neutral forms of the compounds may be regenerated by contacting the salt with a base or acid and isolating the parent compound in the conventional manner . the parent form of the compound differs from the various salt forms in certain physical properties , such as solubility in polar solvents , but otherwise the salts are equivalent to the parent form of the compound for the purposes of the present invention . in addition to salt forms , the present invention provides compounds which are in a prodrug form . prodrugs of the compounds described herein are those compounds that readily undergo chemical changes under physiological conditions to provide the compounds of the present invention . additionally , prodrugs can be converted to the compounds of the present invention by chemical or biochemical methods in an ex vivo environment . for example , prodrugs can be slowly converted to the compounds of the present invention when placed in a transdermal patch reservoir with a suitable enzyme or chemical reagent . certain compounds of the present invention can exist in unsolvated forms as well as solvated forms , including hydrated forms . in general , the solvated forms are equivalent to unsolvated forms and are intended to be encompassed within the scope of the present invention . certain compounds of the present invention may exist in multiple crystalline or amorphous forms . in general , all physical forms are equivalent for the uses contemplated by the present invention and are intended to be within the scope of the present invention . the invention also provides a pharmaceutical composition , comprising an effective amount a compound described herein and a pharmaceutically acceptable carrier . in an embodiment , compound is administered to the subject using a pharmaceutically - acceptable formulation , e . g ., a pharmaceutically - acceptable formulation that provides sustained delivery of the compound to a subject for at least 12 hours , 24 hours , 36 hours , 48 hours , one week , two weeks , three weeks , or four weeks after the pharmaceutically - acceptable formulation is administered to the subject . actual dosage levels and time course of administration of the active ingredients in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient , composition , and mode of administration , without being toxic ( or unacceptably toxic ) to the patient . in use , at least one compound according to the present invention is administered in a pharmaceutically effective amount to a subject in need thereof in a pharmaceutical carrier by intravenous , intramuscular , subcutaneous , or intracerebro ventricular injection or by oral administration or topical application . in accordance with the present invention , a compound of the invention may be administered alone or in conjunction with a second , different therapeutic . by “ in conjunction with ” is meant together , substantially simultaneously or sequentially . in one embodiment , a compound of the invention is administered acutely . the compound of the invention may therefore be administered for a short course of treatment , such as for about 1 day to about 1 week . in another embodiment , the compound of the invention may be administered over a longer period of time to ameliorate chronic disorders , such as , for example , for about one week to several months depending upon the condition to be treated . by “ pharmaceutically effective amount ” as used herein is meant an amount of a compound of the invention , high enough to significantly positively modify the condition to be treated but low enough to avoid serious side effects ( at a reasonable benefit / risk ratio ), within the scope of sound medical judgment . a pharmaceutically effective amount of a compound of the invention will vary with the particular goal to be achieved , the age and physical condition of the patient being treated , the severity of the underlying disease , the duration of treatment , the nature of concurrent therapy and the specific organozinc compound employed . for example , a therapeutically effective amount of a compound of the invention administered to a child or a neonate will be reduced proportionately in accordance with sound medical judgment . the effective amount of a compound of the invention will thus be the minimum amount which will provide the desired effect . a decided practical advantage of the present invention is that the compound may be administered in a convenient manner such as by intravenous , intramuscular , subcutaneous , oral or intra - cerebroventricular injection routes or by topical application , such as in creams or gels . depending on the route of administration , the active ingredients which comprise a compound of the invention may be required to be coated in a material to protect the compound from the action of enzymes , acids and other natural conditions which may inactivate the compound . in order to administer a compound of the invention by other than parenteral administration , the compound can be coated by , or administered with , a material to prevent inactivation . the compound may be administered parenterally or intraperitoneally . dispersions can also be prepared , for example , in glycerol , liquid polyethylene glycols , and mixtures thereof , and in oils . the pharmaceutical forms suitable for injectable use include sterile aqueous solutions ( where water soluble ) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions . in all cases the form must be sterile and must be fluid to the extent that easy syringability exists . it must be stable under the conditions of manufacture and storage . the carrier can be a solvent or dispersion medium containing , for example , water , dmso , ethanol , polyol ( for example , glycerol , propylene glycol , liquid polyethylene glycol , and the like ), suitable mixtures thereof and vegetable oils . the proper fluidity can be maintained , for example , by the use of a coating such as lecithin , by the maintenance of the required particle size in the case of dispersion . in many cases it will be preferable to include isotonic agents , for example , sugars or sodium chloride . prolonged absorption of the injectable compositions can be brought about by the use in the compositions of agents delaying absorption , for example , aluminum monostearate and gelatin . sterile injectable solutions are prepared by incorporating the compound of the invention in the required amount in the appropriate solvent with various of the other ingredients enumerated above , as required , followed by filtered sterilization . generally , dispersions are prepared by incorporating the various sterilized compounds into a sterile vehicle which contains the basic dispersion medium and the required other ingredients from those enumerated above . in the case of sterile powders for the preparation of sterile injectable solutions , the preferred methods of preparation are vacuum - drying and the freeze - drying technique which yields a powder of the active ingredient plus any additional desired ingredient from previously sterile - filtered solution thereof . for oral therapeutic administration , the compound may be incorporated with excipients and used in the form of ingestible tablets , buccal tablets , troches , capsules , elixirs , suspensions , syrups , wafers , and the like . compositions or preparations according to the present invention are prepared so that an oral dosage unit form contains compound concentration sufficient to treat a disorder in a subject . some examples of substances which can serve as pharmaceutical carriers are sugars , such as lactose , glucose and sucrose ; starches such as corn starch and potato starch ; cellulose and its derivatives such as sodium carboxymethycellulose , ethylcellulose and cellulose acetates ; powdered tragancanth ; malt ; gelatin ; talc ; stearic acids ; magnesium stearate ; calcium sulfate ; vegetable oils , such as peanut oils , cotton seed oil , sesame oil , olive oil , corn oil and oil of theobroma ; polyols such as propylene glycol , glycerine , sorbitol , manitol , and polyethylene glycol ; agar ; alginic acids ; pyrogen - free water ; isotonic saline ; and phosphate buffer solution ; skim milk powder ; as well as other non - toxic compatible substances used in pharmaceutical formulations such as vitamin c , estrogen and echinacea , for example . wetting agents and lubricants such as sodium lauryl sulfate , as well as coloring agents , flavoring agents , lubricants , excipients , tableting agents , stabilizers , anti - oxidants and preservatives , can also be present . the recitation of a listing of chemical groups in any definition of a variable herein includes definitions of that variable as any single group or combination of listed groups . the recitation of an embodiment for a variable herein includes that embodiment as any single embodiment or in combination with any other embodiments or portions thereof . the present invention will now be demonstrated using specific examples that are not to be construed as limiting . general experimental procedures . optical rotation was measured on a perkin - elmer 341 polarimeter . uv was measured on a spectramax m5 ( molecular devices ) and ir data obtained on a bruker vector 22 instrument . 1 h and 2d nmr spectra in cdcl 3 were recorded on a bruker avance 500 mhz spectrometer . 1 h and 2d nmr spectra in dmso - d 6 and 1d tocsy experiments in both cdcl 3 and dmso - d 6 were carried out on a bruker avance ii 600 mhz spectrometer using a 1 - mm triple - resonance high - temperature superconducting cryogenic probe . all 100 - mhz 13 c nmr data were recorded on a varian mercury 400 mhz spectrometer . spectra were referenced to residual solvent signals [ δ h / c 7 . 26 / 77 . 0 ( cdcl 3 ) and δ h / c 2 . 49 / 39 . 5 ( dmso - d 6 )]. hmqc and hsqc experiments were optimized for 145 hz , and hmbc experiments were optimized for 10 hz ( cdcl 3 ) and 7 hz ( dmso - d 6 ). hresims were recorded on a bruker apex ii fticr spectrometer in the positive mode . lc - ms data were obtained using an agilent 1100 equipped with a thermofinnigan lcq by esi ( negative mode ). extraction and isolation . samples of lyngbya confervoides were collected off grassy key in the middle florida keys ( 24 ° 43 . 381 ′ n , 80 ° 51 . 696 ′ w ) on may 26 , 2004 . a voucher specimen is maintained at the smithsonian marine station . the freeze - dried organism was extracted with etoac - meoh ( 1 : 1 ) to afford the non - polar extract ( 11 . 34 g ) which was applied to a diaion hp - 20 polymeric resin and subsequently fractionated with h 2 o and increasing concentrations of acetone . the fraction eluting with 100 % acetone ( 608 mg ) was applied to a silica gel column , then eluted with increasing concentrations of isopropanol in ch 2 cl 2 . the fraction eluting with 100 % isopropanol was purified by semipreparative reversed - phase hplc ( ymc - pack ods - aq , 250 × 10 mm , 2 . 0 ml / min ; uv detection at 220 and 254 nm ) using a meoh — h 2 o linear gradient ( 60 - 100 % over 30 min , then 100 % meoh for 20 min ), to furnish compound 1 , t r 34 . 2 min ( 11 . 2 mg ). grassypeptolide ( 1 ): colorless amorphous solid ; [ α ] 20 d + 76 ( c 0 . 1 , ch 2 cl 2 ); uv ( ch 2 cl 2 ) λ max ( log ∈) 230 ( 2 . 20 ), 260 ( 1 . 95 ), 330 ( 1 . 37 ); ir ( film ) ν max 3307 ( br ), 3054 ( w ), 2958 , 2925 , 2873 , 2851 , 1733 , 1640 ( s ), 1532 , 1456 , 1266 , 1085 , 1023 , 738 , 702 cm − 1 ; 1 h nmr , 13 c nmr , cosy , hmbc and roesy data see table 1 ( cdcl 3 ), table s1 ( cdcl 3 ) and table s2 ( dmso - d 6 ); hresims m / z [ m + na ] + 1124 . 5264 ( calcd for c 56 h 79 n 9 o 10 s 2 na , 1124 . 5284 ), [ m + h ] + 1102 . 5438 ( calcd for c 56 h 80 n 9 o 10 s 2 , 1102 . 5464 ), [ m + h 2 ] 2 + 551 . 7756 ( calcd for c 56 h 81 n 9 o 10 s 2 , 551 . 7771 ). acid hydrolysis and chiral hplc analysis . a sample of 1 ( 0 . 2 mg ) was treated with 6 n hcl at 110 ° c . for 18 h . the hydrolyzate was concentrated to dryness and analyzed by chiral hplc [ column , chirex phase 3126 ( d ) ( 4 . 6 × 250 mm ), phenomenex ; solvent , 2 mm cuso 4 ; flow rate , 0 . 8 ml / min ; detection at 254 nm ] for its amino acid content . d - allo - thr , n - me - l - val , l - pro , and d - aba eluted at t r 21 . 7 , 26 . 1 , 29 . 2 and 34 . 8 min , respectively . the retention times ( t r , min ) of the authentic amino acids were as follows : l - thr ( 13 . 4 ), d - thr ( 15 . 6 ), l - allo - thr ( 18 . 7 ), l - aba ( 21 . 3 ), d - allo - thr ( 21 . 7 ), n - me - l - val ( 26 . 1 ), l - pro ( 29 . 2 ), d - aba ( 34 . 8 ), n - me - d - val ( 43 . 0 ), and d - pro ( 64 . 3 ). to detect phenyllacetic acid ( pla ), the hydrolyzate was analyzed using different chiral hplc conditions [ column , chiralpak wh ( 4 . 6 × 250 mm ), daicel ; solvent 2 mm cuso 4 ; flow rate , 2 . 5 ml / min ; detection at 254 nm ]. n - me - d - phe eluted with the other early - eluting peaks ( t r ˜ 5 . 7 min ), and l - pla eluted at t r 15 . 6 min . there was no peak corresponding to n - me - l - phe . the retention times ( t r , min ) of the authentic amino acids were as follows : n - me - d - phe ( 5 . 7 ), n - me - l - phe ( 23 . 5 ), d - pla ( 11 . 1 ), and l - pla ( 15 . 6 ). all other amino acid standards eluted at t r & lt ; 9 min . ozonolysis , acid hydrolysis and chiral hplc analysis . ozone was bubbled through a sample of 1 ( 0 . 25 mg ) dissolved in 3 ml ch 2 cl 2 at room temperature for 10 min . the solution was then dried down and treated with 6 n hcl at 110 ° c . for 26 h . the resulting hydrolyzate was concentrated to dryness and analyzed by chiral hplc [ column , chirex phase 3126 ( d ) ( 4 . 6 × 250 mm ), phenomenex ; solvent , 2 mm cuso 4 - mecn ( 97 . 5 : 2 . 5 ); flow rate , 0 . 8 ml / min ; detection at 254 nm ] for its amino acid content . d - allo - thr , n - me - l - val / l - pro , l - cya , d - aba , and d - cya eluted at t r 15 . 9 , 18 . 4 - 18 . 8 , 22 . 0 , 23 . 6 and 26 . 9 respectively . the retention times ( t r , min ) of the authentic amino acids were as follows : l - thr ( 10 . 9 ), d - thr ( 12 . 3 ), l - allo - thr ( 14 . 9 ), d - allo - thr ( 15 . 9 ), l - aba ( 16 . 5 ), l - pro ( 18 . 5 ), n - me - l - val ( 18 . 8 ), l - cya ( 22 . 0 ), d - aba ( 23 . 6 ), d - cya ( 26 . 9 ), n - me - d - val ( 27 . 9 ), and d - pro ( 38 . 2 ). advanced marfey &# 39 ; s analysis . the n - benzoyl o - methyl esters of ( 2r , 3r )- and ( 2r , 3s )- 2 - methyl - 3 - aminobutyric acid ( maba ) were treated with 6 n hcl at 110 ° c . for 22 h . the products of each reaction were dried down and made up to 50 mm solutions in water . the other amino acid standards were also made into 50 mm stock solutions in water . then , 10 μl 1 m nahco 3 and 50 μl 1 - fluoro - 2 , 4 - dinitrophenyl - 5 - l - leucinamide ( l - fdla , 1 % w / v in acetone ) were added to 25 μl of these solutions . after heating at 35 ° c . for 1 h , with frequent mixing , the reaction mixtures were acidified with 5 μl 2 n hcl , concentrated to dryness and then reconstituted with 250 μl mecn — h 2 o ( 1 : 1 ). fdla derivatives of the hydrolyzate and hydrolyzed ozonolysis products were prepared in a similar way . standards and hydrolyzates were subjected to reversed - phase hplc analysis [ column , alltima hp c18 hl ( 4 . 6 × 250 mm ), 5 μm , alltech ; flow rate , 1 . 0 ml / min ; pda detection from 200 - 500 nm ] using a linear gradient of mecn in 0 . 1 % ( v / v ) aqueous tfa ( 30 - 70 % mecn over 50 min ). l - fdla derivatives of the synthetic maba standards gave two peaks each in an approximate ratio of 2 . 5 : 1 , indicating partial epimerization at the 2 - position ( this accounted for the minor peak each time ). retention times were as follows ( t r , min ): ( 2r , 3s )- maba ( 24 . 3 ), ( 2s , 3s )- maba ( 24 . 6 ), ( 2r , 3r )- maba ( 26 . 4 ), ( 2s , 3r )- maba ( 27 . 0 ). as with the standards , there were two maba peaks in the l - fdla - derivatized hydrolyzate , the major corresponding with ( 2r , 3r )- and the minor with ( 2s , 3r )- maba . therefore this unit was assigned 2r , 3r . all other previous assignments were confirmed by marfey &# 39 ; s analysis . additionally , there was a peak corresponding to n - me - d - leu ( t r 36 . 6 ). there were no clear peaks above the noise at the retention times expected for l - and d - cya , so the l - fdla - adduct mixture of the hydrolyzed ozonolysis products was subjected to lc - ms analysis [ column , zorbax eclipse sdb - c18 ( 3 . 0 × 250 mm ), 5 μm , agilent ; flow rate 0 . 15 ml / min ; uv and esims detection , 338 nm and negative ion mode , respectively ] using a step gradient of 0 . 2 % hcooh in mecn ( a ) and 0 . 2 % aqueous hcooh ( b ) ( 5 - 40 % a over 20 min , followed by 40 - 50 % a over 20 min , then 50 - 95 % a over 15 min ). both d - cya and l - cya were detected , eluting at t r 25 . 3 and 25 . 8 min , respectively , with peak volumes in the ratio of 1 : 1 . 64 ( base peak had expected [ m − h ] − m / z 462 . 1 for both ). retention times ( t r , min , base peak m / z ) of authentic standards were as follows : d - cya ( 25 . 3 ; 462 . 1 ) and l - cya ( 25 . 8 ; 462 . 1 ). x - ray crystallography . data were collected at 173 k on a siemens smart platform equipped with a ccd area detector and a graphite monochromator utilizing mok α radiation ( λ = 0 . 71073 å ). cell parameters were refined using up to 8192 reflections . a full sphere of data ( 1850 frames ) was collected using the co - scan method ( 0 . 3 ° frame width ). the first 50 frames were re - measured at the end of data collection to monitor instrument and crystal stability ( maximum correction on i was & lt ; 1 %). absorption corrections by integration were applied based on measured indexed crystal faces . the structure was solved by the direct methods in shelxtĺ6 , and refined using full - matrix least squares . the non - h atoms were treated anisotropically , whereas the hydrogen atoms were calculated in ideal positions and were riding on their respective carbon atoms . all acidic protons were obtained from a difference fourier map and refined freely . in addition to the molecule , the asymmetric unit contains a methanol molecule . the value of the flack x parameter is − 0 . 16 ( 14 ). a very small value and a very small standard uncertainty mean that the current enantiomer is the correct one , consistent with the analysis of chemical degradation products . we believe that the deviation of our flack x parameter from zero is due to the low diffraction of the small crystal used thus giving weak higher 2 - theta reflections . a total of 740 parameters were refined in the final cycle of refinement using 4937 reflections with i & gt ; 2σ ( i ) to yield r 1 and wr 2 of 7 . 43 % and 15 . 81 %, respectively . refinement was done using f 2 . molecular modeling . the simulations were performed on a dell pc with a 3 . 2 ghz intel pentium 4 processor , running sybyl 7 . 3 under the ubuntu linux 7 . 04 operating system . the tripos forcefield was used for all simulations . random starting structures were generated by drawing 1 differently in chemdraw ultra 10 . 0 , then they were converted to three dimensional mol2 files using chem3d pro 10 . 0 . roesy constraints were obtained by integration of correlations in mestrenova 5 . 0 . 3 - 2367 , of spectra obtained using the following mixing times : 100 , 200 , 300 and 400 ms ( in dmso - d 6 ). the correlation between the geminal protons h 2 - 22 was used as the calibration reference , as it was consistently one of the largest signals across mixing times , indicating little tocsy - type interference . correlations were stratified into weak , medium and strong noes ( 3 . 5 - 5 . 0 , 2 . 5 - 3 . 5 , & lt ; 2 . 5 å , respectively ) for each spectrum . interresidue correlations occurring in two or more of the spectra were used , resulting in 46 restraints . pseudoatoms were used for methylenes where the protons could not be stereospecifically assigned , as well as for magnetically equivalent h - 31 / h - 35 . in these cases a correction of 1 . 0 å per pseudoatom was added to the upper limit of the constraint . pseudoatoms were also used in the case of methyls , although a correction was not added to constraints involving them . additionally , torsional angle constraints could be obtained from the three amide nh signals , using a karplus equation derived from protein φ angles . 21 for these , a relatively weak force constant of 0 . 005 kcal / mol deg 2 was used . the trans conformation of amide bonds could be ascertained by the relevant roesy correlations . in the simulations these were locked into planar conformations using a strong force constant of 2 . 0 kcal / mol deg 2 . 21 using modified karplus equation 3 j nh - αh = 8 . 40 cos 2 φ - 1 . 36 cos φ + 0 . 33 , see vögeli , b . ; ying , j . ; grishaev , a . ; bax , j . am . chem . soc . 2007 , 129 , 9377 - 9385 . the random structures were subjected to the following steps : 1 . restrained energy minimization ( rem ), 2 . distance geometry ( dg ), 3 . rem , 4 . restrained molecular dynamics ( rmd ), and 5 . rem . chirality and distance constraints ( force constant 2 . 0 kcal / molå 2 ) were applied throughout the process . charges were calculated in sybyl using the gasteiger - huckel option , and a dielectric constant of 47 . 24 was used ( dmso at 20 ° c .). the dg procedure consisted of bounds generation , bounds smoothening , and embedding of coordinates ; this was followed by an optimization procedure , where the structure was minimized then subjected to simulated annealing ( sa , 2000 k to 200 k over 100 , 000 fs , step time 0 . 3 fs ) and then another round of minimization . rmd was run at 500 k for 1 ns , with a step size of 1 fs . following simulation , the structures were overlayed in pymol 0 . 99rc6 . cell culture medium was purchased from invitrogen and fetal bovine serum ( fbs ) from hyclone . cells were propagated and maintained in dmem medium ( high glucose ) supplemented with 10 % fbs at 37 ° c . humidified air and 5 % co 2 . ht29 colon adenocarcinoma cells were used for the bioassay - guided fractionation . to determine cell type selectivity , cells from four cancer cell lines ( u2os , hela , ht29 and imr - 32 ) were plated in 96 - well format and incubated at 37 ° c . ( 5 % co 2 ) for 24 hours . a dilution series of 1 in dmso ( 1 μl ) was then added , and after further 48 hours of incubation the cell viability was quantified using a standard assay kit based on mtt dye according to the manufacturer &# 39 ; s instructions ( promega ). the antiproliferative activity of 1 was evaluated in four cell lines derived from human osteosarcoma ( u2os ), cervical carcinoma ( hela ), colorectal adenocarcinoma ( ht29 ), and neuroblastoma ( imr - 32 ). compound 1 showed moderate broad - spectrum activity with ic 50 s of 2 . 2 μm , 1 . 0 μm , 1 . 5 μm , and 4 . 2 μm , respectively . this data is within the range of ic 50 values reported for lissoclinamide 7 ( 53 . 7 nm to 20 μm ), but in different cell lines which were not tested here . 4 , 22 22 hawkins , c . j . ; lavin , m . f . ; marshall , k . a . ; van den brenk , a . l ; watters , d . j . j . med . chem . 1990 , 33 , 1634 - 1638 . the contents of all references ( including literature references , issued patents , published patent applications , and co - pending patent applications ) cited throughout this application are hereby expressly incorporated herein in their entireties by reference . those skilled in the art will recognize , or be able to ascertain using no more than routine experimentation , many equivalents of the specific embodiments of the invention described herein . such equivalents are intended with be encompassed by the following claims .

the instant invention describes macrocyclic compounds having antiproliferation activity , and methods of treating disorders such as cancer , tumors and cell proliferation related disorders .

the composition of the present invention may be effectively used in preserving the color and freshness of fresh meats and meat products and finds its greatest utility in this application ; however , its use is not limited thereto and it may also be used to treat aged and cured meats , fish , fruits and vegetables . in accordance with the present invention , the product to be treated , such as cuts of meat or whole carcasses , may be treated by dusting the exposed surfaces with the composition of the present invention or by spraying the surfaces with a solution thereof . for carcasses , treatment may be accomplished by injecting a solution of the composition of the present invention into the arteries and veins . for ground meat , the treating materials may be applied to the exposed surface of the ground meat or added to the meat before or during grinding to permit distribution thereof throughout the ground mass . it is preferred in accordance with the present invention that the components thereof be thoroughly mixed together before application to the product . in accordance with the present invention , the ascorbic acid component may be ascorbic acid itself and / or the sodium and / or potassium salts thereof . similarly , the citric acid component may be the citric acid itself and / or the sodium and / or potassium salts thereof , i . e ., sodium or potassium citrate . either sodium and / or potassium carbonate may be employed . the sulfite component may be a sulfite , bisulfite and / or metabisulfite of sodium and / or potassium . the amounts of the components of the present invention are as stated hereinabove . preferably , substantially equal quantities of each of the components are employed . in accordance with a preferred embodiment of the present invention , a suitable quantity of ground meat is first ground and mixed with a suitable quantity of the composition of the present invention and the mixture reground . in accordance with an alternate embodiment for red meats , poultry , fish , fruits and vegetables , a suitable quantity of the composition of the present invention is dissolved in water and the edible meat product sprayed with the aqueous solution . naturally , alternate methods of application of the composition of the present invention may be readily employed . naturally , additional freshness or color preservatives may , if desired , be added to the product such as nitrates or nitrites , phosphates , nicotinic acid or other known color or freshness preservatives . the surprising feature of the composition of the present invention is the synergistic combination of the components thereof which effectively preserves color and freshness and retards bacterial growth for an inordinately long period of time far beyond what would normally be anticipated . the foregoing will be more clearly apparent from the examples which form a part of the present specification . a composition of the present invention was formulated by mixing together equal amounts of sodium bisulfite , ascorbic acid , citric acid and sodium carbonate . fifty pounds of fresh red hamburger was first ground and then thoroughly mixed with two ounces of the foregoing mixture . the mixture was then reground and stored in a refrigerated condition at a temperature of approximately 35 ° f . the resultant meat retained its bright red color and freshness for approximately two weeks . untreated meat darkened after about one week and at the end of the two week period was quite dark and no longer fresh . two ounces of the composition of example i were thoroughly dissolved in two quarts of water . the composition was sprayed on various samples of poultry and red meats . the resultant sprayed samples were stored in a refrigerated condition as in example i and maintained their color and freshness for approximately two weeks . comparable materials lost their color after about one week and were no longer fresh after the two week period . a piece of veal which had started to discolor was tested in a variety of ways . firstly , a portion of this material was treated with two ounces of a composition containing equal amounts of ascorbic acid , citric acid and sodium carbonate . the material was stored in the refrigerated condition at about 35 ° f . after about three days , the material showed clear signs of decay . another portion of this material was treated with two ounces of sodium bisulfite only under the same conditions and showed clear signs of decay after five days . a third sample was treated with two ounces of the composition of example i as aforesaid . the material showed no signs of decay after two weeks of storage . a variety of experiments were conducted with a variety of compositions on beef which had been previously stored to the point where the meat was starting to discolor . composition a was 1 / 10 of an ounce each of ascorbic acid , citric acid and sodium bisulfite . the material thus treated showed clear signs of decay after five days &# 39 ; storage in the refrigerated condition at approximately 35 ° f . composition b represented 1 / 10 of an ounce each of ascorbic acid and sodium bisulfite . the treatment conditions were the same as above and the material showed clear signs of decay after three days &# 39 ; storage . composition d represented 1 / 10 of an ounce of sodium carbonate . the meat showed clear signs of decay after three days &# 39 ; storage . composition e represented 1 / 10 of an ounce each of sodium carbonate , ascorbic acid and citric acid . the material showed clear signs of decay after five days . composition f represented the composition of the present invention with 1 / 10 of an ounce each of sodium bisulfite , citric acid , ascorbic acid and sodium carbonate . the material showed no signs of decay after two weeks &# 39 ; storage . example i was substantially repeated using potassium bisulfite , potassium carbonate , potassium citrate and potassium ascorbate . the same excellent results were obtained as in example i . in this example , eleven individual packages of beef were prepared , cut into approximately 1 &# 34 ; cubes . the beef had previously been stored for a period of 7 days . each cube was treated with one - tenth ounce of the composition of the present invention containing equal amounts of ascorbic acid , citric acid , sodium carbonate and sodium bisulfite . daily an unopen package was removed , ground under sterile conditions with sterile phosphate buffer , serially diluted and tested for aerobic plate count and coliform count . all samples were held under refrigerated conditions at approximately 35 ° f . during the course of the study . in accordance with this study , a bacterial population of below 1 , 000 , 000 per milliliter is the generally recommended standard for beef . the results are shown in the following table . table i__________________________________________________________________________ aerobic coliformday color odor count 35 ° f . contamination__________________________________________________________________________1 - initial count good good 220 , 000 & lt ; 12 - 24 hr . count good good 240 , 000 93 - 48 hr . count good good 240 , 000 44 - 72 hr . count turning brown good 260 , 000 45 - 96 hr . count turning brown good 250 , 000 & lt ; 16 - 120 hr . count turning brown good 280 , 000 & lt ; 17 - 144 hr . count brownish red good 12 , 000 , 000 & lt ; 18 - 168 hr . count brownish red good 16 , 000 , 000 & lt ; 19 - 192 hr . count brownish red good 20 , 000 , 000 & lt ; 110 - 216 hr . count brownish red good 150 , 000 & lt ; 111 - 240 hr . count brownish red good 600 , 000 & lt ; 1__________________________________________________________________________ the results of the study clearly showed that the preservative maintained the bacterial population well below the 1 , 000 , 000 count per milliliter generally recommended as a standard for beef for the first six days of the study . this was supported by organalyptic testing . after five days the counts increased markedly to the tenth day . coliform counts did not seem a factor . spurious coliform counts on the second , third and fourth days were believed to have resulted from contamination during the packaging of the samples . on the tenth and eleventh days , the counts again dropped so that the particular packages in question may have received more of the preservatives . the foregoing data clearly shows that the composition of the present invention is capable of maintaining acceptable bacterial counts for at least six days and possibly longer even after the meat has been previously stored for an extended period of time when the meat is held at normal refrigeration temperatures . ______________________________________composition i . sodium bisulfite equal parts sodium carbonate ascorbic acidcomposition ii . sodium bisulfite equal parts sodium carbonate citric acidcomposition iii . sodium bisulfite equal parts sodium carbonate citric acid ascorbic acidcomposition iv . sodium bisulfite 85 % sodium carbonate 10 % citric acid 5 % composition v . sodium bisulfite 85 % sodium carbonate 10 % citric acid 21 / 2 % ascorbic acid 21 / 2 % ______________________________________ a variety of experiments were conducted with beef . all experiments were conducted on the same piece of beef . the samples were cut into equal quantities and two ounces of each of the compositions were used to treat each portion of meat . all portions of meat were stored under identical refrigerated conditions and the condition of each portion evaluated daily for a period of sixteen days . the results are shown in the following table . table ii______________________________________color of meat treated with formuladay i ii iii iv v______________________________________1 good good good good good2 good good good good good3 good brown good good good4 brown dark brown good good good5 dark decayed good brown goodbrown6 decayed good dark good brown7 good decayed brown8 good dark brown9 good decayed10 good11 good12 good13 good14 good15 good16 good______________________________________ sample iii is the composition of the present invention . it can be seen that the meat treated with the composition of the present invention retained its good color characteristics for the full sixteen days of the test . the meat treated with sample i , sodium bisulfite , sodium carbonate and ascorbic acid only , retained its good color for only three days . on the fourth day it was brown , the fifth day it was dark brown and on the sixth day it had decayed . the meat treated with formula ii , the formula without ascorbic acid , retained its good color for only two days . the meat turned brown on the third day , on the fourth day it turned dark brown and on the fifth day it was decayed . the meat treated with formula iv retained its good color for four days . the meat turned brown on the fifth day , dark brown on the sixth day and had decayed on the seventh day . the meat treated with formula v retained its good color for six days . on the seventh day it turned brown , on the eighth day it turned dark brown and on the ninth day it had decayed . a three pound piece of fresh codfish and a three pound piece of fresh bluefish were cut into equal portions . a two pound portion of fresh scallops was divided into equal portions . thirty grams of the composition of example i was thoroughly dissolved in one quart of water . one of the portions of codfish , one of the portions of bluefish and one of the portions of scallops were left untreated and one treated with a fine spray of the aqueous composition so that the treated materials were thoroughly wetted . the treated and untreated materials were stored under ambient conditions . all untreated samples were spoiled in two days . all treated samples maintained their freshness for 25 days under the ambient conditions of storage . this invention may be embodied in other forms or carried out in other ways without departing from the spirit or essential characteristics thereof . the present embodiment is therefore to be considered as in all respects illustrative and not restrictive , the scope of the invention being indicated by the appended claims , and all changes which come within the meaning and range of equivalency are intended to be embraced therein .

this invention resides in a composition for treatment of meat , poultry , fruit and vegetables to maintain the color and to preserve same . the composition comprises as essential constituents between about 10 and 40 % each of the following materials : ascorbic acid and / or the sodium or potassium salts thereof ; citric acid and / or the sodium or potassium salts thereof ; sodium or potassium carbonate ; and sulfite , bisulfite or metabisulfite of sodium or potassium . these materials represent a synergistic combination which preserves the color and freshness of these products for a surprisingly long period of time .

in fig1 of the drawing , a device for the coherent amplification of electromagnetic oscillations is designated with the numeral 4 . the device 4 consists of a laser tube 15 containing an argon - ion gas , for example , for burns . energy is transmitted to the laser device 4 through an electric line 16 . the electromagnetic oscillations , waves or the laser beam emerging from the laser device 4 can have frequencies of 5 × 10 14 hz to 10 15 hz ( visible range ). depending on the curative treatment or type of application , the laser device can be designed in such a way that it can be used in the ultraviolet or infrared range . the frequencies given here constitute the visible part ( light ) of the electromagnetic spectrum . a laser beam or a light beam 10 is conducted through a cable 2 whose inlet opening 5 is connected to the laser device 4 and to its outlet opening , and to an inlet opening 19 of a treatment probe or receptacle 3 . the laser beam 10 emerges to the outside via the outlet opening 6 and is directed at a biological system 11 . the receptacle 3 consists of a cylindrical housing part 17 with an adjacent housing part 18 that is tapered towards the front . over the entire length of the receptacle 3 , there is a longitudinal opening 9 that opens up into the outlet opening 6 . thus , the light or laser beam 10 is conducted via the longitudinal opening 9 , said light or laser beam is then conducted via the outlet opening 6 provided in the receptacle , it strikes the biological system 11 or a human body , an animal body or a plant body , where it brings about the desired healing effect or change in the biological system . in the range of the outlet opening 6 of the receptacle 3 , there is a crosswise opening 1 that intersects the longitudinal opening 9 at an angle , advantageously at a right angle . as can be seen in fig2 a container 12 is inserted into the crosswise opening 1 in such a way that it intersects the beams of the laser beam at an angle of 90 °. as a result , the laser beams are conducted via or through the container 12 . the container 12 is advantageously made of glass , especially of quartz glass , so that almost no losses occur when the laser beam passes through the quartz glass . the container may be closed by a removable closure mechanism 14 , such as a lid or stopper . therefore , the container 12 can advantageously be cylindrical in shape . however , it is also possible to configure the container 12 so as to be conical and to adapt the corresponding crosswise opening 1 likewise to the conical shape of the container 12 so that a clamp connection between the receptacle 3 and the container 12 is achieved . the container 12 serves to receive one or more solid elements or else to receive substances in pulverulent form or to receive a gaseous or liquid solution . in addition , a carrier solution , for example , water and ethanol at a ratio of 1 : 1 , can be filled into the container 12 . the admixtures or substances are placed into the carrier solution in a concentration of 50 vol .-% to 10 × 10 - 24 vol .-% in a decreasing direction . additionally , for example , mineral , plant , animal or human extracts or products or else toxins are added to this carrier solution . these additives are referred to as admixture 8 , which is decisive for exerting a positive influence on the biological system 11 or for the medical treatment in question . thus , the filling of the container 12 can be a true solution , a solution mixture or a colloidal solution . depending on the composition of the admixture , it is also possible to do without the carrier solution . the laser beam 10 is conducted through the container 12 with the substances or admixtures and then strikes the biological system 11 . in an advantageous manner , the light radiation is specifically scattered ( utilization of the ramann effect ) in every atomic or molecular compound , and the emerging light practically contains the fingerprint of the admixtures . if , for example , an argon - ion laser is used , this laser beam provides the appropriate basic energy for the biological processes . the emerging laser beam then passes on the information to the biological system and brings about the healing process , for example , in the case of a burn . the distance between the outlet end of the receptacle 3 and the biological system 11 is usually constant during the treatment process . if the distance between the outlet end of the receptacle 3 and the biological system 11 is increased , then a larger surface area of the biological system is also reached by the laser beam 10 . if a neodymium - yag laser is used , for instance , for treating wounds or for another type of treatment , it is advantageous if the wavelength of 532 nm ( green ) and 473 nm ( blue ) are used . it is especially advantageous for the laser emission to lie in the visible range , that is to say , between 650 nm and 300 nm ( uv ). the selection of the wavelength depends on which biological system 11 is to be irradiated . infrared light should not be used for human cells since it can kill them . if the laser device is used , for example , for tumor treatment , then the laser consists of an argon - ion - krypton mixed - gas laser between 2 mm and 100 mm . a ) local : extracts from pathogens of tuberculosis and / or gonorrhea and / or syphilis in a concentration of 10 × 10 - 6 vol .-% to 10 × 10 - 8 vol .-%. b ) limbic system ( brain ): extract from salamandra 10 × 10 - 6 vol .-% to 10 × 10 - 8 vol .-%. for the treatment of broken bones , it is advantageous to use an argon - ion laser device between 2 mm and 100 mm . for this treatment , substances of the type listed below are used as admixtures . the explanations given above show that a very specific type of laser with a corresponding probe has to be used for the medical treatment of the biological system 11 , depending on the type of illness , whereby a certain admixture 8 is incorporated into each probe or receptacle . a patient born in 1927 was found to have an open wound on the left thigh that would not heal . this wound could not be positively influenced by any of the classical treatments ( e . g ., administration of antibiotics , surgical treatment of the edge of the wound ). this wound was treated with the described argon - ion laser , whereby the frequencies emitted were in the visible range . the power output of the laser device 4 was 50 mw . the laser beam 10 was directed at the burn 11 through the substances 8 present in the quartz glass container 12 . several substances were contained in the carrier solution in the following concentration : extract from aconitum 10 × 10 - 4 vol .-% and extract from arnica 10 × 10 - 3 vol .-%. the emerging laser beam 10 , as already mentioned , was radiated over the entire wound through the container 12 that functioned as an optical device . the treatment duration was 30 minutes each time . already after a week , an intense healing reaction set in . after one week of treatment , the wound that had been 10 cm long and 2 . 5 cm wide in the middle at the beginning of the laser treatment was 2 cm in diameter after one week and 7 mm in diameter after two weeks . after three weeks , the wound had healed completely . the laser radiation was used successfully for treating wounds , broken bones , sprains , compressions and concussions . following a severe concussion and laser treatment applied within five minutes , the patient was already completely free of symptoms after a ten - minute treatment , and a normal neurological reaction was observed . depending on the type of treatment , the appropriate laser with the appertaining container 12 containing an appropriate admixture is used . the laser treatment or irradiation can also exert a positive influence on the metabolism . the appropriate admixtures contain extracts from plants , from animal and human products , also extracts from viruses , bacteria , fungi and other pathogens as well as extracts from tumors and pathological secretions . cell cultures and living cells can be positively influenced in the case of organ donation . moreover , it is advantageous to use the laser radiation for microorganisms and also viruses outside of living organisms . the following solutions have been successfully used for wound treatment in the following concentrations : ______________________________________extract from aconitum 10 × 10 . sup .- 4 vol .-% extract from arnica 10 × 10 . sup .- 3 vol .-% extract from belladonna 10 × 10 . sup .- 4 vol .-% extract from bellis 10 × 10 . sup .- 4 vol .-% extract from calendula 10 × 10 . sup .- 5 vol .-% extract from chamomilla 10 × 10 . sup .- 4 vol .-% extract from echinacea ang . 10 × 10 . sup .- 4 vol .-% extract from echinacea purp . 10 × 10 . sup .- 4 vol .-% extract from hamamelis 10 × 10 . sup .- 3 vol .-% extract from millefolium 10 × 10 . sup .- 4 vol .-% extract from symphytum 10 × 10 . sup .- 9 vol .-% solution of hepar sulf . 10 × 10 . sup .- 9 vol .-% solution of mercurius sol . 10 × 10 . sup .- 9 vol .-% solution of quartz 10 × 10 . sup .- 6______________________________________ vol .-% these and other concentrations are placed into the container 12 . the container 12 functions as an optical element or as a lens and amplifies the laser beam 10 . when the laser beam strikes an atom or molecule , the laser beam is scattered , i . e ., the above - mentioned ramann effect is utilized . the emerging laser beam contains the above - mentioned optical fingerprint of the substances listed above and has an influence on the treatment of the biological system 11 . the scattered beams produce a bio - photon field . argon - ion lasers are used to treat broken bones , and substances 8 are placed into the container 12 . this admixture or substance has a concentration of 10 × 10 - 3 vol .-% to 10 × 10 - 12 vol .-%. a red diode laser 632 nm is used for the treatment of wild roses and a mixed quartz is added in the concentration of 10 × 10 - 6 . ( when wild roses are treated with a laser , germs or fungi can be controlled , and wild roses can be grafted better after a laser treatment . this underscores the fact that a laser treatment can easily be carried out in plants .) if , for example , the laser device is used for allergy treatment , then the laser consists of a red he -- ne or diode laser at 632 nm and a green he -- ne / neodymium - yag laser . in this case , the following admixtures are placed into the container : extract from dioscorea vilosa in the concentration of 10 × 10 - 5 vol .-% and kalium carb . in the concentration of 10 × 10 - 6 vol .-%. for treating hair loss , the laser consists of a green he -- ne or neodymium - yag laser . in this case , the following admixtures are placed into the container : extract from tuberculosis and / or placenta and / or extract from pel talpae in the concentration of 10 × 10 - 3 vol .-% to 10 × 10 - 9 vol .-%. if the laser device is used for treating enteritis , then the laser consists of a green he -- ne or neodymium - yag laser alternating with a yellow he -- ne laser . in this case , the following admixtures are placed into the container : extracts from pathogens in the concentration of 10 × 10 - 4 to 10 × 10 - 12 vol .-%. if the laser is used , for example , for the treatment of circulatory disorders , then the laser consists of a red he -- ne diode laser . in this case , the following admixtures are placed into the container : extracts from pathogens and / or snake venom in the concentration of 10 × 10 - 4 vol .-% to 10 × 10 - 12 vol .-%. in order to treat eczema , the laser consists of a green laser alternating with an argon - ion multi - line laser . in this case , the following admixtures are placed into the container : extracts from pathogens in the concentration of 10 × 10 - 4 to 10 × 10 - 12 vol .-%. for the treatment of lowered resistance ( weakened immune system ), the laser consists of a red he -- ne diode laser . in this case , the following admixtures are placed into the container : extracts from pathogens in the concentration of 10 × 10 - 4 to 10 × 10 - 12 vol .-%. in order to treat hepatic colic , the laser consists of a green he -- ne or neodymium - yag laser . in this case , the following admixtures are placed into the container : extracts from pathogens , magnesium phosphate and calcium phosphate in the concentration of 10 × 10 - 4 vol .-% to 10 × 10 - 12 vol .-%. if the laser is used , for example , for the treatment of stomach ailments , then the laser consists of a red he -- ne diode laser . in this case , the following admixtures are placed into the container : extracts from pathogens in the concentration of 10 × 10 - 4 to 10 × 10 - 12 vol .-%. if the laser device is used to treat joint disorders , then the laser consists of an argon - ion multi - line laser . in this case , the following admixtures are placed into the container : extracts from pathogens in the concentration of 10 × 10 - 4 to 10 × 10 - 12 vol .-%. for the treatment of digestive organs and the kidneys , the laser consists of a yellow and a green he -- ne laser . in this case , the following admixtures are placed into the container : extracts from pathogens in the concentration of 10 × 10 - 4 to 10 × 10 - 12 vol .-% and / or minerals in the concentration of 10 × 10 - 3 vol .-% to 10 × 10 - 24 vol .-% and / or extract from salamandra in the concentration of 10 × 10 - 8 vol .-%. if the laser is used for the treatment of herpes and herpes zoster , then the laser consists of an argon - ion multi - line laser . in this case , the following admixtures are placed into the container : extract from tuberculosis in the concentration of 10 × 10 - 6 vol .-%. for the treatment of neuritis ( ischialgia ), the laser consists of an argon - ion multi - line laser . in this case , the following admixtures are placed into the container : extract from tuberculosis in the concentration of 10 × 10 - 6 vol .-%. in order to treat cardiac insufficiency , anginal disorders , the laser consists of an orange he -- ne laser . in this case , the following admixtures are placed into the container : extracts from pathogens in the concentration of 10 × 10 - 4 to 10 × 10 - 12 vol .-% and / or minerals in the concentration of 10 × 10 - 3 to 10 × 10 - 24 vol .-% and / or extract from salamandra in the concentration of 10 × 10 - 8 vol .-%. if the laser device is used , for example , to treat migraine , then the laser consists of an argon - ion multi - line laser and a red he -- ne diode laser . in this case , the following admixtures are placed into the container : extract from tuberculosis in the concentration of 10 × 10 - 6 vol .-%. in order to treat neurodermatitis , the laser consists of an argon - krypton mixed gas laser and a red he -- ne diode laser . in this case , the following admixtures are placed into the container : extracts from pathogens in the concentration of 10 × 10 - 4 to 10 × 10 - 12 vol .-% and / or minerals in the concentration of 10 × 10 - 3 to 10 × 10 - 24 vol .-% and / or extract from salamandra in the concentration of 10 × 10 - 8 vol .-% and an extract from dioscorea vilosa in the concentration of 10 × 10 - 5 vol .-% and kalium carb . in the concentration of 10 × 10 - 6 vol .-%. if the laser is used to treat parkinson &# 39 ; s disease , then the laser consists of argon - ion multi - line laser and an argon - krypton mixed - gas laser . in this case , the following admixtures are placed into the container : extracts from pathogens in the concentration of 10 × 10 - 4 to 10 × 10 - 12 vol .-% and extracts from hormones in the concentration of 10 × 10 - 6 to 10 × 10 - 24 vol .-%. this application relates to subject matter disclosed in german application number 197 42 299 . 3 , filed on sep . 25 , 1997 , the disclosure of which is incorporated herein by reference . while the description above refers to particular embodiments of the present invention , it will be understood that many modifications may be made without departing from the spirit thereof . the accompanying claims are intended to cover such modifications as would fall within the true scope and spirit of the present invention . the presently disclosed embodiments are therefore to be considered in all respects as illustrative and not restrictive , the scope of the invention being indicated by the appended claims , rather than the foregoing description , and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein .

a system composed of a device 4 for the coherent amplification of electromagnetic oscillations by means of induced emission through a solid element , crystals or glasses doped with neodymium , semiconductor diodes or liquids or gases , whereby the electromagnetic oscillations emerging from the device are conducted through a cable or optical fiber cable 2 in order to influence a biological system , especially a human body or an animal body 11 . the cable 2 has an outlet opening 7 and the oscillations emerging from the cable 2 are conducted through a solid element , a mixture or a liquid or gaseous solution 8 in order to influence the biological system 11 , whereby the solid element , the mixture or the liquid or gaseous solutions contain mineral , plant , animal or human extracts or products or else toxins as admixtures .

referring to fig1 , a chessboard device with auto - electronic scoring according to the present invention provides a user display 11 , a score display 12 , an id color display 200 , functional keys 13 , a loudspeaker 15 and etc . next to the main body 10 of the chessboard for performing functions of automatic voice scoring and score display . display components 60 with such as displaying light , color or figure at the center of the chessboard . a light - transmittable component 20 and a touch device 30 are arranged on each of the display components 60 respectively . the display components 60 or the light - transmittable components 20 are employed to identify the players . the touch devices 30 are connected to an induction switch device 50 ( not shown ) respectively . when the touch devices 30 are touched , signals are sent out via the central processing unit ( cpu ) to allow the display components 60 working . in this way , the players can select available options manually to play the chessboard game and the winner or loser is capable of being determined automatically with a microcomputer . additional touch devices 30 and the induction switches device 50 can be arranged in the vicinity of the display components 60 and the light - transmittable components 20 . that is , the display components 60 and the light - transmittable components 20 are surrounded with one of the touch devices 30 and one of the induction switches device 50 or the central positions of the display components 60 and the light - transmittable components 20 are arranged one of the touch devices 30 and one of the induction switches device 50 or each of the display components 60 and the light - transmittable components 20 occupies a semicircular portion and each of the touch devices 30 and the induction switches device 50 occupies another semicircular portion respectively . the respective display component 60 can be liquid crystal display ( lcd ), backlight lcd , light emitting diode ( led ), digital tube or the like . the shapes , contours , structures , sizes and quantities of the display components 60 , light - transmittable components 20 and the touch devices 30 are capable of being arranged as desire while the chessboard is designed . the display components 60 can be associated with the touch devices 30 and the induction switches 50 to allow the cpu of the microcomputer accessing automatic scoring with lighting and voice without the light - transmittable components 20 . referring to fig2 , the display components 60 of the main body 10 of the chessboard according to the present invention can show figures or colors such as characters , digits , circular points , rectangular points , polygons , multiple strips , dots and etc . for identifying players . the light - transmittable components 20 can be provided on the display components 60 or provided without the light - transmittable components 20 . referring to fig3 , score displays 12 , identification colors 200 of the users , functional keys 13 and loudspeakers 15 are provided around the main body 10 of the electronic chessboard according to the present invention for performing the automatic scoring with voice and score display . when the touch devices 30 and the induction switches device 50 are pressed , signals are transmitted via the cpu to allow the display components 60 become working displays 600 such as light , digits , characters , figures , colors and any figures of the chesses . in this way , the players are capable of selecting available options manually to play the chessboard and winner and loser are determined automatically by means of a microcomputer . arc shaped touch devices 30 , u - shaped touch devices 30 , ellipse strips shaped touch devices 30 and semi - hexagon touch devices 30 are provided to surround the display components 60 . the respective display component 60 can be liquid crystal display ( lcd ), backlight lcd , light emitting diode ( led ), digital tube or the like . the shapes , contours , structures , sizes and quantities of the display components 60 , light - transmittable components 20 and the touch devices 30 are capable of being arranged as desire while the chessboard is designed . the light - transmittable components 20 can be provided on the display components 60 to join the touch device 30 for the cpu of the microcomputer accessing automatic scoring with lighting and voice . referring to fig4 , an example of the traditional chessboard 70 with three chesses is illustrated . the feature of the traditional chessboard 70 is in that the player , who completes the three chesses 72 being lined up in a line first , is the winner . it can be seen that the player , who only completes two chesses 71 being lined up , is the loser . referring to fig5 , the main body 10 of the chessboard device with auto - electronic scoring the electronic chessboard according to the present invention is provided with light - transmittable components 20 . a printed circuit board ( pcb ) 40 is disposed at the bottom of the light - transmittable components 20 and two display components 60 are attached to the pcb corresponding to the light - transmittable components 20 respectively . a touch device 30 is at the center of the chessboard between the light - transmittable components 20 . when the touch device 30 is pressed , a first conductive layer 51 of the induction switch device 50 at the bottom of the chessboard is bent downward to touch a second conductive layer 52 under a partition 53 such that the microcomputer is capable of receiving inductive signals to light up the display components 60 and become working display components 600 for standing for the identifications of the users in the chessboard game . referring to fig6 , the main body 10 of the chessboard device with auto - electronic scoring according to the present invention is provided with display components 60 and each of the display components 60 is next to a touch device 30 . when the touch device 30 is pressed down , the first conductive layer 51 of the inductive switch device 50 is bent downward to touch a second conductive layer 52 under a partition 53 such that the microcomputer is capable of receiving inductive signals . in this way , the display components 60 becomes working display components 600 . it is noted that shape and size of the touch device 30 can be arranged as desired while the chessboard is designed . referring to fig7 , each display component 60 is surrounded with a plurality of touch devices 30 . when the touch devices 30 are pressed down , the induction switches device 50 are touched such that the microcomputer is capable of receiving inductive signals for the display components 60 becoming working display components 600 . referring to fig8 , the main body 10 of the chessboard device with auto - electronic scoring according to the present invention is provided with a light - transmittable component 20 and an induction switch device 50 is disposed between the light - transmittable component 20 and a pcb 40 . the induction switch device 50 provides a structure of conventional magnetic spring switch . the magnetic spring switch has conductive plates and a first conductive layer 51 and a second conductive layer 52 are arranged on the conductive plates respectively . the light - transmittable component 20 is slidable to allow the first conductive layer 51 pressing the second conductive layer 52 in addition to admitting light penetrating through such that the micro computer is capable of receiving the inductive signals for the display component 60 being lighted up to stand for identifications of the users during playing chessboard game . the display component 60 has a first emitting chip and a second emitting chip 61 , 62 to allow the display component displaying with at least two different colors . similarly , the emitting chip can be provided with the conventional type in material , structure and color displayed instead . one of the colors of the same display component 60 is employed to stand for identification of the user . the light - transmittable component 20 and the induction switch device 50 can be designed specifically as desired in shape , size or structure . referring to fig9 , the main body 10 of the chessboard device with auto - electronic scoring according to the present invention is provided with light - transmittable components 20 . an induction switch device 50 is disposed between each of the light - transmittable components 20 and the pcb 40 . the induction switch 50 can be conventional conductive plastic ( or rubber ) switch and the conductive plastic ( or rubber ) switch has a first conductive layer 51 being joined to a second conductive layer 41 on the pcb . the respective light - transmittable component 20 is slidable to allow the first conductive layer 51 pressing the second conductive layer 41 of the pcb 40 in addition to being capable of being penetrated by the light such that the micro computer is capable of receiving the inductive signals and lighting up the display component 60 for standing for identifications of the users while playing the chessboard game . it is noted that there are three display components 60 under the respective light - transmittable component 20 . once any one of the display components is lit up , it becomes working display component 600 . the display components 60 can be any conventional display components with light emitting structure . referring to fig1 , the main body 10 of the chessboard device with auto - electronic scoring according to the present invention is provided with light - transmittable components 20 . an induction switch device 50 is disposed between each of the light - transmittable components 20 and the pcb 40 . the induction switch device 50 can be conventional micro switch and the inductive switch device 50 has a stir rod 54 to press an induction switch 55 on the induction switch device . the respective light - transmittable component 20 is slidable to allow the stir lever 54 pressing the induction switch 55 in addition to being penetrated by the light such that the micro computer is capable of receiving the inductive signals and lighting up the display component 60 for standing for identification of the user while the chessboard game being played . referring to fig1 , the induction switch devices 50 are attached to the main body 10 of the electronic chessboard and a light - transmittable component 20 is provided on top of the respective induction switch device 50 . at least a display component 60 is disposed under the light - transmittable component 20 . when the slidable light - transmittable component 20 is pressed downward , a button key gap 23 becomes smaller such that the micro computer is capable of receiving the inductive signals and lighting up the display component 60 for standing for identification of the user while the chessboard being played . referring to fig1 , the main body 10 of the chessboard device with auto - electronic scoring according to the present invention is provided with light - transmittable components 20 . each of the light - transmittable components 20 is stationary and the respective light - transmittable component 20 is surrounded with slidable touch devices 30 for pressing induction switch devices 50 against the conductive layer 41 on the pcb 40 . referring to fig1 and 14 , the main body 10 of the chessboard device with auto - electronic scoring according to the present invention is attached with a plastic thin plate 100 by means of conventional ways such as gluing , fixing , thermo - adhering or cold adhering . the plastic thin plate 100 is arranged with conductive layer , which is associated with circuit . light - transmittable components 20 are integrally formed with the plastic plate 100 and each of the light - transmittable components 20 is provided with a conduction switch device 50 , which has an upper and lower conductive layers 51 , 52 . when the upper conductive layer 51 is pressed down to touch the lower conductive layer 52 , a closed circuit signal can be transmitted to the cpu of the micro computer such that a display component 60 under the respective light - transmittable component 20 becomes a working display component 600 . referring to fig1 , the main body 10 of the chessboard device with auto - electronic scoring according to the present invention is attached with a plastic thin plate 100 by means of conventional ways such as gluing , fixing , thermo - adhering or cold adhering . the plastic thin plate 100 is arranged with conductive layer , which is associated with circuit . light - transmittable components 20 are integrally formed with the plastic plate 100 and each of the light - transmittable components 20 is provided with a conduction switch device 50 , which has an upper and lower conductive layers 51 , 52 . when the upper conductive layer 51 is pressed down to touch the lower conductive layer 52 , a closed circuit signal is transmitted to the cpu of the micro computer such that a display component 60 under the respective light - transmittable component 20 is capable of showing at least a single light , at least a color or at least a figure as desired for the cpu being able to distinguish identification of the user , changes of playing rules and winner and loser . the display component 60 can be conventional display such as lcd , back light lcd , led , liquid crystal screen or digital tube . referring to fig1 , the main body 10 of the chessboard device with auto - electronic scoring according to the present invention is attached with a plastic thin plate 100 by means of conventional ways such as gluing , fixing , thermo - adhering or cold adhering . light - transmittable components 20 are integrally formed with the plastic thin plate 100 . a display component 60 is disposed under the respective light - transmittable component 20 . the respective light - transmittable component 20 can be formed as an induction device with an upper and lower conductive layers 51 , 52 . a partition 53 is sandwiched between the upper conductive layer 51 and the lower conductive layer 52 . when the upper conductive layer 51 is pressed to touch the lower conductive layer 52 , the electrically on signals are transmitted to the cpu of the micro computer to allow the display component 60 becoming working display component 600 . the partition 53 is capable of allowing the upper conductive layer 51 moving back to the original position after being pressed and touching the lower conductive layer 52 more effectively . referring to fig1 , the main body 10 of the chessboard device with auto - electronic scoring according to the present invention is provided with display components 60 and a light - transmittable component 20 is disposed on top of the respective display component 60 . induction switch devices 50 are arranged between the light - transmittable component 20 and a pcb 40 . the induction switch device 50 is conventional conductive plastic ( or rubber ) switch . the light - transmittable component 20 is capable of sliding to press the induction switch device 50 in addition to being capable of being penetrated by the light such that the micro computer is capable of receiving the inductive signals to allow the display component 60 showing at least a single light , at least a color or at least a figure as desired for standing for identifications of the users . the display component 60 can be conventional display such as lcd , back light lcd , led , liquid crystal screen or digital tube . referring to fig1 , the main body 10 of the chessboard device with auto - electronic scoring according to the present invention is attached with a plastic thin plate 100 by means of conventional ways such as gluing , fixing , thermo - adhering or cold adhering . light - transmittable components 20 are integrally formed with the plastic plate 100 . a display component 60 is disposed under the respective light - transmittable component 20 and surrounded with touch switch devices 30 at the bottom of the plastic thin plate 100 . when the touch devices 30 are pressed downward , an induction switch device 50 , which has an upper and lower conductive layers 51 , 52 , the upper conductive layer 51 bends downward at the pressed positions to press the lower conductive layer 52 via a partition 53 between the upper and lower conductive layer 51 such that the micro computer is capable of receiving the inductive signals to allow the display component 60 showing a desired display for standing for identifications of the users . the display component 60 can be conventional display such as lcd , back light lcd , led , liquid crystal screen or digital tube . referring to fig1 , the main body 10 of the chessboard device with auto - electronic scoring according the present invention is attached with a plastic thin plate 100 by means of conventional ways such as gluing , fixing , thermo - adhering or cold adhering . light - transmittable components 20 are integrally formed with the plastic plate 100 . a display component 60 is disposed under the respective light - transmittable component 20 and surrounded with touch switch devices 30 at the bottom of the plastic thin plate 100 . an induction switch device 50 is provided at the lower end of the respective touch switch devices 30 . when the induction switch device 50 is pressed downward to touch conductive layers 41 on a pcb 40 , electrical signals are transmitted to the micro computer to allow the display component 60 becoming working display component 600 . the display component 60 can be conventional display such as lcd , back light lcd , led , liquid crystal screen or digital tube . referring to fig2 , the main body 10 of the chessboard device with auto - electronic scoring according to the present invention is attached with a plastic thin plate 100 by means of conventional ways such as gluing , fixing , thermo - adhering or cold adhering . light - transmittable components 20 are integrally formed with the plastic plate 100 . a display component 60 is disposed under the respective light - transmittable component 20 and surrounded with touch switch devices 30 at the bottom of the plastic thin plate 100 . when the touch devices 30 are pressed downward , an induction switch device 50 , which is a conductive layer switch has an upper and lower conductive layers 51 , 52 , the upper conductive layer 51 bends downward at the pressed positions to press the lower conductive layer 52 via a partition 53 between the upper and lower conductive layer 51 such that inductive signals are generated and the micro computer is capable of receiving the inductive signals to allow the display component 60 becoming working display component 600 for standing for identifications of the users . referring to fig2 , the main body 10 of the chessboard device with auto - electronic scoring according to the present invention is attached with a plastic thin plate 100 by means of conventional ways such as gluing , fixing , thermo - adhering or cold adhering . light - transmittable components 20 are integrally formed with the plastic plate 100 . a display component 60 is disposed under the respective light - transmittable component 20 and surrounded with touch switch devices 30 at the bottom of the plastic thin plate 100 . when the touch devices 30 are pressed downward , an induction switch device 50 , which has an upper and lower conductive layers 51 , 52 , the upper conductive layer 51 bends downward at the pressed positions to press the lower conductive layer 52 via a partition 53 between the upper and lower conductive layer 51 such that the micro computer is capable of receiving the inductive signals to allow the display component 60 showing a desired display for standing for identifications of the players . the display component 60 is provided with a first light emitting chip 61 and a second light emitting chip 62 to allow at least two colors of lights being emitted from the display component 60 . similarly , light emitting chips with conventional material , quantity , structure and colors can be used instead . of course , the same display component 60 at least has one color light emitted to stand for identification of the player . the induction switch 55 can be used instead of the induction switch device 50 to generate needed display . the light - transmittable component 20 and the induction switch device 50 can be changed in shape , size , quantity or structure as desired . referring to fig2 , the main body 10 of the chessboard device with auto - electronic scoring according to the present invention is provided with an induction switch device 50 , which is a touch panel 500 and used as a switch for being touched and generating inductive signals , such that the micro computer is capable of receiving the inductive signals to allow the display component 60 showing a desired display for standing for identification of the player . the principle of technique for the touch panel is in that when a finger or any other medium contacts the screen , resistance , capacitance , voltage , current , sound wave , infrared or temperature can be detected based on different induction type such that coordinates of the touch point can be measured out accordingly . technique of the touch panel mostly is classified as resistance type ( film on glass ), capacitance type , supersonic type and optical ( infrared ) type . the resistance type touch panel is further classified as digital type and analog type . the analog type touch panel further can be divided into 4 - line type , 5 - line type , 6 - line type and 8 - line type . the touch panel 500 can be changed as desired in shape , size or structure . it is noted that the light - transmittable component 20 on top of the display component 60 can be designed with different figures , pictures and shapes at the surface thereof to comply with at least one light , at least one figure or at least one color provided by the display component 60 while becoming the working display component 600 . the display component 60 can be made of conventional display instead such as led , lcd , backlight lcd , liquid crystal screen , plasma screen , light tube , quartz tube , light bulb or the like . the electronic chessboard of the invention can provide different display components 60 , arrangements and induction switch devices 50 and a variety of playing ways available for the user . the shape , size and structure of the touch device 30 of the invention can be designed according to specific needs . various conventional induction switch devices 50 can be employed in the electronic chessboard of the invention . the conductive layer switch can be provided with a partition 53 between the upper conductive layer 51 and the lower conductive layer 52 or no partition is provided . the principle of induction applied by the induction switch device 50 and the shape , size or structure of the induction switch device 50 can be designed to comply with specific needs of the user . the shape , size or structure of the light - transmittable component 20 of the invention can be designed to accommodate to specific needs of the user . a light - transmittable component 20 can be disposed either on top of the display component 60 or not on top of the display component 60 . as the foregoing , it is appreciated that the chessboard device with auto - electronic scoring according to the present invention has the following advantages with regard to novelty and inventiveness : 1 . at least a light - transmittable component is provided on the chessboard with at least a display component being disposed at the back of the light - transmittable component and the display component is lighted up once a touch induction switch device is pressed such that the light from the display component penetrates the light - transmittable component and identification of the user can be distinguished at least a color of the light or the display component . in this way , the cpu of a computer is capable of generating different effects of the chessboard game during playing . 2 . the light - transmittable component can be slidably pressed such that electrical connection signal can be obtained once the light - transmittable component is pressed . 3 . the light - transmittable component is surrounded with at least a touch device . when the touch device is pressed to touch the induction switch device , the electrical connection signal is induced for the cpu capable of distinguishing the signal , generating voice , automatic scoring and showing winner and loser of the players . 4 . the display component can be associated with the touch device even if no light - transmittable component is provided such that the display is capable of emitting light with at least one color or at least one working display component and the user can be identified . in this way , the cpu is capable of determining and outputting different game effects of the chess playing . 5 . the structure and principle of the conventional induction switch device can be applied in the auto - electronic scoring chessboard of the present invention . 6 . the structures of light - transmittable component and the touch device can be designed and changed to meet specific needs . 7 . the surface of the light - transmittable component can be printed with various figures to meet needs of the game and to accommodate design changes . while the invention has been described with referencing to preferred embodiments thereof , it is to be understood that modifications or variations may be easily made without departing from the spirit of this invention , which is defined by the appended claims .

a chessboard device with auto - electronic scoring at least provides a display component to generate at least a light , a color and a figure once an induction switch device is pressed , touched or felt . the central processing unit of a microcomputer is capable of distinguish electronic signals produced by the induction switch device to calculate scores of the players and figure out the winner and the loser . at least a light - transmittable component is placed on top of the display component and each user can be identified by means of light points , quantity of the light , color of the light or figures on the surface of the light - transmittable component . hence , scores of players can be obtained automatically in company with provisions of lighting , voice , music , light emitting diode , liquid crystal display , backlight lcd , backlight board or liquid crystal screen . not only funs for the players can be enhanced but also fairness and justice of the chessboard game can be maintained completely .

a crust fracturing implement of the present invention is generally illustrated in fig1 at 10 . the crust fracturing implement 10 is towed by a tractor 12 or any other prime mover and fractures the crust on a field while significantly reducing if not eliminating debris from becoming entangled within discs 20 of a crust fracturing unit 18 . the crust fracturing implement 10 includes a plurality of crust fracturing units 18 that typically correspond to the number of rows of a planter that was used to plant the field . the crust fracturing implement 10 typically is a pull behind row cultivator 14 that is modified into the crust fracturing implement 10 of the present invention by removing the spring shanks ( not shown ) that support shovels ( not shown ) from each gang 15 . while modifying a pull behind row cultivator 14 is typical , the crust fracturing implement 10 of the present invention may be manufactured as a separate implement or by modifying other pieces of equipment . the shovels ( not shown ) are typically utilized to uproot and kill weeds that sprout up between the rows of the crops . however , the shovels tend to break up the crust into larger chunks which may uproot the young seedlings or cover the row of seedlings with additional soil which may also kill the young seedlings . further having the shovels tilling the soil would inhibit the ground speed at which the crust fracturing implement 10 operates effectively , typically in the range of between about 5 miles per hour and about 8 miles per hour . referring to fig2 and 3 , each crust fracturing unit 18 is typically mounted to a tool bar 16 where the tool bar 16 is mounted to a main frame 13 of the cultivator 14 . the tool bar 16 is typically secured substantially along a length of the cultivator 14 and typically supports cutting discs ( not shown ) that penetrate the soil proximate the rows and move the soil away from the rows and thereby uprooting weeds without harming the rows of crops . with the cutting discs removed from the tool bar 16 , a substantially vertical shank 22 of a support 23 is secured within a bore in a mounting bracket 24 that previously supported the cutting discs ( not shown ). a typical shank 22 is a solid member having a rectangular cross - section approximately ¾ ″ by 3 ″ that is positioned within the bore in the mounting bracket 24 . the shank 22 is secured in a selected position with a set screw 26 that threadably engages a threaded bore in the mounting bracket 24 to frictionally secure the shank 22 in the selected position . while a ¾ ″ by 3 ″ rectangular shank 22 is typical , any configured shank that mounts to any mounting bracket is within the scope of the present invention . the support 23 includes left and right substantially horizontal members 33 , 35 that are pivotally secured to the shank 22 with a bolt 31 positioned through aligned apertures in each of the left and right supports 33 , 35 and an aperture located proximate a distal end of the shank 22 . left and right inside arms 27 , 28 are welded to distal ends of the members 33 , 35 , respectively . the arms 27 , 28 have a similar configuration including an arcuate portion 32 proximate a distal end 34 . left and right outside arms 26 , 29 are aligned with the left and right inside arms 27 , 28 and are secured in selected positions with a plate 31 . the plate 31 is fixedly attached proximate the seam created by the left and right supports 33 , 35 and the left and right inside arms 27 , 28 , respectively . proximal ends of the left and right outside arms 26 , 29 are fixedly attached to the plate 31 . referring to fig4 , the left and right outside arms 26 , 29 are similarly constructed and have the same arcuate configuration as the left and right inside arms 27 , 28 . the outside arms 26 , 29 include apertures 33 that accept bearings ( not shown ). the left and right arms 27 , 28 also include apertures that align with the apertures 33 in the left and right outside arms 26 , 29 . each arm 26 , 27 , 28 , 29 includes a back portion that extends toward the perimeter of the discs 20 . an arcuate surface 37 of the back portion 35 engages debris that is carried by the discs 20 and discharges the debris from the crust fracturing unit 18 . as the discs 20 rotate , the angle created between the arcuate surface 37 and teeth 42 spaced around the disc 20 is typically between about 80 ° and about 130 °. the relatively large angle between the arcuate surface 37 and the teeth 42 causes any debris to be discharged from the unit 18 such that the discs 20 freely rotate therein , unlike a typical rotary hoe which creates a relatively small angle between the teeth of the disc and the support which tends to bind the discs of a typical rotary hoe . referring to fig5 , the discs 20 are positioned between the arms 26 , 27 , 28 , 29 in an alternating fashion and are retained between the arms 26 , 27 , 28 , 29 with an axle 38 positioned through the bearings ( not shown ). preferably the axle 38 has a substantially hexagonal cross - sectioned mid portion 39 that engages a substantially hexagon - shaped aperture 40 substantially centrally located on each disc 20 . the engagement of the flat surfaces on the axle 38 with the flat surfaces of the aperture 40 prevent the disc from rotating about the axle 38 . while a hexagon shaped aperture 40 and axle 38 are typical , any mechanism that prevents the discs 20 from rotating on the axle 38 is within the scope of the present invention including any polygonal configuration , at least one non - arcuate surface on the shaft 38 and the aperture 40 and a weld . the axle 38 is retained within the bearing ( not shown ) with a threaded engagement of nuts with threaded ends 37 of the axle 38 as best illustrated in fig2 and 3 . however , other retaining mechanisms are within the scope of the present invention including a cotter pin , a roller pin , a spring loaded pin within a collar , and a bolt with a locking nut and washers . typically each unit 18 includes five discs 20 that are separated by the four arms 26 , 27 , 28 , 29 . however it is within the scope of the present invention for a unit to include two or more discs and at least one arm . each disc 20 typically has sixteen substantially evenly spaced teeth 42 positioned about a perimeter of the disc 20 . while a disc with sixteen substantially evenly spaced teeth 42 is typical a disc with more or less than sixteen teeth are within the scope of the present invention . a disc 20 with teeth having a non - uniform length are also within the scope of the present invention . each tooth includes a convex surface 44 and a concave surface 46 that converge at a distal end 48 . preferably the distal end 48 includes a flat or angular surface 50 that penetrates the crust substantially in a chiseling manner as the disc 20 is rotated . a typical angle of the surface includes an angle of about 15 °. however a pointed distal end 48 or other configured distal ends are within the scope of the present invention . the discs 20 are typically positioned on the shaft 38 such that only one tooth 42 penetrates the crust at one time . staggering the position of the teeth relative to each other aids in penetrating and fracturing the crust . while only one tooth typically penetrates the crust at a time , it should be understood that more than one tooth 42 will be in the soil at any time . the discs 20 and the axle 38 rotate in the direction of arrow 52 , as illustrated in fig2 , such that the angular surface 50 and the convex surface 44 fracture the crust . fracturing the crust with the convex surface 44 forces any crop debris or residue , rocks , sticks or other obstacle into the ground such that as the tooth exits the ground the debris tends to remain in the ground thereby leaving the discs to freely rotate . the combination of the angular surface 50 and the convex surface 44 engaging and penetrating the crust along with the positioning of the arms 26 , 27 , 28 , 29 between the discs 20 prevents debris from becoming entangled with the discs 20 such that a field can be fractured without unnecessary interruption . because the convex surfaces 44 of the teeth 42 engage the crust , each unit 18 must provide a sufficient amount of force for the teeth 42 to penetrate the crust . a typical unit 18 with five discs 20 and four arms 26 , 27 , 28 , 29 weighs about fifty pounds which in most instances will provide enough force for the angular surface 50 and the convex surface 44 to penetrate the crust . if additional force is necessary , a coil spring 60 is positioned about the bolt 31 on each end where a proximal end 62 of the coil spring engages the shank 22 and a distal end 64 engages the plate . the coil spring 60 applies a downward force typically in the range of five to ten pounds on the discs 20 and aids the teeth 42 in penetrating the crust . however , a coil spring is not necessary to practice the present invention . the coil spring 60 also provides the additional benefit of retaining the teeth 42 in the ground when the unit 18 contacts an obstacle . without the coil spring 60 , the unit 18 would have a tendency of raising when encountering a larger rock or clump of soil which would result in the teeth 42 disengaging the crust . although the present invention has been described with reference to preferred embodiments , workers skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention .

an apparatus for fracturing a crust on an agricultural field includes a tool bar and a support attached to the tool bar . a plurality of discs are non - rotatably attached to an axle that is rotatably supported by the support . each of the plurality of discs include a plurality of spaced apart teeth about the perimeter of each disc . the teeth comprise convex surfaces and concave surfaces that converge at distal ends where the plurality of discs rotate about the support such that the convex surfaces penetrate and fracture the crust and that any debris or trash picked up by the teeth is ejected by the angles of the teeth and angles of the support brackets preventing plugging and destruction of the rowed crop .

this document generally describes techniques for extracting solid - phase material from a fluid sample for purposes of testing the extracted material as an analyte . such testing can take a variety of familiar forms , and particularly can involve testing for levels of methadone or amphetamine in a patient . the techniques described here focus on the manufacture and use of porous tablets and similar forms made of a molecularly imprinted polymer , carbon material , silica , or sol - gel , and restricted access material ( ram ). the developed tablets include voids that match the form of the particular solid analyte that is sought to be captured , by forming the tablet around a sample of such analyte , and then vacating the production - time analyte from the tablet so as to make room for analyte from a testing sample to enter it . fig1 a shows a plurality of extraction tablets in a sample dish , e . g ., a petri dish or other liquid - resistant dish that can hold the sample without contamination . the tablets are porous in form and on the order of a cm in diameter and less than a cm thick ( e . g ., less than 0 . 5 cm thick ). they may be constructed from molecularly - imprinted polymers , carbon material , silica , sol - gel , and restricted access material ( ram ). the porosity and internal cavity sizes may be adjusted to be appropriate to desired adsorption capacity and the material to be absorbed — i . e ., the internal passages may be sized to accept the solid phase material from outside the tablet and to them hold the material from easily escaping . such adjustment may be achieved , for example , by forming the form of the tablet around a matrix made up of the analyte that is desired to be tested by the particular tablet . in other words , a first tablet may be indicated as a methadone tablet , while another could be indicated as an amphetamine tablet . a tablet may also have multiple zones , where each zone is formed to absorb a particular analyte , such as a tablet whose left half absorbs methadone as an analyte and whose right side absorbs amphetamine . the solid phase material may then be desorbed by a solvent such as methanol , which may in turn be injected into lc - ms . the material may also be removed by heating the tablet directly into gc - ms . and the tablet may be used for maldi mass spectrometry . where the tablet has multiple different zones , it may be cut into pieces at or near the transition area ( and a small zone on each side of the transition may be discarded ), with each side being subjected to testing independently . where the analytes are known to not interfere with each other as part of the analysis process , they can both or all be left in the tablet and processed together . fig1 b shows a single extraction tablet in a small liquid sample . here , the sample is held in a small ampoule so as to make complete immersion of the tablet easier to perform . in other implementations , a caplet - shaped tablet may better fit within the ampoule . in various examples , the sample volume may be relatively small , such as in a range from 100 to 200 micro - liters , suitable for biological fluids from humans and smaller animals such as mice . as noted , the tablet may also be placed in a subject &# 39 ; s mouth for an appropriate period where the sample is to be in the form of saliva . the analyte may also be enriched after it is captured , by using , for example , a sample size greater than 200 micro - liters , and then desorbing the analyte into a smaller volume of solvent ( e . g ., less than 100 micro - liter ). although a short cylinder tablet is shown in the images , other shapes and sizes of tablet or other forms may be employed in appropriate circumstances . for example , a tubular form ( perhaps with rounded ends ), such as in the form of a caplet , may be used to provide additional surface area in a form factor that can still be placed easily longitudinally in an ampoule or held in a patient &# 39 ; s mouth , and also be seen as a familiar shape by a patient for oral insertion . fig1 c shows the tablet formation process in terms of its chemistry , and is representative of the process discussed in more detail next with respect to fig2 . fig2 is a flow chart of a process for extracting and testing solid - phase material . in general , the process involves sonicating a relevant solution with a catalyst to form a tablet , and then immersing a prepared tablet in a molecularly imprinted polymer ( mip ) sol - gel solution , followed by dessication and poly - condensation at elevated temperature to set the tablet , followed by methanol washing to remove the analyte matrix and make the tablet ready for use . the process may be carried out using an initial liquid material ( liquid polymer or sol - gel ) such as polyethelene in tablet form as a backbone and a polymer surrounding the polyethylene . the process may also use a powdered starting material such as graphitic , silica , or mip . a thin film may be applied to the tablet , in particular , for use with gathering saliva samples . the process begins at step 202 , where a solution is prepared that contains a mixture of 0 . 1 mmol / l template molecule ( an analyte of interest ) and 3 -( propylmethacrylate ) trimethoxysilane ( used as precursor ) in acetonitrile as solvent ( 400 μl ). the analyte of interest may take any of a variety of desired forms , and in the examples discussed here may be methadone or amphetamine . at box 204 , that solution is then sonicated for approximately 30 min . that process agitates the components of the solution and causes them to be evenly dispersed in a relevant pattern within the solution . in this manner , the matrix is evenly dispersed , and the in - polymer pattern that will be created by the matrix will also be evenly dispersed , so as to maximize the performance of the formed tablet . at box 206 , 400 μl of trifluoroacetic acid ( tfa ) is added to the mixture to act as a catalyst . the tfa causes a reaction to occur among the other components of the mixture so that they begin to solidify into the final form for the tablet , around the matrix . other appropriate solidifying catalysts may also be used , depending on the type of polymer that us used to form the tablet . at box 208 , the resulting mixture is sonicated for approximately 2 min . such action causes the catalyst to be spread more evenly among the mixture as it works and to catalyze the mixture more evenly throughout the mixture , so that full chemical reaction is performed in the material . at box 210 , approximately 100 μl of milli - q water ( emd millipore corporation , billerica , mass .) or other ultra - pure type 1 water is added . the solution is then kept at room temperature for approximately 30 minutes . during this time , the polymer may better set into its final form . at box 212 , to prepare an imprinted sol - gel layer on both sides of the polyethylene as a tablet form , the material is immersed in the mip sol - gel solution for 10 min at room temperature , and then placed in a desiccator for 10 min . the step may be repeated , such as two times . the form in this example is 6 × 1 . 2 mm , though larger dimensions can be used , consistent with a level of solids that need to be captured for whatever relevant investigation is to be performed using the tablet . the mip - tablet so formed may then be stored in a desiccator for 24 hours or other appropriate time to sufficiently dessicate the material ( box 214 ). at box 216 , for poly - condensation , the mip - tablet is subjected to a temperature gradient started at 50 for one minute and increased to 130 ° c . and then kept at 130 ° c . 6 hours . such action finalizes the polymer form for the tablet . and at box 218 , to remove the trapped template and create a porous selective surface , the mip - tablet is washed with methanol or other appropriate chemical for removing the template , for 2 hours and with 0 . 2 % formic acid in water for 30 min . the mip - tablet in this example is then ready to use , though it may be conditioned with methanol and water before using for plasma or urine matrices . for such use then , the tablet may be partially or fully submerged in a sample of plasma , urine , saliva , or other appropriate fluid sample . it may be left there for an appropriate period to permit intrusion of the relevant solid - phase component from the sample . the tablet may also be moved or the sample may be stirred or agitated to increase the speed with which the analyte moves into the tablet . the tablet may then be removed from the sample , or the sample removed from around the tablet , and the tablet may be washed in an appropriate chemical to cause the solid - phase material to exit from the tablet . such material may then be tested by an appropriate instrument such as a chromatograph , in known manners . where the sample is saliva , a tablet may be inserted into a test subject &# 39 ; s mouth and held there for an appropriate period of time , thereby eliminating other steps from the process of gathering the saliva and isolating solid - form materials from it . for powdered materials used in such a process ( e . g ., silica , carbon , or polymer ), the materials may be compressed together and added in stainless steel thick tubing with an internal diameter of 5 - 10 mm , with a tablet prepared under high pressure ( ton / in2 ). other formation techniques may , in appropriate circumstances , also be used , including extrusion followed by chopping of the extruded column at tablet thickness locations , insertion into tablet - shaped molds , and other appropriate polymer or similar techniques , where the relevant analyte may be included in the material before it hardens into final form so as to create a mold around which the material is formed , and may then be removed by appropriate action such as subjecting the combination to a solvent that is effective on the analyte but not on the tablet itself . fig3 shows a chromatogram for methadone in a plasma sample and blank plasma extracted by a tablet like that shown in fig1 a and 1b . generally , the data shows validation for determining methadone in plasma and amphetamine in urine . the methadone concentration in the plasma sample was 5 ng / ml , and the data in the figure shows good selectivity for the extraction of methadone from plasma using the tablets described above and below . the graphs show mrm transitions obtained from the analysis of methadone at lloq with internal standard ( a ) and blank plasma sample ( b ). fig4 is a table that compares lod , lloq extraction time and accuracy for different solid - phase extraction techniques . in general , the comparison sets the mip - tablet described herein with published results for spme and sbse techniques . the data shown here indicates that the mip - tablet technique considerably reduced the extraction time compared to spme ( decreased by three - fold ) and sbse ( decreased by nine - fold ). in addition , the sample volume for performing the operations was reduced by 5 times and 25 times as compared to using spme and sbse respectively . the sample sizes for the different methods varies because it is largely dictated by the selected method . for example , sbse requires relatively large sample volumes compares to spe and the tablet method discussed here . as a result , the latter methods can be used for smaller sample volumes such as 100 - 200 micro - liters and for large sample volumes , such as 1 ml , while spme and sbse may require volumes of about 1 - 5 ml . the linear range in the table indicates the concentration levels at which a particular method can be used accurately . a higher linear range indicates that a method is suitable for lower and higher concentration levels of an analyte of interest in a sample . the extraction time for the subject tablet method is faster than the other methods because a thing film of polymer results in faster analyte diffusion into and out of the tablet than with other methods , and faster equilibrium times . precision in this example is measured as rsd % of quality control samples . quality control samples ( qsc ) are used at three concentration levels as recommended by relevant fda guidelines . in spme data shown here , one concentration level was used . while this specification contains many specific implementation details , these should not be construed as limitations on the scope of any inventions or of what may be claimed , but rather as descriptions of features specific to particular implementations of particular inventions . certain features that are described in this specification in the context of separate implementations can also be implemented in combination in a single implementation . conversely , various features that are described in the context of a single implementation can also be implemented in multiple implementations separately or in any suitable subcombination . moreover , although features may be described above as acting in certain combinations and even initially claimed as such , one or more features from a claimed combination can in some cases be excised from the combination , and the claimed combination may be directed to a subcombination or variation of a subcombination . similarly , while operations are depicted in the drawings in a particular order , this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order , or that all illustrated operations be performed , to achieve desirable results . in certain circumstances , multitasking and parallel processing may be advantageous . moreover , the separation of various system components in the implementations described above should not be understood as requiring such separation in all implementations , and it should be understood that the described program components and systems can generally be integrated together in a single software product or packaged into multiple software products . thus , particular implementations of the subject matter have been described . other implementations are within the scope of the following claims . in some cases , the actions recited in the claims can be performed in a different order and still achieve desirable results . in addition , the processes depicted in the accompanying figures do not necessarily require the particular order shown , or sequential order , to achieve desirable results . in certain implementations , multitasking and parallel processing may be advantageous .

a method of producing a biologic liquid sampling tablet is disclosed and includes molecularly imprinting a polymer over a matrix of an analyte of interest for biological testing ; and removing the matrix from the imprinted polymer to form a porous tablet . the tablet is sized to be inserted in an ampoule or human oral cavity .

fig1 shows the outside of a heart 1 with epicardial coronary arteries 2 visible . in the event of a coronary artery blockage , for example at area 3 in fig1 , blood flow is restricted or cut off to downstream tissue , for example affected tissue area 4 , i . e ., ischemic myocardium 4 , in fig1 . reperfusion can be achieved by various methods known in the art , such as thrombolytic therapy , percutaneous coronary intervention ( pci ) such as angioplasty , stenting , and / or ablation , and bypass surgery . when reperfusion occurs , blood flow is restored to the ischemic myocardium 4 . fig2 shows a magnetic particle 20 in accordance with an embodiment of the invention to help prevent and / or treat reperfusion injury when blood flow is restored to the ischemic tissue . the magnetic particle in this embodiment is a nanoparticle having a ferromagnetic core 22 and a coating 24 in which a therapeutic agent 26 is contained . the therapeutic agent 26 can be one or more drugs that , when released at the site of the ischemic tissue to which blood flow is restored , will help prevent and / or treat reperfusion injury . magnetic particles with therapeutic agent such as that shown in fig2 can be used in conjunction with one or more magnetic devices such as those fig1 and fig6 ( described below ) for attracting the magnetic particles to the ischemic tissue . fig1 shows a magnetic device 10 that includes an elongated member 12 and a series of magnetic elements 14 . in accordance with certain embodiments of the invention , a technique is provided in which particles that are magnetic and that contain therapeutic agent , such as the magnetic particles 20 , are delivered and drawn by magnetism to a specific target area . for example , nanoparticles 20 are released into the artery 5 during angioplasty of the obstructed area 3 . this may be accomplished , for example , through a perfusion lumen of an angioplasty catheter , by a separate infusion catheter , or by any other suitable mechanism . the infusion of the magnetic particles can be done simultaneously with the angioplasty procedure or nearly simultaneously with the angioplasty procedure . in accordance with this example procedure , the magnetic device 10 is placed as shown in fig1 , with the magnetic elements 14 positioned epicardially as shown in fig1 . because the nanoparticles 20 have magnetic cores 22 , they are attracted by the magnetic elements 14 to the area of the ischemic myocardium 4 which is prone to reperfusion injury . in this way , the therapeutic agent 26 is delivered in a targeted way to the affected area . the magnetic device generally keeps the magnetic particles in the target area , preventing them from diffusing away from the target tissue through the vasculature . in this way , the therapeutic agent is mostly released into the affected or infarct region , where it prevents or treats reperfusion injury . the particles that are used in accordance with the invention can be sized in a manner to facilitate infusion into the affected tissue . the particles can diffuse through the vessel wall and into the tissue and can be taken up into the tissue easily . in certain embodiments , the particles are on a nanometer scale , for example around 200 nm or less for cardiac applications . other sizes are possible , including , for example , particles on a micrometer scale , for example around 50 μm . the magnetic device may be any suitable magnetic mechanism for attracting the magnetic particles to the desired location . for example , the magnets on the end of the catheter magnetic elements may be made of any suitable magnetic material , for example very strong magnets such as rare earth magnets like neodymium - iron - boron . the magnets can also electromagnets . the magnetic elements can be , for example , strands that are magnetized on their ends and / or wires capable of carrying a current for electromagnets on the ends of the strands . alternatively , the magnetic device may have a single magnetic element . other embodiments are of course possible . in certain embodiments , the magnetic field generated by the magnetic device can be alternated in order to agitate the magnetic particles and encourage permeation into the tissue . the alternation can be achieved by changing the current in an electromagnet or by moving permanent magnets back and forth . the magnetic material of the magnetic particles can be any suitable magnetic material capable of being attracted by the magnetic device such that the magnetic particles are drawn to the target area . for example , suitable materials include those strongly attracted by a magnetic field , i . e . ferromagnets : iron , nickel , cobalt , nickel - iron , nickel - zinc - iron , feo ( magnetite ), and rare earth magnet alloys like neodymium - iron - boron . the therapeutic agent in the magnetic particles can be any of a number of therapeutic agents suitable for preventing and / or treating ( e . g ., alleviating ) reperfusion injury . the therapeutic agents may include , for example , anti - inflammatory agents , free radical scavengers , and / or vasodilators , as are known in the art . in the embodiment of fig2 , the magnetic particle has a ferromagnetic core and a coating with a therapeutic agent . the coating may be , for example , a polymer coating in which the therapeutic agent is carried . upon delivery , the therapeutic agent can elute from the polymer coating into the target tissue . the polymer in certain embodiments can be a biodegradable polymer . fig3 shows a magnetic particle in accordance with another embodiment of the invention . the magnetic particle in this embodiment is a nanoparticle 30 having a core 32 in which a therapeutic agent is contained . the core 32 may be , for example , a liquid or solid core . outside of the core 32 , the nanoparticle 30 has a coating 34 formed of or containing a magnetic material . the coating 34 may be , for example , porous , to allow therapeutic agent to diffuse from the core 32 through the coating 34 to the affected tissue at the target area . the magnetic particles may be formed in any of a number of suitable ways . for example , magnetic particles having a magnetic core and outer coating can be formed by dip coating magnetic particles in a mixture of polymer , therapeutic agent and solvent . when the solvent evaporates or is driven off , the magnetic particle is left with a polymer coating containing the therapeutic agent . as another example , magnetic particles can be spray coated with a mixture of polymer , therapeutic agent and solvent , after which the solvent evaporates or is driven off . magnetic particles having a porous magnetic coating and inner core can be made by coating a removable material , such as a meltable material , with a porous magnetic coating , and then removing the removable material , e . g ., by melting it and allowing it to diffuse through the porous outer coating . then , the porous outer coating can be filled with the therapeutic agent by dipping or by any other suitable method . in order to facilitate the loading of the therapeutic agent into the porous shells , the porous shells may be loaded into a vacuum chamber which evacuates the internal volume . then the chamber is flushed with the therapeutic agent and the pressure is elevated to force the therapeutic agent through the pores and into the magnetic particle . as another example , a solid core containing therapeutic agent can be coated with a porous magnetic shell by nanoparticle bombardment . equipment for such a technique can obtained from or adapted from that obtained from mantis deposition ltd . as an alternative to the magnetic particles shown in fig2 and 3 , and particle may be formed in which there is no distinct core but rather a continuous porous magnetic material loaded with therapeutic agent . an example of such a particle is shown in fig4 . fig4 shows a magnetic particle 40 comprising a porous magnetic material 42 in which therapeutic agent 44 is loaded in the pores . such particles can be made by first forming the porous particles and then loading them with therapeutic agent as described above . for example , the porous particles can be filled with therapeutic agent by dipping or by any other suitable method . the porous particles may be loaded into a vacuum chamber which evacuates the pores , and then the chamber can be flushed with the therapeutic agent and the pressure elevated to force the therapeutic agent through the pores and into the magnetic particle . as another alternative magnetic particle , a particle may be formed with a matrix in which magnetic material is carried as particles and in which therapeutic agent is also carried . an example of such a particle is shown in fig5 . fig5 shows a magnetic particle 50 comprising a matrix 52 , such as a polymer matrix , carrying magnetic material 54 as particles as illustrated . therapeutic agent 56 is also carried in the matrix . such particles 50 can be made in various ways . for example , the polymer can be dissolved in a solvent and then the magnetic material and therapeutic agent can be mixed in with the polymer . then the mixture is formed into particles and the solvent is evaporated or driven off , leaving particles like that shown in fig5 . it will be appreciated that the magnetic particles of fig2 - 5 , or other alternative embodiments , have magnetic properties and carry therapeutic agent . as such , they are capable of being attracted to a target site by a magnetic device and thereby delivering therapeutic agent to the target site . fig6 shows an alternative structure and placement for a magnetic device in accordance with another embodiment of the invention . fig6 shows the inside of a heart 1 with a magnetic device 60 delivered endocardially , i . e ., through the heart . the magnetic device 60 may be delivered to the heart through delivery procedures known in the art . similar to magnetic device 10 , the magnetic device 60 includes an elongated member 62 and a series of magnetic elements 64 . in accordance with an example procedure corresponding to the illustration of fig6 , the magnetic device 60 is extended into the desired heart chamber with the magnetic elements 64 placed adjacent the target area 4 . similar to the embodiment of fig1 , the magnetic particles 70 delivered through the vasculature are attracted by the magnetic elements 64 to the area of the ischemic tissue 4 which is prone to reperfusion injury . in this way , similar to that described above , the therapeutic agent is delivered in a targeted way to the affected area . in a procedure like that of fig6 , the magnetic particles 70 are drawn to the inside layers of the myocardium wall 6 , which can often be the area most vulnerable to reperfusion injury . it will be appreciated that the procedures as described in conjunction with fig1 and 6 can be performed with variations of the magnetic device for attracting the magnetic particles to the target area . similarly , such procedures can be performed with magnetic particles as shown in fig2 - 5 , or other alternative embodiments , with the magnetic particles carrying therapeutic agent and having magnetic material such that they are attracted to the target area by the magnetic device . in embodiments such as those described above , the therapy is localized by drawing the magnetic particles containing the therapeutic agent to the desired area . a high concentration of therapeutic agent can thus be targeted to the required site , and high systemic levels of the particles and therapeutic agent can be avoided . while certain embodiments described above are described in the context of heart tissue , magnetic particles as described herein may also be used to target ischemic tissue elsewhere , for example in the brain . in general , similar procedures can be used to deliver the magnetic particles and to attract the magnetic particles to the target site . for use in the brain , the magnetic particles may be sized differently ; for example , they may be 100 nm or less to facilitate infusion into the target tissue . in addition to heart and brain tissue as described above , other target locations are possible . for example , the therapeutic agent may be useful for treating a tumor , e . g ., for chemotherapy . magnetic particles with such therapeutic agent may be provided as described above . a magnetic device as described above may be used for attracting the magnetic particles to the tumor . this system and method may be particularly useful for hard to reach tumors . as another example , the therapeutic agent may be useful for localized neuroprotection . magnetic particles with such therapeutic agent may be provided as described above . a magnetic device as described above may be used for attracting the magnetic particles to neural cells for neuroprotection , such as to retinal ganglion cells for the prevention of glaucoma progression . possible therapeutic agents for this purpose may include memantine or another suitable therapeutic agent . the therapeutic agent used in the present invention may be any pharmaceutically - acceptable agent , particularly those useful in the treatments described above , such as for preventing and / or treating reperfusion injury as discussed above . other therapeutic agents may also be delivered using magnetic particles as described herein . example drugs include anti - proliferative agents or anti - restenosis agents such as paclitaxel , sirolimus ( rapamycin ), tacrolimus , biolimus , everolimus , and zotarolimus . exemplary non - genetic therapeutic agents include anti - thrombogenic agents such heparin , heparin derivatives , prostaglandin ( including micellar prostaglandin e1 ), urokinase , and ppack ( dextrophenylalanine proline arginine chloromethylketone ); anti - proliferative agents such as enoxaparin , angiopeptin , sirolimus ( rapamycin ), tacrolimus , everolimus , zotarolimus , monoclonal antibodies capable of blocking smooth muscle cell proliferation , hirudin , and acetylsalicylic acid ; anti - inflammatory agents such as dexamethasone , rosiglitazone , prednisolone , corticosterone , budesonide , estrogen , estrodiol , sulfasalazine , acetylsalicylic acid , mycophenolic acid , and mesalamine ; anti - neoplastic / anti - proliferative / anti - mitotic agents such as paclitaxel , epothilone , cladribine , 5 - fluorouracil , methotrexate , doxorubicin , daunorubicin , cyclosporine , cisplatin , vinblastine , vincristine , epothilones , endostatin , trapidil , halofuginone , and angiostatin ; anti - cancer agents such as antisense inhibitors of c - myc oncogene ; anti - microbial agents such as triclosan , cephalosporins , aminoglycosides , nitrofurantoin , silver ions , compounds , or salts ; biofilm synthesis inhibitors such as non - steroidal anti - inflammatory agents and chelating agents such as ethylenediaminetetraacetic acid , o , o ′- bis ( 2 - aminoethyl ) ethyleneglycol - n , n , n ′, n ′- tetraacetic acid and mixtures thereof ; antibiotics such as gentamycin , rifampin , minocyclin , and ciprofloxacin ; antibodies including chimeric antibodies and antibody fragments ; anesthetic agents such as lidocaine , bupivacaine , and ropivacaine ; nitric oxide ; nitric oxide ( no ) donors such as linsidomine , molsidomine , l - arginine , no - carbohydrate adducts , polymeric or oligomeric no adducts ; anti - coagulants such as d - phe - pro - arg chloromethyl ketone , an rgd peptide - containing compound , heparin , antithrombin compounds , platelet receptor antagonists , anti - thrombin antibodies , anti - platelet receptor antibodies , enoxaparin , hirudin , warfarin sodium , dicumarol , aspirin , prostaglandin inhibitors , platelet aggregation inhibitors such as cilostazol and tick antiplatelet factors ; vascular cell growth promotors such as growth factors , transcriptional activators , and translational promotors ; vascular cell growth inhibitors such as growth factor inhibitors , growth factor receptor antagonists , transcriptional repressors , translational repressors , replication inhibitors , inhibitory antibodies , antibodies directed against growth factors , bifunctional molecules consisting of a growth factor and a cytotoxin , bifunctional molecules consisting of an antibody and a cytotoxin ; cholesterol - lowering agents ; vasodilating agents ; agents which interfere with endogenous vascoactive mechanisms ; inhibitors of heat shock proteins such as geldanamycin ; angiotensin converting enzyme ( ace ) inhibitors ; beta - blockers ; βar kinase ( βark ) inhibitors ; phospholamban inhibitors ; protein - bound particle drugs such as abraxane ™; structural protein ( e . g ., collagen ) cross - link breakers such as alagebrium ( alt - 711 ); any combinations and prodrugs of the above . exemplary biomolecules include peptides , polypeptides and proteins ; oligonucleotides ; nucleic acids such as double or single stranded dna ( including naked and cdna ), rna , antisense nucleic acids such as antisense dna and rna , small interfering rna ( sirna ), and ribozymes ; genes ; carbohydrates ; angiogenic factors including growth factors ; cell cycle inhibitors ; and anti - restenosis agents . nucleic acids may be incorporated into delivery systems such as , for example , vectors ( including viral vectors ), plasmids or liposomes . non - limiting examples of proteins include serca - 2 protein , monocyte chemoattractant proteins ( mcp - 1 ) and bone morphogenic proteins (“ bmp &# 39 ; s ”), such as , for example , bmp - 2 , bmp - 3 , bmp - 4 , bmp - 5 , bmp - 6 ( vgr - 1 ), bmp - 7 ( op - 1 ), bmp - 8 , bmp - 9 , bmp - 10 , bmp - 11 , bmp - 12 , bmp - 13 , bmp - 14 , bmp - 15 . preferred bmp &# 39 ; s are any of bmp - 2 , bmp - 3 , bmp - 4 , bmp - 5 , bmp - 6 , and bmp - 7 . these bmps can be provided as homodimers , heterodimers , or combinations thereof , alone or together with other molecules . alternatively , or in addition , molecules capable of inducing an upstream or downstream effect of a bmp can be provided . such molecules include any of the “ hedghog ” proteins , or the dna &# 39 ; s encoding them . non - limiting examples of genes include survival genes that protect against cell death , such as anti - apoptotic bcl - 2 family factors and akt kinase ; serca 2 gene ; and combinations thereof . non - limiting examples of angiogenic factors include acidic and basic fibroblast growth factors , vascular endothelial growth factor , epidermal growth factor , transforming growth factors α and β , platelet - derived endothelial growth factor , platelet - derived growth factor , tumor necrosis factor α , hepatocyte growth factor , and insulin - like growth factor . a non - limiting example of a cell cycle inhibitor is a cathespin d ( cd ) inhibitor . non - limiting examples of anti - restenosis agents include p15 , p16 , p18 , p19 , p21 , p27 , p53 , p57 , rb , nfkb and e2f decoys , thymidine kinase and combinations thereof and other agents useful for interfering with cell proliferation . exemplary small molecules include hormones , nucleotides , amino acids , sugars , and lipids and compounds have a molecular weight of less than 100 kd . exemplary cells include stem cells , progenitor cells , endothelial cells , adult cardiomyocytes , and smooth muscle cells . cells can be of human origin ( autologous or allogenic ) or from an animal source ( xenogenic ), or genetically engineered . non - limiting examples of cells include side population ( sp ) cells , lineage negative ( lin − ) cells including lin − cd34 − , lin − cd34 + , lin − ckit + , mesenchymal stem cells including mesenchymal stem cells with 5 - aza , cord blood cells , cardiac or other tissue derived stem cells , whole bone marrow , bone marrow mononuclear cells , endothelial progenitor cells , skeletal myoblasts or satellite cells , muscle derived cells , go cells , endothelial cells , adult cardiomyocytes , fibroblasts , smooth muscle cells , adult cardiac fibroblasts + 5 - aza , genetically modified cells , tissue engineered grafts , myod scar fibroblasts , pacing cells , embryonic stem cell clones , embryonic stem cells , fetal or neonatal cells , immunologically masked cells , and teratoma derived cells . any of the therapeutic agents may be combined to the extent such combination is biologically compatible . the foregoing description and examples have been set forth merely to illustrate the invention and are not intended to be limiting . each of the disclosed aspects and embodiments of the present invention may be considered individually or in combination with other aspects , embodiments , and variations of the invention . modifications of the disclosed embodiments incorporating the spirit and substance of the invention may occur to persons skilled in the art and such modifications are within the scope of the present invention .

a system for delivering therapeutic agent to a target location in a body in accordance with one embodiment is provided comprising a plurality of magnetic particles , each magnetic particle carrying a therapeutic agent , and a magnetic device for attracting the magnetic particles to a target location . the magnetic particles may be delivered by a catheter into a blood vessel upstream from the target location so that they travel toward the target location . a method for delivering therapeutic agent to a target location in a body in accordance with another embodiment comprises providing a plurality of magnetic particles , each magnetic particle carrying a therapeutic agent , placing a magnetic device in a position to attract the magnetic particles to a target location , and allowing the magnetic particles to infuse the target location by the attraction of the magnetic particles to the magnetic device . the therapeutic agent may comprises a therapeutic agent for preventing or treating reperfusion injury , and the step of providing the plurality of magnetic particles may comprise delivering the plurality of magnetic particles through a blood vessel .

as it appears from fig1 - 3 , the lower part of the apparatus shown therein comprises a subframe 1 having four legs 2 . by means of springs 3 , 4 an inner frame 5 is suspended in the subframe 1 . at the left hand end thereof , the inner frame 5 supports different screens 6 , 7 for screening bulbs in accordance with their sizes . the portion of the inner frame 5 shown at the right hand end of fig1 carries a support formed as a grid which as a whole is provided with the reference numeral 8 . the grid consists of grid rods 9 arranged pair by pair and having triangular cross section areas with the corners of the triangles facing upwardly . on the drawing , only two such pairs of grid rods are shown but it will be understood that further pairs of grid rods are arranged along each side of the pairs shown . however , for the sake of clarity such further pairs of grid rods have been omitted from the drawing . to the sub - frame 1 inwardly extending abutments 10 are secured , the lower surface of which are covered with felt pieces 11 for cooperation with the top surface of the inner - frame 5 . the frame 5 , which carries the screens 6 , 7 and the grid 8 is at the lower surface thereof is provided with two u - formed brackets 12 , 13 , having lower transversally extending beams 14 , fig3 . beams 14 cooperate with two inclined guiding plates 15 , 16 , fig2 . between the two legs 2 at the right hand end of the apparatus in fig2 a motor 18 is secured which via a gear train drives an excentric 19 , the form of which appears clearly from fig3 . the excentric is driven by the motor 18 in the direction of rotation indicated by the arrow 20 , fig3 and cooperates with the outer race of a ball bearing 20a which by means of a longitudinally extending rod 21 and two transversely extending stays 22 is connected to the two downwardly extending brackets 12 and 13 . by means of a handle 24 , fig3 it is possible to adjust the inclination of the guiding plates 15 and 16 via a shaft 25 to which the handle 24 is connected . the shaft 25 is journalled in bearings ( not shown on the drawing ) secured to the legs 2 and is rigidly connected to the guiding plate 16 . a connecting member 26 connects the guiding plate 16 and the guiding plate 15 which by means of a shaft 27 is journalled in brackets ( not shown on the drawing ) secured to the legs . the part of the apparatus illustrated in fig1 - 3 works in the following way : when the motor 18 rotates the excentric 19 , the excentric will move the frame 5 downwardly due to the cooperation with the ball bearing 20a and during such movement the screen plates 6 , 7 and the grid 8 will be subjected to a movement directed downwardly to the left in fig2 due to the cooperation between the beams of the two brackets 12 , 13 and the inclined guiding plates 15 , 16 . when the wide portion of the excentric 19 moves from the position shown in fig3 the excentric will release the ball bearing 20a and , accordingly , the springs 3 , 4 will pull the screen plates 6 , 7 and the grid 8 upwardly . during this movement the inner frame 5 will be guided by means of the guiding plates 15 , 16 and the upward movement will be interrupted when the frame 5 hits the felt pieces 11 on the abutments 10 . due to the abrupt movement , bulbs positioned upon the screens 6 , 7 will be thrown in an inclined direction upwards and to the right in fig2 . in this way the bulbs will be screened by means of the screen plates 6 and 7 , as it is generally known from throw - screens . only bulbs having the correct size will pass the last screen 7 and will be thrown over upon the grid 8 . in the embodiment illustrated on the drawing , the grid rods 9 are arranged pair by pair with a distance between two adjacent pairs which is a little greater than the distance between the two grid rods of each pair . in order to avoid the bulbs from falling down through the spacings between adjacent pairs of grid rods , guiding means 28 as indicated in fig1 are provided , but it will be understood that also a grid may be used having equidistant grid rods . the apparatus also comprises an upper part 30 indicated in dotted lines in fig3 . the upper part is shown on an increased scale in fig4 and 6 and consists of a rectangular upper frame 31 which , as indicated in fig3 is arranged over the portion of the lower part of the apparatus comprising the grid 8 . in the upper frame and in the longitudinal direction thereof pairs of rollers 32 , 33 are journalled , of which , however , only one pair is shown in fig4 whereas two pairs are shown in fig3 . from fig3 it will be seen that each pair of rollers is arranged directly above the groove formed between each pair of grid rods 9 . the two rollers of each pair are pressed towards each other by means of springs 34 , 35 , fig4 and the shaft of each roller is at the right hand end , as seen in fig4 provided with a worm gear 37 and 38 , respectively . each of the worm gears engages a screw spindle 39 and 40 , respectively , journalled in the upper frame 31 . the screw spindles 39 and 40 are driven at one end thereof by means of a motor 42 arranged on the upper frame 31 . the two screw spindles 39 and 40 are arranged at different levels , viz . so that the screw spindle 39 engages the worm gears 37 of the rollers 32 from beneath , whereas the spindle 40 engages the worm gears 38 of the rollers 33 from above . the two spindles 39 and 40 are driven in the same direction of rotation by means of the motor 42 via two belts 43 and 44 as shown in fig5 . accordingly , the two rollers 32 and 33 of each pair of rollers are driven in opposite directions as indicated by the arrows 47 and 48 in fig7 . the rollers are coated with a plastic material available on the market under the registered trade mark &# 34 ; neopren whv 50 - 70 shore .&# 34 ; above each pair of rollers a suction box 50 is arranged as indicated in fig7 . after the transfer of the bulbs to the grid by means of the throw - action explained above , the bulbs will , due to the inclined walls of the grooves , occupy a position inversed with respect to the position the bulbs occupy when growing . in other words , the bulb will be orientated with their root balls uppermost as shown in fig7 . this orientation will result almost immediately when the bulbs fall into the grooves . in order to offer the bulbs an opportunity to occupy this position , the upper part 30 of the apparatus is arranged a little offset to the right with respect to the left hand end of the grid 8 as shown in fig5 . during the throw - movements explained above and applied to the bulbs by means of the grid , the root balls of the bulbs will be caught by the nips of the pair of rollers 32 , 33 and it has been proved that if a pair of rollers catches only a portion of the root ball of a bulb , the complete root ball will be pulled off and sucked out through the box 50 as indicated by the arrows 51 , fig7 . due to the position which the bulbs occupy and due to the reciprocating movement , the bulbs cannot be caught anywhere in the apparatus and , accordingly , the root ball is removed in a very gentle way . in fig7 the grid 8 , represented by a pair of grid rods 9 , is shown in its uppermost position wherein the frame 5 contacts the abutments 10 and the throw movement is initiated . in this position the average height h of the lowermost portions of the rollers 32 , 33 above the centers of the bulbs is 50 - 80 mm ( depending upon the sizes of the bulbs ) and , accordingly , the bulbs move the remaining distance up to the rollers solely due to the throw movement . experiments have proved that a speed of the rollers amounting to 150 - 300 revolutions per minute combined with a diameter of the rollers between 20 - 50 mm gives satasfactory results .

in apparatus for removing roots from bulbs or the like corms , the bulbs are thrown upwards towards pairs of cooperating rollers , which catch the roots of the bulbs in the nips between the rollers and draw off the roots from the bulbs .

fig1 illustrates a cat activity apparatus 100 . the cat activity apparatus 100 is intended for use by one or more felines for entertainment and exercise , as well as entertaining their human companions . the cat activity apparatus 100 fits into a residential , shelter , or retail atmosphere . the cat activity apparatus 100 has a collapsible design . the collapsible design enables the cat activity apparatus 100 to be shipped in a relatively small carton / s and assembled easily by one person . the cat activity apparatus 100 has a multiple piece design that allows the cat activity apparatus 100 to be easily disassembled for relocation and storage . the cat activity apparatus 100 comprises four plywood members . in some embodiments , the plywood members are ¾ inch thick . in another embodiment , the plywood members have other thicknesses . the plywood members are covered in carpeting made of various colors , styles and thicknesses . the plywood members include frame members 102 , 104 and shelf members 106 , 108 . in various embodiments , the frame members 102 , 104 and the shelf members 106 , 108 have various lengths and widths . for example , the frame members 102 , 104 can be 53 inches long and eighteen inches wide . in this example , the shelf member 106 can be 43 inches long and the shelf member 108 can be 30 inches long . in this example , the shelf members 106 , 108 can be 12 inches wide . in another example , the frame members 102 , 104 can be thirteen inches wide . there are two metal hinges 112 attached with twelve screws to the frame members 102 , 104 at ends 114 . the hinges 112 attach the frame members 102 , 104 to each other . the frame members 102 , 104 have two notches 200 ( fig2 ) cut from the edges of the wood extending perpendicularly toward the center . the shelf members 106 , 108 also have notches 300 ( fig3 ) extending toward their centers . in various embodiments , the notches 200 , 300 can have various depths . for example , the notches 200 , 300 can have depths of six inches . the notches 200 on the frame members 102 , 104 are disposed on opposing sides . in various embodiments , the notches 200 are disposed at various distances from ends 110 . for example , the notches 200 on the frame members 102 and 104 can be disposed at 17 and 35 inches from ends 110 . in another example , the notches 200 on the frame members 102 and 104 can be disposed at 17 and 44 inches from the ends 110 . the notches 300 in the shelf member 106 are disposed on the same side of the shelf member 106 . in various embodiments , the notches 300 in the shelf member 106 are disposed at various distances from the ends of the shelf member 106 . for example , the notches 300 in the shelf member 106 can be disposed at 10 inches from each end of the shelf member 106 . the shelf member 108 has notches that are disposed on the same side of the shelf member 108 . in various embodiments , the notches 300 in the shelf member 108 are disposed at various distances from the ends of the shelf member 108 . for example , the notches 300 in the shelf member 108 can be disposed at 8 inches from each end of the shelf member 108 . an example manufacturing process comprises cutting sheets of four foot by eight foot , ¾ inch plywood to the above specified dimensions to create the frame members 102 , 104 and the shelf members 106 , 108 . the frame members 102 , 104 and the shelf members 106 , 108 are then covered in carpeting by means of a staple gun or other tool . assembly done before shipment to a customer comprises attaching the two hinges 112 to the ends 114 of the frame members 102 and 104 . once the customer receives the cat activity apparatus 110 , the frame members 102 , 104 are laid on their sides with the notches 200 closer to the hinged end 114 facing up . then , the ends 110 would be moved approximately 35 inches apart to form a “ v ” shape . next , the customer lines up the notches 300 on the shelf member 108 to the notches 200 facing up on the frame members 102 and 104 . once the notches 200 and 300 are lined up , the shelf member 108 would be inserted far enough that the plane of the front edge of the shelf member 108 is even or nearly even with the plane of the edge of the frame members 102 and 104 . after that is accomplished , the customer stands the cat activity apparatus 100 upright and then lays the cat activity apparatus 100 down on its other side so that the notches 200 closer to ends 110 are facing up . the notches 300 on the shelf member 106 would then be lined up with the notches 200 facing up on the frame members 102 and 104 . the customer then inserts the shelf member 106 into the notches 200 of the frame members 102 and 104 until the plane of the edge of the shelf member 106 is even with or nearly even with the plane of the edge of the frame members 102 and 104 . furthermore , some embodiments include an l bracket 116 . the “ l ” bracket can be three inches . the “ l ” bracket 116 can be used to attach the cat activity apparatus 100 to a wall to prevent the cat activity apparatus 100 from tipping . in some embodiments , the customer attaches the stabilizer bar 118 to the bottom end of one of the frame members 102 or 104 . the length of the stabilizer bar 118 is greater than the widths of the frame members 102 , 104 . for example , in some embodiments , the stabilizer bar 118 is 23 inch long , 3 inches wide , ¾ inch deep . the stabilizer bar 118 can prevent the cat activity apparatus 100 from tipping . the stabilizer bar 118 and / or the “ l bracket ” 116 are not necessarily present in embodiments where the frame members 102 , 104 are sufficiently deep ( e . g ., 18 or more inches ) to prevent the cat activity apparatus 100 from tipping . in alternative designs , another stabilizer could include a removable cat scratching post attached to the lower and / or middle shelf members 106 and 108 extending to the floor , or a large diameter base that is attached to one or both of the ends 110 of the frame members 102 and 104 . the length of the stabilizer scratching post would vary between 20 and 30 inches , and the diameter of the covered base would be approximately 24 inches . the cat activity apparatus 100 is meant to be placed in an area where cats would enjoy it . the cat activity apparatus 100 is intended to be climbed on , jumped on , run on or through and laid or sat upon by cats providing them with entertainment , exercise , or relaxation . it is possible for cats to be interactive with each other , as well as their human companions . the cat activity apparatus 100 would be enjoyed by a single cat as well multiple cats . the cat activity apparatus 100 is designed to be easily disassembled for relocation or storage . in other embodiments , the plywood may be replaced of a more earth - friendly material , such as recycled plastic , cardboard , or metal . the metal hinges 112 may be replaced by a heavy duty plastic interlocking device . other embodiments may include things such as a scratching area . the scratching area can be made out materials including , but not limited to , sisal rope , burlap or cardboard . furthermore , other embodiments can include a longer shelf with edges to form a bed or hammock and / or some variation of a bed on the top part of the unit . larger and smaller embodiments exist . the measurements provided in this document are examples and do not represent the only possible measurements . for example , a larger embodiment can be approximately six feet in height and have three shelves . a smaller embodiment can be approximately three feet tall and have one shelf . furthermore , some embodiments can have holes on the frame members 102 , 104 large enough for cats to get through making a direct path from outside the “ a ” shape to inside .

an example cat activity apparatus includes : a first frame member ; a second frame member , the second frame member being attached to the first frame member at an end by a hinge mechanism to form “ v ” shape ; a first shelf member extending between the first frame member and the second frame member , the first shelf member being positioned in notches defined by the first frame member and the second frame member ; and a second shelf member extending between the first frame member and the second frame member and being vertically spaced from the first shelf member , the second shelf member being positioned in notches defined by the first frame member and the second frame member .

reference is made first to fig1 for a brief description of the implementation of a first embodiment of the present invention on a standard crib enclosure . fig1 shows crib 10 as a typical crib enclosure with one removable side , leaving a mattress 11 surrounded on three sides by the crib end panels and side railing and open on a fourth side for placement of the present invention . ramp / rail assembly 12 is positioned and attached to crib 10 as shown in fig1 . ramp / rail assembly 12 includes rail sub - assembly 14 which is positioned directly onto crib 10 through the use of attachment bands 18 a and 18 b . the mechanism for attachment in this manner is described in more detail below with reference to fig3 and 3 a . ramp / rail assembly 12 also comprises ramp sub - assembly 16 which extends downward and away from rail sub - assembly 14 positioned on crib 10 . ramp sub - assembly 16 is comprised of ramp frame sub - assembly 22 and ramp surface 20 . in the preferred embodiment shown in fig1 , ramp frame sub - assembly 22 is made up of semi - rigid tubular components joined together to form a generally rectangular frame as indicated in the drawing . ramp surface 20 is positioned over and around ramp frame sub - assembly 22 so as to provide a light - weight , flexible surface to the rectangular plane defined by ramp frame sub - assembly 22 . as indicated in fig1 , ramp surface 20 may be a fabric material that is stretched across ramp frame sub - assembly 22 , around the individual edge components of ramp frame sub - assembly 22 , and sewn ( or snapped , zipped , etc .) back onto itself or the ramp frame sub - assembly to form a secure platform made of fabric . as shown in fig1 , ramp sub - assembly 16 is pivotally connected to rail sub - assembly 14 in a manner described in more detail below . in this configuration , the two primary components of ramp / rail assembly 12 define a first vertical plane comprising rail sub - assembly 14 and a second horizontally - angled plane defined by ramp sub - assembly 16 . the child may utilize the ramp / rail assembly 12 of the present invention by crawling up or down the ramp sub - assembly 16 of the device . the height of rail sub - assembly 14 is sufficiently low such that the child may readily enter the crib enclosure or exit the crib enclosure if such is the intent . rail sub - assembly 14 is , however , sufficiently high as to prevent the child , when asleep or partially asleep , from unintentionally falling out of crib 10 . in this manner , the ramp / rail assembly 12 of the present invention provides an easy and safe means for a child to enter or exit crib 10 , when such is the child &# 39 ; s intent . reference is now made to fig2 for a more detailed description of the structure of ramp / rail assembly 12 of the present invention as shown in fig1 . once again ramp / rail assembly 12 is comprised of rail sub - assembly 14 and ramp sub - assembly 16 . the additional components not shown in fig1 , but which make up part of ramp / rail assembly 12 , include mattress legs 24 a and 24 b . these mattress legs 24 a and 24 b are capped respectively with leg caps 25 a and 25 b . mattress legs 24 a and 24 b are attached to rail sub - assembly 14 in a manner described in more detail below and are utilized for the purpose of helping to stabilize rail sub - assembly 14 in its attachment to crib 10 . mattress legs 24 a and 24 b are inserted and positioned below mattress 11 ( shown in fig1 ) and in conjunction with attachment bands 18 a and 18 b serve to stabilize and position rail sub - assembly 14 on crib 10 , closely adjacent to mattress 11 . as indicated above , ramp sub - assembly 16 is made up of ramp frame sub - assembly 22 and ramp surface 20 ( not shown in fig2 for clarity ). ramp frame sub - assembly 22 is made up of a generally rectangular set of tubular components and joint connectors as shown . these components include ramp side braces 36 a and 36 b , ramp base brace 37 , and ramp center brace 34 . ramp base corner joints 26 a and 26 b serve to connect ramp side braces 36 a and 36 b to ramp base brace 37 . ramp base center joint 28 serves to connect ramp center brace 34 to ramp base brace 37 . ramp frame sub - assembly 22 , and therefore ramp sub - assembly 16 , is connected to rail sub - assembly 14 by way of ramp top corner pivot joints 30 a and 30 b and ramp top center pivot joint 32 . ramp top corner pivot joints 30 a and 30 b , as well as ramp top center pivot joint 32 , are designed to position and fix ramp sub - assembly 16 side - to - side on rail sub - assembly 14 , but to permit the angular rotation of ramp sub - assembly 16 up and down in pivoting relationship to the plane of rail sub - assembly 14 . in other words , the corner and center pivot joints allow the user to lift ramp sub - assembly 16 and additionally allow variability in the height of the crib to which the present invention is mounted . rail sub - assembly 14 is comprised of rail top brace 45 , rail center brace 47 , and rail base brace 46 , all of which are in generally parallel , coplanar relationship to one another . extending between rail top brace 45 and rail center brace 47 are a plurality of rail bars 38 . the base of rail sub - assembly 14 is made up of rail side braces 40 a and 40 b which are connected to rail top brace 45 by way of rail top joints 42 a and 42 b , and are connected to rail base brace 46 by way of rail base joints 44 a and 44 b . rail side braces 40 a and 40 b are connected to rail center brace 47 by way of rail side joints 48 a and 48 b . as identified above , the pair of mattress legs 24 a and 24 b , are connected to rail base brace 46 by way of mattress leg joints 50 a and 50 b . in the preferred embodiment , these mattress leg joints 50 a and 50 b are fixed both laterally on rail base brace 46 and pivotally fixed ( non - rotational ) so as to facilitate the rigid placement of rail sub - assembly 14 adjacent the mattress of the crib . finally , additional support within rail sub - assembly 14 is provided by rail center brace support joints 52 a , 52 b , 54 a , and 54 b , which extend between and fix in parallel relationship , rail center brace 47 and rail base brace 46 . reference is now made to fig3 for a brief description of the use of attachment bands 18 a and 18 b in facilitating the fixed positioning of ramp / rail assembly 12 of the present invention on crib 10 . in this reverse view , and in the detailed view shown in fig3 a , rail sub - assembly 14 of ramp / rail assembly 12 is positioned adjacent the mattress within crib 10 , but inside the posts or legs of crib 10 as shown . in this manner some rigidity is immediately obtained by the pressure of being positioned between the edge of the mattress , and the inside faces of the legs or posts of the crib . it is clear from fig3 that the dimensions of rail sub - assembly 14 of the present invention are dependent upon the dimensions of crib 10 , and derive from the distance between the center points of the interior faces of the legs or posts of the crib . in this manner , safe and secure placement and positioning of rail sub - assembly 14 is possible . as shown in fig3 a , rail side brace 40 b and rail sub - assembly 14 are positioned against the interior face of the crib leg or post as shown . attachment band 18 b is wrapped around both rail side brace 40 b and the leg or post of crib 10 as indicated . this attachment , in combination with the use of mattress legs 24 a and 24 b described above , provides a sufficiently rigid means for positioning the present invention on the crib . attachment band 18 b is , in the preferred embodiment , a “ hook and loop ” material type strap that may be wrapped back on itself to provide a secure but removable attachment point . alternate methods for fixing rail sub - assembly 14 to the leg or post components of crib 10 are anticipated based upon the example of the attachment strap 18 b shown . it is understood that the detail shown in fig3 a is repeated on the opposite end of crib 10 in a mirrored fashion . reference is now made to fig4 a and 4b for a detailed description of one method for removably attaching ramp sub - assembly 16 of the present invention to rail sub - assembly 14 . fig4 a and 4b show an alternate attachment joint that would replace ramp top corner pivot joints 30 a and 30 b , all as shown in fig2 . ramp top center joint 32 would likewise be modified into a partially open hook configuration , similar to the attachment joint structure shown in fig4 a and 4b but without the closure mechanism . under some circumstances it may be desirable to allow the user to completely remove ramp sub - assembly 16 from rail sub - assembly 14 for a variety of reasons , including more direct access to the side of the crib . the pivot joint structures shown in fig4 a and 4b are designed to permit this separation of the components of the present invention . in fig4 a , releasable top pivot joint 60 is shown comprised of release handle 62 , joint yoke 64 , and joint jaw 66 . release handle 62 and joint jaw 66 are pivotally connected to joint yoke 64 by means of joint pivot bolt 68 . release handle spring 69 is positioned in association with this pivot joint . releasable top pivot joint 60 is positioned on ramp side brace 36 a ( in this example ) and serves to replace ramp top corner pivot joint 30 a , shown in fig2 . in this manner , ramp side brace 36 a is releasably attachable to rail center brace 47 of rail sub - assembly 14 . rail center brace 47 is received into joint yoke 64 and maintained there , initially , by the downward weight of ramp sub - assembly 16 . movement of release handle 62 , and therefore joint jaw 66 , closes joint jaw 66 around rail center brace 47 to adequately secure the pivoting joint . fig4 b shows in greater detail the manner in which the release of release handle 62 closes joint jaw 66 around rail center brace 47 so as to hold rail center brace 47 captive within joint yoke 64 . the above described first preferred embodiment of the present invention is designed to used by a child that is capable of climbing or crawling up the ramp component to the rail component and thereafter climbing over the rail component into the crib to sleep on the mattress . when the child wakes from sleep and wishes to exit the crib , the present invention provides such an exit . the child , when awake and alert , is capable of climbing over the rail component to land on the ramp component . the ramp component is sized and angled so that the child crawling or “ falling ” from over the rail component would be stopped in his or her vertical descent by the ramp platform material and would be slow to slide down the ramp because of the friction the surface provides . in this manner the child may exit to the floor from the otherwise too high crib mattress surface without the assistance of an adult . the ramp may be left permanently positioned on the side of the crib for this purpose or may be removed as needed if it is configured with the releasable connector joints described in fig4 a and 4b . reference is now made to fig5 - 7 for a detailed description of a second preferred embodiment of the present invention . ramp / rail assembly 12 shown in fig5 is designed to have a folding function that permits the user to move ramp sub - assembly 16 into a planar position adjacent the side of crib 10 , so as to allow the user more direct access to the crib . the folded configuration of this embodiment is shown in fig6 . fig5 discloses the extended configuration of the embodiment , wherein ramp / rail assembly 12 is made up of folding ramp sub - assembly 70 , which itself is comprised of folding ramp lower frame sub - assembly 72 , and folding ramp upper frame sub - assembly 74 . joints that are described in more detail below connect folding ramp lower frame sub - assembly 72 to folding ramp upper frame sub - assembly 74 and permit the folding or bending of folding ramp sub - assembly 70 in a manner that allows it to be flatly positioned against the side of crib 10 as shown in fig6 . reference is now made to fig7 for a detailed description of the specific components that make up the second preferred embodiment shown in fig5 and fig6 . it should be noted that rail sub - assembly 14 in this embodiment remains structured exactly the same as rail sub - assembly 14 in the initial preferred embodiment mentioned above . folding ramp sub - assembly 70 once again is comprised of folding ramp lower frame sub - assembly 72 and folding ramp upper frame sub - assembly 74 . folding ramp lower frame sub - assembly 72 , itself is comprised of ramp lower side braces 76 a and 76 b , as well as ramp lower center brace 78 . ramp lower base brace 79 is essentially identical to ramp base brace 37 shown in the first embodiment described above . folding ramp upper frame sub - assembly 74 is comprised of ramp upper side braces 80 a and 80 b , as well as ramp upper center brace 82 . ramp upper side braces 80 a and 80 b are respectively connected to ramp lower side braces 76 a and 76 b by means of ramp brace hinges 84 . ramp upper center brace 82 is likewise connected to ramp lower center brace 78 by means of a ramp brace hinge 84 . ramp brace hinges 84 are constructed so as to fold in the direction indicated in the drawings , such that folding ramp upper frame sub - assembly 74 may be rotated upward , thereby drawing in folding ramp lower frame sub - assembly 72 into the coplanar position described above . the hinges 84 , however , are structured so as to alternately ( and normally ) bring the ramp lower side braces 76 a and 76 b into alignment with ramp upper side braces 80 a and 80 b ( likewise with center braces 82 and 78 ) and to remain rigid in that position preventing the further bending or collapsing of the frame downward . such hinges structured to stop once the alignment described above has occurred , are well known in the art . the above described second preferred embodiment of the present invention finds practicality where the parent or caregiver finds it necessary to frequently access the side of the crib to attend to the child . in so far as the ramp , in its lowered position , would likely serve as a barrier to close access , the second embodiment provides a folding ramp that almost entirely eliminates the “ protrusion ” that the extended ramp would provide on the side of the crib . the hinge structure , and its location on the ramp frame , is such that the ramp may be folded upward with the appropriate force being exerted inward on the lower edge of the ramp towards the crib . in this manner , the adult or care giver may generally fold the ramp by pushing against the lower edge of the ramp with their foot . extending the ramp again can be accomplished by drawing the lower edge of the ramp out again from the crib and allowing gravity to pull the ramp sections once again into an inclined plane configuration . hinges of the type that bend in only one direction ( and provide stiff resistance to bending in the opposite direction ) are well known in the art . reference is now made to fig8 a , 9 b , 9 c and 10 for a detailed description of a third alternative preferred embodiment of the present invention . in fig8 , ramp / rail assembly 12 is seen once again to be comprised of rail sub - assembly 14 , but instead of a single ramp sub - assembly attached to rail sub - assembly 14 , a dual folding ramp structure is disclosed . this dual folding ramp system is comprised of dual - folding ramp right sub - assembly 90 , and dual - folding ramp left sub - assembly 96 . dual - folding ramp right sub - assembly 90 is comprised of dual - folding ramp right lower frame sub - assembly 92 , and dual - folding ramp right upper frame sub - assembly 98 . likewise , dual - folding ramp left sub - assembly 96 is comprised of dual - folding ramp left lower frame sub - assembly 94 , and dual - folding ramp left upper frame sub - assembly 100 . the manner in which the assemblies of the dual - folding ramp structure fold with respect to one another is identical to that described above in the second preferred embodiment utilizing hinges 84 . in this case , however , two separate folding ramps are positioned so as to permit the user to either fold both ramps at the same time , or a single ramp at a time . these various folding configurations are shown in fig9 a , 9b , and 9 c . fig9 a shows the dual folding ramp system wherein both dual - folding ramp right sub - assembly 90 and dual - folding ramp left sub - assembly 96 are each folded into coplanar relationship with rail sub - assembly 14 , close to the side of crib 10 . fig9 b shows dual - folding ramp right sub - assembly 90 extended into its ramp configuration while dual - folding ramp left sub - assembly 96 remains folded against the side of crib 10 . in the opposite configuration , fig9 c discloses dual - folding ramp left sub - assembly 96 extended and dual - folding ramp right sub - assembly 90 folded against the side of crib 10 . reference is finally made to fig1 for a detailed description of the additional components incorporated into the structure associated with the above described dual - folding ramp system . here again , rail sub - assembly 14 is identical to the rail sub - assembly described above with respect to the first and second preferred embodiments . dual - folding ramp right lower frame sub - assembly 92 is made up of right ramp lower side brace 110 a , right ramp lower base brace 111 a , and right ramp lower center brace 112 a . likewise , dual - folding ramp left lower frame sub - assembly 94 is made up of left ramp lower side brace 110 b , left ramp lower base brace 111 b , and left ramp lower center brace 112 b . the joints for connecting the center and side braces described above include right ramp lower center base joint 114 a , left ramp lower center base joint 114 b , right ramp lower corner base joint 116 a , and left ramp lower corner base joint 116 b . the dual - folding ramp right upper frame sub - assembly 98 is comprised of right ramp upper center brace 118 a and right ramp upper side brace 122 a . the dual - folding ramp left upper frame sub - assembly 100 is comprised of left ramp upper center brace 118 b and left ramp upper side brace 122 b . the joints for connecting the center and side braces of dual - folding ramp right upper frame sub - assembly 98 and dual - folding ramp left upper frame sub - assembly 100 include right ramp upper side pivot joint 120 a , left ramp upper side pivot joint 120 b , right ramp upper center pivot joint 124 a , and left ramp upper center pivot joint 124 b . the third preferred embodiment described above finds practicality where both use of the ramp and direct access to the side of the crib are desired . although it is obviously necessary for the railing of the present invention to extend down the entire length of the open side of the crib , it is not typically necessary for the ramp to be this wide . the third embodiment therefore provides for a system that accommodates both the use of the ramp by the child and access to the side of the crib by the adult . the process of folding or extending each ramp section is the same as with the second embodiment described above but may be accomplished with both ramp sections together or each ramp section independently . the division of the ramp may be into two sections ( as shown ) or may be more under certain circumstances . likewise the division of the ramp may be into equal sections ( as shown ) or unequal under certain circumstances . in any event , the third embodiment provides versatility in user configuration of the ramp component of the present invention . although the present invention has been described in conjunction with a number of preferred embodiments , those skilled in the art will recognize further alterations of the structures described that still fall within the scope of the invention as defined by the claims that follow . for example , but without limitation , the components of the frame structures of the invention as described are generally shown as round tubular sections . those skilled in the art will recognize that longitudinal sections of a solid nature and / or of alternate cross - section ( such as square ) are possible . likewise , the material from which these frame sections might be constructed could be any of a number of rigid or semi - rigid compositions available for such longitudinal elements . for example , but again without limitation , the tubular sections might be constructed of strong ( schedule 40 or greater ) pvc pipe sections or may be constructed of metal tubular components . those skilled in the art will recognize the balance required between rigidity and flexibility in selecting the most appropriate materials . finally , again without limitation , the construction of the platform that provides the climbing surface in the present invention may be from any of a number of different materials from a coarse mesh to a tightly woven fabric . comfort and strength will generally govern the choice of material for the platform .

a system for attachment to a child &# 39 ; s crib combining a side rail and a ramp structure that serve to prevent the child from rolling out during sleep , and at the same time provide a means for the child to climb or crawl into or out from the crib . components include a side rail fixed to the crib at each end by removable straps or the like , and rigidly connected to a pair of legs that slide between the mattress and box spring of the crib . a generally larger ramp component extends pivotally outward and downward from the side rail component to a point in contact with the floor . embodiments include multiple hinged components within the ramp system to allow alternate positioning of the ramp in an extended or a collapsed configuration .