Datasets:

farleyknight

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big_patent_10_percent

like 1

the chart used in the identification of the colors is that of the royal horticultural society ( r . h . s . colour chart ). the description is based on the observation of eighteen month - old plants during august while budded on rosa froebelli understock and growing outdoors at le cannet des maures , var , france . height .— approximately 30 to 40 cm on average at the end of the growing season . width .— approximately 40 to 45 cm on average at the end of the growing season . habit .— low , bushy and compact . color .— young stems : near green group 143c . — adult wood : near yellow - green group 144b . thorns .— size and quantity : on 16 cm of young stems approximately 14 on average approximately 0 . 6 cm in length ; and on 18 cm of adult stems approximately 22 on average approximately 0 . 6 cm in length . — color : near greyed - orange group 176a on young stems , and near greyed - orange group 176b on adult stems . — configuration : very longish pointed and curved downwards on the upper surface and slightly concave on the under surface with an obovate base . small prickles .— size and quantity : on 16 cm of young stems approximately 6 on average approximately 0 . 3 cm in length . — color : near greyed - yellow group 161a suffused with greyed - orange group 176b . — configuration : possess an obovate base . stipules .— adnate , pectinate , smooth , broad , approximately 2 . 5 cm in length on average , approximately 0 . 8 cm in width on average , near yellow - green group 147a on the upper surface , and near yellow - green group 146b on the under surface . petioles .— upper surface : non - glandular and near yellow - green group 147b in coloration . — under surface : bears a few prickles and near yellow - green group 146c in coloration . — length : approximately 0 . 3 cm for the terminal leaflet . petiole rachis .— upper surface : near yellow - green group 147b in coloration . — under surface : near yellow - green group 146b in coloration . leaflets .— number 3 , 5 and 7 ( most often ). — shape : generally oval with an obtuse base and a pointed tip . — size : the terminal leaflets commonly are approximately 2 . 6 cm in length on average , and approximately 1 . 2 cm in width on average . — serration : single and fine . — texture : firm and consistent . — general appearance : very dense , dark green with a semi - glossy aspect . — color ( young foliage ): upper surface : near yellow - green group 147a . under surface : near yellow - green group 146b . — color ( adult foliage ): upper surface : near yellow - green group 147a . under surface : near yellow - green group 146b . number of flowers .— commonly approximately 6 to 15 flowers per stem in a cluster . peduncle .— rigid , near yellow - green group 144a in coloration , glandular , approximately 2 . 5 cm in length on average , and approximately 0 . 1 cm in diameter on average . sepals .— upper surface : tomentose consistent and near green group 138b and 138c in coloration . — under surface : glandular and near green group 143a in coloration . — configuration : narrow with a longish point and uncurved at the base . — size : approximately 1 . 1 cm in length on average , and approximately 0 . 8 cm in width at the widest point on average . buds .— shape : conical . — size : small . — length : approximately 1 . 1 cm on average . — width : approximately 0 . 8 cm at the widest point on average . — color : upper surface : near red group 54b amply suffused with red group 45b as the calyx breaks . undersurface : near red group 54b amply with red group 45b as the calyx breaks . basal petal spot : near yellow group 8b on both surface . flower .— shape : generally cup - shaped . — diameter : approximately 4 cm on average . — color ( in course of opening ): uppersurface : red - purple group 57a and amply suffused with red - purple group 58a . under surface : near red - purple group 57a and amply suffused with red - purple group 58a . basal petal spot : near yellow group 6d . — color ( open flower ): upper surface : near red - purple group 57a and amply suffused with red - purple group 58a . under surface : near red - purple group 57a and amply suffused with red - purple group 58a . basal petal spot : near yellow group 6d . — color stability : very good . — fragrance : none . — lasting quality : the blossoms commonly last approximately 2 to 3 weeks on the plant on average depending upon the environment conditions . — petal number : approximately 14 on average under normal growing conditions . — petal size : approximately 1 . 7 cm in length on average , and approximately 1 . 5 cm in width on average . — petal texture : smooth . — petaloids : small and present at center . — petal shape : rounded tip and obtuse base . — petal arrangement : imbricated . — petal drop : good with the petals commonly detaching cleanly before drying . — stamen number : approximately 30 on average . — anthers : regularly arranged around the styles , the approximately 0 . 1 cm in size on average , and near greyed - orange group 166a in coloration . — pollen : sparsely present and near greyed - orange group 166a in coloration . — filaments : near yellow group 12c in coloration , and approximately 0 . 4 cm in length on average . — pistils : approximately 15 on average . — stigmas : near greyed - green group 160b in coloration , and approximately 0 . 1 cm in size . — styles : near greyed - green group 191c in coloration , and approximately 0 . 3 cm in length on average . — receptacle : glandular , near yellow - green group 144a in coloration , and pitcher - shaped in longitudinal section . the length commonly is approximately 0 . 5 cm on average and the width commonly is approximately 0 . 3 cm on average . — hips : none observed . vegetation .— medium . blooming .— abundant and nearly continuous . resistance to diseases .— good disease tolerance and resistant to black spot during observations to date . aptitude to bear fruit .— none observed during observations to date .

a new and distinct variety of landscape shrub rose plant is provided which abundantly forms on a nearly continuous basis attractive small brilliant red - pink blossoms having good color stability . the plant exhibits a low , compact and bushy growth habit . good disease tolerance including resistance to black spot has been displayed . the attractive dark green foliage contrasts nicely with the red - pink blossom coloration . the new variety is particularly well suited for growing as attractive ornamentation in the landscape .

it is to be distinctly understood at the outset that the present invention shown in the drawings and described in detail in association with a collapsible support assembly , with extendable and retractable legs , which is adaptable for use on a golf flag pin , is not intended to serve as a limitation upon the scope or teachings thereof , but is to be considered merely for the purpose of convenience of illustration of one example of its application . referring now in detail to the drawings , wherein like reference characters designate like or corresponding parts throughout the several views , there is illustrated in fig1 through 6 a collapsible support assembly 10 , with extendable and retractable legs , which is adaptable for use on a golf flag pin 1 , constructed in accordance with the principles of the present invention . as shown in fig1 - 3 , a collapsible support assembly 10 is adapted for use to a shaft 2 of a golf flag pin 1 . the collapsible support assembly 10 includes a stop ring 12 , a movable leg ring 14 , a spring 16 , a fixed leg ring 18 , an actuating sheath member 20 , a first leg member 22 and a second leg member 24 . fig1 and 2 depict the collapsible support assembly 10 in an uncollapsed state while fig3 depicts the collapsible support assembly 10 in a collapsed state . referring to fig2 , the actuating sheath member 20 has been removed in order to illustrate in detail the other elements of the collapsible support assembly 10 . fixed leg ring 18 is securely attached to the shaft 2 of the golf flag pin 1 by a screw ( not shown ) inserted through a threaded aperture 26 centrally located on the outer periphery of fixed leg ring 18 . it is entirely conceivable that other attachment means such as nut and bolt type fasteners or glue - based adhesives , to name a few examples , may be used instead to fixedly secure the fixed leg ring 18 to the shaft 2 . the fixed leg ring 18 is in a hinged association with a first arm 28 and a second arm 30 . both first arm 28 and second arm 30 have a finger 32 and 34 , respectively . located on the fixed leg ring 18 are slots 36 and 38 ( shown in fig5 ), which hingedly receive fingers 32 and 34 , respectively , so that the arms 28 , 30 are operable to move between an extended position and a retracted position , relative to the shaft 2 of the golf flag pin 1 , when the collapsible support assembly 10 is in an uncollapsed state and a collapsed state , respectively . the first arm 28 has a substantially convex - shaped side 40 and a substantially concave - shaped side 42 , which is contoured to fit closely to the shaft 2 when the collapsible support assembly 10 is in a collapsed state . shown in more detail in fig4 - 6 , located opposite finger 32 is a channeled groove 44 , which securely receives the top end 46 of first leg member 22 . the first leg member 22 is further secured to the channeled groove 44 by a set of screws ( not shown ), which are inserted through threaded holes 48 located on the concave - shaped side 42 of the first arm 28 . although screws are the preferred mode of attachment , first leg member 22 may be attached to the first arm 28 by snap - fit , adhesives or other conventional means of attachment . the first leg member 22 has a substantially concave - shaped side 50 , which is contoured to fit closely to the shaft 2 when the collapsible support assembly 10 is in a collapsed state . located substantially near top end 46 of first leg member 22 is a protruding portion 52 , which engages with the actuating sheath member 20 . similarly , the second arm 30 also has a convex - shaped side 54 and a substantially concave - shaped side 56 , which is contoured to fit closely to the shaft 2 when the collapsible support assembly 10 is in a collapsed state . shown in more detail in fig4 - 6 , located opposite finger 34 is a channeled groove 58 , which securely receives the top end 60 of second leg member 24 . the second leg member 24 is further secured to the channeled groove 58 by a set of screws ( not shown ), which are inserted through threaded holes 62 located on the concave - shaped side 56 of second arm 30 . although screws are the preferred mode of attachment , second leg member 24 may be attached to the second arm 30 by snap - fit , adhesives or other conventional means of attachment . the second leg member 24 has a substantially concave - shaped side 64 , which is contoured to fit closely to the shaft 2 when the collapsible support assembly 10 is in a collapsed state . located substantially near top end 60 of second leg member 24 is a protruding portion 66 , which engages with the actuating sheath member 20 . moving forward and with reference to the various views of the figures , the movable leg ring 14 is positioned around the shaft 2 a predetermined distance above fixed leg ring 18 and is operable to move along the shaft 2 , with respect to the fixed leg ring 18 and in accordance with the principles of the spring 16 . the spring 16 , for biasing the collapsible support assembly 10 to the collapsed state , is positioned around the shaft 2 and located between the movable leg ring 14 and the fixed leg ring 18 . a first end 68 of a first wire 70 is disposed onto the movable leg ring 14 at a first pin 84 while a second end 72 of the first wire 70 is attached to the substantially convex - shaped side 40 of the first arm 28 . similarly , a first end 74 of a second wire 76 is disposed onto the moveable leg ring 14 at a second pin 86 while a second end 78 of the second wire 76 is attached to the substantially convex - shaped side 54 of the second arm 30 . although a first wire and second wire 70 , 76 have been described to link the movable leg ring 14 to the first and second arms 28 , 30 , any suitable linking members may be used in place of the wires 70 , 76 . with reference to the actuating sheath member 20 as best shown in fig1 and 3 , the actuating sheath member 20 is disposed concentrically around the shaft 2 and is cylindrical in shape and has a substantially circular radial cross section . when collapsible support assembly 10 is in the collapsed state protruding portion 52 and protruding portion 66 abuttingly engage one another around shaft 2 creating a measurable outer circumference , which is approximately larger than the circumference of the shaft 2 yet only a fraction slightly smaller than the inner circumference of the actuating sheath member . as shown in fig3 , the actuating sheath member 20 is in slidable engagement with the protruding portion 52 of first leg member 22 and with the protruding portion 66 of second leg member 24 , thus the substantially concave - shaped sides 50 , 64 of first and second leg members 22 , 24 , respectively , are fitted closely in a snug relationship to the shaft 2 . while in this collapsed state , a top end 80 of the actuating sheath member 20 rests on top of movable leg ring 14 to prevent the actuating sheath member 20 from moving any further down ( away from the flag 3 ) the length of the golf flag pin 1 . when the actuating sheath member 20 is slid upwardly ( toward the flag 3 ) and as the bottom end 82 of the sheath member 20 moves above the protruding portions 52 , 66 of first and second leg members 22 , 24 , respectively , the potential energy stored in the spring 16 is released and first and second leg members 22 , 24 move to their extended , uncollapsed state ( as shown in fig1 ). because the stop ring 12 is disposed onto the shaft 2 a set distance from the movable leg ring 14 , the actuating sheath member 20 is prevented from moving any further up ( toward the flag 3 ) the golf flag pin 1 , ensuring that the collapsible support assembly 10 remains in the uncollapsed state , forming a tripod configuration with the first and second leg members 22 , 24 and the bottom end of the golf flag pin 1 . from this uncollapsed state , the sheath member 20 can be slid downward toward the bottom end of the golf flag pin 1 to retract the first and second leg members 22 , 24 and return the collapsible support assembly 10 to the collapsed state . as the sheath member 20 is slid downward , the bottom end 82 of the sheath member 20 engages with the protruding portions 52 , 56 of first and second leg members 22 , 24 , respectively , forcing the first and second leg members to move back to the fitted , snug relationship with the shaft 2 , while also forcing the movable leg ring 14 towards fixed leg ring 18 , via first and second wires 70 , 76 , causing the spring 16 to move back to a compressed state . although the preferred embodiment of the present invention as described above , discusses a collapsible support assembly adapted for use with a golf flag pin , in an alternative embodiment , the collapsible support assembly could be formed integrally with the golf flag pin as one unit . from the foregoing detailed description , it can thus be seen that the present invention provides a collapsible support assembly , adaptable for use with a golf flag pin , with an actuating sheath member , operable to extend retractable legs so as to support the pin above the surface of the green of a golf course . while there has been illustrated and described what is at present considered to be a preferred embodiment of the present invention , it will be understood by those skilled in the art that various changes and modifications may be made , and equivalents may be substituted for elements thereof without departing from the true 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 central scope thereof . therefore , it is intended that this invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out the invention , but that the invention will include all embodiments falling within the scope of the appended claims .

a collapsible support assembly is provided , which is adapted for use with a golf flag pin in order to easily maneuver between a collapsed vertical position and an uncollapsed extended position . the collapsible support assembly includes an actuating sheath member , which , in combination with biasing means , is capable of extending or retracting a first leg and a second leg , so as to support the golf flag pin above the ground when in the extended position . the collapsible support assembly also includes a movable leg ring and a fixed leg ring , which is adaptable for attachment to the golf flag pin .

the invention will be better understood through the following illustrative and non - limitative description and examples of preferred embodiments of the invention . step 1 : to 1000 g of micronized progesterone were added 280 g of distilled water , with mixing using a planetary mixer , over a period of 30 minutes . after mixing , the wetted micronized progesterone was spread on pans to thickness of about 4 - 5 mm , and the pans then placed in an oven at 58 ° c . the humidity was checked periodically using a humidity checker . when the humidity of the micronized progesterone was reduced to substantially 0 %, the dried micronized progesterone was either used immediately in step 2 as described below , or was stored in dry , sealed containers for later use in step 2 . step 2 : colloidal anhydrous silica ( aerosil 380 , 25 g ) was sieved through a russel sieve having pores of 425 micron size , and mixed for 10 minutes with 1000 g of micronized progesterone from step 1 and 2100 g of maize 1500 starch , using an angelsman mixer at 32 rpm , to form mixture a . at the end of the 10 minutes of mixing , 490 g of povidone 30 were added to mixture a , and mixing was continued for another ten minutes , to prepare “ mixture b ”. step 3 : lactose ( ludipress , basf , 3800 g ), adipic acid ( 570 g ) and sodium bicarbonate ( 430 g ) were mixed for 10 minutes at room temperature using an angelsman mixer at 32 rpm . following mixing , these ingredients were sieved through a russel sieve having pores of 425 microns to obtain “ mixture c ”. step 4 : mixtures b and c were mixed for 10 minutes at room temperature using an angelsman mixer at 32 rpm to obtain “ mixture d ”. step 5 : mixture d ( 8415 g ) was mixed with 3800 g of lactose ( ludipress ) for 10 minutes at room temperature using an angelsman mixer at 32 rpm , to obtain “ mixture e ”. step 6 : magnesium stearate ( 230 g ) and sodium lauryl sulfate ( 50 g ) were sieved through a russel sieve ( pore size 125 microns ). the sieved magnesium stearate and sodium lauryl sulfate were then mixed for with mixture e for 20 minutes at room temperature using an angelsman mixer , to obtain “ mixture f ”. step 7 : tablets were obtained from mixture f by direct compaction using an eko korsch press . the amounts of ingredients listed in this example are suitable for production of 10 , 000 tablets each containing about 100 mg progesterone . using the above process , tablets of 1187 mg to 1312 mg total weight , containing from 90 to 110 mg progesterone , were obtained . the process described in example 1 was modified by doubling the amount of filler ( ludipress ) to obtain tablets containing on average 50 mg progesterone . the pharmacokinetics and clinical use of tablets prepared in accordance with the invention were evaluated as follows : 50 healthy , post - menopausal women with intact uteri , 39 of whom had suffered premature menopause and 11 who were truly postmenopausal , all of whom were undergoing hormone replacement therapy ( hrt ), submitted blood samples for determination of baseline profiles of hormones ( progesterone and other hormones ) and other biochemicals ( bilirubin , cholesterol , etc .). the blood samples were taken at 8 am on the first day of the evaluation ( day 0 ) in a fasting state , by intravenous indwelling catheter which was introduced into the cubital vein . non - estrogen primed postmenopausal women were chosen in order to avoid confusion with endogenous progesterone secretion and estrogen influence on vaginal mucosa absorption ( villanueva et al ., fertil . steril . 35 ( 1981 ), 433 - 437 ). the women then self - administered the progesterone vaginal tablet using a plastic applicator and lay down for 20 minutes . repeat blood samples for progesterone concentration were withdrawn 0 . 5 , 1 , 2 , 4 , 6 , 8 , 10 , 12 and 24 hours after the vaginal insertion . blood was allowed to clot at room temperature for 1 hour , after which the serum was separated by centrifugation and stored at − 20 ° c . until analysis . to evaluate clinical use of the drug , the women were instructed to insert tablets prepared in accordance with the present invention , containing the same dose as administered on day 0 , twice daily starting on day 1 , and to recline for 20 minutes after each insertion . on days 14 and 30 , blood samples for comparison with the baseline were drawn in the morning while the subjects were in a fasting state . of the 50 women who participated in the evaluation , 20 were allocated tablets containing 50 mg progesterone , and the remainder of the participants received tablets containing 100 mg progesterone . the baseline details of the participants are summarized in table i . data are expressed as mean ± standard deviation unless otherwise specified . body mass index ( bmi ) was calculated as weight in kg divided by the square of height in meters . a single vaginal application of a 50 mg progesterone - containing tablet prepared in accordance with the invention resulted in the rapid increase of plasma progesterone concentration . the mean peak plasma level ( t max ), mean elimination half - life ( t 1 / 2 ), maximal serum concentration ( c max ), and auc ( area under the curve , i . e . total amount of plasma progesterone observed ) derived from the blood samples taken on day 0 of the evaluation are summarized in table ii . values are mean ± standard deviation ; a p = 0 . 0004 ; b p = 0 . 001 . as shown in table iii , after 14 and 30 days of continuous application twice daily , the serum p levels were significantly higher compared to baseline values on day 0 . no statistically significant difference in plasma levels of follicle stimulating hormone , leutinizing hormone , estradiol , cortisol , dehydroepiendosterone sulfate , or aldosterone were observed in the study groups between baseline values and after continued administration of the tablets of the invention . similarly , the plasma levels of serum glutamic oxaloacetic transaminase , alkaline phosphatase , cholesterol , triglycerides , high density lipoprotein , low density lipoprotein , and very low density lipoprotein did not change significantly between the baseline measurement and the measurements at 14 and 30 days of twice - daily administration . a p = 0 . 0001 , significant difference between progesterone baseline values on day 0 compared to day 14 and day 30 ; b p = 0 . 02 . the efficacy of tablets prepared in accordance with the present invention was compared with the efficacy of prior art tablets as follows : thirteen healthy , postmenopausal women with intact uteri who were undergoing hormonal replacement therapy ( hrt ) were given complete medical evaluation by history , physical and gynecological examination , and instructed to discontinue hrt two weeks prior to the comparative trial . part a : single - dose pharmacokinetics of micronized progesterone in the form of a gelatin capsule ( utrogestan , produced by basins - iscovesco , paris , france ) participants received oral ethinyl estradiol ( estrofem , novo - nordisk , denmark ), 4 mg per day for 14 days . on day 14 at 8 am , in a fasting state , an intravenous indwelling catheter was inserted into the cubital vein and blood was drawn for baseline progesterone and estrogen levels . the women were then instructed to self - administer a single gelatin capsule containing 100 mg of micronized progesterone high in the vagina . repeat blood samples for progesterone concentrations were drawn ½ , 1 , 2 , 4 , 6 , 8 , 10 , 12 and 24 hours after the vaginal insertion . part b : single - dose pharmacokinetics of micronized progesterone in the form of a vaginal tablet according to the present invention . after a washout period of 2 weeks , the same subjects as in part a were again administered 4 mg or ethinyl estradiol ( estrofem ) for 14 days . on day 14 the same procedure as recited in part a was repeated , except that this time the women were instructed to insert 100 mg of progesterone in the form of an effervescent tablet according to the present invention , using a plastic applicator . blood samples for progesterone levels were drawn at the same intervals as in part a . samples were assayed using an immulite enzyme immunoassay ( diagnostic products corporation , los angeles , calif .) to measure plasma progesterone ( si conversion factor 3 . 18 ; sensitivity 0 . 2 ng / ml ( 0 . 6 nmol / l , inter - and intra - assay coefficients of variation precision & lt ; 10 %)) and estradiol ( e 2 ) ( si conversion factor 3 . 67 ; sensitivity 12 pg / ml ( 44 pmol / l , inter - and intra - assay coefficients of variation precision & lt ; 10 %). the pharmacokinetic parameters calculated from the concentration curve were compared between the two study groups by the wilcoxon 2 - sample test , the kruskal - wallis test and by analysis of variance ( anova ). students t - test was used to compare estrogen levels for the two treatment parts . table iv summarizes the baseline details of the of the thirteen women who participated in the study of example 5 . data are expressed as mean ± standard deviation unless otherwise specificed . body mass index ( bmi ) was calculated as weight in kg divided by the square of height in meters . the mean peak plasma level ( t max ), mean elimination half - life ( t 1 / 2 ), maximal serum concentration ( c max ), and auc ( area under the curve , i . e . total amount of plasma progesterone observed ) derived from the blood samples taken on day 0 of the evaluation are summarized in table v . values are mean ± standard deviation ; a p = 0 . 0472 ; b statistically significant difference of variance , p = 0 . 02 . a single dose of 100 mg micronized progesterone in the form of both gelatin capsules and vaginally administrable tablets in accordance with the present invention resulted in a similar rapid increase in plasma progesterone levels within 2 . 5 - 3 hours after administration . the statistically significant difference of variance between the two groups indicates a more predictable t max for the tablets of the present invention than for the prior art gelatin capsules . it is to be understood that the amounts and proportions of ingredients recited in the foregoing examples are illustrative only , and that these amounts and proportions may be varied within the scope of the invention . for example , the example 1 the amount of effervescent recited is about 8 wt . % of the tablets which are the final product of the process described in example 1 . however , the effervescent may be omitted in the practice of the invention , or it may be included in an amount of up to about 12 wt . % of the tablet . preferably the effervescent constitutes between about 5 - 12 wt . %, more preferably between about 6 - 8 wt . % of the tablet . similarly , progesterone may constitute up to about 20 wt . % of the tablet , preferably between about 6 - 20 wt . %, more preferably between about 8 - 12 wt . % of the tablet . it will be appreciated that various features of the invention which are , for clarity , described in the contexts of separate embodiments may also be provided in combination in a single embodiment . conversely , various features of the invention which are , for brevity , described in the context of a single embodiment may also be provided separately or in any suitable subcombination . it will also be appreciated by persons skilled in the art that the present invention is not limited by what has been particularly shown and described hereinabove . rather the scope of the invention is defined only by the claims which follow :

there is provided a method for preparing a tablet for the vaginal administration of progesterone for systemic use , comprising the steps of : slowly mixing water with micronized progesterone , the total amount of water mixed with said micronized progesterone not exceeding the maximum wetting capacity of the micronized progesterone , whereby to obtain wetted micronized progesterone ; drying said wetted , micronized progesterone to a humidity content of substantially 0 %, whereby to form substantially dry micronized progesterone ; mixing said substantially dry micronized progesterone with other pharmaceutically acceptable excipients or diluents therefor ; and forming a tablet by direct compaction of said substantially dry micronized progesterone which has been mixed with said other pharmaceutically acceptable excipients or diluents therefor . tablets so prepared , as well as a tablet comprising between about 6 to 20 wt . % progesterone and between about 5 to 12 wt . % effervescent , are also provided .

the aforementioned problems with current anti - microbial products for agricultural applications can be solved by the use of compositions and methods according to the present invention . such compositions and methods allow the user to treat both fungal and bacterial pathogens that attack plants and / or the fruits and vegetables produced by such plants . compositions according to the invention are comprised of ( 1 ) hydrogen peroxide , an organic peroxide or a combination thereof ; and ( 2 ) phosphorous acid , mono - and / or di - salts of phosphorous acid or a combination thereof . the organic peroxides that can be used in the inventive compositions include peroxycarboxylic acids and their salts . the mono and / or di - salts of phosphorous acid include alkali metal salts , sodium salts , ammonium salts including mono -, di - and tri - c 1 - 5 alkyl ammonium salts and combination of potassium and sodium salts . mono - and / or di - potassium salts of phosphorous acid are preferred . the amount of hydrogen peroxide , an organic peroxide or a combination thereof can range from about 12 to about 18 % by weight of the composition . the amount of the phosphorous acid , mono - and / or di - salts of phosphorous acid or a combination thereof can range from about 25 to about 30 % by weight of the composition . the compositions according to the invention can also contain additives such as corrosion inhibitors such as hedp ( hydroxyethylidene - 1 , 1 - diphosphonic acid ), chelating agents such as edta , surfactants , and the like . the typical amount of the compositions according to the invention that can be used in the methods described herein can range from 1 : 2 . 5 dilution to about 1 : 1000 dilution rate applied at from about 30 to about 100 gallons of spray solution per treated acre . the optimal amount can vary depending upon crop commodity and disease and can be readily determined by those of ordinary skill in the art . the compositions according to the invention can be applied to a plant by contacting it any means known to those skilled in the art . examples of such methods include , but are not limited to foliar spraying , foliar painting , root injection , tree trunk injection , plant stem injection and in - furrow at the time of planting wherein the composition is applied as a band directly over the seed pieces prior to row closure . typically , spraying is carried out from tractor - mounted sprayers , by crop dusting , through pressurized sprinklers , and through systems such as elevated hoses used to spray grapevines . the term “ contacting ” as used herein means causing the plant , plant root or plant seeds to come into proximity with an exogenous liquid or solid ( such as a powder ) form of a composition according to the invention . the following example is meant to illustrate but not to limit the invention . example : in vitro screening of comp . a against phytophthora infestans , phytophthora erythroseptica and helminthosporium solani . the ingredients of “ comp . a ,” a composition according to the invention , are listed . the entries under the treatments column refer to the relative amounts of comp . a to water . for example , 1 : 17 means 1 part of comp . a to 17 parts of water , etc . p . infestans ( isolate p12010 - 028nb and isolate p12010 - 034pe ), p . erythroseptica ( isolate pe2008 - 152nb and isolate pe364 - 2nb ) and h . solani ( isolate hs2001 pe and isolate hs - pot - 1 - col - 1 - ab ) from the culture collection of potato development centre , wicklow , new brunswick , canada were sub - cultured on rye seed agar ( rsa ), 15 % clarified v8 juice agar or potato dextrose agar ( pda ) ( emd chemicals , inc ., germany ) respectively before the test started . comp . a ; confine ™ ( 45 . 8 % mono - and di - potassium salts of phosphorous acid ) a trademark of agromart company of canada ltd ., thorndale , ontario , canada , and storox ® ( 27 % by weight of hydrogen peroxide ), a registered trademark of biosafe systems llc , were used in the testing below . the trial included eight treatments : [ 1 ] control ; [ 2 ] comp . a 1 : 17 ; [ 3 ] comp . a 1 : 100 ; [ 4 ] comp . a 1 : 300 ; [ 5 ] comp . a 1 : 1000 ; [ 6 ] comp . a 1 : 3000 ; [ 7 ] storox1 : 100 ; and [ 8 ] confine 1 : 17 . p . infestans isolates were cultured on 15 ml of rsa containing comp . a , storox or confine according to the above ratios . isolates of p . erythroseptica and h . solani were cultured on similarly amended v8 agar or pda plates , respectively . the plates were inoculated with agar plugs of 5 mm diameter fungal cultures obtained from growing edges of each isolate . all plates were sealed using parafilm before incubation . six replicates ( plates ) were employed for each treatment and were incubated at 22 ec under normal light and dark regimen . two perpendicular measurements along the radial mycelial growth of the pathogens were taken until the respective control plates reached the edge of the plates . however , the measurement with relation to h . solani growth was terminated in advance due to the normal slower growth rate of this pathogen . statistical analyses : analysis of variance ( anova ) was used to separate means according to lsd ( 0 . 05 ) using costat ( cohort software , monterey , calif ., usa ) and the treatment means were compared using lsd test at p & lt ; 0 . 05 . tables 1 and 2 demonstrate the dynamics of in vitro growth of two isolates of p . erythroseptica ( isolate pe2008 - 152nb and isolate pe364 - 2nb respectively ) on clarified v - 8 agar amended with comp . a at different ratios . two isolates were completely inhibited by comp . a at 1 : 300 and higher concentrations such as 1 : 100 and 1 : 17 . comp . a was not inhibitive for both isolates at 1 : 1000 and higher dilutions such as 1 : 3000 . tables 3 and 4 demonstrate the in vitro growth of two isolates of p . infestans ( isolate p12010 - 028nb and isolate p12010 - 034pe respectively ) on rsa amended with comp . a at different ratios . none of the used concentration of comp . a in rsa was favorable for the growth of both p . infestans isolates . tables 5 and 6 show the in vitro growth of two isolates of h . solani ( isolate hs2001pe and isolate hs - pol - 1 - col - 1 - ab , respectively ) on pda amended with comp . a at different ratios . as the growth of the two isolates on pda was too slow , but comparable , we were compelled to finalize the results in advance . according to the results , comp . a at 1 : 17 was completely inhibitive for both of the h . solani isolates , which is comparable to the inhibition due to confine at 1 : 17 or storox at 1 : 100 . comp . a at dilutions over 1 : 17 such as 1 : 100 was completely inhibitive to both of the h . solani isolates up to 22 days . however , thereafter h . solani ( isolate hs2001 pei and isolate hs - pol - 1 - col - 1 - ab ) started growing slowly , although the inhibition at the end of the assessment was 80 . 2 % and 40 . 6 % respectively . similarly , comp . a at 1 : 300 in agar inhibited the in vitro growth of h . solani ( isolate hs2001 pei and isolate hs - pol - 1 - col - 1 - ab respectively ) by 21 . 2 % and 2 . 2 %, respectively . * calculated based on measurements taken after 5 days . values with different letters in columns are significantly different from each other according to the lsd at p ≧ 0 . 05 . * calculated based on measurements taken after 5 days . values with different letters in columns are significantly different from each other according to the lsd at p ≧ 0 . 05 . * calculated based on measurements taken after 22 days . values with different letters in columns are significantly different from each other according to the lsd at p ≧ 0 . 05 . * calculated based on measurements taken after 22 days . values with different letters in columns are significantly different from each other according to the lsd at p ≧ 0 . 05 . * calculated based on measurements taken after 36 days . values with different letters in columns are significantly different from each other according to the lsd at p ≧ 0 . 05 . * calculated based on measurements taken after 36 days . values with different letters in columns are significantly different from each other according to the lsd at p ≧ 0 . 05 .

compositions comprising an effective amount of hydrogen peroxide , an organic peroxide or a combination thereof ; and phosphorous acid , mono - and / or di - salts of phosphorous acid or a combination thereof are effective in preventing or controlling diseases in plants caused by pathogens . the disclosed compositions can be used by contacting a plant with an effective amount of such compositions .

the preferred embodiment of the present invention is illustrated in various stages of construction in fig1 through 4 . a bag 10 is manufactured from a rectangular sheet 12 of thin , flexible material shown best in fig1 which material in the preferred embodiment is a clear plastic such as polyethylene , ethylene - vinyl acetate ( eva ), or polypropylene . the sheet 12 is of a width sufficient to easily accommodate the portable miniature infusion pump ( fig5 - 7 ) or other device to be secured within the bag 10 . typically , the sheet 12 is approximately 4 - 8 inches wide . the sheet 12 of thin material will be folded across two major fold lines extending across the narrow width of the sheet 12 , the first being line a -- a near the bottom of the sheet 12 and the second being line b -- b above the middle of the sheet 12 . the portion of the sheet 12 below line a -- a is a flap 14 , which flap 14 is folded across the line a -- a shown in fig1 against the sheet 12 , as shown in fig2 . by folding the top edge of the flap 14 against the sheet 12 , a pouch 18 ( best shown in fig3 ) is created therebetween . the flap 14 is of a height sufficient to protect a pump ( fig5 - 7 ) or other device contained in the pouch 18 by preventing water entering over the top edge 15 of the flap 14 and into the pouch 18 . typically , the flap 14 is 1 - 4 inches high . the other edge 16 of the sheet 12 , which is on the end of the sheet 12 away from the flap 14 , is then folded down across line b -- b of fig2 to form the folded shape bag 10 illustrated in fig3 . when folded , the edge 16 of the sheet 12 preferably extends nearly to the bottom of the pouch 18 formed in the folded shape bag 10 , as shown in fig3 although it is certainly possible for the edge 16 of the sheet 12 to extend beyond the bottom of the pouch 18 . it is necessary for the edge 16 of the sheet 12 to extend well past the top edge 15 of the flap 14 to provide a water - resistant closure for the pouch 18 . the pouch 18 , which as thus far described is bounded by the fold a -- a ( fig1 ) on the bottom , is bounded on the top by a seam c -- c formed between the portion of the sheet 12 between folds a -- a and b -- b and the portion of the sheet 12 folded over across line b -- b . it is preferable that the pouch 18 extend sufficiently above the top edge 15 of the flap 14 toward the seam c -- c to allow the pump ( shown in fig5 - 7 ) or other device to be inserted into the pouch 18 from between the edge 16 of the sheet 12 and the top edge 15 of the flap 14 . such a pouch 18 would , for example , be approximately 2 - 8 inches high . the seam c -- c extends across the width of the bag 12 , and thereby below the seam c -- c defines the pouch 18 and above the seam c -- c defines the portion of the bag 12 which will be made into a strap ( to be discussed more fully below ). the seam c -- c is preferable a heat - sealed seam , the making of which is well known in the art . instead of a heat - sealed seam , however , an adhesive seam or an ultrasonic seam could also be utilized . the only limitation is that the seam c -- c must be both durable and waterproof . at this time , the adhesive means to seal the pouch 18 may be installed . in the preferred embodiment shown in fig3 a strip of tape 20 is used to provide the seal . the strip of tape 20 has an adhesive surface 22 along approximately two - thirds of the width thereof . the additional third of the width of the tape 20 does not have an adhesive applied thereto , and is therefore not sticky . part of the adhesive surface 22 of the tape 20 is secured along the outside surface of the edge 16 of the sheet 12 , with a portion of the adhesive surface 22 of the tape 20 extending downwardly over the edge 16 of the sheet 12 . it will therefore be appreciated that a portion of the adhesive surface 22 extends downwardly beyond the edge 16 of the sheet 12 , and faces the outside surface of the flap 14 near the bottom thereof . this portion of the adhesive surface 22 is used to secure to pouch 18 in water - resistant fashion . in the process of constructing the bag 10 , the portion of the adhesive surface 22 extending beyond the end 16 is fastened to the flap 14 , and the bag 10 will be essentially flat . it should be noted that the tape 20 may have more or less than two - thirds of its width coated with the adhesive surface 22 , since the two - thirds figure is used as an example only . referring now to fig4 two additional seams are formed on the bag 10 of fig4 at the long sides thereof , these seams being seam d -- d on one side and seam e -- e on the other side . the portions of these seams d -- d and e -- e below the seam c -- c complete the construction of the water - resistant interior of the bag 10 , as defined by the pouch 18 , and the end 16 . the seams d -- d and e -- e may be made in the same manner as the seam c -- c . it may be noted that it is not necessary to extend the seam d -- d and e -- e above the seam c -- c , but that to do so is a manufacturing expedient . it will be appreciated that the orientation of the bag 10 in operation will be in the orientation shown in fig3 namely with the pouch 18 extending in a downwardly direction . since water from a showerhead , or from rain , falls essentially downwardly , it is apparent that water will not be permitted into the pouch 18 . the bag 10 may not be submersible , but submersion of the bag 10 is neither a design requirement nor a feature necessary to most infusion pump users . the construction of the bag 10 is completed by perforating or otherwise partially cutting the portion of the bag 10 above the seam c -- c , which portion is generally indicated as 30 , to facilitate use of this portion 30 of the bag 10 as a strap 32 when the perforated areas are opened . ( the strap 32 is shown in fig7 in an opened position ). it will be appreciated that since the bag 10 is folded over at the top thereof , the portion 30 is two layers thick . fig5 - 7 illustrate the installation of a portable miniature infusion pump 40 into the bag 10 . referring first to fig5 the portion of the tape 20 not having adhesive 22 thereon may be pulled to open the bag 10 , whereupon the end 16 is pulled apart from the flap 14 to provide access to the pouch 18 . as shown in fig5 the bag 12 is held upside down to facilitate opening the bag 12 . the pump 40 is dropped into the pouch 18 in a sideways position as illustrated . note that there must be sufficient room inside the bag 10 to allow the pump to fit between the seam c -- c ( fig3 - 4 ) and the edge 15 of the fold 14 , to allow the pump 40 to fit into the pouch 18 . the bag 10 is still held in an inverted position in fig6 and the bag 10 may be closed by pulling on the sides of the bag 10 near the bottom as shown . note that an infusion set 42 extends from the bag 10 , but that the adhesive surface 22 ( fig3 ) of the tape 20 will seal around the infusion set 42 . the user will then run his or her fingers along the tape 22 to tightly seal the bag 10 . referring now to fig7 the bag 10 may be returned to right side up , and the pump 40 will fall into the pouch 18 . it is important that the pump 40 fit inside the pouch 18 ( inside the flap 14 ) for proper water resistance . the perforated area 30 may be opened to form the strap 32 , which strap 32 is sized as desired to fit around the user &# 39 ; s neck ( or shoulder ), as well as on a hook or over a showerhead . typically the length of the strap will be 20 - 45 inches , depending on where the bag 10 is to be worn or installed . it will be apparent to those skilled in the art that a variety of design differences may be made in the present invention . two such differences in the method used to achieve an adhesive seal are illustrated in fig8 and 9 . referring first to fig8 a length of two sided tape 50 is used instead of the tape 20 shown in fig3 . the two sided tape 50 is preferably secured to the side of the edge 16 facing the flap 14 with an adhesive surface facing the flap 14 . it would be just as possible to install the tape 50 on the flap instead of on the edge 16 . similarly , in fig9 an adhesive material 60 is shown applied to the side of the edge 16 facing the flap 14 . the adhesive material could also be located on the flap 14 instead of on the edge 16 . another possible modification would be to form all the seams ( c -- c , d -- d , and e -- e ) before installation of the tape 20 . the tape would then be applied to the edge 16 after the bag 10 is otherwise completed . this in no way departs from the present invention . the bag 10 is preferably made of a clear material to allow the user to monitor the operation of the pump 40 and view any displays thereon ( not shown ). the tape 20 in fig3 may also be provided with a colored surface in the areas of the tape 20 not treated with the adhesive surface 22 . this will indicate to the user where to pull the tape 20 to open the bag 10 . likewise , in the embodiments shown in fig8 and 9 , a colored surface could be provided along the edge 16 . it will be appreciated that the present invention teaches the construction of a protective bag 10 which may be used to safeguard an infusion pump 40 from water in a shower or in the rain ( or just as easily to protect other water sensitive electronic devices , including portable radios , tape players , and cameras ). the pouch 18 is secure , and since the pump 40 is within the pouch 18 on the inside of the flap 14 , no strain is put on the tape 20 which might inadvertently open the bag 10 . the bag 10 may be economically constructed , and of a disposable nature . a display on the pump 40 in the bag 10 may be seen through the bag 10 if it is constructed of clear material . the water resistance of the bag 10 of the present invention is quite good , and the bag 10 thus presents substantial advantage without presenting any relative disadvantage . although an exemplary embodiment of the present invention has been shown and described , it will be apparent to those having ordinary skill in the art that a number of changes , modifications , or alterations to the invention as described herein may be made , none of which depart from the spirit of the present invention . all such changes , modifications , and alterations should therefore be seen as within the scope of the present invention .

an enclosure for use to safely secure a water - sensitive medical or electronic device such as a medication infusion pump in a water - resistant manner is disclosed which utilizes a pouch made of a sheet of thin plastic material to store the apparatus , the pouch being adhesively sealable to secure the device . the enclosure also includes a perforated area which may be opened to form a strap to carry or hang the device , and is constructed inexpensively to be of a disposable nature .

referring to fig1 and 2 , an electronic coin bank in accordance with a first embodiment of the present invention comprises a coin bank 10 , a coin - throwing device 20 ( not shown ) and a circuit structure 30 ( not shown ). the coin bank 10 is provided for collecting coins 40 ( not shown ), an upper surface of the coin bank 10 is defined with a hole 11 , a displaying panel 12 and a plurality of setting buttons 13 are disposed adjacent to the hole 11 , and the bottom of the coin bank 10 is formed with a hole 141 ( not shown ) having a cover 14 , a battery container 15 and a transmission hole 16 . the coin - throwing device 20 ( not shown ) and the circuit structure 30 ( not shown ) are mounted in the coin bank 10 that are located correspondingly to the hole 11 , and the coin - throwing device 20 is electrically connected to the circuit structure 30 , such that the circuit structure 30 can receive the signals of the coin - throwing device 20 . the displaying panel 12 and the setting buttons 13 of the coin bank 10 are electrically connected to the circuit structure 30 so as to show the set functions and the operation of the set functions of the circuit structure 30 , and the battery container 15 is provided for supplying power to the circuit structure 30 . the cover 14 is electrically connected to the circuit structure 30 , so that when the user opens the cover 14 to take the coins 40 of the coin bank 10 out of the hole 141 , part of the functions will return to zero ( described in detail later ). the transmission hole 16 of the coin bank 10 is electrically connected to a transmission connector 34 provided by the circuit structure 30 , such that the user can communicate with the computer by means of substantial transmission lines or wireless transmission ( such as infrared ray , wireless electric wave and bluetooth ). by such arrangements , the user can program and manage the coins stored in the coin bank 10 and show the value of each coin 40 by the finance - managing software installed in the computer and compatible with the circuit structure 30 of the coin bank 10 . with reference to fig3 , one side of the coin - throwing device 20 is repeatedly disposed with a circuit structure 30 and is provided for measuring and throwing the coin 40 ( not shown ), and the coin - throwing device 20 includes a front and a rear plates 21 , a left and a right sliding blocks 22 , a sensing assembly 23 and an elastic element 24 . the front and rear plates 21 are combined to form a coin - entering hole 211 located correspondingly to the hole 11 of the coin bank 10 , and both sides of the plate 21 are disposed with a sliding block 22 that can moved outward . between the front and the rear plates 21 is formed two protruded points 221 that are located correspondingly to each other , and the distance between the protruded points 221 is smaller than the outer diameter of the smallest coin 40 . at least one outer side of the plate 21 is disposed with one elastic element 24 , and since both ends of the elastic element 24 are combined to the sides of the sliding blocks 22 , the sliding blocks 22 can be repositioned after being moved outward which is equal to one surface of the elastic element 24 . the bottom of the sliding block 22 is disposed with the sensing assembly 23 having an electronic brush connecting foot 231 and a brush piece 232 , the electronic brush connecting foot 231 is combined to one sliding block 22 , and the brush piece 232 is combined to another sliding block 22 . the electronic brush connecting foot 231 and the brush piece 232 are made of metal and are electrically connected to the circuit structure 30 , thus forming the structure of the coin - throwing device 20 . referring to fig4 and 5 , when the coin - throwing device 20 is in a normal condition , the distance between the protruded points of the sliding blocks 22 is smaller than the outer diameter of the smallest coin 40 ( as shown in fig4 ). when the coin 40 is thrown into the hole 11 of the coin bank 10 and via the coin - entering hole 211 of the coin - throwing device 20 , the sliding blocks 22 will be moved outward by the biggest outer diameter of the coin 40 . when the distance between the protruded points 221 of the sliding blocks 22 is the same as the biggest outer diameter of the coin 40 , it is the biggest moving distance of the sliding blocks 22 . the sliding blocks 22 are not moved equally , with respect to the change of the reinforcing point when throwing the coin 40 , so the total distance of the moving distance of the sliding blocks 22 and the distance between the sliding blocks 22 in the normal condition is the moving distance of the sliding blocks 22 . at that time , by the connecting method of the electronic brush connecting foot 231 and the brush piece 232 , and according to the actual moving distance of the sliding blocks 22 , the circuit structure 30 will receive a signal . when the coin 40 is thrown into the coin bank 10 via the coin - throwing device 20 , by the function of repositioning simultaneously of the sliding blocks 22 and the sensing assembly 23 by the elastic element 24 , the coin can be thrown and measured to fix the value of the coin 40 . with reference to fig6 , an electronic coin bank in accordance with a second embodiment of the present invention is shown , wherein one side of the coin - throwing device 20 is disposed with the circuit structure 30 , and the position and the shape of the sensing assembly 23 of the coin - throwing device 20 of fig6 is different from that of fig4 and 5 . the sensing assembly 23 is disposed at the side of the bottom of the sliding blocks 22 relative to the surface of the circuit structure 30 , and having two electronic brush connecting feet 231 and a brush piece 232 , the electronic brush connecting feet 231 are combined to the sliding blocks 22 respectively , and the brush piece 232 is combined to the surface of the circuit structure 30 . the electronic brush connecting feet 231 and the brush piece 232 are made of metal and are electrically connected to the circuit structure 30 , thus forming the structure of the coin - throwing device 20 . referring to fig7 and 8 , an electronic coin bank in accordance with a third embodiment of the present invention is shown , when the coin - throwing device 20 is in a normal condition , the distance between the protruded points of the sliding blocks 22 is smaller than the outer diameter of the smallest coin 40 ( as shown in fig7 ). when the coin 40 is thrown into the hole 11 of the coin bank 10 and via the coin - entering hole 211 of the coin - throwing device 20 , the sliding blocks 22 will be moved outward by the biggest outer diameter of the coin 4 . the sliding blocks 22 are not moved equally , with respect to the change of the reinforcing point when throwing the coin 40 , so the total distance of the moving distance of the sliding blocks 22 and the distance between the sliding blocks 22 in the normal condition is the actual moving distance of the sliding blocks 22 . at that time , by the connecting method of the electronic brush connecting foot 231 and the brush piece 232 , and according to the moving distance of the sliding blocks 22 , the circuit structure 30 will receive a signal . referring to fig9 , an electronic coin bank in accordance with a fourth embodiment of the present invention is shown , wherein one side of the coin - throwing device 20 is disposed with the circuit structure 30 , and the position and the shape of the sensing assembly 23 of the coin - throwing device 20 of fig9 is different from that of fig4 - 8 . the sensing assembly 23 is disposed at the bottom of the sliding blocks 22 correspondingly to a lower portion of the plate 21 and the relative surface of the circuit structure 30 , and having a raster plate 231 ′ and infrared rays 232 ′ that combined to the surface of the circuit structure 30 . the infrared rays 232 ′ are electrically connected to the circuit structure 30 , thus forming the structure of the coin - throwing device 20 . referring to fig1 and 11 , an electronic coin bank in accordance with a fifth embodiment of the present invention is shown , when the coin - throwing device 20 is in a normal condition , the distance between the protruded points of the sliding blocks 22 is smaller than the outer diameter of the smallest coin 40 ( as shown in fig7 ). when the coin 40 is thrown into the hole 11 of the coin bank 10 and via the coin - entering hole 211 of the coin - throwing device 20 , the sliding blocks 22 will be moved outward by the biggest outer diameter of the coin 4 . the sliding blocks 22 are not moved equally , with respect to the change of the reinforcing point when throwing the coin 40 , so the total distance of the moving distance of the sliding blocks 22 and the distance between the sliding blocks 22 in the normal condition is the actual moving distance of the sliding blocks 22 . at that time , by the raster plate 231 ′ and the infrared rays 232 ′ combined to the circuit structure 30 to form the pulse of the infrared rays 232 ′ by the simultaneous moving of the sliding blocks 22 , and according to the pulse times to obtain the diameter of the coin 40 , and transmit a signal to the circuit structure 30 . referring further to fig2 , 12 and 13 , wherein a memory 31 of the circuit structure 30 is stored with plural values correspondingly to the diameters of the coins and the forms of sound effects ( for example , 19 . 05 mm = one cent / 21 . 21 mm = five cents / 17 . 91 mm = one dime / 24 . 26 mm = quarter dollar / 30 . 61 mm = half dollar / 26 . 50 mm = one dollar ). if there is no setting , the diameters of the coins are unable to distinguish . the displaying panel 12 is provided for showing the saving values or amounts 121 , the saving progress 122 , value displaying lights 123 and time 124 via a microprocessor 32 . the setting buttons 13 includes goal setting 131 , goal adjusting 132 , saving content 133 , time setting 134 , hour setting 135 and minute setting 136 . when the circuit structure 30 is operated , there are five conditions : saving counting ( normal mode ), saving goal setting , time setting , alarm clock setting and saving content inquiry . with regard to the condition of saving goal setting , when the user presses the goal setting 131 of the setting button 13 , the lights 123 of the system will be lighted from the second light from upper to lower , and the number of the saving values or the amounts 121 will be glittered . when the user presses the button of the goal adjusting 132 , the microprocessor 32 will receive the signals from the goal setting 131 and the goal adjusting 132 , and the progression of a suitable value ( such as 1000 or 2000 ) serves as a saving goal and shows on the column of the saving values or the amounts 121 of the displaying panel 12 . when reaching the required value , the user presses the button of the goal setting 131 again to send a signal to the microprocessor 32 , and one saving goal will be stored in the memory 31 when the number of the column of the saving values or the amounts 121 are not glittered . the biggest value of the saving goal is usd500 , and then returned to zero . when entering the condition of saving goal setting , if there has no input information and exceeded the suitable time , the system will return to the condition of saving counting ( normal mode ). with regard to the condition of saving counting , when the user throws the coins of one cent , five cents , one dime , quarter dollar , half dollar or one dollar via the coin - throwing device 20 , the coin - throwing device 20 will send a signal to the microprocessor 32 , and the microprocessor 32 will show the value of the coin by the diameter of the coin obtained from the signal corresponded to that of the memory 31 on the column of the time 124 of the displaying panel 12 . furthermore , the microprocessor 32 will add up the present values and show on the fields of the saving values or the amounts 121 of the displaying panel 12 , store the accumulation of several values in the memory 31 , and broadcast the music via a loudspeaker 33 by intercepting the corresponding form of the sound effects in the memory 31 . at the same time , the displaying panel 12 will produce glittering effects . when the saving value reaches one - fifth of the set saving goal , the microprocessor 32 will send a signal to the displaying panel 12 and a first light of the column of the saving progress 122 of the displaying panel 12 will glitter , and will broadcast the music via the loudspeaker 33 by intercepting the corresponding form of the sound effects in the memory 31 . at the same time , the displaying panel 12 will produce glittering effects , and a second light and a third light will glitter and broadcast the corresponding music orderly in turns . referring to the condition of saving counting , the displaying panel 12 will show the time on the column of the time 124 ( the value of the coin will be showed only when the user throws the coin ), the fields of the saving values or the amounts 121 will show the accumulated total of the present savings , and the saving progress 122 will show the reached condition of the saving goal . referring to saving content inquiry , when the user presses the button of the saving content 133 of the setting buttons 13 , the lights 123 of the system will be lighted from the first light from upper to lower , and the microprocessor 32 will receive a signal . at the same time , the column of the saving values and the amounts 121 of the displaying panel 12 will show the amount of the copper coin of one cent , and the field of the time 124 of the displaying panel 12 will show 00 : 01 . when the user presses the button of the saving content 133 of the setting buttons 13 again , the column of the saving values and the amounts 121 will show the amount of the copper coin of five cents , and the field of the time 124 of the displaying panel 12 will show 00 : 05 . after a suitable time , if the system didn &# 39 ; t implement those functions , the system will return to the normal mode of the saving counting . referring to the condition of time setting , when the user presses the button of the time setting 134 of the setting buttons 13 , the lights 123 of the system will be lighted from the third light from upper to lower , and choose the button of the hour setting 135 or minute setting 136 . at that time , the microprocessor 32 will receive a signal , and the number of the chosen button of the hour setting 135 or minute setting 136 will be showed on the fields of the time 124 of the displaying panel 12 . then presses the button of the hour setting 135 or minute setting 136 to adjust the time , and then presses the button of the time setting 134 again , the microprocessor 32 will receive the set signal . referring to the condition of alarm clock setting , after the condition of time setting , the system will enter the condition of alarm clock setting automatically , and the lights 123 of the system will be lighted from the fourth light from upper to lower . and chooses the button of the hour setting 135 or minute setting 136 , at that time , the microprocessor 32 will receive a signal , and the number of the chosen button of the hour setting 135 or minute setting 136 will be showed on the fields of the time 124 of the displaying panel 12 . then presses the button of the hour setting 135 or minute setting 136 again to adjust the time , and then presses the button of the time setting 134 again , the microprocessor 32 will receive the set signal and enter the condition of setting the music of the alarm clock . at that time , the microprocessor 32 will intercept and broadcast the stored form of the sound effects in the memory 31 , and adjust the music by the button of the hour setting 135 or minute setting 136 . then presses the button of the time setting again , the microprocessor 32 will receive the signal and return to the normal mode of the condition of saving counting . when the voltage is insufficient , the microprocessor 32 will send a warning information , namely , the columns of the saving values , the amounts 121 and the saving progress 122 will be glittered continuously , and when changing the battery , the microprocessor 32 will store all the data in the memory 31 . when the user opens the cover 14 of the coin bank 10 , the microprocessor 32 will receive a signal , namely , all the data except the time setting will return to zero , and the thrown coins must be set again . when the transmission hole 16 of the coin bank 10 is electrically connected to the transmission connector 34 of the circuit structure 30 , the user can communicate with the computer by means of substantial transmission lines or wireless transmission ( such as infrared ray , wireless electric wave and bluetooth ). by such arrangements , the user can program and manage the coins stored in the coin bank 10 and show the value of each coin 40 by the finance - managing software installed in the computer and compatible with the circuit structure 30 of the coin bank 10 . in addition , the above - mentioned form of sound effects of the circuit structure 30 can be stored by music ic 35 , and the music will be broadcasted by the loudspeaker 33 via the music return route by the microprocessor 32 . one of the sliding blocks 22 of the coin - throwing device 20 can be fixed to one side of the front and rear plates 21 , and the other sliding block 22 can be moved outward , and the moving distance of the other sliding block 22 plus the distance formed in the normal condition is the actual moving distance of the other sliding block 22 . while we have shown and described various embodiments in accordance with the present invention , it should be clear to those skilled in the art that further embodiments may be made without departing from the scope of the present invention .

an electronic coin bank comprises a coin bank , a coin - throwing device and a circuit structure , which changed the single function of saving money of a conventional coin bank into an electronic coin bank , wherein a coin - throwing device is provided for setting the values of the coins and throwing the coins , a circuit structure is provided for setting the stored values , the preparedly stored values , the saving progress , the rewarding music , time and alarm clock , and a transmission connector is connected to a computer . since the diversifying of the functions and by using the finance - managing software installed in the computer , the children will form a good habit of saving .

fig1 depicts a prior art snowboard 100 designed to support the weight of a person and to enable motion on snow . the snowboard 100 contains at least one rigid element , wherein each rigid element has an upper surface ( not shown ), a lower surface 203 and one or more stiffened peripheral edges 101 ( a ) and ( b ). edges 101 ( a ) and ( b ) are located on left and right ends and , in some embodiments , may line the entire periphery of the system . edges 101 may be made of metal , alloy or any other suitable material . fig2 depicts a cross - sectional detail of the prior art snowboard of fig1 . the snowboard 100 has an upper surface 201 , a lower surface 203 , and a plurality of inner - layers 202 positioned between the upper surface 201 and lower surface 203 . edges 101 ( a ) and ( b ) are located on left and right ends , respectively . the lower surface 203 rests on the snow surface 204 . the downward force 206 is transferred through the system 100 and is balanced by the normal force 207 . upper surface 201 may be made of a glossy material , which serves as a medium to place graphic designs and also a uv protectant layer . lower surface 203 is typically a polyethylene and serves to reduce friction between the bottom of the system and the surface of travel . inner - layers 202 are made of hardwood placed in between layers of fiberglass . during operation , the snowboard 100 reaches a physical equilibrium state wherein the normal force 207 is equal to downward force 206 . the downward force 206 is determined , in part , by weight of the person on the snowboard 100 . the normal force 207 is distributed across the snow 204 on an area snow - to - board contact ( not shown ), which is determined , in part , by the width of snow - to - board contact 205 . for the prior art snowboard , the width of contact 205 remains constant even as the downward force 206 increases . fig3 depicts one embodiment of the snowboards described herein . specifically , fig3 depicts the lower surface of a snowboard having two rails separated by a recess . as shown , the snowboard 300 has an upper surface ( not shown ), a lower surface 305 , and one or more stiffened peripheral edges 304 ( a ) and ( b ), which are located on the left side and right side of the board , respectively . the peripheral edges 304 a and 304 b may form a single edge that surround the full periphery of the snowboard 300 . alternatively , in other embodiments , the edges 304 a and 304 b are separate edges on opposing longitudinal sides of the board . the lower surface 305 is continuous across the rails 301 and a recessed region 302 is arranged between the two rails 301 a and 301 b . in some embodiments , the board is laminated from a series of layers . typically the layers are wood , fiberglass and / or plastic , although other materials may be employed . these form the inner structure of the snowboard 300 and the inner layers ( not shown ) may be contoured in a shape that is similar to that of the lower surface 305 . in other embodiments , the inner layers ( not shown ) may be formed as a generally flat board and the rails 301 may be distinct components of the system that are attached separately to the lower surface 305 . in either case , the contour of the lower surface 305 may be similar . when in use , the system makes contact with the snow across the width of contact 306 . the dimensions of the snowboard 305 may vary , and typically will be between 90 - 170 cm in length as measured along a longitudinal axis extending along the length of the snowboard 305 and between 20 - 30 cm in width as measured along a beam axis extending perpendicular to the longitudinal axis . the snowboard 305 has a generally hourglass shape , with curved lateral sides . typically , both the front end and the back end are curved upward to lift the ends of the snowboard off the surface of eh snow when the lower surface 305 is placed on the snow surface . other dimensions and shapes may be used without departing from the scope of the invention . fig4 depicts a cross - sectional detail of one embodiment of the snowboards described herein . according to one embodiment , system 300 has an upper surface 401 and a lower surface 305 . the lower surface 305 is continuous across the left rail 301 ( a ), the recessed region 302 and the right rail 301 ( b ). stiffened peripheral edge 304 ( a ) and edge 304 ( b ) are located at the left end and right ends , respectively . the downward force 406 is determined , in part , by weight of the person using the snowboard . the normal force 407 is distributed across the snow 404 on an area snow - to - board contact ( not shown ), which is determined , in part , by the width of snow - to - board contact 305 . as the downward force 406 increases , the width of contact 305 may also increase . likewise , as the downward force 406 decreases , the width of contact 305 may also decrease . in operation , the snowboards described herein adjust to varying snow conditions . in soft snow , the board sinks lower in the snow thereby increasing the width of contact 306 , which increases the normal force supporting the rider . in some soft snow conditions , the width of contact 306 may be large enough to include the entire width of the lower surface 305 , including the surface area of rails 301 and the recessed region 302 . in hard snow , the snowboard may rise toward the top of the surface and thereby decrease the area of contact 306 . in some hard snow conditions , the width of contact 306 may be small and may only include the peak of rails 301 ( a ) and ( b ) and not the surface of the recessed region 302 . for conditions in between the soft and hard , the amount of board - to - snow contact varies as needed , such that the downward force 406 is equal to the normal force 407 . turning to fig3 and 4 , the rails 301 run the length of the board . thus , the length of contact is not altered relative to the conventional design but the width of contact is decreased . by keeping the length of contact between the system and the snow constant , and by decreasing the width of contact between the system and the snow , the claimed system is able to attain higher speeds on snow than a conventional system . not to be bound by theory , but the snowboard having the two rails on the bottom surface , may be faster than a conventional snowboard . for the same physical principles that a pair of skis is faster than a standard snowboard of the same length , and a catamaran is faster than a mono - hull boat of the same length . also depicted in fig4 , the twin rails 301 , may optionally not be rectangular in shape . instead , they maybe angled upwards from the peak of the rail towards the periphery of the board . thus , the rails have a tapered surface that progresses from the interior of the board to the peripheral edge . this design feature raises the edges 304 up above the snow when the operator is initiating a turn while operating the snowboard . the raised edges allow the user to travel on width of contact 306 , without fear of unintentionally catching an edge . the result is increased comfort and , in part , safety and stability at high speeds . to initiate a carving turn , the rider must rotate the claimed system slightly further than the conventional system , ensuring that any edge - to - snow contact is intentional . fig5 depicts the snowboard of fig3 and 4 placed on a snow surface that is less firm and compact than the snow surface of fig4 . specifically , fig5 illustrates the snowboard 300 disposed over a snow surface 404 . a force 406 , typically the weight of the rider , pushes the snowboard 300 against the snow surface 404 . in the conditions represented by fig5 , the rails 301 ( a ) and 301 ( b ) press more deeply into the snow surface 404 than under the conditions depicted by fig4 . the areas of contact 306 ( c ) and 306 ( d ) of the rails 301 ( a ) and 301 ( b ) against the snow 404 are larger than the areas of contract 306 ( a ) and 306 ( b ) depicted in fig4 . in still less firm conditions , the snow 404 may contact the recessed region 302 and press against the snowboard 302 , at the rails 301 ( a ) and 301 ( b ) and at the recessed regions . fig6 depicts the lower surface 305 of the snowboard 300 and partially depicts binders and boots of a rider . as shown , the binders or bindings grip the rider &# 39 ; s boot and hold the boot on the upper surface of the snowboard 300 . the binding is arranged to position the heel of the boot 602 over one rail 301 b and a toe of the boot ( not shown ) over a different rail 301 a . to turn , the rider can lean forward or back to tip the snowboard 300 onto an edge 304 to carve a turn into the snow . the manufacture of the disclosed snowboard may be accomplished employing methods that are familiar to those skilled in the art . for example , the layers of the disclosed snowboard may be constructed , in part , using a mold , which is designed having a shape consistent with the contours of the claimed system . other example manufacturing methods may have an expandable bladder , placed in an enclosure with the layers of the system and the mold . as the bladder expands , it applies pressure to the layers , forcing them against the mold and imparting the contours of the mold . in some embodiments of a manufacturing system struts , made of wood , are used to help distribute the pressure from the bladder to the layers of the system . in other embodiments of a manufacturing method , the layers of the system may be pressed together using a pneumatic press , which applies pressure to the layers , forcing them against the opposing surface of the press and imparting the contours of the claimed system . in other embodiments , the layers of the system are attached to one another using adhesives , epoxy , or other suitable attachment systems . those skilled in the art will know or be able to ascertain using no more than routine experimentation , many equivalents to the embodiments and practices described herein . for example , the claimed system and the knowledge disclosed herein may be utilized to modify or to create systems designed to carry a person or objects across a surface of water , sand , or other materials . more specific example applications may include , among other things , snowboards , water skis , wake boards , kayaks , winder surfers , or paddle boards . accordingly , it will be understood that the invention is not to be limited to the embodiments disclosed herein , but is to be understood from the following claims , which are to be interpreted as broadly as allowed under the law .

the disclosure herein is directed toward systems and methods for supporting a person and enabling motion of a person across a surface of snow can while satisfying the countervailing requirements of increasing surface area for weight - carrying capacity on soft snow and reducing the opposing forces , like for example drag and friction , in hard snow . more specifically , a snowboard with improved rider support , increased speed and enhanced safety performance .

fig1 shows a golf club 101 having a shaft 113 extending from grip 107 to head 117 . while depicted in fig1 as a driver , any style of club is suitable for use with a grip 107 of the invention . golf club 101 may be a driver , hybrid , wood , iron , wedge , or putter and may be described with a name such as a mashie or niblick . grip 107 can be made from any suitable material and method . fig2 gives a top - perspective view of the golf club 101 , showing head 117 connected to shaft 113 extending to grip 107 . grip 107 may generally have an elongated shape , preferably slightly tapered on the outside . grip 107 may be substantially cylindrical and tapered , or may have a pistol - grip , handlebar - grip , or blade - like shape . for example , where the invention provides a putter grip with a housing , the grip can be tubular , tapered , a paddle style ( with a flat area for the thumbs ), a pistol style ( with a protruding area ), or any other style known in the art . grip 107 may be substantially evenly round or have a reminder ( i . e ., a line or rib on the grip that reminds the golfer where the hand should be placed ). grip 107 may be described as having a sleeve member with a gripping surface . one end of the sleeve is open to fit over the shaft of a golf club . the other end may be open , formed into a cap , or have another structure . generally , grip 107 will have an internal bore to complement shaft 113 . the maximum length of the grip may generally be between about 20 cm and about 45 cm , e . g ., between about 23 cm and about 31 cm . generally , the grip may have a mass between about 5 grams and about 100 grams , e . g ., between about 20 grams and about 70 grams . in some embodiments , grip 107 has a mass between about 45 grams and about 55 grams . for example , grip 107 may have a mass between about 40 grams and about 55 grams , or between about 15 grams and about 70 grams ( e . g ., between about 44 grams and about 53 grams ). in certain embodiments , the mass is between about 48 grams and about 52 grams . grip 107 can be made with rubber , cotton , synthetic materials , leather , or a composite . it can be formed monolithically ( i . e ., all of one piece of one material ) or as an assemblage . grip 107 can formed by injection molding , compression molding , or co - molding . natural rubber , synthetic rubber and compound materials can be used alone or in conjunction with a number of cord and surface configurations to offer a certain tactile , softness or gripping characteristics . a grip of the invention can be made with cord made of cotton , and grips can be half or full corded . rubber grips can be made from a blend of liquid rubber and granulated cork , optionally pressure molded , sanded , or painted . grips can be made of plastics or polymer materials such as , for example , ethylene propylene diene monomer ( epdm ). grips can be made to include materials such as cowhide , calfskin , kangaroo , snakeskin , or others . they can be spiral wrapped . corded grips can be corded with strands of thread , e . g ., to create a non - slip “ rain grip ”. a recess or device can either be co - molded into the grip material , or inserted after the grip is made . co - molding into the grip saves weight , allows for greater tolerance , and makes application more streamlined and results in a more attractive grip to some users . a grip or a component of a grip according to the invention can be injection molded , compression molded , or a combination thereof . suitable materials or methods of making a grip are described in golf club grip , u . s . pub . 2007 / 0072696 . grip 107 may include a graphic , emblem , or marked area . a mark , graphic , or emblem can include an area of a different thickness or texture ( e . g ., a bas - relief ), a pigment , a sticker , a medallion , or other indicator ( e . g ., fig1 ). generally , such an indicator may be a corporate logo or other visible element , a reminder ( e . g ., tactile ), or both . in some embodiments , a grip of the invention is designed to complement a club with a repositionable shaft . exemplary club systems are described in u . s . pat . no . 7 , 878 , 921 ; u . s . pat . no . 7 , 476 , 160 ; u . s . pub . 2011 / 0143854 ; u . s . pub . 2010 / 0261543 ; and u . s . pub . 2008 / 0254909 , the contents of each of which are herein incorporated by reference in their entirety . fig3 shows a cross - sectional view of a golf club shaft and grip . it will be appreciated that the view presented in fig3 can also be taken to represent an end - view of grip 107 mounted on shaft 113 with no butt cap . moreover , as a cross - sectional view through the grip portion of club 101 as shown in fig1 , fig3 may be taken at any position along grip 107 . as shown in fig3 , grip 107 has a substantially circular cross - sectional shape . in some embodiments , a cross - sectional shape of grip 107 is oblong , oval , tear - drop or other , or circular but with a protruding reminder . in general , grip 107 will include a recess for housing an electronic device . fig4 presents a perspective view into a golf club grip 107 showing a recess 121 therein . recess 121 is shown here as a shallow depression on an inside surface of grip 107 , generally having a rectangular perimeter . as shown in fig4 , recess 121 is configured to house a thin device that may optionally be flat , pliable , or curved and that fits within a rectangular area . one exemplary device is an rfid tag . one exemplary rfid tag is the general purpose rfid tag sold under the trademark squiggle by alien technology corporation ( morgan hill , calif .). an rfid tag may be about 98 . 2 mm long × 12 . 3 mm wide × 0 . 3 mm thick and includes a uhf rfid integrated circuit , such as the one sold under the trademark higgs by alien technology corporation , and a squiggle antenna design housed in a pliable poly - vinyl chloride sleeve with a rubber - based adhesive backing . such an rfid tag may be disposed within recess 121 with grip 107 installed on shaft 113 . while shown in fig4 as having an open , substantially featureless end , grip 107 may have any suitable end - form , such as a close end or butt cap or decorative finish or flange . in certain embodiments , grip 107 is provided with an integrated or separate cap , such as a butt cap , to cover or close an end of the grip . a butt cap can screw on ( for example by molded threads in the cap and in the grip ), be glued on , sewn on , snap on , press - fit and can be a separate piece or can be formed with the grip by a flap or strap of material . a butt cap can be styled to make the grip appear as a standard grip , or it can be fashioned to call attention to the functionality of the grip ( e . g ., with a logo or indicia showing that it is part of a grip with recess 121 ). as shown in fig4 , recess 121 allows an electronic device to be held and optionally concealed within the grip area of golf club 101 . fig5 shows a cross - sectional view of the grip of fig4 , installed onto golf club shaft 113 . as shown in fig5 , recess 121 generally parallels a surface of shaft 113 or an outer surface of grip 107 , although other forms are within the scope of the invention . due to the pliable nature of an rfid tag , such a tag may be disposed within recess 121 . the tag may be held in place solely by the enclosure of recess 121 , or also through the use of an adhesive . the tag and recess 121 may have a thin , rectangular shape suited to the above - described rfid tags , or may have any other suitable shape . for example , recess 121 may be a deep rectangle ( like a trench ), an oblong shape , a fully enclosed volume such as a sphere , ovoid , or rectangle , a channel , an irregular shape , a slit , or other shape . fig6 shows a cross - sectional view of a golf club shaft 113 and grip 107 having a recess 121 with a deep rectangle shape , having a device 125 disposed therein . device 125 may be any suitable device . for example , device 125 may be the implantable rfid microchip sold as the unique device identifier ( udi ) by veriteq ( delray beach , fla .). the udi is approximately the size of a grain of rice , and can encode a 16 - digit character string . device 125 may be seated in recess 121 snugly or loosely , or may be surrounded by a secondary material . that is , in some embodiments , grip 107 is made substantially of a first material , and has a recess 121 that is filled with a second material , such as a shock - absorbing foam or a viscoelastic dampening material . embedded therein is device 125 ( e . g ., the udi ). fig7 shows another embodiment of a recess 121 in a grip 107 . here , recess 121 may be substantially slot - shaped . the slot may extend from an exterior surface of grip 107 into an interior . fig8 shows recess 121 as a slot in a cross - sectional view of grip 107 from fig7 . fig9 is shows a slot - shaped recess 121 in grip 107 having a device 125 inserted therein . device 125 may be fastened into slot - shaped recess 121 by pressure ( e . g ., the ambient compressive force from the material of grip 107 exerted through the sides of slot - shaped recess 121 ); by an adhesive , or a combination thereof . fig1 shows a grip 107 and shaft 113 and shows where insert 125 may be located in recess 121 underneath grip 107 . device 125 may be , for example , an rfid tag such as the hf - i standard transponder having part number ri - i11 - 114b - 01 and sold under the trademark tag - it by texas instruments ( dallas , tex .). the hf - i standard transponder includes a resonance circuit and microchip on a pet foil . aluminum is used for the antenna and to provide a capacitor that can tune the tag to a specific frequency . frequency offset can compensate for detuning that may be associated with use with different materials , such as a paper or pvc sleeve or material of grip 107 or shaft 113 . in certain embodiments , an rfid tag conforms to iso standards that meet certain international radio regulations . transmission from a tag reader to the tag can use amplitude shift keying with index between 10 % and 30 % or 100 % and data coding , while tag to tag reader can use ask or frequency shift keying . in some embodiments , the tag will respond in the mode of the reader . each rfid tag can have a 64 - bit unique identifier . collisions of a multiplicity of rfid tags may also be implemented to allow multiple tags to be used simultaneously . also , the application family identifier ( afi ) may be supported by an rfid tag such as the hf - i standard transponder . an rfid tag may be provided for device 125 having any suitable dimensions . for example , device 125 may be about 15 mm × 15 mm × 0 . 3 mm . while depicted as having roughly certain dimensions , device 125 may have other dimensions . for example , device 125 may be about 45 mm × 45 mm × 0 . 3 mm ( and , if wrapped around shaft 113 with an edge parallel to an axis of shaft 113 , device 125 may extend around 80 - 90 % of a circumference of shaft 113 ). in some embodiments , an edge of device may be between about 10 mm and about 20 mm , e . g ., between about 15 mm and about 18 mm . fig1 gives a cross section of grip 107 and shaft 113 along the dotted line shown in fig1 . here , recess 121 is shown as being thin , or shallow . recess 121 may have dimensions of about 18 mm × 18 mm × 0 . 5 mm ( e . g ., 17 . 6 mm × 17 . 6 mm × 0 . 3 mm ). in certain embodiments , recess 121 is made to have a depth between about 0 . 15 mm and about 0 . 25 mm . for example , where device 125 has a thickness of about 0 . 3 mm , if recess 121 has a slightly shallower depth , then a material of grip 107 will press against device 125 and even exhibit increased pressure due to local pliable deformation of the material to accommodate device 125 . even with device 125 in contact with shaft 113 , a material of grip 107 may provide vibration dampening necessary for protection of device 125 . for example , when club 101 is used to strike a ball , shock waves of energy ( compression , motion , heat , sound , etc .) may propagate through club 101 . upon arrival at device 125 , recess 121 , and grip 107 , a material of grip 107 may provide a deadening effect . energy from the shock waves may dissipate in myriad elastic and resonant deformations of material within grip 107 while also being transferred to a golfer . in some embodiments , a dimension of recess 121 is between about 50 % and about 99 % of a dimension of device 125 , for example , between about 75 % and about 95 % ( e . g ., between about 85 % and about 90 %). any dimension of recess 121 can be provided slightly smaller than a corresponding dimension of device 125 such as , for example , length , width , diameter , depth , or an irregular dimension . while discussed with reference to fig1 as being relatively thin and flat , an object ( device 125 or other insert ) can have more substantial forms . fig1 shows a cross section of grip 127 and shaft 113 in which an insert 129 is positioned in recess 121 . insert 129 may be provided in the form of a case or box , for example , a small plastic box . here , insert 129 has a base portion 131 fit with lid portion 133 . insert 129 as a case or box may be dimensioned to accommodate a device 125 ( not pictured ) as well as optionally other elements such as a battery or other tool . in certain embodiments , insert 113 has a hole in it . in certain embodiments , shaft 113 has a hole through it . in certain embodiments , a wire extends through a hole in insert 129 and shaft 113 connecting a device 125 within insert 129 to some other element in club 101 . in some embodiments , insert 129 further contains an additional dampening material ( e . g ., a foam or polymer ) and device 125 may be dimensioned like a grain of rice , e . g ., the rfid microchip sold as the unique device identifier ( udi ) by veriteq ( delray beach , fla .). fig1 shows another embodiment of insert 129 . here , insert 129 may be provided in the illustrated form to provide substantial protection and vibration dampening to device 125 . it is reported that some prior art attempts to locate electronic devices in the grip region of a golf club meet with failure apparently due to shock waves whereby discontinuities in pressure or energy propagate rapidly through a club in connection with use of the club . insert 129 may provide a viscoelastic dampening material , such as thermoplastic polyurethane , a springy foam , d30 , or a thixotropic material to mitigate stresses associated with use of the club . in certain embodiments , material of insert 129 ( e . g ., a dampening material ) works in conjunction with an elastic material ( e . g ., rubber ) of grip 107 to provide sufficient shock mitigation . for example , in some embodiments , the grip includes a dilatant material such as d30 . a dilatant material ( e . g ., d30 ) is sometimes called a shear thickening material and is one in which viscocity increases with a rate of shear strain . d30 is known in the art and is used in football protective pads . where , for example , a device 125 would benefit from heightened vibration dampening , combining the dampening of insert 129 with the elasticity of grip 107 may provide protection so that electronic devices may operate . fig1 shows grip 107 having recess 121 optionally filed with a device 125 . here , device 125 may be dimensioned like a grain of rice , e . g ., the rfid microchip sold as the unique device identifier ( udi ) by veriteq ( delray beach , fla .). while shown here as having a teardrop - shaped outline , this may be attributable to viewing angle . for example , a major axis of an oblong device 125 may be oblique and neither perpendicular nor parallel to an axis of shaft 113 . in such a case , if the view is down an axis of 113 , an outline of device 125 or recess 121 may appear teardrop - shaped due to foreshortening . in other related embodiments , recess 121 or device 125 has a major axis that is either perpendicular to or parallel to an axis of shaft 113 . one unexpected benefit of the embodiment depicted in fig1 is that an electronic device 125 such as an rfid tag or microchip may be provided for golf club 101 with no part of device 125 making direct contact with an inelastic or non - dampening material ( e . g ., shaft 113 or head 117 ) of club 101 . for example , even if device 125 is housed in a plastic or inelastic shell , that shell may be surrounded continually in all directions by an elastic or dampening material of grip 107 . accordingly , the invention provides a golf club 101 having device 125 in grip 107 that is not in direct contact with shaft 113 or other inelastic portion of the club . the device is surrounded on all sides , and in all directions , by the pliable or elastic material of grip 107 . this device 125 may be an rfid tag such as , for example , the unique device identifier ( udi ) by veriteq ( delray beach , fla .). this device 125 may be covered in all directions by material of grip 107 and thus not exposed to environmental elements such as direct sunlight , moisture , extremes of temperature . a device can be fully surrounded material of grip 107 by molding it into grip 107 when grip 107 is first molded , or grip 107 can be molded as two parts ( e . g ., halves ) that are then cemented together . fully surrounding device 125 can protect it from loss as well as ensuring that any one of device 125 stays uniquely associated with any one club 101 so that information gathering methods that use 125 may operate reliably . while depicted in fig1 as fully enclosed by continual material of grip 107 , a device 125 may be fully enclosed by a material of grip 107 that is continual but for an access aperture . an access aperture may be provided in the form of a slit , such as the slits depicted in fig7 - 9 . a device 125 may be inserted into recess 121 in grip 107 as depicted in fig1 through a slit that is provided from an exterior surface of grip 107 , an interior surface of grip 107 , or an end surface of grip 107 . a slit may be substantially closed after insertion by compressive force of material of grip 107 , by an adhesive , or a combination thereof . in certain aspects , the invention provides or includes methods and systems for improving a golfer &# 39 ; s game or increasing the enjoyment of golf that make use of information gathering . information gathering systems and methods may make use of a mobile computing device , a computer - based system , or a combination thereof . typical mobile computing devices include a smart phone such as the iphone or samsung galaxy sii or a tablet such as the ipad or samsung galaxy tab . a computer based system may be server computer , such as the rack - mounted server sold under the trademark blade by hitachi america , ltd . ( tarrytown , n . y .) or a general purpose desktop or laptop computer ( e . g ., laptop sold under the trademark portege by toshiba america information systems , inc . ( irvine , calif .). generally , a mobile computing device or a computer - based system will include a tangible , non - transitory memory coupled to a processor via a bus , as well as mechanisms for input and output ( e . g ., screen , touchscreen , wi - fi card , network interface card , ethernet port , usb port , keyboard , pointing device , other , or combination thereof ). information gathering may employ an rfid tag reader such as the ri - ctl - mb68 control module with usb and rs422 / 485 interface from texas instruments ( dallas , tex .) or the socket compactflash 6e rfid reader card from dell inc . ( round rock , tex .). such a reader may be plugged directly into a variety of mobile computing devices . in this way , data from an rfid tag can be detected by an rfid tag reader and relayed to a mobile computing device , from which it may optionally be transferred to a computer system . this allows use of a specific club to be detected or monitored with the relevant information being gathered and stored in a file in the memory of the mobile computing device , computer system , or both . communicating sports - related information is discussed in systems and methods for communicating sports - related information , u . s . patent application ser . no . 13 / 156 , 116 to tim beno , et al ., filed jun . 8 , 2011 , the contents of which are hereby incorporated by reference in their entirety . golf information gathering is discussed in u . s . pat . no . 6 , 366 , 205 ; u . s . pub . 2012 / 0277018 ; u . s . pub . 2012 / 0249330 ; u . s . pub . 2012 / 0139729 ; 2012 / 0035003 ; u . s . pub . 2011 / 0304460 ; u . s . pub . 2010 / 0308105 ; u . s . pub . 2010 / 00113174 ; u . s . pub . 2009 / 0017944 ; u . s . pub . 2006 / 0261938 ; u . s . pub . 2006 / 0255918 ; and u . s . pub . 2005 / 0272516 , the contents of each of which are incorporated by reference herein in their entireties . the relevant information can include data representing what club or clubs are used , when they are used , shots made , shot - tracking , scores , extrinsic data such as a average scores or score of pro golfers for comparison , other data , or a combination thereof . fig1 shows a grip 107 with recess 121 housing device 125 . here , a wire extends from device 125 into shaft 113 . one or more such wire may extend through a hole in shaft 113 , around an end of shaft 113 , or an electrical conductor and inside / outside contact points may be formed in shaft 113 . by such means , device 125 may include , or may be connected to other devices which may include , a battery , accelerometer , light or moisture detector , memory , processor , piezoelectric material , integrated circuit , other antenna or chip , rfid tag , led , switch , others , or a combination thereof . in some embodiments , which may be represented by fig2 - 15 , grip 107 is substantially monolithic — e . g ., mostly formed primarily of a single material ( may have caps , trim , adhesive , surface finish or a combination thereof ). in certain embodiments , grip 107 is structured to include an underlisting and an outer grip . fig1 shows a grip 107 with underlisting 109 surrounded by outer grip 115 . with such an arrangement , an insert 121 may be provided in underlisting 109 , outer grip 115 , or a combination thereof . fig1 shows insert 121 in underlisting 109 of the grip 107 shown in fig1 . recess 121 may have any suitable dimensions . for example , recess 121 may be a shallow rectangular cutout , and may be about 10 cm long × about 1 . 3 cm wide × about 0 . 3 - 0 . 5 mm deep . in some embodiments , recess 121 is about 4 . 5 cm × about 4 . 5 cm × about 0 . 3 - 0 . 5 mm deep . recess 121 may be an oblong channel having dimensions similar to a grain of rice , or recess 121 may be hollow , cavity , bowl - shaped depression , crater - shaped , rectangular shaped , or have an irregular shape . fig1 is a cross section of grip 107 as shown in fig1 ( along the area indicated by the dotted line in fig1 ) with a shaft 113 inserted therethrough . use of a grip 107 with underlisting 109 provides functional and manufacturing benefits in terms of an easy to form recess 121 ( e . g ., can be relatively inexpensive to mold or rout ) due to being open on a surface that still results in an electronic device 125 being included in golf club 101 with no part of device 125 making direct contact with an inelastic or non - dampening material ( e . g ., shaft 113 or head 117 ) of club 101 . a device 125 may be surrounded continually in all directions by an elastic or dampening material of underlisting 109 and outer grip 115 . accordingly , the invention provides a golf club 101 having device 125 in grip 107 that is not in direct contact with shaft 113 or other inelastic portion of the club . the device is surrounded on all sides , and in all directions , by the pliable or elastic material of grip 107 and thus not exposed to environmental elements such as direct sunlight , moisture , extremes of temperature . this can protect device 125 from loss as well as ensure that any one of device 125 stays uniquely associated with any one club 101 so that information gathering methods that use 125 may operate reliably . use of an underlisted grip 107 allows recess 121 to be positioned in other locations , as well . fig1 is a cross section through a grip 107 with underlisting 109 showing recess 121 along an inner surface of outer grip 115 . this structure may provide the benefit of maximal vibration dampening to device 125 , by allowing a full thickness of underlisting 109 to everywhere separate device 125 from shaft 113 . it is noted that embodiments such as those depicted in fig1 , 18 , 17 , 14 , 13 , 12 , 8 , 9 , and 6 provide a golf club 101 in which a device 125 such as an rfid tag can be included that is everywhere spaced away from a shaft 113 ( and club head 117 ) of the club . due to the insight that shock waves from impact may propagate through inelastic portions of club 101 ( e . g ., shaft 113 and head 117 ), benefit is had by mitigating the interference of shock waves with device 125 , allowing more delicate devices to be included . in some embodiments , an underlisted grip 107 allows a club to include an interchangeable outer grip 115 in which a device 125 or recess 121 is concealed from a user and device 125 is made to be retained in recess 121 even when outer grip 115 is removed . fig2 shows a recess 121 in an inner surface of underlisting 109 . outer grip 115 could be removed and recess 121 would not be exposed , thus retaining , protecting , or concealing , for example , device 125 . references and citations to other documents , such as patents , patent applications , patent publications , journals , books , papers , web contents , have been made throughout this disclosure . all such documents are hereby incorporated herein by reference in their entirety for all purposes . various modifications of the invention and many further embodiments thereof , in addition to those shown and described herein , will become apparent to those skilled in the art from the full contents of this document , including references to the scientific and patent literature cited herein . the subject matter herein contains important information , exemplification and guidance that can be adapted to the practice of this invention in its various embodiments and equivalents thereof .

the invention relates to golf clubs , more particularly to mechanisms for fastening accessories to clubs . the invention provides a golf club configured to house an electronic device such as an rfid tag within a recess within the grip , thereby protecting the device from the stress , shock , and exposure that arises when a golf club is used .

with reference to fig1 a decorative plaque 10 embodying features of the present invention is shown attached to a belt 12 . referring to fig1 and 2 , the plaque 10 comprises a frame 15 having an elongated cover plate 20 , which has a decorative front face 25 and a back face 26 . the cover plate 20 has an elongated opening 30 therethrough . the frame 15 further comprises a backing plate 35 similar in shape to the cover plate 20 . the backing plate 35 has a front face 40 and a back face 41 . preferably a decorative fabric 45 is affixed to the front face 40 of the backing plate 35 , the fabric 45 showing through the elongated opening 30 of the cover plate 20 . the plaque also comprises at least one decorative element 50 sized and adapted for removable insertion beween the cover plate 20 and the backing plate 35 , such that at least an exposed portion 55 of the decorative element 50 shows through the elongated opening 30 of the cover plate 20 . preferably the exposed portion 55 is substantially flush with the decorative front face 25 of the cover plate 20 . each decorative element 50 is no wider than the length of the elongaged opening 30 . each decorative element 50 has a front face 60 and a back face 61 . typically the decorative element 50 is in the shape of a letter of an alphabet , or other decorative designs , such as a star , an animal such as a horse , a horoscopic sign , etc . there are affixing means 65 for removably affixing the backing plate 35 to the cover plate 20 so that the decorative element 50 is firmly held in place therebetween . preferably the affixing means comprise screw nuts 70 affixed to the back face 26 of the cover plate 20 , and screws 75 passing through holes 77 in the backing plate 35 . each screw 75 has a head 80 too large to pass through the hole 77 in the backing plate 35 , and is therefore capable of holding the backing plate 35 firmly against the cover plate 20 . the frame 15 and the decorative element 50 have interlocking engaging means 85 for preventing the decorative element 50 from moving along the length of the elongated opening 30 . preferably the engaging means comprise at least one row of serrations in the frame 15 extending along substantially the entire length of the elongated opening 30 , and at least one row of serrations on the decorative element capable of interlockingly engaging the serrations in the frame 15 . preferably the serrations are uniformly sized and evenly spaced . for example , the serrations can be spaced about 1 / 32 inch apart . the serrations can be rounded or angular . fig2 shows a version of the plaque having two rows of serrations , 90 and 91 , being above and below the elongated opening 30 , on the back face 26 of the cover plate 20 . there are corresponding rows of serrations 95 and 96 on the front face 60 of each decorative element 50 . when the decorative element 50 is placed between the cover plate 20 and the backing plate 35 , and is pressed against the cover plate 20 by the backing plate 35 , the serrations 90 and 95 , and 91 and 96 , respectively , will interlockingly engage each other to prevent the movement of the decorative element 50 along the length of the elongated opening 30 . preferably the frame 15 further comprises at least one strip of resilient material 100 affixed to the frame 15 . the strip 100 is preferably formed of rubber or plastic . the strip 100 is sized and located such that , when the backing plate 35 is affixed to the cover plate 20 , the strip 100 runs substantially along the entire length of , and proximate to , one of the rows of serrations 90 and 91 on the frame 15 , without the strip 100 showing through the elongated opening 30 in the cover plate 20 . the strip 100 is capable of resiliently and firmly holding the decorative elements against the frame 15 . for example , when the two rows of serrations 90 and 91 are on the back face 26 of the cover plate 20 , there are preferably two strips 100 affixed to the front face 40 of the backing plate 35 , corresponding in position to the two rows of serrations 90 and 91 . alternatively , the rows of serrations 90 and 91 on the frame 15 could be on the front face 40 of the backing plate 35 ; the rows of serrations 95 and 96 on the decorative element 50 could be on the back face 61 of the decorative element 50 ; and the strips 100 could be on the back face 26 of the cover plate 20 . preferably there are attachment means 105 for removably attaching the decorative plaque 10 to a belt 12 . the attachment means 105 can comprise backing screw nuts 110 affixed to the back face 41 of the backing plate 35 , and backing screws 115 passing through holes 117 in the belt 12 , and threadingly engaging the backing screw nuts 110 on the backing plate 35 . the backing screw 115 has a head 120 too large to pass through the hole 117 in the belt 12 , and is therefore capable of holding the belt 12 firmly against the backing plate 35 . no special training is required to assemble or dismantle the plaque 10 from or to its component parts . a small screwdriver ( not shown ) is the only tool needed . the decorative element 50 can be changed quickly at will thereby changing the information displayed on the plaque . the assembler simply selects the desired decorative elements , places them into frame members so that the serrations on the elements and the frame engage , then screws the backing plate down so that the decorative elements are held firmly against the frame member . the evenly spaced serrations ensure even spacing of the decorative elements , and serve to hold the decorative elements in place until the backing plate is installed . the plaque is then ready for attachment to a belt . the background appearance can also be changed by using a backing plate having a different decorative fabric attached thereto . by purchasing several backing plates , each with a distinctive decorative fabric attached thereto , and keeping on hand a reasonable stock of decorative elements , the owner of the decorative plaque according to the present invention can create a plaque with many different looks . manufacture of the decorative plaque according to the present invention is easy and economical . to maintain a &# 34 ; handmade &# 34 ; look , it is preferable that at least the frame 15 and the decorative element 50 be formed of metal , such as silver , or silver plated brass , etc . preferably the cover plate 20 should have attractive designs thereon . another alternative is to form any or all the frame 15 and the decorative element out of silver plated plastic . although the present invention has been described in considerable detail with reference to certain preferred versions thereof , other versions are possible . for example , the interlocking engaging means 85 need not be rows of serrations , but could be any other means for preventing lateral movement of the decorative elements . the interlocking engaging means could comprise friction - providing rubber strips on the frame 15 and the decorative element 50 . alternatively , the frame 15 and the decorative element 50 can have interlocking strips of small hooks , such as the attachment means sold under the trademark &# 34 ; velcro &# 34 ;. therefore , the spirit and scope of the appended claims should not necessarily be limited to the description of the preferred versions contained herein .

a decorative plaque with replaceable decorative elements is suitable for use with belts . the plaque has a frame having a front opening for the viewing of replaceable decorative elements , such as alphabets and letters , set on a decorative fabric . the frame and the decorative elements have interlocking serrations for preventing movement of the decorative elements along the width of the opening .

the soft edging for a water bed shown in these figures rests on a generally rectangular plate 2 which , in turn , is positioned on a base or socle 1 in a usual manner . base or socle 1 and plate 2 do not pertain to the essence of the invention and can therefore have different structures . upon referring now to known embodiments pertaining to the state of the art according to fig1 to 4 , it will be noticed that the so - called soft edges for a water mattress 3 never solve at the same time the problem of comfort for the user of the water bed and ease and convenience for securing sheets and blankets . the soft edging for a water bed according to the prior art is formed by the presence of continuous blocs 4 around the periphery of the mattress . if necessary , blocs 4 can be positioned on blocs 4 &# 39 ; which surround the periphery of the mattress . the blocs 4 , 4 &# 39 ; can be made from a more or less soft deformable elastic material or a non - resilient material . the present invention proposes the use of an extrusion or profile 5 the external form , the internal structure and the cross profile or cross section of which clearly become apparent from the fig6 to 14 . referring first to fig5 and 6 , the profile 5 has a polygonal cross - section and has inter alia , an upper side 6 and a lower side 7 generally directed or angled towards each other . a side 8 connects sides 6 and 7 to each other , and side 8 is situated with at least one , but preferably two or more continuous grooves 9 into which an auxiliary profile 10 can be slid and held in place such as with a hook and loop fastener . the profile 5 includes a lower side 11 which may be generally parallel to upper side 6 and a similar groove 9 , for a second auxiliary profile 10 provided in the lower side 11 of the profile 5 . since the profile is to be provided or covered with a textile upholstery 12 , ( fig7 ) this upholstery can easily be connected to the hook and loop fasteners of the two auxiliary profiles . according to fig7 a modified auxiliary profile 13 is used which can clamp the upholstery 12 in the groove 9 without having to use a hook and loop fastener . end caps 24 ( fig1 ) are provided and the end caps match the cross - sectional configuration of the profile . thus when the profiles are covered with upholstery which is first folded inwards at the ends of the profiles , then the caps 24 are forced into the ends of the profiles to secure or clamp the upholstery in the profile . in the corners they join each other under an angle of 45 °. an alternate configuration of the profile is illustrated in fig8 and 10 wherein a profile 5 &# 39 ; has an outwardly directed side 14 ( i . e ., remote from the mattress ). a continuous slot 15 with a swallow &# 39 ; s tail shaped cross section is provided in the outwardly directed side 14 of the profile 5 &# 39 ; and finishing panels 16 can be snap - fit into the continuous slot 15 to enhance the outward appearance of the profiles 5 &# 39 ;. referring back to fig5 and 6 , and , in addition , referring to fig7 and 11 through 14 , the profile 5 includes a hollow chamber 17 or slot extending in the longitudinal direction thereof , which can be slid over a vertical base socle 25 of a water bed . a corresponding chamber or slot 17 is provided in the end caps 24 . ( fig1 ). profile 5 can be immobilized with respect to the verticle base socle 25 and the profile is supported from underneath because the profile rests on the plate 2 . fig1 and 12 illustrate additional important features and benefits of the present invention . as noted previously , the profile 5 enables the user to provide a soft edging around the periphery of the water bed . the soft edging improves the comfort of the bed . furthermore , according to the present invention , mounting or positioning the edging , and inserting a mattress protector , sheets and blankets , are simplified . specifically , two sleeves 18 , 18 &# 39 ;, formed of a textile material , are provided and the two sleeves are interconnected by a textile strip 21 which functions as a hinge component . a polygonal foam rail 19 is inserted in sleeve 18 . a wedge or triangle shaped component 20 is inserted within sleeve 18 &# 39 ;. the foam rail 19 and wedge component 20 are capable of hinge movement relative to each other because of the textile strip 21 . the foam rail 19 ( within sleeve 18 ) is positioned on the top 6 of the profile 5 . the wedge component 20 ( within sleeve 18 &# 39 ;) is forced into the space which is created between the plate 2 and the upwardly inclined surface 7 of the profile 5 . this wedging action conveniently maintains the foam rail 19 in proper position on profile 5 . it should be appreciated that the arrangement of the foam rail 19 as just described may be used on all four sides of a water bed . however , if the water bed includes a headboard , an alternate arrangement may be preferred . specifically , referring to fig1 and 14 , the foam rail 19 and wedging - shaped component 20 which are connected as if by means of hinges connected to each other , can be used in combination with an adapter 22 along the side of the water bed adjacent the headboard 23 . the adapter has a cross - section which includes a first portion to rest on the plate 2 , a second portion to receive the wedging component 20 , a third portion on which the textile strip 21 is positioned , a fourth portion upon which the foam rail 19 is supported , and a fifth or curved portion which rests on both the sides 6 and 7 of the profile 5 . the foregoing is a complete description of the invention . various changes and modifications may be made without departing from the spirit of the invention . the present invention provides a soft edging which increases the comfort of the bed and improves considerably the insertion of mattress protectors , sheets and blankets . the invention should be limited only by the scope of the following claims .

a soft edging for a water bed formed by a hollow profile having two sides directed towards each other . the uppermost of these sides is an inwardly and downwardly directed surface which supports a foam rail . the lowermost of these sides is configured at an angle relative to a plate defining therebetween a continuous hollow space . a wedging - shaped component , connected to the foam rail by a flexible material , such as a strip of textile is clamped in the continuous hollow space .

in the following description , color references are made to the royal horticultural society colour chart , 2007 edition , except where general terms of ordinary dictionary significance are used . plants used for the description were approximately 2 - years - old and were grown in 11 . 8 l containers under outdoor conditions in watkinsville , ga . botanical classification : distylium sp . hybrid , cultivar ‘ piidist - iii ’. parentage : distylium sp . hybrid ( unnamed and unpatented ). propagation : stem cuttings . time to initiate roots in summer : about 28 days at 32 ° c . plant description : broadleaf evergreen flowering shrub ; multi - stemmed ; compact , rounded to spreading growth habit . freely branching ; removal of the terminal bud enhances lateral branch development . root description .— medium , well - branched . plant size .— the original plant , now about four and a half - years - old in the ground , is about 91 cm high from the soil level to the top of the foliage and about 147 cm wide . first year stems having a diameter of about 2 mm . shape : round . fine pubescence . few small lenticels about 1 mm in diameter and n199b in color . first year stem color .— 146b . second year and older stems have a diameter of about 4 mm or more . shape : round . second year and older stem color .— 199b . stem strength .— flexible when young , less so with maturity . internode length .— about 1 . 3 cm . trunk diameter .— about 3 . 1 cm at the soil line . color : 199a . bark : does not exfoliate , covered with many lenticels about 1 mm in diameter and n199b in color . arrangement .— alternate . shape .— ovoid with fused , pubescent bud scales . size .— about 3 mm in length and about 1 . 5 mm in width . color .— 164b . arrangement .— alternate , simple . length : about 6 . 1 cm . width : about 2 . 3 cm . shape : elliptical . apex : acute . base : cuneate . margin : entire and undulating , occasionally with up to 3 teeth toward apex . texture ( upper and lower surfaces ).— thick , leathery , also glaucous on upper surface . venation pattern .— pinnate . venation color ( upper and lower surfaces ): color is 147b . color of emerging foliage ( upper surface ).— a combination of 181c and n77d . color of emerging foliage ( lower surface ): 193b . color of mature foliage ( upper surface ): n189a . color of mature foliage ( lower surface ): 138b . petiole length .— about 3 mm . petiole diameter : about 1 mm . fine pubescence 199b in color . petiole color ( upper and lower surfaces ): 146b . flower type and habit .— apetalous flowers with a pubescent , 5 - parted calyx are borne on short racemes from the leaf axils . natural flowering season : late winter , approximately january to february in watkinsville , ga . individual flowers are showy for approximately 1 week and are self - cleaning . flower size .— about 1 cm in diameter and about 1 cm in height . pedicels .— about 1 . 9 mm in length . peduncles : about 1 . 1 cm in length . color : pedicels and peduncles 146c in color with pubescence 165a in color . quantity / arrangement .— 7 to 10 per flower . filament : about 3 mm in length , less than 1 mm in width , and 146d in color . anthers : about 2 mm in length , about 1 mm in width , and 185a in color . pollen : produced in moderate quantities and is 158d in color . position .— superior . size : about 1 . 1 cm in length and about 2 mm in width . color : 146b . stigma : 2 per pistil , about 6 mm in length , 178b in color . style : 2 per flower , about 3 mm in length , and 146b in color . ovary : two per flower , about 2 mm in diameter , about 2 mm in height , and 146b in color . fruit : none observed to date . disease / pest resistance : plants of the new distylium grown in the nursery and garden have not been noted to be susceptible to pathogens or pests .

a new and distinct cultivar of distylium plant named ‘ piidist - iii ’, characterized by its compact , rounded to spreading growth habit , bronze - purple new growth , dark bluish green mature foliage , and reddish maroon flowers .

the preferred embodiments of the present invention will now be described with reference to the drawings . identical elements in the various figures are identified with the same reference numerals . reference will now be made in detail to each embodiment of the present invention . such embodiments are provided by way of explanation of the present invention , which is not intended to be limited thereto . in fact , those of ordinary skill in the art may appreciate upon reading the present specification and viewing the present drawings that various modifications and variations can be made thereto . referring to fig1 , a perspective view of an embodiment of the invention is shown . this view shows an embodiment of the invention while in use . specifically , sleeping apparatus 100 is comprised of net 101 , a plurality of suspension cords 102 , base 103 , a plurality of support cords 104 , a plurality of gear loops 121 , and zipper seam 107 . in a preferred embodiment , sleeping apparatus 100 is optionally equipped with storage pouch 105 . in another preferred embodiment , net 101 has a density of at least 2000 holes per square inch , preferably at least 2100 holes per square inch . nets of this density serve as an effective barrier against all manner of insects , including ceratopogonidae , colloquially known as “ no see ums .” suspension cords 102 serve to keep net 101 taught such that when zipper seam 107 is engaged , there exists a space for a user to relax in a bug - free space in the area between base 103 and net 101 . when equipped , storage pouch 105 provides a means to easily carry sleeping apparatus 100 when not in use . this makes sleeping apparatus 100 particularly well - suited for use while hiking , and performing other outdoor activities . plurality of gear loops 121 provide a means for a user to hang gear outside of the enclosure created by base 103 and net 101 . in a preferred embodiment , plurality of gear loops 121 will extend into the enclosure , allowing a user to hang and access items from within the enclosure . referring to fig2 , a side view of an embodiment of the invention is shown . specifically , sleeping apparatus 100 is displayed , highlighting a number of features . one such feature , is the ability of net 101 and base 103 to be separated along zipper seam 107 so that a user may easily enter sleeping apparatus 100 . additionally , in a preferred embodiment , sleeping apparatus 100 is optionally equipped with pad 108 . pad 108 provided additional support for a user resting in sleeping apparatus 100 . further , pad 108 provides insulation for a user , allowing sleeping apparatus 100 to be used in a wider range of climates . referring to fig3 , a side view of an embodiment of the present invention in shown . this view shows an embodiment of the present invention while suspended . of note here is how plurality of gear loops 121 is used to support suspension cord 102 while extending into the enclosure between net 101 and base 103 to provide for additional loops for gear to be attached to . referring to fig4 , a top view of an embodiment of the invention is shown . this view highlights the asymmetrical nature of the present invention . specifically , fig4 shows how sleeping apparatus 100 is shaped so that a user may enjoy a substantially flat sleeping experience while being suspended in the air . additionally , the location of pad 108 is shown in relation to the entirety of this preferred embodiment of sleeping apparatus 100 . this functionality is intended to greatly increase the ease of insertion of pad 108 . referring to fig5 , a front view of an embodiment of the present invention is provided . this view highlights how pad 108 interfaces with the present invention . as can be seen , pad 108 slides directly into integrated sleeve 110 . in a preferred embodiment , pad 108 is inflatable , and contains air valve 109 . by having air valve 109 located within the area enclosed by base 103 and net 101 , a user is able to first slide an uninflated pad 108 into base 103 and subsequently inflate said pad 108 . this can assist with the insertion of pad 108 into integrated sleeve 110 . referring to fig6 , a top view of an embodiment of the present invention is provided for . specifically , this view highlights the asymmetrical nature of base 103 . due in part to this asymmetrical shape , when in use , sleeping apparatus 100 is substantially more planar than a traditional hammock . in a preferred embodiment , base 103 is equipped with pad 108 or some other pad inside of integrated sleeve 110 to provide further rigidity in base 103 . here , a top view of base 103 of sleeping apparatus 100 laid flat is shown . in a preferred embodiment , base 103 is comprised of middle panel 106 , first longitudinal panel 114 , second longitudinal panel 115 , first support panel 112 , second support panel 113 , first lateral panel 120 , and second lateral panel 121 . in another preferred embodiment , base 103 is equipped with a plurality of internal pockets 118 . in yet another preferred embodiment , base 103 is equipped with first base support receiving member 116 , and second base support receiving member 117 . first and second base support receiving members 116 and 117 , when used in conjunction with base suspension cord 104 provide a mechanism to allow base 103 to be suspended . it should be noted that while this embodiment is comprised of 7 different panels , it is possible to construct the present invention out of three panels . for example , first support panel 112 , second longitudinal panel 115 and first lateral panel 119 can be combined to make a single panel . in an alternative embodiment , second longitudinal panel 115 , middle panel 106 , and first longitudinal panel 114 could be combined to create a single panel . in one embodiment , first and second longitudinal panels 114 and 115 are each connected to at least one edge of middle panel 106 . in that same embodiment , first and second lateral panels 119 and 120 are each connected to at least one edge of the middle panel , and first and second support panels 112 and 113 are also each connected to at least one edge of the neighboring longitudinal and lateral panels . in one embodiment first and second base support receiving members 116 and 117 are optionally omitted from the invention . in alternative embodiments first and second base support receiving portions 116 and 117 are attached to the edges of first and second support panels 112 and 113 that are not shared with an adjacent panel . it should be noted that while preferable , it is not necessary to have an inflatable pad to utilize the present invention . it should be noted that the relative size and shape of the middle panel 106 , first and second longitudinal panels 114 and 115 , first and second lateral panels 103 and 109 , and support panels 104 and 108 shown in fig1 are meant to be illustrative of one embodiment of the invention , but other embodiments wherein the panels deviate from the exact proportions of fig1 . in a preferred embodiment , the present invention has a total length of approximately 320 cm , where the zippers on the invention extend approximately 280 cm with 20 cm on either side of the zipper being sewn shut . further , the netting is able to be opened fully and folder over the top of the hammock portion of the present invention . in a preferred embodiment , the hammock has zippers to make it easy to get in and out of the present invention . double pull ykk zippers are the desired component for these zippers , but alternative zippers may also be used . in an alternative embodiment , said netting may be attached to the entire perimeter of the hammock portion of the present invention . this provides the additional benefit of making the present invention reversible . in yet another preferred embodiment , net 101 is not attached to first lateral panel 119 nor second lateral panel 120 . this allows less netting to be used , resulting in the present invention being lighter . further , the space created by not attaching the net to first lateral panel 119 nor second lateral panel 120 is closed when support cord 104 is gathered at the ends and a knot is used to tie support cord 104 off . additionally , pad 108 may be secured by a fold over flap to keep the pad in place . that is , a flap of fabric where pad 108 may be inserted and then excess material may be folded over the top to have pad 108 retain its position . it should be noted that in the vast majority of the numerous embodiments of the invention , that the panels are secured by reinforced webbing . in an alternative embodiment , all of the seams of the present invention are reinforced by webbing . in yet another alternative embodiment , the seams may not be reinforced at all . when introducing elements of the present disclosure or the embodiment ( s ) thereof , the articles “ a ,” “ an ,” and “ the ” are intended to mean that there are one or more of the elements . similarly , the adjective “ another ,” when used to introduce an element , is intended to mean one or more elements . the terms “ including ” and “ having ” are intended to be inclusive such that there may be additional elements other than the listed elements . while the disclosure refers to exemplary embodiments , it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the disclosure . in addition , many modifications will be appreciated by those skilled in the art to adapt a particular instrument , situation or material to the teachings of the disclosure without departing from the spirit thereof . therefore , it is intended that the disclosure not be limited to the particular embodiments disclosed .

the present disclosure provides for a sleep apparatus with a base having an asymmetric design , featuring an integrated sleeve such that a pad may be inserted into the sleeve . the sleep apparatus may also have a net that provides for an enclosure . the asymmetric design of the base and the pad that fits into the integrated sleeve provide for a substantially flat surface for a user to lie on while using this sleep apparatus . this substantially flat surface creates a more - uniform pressure against a user &# 39 ; s body allowing for the sleep apparatus to be comfortably resided - in for longer periods of time when compared with a traditional hammock . the net of the present invention creates a means for suspending the insect net above a user . the sleep apparatus may be optionally equipped with a storage pouch .

fig1 is a perspective view of a lead according to the present invention . as seen , lead 1 essentially has two portions : a connector portion 2 and a lead body portion 3 . distal end of lead body portion features an electrode / anchoring section 4 . connector portion is a standard connector used in the pacing area , such as an is - 1 uni or an is - 1 bi . of course , other connector designs may be used . lead body portion 3 is coupled to connector portion 2 and further coupled to electrode / anchoring section 4 . as seen , electrode / anchoring section features a tine 5 disposed on a first side of the lead and an electrode 10 disposed on the opposite side of the lead ( in a bi polar configuration a second electrode 10 &# 39 ; shown here in phantom is also positioned on electrode / anchoring section .) fig2 is an end view showing clearly the disposition of tine 5 opposite electrode 10 . as seen in this view tine extends in a straight manner . it should be understood , however , tine may also extend in manners other than straight , such as curved or having an arc , for example . fig3 is a cross - sectional view showing the lead body portion joining into the electrode / anchoring portion . as seen , lead body portion 3 is constructed of an insulative sheath 11 surrounding a coiled conductor 12 . insulative sheath preferably is a biocompatible polymer such as silicone and coiled conductor preferably is a multi - filar coil of a biocompatible material such as mp35n . of course , other materials may also be selected for each of these components , if desired . as seen , coiled conductor 12 has fitted , within its distal end , a crimping core 13 . core preferably is made of a platinum - iridium alloy . surrounding the distal end of coiled conductor and crimp core is an electrode tube 14 . as seen , tube is crimped in the area 15 to thereby mechanically as well as electrically join coiled conductor with tube . tube preferably is formed also of a platinum - iridium alloy . as seen , tube further features a cavity 16 into which is disposed a monolithic controlled release device ( mcrd ) 17 . mcrd is of standard construction and is designed to elute or dispense a drug from the electrode into the surrounding tissues , as is well known in the pacing art . in the preferred embodiment mcrd is a silicone rubber having the sodium salt of dexamethasone impregnated therein . a hole communicates through the tube from cavity to the outer portion of the lead . the hole is covered with an electrode cap 18 . electrode cap preferably is constructed using spherical platinum porous powder which has further a platinum black electroplate thereon as is well known in the pacing art . disposed on the end of the electrode tube is electrode cap 20 preferably of the same material as insulative sheath . fitted completely over the end of lead body and electrode tube is a tine part 21 . tine part preferably is glued along overlapping joint 22 to sheath 11 . tine part , moreover , further features a single tine 5 disposed at an approximately 45 ° angle . as seen , tine is disposed on a side opposite that of electrode . tine extends at an angle 97 of between approximately 30 to 70 degrees relative to the center axis of the lead body , with 45degrees preferred . tine has a length 83 which is between approximately 3 to 12millimeters in length , with 4 millimeters preferred . in such a manner tine extends upwards from lead body for a distance 87 as compared to the lead body diameter 88 . in the preferred embodiment distance 87 is between approximately 2 - 8 millimeters and diameter 88 is between approximately 2 - 3 millimeters such that the distance 87 to diameter 88 ratio is between 1 - 4 to 1 . as discussed in more detail below , the provision of the tine permits the lead , when inserted into the coronary sinus to have the electrode brought in contact with the coronary sinus wall . moreover , because the electrode is only a discrete point along the circumference of the lead body ( as compared to ring electrode ), the electrode may be positioned so as to point or contact the tissue of the heart most suitable for stimulation or sensing , or both . most importantly however , is that due to the relative slight sizes of the tine length and width as related to the lead body diameters , such electrical contact to be achieved without occluding the vessel . thus the dimension selected for the lead body and tine are essential to the proper performance of the lead within the coronary sinus . fig4 depicts an alternate embodiment of the present invention . as seen , in this embodiment the lead 40 is also designed for disposition or placement into the coronary sinus 41 . in this embodiment , however , the lead features a pair of tines 42 and 43 to assist in anchoring the lead into the coronary sinus . as discussed above , the lead is designed so as to have no significant impact on the flow of blood through the coronary sinus or whatever vessel the lead is placed in . in the present figure this is depicted through lines 44 which represent the flow of blood fig5 a is an end view of the alternate embodiment shown in fig4 . as seen in this view , the lead 40 has tines 42 and 43 disposed in a symmetrical fashion about the lead body and opposite electrode 45 . tines are disposed at a radial angles 95 and 96 from the top of the lead body , preferably these radial angles are the same and are between approximately 15 and 90 with 30 degrees preferred for each . or , with respect to the electrode , the tines are each disposed along the lead body at a radial distance between approximately 110 - 150 degrees opposite the electrode . moreover each tine has a length 93 which is between approximately 3 to 5millimeters in length , with 4 millimeters preferred . fig5 b shows a side plan view of the distal end of the lead and , in particular , details the longitudinal positioning of the tines which are staggered along the lead body and has electrode disposed there between . both tines extends at an angle 94 of between approximately 30 to 70 degrees relative to the center axis of the lead body , with 45 degrees preferred . although not shown , the construction of the alternate embodiment of the lead depicted in fig4 and 5 is exactly the same as that shown in fig3 but for the addition of the additional tine along electrode / anchoring portion . fig6 shows a still further alternate embodiment of the present invention . in this embodiment lead 50 features a different design for electrode / anchoring section 51 . in particular , in this design electrode / anchoring section features a wedge 52 . wedge is preferably constructed from the same material as that used in the rest of the electrode / anchoring section and is integrally therewith similar to the tine discussed above . fig7 is an end view of the embodiment shown in fig6 . as seen , wedge 52 is disposed opposite electrode 53 . other than the use of wedge , lead 50 is constructed in a similar fashion to the lead which is described in fig1 - 3 , i . e . all the materials are the same and only a particular design of the wedge is different . fig8 shows a still further alternate embodiment of the present invention . in this embodiment lead 60 is essentially the same as the lead 1 described in fig1 - 3 above but for a different design on the electrode / anchoring section 64 . in this view the lead 60 is disposed within the coronary sinus 61 . in this design electrode / anchoring section features a bent - tail 63 disposed away from electrode / anchoring section so as to engage the wall of the coronary sinus . fig9 a is a plan view of the lead 60 showing the orientation of the bent - tail 63 of the electrode / anchoring portion . as seen , bent - tail comprises a solid piece of a polymer , the piece disposed at an angle 92 between approximately 30 to 60 degrees with 45 degrees preferred away from the electrode / anchoring section and further having a curve in the center so that the distal end of the bent - tail is disposed towards the electrode / anchoring portion . a furrow 65 is further provided in the electrode / anchoring section to accommodate the distal end of the bent - tail once the middle portion engages into the vessel wall to thereby fix the lead . as best seen in fig9 b the electrode 66 is disposed on the opposite side of the lead from bent - tail . electrode 66 is similar to that already discussed above in regards to fig1 - 3 . fig1 is a top view of the lead 60 and , in particular , shows the orientation of the bent - tail and furrow . as seen furrow is slightly longer than the bent - tail to permit the accommodation of the distal end of the bent - tail into the furrow once the middle portion engages into the vessel wall and the bent tail is flattened . moreover , there is a gap between the bent - tail and the furrow , i . e . the furrow is wider than bent - tail . fig1 shows a still further alternate embodiment of the present invention . as seen , lead 70 is positioned inside coronary sinus 71 . in this embodiment lead 70 features a loop 72 along electrode / anchoring section 73 to thereby engage into the vessel wall and wedge or fix the lead in position . fig1 a is a side plan view of the lead shown in fig1 . as seen , loop 72 is circular in shape when not deformed at body structure , such as the vessel wall . electrode / anchoring section further features electrode 74 . as best seen in fig1 b electrode 74 is positioned opposite loop . electrode 74 is similar to that already discussed above in regards to fig1 - 3 . fig1 is a top plan view of the lead shown in fig1 a . as seen in this view , loop 72 extends in a longitudinally parallel direction along electrode anchoring portion 73 . each of the above described embodiments may further be provided with a coating of one or more various compounds or be surface treated to increase biocompatibility . such coating may include heparin or other anti - thrombus agents , for example . in an alternative design , the electrode may be fabricated without an mcrd , and instead the electrode may be treated with a very slightly soluble in water steroid , such as beclomethasone dipropionate anhydrous . preferably the steroid is applied to the surface of the electrode which contacts tissue when implanted . further details of such a coating process may be found in the copending u . s . patent application of williams &# 34 ; medical electrical lead &# 34 ; ser . no . 081605 , 591 , incorporated herein by reference . it must be understood that the particular dimensions and ratios of the various lead components are crucial and essential to the effective operation of the present invention . it is to be understood that the present invention is not limited to use only in pacing leads , and may be employed in the construction of may of various type of therapeutic and diagnostic devices , including defibrillation leads , intended to be disposed within the coronary sinus . in fact , for the purposes of this specification and claims , the term &# 34 ; lead &# 34 ; is used herein in its broadest sense and includes any stimulation lead or sensing lead , a combination thereof or any other elongated member , such as a catheter , which may usefully be introduced into a body . for purposes of illustration only , however , the present invention has been described in the context of transvenous pacing lead . moreover , the present invention may be used in any of the various venous and arterial pathways along the heart or anywhere else within the body , thus the term &# 34 ; coronary sinus &# 34 ; is also used herein in its broadest sense and includes , without limitation , the great cardiac vein , as well as any other cardiac vessel . although a specific embodiment of the invention has been disclosed , this is done for purposes of illustration and is not intended to be limiting with regard to the scope of the invention . it is contemplated various substitutions , alterations and / or modifications may be made to the disclosed embodiment without departing from the spirit and scope of the invention . such modifications may include substituting elements or components which perform substantially the same function in substantially the same way to achieve substantially the same result for those described herein .

a transvenous lead specifically designed for coronary sinus implantation . in the preferred embodiment the lead features an electrode which is eccentricity placed along the lead body . disposed on the opposite side of the lead body is a tine - like member to push or maintain the electrode into contact with the vessel wall . because the electrode and tine - like member do not entirely block the cross sectional area of the vessel , blood flow through the vessel is not impeded . through such a configuration electrical stimulation with the tissue comprising the left side of the heart may be accomplished . in alternative embodiments other mechanisms besides tine - like member are used to maintain the contact of the electrode with the vessel wall . in a still further alternative embodiment the eccentricity disposed electrode is positioned instead upon the tip of the tine .

referring now to the drawings , and in particular fig1 and 2 , there is illustrated a separator assembly , generally indicated as 10 comprised of a generally cylindrically - shaped outer wall 12 , a conically - shaped top wall 14 , a conically - shaped bottom wall 16 and a conically - shaped intermediate wall member 18 including an opening 20 defining an upper separation chamber 22 . the top wall 14 is formed with a vertically - disposed conduit member 26 extending therethrough and into the chamber 22 defining a gas - liquid separation zone 28 defined by an inner surface portion 30 of the top wall 14 with an outer cylindrically - shaped surface portion 32 of the conduit member 26 . extension of the conduit member 26 defined by the surface portion 32 may be omitted depending on the proportions and relationships of surfaces and dimensions of the separator assembly 10 . in a mid portion of the outer wall 12 , there is provided a horizontally - disposed inlet conduit member 34 leading to an opening 36 in the outer wall 12 . a portion 38 of the outer wall 12 , referring to fig2 extends beyond an end portion 40 of the conduit member 34 to direct fluid flow against interior surface portion 42 of the conduit member 34 and inner surface of the outer wall 12 thereby to enhance liquid contact with such interior surface and concomitant gas - liquid separation about such surface portion 42 . the frusto - conically - shaped intermediate wall member 18 extends inwardly and downwardly from the outer wall 12 . the intermediate wall member 18 is generally parallelly disposed with respect to the bottom wall 16 defining a liquid - liquid - solids lower separation chamber 24 . the bottom wall member 16 is formed with a centrally - disposed opening 43 in communication via a channel 44 with a lower vertically - disposed conduit 46 to allow a predetermined amount of liquid and the heavier than liquid particles to drain through the channel 44 . extending upwardly into the lower separation chamber 24 , there are provided a vertically - disposed first conduit member 48 having an upper opening 50 and a second vertically - disposed conduit member 52 having an upper opening 54 . the opening 50 and 54 of the first and second conduit members 48 and 52 , respectively , are positioned below the intermediate wall member 18 and outside a horizontal area defined by the opening 20 , as more fully hereinafter described . it is also the function of member 18 to act as a baffle and fluid diverter to prevent fluid borne debris from droping directly into the openings 50 and 54 upon entering chamber 24 . the opening 50 of the first conduit member 48 is disposed in a horizontal plane above the opening 54 of the second conduit member 52 with the opening 50 of the first conduit member 48 functioning as a weir for overflow of liquids and lighter than liquid particles and the opening 54 of the second conduit member 52 functioning to allow extraction of liquids from which significantly heavier and lighter than liquid particles have been removed . the conduit member 48 is in fluid communication via an opening 56 with the lower conduit member 46 which is in fluid flow communication by line 58 through a plumbing trap 60 to a disposal system ( not shown ). alternately , conduits 48 and 46 may be configured to not join at opening 56 , thereby allowing liquid with predominantly lighter than water particles and liquid with predominantly heavier than liquid particles to be drained separately . such separate draining , for example could enhance the separation of small amalgam particles from the disposal system . the second conduit member 52 is in fluid flow communication by line 64 under the control of valve 66 with the vacuum pump assembly , as more fully hereinafter described . vertically - disposed and extending downwardly through the opening 43 , there is provided an agitating wire member 68 mounted ( not shown ) for lateral and / or rotational movement within the channel 44 to prevent solids build - up about the opening 43 and within channel 44 . the conduit member 26 is in gaseous communication in the direction of line 70 with the atmosphere . the separator assembly 10 of the present invention is included in another aspect of the present invention to provide a portion of the water requirement for the water rings of the prime mover of a vacuum pump assembly for creation of vacuum , generally indicated as 80 , referring now to fig3 . the vacuum pump assembly 80 is comprised of a vacuum pump 82 including an inlet conduit 84 and an outlet conduit 86 , pump motor 88 and an electrical box 90 . the vacuum pump 82 is provided with a water supply line 92 in fluid flow communication with water rings 94 and the housing chamber 96 of the vacuum pump 82 as more fully hereinafter described . the inlet conduit 84 of the vacuum pump 82 is in fluid flow communication with a solid filter assembly 98 which is in fluid flow communication by line 100 with a vacuum valve assembly , generally indicated as 102 , such as described in copending u . s . application ser . no . 193 , 769 , filed may 13 , 1988 , assigned to the same assignee as the present invention and incorporate herein by reference . the outlet conduit 86 of the vacuum pump 82 is connected by line 104 to the inlet conduit member 34 of the separator assembly 10 . the water supply line 92 is in fluid flow communication with an eductor assembly , generally indicated as 106 , with a source of fresh water in line 92 and recirculated water in line 64 as more fully hereinafter described . the eductor assembly 106 includes an eductor housing 110 having a fresh water inlet conduit 112 , a recirculation inlet conduit 114 and an outlet conduit 116 and is provided with a nozzle 118 and a venturi device 120 . the outlet conduit 116 of the eductor assembly 106 is in fluid flow communication via line 122 under the control of three way valve ( or tee and check valve ) 124 with the water supply line 92 for the vacuum pump assembly 80 . the three way valve 124 is in fluid flow communication by line 126 with the three - way valve 128 as more fully hereinafter described . the fresh water supply line 108 is in fluid flow communication with the fresh water inlet conduit 112 of the eductor assembly 106 via a strainer 130 , a valve assembly 132 under the control of a solenoid ( not shown ) operated by the electric control assembly 90 , one way valve 134 , a flow restrictor 136 and thence through three - way valve 128 via line 138 under the control of pressure regulator 140 . in operation referring to fig3 a vacuum stream in line 100 from the vacuum valve assembly 102 including liquids , water , water vapor , gaseous components and solid particulate material including tooth particles , filling materials , decay , etc . is passed by line 100 through the solids filter unit 98 and thence by line 84 to the suction side or inlet of the vacuum pump 82 . in the solids filter assembly 98 , particulate material having a particular size of greater than about 400 μ are separated from the stream prior to inhalation of a resulting gas - liquid - solid mixture in line 84 into the vacuum pump 82 . water introduced by line 92 to the water rings 94 and into the chamber 96 is combined with the mixture and passed by line 104 from outlet conduit 86 of the vacuum pump 82 into the separator assembly 10 for processing as more fully hereinafter described , to provide a recirculation water stream in line 64 . the liquid stream in line 64 from the separator assembly 10 is passed to the inlet conduit 114 of the eductor assembly 106 . the water requirements for the vacuum pump assembly 82 are provided by fresh water in line 108 and the recirculation water in line 64 with the pressure of the fresh water stream in line 138 providing the means for forming the water stream in line 92 introduced into the vacuum pump 82 . the pressure of the fresh water stream in line 108 is generally of from about 30 to about 100 psig . regulated to 30 psig . by pressure regulator 140 and under the control of valve 132 in response to an on - mode condition of the motor 88 is passed through the strainer 130 to remove any particulate material of a particulate size greater than 200 μ , and is thence passed through the flow restrictor 136 to control waterflow rate , generally 0 . 5 to 0 . 75 gpm . depending on pump size prior to introduction into the eductor assembly 106 for passage through the nozzle 118 to entrain recirculating water in line 64 introduced by conduit 114 and form a combined water stream in line 122 after passage through the venturi 120 , which is preferably of like pressure and of a like quantity of a fresh water stream , per se , which would be necessary to operate the vacuum pump assembly 82 by passage thereto by line 126 under the control valves 128 and 124 and thence through line 92 in the absence of such recirculation water stream , sometimes referred to as the by - pass path . in such manner , fresh water requirements for the vacuum pump 82 are substantially reduced , e . g . of from 25 to 40 percent of usual fresh water requirements , and thus provides a corresponding savings of from 75 to 60 percent of fresh water as well as concomitantly reducing discharge requirements of an untreated effluent stream withdrawn from the discharge side of the vacuum pump 82 . the amount of recirculated water flow will vary slightly depending on operating condition of the system at any given time , but is always sufficient to provide for proper operation of the vacuum pump 82 . generally , fresh water supply is a relatively fixed value depending primarily on the pressure of the fresh water supply and the nozzle orifice size . should the eductor assembly 106 become inoperative , the fresh water requirements for the vacuum pump assembly 82 in line 92 may be supplied from the fresh water supply line 108 via line 126 under the control of by - pass valves 128 and 124 . it has been found that the pump performance , as measured and judged by both the volume flow rate of ingested gases , such as air at a given vacuum pressure and the highest vacuum pressure attainable , is a function of both the amount of liquid and the temperature of the liquid entering the pump . there is an optimum liquid rate below and above which the performance of a liquid ring pump deteriorates and as the liquid temperature increases the performances decreases , the latter being the stronger influence . increasing the liquid rate also increases the load on the pump and hence the power requirement . increasing the temperature of the liquid into the pump decreases the performance of the pump due to the increased vapor pressure of the liquid . recirculated liquid has an increased temperature , therefore , mixing recirculated liquid with fresh liquid increases the temperature of the pump supply liquid correspondingly . based on liquid supply flow rate only , it would seem that the recirculated fluid plus fresh fluid should total the design flow rate for maximum performance . however , because of the stronger dependence of performance on liquid temperature , it is desirable to entrain less than the full amount of recirculated liquid for optimal recirculation performance , which because of temperature reasons is always less than total fresh water injection performance . in any case , the fresh water supply rate in the recycling mode of this manifestation is independent of and unaffected by the variation of recirculated water flow rate , being determined by the regulated liquid supply pressure and the diameter of the nozzle opening in the eductor hereinafter described . the gas - liquid - solid effluent stream withdrawn from the outlet conduit 86 of the vacuum pump 82 is passed by line 104 to the inlet conduit member 34 of the separator assembly 10 , referring now to fig1 . the effluent stream is tangentially introduced into the chamber 22 of the separator assembly 10 along inner surface of the wall 12 thereof at force sufficient to permit gas - liquid separation with eventual gas removal via conduit 26 and vented via line 70 to the atmosphere . to insure gas separation from the liquid and solids , the separator assembly 10 is formed with the gas - liquid separation zone 28 whereby any liquid and entrained solids rising up the surface of the wall 12 contacts the outer surface 32 of the conduit member 26 for gravity flow downwardly along the outer surface 32 through the upper chamber 22 into the liquid - solids collection and separator chamber 24 . the liquid and entrained solids flow downwardly through the opening 20 in the intermediate plate member 18 and thence into the separator and collection chamber 24 with solids build - up about the base portion of the bottom wall member 16 . in the lower separation chamber 24 , the liquid phase is collected under conditions establishing a liquid level ( l ) as determined by the height of the opening 50 with lighter than liquid particles and lighter liquids permitted to overflow the opening 50 and flow down the conduit 48 to be admixed in conduit 46 with heavier than liquid particulate matter and heavier liquids passing through the channel 44 . the agitating member 68 is freely disposed through the orifice 43 and into the channel 44 to minimize solids build - up . the liquid flow rate through orifice 43 and channel 44 is fixed by the diameter of orifice 43 thereby establishing the diameter of agitating member 68 and the head of liquid to the level of opening 50 , as understood by one skilled in the art . the combined liquid - solids stream in conduit 46 is withdrawn by line 58 and passed to waste discharge . by keeping conduits 48 and 46 separate , it is possible to separately discharge lighter and heavier than liquid particles . intermediate density liquids , primarily water , is withdrawn through the opening 54 and passed by conduit member 52 to line 64 under the control of valve 66 as the recirculation water stream to be passed to the inlet conduit 114 of the eductor assembly 104 as hereinabove discussed . it is well known that the total energy of a system consists of the sum of kinetic energy , potential energy and thermal energy . in a gas stream , by comparison , the potential energy is negligible and can therefore be ignored . if a gas stream contains kinetic energy of motion and this motion is abruptly and turbulently brought to a significantly smaller velocity , the organized kinetic energy of the gas stream is converted into thermal energy primarily through frictional effects . if another fluid , such as a liquid is intermixed with the gas , this thermal energy is absorbed by the liquid thus raising its temperature . if , on the other hand the liquid is significantly separated from the gas prior to any frictional deceleration , and such deceleration is minimized by proper aerodynamic design , a significant amount of kinetic energy can be transported to be lost in a region remote from where the liquid can absorb that converted heat , then the separated water would have a temperature below that of the abrupt and turbulent deceleration previously described . the present invention possesses the characteristics of heat dissipation , such that heat is transported away by a highly vortical exiting air stream where the heat is dissipated in the gas vent instead of being transmitted to the fluid within the gas - liquid separation chamber . this is achieved by means of the tangential and smooth surface junctions of surfaces , the introduction of fluids into the separation chamber in a smooth , tangential manner via a slowly varying cross sectional area inlet and the imparting to the gas a high vortical or angular velocity . the concomitant centrifugal and centripetal forces created by the configuration design separate the fluid very quickly from the gas , then draining peripherally under the action of gravity to expose minimal surface area to the gas for absorption of thermal energy . the turbulent discharge cited as an example of the prior art contains many droplets which in total have a very large surface area and are in the abruptly slowed warmed gas flow , therefore providing an enhanced liquid warming environment . although this effect is not a major thermal load , it nevertheless underscores another advantage of the embodiment of this invention . operation of the process and apparatus of the present invention is described in the following example which is intended to be merely illustrative and the invention is not to be regarded as limited thereto . a nominally rated 1 . 0 horsepower motor drives a water ring vacuum pump capable of evacuating about 900 standard cubic feet per minute of air ( and / or gas mixture ) at a vacuum pressure of about 5 inches of mercury ( and about 700 scfm at about 9 inches of mercury ) requiring about one half gallon per minute of water for optimum performance . the eductor is constructed with a nozzle diameter to deliver water with a flow rate of 25 % of 1 / 2 gpm or about 1 / 8 gpm and consistent with a regulated fresh water supply pressure of about 30 psig . low pressure recirculated water is entrained by the fresh water in the eductor for delivery at the intermediate pressure into the regular injection ports of the pump housing . the clean water separator extracts a portion of the 400 μ debris from the recirculated water thereby reducing the total amount of debris which is reintroduced into the vacuum pump , as compared to systems of the prior art . recirculation in accordance with the present embodiment reduces pump performance by only between 2 % and 8 % depending on the vacuum and suction flow rate , as compared to the recirculation methods of the prior art which exhibit reductions of from 4 % to 16 % for similar recirculation water temperature and flow rate . reducing the amount of fresh water into the pump and recirculating a portion of the total amount of water required by the pump for optional operation also reduces the amount of water discharged as actual waste stream . thus , in accordance with the present invention , there is a significant reduction in quantity of a waste stream to enter the local disposal treatment plants . additionally , there is a significant reduction in fresh water requirements providing economic benefits through reduced fresh water consumption . the system permits facile operation with minimum requirements for operator maintenance and control as well as providing for emergency override fluid by - pass to minimize potential damage and / or downtime to the vacuum pump assembly . while the present invention has been described with reference to cylindrical and circular shapes , and it is obvious to one skilled in the art that spiral and elliptically shaped surfaces and shapes such as frustum conical surfaces create equivalent boundaries for providing centripetal forces for liquid separation from gases and heavier than liquid particles from liquids . it is also recognized that the aspect ratio of diameter to height of various components can be varied within the context of these separation phenomena . furthermore it is essential to recognize that the conical member 18 whether implemented as show in fig1 or inverted as alternately described herein earlier , performs the same function of baffling and in the limit could be a flat disk with suitable perforations . the importance of this baffle member is that it acts as a baffle serving both to direct liquid and shield the drainage openings as well as to separate the turbulent and agitated gasflow from the smoother desired liquid discharge flow . in addition , should a recycling liquid system not be required , the gas - liquid separation device pictured in fig1 can be used strictly as a gas - liquid separator in such a manner that all drainage paths are combined to form one leading into a common plumbing trap for liquid discharge . a simplification of the discharge channels is then possible by eliminating conduits 52 and 48 , enlarging orifice 42 and thus duct 44 , and eliminating the agitation device 68 . the baffle 18 is then an optional component and is not required , except to reduce internal splashing . the curved inlet duct 34 can also be shaped in such a fashion that the cross sectional flow area increases gradually and smoothly to allow smooth deceleration of the pump discharge flow while simultaneously being curved to provide simultaneous centrifugal separation of the liquid from the gases . smooth deceleration of the incoming stream allows gravity to contribute to the separation process early on . 1 . a defined and specific reduction in fresh water consumption , 75 % in this example ; 2 . a defined and specific reduction of liquid subject to disposal into the environment , 75 % in this example ; 4 . injection of recirculated and fresh water directly into the pump housing water injection ports ; 5 . optimization of recirculated water quantity to minimize reduction of performance due to water temperature rise ; 6 . internal aerodynamic design to preclude blowing out of traps , and to minimize the expulsion of water droplets with the separated air stream . while the invention has been described in connection with an exemplary embodiment thereof , it will be understood that many modifications will be apparent to those of ordinary skill in the art ; and that this application is intended to cover any adaptations of variations thereof . therefore , it is manifestly intended that this invention be only limited by the claims and equivalents thereof .

there is disclosed an improved liquid - solids - gas separator assembly permitting recovery of a major portion of the liquid stream for recirculation to a vacuum producing assembly wherein the separator assembly includes a gas - liquid and solids separator chamber and a liquids separator chamber for recovery of a recycle water stream and wherein the separator assembly comprises a vessel defining a cylindrically - shaped chamber into which a dental effluent including water , gases and lighter and heavier than water particles and from which a gas is vented through an upper conduit and liquid streams are recovered from a liquid pool wherein one liquid stream includes lighter than water particles and in one aspect is combined with heavier than water particles and a second liquid stream is recovered for recycling purposes .

fig1 shows an embodiment of a combination electrosurgical dissector and snare device 10 . dissector and snare device 10 has a handle 12 and an elongate shaft 14 having a pre - curved distal section 15 . the shaft is preferably rigid or semi - rigid so as to allow it to approximately retain its shape during use , although in alternative embodiment flexible shafts may be used . a jaw tip 16 is positioned at the distal end of the shaft 14 . referring to fig2 a , in one embodiment , the jaw tip 16 is a tubular element having integrally formed first and second jaw members 18 a , 18 b extending from a tubular coupling 20 . the single piece construction of the jaw tip biases the jaw members 18 a , 18 b in the closed position shown in fig2 a . each jaw member has a pair of teeth 19 extending towards the opposed jaw member . when in the closed position , the jaw members 18 a , 18 b define a distal gap or passage 22 at their distal ends . referring to fig2 b , the jaw tip 16 includes a cylindrical lumen 24 aligned with the passage 22 . walls defining the lumen 24 having longitudinally - extending edges 26 between the jaw members 18 a , 18 b . the edges 26 define a space between the jaw members 18 a , 18 b . due to the varying contour of the edges 26 , the space has a broad distal section 28 a and a narrow section 28 b proximal to the distal section 28 a . the distal end of the shaft 14 , with the jaw tip 16 removed , is shown in fig3 . a snare guide tube 30 extends through the lumen of the shaft 14 . a distal element 32 is positioned at the tip of the guide tube 30 and has an opening 34 aligned with the lumen of the snare guide tube 30 . in the illustrated embodiment , the distal element 32 is a spherical bead , the surface of which , as shown in fig4 a , extends into the broad distal section 28 a of the space between the jaw members 18 a , 18 b . the opening 34 in the distal element 32 is aligned with the distal passage 22 defined by the jaws in the closed position . referring to fig7 a the proximal end of the snare guide tube 30 is coupled to a piston 35 disposed within the handle 12 . as will be discussed in detail below , the piston 35 is longitudinally moveable within the handle to a retracted position to withdraw the snare guide tube 30 and thus its distal element 32 in a proximal direction . when the distal element is moved proximally , it cams the jaws to the open position shown in fig4 b as it moves from within the broad distal section 28 a to the narrow section 28 b of the space defined by the edges 26 . as shown , the jaw members 18 a , 18 b flex at flex regions 33 when they are moved to the open position . when the distal element is returned to a more distal position within the broad section 28 a , it moves out of contact with the edges 26 , allowing the spring bias of the jaw members 18 a , 18 b to return them to the closed position . a snare 36 is disposed within the snare guide tube 30 . the snare 36 is formed of a wire strand formed into a loop 38 . fig5 a shows the snare 36 in a fully deployed position in which the loop 38 is fully extended from the guide tube 30 . a v - shaped tip section 40 is positioned at the distal end of the loop 38 . the snare is advanceable from the fully retracted position shown in fig4 a in which the snare loop is fully contained within the snare guide tube 30 , to a partially extended position shown in fig5 b in which the tip section 40 extends from the snare guide tube 30 . when the snare loop is in the partially extended position , the portions of the wire loop just proximal to the “ v ” may extend in parallel contact with one another as shown in fig5 c . the snare loop is further advanceable to the fully deployed position shown in fig5 a . the snare 36 is formed of an electrically conductive wire so that the tip can function as an rf dissection wire . the snare 36 may be conductive only at the tip 40 , with the remainder of the loop 38 covered by insulative material , or the entire loop 40 ( including the tip 40 ) may be conductive . as most easily viewed in fig6 , the snare 36 includes two parallel proximal end sections 42 a , 42 b of the snare wire . the end sections 42 a , 42 b are connected to a snare conductor 43 by soldering , using a short piece of tubing 47 to cover and complete the joint . referring now to fig7 a and 7b , the snare conductor 43 extends through the snare guide tube 30 , around a pin 44 , and is coupled to a slider 46 . the slider 46 includes first and second pins 48 a , 48 b , each of which is connected to the snare conductor 43 . as shown in fig8 , the ends of each pin 48 a , 48 b are slidably disposed in slots 50 in opposite sides of the handle housing ( one side of which is shown ). a head 52 on the slider 46 is slidably positioned within slots 53 parallel to the slots 50 . an upper surface of the head includes a sawtooth pattern of ridges 55 a . corresponding ridges 55 b are formed in the slots 53 such that the ridges 55 a , 55 b engage one another to maintain the longitudinal position of the slider 46 within the slots 53 . the snare conductor 43 extends from the second pin 48 b of the slider 46 , around another pin 56 and a series of pulleys 58 , 60 , 62 and is coupled to a proximal side of the piston 35 . pulley 58 is supported by a bracket 64 mounted to a compression spring 66 . the compression spring 66 is seated within a slot 68 ( fig7 a ) in the handle 12 . the snare conductor 43 is electrically coupled to an energy source such as a monopolar rf source 45 ( fig1 ). fig7 b shows that in the illustrated embodiment , a conductor 59 is coupled to one of the pins 56 with which the snare conductor 43 is in contact , so that the pin 56 electrically couples the snare conductor 43 to conductor 59 . a pair of jaw actuation cables 70 is connected to the piston 35 . the cables 70 extend around a pin and are connected to spool 72 connected to a grip 74 . the spool 72 is pivotally mounted within the handle 12 by a pin 76 . referring again to fig1 , a preferred handle housing is comprised of shell halves 78 a , 78 b which , when assembled , leaved an exposed cutout 80 . the cutout 80 is covered by a cover 82 having flexible end sections 84 that extend into the cutout 80 . the cover 82 includes a button 86 disposed between the end sections 84 . the button 86 is coupled to a standoff 87 ( fig7 a ) that extends towards the button 86 from the head 52 of slider 46 ( fig8 ). the sawtooth ridges 55 b in the handle 12 ( described with reference to fig8 ) contact the head 52 on opposite sides of the standoff 87 . pressing the button 86 towards the cutout 80 depresses the head 52 to move the ridges 55 a of the head out of engagement with the ridges 55 b in the handle . sliding the button 86 distally after disengaging the ridges 55 a , 55 b slides the slider 46 distally within the handle . when the button slides 86 , its flexible end sections 84 slide within slots 85 ( fig8 ) in the housing . operation of the device 10 will next be described . a user will typically hold the device with his / her palm against the handle 12 , his / her index finger extending through the grip 74 , and his / her thumb on the button 86 . to open the jaws 18 a , 18 b , the user squeezes the grip 74 towards the handle 12 , causing the grip 74 and spool 72 to pivot relative to the pin 76 and to thus apply tension to the jaw actuation cables 70 . the actuation cables 70 pull the piston 35 in a proximal direction and in doing so they withdraw the snare guide tube 30 proximally . the distal element 32 on the snare guide tube 30 spreads the jaws apart by camming the jaws into the open position by acting on the edges 26 as described above . releasing the grip 74 causes the jaws to return to the open position under their own spring bias . the features for retracting the snare guide tube 30 to open the jaws and for deploying the snare operate cooperatively to maintain the longitudinal alignment of the snare loop 38 and the snare guide tube 30 . in particular , when the piston 35 is moved proximally to retract the snare guide tube 30 , it pulls the distal end of the snare cable 43 ( i . e . the portion anchored to the piston 35 near pulley 62 ) proximally , applying tension to the slider 46 and thus the portion of the snare cable 43 that extends into the snare guide tube 30 , to retract the snare 36 by a corresponding amount . this avoids inadvertent exposure of the snare loop 38 when the jaws are opened . the bracket 64 and spring 66 act as a tensioning system to aid in maintaining the position of the snare loop 38 relative to the jaws 18 a , 18 b . to extend the snare loop 38 , the user presses button 86 using his or her thumb . the button 86 presses downwardly against the head 52 of the slider 46 , releasing the engagement between the sawtooth ridges 55 a , 55 b . once released , the slider 46 is free to slide longitudinally within the handle . the user advances the button 86 to slide the slider 46 in a distal direction , thus pushing the snare loop 38 from the distal end of the snare guide tube 30 . because of the passage 22 in the jaw tip , the snare loop 38 can be advanced whether the jaws are closed or open . it should be noted that the jaw tip 16 is preferably formed of material that is not electrically conductive so as to prevent conduction of rf energy from the snare to the jaws . the user may advance the snare loop 38 by a first amount to expose only the tip 40 ( fig5 b ), or s / he may advance the snare loop 38 by a greater amount to fully deploy the snare ( fig5 a ). the user can engage the snare loop 38 in an extended position by releasing pressure against the button 86 , allowing the sawtooth ridges of the head 52 to re - engage with the corresponding ridges in the handle . when it is time to retract the snare loop 38 , the user applies downward pressure to the button 86 to disengage the ridges 55 a , 55 b and s / he then retracts the button 86 proximally to return the slider to its original position . in a typical procedure , the device 10 is advanced through a single port or laparoscopic access device into the abdominal cavity and advanced towards the stomach . the snare loop 38 is advanced to the position shown in fig5 b , exposing the tip 40 . the snare loop 38 is energized by activating the rf energy source 45 ( e . g . by depressing a foot pedal ). the tip 40 is advanced around the posterior side of the stomach , electrosurgically forming a tunnel t through the fascia , connective tissue and / or other tissue posterior to the stomach as shown in fig9 a . the user may begin the electrosurgical step adjacent to the lesser curvature lc of the stomach and continue formation of the tunnel under the stomach to the greater curvature gc , or the electrosurgical step may be at the greater curvature and work towards the lesser curvature . the electrosurgically formed tunnel t is expanded using the dissecting jaws 18 a , 18 b as shown in fig9 b . this step may be performed during the electrosurgical step , with the jaws being opened and closed behind the energized tip 40 as the tip 40 forms the tunnel through the tissue . alternatively , or in addition to using the jaws during electrosurgical dissection , the distal end of the device may be retracted back through tunnel and the jaws used at that time ( during retraction and / or subsequent re - advancement of the device within the tunnel ) to increase the size of the tunnel using known dissection techniques . use of the jaws for dissection can involve opening the jaws to separate tissue layers on opposite sides of the jaws the curvature of the distal section 15 aids in directing the operative tip around the stomach and into a more anterior position ( fig9 c ) appropriate for full deployment of the snare for retrieving the gastric band g . once the tunnel has been dissected to an appropriate size , the snare is moved to the fully deployed position of fig5 a , and a portion of a gastric banding device is placed within the loop of the snare . the snare is withdrawn somewhat to cinch the loop against the gastric banding device . the device 10 is withdrawn , passing again around the posterior side of the stomach , thus drawing the engaged end of the gastric banding device with it . the banding device is closed into a loop and retained in place using known techniques . the dissector and snare device 10 is removed from the body cavity , leaving the banding device implanted around the stomach . it should be recognized that a number of variations of the above - identified embodiments will be obvious to one of ordinary skill in the art in view of the foregoing description . accordingly , the invention is not to be limited by those specific embodiments and methods of the present invention shown and described herein . rather , the scope of the invention is to be defined by the claims and their equivalents . any and all applications referred to herein , including for purposes of priority , are hereby incorporated herein by reference .

a medical device includes a tissue dissector and a snare loop on a common shaft . at least the distal tip of the snare loop is energizable to function as an electrosurgical element for tissue dissection . in use the snare loop is partially extended from the shaft to expose the electrosurgical element for electrosurgical dissection , and the snare loop is fully extended from the shaft to deploy the snare loop for retrieval and positioning of an implant such as a gastric banding device . the snare loop may be deployed through a pair of jaws also mounted on the shaft for use in tissue dissection .

provided herein are splints for use in orthodontic treatment . in preferred embodiments , the splints provides anchorage as part of a system of appliances that are bonded to some or all of the central , lateral , cuspid , bicuspid , and molar teeth of a dental arch and cooperate with a suitable archwire for moving teeth to proper respective locations . the splints couple two or more teeth to each other and may have a configuration for attachment to either facial or lingual surfaces of the teeth , and can be adapted for use on either the upper or lower arches . while embodiments described herein are directed to lingual splints , it should be understood that similar features and benefits may also apply for labial splints with references to facial and lingual directions reversed . the provided splints may have a universal configuration reflecting normative tooth shapes in the patient population . alternatively , the splints can be custom manufactured according to the shapes of a particular patient &# 39 ; s teeth , and thus may have configurations that differ substantially from one patient to the next . some of these possibilities are further explored in the sections below . while particular splint configurations and features are shown herein by way of illustration and example , however , these embodiments should not be construed as unduly limiting the scope of the invention . a lingual splint , according to one exemplary embodiment , is shown in fig2 - 3 and broadly designated by the numeral 100 . the splint 100 has a mesial base 102 and a distal base 104 . each of the bases 102 , 104 has a bonding surface 106 , 108 for attachment to a corresponding tooth . as shown in fig2 , the bases 102 , 104 and respective bonding surfaces 106 , 108 are customized to substantially match the lingual contours of the first and second bicuspid teeth of a patient . the bonding surfaces 106 , 108 can have a surface structure that assists in providing mechanical retention with a suitable bonding adhesive . the surface structure can improve adhesion , for example , by forming a mechanical lock or chemical bond with a suitable adhesive disposed between the bonding surface 106 , 108 and the tooth surface . the surface structure may include holes , grooves , particles , recesses , undercuts , a micro - etched surface , a chemical bond enhancement material , or any other structure , material or combination thereof . the bases 102 , 104 can extend over a significant portion of its associated tooth surface to provide for adhesion over a larger surface area and a stronger overall bond . although not shown here , one or both of the bases 102 , 104 could even extend entirely around the tooth , resulting in a banded appliance . the bases 102 , 104 also have respective outer surfaces 110 , 112 opposite the bonding surfaces 106 , 108 and facing the lingual direction . preferably , the outer surfaces 110 , 112 substantially match the contours of the underlying teeth surfaces , giving the splint 100 a low overall profile for enhanced patient comfort . each of the bases 102 , 104 also has a respective outer edge 114 , 116 ( shown in fig3 ) that extending along the periphery of the bonding surfaces 106 , 108 as viewed from a direction generally perpendicular to the surfaces 106 , 108 . as shown in the embodiment of fig3 , each outer edge 114 , 116 fully surrounds its respective surface 106 , 108 . an elongated connector beam 120 connects the mesial and distal bases 102 , 104 to each other . the connector beam 120 has a mesial end 122 and a distal end 124 and a longitudinal midpoint 126 . in a preferred embodiment , the connector beam 120 is made from a flexible material that allows the splint 100 to visibly deflect , or “ flex ,” within its elastic limit in response to usual forces encountered during orthodontic treatment . optionally , the connector beam 120 is also resilient along essentially its entire length , such that the beam 120 substantially returns to its original shape when relaxed . the connector beam 120 acts as a “ shock absorber ” that allows the mesial and distal bases 102 , 104 to shift relative to each other during orthodontic treatment without inducing a significant degree of permanent deformation in either the bases 102 , 104 or the connector beam 120 . this can be beneficial to the treating professional because it allows two ( or more ) teeth to be joined together to provide increased anchorage , while tolerating a small degree of relative movement that naturally occur between teeth as a result of chewing forces and treatment mechanics . the mesial and distal ends 122 , 124 are joined to the respective outer surface 110 , 112 of the bases 102 , 104 along locations remote from ( or away from ) the outer edges 114 , 116 . by spacing the joint between the connector beam 120 and each base 102 , 104 to locations remote from the outer edge 114 , 116 , the stress on the adhesive can be moved away from the edges of the bonding interface , where the bond between the tooth and the splint 100 is most vulnerable to shear - peel failure . as will be later shown in the examples section , this aspect was found to significantly reduce the likelihood of shear - peel failure of the splint 100 . as further shown in fig2 - 3 , the connector beam 120 has a generally rectangular cross - section as defined along reference planes perpendicular to the longitudinal axis of the connector beam 120 . in a preferred embodiment , the long axis of the rectangular cross - section is aligned along a generally occlusal - gingival direction . optionally , the rectangular connector beam 120 is canted so that it lies approximately parallel with the underlying bonding surfaces 106 , 108 in consideration with the inclination of the teeth to which the splint 100 is bonded . such alignment can reduce facial - lingual height , thereby reducing the overall profile of the splint 100 and promoting patient comfort . unlike the banded splint configuration shown in fig1 , the splint 100 has a cross - section whose size and shape vary along the longitudinal axis of the connector beam 120 . in the present instance , the connector beam 120 has a cross - sectional dimension that varies along two orthogonal axes . in fig2 , for example , the facial - lingual thickness of the connector beam 120 generally increases with increasing proximity to the nearest mesial or distal end 122 , 124 , and generally decreases when approaching the midpoint 126 from either the first or second base 102 , 104 . stated another way , the cross - sectional dimension generally increases with increasing proximity to the nearer of the first or second base 102 , 104 . this is also shown in fig3 , in which the splint has its largest gingival - occlusal dimension “ a ” toward the ends 122 , 124 and its smallest gingival - occlusal dimension “ b ” toward the midpoint 126 . in some embodiments , the ratio between a cross - sectional dimension of the connector beam 120 at its widest point and the cross - sectional dimension at its narrowest point is at least 1 , at least 1 . 25 , at least 1 . 5 , or at least 1 . 75 . in some embodiments , the ratio between a cross - sectional dimension of the connector beam 120 at its widest point and the cross - sectional dimension at its narrowest point is at most 3 , at most 2 . 5 , at most 2 , or at most 1 . 75 . in some embodiments , the cross - sectional dimension itself at its narrowest point is at least 0 . 18 millimeters , at least 0 . 4 millimeters , or at least 0 . 5 millimeters . in some embodiments , the cross - sectional dimension at its narrowest point is at most 1 . 4 millimeters , at most 1 . 1 millimeters , or at most 0 . 8 millimeters . it can be advantageous for the facial - lingual dimension of the connector beam 120 to vary over a narrower range compared with the occlusal - gingival direction . in some embodiments , for example , the facial - lingual thickness of the connector beam 120 can be essentially uniform throughout its length while the occlusal - gingival thickness varies substantially along its length . greater uniformity in thickness can allow the splint 100 to have a lower overall profile , a feature that could advantageously enhance patient comfort by reducing the extent to which the splint 100 impinges against the cheek of the patient . as further shown in fig2 - 3 , an orthodontic bracket 128 is joined to the mesial base 102 of the splint 100 , providing options for engagement with an archwire , force module ( such as a power chain or elastic ), trans - palatal device or other ancillary orthodontic appliance . optionally , the bracket 128 and splint 100 have a unitary construction and are manufactured as a unitary component . the bracket 128 has a slot for accommodating an archwire during the course of treatment . by fastening two or more teeth together , the splint 100 can provide enhanced anchorage when an archwire is activated in the slot of the bracket 128 . if desired , anchorage can be further improved by incorporating one or more additional bonding bases into the splint 100 , thereby leveraging the collective anchorage of three or more teeth . the shape of the connector beam 120 can impart significant and unexpected advantages to the splint 100 . first , by having a cross - sectional dimension that is enlarged near the ends 122 , 124 and reduced near the midpoint 126 , the principal stresses on the splint 100 are delocalized , or distributed more evenly , along the length of the connector beam 120 as the teeth move relative to each other . this has the effect of lowering the principal stress at the ends 122 , 124 where the adhesive / appliance and adhesive / tooth interface present weak boundary layers where debonding of the splint 100 can occur . second , the distribution of stress over an extended portion of the connector beam 120 can provide superior fatigue resistance . as a result , the splint 100 can display dramatically improved robustness over previous splint configurations disclosed in the art . optionally and as shown , the ends 122 , 124 of the connector beam 120 extend outwardly from the bases 102 , 104 along a direction approximately normal to planes 111 , 113 tangent to the underlying outer surfaces 110 , 112 ( in fig3 , for example , the tangent planes 111 , 113 are defined where the instantaneous longitudinal axis 123 , 125 of the connector beam 120 intersects with each outer surface 110 , 112 ). referring to fig2 , the ends 122 , 124 ( as represented by the longitudinal axes 123 , 125 ) extend outwardly at respective angles θ 1 and θ 2 relative to the tangent planes 111 , 113 , where θ 1 is approximately 90 degrees and θ 2 is somewhat less than 90 degrees . advantageously , this configuration can distribute principal stresses evenly along the cross - section of the connector beam 120 where each end 122 , 124 is joined with its base 102 , 104 , and reduce the likelihood of shear - peel failure at the joint connecting the connector beam 120 to the bases 102 , 104 . such a construction can also provide a minimal amount of facial - lingual separation between the connector beam 120 and the underlying bases 102 , 104 to facilitate manufacturing of the splint 100 , for example , by microcasting . in some embodiments , each end of the connector portion extends outwardly away from each base 102 , 104 at an angle θ of at least 10 degrees , at least 30 degrees , or at least 70 degrees , relative to a tangent plane 111 , 113 where the longitudinal axis of the connector beam 120 intersects respective outer surface 110 , 112 . in some embodiments , each end of the connector portion extends outwardly away from each base 102 , 104 at an angle θ of up to 80 degrees , up to 85 degrees , or up to 90 degrees , relative to the tangent plane 111 , 113 above . the connector beam 120 need not extend along a path that continually travels away from one base 102 , 104 and toward the other . for example , the connector beam 120 could initially extend from base 102 in a direction away from the base 104 , then subsequently bend back toward base 104 . fig4 - 5 present views of a splint 100 ′ as it would appear when bonded to the lower first bicuspid 130 and second bicuspid 132 teeth of a patient . a connector beam 120 ′, having outer ends that extend outwardly away from the surface of each tooth 130 , 132 , resiliently interconnects respective bases 102 ′, 104 ′. optionally and as shown , the bases 102 ′, 104 ′ of the splint 100 ′ cover essentially all of the lingual surfaces of the teeth 130 , 132 , providing an increased surface area for attachment and enhanced bond reliability . while the teeth 130 , 132 are adjacent teeth as shown here , this need not be the case . in some embodiments , for example , the connector beam 120 ′ of the splint 100 ′ could extend over the lingual surfaces of one or more intermediate teeth without being directly bonded to them . also , the splint 100 ′ can be bonded to three or more teeth in a consecutive manner if even greater anchorage is desired by the treating professional . to better understand the result of having the connector beam contacting respective bases of the splint at locations remote from ( as opposed to adjacent to ) the outer edge of the base , finite element analysis ( fea ) was used to simulate the three - dimensional ( 3d ) stress profiles of seven different splint configurations , shown in fig6 ( a )- 6 ( g ). the fea was performed on 3d models of the splints using ansys brand simulation software ( v . 13 , available from ansys inc ., canonsburg , pa .). each of the splint configurations included bases that were adhesively bonded to virtual first and second bicuspid teeth , and in some cases , the first molar tooth . in this model , the teeth were surrounded by periodontal ligaments , which connected each tooth to its surrounding bone . the adhesive pad connecting each base to its underlying tooth had a defined thickness of 0 . 127 millimeters . the thickness of the periodontal ligaments (“ pdl ”) was defined to be 0 . 15 millimeters for the bicuspid teeth and 0 . 20 millimeters for the first molar tooth . the thickness of the splint itself was defined as 0 . 508 millimeters , and the splint has a generally constant cross - sectional shape . the analysis also made certain assumptions concerning young &# 39 ; s modulus and poisson ratio of the component materials represented in the simulations . these values are provided in table 1 below . the splints were then subjected to two different loading conditions to observe the resulting stress profiles : 1 ) a 178 n ( 40 lb .) occlusal force on the occlusal surface of the second bicuspid , and 2 ) an 89 n ( 20 lb .) occlusal force on the occlusal surface of the splint between the first and second bicuspids . the simulated force levels on the adhesive and pdl , and simulated principal stress imposed on splint , are shown for each splint configuration in tables 2 and 3 below . the fea showed significant differences in force and stress levels amongst concepts a - g , particularly in response to occlusal forces to the second bicuspid as shown in table 2 . referring to the results obtained for concepts a , b , and c in table 2 above , the application of about 178 n ( 40 lbs .) of bite force to the second bicuspid generated a force on the adhesive ranging from about 11 to 115 n . as to concepts d and e , the inclusion of either a 0 . 51 × 0 . 76 mm or 0 . 51 × 0 . 76 mm connector beam reduced the force on the adhesive to less than 40 n ( 9 lbs . ), with the majority of the force absorbed by the pdl . however , the stresses on the connector beams are still higher than those in concepts a and b . concept g transmitted the lowest force to the adhesive of 10 . 7 n , while also showing decreased stress on the splint compared with other flexible splint concepts . concept g also appeared to impart greater forces to the pdl , up to about 169 n . fig7 and 8 show the simulated stress profile obtained for a simulated splint 200 ( similar to splint concept g above ). as shown , the splint 200 has bonding bases 202 , 204 and includes a connector beam 220 , with a cross - sectional area increasing toward its ends and decreasing toward its midpoint . in this concept , both the occlusal - gingival and facial - lingual components of the cross - sectional area vary along the longitudinal axis of the connector beam 220 . fig7 and 8 show the distribution of the maximum principal stress from the ends of the connector beam toward the center of the connector beam 220 . areas of relatively high stress are indicated by darker shading , while areas of relatively low stress are indicated by lighter shading . the simulation showed that the beam 220 has a geometry that allows stress to be spread over a significant length of the beam , rather than being concentrated at its ends . optionally , the configuration of the splint 200 can be further modified such that that the locations subjected to the highest levels of stress are provided with an enlarged cross - section to strengthen the splint 200 in locations where failure is most likely to occur . objects and advantages of the provided orthodontic splints are further illustrated by the following examples . “ sil ” refers to sil brand silane primer , provided by 3m espe in st . paul , minn . ; “ concise ” refers to concise brand orthodontic chemical cure adhesive ( ref 196 - 002 & amp ; 196 - 003 ), provided by 3m unitek in monrovia , calif . ; and “ rocatec plus ” refers to a rocatec brand jr . blasting module using rocatec brand plus media , both provided by 3m company in st . paul , minn . splints were manufactured using a “ lost - wax ” investment casting procedure , similar to those described in u . s . pat . no . 6 , 776 , 614 ( wiechmann , et al .). in brief , the procedure begins with obtaining a 3d model of the splint configuration , as shown for example in fig2 . the 3d model was then exported to a rapid prototyping machine ( a 3d printer ) that constructed , layer - by - layer , a resin model of the splint . after printing , the resin model is used as a core in an investment casting process , where the model is embedded in cement and then melted to afford a negative mold . the negative mold is used to cast the final splint from gold alloy , after which the splint is removed by quenching the mold in water . each splint was bonded to two stainless steel rings having convex , knurled surfaces and positioned side - to - side . each ring accommodated a respective base of the splint . the bonding surface of each base was sandblasted with rocatec plus ( 110 micrometer diameter silica , coated with aluminum oxide ) according to manufacturer &# 39 ; s instructions . a thin layer of sil was then lightly brushed onto the sandblasted surfaces according to manufacturer &# 39 ; s instructions . the splint was then bonded to the knurled rings using concise in accordance with manufacturer instructions . debonding was conducted on each test specimen using a q - test brand 5 universal test machine ( from mts in eden prairie , minn .) outfitted with a 1000 newton load cell . once the splint to be tested has been bonded to the pair of knurled rings , the rings were mounted to a two - part fixture and subjected to a simple displacement test . in this test , the first part of the fixture is held in a fixed position , while the second part is translated upward by the test machine at a fixed crosshead speed of 2 . 54 millimeters / second ( 0 . 1 inches / second ). crosshead displacement and load were continuously recorded until splint failure occurred . failure was defined as either debonding , fracture , or substantial permanent deformation of the splint . the maximum force , and displacement at the maximum force , were then recorded for the test run . depending on the orientation of the rings in the fixture , the splint can be tested either in the facial - lingual direction or the occlusal - gingival direction . facial - lingual fracture testing was conducted by orienting the rings such that the bonding surfaces of the splint were approximately parallel to the direction of the displacement . occlusal - gingival testing was conducted by rotating the rings 90 degrees such that the bonding surfaces are approximately perpendicular to the direction of displacement . since the splints were asymmetric when tested in the facial - lingual configuration , the orientation of the splint was flipped to provide an average measurement reflecting the results for both orientations . facial - lingual fracture testing was performed on various splint samples according to the fracture test procedure above . this test examines a failure mode in which one tooth shifts in along a facial - lingual direction relative to its neighbor . examples 1 and example 2 were fabricated based on the splint configuration shown in fig6 - 7 . examples 1 and 2 differed in that the former used a solidscape brand 3d printer ( from stratasys , eden prairie , minn . ), while the latter used a perfactory brand 3d printer ( from envisiontec gmbh , gladbeck , germany ). comparative ce - 1 used a band splint configuration shown in fig1 made using the solidscape brand printer . the results of these tests are shown in table 4 below . as further noted below , some but not all splints debonded entirely from one of the rings during testing . occlusal - gingival fracture testing was performed in examples 3 - 4 and ce - 2 . in these measurements , each splint was oriented in the fixture to simulate the failure mode caused by occlusal - gingival movement of one tooth relative to its neighbor . like examples 1 and 2 above , examples 3 and 4 were prepared using a solidscape brand 3d printer and a perfactory brand 3d printer , respectively . fracture test results for examples 3 and 4 are given in table 5 below . fatigue testing was then conducted on the splints of examples 1 and 2 , respectively , in an occlusal - gingival orientation . in these tests , all splints tested survived 500 cycles at a strain amplitude of ± 0 . 30 mm . when the amplitude was subsequently increased to ± 0 . 45 mm , all samples eventually failed . the average cycle life of each example is shown in table 6 below . all of the patents and patent applications mentioned above are hereby expressly incorporated into the present disclosure . the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity and understanding . however , various alternatives , modifications , and equivalents may be used and the above description should not be taken as limiting in the scope of the invention which is defined by the following claims and their equivalents .

provided is an orthodontic splint and related methods , which use two or more bonding pads and a flexible connector beam that deflects in response to stress , effectively reducing the amount of stress felt by the adhesive . the connector beam has a non - uniform cross - section along its length , thereby shifting the maximum stress away from the ends of the beam and toward the mid - point of the beam . further , the connector beam attached to each base along locations remote from the outer edge of the base . these splint configurations can decrease the likelihood of bond failure and improve fatigue performance by causing stress , and associated strain , encountered during treatment to be spread more evenly along the length of the beam .

fig1 is a side cut - away view of the fluid - delivery emitter ( 1 ). there is a plurality of fluid channels ( 5 ) gently sloping inward to the center direction as they terminate at a release opening ( 6 ). small polarized magnets ( 7 ) are near the outer side boundaries . these magnets ( 7 ) are aligned alike , such that the north ends all point in the same direction ; either in towards the central axis , or away from the axis . hashed line ( 8 ) isolates a cross - section that will be depicted in fig4 to clarify this . hashed line ( 9 ) harkens a region of emitter ( 1 ) that is manufactured from a soft plastic similar to that used for plastic tubing . thus , the release end of emitter ( 1 ) can be pulled to , or pushed away from , a variable strength polarized magnetic field generator ( 10 ) attached to an arm of stabilizing fixture ( 3 ). operator control reversing the polarity of field generator ( 10 ) either pulls or repels the magnets ( 7 ) embedded in the spinning outer edge of emitter ( 1 ), which either pulls or repels the entire release end of emitter ( 1 ), causing a bending effect allowed by the elasticity of the middle region of emitter ( 1 ). electrical current is supplied to field generator ( 10 ) by wire ( 11 ), which enters stabilizing fixture ( 3 ) at electrical connector ( 12 ). additional wire ( 13 ) supplies electricity to a small motor ( 14 ) securely fastened to fixture ( 3 ). when energized , motor ( 14 ) spins its toothed gear ( 15 ). the teeth of gear ( 15 ) engage complementary spokes ( 16 ) lining the inside lower end of emitter ( 1 ), which causes emitter ( 1 ) to spin around on command . water union ( 2 ) has a release end ( 17 ) that spins together with exit fluid pipe ( 18 ). however , entry pipe ( 19 ) passes fluid delivered in by input channel ( 4 ) on through to exit pipe ( 18 ), as is the innate utility of water unions . the junction ( 20 ) of pipe ( 18 ) and pipe ( 19 ) is fashioned to contain leaks while fluid is being passed from one pipe to the other . nexus ( 21 ) is the position along pipe ( 18 ) where the fluid is routed into the plurality of channels ( 5 ). pressurized fluid delivered through stabilizing fixture ( 3 ) is initially routed through solenoid valve ( 22 ), which alternately stops and releases the inflow as programmed . a desired operational value would engage multiple times a second , which causes fluid microbursts to leave each release opening ( 6 ), rather than continuous micro jets . pressurized gas ( 23 ) is mixed with incoming fluid at crossing junction ( 24 ) after passing through gas entry valve ( 25 ). operator control of regulation lever ( 26 ) sets the amount of pressurized gas admixed with the incoming fluid . hashed line ( 27 ) isolates a cross - section of the lower end of emitter ( 1 ) as depicted in fig5 . fig2 is an end perspective view of emitter ( 1 ), which spins around central axis ( 28 ), which is further identified by the letter “ x ”. the plurality of release openings ( 6 ) are each placed at varying distances from axis ( 28 ). the further a particular release opening is from axis ( 28 ), there is an increase in diameter . this increases the volume of fluid released at the outer edges of emitter ( 1 ), and lessens the relative volume of fluid released in the central regions when emitter ( 1 ) is spinning . to further evenly distribute the entire discharge across a desired target surface , a polarized ring of small magnets ( 7 ) can be attracted or repulsed from polarized magnetic field generator ( 10 ), which is immobile because it is attached to stabilizing fixture ( 3 ). because the central torso region ( 9 ) of emitter ( 1 ) is somewhat flexible , the entire fluid discharge is swept back and forth at high speed to inundate the target dental surface . this happens as the polarity of generator ( 10 ) is reversed from north attracting to north repulsing by operator programming . fig3 is a side view of the discharge end of emitter ( 1 ) showing the effect of directing the fluid channels ( 5 ) to an inwards slope angle . ejected fluid ( 29 ) from channel ( 5 ) strikes a juxtaposed target surface ( 30 ) flush on , which causes the majority of deflected splash ( 31 ) to head towards the inner spin axis . this splash ( 31 ) is designed to be nullified and lose further impact strength as it collides with a counter splash from an opposing channel of emitter ( 1 ). this nullification effect , as the emitter spins , severely limits the outwards splash created by the overall fluid impacting a target surface . fig4 is an end perspective view of emitter ( 1 ) similar to that of fig2 , where one of the innermost pair of release openings ( 32 ) together with its paired nullification partner , are moved to a 90 degree position from the linear orientation of the two outermost openings . this is the release opening orientation of the preferred embodiment . a 90 degree orientation reduces the chance of splashed fluid from the outermost pair of release openings blocking the incoming flight of fluid from the innermost pair of openings , as is depicted in fig3 where four release openings are arranged in perfect linear fashion . fig5 is a cross section along section line ( 27 ) as seen in fig1 . this shows the propulsion of emitter ( 1 ) into a steady spin by the action of motor - driven gear ( 15 ) engaging a ring of matching spokes ( 16 ) encircling the inner lower portion of emitter ( 1 ). delivery pipe ( 19 ) does not spin , and holds a central location as fluid pass through it up into spinning emitter ( 1 ). the preferred instant invention is a low - splash fluid distribution implement that spins around a central axis for fluid elongation . its discharge is unlike a single jet of water which continually drives fluid onto fluid . as a result of the spin - induced elongation effect , the paired inward - sloping beams from the instant invention continually strike substrate before splashing towards each other . an improvement is the addition of a sweep action to the discharge . further dependent improvements to the invention include water mass reduction by both use of a solenoid valve ( 22 ) and aeration . the latter by admission of gas particles to the fluid stream at a crossing junction ( 24 ). means to laterally sweep the discharge end of the emitter are described using magnetic attraction and repulsion . this feature is termed lateral displacement sweeping . other patterns can be created . for example , another magnetic field generator placed 90 degrees from the first could cross - sweep the emitter &# 39 ; s release end in tandem with the original displacement pattern . this combined sweeping motion is termed circular displacement sweeping . other travel patterns and sweep schemes than magnetic can be designed . the described electric motor ( 14 ) and gear ( 16 ) used in fig1 to propel the emitter can be replaced by air driven motors , magnetic circuits , or other propulsion technology known to the art . the instant invention can be applied to other categories within dentistry such as removing tartar , orthodontic adhesive , or old bonding layers for porcelain cap re - fittings , etc , or other fields such as veterinarian medicine . the foregoing description of the preferred and alternate embodiments of the invention has been presented for purposes of illustration and description . it is not intended to be exhaustive or to limit the invention to the precise form disclosed , as many modifications and variations are possible in light of the above teaching without deviating from the spirit and the scope of the invention . the embodiments described are selected to best explain the principles of the invention and its practical application to thereby enable others skilled in the art to best utilize the invention in various embodiments and with various modifications as suited to the particular purpose contemplated . it is intended that the scope of the invention be defined by the claims appended hereto .

the invention is a low - splash dental fluid distribution implement with the ability to evenly wear down tooth decay , diseased tissue , or undesired dentin in oral applications with live patients . the directed multi - beams of pressurized fluid are a combined plurality of individual beams paired in such a manner that the reflected fluid bursts are inwardly directed against each other . this canceling effect prevents damage to the oral tissues of the patient &# 39 ; s mouth by curtailing outward bound bursts of fluid arising from the initial directed impact . also , the outer edges of the strike zone receive a comparable force as that which hits the center .

this sequence of oscillations causes the rotor within sport device to spin rapidly thereby winding the watch in a manner closely simulating the spinning of the rotor that occurs during normal aerobic activity when the sport device is worn by a user . due to the forces that are exerted , the rotor spins around the sport device shaft during the oscillations , as opposed to the partial rotation observed in prior art mechanisms . therefore , the time required to charge the sport device , and the energy required , is substantially reduced . moreover , since the rotor is spinning about the shaft , as opposed to merely being held in a downward position while the sport device is rotated , recharging more closely approximating the design mechanism is achieved , thereby putting less wear on the sport device . prior art fig1 rear face 32 of watch carrier includes a central bore 44 for receiving shaft . bore 44 is surrounded by bearings 46 or a friction reducing bushing , so that watch carrier is freely rotatable on shaft . a torque arm engaging projection in the form of pin 48 extends rearwardly from rear face 32 into the pathway of torque arm . pin 48 is offset in a given direction from shaft . a counterweight 50 is also mounted on rear face 32 in the same given direction . preferably , watch is mounted in watch carrier so that watch is in an upright position facilitating viewing when the given direction is downward , i . e ., when counterweight 50 is beneath shaft . reference is made first to fig2 which is a top plan view of the playing arena of the first preferred embodiment of the present invention . fig2 discloses playing arena 60 as comprising a generally diamond or oval enclosure surrounding a playing field and , in the preferred embodiment , providing adequate seating for an array of fans surrounding playing field 2 . in the preferred embodiment of the present invention it is anticipated that the fan audience seating arrangement for the arena baseball game will be generally smaller than that of existing major league baseball ( mlb ) fields . one object of the present invention is to create more of an audience participatory environment for the fans attending the baseball game . towards such end , the collapsible retractable enclosure defining playing arena 60 should be smaller than a typical open air baseball stadium , but somewhat larger than the typical closed basketball arena . further disclosed in fig2 ( in this top plan view ) are outfielder with sport device 66 , first base side dugout enclosure 67 , and third base side dugout enclosure 65 . the specific structure of each of these devices is described in more detail below . traversing the entire playing field 60 is a communication network data manager 69 . coaching and trainers 61 , 63 are supported by constant contact and performance graphic 320 data derived form sport device 66 in this first preferred embodiment by a voice 308 text arena baseball system . comprising an arching communication conveying through the exchange of thoughts , messages , or information , as by speech 308 , visuals 316 , signals , writing , or behavior . data manager computer 69 support component extending from behind home plate monitors info from the infielders and outfielders ( sport device 66 in the vicinity of center field ) and relays the filtered “ sounds of the game ” delayed . associated with what is the equivalent of the infield in the standard american baseball field configuration are the usual home plate , first base , second base , and third base . defined in fig2 and utilized as part of the method of play for the arena baseball game , are home slide zone 54 , first base slide zone 51 , second base slide zone 52 , and third base slide zone 53 . positioned in the center of the infield area is pitcher &# 39 ; s mound 55 . overall , the components of the arena baseball game structure of the present invention , shown generally as the playing arena 60 of fig2 , are structured to be similar to standard american baseball , but fully enclose the playing area so as to allow the audience to position themselves very close to the activity within the playing area . the various surrounding enclosures and retractable netting components allow for the continuous play of the arena baseball game , according to the various rules described in more detail below , especially those relating to the play of balls off of the walls and collapsible retractable ceiling enclosure components . reference is next made to fig3 which is a side elevational view of the playing arena of the second preferred embodiment of the present invention . in this view of fig3 , playing arena is again shown to be framed as a clam top retractable outfield enclosure 74 and home plate backstop enclosure with louver overhang 77 . likewise , first base side enclosure and third base side enclosure 16 are disclosed with their elevational configuration . retractable netting 72 is shown to comprise an array of net awning panels forming the upper sections of the sidewalls and the arching sections of the ceiling for the overall collapsible enclosure . fig4 helmet 80 smart device sport device 82 also includes speaker system 86 for distributing audio information from earphone 84 . speaker system 86 can include an audio 89 port at the end of the earbud and a speaker disposed adjacent the audio port 89 . the audio port may be covered with a grill 87 . sport device 82 is shown by dotted lines in fig4 because they are not visible when looking at helmet 80 protective mask 81 from a perspective view . fig4 illustrates a physiological monitoring system . a user may use conventional heart rate monitoring system to monitor the user &# 39 ; s heart rate , e . g ., while the user is performing an exercise routine . conventional heart rate monitoring system can be equipped with heart rate sensor 88 , which the user can attach onto the user &# 39 ; s neck using a sticky pad . heart rate monitoring system device 82 also can have receiver , which can accept wireless data signals transmitted from heart rate sensor and display such information for the user &# 39 ; s consideration . fig5 illustrates a wireless helmet 80 sport device 82 diagram which may generate an audio representation of a heart rate , in accordance with the method of the invention changes in light are measured through an user &# 39 ; s skin . for example , changes in light are measured using an infrared sensor 88 unit . after changes in light are measured through a user &# 39 ; s skin , a heart rate is calculated using input signals from the sensor unit and the micro - processor based on the changes in the light measured by the sensor unit . after the heart rate is calculated in the step , the micro - processor generates output signals that are transmitted to the output unit where the output signals are played to generate an audio signal representative of the heart rate . the fig5 designated fielder 90 or hitter for the pitcher is available for fielding at least one out per inning or a cumulative number for the game duration . in major league baseball , the designated hitter is a hitter who does not play a position , but instead fills in the batting order for the pitcher . dh at the mlb level may be used for the pitcher only . in any case , use of the dh is optional , however , the manager must designate a dh prior to the start of the game ; failure to do so forfeits the right to use the dh , and the pitcher must then take his turn at bat . the designated fielder 90 may play a field position , he may only be replaced by another player not currently in the lineup and increases the defensive alignment by one . however , the designated fielder 90 may become a position player at any point during the game ; if he does so , his team forfeits the role of the designated hitter , and the pitcher or another player ( possible only in case of a multiple substitution ) must bat in the newly opened spot in the batting order . helmet 80 protective mask 81 sport device 82 also includes a communication terminal for communicating with a host device . the communication terminal may be configured for wired or wireless connections . fig6 & amp ; 7 illustrates an earbud 102 of a headset having one or more integrated physiological sensors 88 , 104 in accordance with one embodiment of the present invention . earbud 102 can have housing 110 and internal cavity 111 . internal cavity 111 can be bisected by internal wall 208 into separate acoustical chambers . speaker 86 , 210 can be positioned within internal cavity 111 ( e . g ., mounted onto internal wall 208 ) so that sound waves emanating from the speaker 210 are directed out of acoustical aperture 109 . speaker 210 can be coupled to wires 214 that transmit audio signals from an electronic device . fig6 sport device 100 removed or stand alone can be configured as a small compact unit with a simple earpiece 84 that can be placed in a user &# 39 ; s ear . the fig7 sport device 100 can include a primary housing 110 and an earphone 102 that extends from the primary housing . earphone 102 can fit into the user &# 39 ; s ear thereby placing the primary housing next to the user &# 39 ; s face . earphone 102 alone may retain sport device 100 in the user &# 39 ; s ear , or a retaining arm — which may be curved — may be provided that wraps around the user &# 39 ; s ear or the user &# 39 ; s head . each of these members can surround and protect various internal components and can also support thereon various external components associated with operating sport device 100 . the components may be a plurality of electrical components that provide specific functions for the electronic device . for example , the components may generally be associated with generating , receiving , and / or transmitting data associated with operating the device . similarly , any connector ( usb 350 ) may be covered by a removable cap 101 or key chain attachment . fig8 sport device 100 also includes one or more input mechanisms for providing sensor 104 , 312 inputs to the smart device . the input mechanism may be placed at primary housing 110 and / or at earphone 102 . the input mechanisms may be widely varied and may include for example sensors 104 , 312 , slide switches , keyboard 319 , depress able buttons 317 , dials , wheels , navigation pads , touch 302 pads , and / or pointing devices 303 . for aesthetic reasons , the input mechanism may be placed at a select location as an optical camera 103 , 304 . fig9 schematically illustrates a roaming point - of - sale system , which includes a scanning device 100 and in response to the barcode - scan 301 command , the barcode scanner 301 scans baseball tube 105 and baseball kettle 106 the scanning device processor 309 . receives the scanned data and decodes the barcode information and sends the decoded data to the handheld computing device 100 using the athletic performance application / program . in some embodiments , the barcode scanner 301 can be manually activated by a manual scanner activation button 317 , which also causes the scanning device to scan and decode the barcodes and send the decoded data to the handheld computing device . fig1 is a flowchart diagram showing a high level sequence of steps that begin by start / run the device 200 and stop the device 201 . the relay flow is associated with the game method of play of the present invention . one goal of the device 200 , 201 communication rendered game method of play of the present invention is to provide the pitcher with an opportunity to maintain performance endurance throughout the shortened length contest . play ball on a defined provided playing surface 60 with a provide base force adjacent slide zone 222 . by delivering quality pitches , and limiting the number of pitch attempts to each offensive batter who communicates with coach 223 a . the object of the competition is to advance offensive players by sequential baserunners communicating with coach , advances to base 223 b from base . where defensive fielders inhibit advancement , relays position 223 c inhibit scoring by obtaining three outs per inning advancement while accumulating outs and progress score aces or runs 223 until end game . this is reflected by a game rule wherein the defensive pitcher throws by communication with catcher , selecting type and location of is pitch 223 d for the game . a defensive fielder 90 limits long stays in the field and promotes aerobic activity employing a positions range and a greater area to cover defensively . the ball utilized provides greater bounce and requires higher concentration to field and / or defend . the pitcher &# 39 ; s mound 55 projects the pitcher as the center of action and creates a downward plane of projection towards the batter . a designated fielder 90 player is allowed to field defensively at least one out per inning . fig1 sport device 300 may include a processor 309 for controlling the smart device &# 39 ; s functions . in the illustrated embodiment , processor 309 can be provided in earphone 102 . in other embodiments , processor 309 can be located anywhere in sport device 300 . processor 309 can be electrically coupled to the other components of sport device 300 through circuit boards and / or cables . processor 309 may facilitate wireless communications with a host device in conjunction with transceiver 310 and antenna 318 . for example , processor 309 can generate signals for wireless transmission and process received wireless signals , in accordance with the aforementioned bluetooth ® protocol or other communications standard . in addition to facilitating wireless communications , processor 309 may coordinate the operation of the various components of sport device 300 . for example , processor 309 may control the charging of a battery 305 or the operation of a display 316 system . as discussed above , the presence of microphone 315 may allow the provision of a voice - command 308 interface ( controlled , e . g ., by processor 309 ) to replace or supplement the various switches , etc ., described above . in addition , processor 309 can adjust the volume level , once set by the user , to accommodate changes in ambient noise levels as detected by microphone 315 . sport device 300 also includes battery 305 . battery 305 may provide electrical power to components of sport device 300 . charging circuitry may also be provided to charge battery 305 when an external power supply is connected to sport device 300 . media player 311 circuitry 300 may also be able to make sound recordings for storage in memory 306 . the source of sound for such recordings may be microphone 315 , allowing the user to record voice memoranda , etc ., and also may include sound played back through speaker 307 . in the latter case , where both speaker 307 and microphone 315 may be sources of sounds for recording , the user may be able to record telephone conversations when the sport device 300 is being used for conducting a conversation over an associated telephone . in either case , a further button 317 may be provided to initiate the recording mode , or the recording mode may be one more mode through which the aforementioned single button 317 may cycle . sport device 300 also includes a communication terminal for communicating with a host device . the communication terminal may be configured for wired or wireless connections . in the illustrated embodiment , the communication terminal is antenna 318 that supports wireless connections , such as the aforementioned bluetooth ® protocol . antenna 318 may be located internal to primary housing 110 or earphone 102 . if primary housing 110 or earphone 102 is not formed from a radio - transparent material then a radio - transparent window may be provided . in the illustrated embodiment , antenna 318 is located at one end of the sport device 300 . sport device 300 improvements also includes microphone 315 for capturing speech provided by the user . the microphone 315 is typically located internal to primary housing 110 . for example , the ports may be placed at the seam between the connector assembly and the primary housing . similarly , any connector 313 may be covered by a removable cap 101 . this can be accomplished , for example , through micro perforations in primary housing 110 . the micro perforations allow light to pass through , but are so small that they are undetectable to a user . the system also includes a transceiver 310 which is connected to the microphone . in one embodiment , the system includes a protective box 110 secured to the baseplate and a cover removably attached creating a protective box 110 . sealing material is placed between the box and the protective helmet shell . the transmitter 310 is housed within the protective box 110 such that the transmitter 310 is protected from moisture and dust . sport device 300 can also include support circuitry for the aforementioned components . for example , this may include circuit boards , various electrical components , processors 309 and controllers 314 . the support circuitry 319 can be placed inside primary housing 110 and / or earphone 102 . in one embodiment , the support circuitry 319 can be split or divided between the two locations in order to make a more compact device , i . e ., the various electronics are distributed among volumes as needed . in order to further save space , the electronics may be stackable . in one embodiment , the electronics are placed on a circuit 319 board with one or more flexible portions so that a stack is created by folding or bending the circuit 319 board . the circuit 319 boards can even be completely flexible to fit within the confined spaces of sport device 300 . fig1 and fig1 the electronic components of mobile terminal 300 and 400 receive power from a power unit 333 and 444 . for convenience , bold broken - line arrows are used to show housing in fig1 and fig1 . solid line arrows are used to show signal flows . power unit 333 includes a rechargeable battery 305 housed within a energy extractor (“ ee ”) assembly . whereas , power unit 444 includes multiple rechargeable battery 305 housed within a energy extractor (“ ee ”) assembly in more detail below , ee extractor includes multiple quartz piezoelectric 505 elements that generate voltages in response to movement of mobile terminal 300 and 400 . electrical energy output from these piezoelectric elements is received by a power controller 314 . power controller 314 includes electrical circuits that apply the energy output from orb assembly 333 and 444 as it is needed . when the electrical load of components in mobile terminal 11 & amp ; 12 is higher , controller 314 uses energy from orb assembly 333 to help satisfy that load . when the electrical load of mobile terminal is lower , controller 314 applies the energy from orb assembly 333 and 444 to battery 305 so as to recharge battery 305 . controller 314 can also receive power from a conventional ac adapter for charging battery 305 . in operation , as illustrated in fig4 - 5 and fig1 - 12 , is periodically energized by movement to rotate orb in either a clockwise or counterclockwise direction . the length of time or activity is energized , and the length of time between the period when the battery is energized , will depend on the particular sport device design . as the orb rotates , the outer end of the disk moves along a 360 ° circular pathway to push against with forward and rearwardly spinning upon engagement of the orb , sport device disk is rotated until carried to the apex or top of the circular pathway . upon reaching the apex , the gravitational force or counterweight 50 promotes additional oscillation . sport device movement rapidly rotate on orb at a rotational speed greater than the speed of rotation of orb . counterweight 50 is then carried beyond the bottom or lowest point of the pathway by its momentum to a point near the apex on the opposite side of the pathway . the cycle is repeated through multiple increasing oscillations of the sport device until counterweight 50 stops at the bottom position , or until once again engages to again move counterweight to the top of its circular pathway . in operation the heart rate monitor sport device 100 is connected to the computer 69 through the bluetooth ® or usb coupling means . workout history data that has been collected by the heart rate monitor and in the memory unit 306 is downloaded to the computer 69 . the computer 69 is preferably programed with the appropriate driver to read workout history data from the heart rate monitor device 100 and also is preferably programmed with software , such the computer 69 is capable of generating a graphical representation of the workout history data . it will be clear to one skilled in the art that the workout history data can be manipulated in any number of ways to generate a number of different geographical representations of the workout heart rate data to provide insight into the user &# 39 ; s workout and the users &# 39 ; s workout performance . fig1 is a flow chart showing generation of energy using a rotor according to one or more of the above - described embodiments . first , the mobile terminal is oscillated 501 . in response to this acceleration , forces are imposed on one or more rotation 502 piezoelectric 505 devices . in response to those forces , the piezoelectric devices output electrical energy , which energy is extracted 503 at a power controller . the power controller then makes this energy available to recharge 504 a battery and / or to electronic components of the mobile terminal . although fig1 shows a serial flow of events , it is to be appreciated that the events of blocks 502 , 503 and 504 occur substantially instantaneously upon acceleration of the mobile terminal . certain modifications and improvements will occur to those skilled in the art upon a reading of the foregoing description . it should be understood that all such modifications and improvements have been deleted herein for the sake of conciseness and readability but are properly within the scope of the following claims . in an embodiment of the present invention , the sport device can accept data from one or more physiological sensors , along with data from one or more other sensors that track the user &# 39 ; s movements . the movement sensors 104 , 312 can be disposed within the electronic device itself or attached to or incorporated within the user &# 39 ; s helmet 80 . the sport device will be configured to condition the data from the physiological sensors 104 , 312 using the data from the movement sensors . for example , because the physiological sensor may contain anomalies due to the user &# 39 ; s movements , the electronic device can identify the anomalies based on data indicative of the user &# 39 ; s movements and thereafter remove or filter out their effects before relay to computer application program . in one embodiment of the present invention , earphone 102 also can be equipped with one or more physiological sensors 104 , 312 . for example , sensors 104 , 312 can include one or more infrared 507 photodetectors for tracking the user &# 39 ; s temperature , heat flux , heart rate and barcode scan 301 . from infrared radiation in the user &# 39 ; s ear , sensors 104 , 312 can detect minute temperature variations due to the user &# 39 ; s heart beats . heart rate can be calculated based on the time between beats and the user &# 39 ; s temperature can be set as the “ dc component ” of the detected temperature distribution . other sensors 104 , 312 also can be used for tracking the same physiological metrics or different physiological metrics . in one embodiment of the present invention , one sensor 104 , 312 can be centered with respect to acoustical aperture 109 to ensure that the sensor 104 , 312 receives a sufficient infrared signal regardless of how the user positions earphone 102 in the user &# 39 ; s ear . alternatively , speaker 307 can be centered with respect to acoustical aperture 109 and two or more of the same sensors 104 , 312 can be positioned around the periphery of speaker 307 . this can increase the likelihood that at least one sensor 104 , 312 can obtain a sufficient infrared 507 signal regardless of how the user positions earphone 102 in the user &# 39 ; s ear . electronic device 100 , 300 , 400 can have one or more antennas 318 for wirelessly communicating with a data network and / or with one or more . for example , the electronic device can include one or more antennas for communication with bluetooth 340 - enabled devices , wifi network , cellular network ( gps 360 ), radio frequency network 330 , or any combination thereof . in one embodiment of the present invention , antenna ( s ) 318 can permit a user to stream or otherwise download audio and / or visual 316 media to entertain and motivate the user during performance of an activity . removably attached , electronic device 100 , 300 , 400 also can be any electronic device suitable for processing signals from sensors that track a user &# 39 ; s performance metrics during physical activity . the helmet smart device offers three useful functionalities — bluetooth , memory 306 , and wired : four different bluetooth modes are available ( master , slave , usb hid , ios ) to communicate between pc , mobile phone and pda ; in memory 306 mode , it can store up to 500 barcode 301 readings with time stamps for later download ; in wired mode , with the supplied usb cable ( supplied ) connected , it can be used as a tethered scanner , transferring data to and from internal flash memory 306 , as well as charging the device . thus it is seen that a wireless sport device with integrated media player and / or recorder has been provided . it will be understood that the foregoing is only illustrative of the principles of the invention , and that various modifications can be made by those skilled in the art without departing from the scope and spirit of the invention , and the present invention is limited only by the claims that follow .

arena baseball game system method of play includes base excessive force , no collision contact slide zones and describes a protective helmet apparatus for use by baseball fielders . the protective sport television or radio audio device means of communication equipped with display , gps , infrared scan and sensors to monitor performance and physiological parameters . in operation one or more infrared sensor sits against skin of a user to measure his or her heart rate . in response to oscillation translation and / or rotation of the electronic sport device , portions of forces induced by the mass are transferred to the piezoelectric elements . electrical energy output by these piezoelectric elements is received in a power controller and can be applied to the battery as self charging .

the nucleic acid sequences of the invention include nucleic acid sequences which encode dnkv product and fragments and analogs thereof . the nucleic acid sequences may alternatively be sequences complementary to the above coding sequence , or to a region of said coding sequence . the length of the complementary sequence is sufficient to avoid the expression of the coding sequence . the nucleic acid sequences may be in the form of rna or in the form of dna , and include messenger rna , synthetic rna and dna , cdna , and genomic dna . the dna may be double - stranded or single - stranded , and if single - stranded may be the coding strand or the non - coding ( anti - sense , complementary ) strand . the nucleic acid sequences may also both include dntps , rntps as well as non naturally occurring sequences . the sequence may also be a part of a hybrid between an amino acid sequence and a nucleic acid sequence . in a general embodiment , the nucleic acid sequence has at least 90 %, identity , preferably 95 % with any one of the sequence identified as seq id no : 1 to seq id no : 91 provided that this sequence is not completely identical with that of the original sequence . the nucleic acid sequences may include the coding sequence by itself . by another alternative the coding region may be in combination with additional coding sequences , such as those coding for fusion protein or signal peptides , in combination with non - coding sequences , such as introns and control elements , promoter and terminator elements or 5 ′ and / or 3 ′ untranslated regions , effective for expression of the coding sequence in a suitable host , and / or in a v actor or host environment in which the dnkv nucleic acid sequence is introduced as a heterologous sequence . the nucleic acid sequences of the present invention may also have the product coding sequence fused in - frame to a marker sequence which allows for purification of the dnkv product . the marker sequence may be , for example , a hexahistidine tag to provide for purification of the mature polypeptide fused to the marker in the case of a bacterial host , or , the marker sequence may be a hemagglutinin ( ha ) tag when a mammalian host , e . g . cos - 7 cells , is used . the ha tag corresponds to an epitope derived from the influenza hemagglutinin protein ( wilson , i ., et al . cell 37 : 767 ( 1984 )). also included in the scope of the invention are fragments as defined above also referred to herein as oligonucleotides , typically having at least 20 bases , preferably 20 - 30 bases corresponding to a region of the coding - sequence nucleic acid sequence . the fragments may be used as probes , primers , and when complementary also as antisense agents , and the like , according to known methods . as indicated above , the nucleic acid sequence may be substantially a depicted in any one of seq id no : 1 to seq id no : 91 or fragments thereof or sequences having at least 90 % identity to the above sequence as explained above . alternatively , due to the degenerative nature of the genetic code , the sequence may be a sequence coding for any one of the amino acid sequence depicted in seq id no : 92 to seq id no : 182 , or fragments or analogs of said amino acid sequence . the nucleic acid sequences may be obtained by screening cdna libraries using oligonucleotide probes which can hybridize to or pcr - amplify nucleic acid sequences which encode the dnkv products disclosed above . cdna libraries prepared from a variety of tissues are commercially available and procedures for screening and isolating cdna clones are well - known to those of skill in the art . such techniques are described in , for example , sambrook et al . ( 1989 ) molecular cloning : a laboratory manual ( 2nd edition ), cold spring harbor press , plainview , n . y . and ausubel f m et al . ( 1989 ) current protocols in molecular biology , john wiley & amp ; sons , new york , n . y . the nucleic acid sequences may be extended to obtain upstream and downstream sequences such as promoters , regulatory elements , and 5 ′ and 3 ′ untranslated regions ( utrs ). extension of the available transcript sequence may be performed by numerous methods known to those of skill in the art , such as pcr or primer extension ( sambrook et al ., supra ), or by the race method using , for example , the marathon race kit ( clontech , cat . # k1802 - 1 ). alternatively , the technique of “ restriction - site ” pcr ( gobinda et al . pcr methods applic . 2 : 318 - 22 , ( 1993 )), which uses universal primers to retrieve flanking sequence adjacent a known locus , may be employed . first , genomic dna is amplified in the presence of primer to a linker sequence and a primer specific to the known region . the amplified sequences are subjected to a second round of pcr with the same linker primer and another specific primer internal to the first one . products of each round of pcr are transcribed with an appropriate rna polymerase and sequenced using reverse transcriptase . inverse pcr can be used to amplify or extend sequences using divergent primers based on a known region ( triglia , t . et al ., nucleic acids res . 16 : 8186 , ( 1988 )). the primers may be designed using oligo ( r ) 4 . 06 primer analysis software ( 1992 ; national biosciences inc , plymouth , minn . ), or another appropriate program , to be 22 - 30 nucleotides in length , to have a gc content of 50 % or more , and to anneal to the target sequence at temperatures about 68 - 72 ° c . the method uses several restriction enzymes to generate a suitable fragment in the known region of a gene . the fragment is then circularized by intramolecular ligation and used as a pcr template . capture pcr ( lagerstrom , m . et al ., pcr methods applic . 1 : 111 - 19 , ( 1991 )) is a method for pcr amplification of dna fragments adjacent to a known sequence in human and yeast artificial chromosome dna . capture pcr also requires multiple restriction enzyme digestions and ligations to place an engineered double - stranded sequence into a flanking part of the dna molecule before pcr . another method which may be used to retrieve flanking sequences is that of parker , j . d ., et al ., nucleic acids res ., 19 : 3055 - 60 , ( 1991 )). additionally , one can use pcr , nested primers and promoterfinder ™ libraries to “ walk in ” genomic dna ( promoterfinder ™; clontech , palo alto , calif .). this process avoids the need to screen libraries and is useful in finding intron / exon junctions . preferred libraries for screening for full length cdnas are ones that have been size - selected to include larger cdnas . also , random primed libraries are preferred in that they will contain more sequences which contain the 5 ′ and upstream regions of genes . a randomly primed library may be particularly useful if an oligo d ( t ) library does not yield a full - length cdna . genomic libraries are useful for extension into the 5 ′ nontranslated regulatory region . the nucleic acid sequences and oligonucleotides of the invention can also be prepared by solid - phase methods , according to known synthetic methods . typically , fragments of up to about 100 bases are individually synthesized , then joined to form continuous sequences up to several hundred bases . b . use of dnkv nucleic acid sequence for the production of dnkv products in accordance with the present invention , nucleic acid sequences specified above may be used as recombinant dna molecules that direct the expression of dnkv products . as will be understood by those of skill in the art , it may be advantageous to produce dnkv product - encoding nucleotide sequences possessing codons other than those which appear in any one of seq id no : 1 to seq id no : 91 which are those which naturally occur in the human genome . codons preferred by a particular prokaryotic or eukaryotic host ( murray , e . et al . nuc acids res ., 17 : 477 - 508 , ( 1989 )) can be selected , for example , to increase the rate of dnkv product expression or to produce recombinant rna transcripts having desirable properties , such as a longer half - life , than transcripts produced from naturally occurring sequence . the nucleic acid sequences of the present invention can be engineered in order to alter a dnkv product coding sequence for a variety of reasons , including but not limited to , alterations which modify the cloning , processing and / or expression of the product . for example , alterations may be introduced using techniques which are well known in the art , e . g ., site - directed mutagenesis , to insert new restriction sites , to alter glycosylation patterns , to change codon preference , etc . the present invention also includes recombinant constructs comprising one or more of the sequences as broadly described above . the constructs comprise a vector , such as a plasmid or viral vector , into which a nucleic acid sequence of the invention has been inserted , in a forward or reverse orientation . in a preferred aspect of this embodiment , the construct further comprises regulatory sequences , including , for example , a promoter , operably linked to the sequence . large numbers of suitable vectors and promoters are known to those of skill in the art , and are commercially available . appropriate cloning and expression vectors for use with prokaryotic and eukaryotic hosts are also described in sambrook , et al ., ( supra ). the present invention also relates to host cells which are genetically engineered with vectors of the invention , and the production of the product of the invention by recombinant techniques . host cells are genetically engineered ( i . e ., transduced , transformed or transfected ) with the vectors of this invention which may be , for example , a cloning vector or an expression vector . the vector may be , for example , in the form of a plasmid , a viral particle , a phage , etc . the engineered host cells can be cultured in conventional nutrient media modified as appropriate for activating promoters , selecting transformants or amplifying the expression of the dnkv nucleic acid sequence . the culture conditions , such as temperature , ph and the like , are those previously used with the host cell selected for expression , and will be apparent to those skilled in the art . the nucleic acid sequences of the present invention may be included in any one of a variety of expression vectors for expressing a product . such vectors include chromosomal , nonchromosomal and synthetic dna sequences , e . g ., derivatives of sv40 ; bacterial plasmids ; phage dna ; baculovirus ; yeast plasmids ; vectors derived from combinations of plasmids and phage dna , viral dna such as vaccinia , adenovirus , fowl pox virus , and pseudorabies . however , any other vector may be used as long as it is replicable and viable in the host . the appropriate dna sequence may be inserted into the vector by a variety of procedures . in general , the dna sequence is inserted into an appropriate restriction endonuclease site ( s ) by procedures known in the art . such procedures and related sub - cloning procedures are deemed to be within the scope of those skilled in the art . the dna sequence in the expression vector is operatively linked to an appropriate transcription control sequence ( promoter ) to direct mrna synthesis . examples of such promoters include : ltr or sv40 promoter , the e . coli lac or trp promoter , the phage lambda pl promoter , and other promoters known to control expression of genes in prokaryotic or eukaryotic cells or their viruses . the expression vector also contains a ribosome binding site for translation initiation , and a transcription terminator . the vector may also include appropriate sequences for amplifying expression . in addition , the expression vectors preferably contain one or more selectable marker genes to provide a phenotypic trait for selection of transformed host cells such as dihydrofolate reductase or neomycin resistance for eukaryotic cell culture , or such as tetracycline or ampicillin resistance in e . coli . the vector containing the appropriate dna sequence as described above , as well as an appropriate promoter or control sequence , may be employed to transform an appropriate host to permit the host to express the protein . examples of appropriate expression hosts include : bacterial cells , such as e . coli , streptomyces , salmonella typhimurium ; fungal cells , such as yeast ; insect cells such as drosophila and spodoptera sf9 ; animal cells such as cho , cos , hek 293 or bowes melanoma ; adenoviruses ; plant cells , etc . the selection of an appropriate host is deemed to be within the scope of those skilled in the art from the teachings herein . the invention is not limited by the host cells employed . in bacterial systems , a number of expression vectors may be selected depending upon the use intended for the dnkv product . for example , when large quantities of dnkv product are needed for the induction of antibodies , vectors which direct high level expression of fusion proteins that are readily purified may be desirable . such vectors include , but are not limited to , multifunctional e . coli cloning and expression vectors such as bluescript ( r ) ( stratagene ), in which the dnkv polypeptide coding sequence may be ligated into the vector in - frame with sequences for the amino - terminal met and the subsequent 7 residues of beta - galactosidase so that a hybrid protein is produced ; pin vectors ( van heeke & amp ; schuster j . biol . chem . 264 : 5503 - 5509 , ( 1989 )); pet vectors ( novagen , madison wis . ); and the like . in the yeast saccharomyces cerevisiae a number of vectors containing constitutive or inducible promoters such as alpha factor , alcohol oxidase and pgh may be used . for reviews , see ausubel et al . ( supra ) and arrant et al ., ( methods in enzymology 153 : 516 - 544 , ( 1987 )). in cases where plant expression vectors are used , the expression of a sequence encoding dnkv product may be driven by any of a number of promoters . for example , viral promoters such as the 35s and 19s promoters of camv ( brisson et al ., nature 310 : 511 - 514 . ( 1984 )) may be used alone or in combination with the omega leader sequence from tmv ( takamatsu et al ., embo j ., 6 : 307 - 311 , ( 1987 )). alternatively , plant promoters such as the small subunit of rubisco ( coruzzi et al ., embo j . 3 : 1671 - 1680 , ( 1984 ); broglie et al ., science 224 : 838 - 843 , ( 1984 )); or heat shock promoters ( winter j and sinibaldi r . m ., results probl . cell differ ., 17 : 85 - 105 , ( 1991 )) may be used . these constructs can be introduced into plant cells by direct dna transformation or pathogen - mediated transfection . for reviews of such techniques , see hobbs s . or murry l . e . ( 1992 ) in mcgraw hill yearbook of science and technology , mcgraw hill , new york , n . y ., pp 191 - 196 ; or weissbach and weissbach ( 1988 ) methods for plant molecular biology , academic press , new york , n . y ., pp 421 - 463 . dnkv product may also be expressed in an insect system . in one such system , autographa californica nuclear polyhedrosis virus ( acnpv ) is used as a vector to express foreign genes in spodoptera frugiperda cells or in trichoplusia larvae . the dnkv product coding sequence may be cloned into a nonessential region of the virus , such as the polyhedrin gene , and placed under control of the polyhedrin promoter . successful insertion of dnkv coding sequence will render the polyhedrin gene inactive and produce recombinant virus lacking coat protein coat . the recombinant viruses are then used to infect s . frugiperda cells or trichoplusia larvae in which dnkv protein is expressed ( smith et al ., j . virol . 46 : 584 , ( 1983 ); engelhard , e . k . et al ., proc . nat . acad . sci . 91 : 3224 - 7 , ( 1994 )). in mammalian host cells , a number of viral - based expression systems may be utilized . in cases where an adenovirus is used as an expression vector , a dnkv product coding sequence may be ligated into an adenovirus transcription / translation complex consisting of the late promoter and tripartite leader sequence . insertion in a nonessential e1 or e3 region of the viral genome will result in a viable virus capable of expressing dnkv protein in infected host cells ( logan and shenk , proc . natl . acad . sci . 81 : 3655 - 59 , ( 1984 ). in addition , transcription enhancers , such as the rous sarcoma virus ( rsv ) enhancer , may be used to increase expression in mammalian host cells . specific initiation signals may also be required for efficient translation of a dnkv product coding sequence . these signals include the atg initiation codon and adjacent sequences . in cases where dnkv product coding sequence , its initiation codon and upstream sequences are inserted into the appropriate expression vector , no additional translational control signals may be needed . however , in cases where only coding sequence , or a portion thereof , is inserted , exogenous transcriptional control signals including the atg initiation codon must be provided . furthermore , the initiation codon must be in the correct reading frame to ensure transcription of the entire insert . exogenous transcriptional elements and initiation codons can be of various origins , both natural and synthetic . the efficiency of expression may be enhanced by the inclusion of enhancers appropriate to the cell system in use ( scharf , d . et al ., ( 1994 ) results probl . cell differ ., 20 : 125 - 62 , ( 1994 ); bittner et al ., methods in enzymol 153 : 516 - 544 , ( 1987 )). in a further embodiment , the present invention relates to host cells containing the above - described constructs . the host cell can be a higher eukaryotic cell , such as a mammalian cell , or a lower eukaryotic cell , such as a yeast cell , or the host cell can be a prokaryotic cell , such as a bacterial cell . introduction of the construct into the host cell can be effected by calcium phosphate transfection , deae - dextran mediated transfection , or electroporation ( davis , l ., dibner , m ., and battey , i . ( 1986 ) basic methods in molecular biology ). cell - free translation systems can also be employed to produce polypeptides using rnas derived from the dna constructs of the present invention . a host cell strain may be chosen for its ability to modulate the expression of the inserted sequences or to process the expressed protein in the desired fashion . such modifications of the protein include , but are not limited to , acetylation , carboxylation , glycosylation , phosphorylation , lipidation and acylation . post - translational processing which cleaves a “ pre - pro ” form of the protein may also be important for correct insertion , folding and / or function . different host cells such as cho , hela , mdck , 293 , wi38 , etc . have specific cellular machinery and characteristic mechanisms for such post - translational activities and may be chosen to ensure the correct modification and processing of the introduced , foreign protein . for long - term , high - yield production of recombinant proteins , stable expression is preferred . for example , cell lines which stably express dnkv product may be transformed using expression vectors which contain viral origins of replication or endogenous expression elements and a selectable marker gene . following the introduction of the vector , cells may be allowed to grow for 1 - 2 days in an enriched media before they are switched to selective media . the purpose of the selectable marker is to confer resistance to selection , and its presence allows growth and recovery of cells which successfully express the introduced sequences . resistant clumps of stably transformed cells can be proliferated using tissue culture techniques appropriate to the cell type . any number of selection systems may be used to recover transformed cell lines . these include , but are not limited to , the herpes simplex virus thymidine kinase ( wigler m ., et al ., cell 11 : 223 - 32 , ( 1977 )) and adenine phosphoribosyltransferase ( lowy i ., et al ., cell 22 : 817 - 23 , ( 1980 )) genes which can be employed in tk - or aprt - cells , respectively . also , antimetabolite , antibiotic or herbicide resistance can be used as the basis for selection ; for example , dhfr which confers resistance to methotrexate ( wigler m ., et al ., proc . natl . acad . sci . 77 : 3567 - 70 , ( 1980 )); npt , which confers resistance to the aminoglycosides neomycin and g - 418 ( colbere - garapin , f . et al ., j . mol . biol ., 150 : 1 - 14 , ( 1981 )) and als or pat , which confer resistance to chlorsulfuron and phosphinotricin acetyltransferase , respectively ( murry , supra ). additional selectable genes have been described , for example , trpb , which allows cells to utilize indole in place of tryptophan , or hisd , which allows cells to utilize histinol in place of histidine ( hartman s . c . and r . c . mulligan , proc . natl . acad . sci . 85 : 8047 - 51 , ( 1988 )). the use of visible markers has gained popularity with such markers as anthocyanins , beta - glucuronidase and its substrate , gus , and luciferase and its substrates , luciferin and atp , being widely used not only to identify transformants , but also to quantify the amount of transient or stable protein expression attributable to a specific vector system ( rhodes , c . a . et . al ., methods mol . biol ., 55 : 121 - 131 , ( 1995 )). host cells transformed with a nucleotide sequence encoding dnkv product may be cultured under conditions suitable for the expression and recovery of the encoded protein from cell culture . the product produced by a recombinant cell may be secreted or contained intracellularly depending on the sequence and / or the vector used . as will be understood by those of skill in the art , expression vectors containing nucleic acid sequences encoding dnkv product can be designed with signal sequences which direct secretion of dnkv product through a prokaryotic or eukaryotic cell membrane . the dnkv product may also be expressed as a recombinant protein with one or more additional polypeptide domains added to facilitate protein purification . such purification facilitating domains include , but are not limited to , metal chelating peptides such as histidine - tryptophan modules that allow purification on immobilized metals , protein a domains that allow purification on immobilized immunoglobulin , and the domain utilized in the flags extension / affinity purification system ( immunex corp , seattle , wash .). the inclusion of a protease - cleavable polypeptide linker sequence between the purification domain and dnkv product is useful to facilitate purification . one such expression vector provides for expression of a fusion protein compromising a dnkv polypeptide fused to a polyhistidine region separated by an enterokinase cleavage site . the histidine residues facilitate purification on imiac ( immobilized metal ion affinity chromatography , as described in porath , et al ., protein expression and purification , 3 : 263 - 281 , ( 1992 )) while the enterokinase cleavage site provides a means for isolating dnkv polypeptide from the fusion protein . pgex vectors ( promega , madison , wis .) may also be used to express foreign polypeptides as fusion proteins with glutathione s - transferase ( gst ). in general , such fusion proteins are soluble and can easily be purified from lysed cells by adsorption to ligand - agarose beads ( e . g ., glutathione - agarose in the case of gst - fusions ) followed by elution in the presence of free ligand . following transformation of a suitable host strain and growth of the host strain to an appropriate cell density , the selected promoter is induced by appropriate means ( e . g ., temperature shift or chemical induction ) and cells are cultured for an additional period . cells are typically harvested by centrifugation , disrupted by physical or chemical means , and the resulting crude extract retained for further purification . microbial cells employed in expression of proteins can be disrupted by any convenient method , including freeze - thaw cycling , sonication , mechanical disruption , or use of cell lysing agents , or other methods , which are well know to those skilled in the art . the dnkv products can be recovered and purified from recombinant cell cultures by any of a number of methods well known in the art , including ammonium sulfate or ethanol precipitation , acid extraction , anion or cation exchange chromatography , phosphocellulose chromatography , hydrophobic interaction chromatography , affinity chromatography , hydroxylapatite chromatography , and lectin chromatography . protein refolding steps can be used , as necessary , in completing configuration of the mature protein . finally , high performance liquid chromatography ( hplc ) can be employed for final purification steps . the nucleic acid sequences of the present invention may be used for a variety of diagnostic purposes . the nucleic acid sequences may be used to detect and quantitate expression of the dnkv in patient &# 39 ; s cells , e . g . biopsied tissues , by detecting the presence of mrna coding for dnkv product . alternatively , the assay may be used to detect soluble dnkv in the serum or blood . this assay typically involves obtaining total mrna from the tissue or serum and contacting the mrna with a nucleic acid probe . the probe is a nucleic acid molecule of at least 20 nucleotides , preferably 20 - 30 nucleotides , capable of specifically hybridizing with a sequence included within the sequence of a nucleic acid molecule encoding dnkv product under hybridizing conditions , detecting the presence of mrna hybridized to the probe , and thereby detecting the expression of dnkv . this assay can be used to distinguish between absence , presence , and excess expression of dnkv product and to monitor levels of dnkv expression during therapeutic intervention . in addition , the assay may be used to compare the levels of the dnkv of the invention to the levels of the original kinase sequence from which it has been varied or to levels of other dnkvs , which comparison may have some physiological meaning . the invention also contemplates the use of the nucleic acid sequences as a diagnostic for diseases resulting from inherited defective dnkv sequences , or diseases in which the ratio of the amount of the original kinase sequence from which the dnkv was varied to the novel dnkvs of the invention is altered . these sequences can be detected by comparing the sequences of the defective ( i . e ., mutant ) dnkv coding region with that of a normal coding region . association of the sequence coding for mutant dnkv product with abnormal dnkv product activity may be verified . in addition , sequences encoding mutant dnkv products can be inserted into a suitable vector for expression in a functional assay system ( e . g ., calorimetric assay , complementation experiments in a variant protein deficient strain of hek293 cells ) as yet another means to verify or identify mutations . once mutant genes have been identified , one can then screen populations of interest for carriers of the mutant gene . individuals carrying mutations in the nucleic acid sequence of the present invention may be detected at the dna level by a variety of techniques . nucleic acids used for diagnosis may be obtained from a patient &# 39 ; s cells , including but not limited to such as from blood , urine , saliva , placenta , tissue biopsy and autopsy material . genomic dna may be used directly for detection or may be amplified enzymatically by using pcr ( saiki , et al ., nature 324 : 163 - 166 , ( 1986 )) prior to analysis . rna or cdna may also be used for the same purpose . as an example , pcr primers complementary to the nucleic acid of the present invention can be used to identify and analyze mutations in the gene of the present invention . deletions and insertions can be detected by a change in size of the amplified product in comparison to the normal genotype . point mutations can be identified by hybridizing amplified dna to radiolabeled rna of the invention or alternatively , radiolabeled antisense dna sequences of the invention . sequence changes at specific locations may also be revealed by nuclease protection assays , such rnase and s1 protection or the chemical cleavage method ( e . g . cotton , et al proc . natl . acad . sci . usa , 85 : 4397 - 4401 , ( 1985 )), or by differences in melting temperatures . “ molecular beacons ” ( kostrikis l . g . et al ., science 279 : 1228 - 1229 , ( 1998 )), hairpin - shaped , single - stranded synthetic oligo - nucleotides containing probe sequences which are complementary to the nucleic acid of the present invention , may also be used to detect point mutations or other sequence changes as well as monitor expression levels of dnkv product . such diagnostics would be particularly useful for prenatal testing . another method for detecting mutations uses two dna probes which are designed to hybridize to adjacent regions of a target , with abutting bases , where the region of known or suspected mutation ( s ) is at or near the abutting bases . the two probes may be joined at the abutting bases , e . g ., in the presence of a ligase enzyme , but only if both probes are correctly base paired in the region of probe junction . the presence or absence of mutations is then detectable by the presence or absence of ligated probe . also suitable for detecting mutations in the dnkv product coding sequence are oligonucleotide array methods based on sequencing by hybridization ( sbh ), as described , for example , in u . s . pat . no . 5 , 547 , 839 . in a typical method , the dna target analyte is hybridized with an array of oligonucleotides formed on a microchip . the sequence of the target can then be “ read ” from the pattern of target binding to the array . the nucleic acid sequences of the present invention are also valuable for chromosome identification . the sequence is specifically targeted to and can hybridize with a particular location on an individual human chromosome . moreover , there is a current need for identifying particular sites on the chromosome . few chromosome marking reagents based on actual sequence data ( repeat polymorphisms ) are presently available for marking chromosomal location . the mapping of dnas to chromosomes according to the present invention is an important first step in correlating those sequences with genes associated with disease . briefly , sequences can be mapped to chromosomes by preparing pcr primers ( preferably 20 - 30 bp ) from the dnkv cdna . computer analysis of the 3 ′ untranslated region is used to rapidly select primers that do not span more than one exon in the genomic dna , which would complicate the amplification process . these primers are then used for pcr screening of somatic cell hybrids containing individual human chromosomes . only those hybrids containing the human gene corresponding to the primer will yield an amplified fragment . pcr mapping of somatic cell hybrids or using instead radiation hybrids are rapid procedures for assigning a particular dna to a particular chromosome . using the present invention with the same oligonucleotide primers , sublocalization can be achieved with panels of fragments from specific chromosomes or pools of large genomic clones in an analogous manner . other mapping strategies that can similarly be used to map to its chromosome include in situ hybridization , prescreening with labeled flow - sorted chromosomes and preselection by hybridization to construct chromosome specific - cdna libraries . fluorescence in situ hybridization ( fish ) of a cdna clone to a metaphase chromosomal spread can be used to provide a precise chromosomal location in one step . this technique can be used with cdna as short as 50 or 60 bases . for a review of this technique , see verma et al ., human chromosomes : a manual of basic techniques , ( 1988 ) pergamon press , new york . once a sequence has been mapped to a precise chromosomal location , the physical position of the sequence on the chromosome can be correlated with genetic map data . such data are found , for example , in the omim database ( center for medical genetics , johns hopkins university , baltimore , md . and national center for biotechnology information , national library of medicine , bethesda , md .). the omim gene map presents the cytogenetic map location of disease genes and other expressed genes . the omim database provides information on diseases associated with the chromosomal location . such associations include the results of linkage analysis mapped to this interval , and the correlation of translocations and other chromosomal aberrations in this area with the advent of polygenic diseases , such as cancer , in general and prostate cancer in particular . nucleic acid sequences of the invention may also be used for therapeutic purposes . turning first to the second aspect of the invention ( i . e . inhibition of expression of dnkv ), expression of dnkv product may be modulated through antisense technology , which controls gene expression through hybridization of complementary nucleic acid sequences , i . e . antisense dna or rna , to the control , 5 ′ or coding regions of the gene encoding dnkv product . for example , the 5 ′ coding portion of the nucleic acid sequence which codes for the product of the present invention is used to design an antisense oligonucleotide of from about 10 to 40 base pairs in length . oligonucleotides derived from the transcription start site , e . g . between positions − 10 and + 10 from the start site , are preferred . an antisense dna oligonucleotide is designed to be complementary to a region of the nucleic acid sequence involved in transcription ( lee et al ., nucl . acids , res ., 6 : 3073 , ( 1979 ); cooney et al ., science 241 : 456 , ( 1988 ); and dervan et al ., science 251 : 1360 , ( 1991 )), thereby preventing transcription and the production of the dnkv products . an antisense rna oligonucleotide hybridizes to the mrna in vivo and blocks translation of the mrna molecule into the dnkv products ( okano j . neurochem . 56 : 560 , ( 1991 )). the antisense constructs can be delivered to cells by procedures known in the art such that the antisense rna or dna may be expressed in vivo . the antisense may be antisense mrna or dna sequence capable of coding such antisense mrna . the antisense mrna or the dna coding thereof can be complementary to the full sequence of nucleic acid sequences coding for the dnkv protein or to a fragment of such a sequence which is sufficient to inhibit production of a protein product . turning now to the first aspect of the invention , i . e . expression of dnkv , expression of dnkv product may be increased by providing coding sequences for coding for said product under the control of suitable control elements ending its expression in the desired host . the nucleic acid sequences of the invention may be employed in combination with a suitable pharmaceutical carrier . such compositions comprise a therapeutically effective amount of the compound , and a pharmaceutically acceptable carrier or excipient . such a carrier includes but is not limited to saline , buffered saline , dextrose , water , glycerol , ethanol , and combinations thereof . the formulation should suit the mode of administration . the products of the invention as well as any activators and deactivators compounds ( see below ) which are polypeptides , may also be employed in accordance with the present invention by expression of such polypeptides in vivo , which is often referred to as “ gene therapy .” cells from a patient may be engineered with a nucleic acid sequence ( dna or rna ) encoding a polypeptide ex vivo , with the engineered cells then being provided to a patient to be treated with the polypeptide . such methods are well - known in the art . for example , cells may be engineered by procedures known in the art by use of a retroviral particle containing rna encoding a polypeptide of the present invention . similarly , cells may be engineered in vivo for expression of a polypeptide in vivo by procedures known in the art . as known in the art , a producer cell for producing a retroviral particle containing rna encoding the polypeptide of the present invention may be administered to a patient for engineering cells in vivo and expression of the polypeptide in vivo . these and other methods for administering a product of the present invention by such method should be apparent to those skilled in the art from the teachings of the present invention . for example , the expression vehicle for engineering cells may be other than a retrovirus , for example , an adenovirus which may be used to engineer cells in vivo after combination with a suitable delivery vehicle . retroviruses from which the retroviral plasmid vectors mentioned above may be derived include , but are not limited to , moloney murine leukemia virus , spleen necrosis virus , retroviruses such as rous sarcoma virus , harvey sarcoma virus , avian leukosis virus , gibbon ape leukemia virus , human immunodeficiency virus , adenovirus , myeloproliferative sarcoma virus , and mammary tumor virus . the retroviral plasmid vector is employed to transduce packaging cell lines to form producer cell lines . examples of packaging cells which may be transfected include , but are not limited to , the pe501 , pa317 , psi - 2 , psi - am , pa12 , t19 - 14x , vt - 19 - 17 - h2 , psi - cre , psi - crip , gp + e - 86 , gp + envam12 , and dan cell lines as described in miller ( human gene therapy , vol . 1 , pg . 5 - 14 , ( 1990 )). the vector may transduce the packaging cells through any means known in the art . such means include , but are not limited to , electroporation , the use of liposomes , and capo 4 precipitation . in one alternative , the retroviral plasmid vector may be encapsulated into a liposome , or coupled to a lipid , and then administered to a host . the producer cell line generates infectious retroviral vector particles which include the nucleic acid sequence ( s ) encoding the polypeptides . such retroviral vector particles then may be employed , to transduce eukaryotic cells , either in vitro or in vivo . the transduced eukaryotic cells will express the nucleic acid sequence ( s ) encoding the polypeptide . eukaryotic cells which may be transduced include , but are not limited to , embryonic stem cells , embryonic carcinoma cells , as well as hematopoietic stem cells , hepatocytes , fibroblasts , myoblasts , keratinocytes , endothelial cells , and bronchial epithelial cells . the genes introduced into cells may be placed under the control of inducible promoters , such as the radiation - inducible egr - 1 promoter , ( maceri , h . j ., et al ., cancer res ., 56 ( 19 ): 4311 ( 1996 )), to stimulate dnkv production or antisense inhibition in response to radiation , e . g ., radiation therapy for treating tumors . the substantially purified dnkv product of the invention has been defined above as the product coded from the nucleic acid sequence of the invention . preferably the amino acid sequence is an amino acid sequence having at least 90 % identity to any one of the sequences coded by the nucleic acid sequence of seq id no : 1 to seq id no : 91 provided that the amino acid sequence is not identical to that of the original sequence from which it has been varied . the protein or polypeptide may be in mature and / or modified form , also as defined above . also contemplated are protein fragments having at least 10 contiguous amino acid residues , preferably at least 10 - 20 residues , derived from the dnkv product , as well as homologues as explained above . the sequence variations are preferably those that are considered conserved substitutions , as defined above . thus , for example , a protein with a sequence having at least 90 % sequence identity with any of the products depicted by seq id no : 92 to seq id no : 182 , preferably by utilizing conserved substitutions as defined above is also part of the invention , and provided that it is not identical to the original peptide from which it has been varied . the dnkv product may be ( i ) one in which one or more of the amino acid residues in a sequence listed above are substituted with a conserved or non - conserved amino acid residue ( preferably a conserved amino acid residue ), or ( ii ) one in which one or more of the amino acid residues includes a substituent group , or ( iii ) one in which the dnkv product is fused with another compound , such as a compound to increase the half - life of the protein ( for example , polyethylene glycol ( peg )), or a moiety which serves as targeting means to direct the protein to its target tissue or target cell population ( such as an antibody ), or ( iv ) one in which additional amino acids are fused to the dnkv product . such fragments , dnkvs and derivatives are deemed to be within the scope of those skilled in the art from the teachings herein . recombinant methods for producing and isolating the dnkv product , and fragments of the protein are described above . in addition to recombinant production , fragments and portions of dnkv product may be produced by direct peptide synthesis using solid - phase techniques ( cf . stewart et al ., ( 1969 ) solid - phase peptide synthesis , wh freeman co , san francisco ; merrifield j ., j . am . chem . soc ., 85 : 2149 - 2154 , ( 1963 )). in vitro peptide synthesis may be performed using manual techniques or by automation . automated synthesis may be achieved , for example , using applied biosystems 431a peptide synthesizer ( perkin elmer , foster city , calif .) in accordance with the instructions provided by the manufacturer . fragments of dnkv product may be chemically synthesized separately and combined using chemical methods to produce the full length molecule . the dnkv product of the invention is generally useful in treating diseases and disorders which are characterized by a lower than normal level of dnkv expression , and or diseases which can be cured or ameliorated by raising the level of the dnkv product , even if the level is normal . dnkv products or fragments may be administered by any of a number of routes and methods designed to provide a consistent and predictable concentration of compound at the target organ or tissue . the product - containing compositions may be administered alone or in combination with other agents , such as stabilizing compounds , and / or in combination with other pharmaceutical agents such as drugs or hormones . dnkv product - containing compositions may be administered by a number of routes including , but not limited to oral , intravenous , intramuscular , transdermal , subcutaneous , topical , sublingual , or rectal means as well as by nasal application . dnkv product - containing compositions may also be administered via liposomes . such administration routes and appropriate formulations are generally known to those of skill in the art . the product can be given via intravenous or intraperitoneal injection . similarly , the product may be injected to other localized regions of the body . the product may also be administered via nasal insufflation . enteral administration is also possible . for such administration , the product should be formulated into an appropriate capsule or elixir for oral administration , or into a suppository for rectal administration . the foregoing exemplary administration modes will likely require that the product be formulated into an appropriate carrier , including ointments , gels , suppositories . appropriate formulations are well known to persons skilled in the art . dosage of the product will vary , depending upon the potency and therapeutic index of the particular polypeptide selected . a therapeutic composition for use in the treatment method can include the product in a sterile injectable solution , the polypeptide in an oral delivery vehicle , the product in an aerosol suitable for nasal administration , or the product in a nebulized form , all prepared according to well known methods . such compositions comprise a therapeutically effective amount of the compound , and a pharmaceutically acceptable carrier or excipient . such a carrier includes but is not limited to saline , buffered saline , dextrose , water , glycerol , ethanol , and combinations thereof . the present invention also includes an assay for identifying molecules , such as synthetic drugs , antibodies , peptides , or other molecules , which have a modulating effect on the activity of the dnkv product , e . g . activators or deactivators of the dnkv product of the present invention . such an assay comprises the steps of providing an dnkv product encoded by the nucleic acid sequences of the present invention , contacting the dnkv protein with one or more candidate molecules to determine the candidate molecules modulating effect on the activity of the dnkv product , and selecting from the molecules a candidate &# 39 ; s molecule capable of modulating dnkv product physiological activity . the dnkv product , its catalytic or immunogenic fragments or oligopeptides thereof , can be used for screening therapeutic compounds in any of a variety of drug screening techniques . the fragment employed in such a test may be free in solution , affixed to a solid support , borne on a cell membrane or located intracellularly . the formation of binding complexes , between dnkv product and the agent being tested , may be measured . alternatively , the activator or deactivator may work by serving as agonist or antagonist , respectively , of the dnkv receptor , binding entity or target site , and their effect may be determined in connection with any of the above . another technique for drug screening which may be used provides for high throughput screening of compounds having suitable binding affinity to the dnkv product is described in detail by geysen in pct application wo 84 / 03564 , published on sep . 13 , 1984 . in summary , large numbers of different small peptide test compounds are synthesized on a solid substrate , such as plastic pins or some other surface . the peptide test compounds are reacted with the full dnkv product or with fragments of dnkv product and washed . bound dnkv product is then detected by methods well known in the art . substantially purified dnkv product can also be coated directly onto plates for use in the aforementioned drug screening techniques . alternatively , non - neutralizing antibodies can be used to capture the peptide and immobilize it on a solid support . antibodies to the dnkv product , as described in example iv below , may also be used in screening assays according to methods well known in the art . for example , a “ sandwich ” assay may be performed , in which an anti - dnkv antibody is affixed to a solid surface such as a microtiter plate and dnkv product is added . such an assay can be used to capture compounds which bind to the variant dnkv . alternatively , such an assay may be used to measure the ability of compounds to influence with the binding of variant product to the variant receptor , and then select those compounds which effect the binding . in still another aspect of the invention , the purified dnkv product is used to produce anti - dnkv antibodies which have diagnostic and therapeutic uses related to the activity , distribution , and expression of the dnkv product . as indicated above , the antibodies may also be directed solely to amino acid sequences present in the variant but not present in the original kinase sequence , or to sequences present only in the original kinase sequence but not in the dnkv ( distinguishing antibodies ). antibodies to the dnkv product or to the distinguishing sequence present only in the dnkv or only in the original kinase sequence ( the latter termed “ distinguishing antibodies ”) may be generated by methods well known in the art . such antibodies may include , but are not limited to , polyclonal , monoclonal , chimeric , humanized , single chain , fab fragments and fragments produced by an fab expression library . antibodies , i . e ., those which inhibit dimer formation , are especially preferred for therapeutic use . a fragment of the dnkv product for antibody induction does not require biological activity but have to feature immunological activity ; however , the protein fragment or oligopeptide must be antigenic . peptides used to induce specific antibodies may have an amino acid sequence consisting of at least five amino acids , preferably at least 10 amino acids of any sequences coded by the nucleic acid sequence of seq id no : 1 to seq id no : 91 or in distinguishing sequences present only in the dnkv or only in the original kinase sequence as explained above . preferably they should mimic a portion of the amino acid sequence of the natural protein and may contain the entire amino acid sequence of a small , naturally occurring molecule . short stretches of dnkv protein amino acids may be fused with those of another protein such as keyhole limpet hemocyanin and antibody produced against the chimeric molecule . procedures well known in the art can be used for the production of antibodies to dnkv product . for the production of antibodies , various hosts including goats , rabbits , rats , mice , etc may be immunized by injection with dnkv product or any portion , fragment or oligopeptide which retains immunogenic properties . depending on the host species , various adjuvants may be used to increase immunological response . such adjuvants include but are not limited to freund &# 39 ; s , mineral gels such as aluminum hydroxide , and surface active substances such as lysolecithin , pluronic polyols , polyanions , peptides , oil emulsions , keyhole limpet hemocyanin , and dinitrophenol . bcg ( bacilli calmette - guerin ) and corynebacterium parvum are potentially useful human adjuvants . monoclonal antibodies to dnkv protein may be prepared using any technique which provides for the production of antibody molecules by continuous cell lines in culture . these include but are not limited to the hybridoma technique originally described by koehler and milstein ( nature 256 : 495 - 497 , ( 1975 )), the human b - cell hybridoma technique ( kosbor et al ., immunol . today 4 : 72 , ( 1983 ); cote et al ., proc . natl . acad . sci . 80 : 2026 - 2030 , ( 1983 )) and the ebv - hybridoma technique ( cole , et al ., mol . cell biol . 62 : 109 - 120 , ( 1984 )). techniques developed for the production of “ chimeric antibodies ”, the splicing of mouse antibody genes to human antibody genes to obtain a molecule with appropriate antigen specificity and biological activity can also be used ( morrison et al ., proc . natl . acad . sci . 81 : 6851 - 6855 , ( 1984 ); neuberger et al ., nature 312 : 604 - 608 , ( 1984 ); takeda et al ., nature 314 : 452 - 454 , ( 1985 )). alternatively , techniques described for the production of single chain antibodies ( u . s . pat . no . 4 , 946 , 778 ) can be adapted to produce single - chain antibodies specific for the dnkv protein . antibodies may also be produced by inducing in vivo production in the lymphocyte population or by screening recombinant immunoglobulin libraries or panels of highly specific binding reagents as disclosed in orlandi et al . ( proc . natl . acad . sci . 86 : 3833 - 3837 , 1989 )), and winter g and milstein c ., ( nature 349 : 293 - 299 , ( 1991 )). antibody fragments which contain specific binding sites for dnkv protein may also be generated . for example , such fragments include , but are not limited to , the f ( ab ′) 2 fragments which can be produced by pepsin digestion of the antibody molecule and the fab fragments which can be generated by reducing the disulfide bridges of the f ( ab ′) 2 fragments . alternatively , fab expression libraries may be constructed to allow rapid and easy identification of monoclonal fab fragments with the desired specificity ( huse w . d . et al ., science 256 : 1275 - 1281 , ( 1989 )). a variety of protocols for competitive binding or immunoradiometric assays using either polyclonal or monoclonal antibodies with established specificities are well known in the art . such immunoassays typically involve the formation of complexes between the dnkv product and its specific antibody and the measurement of complex formation . a two - site , monoclonal - based immunoassay utilizing monoclonal antibodies reactive to two noninterfering epitopes on a specific dnkv product is preferred , but a competitive binding assay may also be employed . these assays are described in maddox d . e ., et al , ( j . exp . med . 158 : 1211 , ( 1983 )). antibodies which specifically bind dnkv product or distinguishing antibodies which bind to sequences which distinguish the dnkv from the original kinase sequence ( as explained above ) are useful for the diagnosis of conditions or diseases characterized by expression of the novel dnkv of the invention ( where normally it is not expressed ) by over or under expression of dnkv as well as for detection of diseases in which the proportion between the amount of the dnkv of the invention and the original kinase sequence from which it varied is altered . alternatively , such antibodies may be used in assays to monitor patients being treated with dnkv product , its activators , or its deactivators . diagnostic assays for dnkv protein include methods utilizing the antibody and a label to detect dnkv product in human body fluids or extracts of cells or tissues . the products and antibodies of the present invention may be used with or without modification . frequently , the proteins and antibodies will be labeled by joining them , either covalently or noncovalently , with a reporter molecule . a wide variety of reporter molecules are known in the art . a variety of protocols for measuring the dnkv product , using either polyclonal or monoclonal antibodies specific for the respective protein are known in the art . examples include enzyme - linked immunosorbent assay ( elisa ), radioimmunoassay ( ria ), and fluorescent activated cell sorting ( facs ). as noted above , a two - site , monoclonal - based immunoassay utilizing monoclonal antibodies reactive to two non - interfering epitopes on dnkv product is preferred , but a competitive binding assay may be employed . these assays are described , among other places , in maddox , et al . ( supra ). such protocols provide a basis for diagnosing altered or abnormal levels of dnkv product expression . normal or standard values for dnkv product expression are established by combining body fluids or cell extracts taken from normal subjects , preferably human , with antibody to dnkv product under conditions suitable for complex formation which are well known in the art . the amount of standard complex formation may be quantified by various methods , preferably by photometric methods . then , standard values obtained from normal samples may be compared with values obtained from samples from subjects potentially affected by disease . deviation between standard and subject values establishes the presence of disease state . the antibody assays are useful to determine the level of dnkv product present in a body fluid sample , in order to determine whether it is being expressed at all , whether it is being overexpressed or underexpressed in the tissue , or as an indication of how dnkv levels of variable products are responding to drug treatment . in addition to their diagnostic use the antibodies may have a therapeutical utility in blocking or decreasing the activity of the dnkv product in pathological conditions where beneficial effect can be achieved by such a decrease . again , distinguishing antibodies may be used to neutralize differentially either the dnkv or the original kinase sequence as the case may be . the antibody employed is preferably a humanized monoclonal antibody , or a human mab produced by known globulin - gene library methods . the antibody is administered typically as a sterile solution by iv injection , although other parenteral routes may be suitable . typically , the antibody is administered in an amount between about 1 - 15 mg / kg body weight of the subject . treatment is continued , e . g ., with dosing every 1 - 7 days , until a therapeutic improvement is seen . although the invention has been described with reference to specific methods and embodiments , it is appreciated that various modifications and changes may be made without departing from the invention .

the present invention concerns nucleic acid sequences and amino acid sequences of dominant negative variants of kinases , i . e . of sequences which inhibit activity of kinases in a dominant manner . the invention also concerns pharmaceutical compositions and detection methods using these sequences .

fig1 a - 1 d and 3 d show the skeletal structure 10 embodying the principles of the present invention and comprising a pair of inverted , substantially u - shaped , hollow , tubular members 12 and 14 respectively having depending legs 12 a - 12 b , 14 a - 14 b extending downwardly , and a yoke portion 12 c , 14 c . a pair of hollow curved tubular members 16 , 18 are each joined to retractable wheel assemblies 20 - 22 and 24 - 26 respectively mounted at opposite ends thereof . the retractable wheel assemblies , as shown in fig1 d are each provided with a recess for receiving an end 16 b , 16 c of a curved member 16 . the tubular member 18 is secured to the wheel assemblies 24 , 26 in like fashion to that shown in fig1 d . fig1 e is a detailed view of one wheel assembly 24 showing the recess 24 b for receiving an end of tubular member 18 . the retractable wheels shown in fig1 a are in the “ down ” position where the skeletal structure is capable of being easily rolled along a surface . the wheels are moved upwardly to a retracted position by operating a toggle button 24 c and an operating lever 24 d surrounding toggle switch 24 c . toggle button 24 c pivots about a vertical axis a and is normally urged into a locked position . pushing button 24 c at the right - hand end unlocks the castor assembly 24 a , allowing lever 24 d to be rotated in order to rotate caster 24 a clockwise about the disc - shaped portion 24 i at the upper end of the arm 24 j holding caster 24 a , disc - shaped portion being swingably mounted within an opening 24 b in housing 24 l . lowering the caster 24 a is performed by operating the toggle button in a similar manner , however , the lever 24 d is rotated counter - clockwise to lower the caster 24 a . when pressure on the right - hand end of toggle button 24 c is released , the toggle button returns to the locked condition . moving the casters 20 a , 22 a 24 a , 26 a into their recesses enables the skeletal structure to be rocked by the curved convex central portions 16 a , 18 a of tubular members 16 , 18 . even though the wheels 20 a , 22 a , 24 a and 26 a are retracted , the underside of their housings such as 16 b , 16 c , can engage the surface supporting the skeletal structure , preventing the structure , when it is rocked , from toppling over ( see fig1 d ). the wheel assemblies are provided with conventional locking members , such as the slide switch 24 f ( not shown in detail for purposes of simplicity ), which , when moved in one direction , lock the wheels 22 a - 26 a from rolling when they are in the “ down ” position . sliding the switch 24 f in the opposite direction unlocks the wheels allowing them to roll freely . the outwardly projecting housings for the wheels provide a wider “ footprint ” to greatly enhance the stability of the skeletal structure . wheel assemblies 20 - 26 are further provided with integral , upwardly directed , hollow tubular projections 20 g - 26 g ( see fig1 e ) each adapted to receive the lower end of one of the elongated , hollow , tubular , upright members 28 - 30 and 32 - 34 , which extend into the hollow projections 20 g - 26 g of assemblies 20 - 26 . the upper ends of tubular members 28 - 34 each telescope into a lower end of one of the legs 12 b - 14 b , 12 a - 14 a . the legs 12 b - 14 b , 12 a - 14 a are provided with an array of spaced openings , such as , for example , the openings o shown provided on legs 14 a , 14 b , for purposes of receiving a conventional spring loaded button b provided on an upper end of each tubular member which locks into one of the openings provided on each leg , enabling the tubular members 12 and 14 to be raised ( or lowered ) to a desired height . the legs of each tubular member 28 - 34 can be adjusted simply by pressing the buttons b inwardly so that they are cleared of the openings o and moving the members 12 and 14 relative to the members 28 - 30 and 32 - 34 . as soon as the spring loaded button b aligns with an opening , the spring loaded button b will snap into the opening and lock the associated leg at a desired height . all of the buttons b for each of the remaining three legs operate in a similar manner . integral hollow projections 29 - 33 provided on assemblies 22 , 20 receive a rod 37 which provides additional structural support . a similar rod 39 extends between similar integral , hollow projections 31 - 35 to provide similar structural support . rods 39 and 37 are snap - filled into the projections and extend through sleeves b 3 , b 4 in storage basket 70 , shown in fig1 c , 1 d and 4 . the basket 70 is formed of a light - weight , open weave , mesh fabric which enables the contents of the basket to be easily observed through the side panels 76 , 78 and end panels 80 , 82 the vertically aligned corners c 1 - c 4 are each comprised of strips formed of a suitable , rugged , tight - weave , durable fabric to support the basket . bottom end strips b 1 and b 2 are similar to strips c 1 - c 4 . likewise top side strips t 1 , t 2 and top end strips t 3 , t 4 each serve to rigidify the basket to assist in retaining its rectangular , box - like shape . the elongated strips t 1 - t 4 , c 1 - c 4 and b 1 - b 4 are preferably formed of more rugged , tightly - woven , rugged , strips of material which are sewn to the mesh material to form a basket . the basket 70 makes excellent use of the open region beneath board 56 supported by tubular members 36 , 38 . the basket 70 is suspended from the skeletal structure by means of four ( 4 ) elongated straps s 1 - s 4 arranged in each of the four corners of the basket 70 . the straps are each provided with a plurality of spaced , female snap members 84 . one of the snaps 84 is snap - fitted with a cooperating male snap member 86 each male snap member being provided at opposite ends of yokes 12 c , 14 c ( see fig1 c ). the female snap member 84 which is snap - fitted to member 86 is chosen so as to keep the basket 70 upright and suitably taut . pairs of tie members 80 , 90 , 92 and 94 are provided at the upper corners of basket 70 and are tied about the upper portions of legs 12 a - 12 b , 14 a - 14 b to hold the basket taut in the horizontal direction . the pair of upright , substantially u - shaped tubular members 36 , 38 have yoke portions 36 a , 38 a resting upon the yoke portions 12 c , 14 c and preferably joined thereto , for example , by suitable fasteners , which also secure the board 56 thereto . standoffs 56 a maintain board 56 parallel to yokes 12 c and 14 c , see fig1 c and 1 d . members 36 and 38 are arranged substantially at right angles to yokes 12 c and 14 c . member 36 has upwardly directed arms 36 b , 36 c and member 38 has upwardly directed arms 38 b , 38 c . brackets 40 and 42 join the free ends of 44 a , 44 b of the curved tubular member 44 and first ends 46 a , 48 a of straight tubular members 46 and 48 to the upright arms 36 a and 36 b . similar brackets 50 , 52 join the opposite ends 46 b , 48 b of tubular members 46 and 48 and the free ends 54 a , 54 b of curved tubular member 54 to the upright arms 38 b , 38 c . the tubular members 44 and 36 b are pivotally mounted to bracket 42 to allow these members to fold into a compact arrangement when disassembled and stored . the brackets 40 , 50 and 52 are similar in design and function . rigid board 56 is secured to the yoke portions 36 a , 38 a of tubular members 36 and 38 by the aforementioned suitable fasteners ( not shown ) and serves as the base of the bassinet / changing table / bedside sleeper and as a support for a mattress 120 ( fig3 ). brackets 58 and 60 are releasably , mounted to locking projections arranged on the underside of rods 46 , 48 , for example , fig1 f shows rod 48 , having cooperating projection 48 c secured to rod 48 by pin 49 . bracket 60 has a cooperating slot 60 a which is slidably mounted upon projection 48 c . the free ends of curved gusset members 62 , 64 and 66 are pivotally mounted upon the brackets 58 , 60 by pin 67 . gusset members 62 , 64 and 66 serve as the means for supporting a hood h ( see fig2 ) to shield the infants &# 39 ; eyes from overhead light , as will be more fully described . the brackets 58 , 60 which slidably mount to the rods 46 , 48 as set forth above , may be removed by sliding the brackets 60 away from the projections , such as projection 48 c , enabling the canopy h to be easily removed / replaced . the gussets 62 - 66 are swingably mounted to brackets 58 - 60 to enable hood h to be easily raised and lowered . the tubular members 35 , 44 , 46 & amp ; 48 are preferably enclosed in elongated , resilient , foam - type , plastic sleeves , such as sleeve s , shown in fig1 f , to cushion these rods and reduce injury to an infant or other person engaging these rods . fig2 shows the skeletal structure 10 covered with a fabric member 100 . making reference to fig3 as well as fig2 , the fabric member 100 is comprised of interior sidewalls , fig2 showing two ( 2 ) straight sidewalls 102 , 106 and two ( 2 ) curved sidewalls 104 , 108 . the straight sidewalls 102 , 106 , shown in the sectional view of fig3 , as well as curved sidewall 104 , have their lower ends joined , preferably by being sewn , to a bottom sheet 110 . the sewn portions joining sidewalls 102 and 106 to the bottom sheet are shown at 112 and 114 . the two curved sidewalls 104 and 108 are joined in a like manner , being sewn to the outer perimeter of bottom sheet 110 . bottom sheet 110 rests upon the upper surface of board 56 . a mattress 120 ( shown in dotted fashion ), is placed upon bottom sheet 110 . the upper ends of straight sidewalls 102 and 106 respectively rest on rods 46 and 48 and a portion of their free ends are each sewn to an integral skirt portions 118 , 116 which skirt portions hang downwardly preferably to a point below the board 56 . the short sidewalls are likewise joined to skirt portions 117 , 119 in a like manner , as by sewing . the surfaces 102 a and 106 a of the sidewalls 102 and 106 are provided with male - type snap buttons 103 a , 103 b . the surfaces 118 a , 116 a are each provided with male - type snap buttons 105 a , 105 b . the buttons 105 a , 105 b are arranged to be snap - fitted with buttons 103 a , 103 b . it should be understood that a plurality of pairs of cooperating snap - buttons 103 a , 103 b and 105 a , 105 b are arranged at spaced intervals along the straight sidewalls 102 , 106 ( as well as curved sidewalls 104 and 108 ), all of which pairs are snap - fitted together to retain the cover member in place draped over the skeletal frame . if desired , cooperating loop - type and hook - type strips may be substituted for the buttons without any change in effectiveness . the placement of the mattress 120 upon the bottom sheet 110 cooperates with the button pairs to retain the cover member 100 in place . the sidewall 106 of cover member 110 is capable of being pulled away from the adjacent curved sidewalls 104 , 108 . as shown in fig3 a , which shows lower portions of the skirt removed to assist in an understanding of fig3 a , ends of the straight sidewall 106 are each provided with elongated hook - type strips 107 a , 107 b which are aligned to be joined with elongated loop - type strips 109 a , 109 b , shown in dotted fashion , along adjacent ends of the curved sidewalls 104 , 108 . in order to convert the bassinet to a beside co - sleeper , the gussets 62 - 66 are removed by removing the brackets 58 and 60 , brackets 58 and 60 being slidably joined to projections on the rods 46 and 48 . the fabric member 100 is provided with elongated slits aligned with the projections on rods 46 and 48 for receiving the brackets 58 , 60 and to enable the brackets 58 and 60 to be easily assembled or disassembled from the aforesaid cooperating projection . end 48 a of rod 48 has a reduced diameter and is removably insertable into opening 42 a in bracket 42 , as shown in fig1 g . opposite end 48 b also has a reduced diameter and is longer than end 48 a . end 48 b is snap - fittingly received in the substantially u - shaped projection 52 a at the end of bracket 52 . in order to remove rod 48 , after removal of bracket 60 and lifting of the skirt portion 108 ( see fig3 a ), end 48 b is lifted upward in the direction of arrow b and out of the projection 52 a . when end 48 b is released from the reduced diameter portion 52 b of projection 52 a , rod 48 is moved in the direction of arrow a to remove end 48 a from opening 42 a . rod 48 is replaced by inserting end 48 a into opening 42 a and then lowering end 48 b into projection 52 a until end 48 b moves below the reduced diameter portion 52 b , causing end 48 b to be snap - fitted into the projection 52 a . rod 48 is removed by lifting end 48 b upwardly and out of a locking recess in bracket 52 , similar to the locking recess 24 h on wheel assembly 24 ( see fig1 e ), and sliding rod 48 to the right out of the interior of bracket 42 until its left - hand end clears a receiving opening bracket 52 , at which time the rod 48 may be removed . as a safety feature , rod 35 has both of its ends secured to arms 36 b , 38 a . the distance between rod 35 and board 56 is sufficiently small to prevent an infant &# 39 ; s head from becoming wedged between rod 35 and board 56 , while providing a barrier to prevent an infant from rolling out of the bassinet , even though rod 48 is removed . prior to removal of rod 48 , the skirt portion 116 joined to straight sidewall 106 is lifted to gain access to rod 48 . after the brackets 58 , 60 and rod 48 are removed , the ends of straight sidewall 106 are pulled away from adjacent curved sidewalls 104 , 108 causing the cooperating button pairs to be moved apart to allow the straight sidewall 106 to be lowered and draped over rod 35 , providing easier access to the interior of the sleeper while still providing a barrier ( rod 35 ) to prevent an infant from rolling out , of the beside co - sleeper . the thick , quilted sidewall 106 , together with the resilient sleeves ( see sleeve s in fig1 f ), acts as a cushion to protect the infant from injury . when the skirt portion 106 is pulled over the lower rod 35 , the upper flounce portion 106 a of skirt portion 106 is preferably aligned with the lower flounce position of the adjacent skirt portions , to enhance the aesthetic appearance even when the rod 48 is removed . fig3 b shows the manner in which the co - sleeper may be retained against one side of an adult bed b . an elongated pair of straps 130 , 131 each have loops 130 a , 131 a , provided at their free ends . the legs 12 a - 12 b are preferably respectively passed through loops 130 a , 131 a when the skeletal structure is initially assembled . the straps 130 , 131 are joined to a strap , 133 , which is preferably passed between the mattress 134 and box spring 135 ( or between the mattress 135 and bed frame 137 ). a flat , rectangular - shaped anchoring member 136 having slot through which the strap 133 is threaded 134 , when aligned vertically , bridges across the region between and presses against the mattress and box spring 135 and rests against portions of the mattress and box spring . an adjustable , slidable locking member 136 a allows the strap 133 to be tightened , holding the beside sleeper in place against the left - handed side of the bed and holds the anchoring member in place against the right - hand side of the bed . it should be understood that the casters should be in the down position with the casters locked to prevent rolling . the loops 130 a , 131 a of straps 130 , 131 shown in fig3 b may be released from the strap by conventional clip assemblies 138 , 140 , to allow the unit to be moved away from the adult bed without disturbing the straps 130 , 131 and 133 and the anchoring member 136 . the sidewall 106 may be placed either over rod 35 or rod 48 when employed as a changing table . the height of the changing table may be raised or lowered to assure a comfortable height for use as a changing table . the gussets 62 - 66 are covered with hood h , which is formed of an aesthetically pleasing fabric , to shade the infant &# 39 ; s eyes from bright light and having elongated passageways ( not shown ) for receiving and concealing the gussets . the convertible apparatus may be easily and quickly assembled and disassembled . when disassembled , the apparatus fits into a compact space and is easily transported due to the light - weight and yet rugged materials which are preferably either aluminum or rugged plastic or a combination thereof .

a combination bassinet , bedside sleeper and changing table apparatus including a supporting frame having a rocking feature convertible through adjustable locking casters for easy rolling . a fabric member comprised of sidewalls and a skirt is draped over the frame . the apparatus may be placed against one side of an adult bed for easy access by a parent . the bedside sleeper is secured to the parents &# 39 ; bed with safety straps . one sidewall may be lowered to facilitate access to an infant by removal of a removably mounted sidewall / skirt supporting rod . the apparatus is adjustable in height to align the bedside sleeper with the parents &# 39 ; bed and when used as a changing table to accommodate for differences in the height of the parent . the bassinet is provided with a removable , adjustable hood for shielding light from the baby &# 39 ; s eyes . the apparatus comprises a skeletal structure covered with a soft , aesthetically pleasuring and yet sturdy cloth which is easily removable and washable and includes two convenient storage areas .

embodiments of the present inventions will be described by referring to drawings of the device and examples of how the inventions can be made and used . in these drawings reference characters are used throughout the several views to indicate like or corresponding parts . in the description of the invention , certain terms are employed to refer to the parts and structures of the device . the term “ endoscope ” means an instrument for visually examining the inside of a body cavity accessible through a natural orifice . the term “ tongue blade ” is used to mean a wooden or plastic tongue depressor of the type well known in the art . the term “ graphics ” means visible markings and is intended to encompass all manner of printing , engraving , letters , characters , insignia , drawings , symbols , logos , trademarks , and the like . fig1 - 4 illustrate a new device shown securing a tongue blade to a light source , for example , an endoscope . referring primarily to fig1 in general , the device 10 has a clamp portion 12 and a blade holder portion 14 . the clamp portion 12 secures the device to an instrument such as , for a more specific example , an otoscope o . the tongue blade holder portion 14 holds a tongue blade b . neither the otoscope o , nor the tongue blade b , are part of the invention . in the description of the invention , certain terms are employed to refer to the positional relationship of certain structures relative to other structures . in all figures , the term “ longitudinal ” means the direction defined by the axis of body of the otoscope o . correspondingly , the term “ transverse ” means the direction perpendicular to the longitudinal axis . the terms “ upper ” or “ top ” and “ lower ” or “ bottom ,” “ front ” and “ rear ,” “ vertical ” and “ horizontal .” are used for convenience in reference to the orientations shown in the drawings and are not intended to be assignatory in the context of making and using the invention . with reference to fig1 - 4 , the device 10 for securing a tongue blade b to an endoscope is more fully described . the device is preferably made from rigid plastic but may also be made from metal or other rigid material . the clamp portion 12 of the device 10 has a split ring 16 for receiving the body of an instrument , and an integral transverse arm 18 extending radially . in this description , the instrument is an otoscope o with a substantially cylindrical body as is common in the art . of course the invention may be practiced with otoscopes , as shown , or other instruments known in the arts . the split ring shown in this example could be a clamp made in any shape to substantially correspond to an existing endoscope body . the split ring 16 defines a longitudinal hollow cylinder open at its top end 20 and bottom end 22 . the split ring 16 has an inner surface 24 and an outer surface 26 . the arm 18 is composed of two shanks : a short shank 28 and a long shank 30 . the short shank 28 has an inner surface 32 , and an outer surface 34 . the long shank 30 also has an inner surface 36 , and an outer surface 38 . respectively . the shanks 28 , 30 , are adjacent at their respective inner surfaces 32 , 36 , and parallel to one another . the short shank has a terminal end 40 , and the long shank has a terminal end 42 . the arm 18 has a cylindrical fastener hole 44 extending through both shanks 28 , 30 , perpendicular to the transverse and longitudinal axes . fastener hole 44 is threaded to accept a screw 45 . the arm 18 also has a cylindrical attachment hole 46 through the long shank 30 perpendicular to the longitudinal and transverse axes . attachment hole 46 is threaded to accept a threaded fastener . a plurality of ridges 48 on the inner surface 36 radiate around the attachment hole 46 . it will be clear to those skilled in the arts that different types of fasteners may be used such as a bolt or a removable pin or rivet . the tongue blade holder 14 preferably has a rectangular box - like outer shape with an upper surface 50 parallel to a lower surface 52 , two opposing sides 54 , 56 , and a front 58 and a rear 60 . the front 58 of the tongue blade holder 14 has a slot 62 of a size to receive a tongue blade b end lengthwise in a horizontal orientation . the slot 62 preferably has parallel opposing sides 61 , 63 , and a top 65 and bottom 67 slightly angled toward one another at the rear . the tongue blade holder 14 has an integral pivot arm 64 approximately perpendicular and centered at the rear 60 . the pivot arm 64 has an outer surface 66 and an inner surface 68 . the pivot arm 69 is rounded or shortened to permit the pivoting described below . the pivot arm 64 has a cylindrical pivot hole 70 corresponding to the size and orientation of the attachment hole 46 of the clamp 12 . grooves 72 on the inner surface 68 radiate from around the circumference of the pivot hole 70 . the grooves 72 are sized to receive the ridges 48 of the inner surface 36 of the long shank 30 of the clamp 12 . the grooves 72 and ridges 48 are designed to lock together in an interdigital manner forming a ridge - and - groove joint 73 . a fastener , preferably a thumbscrew 74 , is provided for passing through the pivot hole 70 and fastening with the threads of attachment hole 46 . it should be understood that other types of adjustable joints and fasteners may be used to provide an adjustable yet securable joint . the use of the device 10 for securing a tongue blade to a light source l of the otoscope o is best seen in fig1 and 2 . the split ring 16 of the clamp 12 is placed so that it encircles the body of an endoscope or other light source . in this case an otoscope o familiar in the art is shown . the screw 45 is tightened sufficiently to secure the split ring 16 to the otoscope o body without slipping . the pivot arm 64 is fastened to the arm 18 of the clamp 12 by a thumbscrew 74 inserted through pivot arm hole 70 and tightened into the threads in the attachment hole 46 . when thumbscrew 74 is fully tightened , the pivot arm inner surface 68 contacts the inner surface 36 of long shank 30 . the grooves 72 receive ridges 48 , providing an interlocking ridge - and - groove joint 73 firmly securing the blade holder 14 to the clamp 12 at a desired angle a with respect to the light source l . subsequent adjustments may be made by loosening the thumbscrew 74 , pivoting the holder about the thumbscrew to a desired angle , and re - tightening the thumbscrew 74 . a tongue blade b may be removed and replaced from the slot 62 as desired . a tongue blade is preferably held in place by pressure from the top 65 and bottom 67 of the slot , although other methods such as a leaf spring arrangement or set screw may also be used . if an endoscope larger than the diameter of the split ring 16 is encountered , the split ring may nevertheless be fastened to the body of the endoscope as above . this will result in the inner surfaces 28 , 36 of the shanks 28 , 30 being held substantially parallel , but not touching , by threaded fastener 45 , in this case , a screw . this aspect of the invention is best seen in fig2 . if an endoscope smaller in diameter than the diameter of the split ring 16 is to be used with the invention , one or more sleeves , preferably of flexible material such as flexible plastic or expanded plastic foam , may be inserted between the inner surface 24 of the split ring 16 and the endoscope body . as can be seen with reference to fig4 tightening screw 45 , then secures the split ring 16 and sleeve around the otoscope body o . as shown in fig1 - 4 , the invention includes several surfaces capable of displaying graphics 80 . namely , the external peripheral surface of the split ring 26 , and the upper surface 50 and lower surface 52 of the holder 14 . for example , these surfaces are advantageous for the display of logos , initials , trademarks , trade names , a particular physician &# 39 ; s name , decorative design , or other graphic content . the embodiments shown and described above are only exemplary . many details are often found in the art such as variations in the size and shape of endoscopes or other light sources . therefore many such details are neither shown nor described . it is not claimed that all of the details , parts , elements , or steps described and shown were invented herein . even though numerous characteristics and advantages of the present inventions have been set forth in the foregoing description , together with details of the structure and function of the inventions , the disclosure is illustrative only , and changes may be made in the detail , especially in matters of shape , size and arrangement of the parts within the principles of the inventions to the full extent indicated by the broad general meaning of the terms used in the attached claims . for example , the placement of the interlocking grooves and ridges of the clamp / holder portions of the invention could be rearranged . similarly , different materials could be used , or different types of fasteners or thumbscrews , all within the concept of the invention . the restrictive description and drawings of the specific examples above do not point out what an infringement of this of this patent would be , but are to provide at least one explanation of how to make and use the inventions . the limits of the inventions and the bounds of the patent protection are measured by and defined in the following claims .

the present invention contemplates a new device for adjustably attaching a tongue blade to an endoscope . in general , the device secures a tongue blade holder to the body of an endoscope and permits adjustment of the angle of the tongue blade with respect to the light source of the endoscope . typically , the device has a clamp for receiving an endoscope body near the juncture of the handle and the light source of the endoscope . the clamp has a fastener for securing the clamp to the outer surface of the endoscope body and may be adapted for use with endoscopes somewhat larger or smaller in cross section than the clamp opening . the clamp has an attached tongue blade holder pivotably attached to the clamp and securable at an angle relative to the endoscope light source . the device also has several surfaces for the display of graphics .

the casket enclosure 1 of the present invention is depicted in fig1 and 3 in assembled condition . the casket enclosure 1 includes a flexible casket cover 14 and a tray 2 , which are attachable to one another to enclose a casket therein . the tray 2 , which suitably may be generally rectangular , is rigid , and can conveniently be formed , as by vacuum forming , from a synthetic resin , which may conveniently be one continuous sheet of thermoplastic resinous material , which is impervious to gases and embalming fluids . suitably , the tray 2 can be formed with a reinforcing grid pattern in the bottom of the tray . the tray 2 has edges 4 extending generally upwardly from the bottom 5 of the tray 2 . the uppermost portion 20 of the edges 4 has a flange portion 21 extending downwardly from the uppermost portion . this edge with flange configuration facilitates the carrying of the casket enclosure by the sides of the tray , without having to support the tray from the bottom . the flange portion 21 preferably has a plurality of apertures 8 therethrough for receiving fasteners therewithin , as described below . preferably , these apertures are pre - drilled . conveniently , the uppermost portion 20 and flange 21 can be rolled to form a shape similar to an inverted u , although numerous other configurations are equally suitable . one preferred aspect of the enclosure 1 is the fact that it is able to support a casket while being carried by the sides . after a casket is placed in the tray 2 , a flexible , fluid - tight cover 14 is placed over the casket and flange portions 21 . preferably , the cover 14 can be pulled approximately one inch ( 1 ″) down past the bottom of the flange 21 . the cover 14 may suitably be fabricated from a coextruded , flexible film of multiple layers of synthetic resin , such as omniflex c44 ® by printpack inc . preferably , the cover 14 is transparent , with good sealing and puncture strength . the cover , conveniently , may have a high aroma and odor barrier . an adhesive material 6 is interposed between the flange portions 21 and the cover 14 . this adhesive may conveniently be a pressure sensitive , double - sided foamed synthetic resin tape , which may conveniently be stik - ii ® by the october company . the enclosure 1 has a check valve 12 for releasing gas pressure from within the enclosure . the check valve 12 may be located either on the cover 14 or the tray 2 , and can preferably vent when the internal pressure reaches one - tenth ({ fraction ( 1 / 10 )}) psi . using the adhesive material 6 , the cover 14 and the flange portion 21 are engaged . this engagement creates a seal . a clamping device 22 engages the flange portion 21 to urge the cover 14 into sealing engagement with the adhesive material 6 . preferably , the clamping devices 22 comprise a plurality of locking rails 10 , each corresponding in length to a flange portion 21 and comprising an elongated , rigid member , which has an aperture 9 therethrough positioned to align with the apertures 8 in the flange portion 21 . the clamping devices 22 can conveniently be generally l - shaped and may suitably be formed of metal or a rigid synthetic resin . preferably , fasteners 18 are receivable through the apertures 8 and 9 on the flange portion 21 and locking rails 10 , respectively . the fasteners 18 may be constructed of metal , rigid synthetic resin , or any other suitable material , and may be threaded , serrated , or of other configurations . while the foregoing describes particularly preferred embodiments of the method and apparatus of this invention , it is to be understood that these embodiments are illustrative only of the principals of this invention and are not to be considered limitative thereof . because numerous variations and modification of the apparatus and method of this invention , and within the scope of the invention , will readily occur to those skilled in the art , the scope of this invention is to be limited solely by the claims appended hereto .

a method and apparatus for hermetically sealing a casket in an enclosure to be entombed in a mausoleum crypt . the casket enclosure comprises a tray and a flexible cover . an adhesive material is used to affix the cover to the tray . the enclosure includes a check valve to vent any gases that may build up over time .

further scope of applicability of the present invention will become apparent from the detailed description given hereinafter . however , it should be understood that the detailed description and specific examples , while indicating preferred embodiments of the invention , are given by way of illustration only , since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description . fig1 shows an apparatus 10 for the determination and regulation of the concentration of at least one dissolved substance in a fluid circuit , in detail for the sodium regulation , sodium balancing and sodium display , which comprises , in addition to the components required for a dialysate circuit 14 which corresponds to a first partial circuit 14 , a detection unit 20 having first and second means 22 , 24 made as measurement apparatus 22 , 24 for the determination of the temperature - compensated conductivity upstream and downstream of the dialyzer 60 as well as an apparatus , not shown in more detail , for the precise determination of the dialysate flow ( balance chamber , flowmeter , etc .). the detection unit 20 furthermore includes a regulation unit and regulation and storage means of the regulation unit , which are not shown in any more detail , which enable a determination unit for the dynamic determination of sodium in the second partial circuit , comprising the extracorporeal blood circuit 12 a and the vascular blood circuit 12 b . provision can generally also be made that the detection unit 20 and the regulation unit are made constructionally separate . the data of the conductivity sensors 22 , 24 are registered and processed by the detection unit 20 and the values for the plasma sodium concentration as well as the sodium balance are calculated . the input of user data and parameters of the regulation as well as the output of the calculated data take place via the user interface 30 . the detection unit 20 furthermore contains further regulation means which continuously transfer desired values to the metering unit 40 for the dialysis concentrate on the basis of the measurement data and of the user data . a storage apparatus 50 is furthermore provided for the storage of an initial desired value for the plasma sodium , with a chip card being able to be inserted into the storage apparatus 50 . this chip card can be a patient card and can provide e . g . the stored standard values of the patient . the determination unit of the detection unit 20 has a regulation model which includes the behavior of the dissolved substances in the second partial circuit 12 a and 12 b , the transfer behavior of dissolved substances via the semipermeable membrane of the dialyzer 60 as well as its time change and / or initial starting values for the iterative desired value averaging . provision is made in this respect that the determination unit can be adapted dynamically and e . g . takes up changes in the supplementary conditions such as shifts in concentration . it generally applies to the regulation model that the following regularities are stored or that the regulation model is based on the following regularities and is equipped with corresponding calculation means : the mass balance relative to the flow of an electrolyte (= mass flow per time unit ) j b from the patient is or can be written for the electrolyte flow on the patient side : δ j b =( q b − q f ) c bo − q b c bi = q b ( c bo − c bi )− q f c bo ( equation 1 ) the electrolyte flow j d on the dialysate side is : δ j d =( q d + q f ) c do − q d c di =− q d ( c di − c do )+ q f c do ( equation 2 ) where c bi and c bo are the blood side concentrations of an electrolyte before or after the dialyzer 60 , c di and c do are the corresponding concentrations on the dialysate side , q b and q f are the blood flow or uf rate and q d is the dialysate flow including the substitute flow . the blood and dialysate are connected via the dialyzer membranes so that the following must apply due to the mass maintenance in the stationary state : it thus results for the mass balance or instant electrolyte balance at the patient side in the dialysis , expressed by values at the dialysate side : δ j b = q d c di −( q d + q f ) c do = q d ( c di − c do )− q f c do ( equation 3 ) δj & gt ; 0 means that an electrolyte is transferred into the patient ; δj & lt ; 0 that it is removed from him . it is assumed in simplified terms for the splitting off of the diffuse portion that the convective transport through the ultrafiltration does not influence the output concentration at the dialyzer 60 . this assumption is satisfied very well for small molecules and ions in general . δ j diff = q d ( c di − c do ) ( equation 4 ) it must be taken into account in the calculation of the electrolyte balance that a delay time t f passes between the inlet of fresh dialysate with the concentration c do . this depends on the machine hydraulics , the dialyzer volume and the dialysate flow . the electrolyte quantity transferred between the dialysate and the patient is obtained by integration while taking account of the delay time ( accumulative balance while taking account of the delay time ): if the distribution volume v of the patient is known , it can be estimated at any time in the 1 - pool model by which amount dc pat the mean electrolyte concentration in the patient has changed . this change would then also to be observed in the patient plasma after a sufficient equilibration time ( concentration change in the patient ). the diffuse flow δj j , diff of an ion type j between the blood and the dialysate is determined by the concentration difference between the blood and the dialysate corrected by the substance - specific donnan factor α j and the substance - specific clearance d j ( diffusion flow between the blood and the dialysate ). the diffusion flow leads to a concentration change in the patient which moreover depends on the substance - specific number and size of the compartments in which the substance is distributed . since in the following the concentration development in the patient is only used for a conductivity correction on the dialysate side , a good approximation in the 1 - pool model is possible within the framework of the required accuracy . in this model , δj j , diff in the patient with a distribution volume v results in a differential concentration change dc j , bi : the time development of the concentration in the patient c j , bi can thus be calculated continuously with a known starting concentration c j , o ( calculation of the development of the ion concentration in the patient ): the plasma - sodium concentration can be calculated on the basis of a measurement of the conductivity of the dialysate upstream and downstream of the dialyzer 60 , of the dialysance d as well as the influences of the dialysate , the substitute and the ultrafiltration . in detail , it applies to the plasma conductivity : the results of the regulation as well as the user settings before the start or during the regulation can be stored internally or externally ( patient card , network with database system ) individual to the patient . the temperature - compensated conductivity σ of a solution is generally a function of the concentration of all its components . in the range of the concentration occurring in the dialysate in practice , it can be approximated as a linear combination of the concentrations of its essential components ( general representation of the conductivity as a function of the substance concentrations ): here , c j represents the ion concentrations and γ j their known molar conductivities for typical dialysate compositions and σ ofs the offset from the linearization . since the charge neutrality ∑ j ⁢ c j ⁢ z j = 0 ⁢ ⁢ ( z j ⁢ ⁢ valence ⁢ ⁢ of ⁢ ⁢ the ⁢ ⁢ ion ⁢ ⁢ j ) has to be ensured , the concentration of the chloride ions with z cl − =− 1 can be eliminated : in a typical dialysate composition , it therefore applies to the conductivity ( linearized conversion between substance concentration and conductivity ) with { tilde over ( γ )} j ≡ γ j + z j γ cl − : σ = c na + { tilde over ( γ )} na + + c k + { tilde over ( γ )} k + + c ca ++ { tilde over ( γ )} ca ++ + c mg ++ { tilde over ( γ )} mg ++ + c bi c { tilde over ( γ )} bi c + c a c { tilde over ( γ )} a c + c glu { tilde over ( γ )} glu + σ ofs ( equation 11 ) the coefficients { tilde over ( γ )} j can be determined empirically from measurement data . coefficients γ j & lt ; 0 are conceivable , such as for glucose and urea , which is can be attributed to the fact that non - ionogenic substances disturb the movement of ions and thus reduce conductivity . a conductivity balance can be determined very precisely by means of the conductivity sensors 22 , 24 used in the dialysis machine . a sodium balance can then be estimated from this if the change in the sodium concentration can be calculated from the conductivity change between the dialyzer inlet and outlet . for this purpose , the contribution of the concentration change of the remaining dialysate components must be estimated for the conductivity change , for which purpose the following model is used as an approximation : 1 . in addition to na + ions as well as the implicitly considered cl − ions , essentially concentration changes of the k + ions and bic − ions contribute to the conductivity change since generally the concentration of these ions changes the most in the patient in the course of a dialysis . 2 . the change in the concentration of the remaining dialysate components does not have any real influence on the conductivity change , either because the concentration changes are too low or because the conductivity changes effected by the concentration changes of the individual components mutually compensate one another . their concentration can therefore be assumed to be constant ( see below ). the conductivity σ di at the dialyzer inlet can thus be given on the basis of equation 11 : σ di ={ tilde over ( σ )} ofs ( di ) +{ tilde over ( γ )} na + c na + ( di ) { tilde over ( σ )} ofs ( di ) = c k + ( di ) { tilde over ( γ )} k + + c ca ++ ( di ) { tilde over ( γ )} ca ++ + c mg ++ ( di ) { tilde over ( γ )} mg ++ + c bic − ( di ) { tilde over ( γ )} bic − + c ac − ( di ) { tilde over ( γ )} ac − + c glu ( di ) { tilde over ( γ )} glu + σ ofs the constant { tilde over ( σ )} ofs contains the contribution of all components of the fresh dialysate except for na + . it applies analogously to the conductivity σ do at the dialyzer outlet : σ do ={ tilde over ( σ )} ofs ( do ) +{ tilde over ( γ )} na + c na + ( do ) in accordance with the above assumptions , { tilde over ( σ )} ofs ( do ) can be written as the contribution of the concentration change of k + and bic − is then contained in δσ do ( conductivity compensation at the dialyzer outlet ): in this respect , the δj j , diff can be determined iteratively by means of equation 8 and equation 7 , with j being representative of k and bic − . inserting the sodium concentrations from the above expressions for σ di and σ do in equation 5 then produces , under the assumption that the bic and k concentrations do not change in the time t f , for the diffuse sodium balance ( conductivity - based diffuse sodium balance ): the diffuse sodium balance can thus be broken down into a conductivity balance m diff ( lf ){ tilde over ( γ )} na + which is determined directly from the conductivity measurement before and after the dialyzer 60 and into a correction term for the ion exchange via the dialyzer membrane m diff ( ic ) { tilde over ( γ )} na + , which is calculated by means of a patient and dialyzer module . it is the job of the regulation to achieve the diffuse sodium balance in the patient preset by the user by the end of the dialysis . when the set - point hypothesis is used , the goal is an isonatremic dialysis , that is , a zero sodium balance . if the zero balance should be deviated from , the user can initially preset an additional sodium quantity m diff ( user ) ( t end ) which should be transferred diffusely up to the end of the treatment , m diff ( user ) is & gt ; 0 if nacl should be supplied to the patient ; & lt ; 0 if nacl should be removed from him . the sodium regulation distributes this quantity linearly to the time up to 30 min before the end of the uf time ( t end = t uf − 30 min ): it is assumed in this respect that this additional sodium transfer does not influence the exchange of the other ions , even if the regulation for the realization differs from those concentration settings which were made to achieve the zero sodium balance . the regulation must satisfy two conditions to achieve the balancing goal : 1 . the diffuse sodium flow between the patient and the dialysate ( see equation 4 ) must disappear . when taking account of a dialysate running time t f between the two conductivity sensors and the conductivity compensation for the ion displacements , this is equivalent to the demand that applies : σ do ( t )− δσ do ( t )= σ di ( t − t f ) 2 . at the same time , the user preset for the diffuse balance should be satisfied at any time , with an accumulated imbalance also having to be balanced . it must therefore additionally apply ( cf . equation 13 ): these demands are realized in the determination unit or in the regulation model by a pi controller with a time lag . this first calculates the then currently to be set desired conductivity from the measured conductivity : σ soll ( t )= σ di ( t − t f )+ f 2 { tilde over ( γ )} na + (( σ do ( t )− δσ do ( t ))− σ di ( t − t f ))− f 1 ( m diff ( t )− m diff ( user ) ( t )) ( equation 15 ) the delay time t f is determined so that the volume element then currently located in the conductivity cell 24 disposed downstream was located in the conductivity cell 22 disposed upstream before the time t f . the control variable of the controller in equation 15 therefore depends on the measured conductivity at the dialyzer inlet and outlet as well as on correction terms of a model whose parameters are initially fixed . f 1 and f 2 are controller constants which can be determined empirically or analytically with methods of system theory known to the skilled person so that a best possible controller behavior results , in particular in view of the step response . the calculation of a plasma equivalent conductivity σ bi initially takes place from the measured conductivity before and after the dialyzer 60 in accordance with equation 9 . the sodium concentration is then calculated from this as the inversion of equation 11 ( calculation of the plasma sodium ): in this respect , the concentrations of potassium and bicarbonate are estimated as described in equation 8 by means of an i - pool patient model . the following concentrations are assumed as constant for the other dialysate components : c ca ++ = 1 . 2 mmol / l , c mg ++ = 0 . 5 mmol / l , c ac − − 2 . 0 mmol / l , c glu = 1 . 2 g / l to be able already to start the next dialysis from the start with that dialysate sodium c di ( zbal ) which is necessary for this patient for the reaching of the zero sodium balance , this value can be determined by the regulation and can be stored on the patient card at the end of the dialysis . if the diffuse zero sodium balance was reached , c di ( zbal ) is usually equal to the desired sodium value set at the end by the regulation . it is , however , possible , that no zero balance was reached , e . g . because a sodium displacement was selected by the user or the value required to reach the zero balance could not be set within the window limits . it can equally be possible that the zero balance was admittedly reached at the end of the dialysis treatment , but that , to compensate an imbalance , the last desired sodium value differs from that value which would correspond to a zero sodium balance . c di ( zbal ) is therefore approximated via a model . it is assumed by way of simplification here that the patient can be described by a distribution volume v which is dialyzed with respect to an average dialysate concentration c di with it follows from equation 6 and equation 7 , while neglecting the donnan effect : a zero sodium balance ( m diff ( t )= 0 ) is reached precisely when c di ( zbal ) = c bi ( 0 ). it follows from this for c di ( zbal ) the desired value of the sodium content of the dialysate can thus be determined from equation 18 for isonatremic dialysis and can be stored on the patient card . the detection unit 20 and the storage apparatus 50 into which the patient card ( s ) can be inserted are connected to data exchange means for this purpose . the user presets the regulation range before the start of the dialysis . this can be a value for the dialysate sodium usual for the center , an estimated value for the dialysate sodium required to achieve the isonatremic state , a lab measurement of the patient sodium or a value determined by the regulation from earlier treatments . for safety reasons , the regulation is only allowed to deviate from this value during the treatment within a fixed tolerance range , e . g . +/− 5 %, without querying the user . if larger deviations from the preset value are required to reach the isonatremia , the user is prompted to make changes to the preset value . in addition , the distribution volume of the patient must be input for the application of the model for the correction of the diffuse balance . it can be calculated by means of an anthropometric formula or can be determined by means of bioimpedance or kinetic modeling . furthermore , the initial concentrations of bicarbonate and potassium in the patient are required . they can come from an analysis by means of a blood gas analyzer before the start of the dialysis treatment . all the required parameters ( distribution volume , initial dialysate sodium , initial values for bicarbonate and potassium ) are frequently largely the same for a patient at the start of the dialysis treatment and can therefore be stored on a patient card and can be read in at the start of the treatment in an automated fashion . after the start of the treatment , the dialysate flow and the conductivity are determined upstream and downstream of the dialyzer 60 . furthermore , the calculation of the then current bicarbonate and potassium concentration takes place in accordance with equation 7 and equation 8 , with it being assumed that the potassium clearance corresponds to the sodium clearance and that the bicarbonate clearance corresponds to 70 % of the sodium clearance . the sodium clearance from the blood flow is estimated until the presence of the first clearance measurement ( after approx . 20 min ). in accordance with equation 12 and equation 13 , the calculation of the conductivity balance and of the correction term for the ion exchange and thus for the sodium balance then takes place from these data . the dialysate conductivity measured upstream and downstream , the sodium balance and the correction term for the dialysate conductivity downstream of the dialyzer 60 ( see equation 12 ) are then the input values for the sodium regulation in accordance with equation 15 . the desired conductivity thus determined is finally converted into a desired value for the dialysate sodium while taking account of the composition of the dialysis concentrate and this preset value is transmitted to the metering unit 40 . fig2 a and 2 b show the developments of the sodium and potassium concentration during a dialysis treatment for an artificial patient who was simulated by a container with 20 l saline solution while using the regulation in accordance with the invention for the sodium concentration . in this respect , the starting concentrations in the patient are 6 mmol / l potassium and 130 mmol / l sodium , for the dialysate 2 mmol / l potassium and 145 mmol / l sodium . the regulation in accordance with the invention adapts the dialysate composition such that the sodium concentration changes as little as possible over the dialysis duration , as shown in fig2 a . fig2 b shows the development of the potassium concentration in the patient , with the solid line representing measured values and the broken line representing the values calculated by the model . a regulation which only keeps the conductivity of the dialysate constant would compensate the loss of approx 3 . 5 mmol / l potassium by the supply of approx . 4 . 5 mmol / l sodium in the present example , which would result in an unwanted increase in the sodium concentration in the patient . the regulation in accordance with the invention keeps the sodium concentration in the patient approximately constant even though the concentrations of sodium and potassium in the dialysate differ greatly from that in the blood of the patient at the start of the dialysis . fig3 shows a lab experiment in vitro for zero sodium balance regulation using the compensation for the exchange of potassium and bicarbonate . the desired value of the regulation is shown for the dialysate sodium ( lower curve , left hand scale ) as well as the measured development of the conductivity in the model patient ( upper curve , right hand scale ). the model patient ( distribution volume 10 l ) had 14 . 6 ms / cm at the start o the conductivity . without compensation , the regulation would therefore have set a dialysate sodium of approx . 146 mmol / l and would have kept the conductivity constant with the present dialysate composition . transferred to a patient , the conductivity drop due to potassium loss and ingestion of bicarbonate would in this connection be compensated by a supply of sodium so that the final sodium would have been much higher than the starting sodium . by use of the compensation , the regulation already sets a much lower sodium value at the start of the treatment and keeps this largely constant . the drop in the conductivity of the patient corresponds to the situation that the value of the plasma sodium admittedly remains constant , but the plasma conductivity falls due to potassium loss and ingestion of bicarbonate . fig4 shows an in vitro lab experiment for the user - defined removal of nacl . in contrast to the prior art , according to which only the regulation of the plasma sodium to a preset value is possible , the user can initiate relative changes to the then current value of the plasma sodium , i . e . set the extent to which it is possible to deviate from the isonatremic state . for this purpose , the distribution volume of the patient must be input or read from a data carrier . in addition , the treatment duration typically has to be given as the duration of the ultrafiltration . the user can now give a desired value for the sodium concentration change in mmol / l . equally , the initial values of potassium and bicarbonate are required so that the correction of the balancing described above can be carried out . it is then distributed linearly over the planned treatment duration by the regulation as likewise described above . in this connection , changes in the clearance and changes in the conductivity caused by the ion exchange are taken into account automatically in the course of the treatment . this results in a treatment with largely constant diffusion gradients between the plasma and the dialysate . alternatively , the user can also preset a total sodium quantity which should be removed from or supplied to the patient during the dialysis by ultrafiltration and by diffusion . this is useful for applications in which the sodium ingestion between the dialyses is known precisely due to the diet . fig4 shows an in vitro lab experiment for the user - defined removal of nacl ( user preset 4 . 5 mmol / l ) from a model patient ( nacl solution , distribution volume 10 l ). in this connection , the curve extending at the bottom in the left hand part illustrates the desired value of the regulation for the dialysate sodium and the curve extending at the top illustrates the measured extent of the conductivity in the model patient . no compensation for the ion exchange was carried out in the experiment so that the development of the dialysate sodium set by the regulation was only caused by the algorithm to achieve the concentration displacement . the constant value of the dialysate sodium at approx . 3500 s is created in that the lower end of the regulation range was reached at this point in time . only at 5000 s was this displaced by the user toward lower sodium concentrations so that as a consequence the “ making up ” of the planned sodium withdrawal took place . the invention being thus described , it will be apparent that the same may be varied in many ways . such variations are not to be regarded as a departure from the spirit and scope of the invention , and all such modifications as would be recognized by one skilled in the art are intended to be included within the scope of the following claims .

an apparatus and a method for the determination and regulation of the concentration of at least one dissolved substance in a fluid circuit , in which the fluid circuit includes at least two partial circuits separated by a filter in a semi - permeable manner , includes a detection unit for determining a concentration difference of at least one first dissolved substance , a determination unit for determining the influence of at least one second dissolved substance which is not identical to the at least one first dissolved substance , and a regulation unit for regulating the concentration of the at least one dissolved substance in the fluid circuit .

the transmitter of the present invention , for which an electrical diagram is shown in fig1 comprises a blocking oscillator using a ferrite torus 1 as a transformer , having for example an outer diameter of 4 mm , comprising twice 50 hand wound turns . the relaxation frequency is situated around 1 khz . the antenna consists of a printed spiral coil 2 , comprising for example 40 turns of 25 mm external diameter . the components of the transmitter are preferably of the subminiature type ( for hydrid circuits ). power is supplied to the transmitter by a 1 . 35 volt microbattery 3 . in the mode of embodiment shown in fig1 and 5 , the transmitter is separated into two portions , one portion 4 consisting of the detector ( torus 1 ) and the other portion 5 by the transmitter proper , these two portions preferably being connected by a teflon coated cable 6 sheathed in a &# 34 ; silastic &# 34 ; ( dow corning company ) extra flexible tube . the printed circuit of the transmitter is manufactured , for example , by photographic reduction , the coil constituting antenna 2 being designed by an analog computer . transmitter 5 is vacuum moulded in an epoxide resin such as &# 34 ; medical araldite &# 34 ;. the ferrite torus 1 is preferably embedded ( fig5 ) in an epoxide resin 7 , as shown in fig5 . the detector 4 so constituted is integral with a pre - scoured osteosynthesis plate 8 adapted to be screwed to the bone to be studied facing the fracture or crack . the osteosynthesis plate 8 may be made of any suitable material well known in the art . see , for example , webster &# 39 ; s third new international dictionary unabridged ( 1971 ) under &# 34 ; osteosynthesis &# 34 ; ( p . 1597 ); and larousse medical pages 463 - 464 ( 1975 edition ), imprimerie herissey , france . detector 4 is encased in a special elastomer such as a silicone 9 ( which may be that known as &# 34 ; silastic &# 34 ; which is manufactured by the dow corning company ). the receiver shown in fig6 comprises a square loop antenna 10 , a wide band amplifier 11 , a band - pass filter 12 , a schmitt trigger 13 , a monostable trigger circuit 14 the output of which is connected to a sound producing device 15 and an output 16 for recording on a magnetophone . the receiver of fig6 is preferably small , autonomous and can be carried on the patient . it it is desired to effect telemetering , an hf telemeter transmitter 17 is associated with the receiver . fig7 shows a signal processor and recorder 50 having three inputs : a radio telemetering input 20 , a magnetophone input 21 and a direct input 22 . input 20 is connected to the telemetering receiver 23 tuned to the telemetering transmitter 17 of the receiver of fig6 . input 21 is a magnetophone read - out input and input 22 is connected to a square loop antenna 24 similar to the square loop antenna 10 of the receiver of fig6 . inputs from 20 , 21 or 22 may be processed through any suitable signal processor and recorder 50 . recorder 50 may include a sound output device 52 , a digital display 54 , and / or an analog signal recorder 56 . the detector 4 and emitter 5 integral with the osteosynthesis plate 8 are implanted on the fractured or cracked bone . after the operation , known forces and moments of flexion are applied to the limb in question once a week , for example . any slight stresses transmitted to torus 1 or the detector 4 result in variations in inductance which may be greater than 50 % ( fig3 ). such variations in inductance induce variations in the frequency of the oscillator of emitter 5 . fig2 illustrates the spectrum as a linear percent of maximum by a emitter having a power output of 3 μw and a range of 20 cm . the probe ( square shaped loop antenna 10 although one skilled in the art will understand that a circular loop may be used ) of the receiver of fig6 should be positioned at a maximum distance of 20 cm from the implantation site of the transmitter . the receiver permits both auditive control by means of the sound device 15 and recording on an ordinary magnetophone . if coupled to the telemetering emitter 17 and worn by the patient , the receiver permits telemetering to be effected at a distance to monitor bone stress during walking , running , or the like . the signal processor and recorder 50 of fig7 permits sound control by device 26 at a distance , permits measurement of stress to be digitally displayed at 54 and has an analog output which may be connected to a recorder 56 . it should be emphasized that development over a period of time of measurements obtained after calibration determine the bone consolidation curve . input 21 of the signal processor and recorder 50 permits reuse of previous recordings . input 22 permits direct use of the signal processor and recorder 50 without passing through the receiver of fig6 by placing the square loop antenna 24 at maximum of 20 cm from the transmitter . the very low power consumption of the transmitter ( 6 μw ) provides real autonomy of considerably longer than 18 months . its small size ( diameter 30 mm , thickness 4 mm ) enables it to be used without distress to the patient . in the preferred embodiment of fig1 and 5 , the transmitter is made in two parts 4 and 5 , but it is obviously possible to miniaturize the transmitter proper ( 5 ) even further to incorporate it in the detector 4 and secure it directly onto the osteosynthesis plate 8 . it should further be noted that such a detector - transmitter can easily be adapted to measure parameters other than stresses ( such as temperature , an electrocardiogram , or the like ). finally , the invention is obviously not limited to the modes of embodiment shown and described above but covers all the variants .

a process for the measurement in vivo of the degree of bone consolidation , characterized in that it consists of implanting directly on the surface of the bone a transmitter with its power supply circuit , the oscillation frequency of the transmitter being capable of varying about a predetermined value during stresses applied to the bone to which the transmitter is secured . signals emitted by the transmitter are received on a suitable external receiver positioned adjacent the transmitter . the receiver output signals are utilized for various purposes , such as checking , measurement and recording .

all documents cited are , in relevant part , incorporated herein by reference ; the citation of any document is not to be construed as an admission that it is prior art with respect to the present invention . the present invention relates to controlled release potassium chloride tablets and to processes for producing the same . the controlled release tablets provide treatment for potassium deficiency in humans while minimizing adverse side effects . the tablets of the present invention are characterized by a total tablet weight of about 2 g with acceptable hardness ( not less than 14 kp ) and friability ( not more than 0 . 3 %). in accordance with the present invention , a plurality of potassium chloride crystals , typically from about 20 mesh to about 70 mesh , more particularly from about 30 mesh to about 50 mesh , are coated with two distinct layers . the first layer applied to the crystals comprises ethylcellulose . utilization of a high viscosity ethylcellulose such as one with a viscosity of from about 90 to about 110 cps , e . g ., ethocel 100 ( dow chemical corp .) allows the crystals to retain their diffusion controlling characteristics even after compression into a tablet form . the ethylcellulose may be applied by any suitable technique known in the art , but is preferably applied by coacervation using polyethylene as a phase separator as described in u . s . pat . no . 5 , 422 , 122 . if coacervation is used , trace amounts of the phase separator may be present in the first layer , preferably in an amount less than about one percent by weight of the ethylcellulose coated crystals . the ethylcellulose layer is preferably applied to the kcl crystals in an amount of about 8 to about 20 percent , more specifically from about 10 to about 17 percent , of the total weight of the potassium chloride microcapsules . this first layer controls the release of the potassium chloride over time , total release time being proportionally dependent upon the thickness of the ethylcellulose membrane . after application of the ethylcellulose , a drying step should preferably be carried out so that the residual cyclohexane level is less than 1000 parts per million . the resultant ethylcellulose encapsulated potassium chloride microcapsules are preferably of such a size that less than 5 % are greater than 20 mesh . a second , discrete layer of a plasticized compressible polymer coating , is applied as an outer membrane over the inner membrane of ethylcellulose . pharmaceutically acceptable polymers suitable for use in the compressible coating include ethylcellulose available as an aqueous dispersion , polyvinylpyrrolidone ( pvp ), and hydroxypropyl methylcellulose ( hpmc ). this outer coating membrane may comprise from about 0 . 5 to about 5 % based on the weight of the compressible coated microcapsules . no plasticizer is required for the inner dissolution rate controlling membrane of the compressible coated microcapsules while the water - insoluble polymer or water - soluble polymer forming the outer membrane requires a plasticizer to impart proper compressibility properties on the ethylcellulose coated microcapsules . representative examples of plasticizers that may be used to plasticize the outer membrane include dibutyl sebacate , diethyl phthalate , triacetin , triethyl citrate , polyethylene glycols of different molecular weights ranging from about 200 to 8 , 000 ( e . g ., a blend of peg 400 and peg 4000 ) and mixtures thereof . the plasticizer may comprise about 2 to 40 wt . % and more typically about 3 to 30 wt . % based on the weight of the plasticized polymer . the amount may vary with the type of plasticizer and the nature of the polymer . for example , for a plasticized polymer comprising hpmc and peg400 , the ratio may typically vary from about 90 / 10 to 97 / 3 . for a plasticized polymer comprising pvp and dbs or triethyl citrate , the typical ratio of polymer to plasticizer can range from about 94 / 6 to about 97 / 3 . the ethylcellulose used in the outer membrane is typically applied from an aqueous dispersion of ethylcellulose . the aqueous dispersion preferably includes an effective amount of plasticizer . commercially available ethylcellulose dispersions suitable for use in forming the outer membrane include aquacoat ® and surelease ® aquacoat ® requires the addition of a separate plasticizer , while surelease ® is supplied with a plasticizer . the plasticized polymer is applied by conventional techniques , such as from an aqueous solution using a fluidized bed coater , to the preformed layer of ethylcellulose . the plasticized polymer coating layer inclusive of the plasticizer is applied in an amount of about 0 . 5 to 5 % w / w ( in accordance with certain embodiments , about 1 to 3 % w / w and more specifically about 2 % w / w ) of the weight of the compressible coated microcapsules . the plasticized polymer does not significantly diffuse into the ethylcellulose , but rather forms a distinct second layer . the first membrane of ethylcellulose coacervated in the absence of any plasticizer can be easily distinguishable from the plasticized polymeric membrane by microscopic / spectroscopic techniques . as the outer membrane layer is soluble to gastric fluids , the plasticized polymer coating dissolves following ingestion of the resultant tablet . for all practical purposes , it does not contribute to the controlled release of potassium chloride . rather , the plasticized polymer coating is present primarily to impart compressibility to the ethylcellulose coated potassium chloride microcapsules so that a high dosage rate tablet having the necessary hardness and friability properties can be formed with a minimal amount of conventional excipients and low compaction pressures to allow minimal disruption of the rate controlling ethylcellulose membrane . in addition , this formulation allows the microencapsulated potassium chloride to be dispersed essentially intact over a wide area , reducing the risk of gastric irritation . after the plasticized polymer coating layer is applied , the now twice coated crystals are subjected to a final drying step . the resultant coated potassium chloride microcapsules are preferably of such a size that less than 15 %, are greater than 20 mesh . the coated crystals may then be formed into tablets by compression using conventional techniques . preferably a minimal amount of excipients , no more than about 20 %, preferably no more than about 15 %, by weight based on the weight of the final dosage tablet , is added to the coated crystals prior to compression . the term “ excipients ,” as used herein , refers to any additional pharmaceutically acceptable ingredients which may be used in a tablet . these excipients include , but are not limited to , ingredients such as diluents , binders , disintegrants , and wetting agents . however , these tablets in certain embodiments do not comprise any lubricant , either internally ( blended intergranularly ) or externally ( sprayed on to the punch and die surfaces during tableting ) including , but not limited to , stearates ( e . g ., magnesium , calcium , and sodium ), stearic acid , sterotex ®, talc , waxes , and stearowet ®. binders include , but are not limited to , low viscosity hydroxypropyl - cellulose ( klucel ® lf ), polyvinylpyrrolidone ( pvp ), and low viscosity hydroxypropylmethylcellulose ( hpmc with an average viscosity of about 3 to 15 cps ). disintegrants include , but are not limited to , cornstarch , sodium starch glycolate , croscarmellose sodium , and crospovidone ® ( cross linked polyvinyl pyrrolidone ). diluents / compression aids include , but are not limited to avicel ® or ceolus ® ( microcrystalline cellulose ), lactose , mannitol , emcompress ® ( dibasic calcium phosphate dihydrate ), and tricalcium phosphate . surfactants ( wetting agents ) include , but are not limited to , sodium lauryl sulfate . in a particular embodiment of the invention , compressible coated microcapsules comprising ethylcellulose kcl microcapsules coated with a plasticized polymer coating solution are blended with a colloidal silicon dioxide , a compression aid , preferably microcrystalline cellulose , and optionally a disintegrant and / or a surfactant to form a compressible blend . the compressible blend is compressed into capsule shaped tablets . in accordance with certain embodiments , a surfactant , such as sodium lauryl sulfate , at a level of about 0 . 1 to about 1 . 0 % w / w , in combination with a disintegrant , such as crospovidone at a level of about 0 . 5 to about 3 % w / w , is optionally blended with the compressible blend . in the course of these investigations , it was discovered that a compressible blend comprising from about 0 . 1 to about 0 . 3 %, more particularly about 0 . 2 % colloidal silicon dioxide and not more than about 15 %, more specifically not more than about 12 %, and in certain embodiments not more than 10 % by weight of a compression aid , preferably microcrystalline cellulose , produced strong tablets with low friability . it was also discovered that microcapsules fluid bed coated with the plasticized polymeric systems described herein could be compressed into strong tablets with low friability without a lubricant ( e . g ., magnesium stearate ). a disintegrant normally results in a rapid disintegration of the tablet into constituent granules . the disintegrant has been observed to speed up the drug release from the granules in certain embodiments . however , if a surfactant ( sodium lauryl sulfate ) is used in combination with the disintegrant , the detrimental effect of the disintegrant in terms of speeding - up of the drug release from the granules is surprisingly minimized . the final tablets will contain a pharmaceutically acceptable amount of potassium chloride . acceptable daily dosages may be found in the physicians &# 39 ; desk reference , 45th ed . ( 1991 ), e . g ., 20 - 200 meq / day thereof , preferably from about 8 meq to about 20 meq . the pharmaceutically elegant 20 meq microcaps kcl tablets prepared in accordance with the present invention will exhibit sustained release properties ( releasing not more than 40 % in one hr and not less than 80 % over 8 hrs when tested in usp apparatus 2 ( paddles @ 50 rpm ) in purified water , thereby providing treatments for potassium deficiency in humans with minimal adverse side effects . in accordance with certain embodiments , the present potassium chloride tablets are substantially lubricant - free . the term “ lubricant ” as used herein refers to internal lubricants which are present as a component of the formulation and external lubricant applied to the material contacting punch and die surfaces to facilitate compression and ejection of the tablet from the die . as used herein , the term “ substantially lubricant - free ” means that conventionally used lubricants are not present in the compositions or on the die surfaces in amounts typically used to provide lubrication . thus , it should be appreciated that reference to “ substantially lubricant - free ” in accordance with particular embodiments of the present invention does not exclude the presence of small amounts of lubricants as impurities . thus , “ substantially lubricant - free ” should be understood as meaning free of added lubricants , and containing less than 0 . 5 %, preferably essentially 0 %, of conventional lubricants . tablet hardness is a physical strength measurement of the tablet . hardness measurement provides an indication of the resistance of the tablet to chipping , abrasion , or breakage under conditions of storage , transportation and handling . hardness is expressed as kp , newtons , kg , or strong cobbs and typically measured using one of the many commonly available tablet hardness testers . hardness in accordance with the present invention is determined using a schleuniger pharmatron tablet hardness tester following procedures in the operation manual . tablet friability is a physical strength measurement of the tablet and is defined as the ability of the compressed tablet to resist abrasion and attrition . it is typically measured by turning tablets in a rotating vessel and determining weight loss . the loss of weight is measured after a fixed number of revolutions of a drum rotating in a controlled rate . friability is determined with the present invention is determined using a erweka friability tester following the procedures in united states pharmacopoeia , volume 26 , page 2439 . the following non - limiting examples illustrate the tablet dosage forms manufactured in accordance with the invention , which exhibit acceptable tableting properties ( mean high hardness in the range of 14 - 25 kp and low friability (& lt ; 0 . 2 %)). the 20 meq tablets comprising no disintegrant remain intact , i . e ., do not disperse upon contact with water or body fluids . still , these tablets exhibit in vitro drug release profiles similar to that of and bioequivalency to the marketed product based on the disclosure of hsiao and chou in u . s . pat . no . 4 , 863 , 734 . in contrast , the 20 meq tablets comprising compressible microcaps kcl coated with plasticized ethylcellulose and a disintegrant , or tablets comprising compressible microcaps kcl coated with plasticized pvp or hpmc and a combination of a disintegrant and a surfactant , rapidly disperse upon contact with water and exhibit in vitro drug release profiles similar to that of the marketed product based on the disclosure of hsiao and chou in u . s . pat . no . 4 , 863 , 734 . potassium chloride microcapsules were coated with an aqueous solution of low viscosity hydroxypropyl methylcellulose ( hpmc , methocel e - 5 from dow chemical company ) and triethyl citrate at a ratio of 90 / 10 in a laboratory fluid bed coater for a weight of 2 % w / w ( batch size : 1 kg ). a compression blend was prepared by blending 450 g ( 88 %) of the compressible coated microcapsules , 48 . 6 g ( 9 . 5 %) of microcrystalline cellulose known by the trade name as ceolus , 10 . 2 g ( 2 . 0 %) of crospovidone , and 2 . 6 g ( 0 . 5 %) of magnesium stearate and compressed into 20 meq tablets on an r & amp ; d rotary tablet press . the tablets thus obtained exhibited extremely poor hardness ( 1 - 2 kp ). another batch of potassium chloride microcapsules was coated with 2 % w / w of hpmc and triethyl citrate at a ratio of 80 / 20 as stated in example 1 . the compressible coated microcapsules ( 88 %) were blended with ceolus ( 9 . 5 %) and crospovidone ( 2 %) and magnesium stearate ( 0 . 5 %) and compressed into 20 meq tablets . poor results were obtained as in example 1 ( see table 1 ). this batch of compressible microcapsules was obtained by coating with hpmc and polyethylene glycol ( peg 400 ) at a ratio of 70 / 30 to achieve 1 % weight gain . the compressible coated microcapsules were blended with ceolus , crospovidone , and magnesium stearate and compressed into 20 meq tablets . once again extremely poor results were obtained as in examples 1 and 2 ( see table 1 ). potassium chloride microcapsules in examples 4 - 6 were coated with an aqueous solution of polyvinylpyrrolidone ( pvp ) and dibutyl sebacate at a ratio of 97 / 3 in an r & amp ; d or production fluid bed coater for a weight gain of 2 % w / w . while the batch size in the r & amp ; d coater was about 10 kg , the production equipment was used to coat about 700 kg of microcapsules . the tablets of examples 4 to 6 thus obtained exhibited acceptable hardness ( 15 kp or higher ). in general , the friability values were poor , especially when scored punches were used for tableting . these tablets failed to disperse rapidly on contact with water , though the drug release profiles were similar to that of the tablets of hsiao . from the comparative examples provided above , it is apparent that the process or the method of manufacturing of controlled release of potassium chloride tablets fails to meet the industrial applicability criteria , namely , product quality , transportation , commercial distribution , and use . a batch of compressible coated ( 1 . 5 % coating of 70 / 30 pvp / peg 400 ) microcapsules ( 88 . 5 %) was compressed into 20 meq tablets with ceolus ( 10 %), crospovidone ( 1 %), and sodium lauryl sulfate ( 0 . 5 %), a surfactant which is normally used as a wetting agent . these tablets containing no lubricant exhibited good hardness but high friability . potassium chloride microcapsules were coated with an aqueous solution of polyvinylpyrrolidone ( pvp ) and triethyl citrate at a ratio of 94 / 6 in a laboratory fluid bed coater for a weight gain of 2 % w / w . a compression blend was prepared by blending 442 . 5 g of the compressible coated microcapsules , 50 g of microcrystalline cellulose known by the trade name as ceolus , 5 g of crospovidone , and 2 . 5 g of sodium lauryl sulfate and compressed into 20 meq tablets on a rotary tablet press . the tablets thus obtained exhibited moderate hardness ( 10 . 2 kp ) although the friability was poor . potassium chloride microcapsules were coated with an aqueous solution of polyvinylpyrrolidone ( pvp ) and dibutyl sebacate at a ratio of 97 / 3 in a production fluid bed coater for a weight gain of 2 % w / w ( batch size : 700 kg ). a compression blend was prepared by blending the compressible coated microcapsules and ceolus at a ratio of 90 / 10 and compressed into 20 meq tablets on a production rotary tablet press using scored tooling . the tablets exhibited poor hardness and friability values . examples 10 to 13 in accordance with aspects of the invention microcapsules of kcl crystals ( 690 kg ) were coated to achieve a weight gain of 2 % with an aqueous solution of polyvinylpyrrolidone ( 13 . 7 kg ) and dibutyl sebacate ( 0 . 42 kg ) at a ratio of 97 / 3 in a fluid bed coater . a compression blend ( batch size : about 780 kg ) comprising 89 . 87 parts of the compressible coated microcapsules , 9 . 98 parts of microcrystalline cellulose ( ceolus ) and 0 . 15 part of colloidal silicon dioxide ( cab - o - sil ), was compressed into 20 meq tablets . the capsule shaped monogrammed tablets ( ¾ ″× ⅜ ″) weighing about 2 g , exhibited a mean hardness of about 18 kp and a friability of 0 . 1 % and a controlled release profile ( fig1 ) equivalent to the commercially available k - dur 20 . the results of an open - label , single dose , randomized , two - way crossover bioequivalence study comparing 20 meq potassium chloride controlled release tablets of example 10 ( marked a in fig2 ) and reference tablets manufactured and marketed per disclosure of hsiao and chou ( marked b in fig2 ) confirmed bioequivalence between the two tablet formulations based on ( eai pf220ea001 versus k - dur 20 ( lot # 1d0110 )), in healthy subjects under fasting conditions . thirty ( 30 ) healthy , non - smoking , male subjects aged 20 to 40 years , meeting a set of acceptance and exclusion criteria , were selected , confined to the clinic , and conditioned with standardized meals ( maintaining both sodium and potassium intakes ) and fixed quantity of water at predetermined intervals during the equilibration periods . urine samples were collected at the end of equilibrium period ( days 5 , 6 and days 13 , 14 ) and on dosing days ( days 7 and 15 ) for timed intervals of 0 - 1 , 1 - 2 , 2 - 4 , 4 - 6 , 6 - 8 , 8 - 12 , 12 - 16 , 16 - 24 . the urine samples collected during the be study were tested for potassium and creatinine concentrations using validated bioanalytical methods . even though the tablets of example 10 were bioequivalent to k - dur 20 , the tablets were not considered to be generically equivalent to k - dur 20 because the tablets of example 10 failed to disperse in water within 2 minutes as required for k - dur ® ( see physicians &# 39 ; desk reference , page 3047 of pdr edition 57 , 2003 ). microcapsules of kcl crystals ( batch size : 400 kg ) were coated to achieve a weight gain of 2 % with an aqueous dispersion of ethylcellulose ( commercially available as aquacoat ecd30 latex dispersion from fmc , philadelphia , pa .) and diethyl phthalate at a ratio of 76 / 24 in a fluid bed coater . a compression blend comprising 85 . 5 parts of compressible coated microcaps kcl , 11 . 9 parts of ceolus , 2 . 0 part of crospovidone , 0 . 3 part of colloidal silicon dioxide , and 0 . 3 part of sodium lauryl sulfate were compressed into 20 meq er tablets . the capsule shaped monogrammed tablets ( ¾ ″× ⅜ ″) weighing about 2 g , exhibited a mean hardness of about 19 . 1 kp and a friability of 0 . 17 % and rapidly dispersed into granules ( microcapsules ) on contact with water like the reference tablets , k - dur 20 manufactured based on the disclosure of hsiao . furthermore , these tablets exhibited a controlled release profile similar to that of reference tablets , as shown in fig3 . 400 kg of microcaps kcl from production were coated with an aqueous dispersion of ethycellulose , aquacoat ® ecd - 30 plasticized with diethyl phthalate ( ratio : 60 / 40 ) for 4 % weight gain . 85 . 85 parts of compressible coated microcaps kcl , 12 . 0 parts of ceolus , 2 . 0 part of crospovidone , and 0 . 15 part of colloidal silicon dioxide were blended and compressed into 20 meq er tablets with a mean hardness of 22 . 4 kp and a friability of 0 . 13 %. these tablets disintegrated within a minute and exhibited a drug release profile as shown in fig3 . microcaps kcl from production coated with an ethylcellulose dispersion , plasticized with diethyl phthalate ( ratio : 76 / 24 ) for 2 % weight gain . 85 . 7 parts of compressible coated microcaps kcl , 12 parts of ceolus , 2 parts of crospovidone , and 0 . 3 part of colloidal silicon dioxide were compressed into 20 meq er tablets with a mean hardness of 19 . 8 kp and a friability of 0 . 25 %. these tablets disintegrated within a minute and exhibited a drug release profile as shown in fig3 . the above examples are provided to show how to practice the present invention and are not intended to be exhaustive or to include all obvious modifications and variations which will become apparent to those skilled in formulation development . however , all these modifications are within the scope of the present invention and by the following claims :

a unit dosage form , such as a tablet for delivering potassium into the body in a controlled release fashion , comprises of a multiplicity of microencapsulated potassium chloride crystals , which are further coated with a plasticized polymer to improve compressibility of the microcapsules . the compressible microcapsules are blended with a compression aid , such as microcrystalline cellulose and a glidant , such as colloidal silicon dioxide , to form controlled release potassium chloride tablets . the tablets may optionally include other excipients such as surfactants and disintegrants . the tablets thus produced exhibit not only high crushing strength and low friability but also release potassium in humans in a desired controlled release fashion similar to commercially available potassium chloride tablets .

the following description and drawings are illustrative and are not to be construed as limiting . numerous specific details are described to provide a thorough understanding . however , in certain instances , well known or conventional details may not be described in order to avoid obscuring the description . in accordance with the present invention , a novel and improved system for aseptic irrigation and urine specimen collection from the catheterized bladder is provided . fig1 and 2 are illustrations of a self closing port and valve assembly 10 according to one embodiment of the present invention . within this embodiment the device has a fully sanitizable self closing irrigation port 12 that allows a urinary catheter to remain attached to a urine collection device while being irrigated without disconnecting the urine collection device drainage tubing 14 from the urinary catheter ( not shown ). this allows for an aseptic , closed system , which keeps bacteria from entering the catheter and also prevents exposure to body fluids during the irrigation or sampling process . the self closing port and valve assembly 10 could be located in numerous places on a urinary catheter drainage system . for instance , it could be a part of a urinary catheter itself . it could be a separate device that connects between the catheter and the drainage bag , or it could be a part of the urine collection device . in the embodiment of fig1 and 2 , it is a part of the urine collection device , and is located at the junction between the catheter connector port 7 in the catheter connector 11 and the urine exit port 8 in the drainage tube 14 which drains urine from the catheter into the urine collection device . in the embodiment of fig1 and 2 , an internal valve 15 has a tension spring 17 . the spring tension keeps the internal valve biased in a first position in which a urine exit port 18 is open to the urine drainage tube 14 . spring 17 can be , for example , a torsion spring , leaf spring or any other spring or spring - like element . insertion of a catheter tip irrigation syringe or other similar device 13 into the self closing irrigation port 12 pushes the internal valve 15 to a second position against the urine exit port to the urine collection device drainage tube 14 , closing it off and bypassing any flow to the drainage tube while keeping the irrigation port open . in the present embodiment , the valve 15 is fashioned so that a portion of it protrudes into the path of a device 13 inserted into the self closing irrigation port 12 . the device inserted into the port pushes the protruding portion of the valve in the direction of the urine exit port , closing the valve when the device is inserted into the irrigation port . this automatically shuts off the flow of fluid and air to the drainage bag allowing for irrigation of the catheter and bladder without the irrigation fluid entering the drainage tube . when the irrigation procedure is complete and the syringe 13 is removed , the spring 17 moves the valve back to the open position to allow urine to flow from the catheter , into the urine collection device and to the drainage collection receptacle . in the embodiment of the device in fig1 and 2 , a port and valve assembly 10 also has a valve control mechanism 16 to externally shut the valve 15 without the insertion of a syringe or other object into the port 17 . this would allow the valve 15 to be closed even when not irrigating or collecting samples from the catheter . keeping the valve closed would stop the flow of urine from the bladder to the urine collection device drainage tube 14 , and allow the bladder to fill with urine , an important physiological function that is normally inhibited in state of the art urinary catheter systems . in some embodiments , the valve control mechanism 16 may be designed in such a way as to allow for the valve to stay closed for a specific prescribed and adjustable amount of time , allowing for the bladder to fill for a prescribed amount of time and then empty when that time period ends . examples of the valve control mechanism are described below . fig3 is an illustration of an alternative embodiment of the port and valve assembly 10 ′. in fig3 a syringe is not inserted through a self closing port , and fluid 20 is free to flow through an internal valve 31 through an opening in the valve 30 . in fig4 the flow of fluid to the drainage bag is shut off when an irrigation syringe is inserted into the port and valve assembly by means of an internal valve 31 which mates with the tip of the irrigation syringe when inserted . the tip of the irrigation syringe fits snugly into the internal valve , sealing flow of fluid or air from the drainage bag . the internal valve 31 in the embodiment of fig3 and fig4 is made by a thickening in the wall of the port and valve assembly , which decreases the diameter of the channel , forming the valve opening 30 . the internal valve 31 created by the thickened wall may in some embodiments be lined with a flexible material such as foam , latex , or silicone to form a valve seat 32 adapted to cooperate with an exterior surface of the syringe . when an irrigation device is inserted through the irrigation port , it enters the valve opening , and the syringe compresses the expandable material 32 lining the internal valve . the syringe is held tightly in place by this compression and creates an air and fluid seal . fig5 shows the self closing irrigation port 12 in more detail . irrigation port 12 has a self sealing membrane 9 made of latex or other highly flexible and pliable material . the membrane has a small pliable hole 23 within in the center which runs from the external portion to the internal portion . when a syringe or other irrigation device is pushed against the external portion of the membrane , the pliable hole 23 spreads open and the irrigation device can be passed through the membrane to the internal portion of the port . when the syringe is removed , the opening in the port closes tightly , forming a seal which keeps urine in , and bacteria out of the urinary drainage system . the flat surface of the port is easily sanitizable with 70 % alcohol or other standard medical sanitizer , allowing for aseptic port access without introduction of bacteria into the drainage system . fig7 is a flow diagram of an aseptic port access procedure . the embodiment of the valve control mechanism in fig5 consists of a small compliant balloon 21 which is inflated by an air filled chamber 22 which is made of a soft compressible material . by applying pressure to the air filled chamber manually , typically with the push of a finger or thumb , air is squeezed out of the chamber and into the balloon , which , in turn closes the valve stopping the flow of urine out of the bladder . the chamber is fashioned in such a way as to allow air to pass without resistance into the balloon through a one way valve 24 . once inside the balloon , the air must pass through a block 27 in which one or more holes form a balloon deflation orifice . the time period over which balloon 21 deflates can be controlled by the size and / or number of holes in block 27 , which allows for control of the amount of time the valve 15 stays open . the air passes through the block and out the air exit hole 26 . fig6 is an illustration of an embodiment of a valve control mechanism for use with the port and valve assembly of fig3 and 4 . this figure demonstrates how the balloon 21 inflates to close off the flow of fluid from the catheter to the drainage bag by blocking flow from the opening 30 to the urinary drainage end of the port and valve assembly . in other embodiments the balloon may be inflated by other means such as a syringe . fig6 a and 6b show one embodiment of the port and valve assemble in which the compliant balloon is inflated by a syringe 28 . air or fluid is introduced into the balloon by the syringe which attaches onto a luer locking connection 29 , which has a valve 61 attached to a spring 62 . when the syringe is attached it pushes prongs 63 on the surface of valve 61 , depressing the valve and spring and opening a fluid connection between the syringe and balloon cavity 64 . when the syringe is removed , the spring pushes the valve closed sealing the compartment and trapping the air or fluid within the balloon , keeping it inflated . in order to restart the flow of urine from the bladder to the urinary drainage bag , a syringe is simply re - attached to the luer locking port and the air or fluid is removed from the balloon . in some embodiments the air in the balloon slowly leaks out through a different air passage 26 from which it entered and through a block 27 with one or more holes , as described above . the valve control mechanism 16 in some embodiments may employ a lever instead of a balloon which pushes the valve shut . it will be apparent to a skilled artisan that the embodiments described herein are exemplary of inventions that may have greater scope than any of the singular descriptions presented . there may be alterations made in these examples without departing from the spirit and scope of the invention disclosed . for example , any aspect of an improved aseptic urinary drainage device and system may have components with different shapes or designs within different embodiments . for instance spring types , housing shape , valve diameter and compositions may vary in design from one embodiment to another , but not overall function . in some embodiments the catheter connection port may be the drainage end of a urinary catheter . in some embodiments the urine exit port may be an intrinsic part of the urine collection device , and in some embodiments the port and valve assembly may be separate from the urine collection device . these or other features may change in different embodiments .

a urinary catheter connector system having a housing ; a catheter connector port supported by the housing and configured to attach to a urinary catheter ; a urine exit port supported by the housing and configured to connect to a urine collection device ; an irrigation port supported by the housing and configured to receive an irrigation syringe ; a channel in the housing fluidly connecting the catheter connector port , the urine exit port and the irrigation port ; and a valve supported by the housing and adapted to cooperate with the irrigation syringe to shut off flow of fluid and air to the urine exit port when the irrigation syringe is inserted and allow for flow of fluid and air to the urine exit port when the irrigation syringe is removed . the invention also includes methods of using the system .

the foregoing description of the invention is presented for purposes of illustration and is not intended to limit the invention to the form disclosed herein . conventionally a swing consists of a strong horizontal cross - beam supporting a pair of flexible swing lines made of cords or chain at the bottom of which is suspended a seat , a chairs platform or any other element . the horizontal cross - beam may be secured to a building structure or as commonly seen in playgrounds , supported at its extremities by a pair of triangular support frame . it could even be constituted by a branch of a tree if the latter happens to be horizontal and strong enough . there are no special requirements for the horizontal cross - beam as long as it is strong enough to support the swing with the required level of security . in accordance with the invention , the mechanism may either be : a ) directly mounted to the horizontal cross - beam of the swing through hinges b ) or integrated to an existing swing installation and make use of the existing oscillatory axis of the swing lines by insertion of the existing swing lines into the mechanism . the base principle of the mechanism consists in oscillating the seat of the swing suspended from the pair of flexible swing lines fig1 , item 7 , by exerting an alternating force displacement on the pair of swing lines . the latter is exerted somewhere below the oscillatory axis of the swing in the direction of the normal oscillation of the swing . these alternating force displacements originate from another person action pulling alternatively on two handles . the basic functionality of the mechanism is expressed in the embodiment depicted in fig1 . the supporting swinging element is chosen as a seat and steel is the fabricating material used . it basically consists of : a swaying member , item 1 , extending lengthways , below and alongside the horizontal cross - beam of the swing , item 8 , firmly fixed to the latter through hinges , item 9 , and free to oscillate around them . a pair of rigid swinging arms , item 4 , extending vertically , secured perpendicularly to above described swaying member in the direction of the pair of flexible swing lines , item 7 . the pair of rigid swinging arms attaches and suspends the swing lines at their extremities . a rocking arm , item 2 , perpendicularly fixed by its longitudinal centre to one end of the swaying member , item 1 , and forming with the latter a t - shaped assembly extending on a horizontal plane . a pair of flexible or rigid pulling lines , item 3 , extending vertically , are attached by their upper ends to both extremities of the rocking arm and suspend pulling handles , item 6 , at their ground ends . alternating pulls on the pulling handles bring the rocking arm in a pivoting movement . this pivoting movement leads an alternating rotating torque action around the hinges of the swaying member . that causes the latter to rotate slightly back and forth and to sway by the hinges , item 9 , located between the cross - beam and the swaying member . an amplified swaying movement is instantaneously transmitted to the lowers ends of the pair of swinging arms dragging the attached swing lines , item 7 , in an oscillating arc displacement . a pendulum movement is thus initiated on the seat suspended from the pair of swing lines and is maintained for as long as the assisting person maintains the alternating pulling action in order to keep : c ) the extremities of the swinging arms , the swing lines and the swing seat oscillating . the arc displacement path of the seat is the one with the maximum amplitude . the following exposes another application of the invention for already existing swings . as compared to the basic manual swing drive mechanism , it incorporates the following technical changes : a ) the swinging arms consist in two hollow , vertical and rigid arms . the swing lines insert in them up to the existing oscillatory axis of the swing lines fixed to the horizontal cross - beam . the hollow swinging arms are mechanically secured in that position to the swing lines . in a preferred embodiment using chains as flexible swing lines , a side bolt , item 12 of fig2 , cross travelling through the swinging arms and through a mesh of the chains is a particularly suitable arrangement for securing the swinging arms to the chains . b ) the swaying member is further equipped with an extension mechanism so to adapt the inter - distance between the swinging arms to the distance between the swing lines . the swaying member then consists in : a two pieces member as it may be represented by the original one piece swaying member separated in two members by about its mid point between the pair of swinging arms . an adjustable linking mechanism joining the two extremities of the above two pieces members and clamping them in final adjusted position . in a preferred embodiment where a metallic swaying member of square cross - section is used , the linking consists in a third member of slightly less small cross - section . the latter is slipped at appropriate distance within each respective extremity of both separated swaying members . it is then locked in place within each extremity of the two pieces by a fine thread cross driven side screw , item 13 of fig2 . the third member could alternatively be jammed in place in its final position by press fit or other means . when circumstances and needs require , an optional embodiment of the above manual swing drive allows technical and economical optimisation of the manufacturing . in such embodiment the swaying member , the swinging arms and the rocking arms would be moulded into a one piece assembly . it could be of steel or even plastic if allowed by rigidity criteria . furthermore , an other optional embodiment of the above manual swing drive mechanism for application on low supporting structure of swings would consist in using a swaying member having a vertically wide plate - shaped . the latter would extend horizontally alongside and below the cross - beam of the swing to which the upper part of this wide plate - shaped swaying member would be hooked by hinges . the lower part of the wide plate - shaped swaying member would directly attach and suspend the pair of swing lines , thus replacing the need for dedicated swinging arms on the swaying member . for a similar embodiment and adaptation of the mechanism on an already existing swing , the swaying member would consist in a vertically wide plate running in parallel and below the horizontal cross - beam of the swing and attaching each flexible swing line to the wide plate - shaped swaying member at both lower and upper parts locations . the use of two pairs of u bolts would constitute among other a good means to attach the swing lines to the wide plate - shaped swaying member . the need for specifically dedicates hollow swinging arms as described above on paragraph “ manual swing drive for mounting on existing swing ” becomes no longer required . the length of the pulling lines to which the pulling handles are attached to , should be chosen to provide a comfortable position for the assisting person . to this end , a length adjustment mechanism may be provided to adjust the height of the pulling handles in accordance with the height of the assisting person . in a preferred embodiment using a chain as pulling lines and depicted in fig1 , such mechanism would consist in : pulling handles with associated top mounted rings , item 6 of fig1 . chain mesh hooks , item 10 , attached to the lower extremity of the pulling lines . the height adjustment mechanism would then be achieved by running the hooks attached to the extremity of the pulling lines inside the top mounted rings of the handles . the hook makes a u turn path travel within the rings and keeps travelling upward alongside the adjacent twin part of the pulling lines so rising up the handles . when the pulling handles are raised and adjusted to the appropriate height , the hooks at the ends of the pulling lines are then inserted into the closest side mesh of the adjacently running pulling line . in an alternative embodiment for the height adjustment mechanism , a s hook , item 21 of fig2 , is mounted at the lower end of the pulling lines close to the handles . one end of the s is gripped around a mesh and the other end is let open to be attachable anywhere upward on a mesh of the pulling lines so rising up the handles at the appropriate height . using the same principle for an embodiment using cords as pulling lines , the hook mechanisms may consist in nautical type devises such as illustrated in fig6 , twisting and gripping the cords in its two slots when the appropriate height is reached . in spite of above described height adjustment mechanism , from our experienced embodiments , a height of approximately 5 feet between the ground and the bottom ends of the handles will provide for most adults a good height compromise thus removing the need for a height adjustment devise . in the case of exceptionally low swing supporting cross - beam , the handles could directly be fixed to the extremities of the rocking arms , thus eliminating the need of pulling lines . the following intends to bring a technical optimisation on the hand pulling system of the above described swing drive mechanism by the addition of a constant torque pulling mechanism . due to the vertical direction that characterises the force exerted on the pulling lines to rotate the swaying member , the resulting torque around the swaying member varies with the angular position of the rocking arm . in fact the torque is at maximum when the rocking arm is at horizontal and decrease towards zero when rotating toward the vertical line above and below the horizontal . it could be desirable to maintain a constant torque around the swaying member as pulling lines are being pulled down . one embodiment for so doing consists in fixing a pulley by its centre at the end of the swaying member in place of the existing rocking arm . the diameter of the pulley would be the length of the replaced rocking arm . each pulling lines is then attached on the upper part of the pulley and travels downward within the groove on each side of the pulley toward their respective pulling handle . another and somehow more technically optimised embodiment would consist in fixing two arc channel sections face to face to each end of the rocking arm . as shown in fig7 item 21 , each arc channel section would be fixed by mid points within their internal arc circumference . pulling lines are attached each one to each upper part of the channel sections and travel down toward their respective pulling handle in winding the bottom of the grooves . in both above described embodiments , like the two sides of a belt , the pulling lines wind around the internal grooves of a pulley or a pulley like assembly , and exert a constant torque around the swaying member by rotating it into angular rotation when being alternately pulled down . the functionality of the above described manual swing drive mechanism may be expanded into a multi - swing drive mechanism . the latter would permit an assisting person to activate more than one swing and to even do it in company of another assisting person if desired . the following description presents our preferred embodiment for a multi - swing drive mechanism and incorporates the following choices : the supporting swinging elements of the swings are seats . the manufacturing material is metal due to the overall strength required on the complete assembly mostly at linking points of the swing drive mechanisms . the cross section of the swaying members is rectangular or square . referring to fig3 , the multi - swing drive mechanism then consists in a row of close identical swing drive mechanisms . each one attaches and suspends its own pair of seat lines . in this row of swing drives : a ) the first swing drive , item 14 of fig3 , is mounted and designed as the one described for the basic swing drive mechanism and illustrated in fig1 . the swaying member is yet lengthened on the opposite side of the rocking arm , item 18 fig3 , to allow mechanical attachment to the next swaying member of the row . b ) all middle swing drives item 15 fig3 , are also mounted and designed as the basic swing drive mechanism illustrated in fig1 . yet , instead of incorporating a rocking arm as on the first one , item 2 fig3 , the swaying members are lengthened on each side , item 18 fig3 , to allow attachment to each of their neighbouring swaying members . c ) the last swing drive in the row , item 16 fig3 , is also identical mechanically and in the mounting to the first one , item 14 . but it incorporates a rocking arm at the opposite extreme end of the row of swings so as to provide pulling lines and pulling handles on the last swing of the row for a second assisting person . d ) linking mechanisms allow solid mechanical attachments between the individual swaying members when the assisting person requires it . although various designs of linking mechanisms may be selected , in our preferred embodiment , our choice has been fixed on a move - and - lock sliding carriage such as depicted in detail in fig4 and 5 . it consists in a channel as illustrated in item 17 fig4 , inserting lengthways a clamping plate , item 19 of fig4 , which is moved across by a t - shaped handle screw , item 20 of fig4 . by sliding the carriage sideways , the two ends of the neighbouring swaying members slip into and get inserted within the carriage between the bottom of the channel and the clamping plate . by screwing the t - shaped handle , the two ends of the swaying members are jammed in place .

this invention relates to a manual swing drive mechanism to be mounted on a swing in order to transmit the swinging movement to a person who cannot do it alone , notably a child . through a hand operated rocking arm , the assisting person transmits a swinging movement to a swaying member which transfers a pendulum swinging movement to the seat lines of the swing through a set of elongated swinging arms fixed perpendicularly to the swaying member . the functionality of the invention could be expanded into a multi - swing drive mechanism thus allowing one or several assisting persons to transmit a swinging movement to a group of two or more assisted persons .

accordingly , the present invention is intended to propose a ct radiography device in which a space required for a rotation of an x - ray generator is reduced when radiographing . therefore , the device can be installed in smaller space . also , the present invention is also intended to propose a ct radiography device in which a design and a production method are simplified and mechanical reliability of the device is realized when providing such ct radiography device . in order to achieve the above object , a ct radiograph device according to the present invention may include a column ; a first facing part provided on a first side of the column to face a subject and including one of an x - ray generator and an x - ray sensor ; a rotation arm connected to the column and configured to rotate relative to the subject within at least a predetermined angular range ; and a second facing part provided on a first end of the rotation arm to face the first facing part with the subject being interposed between the first and second facing parts , and including a remaining one of the x - ray generator and the x - ray sensor . the x - ray generator and the x - ray sensor may be placed to arrange at least a part of the x - ray sensor facing the x - ray generator with the subject being interposed therebetween within an x - ray irradiation range of the x - ray generator , while the rotation arm is placed within the predetermined angular range . the x - ray sensor may be provided on the first facing part and the x - ray generator may be provided on the second facing part . in this case , the x - ray sensor may move within the first facing part along a rotational direction of the rotation arm such that at least a part of the x - ray sensor faces the x - ray generator within an x - ray irradiation range of the x - ray generator , with the subject being interposed therebetween . the x - ray sensor may move along tracks having various shapes within the first facing part . in one embodiment , the x - ray sensor may move along a track having a constant distance from the subject . in other embodiment , the x - ray sensor may move along a track having a constant distance from the x - ray generator . in another embodiment , the x - ray sensor may move along a track that has a constant ratio of a distance between the x - ray generator and the subject and a distance between the x - ray generator and the x - ray sensor . meanwhile , the x - ray sensor may be a curved sensor configured to place at least a part of the x - ray sensor facing the x - ray generator , with the subject being interposed therebetween within a rotation angular range of the rotation arm . the ct radiograph device according to the present invention may further include a first driving part reciprocally rotating the second facing part within a predetermined angular range ; and a second driving part simultaneously or alternatively operated with the first driving part and moving at least one of the first facing part and the second facing part in a direction of a longitudinal axis of the subject . in this case , the first driving part may a rotary driving part connecting the column and the rotation arm and rotates the rotation arm on an axis of the column , and the second driving part may a linear driving part lifting and lowering at least one of the first facing part and the second facing part relative to the column . according to the present invention , a space required for a rotation is reduced by reciprocally moving an x - ray generator and an x - ray sensor within a certain angular range while radiographing , and a proper scanning method is applied to obtain radiographs in the reduced space . therefore , a ct radiography device that can be installed in smaller space is provided . when providing such a ct radiography device , the present invention provides a simplified design and a production method in which the x - ray generator and the x - ray sensor are connected to the column such that they are properly operated in the reduced space . accordingly , there is an effect of providing a ct radiography device with improved mechanical reliability . fig1 is a schematic diagram showing a track of a ct radiography device according to an embodiment of the present invention . fig2 is a schematic diagram showing various tracks in which various angular ranges are applied to the ct radiography device of the embodiment of fig1 . fig3 is a perspective view of a ct radiography device according to an embodiment of the present invention . fig4 is a schematic diagram showing a part of a track of the ct radiography device according to the embodiment of fig3 . fig5 is a schematic diagram showing a first track of a first facing part of a ct radiography device according to an embodiment of the present invention when a second facing part rotates . fig6 is a schematic diagram showing a second track of the first facing part of the ct radiography device according to the embodiment of the present invention when a second facing part rotates . fig7 is a schematic diagram showing a third track of the first facing part of the ct radiography device according to the embodiment of the present invention when a second facing part rotates . fig8 is a schematic diagram showing a part of a track of a ct radiography device including a curved sensor according to an embodiment of the present invention . reference will now be made in greater detail to an exemplary embodiment of the present invention , an example of which is illustrated in the accompanying drawings . wherever possible , the same reference numerals will be used throughout the drawings and the description to refer to the same or like parts . fig1 is a schematic diagram showing a track of a ct radiography device according to an embodiment of the present invention . as shown in the figure , an x - ray sensor 20 and an x - ray generator 30 are provided to face each other with a subject being interposed between the x - ray sensor 20 and an x - ray generator 30 . as shown in the embodiment of fig1 , the x - ray sensor 20 and the x - ray generator 30 are maintained to face each other and scan the subject while forming a zigzag track 31 z within a predetermined angular range while maintaining the subject interposed therebetween . in fig1 , for the sake of convenience , the rotation axis of each of the x - ray sensor 20 and the x - ray generator 30 is shown as parallel to the longitudinal axis z of the subject . however , a direction of a rotation axis of a ct radiography device according to the embodiment of the present invention may be the same as the fig1 , or may have a predetermined angle relative to the longitudinal axis z of the subject . in addition , as shown in fig1 , the rotation axis may be placed between the x - ray sensor 20 and the x - ray generator 30 , in the x - ray sensor 20 , or in the x - ray generator 30 . in the ct radiography device according to the present invention , the x - ray sensor 20 and the x - ray generator 30 reciprocally rotate within a predetermined angular range and the x - ray sensor 20 and the x - ray generator 30 move in a direction of the longitudinal axis z . other examples may be readily understood to a person of ordinary skills in the art through the following description . for example , the reciprocal rotation of the x - ray sensor 20 and the x - ray generator 30 may be understood to include all operations in which the x - ray sensor 20 receives an x - ray beam having been transmitted through the subject . a rotational motion mc is applied to at least one of the x - ray sensor 20 and the x - ray generator 30 relative to the longitudinal axis z by a first driving part d 1 , and the x - ray beam transmits through the subject . in the same manner as a sensor used in a panoramic radiography device for dental clinics , the x - ray sensor 20 may be a bar type sensor that is rotated at 90 degrees from an angle that is set when radiographing a panoramic image to be perpendicular to the longitudinal axis z of the subject . in addition , the x - ray sensor 20 may be a sensor having a large size such that the sensor may correspond to the x - ray generator 30 of a cone beam type . various sensors may be used for the x - ray sensor 20 including a sensor obtaining radiograph information of a single slice and a sensor having various aspect ratios and being capable of obtaining multiple slices such as multiple detector computed tomography ( mdct ). the x - ray sensor 20 may be a curved sensor in which a part facing the subject has a concave shape . the x - ray generator 30 is an x - ray source , and the x - ray source may emit a collimated x - ray beam in the shape of the x - ray sensor 20 . the first driving part d 1 may be configured to rotate the x - ray sensor 20 and the x - ray generator 30 such that an irradiation direction of an x - ray beam and / or a receiving direction of an x - ray beam are rotated on the longitudinal axis z of the subject . herein , the first driving part d 1 may be configured to move at least one of the x - ray sensor 20 and the x - ray generator 30 , or to separately move the x - ray sensor 20 and the x - ray generator 30 . the first driving part d 1 is configured to move the irradiation direction of the x - ray beam or the receiving direction of the x - ray beam of the subject by reciprocally rotating the x - ray sensor 20 and the x - ray generator 30 , and to maintain a relative positional relationship in which the x - ray sensor 20 and the x - ray generator 30 face each other . the ct radiography device according to the present invention may further include a second driving part d 2 that moves a rotation arm of the ct radiography device for dental clinics or a corresponding structure thereof in a direction of the longitudinal axis mz of the subject . the second driving part d 2 may be configured to move a structure that guides each of the x - ray sensor 20 and the x - ray generator 30 to the direction of the longitudinal axis mz of the subject . the detailed configuration thereof is described later and the configuration may be embodied in various forms including the disclosed embodiment . the predetermined angular range may be predetermined according to a reconfiguration method of ct images and a characteristic of the device , and may be adjusted within a maximum predetermined range according to an object of ct radiography or a characteristic of the subject . however , the maximum predetermined range may be less than 360 degrees , or from 30 degrees to 90 degrees . fig2 is a schematic diagram showing various tracks in which various angular ranges are applied to the ct radiography device of the embodiment of fig1 . a track 31 z displayed in the present figure is based on a position of the x - ray generator 30 . a zigzag track 31 z with 360 degrees , 180 degrees , 90 degrees , or an angle within a certain angular range from 90 to 360 degrees may be formed according to an angular range of a partial reciprocal rotation that is performed by the first driving part d 1 as described above . meanwhile , the zigzag track 31 z shown in fig1 and 2 is formed by simultaneously operating the first driving part d 1 and the second driving part d 2 , and then a point , in which a direction of reciprocal rotation is changed , appears such that the track is bent in a shape of “ z ”. alternatively , when the first driving part d 1 and the second driving part d 2 are alternatively operated , then the point , in which the direction of reciprocal rotation is changed , appears such that the track is bent in a shape of “ ”. fig3 is a perspective view of a ct radiography device according to an embodiment of the present invention . a ct radiography device according to an embodiment of the present invention includes a column 100 installed to be fixed on the floor , a first facing part 25 that is provided on a first side of the column 100 to face a subject and includes an x - ray sensor 20 , a rotation arm 45 that is connected to the column 100 such that the rotation arm 45 is able to rotate relative to the column 100 within at least a predetermined angular range , and a second facing part 35 that is provided on a far side of the column 100 to face the first facing part 25 with the subject being interposed therebetween and includes an x - ray generator 30 . the ct radiography device according to the embodiment connects the rotation arm 45 and the column 100 , and further includes a rotary driving part that rotates the rotation arm 45 relative to an axis a 1 of the column 100 , and a linear driving part ( not shown ) that moves the first facing part 25 to a length direction of the column 100 . meanwhile , the linear driving part simultaneously moves the rotation arm 45 and the first facing part 25 such that the x - ray generator 30 of the second facing part 35 and the x - ray sensor 20 of the first facing part 25 may move in a direction of a longitudinal axis z of the subject ( herein , parallel to the length direction of the column 100 ). the x - ray sensor 20 may be installed to move along a certain track within the first facing part 25 . for example , the x - ray sensor 20 may be installed to be interlocked with a rotation of the rotation arm 45 , to move along a rail or a rack provided on a case of the first facing part 25 and to face the x - ray generator 30 . a structure , for example , a bite - block , a headrest , a temple support , etc . may be installed to fix a patient &# 39 ; s head . meanwhile , the second facing part 35 including the x - ray generator 30 may be installed to rotate on a rotation axis a 2 . when the second facing part 35 is fixed to a body of the rotation arm 45 and a center of an x - ray beam emitted from the x - ray generator 30 is always directed toward the rotation axis a 1 of the rotation arm 45 , then , the center of the x - ray beam may be directed away the subject and the x - ray sensor 20 . however , if an irradiation range of the x - ray beam does not bound the subject and the x - ray sensor 20 , then , a reciprocal rotation of the rotation arm 45 is available . in addition , if the second facing part 35 separately rotates from the body of the column 100 , the second facing part 35 may rotate on the rotation axis a 2 such that the x - ray beam emitted from the x - ray generator 30 may be directed toward the subject according to the rotation of the rotation arm 45 . in the present embodiment , the first driving part d 1 described above corresponds to the rotary driving part that rotates the rotation arm 45 and mechanical elements that are interlocked with the driving part , and move or rotate the x - ray generator 30 and the x - ray sensor 20 such that the x - ray generator 30 and the x - ray sensor 20 face each . further , the second driving part d 1 corresponds to mechanical elements that move the x - ray generator 30 and the x - ray sensor 20 to the direction of the longitudinal axis z of the subject , and the detailed configuration can be variously modified differently than disclosed in the embodiment . fig4 is a schematic diagram showing a part of a track of the ct radiography device according to the embodiment of fig3 . according to the present figure , a track 21 of the x - ray sensor 20 , a track 31 of the x - ray generator 30 , and a location relation of the tracks and the subject h are displayed . as described above , the x - ray sensor 20 may be installed to be interlocked with the rotation of the rotation arm 45 and to move along a certain track 21 . thus , a position and an angle of the x - ray sensor 20 may be changed . therefore , when the rotation arm 45 is placed at a certain position , then at least a part or the entire part of the x - ray sensor 20 may be placed within an irradiation range of an x - ray beam b emitted from the x - ray generator 30 and may face the x - ray generator 30 with the subject h being interposed therebetween . meanwhile , the x - ray generator 30 may also rotate on an axis a 2 of the rotation arm 45 to an arrow direction d 35 shown in a dotted line while being interlocked with the rotation of the rotation arm 45 . thus , the x - ray beam b may also be directed toward the subject h , and not toward the rotation axis a 1 . when the second facing part 35 in which the x - ray generator 30 or the x - ray sensor is installed rotates to be directed toward the subject h along the rotation of the rotation arm 45 , the x - ray sensor 20 that is movably installed may move along various tracks . hereinafter , some examples of the various tracks are described . however , the configuration is not limited to the examples described herein . in the embodiment to be described below , as the embodiment of fig3 and 4 , the x - ray sensor 20 may be installed on the first facing part ( not shown ) and the x - ray generator 30 may be installed on the second facing part 35 . the x - ray generator 30 may rotate on the rotation axis a 2 such that a center of the x - ray beam is directed toward a center of the subject h even if the rotation arm 45 is rotated . fig5 is a schematic diagram showing a first track of a first facing part of a ct radiography device according to an embodiment of the present invention when a second facing part rotates . when a position of the second facing part 35 is changed along a track 31 , which has a circular arc form , of the x - ray generator 30 by the rotation of the rotation arm 45 , as described above , the second facing part 35 rotates on a rotation axis a 2 and a center of an x - ray beam emitted from the x - ray generator 30 may pass through the longitudinal axis z of the subject h . the x - ray sensor 20 may move to face the center of the x - ray beam , and a direction of the x - ray sensor 20 may move to face the x - ray generator 30 . herein , the x - ray sensor 20 may move along a first track 211 which has a circular arc form having a radius , the radius being a distance zs 1 between the longitudinal axis z of the subject h and the x - ray sensor 20 . when radiographing , a magnification power of a radiograph is determined by a ratio of a distance between the x - ray generator 30 and the subject h to a distance between the x - ray generator 30 and the x - ray sensor 20 . in other words , gz : gs 1 . when the x - ray generator 30 moves along a track 31 having a circular arc form of the x - ray generator 30 , the gz value is changed according to a position of the x - ray generator 30 and satisfies the following formula : gs 1 = gz + zs 1 . when the x - ray sensor 20 moves along a first track 211 , the zs 1 becomes a constant . then , the magnification power becomes gz : gs 1 = 1 : 1 +( zs 1 / gz ), and the magnification power is changed as the gz value is changed ( gz is changed according to the position change of the x - ray generator 30 when radiographing ). in a ct radiography device that obtains a ct image by reconfiguring multiple radiographs that are obtained at various angles , information of magnification power may be obtained while obtaining each radiograph since a magnification power of the multiple radiographs needs to be uniform . this information is used to calibrate the magnification powers before reconfiguring the ct image . fig6 is a schematic diagram showing a second track of the first facing part of the ct radiography device according to the embodiment of the present invention when the second facing part rotates . the present embodiment is the same as the embodiment of fig5 in that a movement of the second facing part 35 , a track 31 of the x - ray generator 30 , and a center of the x - ray sensor 20 move to face a center of the x - ray beam emitted from the x - ray generator 30 , and the x - ray sensor 20 moves to face the x - ray generator 30 . however , in the present embodiment , a characteristic of a second track 212 of the x - ray sensor 20 , which shows a movement of a center of the x - ray sensor 20 , is that a distance gs 2 between the x - ray generator 30 and the x - ray sensor 20 is constantly maintained . a magnification power of the ct radiography device according to the present embodiment is gz : gs 2 , herein , the gs is a constant . when the x - ray generator 30 is placed on an extension of a rotation axis a 1 of the rotation arm 45 and a longitudinal axis z of the subject h , the gz value becomes the minimum and the magnification power becomes the maximum . alternatively , when the x - ray generator 30 moves to the left or the right from its position along a track 31 of the x - ray generator 30 , the gz value gradually becomes higher and the magnification power becomes lower . in the present embodiment , considering such changes , the magnification power may also be calibrated to reconfigure a ct image . fig7 is a schematic diagram showing a third track of the first facing part of the ct radiography device according to an embodiment of the present invention when the second facing part rotates . the present embodiment is the same as the embodiment of fig5 in that a movement of the second facing part 35 , a track 31 of the x - ray generator 30 , and a center of the x - ray sensor 20 move to face a center of the x - ray beam emitted from the x - ray generator 30 , and the x - ray sensor 20 moves to face the x - ray generator 30 . however , a third track 213 of the x - ray sensor 20 , which shows a movement of a center of the x - ray sensor 20 , may be designed in that a magnification power of a radiograph is constantly maintained even if the x - ray generator 30 moves in various positions within the track 31 thereof . in order to constantly maintain the magnification power , in other words , gz : gs 3 , when the gz value is changed according to the position of the x - ray generator 30 , then , the gs 3 may be changed in the same manner as the ratio of change of the gz value . in this case , when the x - ray generator 30 is placed on an extension of a rotation axis a 1 of the rotation arm 45 and a longitudinal axis z of the subject h , the gz value becomes the minimum , and a distance zs 3 between the subject h and the x - ray sensor 20 also becomes the minimum . therefore , at this position , there is a need that the x - ray sensor 20 should not be bumped into a surface of the subject h . in a ct radiography device according to the embodiment , magnification powers of radiographs obtained in various angles are constantly maintained . thus , a ct image may be obtained by reconfiguring radiographs without calibrating the magnification powers . fig8 is a schematic diagram showing a part of a track of a ct radiography device including a curved sensor according to an embodiment of the present invention . this embodiment is different from the embodiments of fig3 and 4 in that a curved sensor 22 is used instead of the x - ray sensor 20 of a planar type . the curved sensor 22 may be installed such that at least a part of the curved sensor 22 faces the x - ray generator 30 with the subject h being interposed therebetween along a rotation angular range of the rotation arm 45 . alternatively , the curved sensor 22 may be installed to steadily cover the entire area in which the x - ray sensor 20 moves along the track 211 . meanwhile , a first facing part 25 ( refer to fig3 ) is not shown in fig4 to 8 such that shapes of the x - ray sensor 20 and 22 or moving tracks 21 , 211 , 212 , and 213 thereof are clearly shown .

disclosed is a dental x - ray ct photographic device . in order to resolve this issue , the ct photographic device according to the present invention comprises : a column ; a first facing part which is disposed oriented towards an object to be examined on one side of the column , and comprises one or other of an x - ray generator and an x - ray sensor ; a rotational arm coupled in such a way as to be able to rotate through at least a predetermined angular range with respect to the column ; and a second facing part which is disposed on the rotating arm , on the far side from the column , facing the first facing part with the object to be examined placed in between , and which comprises the other of an x - ray generator and an x - ray sensor .

when describing the present invention , the following terms have the following meanings , unless indicated otherwise . all terms not defined herein have their common art - recognized meanings . the term “ neurological impairment ” refers to a disease or condition which is caused by or is characterized by a degeneration in nerve conduction . examples of neurological impairments , as used herein , include without limitation multiple sclerosis , parkinson &# 39 ; s disease , head trauma , alzheimer &# 39 ; s disease , and sequelae from a stroke . in general terms , and with reference to fig1 the invention comprises a combined visual and tactile test apparatus designed to measure a patient &# 39 ; s simultaneity thresholds between two sensory stimuli such as visual stimuli or tactile stimuli . the time interval ( stimulus onset asynchrony or soa ) between the onset of the first stimulus to the onset of the second stimulus is adjusted until the threshold soa is determined . a simultaneity threshold is the longest duration of time between onset of a first stimulus and the onset of a second stimulus which is perceived by the patient to be simultaneous onsets and not sequential onsets . in one embodiment , perceived simultaneity of visual stimuli is tested with an apparatus ( 5 ) comprising of at least one pair of red light emitting diodes ( leds ) ( 10 ) and a head / chin rest ( not shown ) which immobilizes the patient in position to view the leds ( 10 ). other suitable visual stimuli may be known to those skilled in the art . a black cross ( 12 ) or other mark is centred between the pair of leds ( 10 ) which serves as a central fixation point for the patient . in an alternative embodiment , multiple pairs of leds may be used , preferably in a horizontal plane as shown in fig1 . in the embodiment shown , the inner pair ( 10 a ) of leds are spaced from the fixation point by 3 . 3 ° of visual angle . each led is separated from an adjacent led by the same 3 . 3 ° of visual angle . at a viewing distance of 57 cm , one cm of lateral distance subtends to one degree of visual angle . the leds may be placed in various positions in the patient &# 39 ; s visual field . different results from different placements may provide localization information to the practitioner . for example , with the led configuration shown in fig1 if statistically different results are obtained using the two far right leds in a unilateral test , as opposed to the inner pair of right leds in a unilateral test , that result may provide clinically significant information to the practitioner . similarly , if a left field unilateral test is significantly different from a right field unilateral test , that result may be clinically significant . the different combinations of testing will be apparent to one skilled in the art . in one embodiment , the leds emit a red light of an intensity of about 123 cd / m 2 against a light background having a luminance of about 46 cd / m 2 . the illumination and contrast must be sufficient that visual ability or acuity is not a factor when testing . the leds are activated by a control program ( 14 ) running on a computer which includes or is connected to an accurate timing mechanism capable of delivering a consistent timing signal in the millisecond range . in one embodiment , a timing control box ( 16 ) uses a crystal controlled oscillator which runs at 4 . 096 mhz to deliver the stimuli in a precise manner . the oscillator signal is divided by 4096 to provide a very accurate and highly stable 1 ms output signal which is used by the control program to deliver the stimuli with precise timing . the control program allows the practitioner to choose the two leds to be illuminated and the soa between the illumination of the first led and the second led . the leds may be illuminated in a bilateral fashion where a led in the left visual field which projects to the right hemisphere and a led in the right visual field which projects to the left hemisphere are illuminated in pairs . alternatively , the leds may be illuminated in a unilateral manner , where both leds are illuminated in succession in one of the left or right visual fields . the control program may control the tactile stimulators in like fashion . as shown in fig2 and 3 , in one embodiment , the tactile stimulators ( 20 ) comprise four solenoid activated pins , grouped in pairs , for delivering a punctate stimulation to the patient &# 39 ; s fingertips . a box ( 22 ) which houses the four pins may include a hand / wrist rest ( not shown ) which positions the fingertips over the openings through which the pins are activated . one embodiment of the tactile stimulus delivery apparatus is illustrated in fig2 . when the solenoids ( 24 ) are charged , the pin ( 26 ) or rod is thrust upwards through the core of the solenoid and delivers a punctate stimulation to the palmar surface of the fingertip that is resting on the holder . in one embodiment , the duration or hang time of the rod can be as short as 10 ms with 1 mm vertical extension above the housing ( skin depression ). these values may be programmed into the control program and may be varied as desired . for comparison purposes , it is desirable to have the same settings for the two stimulators . it is preferable to isolate the limbs being tested as well as mask aural cues of the solenoids so that the patient may only rely on the tactile sensation in making the requested judgements . for example , if the fingertips are being tested , it is preferred to rest the patient &# 39 ; s forearms against foam padding to minimize any vibrations that may result from the stimulus delivery . the patients may be fitted with earplugs and headphones which provide sound - proofing in order to mask the noise of the firing of the solenoids . in addition , if necessary , the headphones may deliver pink noise to mask any aural cues of the solenoids . the computer controller may be programmed with an algorithm in order to control the delivery of the visual or tactile stimuli . any method of determining a psychophysical threshold may be used such as ascending or descending soas where the soa is set well above or well below the threshold level and is increased or decreased until the threshold is passed . in a preferred embodiment , a version of the well - known parameter estimation by sequential testing ( pest ) algorithm is well suited for this application , as it permits the determination of the simultaneity threshold in as few trials as possible . suitable pest algorithms are described in findlay j . m . ( 1978 ); estimates on probability functions : a more virulent pest . perception and psychophysics , 23 , 181 ; and in pentland , a . ( 1980 ) maximum likelihood estimation : the best pest . perception and psychophysics , 28 , 377 ; the contents of which are incorporated herein by reference . the testing values of the pest technique are determined by a set of rules which operate by using a binary forced - choice ( yes / no ) paradigm . the time interval or soa between the onset of the first stimulus to the onset of the second stimulus was adjusted , either increased or decreased according to the patient &# 39 ; s previous response . pest algorithms are characterized by large step sizes at the beginning of testing , which step sizes reduce as the test value gets closer to the threshold value . in one embodiment , the soa step size changed by a constant value in association with no responses , and the soa step size would increase by half the previous soa value in association with yes responses . thus , a value change in soa step sizes only occurred with step reversals associated with yes responses . the program would terminate when the soa step size reached 1 ms . where there are three leds in each visual field , on either side of the central fixation point , many different bilateral and unilateral pairings may be used . in one embodiment , the outer leds may be used in one bilateral pairing , the middle leds used in another bilateral pairing and the inner leds in yet another pairing . unilateral pairings will be apparent . in each pairing , one led will be illuminated before the other , and then both will remain illuminated for the same length of time after the second led is illuminated ; ensuring that both leds go dark at the same time . the initial soa step size may be set at 10 ms and the termination step size soa may be set at 1 ms . the timing mechanism of the present invention preferably permit accurate timing down to the 1 ms level . the simultaneity threshold was that soa value which terminated the pest program . in visual testing , a patient is instructed to focus on the central fixation point with their chin resting on the chin rest . the patient may be instructed that there are no right or wrong answers and they are simply to use their best judgement . after each delivery of a stimulus pair , the patient is asked to respond yes if they judged the illumination onsets to be simultaneous and no if they judged the illumination onsets to be staggered . verbal responses are then recorded by the tester , after each answer , the tester may then trigger the next stimulus pair . the pest algorithm terminates when the soa step size reaches its smallest value . the simultaneity threshold is the highest value of the soa where the patient still perceives simultaneous stimuli . we have found that average simultaneity thresholds support the hemispheric equivalence model as proposed by geffen et al . ( 1996 ). typically , there are no significant threshold differences in stimulus order ( left before right , or right before left ) in bilateral testing . unilateral testing in the different visual fields also do not indicate a hemispheric advantage . bilateral simultaneity thresholds versus unilateral thresholds testing were significantly greater , suggesting that interhemispheric transfer was required for simultaneity judgements . we have found that the ability to make simultaneity judgements becomes impaired with advancing age . overall mean visual simultaneity thresholds increased with age among healthy adults . the threshold for young adults ( 18 to 39 years of age ) was 28 . 33 ms ( sd = 10 . 97 ), for middle aged adults ( 40 to 55 years of age ) the threshold was 38 . 56 ms ( sd = 17 . 46 ), and for older adults ( 60 to 80 years of age ) the threshold observed was 65 . 84 ms ( sd = 22 . 69 ). a significant deterioration is observable in patients known to have ms . average visual simultaneity thresholds for ms patients was 63 . 82 ms ( sd = 21 . 35 ), as compared to 38 . 56 ms ( sd = 17 . 46 ) recorded for age - and - gender matched controls ( baseline , normalized data ). therefore , if a patient who is suspected of having ms demonstrated simultaneity thresholds significantly higher than the average thresholds for individuals of similar age and gender , that is a diagnostic indicator that the patient does indeed have ms . it of course is not a sole and conclusive diagnostic test , but can be diagnostic in combination with other known tests and observations . once threshold data for an individual suffering from a neurological impairment such as ms is determined , continued periodic testing may monitor the progression or regression of the impairment in the normal course or in response to some therapy . visual interhemispheric transfer times ( ihtts ) are calculated by subtracting the mean thresholds of the two inner unilateral conditions ( the two inner leds on each side of the center mark ) from the mean threshold of the bilateral condition ( the inner pair of leds ). interhemispheric transfer times increased significantly for both older adults and for ms patients . data for ihtts are as follows : 5 . 64 ms ( sd = 6 . 99 ) for older adults ; 3 . 21 ms ( sd = 5 . 18 ) for younger adults ; 9 . 61 ms ( sd = 7 . 60 ) for ms patients compared with 3 . 15 ( sd = 5 . 10 ) for gender - and - age matched controls . these results support the hypothesis that ms induced damage to the corpus callosum slows central nerve conduction considerably . all of the above findings were statistically significant . in addition to visual simultaneity temporal testing , tactile testing may be used alternately or in conjunction with the visual testing . the same pest algorithm may be employed , however , the computer control program is used to actuate solenoid activated blunt pins which stimulate a body part of the patient , rather than led visual stimuli . similar to the visual testing , pairs of innocuous stimuli such as blunt pins or mild electric shocks are delivered to the patient &# 39 ; s body . other tactile stimuli and stimulators may be known to those skilled in the art . the patient &# 39 ; s ability to time the onset of the tactile stimuli may be tested in a bilateral situation where each of the pair of stimuli is delivered to both sides of the body or in unilateral situations where both stimuli of the pair is delivered to one side of the body . in one embodiment , where pins are used to stimulate the fingertips of the patient , the patient rests the index and middle fingers ( same bundle of nerve fibers ) of both hands in an interwoven manner on holders that are located above the pins . when activated , the stimulator delivers a punctate stimulation to a pair of fingertips . bilateral stimulation involves both index fingers on both hands , while unilateral stimulation involves the index and middle fingers of each of the left and right hand . bilateral stimulation to the body involves interhemispheric transfer since the somatosensory system is a crossed modality . tactile interhemispheric transfer times ( ihtts ) are calculated by subtracting the mean threshold of the two unilateral conditions ( index and middle finger stimulation of either left or right hand ) from the bilateral condition ( index or middle finger stimulation of both hands ). the same pest algorithm described above in connection with visual testing may be used to determine the simultaneity threshold . the simultaneity threshold may vary according to the body part being stimulated . for example , longer nerve pathways ( e . g ., leg stimulation ) will result in higher thresholds relative to shorter pathways ( e . g ., arm ). however , if the simultaneity threshold is much higher , it may indicate that peripheral nerve conduction in that part of the body is impaired . likewise , significantly different simultaneity threshold values for the left - and - right side of the body may indicate a differential decline in neural processing . with tactile testing , we have again found that significant age related differences exist : simultaneity thresholds of young adults ( 18 to 39 years of age ) averaged about 26 ms ( sd = 9 . 85 ) while those of older adults ( 60 to 80 years of age ) averaged about 61 ms ( sd = 16 . 03 ). in a population of patients known to have ms , the simultaneity thresholds averaged 56 ms ( sd = 19 . 82 ), compared with 33 ms ( sd = 13 . 04 ) for age and gender matched controls . measurement of central conduction ( ihtt ) demonstrated similar differences . ihtts in older adults averaged 20 . 33 ms ( sd = 15 . 36 ) while ihtts in younger adults averaged 9 . 23 ms ( sd = 6 . 71 ). ms patients demonstrated ihtts averaging 22 . 7 ms ( sd = 10 . 10 ), compared to 8 . 73 ms ( sd = 3 . 17 ) for age - and gender matched controls . given the pathways of the corpus callosum , interhemispheric transfer is typically longer for somatosensory information relative to visual information . the reported findings above were all statistically significant . it is notable that simultaneity thresholds for both visual and tactile tests nearly doubled for ms patients compared to a control population , whereas ihtts showed an increase of about 2 . 6 × in ms patients . these results demonstrate that measurement of both simultaneity thresholds and of ihtts may be reliable diagnostic indicators . in one preferred embodiment , tactile testing is alternated with visual testing and bilateral testing is alternated with unilateral testing . as is apparent , four different tests may be conducted in a test procedure : bilateral visual , unilateral visual , bilateral tactile , and unilateral tactile . for example , a first round of testing may involve a bilateral visual test , followed by bilateral tactile testing using the patient &# 39 ; s index fingers , followed by right visual field unilateral test , followed by tactile testing using the patient &# 39 ; s torso . the course and sequence of testing may continue as the tester may desire until a sufficiency of statistically significant data is obtained . as will be apparent to those skilled in the art , various modifications , adaptations and variations of the foregoing specific disclosure can be made without departing from the scope of the invention claimed herein .

20a method of diagnosing neurological impairments such as multiple sclerosis includes the determination of the simultaneity threshold of a pair of sensory stimuli , such as visual or tactile stimuli , separated temporally by a stimulus onset asynchrony . the stimuli may be presented unilaterally or bilaterally . interhemispheric transfer times may also be determined by determining the difference in simultaneity thresholds for bilateral and unilateral presentations . simultaneity thresholds and interhemispheric transfer times are significantly elevated in patients with ms and other neurological impairments . an apparatus for delivering such sensory stimuli includes an array of visual stimuli and tactile stimulators , a computer - implemented control program and a precise timing mechanism .

in accordance with the present invention , it has been surprisingly found that compression of highly substituted ( 49 . 6 - 54 . 88 % ethoxyl content ), low viscosity ( less than 53 cps ) ec yields tablets of superior mechanical strength when compared to the analogous dosage form prepared with ec of lower ethoxyl content and / or higher viscosity . furthermore , this form of ec has been found to yield compressed tablets that surpass the mechanical strength of comparable tablets using commercially available pharmaceutical grades of micronized ec . furthermore , this form of ec is found to possess good powder flow and low dusting . ethylcellulose is a cellulose ether that is versatile with many uses . the following grade types of ec are commercially available from hercules incorporated : types k , n , and t of ec are used in food and food contact applications . more specifically , k and t are used for food and contact such as paper or paperboard in contact with food . prior to this invention , n types were used as a binder or coating in pharmaceutical applications . type x is used in inks and other industrial applications . it is well known in the art how to make ec . normally , either chemical grade cotton linters or wood pulp is used to prepare ec . the sequence of chemical reactions is similar to that for methylation of cellulose . in commercial practice , sodium hydroxide concentrations of 50 % or higher are used to prepare the alkali cellulose . staged additions of solid sodium hydroxide during the reactions can be used to reduce side reactions . ethyl chloride is added to the alkali cellulose in nickel - clad reactors at 90 - 150 ° c . and 828 to 965 kpa ( 120 to 140 psi ) for 6 - 12 hours . diluents such as benzene or toluene can be used . at the end of the reaction , the volatiles such as ethyl chloride , diethyl ether , ethanol , and diluent are recovered and recycled . the ethylcellulose in solution is precipitated in the form of granules with further recovery of the carrier solvents . washing with water completes the processing . control of metallic impurities is important to achieve stability during storage . anitoxidants can also be incorporated to inhibit loss of viscosity . in accordance with the present invention , the ec does not undergo micronization after completion of the synthesis . this form of ec distinguishes itself from the prior art in that it has a higher ethoxyl content ( greater than 49 . 6 %) and simultaneously a low viscosity ( less than 53 cps ) and the average particle size is greater than 50 micrometers . according to the present invention , ethylcellulose has an ethoxyl content lower limit of 49 . 6 %, preferably 49 . 8 %, and more preferably 50 . 0 %. the upper limit of the ethoxyl content of the ec is 54 . 88 %, preferably 53 . 0 % and more preferably 52 . 0 %. the viscosity of the ec is less than 53 . 0 cps , preferably less than 25 cps and more preferably less than about 17 cps , with a lower limit of about 3 cps . uniquely , it has been found that this high ethoxyl , low viscosity ethylcellulose possesses superior compactibility and compressibility , so resulting in tablets with superior mechanical strength when compared to analogous tablets made of ec with lower ethoxyl content and / or higher viscosity . furthermore their mechanical strength is also superior to analogous tablets prepared with micronized ec . ec tablets containing 1 % stearic acid nf as a lubricant were compressed on a instrumented rotary tablet press ( manesty beta press , thomas engineering , hoffman estates , ill .) as described under standard methods . the mechanical strength was determined by measuring the diametrical crushing strength as described under standard methods . in ec matrix tablets , superior mechanical strength is a key parameter assuring longer release duration . furthermore increased mechanical strength is a desirable attribute in compressed dosage forms as this assures their physical and dimensional stability and robustness during bulk handling operations such as tablet coating , conveying and filling into final containers and transportation . a further distinguishing characteristic of the form of ec of this invention is that this material which provides superior compressibility has a lower glass transition temperature ( tg ) than analogous materials with poorer compressibility . the preferred form generally has a tg that is less than 130 ° c ., preferably less than 128 ° c . ( table 2 ). the tg was determined by differential scanning calorimetry ( ta instruments dsc 2920 , newark , del .) as described under standard methods . furthermore , this preferred form of ec also has the desirable attribute of good powder flow characteristics and low dustiness . while no single parameter or method to assess powder flow may allow one to completely quantify , describe or predict the flow of a powder , it is accepted industrial practice to jointly consider a number of different parameters which may be indicative of particle - particle interactions and flowability ( banker et al , 1986 , ibid ). frequently used parameters include the angle of repose , angle of slide ( also known as the internal angle ), the compressibility index , as well as determination of the flow rate through the powder through a defined orifice such as that of a glass funnel or tablet press hopper . these are described under the standard methods section . the angle of repose method is generally not predictive for the flow behavior of powders with only small differences in flow ( amidon , g . e ., physical and mechanical property characterization of powders in “ physcial characterization of pharmaceutical solids ”, ( brittain , h . g ., ed . ), marcel dekker inc ., new york , n . y ., 1995 , pp . 293 - 309 ). however , it is widely accepted that powders with angles of repose equal to or greater than 50 ° tend to be cohesive powders with poor or no flow through an orifice of a tablet press hopper . powders with angles of repose close to the practically minimum observable values of 18 - 25 ° are generally characterized by good flowability ( marshall , k ., compression and consolidation of powdered solids , in “ the theory and practice of industrial pharmacy ,” ( lachman , l ., lieberman , h . a . and kanig , j . l ., eds . ), 3 rd edition , lea and febiger , philadelphia , pa ., 1986 , p . 67 ). further , generally low compressibility values ( 18 %) are frequently correlated with good flow . generally as this value increases , flow tends to decrease . it should however be noted that exceptions have been documented ( amidon , 1995 , ibid ). determining the flow rate of powder through a defined orifice of a funnel is perhaps the simplest test that closely simulates the actual flow conditions to which powders are subjected during tableting . from table 1 it is evident that the high ethoxyl , low viscosity ec was characterized as having good flowability as measured by the aforementioned criteria . conversely , micronized ec demonstrated poor flow . according to the present invention , the high ethoxyl , low viscosity ec can be combined with medicaments ( or active pharmaceutical ingredients ) to prepare a blend suitable for tableting or pelletizing . one or more medicaments may be combined in a single dosage form , depending on the chemical compatibility of the combined active ingredients and the ability to obtain the desired release rate from the dosage form for each active ingredient . the determination of the effective amount of the medicament per dosage unit is easily determined by skilled clinicians . representative types of active medicaments include antacids , anti - inflammatory substances , anti - infectives , psychotropics , antimanics , stimulants , antihistamines , laxatives , decongestants , nutritional supplements , gastrointestinal sedatives , antidiarrheal preparations , antianginal drugs , antiarrhythmics , antihypertensive drugs , vasoconstrictors and migraine treatments , anticoagulants and anti - thrombotic drugs , analgesics , anti - pyretics , hypnotics , sedatives , antiemetics , anti - nauseants , anticonvulsants , neuromuscular drugs , hyper - and hypoglycemic agents , thyroid and antithyroid preparations , diuretics , antispasmodics , uterine relaxants , mineral and nutritional additives , anti - obesity drugs , anabolic drugs , erythropoietic drugs , antiasthmatics , expectorants , cough suppressants , mucolytics , antiuricemic drugs , topical analgesics , local anesthetics , polypeptide drugs , anti - hiv drugs , chemotherapeutic and anti - neoplastic drugs . examples of specific active medicaments include aluminum hydroxide , prednisolone , dexamethasone , aspirin , acetaminophen , ibuprofen , isosorbide dinitrate , nicotinic acid , tetracycline , ampicillin , dexbrompheniramine , chlorpheniramine , albuterol pseudoephedrine , loratadine , theophylline , ascorbic acid , tocopherol , pyridoxine , methoclopramide , magnesium hydroxide , verapamil , procainamide hydrochloride , propranolol , captopril , ergotamine , furazepam , diazepam , lithium carbonate , insulin , furosemide , hydrochlorothiazide , guaiphenesin , dextromethorphan and benzocaine . it should be understood that any active medicament that is physically and chemically compatible with the ec of the present invention and other dosage form ingredients can be used in the present invention . these active ingredients can be combined and dry blended with the ec to achieve a blend suitable for tableting which is then compressed as described under standard methods . typically such a blend would also include small quantities ( less than 5 %) of other excipients such as lubricants ( e . g ., magnesium stearate , stearic acid , calcium stearate , and hydrogenated vegetable oil ), antiadherents and flow promoting agents ( e . g ., talc , colloidal silicon dioxide ). such excipients are necessary for successful high speed , commercial tableting and are well known to those skilled in the art . furthermore , a blend may also include other excipients such as fillers , diluents , binders , coloring agents , flavoring agents , and disintegrants . one or more fillers or bulking agents may include dibasic calcium phosphate dihydrate , lactose or starch , with microcrystalline cellulose being the preferred filler . the filler may be present in an amount in the range of from about 0 to about 94 percent of the total weight of the uncoated dosage form , with from about 1 to about 5 weight percent being preferred for high dosage actives and with from about 80 to 85 weight percent being preferred for low dosage actives . the tablets can be compressed as simple monolithic , cylindrical dosage forms , but are not limited to this simple geometry . modifications in geometry can include compacts of other shapes as well as compacts having a core that is compression coated with additional barrier coatings . such a dry compression coat can be applied by means of commercially available compression coating tablet presses such a drycota ® press ( manesty co .). the barrier coatings may contain high ethoxyl , low viscosity ec and other excipients as mentioned above , however , it may also contain an active medicament . alternately , the ec may also be contained in the core . the processing of these high compression sustained release polymer blends can be done by bag mixing two or more components , by twin shell v - blending , or co - extrusion . other standard pharmaceutical processing techniques can also be used to form blends with ec . examples are high - speed roll compaction and direct compaction . although the tablet dosage form has been referred to throughout this description , it should be understood that other dosage forms exist , such as multiparticulates in the form of pellets or mini - tablets . if desired , capsules such as hard or soft gelatin capsules can contain the multipariculates . if desired , the multiparticulate oral dosage forms can comprise a blend of at least two populations of pellets or mini - tablets having different controlled - release profiles that are conventional in the sustained release drug industry . the tablets or pellets of this invention can be coated or uncoated depending on the manufacturer &# 39 ; s desires . the coating can be for any purpose such as aesthetics , flavoring , taste masking , or to provide additional controlled release properties . in accordance with astm d4794 , ethoxyl content was determined by a zeisel ( sealed ) tube method by reacting ec with hydriodic acid , liberating one mole of ethyl iodide for each mole of ethoxyl substitution on the cellulose chain . the ethyl iodide was then extracted with o - xylene and quantitated by gas chromatography using toluene as an internal standard . a typical set of apparatus , reagents and procedures for this test are listed below : 1 . gas chromatograph , perkin - elmer 900 , or equivalent equipped with thermal conductivity detector , chart recorder , and integrator . 2 . column 6 ′× ⅛ ″ stainless steel packed with 10 % sp - 2100 on 100 / 120 supelcoport , supelco , inc ., bellefonte , pa . upon receipt , columns were conditioned overnight at 200 ° c . 3 . reacti - vials , 5 ml , equipped with mininert valves . ( pierce chemical co ., # 13223 and # 10135 ). 4 . silli - therm heating module , 110 v , 19791 , pierce chemical co ., rockford , ill . 6 . cover , stainless steel , fabricated to cover six ( 6 ) reacti - bar 21 units on the silli - therm heating module 7 . dispenser 0 - 5 ml , labindustries repipet , or equivalent . syringe , 100 μl , hamilton 710 n or equivalent . 9 . micro - set pipet adjusted to deliver 2 . 0 ml ( lancer product # 8885 - 890007 ). 1 . dried about 0 . 5 grams of sample in 105 ° c . oven for 1 hour . 3 . into a tared 5 ml reacti - vial , weighed 0 . 05 - 0 . 08 gram of cooled sample . recorded weight to the nearest 0 . 0001 gram , samples were run in duplicate or triplicate . 4 . added 2 ml of hydriodic acid using a transfer pipet . capped sample . 5 . added 2 ml of internal standard solution using the repipet dispenser or equivalent . 6 . immediately recapped vials with mininert valve tops and shook vials . monitored block temperature at 180 +/− 5 ° c . with a thermometer . 7 . placed vials into block and replaced metal cover . kept samples behind safety shield while heating . 10 . shook each sample vigorously and allowed to stand for about 20 minutes . 11 . chromatographed 1 . 0 μl of the upper solvent layer of each sample on the gas chromatograph . viscosity was determined by preparing a 5 % solution of ec in a toluene : ethanol ( 80 : 20 ) solvent mixture . viscosity of the solution was measured using a hercules horizontal capillary viscometer ( following astm d914 - 00 , 33 . 1 ). the list of apparatus , reagents and procedures are described below . 6 . viscometer , hercules horizontal capillary viscometer — calibrated to give viscosity readings in centipoise . 1 . determined the temperature of the 80 : 20 solvent to be used . the temperature of the solvent must be between 20 and 30 ° c . if 111 . 8 ml . burette is to be used in this determination . 3 . measured 111 . 8 ml . of 80 : 20 solvent from burette ( the equivalent of 95 . 0 grams of solvent ) into an 8 - oz . bottle . added the sample to the solvent , making an effort to disperse the sample and avoid lumping . covered the neck of the bottle with a sheet of cellophane and applied the screw cap . 4 . placed the sample on a shaker and allowed it to shake until dissolution is complete . 5 . placed the bottle into a 25 ° c . bath for 30 minutes and the solution was free of air bubbles . 6 . with the viscometer in the raised position ( reservoir vertical ), filled the reservoir to the etched mark . made sure that no air remained trapped in the sample . placed a finger over the end of the capillary . released brace and carefully lowered the viscometer to horizontal . ( it was essential that the liquid was allowed to come to an equilibrium level before placing the finger over the end of the capillary and lowering it to the horizontal .) 7 . released the finger and measured the time for the liquid to flow from the first to the second mark in the capillary tube . reported as time t . ethylcellulose tablets were prepared by blending 198 g of ec powder with 2 g of stearic acid nf powder ( marketed by spectrum chemical , gardenia , calif .). the stearic acid powder was hand screened through a 20 mesh hand screen before it was placed in a 1 qt v - blender together with the ec powder . the powders were blended for 3 minutes . the ec and stearic acid blend was compressed on an instrumented manesty beta - press ( thomas engineering , hoffman estates , ill .) using ⅜ inch flat face beveled edge ( ffbe ) tooling . die fill depth was set to achieve 275 mg tablets . the tablets were compressed using 5 kn , 15 kn and 25 kn compression force with the press running at 37 . 5 rpm . drug containing tablets were manufactured by blending the requisite proportion of ec and drug to achieve a batch size of 198 g . the drugs used included phenylpropanolamine usp ( marketed by spectrum chemical , gardenia , calif . ), theophylline , anhydrous , usp ( marketed by basf corp , mount olive , n . j . ), and acetaminophen usp ( marketed by rhodia inc , cranbury , n . j .). the drugs and powders were passed through a 20 - mesh screen by hand before placing them together in a 1 qt v - blender . the powders were then mixed for 15 minutes . thereafter , 2 g of stearic acid was blended into the mixture that was then tableted as described above . additional batches of the drugs and ec were blended together with additional amounts of microcrystalline cellulose to form the tablets . a schleuniger model 6d hardness tester ( vector corp .) was used to measure the diametrical crushing force in order to assess the mechanical strength of the tablets . the results were reported in kp ( kilopond ) units for an average of 10 tablets . a modified compression procedure was used for micronized ec ( to be described in example 2 ). the tg was determined from a differential scanning calorimetry thermogram . differential scanning calorimetry was performed using a ta instruments ( newark , del .) dsc 2920 standard cell attached to a refrigerated cooling accessory . to obtain accurate results , the dsc 2920 was calibrated using the same heating rate and purge conditions used for the samples . calibration included heating the empty cell through the temperature range of interest to perform the baseline slope and offset calibration . and secondly , heating a certified indium standard ( 99 . 99 % pure ) through the melting point to obtain both the dsc cell constant and the onset slope values . to prepare a sample , approximately 10 . 0 milligrams of ethylcellulose ( accurately weighed ) was encapsulated into a ta instruments crimped aluminum robot pan with lid . the sample was then loaded into the dsc 2920 cell , cooled 5 ° c ./ minute from room temperature to − 20 ° c ., then heated at 5 . 0 ° c ./ minute under a zero grade nitrogen purge from − 20 ° c . to 280 ° c . the heat flow and temperature data , from the heating cycle , were recorded . the heat data were analyzed using ta universal analysis 2000 software . the glass transition measurement reported the onset temperature , the half - height temperature ( half height defines the midpoint as the y - axis value halfway between the onset and end of the step / glass transition region ) and the transition ending temperature . a standard laboratory glass funnel with smooth surfaces and an orifice whose inner diameter is 9 mm was affixed two inches above a stainless steel platform . while keeping the orifice blocked , 10 . 0 g of powder was loaded into the funnel . by unblocking the orifice , the powder was allowed to flow onto the platform under the force of gravity and , when necessary , with the use of light tapping . the angle of repose was then determined by measuring the apex angle with a protractor ( starrett , model c 183 ) and performing the following calculation : in addition , photographs were taken of the powder cone , to further validate the angle measurements . the angle of slide was determined by placing 1 g of powder in a 1 - inch square stainless steel frame ( 0 . 5 inch high ), which was resting on a stainless steel platform . the frame was then removed leaving behind an approximately square shaped heap of powder on the platform . one end of the platform was then incrementally raised until the entire powder sample slid off the platform . the angle of slide was then calculated from the height of lift and the length of the platform : to determine the compressibility index , the aerated and tapped bulk densities were first measured . aerated bulk density was determined as follows . the test material in powder form was slowly added up to the 100 - ml marking of a pretared , graduated 100 - ml cylinder . care was taken so as not to disturb the powder bed during addition . the weight of the added material was then recorded . bulk density was then calculated from the weight and volume of the material . tapped bulk density was then determined as follows . the filled graduated cylinder from the bulk density determination was placed on a vanderkamp tap density tester . the apparatus was set for 100 taps . at the end of the test , the volume of the powder in the cylinder was recorded . the tap density was then calculated dividing the bulk density weight by the powder volume . the compressibility index was then calculated as follows : compressibility   % = 100 × ( tapped   bulk   density - aerated   bulk   density ) tapped   bulk   density the flow rate was measured by affixing a standard laboratory glass funnel with an orifice of 9 . 37 mm inner diameter at a distance of 100 mm above the weighing platform of an analytical balance ( mettler toledo , columbus , ohio ). while blocking the orifice , 18 . 0 g of powder was loaded into the funnel . the orifice was then unblocked and the powder was allowed to flow under force of gravity into a pretared glass beaker located on the weighing platform . the elapsed time between unblocking the orifice and the cessation of powder flow was recorded with the aid of a digital stopwatch . five sets of mass and time measurements were then used to calculate the average flow rates . ethylcellulose materials ( marketed by aqualon , division of hercules incorporated , wilmington , del .) with varying viscosities and ethoxyl percentages were blended with 1 % stearic acid as a lubricant and compressed on an instrumented rotary tablet press as previously described in the standard method section . the results presented are for 275 mg tablets compressed at a constant force of 25 kn , while operating at a press speed of about 37 . 5 rpm . as can be seen in table 2 , the three ec samples with an ethoxyl content with a lower limit of 49 . 65 % and a viscosity less than 50 cps yield tablets with clearly superior crushing strength . these are further identified by the clearly lower tg values of 124 . 6 ° c . and 124 . 2 ° c ., respectively . high ethoxyl ( 50 . 8 %), low viscosity ( 9 cps ) ec powder ( marketed by aqualon , division of hercules incorporated , wilmington , del .) was compared with commercially available pharmaceutical grade micronized ec nf powder ( ethocel ® premium products , standard 10 fp , marketed by the dow chemical co ., midland , mich .) having 48 . 4 % ethoxyl and 10 . 2 cps viscosity and average particle size of less than or equal to 15 micrometers . the powders were lubricated with 1 % stearic acid nf ( marketed by spectrum , gardenia , calif .) in a v - blender and were then compressed on the previously described instrumented rotary press fitted with a single set of compression tooling . due to the inability of the micronized ec to flow from the tablet hopper , the die cavity was filled manually with 180 mg of lubricated ec powder . the powder to be filled was accurately weighed on an analytical balance . due to the low bulk density of micronized ec powder only 180 mg could be accommodated in the die cavity . this mass was , therefore , also used for comparison purposes with high ethoxyl , low viscosity ec . the results are shown in table 3 below . high ethoxyl ( 50 . 8 %), low viscosity ( 9 cps ) ec powder was blended in a 3 : 1 ratio with acetominophen usp powder ( marketed by spectrum chemical co ., gardenia , calif .) in a 1 qt v - blender for 15 minutes . 2 g of stearic acid were then added to 198 g of the blend by handscreening through a 20 mesh screen . the mixture was further blended for 3 minutes and was then compressed at constant pressure ( 25 kn compaction force ) and speed ( 37 . 5 rpm ) on an instrumented rotary tablet press as previously described under standard methods . for reference , additional batches were prepared which contained ec with lower ethoxyl content than 49 . 6 % and / or higher viscosity than 10 cps . the results clearly show that the high ethoxyl , low viscosity ec containing tablets have a superior crushing strength ( table 4 ). high ethoxyl ( 50 . 8 %), low viscosity ( 9 cps ) ec powder was blended in a 1 : 1 ratio with acetominophen usp powder in a 1 qt v - blender for 15 minutes . 2 g of stearic acid were then added to 198 g of the blend by handscreening through a 20 - mesh screen . the mixture was further blended for 3 minutes and was then compressed at constant pressure ( 25 kn compaction force ) and speed ( 37 . 5 rpm ) on an instrumented rotary tablet press as previously described under standard methods . the crushing strength of the tablets was 9 . 8 kp . the analogous powder blend containing micronized ec nf powder could not be compressed into tablets because of inadequate powder flow . high ethoxyl ( 50 . 8 %), low viscosity ( 9 cps ) ec powder was blended with acetominophen usp powder and microcrystalline cellulose ( avicel (® ph102 , fmc corporation , philadelphia , pa .) in a 1 qt v - blender for 15 minutes . the relative proportions were ec : acetaminophen : microcrystalline cellulose ( 40 : 25 : 35 ). 2 g of stearic acid was then added to 198 g of the blend by hand screening through a 20 - mesh screen . the mixture was further blended for 3 minutes and was then compressed at constant pressure ( 25 kn compaction force ) and speed ( 37 . 5 rpm ) on an instrumented rotary tablet press as previously described under standard methods . the crushing strength of the tablets was 15 . 0 kp . high ethoxyl ( 50 . 8 %), low viscosity ( 9 cps ) ec powder was blended in a 3 : 1 ratio with theophylline usp powder ( marketed by basf corporation , mount olive , n . j .) in a 1 qt v - blender for 15 minutes . 2 g of stearic acid were then added to 198 g of the blend by hand screening through a 20 - mesh screen . the mixture was further blended for 3 minutes and was then compressed at constant pressure ( 25 kn compaction force ) and speed ( 37 . 5 rpm ) on an instrumented rotary tablet press as previously described under standard methods . for comparison purposes , additional batches were prepared that contained ec with lower ethoxyl content than 49 . 6 % and / or higher viscosity than 10 cps . the results reported in table 5 clearly show that the high ethoxyl , low viscosity ec containing tablets have a superior crushing strength . high ethoxyl ( 50 . 8 %), low viscosity ( 9 cps ) ec powder was blended in a 3 : 1 ratio with phenylpropanolamine usp powder ( marketed by spectrum chemical co ., gardenia , calif .) in a 1 qt v - blender for 15 minutes . 2 g of stearic acid were then added to 198 g of the blend by hand screening through a 20 - mesh screen . the mixture was further blended for 3 minutes and was then compressed at constant pressure ( 25 kn compaction force ) and speed ( 37 . 5 rpm ) on an instrumented rotary tablet press as previously described under standard methods . for comparison , additional batches were prepared that contained ec with lower ethoxyl content than 49 . 6 % and / or higher viscosity than 10 cps . the results clearly show that the high ethoxyl , low viscosity ec containing tablets have a superior crushing strength ( table 6 ). while this invention has been described with respect to specific embodiments , it should be understood that these embodiments are not intended to be limiting and that many variations and modifications can be made without departing from the spirit and scope of the invention ; therefore , only such limitations should be imposed as are indicated by the appended claims .

a pharmaceutical dosage form composition is composed of an ethylcellulose that has an ethoxyl range lower limit of 49 . 6 %, an a viscosity of less than 53 cps and at least one active pharmaceutical ingredient . this dosage form is highly compressible and compactible forming harder tables or pellets with better release retardation than comparable prior art tablets .

the invention comprises the feature of construction , combination of elements , and arrangements of parts , which will be exemplified in the construction hereinafter set forth , and the scope of the invention will be indicated in the claims . the invention has a wide application for testing people ; it permits studying the precision of hand and arm motion and of the related tremors of the hands , which appear in afflictions of the nervous system , in alcoholism , neurosis , and also in old age . this device is intended primarily for psychological testing of drivers of all types of motor vehicles , as well as of other people , either in qualifying tests for candidates in various professions , or for controlling tests for people already employed ( industrial tests ). the equipment forms a part of a group of other testing instruments which together form a set of equipments for a method of psychological tests for drivers . these tests are aimed at reducing the number of traffic accidents and thus increasing the safety on the streets and highways . for a fuller understanding of the nature and objects of the invention , reference should be had to the following detailed description , taken in connection with the accompaying drawings , in which : fig1 -- perspective view of the apparatus of the invention , shown from the side of the tested person . fig3 -- section of measuring elements of the lever : the contact plates . fig4 -- cross - section of the driving mechanism of the disturbing stimulus of the measuring levers , and of the disc of the disturbing stimulus . fig1 presents in perspective a general view of the equipment with all its elements : controlling , measuring and driving . all the electrical elements are placed in the equipment casing 11 . they serve for driving and controlling the operation of the equipment . the front plate 15 is located on the casing 11 , and on this plate are fixed the following elements : the recording scale 12 , which registers the results of the tests ; the four - position push - button switch , where the switch 16 serves for starting the system ; a signal lamp 21 , signaling that the system is in operation ; switch 17 for switching on the supply of current ; switch 18 , for starting the disc 5 of the disturbing interference ; switch 19 for cancelling the results of the test from the recording scale 12 ; the fuse socket 13 of the network and the fuse socket 14 of the electric feeding system of the equipment . from the back of the equipment casing 11 extends a conductor 8 , at the end of which an electric probe 6 is placed in a protective insulated shield 7 . on the upper wall of the casing 11 a metal column 10 is fixed , in the upper part of which the following elements are located : a system of two measuring levers in the form of a double - arm lever : the upper lever 1 , and the lower lever 2 , and their thirty six upper and thirty six lower contact plates , where one plate of the upper lever is marked as 3 , and one plate of the lower lever is marked as 4 . a shield 9 covers the fastening of the measuring lever ; the disc of the interference stimulus 5 , on which as an example , black stripes 20 on a white background are shown ; this disc is exchangeable , one can utilize different discs with a variety of designs , such as a black spiral on white background , etc . the measuring levers 1 and 2 are placed at an angle between themselves , forming a certain acute angle . the entrance leading between the levers 1 and 2 is somewhat wider than the space further along between such levers . the ends of the measuring levers thus approach closer together , so that the last contact plates of the double - arm lever , a36 and b36 near the edge of the cover 9 , are separated at a distance almost equal to the diameter of the probe 6 ( the clearance between the last contact plates and the probe 6 - the play - is circa 0 . 5 mm ). testing method . the tested person holds the probe 6 by its casing 7 . the tested person has to guide the probe along the slot between the two arms 1 and 2 of the levers starting from the wider opening between them and proceeding towards the point where the arms join . the probe has to be guided in such a way as not to touch any one of the contact plates of the levers 1 or 2 . every touching of the probe 6 with any one of the contact plates is electrically registered on the recording scale 12 , where a signal lamp l1 , l2 , . . . . l35 , l36 , is switched on by the corresponding relay s1 , s2 . . s3 . . . s35 , s36 , see fig6 . the lamps illuminate a corresponding number on the recording scale 12 , which fact is considered as an error for the tested person . the farther the numbers are from the wider opening of the double - arm measuring lever , the smaller is the error , considering that at the end of the angle near the column 10 , the distance between the last upper and lower contact plates is almost exactly equal to the diameter of the probe 6 . also it is to be noted that , the recording scale shows not only the distance of the contact plate from the beginning of the test range , but also registers the quantity of plates touched . the probe 6 has to be held in such a way that the forearm of the tested person will not rest either on a support or on any part of the tested person &# 39 ; s body . during the test , the disc 5 rotates at various speeds , thus creating a disturbing interference . fig2 represents a view of the measuring levers 1 and 2 . their electric contact plates , the upper a1 , a2 , a3 . . . a36 , and the lower b1 , b2 , b3 , . . . b36 , constitute the basic elements of the double - arm lever 1 and 2 . these contacts are made from plates of metal with good electric conductance . they are electrically isolated from each other ; their length along the run of the levers is approximately 10 mm each . the separate borders of the contact plates of each lever are located on one level , and form a straight line on all its measuring length , which is marked 22 for the upper lever , and 23 for the lower one . every contact plate of the upper and the lower levers is connected with an electric cconductor . as an example , a cut has been made in the right - hand cover of the upper lever , exposing three contact plates : a1 , a2 , and a3 , and also three conductors : c1 , c2 , c3 , which are soldered to the tops of the contact plates . the conductors of the contact plates of the lower lever are connected in the same way as of the upper one . all the contact plates , together with their conductors , are enclosed in casings . the upper lever &# 39 ; s casing is marked 31 , the lower &# 39 ; s as 32 , see fig3 . all contact plates together with their conductors are sealed in epoxy resin . all conductors outgoing from the separate contact plates of the upper lever , and the corresponding conductors outgoing from the corresponding plates of the lower lever , are joined in pairs . thus every contact plate of the upper level is connected electrically with every corresponding contact plate of the lower lever . for example , the contact plate a1 of the upper lever is connected by an electric conductor with the contact plate b1 the lower lever ; similarly , the plate a2 is connected with the plate b2 , a3 with b3 , etc . fig3 represents a cross - section of both levers , made between two contact plates of the levers : d1 and g1 are the contact plates ; 31 and 32 are the metal covers of the upper and the lower levers ; 33 and 34 are the insulation layer , which separates the contact plates in the same lever from each other ; 35 and 36 are the epoxy resin , in which the contact plates of the levers are sealed together with their electric conductors . fig4 represents a plane section made across the rotation axis of the disturbing interference disc . there , we see the electric drive 41 of the interference disc , the transmission gear 40 of the drive 41 , the column k10 , the interference disc k5 , the lower measuring lever k2 , and a multicore cable 42 , which consists of the separate conductors , and leads to the relays , see fig6 . fig5 represents the recording scale 12 , see fig1 which registers results of the tests . the scale is made of plexiglass . its reverse side is painted in black , and numbers from 1 to 36 are engraved on it . the number 1 on the scale corresponds to the two first contact plates a1 and b1 of the upper and the lower levers 1 and 2 of the double - arm lever , see fig2 . every following number on the indicating scale corresponds to the following corresponding pair of contact plates of the double - arm lever 1 and 2 . fig6 represents the electric connections diagram of the equipment which is supplied from the 115 - v , 60 hz network . fast - operating electric relays s1 , s2 , s3 , . . . s36 , constitute the 36 basic electric elements of the equipment . all relays have identical electric parameters , and the same number of contacts each , i . e ., two pairs of break contacts per relay . one pair of contacts serves for maintaining the switching of the given relay , while the second pair serves for switching on the indicating lamp on the indicating scale 12 , see fig5 which corresponds to the contacted plates of the measuring levers 1 and 2 . the contact plates of the upper lever n1 , and of the lower lever m1 , which corresponds on fig2 to contact plates a1 and b1 , have their separate relay s1 . thus , each relay serves two contact plates of the measuring levers 1 and 2 . for example , the first contact plate of the upper lever n1 is connected by the electric conductor c1 of fig2 with the contact plate m1 of the lower lever ; the contact plate n2 is connected with the contact plate m2 etc , and finally , the contact plate n36 is connected electrically with the contact plate m36 . the touching of the n2 or m2 contact plates by the probe q6 causes the operation of the corresponding relay s2 . after plugging the equipment into the 115 - v / 60 - hz network 50 , and switching on the switch r16 , the transformer 51 , and the diode converter system 52 become connected with each other . this operation is signaled by the control lamp h21 . after the connecting of the switch e17 , all the testing system is under a 24 - v d - c current . the switch x18 serves for switching the drive of the disk of the disturbing stimulus . the w13 fuse serves for protecting the 115 - v network , and the fuse f14 serves for protecting the 24 - v d - c network . every pair of contact plates n1 , and m1 , n2 and m2 , etc ., . . . n36 and m36 , are controlled by one separate relay , s1 , s2 , etc ., . . . s36 . every individual relay has two pairs of break contacts , p1 and z1 , p2 and z2 , etc ., . . . p36 and z36 . contacts p1 , p2 , p3 , etc ., up to p36 , serve for maintaining the switching in of the given relay . contacts z1 , z2 , z3 , . . . z36 , serve for switching on the indicating lamps l1 , l2 , etc ., up to l36 , on the recording scale 12 , see fig5 . the tested person holds the probe q6 , and leads it between the contact plates n1 and m1 , n2 and m2 , n3 and m3 , etc ., . . . up to n36 and m36 , at the end of the double - arm measuring lever 1 and 2 . if the tested person will touch during the test any contact plate with the probe q6 , for example n23 , then the relay s23 will be switched on , and will connect the contacts p23 , which maintain the switching in of the s23 relay , and the z23 contacts will switch on the indicating lamp l23 on the recording scale , and the fig2 on the scale will be lighted from below the scale , see fig5 indicating that the touching occurred at a distance of the 23rd centimeter from the beginning of the measuring lever . the same will occur with any further upper or lower contact plate , giving at the end of the test not only the number of contact plates touched by the probe q6 , but also their distances from the beginning of the measuring lever . after having recorded the results of the test from the recording scale 12 , see fig1 these results have to be cancelled from the scale by pressing the trip button y19 , which breaks the current supply to the relays ; then the relays are de - energized and the contacts maintaining the relays at this time , as well as the contacts switching on the indicating lamps of the recording scale 12 , become disconnected . in this way , the first cycle of the test comes to an end and the equipment is prepared for another measuring cycle . by analyzing the results obtained during the tests , one can evaluate the given person as to the possession of the necessary characteristics of the given psycho - physiological function , and thus one will have evidence to anticipate good or bad results by this person for the task he has applied . the above described equipment has been built in a model . all its electric and mechaical systems operate accurately , and perfectly meet the requirements . the equipment can unreservedly be used for psychological tests .

this device tests drivers of all kinds of motor vehicles psychologically , and can be also used in a variety of different situations . it includes the following main components : a . arrangement of two measuring levers at a certain angle to each other ; the inner rims of the levers form a measuring scale , which is connected by wires to a recording device . b . optical interference device in the form of a rotating disc on which certain lines are painted . c . probe . d . recording scale . the tested subject holds the probe in his hand and leads it between the two measuring levers , starting from the wider end towards the narrow end . behind the measuring levers is a rotating disc which serves as an optical interference device . each contact of the probe with the measuring levers is recorded electrically on the recording scale .

in fig1 there is illustrated a mattress pad generally designated 10 preferably formed of polyurethane foam . the pad 10 is usually placed upon a bed in a hospital or elsewhere and is particularly useful for patients that are bed ridden and might suffer from decubitus ulcers , otherwise known commonly as bed sores . in view of the construction of the mattress pad 10 there are air spaces and air passages within the mattress pad to allow the circulation of air under a patient whereby decubitus ulcers may be prevented . the mattress pad 10 is preferably of a length and width to fit over a conventional mattress and corresponds to the perimeter dimension of such a mattress as for example a single bed , double bed , etc . the mattress pad 10 includes a head section generally designated 12 and a feet and legs section generally designated 14 . uniting the two sections 12 and 14 is a torso bridge section designated 16 and mounted on the torso bridge section 16 is a torso support insert member generally designated 18 . the head , feet , and legs sections 12 and 14 include a bottom surface 20 that is common along the entire mattress pad 10 . each of the sections 12 and 14 include convolutions of foam 22 that project upwardly and include a number of peaks 24 that may be arranged in rows across the mattress pad 10 from side 26 to side 28 . the peaks 24 are separated by valleys 30 between the rows of peaks . the process of forming convoluted foam such as illustrated and described is well known in the art and does not form a part of the present invention . as can be seen by the drawing the convolutions formation allow air to pass around the peaks 24 through the valleys 30 . the head section 12 and feet and legs section 14 are both formed with convolutions 22 . the only preferably difference resides in the preferred length of each section . the feet and legs section 14 is longer than the head section 12 as best seen in fig1 . this allows for an accommodation of a patient &# 39 ; s feet and legs to a point above the knees whereas the head portion 12 made be shorter as it is to accommodate the head and possibly the shoulders only of the patient . each section 12 and 14 terminates inwardly of bottom end 32 and top end 34 respectively in inner ends 36 and 38 . the inner ends 36 and 38 terminate at inner cut out top surface 40 forming the recess torso bridge section 16 between the top surface 40 and bottom surface 20 . thus , as can be seen there is a cut - out or recess 42 formed between ends 36 and 38 and top surface 40 . mounted within the cut - out 42 is the torso support insert member 18 . the torso support insert member 18 is of a peripheral dimension to fit between sides 26 and 28 and ends 36 and 38 . the insert member 18 is also preferably of laminated layers 39 and 41 of polyurethane . the ild and density of both of the laminants 39 and 41 are of different construction than the head and feet and legs sections 12 and 14 due to the fact that the torso of a patient will lay thereupon . the insert member 18 preferably includes a &# 34 ; waffle weave &# 34 ; construction on the top surface of upper laminant 41 . the construction includes a plurality of parallel spaced apart grooves such as v shaped grooves 44 running in a first direction such as across the pad 10 from side 26 to 28 . in addition , there are a plurality of parallel spaced apart grooves such as v shaped grooves 46 running normal to the grooves 44 and crossing the same between ends 36 and 38 of sections 12 and 14 . each of the grooves 44 and 46 include side walls 48 and 50 , see fig2 and formed between intersecting grooves 44 and 46 are formed a number of rectangular support squares 52 . the angle of the side walls 48 and 50 can be angularly varied to increase or decrease air flow as well as change the support characteristic of the insert 18 . the insert member 18 also includes a bottom surface 54 which rests on the inner cut - out top surface 40 of the torso bridge section 16 . with the construction just described it will be see that the grooves 44 and 46 will act as passages and allow air circulation to prevent the formation of decubitus ulcers . depending upon the weight of the patient the insert section 18 , which supports the heaviest part of the body , may vary in hardness ( ild ) and density . in other words , the stiffness may vary so that the rectangular support squares 52 will not be crushed completely flat and close off the grooves 44 and 46 and remain that way losing resiliency . in addition , with the interchangeable feature the patient mattress pad 10 may be sterilized and reused with a different insert member 18 for a different patient . also the interchangability allows the tailoring of mattress pads 10 to individuals weights . in fig3 there is illustrated a modified form of the patient mattress pad 10 wherein all the parts remain of the same construction . the difference resides in the fact that the insert member 18 is permanently affixed within the cut out or recess 42 by means of an adhesive 58 . the adhesive 58 bonds the bottom 54 and the inner cut out top surface 40 together . the modification of fig3 is particularly useful where only one person or patient plans to use the mattress pad 10 or it is known that the pad 10 will be used for an indefinite period of time . while the insert 18 is preferably constructed of laminated foam as above described , it should be realized that the insert 18 may be of a single piece of foam without departing from the spirit of the invention . the invention and its attendant advantages will be understood from the foregoing description and it will be apparent that various changes may be made in the form , construction and arrangements of the parts without departing from the spirit and scope thereof or sacrificing its material advantages , the arrangements herein before described being merely by way of example . i do not wish to be restricted to the specific forms shown or uses mentioned , except as defined in the accompanying claims , wherein various portions have been separated for clarity of reading and not for emphasis .

a mattress pad particularly adopted to prevent decubitus ulcers of a person laying thereon wherein there are a head section and a feet and legs section having similar top configurations and an intermediate torso support insert section therebetween of a top configuration different than said other two sections . the insert section is capable of being a replaceable insert within said pad or permanently affixed thereto .

as best seen in fig1 and fig2 , prior art lensectomy probe 10 generally consists in tube 12 made of metal or a rigid polymer . distal tip 16 of tube 12 can be flared or belled . distal tip 16 can include a rigid or elastomeric termination 26 conforming a stable aspiration port opening with a smooth rounded aspiration port rim 28 having an inner wall 29 shown in fig2 . as seen in views depicted in fig1 and fig2 , when an irregularly shaped lens fragment 50 is drawn by vacuum inside tube 12 into the aspiration port 16 and termination 26 , fluid aspiration across central aspiration channel 15 produces a fluid current through gaps 30 around fragment 50 walls 23 and distal port rim 28 inner edge 29 . fragment section corners 52 are stopped from advancing into tube 15 by inner edge 29 also promoting persistence of gaps 30 . the fixed form nature of this prior art distal tip 16 impedes or delays occlusion of fragment - tip gaps 30 also retarding vacuum build - up leading to reduced efficiency and excessive fluid circulation . as best seen in fig3 , a lensectomy probe tip 110 of the present invention generally includes a tube 112 that can be straight or curved . aspiration port 116 includes an elastomer portion 126 conforming a soft and deformable aspiration port rim 129 capable of forming an inner edge 128 . as seen in the lateral view depicted in fig3 and in the cross - section view depicted in fig4 , when an irregularly shaped lens fragment 50 with corners 52 is drawn by a fluid current or by a surgical maneuver into close contact with aspiration port 116 a fluid aspiration and a vacuum inside central aspiration channel 115 produces a pulling effect of the fragment toward deformable elastomer portion 126 with a force producing a contour deformation and adaptation of inner wall 128 of adaptive tip rim 129 and a 3d matching between the fragment perimeter shape and elastomeric rim 126 . fluid leaking gaps 30 between section 23 of fragment facets 50 and other irregularities are minimized by the seal provided by rim 129 inner edge 128 building a vacuum . the deformable nature of elastomer portion 126 of aspiration port 116 changes its perimeter shape to adapt under the force produced by vacuum supplied across a fluidic path to aspiration channel 15 by a controllable vacuum source usually provided by a surgical console . this adaptation by deformation complements the diverse shapes of lens fragment 50 both circularly narrowing and expanding contributing to an improved seal of the fragment - tip gaps 30 . this adaptive condition promoting tight fluidic seals between the probe rim and lens fragments of varying shape has a positive feedback effect . the tighter the seal , the higher the built vacuum , further enhancing the seal quality until the fragment brakes down and is aspirated through channel 15 . this enhanced fluidic seal speeds up the process of vacuum build - up and increases efficiency reducing fluid circulation as fragments 50 are aspirated . the deformation process of elastomer portion 126 that contributes to adapt to the lens fragments variable and evolving section contour involves controlled inward , outward , advance and recession , bending and deformation according to the variable three - dimensional shape of the lens fragments 50 including facets 23 , corners 52 and recesses . port 116 can have a diameter ranging between 0 . 1 and 2 . 0 mm . the amount of deformation departing from the resting state for elastomer portion 126 is typically in the range of 0 . 4 mm or less . according to fragment shapes , the inner edge 128 can have portions that displace inwards shown with 131 and other portions that displace outwards shown with 132 as well as limited forward and backward displacements . fig5 illustrates the elastomer portion 126 of adaptive aspiration port 116 with port rim 129 inner wall 128 adapting to a ccw rotating lens fragment as compared to fig4 . it is shown that the tip rim 129 inner wall 128 deforms to adapt to the rotated lens fragment in a way that the inwardly bent portions 131 of inner wall 128 shown in fig4 dynamically change to outwardly bent portions 132 and vice versa . in fig6 a four facet section lens fragment that could be a corner of a cubic shaped lens fragment produced by an uf laser treatment . shown is as a mode of example with adaptive distal tip 116 inner wall 132 sealing the gaps 130 to promote occlusion , reduce flow , enhance vacuum build up and increase efficiency to remove lens fragments . as depicted in fig7 adaptive aspiration port 116 has elastomer portion 126 with a tip rim 129 inner wall 128 displaced inwards ( portion 131 ) or outwards ( portion 132 ) typically in the range of 0 . 4 mm . to adapt to the diverse possible shapes of lens fragments 50 and to effectively seal gaps 30 . a differential polymerization process or a layered combination of elastomers producing different durometer readings can be incorporated with advantage to provide a range of suitable durometer readings such as shown portion 136 diametrically or axially across the elastomer portion 126 to improve adaptation to irregular lens fragment 150 shapes with improved gap 30 sealing properties . in this example , an annular embedded portion 136 of tip 126 is made of an elastomer with a lower durometer reading to provide enhanced deformability and adaptability to better adjust to changing shapes lens fragments than a homogeneous elastomer tip would do . fig8 depicts an alternative embodiment where adaptive aspiration port 116 has a more rigid elastomer portion 29 transforming into a softer elastomer portion 126 having rim 129 and inner wall 128 displacing inwardly or outwardly , forward or backward typically in the range of 0 . 4 mm to adapt to the diverse possible shapes of a lens fragment 50 and to effectively seal fluid leaking gaps 30 . also depicted in fig8 , one or more pockets 137 can be incorporated within elastomer portion 126 to further improve the adaptive properties of distal tip 116 to irregular lens fragment 50 section shapes . pockets 137 can be filled with a gas , a biocompatible liquid or with a different durometer reading cured elastomer material than the one composing the body of elastomer portion 126 . the improved lens fragments 50 occlusion characteristics of the lensectomy probe 110 of the present invention promotes rapid and stable dynamic occlusions of aspiration port opening 117 acting in a cushion - like form adapting to irregularly shaped lens fragments 150 . also , the adaptive lensectomy probe 110 of the present invention improves the quality of the occlusion obtained when aspirating irregularly shaped lens fragments 50 . the improved occlusion is particularly efficient to aspirate uf laser produced lens fragments , such as small cubes , that can have flat walls and corners . the improved vacuum build up is obtained by the rapid and effective occlusion provided by the adaptive aspiration port 116 . irrigant circulation is limited by the rapid and effective occlusion produced by the adaptive nature of distal tip 116 . shown in fig9 a and 9b is an alternative embodiment shown in resting condition where an inner tube 12 has an opening 200 . an elastomer portion 210 is adhered to tube 12 by suitable means , compression force , adhesive or other . elastomer portion 210 has a section comprised by a deformable elastic membrane 220 located on top of opening 200 . membrane 220 with a circular perforation 230 centered with respect to underlying tube opening 200 . when a vacuum is applied inside a tube 12 aspiration channel 15 , a flow is created across perforation 230 . fig9 c and 9d show the embodiment from fig9 a and 9b with a vacuum applied in aspiration channel 15 inside tube 12 . as can be seen in a lateral cross section in fig9 c and in a lateral top view in fig9 d , the inflow produced by vacuum across perforation 230 produces an inward elongation of membrane 220 and a subsequent increase in diameter of perforation 230 . in the same manner explained in fig3 to 8 , irregularly shaped lens fragments drawn into contact with membrane 220 and perforation 230 will be attached and with increasing seal and adaptation , vacuum build up will forcefully aspirate the lens segments with high efficiency and minimal fluid leakage . fig1 a and 10b depict another embodiment of the present invention . in this embodiment the elastomeric tip 300 fit to an aspirating tube 12 with an inner channel 15 has a particular shape progressively narrowing and thinning toward the distal end . typical dimensions are inner diameter 0 . 8 mm , outer diameter 1 . 1 mm , wall thickness at the base 320 of 300 microns , distal projection from base 1 . 2 mm and wall thickness at the distal end 200 of 50 microns . as seen in fig1 , adaptive tip 300 is in resting position . fig1 b depicts an example of the deformation and adaptation when a lens fragment 330 is being aspirated . tip 300 encircles the perimeter of the lens fragment effectively sealing the periphery for enhanced vacuum build up and efficiency . fig1 illustrates a single piece aspirating probe similar to fig1 . the elastomer termination of the aspiration ports of the present invention provides the added benefit of a lensectomy probe with improved lens capsule safety characteristics . this description is given for purposes of illustration and explanation . it will be apparent to those skilled in the relevant art that changes and modifications may be made to the invention described above without departing from its scope or spirit . for example , it will be recognized by those skilled in the art that the present invention may also be combined with ultrasonic , laser or rotatory powered lensectomy tips to enhance occlusion and vacuum build up to increase efficiency and to reduce fluid consumption improving the outcomes of the surgical procedures .

a surgical tip having a soft adaptive distal end that conforms to the irregular cross sectional contours of lens fragments , this construction allowing better occlusion of the tip distal end by adapting to the irregular shapes of the lens fragments thus improving the efficiency of the lensectomy probe by enhancing vacuum build up , reducing the total irrigant volume required to complete the lensectomy process and protects the lens capsule from accidental rupture said soft tip being usable with vibratory based , laser - based and water - jet based lensectomy handpieces as well as lens aspiration cannula .

the set of equipment illustrated as an exemplary embodiment in fig1 - 11 for implanting a knee joint endoprosthesis comprises two awls 90 , 91 ( see fig1 ) and a rasp / broaching awl 92 ( see fig2 ), a base frame 1 , pins 99 as a fastening device for fastening to a femur bone , an aligning insert 3 , a frontal - sawing insert 40 , spacers 34 , a feeler gauge 39 , a first milling insert 4 , a second milling insert 5 , a third milling insert 6 as a slotted link guide , and a curved milling gauge 7 with a condyle milling cutter 85 . the base frame 1 comprises a guiding plate 12 and a primary gauge 11 protruding orthogonally laterally therefrom . a first saw blade guide 20 , which is used to compensate for different condyle heights , is formed on the primary gauge 11 in the upper region , and a second saw blade guide 21 , which is used to machine the condyles with use of femoral segments , is formed on the primary gauge 11 in the lower region . furthermore , bores 22 for fastening pins are formed in the region between the saw blade guides . in the region of transition to the guiding plate 12 , receiving bores 26 for spacers are provided , aligned in the direction of extension of the guiding plate 12 . the base frame 1 is provided in different sizes . in this case , the distance between the reference plane 10 and the saw blade guides 20 , 21 and also the receiving bores 26 for the spacers is identical for the different sizes . the guiding plate 12 is formed with its underside as a reference plane 10 . this serves as a bearing surface for condyles of the femur . a planarity is formed on the upper side and acts as a tool plane 14 . it is the reference plane for the different inserts that are received on the guiding plate 12 . in this case , the dimension between the reference plane 10 and the tool plane 14 is matched to the respective size of the implant to be inserted . a linear guide 2 is arranged on either side of the tool plane 14 and comprises two undercut edges between the tool plane 14 and the upper side of the guiding plate 12 . these act as a dovetail guide for the inserts 3 , 4 , 5 and 6 . a milled recess 15 is formed on the guiding plate 12 on each of the lateral sides . it is of such a depth that the breadth remaining between said milled recesses corresponds to the width of the width dimension of the implant associated with the respective base plate 1 . the milled recess 15 thus acts as a visual aid for selecting the implant sizes . an aligning bore 23 with an inner thread , which indicates the position by means of an aligning rod 38 to be screwed in , is provided in each milled recess 15 . bores 28 for fastening pins 99 are provided in a manner flanking the milled recesses 15 . in the central region of the guiding plate 12 , a central opening of an approximately rectangular basic shape is formed , which on its two lateral faces pointing to the side acts as a lateral delimitation 66 and by means of its edge 65 ′ facing away from the primary gauge acts as a rear delimitation for a milled mortise recess . guiding slots 17 for an insertion implement 76 of the curved milling gauge 7 are formed in the lateral sides 66 . drill guides 18 for a pin - hole drill are provided on either side in the guiding plate 12 adjacently to said guiding slots . a posterior saw blade guide 19 for condyle machining is formed in the rearward region in the vicinity of the rear delimitation 65 ′ for the milled mortise recess . at the opposite end of the large central opening , a diagonal changeover guide 16 , 16 ′ is formed in the end pointing toward the primary guide 11 and is oriented parallel thereto . at its respective side faces , said changeover guide has a double curve shape and thus forms a bipolar receptacle for the frontal - sawing insert 40 . this is inserted in the position denoted by reference numeral 16 for processing for a left - side position , and is inserted in the positioning denoted by reference numeral 16 ′ for machining of a right - side implantation . a central fastening 14 is provided centrally on the base plate 12 above the primary gauge 11 . said fastening is used to fasten the individual inserts . it is always located at the same point on the base frame 1 for the different sizes , such that the different inserts can be used without difficulty with base frames of different size . free spaces 29 are formed on either side thereof and create the necessary clearance for fastening pins on the curved milling gauge 7 for fastening thereof to the femur . the rasp / broaching awl denoted in its entirety by reference numeral 92 comprises a plurality of cutting edges 93 in its lower region , which are each provided with a multiplicity of teeth 94 . a tooth - free region 95 with reduced diameter upwardly adjoins the cutting edges 93 provided with the teeth 94 . a recess is formed thereabove . this recess serves as a receptacle for a stop plate 97 . the cutting edges 93 are preferably formed in a triangle configuration , which means that three cutting edges 93 are provided , which are arranged at an angular distance of 120 °. it is noted that a different number of cutting edges , in particular two cutting edges or four cutting edges , could also be provided ( see illustrations in fig2 b ). in the embodiment illustrated in fig2 a , the arrangement of the teeth 94 is selected such that the teeth 94 of a cutting edge 93 are arranged so as to be offset vertically in relation to the teeth 94 ′ of the adjacent cutting edge 93 ′, as measured from the tip of the rasp / broaching awl 92 . this has the advantage that , as the rasp / broaching awl 92 is rotated , a more uniform shaping of the bone wall is achieved . it is specially designed to preserve the bone in the region close to the edge . for this purpose , it has a flattened portion , with which it is oriented relative to the bone edge . after introduction into the depth of the medullary cavity and after rasping , it is then used as a reamer . the rasp / broaching awl 92 acts via its upper shaft region above the recess 96 as an aligning aid and cooperates with the aligning insert 3 for this purpose . this insert has an opening 31 , which is open toward the side via a constriction 31 ′. the rasp / broaching awl 92 can be introduced via its recess 96 into the opening 31 by being inserted through the constriction 31 ′. a relative positioning between the rasp / broaching awl 92 and the base plate 1 , in which the aligning insert 3 is inserted , is thus achieved . the aligning rods 38 are screwed into the aligning bores 23 and in doing so indicate to the surgeon the position of the base frame and thus act as an aligning aid . in the illustrated exemplary embodiment , the opening 31 is not oriented orthogonal to the reference plane 10 , but is arranged at an oblique angle thereto . the deviation from the orthogonal direction is denoted as a shaft angle α and is a characterizing dimension for the prosthesis ( in the example 6 degrees ). in order to allow the surgeon to visualize this shaft angle , an opening 30 is also formed on the aligning insert 3 and is formed on a pair of tongs protruding via the front delimitation of the base plate 1 , a tracer pin 30 ′ being plugged through this opening 30 , being arranged outside the femur to be machined , and therefore indicating to the surgeon the shaft angle of the rasp / broaching awl 92 inserted in the medullary cavity of the femur to be machined ( see fig1 b and c ). the aligning insert 3 is chamfered in a wedge - like manner on its lateral sides 33 ( wedge angle γ is 4 to 10 degrees , preferably 6 degrees ), more specifically at least by the shaft angle α . on the one hand , sufficiently accurate positioning in the linear guide 2 is thus achieved , and on the other hand , unlike with an actual dovetail guide , the insert can be removed upwardly , more specifically at the end of the aligning process ( see fig1 ). it is noted that a concavity can be premachined in the medullary cavity of the femur using a broach milling cutter 37 , which may possibly have a recess 37 ′, similarly to the recess 96 on the rasp / broaching awl 92 , and can be inserted accordingly via the constriction 31 ′ into the opening 31 ( see fig1 ). the broach milling cutter 36 is in this case tilted by the same shaft angle α as the rasp / broaching awl 92 . it is thus made possible to mill out a deep region for the shaft of the prosthesis . the maximum milling depth is limited in this case by a depth stop 37 ″ formed as a shaft collar . the required erosion can thus be produced even deep in the bone , more specifically at the correct angle , without the need for specific skills on the part of the surgeon for this purpose . generally , the base frame 1 will rest directly via its reference plane 10 on the end of the femur . this is not always the case however , but in particular in cases of reoperation and in other cases , in which bone material is already absent ( if it was removed in a previous operation or is absent due to a defect ), spacers 35 can be arranged on the underside 10 of the base plate 1 ( see fig3 ). these are formed in pairs and are held via fastening pins 36 , which are inserted into the receiving bores 26 , on the primary gauge 11 of the base plate 1 ( see fig1 a ). they are available in different thicknesses ( see fig1 b ), such that a fine adjustment can be made herewith . alternatives for the spacers are illustrated in fig1 . the simplest alternative consists in arranging adjusting screws at the edge of the base frame ( see fig1 a ). alternative spacers 35 , 35 ′ for forming a base may also be provided and are held with a form fit on the lateral sides via hook connections or pin connections ( see fig1 b and c ). these spacers may also be provided in the lower region with pin openings through which fastening pins 99 are inserted ( see fig1 d ). if the position of the base frame 1 is then defined by means of the aligning insert 3 , the base frame is thus fixed relative to the femur by introducing the fastening pins 99 into the openings 28 . the aligning insert 3 and the rasp / broaching awl 92 can then be removed . the aids used for positioning , in particular the aligning rods 38 and the tracer pin 30 ′, are likewise removed . by means of a bone saw known per se and not described in greater detail , the condyles at the dorsal end can then be machined with use of the posterior saw blade guide 19 ( see fig1 c ). in the next step , the frontal - sawing insert 40 is inserted into the corresponding diagonal changeover guide 16 , 16 ′, more specifically irrespective of whether the implantation is a left - side or right - side implantation . the orientation given by the double arc - shaped recess 16 , 16 ′ is defined by the bipolar fixing by means of the slot 42 , in each of the end positions 43 , 43 ′ of which a fastening screw 13 is screwed into the central fastening 14 . the frontal condyle side is then machined along the v - shaped saw blade guides 41 , 41 ′ by means of the bone saw known per se ( see fig1 a , b ). in the next step , the plane of rotation can then be fixed in one direction by means of the feeler gauge 39 , which is plugged into the slot 27 on the base frame 1 , and the plane of rotation in another direction , oriented transverse to the first - mentioned direction , can then be fixed by insertion into the sawing slot 40 , 40 ′. the pivot point is determined by the point of intersection of the planes of rotation . an alternative implement is illustrated in fig1 . it comprises a bridge support as a direction gauge 39 ′ with indexings 39 ″ arranged on either side . the bridge support 39 ′ is inserted into receiving slots 17 on the base frame 1 , and the orientation of the base frame 1 can be set by the form - fitting connection thus produced . the length of the indexings 39 ″ is dimensioned such that they indicate via their end the respective resulting position of the pivot point z ( see fig1 b and c ). this enables quick alignment that can be easily checked . in the following step , the first milling insert 4 is inserted into the base frame 1 and is fixed by means of the central fastening 14 , which is accessible through an opening 44 , and by means of the fastening screw 13 . the insert 4 has a large central opening 45 with an upwardly protruding guiding sleeve 45 ′ which form a receptacle for a broach milling cutter 49 . this has a collar 49 ′ in its upper region , said collar cooperating with the upper edge of the guiding sleeve 45 ′ in such a way that a depth stop for the broach milling cutter 49 is formed . part of the concavity in the medullary cavity necessary for implantation is thus created , and on the other hand the wall left by the reamer is reduced in the front region , defined in terms of its height ( see fig1 ). the reduction of the height of the wall in the front region can alternatively also be achieved by means of a chisel 46 , as illustrated in fig2 . the chisel 46 has a main body which , in cross section , has the shape of a segment of a circular arc and , at the rear end , has an impact head 46 ′ also acting as a depth stop . a guiding slot 47 complementary to the cross - sectional shape of the chisel 46 is provided in the base frame 1 on the primary gauge 11 . in the following step , the first milling insert 4 is replaced for a second milling insert 5 . this has a double receptacle 51 , which is octagonal in cross section and forms two receiving positions 52 , 53 for a bulk milling cutter 59 . the two receptacles 52 , 53 are not arranged centrally , but both with a different offset in relation to the side ( lateral offset ). each of the two receiving positions 52 , 53 is assigned an upwardly protruding sleeve 52 ′, 53 ′. the bulk milling cutter 59 in its upper region likewise has a protruding collar 59 ′, which cooperates with the upper edge of the sleeve 52 ′, 53 ′ assigned to the respective receptacle 52 , 53 and thus forms a depth stop for the bulk milling cutter 59 ( see fig2 a ). a large part of the cavity can thus be preformed for the reception of the implant . it is noted that the second milling insert 5 , similarly to the first milling insert 4 , is positioned clearly on the base frame 1 by means of an opening 54 in line with the central fastening . due to the different depth stops of the two receptacles 52 , 53 of the double receptacle 51 , the cavity in the bone can be efficiently broached . if this is not necessary , a simplified second milling insert 5 ′ can be provided and has a double receptacle 55 without lateral offset . here , the depth stops may be arranged at the same height however ( see fig2 b ); it is not to be ruled out however that they are arranged at different heights ( in accordance with the illustration in fig2 a ). it is further noted that the second milling insert 5 is contained in the set of equipment in two versions . one version is for left - sided implantation , and a second version , which is axially symmetrical , is formed for right - sided implantation ( see the milling inserts 5 in fig4 marked by “ l ” and “ r ”). in the following step , the second milling insert 5 is replaced by a third milling insert 6 , which is formed as a slotted link insert ( see fig5 and 23 a - c ). this has two slotted link windows 60 , 61 oriented in a t - shaped manner and two inspection windows 62 , 63 . the slotted link window 60 is formed as a slot and acts as a receptacle for the fastening screw 13 , by means of which the slotted link insert is guided on the base frame 1 . the slotted link insert 6 can therefore be moved to and fro frontally and dorsally . a slotted link slider 65 is inserted displaceably into the transversely oriented slotted link window 61 and has a handle 64 with a receptacle 67 for a milling tool 68 , 69 . the milling tools 68 , 69 are a pre - milling cutter and an end - milling cutter , which are designed for different milling depths by means of a stop collar 68 ′, 69 ′ arranged at different distances from the tip ( see fig5 and fig2 c ). they can be inserted through a central opening 67 in the handle 64 into the slotted link slider 63 . by moving the slotted link slider 63 along its slotted link window 61 and by moving the slotted link insert 6 along the slotted link window 60 ( x / y movement ), a rectangular cavity cross section can be milled out with high precision . thanks to the precise slotted link guidance , the cavity can be produced with high dimensional accuracy , and the box - like receiving space for the knee prosthesis can thus be prepared in the femur cavity . an alternative embodiment for the slotted link insert 6 is illustrated in fig2 . it is a hinged slotted link insert 6 ′. it has two guiding levers 60 ′, 61 ′ hinged to one another . at one end , they are mounted rotatably via a pivot pin 62 ′ on a main plate of the insert 6 ′, and at the other end a receptacle 67 ′ for the milling tools 68 , 69 is formed . a u - shaped slotted link path 63 ′ is cut out on the base plate of the slotted link insert 6 ′, and the milling tool 68 , 69 inserted into the receptacle 67 ′ is forcibly guided in said path by the guiding levers 60 ′, 61 ′. the pivot pin 62 ′ is provided with a flattened portion 64 ′, such that the guiding levers 60 ′, 61 ′ can only be fitted thereon and removed therefrom in a predetermined assembly position . the flattened portion 64 ′ is aligned here such that , in the assembly position , the receptacle 67 ′ is arranged aside the slotted link path 63 ′. it is thus ensured that the assembly and disassembly processes can only be performed when the milling tool 68 , 69 is removed . an additional securing of the inserts 3 , 4 and 5 in the base frame 1 is illustrated in fig2 . the securing opening 14 on the base frame is formed twice , more specifically once for the left - hand side 14 ′ and once for the right - hand side 14 ″. the fastening openings 34 , 44 and 54 on the inserts 3 , 4 and 5 are formed as grooves 34 ′, 34 ″ running as far as the edge and offset laterally with respect to one another , depending on whether the respective insert is provided for left - side or right - side implantation . a securing lever 66 ′ comprises a toggle 66 ″ at the end of a shaft stump . the securing lever 66 ′ can be inserted in the orientation illustrated in fig2 b into one of the fastening openings 14 ′, 14 ″ from the side . by moving the securing lever 66 ′, the toggle 66 ″ is moved through a right angle , whereby a locking effect is achieved . in order to avoid accidental actuation of the securing lever 66 ′, a securing bolt 14 ′″ is preferably provided and is inserted into the base frame 1 from the side and rests in an aligned manner against a flattened portion 66 ′″ of the shaft stump , in such a way that the shaft stump and therefore the securing lever 66 ′ are prevented from rotating . the securing lever 66 ′ can then only be moved again when the securing bolt 14 ′″ is removed . the corresponding inserts are expediently provided on their underside with an undercut bore 50 ′ in the case of an insert 5 ′ to be secured against lifting out ( see fig2 a ) and / or with the groove 34 ′, 34 ″ and a widened end in the case of an insert 3 ′ to be secured against displacement ( see fig2 b ). the open position is illustrated in each of the two smaller images ( at the top in fig2 a and to the left in fig2 b ) as well as the closed position ( at the bottom in fig2 a and to the right in fig2 b ). once the box - shaped receiving space has been developed in the femur , the sliding paths on the condyles are then machined . reference is made in particular to fig7 to 10 . to machine the condyles , the curved milling gauge 7 is used . it is inserted by means of a pair of insertion tongs 76 . the pair of tongs comprises two tong halves 78 , which , at their front ends , have two grippers 79 cooperating with a form fit with the curved milling cutter 7 . on the outer face of the tong halves , aligning lugs 77 pointing away from one another are formed . they are designed such that they are congruent to the shape of the guiding slots 17 on the base frame 1 . precise positioning of the curved milling gauge 7 relative to the base frame 1 is thus ensured by inserting the insertion tongs 76 into the base frame 1 , the aligning lugs 77 engaging with a form fit in the guiding slots 17 ( see fig1 ). it is noted that the curved milling gauge 7 is available in different ( preferably four ) sizes , the positioning by means of the insertion tongs 76 being achieved similarly by form - fitting engagement in the guiding slots 17 irrespective of the size used . the curved milling gauge 7 comprises a main body 70 , of which the basic shape corresponds approximately to a cuboid - like box ( see fig7 ). grooves 71 running vertically from top to bottom are formed on the lateral sides of the curved milling gauge . the grooves are used for sturdier and position - maintaining anchoring in the cavity of the femur . on the upper side of the main body 70 , an upwardly protruding circular arc segment 72 is formed in one piece and covers an angular range of approximately of 100 to 120 degrees and , in the front region , is pulled down to approximately half the height of the main body 70 . in the region close to the edge , it has a recessed guiding path 74 on one of its side faces . said path is delimited via a web 75 toward the upper edge of the circular arc segment 72 , wherein , in the downwardly pointing front region , an extension 74 ′ of the guiding path 74 is formed and is web - free . an opening is thus created , through which a follower 84 of the guiding piece 8 can be inserted into the guiding path 74 or removed therefrom . this can occur only in the position when the follower 84 is located in the region of the extension 74 . the guiding path 74 is closed at the other , rear end and forms a stop 76 for the follower 84 . from a rear side of the main body 70 , a double slit 77 extends as far as the upper side of the main body 70 . a receiving bore for a securing screw 79 is arranged transverse thereto . it acts as a pivot bearing for a toggle linkage 80 , of which the free end protrudes from the main body 70 and which is pivotable along the double slit 77 ( see fig7 ). at its free end , the toggle linkage 80 carries a pivot pin 81 , of which the cross section is approximately rectangular with straight long sides and circular - arc - shaped convex short sides ( see fig1 a ). between the circular - arc - shaped convex short sides , the pivot pin 81 has a meridian of greatest width d , and between the straight sides a meridian of smallest width d . the guiding piece 8 is generally of t - shaped design with a transverse segment 89 and a longitudinal segment 88 ( see fig8 ). in each of the outer regions , a stepped bore 87 with a peripheral shoulder is arranged on the transverse segment 89 . said stepped bores are oriented with their axis 87 ′ such that they form an angle α from 75 to 85 degrees , preferably 80 degrees , to the transverse segment 89 . the axes 87 ′ are therefore divergent . the stepped bore 87 forms a guide for a condyle milling cutter 85 , which is inserted via a lateral opening 82 into the stepped bore 87 . the condyle milling cutter 85 comprises a milling head and a shaft , on which a cylindrical thickening 86 distanced from the milling head is formed . since it is placed on the peripheral shoulder of the stepped bore 87 , it delimits the milling depth . the longitudinal segment 88 of the guiding piece 8 is angled ; it forms an angle from approximately 15 to 25 degrees , preferably 20 degrees , to the plane spanned by the axes 87 ′. the follower 84 is arranged laterally on the longitudinal segment 88 and guides the guiding piece 8 along the guiding path 74 . at the free end , the longitudinal segment 88 is formed in a fork - like manner and is provided with a transverse bore , which acts as a pivot bearing sleeve 83 . it is open toward the free end via a constriction 83 ′. the width of the constriction 83 ′ is dimensioned such that it is larger than the meridian of smallest width 82 and smaller than the meridian of greatest width 82 ′. if the pivot bearing sleeve 83 and the pivot pin 81 are oriented such that the constriction 83 ′ contacts the meridian of smallest breadth 82 , the guiding piece 8 can be pushed with its pivot bearing sleeve 83 onto the pivot pin 81 , and in any other orientation the pivot pin 81 is prevented from passing through the constriction 83 ′. an angular lock is thus provided , which can be opened and closed only in one position and is otherwise locked ( see fig1 a and b ). the pivot pin 81 is oriented on the toggle linkage 80 such that the guiding piece 8 can be coupled and removed only in an elongate position when the guiding piece 8 forms a line with the toggle linkage 80 ( see fig1 a ). if the guiding piece 8 is coupled , it is inserted via its follower 84 in the region of the extension 74 ′ into the guiding path , the guiding piece 8 being arranged at an angled position ( that is to say no longer elongate ) relative to the toggle linkage 80 . the pivot pin 81 is therefore prevented from passing through the constriction 83 ′. the guiding piece 8 inserted into the guiding path 74 is therefore locked securely to the toggle linkage 80 ( see fig1 b ). the kinematics thus achieved for the guidance of the condyle milling cutter 85 is illustrated in fig1 as a multi - phase diagram . the pivot bearing 78 is illustrated at the bottom in the middle of the image . it forms a fixed pivot point for the curve guidance consisting of guiding path 74 , guiding piece 8 , and toggle linkage 80 . the guiding piece 8 is guided via its follower 84 over the entire pivot range along the guiding path 74 . the guiding path 74 has an increasing curvature ( from left to right in the figure ), whereby the radial distance between the pivot bearing 78 and follower 84 increases . as a result , not only does the condyle milling cutter 85 inserted into the guiding piece 8 become increasingly removed from the pivot bearing 78 ( it thus describes an arc becoming continuously greater ), but it also changes its orientation . due to the articulation via the toggle linkage 80 , the guiding piece rotates , such that the axis 87 for the milling cutter 85 is directed toward the pivot bearing 78 at the start of the pivot motion , but rotates increasingly dorsally ( to the right in fig1 ) with the movement of the guiding piece 8 along the guiding path . a condyle shape is thus produced on the bone by means of the milling cutter 85 , the current center of rotation of the milling cutter not being stationary as the knee joint flexes , but shifting dorsally . a path of movement that corresponds practically fully to that of the natural knee and is therefore physiologically extremely favorable is thus enabled for the knee prosthesis implanted using the equipment according to the invention . knee prostheses implanted in this way provide the best preconditions for long - term therapy success without the need for revision surgery after a short period of time . an alternative embodiment of the guiding piece for different condyle milling is illustrated in fig1 a and b . in this case , guiding pieces 8 ′, 8 ″ are provided and receive a horizontal milling cutter 85 ′, 85 ″. in the variant illustrated in fig1 a , the horizontal milling cutter 85 ′ is mounted from the side into the guiding piece 8 ′, and is mounted there in a one - sided manner . the movement kinematics corresponds to that illustrated in fig1 . in the variant illustrated in fig1 b , the toggle linkage and the guiding piece 8 ″ are arranged externally , and the horizontal milling cutter 85 ″ is inserted through the guiding piece 8 ″. in this variant , it is necessary to reassemble the toggle linkage and the guiding piece 8 ″ in order to machine the other side . the equipment further comprises an awl set for creating and preparing a prosthesis receptacle in the femur . the awl set ( see fig6 ) comprises an access awl 90 , which is used to open the medullary cavity of the femur . by means of reamers 91 , which are preferably contained in the set in different lengths and diameters , the medullary cavity is enlarged successively . the special rasp / broaching awl 92 with the stop plate 97 is further provided and has already been described above . lastly , a pin - hole drill 98 with stop is provided and is inserted into the drill guides 18 in order to form receptacles for anchoring pins ( not illustrated ) on a condyle part of the knee joint endoprosthesis .

equipment for inserting a joint prosthesis , in particular a femur component of a knee prosthesis , comprises a base frame having a guiding plate and a laterally protruding primary gage , a fastening device on the bone , and a curved milling gage having a main body and a guiding piece , which can be moved along a curved guiding path relative to the main body and has a receptacle for an abrasive tool . furthermore , the equipment comprises an aligning device , which places the curved milling gage in a clearly defined relative position when the curved milling gage is inserted into the base frame . due to the precise positioning in conjunction with the curved guiding path , the mounting seat can be prepared easily without damaging surrounding tissue . thus , even large and complexly shaped prostheses , such as knee joint prosthesis , can be reproducibly inserted in an easy and safe manner .

fig1 is a diagrammatic representation of air bed system 10 in an example embodiment . system 10 may include bed 12 , which may comprise at least one air chamber 14 surrounded by a resilient border 16 and encapsulated by bed ticking 18 . the resilient border 16 may comprise any suitable material , such as foam . as illustrated in fig1 , bed 12 may be a two chamber design having a first air chamber 14 a and a second air chamber 14 b . first and second air chambers 14 a and 14 b may be in fluid communication with pump 20 . pump 20 may be in electrical communication with a remote control 22 via control box 24 . remote control 22 may communicate via wired or wireless means with control box 24 . control box 24 may be configured to operate pump 20 to cause increases and decreases in the fluid pressure of first and second air chambers 14 a and 14 b based upon commands input by a user through remote control 22 . remote control 22 may include display 26 , output selecting means 28 , pressure increase button 29 , and pressure decrease button 30 . output selecting means 28 may allow the user to switch the pump output between the first and second air chambers 14 a and 14 b , thus enabling control of multiple air chambers with a single remote control 22 . for example , output selecting means may by a physical control ( e . g ., switch or button ) or an input control displayed on display 26 . alternatively , separate remote control units may be provided for each air chamber and may each include the ability to control multiple air chambers . pressure increase and decrease buttons 29 and 30 may allow a user to increase or decrease the pressure , respectively , in the air chamber selected with the output selecting means 28 . adjusting the pressure within the selected air chamber may cause a corresponding adjustment to the firmness of the air chamber . fig2 is a block diagram detailing data communication between certain components of air bed system 10 according to various examples . as shown in fig2 , control box 24 may include power supply 34 , processor 36 , memory 37 , switching means 38 , and analog to digital ( a / d ) converter 40 . switching means 38 may be , for example , a relay or a solid state switch . switching means 38 may be located in the pump 20 rather than the control box 24 . pump 20 and remote control 22 may be in two - way communication with the control box 24 . pump 20 may include a motor 42 , a pump manifold 43 , a relief valve 44 , a first control valve 45 a , a second control valve 45 b , and a pressure transducer 46 , and may be fluidly connected with the first air chamber 14 a and the second air chamber 14 b via a first tube 48 a and a second tube 48 b , respectively . first and second control valves 45 a and 45 b may be controlled by switching means 38 , and may be operable to regulate the flow of fluid between pump 20 and first and second air chambers 14 a and 14 b , respectively . in an example , pump 20 and control box 24 may be provided and packaged as a single unit . alternatively , pump 20 and control box 24 may be provided as physically separate units . in operation , power supply 34 may receive power , such as 110 vac power , from an external source and may convert the power to various forms required by certain components of the air bed system 10 . processor 36 may be used to control various logic sequences associated with operation of the air bed system 10 , as will be discussed in further detail below . the example of the air bed system 10 shown in fig2 contemplates two air chambers 14 a and 14 b and a single pump 20 . however , other examples may include an air bed system having two or more air chambers and one or more pumps incorporated into the air bed system to control the air chambers . in an example , a separate pump may be associated with each air chamber of the air bed system or a pump may be associated with multiple chambers of the air bed system . separate pumps may allow each air chamber to be inflated or deflated independently and simultaneously . furthermore , additional pressure transducers may also be incorporated into the air bed system such that , for example , a separate pressure transducer may be associated with each air chamber . in the event that the processor 36 sends a decrease pressure command to one of air chambers 14 a or 14 b , switching means 38 may be used to convert the low voltage command signals sent by processor 36 to higher operating voltages sufficient to operate relief valve 44 of pump 20 and open control valves 45 a or 45 b . opening relief valve 44 may allow air to escape from air chamber 14 a or 14 b through the respective air tube 48 a or 48 b . during deflation , pressure transducer 46 may send pressure readings to processor 36 via the a / d converter 40 . the a / d converter 40 may receive analog information from pressure transducer 46 and may convert the analog information to digital information useable by processor 36 . processor 36 may send the digital signal to remote control 22 to update display 26 on the remote control in order to convey the pressure information to the user . in the event that processor 36 sends an increase pressure command , pump motor 42 may be energized , sending air to the designated air chamber through air tube 48 a or 48 b via electronically operating corresponding valve 45 a or 45 b . while air is being delivered to the designated air chamber in order to increase the firmness of the chamber , pressure transducer 46 may sense pressure within pump manifold 43 . again , pressure transducer 46 may send pressure readings to processor 36 via a / d converter 40 . processor 36 may use the information received from a / d converter 40 to determine the difference between the actual pressure in air chamber 14 a or 14 b and the desired pressure . processor 36 may send the digital signal to remote control 22 to update display 26 on the remote control in order to convey the pressure information to the user . generally speaking , during an inflation or deflation process , the pressure sensed within pump manifold 43 provides an approximation of the pressure within the air chamber . an example method of obtaining a pump manifold pressure reading that is substantially equivalent to the actual pressure within an air chamber is to turn off pump 20 , allow the pressure within the air chamber 14 a or 14 b and pump manifold 43 to equalize , and then sense the pressure within pump manifold 43 with pressure transducer 46 . thus , providing a sufficient amount of time to allow the pressures within pump manifold 43 and chamber 14 a or 14 b to equalize may result in pressure readings that are accurate approximations of the actual pressure within air chamber 14 a or 14 b . in various examples , the pressure of 48 a / b is continuously monitored using multiple pressure sensors . in an example , another method of obtaining a pump manifold pressure reading that is substantially equivalent to the actual pressure within an air chamber is through the use of a pressure adjustment algorithm . in general , the method may function by approximating the air chamber pressure based upon a mathematical relationship between the air chamber pressure and the pressure measured within pump manifold 43 ( during both an inflation cycle and a deflation cycle ), thereby eliminating the need to turn off pump 20 in order to obtain a substantially accurate approximation of the air chamber pressure . as a result , a desired pressure setpoint within air chamber 14 a or 14 b may be achieved without the need for turning pump 20 off to allow the pressures to equalize . the latter method of approximating an air chamber pressure using mathematical relationships between the air chamber pressure and the pump manifold pressure is described in detail in u . s . application ser . no . 12 / 936 , 084 , the entirety of which is incorporated herein by reference . fig3 is illustrates an example air bed system architecture 300 . architecture 300 includes bed 301 , central controller 302 , firmness controller 304 , articulation controller 306 , temperature controller 308 , external network device 310 , remote controllers 312 , 314 , and voice controller 316 . while described as using an air bed , the system architecture may also be used with other types of beds . as illustrated in fig3 , network bed architecture 300 is configured as a star topology with central controller 302 and firmness controller 304 functioning as the hub and articulation controller 306 , temperature controller 308 , external network device 310 , remote controls 312 , 314 , and voice controller 316 functioning as possible spokes , also referred to herein as components . thus , in various examples , central controller 302 acts a relay between the various components . in other examples , different topologies may be used . for example , the components and central controller 302 may be configured as a mesh network in which each component may communicate with one or all of the other components directly , bypassing central controller 302 . in various examples , a combination of topologies may be used . for example , remote controller 312 may communicate directly to temperature controller 308 but also relay the communication to central controller 302 . in yet another example , central controller 302 listens to communications ( e . g ., control signals ) between components even if the communication is not being relayed through central controller 302 . for example , consider a user sending a command using remote 312 to temperature controller 308 . central controller 302 may listen for the command and check to determine if instructions are stored at central controller 302 to override the command ( e . g ., it conflicts with a previous setting ). central controller 302 may also log the command for future use ( e . g ., determining a pattern of user preferences for the components ). in various examples , the controllers and devices illustrated in fig3 may each include a processor , a storage device , and a network interface . the processor may be a general purpose central processing unit ( cpu ) or application - specific integrated circuit ( asic ). the storage device may include volatile or non - volatile static storage ( e . g ., flash memory , ram , eprom , etc .). the storage device may store instructions which , when executed by the processor , configure the processor to perform the functionality described herein . for example , a processor of firmness control 304 may be configured to send a command to a relief valve to decrease the pressure in a bed . in various examples , the network interface of the components may be configured to transmit and receive communications in a variety of wired and wireless protocols . for example , the network interface may be configured to use the 802 . 11 standards ( e . g ., 802 . 11a / b / c / g / n / ac ), pan network standards such as 802 . 15 . 4 or bluetooth , infrared , cellular standards ( e . g ., 3g / 4g etc . ), ethernet , and usb for receiving and transmitting data . the previous list is not intended to exhaustive and other protocols may be used . not all components of fig3 need to be configured to use the same protocols . for example , remote control 312 may communicate with central controller 302 via bluetooth while temperature controller 308 and articulation controller 306 are connected to central controller using 802 . 15 . 4 . within fig3 , the lightning connectors represent wireless connections and the solid lines represent wired connections , however , the connections between the components is not limited to such connections and each connection may be wired or wireless . moreover , in various examples , the processor , storage device , and network interface of a component may be located in different locations than various elements used to effect a command . for example , as in fig1 , firmness controller 302 may have a pump that is housed in a separate enclosure than the processor used to control the pump . similar separation of elements may be employed for the other controllers and devices in fig3 . in various examples , firmness controller 304 is configured to regulate pressure in an air mattress . for example , firmness controller 304 may include a pump such as described with reference to fig2 ( see e . g ., pump 20 ). thus , in an example , firmness controller 304 may respond to commands to increase or decrease pressure in the air mattress . the commands may be received from another component or based on stored application instruction that are part of firmness controller 304 . as illustrated in fig3 central controller 302 includes firmness controller 304 . thus , in an example , the processor of central controller 302 and firmness control 304 may be the same processor . furthermore , the pump may also be part of central controller 302 . accordingly , central controller 302 may be responsible for pressure regulation as well as other functionality as described in further portions of this disclosure . in various examples , articulation controller 306 is configured to adjust the position of a bed ( e . g ., bed 301 ) by adjusting the foundation that supports the bed . in an example , separate positions may be set for two different beds ( e . g ., two twin beds placed next to each other ). the foundation may include more than one zone that may be independently adjusted . articulation control 306 may also be configured to provide different levels of massage to a person on the bed . in various examples , temperature controller 308 is configured to increase , decrease , or maintain the temperature of a user . for example , a pad may be placed on top of or be part of the air mattress . air may be pushed through the pad and vented to cool off a user of the bed . conversely , the pad may include a heating element that may be used to keep the user warm . in various examples , temperature controller 308 receives temperature readings from the pad . in various examples , additional controllers may communicate with central controller 302 . these controllers may include , but are not limited to , illumination controllers for turning on and off light elements placed on and around the bed and outlet controllers for controlling power to one or more power outlets . in various examples , external network device 310 , remote controllers 312 , 314 and voice controller 316 may be used to input commands ( e . g ., from a user or remote system ) to control one or more components of architecture 300 . the commands may be transmitted from one of the controllers 312 , 314 , or 316 and received in central controller 302 . central controller 302 may process the command to determine the appropriate component to route the received command . for example , each command sent via one of controllers 312 , 314 , or 316 may include a header or other metadata that indicates which component the command is for . central controller 302 may then transmit the command via central controller 302 &# 39 ; s network interface to the appropriate component . for example , a user may input a desired temperature for the user &# 39 ; s bed into remote control 312 . the desired temperature may be encapsulated in a command data structure that includes the temperature as well as identifies temperature controller 308 as the desired component to be controlled . the command data structure may then be transmitted via bluetooth to central controller 302 . in various examples , the command data structure is encrypted before being transmitted . central controller 302 may parse the command data structure and relay the command to temperature controller 308 using a pan . temperature controller 308 may be then configure its elements to increase or decrease the temperature of the pad depending on the temperature originally input into remote control 312 . in various examples , data may be transmitted from a component back to one or more of the remote controls . for example , the current temperature as determined by a sensor element of temperature controller 308 , the pressure of the bed , the current position of the foundation or other information may be transmitted to central controller 302 . central controller 302 may then transmit the received information and transmit it to remote control 312 where it may be displayed to the user . in various examples , multiple types of devices may be used to input commands to control the components of architecture 300 . for example , remote control 312 may be a mobile device such as a smart phone or tablet computer running an application . other examples of remote control 312 may include a dedicated device for interacting with the components described herein . in various examples , remote controls 312 / 314 include a display device for displaying an interface to a user . remote control 312 / 314 may also include one or more input devices . input devices may include , but are not limited to , keypads , touchscreen , gesture , motion and voice controls . remote control 314 may be a single component remote configured to interact with one component of the mattress architecture . for example , remote control 314 may be configured to accept inputs to increase or decrease the air mattress pressure . voice controller 316 may be configured to accept voice commands to control one or more components . in various examples , more than one of the remote controls 312 / 314 and voice controller 316 may be used . with respect to remote control 312 , the application may be configured to pair with one or more central controllers . for each central controller , data may be transmitted to the mobile device that includes a list of components linked with the central controller . for example , consider that remote control 312 is a mobile phone and that the application has been authenticated and paired with central controller 302 . remote control 312 may transmit a discovery request to central controller 302 to inquiry about other components and available services . in response , central controller 302 may transmit a list of services that includes available functions for adjusting the firmness of the bed , position of the bed , and temperature of the bed . in various embodiments , the application may then display functions for increasing / decreasing pressure of the air mattress , adjusting positions of the bed , and adjusting temperature . if components are added / removed to the architecture under control of central controller 302 , an updated list may be transmitted to remote control 312 and the interface of the application may be adjusted accordingly . in various examples , central controller 302 is configured to analyze data collected by a pressure transducer ( e . g ., transducer 46 with respect to fig2 ) to determine various states of a person lying on the bed . for example , central controller 302 may determine the heart rate or respiration rate of a person lying in the bed . additional processing may be done using the collected data to determine a possible sleep state of the person . for example , central controller 302 may determine when a person falls asleep and , while asleep , the various sleep states of the person . in various examples , external network device 310 includes a network interface to interact with an external server for processing and storage of data related to components in architecture 300 . for example , the determined sleep data as described above may be transmitted via a network ( e . g ., the internet ) from central controller 302 to external network device 310 for storage . in an example , the pressure transducer data may be transmitted to the external server for additional analysis . the external network device 310 may also analyze and filter the data before transmitting it to the external server . in an example , diagnostic data of the components may also be routed to external network device 310 for storage and diagnosis on the external server . for example , if temperature controller 308 detects an abnormal temperature reading ( e . g ., a drop in temperature over one minute that exceeds a set threshold ) diagnostic data ( sensor readings , current settings , etc .) may be wireless transmitted from temperature controller 308 to central controller 302 . central controller 302 may then transmit this data via usb to external network device 310 . external device 310 may wirelessly transmit the information to an wlan access point where it is routed to the external server for analysis . fig4 is a block diagram of machine in the example form of a computer system 400 within which instructions , for causing the machine to perform any one or more of the methodologies discussed herein , may be executed . in alternative embodiments , the machine operates as a standalone device or may be connected ( e . g ., networked ) to other machines . in a networked deployment , the machine may operate in the capacity of a server or a client machine in server - client network environment , or as a peer machine in a peer - to - peer ( or distributed ) network environment . the machine may be a personal computer ( pc ), a tablet pc , a set - top box ( stb ), a personal digital assistant ( pda ), a cellular telephone , a web appliance , a network router , switch or bridge , or any machine capable of executing instructions ( sequential or otherwise ) that specify actions to be taken by that machine . further , while only a single machine is illustrated , the term “ machine ” shall also be taken to include any collection of machines that individually or jointly execute a set ( or multiple sets ) of instructions to perform any one or more of the methodologies discussed herein . the example computer system 400 includes a processor 402 ( e . g ., a central processing unit ( cpu ), a graphics processing unit ( gpu ), asic or a combination ), a main memory 404 and a static memory 406 , which communicate with each other via a bus 408 . the computer system 400 may further include a video display unit 410 ( e . g ., a liquid crystal display ( lcd ) or a cathode ray tube ( crt )). the computer system 400 also includes an alphanumeric input device 412 ( e . g ., a keyboard , touchscreen ), a user interface ( ui ) navigation device 414 ( e . g ., a mouse ), a disk drive unit 416 , a signal generation device 418 ( e . g ., a speaker ) and a network interface device 420 . the disk drive unit 416 includes a machine - readable medium 422 on which is stored one or more sets of instructions and data structures ( e . g ., software ) 424 embodying or utilized by any one or more of the methodologies or functions described herein . the instructions 424 may also reside , completely or at least partially , within the main memory 404 and / or within the processor 402 during execution thereof by the computer system 400 , the main memory 404 and the processor 402 also constituting machine - readable media . while the machine - readable medium 422 is shown in an example embodiment to be a single medium , the term “ machine - readable medium ” may include a single medium or multiple media ( e . g ., a centralized or distributed database , and / or associated caches and servers ) that store the one or more instructions or data structures . the term “ machine - readable medium ” shall also be taken to include any tangible medium that is capable of storing , encoding or carrying instructions for execution by the machine and that cause the machine to perform any one or more of the methodologies of the present invention , or that is capable of storing , encoding or carrying data structures utilized by or associated with such instructions . the term “ machine - readable medium ” shall accordingly be taken to include , but not be limited to , solid - state memories , and optical and magnetic media . specific examples of machine - readable media include non - volatile memory , including by way of example semiconductor memory devices , e . g ., erasable programmable read - only memory ( eprom ), electrically erasable programmable read - only memory ( eeprom ), and flash memory devices ; magnetic disks such as internal hard disks and removable disks ; magneto - optical disks ; and cd - rom and dvd - rom disks . the instructions 424 may further be transmitted or received over a communications network 426 using a transmission medium . the instructions 424 may be transmitted using the network interface device 420 and any one of a number of well - known transfer protocols ( e . g ., http ). examples of communication networks include a local area network (“ lan ”), a wide area network (“ wan ”), the internet , mobile telephone networks , plain old telephone ( pots ) networks , and wireless data networks ( e . g ., wifi and wimax networks ). the term “ transmission medium ” shall be taken to include any intangible medium that is capable of storing , encoding or carrying instructions for execution by the machine , and includes digital or analog communications signals or other intangible media to facilitate communication of such software . although an embodiment has been described with reference to specific example embodiments , it will be evident that various modifications and changes may be made to these embodiments without departing from the broader spirit and scope of the invention . accordingly , the specification and drawings are to be regarded in an illustrative rather than a restrictive sense . the accompanying drawings that form a part hereof , show by way of illustration , and not of limitation , specific embodiments in which the subject matter may be practiced . the embodiments illustrated are described in sufficient detail to enable those skilled in the art to practice the teachings disclosed herein . other embodiments may be utilized and derived therefrom , such that structural and logical substitutions and changes may be made without departing from the scope of this disclosure . this detailed description , therefore , is not to be taken in a limiting sense , and the scope of various embodiments is defined only by the appended claims , along with the full range of equivalents to which such claims are entitled . as it common , the terms “ a ” and “ an ” may refer to one or more unless otherwise indicated .

a method may comprise receiving , at a central controller , a command , from a remote control , to adjust a feature of a first component of an air mattress framework ; relaying , from the central controller , the command to the first component ; receiving from the first component at the central controller , an indication of the success of the command ; and relaying the indication from the central controller to the remote control .

microorganisms suitable for practicing the processes and procedures of the present invention described herein are exemplified by cultures now on deposit with the american type culture collection , 12301 parklawn drive , rockville , md . 20852 , usa . these cultures were deposited on the tenth day of november , 1983 , and are identified by atcc no . 39507 . prior to the above described deposit , strain kb - 1 was not available outside the research facilities of the joint inventors . forty - two different types of microorganisms were isolated from decaying peanut hulls utilizing water extracted hulls and four different lignin preparations isolated from peanut hulls as shown in table 1 , below . of this number , eleven were isolated from media containing water extracted hulls ( p - 1 , p - 2 , p - 4 through p - 6 , and p - 8 through p - 13 ), ten from media containing klason lignin ( k - 1 and k - 3 through k - 11 ), fourteen from media containing hydrochloric acid lignin ( h - 1 through h - 8 , h - 10 , n - 11 , and h - 14 through h - 17 ), four from media containing dioxane lignin ( d - 1 through d - 4 ), and four from media containing milled wood lignin ( m - 1 through h - 4 ). a majority of the isolates ( thirty ) grew on water extracted hulls and over half ( twenty - three ) grew on the milled wood lignin preparation . only eight of the isolates grew on dioxane lignin , but all of the isolates from the dioxane lignin culture grew on water extracted peanut hulls and three out of four grew on milled wood lignin . it is also interesting to note that very few of the isolates grew on klason lignin , with the exception of the microorganism originally isolated from the klason lignin cultures . only one microorganism isolate was capable of utilizing all five materials as a sole carbon source , although sixteen isolates grew on three of the five preparations . the preferred microorganism capable of growing on all five preparations was k - 7 . this isolate was redesignated kb - 1 to indicate that it was the only isolate capable of utilizing all five peanut hull preparations as a carbon source . when inoculated onto agar plates containing basal salts but without a carbon source , kb - 1 did not grow . when grown in the klason - lignin media for 24 hours at 26 ° c ., kb - 1 appeared as a gram positive , short , stubby rod that possessed a spore - like vacuole situated in the middle of the cell . this vacuole did not retain the gram stain , and thus appeared to be hollow . when kb - 1 was subjected to a spore stain , it failed to show any sign of a spore . when grown in nutrient broth at 26 ° c . in a shaking incubator for 24 hours and gram stained , kb - 1 appeared as a small , gram negative cocci with a few ( less than 1 %) larger cocci that were gram positive . biochemical testing of kb - 1 indicates that it can use a number of carbohydrates as carbon sources including glucose , maltose , xylose , mannose , and sucrose , but it is not capable of using lactose or arabinose as shown in table 2 , below . the inability to utilize arabinose as a carbon source was unexpected because arabinose is one of the primary carbohydrates found in peanut hulls . the microorganism kb - 1 is catalase positive , no 2 positive , and utilizes citrate , which are three of the main biochemical tests used in the identification of arthrobacter . although kb - 1 is gram positive during a portion of its life cycle , it is not sensitive to penicillin or ampicillin , but is extremely sensitive to chloramphenicol , sulfathiozol , tetracycline , and kanamycin . after ten days of incubation , kb - 1 mineralized ( degraded material to co 2 ) a significant fraction of the lignin ( 3 %) and polysaccharide ( 6 . 5 %) portion of spartina 14 c - lignocellulose . kb - 1 degraded the lignin and cellulosic portions of the lignocellulose simultaneously . rates of degradation were most rapid during the first six days of incubation . the 14 c - kraft lignin was mineralized at 30 % of the mineralization rate of 14 c -( lignin )- lignocellulose from spartina . the lignin portion of spartina lignocellulose has been reported to be mineralized approximately 4 to 6 times faster than kraft lignin by natural microbial populations found in salt marsh sediments ( hodson , r . e ., r . benner , and a . e . maccubbin , biodeterioration 5 , 185 - 195 , 1983 ; maccubbin , a . e ., r . benner , and r . e . hodson , biodeterioration 5 , 246 - 256 , 1983 ). in the presence of added cellulose , kb - 1 mineralized 14 c - kraft lignin at 67 % of the rate in the absence of added cellulose . table 1__________________________________________________________________________growth of microorganism isolates onminimal media with various carbon sources . sup . amicroorganism peanut hull . sup . b klason lignin hcl - lignin dioxane - lignin milled wood lignin__________________________________________________________________________p - 1 + - + - + p - 2 + - - - + p - 4 + + - - - p - 5 + - - - - p - 6 + - - - + p - 8 + - + + - p - 9 + - - - + p - 10 + - - - + p - 11 + - - - - p - 12 + - - - - p - 13 + - - - + k - 1 + + - - + k - 3 + + - - + k - 4 - - - - + k - 5 + + - - - k - 6 - + - - - k - 7 ( kb - 1 ) + + + + + k - 8 - + - - - k - 9 + - - - - k - 10 + + + - - k - 11 - + - - + h - 1 + - + - + h - 2 - + + + - h - 3 + - + - + h - 4 + - + - + h - 5 - + + + - h - 6 - + + + - h - 7 - - + - + h - 8 - - + - - h - 10 + - - - - h - 11 + - + - + h - 14 - - + - - h - 15 + - + - + h - 16 - - + - - h - 17 - - + - - d - 1 + - - + + d - 2 + - - + + d - 3 + - + - - d - 4 + - - + + m - 1 + - - - + m - 3 + - - - + m - 4 + - - - + __________________________________________________________________________ . sup . a several ( 7 ) isolates did not grow upon transfer to fresh media , an they were omitted from the table . . sup . b water extracted hulls table 2______________________________________dye sensitivity , antibiotic susceptibility , biochemical , and fermentation reactions of kb - 1______________________________________arginine dihydrolase - ampicillin - lysine decarboxylase - tetracycline ++ ornithine decarboxylase - chloramphenicol ++++ citrate + sulfathiozol +++ h . sub . 2 s - kanamycin ++ urease - novobiocin + tryptophane deaminase - polymyxin b + indole - neomycin + vp + vancomycin - gelatin - lactose - oxidase - mannitol - catalase + inositol - methyl red - sorbitol - maltose + gas rahmnose - glucose + sucrose + xylose + gas melobiose - mannose + gas amygdalin - sucrose + arabinose - dyes - sensitive motility - malachite green + fat hydrolysis - crystal violet + dnase activity - methyl green + starch hydrolysis - antibiotic susceptibility no . sub . 2 - streptomycin ++ n . sub . 2 + penicillin - blood agar gammarifampicin - gram stain + /- bacitracin - morphology variableerythromycin + rods / coccitsislant acidbase acidh . sub . 2 s - gas ++ ______________________________________ of the temperatures tested , maximal growth of the bacterium kb - 1 occurred at 26 ° c . data presented in table 3 , below , demonstrates the ability of the bacterium to grow rapidly on the peanut hulls before and after the various chemical treatments . growth on peanut hulls was comparable to growth in nutrient broth . on the untreated hulls and hulls treated with 2 % naoh or the acetic acid : nitric acid mixture , optimum growth occurred at ph9 . hulls treated with hcl , hno 3 , 1 % naoh , or calcium hypochlorite had optimal growth at ph7 ; whereas , hulls treated with h 2 so 4 , nh 4 oh , or 4 % naoh demonstrated optimal growth at ph5 . the chemical composition of peanut hulls after various chemical treatments at room temperature is given in table 4 . a marked increase in the relative percentage of protein in all cases was observed . the greatest increases were in peanut hulls treated with 4 % naoh , calcium hypochlorite , or the acetic acid - nitric acid mixture , all of which more than doubled the percentage of protein . a minor increase in the relative percentage of protein occurred when the hulls were treated with 1 % naoh or sulfuric acid . while chemical treatments increased the relative percentage of protein , such treatments decreased the relative percentage of lignin in each of the samples . the nitric acid treatment decreased the relative amount of measurable lignin in the hull by over 55 %, while 2 % naoh , 4 % naoh , or calcium hypochlorite decreased it by approximately 36 %. the other treatments decreased the lignin content by less than 25 %. the cellulose content of the treated peanut hulls varied from a relative loss of 46 % for peanut hulls treated with calcium hypochlorite to a relative increase of 58 % for hulls treated with nitric acid . in addition to calcium hypochlorite , sulfuric acid , and 4 % sodium hydroxide treatments reduced the relative percentage of cellulose in the hulls , while the other five treatments increased the relative percentage of cellulose by an average of 28 %. the amount of carbohydrate in the hulls decreased after all the treatments , especially sulfuric acid , hydrochloric acid , and ammonium hydroxide , which decreased the carbohydrate content to less than 1 mg per gram of peanut hull . of the remaining six ( 6 ) treatments , 4 % naoh caused the smallest loss of carbohydrate , 20 %, while the other five treatments effected less than a 50 % loss of carbohydrates . chemical analyses of the various treated and untreated hulls after growth of the bacterium kb - 1 for 24 hours are presented in table 5 . in comparison with the uninoculated peanut hulls as shown in table 2 , below , seven of the ten samples showed an increase in protein content . the most significant increase of protein content was in the untreated hulls which increased by over 100 %. hulls treated with sulfuric acid , 1 % naoh , 2 % naoh also significantly increased the percentage of protein by 82 %, 60 %, and 59 %, respectively . hulls treated with the acetic acid - nitric acid mixture decreased in the percentage of protein ( 52 %), followed by hulls treated with nitric acid ( 16 %) and 4 % naoh ( 15 %). the percentage of lignin decreased in six of the ten samples inoculated with the microorganism kb - 1 as shown in table 5 , below , in comparison with uninoculated hulls as shown in table 4 , below . untreated hulls decreased by 38 % in the percentage of lignin , while hulls treated with sulfuric acid , nitric acid , ammonium hydroxide , acetic acid - nitric acid mixture , or 1 % naoh decreased by less than 25 % in the percentage of lignin . hydrochloric acid , 2 % naoh , 4 % naoh , or calcium hypochlorite treated hulls increased in the percentage of lignin by 9 %, 12 %, 33 %, and 6 %, respectively . in comparison with uninoculated peanut hulls as shown in table 4 , below , after growth of the microorganism kb - 1 the percentage of cellulose remained approximately the same for untreated hulls and hulls treated with nitric acid , but decreased significantly for hulls treated with 1 % naoh , 2 % naoh , calcium hypochlorite , acetic acid - nitric acid mixture , or ammonium hydroxide . peanut hulls treated with hydrochloric acid , sulfuric acid , or 4 % naoh increased in the percentage of cellulose . the amount of carbohydrate decreased in the majority of samples except for the hulls treated with nitric acid , which demonstrated an increase of 18 %. two other samples retained a portion of their original carbohydrate , the peanut hulls treated with 4 % naoh and hulls treated with the acetic acid - nitric acid mixture . in an attempt to increase the protein content of the hulls after chemical treatment and growth of the microorganism kb - 1 , the yeast , saccharomyces cerevisiae , was added to each treatment and incubated for an additional 24 hours . chemical analyses of treatments after growth of s . cerevisiae are presented in table 6 , below . in most cases , the percentage of protein decreased after 24 hour incubation of s . cerevisine in comparison to the percentage of protein after growth of the microorganism kb - 1 . hulls treated with hno 3 or the acetic acid - nitric acid mixture did increase in the percentage of protein ( 30 % and 12 %, respectively ) after growth of s . cerevisiae . peanut hulls are very resistant to biodegradation , and they are only minimally digestible in rumen liquor ( kerr et al ., unpublished data ; barton , f . e ., h . e . amos , w . w . albrecht and d . burdick , j . anim . sci . 38 : 860 - 864 , 1974 ). certain chemical components of plant fiber , such as lignin , impede microbial degradation and thus , reduce digestibility of the material . peanut hulls contain more lignin ( 31 - 33 %) than most hardwoods and softwoods , and the low digestibility of hulls could result from the high lignin concentration . however , after several chemical delignification procedures at elevated temperatures , the digestibility of hulls has been found to decrease ( kerr et al ., unpublished data ; barton , f . e ., h . e . amos , w . w . albrecht and d . burdick , j . anim . sci . 38 : 860 - 864 , 1974 ). likewise , the relatively mild chemical treatments used in this study , which were effective in removing lignin , did not significantly increase the digestibility of the hulls ( except 4 % naoh , table 2 ). instead these treatments decreased digestibility by as much as 93 %. most of the chemical treatments also effectively increased the relative percentages of protein and cellulose in the hulls as shown in table 4 , below . the protein and cellulose portions of plant mateial are generally very digestible , and any relative increase in these components should increase digestibility . however , chemical treatments which increased the relative percentages of protein and cellulose actually decreased the digestibility of peanut hulls as shown in table 4 , below . the chemical treatments used in this study appear to remove the more labile , digestible components of peanut hulls without disrupting the structural integrity of the lignocellulosic fiber . pretreatment of hulls with hno 3 decreased the lignin concentration by 55 %, and increased the cellulose concentration by 58 %. the ratio of lignin to cellulose was 2 : 7 , but digestibility was still lower than digestibility of untreated hulls which had a lignin to cellulose ratio of approximately 1 : 1 . the chemical and physical complexing with the polysaccharide faction and between the remaining lignin and polysaccharide fractions appeared to be intact . after growth of the bacterium kb - 1 on hno 3 pretreated hulls , the ratio of lignin to cellulose dropped even lower to approximately 2 : 9 ( table 5 ). there was a dramatic increase in digestibility from 14 . 9 % to 63 . 2 %, an increase of over 400 %. this compares favorably to commercially available hay . all other treatments effected much higher lignin to cellulose ratios , and they all decreased in digestibility after growth of the microorganism kb - 1 as shown in table 5 , below . treatment with hno 3 appears to remove the &# 34 ; protective &# 34 ; lignin and expose the remaining bonds between the lignin and cellulose to bacterial exoenzymes . more recent tests of the present invention have shown that the autoclaving steps are not necessary . by eliminating such steps digestibility may be increased above the 60 % level . in addition several strains of microorganism ( university of georgia , dept . of microbiology , stock cultures of bacillus subtilis , klebsiella pneumoniae , and escherichia coli ) and a natural soil inoculum failed to increase the protein digestibility of hno 3 treated peanut hulls . the growth of the yeast , s . cerevisiae , on hno 3 treated peanut hulls did not significantly increase protein digestibility as shown in table 6 , below ; therefore , such growth step with yeast is not necessary . therefore a prolonged incubation of the microorganism kb - 1 can be utilized to increase the amount of protein and increase digestibility . table 3______________________________________growth of arthrobacter kb - 1 at 26 ° c . ( cfus ) treatment ph 5 ph 7 ph 9______________________________________nutrient broth 4 . 67 × 10 . sup . 9 2 . 52 × 10 . sup . 9 5 . 15 × 10 . sup . 9untreated hulls 1 . 56 × 10 . sup . 9 1 . 55 × 10 . sup . 9 2 . 61 × 10 . sup . 9hcl 1 . 81 × 10 . sup . 9 1 . 01 × 19 . sup . 10 2 . 31 × 10 . sup . 9h . sub . 2 so . sub . 4 1 . 07 × 10 . sup . 10 2 . 3 × 10 . sup . 9 1 . 7 × 10 . sup . 9hno . sub . 3 1 . 75 × 19 . sup . 9 1 . 15 × 19 . sup . 10 3 . 2 × 10 . sup . 8nh . sub . 4 oh 1 . 18 × 10 . sup . 10 3 . 0 × 10 . sup . 9 1 . 2 × 10 . sup . 91 % naoh 4 . 5 × 10 . sup . 8 1 . 0 × 10 . sup . 9 6 . 6 × 10 . sup . 82 % naoh 1 . 0 × 10 . sup . 9 8 . 3 × 10 . sup . 8 1 . 87 × 10 . sup . 94 % naoh 1 . 14 × 10 . sup . 9 7 . 7 × 10 . sup . 8 2 . 6 × 10 . sup . 8ca . hypochlorite 0 . 1 × 10 . sup . 8 1 . 8 × 10 . sup . 9 1 . 6 × 10 . sup . 9acetic acid - hno . sub . 3 5 . 7 × 10 . sup . 8 9 . 3 × 10 . sup . 8 1 . 2 × 10 . sup . 10______________________________________ table 4______________________________________chemical composition and digestibilityof chemically treated peanut hulls cellu - carbo - protein lignin lose hydrate digestibilitytreatment (%) (%) (%) ( mg / gram ) (%) ______________________________________untreated 6 . 5 31 . 1 32 . 0 17 . 5 17 . 52hullshcl 10 . 2 23 . 4 40 . 0 1 . 0 1 . 20h . sub . 2 so . sub . 4 7 . 4 28 . 8 28 . 0 1 . 0 1 . 24hno . sub . 3 12 . 5 13 . 9 50 . 5 10 . 0 14 . 911 % naoh 7 . 5 24 . 2 42 . 0 10 . 4 14 . 072 % naoh 9 . 1 19 . 9 40 . 0 12 . 0 16 . 854 % naoh 14 . 2 19 . 9 30 . 5 14 . 0 18 . 91ca . hypo - 13 . 1 20 . 1 17 . 0 9 . 2 16 . 72chloriteacetic 14 . 2 27 . 6 40 . 0 11 . 1 7 . 51acid - hno . sub . 3nh . sub . 4 oh 10 . 5 25 . 9 43 . 0 1 . 0 4 . 14______________________________________ table 5______________________________________chemical composition and digestibility of chemicallytreated peanut hulls after growth of arthrobacter kb - 1 cellu - carbo - protein lignin lose hydrate digestibilitytreatment (%) (%) (%) ( mg / gram ) (%) ______________________________________untreated 14 . 0 19 . 3 32 . 0 1 . 0 8 . 56hcl 14 . 0 25 . 5 48 . 5 1 . 0 1 . 74h . sub . 2 so . sub . 4 13 . 5 21 . 9 35 . 5 1 . 0 0 . 47hno . sub . 3 10 . 5 10 . 7 50 . 0 11 . 8 63 . 221 % naoh 12 . 0 23 . 6 26 . 0 1 . 0 7 . 372 % naoh 14 . 5 22 . 3 22 . 8 1 . 0 10 . 474 % naoh 12 . 0 26 . 4 40 . 2 5 . 2 9 . 55ca . hypo - 17 . 5 21 . 4 8 . 0 1 . 0 11 . 52acetic 6 . 8 24 . 8 16 . 0 7 . 0 7 . 45acid - hno . sub . 3nh . sub . 4 oh 11 . 4 19 . 9 36 . 5 1 . 0 1 . 59______________________________________ table 6______________________________________protein content and digestibility of chemically treatedpeanut hulls after growth of arthrobacter kb - 1 and s . cerevisiaetreatment protein (%) digestibility (%) ______________________________________untreated hulls 12 . 7 9 . 07hcl 9 . 0 2 . 09h . sub . 2 so . sub . 4 8 . 2 0 . 86hno . sub . 3 13 . 6 63 . 321 % naoh 5 . 6 9 . 472 % naoh 7 . 8 12 . 864 % naoh 9 . 8 11 . 14ca . hypochlorite 17 . 5 13 . 24acetic acid - hno . sub . 3 7 . 6 9 . 07nh . sub . 4 oh 8 . 5 5 . 84______________________________________ peanut hulls were supplied by the columbian peanut company of ozark , ala ., and stevens industries , dawson , ga . the peanut , arachis hypogeae , was of the florunner variety and was hammer milled to 1 / 4 &# 34 ; in size . hammer milling to less than 1 / 4 &# 34 ; in size is also acceptable . before use as a growth substrate , peanut hulls were extracted with boiling water for 1 hour ( 4 changes of water during extraction ), and dried for 24 hours at 70 ° c . lignin was isolated from peanut hulls by four different procedures : 1 . dioxane lignin -- 1 / 4 &# 34 ; hammer milled peanut hulls were extracted in a soxhlet extractor for 50 hours with a boiling ethanol - benzene ( 1 : 1 ) and dried in a vacuum dissicator . extractive - free hulls were then extracted for 12 hours with boiling dioxane - water ( 9 : 1 ) containing the equivalent of 0 . 2n hcl . the extract was concentrated under vacuum and the lignin was precipitated in deionized distilled water . the precipitated lignin was washed with water three times , dried , and washed with petroleum ether ( browning , b . l ., 1967 . methods of wood chemistry , vol . ii . interscience publishers , inc .). 2 . milled wood lignin -- 1 / 4 &# 34 ; hammer milled peanut hulls were extracted with boiling ethanol - benzene ( 1 : 2 ) for 48 hours , and then with 95 % ethanol for 24 hours . extractive - free hulls were ball milled for 9 days . milled hulls were extracted with boiling dioxane - water ( 9 : 1 ) for 12 hours . the solvent was concentrated under vacuum , and the lignin was precipitated in water . the precipitated lignin was thoroughly washed with petroleum ether ( browning , b . l ., 1967 . methods of wood chemistry , vol . ii . interscience publishers , inc .). 3 . klason lignin -- extractive - free hulls ( as described above ) were treated with 72 % sulfuric acid at 15 ° c . for 2 hours . the mixture was diluted with water to a 3 % acid concentration and refluxed for 4 hours . the residue was washed thoroughly with water ( browning , b . l ., 1967 . methods of wood chemistry , vol . ii . interscience publishers , inc .). 4 . hydrochloric acid lignin -- 1 / 4 &# 34 ; hammer milled hulls were treated with hydrochloric acid ( sp gr 1 . 19 at 5 ° c .) at 5 ° c . for 2 hours in a shaking incubator . the temperature was allowed to rise to room temperature . ice was added to the mixture which was allowed to stand for 18 hours . the precipitate was washed with boiling water , filtered , and dried ( browning , b . l ., 1967 . methods of wood chemistry , vol . ii . interscience publishers , inc .). lignin and peanut hulls ( extracted with boiling water ) were used at a concentration of 0 . 5 g per liter in both solid and liquid media . hulls used in liquid media were ball milled to pass through a 0 . 1 mm sieve . lignins and hulls used in solidified media were dissolved in 0 . 25n naoh ( 0 . 5 g hulls : 10 ml naoh ), filtered , and added to sterile basal media ( 7 g k 2 hpo 4 , 3 g kh 2 po 4 , 1 g ( nh 4 ) 2 so 4 , 0 . 1 g mgso 4 . 7h 2 o per liter of tap water ). an equivalent amount of sterile 0 . 25n hcl was added to the sterile media . the smooth cordgrass , spartina alterniflora , was specifically labelled in the lignin or cellulosic components by feeding cuttings l -[ u - 14 c ] phenylalanine or d -[ u - 14 c ] glucose through their cut stems ( crawford , d . l ., r . l . crawford and a . l . pometto , iii , appl . environ . microbiol . 33 : 1247 - 1251 , 1977 ; maccubbin , a . e . and r . e . hodson , appl . environ . microbiol . 40 : 735 - 740 , 1980 ). the labelled material was dried and ground to pass a 40 - mesh screen . the plant material was then serially extracted in boiling ethanol , ethanol - benzene ( 1 : 2 ), and water ( maccubbin , a . e . and r . e . hodson , appl . environ . microbiol . 40 : 735 - 740 , 1980 ). extractive - free lignocellulose was collected on a glass fiber filter , washed with ethanol , and dried at 55 ° c . the 14 c - labelled lignocelluloses were characterized for the distribution of 14 c between the lignin and polysaccharide components by a klason hydrolysis as previously described ( maccubbin , a . e . and r . e . hodson , appl . environ . microbiol . 40 : 735 - 740 , 1980 ). samples of 14 c - lignocellulose were also digested in the protease , pepsin , to determine the percentage of radiolabel possibly associated with protein ( maccubbin , a . e . and r . e . hodson , appl . environ . microbiol . 40 : 735 - 740 , 1980 ). the specific activities of 14 c - lignocelluloses were determined by combusting 10 mg samples in a r . j . harvey biological oxidizer and trapping the released 14 co 2 is a liquid scintillation medium ( maccubbin , a . e . and r . e . hodson , appl . environ . microbiol . 40 : 735 - 740 , 1980 ). the lignin labelled spartina lignocellulose had a specific activity of 23 , 238 dpm per mg , 70 . 9 % of the label was recovered in the klason lignin fraction , and 19 . 0 % of the label was solubilized during pepsin digestion . the polysaccharide labelled spartina lignocellulose had a specific activity of 6 , 889 dmp . per mg ., 61 . 9 % of the label was recovered in the acid - soluble fraction , and 21 . 9 % of the label was solubilized during pepsin digestion . wood from the slash pine , pinus elliottii , was labelled in the lignin component using the methods described above for labelling spartina . the lignin labelled pine lignocellulose had a specific activity of 2 , 825 dpm per mg , 90 % of the label was recovered in the klason lignin fraction , and 2 . 8 % of the label was solubilized during pepsin digestion . after extracting the wood to remove unincorporated label , the 14 c -( lignin )- lignocellulose was &# 34 ; pulped &# 34 ; using a laborator - scale kraft pulping system ( chang , h . and k . v . sarkanen , tappi 56 : 132 - 134 , 1973 ; crawford , d . l ., s . floyd , a . l . pometto , iii , and r . l . crawford , can . j . microbiol . 23 : 434 - 440 , 1977 ; maccubbin , a . e ., r . benner and r . e . hodson , biodeterioration 5 , p . 246 - 256 , 1983 ). the 14 c - lignocellulose was heated to 160 ° c . for 4 hours in kraft pulping liquor ( 1 : 25m naoh and 0 . 25m na 2 s ). after cooling , the mixture was filtered and 14 c - kraft lignin was precipitated from the pulping liquor by acidification to ph 2 . the precipitated lignin was centrifuged and washed with deionized water ( 3 times ). the specific activity of the 14 c - kraft lignin was 2 , 904 dpm per mg . decaying peanut hulls were obtained from the bottom of a peanut hull pile situated on a farm in salem , ala . the hulls had been weathered in the open for approximately 5 years and showed signs of physical degradation . five ( 5 ) 250 ml flasks were prepared , each containing 100 mls of basal salts solution and 50 mg of hulls or one of the four ( 4 ) lignins . approximately 10 ml of decaying hulls were placed in 100 mls of sterile saline and shaken for 5 minutes . one ( 1 ) ml aliquots were used to inoculate the five ( 5 ) 250 ml flasks . the flasks were incubated at 26 ° c . for 24 hours in a shaking incubator , then 0 . 1 ml aliquots were used to inoculate agar plates containing basal salts and hulls or one of the lignin preparations . plates were incubated for 24 hours at 26 ° c . each colony was picked and streaked on five ( 5 ) agar plates containing basal salts media and one of the five ( 5 ) substrates ( hulls or lignins ) used as carbon sources . the microorganism strain , kb - 1 , that grew on all five ( 5 ) carbon sources was tested for its sensitivity to various dyes , antibiotics , and biochemical reactions as described herein . see table 2 . the bacterial isolate capable of growing on all four lignin preparations as well as water extracted hulls was grown overnight ( shaking , 26 ° c .) in basal salts media containing spartina lignocellulose . after permitting the larger lignocellulose particles to settle , 20 ml portions were added to 125 ml milk dilution bottles containing 10 mg of one of the following : 14 c -( lignin )- lignocellulose from spartina , 14 c -( cellulose )- lignocellulose from spartina , or 14 c - kraft lignin degradation , 20 mg of alpha cellulose were added to one set of bottles . bottes were incubated in duplicate , in the dark , at 30 ° c . with shaking ( 125 rpm ). controls were killed with 5 % formalin . mineralization of the radiolabelled substrates was monitored every 48 hours by trapping the evolved 14 co 2 in a series of two scintillation vials containing liquid scintillation counting medium ( maccubbin , a . e . and r . e . hodson , appl . environ . microbiol . 40 : 735 - 740 , 1980 ). water - soluble 14 c present in the incubations containing 14 c - lignocellulose from spartina was quantified by filtering the contents of the bottle through 1 m nuclepore filters , acidifying the filtrate to remove 14 co 2 , and assaying 1 ml portions for radioactivity . all chemical utilized in the treatment , extraction , and analysis of peanut hulls were reagent grade and were obtained from either fisher chemical co ., norcross , ga ., or sigma chemical co ., st . louis , mo . radioisotopes , d -[ u - 14 c ]- glucose and l -[ u - 14 c ]- phenylalanine were obtained from new england nuclear corp ., boston , mass . peanut hulls utilized in this study were supplied by the columbian peanut company , ozark , ala ., and the damascus peanut company , damascus , ga . the peanut ( arachis hypogeae ) from which the hull was obtained was the florunner variety . hulls were hammer - milled to 1 / 4 &# 34 ; in size . all chemicals used were reagent grade and were obtained from sigma chemical company , st . louis , mo ., or fisher scientific company , norcross , ga . the microorganism kb - 1 was grown for 16 hours in 100 mls of a basal salt solution ( 7 . 0 g k 2 hpo 4 , 3 . 0 g kh 2 po 4 , 1 . 0 g nhso 4 , 0 . 1 g mgso 4 . 7h 2 o ) containing 5 g of hammer milled peanut hulls that had been extracted twice with hot water and then oven dried at 70 ° for 24 hours . the culture was grown in a shaking incubator at 25 ° c . the culture was removed from the incubator and allowed to stand for 1 hour , permitting the peanut hulls to settle to the bottom . the liquid was pipeted off , placed in sterile centrifuge tubes , centrifuged in a sorvall table top centrifuge at 1725 rpm for 15 minutes , washed one time with sterile saline , then resuspended in 100 mls of sterile saline . one ( 1 ) liter portions of hammer milled peanut hulls ( approximately 255 g ) were soaked for one ( 1 ) hour at room temperature ( 25 ° c .) in two ( 2 ) liters of one of the following solutions : 0 . 5n hydrochloric acid , 0 . 5n nitric acid , 0 . 5n sulfuric acid , 0 . 5n ammonium hydroxide , 1 % sodium hydroxide , 2 % sodium hydroxide , 4 % sodium hydroxide , 1m calcium hypochlorite , or 80 % acetic acid : conc . nitric acid ( 1 : 10 ). after treatment , hulls were thoroughly rinsed three ( 3 ) times in tap water . nine ( 9 ) flasks of each treatment were prepared by adding 50 mls of wet hulls to 100 mls of basal salts media ( as above ). of the nine flasks , triplicates of each treatment were adjusted to ph 5 , 7 , or 9 with 1n naoh and 1n hcl . the flasks were then autoclaved for 15 minutes at 15 psi , cooled , and inoculated with 0 . 5 ml of kb - 1 inoculum . one ( 1 ) flask of each treatment adjusted to ph 5 , 7 , or 9 was incubated for 24 hours at 26 °, 30 °, or 45 ° c . in a shaking incubator . after 24 hours , dilutions of the cultures were made into sterile saline and spread plates on nutrient agar were prepared . plates were incubated at room temperature for 20 hours and colonies counted . four ( 4 ) samples of each treatment were prepared by placing 100 mls of wet hulls into a 500 ml erlenmeyer flask and adding 100 mls of basal salts solution . the ph was adjusted for optimal growth and flasks were inoculated with 0 . 5 ml of the microorganism kb - 1 , prepared as described above . all flasks were incubated at 26 ° c . for 24 hours in a shaking incubator . after 24 hours , two flasks of each treatment were autoclaved for 15 minutes at 15 psi , cooled , filtered through cheese cloth and dried at 70 ° c . for 24 hours . the other two flasks from each treatment were inoculated with 0 . 5 mls of s . cereviseae which had been grown overnight in sabouraud dextrose broth on a shaking incubator at 26 ° c ., centrifuged at 1725 rpm for 15 minutes in a sorvall table top centrifuge , washed one time in sterile saline , and then resuspened in 100 mls of sterile saline . flasks were incubated for an additional 24 hours at 26 ° c . in a shaking incubator , autoclaved for 15 minutes at 15 psi , cooled , filtered through cheese cloth and dried at 70 ° c . for 24 hours . samples of the ( 1 ) chemically treated hulls , ( 2 ) chemically treated hulls used as a substrate for the microorganism kb - 1 , and ( 3 ) chemically treated hulls used as a substrate for the microorganism kb - 1 and s . cereviseae were analyzed for protein , cellulose , lignin , total carbohydrate , and digestibility . samples were analyzed for protein by the kjeldhal method ( aoac , official mcmeds of analysis , 12th ed ., 1979 , p . 927 - 928 , association of official analytical chemists , washington , d . c . ), for cellulose by the updergraff method ( updegraff , d . m ., anal . biol . 32 : 420 - 424 , 1969 ), for lignin by a modified klason method ( effland , m . j ., tappi 60 : 143 - 144 , 1977 ), and for in vitro dry matter digestibility ( ivdmd ) by the tilley and terry method ( tilley , j . m . a . and r . a . terry , j . brit . grass soc . 18 : 104 - 111 , 1963 ), wherein all such methods are known in the art . a solid innoculum is prepared for the microorganism kb - 1 comprising the microorganism kb - 1 and a solid carrier containing standard nutrient growth medium . a liquid innoculum is prepared for the microorganism kb - 1 comprising the microorganism kb - 1 and an aqueous carrier containing a standard nutrient growth medium . the microorganism kb - 1 is capable of degrading lignin from any organic material having a high lignocellulose content wherein the organic material is from a natural source such as a plant . a high lignocellulose content is a lignin content of 20 % or greater of the organic material and a cellulose content of 20 % or greater of the organic material . the microorganism kb - 1 is capable of degrading lignin from peanut hulls , softwoods , hardwoods , pulp wood , slash pine , cordgrass , barley hulls , cotton seed hulls , wheat straw , and the like . such organic material having a high lignocellulose content , peanut hulls , wheat straw , barley hulls , cotton seed hulls and the like are converted into animal feed wherein digestibility is increased by degrading the lignin therein utilizing the microorganism kb - 1 . chemical pretreatment improves the production of such animal feed wherein nitric acid is the preferred chemical for chemical pretreatment . the microorganism kb - 1 degrades lignin with maximum efficiency and growth of the microorganism at 26 ° c . the foregoing illustrates specific embodiments within the scope of this invention and is not to be construed as limiting said scope . while the invention has been described herein with regard to a certain specific embodiment , it is not so limited . it is to be understood that variations and modifications thereof may be made by those skilled in the art without departing from the scope of the invention .

a newly discoverd microorganism having characteristics of an arthrobacter and having the ability to utilize peanut hull lignin as a sole source of carbon is disclosed . peanut hulls have a higher lignin content than hardwoods and softwoods . the newly discovered microorganism makes the biodegradation of peanut hulls and other similar lignin containing biological waste products commercially feasible . specifically , a process for converting peanut hulls and other similar lignin containing biological waste products to animal feed is disclosed .

the medical inhaler shown in fig1 has a separate dosing unit 21 , which can be inserted into a housing 22 which also receives a conveyor 2 , a vibrator 3 and a process control means 15 , the dosing unit being removable at will . a cover 29 snaps on to the front of housing 22 and is removable before use . dosing unit 21 , shown separately in fig2 and 3 , comprises a reservoir 1 which houses a pre - filled ampoule 10 , the ampoule having a movable plunger 11 and containing the liquid medicine , the plunger being entered by one end of a threaded rod 13 . an annular pawl 26 of reservoir 1 is inserted into and latches in an annular cavity 25 of an adapter head 18 which carries a feed line 4 . in the inactive position shown in fig2 the pre - filled ampoule 10 still is entirely intact and therefore its shelf life remains undegraded . when , by means of a rotary or translational axial displacement , reservoir 1 containing pre - filled ampoule 10 is forced into annular cavity 25 of adapter head 18 , then an ampoule membrane 24 is pierced by an inner end 23 of feed line 4 which points toward reservoir 1 and , as a result , the liquid medicine can flow from ampoule 10 into feed line 4 . dosing unit 21 thus activated , as shown in fig3 can be inserted in non - rotatable manner into housing 22 ( fig1 ). a geared link 17 at the opposite end of the threaded rod 13 then meshes with an output gear 27 of a drive unit 28 of conveyor 2 . gear 27 in turn meshes with a gear 20 of drive unit 28 which is actuated by power unit 12 , preferably an electric motor . the distal outlet end 6 of feed line 4 is positioned in this process through an aperture 27 in a nozzle 19 into an accurately predefined location directly above a vibrator 3 . vibrator 3 is piezoelectric and generates ultrasonic vibrations . a suitable ultrasonic vibrator is described in european patent document b1 246 , 515 . as shown by fig1 conveyor 2 comprises power unit 12 and drive unit 28 . two batteries 16 provide energy for both the power unit 12 and the electronic process control means 15 . this process control 15 , which preferably is a programmable microprocessor , controls power unit 12 and vibrator 3 , and its operation is initiated by pressing an actuation button 14 ( which in more elaborate applications may be replaced by a keypad ). the european patent document b1 143 , 895 describes a dosing unit part of the conveyor which is suitable for the inhaler of the invention and which consists of a spindle - nut gear unit of which the output member consists primarily of a drive bushing rotatably resting in the inhaler housing and the output member by the spindle . the drive bushing is coaxial with a fastener for the pre - filled ampoule in the housing and the spindle is coaxially insertable into the drive bushing . part of the housing adjoining the fastener secures the nut against axial displacement and keeps it non - rotatably in place . the spindle is non - rotatable , but longitudinally displaceable inside the drive bushing so that it can be advanced by drive - bushing rotation into the fastener to directly advance the plunger of a pre - filled ampoule . the feed line 4 ending directly above the vibrator 3 is sealed in an airtight manner when in the rest position , as shown in fig4 . end 6 of feed line 4 facing vibrator 3 is sealed and has only one aperture 7 in the side of the feed line which is sealed by an elastic membrane 8 in the form of a rubber tubing , preferably silicone rubber , slipped over end 6 of the feed line . this combination forms a valve 5 which is automatically closed in the rest state and which opens automatically in the operational state by liquid pressure . when conveyor 2 is actuated , liquid medicine is moved from reservoir 1 , through feed line 4 and to vibrator 3 . the design of conveyor 2 is such that it generates an operational pressure of 0 . 01 to 5 . 00 bars , preferably between 0 . 5 and 1 . 0 bars , in the pre - filled ampoule . fig5 shows an alternative embodiment wherein the end of feed line 4 ending directly above vibrator 3 comprises a capillary discharge aperture 9 through which liquid moved by the conveyor 2 out of reservoir 1 and through feed line 4 is dispensed to vibrator 3 . a patient uses the inhaler in such a way that inhaler nozzle 19 is moved close to the patient &# 39 ; s mouth . pressing an actuation button 14 electrically actuates control processor means 15 and initiates operation of both conveyor 2 ( with power unit 12 and drive unit 28 ) and vibrator 3 . vibrator 3 may be actuated either simultaneously with conveyor 2 or with a positive or negative delay . by means of the two gears 20 , 27 and gear connector 17 , drive unit 28 drives drive rod 13 which is displaced upwards , axially forcing plunger 11 of ampoule 10 upward and moving liquid medicine into feed line 4 . elastic membrane 8 , slipped over end 6 of feed line 4 , is radially widened at aperture 7 , allowing liquid medicine to discharge and form into a droplet at end 6 of feed line 4 , said droplet being atomized by the high - frequency vibrations of vibrator 3 and being released by nozzle 19 . by pressing the actuation knob 14 and simultaneously inhaling at the nozzle 19 , the lung - destined medicine reaches the patient &# 39 ; s respiratory tract in a controlled manner . when a microprocessor is used as process control means 15 , actuation knob 14 can be converted into a multi - function keypad and , where called for , be equipped with programming . in this manner preselected quantities of atomized medicine can be discharged . on the other hand , different types of dosing units 21 may be employed to dispense different types and quantities of medicines using the same housing 22 , the individual dosing units 21 being disposable in such cases .

a medical inhaler generates an aerosol of pharmaceutically effective medication to be absorbed by the respiratory tract of a patient includes a reservoir of liquid medication , a conveyor to expel the liquid from the reservoir , an atomizing vibrator and a feed line to conduct the liquid between the reservoir and the vibrator . the conveyor and the vibrator can be controlled by a process controller which can include a microprocessor . discharge of liquid medicine is both coordinated with the vibrator and accurately dosable and achieves optimal atomization of the medicine .

before discussing certain practical embodiments of the present invention , the efficacy of the principles of the present invention will be described with reference to an experimental arrangement shown in fig1 . the experimental apparatus comprises an excitation source 1 in the form of a solid - state frequency doubled laser with 200 mw output power at a wavelength of 457 nm . the laser light is delivered to the sample surface through an illumination optics comprising a multimode optical fiber 2 of 20 μm in diameter , a linear polarizer 3 and microlenses 4 ( 1 . 6 mm in diameter ). the fluorescence and reflection signals from a sample 5 are collected by a standard endoscope 6 and imaged to an 8 - bit ccd camera 7 . the angle between the optical axes of the illumination optics and of the endoscope is about 15 ° . the distal tips of the endoscope and of the illumination optics are physically attached to each other and are about 10 mm away from the surface of the sample . the imaged area on the sample surface is about 10 mm × 10 mm and is smaller than the illuminated area . to vary the illumination and collection geometry in order to simulate clinical use , the sample may be rotated about an axis perpendicular to the surface of the sample and passing through the intersection of the illumination and collection optical axes . light collected from the sample is passed through either a long pass filter 8 or a cross - polarizer 9 that is at 90 ° to the polarizer 3 in the illumination optics . cross - polarizer 9 and long pass filter 8 may be interchanged in the collection optics to select either a cross - polarized image or a fluorescence image respectively , the images being grabbed by a frame grabber at a rate of 25 frames per second . to improve the signal to noise ratio , the fluorescence image is formed from an average of 16 frames . as will be explained in more detail below , to compensate for geometrical and illumination irregularities , the fluorescence image is normalised by reference to the cross - polarized image in a computer . the signal to noise ratio of the normalised image is dependent on the quality of the fluorescence and cross - polarized images . to improve the quality of the image by reducing the effects of the “ speckle effect ” on the quality of the images , apart of the illumination optics may be driven by a voice coil 10 to introduce a modulation that has the effect of changing the speckle pattern into a time - varying function that can be averaged out if the modulation frequency is set at about 600 hz . to experimentally demonstrate the efficacy of the present invention , tissue - simulating samples may be constructed made of gelatin with 20 % solids dissolved in boiling deionized water , polystyrene spheres of 0 . 55 μm in diameter , fluorescent dye mixture and dominantly absorbing blood . the samples are made in accordance with well documented procedures . to demonstrate that the present invention is capable of correcting for geometrical effects , six samples are made in accordance with table 1 below . all the samples are homogenous and have a flat surface as shown in fig2 . the imaging geometry was changed by rotating the sample and by changing the illumination angle θ between 0 ° and 60 ° in increments of 15 °. for a fair comparison , the mean gray levels of the raw fluorescence images and the normalised images were adjusted to 128 , ie half the full gray level of an 8 - bit image . fig3 shows a raw fluorescence image and a corresponding grey level histogram . as can be seen from both the raw image and the histogram , the image is highly non - uniform and the gray levels vary widely in range , in spite of the fact that the sample is homogenous and the surface of the sample is flat . fig4 shows the corresponding image and grey level histogram when the raw fluorescence image has been normalized by taking the ratio of the raw fluorescence image with the cross - polarized image . it will be seen that the image is uniform and there grey level has a very narrow distribution around 128 . over the varying illumination angles , the standard deviations of the gray levels in the raw fluorescence images vary from 24 to 41 , while the standard deviations of the ratio images vary from 1 . 8 to 4 . 5 . the samples in table 1 are all homogenous and have a flat surface . inhomogenity in the raw fluorescence images therefore results from geometrical factors in the imaging and collection optics and the results shown in fig3 and 4 show that the present invention is able to effectively compensate for such geometrical factors . fig5 shows an homogenous sample ( blood content 5 % v / v polystyrene content 0 . 35 % w / w ) made with an irregular surface . fluorescence and cross - polarized images are taken at θ = 0 ° and the raw fluorescence and ratio images and gray level line profiles are shown in fig6 and 7 respectively . it can be seen that the inhomogenity in the raw fluorescence image ( fig6 ) is corrected in the normalised ratio image ( fig7 ). to demonstrate that the present invention can detect small variations in fluorescence yield , such as might be caused to tissue by the early stages of diseases such as cancer , inhomogeneous tissue simulating samples were prepared . fig8 shows a first form of tissue simulating sample used in this manner . in this figure , the shaded areas represent areas of the sample where the sample forming mixture has been replaced by a mixture of slightly lower concentration of fluorescent dyes to simulate lesions . the areas are set to give a fluorescence yield of approximately 80 % of the remainder of the tissue simulating sample . the blood concentration and microsphere concentration were set at 5 % and 0 . 35 % respectively . two holes of smooth walls were also constructed to function as artifacts to determine the ability of the present invention to distinguish between areas of lower fluorescence yield and artifacts . fig9 shows the raw fluorescence image and the corresponding line profiles , while fig1 shows the corresponding image normalised by the cross - polarized image together with the corresponding line profile . it will be noted that the raw image in fig9 is incapable of differentiating between the two images of reduced fluorescence yield ( top left and bottom right in the figure ) and the geometric artifacts created by the two holes ( top right and bottom left ). in contrast the normalised image shown in fig1 shows only the areas where a reduced fluorescence yield has been created . in the embodiment shown in fig1 separate illumination and collection optical systems are provided closely adjacent each other . in a real - life clinical situation , however , it would be preferable for the illumination / excitation optics and the collection optics to be integrated into a single endoscopic apparatus . an example of such an apparatus is shown in fig1 . the apparatus comprises a rigid or flexible endoscope 20 comprising two optical channels 21 , 22 . a first optical channel 21 is formed extending along the central axis of the endoscope and comprises the imaging channel for collecting the image of the tissue and returning the image to collection optics shown in the right of the picture and which will be described further below . surrounding the imaging channel 21 is an annular illumination channel 22 . the illumination channel 22 creates polarized light from a remote light source and is used to illuminate the tissue and for eliminating the specular reflection . the imaging optics may , as in the embodiment of fig1 comprise a sensor such as a ccd camera and a computer provided with a frame grabber and means for digitally processing the imaged data . an external cross - polarizer or long pass filter 23 may be provided between the end of the endoscope 20 and the imaging optics . the cross - polarizer has a polarization at 90 ° to the polarization of the illumination light . the polarizer 23 may be moved into a position in which it is in the optical path between the endoscope 20 and the imaging optics so as to provide the cross - polarized image . the polarizer 23 may be removed from the path and replaced with a long pass filter so as to enable the raw fluorescence data to be recorded . fig1 shows an alternative embodiment in which instead of requiring the cross - polarizer to be moved into and out of the optical path , a beam splitter 30 in the form of a dichroic mirror is used to direct part of the beam to a cross - polarizer 31 to form the cross - polarized image . fig1 shows a modification of the distal tip of an endoscope which can be either rigid or flexible . two polarizers with polarization directions perpendicular to each other are placed at the tip of the illumination channel and imaging channel . the external imaging optics for recording the cross - polarized image and the fluorescence is the same as shown in fig1 , the only difference being that the external cross - polarizer is removed .

fluorescence imaging of tissue is used as a diagnostic tool in which geometric effects and specular reflections are compensated for by normalizing a fluorescence image with a cross - polarized image .

referring now to fig1 of the drawing , there is shown the surgical cutting instrument 9 connected to a temperature - measuring and power - controlling system 11 . the cutting instrument 9 includes a thin ceramic card 12 in the desired shape of a surgical cutting blade which is detachable from the handle or holder 10 . an electrically heated element 13 is disposed along the leading edge of the card 12 to form its cutting edge and is electrically connected to the control circuit through the cable 14 and the connectors 16 . the element 13 may be a single filament attached to the edge of the card 12 , for example , using conventional ceramic welding materials or may be a layer of electrically conductive material vapor - deposited along the edge of the card 12 . also , the heating element 13 may have sufficient cross - sectional area to be self - supporting , as shown in fig2 so that the blade 18 is formed entirely by the element 13 alone . the material used in the element 13 ideally should have a negative temperature coefficient of resistance so that as selected portions of the element cool when in contact with tissue , the resistance of such portions will increase and thereby localize the portions of the element 13 in which additional power supplied by the control system will be dissipated . the temperature of the element may thus be maintained substantially constant over the entire length thereof as portions of the element 13 contact tissue . suitable materials having negative temperature coefficients of resistance include silicon carbide , carbon , boron silicate and such semiconductor materials as silicon and germanium . of course , material having a positive coefficient of resistance may also be used . however , when materials of this type are used , care should be taken to shape the element 13 so that substantially the entire length of the element 13 contacts tissue in use . this is required to prevent the additional power supplied by the control system 11 from being dissipated in the portions of the element which do not cool when in contact with tissue and , hence , which have higher resistance than the cooler portions . for cutting applications where it is not convenient to shape the element 13 so that its entire length is in contact with tissue each time it is used , the element 13 may consist of a plurality of electrically isolated elements 13 and 13 &# 39 ;, as shown in fig3 with each of the elements 13 and 13 &# 39 ; connected to a separate temperature measuring and power - controlling system of the type shown in fig1 . the resistance of the element 13 is included in a bridge circuit 15 which is connected to receive alternating signal appearing on lines 17 and 19 . the level of alternating signal appearing on lines 17 and 19 and , hence , the power applied to element 13 is determined by the conduction angles of the controlled rectifiers 21 and 23 which are connected in conduction opposition in parallel across the series resistor 25 . power is supplied to the control system 11 through the primary and secondary windings 26 and 27 of power input transformer 29 . alternating line signal 28 applied to the transformer 29 is stepped down typically to about 24 volts for the safety of the patient and the surgeon and the average current flow per half cycle of the alternating signal is determined in part by the series resistor 25 and by the conduction angle of a silicon - controlled rectifier 21 , 23 . the operating temperature of the element 13 may be determined by adjusting one of the resistors , say resistor 31 , in the bridge circuit 15 . any variation in the operating temperature of element 13 from a set value unbalances the bridge 15 and produces a control signal 33 across the diagonal terminals 35 , 37 of the bridge circuit 15 which is either in phase or out of phase with the applied line signal , depending upon whether the operating temperature of the element is above or below the set value of operating temperature . a phase - shifting network 39 is connected to the output terminals of the bridge circuit 15 for applying the error signal 44 with respect to ground to the input of error amplifier 41 with a small amount of phase shift relative to the applied line signal 28 . this provides control of the conduction angle of the controlled rectifiers 21 , 23 over a greater portion of a half cycle of the applied line signal . the output of amplifier 41 is applied to the threshold detectors 43 , 45 which respond to the amplified error signal attaining selected values slightly above and below zero . the threshold detectors 47 and 49 thus activate the trigger pulse generators 47 and 49 at the proper times in alternate half cycles of applied line signal 28 to apply conduction - initiating pulses to the gate electrodes 51 , 53 of the controlled rectifiers 21 , 23 . thus , increased conduction angle of the controlled rectifiers 21 and 23 increases the power applied to the element 13 to maintain the element at a preselected operating temperature as the element tends to cool down in contact with skin tissue . however , if the operating temperature of the element 13 should exceed the set value due , for example , to thermal overshoot upon removal of the element 13 from contact with skin tissue , the phase of the error signal 33 with respect to the applied line signal reverses . this causes the trigger pulse generators to supply conduction - initiating pulses to the gate electrodes of the controlled rectifiers 21 , 23 during alternate half cycles when these rectifiers are back biased . this causes a decrease in the power delivered to the element 13 with a concomitant drop in its operating temperature to about the set value of operating temperature . when this occurs , the proper phase relationship between error signal and line signal is restored and power is again supplied to the element 13 . conversion of the control system 11 for operation with elements 13 having negative or positive temperature coefficients of resistance merely requires that the trigger pulses from the generators 47 and 49 be applied through reversing switch 55 to the proper controlled rectifier 21 , 23 during the forward - biasing half cycle of line signal 28 . it should be apparent that other temperature control systems may also be used to maintain the operating temperature of the element 13 substantially constant at a preselected value . for example , a thermocouple sensor may be disposed on the card 12 in close proximity with the element 13 or a thermocouple element may even be formed on element 13 using another material or dissimilar work function to form the thermocouple junction . the signal from such thermocouple may then be used to control the operating temperature of the element 13 by controlling the power supplied thereto .

a surgical cutting instrument includes an electrically heated cutting edge and an automatic control system for maintaining the cutting edge at a constant high temperature for sterilizing the blade , cutting tissue , and cauterizing the incised tissue to reduce hemorrhage from the cut surfaces of the tissues .

fig1 a shows a needle for medical applications or uses , wherein the needle has an end portion 1 whose surfaces are faceted with respect to one another . the end portion 1 , which may be referred to as the distal end portion , has a top 2 , and a bottom 3 ( not shown in fig1 a ), which lie opposite one another and extend parallel with respect to one another . perpendicular to the top 2 and the bottom 3 , the end portion 1 has two side surfaces 4 and 5 ( the latter not visible ) which lie opposite one another and form , with the longitudinal axis of the needle , an angle a , which is shown in fig1 b . the two side surfaces 4 and 5 therefore extend parallel in one dimension . the needle region 6 of the embodiment in fig1 a has a rectangular cross section , where the surfaces of the broad side of the needle region 6 correspond to the surfaces of the top 2 and bottom 3 of the end portion 1 , and where narrow surfaces of the needle region 6 which extend perpendicular to the broad surfaces merge into the side surfaces 4 and 5 of the end portion 1 via a beveling about the angle a . however , the needle region 6 could also have another suitable cross section , for example an oval cross section , in which case the top 2 and bottom 3 and the side surfaces 4 , 5 of the end portion 1 could be generated by a correspondingly ground surface of such a needle . in some cases , the top and bottom would then not extend parallel to one another , and instead they would form an angle to one another . in fig1 a , two facets or facet surfaces 7 and 8 ( the latter not visible in fig1 a ) are arranged at the end portion 1 and form a tip 9 and a cutting edge 12 of the needle . the facet surfaces 7 and 8 are oriented in such a way that , starting from the orientation of the top 2 or the bottom 3 , they fall away in the direction of the needle tip 9 and , at the same time , fall away in the direction of the same side surface 4 . the facet surfaces are therefore not oriented parallel to one another in any dimension . the facet surface 7 forms a line of intersection 10 with the top 2 , and the facet surface 8 correspondingly forms a line of intersection 11 with the bottom 3 , although the latter is not visible in fig1 a . because of the orientation of the facet surfaces 7 and 8 , the lines of intersection 10 and 11 and the cutting edge 12 are oriented obliquely with respect to the longitudinal direction or extent of the needle . the facet surfaces 7 and 8 are also oriented obliquely with respect to the planes of symmetry which are perpendicular to one another and intersect the surfaces of the needle region perpendicularly through the longitudinal axis of the needle . fig1 b shows a view of the top 2 , and fig1 c shows a side view of the side 4 , of the needle shown in fig1 a . in fig1 b , the side surfaces 4 and 5 , in relation to the mutually parallel side surfaces of the needle region 6 , are beveled by an angle a of 10 ° relative to the longitudinal axis of the needle , so that an angle of 20 ° results between the side surfaces 4 and 5 . the angle a can , in principle , also be of another magnitude , but in preferred embodiments it may be between 5 ° and 30 °. the cutting edge 12 preferably forms an angle of between 30 ° and 55 ° with the longitudinal axis of the needle . the beveled lines of intersection between the side surfaces of the needle region 6 and the side surfaces 4 and 5 of the end portion 1 are arranged symmetrically with respect to the longitudinal axis of the needle . fig1 c shows the mutually parallel top 2 and bottom 3 and the likewise mutually opposite facet surfaces 7 and 8 . the facet surface 7 is beveled relative to the top 2 in the direction of the longitudinal axis of the needle . at the same time , the facet surface 7 is also beveled in the direction of the side surface 4 . in the same way , the facet surface 8 is beveled relative to the bottom 3 in the direction of the longitudinal axis and at the same time in the direction of the side surface 4 . the result of this is that the lines of intersection of the facet surfaces 7 and 8 form different angles with the side surfaces 4 and 5 . the line of intersection 13 between the facet surface 7 and the side surface 4 and the line of intersection 14 between the facet surface 8 and the side surface 4 form an angle b of about 16 . 5 ° in relation to one another . the angle b can also lie in the range around this value , preferably between 10 ° and 22 °. by contrast , the line of intersection 15 between the facet surface 7 and the side surface 5 , lying opposite the side surface 4 , and the line of intersection 16 between the facet surface 8 and the side surface 5 form an angle c of 23 . 5 °, which can also lie in a range around this value , preferably between 15 ° and 35 °. the facet surfaces 7 and 8 are arranged symmetrically with respect to a plane of symmetry extending along the longitudinal axis of the needle and in the direction of the top and bottom 2 , 3 . the extent of the bevels of the facet surfaces 7 and 8 relative to the top 2 and bottom 3 , respectively , is chosen such that the facet surfaces intersect in the cutting edge 12 and form a tip 9 . the cutting edge 12 and the tip 9 lie on the plane of symmetry in the direction of the top 2 and bottom 3 , and the point of intersection of the mutually perpendicular planes of symmetry of the needle region 6 , i . e ., also the longitudinal axis of the needle , lies on the cutting edge 12 , but not in , on or at the tip 9 . therefore , the tip 9 is not arranged in a center point of symmetry of the needle . the angle a between the side surfaces 4 and 5 , the angles b and c between the facet surfaces 7 and 8 and the distance between the top 2 and bottom 3 are therefore adapted to one another in such a way that , in the end portion 1 , the facet surfaces 8 and 9 intersect , and not the side surfaces 4 and 5 . however , it would also be conceivable to choose the angles a , b and c and the distance between the mutually parallel faces 2 and 3 in such a way that the side surfaces 4 and 5 intersect in the front area of the tip of the end portion 1 , which would result , however , not in the formation of a cutting edge 12 extending obliquely with respect to the longitudinal axis of the needle , but instead in the formation of an edge extending perpendicular to said longitudinal axis . fig1 b shows that the line of intersection 10 and the cutting edge 12 extend obliquely with respect to the longitudinal direction of the needle and thus also obliquely with respect to a direction perpendicular to the longitudinal direction of the needle . fig1 d is a sectional view through the needle region 6 of the needle . the lines of intersection 13 , 14 , 15 and 16 between the facet surfaces 7 and 8 and the side surfaces 4 and 5 are indicated by broken lines . the cutting edge 12 is also indicated by a broken line . it will be seen that the cutting edge 12 lies on the plane of symmetry extending parallel to the top 2 , but the tip 9 lies outside a second plane of symmetry extending perpendicular to said plane of symmetry . it will also be seen that the path from the lateral start of the side surface 4 to the start of the facet surfaces , i . e ., to the line of intersection 12 in fig1 a , and the path between the start of the side surface 5 and the start of the facet surfaces differs . the embodiment shown in fig1 a - d has a pointed tip 9 , by means of which the initial force needed for penetration is decreased . at the same time , this embodiment has a cutting edge 12 by means of which the overall force needed for penetration when inserting the microdialysis needle is likewise reduced . the surfaces of the end portion 1 may be manufactured , shaped or produced by suitable methods , including by wet or dry grinding using , for example , a surface - grinding device with a diamond cutter of grinding degree d500 . the lines of intersection and points of intersection were deburred after the grinding , by which means it was possible to further decrease the force needed for penetration . in the embodiment according to fig1 a and d , the needle is used as the microdialysis needle of a microdialysis probe . for this purpose , the needle region 6 has a slit - like recess 17 which extends partially into the end portion 1 . a dialysis membrane in the form of a hollow fiber 18 is arranged in the slit 17 . the hollow fiber 18 is fitted in the slit 17 in such a way that it forms a supply line and a discharge line for a perfusion solution . for this purpose , two stretches or lengths of hollow fiber are arranged alongside one another and execute a reverse turn in the rounded end area of the slit 17 in or near the end portion 1 . after the microdialysis needle has been introduced into a tissue , an exchange is able to take place between the hollow fiber membrane 18 and the tissue environment along the stretches of hollow fiber membrane and the reverse turn area , by means of which exchange the concentration , for example , of dissolved substances or the viscosity of the tissue fluid can be measured . fig1 d shows how the cross sections of the two stretches of hollow fiber membrane 18 are arranged in parallel alongside one another inside the slit 17 . by means of a suitable method for bending the hollow fiber membrane , the latter can easily be applied inside the slit . such a method is also described in the aforementioned application “ microdialysis probe and method for the production thereof ” owned by the owner of the present invention . fig2 shows a further embodiment of the present invention in which a end 1 of a needle is shown with a needle region 6 generally corresponding to fig1 . the end portion 1 in fig2 has two cone - shaped surfaces 20 arranged on opposite sides and running or extending toward one another . the two cone surfaces 20 extend obliquely in the direction to the longitudinal axis of the needle and intersect at a center point of the cross section of the needle region 6 . this produces two cutting edges 21 and 22 which lie opposite one another and taper to a point and form the needle tip 23 . the needle tip 23 lies on the center point of the cross section of the needle , and the cutting edges 21 and 22 lie on a plane of symmetry which lies on the longitudinal axis of the needle and extends parallel to the narrow side of the rectangular cross section of the needle region 6 . by means of the cone - shaped profile of a surface 20 , the latter is more strongly curved in an area near the needle tip 23 than it is in an area near the needle region 6 . by this means , a gentle transition from the cone - shaped surfaces 20 to the side surfaces of the needle region 6 can be produced . fig3 a shows a further embodiment of the invention in which the end portion 1 has a pyramid - like shape . the needle region 6 of the needle is of rectangular shape as in fig1 a - d . the end portion 1 of the needle has four diamond - like pyramid surfaces 30 which form a pyramid tip as needle tip 31 at the center point of the cross section of the needle region 6 . the pyramid surfaces 30 are arranged symmetrically with respect to the planes of symmetry of the rectangular cross section of the needle region 6 . a wide side of the cross section merges into two pyramid surfaces which together form an obtuse angle . the narrow side of the cross section merges into two pyramid surfaces which together form an acute angle , so that their line of intersection forms a cutting edge 32 . accordingly , a pyramid surface forms an obtuse angle with a pyramid surface adjoining it on one side , and it forms an acute angle with the pyramid surface adjoining it on the other side . the lines of intersection extend on the axes of symmetry of the cross section of the needle region 6 . fig3 b shows another embodiment of a pyramid - like end portion 1 which forms a kind of half pyramid . the needle region 6 is rectangular , as in fig1 a - d . in the end portion 1 , the narrow sides of this rectangle are beveled in the direction of the longitudinal axis of the needle , so that they form side surfaces 33 which are symmetrical with respect to a plane of symmetry of the needle region . the wide surfaces of the needle region 6 are beveled in such a way that they are oriented obliquely with respect to both planes of symmetry of the needle region 6 and at the same time extend parallel to one another in one dimension . this produces two surfaces 35 which lie opposite one another and form a cutting edge 34 . because of the parallel arrangement of the surfaces 35 , however , there is no needle tip , such as is present for example in the embodiment in fig1 a - d . the cutting edge extends obliquely with respect to the lines of symmetry of the cross section of the needle region 1 , but perpendicular to the longitudinal axis of the needle . when producing the needles with a end portion according to the invention , it was found that , if the material is too soft , burrs unavoidably form on the edges and are difficult to remove without damaging the edges . a soft material , however , avoids the development of undesirably fine edges , for example on account of an imprecise processing operation . for this reason , a material of moderate hardness is preferably used . a double - edged cut avoids the development of burrs . it was further found that the provision of polygonal cross sections both in the end portion and also in the needle region makes deburring easier without causing further damage . in the embodiment according to fig1 a - d , a value of 0 . 75 n was measured for the initial penetration force needed for passing through the surface of a tissue with a needle according to the invention , and a value of 0 . 9 n was measured for the complete penetration force needed for insertion of the needle into the tissue . in the case of an end portion configured in this way , the needle tip and the cutting edge of the needle are strong enough to ensure that , when the needle penetrates into a tissue , they are not subject to any bending or to any other change . the penetration forces in a needle according to the prior art , for example the needle from therumo medical corporation , which has a smaller cross - sectional surface area in the needle region than do the needles according to the embodiments of the present invention , have values of 0 . 5 n to 0 . 7 n for the initial penetration force and 0 . 7 n to 0 . 9 n for the complete penetration force . a suture needle , for example with a diameter of 0 . 6 mm , requires a full penetration force of 2 . 5 n and a widely differing initial penetration force . therefore , a needle according to the present invention , while having approximately the same cross section as a suture needle , and an even larger cross section compared to the needle from therumo medical corporation , requires a lower penetration force or equally high penetration force , respectively . the embodiments of the present invention have been described , and shown in the drawing , using the example of a microdialysis needle for a microdialysis probe . in principle , however , the needle according to the invention can also be used in other medical or biological fields , and for other purposes . embodiments of the present invention , including preferred embodiments , have been presented for the purpose of illustration and description . they are not intended to be exhaustive or to limit the invention to the precise forms or steps disclosed . the embodiments were chosen and described to provide the best illustration of the invention and its practical application , and to enable one of ordinary skill in the art to utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated . all such modifications and variations are within the scope of the invention as determined by the appended claims when interpreted in accordance with the breadth they are fairly , legally , and equitably entitled .

a needle for medical uses , for example for inserting a dialysis membrane into human or animal tissue , wherein the needle has an end portion made of solid material and provided with at least two areas which intersect a longitudinal axis of the needle and each other whereby at least one line or point of intersection is formed between the at least two areas , the line or point of intersection in a needle region adjacent to the end portion .

the present invention features novel dietary supplements ( multivitamin - mineral formulations ), hereinafter referred to “ formulation ” or “ formulations .” the present invention features longevity formulations . in some embodiments , the formulation comprises at least 30 of the following supplemental components : pregnenolone at about 30 mg ; natto kinase at about 300 mg ; vitamin k2 at about 32 mg ; coenzyme q10 at about 300 mg ; acetyl l - carnitine arginate at about 700 mg ; l - glutathione at about 250 mg ; vitamin a ( e . g ., as beta - carotene at about 25000 iu , palmitate at about 2500 iu ); vitamin c at about 2000 mg ( e . g ., as ascorbic acid and ascorbyl palmitate ); vitamin d3 ( e . g ., as cholecalciferol ) at about 8000 iu ; vitamin e ( e . g ., as mixed tocotrienols gamma / delta ) at about 1000 mg ; thiamine b1 at about 50 mg ; riboflavin b2 at about 200 mg ; niacinamide at about 1000 mg ; vitamin b6 ( e . g ., as pyridoxine hydrochloride / pyridoxol 5 - phosphate coenymated ) at about 200 mg ; folate ( e . g ., as folic acid and calcium folinate ) at about 1 mg ; vitamin b12 ( e . g ., as methyl cobalamin ) at about 2000 mg ; biotin at about 6 mg ; pantothenic acid ( e . g ., as calcium d - panthothenate and panthethine ) at about 500 mg ; calcium ( e . g ., as calcium carbonate , malate , amino acid cholate or citrate ) at about 1000 mg ; iodine ( e . g ., as potassium iodine ) at about 220 mg ; magnesium ( e . g . ; as magnesium amino acid chelate ) at about 1000 mg ; zinc ( e . g ., as monomethionine plus zinc citrate ) at about 40 mg ; selenium ( e . g ., as l - selenomethionine plus sodium selenite ) at about 200 mg ; copper ( e . g ., as copper sebacate ) at about 2 . 5 mg ; manganese ( e . g ., as manganese citrate ) at about 5 mg ; chromium ( e . g ., as chromium polynicotinate / histidinate ) at about 1200 mg ; molybdenum ( e . g ., as molybdenum amino acid chelate ) at about 2000 mg ; sodium at about 5 mg ; potassium at about 50 mg ; aged garlic at about 1000 mg ; n - acetyl cysteine at about 600 mg ; vacadyl sulphate at about 400 mg ; silymarin ( milk thistle extract ) at about 600 mg ; d - ribose at about 10 grams ; indole 3 carbinol at about 200 mg ; sulphoramane 225 mg at about 225 mg ; cranberry ( vaccinium macrocarpon ) at about 1000 mg ; french maritime pine bark extract ( e . g ., pycnogenol ®) at about 250 mg ; l - glutathione at about 250 mg ; cinnamomum root at about 4000 mg ; choline ( e . g ., as bitartrate ) at about 1000 mg ; inositol at about 1000 mg ; alpha - lipoic acid and / or r lipoic acid at about 600 mg ; polygonum cuspidatum root extract at about 1000 mg ( e . g ., standardized to 53 % trans - reservatrol ); dimethylaminoethanol ( e . g ., as bitartrate ) at about 30 mg ; grape seed extract at about 300 mg ; methylsulfonylmethane at about 250 mg ; hawthorn berry extract at about 1500 mg ; n - acetyl tyrosine at about 25 mg ; turmeric extract ( e . g ., rhizome ) ( e . g ., 95 % curcumin ) at about 8 gms ; green tea extract ( e . g ., 95 % pomphenols , solution epogalocatequina galato ); gingko leaf extract ( 50 : 1 ) ( e . g ., 25 % flavonglylosides ) at about 140 mg ; bilberry extracts ( e . g ., 25 % anthocyanins ) at about 600 mg ; rutin at about 100 mg ; blain pepper fruit extract ( bioperine ) at about 3 mg ; lycopene at about 110 mg ; boron ( e . g ., as amino acid chelate ) at about 12 mg ; lutein at about 20 mg ; astaxanthin at about 20 mg ; bitter melon at about 1000 mg ; dehydroepiandrosterone at about 2000 mg ; black currant seed at about 2000 mg ; carnosine at about 3 gms ; conjugated linoleic acid at about 3000 mg ; and hyaluronic acid at about 80 mg . in some embodiments , the formulation comprises at least 35 of the above components . in some embodiments , the formulation comprises at least 40 of the above components . in some embodiments , the formulation comprises at least 45 of the above components . in some embodiments , the formulation comprises at least 50 of the above components . in some embodiments , the formulation comprises at least 55 of the above components . in some embodiments , the formulation comprises at least 60 of the above components . fig1 - 4 show examples of longevity formulations comprising 50 of the above components , 40 of the above components , 35 of the above components , and 30 of the above components , respectively . the present invention also features anti - dementia formulations . in some embodiments , the formulation comprises at least 25 of the following supplemental components : idebenone at about 180 mg ; rhodiola at about 400 mg ; gingko biloba at about 160 mg ; thionine at about 400 mg ; huperzine a at about 2 mg ; coenzyme q10 at about 400 mg ; alpha lipoic acid at about 600 mg ; melatonin at about 3 mg ; omega 3 fatty acid at about 6000 mg ; zinc carnosine at about 500 mg ; magnesium at about 1000 mg ; vitamin e ( e . g ., mixed tocotrienols gamma / delta ) at about 1000 mg ; n - acetyl cysteine at about 1200 mg ; dehydroepiandrosterone ( dhea ) at about 100 mg ; pregnenolone at about 60 mg ; niacin at about 1000 mg ; phosphatidylserine docasahexanenoic acid at about 300 mg ; vitamin b12 at about 2000 mg ; vitamin b6 at about 200 mg ; iron at about 18 mg ; vinpocetine at about 40 mg ; phospholipid grape seed extract at about 300 mg ; blueberry extract at about 300 mg ; acetyl carnitine arginate 900 mg ; ashwagandha extract ( e . g ., sensoril ®) at about 250 mg ; uridine 5 monophosphate at about 100 mg ; french maritime pine bark extract ( e . g ., pycnogenol ®) at about 250 mg ; l - alpha - glycerylphosphorylcholine at about 1500 mg ; curcumin at about 8 gms ; coconut oil at about 1000 mg ; astaxanthin at about 20 mg ; chromium picolinate at about 1200 mg ; carnosine at about 3000 mg ; n - acetyl - tyrosine at about 1500 mg ; phenylalanine at about 1500 mg ; quercetin at about 150 mg ; inositol hexanicotinate at about 1000 mg ; dimethylethanolamine ( dmae ) at about 100 mg ; s - adenosylmethionine at about 400 mg ; riboflavin 32 at about 200 mg ; thiamine b1 at about 50 mg ; selenium ( e . g ., as l - selenomethionine sodium selenite ) at about 200 mg ; colostrum at about 4000 mg ; lecithin ( e . g ., 26 % phosphaticylcholine ) at about 300 mg ; and vitamin d2 at about 8000 iu . in some embodiments , the formulation comprises at least 30 of the above components . in some embodiments , the formulation comprises at least 35 of the above components . in some embodiments , the formulation comprises at least 40 of the above components . fig5 - 7 show examples of anti - dementia formulations comprising 40 of the above components , 30 of the above components , and 25 of the above components , respectively . the present invention also features diabetic treatment formulations . in some embodiments , the formulation comprises at least 25 of the following supplemental components : bilberry extract at about 600 mg ; alpha lipoic acid at about 600 mg ; chromium picolinate at about 1200 mg ; omega - 3 - fatty acids at about 8 g ; dihydroepiandrosterone ( dhea ) at about 100 mg ; blueberry extract at about 500 mg ; biotin at about 8 mg ; vitamin d3 at about 5000 iu ; taurine at about 3000 mg ; psyllium at about 5 g ; guar gum at about 500 mg ; carnosine at about 3 , 000 mg ; cinnamomum root at about 2 g ; aged garlic at about 1 , 000 mg ; vanadium at about 50 mg ; bitter melon at about 1 , 000 mg ; green tea extract at about 450 mg ; zinc citrate at about 50 mg ; fenugreek ( 1 : 4 ) extract ( e . g ., trigonella foenum - graecum ) at about 80 mg ; vitamin b6 at about 200 mg ; goat &# 39 ; s rue ( e . g ., galega officinalis ); curcumin at about 8 g ; glycyrrhiza glabra at about 500 mg ; vitamin e at about 1 , 000 mg ; coenzyme q10 at about 300 mg ; vitamin c at about 3 , 000 mg ; manganese at about 10 mg ; gymnema at about 400 mg ; l - argenine at about 10 g ; ginseng ; l - carnitine at about 4 g ; pyrroloquinoline quinone ( pqq ) at about 20 mg ; amla extract ( indian gooseberry ); brown seaweed extract ; bladderwrack ; banaba leaf at about 50 mg ; bromocriptine at about 2 . 5 mg ; benfotiamine at about 400 μg ; resveratrol at about 250 mg ; and pterostilbene at about 1 mg . in some embodiments , the formulation comprises at least 30 of the above components . in some embodiments , the formulation comprises at least 35 of the above components . fig8 - 10 show examples of diabetic treatment formulations comprising 35 of the above components , 30 of the above components , and 25 of the above components , respectively . in some embodiments , the formulation further comprises testosterone cypionate at about 100 mg ( administered im ). in some embodiments , the formulation further comprises female testosterone at about 30 mg ( administered im ). in some embodiments , the psyllium is administered 3 times per day . in some embodiments , the guar gum is administered 3 times per day . the present invention also features eye treatment formulations ( e . g ., macular degeneration formulations , cataract formulations , etc .). in some embodiments , the formulation comprises at least 10 of the following supplemental components : lutein at about 20 mg ; astaxanthin at about 20 mg ; vitamin a ( e . g ., as beta carotene 20 , 000 iu , palmitate 2 , 500 iu ); vitamin e at about 1 , 000 mg ; ( e . g ., gamma / delta mixed tocotrienols ); rutin at about 100 mg ; selenium at about 200 mg ( e . g ., l - selenomethionine plus sodium selenite ); bilberry extract at about 600 mg ; blueberry extract at about 500 mg ; french maritime pine bark extract at about 250 mg ; lycopene at about 40 mg ; zinc citrate at about 50 mg ; quercetin at about 150 mg ; chromium picolinate at about 1200 mg ; l - glutathione at about 250 mg ; n - acetyl cysteine at about 500 mg ; taurine at about 400 mg ; vitamin c at about 2 , 000 mg ( e . g ., as ascorbic acid , ascorbyl palmitate ); riboflavin b2 at about 200 mg ; hyaluronic acid at about 80 mg ; carnosine at about 3 , 000 mg ; grape seed extract at about 300 mg ; black currant fruit ; r - lipoic acid at about 600 mg ; tumeric at about 400 mg ; and vitamin b6 at about 200 mg . in some embodiments , the formulation comprises at least 15 of the above components . in some embodiments , the formulation comprises at least 20 of the above components . fig1 - 13 show examples of eye treatment formulations comprising 20 of the above components , 15 of the above components , and 10 of the above components , respectively . the present invention also features male wellness formulations , e . g ., male treatment formulations ( e . g ., to increase testosterone ). in some embodiments , the formulation comprises at least 15 of the following supplemental components : dihydroepiandrosterone at about 100 mg ; pregnenolone at about 60 mg ; zinc citrate at about 60 mg ; diindolylmethane at about 200 mg ; chrysin at about 1500 mg ; resveratrol at about 250 mg ; quercetin at about 150 mg ; saw palmetto at about 320 mg ; finasteride at about 2 . 5 mg ; fenugreek at about 90 mg ; vitamin c at about 1 , 000 mg ; stinging nettle at about 240 mg ; boron at about 3 mg ; norway spruce lignan extract at about 50 mg ; ginger root at about 100 mg ; yohimbine at about 20 mg ; tribulus terrestris at about 300 mg ; eurycoma longifolia at about 50 mg ; muira puama at about 850 mg ; maca at about 320 mg ; bioperine at about 7 . 5 mg ; cernilton ( e . g ., cernitin ®) at about 250 mg ; pumpkin seed oil at about 200 mg ; pygeum africanum at about 100 mg ; lycopene at about 50 mg ; mucuna pruriens at about 300 mg ; red clover flower extract at about 50 mg ; ginkgo biloba at about 60 mg ; korean ginseng at about 50 mg ; grape seed extract at about 300 mg ; panax ginseng at about 100 mg ; ashwagandha at about 300 mg ; epimedium brevicornum herb ; selenium at about 100 mg ; beta sitosterol at about 100 mg . in some embodiments , the formulation comprises at least 20 of the above components . in some embodiments , the formulation comprises at least 25 of the above components . in some embodiments , the formulation comprises at least 30 of the above components . fig1 - 17 show examples of male wellness formulations comprising 30 of the above components , 25 of the above components , 20 of the above components , and 15 of the above components , respectively . the present invention also features anti - oxidant formulations . in some embodiments , the formulation comprises at least 25 of the following supplemental components : vitamin a ( e . g ., as betacarotene 20 , 000 iu , palmitate 2500 iu ); vitamin d3 at about 6 , 000 iu ; vitamin e at about 1 , 000 mg ( e . g ., mixed tocotrienols gamma / delta ); vitamin c at about 2 , 000 mg ( e . g ., as ascorbic acid and ascorbyl palmitate ); vitamin k2 at about 100 mg ; coenzyme q10 at about 400 mg ; trans - resveratrol at about 500 mg ; sulphoraphane at about 225 mg ; inositol hexanicotinate at about 1 , 000 mg ; alpha lipoic acid at about 600 mg ; bioflavonoids at about 2 , 000 mg ; carotenoids at about 30 mg ; alpha carotene at about 12 mg ; lutein at about 20 mg ; lycopene at about 40 mg ; aged garlic at about 1 , 000 mg ; n - acetyl cysteine at about 600 mg ; tumeric at about 400 mg ; fisetin at about 48 mg ; quercetin at about 150 mg ; acetyl 1 - carnitine at about 4 , 000 mg ; astaxanthin at about 20 mg ; idebenone at about 180 mg ; carnosine at about 3 , 000 mg ; dihydroepiandrosterone at about 200 mg ; bilberry extract at about 600 mg ; blueberry extract at about 500 mg ; l - glutathione at about 250 mg ; zinc citrate at about 50 mg ; selenium at about 200 mg ( e . g ., as l - selenomethionine + sodium selenite ); french maritime pine bark extract at about 250 mg ; acai at about 5 , 000 mg ; nicotinamide adenine dinucleotide at about 50 mg ; methylsulfonylmethane ( msm ) at about 500 mg ; pregnenolone at about 60 mg ; hyaluronic acid at about 80 mg ; hawthorne extract at about 1 , 200 mg ; l - argenine at about 10 g ; l - taurine at about 4 g ; pterostilbene at about 1 mg ; grape seed extract at about 300 mg ; melatonin at about 3 mg ; ginger root extract at about 200 mg ; rutin at about 5 mg ; ginseng at about 200 mg ; gingko biloba at about 200 mg ; and chromium picolinate at about 1 mg . in some embodiments , the formulation comprises at least 30 of the above components . in some embodiments , the formulation comprises at least 35 of the above components . in some embodiments , the formulation comprises at least 40 of the above components . fig1 - 21 show examples of anti - oxidant formulations comprising 40 of the above components , 35 of the above components , 30 of the above components , and 25 of the above components , respectively . the present invention also features anti - aging skin formulations ( e . g ., skin creams ). in some embodiments , the formulation comprises at least 10 of the following supplemental components idebenone at about 1 %; hyaluronic acid at about 0 . 5 %; coenzyme q10 at about 1 %; estriol at about 0 . 4 %; retinoic acid at about 0 . 025 %; alpha lipoic acid at about 5 %; vitamin c ester at about 5 %; dimethylethanolarnine ( dmae ) at about 3 %; peptides ( peptides for skin creams are well known to one of ordinary skill in the art , e . g ., peptides derived from collagen , peptides derived from elastin , palmitoyl pentapeptide , etc . ); green tea extract ; squalane ; vitamin b3 at about 5 %; teprenone ( e . g ., geranyl geranylacetone ); caprylic acid ( e . g ., palm / coconut oils ); and acetyl hexapeptide at about 5 %. in some embodiments , the formulation comprises at least 12 of the above components . in some embodiments , the formulation comprises at least 14 of the above components . fig2 - 24 show examples of anti - aging skin formulations comprising 14 of the above components , 12 of the above components , and 10 of the above components , respectively . in some embodiments , a formulation of the present invention is administered to a human patient once a day . in some embodiments , a formulation of the present invention is administered to a human patient once a week . the formulations of the present invention may be a solid tablet , granule , syrup or liquid form . one of ordinary skill would be able to prepare an appropriate form of any formulation of the present invention . as used herein , the unit “ mg ”, for example iodine ( as potassium iodine ) at about 220 mg , means micrograms . a ratio recited above , for example a ratio of 50 : 1 recited above , for example gingko leaf extract ( 50 : 1 ), means 50 parts of the extract to 1 part of water . as used herein , the term “ about ” refers to plus or minus 10 % of the referenced number . for example , an embodiment comprising uridine 5 monophosphate at about 100 mg includes uridine 5 monophosphate between 90 and 110 mg . various modifications of the invention , in addition to those described herein , will be apparent to those skilled in the art from the foregoing description . such modifications are also intended to fall within the scope of the appended claims . each reference cited in the present application is incorporated herein by reference in its entirety . although there has been shown and described the preferred embodiment of the present invention , it will be readily apparent to those skilled in the art that modifications may be made thereto which do not exceed the scope of the appended claims . therefore , the scope of the invention is only to be limited by the following claims .

dietary vitamin - mineral supplements featuring various vitamins and minerals for benefiting individuals suffering from conditions such as nutritional deficiencies , vitamin deficiencies , aging , cancer , high blood pressure , high cholesterol , dementia , alzheimer &# 39 ; s disease , coronary artery disease , fatigue , and stroke . vitamins and minerals may include vitamin c , vitamin a , pregnenolone , coenzyme q10 , vitamin k2 , acetyl l - carnitine arginate , l - glutathione , among others .

the aqueous soluble - chitosan of the present invention is chitosan that is modified by alkyl sultone . examples of alkyl sultone include but not limited to 1 , 3 - propanesultone , 1 , 4 - propylenesultone , 1 , 4 - butanesultone , 2 , 4 - butanesultone , or a mixture thereof . more specifically , the aqueous soluble - chitosan of the present invention is a sulfonic acid - modified chitosan . for example , the aqueous soluble - chitosan is alkyl sulfonic acid - modified chitosan . the alkyl sulfonic acid - modified chitosan may be fabricated by the following procedures : 161 gram of chitosan ( with molecular weight of 140 , 000 ) was put into a flask , and 700 ml of methanol was added in to obtain a mixture . the mixture was heated at 65 to 67 ° c ., and 122 gram of 1 , 3 - propanesultone was slowly dropped in while stirring . the mixture was kept refluxing for 4 hours after all 1 , 3 - oxathiolane was added in . then the flask was cooled down to room temperature , and product ( alkyl sulfonic acid - modified chitosan ) was collected by filtering . the product was washed by methanol from several times and dried overnight in a vacuum oven . the dried product was weighted 282 gram . the yield rate of the alkyl sulfonic acid - modified chitosan was 99 . 7 %. the experiment was conducted by using 4 - weeks old weaned sprague - dawley rats ( purchased from biolasco taiwan co ., ltd ). 64 rats were randomly separated into 8 groups . each group had 8 rats . the experimental rats were maintained in plastic cages with free access to food and water . the temperature of those cages were kept at 25 ± 1 ° c ., and the day - night cycle was 12 hours per day . for experiments , rats were fed with normal diet ( ain - 93g , icn biomedicals , costa mesa , calif ., usa ) or high calorie diet to induce obesity ( modify ain - 93g high fat diet , 20 % lipid ) for 4 weeks before the administration of aqueous soluble - chitosan . beginning from the fifth week , the experimental rats were fed with various dosages ( 10 or 25 mg / kg body weight ) of unmodified chitosan and aqueous soluble - chitosan at every monday , wednesday , friday and saturday . chitosan used was resolved in sterile water for feeding . one group of normal diet and one group of high calorie diet were instead fed with water as control . the experimental period was 8 to 12 weeks ( the experiments were stopped depending on when the body weight of control group and test group show significant difference ). the body weight and feeding amount ( food intake ) of the animals under experiments were measured and recorded every week . the experimental animals were to be sacrificed by applying carbon dioxide after 12 weeks . before sacrificing , those animals were starved for 12 hours . collecting rats &# 39 ; blood , livers , hearts , spleens , kidneys , and colons for biochemical analysis and pathology study . also , the adipose tissues of rat were collected for determining the amount of body fat and analyzing the activity of lipase . the concentration of triglyceride ( tg ), total cholesterol ( tc ), high density lipoprotein ( hdl ) and low density lipoprotein ( ldl ) in blood were examined . briefly , the blood to be examined was collected from abdominal aorta and was examined by enzymatic method and colorimetry method . the results are showed in the following table 1 ( nd : normal diet ; hfd : high fat diet ; ch : chitosan ( unmodified ); as - ch : aqueous soluble - chitosan ( the present invention ); l : low dosage ( 10 mg / kg bw ); h : high dosage ( 25 mg / kg bw )). sd rat was orally administered with various dosages as - ch ( 10 or 25 mg / kg bw ) for 8 wks . data is expressed as means ± sd ( n = 8 ). significance of difference in activities of different compounds was evaluated by tukey &# 39 ; s test statistical analysis . different superscript letters a , b , c blood lipid are statistically different from each other ( p & lt ; 0 . 05 ). the results showed that by applying the aqueous soluble - chitosan of the present invention , the blood tg , tc and ldl was lowered down while hdl ( so called ‘ good lipoprotein ’) remained . after the blood was collected , the liver was washed by saline and the tg and tc therein were extracted by the method taught by folch et al . ( folch et al ., 1957 ) for analysis . the results are showed in the following table 2 ( nd : normal diet ; hfd : high fat diet ; ch : chitosan ( unmodified ); as - ch : aqueous soluble - chitosan ( the present invention ); l : low dosage ( 10 mg / kg bw ); h : high dosage ( 25 mg / kg bw )). sd rat was orally administered with various dosages as - ch ( 10 or 25 mg / kg bw ) for 8 wks . data is expressed as means ± sd ( n = 8 ). significance of difference in activities of different compounds was evaluated by tukey &# 39 ; s test statistical analysis . different superscript letters a , b , c blood lipid are statistically different from each other ( p & lt ; 0 . 05 ). the results indicated that the tg and tc level of the group administrated with the aqueous soluble - chitosan of the present invention were recovered back to normal standard as comparing with the control group of normal diet . after starvation for 12 hours , the experimental animals were anesthetized by ether . then the blood was collected from abdominal aorta for analyzing the blood sugar level by enzymatic method and colorimetry method . the results are showed in the following table 3 ( nd : normal diet ; hfd : high fat diet ; ch : chitosan ( unmodified ); as - ch : aqueous soluble - chitosan ( the present invention ); l : low dosage ( 10 mg / kg bw ); h : high dosage ( 25 mg / kg bw )). the ast , alt , creatinine , uric acid were detected by enzymatic method and colorimetry method for determining the hepatic function . the results are showed in the following table 4 ( nd : normal diet ; hfd : high fat diet ; ch : chitosan ( unmodified ); as - ch : aqueous soluble - chitosan ( the present invention ); l : low dosage ( 10 mg / kg bw ); h : high dosage ( 25 mg / kg bw )). it was showed that the administration of the aqueous soluble - chitosan of the present invention had no harm on the liver and kidney function of the experimental animals . after starvation for 12 hours , the experimental animals were anesthetized by ether . then the blood was collected from abdominal aorta for analyzing the concentration of ketone bodies , na + ion and k + ion in the blood by enzymatic method and colorimetry method . the results are showed in the following table 5 ( nd : normal diet ; hfd : high fat diet ; ch : chitosan ( unmodified ); as - ch : aqueous soluble - chitosan ( the present invention ); l : low dosage ( 10 mg / kg bw ); h : high dosage ( 25 mg / kg bw )). sd rat was orally administered with various dosages as - ch ( 10 or 25 mg / kg bw ) for 8 wks . data is expressed as means ± sd ( n = 8 ). significance of difference in activities of different compounds was evaluated by tukey &# 39 ; s test statistical analysis . different superscript letters a , b , c electrolyte balance are statistically different from each other ( p & lt ; 0 . 05 ). by summarizing with the data in above table 3 , table 4 , and table 5 , the administration of the aqueous soluble - chitosan of the present invention had no effects on blood sugar , the ketone bodies and electrolyte balance in the blood . also , it was showed that the administration of the aqueous soluble - chitosan of the present invention had no harm on the liver and kidney function of the experimental animals . as mentioned in the aforementioned paragraphs , the body weight and food intake of the experimental animals were recorded regularly . based on the recorded body weight , the change in body weight was calculated . moreover , the feed efficiency was also calculated according to the formula : feed efficiency =( weight gain / food intake )× 100 %. also , the organ weight was examined . the results are showed in the following table 6 , table 7 and fig1 , table 8 , and table 9 ( nd : normal diet ; hfd : high fat diet ; ch : chitosan ( unmodified ); as - ch : aqueous soluble - chitosan ( the present invention ); l : low dosage ( 10 mg / kg bw ); h : high dosage ( 25 mg / kg bw )). sd rat was orally administered with various dosages as - ch ( 10 or 25 mg / kg bw ) for 8 wks . data is expressed as means ± sd ( n = 8 ). significance of difference in activities of different compounds was evaluated by tukey &# 39 ; s test statistical analysis . different superscript letters a , b , c body weight are statistically different from each other ( p & lt ; 0 . 05 ) sd rat was orally administered with various dosages as - ch ( 10 or 25 mg / kg bw ) for 8 wks . data is expressed as means ± sd ( n = 8 ). significance of difference in activities of different compounds was evaluated by tukey &# 39 ; s test statistical analysis . different superscript letters a , b , c organs weight are statistically different from each other ( p & lt ; 0 . 05 ). the above results indicated that the administration of the aqueous soluble - chitosan of the present invention did not cause significant change in food intake , body weight gain , feed bioavailability and organ weight . the adipose tissues surrounded kidney and testis were collected and weighted . for determining the activity of lipase , 0 . 1 gram of the adipose tissue surrounded testis was washed with saline and dried by using filter paper . the washed tissues were homogenized by a homogenizer and then put into centrifugation . after centrifugation , the supernatant was taken for determining the activity of lipase . the results are showed in the following table 10 , table 11 and fig2 ( nd : normal diet ; hfd : high fat diet ; ch : chitosan ( unmodified ); as - ch : aqueous soluble - chitosan ( the present invention ); l : low dosage ( 10 mg / kg bw ); h : high dosage ( 25 mg / kg bw )). sd rat was orally administered with various dosages as - ch ( 10 or 25 mg / kg bw ) for 8 wks . data is expressed as means ± sd ( n = 8 ). significance of difference in activities of different compounds was evaluated by tukey &# 39 ; s test statistical analysis . different superscript letters a , b , c organs weight are statistically different from each other ( p & lt ; 0 . 05 ). sd rat was orally administered with various dosages as - ch ( 10 or 25 mg / kg bw ) for 8 wks . data is expressed as means ± sd ( n = 8 ). significance of difference in activities of different compounds was evaluated by tukey &# 39 ; s test statistical analysis . different superscript letters a , b , c intestinal physiology are statistically different from each other ( p & lt ; 0 . 05 ). it was noted that the aqueous soluble - chitosan of the present invention had a dosage - dependent effect on reducing body fat . this effect may due to its function on increasing the activity of adipose lipase ( see table 11 ). those having ordinary skill in the art can understand various modifications according to the disclosed embodiments without departing from the spirit of the present invention . therefore , the above - recited embodiments shall not be used to limit the present invention but shall intend to cover all modifications under the spirit and scope of the present invention along with the attached claims .

the present invention related to a composition comprising an aqueous soluble - chitosan and a pharmaceutically acceptable carrier . said composition can be used to increase lipase activity while having no harm in animal physiology . together with the well known biocompatibility of chitosan , the present invention proves that the aqueous soluble - chitosan may be a potential candidate for body weight control .

this invention entails a use of methyl pyruvate to increase cellular energy production to allow continuous parp activation without the concomitant depletion of atp , nad and necrotic cell death . methyl pruvate is the ionized form of methyl pyruvic acid ( ch3c ( o ) co2ch3 ). at physiologic ph , the hydrogen proton dissociates from the carboxylic acid group , thereby generating the methyl pyruvate anion . when used as a pharmaceutical or dietary supplement , this anion can be formulated as a salt , using a monovalent or divalent cation such as sodium , potassium , magnesium , or calcium . the energy requirements of most cells supplied with glucose are fulfilled by glycolytic and oxidative metabolism , yielding atp . when cytosolic and mitochondrial contents in atp , adp and amp were measured in islets incubated for 45 min at increasing concentrations of d - glucose and then exposed for 20 s to digitonin . the latter treatment failed to affect the total islet atp / adp ratio and adenylate charge . d - glucose caused a much greater increase in cytosolic than mitochondrial atp / adp ratio . in the cytosol , a sigmoidal pattern characterized the changes in atp / adp ratio at increasing concentrations of d - glucose . these findings are compatible with the view that cytosolic atp participates in the coupling of metabolic to ionic events in the process of nutrient - induced insulin release . to gain insight into the regulation of pancreatic beta - cell mitochondrial metabolism , the direct effects on respiration of different mitochondrial substrates , variations in the atp / adp ratio and free ca2 + were examined using isolated mitochondria and permeabilized clonal pancreatic beta - cells ( hit ). respiration from pyruvate was high and not influenced by ca2 + in state 3 or under various redox states and fixed values of the atp / adp ratio ; nevertheless , high ca2 + elevated pyridine nucleotide fluorescence , indicating activation of pyruvate dehydrogenase by ca2 +. furthermore , in the presence of pyruvate , elevated ca2 + stimulated co2 production from pyruvate , increased citrate production and efflux from the mitochondria and inhibited co2 production from palmitate . the latter observation suggests that beta - cell fatty acid oxidation is not regulated exclusively by malonyl - coa but also by the mitochondrial redox state . alpha - glycerophosphate ( alpha - gp ) oxidation was ca ( 2 +)- dependent with a half - maximal rate observed at around 300 nm ca2 +. it was recently demonstrated that increases in respiration precede increases in ca2 + in glucose - stimulated clonal pancreatic beta - cells ( hit ), indicating that ca2 + is not responsible for the initial stimulation of respiration . it is suggested that respiration is stimulated by increased substrate ( alpha - gp and pyruvate ) supply together with oscillatory increases in adp . the rise in ca2 +, which in itself may not significantly increase net respiration , could have the important functions of ( 1 ) activating the alpha - gp shuttle , to maintain an oxidized cytosol and high glycolytic flux ; ( 2 ) activating pyruvate dehydrogenase , and indirectly pyruvate carboxylase , to sustain production of citrate and hence the putative signal coupling factors , malonyl - coa and acyl - coa ; ( 3 ) increasing mitochondrial redox state to implement the switch from fatty acid to pyruvate oxidation . glucose - stimulated increases in mitochondrial metabolism are generally thought to be important for the activation of insulin secretion . pyruvate dehydrogenase ( pdh ) is a key regulatory enzyme , believed to govern the rate of pyruvate entry into the citrate cycle . it has been shown that elevated glucose concentrations ( 16 or 30 vs 3 mm ) cause an increase in pdh activity in both isolated rat islets , and in a clonal beta - cell line ( min6 ). however , increases in pdh activity elicited with either dichloroacetate , or by adenoviral expression of the catalytic subunit of pyruvate dehydrogenase phosphatase , were without effect on glucose - induced increases in mitochondrial pyridine nucleotide levels , or cytosolic atp concentration , in min6 cells , and insulin secretion from isolated rat islets . similarly , the above parameters were unaffected by blockade of the glucose - induced increase in pdh activity by adenovirus - mediated over - expression of pdh kinase ( pdk ). thus , activation of the pdh complex plays an unexpectedly minor role in stimulating glucose metabolism and in triggering insulin release . in pancreatic beta - cells , a rise in cytosolic atp is also a critical signaling event , coupling closure of atp - sensitive k + channels ( katp ) to insulin secretion via depolarization - driven increases in intracellular ca2 +. glycolytic but not krebs cycle metabolism of glucose is critically involved in this signaling process . while inhibitors of glycolysis suppressed glucose - stimulated insulin secretion , blockers of pyruvate transport or krebs cycle enzymes were without effect . while pyruvate was metabolized in islets to the same extent as glucose , it produced no stimulation of insulin secretion and did not block katp . in pancreatic beta - cells , methyl pyruvate is a potent secretagogue and is widely used to study stimulus - secretion coupling . mp stimulated insulin secretion in the absence of glucose , with maximal effect at 5 mm . mp depolarized the beta - cell in a concentration - dependent manner ( 5 - 20 mm ). pyruvate failed to initiate insulin release ( 5 - 20 mm ) or to depolarize the membrane potential . atp production in isolated beta - cell mitochondria was detected as accumulation of atp in the medium during incubation in the presence of malate or glutamate in combination with pyruvate or mp . atp production by mp and glutamate was higher than that induced by pyruvate / glutamate . pyruvate ( 5 mm ) or mp ( 5 mm ) had no effect on the atp / adp ratio in whole islets , whereas glucose ( 20 mm ) significantly increased the whole islet atp / adp ratio . in contrast with pyruvate , which barely stimulates insulin secretion , methyl pyruvate was suggested to act as an effective mitochondrial substrate . methyl pyruvate elicited electrical activity in the presence of 0 . 5 mm glucose , in contrast with pyruvate . accordingly , methyl pyruvate increased the cytosolic free ca ( 2 +) concentration after an initial decrease , similar to glucose . however , in contrast with glucose , methyl pyruvate even slightly decreased nad ( p ) h autofluorescence and did not influence atp production or the atp / adp ratio . therefore , mp - induced beta - cell membrane depolarization or insulin release does not relate directly to mitochondrial atp production . the finding that methyl pyruvate directly inhibited a cation current across the inner membrane of jurkat t - lymphocyte mitochondria suggests that this metabolite may increase atp production in beta - cells by activating the respiratory chains without providing reduction equivalents . this mechanism may account for a slight and transient increase in atp production . furthermore methyl pyruvate inhibited the k ( atp ) current measured in the standard whole - cell configuration . accordingly , single - channel currents in inside - out patches were blocked by methyl pyruvate . therefore , the inhibition of k ( atp ) channels , and not activation of metabolism , mediates the induction of electrical activity in pancreatic beta - cells by methyl pyruvate . as a membrane - permeant analog , methyl pyruvate , produced a block of katp , a sustained rise in [ ca2 +] i , and an increase in insulin secretion 6 - fold the magnitude of that induced by glucose . this indicates that atp derived from mitochondrial pyruvate metabolism does not substantially contribute to the regulation of katp responses to a glucose challenge . supporting the notion of sub - compartmentation of atp within the beta - cell . supra - normal stimulation of the krebs cycle by methyl pyruvate can , however , overwhelm intracellular partitioning of atp and thereby drive insulin secretion . the metabolism of methyl pyruvate was compared to that of pyruvate in isolated rat pancreatic islets . methyl pyruvate was found to be more efficient than pyruvate in supporting the intramitochondrial conversion of pyruvate metabolites to amino acids , inhibiting d -[ 5 - 3h ] glucose utilization , maintaining a high ratio between d -[ 3 , 4 - 14c ] glucose or d -[ 6 - 14c ] glucose oxidation and d -[ 5 - 3h ] glucose utilization , inhibiting the intramitochondrial conversion of glucose - derived 2 - keto acids to their corresponding amino acids , and augmenting 14co2 output from islets prelabeled with l -[ u - 14c ] glutamine . methyl pyruvate also apparently caused a more marked mitochondrial alkalinization than pyruvate , as judged from comparisons of ph measurements based on the use of either a fluorescein probe or 14c - labeled 5 , 5 - dimethyl - oxazolidine - 2 , 4 - dione . inversely , pyruvate was more efficient than methyl pyruvate in increasing lactate output and generating l - alanine . these converging findings indicate that , by comparison with exogenous pyruvate , its methyl ester is preferentially metabolized in the mitochondrial , rather than cytosolic , domain of islet cells . it is proposed that both the positive and the negative components of methyl pyruvate insulinotropic action are linked to changes in the net generation of reducing equivalents , atp and h +. methyl pyruvate was found to exert a dual effect on insulin release from isolated rat pancreatic islets . a positive insulinotropic action prevailed at low concentrations of d - glucose , in the 2 . 8 to 8 . 3 mm range , and at concentrations of the ester not exceeding 1 0 . 0 mm . it displayed features typical of a process of nutrient - stimulated insulin release , such as decreased k + conductance , enhanced ca2 + influx , and stimulation of proinsulin biosynthesis . a negative insulinotropic action of methyl pyruvate was also observed , however , at a high concentration of d - glucose ( 16 . 7 mm ) and / or at a high concentration of the methyl ester ( 20 . 0 mm ). it was apparently not attributable to any adverse effect of methyl pyruvate on atp generation , but might be due to hyperpolarization of the plasma membrane . the ionic determinant ( s ) of the latter change was not identified . the dual effect of methyl pyruvate probably accounts for an unusual time course of the secretory response , including a dramatic and paradoxical stimulation of insulin release upon removal of the ester . pancreatic beta - cell metabolism was followed during glucose and pyruvate stimulation of pancreatic islets using quantitative two - photon nad ( p ) h imaging . the observed redox changes , spatially separated between the cytoplasm and mitochondria , were compared with whole islet insulin secretion . as expected , both nad ( p ) h and insulin secretion showed sustained increases in response to glucose stimulation . in contrast , pyruvate caused a much lower nad ( p ) h response and did not generate insulin secretion . low pyruvate concentrations decreased cytoplasmic nad ( p ) h without affecting mitochondrial nad ( p ) h , whereas higher concentrations increased cytoplasmic and mitochondrial levels . however , the pyruvate - stimulated mitochondrial increase was transient and equilibrated to near - base - line levels . inhibitors of the mitochondrial pyruvate - transporter and malate - aspartate shuttle were utilized to resolve the glucose - and pyruvate - stimulated nad ( p ) h response mechanisms . these data showed that glucose - stimulated mitochondrial nad ( p ) h and insulin secretion are independent of pyruvate transport but dependent on nad ( p ) h shuttling . in contrast , the pyruvate - stimulated cytoplasmic nad ( p ) h response was enhanced by both inhibitors . surprisingly the malate - aspartate shuttle inhibitor enabled pyruvate - stimulated insulin secretion . these data support a model in which glycolysis plays a dominant role in glucose - stimulated insulin secretion . based on these data , it was proposed as a mechanism for glucose - stimulated insulin secretion that includes allosteric inhibition of tricarboxylic acid cycle enzymes and ph dependence of mitochondrial pyruvate transport . pyridine dinucleotides ( nad and nadp ) are ubiquitous cofactors involved in hundreds of redox reactions essential for the energy transduction and metabolism in all living cells . in addition , nad also serves as a substrate for adp - ribosylation of a number of nuclear proteins , for silent information regulator 2 ( sir2 )- like histone deacetylase that is involved in gene silencing regulation , and for cyclic adp ribose ( cadpr )- dependent ca ( 2 +) signaling . pyridine nucleotide adenylyltransferase ( pnat ) is an indispensable central enzyme in the nad biosynthesis pathways catalyzing the condensation of pyridine mononucleotide ( nmn or namn ) with the amp moiety of atp to form nad ( or naad ). in isolated pancreatic islets , pyruvate causes a shift to the left of the sigmoidal curve relating the rate of insulin release to the ambient glucose concentration . the magnitude of this effect is related to the concentration of pyruvate ( 5 -- 90 mm ) and , at a 30 mm concentration , is equivalent to that evoked by 2 mm - glucose . ( 1 ) 2 . in the presence of glucose 8 mm ), the secretory response to pyruvate is an immediate process , displaying a biphasic pattern . ( 2 ) 3 . the insulinotropic action of pyruvate coincides with an inhibition of 45ca efflux and a stimulation of 45ca net uptake . the relationship between 45ca uptake and insulin release displays its usual pattern in the presence of pyruvate . ( 3 ) 4 . exogenous pyruvate rapidly accumulates in the islets in amounts close to those derived from the metabolism of glucose . the oxidation of [ 2 - 14c ] pyruvate represents 64 % of the rate of [ 1 - 14c ] pyruvate decarboxylation and , at a 30 mm concentration , is comparable with that of 8 mm -[ u - 14c ] glucose . ( 4 ) 5 . when corrected for the conversion of pyruvate into lactate , the oxidation of 30 mm - pyruvate corresponds to a net generation of about 314 pmol of reducing equivalents / 120 min per islet . ( 5 ) 6 . pyruvate does not affect the rate of glycolysis , but inhibits the oxidation of glucose . glucose does not affect pyruvate oxidation . ( 6 ) 7 . pyruvate ( 30 mm ) does not affect the concentration of atp , adp and amp in the islet cells . ( 7 ) 8 . pyruvate ( 30 mm ) increases the concentration of reduced nicotinamide nucleotides in the presence but not in the absence of glucose . a close correlation is seen between the concentration of reduced nicotinamide nucleotides and the net uptake of 45 ca . ( 9 ) 10 . pyruvate , in contrast with glucose , markedly inhibits the oxidation of endogenous nutrients . the latter effect accounts for the apparent discrepancy between the rate of pyruvate oxidation and the magnitude of its insulinotropic action . ( 10 ) 11 . it is concluded that the effect of pyruvate to stimulate insulin release depends on its ability to increase the concentration of reduced nicotinamide nucleotides in the islet cells . glucose - stimulated insulin secretion is a multi - step process dependent on cell metabolic flux . previous studies on intact pancreatic islets used two - photon nad ( p ) h imaging as a quantitative measure of the combined redox signal from nadh and nadph ( referred to as nad ( p ) h ). these studies showed that pyruvate , a non - secretagogue , enters - cells and causes a transient rise in nad ( p ) h . to further characterize the metabolic fate of pyruvate , a one - photon flavoprotein microscopy has been developed as a simultaneous assay of lipoamide dehydrogenase ( lipdh ) autofluorescence . this flavoprotein is in direct equilibrium with mitochondrial nadh . using this method , the glucose - dose response is consistent with an increase in both nadh and nadph . in contrast , the transient rise in nad ( p ) h observed with pyruvate stimulation is not accompanied by a significant change in lipdh , which indicates that pyruvate raises cellular nadph without raising nadh . in comparison , methyl pyruvate stimulated a robust nadh and nadph response . these data provide new evidence that exogenous pyruvate does not induce a significant rise in mitochondrial nadh . this inability likely results in its failure to produce the atp necessary for stimulated secretion of insulin . overall , these data are consistent with either restricted pdh dependent metabolism or a buffering of the nadh response by other metabolic mechanisms . glucose metabolism in glycolysis and in mitochondria is pivotal to glucose - induced insulin secretion from pancreatic beta cells . one or more factors derived from glycolysis other than pyruvate appear to be required for the generation of mitochondrial signals that lead to insulin secretion . the electrons of the glycolysis - derived reduced form of nicotinamide adenine dinucleotide ( nadh ) are transferred to mitochondria through the nadh shuttle system . by abolishing the nadh shuttle function , glucose - induced increases in nadh autofluorescence , mitochondrial membrane potential , and adenosine triphosphate content were reduced and glucose - induced insulin secretion was abrogated . the nadh shuttle evidently couples glycolysis with activation of mitochondrial energy metabolism to trigger insulin secretion . to determine the role of the nadh shuttle system composed of the glycerol phosphate shuttle and malate - aspartate shuttle in glucose - induced insulin secretion from pancreatic beta cells , mice which lack mitochondrial glycerol - 3 phosphate dehydrogenase mgpdh ), a rate - limiting enzyme of the glycerol phosphate shuttle were used . when both shuttles were halted in mgpdh - deficient islets treated with aminooxyacetate , an inhibitor of the malate - aspartate shuttle , glucose - induced insulin secretion was almost completely abrogated . under these conditions , although the flux of glycolysis and supply of glucose - derived pyruvate into mitochondria were unaffected , glucose - induced increases in nad ( p ) h autofluorescence , mitochondrial membrane potential , ca2 + entry into mitochondria , and atp content were severely attenuated . this study provides the first direct evidence that the nadh shuttle system is essential for coupling glycolysis with the activation of mitochondrial energy metabolism to trigger glucose - induced insulin secretion and thus revises the classical model for the metabolic signals of glucose - induced insulin secretion . incubation of porcine carotid arteries with 0 . 4 mmol amino - oxyacetic acid an inhibitor of glutamate - oxaloacetate transaminase and , hence the malate - aspartate shuttle , inhibited o2 consumption by 21 %, decreased the content of phosphocreatine and inhibited activity of the tricarboxylic acid cycle . the rate of glycolysis and lactate production was increased but glucose oxidation was inhibited . these effects of amino - oxyacetic acid were accompanied by evidence of inhibition of the malate - aspartate shuttle and elevation in the cytoplasmic redox potential and nadh / nad ratio as indicated by elevation of the concentration ratios of the lactate / pyruvate and glycerol - 3 - phosphate / dihydroxyacetone phosphate metabolite redox couples . addition of the fatty acid octanoate normalized the adverse energetic effects of malate - aspartate shuttle inhibition . it is concluded that the malate - aspartate shuttle is a primary mode of clearance of nadh reducing equivalents from the cytoplasm in vascular smooth muscle . glucose oxidation and lactate production are influenced by the activity of the shuttle . the results support the hypothesis that an increased cytoplasmic nadh redox potential impairs mitochondrial energy metabolism . beta - methyleneaspartate , a specific inhibitor of aspartate aminotransferase ( ec 2 . 6 . 1 . 1 . ), was used to investigate the role of the malate - aspartate shuttle in rat brain synaptosomes . incubation of rat brain cytosol , “ free ” mitochondria , synaptosol , and synaptic mitochondria , with 2 mm beta - methyleneaspartate resulted in inhibition of aspartate aminotransferase by 69 %, 67 %, 49 %, and 76 %, respectively . the reconstituted malate - aspartate shuttle of “ free ” brain mitochondria was inhibited by a similar degree ( 53 %). as a consequence of the inhibition of the aspartate aminotransferase , and hence the malate - aspartate shuttle , the following changes were observed in synaptosomes : decreased glucose oxidation via the pyruvate dehydrogenase reaction and the tricarboxylic acid cycle ; decreased acetylcholine synthesis ; and an increase in the cytosolic redox state , as measured by the lactate / pyruvate ratio . the main reason for these changes can be attributed to decreased carbon flow through the tricarboxylic acid cycle ( i . e ., decreased formation of oxaloacetate ), rather than as a direct consequence of changes in the nad +/ nadh ratio . malate / glutamate oxidation in “ free ” mitochondria was also decreased in the presence of 2 mm beta - methyleneaspartate . this is probably a result of decreased glutamate transport into mitochondria as a result of low levels of aspartate , which are needed for the exchange with glutamate by the energy - dependent glutamate - aspartate translocator . aminooxyacetate , an inhibitor of pyridoxal - dependent enzymes , is routinely used to inhibit gamma - aminobutyrate metabolism . the bioenergetic effects of the inhibitor on guinea - pig cerebral cortical synaptosomes are investigated . it prevents the reoxidation of cytosolic nadh by the mitochondria by inhibiting the malate - aspartate shuttle , causing a 26 mv negative shift in the cytosolic nad +/ nadh redox potential , an increase in the lactate / pyruvate ratio and an inhibition of the ability of the mitochondria to utilize glycolytic pyruvate . the 3 - hydroxybutyrate / acetoacetate ratio decreased significantly , indicating oxidation of the mitochondrial nad +/ nadh couple . the results are consistent with a predominant role of the malate - aspartate shuttle in the reoxidation of cytosolic nadh in isolated nerve terminals . aminooxyacetate limits respiratory capacity and lowers mitochondrial membrane potential and synaptosomal atp / adp ratios to an extent similar to glucose deprivation . variations in the cytoplasmic redox potential ( eh ) and nadh / nad ratio as determined by the ratio of reduced to oxidized intracellular metabolite redox couples may affect mitochondrial energetics and alter the excitability and contractile reactivity of vascular smooth muscle . to test these hypotheses , the cytoplasmic redox state was experimentally manipulated by incubating porcine carotid artery strips in various substrates . the redox potentials of the metabolite couples [ lactate ]/[ pyruvate ] i and [ glycerol 3 - phosphate ]/[ dihydroxyacetone phosphate ] i varied linearly ( r = 0 . 945 ), indicating equilibrium between the two cytoplasmic redox systems and with cytoplasmic nadh / nad . incubation in physiological salt solution ( pss ) containing 10 mm pyruvate ([ lact ]/[ pyr ]= 0 . 6 ) increased o2 consumption approximately 45 % and produced anaplerosis of the tricarboxylic acid ( tca cycle ), whereas incubation with 10 mm lactate - pss ([ lact ]/[ pyr ] i = 47 ) was without effect . a hyperpolarizing dose of external kcl ( 10 mm ) produced a decrease in resting tone of muscles incubated in either glucose - pss (− 0 . 8 +/− 0 . 8 g ) or pyruvate - pss (− 2 . 1 +/− 0 . 8 g ), but increased contraction in lactate - pss ( 1 . 5 +/− 0 . 7 g ) ( n = 12 - 18 , p & lt ; 0 . 05 ). the rate and magnitude of contraction with 80 mm kcl ( depolarizing ) was decreased in lactate - pss ( p = 0 . 001 ). slopes of kcl concentration - response curves indicated pyruvate & gt ; glucose & gt ; lactate ( p & lt ; 0 . 0001 ); ec50 in lactate ( 29 . 1 +/− 1 . 0 mm ) was less than that in either glucose ( 32 . 1 +/− 0 . 9 mm ) or pyruvate ( 32 . 2 +/− 1 . 0 mm ), p & lt ; 0 . 03 . the results are consistent with an effect of the cytoplasmic redox potential to influence the excitability of the smooth muscle and to affect mitochondrial energetics . the cytoplasmic nadh / nad redox potential affects energy metabolism and contractile reactivity of vascular smooth muscle . nadh / nad redox state in the cytosol is predominately determined by glycolysis , which in smooth muscle is separated into two functionally independent cytoplasmic compartments , one of which fuels the activity of na (+)- k (+)- atpase . the effect was examined of varying the glycolytic compartments on cystosolic nadh / nad redox state . inhibition of na (+)- k (+)- atpase by 10 microm ouabain resulted in decreased glycolysis and lactate production . despite this , intracellular concentrations of the glycolytic metabolite redox couples of lactate / pyruvate and glycerol - 3 - phosphate / dihydroxyacetone phosphate ( thus nadh / nad ) and the cytoplasmic redox state were unchanged . the constant concentration of the metabolite redox couples and redox potential was attributed to ( 1 ) decreased efflux of lactate and pyruvate due to decreased activity of monocarboxylate b — h (+) transporter secondary to decreased availability of h (+) for cotransport and ( 2 ) increased uptake of lactate ( and perhaps pyruvate ) from the extracellular space , probably mediated by the monocarboxylate - h (+) transporter , which was specifically linked to reduced activity of na (+)- k (+)- atpase . it was concluded that redox potentials of the two glycolytic compartments of the cytosol maintain equilibrium and that the cytoplasmic nadh / nad redox potential remains constant in the steady state despite varying glycolytic flux in the cytosolic compartment for na (+)- k (+)- atpase . peroxisomal proliferator - activated receptors ( ppars ) belong to a nuclear receptor superfamily of ligand - activated transcription factors . peroxisome proliferator - activated receptor ( ppar ) is activated when a ligand binds to the ligand - binding domain at the side of c - termini . so far , three types of isoforms of alpha form , gamma form and delta form have been identified as ppars , and the expression tissues and the functions are different respectively . peroxisome proliferators are a structurally diverse group of compounds which , when administered to rodents , elicit dramatic increases in the size and number of hepatic and renal peroxisomes , as well as concomitant increases in the capacity of peroxisomes to metabolize fatty acids via increased expression of the enzymes required for the beta - oxidation cycle it is known that the alpha - isoform of peroxisome proliferator - activated receptor ( ppar . alpha ) acts to stimulate peroxisomal proliferation in the rodent liver which leads to enhanced fatty oxidation by this organ . ( ppar ) alpha is a nuclear receptor that is mainly expressed in tissues with a high degree of fatty acid oxidation such as liver , heart , and skeletal muscle . there is a sex difference in pparalpha expression . male rats have higher levels of hepatic pparalpha mrna and protein than female rats . chemicals included in this group are the fibrate class of hypolipidermic drugs , herbicides , and phthalate plasticizers . peroxisome proliferation can also be elicited by dietary or physiological factors such as a high - fat diet and cold acclimatization . the importance of peroxisomes in humans is stressed by the existence of a group of genetic diseases in man in which one or more peroxisomal functions are impaired . most of the functions known to take place in peroxisomes have to do with lipids . indeed , peroxisomes are capable of 1 . fatty acid beta - oxidation 2 . fatty acid alpha - oxidation 3 . synthesis of cholesterol and other isoprenoids 4 . ether - phospholipid synthesis and 5 . biosynthesis of polyunsaturated fatty acids . in animal cells peroxisomes as well as mitochondria are capable of degrading lipids via beta - oxidation . nevertheless , there are important differences between the two systems . ( 2 ) peroxisomal beta - oxidation does not degrade fatty acids completely but acts as a chain - shortening system , catalyzing only a limited number of beta - oxidation cycles . ( 3 ) peroxisomal beta - oxidation is not coupled to oxidative phosphorylation and is thus less efficient than mitochondrial beta - oxidation as far as energy conservation is concerned . ( 4 ) peroxisomal beta - oxidation is not regulated by malonyl - coa and — as a consequence — by feeding as opposed to starvation . insight into the mechanism whereby peroxisome proliferators exert their pleiotropic effects was provided by the identification of a member of the nuclear hormone receptor superfamily activated by these chemicals . this receptor , termed peroxisome proliferator activated receptor alpha ( ppar alpha ), was subsequently shown to be activated by a variety of medium and long - chain fatty acids and to stimulate expression of the genes . the ppar alpha binds to promoter domain of key enzymes concerning in the lipid catabolism system such as acyl - coa synthase existing in the cytosol , acyl - coa dehydrogenase and hmg - coa synthase existing in the mitochondria and acyl - coa oxidase existing in the peroxisome of liver . from the analysis of ppar alpha - deficient mice , it is being considered that the ppar alpha plays an important role for the energy acquisition in starvation state , that is , oxidation of fatty acid and formation of ketone body in liver . since the discovery of ppar alpha additional isoforms of ppar have been identified , ppar beta , ppar gamma and ppar delta , which are spatially differentially expressed . the nuclear peroxisome proliferator - activated receptor gamma ( ppargamma ) activates the transcription of multiple genes involved in intra - and extracellular lipid metabolism . these ppars regulate expression of target genes by binding to dna sequence elements , termed ppar response elements ( ppre ). to date , ppre &# 39 ; s have been identified in the enhancers of a number of genes encoding proteins that regulate lipid metabolism suggesting that ppars play a pivotal role in the adipogenic signaling cascade and lipid homeostasis . because there are several isoforms of ppar , it is desirable to identify compounds which are capable of selectively interacting with only one of the ppar isoforms . hypolipidaemic agents have the ability to stimulate ppar alpha and the ensuing stimulation of peroxisomal proliferation and consequent fatty acid oxidation can account for the reduction in plasma fatty acids . ppar - gamma plays a key role in adipocyte differentiation and insulin sensitivity — its selective synthetic ligands , the thiazolidinediones ( tzd ), are used as insulin sensitizers in the treatment of type 2 diabetes . compounds also exist which exhibit agonist activity at both ppar alpha and ppar gamma and would be particularly effective for the treatment of obesity as well as for the treatment of diabetes / pre - diabetic insulin resistance syndrome and the resulting complications thereof . function of ppar delta is not very understood compared with alpha form or gamma form . knowledge of the mechanisms that regulate pdc activity is important , because pdc inactivation is crucial for glucose conservation when glucose is scarce , whereas adequate pdc activity is required to allow both atp and fa production from glucose . fuel metabolism is highly regulated to ensure adequate energy for cellular function . the contribution of the major metabolic fuels — glucose , lactate and fatty acids ( fas )— often reflects their circulating levels . in addition , regulatory cross - talk and fuel - induced hormone secretion ensures appropriate and co - ordinate fuel utilization . because its activity can either determine or reflect fuel preference ( carbohydrate versus fat ), the pyruvate dehydrogenase complex ( pdc ) occupies a pivotal position in fuel cross - talk . active pdc permits glucose oxidation and allows the formation of mitochondrially - derived intermediates ( e . g . malonyl - coa and citrate ) that reflect fuel abundance . fa oxidation suppresses pdc activity . pdc inactivation by phosphorylation is catalysed by pyruvate dehydrogenase kinases ( pdks ) 1 - 4 , which are regulated differentially by metabolite effectors . most tissues contain at least two and often three of the pdk isoforms . a hypothesis was developed that pdk4 is a “ lipid status ”— responsive pdk isoform facilitating fa oxidation and signalling through citrate formation . substrate interactions at the level of gene transcription extend glucose - fa interactions to the longer term . isoform - specific differences in kinetic parameters , regulation , and phosphorylation site specificity of the pdks introduce variations in the regulation of pdc activity in differing endocrine and metabolic states . thus potential targets for substrate - mediated transcriptional regulation in relation to selective pdk isoform expression and the influence of altered pdk isoform expression in fuel sensing , selection and utilization . adequate flux through pdc is important in tissues with a high atp requirement , in lipogenic tissues ( since it provides cytosolic acetyl - coa for fatty acid ( fa ) synthesis ), and in generating cytosolic malonyl - coa , a potent inhibitor of carnitine palmitoyltransferase ( cpt i ). conversely , suppression of pdc activity is crucial for glucose conservation when glucose is scarce . recent advances relating to the control of mammalian pdc activity by phosphorylation ( inactivation ) and dephosphorylation ( activation , reactivation ), in particular regulation of pdc by pyruvate dehydrogenase kinase ( pdk ), which phosphorylates and inactivates pdc . inactivation of pdc by increased pdk activity promotes gluconeogenesis by conserving three - carbon substrates . pdk activity is that of a family of four proteins ( pdk1 - 4 ). pdk2 and pdk4 appear to be expressed in most major tissues and organs of the body , pdk1 appears to be limited to the heart and pancreatic islets , and pdk3 is limited to the kidney , brain and testis . pdk4 is selectively upregulated in the longer term in most tissues and organs in response to starvation and hormonal imbalances such as insulin resistance , diabetes mellitus and hyperthyroidism . parallel increases in pdk2 and pdk4 expression appear to be restricted to gluconceogenesic tissues , liver and kidney , which take up as well as generate pyruvate . immunoblot analysis with antibodies raised against recombinant pdk isoforms demonstrated changes in pdk isoform expression in response to experimental hyperthyroidism ( 100 microg / 100 g body weight ; 3 days ) that was selective for fast - twitch vs slow - twitch skeletal muscle in that pdk2 expression was increased in the fast - twitch skeletal muscle ( the anterior tibialis ) ( by 1 . 6 - fold ; p & lt ; 0 . 05 ) but not in the slow - twitch muscle ( the soleus ). pdk4 protein expression was increased by experimental hyperthyroidism in both muscle types , there being a greater response in the anterior tibialis ( 4 . 2 - fold increase ; p & lt ; 0 . 05 ) than in the soleus ( 3 . 2 - fold increase ; p & lt ; 0 . 05 ). the hyperthyroidism - associated up - regulation of pdk4 expression was observed in conjunction with suppression of skeletal - muscle pdc activity , but not suppression of glucose uptake / phosphorylation , as measured in vivo in conscious unrestrained rats ( using the 2 -[( 3 ) h ] deoxyglucose technique ). it was proposed that increased pdk isoform expression contributes to the pathology of hyperthyroidism and to pdc inactivation by facilitating the operation of the glucose --& gt ; lactate --& gt ; glucose ( cori ) and glucose --& gt ; alanine --& gt ; glucose cycles . we also propose that enhanced relative expression of the pyruvate - insensitive pdk isoform ( pdk4 ) in skeletal muscle in hyperthyroidism uncouples glycolytic flux from pyruvate oxidation , sparing pyruvate for non - oxidative entry into the tricarboxylic acid ( tca ) cycle , and thereby supporting entry of acetyl - coa ( derived from fatty acid oxidation ) into the tca cycle . regulation of pdc determines and reflects substrate preference and is critical to the ‘ glucose - fatty acid cycle ’, a concept of reciprocal regulation of lipid and glucose oxidation to maintain glucose homoeostasis . mammalian pdc activity is inactivated by phosphorylation by the pdks ( pyruvate dehydrogenase kinases ). pdk inhibition by pyruvate facilitates pdc activation , favouring glucose oxidation and malonyl - coa formation : the latter suppresses lcfa ( long - chain fatty acid ) oxidation . pdk activation by the high mitochondrial acetyl - coa / coa and nadh / nad (+) concentration ratios that reflect high rates of lcfa oxidation causes blockade of glucose oxidation . complementing glucose homoeostasis in health , fuel allostasis , i . e . adaptation to maintain homoeostasis , is an essential component of the response to chronic changes in glycaemia and lipidaemia in insulin resistance . the concept that the pdks act as tissue homoeostats , suggests that long - term modulation of expression of individual pdks , particularly pdk4 , is an essential component of allostasis to maintain homoeostasis . this also describes the intracellular signals that govern the expression of the various pdk isoforms , including the roles of the peroxisome proliferator - acivated receptors and lipids , as effectors within the context of allostasis . agonists of peroxisome proliferator - activated receptors ( ppars ) have emerged as important pharmacological agents for improving insulin action . a major mechanism of action of ppar agonists is thought to involve the alteration of the tissue distribution of nonesterified fatty acid ( nefa ) uptake and utilization . to test this hypothesis directly , the effect of the novel ppara / g agonist tesaglitazar was examined on whole - body insulin sensitivity and nefa clearance into epididymal white adipose tissue ( wat ), red gastrocnemius muscle , and liver in rats with dietary - induced insulin resistance . wistar rats were fed a high - fat diet ( 59 of calories as fat ) for 3 wk with or without treatment with tesaglitazar ( 1 mmol . kg - 1 . d - 1 , 7 d ). nefa clearance was measured using the partially metabolizable nefa tracer , 3h - r - bromopalmitate , administered under conditions of basal or elevated nefa availability . tesaglitazar improved the insulin sensitivity of high - fat - fed rats , indicated by an increase in the glucose infusion rate during hyperinsulinemic - euglycemic clamp ( p & lt ; 0 . 01 ). this improvement in insulin action was associated with decreased diglyceride ( p & lt ; 0 . 05 ) and long chain acyl coenzyme a ( p & lt ; 0 . 05 ) in skeletal muscle . nefa clearance into wat of high - fat - fed rats was increased 52 by tesaglitazar under basal conditions ( p & lt ; 0 . 001 ). in addition the ppara / g agonist moderately increased hepatic and muscle nefa utilization and reduced hepatic triglyceride accumulation ( p & lt ; 0 . 05 ). this study shows that tesaglitazar is an effective insulin - sensitizing agent in a mild dietary model of insulin resistance . furthermore , we provide the first direct in vivo evidence that an agonist of both ppara and pparg increases the ability of wat , liver , and skeletal muscle to use fatty acids in association with its beneficial effects on insulin action in this model . liver contains two pyruvate dehydrogenase kinases ( pdks ), namely pdk2 and pdk4 , which regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex ( pdc ). starvation increases hepatic pdk2 and pdk4 protein expression , the latter occurring , in part , via a mechanism involving peroxisome proliferator - activated receptor - alpha ( pparalpha ). high - fat feeding and hyperthyroidism , which increase circulating lipid supply , enhance hepatic pdk2 protein expression , but these increases are insufficient to account for observed increases in hepatic pdk activity . enhanced expression of pdk4 , but not pdk2 , occurs in part via a mechanism involving ppar - alpha . fatty acid metabolism is transcriptionally regulated by two reciprocal systems : peroxisome proliferator - activated receptor ( ppar ) a controls fatty acid degradation , whereas sterol regulatory element - binding protein - 1c activated by liver x receptor ( lxr ) regulates fatty acid synthesis . to explore potential interactions between lxr and ppar , the effect of lxr activation on ppara signaling was investigated . in luciferase reporter gene assays , overexpression of lxra or b suppressed ppara - induced peroxisome proliferator response element - luciferase activity in a dose - dependent manner . lxr agonists , t0901317 and 22 ( r )- hydroxycholesterol , dose dependently enhanced the suppressive effects of lxrs . gel shift assays demonstrated that lxr reduced binding of ppara / retinoid x receptor ( rxr ) a to peroxisome proliferator response element . addition of increasing amounts of rxra restored these inhibitory effects in both luciferase and gel shift assays , suggesting the presence of rxra competition . in vitro protein binding assays demonstrated that activation of lxr by an lxr agonist promoted formation of lxr / rxra and , more importantly , lxr / ppara heterodimers , leading to a reduction of ppara / rxra formation . supportively , in vivo administration of the lxr ligand to mice and rat primary hepatocytes substantially decreased hepatic mrna levels of ppara - targeted genes in both basal and ppara agonist - induced conditions . the amount of nuclear ppara / rxr heterodimers in the mouse livers was induced by treatment with ppara ligand , and was suppressed by superimposed lxr ligand . taken together with data from the paper ( yoshikawa , t ., t . ide , h . shimano , n . yahagi , m . amemiya - kudo , t . matsuzaka , s . yatoh , t . kitamine , h . okazaki , y . tamura , m . sekiya , a . takahashi , a . h . hasty , r . sato , h . sone , j . osuga , s . ishibashi , and n . yamada , endocrinology 144 : 1240 - 1254 ) describing ppara suppression of the lxr - sterol regulatory element - binding protein - 1c pathway , it has been proposed that the presence of an intricate network of nutritional transcription factors with mutual interactions , resulting in efficient reciprocal regulation of lipid degradation and lipogenesis . heterodimerization partners for retinoid x receptors ( rxrs ) include pparalpha and thyroid - hormone receptors ( trs ). the responses were investigated of hepatic pdk protein expression to high - fat feeding and hyperthyroidism in relation to hepatic lipid delivery and disposal . high - fat feeding increased hepatic pdk2 , but not pdk4 , protein expression whereas hyperthyroidism increased both hepatic pdk2 and pdk4 protein expression . both manipulations decreased the sensitivity of hepatic carnitine palmitoyltransferase i ( cpt i ) to suppression by malonyl - coa , but only hyperthyrodism elevated plasma fatty acid and ketone - body concentrations and cpt i maximal activity . administration of the selective ppar - alpha activator wy14 , 643 significantly increased pdk4 protein to a similar extent in both control and high - fat - fed rats , but wy14 , 643 treatment and hyperthyroidism did not have additive effects on hepatic pdk4 protein expression . pparalpha activation did not influence hepatic pdk2 protein expression in euthyroid rats , suggesting that up - regulation of pdk2 by hyperthyroidism does not involve pparalpha , but attenuated the effect of hyperthyroidism to increase hepatic pdk2 expression . the results indicate that hepatic pdk4 up - regulation can be achieved by heterodimerization of either ppar alpha or tr with the rxr receptor and that effects of ppar alpha activation on hepatic pdk2 and pdk4 expression favour a switch towards preferential expression of pdk4 . the pyruvate dehydrogenase complex ( pdc ) occupies a strategic role in renal intermediary metabolism , via partitioning of pyruvate flux between oxidation and entry into the gluconeogenic pathway . inactivation of pdc via activation of pyruvate dehydrogenase kinases ( pdks ), which catalyze pdc phosphorylation , occurs secondary to increased fatty acid oxidation ( fao ). in kidney , inactivation of pdc after prolonged starvation is mediated by up - regulation of the protein expression of two pdk isoforms , pdk2 and pdk4 . the lipid - activated transcription factor , peroxisome proliferator - activated receptor - alpha ( ppar alpha ), plays a pivotal role in the cellular metabolic response to fatty acids and is abundant in kidney . in the present study ppar alpha null mice were used to examine the potential role of ppar alpha in regulating renal pdk protein expression . in wild - type mice , fasting ( 24 h ) induced marked up - regulation of the protein expression of pdk4 , together with modest up - regulation of pdk2 protein expression . in striking contrast , renal protein expression of pdk4 was only marginally induced by fasting in ppar alpha null mice . the present results define a critical role for ppar alpha in renal adaptation to fasting , and identify pdk4 as a downstream target of ppar alpha activation in the kidney . it has been proposed that specific up - regulation of renal pdk4 protein expression in starvation , by maintaining pdc activity relatively low , facilitates pyruvate carboxylation to oxaloacetate and therefore entry of acetyl - coa derived from fa beta - oxidation into the tca cycle , allowing adequate atp production for brisk rates of gluconeogenesis . factors that regulate pdk4 expression include fa oxidation and adequate insulin action . pdk4 is also either a direct or indirect target of peroxisome proliferator - activated receptor ( ppar ) alpha . ppar alpha deficiency in liver and kidney restricts starvation - induced upregulation of pdk4 ; however , the role of ppar alpha in heart and skeletal muscle appears to be more complex . these observations may have important implications for the pharmacological modulation of pdk activity ( e . g . use of ppar alpha activators ) for the control of whole - body glucose , lipid and lactate homeostasis in disease states and suggest that therapeutic interventions must be tissue targeted so that whole - body fuel homeostasis is not adversely perturbed . regulation of the activity of the pyruvate dehydrogenase complex in skeletal muscle plays an important role in fuel selection and glucose homeostasis . activation of the complex promotes disposal of glucose , whereas inactivation conserves substrates for hepatic glucose production . starvation and diabetes induce a stable increase in pyruvate dehydrogenase kinase activity in skeletal muscle mitochondria that promotes phosphorylation and inactivation of the complex . the present study shows that these metabolic conditions induce a large increase in the expression of pdk4 , one of four pyruvate dehydrogenase kinase isoenzymes expressed in mammalian tissues , in the mitochondria of gastrocnemius muscle . refeeding starved rats and insulin treatment of diabetic rats decreased pyruvate dehydrogenase kinase activity and also reversed the increase in pdk4 protein in gastrocnemius muscle mitochondria . starvation and diabetes also increased the abundance of pdk4 mrna in gastrocnemius muscle , and refeeding and insulin treatment again reversed the effects of starvation and diabetes . these findings suggest that an increase in amount of this enzyme contributes to hyperphosphorylation and inactivation of the pyruvate dehydrogenase complex in these metabolic conditions . it was further found that feeding rats wy - 14 , 643 , a selective agonist for the peroxisome proliferator - activated receptor - alpha ( ppar - alpha ), also induced large increases in pyruvate dehydrogenase kinase activity , pdk4 protein , and pdk4 mrna in gastrocnemius muscle . since long - chain fatty acids activate ppar - alpha endogenously , increased levels of these compounds in starvation and diabetes may signal increased expression of pdk4 in skeletal muscle . the transcriptional coactivator ppar gamma coactivator 1 alpha ( pgc - 1 alpha ) is a key regulator of metabolic processes such as mitochondrial biogenesis and respiration in muscle and gluconeogenesis in liver . reduced levels of pgc - 1 alpha in humans have been associated with type ii diabetes . pgc - 1 alpha contains a negative regulatory domain that attenuates its transcriptional activity . this negative regulation is removed by phosphorylation of pgc - 1 alpha by p38 mapk , an important kinase downstream of cytokine signaling in muscle and beta - adrenergic signaling in brown fat . described here the identification of p160 myb binding protein ( p160 mbp ) as a repressor of pgc - 1 alpha . the binding and repression of pgc - 1alpha by p160 mbp is disrupted by p38 mapk phosphorylation of pgc - 1 alpha . adenoviral expression of p160 mbp in myoblasts strongly reduces pgc - 1alpha &# 39 ; s ability to stimulate mitochondrial respiration and the expression of the genes of the electron transport system . this repression does not require removal of pgc - 1 alpha from chromatin , suggesting that p160 mbp is or recruits a direct transcriptional suppressor . overall , these data indicate that p160 mbp is a powerful negative regulator of pgc - 1 alpha function and provide a molecular mechanism for the activation of pgc - 1 alpha by p38 mapk . in rat pancreatic islets chronically exposed to high glucose or high free fatty acid ( ffa ) levels , glucose - induced insulin release and mitochondrial glucose oxidation are impaired . these abnormalities are associated with high basal atp levels but a decreased glucose - induced atp production ( delta of increment over baseline 0 . 7 +/− 0 . 5 or 0 . 5 +/− 0 . 3 pmol / islet in islets exposed to glucose or ffa vs . 1 2 . 0 +/− 0 . 6 in control islets , n = 3 ; p & lt ; 0 . 01 ) and , as a consequence , with an altered atp / adp ratio . to investigate further the mechanism of the impaired atp formation , in rat pancreatic islets glucose - stimulated pyruvate dehydrogenase ( pdh ) activity was measured , a key enzyme for pyruvate metabolism and for the subsequent glucose oxidation through the krebs cycle , and also the uncoupling protein - 2 ( ucp - 2 ) content by western blot . in islets exposed to high glucose or ffa , glucose - stimulated pdh activity was impaired and ucp - 2 was overexpressed . because ucp - 2 expression is modulated by a peroxisome proliferator - activated receptor ( ppar )- dependent pathway , ppar - gamma contents were measured by western blot and the effects of a ppar - gamma antagonist . ppar - gamma levels were overexpressed in islets cultured with high ffa levels but unaffected in islets exposed to high glucose . in islets exposed to high ffa concentration , a ppar - gamma antagonist was able to prevent ucp - 2 overexpression and to restore insulin secretion and the atp / adp ratio . these data indicate that in rat pancreatic islets chronically exposed to high glucose or ffa , glucose - induced impairment of insulin secretion is associated with ( and might be due to ) altered mitochondrial function , which results in impaired glucose oxidation , overexpression of the ucp - 2 protein , and a consequent decrease of atp production . this alteration in ffa cultured islets is mediated by the ppar - gamma pathway . methyl pyruvate has been described with reference to a particular embodiment . for one skilled in the art , other modifications and enhancements can be made without departing from the spirit and scope of the aforementioned claims . whilst endeavoring in the foregoing specification to draw attention to those features of the invention believed to be of particular importance it should be understood that the applicant claims protection in respect of any patentable feature hereinbefore referred to whether or not particular emphasis has been placed thereon .

the present invention relates to the use of methyl pyruvic acid and / or methyl pyruvate for the purpose of increasing cellular energy production thereby providing energy for the continuous activation of parp - 1 and up - regulation of ppar . it is well known that chronic activation of parp causes atp and nad depletion with concomitant cell death . parp is known to prevent hiv replication by competitive receptor inhibition . use of methyl pyruvate and / or methyl pyruvic acid can be effective when administered orally or infused on either a chronic and / or acute basis . in the following text , the terms “ methyl pyruvate , methyl pyruvate compounds , methyl pyruvic acid ” are used interchangeably .

referring now to the drawings wherein like reference numerals correspond to similar elements throughout the several view and , more specifically , referring to fig1 , the present invention will be described in the context of an exemplary work vehicle 12 having a vehicle support structure to which a plurality of wheels 26 are rotatably mounted . a work vehicle 12 typically has a power source coupled to a transmission with the transmission operatively coupled to at least two of the wheels 26 . the power source can be an internal combustion engine such as a gasoline engine or a diesel engine and it may also be an electric motor or a steam driven turbine . referring still to fig1 and also to fig2 , a tillage assembly 10 is illustrated which is linked to tractor 12 by a tow bar 16 . in addition to tow bar 16 , tillage assembly 10 includes a main frame 14 , wheels , one subassembly of wheels identified by numeral 24 , first through forth disk subassemblies 32 a , 32 b , 32 c and 32 d and first and second rotary spiked tooth harrows 22 a and 22 b , respectively . frame 14 includes a plurality of rigid steel members that are welded or otherwise mechanically secured together to form a rectilinear frame assembly as best seen in fig2 . a frame axis 15 that is perpendicular to a travel direction 50 is shown twice in fig5 . while frame axis 15 are parallel to frame members in the fig5 embodiment , axis 15 need not be parallel to any frame members in other embodiments where frame members are not perpendicular to the travel direction 50 . tow bar 16 extends forward from frame 14 to mount assembly 14 to tractor 12 as illustrated . wheels 24 are mounted to and extend down from main frame 14 to support frame 14 above soil in a field through which tillage assembly 10 is pulled by tractor 12 . referring still to fig1 and 2 and also to fig5 , for the purposes of the present invention , each of the disk subassemblies 32 a , 32 b , 32 c and 32 d have similar constructions and operate in a similar fashion and therefore , in the interest of simplifying this explanation , only subassembly 32 a will be described in any detail . subassembly 32 a includes , among other components , an implement mounting bar 18 , a plurality of disks , two of which are collectively identified by numeral 30 in each of fig2 and 5 , and some type of adjusting mechanism ( e . g ., a hydraulic cylinder 60 , turn buckle , etc .). in at least one embodiment , as illustrated best in fig3 and 4 , each of the disk members 30 include a concave disk that forms outwardly extending teeth 40 a , 40 b , etc ., on its circumferential edge . each of the teeth 40 a and 40 b are identical and therefore , in the interest of simplifying this explanation , only tooth 40 a will be described here in detail . as shown , tooth 40 a is a saw blade type tooth and , to that end , includes a concave leading edge 44 , a convex following edge 48 and a lateral edge 46 that extends from the leading edge 44 to the following edge 48 , the lateral edge 46 and following edge 48 forming a tooth point ( not labeled ). each two adjacent teeth 40 a , 40 b , etc ., are separated by a gap or space ( e . g ., 42 ). each disk 30 forms one or more generally centrally located mounting openings 38 . referring specifically to fig4 , each disk 30 has first and second oppositely facing surfaces 31 and 33 , respectively . surface 31 is convex while surface 33 is concave where each of the surfaces 31 and 33 has a similar radius of curvature r . exemplary disk 30 has a diameter dimension d i and a depth dimension de as illustrated . referring to fig3 and 5 , disks 30 are mounted to implement mounting bar 18 such that the disks are aligned for rotation about a common disk axis 19 that is generally parallel to the length of bar 18 . thus , each disk is mounted so as to be generally perpendicular to bar 18 . referring to fig1 and 5 , bar 18 mounts below frame 14 such that disks 30 extend downward below main frame assembly 14 and engage soil therebelow . in this regard , a first end 51 of bar 18 is pivotally mounted to frame 14 and a second end 53 of bar 18 is journalled in a slot forming member 55 to slide therealong as bar 18 pivots about first end 51 . adjusting mechanism 60 includes a first end mounted to frame 14 and a second end mounted to a central portion of bar 18 . when bar 18 is mounted to frame 14 , bar 18 is juxtaposed so that bar 18 and disk axis 19 form an angle α with respect to frame axis 15 . when bar 18 is angled , disks 30 are inclined at a similar angle α with respect to travel direction 50 . when so inclined , the second surfaces 33 ( see again fig4 ) of disks 30 generally open in the direction of travel 50 . to adjust angle α between bar 18 and frame axis 15 , cylinder 60 is manipulated . when cylinder 60 is extended , angle α is increased and , when cylinder 60 is retracted , angle α is decreased . referring again to fig5 , as assembly 10 is moved through a field , disks 30 engage soil therebelow and form grooves , two of which are collectively identified by numeral 69 . as described in greater detail below , disks 30 are selected such that their dimensions and characteristics and their spacing along bar 18 result in grooves 52 that are separated by loosened / disturbed soil bands ( e . g ., 71 ) therebetween . referring again to fig2 and 5 , in most applications , disk subassemblies 32 a and 32 b will be mounted to frame assembly 14 such that the component mounting bar members ( e . g ., 18 ) form similar angles a with respect to the frame axis 15 . similarly , each of disk subassemblies 32 c and 32 d are mounted to frame assembly 14 so as to form angles a , albeit where the angles formed by subassemblies 32 c and 32 d with respect to frame axis 15 are in the opposite direction ( e . g ., where angle α of subassembly 32 a is − 7 °, angle α of subassembly 32 c and 32 d will be approximately + 7 ). referring to fig2 , harrows 22 a and 22 b are similar and operate in a similar fashion and therefore , in the interest of simplifying this explanation , only harrow 22 a will be described here in detail . referring also to fig1 and 5 , harrow 22 a is a rotary spike toothed harrow that is mounted below frame assembly 14 and behind disk subassemblies 30 along the travel or advancing direction 50 . referring to fig7 , an exemplary perspective view of harrow 22 a is shown where it can be seen that harrow 22 a includes multiple spike toothed members 90 arranged to rotate along a common harrow axis 17 . harrow 22 a has a length dimension along axis 17 . harrow 22 a can be adjusted with respect to frame axis 15 such that an angle β between harrow axis 17 and frame axis 15 can be modified . to this end , a second adjusting mechanism 62 ( e . g ., hydraulic cylinder , turn buckle , etc .) is provided between frame assembly 14 and harrow 22 a . construction and operation of spike toothed rotary harrows is well known in the art and therefore are not described here in detail . here , it should suffice to say that in operation , as harrow 22 a is pulled through a field , the spike toothed members 90 engage soil therebelow and form generally lateral grooves , three of which are collectively identified by numerals 70 in fig5 . here , the lateral grooves 70 form angles p with respect to the travel direction 50 that are similar to the angle β formed between harrow axis 17 and main frame axis 15 . referring to fig1 through 5 , in at least some embodiments , disks 30 are selected to have specific characteristics and are mounted so as to engage soil therebelow in a vary specific manner that minimizes the smearing effect caused by other types of disks . to this end , in a particularly advantageous embodiment , it has been found that smearing can be reduced by selecting disks 30 that have relatively minimal depth d e dimensions and that are scalloped or toothed in some fashion and by mounting the disks to rotate about a disk axis ( e . g ., 19 ) that is only slightly angled from the frame axis 15 . here , the idea is to use the disks to initially disturb the soil to a point where a single spike toothed harrow pass will cause adequate tillage to occur while minimizing soil smearing . in effect , the disks work the soil to a generally optimal point for the harrows to work ideally while causing minimal smearing . in this regard , referring to fig5 , because the disks 30 have a narrow depth d e and angle α is minimal ( e . g ., 7 - 10 °), as the disks 30 rotate , the disks form grooves 69 with loosened bands 71 of soil therebetween . in addition , because the disks have narrow depths and are minimally inclined with respect to travel direction 50 , the disks cause reduced backside disk blade pressure which has several advantages . first , reduced or substantially eliminated backside pressure means that smearing and compaction of the soil is minimized or substantially eliminated . second , reduced backside pressure means that the forces working against disk penetration are minimized and therefore the weight of frame 14 can be advantageously reduced as a light frame 14 can cause sufficient penetration . in at least one advantageous embodiment , disks 30 are selected that have diameters d i that are approximately 20 inches , that have depths d e that are approximately one - half to one and one - half inch and that have radiuses of curvature r of approximately 920 mm and the disks are mounted below frame 14 such that the inclined angle α of the disks with respect to the travel direction 50 is between 7 and 10 degrees . referring again to fig3 , in a particularly advantageous embodiment , saw tooth type disks 30 are employed where the dimension of the portion of each gap 42 between lateral edges ( e . g ., see 46 in fig3 ) of adjacent teeth 40 a and 40 b is approximately twice the dimension of each of the lateral edges 46 . thus , for example , where the dimension of the portion of gap 42 between adjacent lateral edges is 2 . 6 inches , each of the adjacent lateral edges would have a length of approximately 1 . 3 inches . in the illustrated embodiment disk 30 has 16 teeth . in other cases the number of teeth may vary . here , the idea behind toothed disks is to relocate soil while minimizing the actual engagement of the disk with the soil . in the present example , 66 % of the soil engaging portion of the disk is removed yet the rippled or scalloped grooves 69 ( i . e ., continuous grooves with depth variations therealong ) in the soil are essentially continuous because soil that is engaged pushes against adjacent soil and causes the adjacent soil to breakout and loosen . referring again to fig3 , in advantageous embodiments disks 30 are juxtaposed with respect to travel direction 50 such that , as the disks engage field soil and rotate , leading tooth edges 44 are driven toward the soil followed by associated following edges 48 on common teeth ( e . g ., 40 a ). here , edges 46 tend to cut through field debris well and penetrate the soil effectively while only causing minimal soil compaction when compared to non - scalloped or non - toothed type disks or saw tooth type disks where the concave edges lead the convex edges . after the disks 30 loosen the soil and form grooves 69 , rotary harrows 22 a , 22 b , operate at angles ( e . g ., 450 or more with respect to travel direction 50 ) to dislodge undisturbed or loosened soil between the grooves 69 , to level loose soil and evenly distribute residue in the soil . while the dimensions and disk axis angle range described above are believed to be particularly advantageous , it is believed that other similar dimensions and similar axis angles will cause similar effects . for instance , it is believed that the blade depth d e may , in some cases , may be in the one - half to one and one - half inch range , the diameter d i may be between 16 and 24 inches and the radius of curvature r may be between 600 and 1000 millimeters . the angle α may be between 5 ° and 20 ° depending upon disk depth and diameter dimensions . here , the important aspect is that the combination of disk characteristics ( e . g ., depth , diameter , radius of curvature ) and disk juxtaposition ( e . g ., incident angle α with respect to the travel direction ) be selected to reduce or minimize smearing of soil below the assembly 10 . in the present case , while the disk assemblies ( e . g ., 32 a ) form grooves and only loosen much of the top soil , the resulting soil is suitable for a single pass of a harrow to result in effective tillage for most applications . while the invention may be susceptible to various modifications and alternative forms , specific embodiments have been shown by way of example in the drawings and have been described in detail herein . however , it should be understood that the invention is not intended to be limited to the particular forms disclosed . for example , referring to fig6 , a notched disk 80 is illustrated that could be substituted for the saw tooth disks of fig3 to achieve a similar result . disk 80 includes 18 radially extending teeth 82 a , 82 b , etc ., that are separated by semi - circular recesses or gaps 84 . here , disk 80 is concave and would be arranged in a fashion similar to that illustrated in fig5 with the concave side opening in the travel direction 50 . once again the depth de of disk 80 would be minimized and the inclination angle α would be minimal to reduce backside pressure and hence to reduce soil smearing . thus , the invention is to cover all modifications , equivalents , and alternatives falling within the spirit and scope of the invention as defined by the following appended claims . to apprise the public of the scope of this invention , the following claims are made :

a method and apparatus for soil conditioning , the apparatus comprising a frame , a rotary harrow supported by the frame for engaging the soil and a plurality of disks supported by the frame and in front of the rotary harrow along the advancing direction for rotation about disk axis and for engaging soil below the frame , each disk including a scalloped peripheral edge that forms a plurality of teeth and a space between each two adjacent teeth .

four subjects complaining of bad breath were tested for the odor levels ( based on odor judge scoring on an increasing intensity scale of 0 - 5 , and measurement of volatile sulfides using a sulfide monitor [ interscan corp ., chatsworth , calif . model 1170 ]). in addition , the level of beta - galactosidase activity was measured based on a colorimetric assay as follows : a sample of the back of the tongue was taken with a plastic spoon . the sample was removed from the spoon by washing twice with 0 . 2 ml water which were pooled into a single sample . x - gal ( 5 - bromo 4 chloro 3 indoyl beta d galactopyranoside and iptg ( isopropyl thiogalactopyranoside ) were added ( 0 . 05 ml of a 20 mg / ml solution and 0 . 05 ml of a 50 mg / ml solution , respectively ) and the samples were incubated for one hour at 37 degrees celsius in elisa plates . the relative amount of enzymatic activity was recorded as od at 650 nm . table i volatile subject no . elisa od judge score sulfides ( ppb ) 1 0 . 15 2 ( slight ) 20 2 0 . 27 2 . 5 ( slight - moderate ) 20 3 0 . 30 2 . 5 ( slight - moderate ) 30 4 0 . 52 3 ( moderate ) 50 it is clear that the increasing elisa reading of beta - galactosidase activity is in association with the increasing odor judge scores and volatile sulfide levels . it was further found that β - galactosidase activity in saliva or other oral samples can be measured by simply wetting absorbent discs containing β - galactosidase activity detecting agents and incubating them at room temperature for short periods of time . by comparing the amount of color produced to color standards , a semi - quantitative estimate of the β - galactosidase activity in the oral sample can be determined . five mm discs of absorbent paper were cut from sheets of whatman chromatographic paper ( whatman ltd ., maidstone , england ). 100 mg of x - gal were dissolved in 5 ml of dimethylformamide . a second solution of 100 mg iptg in 2 ml of water was prepared . the two solutions were combined . twenty microliters of the combined solution were applied to each of the above paper discs . the discs were then dried for 24 hours before use and then affixed to a plastic backing . to use the test , subjects collected a small amount of saliva and used it to thoroughly wet the above treated discs . the discs were allowed to stand at room temperature for 10 minutes . the color generated was scored using a standard color scale provided to the subjects . breath odor scores from each subject were also measured using a sulfide monitor . a significant degree of correlation was found between the test scores . absorbent paper discs impregnated with 20 mg / ml of x - gal and 50 mg / ml of iptg were used in a self - administered test to evaluate breath odor before and after the use of a breath freshening mouthrinse with active ingredient compared to a placebo mouthrinse . the subjects saturated the discs with samples of their saliva immediately before and 1 , 2 and 3 hours after using the treatment or placebo mouthrinse . the amount of color developed on the discs was scored after standing 5 minutes at room temperature . breath odor scores were also measured with a sulfide monitor and an expert panel . the results obtained with the three different measurements confirmed the breath freshening action of the treatment product compared to the control . the purpose of this study was to test a simple enzymatic color assay for the detection of oral malodor , to test its correlation with other oral malodor - related parameters such as odor judge scores and sulfide monitor measurements . in addition to the color assay , ( organoleptic ) measurements were made by two odor judges . sulfide monitor measurements , microbial counts , bana test and an indole test were similarly carried out . the study included 60 healthy young adult volunteers ( mean age 23 ± 2 years , 35 females ). subjects who were smokers or took antibiotics within one month prior to the study were not allowed to participate . the experiment was conducted according to an approved human subjects protocol and participants signed an informed consent form . participants were asked to refrain from eating or drinking for two hours prior to measurements . initially , subjects were tested for malodor - related parameters : odor judge measurements , sulfide monitor levels , color assays and microbial counts . the subjects were split randomly into three groups : 1 ) treatment group : active chewing gum ( with breathanol tm ). 2 ) placebo chewing gum ( without breathanol tm ). 3 ) control group ( no treatment ). the subjects were given the chewing gum ( or no treatment ) and were asked to chew for 15 minutes . the subjects were reexamined after 1 . 5 and 3 hours following use . at the beginning of the experiment the subjects were asked to form an opinion on their own breath by scoring it using the same scale as the odor judges ( see below ). paper discs ( 6 mm ) were impregnated with enzyme substrates as described below : the paper test was prepared by punching out 6 mm diameter discs from chromatography paper ( whatman paper no . 3 ). two solutions were prepared , one by dissolving 100 mg of 5 - bromo - 4 - chloro - 3 - indolyl - d galactopyranoside ( x - gal , sigma ) in 2 ml of n , n - dimethylformamide ( sigma ), and the other by dissolving 100 mg of isopropyl β - d - thiogalactoside ( iptg , sigma ) in 2 ml of double distilled water . 100 μl from each solution were combined , vortexed and then 20 μl of the mixture was impregnated on each paper disc . the discs were dried overnight at 37 ° c . saliva ( whole , unstimulated ) was collected from each subject at the beginning of the experiment ( before treatment ) as well as at 1 . 5 hours and after 3 hours . a 20 μl drop of each saliva sample was applied to the paper disc and following 10 min incubation at room temperature , the results were recorded after 10 minutes as follows : 0 — no color , 1 — faint color , 2 — dark color . the bana reagent card ( perioscantm , oral - b laboratories , redwood city , calif .) and the indole production slide ( dryslidetm indole , difco laboratories , detroit mich .) were used according to manufacturer &# 39 ; s instructions . samples for these assays were taken from the same posterior tongue dorsum scrapings which were used to determine tongue odor scoring by the odor judges . results were recorded as either : strong reaction = 2 , light reaction = 1 , or no color change = 0 . determination of intraoral headspace volatile sulfur compounds ( vsc ) was carried out using a sulfide monitor ( model 1170 , interscan ). subjects were asked to refrain from talking for 5 minutes prior to measurements . the monitor was zeroed on ambient air , and the measurements were performed by inserting a disposable one quarter inch plastic straw approximately 4 cm into the partially opened oral cavity . subjects were asked to breathe through their nose during measurements . results were recorded as peak ppb sulfide equivalents . two odor judges scored whole mouth malodor and for tongue malodor . for judge scoring of whole mouth subjects were instructed to exhale briefly through the mouth , at a distance of approximately 10 cm from the nose of the judge . tongue malodor was scored by using a plastic spoon to scrape and scoop material from the far back region of the tongue dorsum , and scoring the malodor from the spoon by both judges , sequentially . judge scores were recorded using a semi - integer scale of 0 to 5 , as follows : 0 , no appreciable odor ; 1 , barely noticeable odor ; 2 , slight , but clearly noticeable odor ; 3 , moderate odor ; 4 , strong odor ; 5 , extremely foul odor . viable counts from saliva samples were conducted using diaslides ( savyon diagnostics , ashdod , israel ) containing tryptic soy agar ( tsa ) and mitis salivarius agar ( msa ). diaslides were incubated anaerobically for 72 hours at 37 ° c . viable counts included total on tsa and msa as well as counts of the blue colonies which formed on the msa . spearman correlation coefficients were used to determine the level of association between the various parameters . one way analysis of variance ( anova ) was used to compare the results of the color assay ( 0 , 1 and 2 ) in terms of the other parameters . stepwise multiple regression analysis was carried out in order to test the contribution of the color test results and the sulfide monitor in predicting the odor judges scores . spearman correlation coefficients comparing color assay scores for the three rounds of measurements ( time 0 , 1 . 5 and 3 hours ) with the other parameters are presented in table ii . in this table , the appropriate p value is shown below each r value . table ii judge 1 judge 2 log whole whole microbial counts microbial assays monitor mouth tongue mouth tongue tsa msa blue bana indole time zero ok2ks 0 . 18 0 . 39 0 . 50 0 . 47 0 . 48 0 . 29 0 . 37 0 . 38 0 . 21 0 . 21 p = 0 . 086 0 . 001 & lt ; 0 . 0001 & lt ; 0 . 0001 & lt ; 0 . 0001 0 . 013 0 . 002 0 . 002 0 . 055 0 . 057 1 . 5 hours ok2ks 0 . 3290 0 . 32 0 . 42 0 . 46 0 . 33 0 . 31 0 . 42 0 . 39 − 0 . 12 − 0 . 12 p = 0 . 005 0 . 00 & lt ; 0 . 0001 & lt ; 0 . 0001 0 . 005 0 . 007 & lt ; 0 . 0001 0 . 002 0 . 185 0 . 171 3 hours ok2ks 0 . 41 0 . 32 0 . 44 0 . 49 0 . 60 0 . 21 0 . 25 0 . 17 0 . 08 0 . 15 p = 0 . 001 0 . 006 & lt ; 0 . 0001 & lt ; 0 . 0001 & lt ; 0 . 0001 0 . 053 0 . 025 0 . 136 0 . 263 0 . 120 among the various tests , ok2ks scores were most highly associated with the odor judge scores for whole mouth ( p & lt ; 0 . 007 ) and tongue ( p & lt ; 0 . 005 ) odor . significant correlations were also observed between ok2ks and monitor measurements for the last two time points ( p & lt ; 0 . 005 ) and the microbial counts for the first two time points ( p & lt ; 0 . 013 ). in contrast , no significant association was found between ok2ks and the bana or indole production assays ( p & gt ; 0 . 055 ). the initial correlations between ok2ks scores , sulfide monitor levels , bana test results and microbial counts ( msa ) are compared with odor judge scores in table iii below . correlations between odor judge scores and ok2ks scores were as high or higher than corresponding correlations with sulfide monitor scores in all cases . correlations between organoleptic scores and the bana test were less significant , as were correlations between bacterial counts on msa and odor judge scores . indole scores were not correlated significantly with odor judge scores ( not shown ). table iii ok2ks sulfide monitor bana bacterial color test ( ppb equivalents ) test counts judge 1 whole mouth r = 0 . 39 0 . 37 0 . 25 0 . 27 p = 0 . 002 0 . 002 0 . 048 0 . 030 tongue r = 0 . 50 0 . 26 0 . 26 0 . 20 p & lt ; 0 . 001 = 0 . 036 = 0 . 036 = 0 . 118 judge 2 whole mouth r = 0 . 47 0 . 46 0 . 22 0 . 16 p & lt ; 0 . 001 & lt ; 0 . 001 = 0 . 086 = 0 . 196 tongue r = 0 . 48 0 . 38 0 . 14 0 . 18 p & lt ; 0 . 001 = 0 . 002 = 0 . 282 0 . 160 stepwise multiple regression analysis of odor judges scores for whole mouth and tongue odor ( at time 0 ), in terms of color assay scores and log monitor readings are shown in table iv . table iv dependent ok2ks sulfide level variable intercept coefficient coefficient multiple r_ judge 1 : whole − 1 . 38 0 . 42 0 . 68 0 . 54 mouth p = 0 . 0375 0 . 0137 0 . 0005 p & lt ; 0 . 0001 judge 1 : tongue − 0 . 062 0 . 57 0 . 47 0 . 57 0 . 9148 0 . 0002 0 . 0062 p & lt ; 0 . 0001 judge 2 : whole − 1 . 54 0 . 62 0 . 70 0 . 60 mouth 0 . 028 0 . 0007 0 . 0006 p & lt ; 0 . 0001 judge 2 : tongue 0 . 81 0 . 50 0 . 40 0 . 47 0 . 2239 0 . 0036 0 . 0362 p = 0 . 0007 both sulfide monitor readings and ok2ks scores factored significantly into the regression equation for both judges scores for whole mouth and tongue odors , yielding multiple r values ranging from 0 . 47 ( judge 2 , tongue , p = 0 . 0007 ) to 0 . 60 ( judge 2 , whole mouth , p & lt ; 0 . 0001 ). the results presented hereinabove show that ok2ks was highly significantly correlated with odor judges scores for whole mouth and tongue odor , at all three time points during the study . furthermore , correlations between ok2ks and organoleptic scores were as significant , or more significant than corresponding correlations between the sulfide monitor and organoleptic scores . when multiple regression analysis was carried out to try to account for odor judge scores in terms of ok2ks and sulfide levels , both parameters entered into the regression equations , yielding multiple r values of up to 0 . 6 . the results suggest that ( i ) ok2ks may be used as an assay which correlates with odor judge scores ; and ( ii ) ok2ks can be used alongside sulfide monitor testing to improve the correlation with odor judge scores . the convenience and low anticipated cost of ok2ks may make it useful in both clinical and home settings . while specific embodiments of the invention have been described for the purpose of illustration , it will be understood that the invention may be carried out in practice by skilled persons with many modifications , variations and adaptations , without departing from its spirit or exceeding the scope of the claims .

the invention provides a method for the rapid assessment of the degree of halitosis comprising the steps of a ) obtaining a sample of fluid and / or tissue from the oral cavity of a subject , b ) assessing the amount of β - galactosidase in said sample , c ) determining the degree of halitosis in said subject , by comparing the result obtained in step b ) with appropriate reference values .

this invention is generally relates to blue jeans , and more particularly to blue jeans which hem length is adjustable . the purpose of the invention is to enable user to adjust the length of jean hem with zipper arranged vertically in both side of the jean , thus enabling user to produce desirable jean style . this invention makes blue jean , which adjusts hem in various lengths according to surroundings , thus enables to produce various styles . in addition , this invention supplies blue jean , which adjusts hem length freely for users not to prepare additional clothes owing to surrounding circumstance and temperature . to achieve above - mentioned purpose , this invention has following features ; in blue jean consisted of the waist part , the hip part at which covers user &# 39 ; s hip , and of jean hem arranged vertically on the above - mentioned hip part , above - mentioned blue jean has the first and the second jean tube divided by the joining part which is vertically formed on the femoral region , and zipper is arranged in both side of the first and the second jean tube in order to cut out above - mentioned jean hem from low to high . moreover , above - mentioned blue jean includes more than one fixing device inside of top of the jean hem in order to fold and bind and fix the zipper , after releasing the zipper at certain length . also , above - mentioned fixing device is consisted of a pair of magic tape , which is divided to the first and second sticking part . in addition , in above - mentioned fixing device , a pair of prominence and depression snaps button is arranged and divided to the first and the second sticking part . moreover , the blue jean includes collar layer vertically in one side of the above - mentioned zipper , in order to prevent exposure of the zipper . and , the present blue jean includes stick - upholding unit in the end of the first and the second jean tube in order for jean hem not to flutter by the zipper but to improve airing . fig2 is a convergent view of the outward of the blue jeans , fig3 is a detailed vied of fig2 - a , which shows the function of the invention , fig4 is a cross - sectional view of the other example of the present invention . referring to fig2 or fig3 , the present blue jean ( 10 ) includes the waist part ( 11 ) which covers user &# 39 ; s hip , and hip part ( 12 ) which is made under the waist part ( 11 ) in tube shape and has zipper ( 12 a ), and jean hem ( 13 ) which is divided to both under side of the hip part ( 12 ). jean hem ( 13 ) is divided to two sides and the joining part ( 13 a ) is combined to the end with thread . by the zipper ( 100 ), which is inside of the joining part ( 13 a ), the first and the second jean tube ( 13 b ) ( 13 c ) are divided . the zipper ( 100 ) is extended from the edge of the jean tube ( 14 ) to the femoral region ( 15 ) under the hip part ( 12 ), and the zipper handle ( 101 ) is arranged in the edge of the jean tube ( 14 ) in order to lock or unlock the zipper ( 100 ). the zipper is released from low to high . additionally , more than one fixing device ( 200 ) is shaped in the jean hem ( 13 ) in low and high directions . this fixing device ( 200 ) is normal magic tape . the first sticking part ( 210 ) is shaped in the lower part of the edge of the jean tube ( 14 ) and the second part ( 220 ) in the higher part . the first sticking part ( 210 ) is normal magic tape , and much of projection made of resin plastic is in the tape . in the second sticking part ( 220 ), much of fiber hair is made to couple with the projection . no matter where the projection or hair is , it is consisted of a pair of the first and the second sticking part ( 210 ) ( 220 ). above - mentioned fixing device ( 200 ) can be made in various shapes with current technique and skill . for example , snaps button , which is consisted of a pair of prominence and depression , can be used . referring to the fig3 , effect of the present blue jean ( 10 ) is explained below . firstly , zip up the handle ( 101 ) under the jean hem ( 13 ), then the hook unit ( 101 a ) is released and freed from the zipper ( 100 ). move this zipper handle ( 101 ), then the first and the second jean tube ( 13 b ) ( 13 c ) of the jean hem ( 13 ) are separated to both side , and it is easy to fold and bind the first and the second jean tube ( 13 b ) ( 13 c ) into the jean hem ( 13 ). in this way , fold the edge of the jean tube ( 14 ) under the separated first and second jean tube ( 13 b ) ( 13 c ) inside , and attach the first sticking part ( 210 ) prepared inside of the edge of the jean tube ( 14 ) to the second sticking part ( 220 ) arranged inside of the jean hem ( 13 ). finally , move zipper handle down , and face it downward , then the released projection ( 101 a ) is applied in the zipper ( 100 ) and length adjustment is finished . likewise , length of the jean is adjusted freely by the zipper ( 100 ) arranged in both sides of the jean hem ( 13 ), and it is possible to produces various fashion styles such as calf or ankle jean with merely one jean since it does not fall off due to the fixing device ( 200 ) situated inside . fig4 shows the other example of the blue jean ( 10 ), that is , collar layer ( 300 ) is arranged in order to prevent exposure of zipper ( 100 ) and explain is followed . put one side of the collar layer ( 300 ) to one side of the joining part ( 13 a ) of the divided jean hem ( 13 ) and fix it with thread . inner surface of the other side , the first sticking part ( 310 ) is arranged . in addition , in the joining part ( 13 a ) of the other side , the second sticking part ( 320 ) is arranged along the vertical direction of the jean hem ( 13 ). this attaches with the first sticking part ( 310 ) made inner surface of the above - mentioned collar layer ( 300 ). as mentioned in above example , after adjusting the length of the jean hem , collar layer ( 300 ) covers zipper ( 100 ) and conceals it . this collar layer ( 300 ) can be same in color of jean ( 10 ) or different from the jean ( 10 ) in order to produce more polishing mood . furthermore , it fixes zipper from released freely . referring to the fig5 , it shows the other example of the present invention . arrange stick - upholding unit ( 400 ) in the edge of the jean tube ( 14 ) under the jean hem ( 13 ), and move up zipper ( 100 ). then it is easy to circulate air in the jean without folding and binding the jean hem ( 13 ). firstly , move up zipper handle ( 101 ) arranged under the joining part ( 13 a ), and divide the first and the second jean tube ( 13 b ) ( 13 c ), then stick the stick - upholding unit ( 400 ) arranged under . stick - upholding unit ( 400 ) is consisted of the first sticking part ( 410 ) fit under the first 1 jean tube ( 13 b ), and the second sticking part ( 420 ) arranged in the second jean tube ( 13 c ). this stick - upholding unit ( 400 ) has much resin plastic projection in the first sticking part ( 410 ) like above - mentioned fixing device ( 200 ). in the second sticking part ( 420 ), fiber hair is made to stick to the projection of the first sticking part ( 410 ). stick - upholding unit ( 400 ) can be made of and changed to various ways such as snaps button . as well as , make button hole in the first sticking part ( 410 ) and arrange button in the second sticking part ( 420 ) in accordance with the hole . in addition , arrange many above - mentioned stick - upholding units ( 400 ) upward and downward , and then prevent the jean hem flutter when zipper ( 100 ) is released . also improve airing . this invention is not limited in the certain examples of the article . anyone who has usual knowledge of the technique field where this invention belongs to , can change and practice the invention , thus such change is in the bounds of the claims .

the present jean adjusts the length of the jean hem in various lengths according to the surroundings , it is possible to produce various color compared to the outer color , users don &# 39 ; t need to prepare spare clothes at the change of season .

50 catheter 400 vascular device 402 hollow shaft 402 a proximal termination of hollow shaft 402 b distal termination of hollow shaft 404 actuating member 406 coil 406 a open wound coil section 406 b solid coil section 407 distal section 408 weld 410 distal lumen opening 412 proximal end of solid coil section 414 first lumen 416 second lumen 418 ribbon 420 cutting head 422 first handle 423 third handle 424 cutting shaft 424 a proximal end of cutting shaft 424 b distal end of cutting shaft 425 second handle 426 flattened section of coil 428 solder 430 non - expandable side 432 expandable side 500 vascular device 502 hollow shaft 504 actuating member 505 sheath 506 distal end ( of vascular device ) 508 slit 510 coil 510 a open wound coil section 510 b solid coil section 512 weld 514 first lumen 516 second lumen 517 distal section 518 ribbon 520 cutting head 524 cutting shaft 524 a proximal end of cutting shaft 524 b distal end of cutting shaft 526 flattened section of coil 528 solder 530 non - expandable side 532 expandable side 534 first handle 536 second handle 600 vascular device 602 coating 604 actuating member 606 first lumen 608 coil 610 second lumen 612 ribbon 614 open coil section 615 flattened section of coil 616 distal closed coil section 617 distal section ( of vascular device ) 618 actuating member attachment 620 distal first lumen opening 622 non - expandable side 624 expandable side 626 handle 628 proximal closed coil section 718 cutting shaft 720 cutting head 722 angle in cutting shaft 1000 vascular vessel 1002 vascular obstruction 1002 a attached obstruction 1002 b obstruction debris 1400 vascular device 1410 central space 1412 distal section 1412 a loose wound section 1412 b tight wound section 1414 coil 1415 proximal coil section 1416 flattened section of coil 1418 ribbon 1420 hollow member 1422 lumen 1424 solder 1426 coating 1428 distal end of vascular device 1429 proximal end of coil 1430 actuating member 1432 actuating member attachment 1434 distal end of coil 1436 distal lumen opening 1438 non - expandable side 1440 expandable side 1442 handle “ anatomical conduit ” refers to a naturally occurring vessel or duct within a patient &# 39 ; s body . “ distal ” means further from the point controlled by the operator ( e . g ., physician or technician ) of a device . “ distal force ” means force applied in a distal direction or toward a distal end of the device . “ handle ” means a device used to grip certain components of the invention for the purpose of causing longitudinal movement of additional components . “ prolapse ” refers to an adverse event occurring when a medical device does not follow the desired path at a vascular bifurcation but instead where a relatively stiff device forces a relatively less stiff device straight through the vessel , pulling the less stiff device out of the side branch of the bifurcation . “ proximal ” means closer to the point controlled by the operator ( e . g ., physician or technician ) of a device . “ proximal force ” means force applied in a proximal direction or toward a proximal end of the device . the following detailed description is to be read with reference to the drawings in which similar components in different drawings have the same nomenclature . the drawings , which are not necessarily to scale , show illustrative embodiments and are not intended to limit the scope of the invention . it should be noted that combinations of materials and components described within this specification may be interchangeable and anyone skilled in the art will understand that a combination of materials or exchange of other materials to accomplish the work of the invention will not depart from the spirit of the invention . it is further understood that the invention is not limited to vascular use and can also be applied to use through an endoscope , gastroenterological procedures , laparoscope , artherectomy procedures , urological procedures or neurological procedures . for the purpose of describing the actuation of the embodiments of the invention 600 , 1400 as described below , a handle 626 , 1442 is used . the function of the handle 626 , 1442 is to contact the coated coil 608 , 1414 , move the actuating member 604 , 1430 and provide greater control to the operator . using the handle 626 , 1442 allows the application of a longitudinal force ( distal or proximal ) from a proximal end ( unnumbered ) of the device 600 , 1400 to the attached actuating member 604 and proximal force to the actuating member 1430 , which causes a sliding motion . as described in detail below , the application of longitudinal force causes a distal section 617 , 1412 of the vascular device 600 , 1400 to deflect . in the cases of the embodiments of the invention 400 , 500 a first handle 422 , 534 , contacts the hollow shaft 402 , 502 and is attached to the actuating member 404 , 504 allowing longitudinal force to be applied to the distal section 407 , 517 , causing it to deflect . a second handle 425 , 536 is attached to a cutting head 420 , 520 which distally extends from a distal lumen opening 410 or a sheath 505 and manually rotated in procedures requiring plaque removal . fig1 shows a cross sectional centerline view taken along the longitudinal axis of a vascular device 600 having a first lumen 606 and a second lumen 610 . the vascular device 600 can be used as a guidewire or a catheter or as a combination of the two . the presence of a first lumen 606 and a second lumen 610 allows the device 600 to function as an aspiration device as well as a catheter so that during a medical procedure it can be simultaneously used to deliver other medical devices to a remotely navigated anatomical site and to aspirate fluids . the device 600 can also be used for the delivery of therapeutic fluids through the first lumen 606 to remote anatomical sites following navigation using the device 600 as a guidewire . the device 600 includes a coil 608 defining a proximal open coil section 614 and a distal closed coil section 616 . a proximal closed coil section 628 extends proximally of a distal coil section 617 and is wound in a relatively closed coil configuration similar to the distal closed coil section 616 . in one embodiment , the coil 608 can be made from a radiopaque material such as a platinum - nickel alloy that allows the physician to visualize the position of the coil 608 using radiological means , thereby navigating the vascular device 600 into desired anatomical pathways with minimal forward motion . in a manner similar to the other embodiments of the invention 400 , 500 the device 600 is capable of deflecting by applying longitudinal force to an actuating member 604 which causes the expandable side 624 of the coil 608 to expand while the non - expandable side 622 is prevented from expanding by being fixedly attached to a ribbon 612 as explained below . the actuating member 604 can be made from a variety of materials having sufficient strength to be able to cause the distal section 617 to deflect and still be flexible enough to move with the coil 608 , including but not limited to stainless steel alloys , nickel titanium alloys and reinforced polymeric materials such as kevlar ® or fabric materials . an outer polymer coating 602 covers the device 600 to the proximal point of attachment ( unnumbered ) of the ribbon 612 , leaving the open coil section 614 exposed . the ribbon 612 is attached to the open coil section 614 at a flattened section 615 . means of attaching the ribbon 612 include but are not limited to adhesives , laser welding , or soldering . when negative pressure is applied to the second lumen 610 the device 600 can be used as an aspiration device to remove fluid or debris through the spaces between the open coil section 614 , from an anatomical location the device 600 has been navigated to . the distal closed coil section 616 is close or tight wound and forms an area 618 for attaching a hollow actuating member 604 . the actuating member 604 can be made from a variety of materials having sufficient strength to be able to cause the distal section 617 to deflect and still be flexible to flex enough to curve with the coil 608 , including but not limited to stainless steel alloys , nickel titanium alloys and reinforced polymeric materials such as kevlar ® or fabric materials . the first lumen 606 which extends through the center of the actuating member 604 can also be used for aspirating fluids or debris when negative pressure is applied to the first lumen 606 . likewise , the first lumen 606 can be used for delivery of drugs or therapeutic fluids when positive pressure is applied . a coating 602 such as non - thrombogenic polymers , ptfe , eptfe , fep , polyester , polyurethane , polyethylene , silicone or hydrophilic may be applied over the proximal section ( unnumbered ) of the coil 608 to improve sterility as well as enhancing the outer smoothness of the guidewire 600 , thereby causing less trauma to the patient during introduction , the procedure itself and removal . in one embodiment the coating 602 is applied to the coil 608 by applying a polymer heat shrink tubing such as a ptfe , fep , or polyester , followed by the application of a proper amount of heat or an appropriate length of time . in additional embodiments the coating 602 is applied by dipping the guidewire 600 into a dispersion polymer such as urethane or silicone , by spraying a polymer such as ptfe , fep , polyester or silicone or by a co - extrusion process of a polymer such as ptfe , fep , polyester , urethane or silicone . an additional advantage of a coating 602 is a reduction in adverse reactions due to adhesion of platelets , proteins , cells or other fouling materials , which can cause fibrin clot production . when distal force is applied to the actuating member 604 by the operator , as shown in fig1 a , the distal section 617 deflects due to the non - expandable side 622 to which the ribbon 612 is attached being prevented from expanding while allowing the expandable side 624 to expand , resulting in the distal section 617 assuming a deflected configuration as best shown in fig1 a . as shown in fig1 b , if proximal force is applied to the actuating member 604 the distal section 617 is deflected in another direction than when distal force is applied . this is due to the pitch of the open wound coil section 614 having a relatively loose or open pitch to the coil winds ( unnumbered ), which allows the coil winds ( unnumbered ) on the expandable side 624 , to be forced into a closer configuration . if the actuating member 604 is coupled with an actuating mechanism ( not shown ) such as a vernier type mechanism ( not shown ) a predictable and variable amount of deflection can be achieved with the application of a given amount of longitudinal force . fig1 c shows a lateral cross section of the vascular device 600 taken through the lines 1 c - 1 c and illustrates the locations of the non - expandable side 622 and expandable side 624 . fig2 is a cross sectional centerline view taken along the longitudinal axis of a vascular device 1400 of the present invention having a fibrous actuating member 1430 or metal actuating member ( not shown ) attached 1432 to a distal end 1434 of a coil 1414 enabling the vascular device 1400 to deflect to an alternative shape upon proximal force being applied to the actuating mechanism 1430 . the vascular device 1400 can be used as a guidewire or a catheter or as a combination of the two . the device 1400 includes a coil 1414 defining a distal section 1412 , further defining a loose wound section 1412 a and a tight wound section 1412 b . a proximal coil section 1415 extends proximally of the distal coil section 1412 and may be wound in a relatively closed coil configuration similar to the tight wound section 1412 b . in one embodiment , the coil 1414 can be made from a radiopaque material such as a platinum - nickel alloy that allows the physician to visualize the position of the coil 1414 using radiological means , thereby navigating the vascular device 1400 into desired anatomical pathways with minimal forward motion . the coil 1414 extends between a distal end 1434 and a proximal end 1429 and defines a central space 1410 inside the coil winds . the coil 1414 defines a flattened section 1416 towards the distal end 1434 which is configured to receive a ribbon 1418 which is affixed to the coil 1414 . the ribbon 1418 is made of a suitable metallic material such as austenitic stainless steel alloy or a tungsten alloy such as tungsten - molybdenum and tungsten - rhenium . in some instances , iridium is added to the alloy to increase strength and radiopaqueness . in another embodiment ( not shown ) the ribbon 1418 is not used and instead the deflectable distal section 1412 is defined by a series of welds ( not shown ), gluing ( not shown ) or mechanical fasteners ( not shown ) affixed to the coil winds . in an alternative embodiment ( not shown ), the ribbon 1418 is replaced by the application of a polymer fiber fused to coil 1414 . the fiber ( not shown ) is entangled into the coil 1414 by means of weaving in and out of the coil winds and looping around the individual coil winds to form a solid attachment after application of an adhesive . the ribbon 1418 ( or other means of securing ) functions to bind together the portions of the coil 1414 to which it is attached to form a non - expandable side 1438 as best shown in fig2 b . means of attaching the ribbon 1418 to the flattened section 1416 include but are not limited to adhesives , laser welding , or soldering . thus , when proximal force is applied to the actuating member 1430 by the operator , the distal section 1412 will deflect due to the non - expandable side 1438 of the coil 1414 to which the ribbon 1418 is attached being prevented from expanding while allowing the expandable side 1440 to expand , resulting in the distal section 1412 deflecting from a straight configuration . if the actuating member 1430 is coupled with an actuating mechanism ( not shown ) such as a vernier type mechanism ( not shown ) a predictable and variable amount of deflection can be achieved with the application of a given amount of proximal force . it is also observed that along the distal section 1412 the coil 1414 defines a loose wound section 1412 a where it is wound at a lesser or looser pitch than the remainder of the coil 1414 , imparting a greater degree of flexibility to the distal section 1412 . attached by solder 1424 or other means to the coil 1414 at the distal end 1428 is a hollow member 1420 which resides inside the central space 1410 and extends the length of the vascular device 1400 . the hollow member 1420 functions to add stiffness and stability to the vascular device 1400 , while also defining a lumen 1422 which can be used for such purposes as drug delivery , aspiration or as a general catheter . the hollow member 1420 can be made from a variety of materials having sufficient strength to be able to cause the distal section 1412 to deflect and still be flexible enough to move with the coil 1414 , including but not limited to stainless steel alloys , nickel titanium alloys and reinforced polymeric materials such as kevlar ® or fabric materials . the actuating member 1430 can be made of a polymeric material such as kevlar ® or other suitable metallic material such as stainless steel and is attached by solder 1424 or other means to the distal end 1434 of the coil 1414 and routed through the central space 1410 so as to be able to apply proximal force to the distal section 1412 , allowing an operator to precisely deflect the distal section 1412 thereby enhancing the steerability and overall maneuverability of the vascular device 1400 . a coating 1426 such as non - thrombogenic polymers , ptfe , eptfe , fep , polyester , polyurethane , polyethylene , silicone or hydrophilic may be applied over the coil 1414 to improve sterility as well as enhancing the outer smoothness of the guidewire 1400 , thereby causing less trauma to the patient during introduction , the procedure itself and removal . in one embodiment the coating 1426 is applied to the coil 1414 by applying a polymer heat shrink tubing such as a ptfe , fep , or polyester , followed by the application of a proper amount of heat or an appropriate length of time . in additional embodiments the coating 1426 is applied by dipping the guidewire 1400 into a dispersion polymer such as urethane or silicone , by spraying a polymer such as ptfe , fep , polyester or silicone or by a co - extrusion process of a polymer such as ptfe , fep , polyester , urethane or silicone . an additional advantage of a coating 1426 is a reduction in adverse reactions due to adhesion of platelets , proteins , cells or other fouling materials , which can cause fibrin clot production . as shown in fig2 a , if proximal force is applied to the actuating member 1430 the distal section 1412 is deflected . this is due to the expandable side 1440 being able to expand while the non - expandable side 1438 is prevented from expanding . if the actuating member 1430 is coupled with an actuating mechanism ( not shown ) such as a vernier type mechanism ( not shown ) a predictable and variable amount of deflection can be achieved with the application of a given amount of longitudinal force . fig2 b shows a lateral cross section of the vascular device 1400 taken through the lines 2 b - 2 b and illustrates the locations of the non - expandable side 1438 and expandable side 1440 . fig3 shows a vascular device 400 which can be used as a guidewire or a catheter or as a combination of the two . a hollow shaft 402 defines a first lumen 414 into which is fitted an actuating member 404 which is itself hollow and defines a second lumen 416 . the hollow shaft 402 is proximally attached to a first handle 422 which , as described above , is used to contact the device 400 as a whole . a third handle 423 is attached to the actuating member 404 which provides longitudinal control over the position of the actuating member 404 . the hollow shaft 402 provides strength and support to the vascular device 400 and defines a proximal termination 402 a , which is mounted within the first handle 422 , and a distal termination 402 b . the hollow shaft 402 and actuating member 404 can be made from a variety of materials having sufficient strength to be able to cause the distal section 407 to deflect and still be flexible enough to move with a coil 406 , including but not limited to stainless steel alloys , nickel titanium alloys and reinforced polymeric materials such as kevlar ® or fabric materials . the coil 406 defines an open wound section 406 a which is attached to and extends distally from the distal termination 402 b of the hollow shaft 402 to the proximal end 412 of a solid coil section 406 b . the open wound section 406 a is further defined by the attachment of a ribbon 418 which in one embodiment is attached to a flattened section 426 of the coil 406 . means of attaching the ribbon 418 include but are not limited to adhesives , laser welding , or soldering . in one embodiment , the coil 406 can be made from a radiopaque material such as a platinum - nickel alloy that allows the physician to visualize the position of the coil 406 using radiological means , thereby navigating the vascular device 400 into desired anatomical pathways with minimal forward motion . the vascular device 400 defines a deflectable distal section 407 such that when longitudinal force is applied to the actuating member 404 by the operator , the distal section 407 deflects as a result of preventing the non - expandable side 430 , to which the ribbon 418 is attached , from expanding , while allowing the expandable side 432 to expand , resulting in the distal section 407 assuming a deflected configuration as best shown in fig3 a and 3b . the ribbon 418 is made of a suitable metallic material such as austenitic stainless steel alloy or a tungsten alloy such as tungsten - molybdenum and tungsten - rhenium . in some instances , iridium is added to the alloy to increase strength and radiopaqueness . in another embodiment ( not shown ) the ribbon 418 is not used and instead the deflectable distal section 407 is defined by a series of welds ( not shown ), gluing ( not shown ) or mechanical fasteners ( not shown ) affixed to the coil winds . in an alternative embodiment ( not shown ), the ribbon 418 is replaced by the application of a polymer fiber fused to the open wound coil section 406 a . the fiber ( not shown ) is entangled into the open wound coil section 406 a by means of weaving in and out of the coil winds and looping around the individual coil winds to form a solid attachment after application of an adhesive . the solid , distally located section 406 b of the coil 406 is created by the presence of welds 408 between the individual coil winds ( unnumbered ) which function to prevent flexing of the solid section 406 b from the application of longitudinal force . the solid coil section 406 b terminates at a distal lumen opening 410 which is in fluid communication with the second lumen 416 and can thus be used to either deliver or aspirate substances from the anatomical area accessed by the device 400 . the actuating member 404 extends proximally from the first handle 422 allowing access to the second lumen 416 and distally to the junction between the open wound section 406 a and solid section 406 b of the coil 406 , where it is attached by solder 428 . extending through the second lumen 416 is a rotatably mounted , flexible cutting shaft 424 , defining a proximal end 424 a and a distal end 424 b which terminates distally with a cutting burr 420 mounted thereon which is used to remove plaque or clots from a vessel . a second handle 425 is distally attached to the cutting shaft 424 and is manually rotated by the physician as needed , resulting in the cutting burr 420 simultaneously rotating . flexibility of the cutting shaft 424 is preferably provided by making it of superelastic nitinol , but it is also contemplated to be made of stainless steel , glass - filled polymer or carbon - filled polymer . when distal force is applied to the actuating member 404 by the operator , as shown in fig3 a , the distal section 407 deflects due to the non - expandable side 430 to which the ribbon 418 is attached being prevented from expanding while allowing the expandable side 432 to expand , resulting in the distal section 407 assuming a deflected configuration as best shown in fig3 a . as shown in fig3 b , if proximal force is applied to the actuating member 404 the distal section 407 is deflected in the opposite direction as when distal force is applied . this is due to the pitch of the open wound coil section 406 a having a relatively loose or open pitch to the coil winds ( unnumbered ), which allows the coil winds ( unnumbered ) on the expandable side 432 , to be forced into a closer configuration . if the actuating member 404 is coupled with an actuating mechanism ( not shown ) such as a vernier type mechanism ( not shown ) a predictable and variable amount of deflection can be achieved with the application of a given amount of longitudinal force . fig3 c shows a lateral cross section of the vascular device 400 taken through the lines 3 c - 3 c and illustrates the locations of the non - expandable side 430 and expandable side 432 . fig4 is a cross sectional centerline view taken along the longitudinal axis of an alternative embodiment of the vascular device 500 which is similar to the embodiment of the vascular device 400 shown in fig3 - 3c , with the addition of a covering sheath 505 . the vascular device 500 can be used as a guidewire or a catheter or as a combination of the two . the sheath 505 can be insert molded and surrounds at least the distal section 517 of the vascular device 500 . the sheath 505 functions to make the device 500 more atraumatic , creating a safer device . a distal end 506 of the sheath 505 defines a range of at least one and up to eight slits 508 which are impressed across the center axis of the distal end 506 and which function to enclose a cutting head 520 and thereby protect delicate anatomical structures during introduction . when the cutting head 520 or other medical device ( not shown ) is deployed the slits 508 will open , becoming flaps ( not shown ), allowing the physician to perform a medical procedure , such as loosening and ultimately removing plaque from the interior surfaces of artery walls . when the cutting head 520 or other medical device ( not shown ) is pulled back into the second lumen 516 following completion of the procedure , the flaps 508 may close ( not shown ) or remain open still enclosing the cutting head 520 , allowing the device 500 to be removed in a manner less likely to cause additional trauma to the patient . as shown in fig4 hollow shaft 502 defines a first lumen 514 into which is fitted an actuating member 504 which is itself hollow and defines a second lumen 516 . the hollow shaft 502 and actuating member 504 are proximally attached to a first handle 534 which is used to contact the device 500 as a whole as well as allowing longitudinal control over the position of the actuating member 504 . the hollow shaft 502 provides strength and support to the vascular device 500 as a whole and defines a proximal termination ( unnumbered ), which is mounted within the first handle 534 . the hollow shaft 502 and actuating member 504 can be made from a variety of materials having sufficient strength to be able to cause the distal section 517 to deflect and still be flexible enough to move with a coil 510 , including but not limited to stainless steel alloys , nickel titanium alloys and reinforced polymeric materials such as kevlar ® or fabric materials . the coil 510 defines an open wound section 510 a which is attached to and extends distally from the distal termination ( unnumbered ) of the hollow shaft 502 to a proximal end ( unnumbered ) of a solid coil section 510 b . the open wound section 510 a is further defined by the attachment of a ribbon 518 which in one embodiment is attached to a flattened section 526 of the coil 510 . means of attaching the ribbon 518 include but are not limited to adhesives , laser welding , or soldering . in one embodiment , the coil 510 can be made from a radiopaque material such as a platinum - nickel alloy that allows the physician to visualize the position of the coil 510 using radiological means , thereby navigating the vascular device 500 into desired anatomical pathways with minimal forward motion . the vascular device 500 defines a deflectable distal section 517 so that when longitudinal force is applied to the actuating member 504 by the operator , the deflectable distal section 517 deflects , as described in detail below . the ribbon 518 is made of a suitable metallic material such as austenitic stainless steel alloy or a tungsten alloy such as tungsten - molybdenum and tungsten - rhenium . in some instances , iridium is added to the alloy to increase strength and radiopaqueness . in another embodiment ( not shown ) the ribbon 518 is not used and instead the deflectable distal section 517 is defined by a series of welds ( not shown ), gluing ( not shown ) or mechanical fasteners ( not shown ) affixed to the coil winds . in an alternative embodiment ( not shown ), the ribbon 518 is replaced by the application of a polymer fiber fused to the open wound coil section 510 a . the fiber ( not shown ) is entangled into the open wound coil section 510 a by means of weaving in and out of the coil winds and looping around the individual coil winds to form a solid attachment after application of an adhesive . the solid , distally located section 510 b of the coil 510 is created in this embodiment by the presence of welds 512 between the individual coil winds ( unnumbered ) which function to prevent flexing of the solid section 510 b from the application of longitudinal force . the solid coil section 510 b terminates at a distal lumen opening ( unnumbered ) which is in fluid communication with the second lumen 516 and can thus be used to either deliver or aspirate substances from the anatomical area accessed by the device 500 . the actuating member 504 extends proximally from the first handle 534 allowing access to the second lumen 516 and distally to the junction between the open wound section 510 a and solid section 510 b of the coil 510 , where it is attached by solder 528 . extending through the second lumen 516 is a rotatably mounted cutting shaft 524 , defining a proximal end 524 a and a distal end 524 b which terminates distally and is mounted with a cutting head 520 and is used to remove plaque or clots from a vessel . a second handle 536 is distally attached to the cutting shaft 524 and is manually rotated by the physician as needed , resulting in rotation of the cutting head 520 . flexibility of the cutting shaft 524 is preferably provided by making it of superelastic nitinol , but it is also contemplated to be made of stainless steel , glass - filled polymer or carbon - filled polymer . when distal force is applied to the actuating member 504 by the operator , as shown in fig4 b , the distal section 517 deflects due to the non - expandable side 530 to which the ribbon 518 is attached being prevented from expanding while allowing the expandable side 532 to expand , resulting in the distal section 517 assuming a deflected configuration as best shown in fig4 b . as shown in fig4 c , if proximal force is applied to the actuating member 504 the distal section 517 is deflected in another direction as when distal force is applied . this is due to the pitch of the open wound coil section 510 a having a relatively loose or open pitch to the coil winds ( unnumbered ), which allows the coil winds ( unnumbered ) on the expandable side 532 , to be forced into a closer configuration . if the actuating member 504 is coupled with an actuating mechanism ( not shown ) such as a vernier type mechanism ( not shown ) a predictable and variable amount of deflection can be achieved with the application of a given amount of longitudinal force . fig4 d shows a lateral cross section of the vascular device 500 taken through the lines 4 d - 4 d and illustrates the locations of the non - expandable side 530 and expandable side 532 . fig5 a shows the vascular device 400 as shown in more detail in fig3 in use following introduction into a patient , approaching an obstruction 1002 at the onset of treatment . it is seen that the device 400 has been navigated to the obstruction 1002 in a vessel 1000 which requires opening . cutting head 420 has been deployed from the second lumen 416 to eventually bore through the obstruction 1002 and it is observed that the distal end ( unnumbered this figure ) of the device 400 is in the deflected configuration as a result of applying distal force to the actuating member 404 which allows the device to be precisely navigated through a tortuous vascular pathway . fig5 b shows the vascular device 400 in use during the beginning of treatment . it is seen that the deployed cutting head 420 is being rotated and contacting the obstruction 1002 . it is further seen that some of the obstruction 1002 b has been detached from its main body following treatment . fig5 c shows the vascular device 400 in use following completion of treatment . it is seen that the obstruction 1002 has been crossed and that some obstruction 1002 a remains attached to the vessel 1000 wall while other obstruction 1002 b is detached and has been removed . fig5 d shows the vascular device 400 in use following introduction into a patient , approaching an obstruction 1000 at the onset of treatment , with the vascular device 400 contained in a catheter 50 used to aspirate debris from the treatment site . fig5 e shows a vascular device 500 similar to that shown in fig4 with an additional difference being a predetermined angle 722 formed into the cutting shaft 718 . it is seen that the deployed cutting head 720 extends from the slit 508 at the distal end 506 of the sheath 505 and is being rotated and contacting the obstruction 1002 . the angle 722 confers the advantage of allowing the physician to rotate the proximal end ( not shown ) of the actuating member ( not shown ) causing the cutting head 720 to move in an elliptical path around the inner walls of the vessel 1000 , cutting and removing obstruction 1002 . this allows the sheath 505 to remain stationary and not rotated by the physician . a consistent deflection can be maintained on the distal end 506 of the vascular device 500 and held in the center axis of the vessel 1000 . this advantage also reduces the amount of vascular damage caused by required rotating of conventional guidewires or cutting devices by the physician in the process of navigating the device 500 through vascular obstructions . the outer diameter of the vascular device 400 , 500 , 600 , 1400 is manufactured to dimensions that are industry standards for certain medical procedures and can range from between approximately 0 . 006 inch to 0 . 121 inch which allows passage through a ten french catheter at 0 . 131 inch outer diameter , as an example . the length of the vascular device 400 , 500 , 600 , 1400 is similarly manufactured to conform to industry standards and may range between approximately 10 centimeters to 300 centimeters as required by the particular medical procedure . using the vascular device 400 , 500 , 600 , 1400 of the present invention first requires removal from sterile packaging . standard surgical techniques are employed to incise the proper blood vessel or bodily duct using an introducer having one or more sealed ports . the introducer can range in diameter from 4 to 24 french depending on the vessel or bodily duct size and location . most procedures performed for percutaneous transluminal coronary angioplasty ( ptca ) use a 6 to 10 french device passing through the introducer . a 6 to 10 french catheter having an open and blunt distal end can cause vascular damage passing through the vessels . therefore one embodiment of the invention described herein discloses a rounded , bulleted distal end . the introducer is placed into the vessel lumen and is followed by insertion of a guidewire , catheter or other medical device that can pass transluminally through the vessel to the site of therapy . a rounded distal end will facilitate this task with less vascular damage . the vascular device 400 , 500 , 600 , 1400 is then inserted into the introducer and carefully navigated through the patient &# 39 ; s vasculature until the treatment site is reached . at that point , either the vascular device 400 , 500 , 600 , 1400 is used to complete the procedure or another device is passed over or through the vascular device 400 , 500 , 600 , 1400 . at the completion of the procedure the vascular device 400 , 500 , 600 , 1400 is disposed of . in the embodiments 400 , 500 as described above , the invention may be employed as a combination guidewire and thrombectomy or atherectomy device to remove calcified plaque or venous thrombosis . when these embodiments of the vascular device 400 , 500 are used the physician places the distal end 410 , 506 near the obstruction and a radio opaque contrast material may be injected into the artery through a lumen in the device , after which the physician advances a second handle 425 , 536 at the proximal end ( unnumbered ) to deploy the cutting head 420 , 520 at the distal end 410 , 506 and slowly advance the device while manually rotating the second handle 425 , 536 . aspiration may be used to remove the debris detached and displaced by the cutting head 420 , 520 . upon completion of the procedure , the vascular device 400 , 500 is removed and disposed of . these embodiments allow the physician to navigate a single device to the diseased area and complete the procedure in the shortest time with the least amount of vascular damage . while the invention as described above can be used as a combination guidewire / thrombectomy / atherectomy device , it can also be used a catheter . most transfemoral coronary catheterization employ between a 4 and 10 french catheter . small arteries will utilize around a 4 french catheter while larger arteries could utilize up to a 10 french catheter . cited by the journal of the american medical association , upward of three million cardiac catheterizations are performed annually in the united states . a device to reduce procedural time vascular damage would be an economic advantage to the industry . the vascular device 400 , 500 , 600 , 1400 may be applied to a variety of medical devices capable of being introduced into the vasculature or other anatomy of a patient . for example , the vascular device 400 , 500 , 600 , 1400 could be applied to singular guidewires , guidewire / catheter combination ( e . g ., balloon angioplasty , stent deliver , drug delivery , fluid delivery or fluid removal ), as a conduit for atherectomy devices and nus catheters , laparoscopic and endoscopic devices , spinal or cranial navigation devices , neurostimulation and cardiac resynchronization leads , embolic protection devices , therapeutic devices and other medical devices . when used for drug delivery the invention finds utility by being able to remove fluid causing the surrounding area to lose excess fluid . a drug can then be injected and the affected area will more readily absorb the drug by the osmotic difference in pressure . this allows the drug to remain at the site rather than be carried away by the movement of interstitial fluids . the vascular device 600 , 1400 finds further utility in the implantation of neurostimulation or resynchronization leads which are typically 30 to 60 cm long . currently these leads must include a large lumen for the insertion of a preformed stylet to steer the lead to the target site . as the industry continues to reduce the diameter of these leads to 4 . 1 french or less by removing the stylet lumen , a device is needed to steer the leads to the target site and allow the physician to rotate the lead ( not shown ) at the proximal end to implant the lead . the vascular device 600 , 1400 accomplishes this by providing an open lumen from the proximal end ( unnumbered ) to the distal end 620 , 1436 while allowing the distal end 620 , 1436 to be manipulatively deflected by the physician and the proximal end of the lead manually rotated . following implantation of the lead the invention is removed and disposed of .

a multi - purpose vascular device defines a lumen allowing fluid communication there through and has a coil with a side of the coil winds having solid physical connections between the coil winds to prevent the connected coil wind side from expanding following the application of force by an actuating member which causes the connected coil winds to have a predetermined configuration in an unstressed state . the application of longitudinal force causes the unconnected coil winds to expand , resulting in the vascular device assuming a different configuration .

a test was carried out in accordance with an embodiment of the present invention , and results are shown in table 1 below . peripheral blood was extracted from ten human volunteers for use in ten respective experiments . in each experiment , cells were fractioned from the blood using a ficoll ™ gradient in order to generate a population of peripheral blood mononuclear ( pbmc ) cells as source cells (“ s . cells ”). subsequently , a ccp was generated in accordance with protocols described herein for percoll ( tm ) based enrichment . results in table 1 show enrichment of the percentages of cd34 + cd45 −/ dim cells in the ccp compared to the source cells . enrichment is defined as the percentage of cells having a given characteristic in the ccp , divided by the percentage of cells having that characteristic in the source cells . in a separate set of experiments , in accordance with an embodiment of the present invention , results were obtained as shown in fig1 and table 2 below . peripheral blood was extracted from ten human volunteers for use in ten experiments . a ccp was generated in accordance with protocols described herein ( see example 1 ). results in fig1 and in table 2 show the fluorescent intensity of cd31bright cells in the ccp . cd31 brightness ( dim or bright ) is defined as the ratio between intensity resulting from staining using anti - cd31 fitc - conjugated monoclonal antibodies and intensity resulting from staining using isotype control fitc - conjugated antibodies . fig1 is a graph showing results obtained from ccp cells in one representative experiment , in accordance with an embodiment of the present invention . ccp cells stained using isotype control fitc - conjugated antibodies are represented by the dashed line and ccp cells stained using fitc - conjugated anti - cd31 antibodies are represented by the black line . three different intensity areas were marked : ( a ) m1 — low intensity corresponding to non - specific staining of isotype control or cells that do not express cd31 , located at geometric mean intensity of 5 . 38 ; ( b ) m2 — dim intensity corresponding to cells expressing cd31 at a geometric mean intensity of 46 . 69 ; and ( c ) m3 — bright intensity corresponding to cells expressing cd31 at a geometric mean intensity of 478 . 45 . table 2 is a numerical summary of intensities m1 , m2 and m3 and their respective ratios resulting from ten independent experiments . cd31bright cells &# 39 ; ( m3 ) mean intensity is 86 . 5 ( se = 10 . 42 ) times greater than the negative control intensity ( m1 ) and 10 . 69 ( se = 0 . 66 ) times more than cd31dim cells ( m2 ) ( which themselves have an intensity 8 . 00 ( se = 0 . 63 ) times more than m1 ). thus , results indicate that the ccp was enriched to provide cd31 + cells . in a separate set of experiments , in accordance with an embodiment of the present invention , results were obtained as shown in table 3 below . peripheral blood was extracted from nine human volunteers for use in nine experiments . a ccp was generated in accordance with protocols described hereinabove with reference to example 1 . in a separate set of experiments , a human - pbmc - derived ccp was cultured in order to generate an acp - rich pcp ; the ccp was grown on fibronectin or plasma - coated t75 flasks in the presence of medium containing autologous serum (& gt ;= 10 %), 2 ng / ml vegf , and 5 iu / ml heparin . fig2 is a photograph showing the morphology of a typical angiogenic cell precursor ( acp ) population , produced in the experiments of example 3 , in accordance with an embodiment of the present invention . typically , elongated and spindle - shaped cells are observed in cultures of acps . this image was obtained from × 200 magnification of cultured acps . in a separate set of experiments , a human - pbmc - derived ccp was cultured in order to generate an acp - rich pcp , as described hereinabove with respect to example 4 . the ccp was grown on fibronectin or plasma - coated t75 flasks in the presence of medium containing autologous serum (& gt ;= 10 %), 2 ng / ml vegf , and 5 iu / ml heparin . fig3 contains photographs of a typical angiogenic cell precursor ( acp ) population , produced in the experiments of example 2 , in accordance with an embodiment of the present invention . harvested cells were loaded on a glass slide and fixed prior to their specific staining . stained cells were mounted using a fluorescent mounting solution containing the nuclear stain dapi . figures a1 - a3 are a series of photographs from cells stained with fitc - conjugated ulex - lectin , cells stained with pe - conjugated anti - cd31 , or cells that stained with both ulex - lectin and anti - cd31 , in accordance with respective embodiments of the present invention . a1 is a photograph of cells stained with the nuclear marker dapi . a2 is a photograph showing green emission resulting from staining of the same cells with fitc - conjugated ulex - lectin . a3 is a photograph showing red emission resulting from staining of the same cells with pe - conjugated anti - cd31 antibodies . figures b1 - b3 are a series of photographs from cells stained with isotype control antibodies , in accordance with respective embodiments of the present invention . b1 is a photograph of cells stained with the nuclear marker dapi , b2 is a photograph showing green emission resulting from staining of the same cells with fitc - conjugated mouse igg antibodies , and b3 is a photograph showing red emission resulting from staining of the same cells with pe - conjugated mouse igg antibodies . typically , acp cells fluoresce both red and green indicating adhesion of both ulex - lectin and anti - cd31 thereto . images were obtained from × 200 magnification . in a separate set of experiments , a human - pbmc - derived ccp was cultured in order to generate an acp - rich pcp , as described hereinabove with reference to example 4 . the ccp was grown on fibronectin or plasma - coated t75 flasks in the presence of medium containing autologous serum (& gt ;= 10 %), 2 ng / ml vegf , and 5 iu / ml heparin . fig4 contains photographs of a typical angiogenic cell precursor ( acp ) population , produced in the experiments of example 4 , in accordance with an embodiment of the present invention . harvested cells were loaded on a glass slide and fixed prior to their specific staining . stained cells were mounted with a fluorescent mounting solution containing the nuclear stain dapi . figures a2 - a3 are a series of photographs demonstrating uptake of ac - ldl , cells stained with anti - cd31 , or cells that show both uptake of ac - ldl and staining with anti - cd31 , in accordance with respective embodiments of the present invention . a1 is a photograph of cells stained with the nuclear marker dan , a2 is a photograph showing green emission resulting from uptake of fitc labeled - ac - ldl by the same cells , and a3 is a photograph showing red emission resulting from staining of the same cells with pe - conjugated anti - cd31 antibodies . figures b1 - b3 are a series of photographs from cells stained with isotype control antibodies , in accordance with an embodiment of the present invention . b1 is a photograph of cells stained with the nuclear marker dapi , b2 is a photograph showing green emission resulting from staining of the same cells with fitc - conjugated mouse igg antibodies , and a3 is a photograph showing red emission resulting from staining of the same cells with pe - conjugated mouse igg antibodies . typically , acp cells fluoresce both green and red indicating that acps uptake ac - ldl as well as comprise cd31 . images were obtained from × 200 magnification . in the same set of experiments , the human - pbmc - derived ccp was cultured in order to generate an acp - rich pcp as described hereinabove with respect to example 4 . flow - cytometry percentage staining results from nine independent experiments are summarized in table 4 , and show the average staining results obtained on day 5 of culturing . results using such a protocol typically yield a pcp having an average of 60 . 7 % of cells that both demonstrate uptake of ac - ldl and stain for cd31bright . in a separate set of experiments , a human - pbmc - derived ccp was cultured in order to generate an acp - rich pcp , as described hereinabove with respect to example 4 . harvested acp - rich pcp cells were washed from culture medium and incubated for 24 hours in a serum - free medium . average secretion levels ( pg / ml ) of il - 8 , vegf , and angiogenin as obtained from four independent experiments are summarized in table 5 . in the same set of experiments , a human - pbmc - derived ccp was cultured in order to generate an acp - rich pcp , as described hereinabove with reference to example 4 . angiogenic pattern and vascular tube formation of acp - rich pcp cells were examined microscopically following plating of the cells on an extracellular matrix gel ( ecm ). typically , semi - closed and closed polygons of capillaries and complex mesh - like capillary structures were observed and scored according to a scale published by kayisli et al . ( 52 ) as grade 4 - 5 , indicating the angiogenic - inducing properties of the acp - rich pcp . fig5 is a photograph showing tube formation in an acps , produced in the experiments of example 6 , in accordance with an embodiment of the present invention . typical mesh - like capillary structures generated from a harvested acps are present in the culture and are suitable for administration to a human . in a separate set of experiments , a human - pbmc - derived ccp was cultured in order to generate an acp - rich pcp ; the ccp was grown on fibronectin or plasma - coated t75 flasks in the presence of medium containing autologous serum (& gt ;= 10 %), 2 - 10 ng / ml vegf , and 5 iu / ml heparin . at the end of the culturing period , acp cells were harvested and labeled with 0 . 8 ug / ml ac - ldl - dio for 15 min at 37 c and placed in inserts which were placed in wells . one million labeled acps were placed on microporous membrane inserts with a pore size of 8 micrometer . 200 ul medium was placed at the bottom of each of the wells . negative control ( m199 ), positive control ( e . g ., 20 ng / ml vegf , 20 ng / ml bfgf , and 20 ng / ml scf ) and 0 . 08 - 60 ng / ml human recombinant interleukin - 8 ( hil - 8 ) diluted in m199 medium were plated in respective wells and the acp cells were allowed to migrate toward each respective medium . following 1 hour incubation in the presence of the negative control medium , the positive control medium , and the il - 8 containing media , labeled migrating cells from 10 - 15 random microscopic fields were evaluated using fluorescent microscope and automated counting software ( nth imagej ). calculation of cell number per 1 mm ̂ 2 was based on area of counting field (× 20 ) which equals 0 . 178 mm ̂ 2 , and each mm ̂ 2 contains 5 . 62 fields . assessment of acp migratory potential indicated that acps migrate toward chemokines such as vegf , bfgf , scf , and hil - 8 in a manner dependent on respective concentrations thereof , e . g ., hil - 8 concentration of typically higher than 6 . 7 ng / ml induces substantial migration of acps , and hil - 8 concentrations of about 7 - 20 ng / ml typically induce substantial migration of acps . fig6 a and 6b are graphs showing results obtained in five experiments of example 10 , in accordance with an embodiment of the present invention . fig6 a shows migration toward negative and positive control media of ac - ldl - dio pre - labeled acps . fig6 b shows a dosage - dependence curve reflecting migration of ac - ldl - dio pre - labeled acps in response to increasing concentrations of hil - 8 . acps derived from the human - pbmc - derived ccp show statistically significant migration toward the positive control samples . moreover , acp migration corresponding to increasing hil - 8 doses was observed . dose - dependent acp migration peaked at 6 . 7 - 20 ng / ml of hil - 8 . in a separate set of experiments , the human - pbmc - derived ccp was cultured in order to generate an acp - rich pcp , as described hereinabove with reference to examples 4 or 10 . in some embodiments , generation of the acp - rich pcp is attributed to migration of acp cells to a specific chemokine , in combination with the differentiation of ccp cells . migratory potential of acp - rich pcp was measured as described hereinabove with respect to example 10 . in this example , a conditioned medium ( cm ) was generated using the patients &# 39 ; cells which secrete chemokines into the medium . the patients &# 39 ; cells were then extracted from the medium , leaving a chemokine - rich medium for subsequent plating of acp therein . the potential for acp migration in response to chemokines was then assessed when the acps were incubated for 1 hour with conditioned medium . following 1 hour incubation in the presence of negative control ( m199 ); 20 ng / ml hil - 8 ; or cm ( at concentrations of 2 - 20 ng / ml ), migration of labeled cells from 10 - 15 random microscopic fields was evaluated using a fluorescent microscope and automated counting software ( nih imagej ). calculation of cell number per 1 mm ̂ 2 is based on area of counting field (× 20 )= 0 . 148 mm ̂ 2 and thus each square millimeter contains 6 . 7 fields . it was determined that acps migrate toward chemokines secreted during the production of the acp - rich pcp . for some applications , the generated acp - rich pcp batches were used to treat cardiovascular patients . all patients treated with these batches showed more than 10 % improvement in left - ventricular - ejection fraction both 3 and 6 months following treatment . it is hypothesized that this improvement was enabled at least in part by the migration of acps to the vicinity . fig7 is a graph showing results obtained in four experiments of example 11 , in accordance with an embodiment of the present invention . the acps derived from the human - pbmc - derived ccp show statistically significant migration toward the conditioned medium containing secreted chemokines ; this medium was generated in the process of the production of acp - rich pcp . in a separate set of experiments , migratory potential of human - pbmc toward hil - 8 was measured . in vitro assessment of pbmc migratory capability in response to hil - 8 was used to determine the potential of il - 8 to mobilize blood derived stem / progenitor cells from peripheral blood to locations in which high concentrations of il - 8 are expressed in vivo . peripheral blood was extracted from six human volunteers for use in six respective experiments . in each experiment , a ficoll ™ gradient was used to generate a population of pbmcs . one million pbmcs were placed on 3 um pore size microporous membrane inserts which were placed in wells . 200 ul medium was placed at the bottom of each of the wells . negative control ( m199 ) and positive control ( 20 ng / ml hil - 8 ) diluted in m199 medium were plated in respective wells and the pbmcs cells were allowed to migrate toward each respective medium . following 1 hour incubation in the presence of the negative control medium and the positive control medium , migration of cells from 10 - 15 random microscopic fields was evaluated using a fluorescent microscope and automated counting software ( nih imagej ). calculation of cell number per 1 mm ̂ 2 is based on area of counting field (× 20 ) which equals 0 . 148 mm ̂ 2 , and each square millimeter contains 6 . 7 fields . it was determined that hil - 8 induced mobilization of only a small fraction of the pbmcs , probably the stem / progenitor cells . fig8 is a graph of migration of pbmcs in response to hil - 8 , in accordance with an embodiment of the present invention . the results were obtained from six experiments ( example 12 ), and show that stem / progenitor cells derived from human - pbmcs migrate toward hil - 8 . reference is now made to fig9 a and 9b which are graphs showing results obtained in the experiments following injection into rats of acp - rich pcps derived from a human - pbmc - derived ccp ( as described hereinabove with respect to example 4 ) following acute myocardial infarction , in accordance with an embodiment of the present invention . the human - pbmc - derived ccp was cultured in order to generate an acp - rich pcp as described in example 4 . acp - rich pcp therapeutic potential was then assessed in a rat model of acute myocardial infarction which was induced in 15 male nude rats ( 200 - 225 g ) by ligation of the left anterior descending ( lad ) artery . six days after myocardial infarction , 10 rats were injected with 1 . 5 × 10 ̂ 6 acp - enriched cells ( acp , n = 10 ), while 5 rats were injected with the culture medium ( control , n = 5 ), via the aortic arch . cardiac function ( ejection fraction ) and the ratio of necrotic scar area to left ventricular free wall area were measured 28 days following the acp - rich pcp and the culture medium administrations . it is to be noted that the percentage of ejection fraction of the acp - administered rats , as represented by fig9 a , increased substantially in comparison to the decreased percentage ejection fraction of the control rats . additionally , a percentage reduction of necrotic tissue was observed in the acp - administered rats in comparison to the percentage of necrotic tissue observed in the control rats . paraffin fixed tissue sections obtained from the 10 acp - administered rats were stained in order to trace engrafted human cells and cardiomyocyte ( cmc ) markers in the border area of the scar tissue . fig9 c , 9 d and 9 e are photographs showing typical sections taken from a heart of one of the 10 rats 28 days after the injection of the acps derived from a human - pbmc - derived ccp in the experiments of the present example ( example 13 ) in accordance with an embodiment of the present invention . fig9 c shows staining of the rat &# 39 ; s heart cells with anti - human mitochondria . fig9 d shows the cells stained for cmc markers ( myosin heavy chain ( mhc )), fig9 e shows the rat heart cells stained for cardiac troponin i . ( reference is again made to fig9 c - e . the stained cells are marked by arrows ). these results depicted in fig9 c - d demonstrate that the human acps , derived in accordance with an embodiment of the present invention from the hpbmc - derived ccp , homed to damaged cardiac tissues , engrafted , and is hypothesized to have transdifferentiated into cells expressing cardiomyocyte markers . it is to be noted that acps typically improve systemic endothelial functioning , as expressed by improved ejection fraction and reduced necrosis . particular examples of improvement due to administration of acps , derived in accordance with an embodiment of the present invention , include improved cardiovascular functioning and improved sexual functioning . the scope of the present invention includes identifying a patient having cardiovascular dysfunction or sexual dysfunction , and administering acps to the patient in order to treat the dysfunction . in a production procedure , individual autologous human - pbmc - derived ccps were cultured in order to generate an acp - rich pcp , as described hereinabove . the ccps were grown on autologous plasma - coated t75 flasks in the presence of medium containing autologous serum (& gt ;= 10 %), 2 - 10 ng / ml vegf , and 5 iu / ml heparin . harvested cells , approved by quality control for clinical use , were administrated to patients . the therapeutic potential of acp - rich pcp is summarized in results of administration thereof to 14 patients suffering from end - stage heart failure . left ventricular ejection fraction ( ef ) and disease severity score ( score ) were assessed prior to and 1 - 8 months after the acp cell administration . improvement of these parameters was calculated relative to each patient &# 39 ; s baseline evaluation according to the following equation : results show statistically significant improvement ( p & lt ; 0 . 0001 ; tested using two - tailed , paired t test analysis ) in both parameters following treatment by administering acp - rich pcp . table 6 shows the number of treated patients , averages and individual results relating to ef and disease severity score , as well as the calculated percent improvement thereof . in a separate set of experiments , a human - pbmc - derived ccp was cultured in order to generate a cardiomyocyte ( cmc )- rich pcp ; the ccp was grown on fibronectin or plasma - coated t75 flasks in accordance with protocols described herein ( see medium preparation ). fig1 is a photograph of a typical cmc - rich pcp from the experiments of the current example ( example 15 ), derived in accordance with an embodiment of the present invention . typically , these cells appear elongated with dark cytoplasm , which may indicate high protein content . this image was obtained from × 200 magnification of cultured cmc - rich pcp cells . fig1 a , 11 b , and 11 c are photographs showing immunostaining of ccp - derived cardiomyocytes in the experiments of the current example ( example 15 ), in accordance with an embodiment of the present invention . slide - fixed cmc pcp cells were stained with : cells stained with non - specific mouse igg were detected by anti - mouse igg - fitc or by anti - mouse igg - cy3 and were used as negative controls . fig1 a - c show that cmc - rich pcp cells expressed the typical cardiomyocyte cellular markers : cardiac troponin t ( fig1 a ), alpha - actin ( fig1 b ), as well as the functionally important gap junction marker connexin - 43 ( fig1 c ). the images were obtained from × 100 magnification of slide - fixed cells . in the same set of experiments that produced the results shown in fig1 - 11c , a human - pbmc - derived ccp was cultured in order to generate a cmc - rich pcp ; the ccp was grown on fibronectin or plasma - coated t75 flasks in accordance with protocols described herein ( see medium preparation ). fig1 a and 12b are graphs showing flow cytometry analysis results obtained from immunostaining of a cmc - rich pcp in the experiments of the current example ( example 16 ), in accordance with respective embodiments of the present invention . in fig1 a - b , lines describing control , e . g ., non - specific staining , are marked as “ control ”; specific immunostaining with the cardiac cellular markers desmin and troponin t are marked as desmin ( fig1 a ) and troponin t ( fig1 b ), respectively . the m1 line represents the statistical marker area in which the cells are positively stained for the respective marker . in a separate set of experiments , a human - pbmc - derived ccp was cultured in order to generate a cmc - rich pcp , as described hereinabove . the cmc - rich pcp cells &# 39 ; therapeutic potential was assessed in a rat model of acute myocardial infarction . cmc - rich pcp cells were used for implantation into a rat model of induced acute myocardial infarction as described hereinabove with respect to example 13 ( with the exception that cmc - rich pcp cells were used for implantation into the rat model in the current example , whereas in example 13 , acp - rich pcp cells were used for implantation ). six days after myocardial infarction , heart muscle of 9 rats were injected with 1 . 5 × 10 ̂ 6 cmc pcp cells ( cmc , n = 9 ), while heart muscle of 5 rats were injected with culture medium ( control , n = 5 ). cardiac function ( ejection fraction ) was evaluated 14 days following the administration of the cmc - rich pcp cells or culture medium . fig1 is a graph showing experimental results obtained in the experiments of example 13 , in accordance with another embodiment of the present invention . it is to be noted that the percentage of ejection fraction of the cmc - administered rats increased substantially in comparison to the decreased percentage ejection fraction of the control rats . a series of protocols are described hereinbelow which may be used , as appropriate , separately or in combination with examples 1 - 17 , in accordance with embodiments of the present invention . it is to be appreciated that numerical values are provided by way of illustration and not limitation . typically , but not necessarily , protocols may be derived using values selected from a range of values that is within 20 % of the value shown . similarly , although certain steps are described herein with a high level of specificity , a person of ordinary skill in the art will appreciate that additional or other steps may be performed , mutatis mutandis . in accordance with an embodiment of the present invention ; generation of a single - cell suspension is carried out using the following protocols : receive blood bag and sterilize it with 70 % alcohol . load blood cells onto a ficoll ™ gradient . spin the tubes for 20 minutes at 1050 g at room temperature ( rt ), with no brake . transfer the collected cells to a new 50 ml tube , adjust volume to 30 ml per tube using pbs . spin tubes for 15 minutes at 580 g , rt , and discard supernatant . identify the major vein of the cord , and clamp one end of the vein . release the clamp from one end of the vein and collect the cell suspension . re - suspend the cells in culture medium comprising , for example , x - vivo 15 ™, 10 % autologous serum , 5 iu / ml heparin , and one or more growth factors . re - suspend in culture medium comprising , for example , x - vivo 15 ™, 10 % autologous serum , 5 iu / ml heparin , and one or more growth factors . in accordance with an embodiment of the present invention , generation of a ccp is carried out using the following protocols : protocol 1 : generation of a human ccp from pbmcs using a percoll ™ gradient . prepare gradient by mixing a ratio of 5 . 55 percoll ™ ( 1 . 13 g / ml ): 3 . 6 ddh2o : 1 pbsx10 . for every 50 ml tube of percoll : mix 20 ml of percoll ™ stock , 13 ml of ddh2o and 3 . 6 ml of pbsx10 . mix vigorously , by vortexing , for at least 1 min . load 34 ml mix into each 50 ml tube . centrifuge tubes , in a fixed angle rotor , for 30 min at 17 , 000 g , 21 c , with no brake . gently layer 3 . 0 ml of cell suspension of 150 million - 400 million pbmcs on top of the gradient . prepare a second tube with density marker beads : gently layer 3 . 0 ml of medium on top of the gradient . gently load density marker beads — 10 ul from each bead type . centrifuge tubes , in a swinging bucket rotor , for 30 min at 1260 g at 13 c , with no brake . gently collect all bands located above the red beads , and transfer to tube with 10 ml medium . centrifuge cells for 15 min at 580 g at 21 c . discard supernatant and re - suspend pellet in medium . count cells in trypan blue . centrifuge cells for 10 min at 390 g , 21 c . discard supernatant and re - suspend pellet in medium . take ccp cells for facs staining . protocol 2 : generation of human ccp from pbmcs using an optiprep ™ gradient . take up to 130 million cells for each enrichment tube . spin cells for 10 min at 394 g , 21 c . suspend cell pellet in 10 ml of donor serum . prepare a 1 . 068 g / ml optiprep ™ gradient by mixing a ratio of 1 optiprep ™: 4 . 1 pbs . for every 50 ml enrichment tube : mix 10 ml of cell suspension with 4 ml optiprep ™. for preparation of a 1 . 068 g / ml optiprep ™ gradient , mix 5 ml of optiprep ™ and 20 . 5 ml of pbs . gently layer 20 ml of the 1 . 068 g / ml gradient on top of the cell suspension . gently layer 1 . 5 ml hank &# 39 ; s buffered saline ( hbs ) on top of the gradient layer . centrifuge for 30 min at 700 g at 4 c , with no brake . gently collect the layer of cells that floats to the top of the 1 . 068 g / ml optiprep ™ gradient into a 50 ml tube pre - filled with pbs . centrifuge for 10 min at 394 g , 21 c . discard supernatant and re - suspend pellet in medium . count cells in trypan blue . it is to be noted that culture containers are typically either un - coated or coated with one or a combination of acp - enhancing materials such as collagen , fibronectin , cd34 , cd133 , tie - 2 , or anti - cd117 . in accordance with an embodiment of the present invention , the coating of a tissue culture container is carried out using the following protocols : for 20 t75 flasks — prepare up to seven days before , or on day of pbmc preparation . prepare 50 ml of 25 ug / ml fibronectin solution in pbs . fill every flask with 2 - 5 ml fibronectin 25 ug / ml . incubate at 37 c for at least 30 min . collect fibronectin solution . wash flask twice in pbs . dry flasks keep dry flasks at room temperature . dried flasks can be saved for one week at room temperature ( rt ). protocol 2 : coating t75 flasks with 25 ug / ml fibronectin and 5 ng / ml bdnf coat flasks with fibronectin 25 μg / ml , as described in protocol 1 . prepare 50 ml of 5 ng / ml bdnf solution in pbs . after washing off fibronectin , fill every flask with 2 - 5 ml bdnf 10 ng / ml . incubate at 37 c for 1 hour . collect the solution . wash flask twice in 10 ml pbs . keep dry flasks at room temperature until use . in accordance with an embodiment of the present invention , serum preparation is carried out using the following protocol : ( serum can be obtained directly or prepared from plasma ). take 100 ml of undiluted blood . spin at 1100 g ( 2500 rpm ) for 10 min . transfer the upper layer ( plasma ) to a new 50 ml tube . add 1 . 0 ml 0 . 8m cacl 2 - 2h 2 o for every 40 ml plasma . incubate for 0 . 5 - 3 hours at 37 c . spin coagulated plasma 5 min at 2500 g . collect the serum in a new tube , avoiding clotting . aliquot collected serum and save at − 20 c until use . in accordance with an embodiment of the present invention , medium preparation is carried out using the following protocols : medium can contain one or more additives , such as lif , epo , igf , b - fgf , m - csf , gm - csf , tgf alpha , tgf beta , vegf , bha , bdnf , ngf , egf , nt3 , nt4 / 5 , gdnf , s - 100 , cntf , ngf3 , cfn , admif , estrogen , progesterone , cortisone , cortisol , dexamethasone , or any other molecule from the steroid family , prolactin , an adrenocorticoid hormone , acth , glutamate , serotonin , acetylcholine , no , retinoic acid ( ra ) or any other vitamin d derivative , heparin , insulin , forskolin , simvastatin , mcdb - 201 , mct - 165 , glatiramer acetate , a glatiramer acetate - like molecule , ifn alpha , ifn beta or any other immunoregulatory agent sodium selenite , linoleic acid , ascorbic acid , transferrin , 5 - azacytidine , pdgf , vegf , cardiotrophin , and thrombin or rosiglitazone in various concentrations , typically ranging from about 100 pg / ml to about 100 μg / ml ( or molar equivalents ). typically , medium should not be used more than 10 days from its preparation date . protocol 1 : medium for enhancement of ccp - derived angiogenic cell precursors ( acps ). 200 um bha ( this is added during the last 24 hours of culturing ) 200 um bha ( this is added during the last 24 hours of culturing ) protocol 4a . medium for enhancement of ccp - derived cardiomyocyte ( cmc ) progenitor cells . serum - free medium ( e . g ., x - vivo 15 ™) 10 % autologous serum 20 ng / ml bfgf 20 ug / ml ifn beta 5 iu heparin . five to ten days after culture onset , add 3 um 5 - azacytidine for 24 hours . in accordance with an embodiment of the present invention , conditioned medium preparation is carried out using the following protocol : protocol 1 : preparation of 100 ml enriched medium containing 10 % autologous conditioned medium . dissection of rat blood vessels ( other non - human or human tissues may also be used ): anesthetize animal using anesthetic reagents ( e . g ., 60 - 70 % co2 , isoflurane , benzocaine , etc .). lay animal on its back and fix it to an operating table . using sterile scissors , cut animal &# 39 ; s skin and expose the inner dermis . using a second set of sterile scissors , cut the dermis , cut chest bones , and expose the heart and aorta . cut small pieces , 0 . 2 - 1 cm long , from the aorta and other blood vessels , and place them in a container pre - filled with 50 ml cold culture medium ( e . g . rpmi , x - vivo 15 ™), or any other growth medium ). using forceps and scissors , clean tissue sections , to remove outer layers such as muscle , fat , and connective tissue . using forceps and scalpel , cut each blood vessel along its length , and expose the inner layer of endothelial cells . using forceps and scalpel , cut small pieces of up to 0 . 1 cm2 from the tissue . it is to be understood that whereas this technique is in accordance with one embodiment of the present invention , the scope of the present invention includes extracting a blood vessel from a human , as well . for example , an incision may be made over the saphenous vein , in order to facilitate dissection of a distal 1 cm portion of the vein . tributary veins thereto are tied and transected . distal and proximal ends of the 1 cm portion of the saphenous vein are tied , and the vein is harvested . use the dissected tissue for direct and / or indirect co - culturing with the ccp and / or to generate conditioned medium . lay dissected pieces in culture containers , for example in t75 flasks , or 50 ml tubes . optionally , fill with cell culture medium containing 0 . 1 - 3 ug / ml or 3 - 100 ug / ml apoptotic reagent ( such as valinomycin , etoposide or staurosporine ), until all pieces are covered . spin collected conditioned medium at 450 g for 10 min , at room temperature . details regarding preservation of the conditioned medium , in accordance with an embodiment of the present invention , are described hereinbelow . in accordance with an embodiment of the present invention , culturing of a ccp to produce a pcp is carried out using the following protocols : fill t75 flask with 15 ml enriched medium , and add 5 ml of 10 million ccp cells / ml to attain a final concentration of 50 million ccp cells / flask . incubate t75 flasks , plates and slides at 37 c , 5 % co2 . for some applications , increased expansion and / or differentiation of the ccp may be obtained by exposure of the cell culture to oxygen starvation , e . g ., 0 . 1 - 5 % or 5 - 15 % oxygen ( hypoxia ), for 2 - 12 or 12 - 48 hours . this is typically done one or more times , at different points during cell culturing . set the oxygen pressure at 0 . 1 %, and maintain it at this level for 24 hours . take a sample of ccp cells and test viability by trypan blue exclusion method . re - insert the flasks into the incubator and continue incubation for the rest of the period . this procedure can be repeated , for example , once a week during the culture period and / or within 24 , 48 , or 72 hours before termination of the culture . for some applications , increased expansion and differentiation of the ccp may be achieved by re - seeding collected cells on new pre - coated dishes in culture medium . collect all cultured ccp in tubes . spin tubes for 10 minutes at 450 g , 21 c . discard the supernatant . gently mix pellet and re - suspend cells in 10 ml fresh medium per t75 flask . seed suspended cells in new pre - coated t75 flasks . continue culturing the cells , and perform all other activities ( e . g ., medium refreshment , visual inspection , and / or flow cytometry ), as appropriate , as described herein . this procedure can be performed weekly during the culture period and / or within 24 , 48 , or 72 hours before termination of the culture . ccp with tissue - derived conditioned medium is carried out using the following protocol : protocol 1 : culturing of ccp in the presence of conditioned medium derived from a blood vessel culture . spin ccp cells for 15 minutes at 500 g , 21 c . discard the supernatant . gently mix cell pellet and re - suspend cells to 5 - 50 million / ml in autologous medium containing 1 - 20 % autologous serum and / or 1 - 20 % conditioned medium . seed flasks with 2 - 5 million ccp cells / ml . incubate flasks at 37 c , 5 % co2 . after first three days of culture , non - adherent cells can be removed from the culture . in accordance with an embodiment of the present invention , refreshing of the media in ongoing growing ccp cultures is carried out using the following protocol : refreshing of the media in ongoing growing flasks should occur every 3 - 4 days . fill every flask with 10 ml fresh culture medium enriched with conditioned medium . spin tubes for 10 minutes at 450 g , rt ; discard the supernatant . gently mix cell pellet and re - suspend cells in 10 ml / flask fresh culture medium enriched with condition medium . in accordance with an embodiment of the present invention , indirect co - culture of ccp cells with tissue dissection is carried out using the following protocol : protocol 1 : indirect co - culture of dissected blood vessel and ccp cells in a semi - permeable membrane apparatus . lay dissected tissue pieces in the upper chamber of the apparatus on top of the semi - permeable membrane . lower chamber can be pre - coated with growth - enhancing molecules such as collagen , plasma , fibronectin , a growth factor , tissue - derived extra cellular matrix and an antibody . refresh culture medium in the upper chamber — aspirate conditioned medium into 50 ml tubes and add autologous culture medium . refresh culture medium of the ccp cells with culture medium containing 1 - 20 % autologous serum and / or 1 - 20 % conditioned medium . in accordance with an embodiment of the present invention , co - culturing within a culture container is carried out using the following protocol : protocol 1 : direct co - culturing of autologous dissected blood vessel and ccp cells . using forceps , take out tissue pieces after four days of co - culture . refresh culture medium of the ccp cells with culture medium containing 1 - 20 % autologous serum and / or 1 - 20 % condition medium . in accordance with an embodiment of the present invention , harvesting of the cellular product is carried out using the following protocol : carefully wash flask surface by pipetting with cold pbs to detach adherent cells . optionally , add 5 ml edta to each flask and incubate at 37 c for 5 min . collect the detached cells and add them to the tubes spin tubes for 5 min , at 450 g , room temperature . in accordance with an embodiment of the present invention , cellular product preservation is carried out using the following protocols : cellular product can be kept in preservation media or frozen in freezing buffer until use for transplantation into a patient . prepare freezing buffer containing 90 % human autologous serum and 10 % dmso . prepare preservation medium including growth medium containing 1 - 20 % autologous serum , with few or no other additives . maintain preservation medium with cellular product at 2 - 12 c in accordance with an embodiment of the present invention , conditioned medium collection and preservation is carried out using the following protocol : conditioned medium can be kept until use for growth medium preparation . conditioned medium should be collected under sterile conditions . spin collected conditioned medium for 10 min at 450 g , 21 c . collect supernatant in a new sterile container . filter supernatant through a 22 um membrane . aliquot conditioned medium to 10 and / or 50 ml sterile tubes , pre - marked with donor details . in accordance with an embodiment of the present invention , facs staining is carried out using the following protocol : in accordance with an embodiment of the present invention , immunohistochemistry staining ( ihc ) is carried out using the following protocols : in accordance with an embodiment of the present invention , a tube formation assay is carried out using the following protocol : tube formation was tested using the ecm625 ( chemicon ) in vitro angiogenesis assay kit . angiogenic pattern and vascular tube formation was numerically scored as described by kayisli u . a . et al . 2005 ( 52 ). in accordance with an embodiment of the present invention , secretion of cytokines from harvested cells is assessed using the following protocols : culture 0 . 5 - 1 × 10 ̂ 6 cells / ml over night in 24 well plates in serum - free medium ( e . g ., x - vivo 15 ) collect culture supernatant and spin at 1400 rpm for 5 minutes transfer supernatant to an eppendorf tube and freeze at − 80 c until ready to test cytokine secretion . a commercial duoset cxcr8 / il - 8 ( r & amp ; d systems ) was used for the detection of il - 8 secretion . a commercial cytometric bead array ( cba ) kit for human angiogenesis ( bd 558014 ) was used for the detection of il - 8 , vegf , tnf and angiogenin secretion . it is to be noted that the scope of the present invention includes injecting il - 8 into a human patient in order to recruit acp cells to a given destination within a given patient , in accordance with the needs of the patient . for some applications , techniques described herein are practiced in combination with techniques described in one or more of the references cited in the background section and cross - references section of the present patent application . all references cited herein , including patents , patent applications , and articles , are incorporated herein by reference . it is to be appreciated that by way of illustration and not limitation , techniques are described herein with respect to cells derived from an animal source . the scope of the present invention includes performing the techniques described herein using a ccp derived from non - animal cells ( e . g ., plant cells ), mutatis mutandis . it will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove . rather , the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove , as well as variations and modifications thereof that are not in the prior art , which would occur to persons skilled in the art upon reading the foregoing description .

a composition of matter is provided , comprising a population of cultured cells that comprises a sub - population of cells that both stain as cd31bright and demonstrate uptake of ac - ldl +, and secrete il - 8 . a method is also provided , comprising stimulating in vitro an initiating cell population of at least 5 million cells that have a density of less than 1 . 072 g / ml , wherein at least 1 % of the cells of the icp is cd34 + cd45 −/ dim , and at least 25 % of the cells of the icp are cd31bright , to differentiate into a progenitor / precursor cell population . other embodiments are also described .

the following definitions are provided to aid in construing the claims of the present application : message card : a playing card that either contains a message to be communicated to a player of the card game or a playing card that is blank and on which a player can write a message to be communicated to a player of the card game . progress card : a playing card that is not a message card and that is used in playing the card game . referring to fig1 , a first preferred embodiment of a card game in accordance with the present invention is illustrated . a board 110 , includes five deck locations , 120 , 122 , 124 , 126 , 128 , and 128 , on which message cards are initially placed . board 110 also includes deck locations 130 and 132 where progress cards are initially placed . in the first embodiment , the board further includes ten stars representing the ten commandments , as well as the commercial name of the card game . in other embodiments of the present invention , a different number of deck locations ( or even none at all ) can be used , and additional or different board features can be used . in some embodiments of the present invention , no board is used . message cards 140 a though 140 n include between fifty - two ( 52 ) and eighty ( 80 ) message cards separated into five decks in the first preferred embodiment ; however , in other embodiments of the present invention , any number of message cards can be utilized and any number of decks ( even only one ) can be used . each of the five decks has a different category of card in the first preferred embodiment , one deck relating to “ i need ”, one to “ i promise ”, one to “ i feel ”, one to “ thank you ”, and one to “ forgive me ”. however , in other embodiments of the present invention , different categories can be utilized , or the cards need not be broken down by category . the individual message cards can relate to children &# 39 ; s issues , family issues , religious issues , sexual issues , political issues , or any other type of issues that are relevant . in some embodiments of the present invention , the message cards can be of mixed types so that the cards are relevant to different types of players . in other embodiments , the message cards can be uniform in nature so that the game is appropriate for a particular audience , such as children . in the first preferred embodiment , blank cards are also included so that players can write their own messages . examples of child oriented messages include “ i promise i will take you to the park more often ”, “ i feel that i am old enough to play outside by myself ”, “ thank you for taking me to the zoo and playground ”, “ i need you to help me write my toy list to santa this year ”, and “ forgive me for listening to you when you are on your phone i will stop that i know that you need your privacy ”. a few further examples are included in a list attached hereto as appendix a . in other embodiments , other messages can be used covering virtually any subject of importance to the players of the game . progress cards 150 a through 150 n are also illustrated in fig1 , as is finish envelope 160 . in the first preferred embodiment , progress cards 150 a through 150 n include both start cards and finish cards ; however , in other embodiments of the present invention , separate start and finish cards are not used , and in some embodiments of the present invention no progress cards are used . a finish envelope is also not used in all embodiments of the present invention . out envelope 170 is used to hold discarded cards in the first preferred embodiment . while this envelope is not utilized in all embodiments of the present invention , it , or a functional equivalent does play a useful role of providing a degree of confidentiality in certain circumstances ; hence it provides a useful function , as described below . in a first preferred embodiment of the present invention , the card game is played as followed . each category of message cards is shuffled and placed on its corresponding deck location . the finish cards are shuffled and one is placed in the finish envelope . the start cards are shuffled and placed on their deck location . each of the one or more players playing the game then , in turn , receives his or her message cards as follows . the first player receives six cards from the first deck of message cards , selects two of these message cards and replaces the remaining four message cards . the player chooses these message cards based on the messages that he or she would like to communicate to the other player or players ( or to himself or herself if playing alone ). play then continues to the other players until all players have two cards from the first deck . the same procedure is then followed with respect to the other four decks , so that each player is left with ten cards , two from each deck . each player can then exchange any four message cards for any combination of four new message cards ( picked from any deck ) or blank cards with messages written in by the player . the players then in turn give message cards to other players . on the first turn , a player can give two message cards to any one or more players . on the second turn , a player can give three message cards to any one or more players . on the third turn , a player can give any number of message cards to any one or more players . each card that is played is shown only to the player to whom it is given and then is placed in the out envelope . the only exception is that if a message card is labeled as a whisper card , the player whispers its contents to the player to whom it is given and then the whisper card is replaced in the deck from which it was taken . when a player has no cards left , he or she may draw one start card and compare it to the finish card in the finish envelope . if the two cards match , that player is the winner ; otherwise , play passes to the next player and the players continue to take turns until one player ( who has distributed all of his or her message cards ) has a match . if a player decides not to finish a game before distributing all of his or her message cards , the remaining message cards are placed in the out envelope without being shown to anyone . it is not intended that anyone should inspect the contents of the out envelope at any time prior to shuffling such cards back into the respective decks of message cards . in other embodiments of the present invention , different rules can be used . for example , players can have a greater or lesser degree of choice over the message cards that they receive , progress cards need not be utilized , different numbers of cards can be played each turn , or the game can be played without turns ( such as in real time ), and the game can involve additional elements . in all embodiments , however , message cards are utilized . the present invention may be embodied in other specific forms without departing from the spirit or essential attributes of the invention . accordingly , reference should be made to the appended claims , rather than the foregoing specification , as indicating the scope of the invention .

a game , including a plurality of message cards . in another aspect , a method of playing a card game , including providing a plurality of message cards to each player and each player in his or her turn providing one or more message cards from his or her hand to one or more other players .

although the disclosure hereof is detailed and exact to enable those skilled in the art to practice the invention , the physical embodiments herein disclosed merely exemplify the invention , which may be embodied in other specific structure . while the preferred embodiment has been described , the details may be changed without departing from the invention , which is defined by the claims . referring to fig1 , the preferred embodiment 10 of the present invention is depicted . the present invention comprises a substantially tubular structure 12 having at least one internal pocket 14 and at least one internal resilient object 20 . as disclosed in the view of fig1 , a preferred embodiment utilizes three objects or orbs 20 a , 20 b and 20 c , located in the left end pocket 14 a , the right end pocket 14 b and the centrally located pocket 14 c , respectively . the opening or openings 22 are of a size permitting access of an orb 20 a , 20 b , 20 c to a respective internal pocket 14 a , 14 b and 14 c . the openings 22 may further include resealable fasteners 24 for retaining the resilient object 20 within a respective pocket 14 during use . the tubular structure 12 may be constructed from any suitable web - like material 26 including , but not limited to , cloth , silk , canvas or mesh . the web - like material 26 is preferably strong but soft , flexible , absorbent and able to provide some amount of friction to aid in grip . the material 26 will preferably be an absorbent material , such as “ terry cloth ” commonly used in the manufacture of toweling and capable of being washed and dried by machine . the apparatus 10 may be made from a single web 26 folded lengthwise to provide an enclosing crease 13 substantially coextensive with the length of the structure 12 . the fold is preferably sewn shut at spaced intervals 17 along the side 19 opposite the crease 13 . the end portions 30 of the tubular structure 12 are closed to provide at least one internal pocket 14 formed within the structure 12 . the pockets 14 are each formed by conventional sewing thread stitching 32 , or by adhesive or heat fusion techniques to join the facing internal surfaces of the folded web 26 surfaces at longitudinally spaced intervals , and lying transversely relative to the lengthwise crease 13 to defined pocket dividers 32 . various embodiments of the present invention may contain different numbers and arrangements of the internal pockets 14 . the preferred embodiment 10 includes three internal pockets 14 , including two end pockets 14 a , 14 b and a centrally located pocket 14 c . contained within at least one of said internal pockets 14 a , 14 b , 14 c is at least one resilient object or orb 20 . the object 20 may serve multiple purposes , such as providing a means of gripping the device and providing a substantially rigid shape that is conducive to massage and accupressure therapy . a preferred object or orb 20 is the primary purpose of the centrally located object 20 c is to provide a fairly rigid , but flexible localized area to aid in the transfer of pressure to a pressure point region . a secondary function of the centrally located object 20 c is to provide a gripping area for use when manipulating the invention 10 . although these resilient objects 20 have preferred functions , based on location , each is capable of performing other functions , as well . because the preferred function of any given resilient object 20 may change with its location along the length of the tubular structure 12 , different objects 20 may be chosen for having different properties . properties that may affect the choice may be size , shape , hardness , resilience or flexibility . for example , in the preferred embodiment 10 , the end objects 20 a and 20 b may be fairly large , but somewhat soft , capable of contouring to a user &# 39 ; s hand quickly during a given exercise . the central object 20 c may be a smaller , harder , spherical object that transfers pressure more effectively . it should be noted that no two objects 20 are required to be substantially alike . the objects 20 may also be custom selected for the individual user . additionally , individual pockets 14 may or may not contain an object 20 . individual pockets 14 may also contain multiple objects . the invention preferably utilizes at least one pocket opening 22 . each opening 22 provides reclosable access to an - internal pocket 14 , and may be located anywhere on the device 10 . the openings 22 allow the resilient objects 20 to be removed and exchanged , permitting the device 10 to more easily serve multiple functions . the objects 20 may also be removed while the device 10 is being washed . each opening 22 preferably includes a resealable fastener 24 to secure an object , or objects 20 within a respective pocket 14 a , 14 b , 14 c during use . the resealable fasteners 24 may be of any appropriate type , such as zippers , buttons or snaps . the fasteners 24 will preferably be fairly soft , flexible , and allow an internal connection . the preferred embodiment 10 uses a hook and loop style fastener 24 of the variety commonly known as “ velcro ”®. referring to fig4 , the device is shown used for a muscle stretching exercising usage . the length of the structure 12 is essential to achieving the proper stretching and motion techniques . therefore , various users require a structure 12 of various lengths . as illustrated in fig3 , the device 10 , including an object 20 c , provides a useful , and comfortable , acupressure apparatus . as will be observed , a person being treated for headaches or stiff neck , or difficulty turning the head , merely grips the end portions 30 , containing orbs 20 a and 20 b , and longitudinally stretches the material of the web structure 12 to tighten the area of the orb 20 c and press the orb 20 c against a selected acupressure treating area 35 a or 35 b , known respectively as “ anmian points ”, in the case of treatment for emotional stress which may cause restlessness , tight muscles of the neck , and headaches , or at a centrally located neck muscular area ( not specifically shown ), commonly known as the “ ashi point .” acupressure and massage of a respective anmian or ashi point has been found to reduce tense muscles and also helps to soothe stressful emotions . another use for the device is rotational exercise techniques . such techniques are used to strengthen , stabilize and challenge pre - selected muscle groups that are used in various activities . rotational exercise techniques also increase joint health , muscle flexibility and agility , as well as eye hand coordination . one or more gripping portions of the device are grasped by the user and moved in a predetermined pattern . fig5 demonstrates one of many possible exercise techniques using the device 10 . the demonstrated exercise is one of several warm - up exercises incorporated into an exercise routine , with the warm - up exercises lasting about 10 - 15 minutes . these exercises will warm up the core muscles of the user 100 , as well as increase the range of motion of the user 100 . the user 100 grasps the device 10 at or near one of the end portions 30 and begins to move the device 10 back and forth across the body in a “ figure 8 ” pattern , which will help in warming up the muscles of the user 100 . other warm - up movements may be incorporated as well . the user 100 may also decide to switch the device from one hand 102 a or 104 a to the other 104 a or 102 a , and may also decide to incorporate movement of the legs 106 , 108 into the exercises . for instance , the user 100 may decide to pass the device 10 from one hand 102 a to the other 104 a underneath one of the user &# 39 ; s legs , while lifting that leg 106 . the user 100 can incorporate sideways movement of the legs 106 , 108 into this movement . other movements include moving the device 10 around the body while passing it from one hand to the other . sports style movements , such as practicing a batter &# 39 ; s or golfer &# 39 ; s swing , can be incorporated into the warm - up . any of these movements , and other movements , can be used together in various fashions to provide a warm - up routine . because of the design of the device 10 and the placement of the objects 20 a and 20 b within the pouches 14 a and 14 b , respectively , the device 10 and the exercises provide enough resistance for the user 100 to have an efficient warm - up routine . fig6 depicts further exercises for use with the present invention . the user 100 grabs device 10 on or near one of the objects 20 a or 20 b with one hand 102 a and used the other hand 104 a to grab the device 10 on or near the other object 20 a or 20 b . one of the arms is extended outwards in an archer &# 39 ; s type of pose , which allows the arm muscles to be properly stretched . the arms can be switched to stretch the other arm , as well . along with stretching , the opposing , pulling movement of the arms will assist in strengthening the arms 102 , 104 . the shape and design of the device 10 provides proper length and resistance so that the muscles can be adequately stretched . likewise , the design of the device 10 allows for the length of the device to be changed to accommodate shorter or taller users . the device 10 can be used for various stretching routines , by grasping one end of the device in one hand and securing and positioning the other end of the device 10 near or with one of the user &# 39 ; s other appendages , i . e . the user &# 39 ; s other hand or feet . the user 100 will pull the device 10 taut , as necessary , to perform various stretching exercises . the depicted stretching exercise of fig6 is one of several stretching exercises incorporating the device 10 . as an example of another exercise , one of the end portions 30 can be placed under the user &# 39 ; s foot 106 a , while the other end portion 30 will be gripped by the user 100 to stretch the side muscles . either hand can grip the end portion , in the front or the back of the user 100 , to further stretch and twist various muscles , such as the spine muscles . in another example , the device 10 can be gripped with both hands 102 a , 104 a behind the back to stretch chest and back muscles . other standing and kneeling positions can incorporate use of the device 10 . examples of other stretching drills or exercises were previously shown in fig3 and 4 , which can also incorporate using the “ anmian points ” to further provide an overall stretching regime . these stretching exercises can be incorporated into a routine along with the warm - ups demonstrated according to fig5 . fig7 depicts further uses of the device 10 that help in strengthening the user &# 39 ; s muscles . the user 100 holds the device 10 on a surface and forms a push - up type position . the position specifically shown is sometimes referred to as a “ kung fu ” push - up . the user 100 balances on the objects 20 , which allows the user 100 to perform a push - up that requires more balance than a normal push - up , thereby strengthening the user &# 39 ; s muscles . also , the ability to be able to grasp the objects 20 incorporated in the device 10 , as shown , assists the user in keeping the proper spacing when doing the push - ups and other exercises . the objects 20 are preferably ergonomically designed to fit within the user &# 39 ; s hands . the user 100 can incorporate other movements , such as leg lifts , into this exercise , to provide a work - out for the entire body . similarly , the user 100 could perform the push - ups with the knees on the ground , if more comfortable for the user . other similar exercises include using the device 10 and the objects 20 b to lift one &# 39 ; s self in the sitting position , with the user &# 39 ; s legs either crossed out extended outward . this will assist in strengthening the stomach and related core muscles . alternatively , the device 10 can be placed behind the neck ( see fig3 ), and sit - ups or crunches can be performed . the sit - ups can incorporate movements , such as rowing movements used with a kayak , or martial art style thrusts , all the while holding the ends portions 30 of the device to provide resistance while performing the basic exercise movements . these strengthening exercises address the muscles of the body together and not in an isolated manner , which strengthens the muscles and the body in an efficient manner . fig8 provides a further exercise that not only strengthens muscles , but treats the core muscles , as well . there are many core muscles , including the abdominal muscles , gluteus muscles , as well as back and abductor muscles . the user 100 stretches the device 10 behind his head , holding the device at the objects 14 a and 14 b with a hand 102 a and 104 a connected to each of his arms 102 and 104 . the user 100 rests on his side , while crossing his legs 106 and 108 and feet 106 a and 108 a . the user 100 keeps one hand 102 a and one foot 106 a on the floor , while lifting the user &# 39 ; s body and leg 108 off of the ground . this will strengthen the core muscles of the user 100 . other exercises that treat the core muscles include sit - ups and stretches , previously discussed . the device 10 is designed to keep a proper distance between the hands 102 a and 104 a when doing the various exercises , which helps in more efficient exercises and , also , less stress on the neck and other parts of the body . likewise , any of the other described movements , such as the martial arts moves , can be incorporated into these exercises for treating the core muscles . the device 10 and the described exercises provide an easy and efficient workout process that can be tailored to a specific user &# 39 ; s needs and abilities , such as using heavier objects 20 for more strenuous activities . fig9 provides an exercise that will also strengthen the body and treat the core muscles for the user 100 . the user 100 is sitting or lying on a surface in a basic sit - up position . as done with several of the exercises , the user 100 grabs the device 10 at each end portion 30 with each of the user &# 39 ; s hands 102 a and 104 a . the user 100 raises his legs 106 and 108 in the air and can perform sit - ups while moving the legs 106 and 108 inwardly and outwardly from the body or , alternatively , holding the leg 106 in the position of fig9 while performing sit - ups . the device 10 can also be used to improve the coordination of the user 100 . the design and weight of the device 10 allows the user 100 to improve hand - eye coordination . for example , the exercise in fig5 could incorporate a movement , wherein the user 100 twists the device 10 with one hand 102 a and catches the device with the other hand 104 a , similar to movements that a martial artist would do when using nunchucks . other movements , such as rotating the device 10 and stopping the device 10 with a foot 106 a or 108 a , would mimic the movements of a soccer player dribbling a ball . these and many other movements will assist the user 100 to gain improved coordination . it should be noted that the device 10 and method of the present invention incorporates exercises that treat and train the entire body . for example , fig3 - 9 demonstrate various exercises that help the user 100 warm - up , stretch , strengthen the user &# 39 ; s muscles , as well as treating the core muscles and providing a system for improving coordination . the various exercises are designed to address more than one of these areas of note . for example , the warm - up exercises discussed specifically with respect to fig5 , will also address the coordination issues addressed more specifically with respect to fig9 . likewise , the strengthening exercises discussed with respect to fig7 will also address the core muscle groups related to fig8 . the present invention provides a device 10 that will easily adapt from one exercise to the next to address all of these concerns quickly and efficiently . the foregoing is considered as illustrative only of the principles of the invention . furthermore , 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 . while the preferred embodiment has been described , the details may be changed without departing from the invention , which is defined by the claims .

a flexible fitness and rehabilitation exercising and massaging apparatus formed from tubular , flexible , web - like material and having a plurality of internal pockets , along with an exercise regimen that includes the apparatus . the pockets may hold objects such as resilient balls that aid in gripping the apparatus , and which have also been found to be conducive to self - massage therapy . the objects may be removed , and alternative objects inserted , through openings that allow access to preselected pockets . the openings may include resealable fastener means .

with reference to fig1 blood sample tube holder 10 includes a plurality of apertures 12a and 12b in the first end 13 for accommodation of blood sample tubes 14a and 14b . a venipuncture needle 16 , having a first end 17 for insertion into the patient from whom blood is to be withdrawn and a second end 18 which discharges blood into the blood sample tube holder 10 , is affixed to the second end 19 of sample tube holder 10 . a movable venipuncture needle sheath 20 aligns over the blood sample tube holder 10 and is shown in the retracted position around blood sample tube holder 10 in fig2 . multiple evacuated blood sample tubes 14a - 14b are shown in alignment with the multiple corresponding apertures 12a and 12b in the blood sample tube holder 10 . when the device is to be used , the blood sample tubes 14a - 14b will be partially inserted into the apertures 12a - 12b as shown in fig2 . the movable sheath 20 is positioned manually over and about the blood sample tube holder 10 . the blood sample tube holder 10 is held by grasping the moveable sheath 20 , which is somewhat flexible , and the underlying blood sample tube holder 10 and flange while inserting venipuncture needle 16 into the patient . when the needle 16 is properly positioned , the technician applies pressure to the sample tube loader 24 and forces the blood sample tubes 14a and 14b into the blood sample tube holder 10 , as shown in fig2 where the elastomeric stoppers 15a and 15b are punctured by the first end 34a of sample tube filling needles 34 ( shown in fig3 ). the blood then flows smoothly from the second end 18 of venipuncture needle 16 , through the distribution manifold 30 into second end 34b of blood sample tube filling needle 34 , through blood sample tube filling needles 34 and out first end 34a of filling needles 34 into the evacuated blood sample tubes 14 . when the blood sample tubes 14 have filled to the desired point , the technician grasps the sample tube loader 24 and partially withdraws the blood sample tubes 14 , thereby removing the blood sample filling needles 34 from stoppers 15 and stopping the flow of blood , as will be further described . in the rare situation were more blood samples are required than the number of sample tubes 14 which can be accommodated by the holder 10 , the technician will grasp the sample tube loader 24 , fully withdraw the sample tubes 14 from the blood sample tube holder 10 , and reload the sample tube holder 10 with a second sample tube loader 24 and blood sample tubes 14 , forcing the sample tubes 14 fully into the blood sample tube holder 10 to reinitiate the flow of blood into the second set of sample tubes 14 . alternatively , if no additional blood samples are required , the technician grasps the sample tube loader 24 and partially withdraws it from sample tube holder 10 to stop the flow of blood . the venipuncture needle 16 is then withdrawn from the patient and the movable needle sheath 20 is moved outwardly , as shown in fig6 to the protected position where it is protected from inadvertent contact by the patient , technician or others who may handle the blood sample tube holder 10 . other significant aspects of the invention will now be described , beginning with fig3 which is a partial sectional view of the device with the blood sample tubes 14 in the partially loaded position . the venipuncture needle 16 is retained by venipuncture needle collet 21 which screws into a threaded hole 22 in the manifold assembly 23 . one arrangement of needle 16 , collet 21 and manifold assembly is shown in fig4 . the primary manifold assembly 23 is made up of a molded outer housing 23a and complementary molded insert 23b . the molded outer housing 23a is joined to the molded insert 23b by any suitable means such as ultrasonic bonding , adhesive or a solvent weld . the outer housing 23a and insert 23b are designed to create a central chamber portion 29 of the blood distribution manifold 30 in the region where the second end 18 of venipuncture needle 16 disgorges the withdrawn blood . the dimensions and geometry of the central chamber portion 29 are selected to provide a laminar flow of the blood emerging from the second end 18 of needle 16 . the central chamber portion 29 is symmetrically positioned about the second end 18 of venipuncture needle 16 . chamber 29 has a round interior wall . for needles of 0 . 5 to 2 . 0 mm diameter , chamber 29 has an internal diameter of 2 . 0 mm to 4 . 0 mm in the region adjacent to second end 18 of needle 16 to provide laminar flow of the blood emerging from end 18 of needle 10 . this minimizes the damage to red blood cells . to further minimize the mechanical damage to the red blood cells and to evenly divide the flow of blood into the individual blood sample tubes , chamber 29 includes a blood flow divider 32 positioned directly opposite , and spaced from , the open second end 18 of needle 16 . the tip 32a of blood flow divider 32 has a spherical shape of not less than 0 . 5 mm diameter . the size and shape of tip 32a are selected to reduce the damage to red blood cells due to impact on the tip and to maintain laminar flow of blood in the blood distribution manifold 30 . an alternate manifold assembly is shown in fig5 . in this embodiment , the venipuncture needle 16 is molded in the outer housing 41a and becomes an integral part thereof . the complementary molded insert 41b has the same conforming shape as the insert 41b and performs the same function . outer housing 41a and complementary insert 41a are fastened to each other in the same fashion as previously described with reference to fig4 . central chamber portion 29 of manifold 30 branches symmetrically into a plurality of curved individual passageways 33 leading downwardly to the sample tube filling needles 34 which have first ends 34a for piercing the elastomeric sample tube stopper 14 and second ends 34b centrally positioned within the respective lower regions 35 of passageways 33 . referring again to fig3 the manifold assembly 23 is joined to the blood sample tube holder 10 by suitable means such as ultrasonic bonding , adhesive or a solvent weld . sample tube holder 10 includes a plurality of apertures 12 , symmetrically arranged about the axis of tube 10 , having an interior dimension and shape such that blood sample tubes 14 slide easily into the apertures . the partially inserted position of sample tubes 14 , as shown in fig3 is just prior to the piercing of blood sample tube stopper 15 by sample tube filling needles 34 . each of the first ends 34a of sample tube filling needles 34 is covered with an elastomeric nipple 36 , secured to the lower face 25 of manifold assembly 23 which serves to prevent the flow of blood from needles 34 until pierced . further movement of the sample tubes 14 into sample tube holder 10 causes the end 34a of sample tube filling needle 34 to pierce elastomeric nipples 36 and then to pierce blood sample tube stoppers 15 . when the blood sample tubes 14 are fully inserted into sample tube holder 10 , the end 34a of sample tube filling needle 34 is centrally positioned within the laminar flow extender portion 27 of the elastomeric blood sample tube stoppers 15 . laminar flow extender 27 is a centrally positioned tubular projection on the lower face of stopper 15 . the projection extends approximately 5 . 0 - 15 . 0 mm beyond the end 34a of needle 34 and has a nominal interior diameter approximately 3 . 0 - 5 . 0 mm for use with sample tube filling needles of 1 . 3 mm diameter . the dimensions of laminar flow extender 27 are selected to preserve the laminar flow of blood into sample tubes 14 , thereby avoiding mechanical hemolysis which would otherwise result from the impact of blood against the walls of sample tube 14 . a flange portion 11 , at the bottom of blood sample tube holder 10 , assists the technician in manipulating the device as well as providing a stop which prevents the movable needle sheath 20 from sliding off the device . blood sample tube holder 10 further includes an axially located stop portion 40 which engages a correspond stop portion 51 on blood sample tube loader 24 and serves to limit the distance to which the blood sample tubes 14 may be inserted into apertures 12 . this prevents overcompression of the elastomeric nipples 36 which might cause them to fail to properly reseal when the blood sample tubes 14 are withdrawn . the multiple , symmetrically arranged , sample tube cavities 53 in elastomeric or flexible sample tube loader 24 are dimensioned to provide a tight fit on the ends of sample tubes 14 . the sample tube cavities 53 have a sufficient internal surface area to maintain a friction fit with tubes 14 and thereby ensure that the sample tube loader 24 will successfully remove all the tubes 14 from the sample tube holder 10 when the loader 24 is withdrawn . the lower face 54 of sample tube loader 24 provides the technician with a convenient location for the application of force to pierce nipples 36 and sample tube stoppers 15 . application of the loading and withdrawal force to sample tube loader 24 , instead of directly to sample tubes 14 , solves numerous problems . first , is ensures that all sample tubes 14 will be filled simultaneously , avoiding the situation where some tubes would only be partially filled . second , it allows the technician to avoid direct contact with sample tubes 14 and prevents injury and possible infection should the sample tubes 14 inadvertently fracture . the loader 24 also accommodates the placement of the stop 51 which prevents inadvertent over compression of the nipples 36 by the technician . finally , it allows the use of smaller blood sample tubes than are now in common use . it has long been recognized that the existing , conventional , blood sample tubes having a nominal 13 mm diameter and 75 mm length to provide a blood sample of approximately 4 . 5 cc , are literally hundreds of times larger than need be to collect sufficient blood for analytical purposes . however , because smaller tubes , including the smaller , less common , tube having a nominal 10 mm diameter and 60 mm length , are difficult for the technician to manipulate while withdrawing blood , the use of the now oversized blood sample tubes has continued . the use of the blood sample tube loader 24 allows the technician to conveniently manipulate a much smaller blood sample tube with the attendant advantages previously discussed . the device of this invention can easily accommodate blood sample tubes in the range from 4 mm to 13 mm in diameter and 66 mm to 75 mm in length . preferable , the blood sample tubes for use with this invention have a nominal diameter of 6 mm and a nominal length of 75 mm , which accommodates a blood sample of 2 cc . fig4 is an exploded side view in partial cross section of a venipuncture needle 16 incorporated into the manifold assembly 23 including the molded outer housing 23a , the manifold insert 23b and their associated components where all numerals correspond to those elements previously described . illustrated in particular is one of the passageway half members 33 &# 39 ; of passageway 33 illustrated on one side of the conical shaped manifold insert 23b and a passageway half member 33 &# 34 ; illustrated on one of the inside conical surfaces 26 of the molded outer housing 23a . the appropriate corresponding passage halfway members 33 &# 39 ; and 33 &# 34 ; align together to form passageways 33 as illustrated in fig3 . fig5 an alternate embodiment , is an exploded view in partial cross section of a venipuncture needle 16 molded or otherwise permanently secured into the distal end of a manifold assembly 41 including a molded outer housing 41a , the manifold insert 41b and their associated components where all numerals correspond to those elements previously described . the passageways 33 are formed as described in fig4 . fig6 shows the details in cross section of the movable venipuncture needle sheath 20 which is designed to be used when the needle 16 is withdrawn from the patient . the interior cylindrical surface of sheath 20 has a diameter which provides an interference fit over the exterior surface of the sample tube holder 10 . a plurality of latch projections 60 bear against the exterior of the sample tube holder 10 and provide the desired interference fit . when the sheath 20 is moved outwardly to the protected position the projections 60 snap into the annular groove 61 ( fig3 ) in sample tube holder 10 to hold the sheath 20 in the extended , protective position . since the annular groove 61 extends completely around the sample tube holder 10 , the needle sheath 20 will lock in the protective position regardless of its rotational position relative to sample tube holder 10 . fig7 is a top view of the two - tube sample tube holder along view line 7 -- 7 of fig6 showing the two apertures 12 for sample tubes and the air passage 70 which allows air to escape when the sample tubes 14 are forced into the sample tube holder 10 where all numerals correspond to those elements previously described . the air passages 70 aligns in the top of the sample tube holder 10 . fig8 is a bottom view of a sample tube holder having a flange 44 and six like apertures 12 designed to accommodate 6 sample tubes 14 . any number of apertures can be used to accommodate a like number of corresponding aligned sample tubes . fig9 is a bottom view of a sample tube holder 45 having a flange 46 which is designed to accommodate triangular shaped sample tubes and having a plurality of triangular shaped apertures 47 . it can be seen that the holder diameter can be reduced by using sample tubes of non - cylindrical cross section . fig1 is an exploded cross section view of the round sample tube 14 for use with this invention showing the sample tube stopper 15 with the laminar flow extender 27 . fig1 is an exploded view of an alternative blood sample tube 48 , having for purpose of example and illustration , an equilateral triangular shaped cross section of 1 . 4 mm on a side and a nominal length of 40 mm to provide a capacity of 1 . 96 cc . a triangular shaped elastomeric stopper 49 includes a laminar flow extender 50 . fig1 is a top view of the triangular stopper 49 for use with the triangular shaped blood sample tube 48 of fig1 . the multiple tube perfusion sampler of this invention is readied for use by grasping the blood sample tube loader 24 and partially inserting a plurality of blood sample tubes 14 into the apertures 12 . the phlebotomist then inserts the first end 17 of the venipuncture needle 16 into the vein of the patient . when suitable placement of the needle 16 in the vein has been achieved , sufficient manual pressure is applied to the base 54 of the sample tube loader 24 to force the sample tube filling needles 34 through the elastomeric nipples 36 and sample tube stoppers 15 until the sample tube loader stop portion 51 comes to bear against the corresponding stop portion 40 on sample tube holder 10 . the desired manual pressure is easily achieved without disturbing the placement needle 16 within the vein since flange 11 provides a secure grip on holder 10 and the phlebotomist need not worry about damaging the nipples 36 with over pressure . when the sample tube filling needles emerge from the inner surface of blood sample tube stoppers 15 , the pressure differential between the vein and the evacuated blood sample tube 14 causes venous blood to flow from the pierced vein through the interior of venipuncture needle 16 to the central chamber 29 of blood distribution manifold 30 where the flow is smoothly divided into the individual passageways 33 leading to the blood sample tube filling needles 34 and the laminar flow extender portion 27 of blood sample tube stoppers 15 . the bernoulli flow energy leveling provided by the laminar flow arrangement of the manifold chamber 30 and laminar flow extender portion 27 of blood sample tube stoppers 15 inhibits mechanical hemolysis which would damage the blood sample . the blood sample tubes 14 fill at the same rate since any differential in pressure due to unequal flow causes a corrective , equalizing flow to the blood sample tubes . when the blood sample tubes 14 have filled to the desired level , the blood sample tube loader 24 is withdrawn from the sample tube holder 10 a distance sufficient to retract the sample tube filling needles 34 from the stoppers 15 and restore them to the position within nipples 36 , thereby effectively resealing the device and stopping the flow of blood . the needle 16 is then withdrawn from the vein of the patient and the protective sheath 20 is slid into the extended and locked position . depending on the desired procedure , the plurality of filled sample tubes 14 may be withdrawn with the loader and sent to the laboratory or , alternatively , the entire device may be sent to the laboratory for blood analysis and subsequent disposal . various modifications can be made to the present invention without departing from the apparent scope hereof .

an apparatus for withdrawing blood from a vein and simultaneously filling multiple collection tubes . the apparatus includes a movable sheath which protects the technician from inadvertently contacting the withdrawn needle after use and a laminar flow transition chamber between the blood withdrawal needle and the multiple collection tubes .

the invention is an improvement to prior art . fig1 shows a perspective view of prior art , an enclosed rectangular shaped ladder 20 traversed horizontally by a human . the elements of said ladder consist of two elongated rigid , rectangular rails 21 each rail of equal dimensions . the rails are joined by rungs 22 of equal length , perpendicularly affixed to the interior side of each rail serving to hold the rails in a fixed parallel relationship to each other . each affixed rung is of a height substantially the same . the rails are also held in place by two rectangular , rigid end boards 23 equal in height to the rails . a preferred embodiment of the invention comprises straight 30 , arced 40 , and curved 50 tracks , each track comprising two rails joined together by readily detachable steps with a geometrically shaped colored footing 70 and a means 60 to connect to other tracks . said preferred embodiment is described below and claimed in independent claim 1 . for purposes of the specification and claims , an arc is defmed as a segment of a circle , and a curve is defined as a line deviating from straightness . fig2 a shows a topside view of a straight track 30 . said straight track comprises two rigid , rectangular rails each rail 31 of substantially equal dimensions joined together by readily detachable steps 70 . each rail 31 comprises step insertion elements 63 located in whole or part at the interior side 32 of a rail into which a step 70 is inserted . an element 63 may accommodate the insertion of a step 70 into or through the interior side of the rail 32 , the top side of the rail 33 , or the exterior side of the rail 34 . the drawing depicts a straight track 30 comprising two rigid , rectangular rails 31 joined together by readily detachable rungs 71 , a type of step 70 . each rail 31 comprises square shaped rung insertion elements 64 into which a rungs 71 with squared closures 75 are inserted . the elements 64 bore through each rail 31 from the exterior side 34 to the interior side 32 . the straight track comprises elements 60 used to effect connections to a contiguous track or tracks , straight 30 , arced 40 , or curved 50 , or to a distinct end coupler 90 , thereby bridging the non - contiguous ends of tracks . the drawing depicts two interfitting male connections 61 in the shape of a tenon comprising the ends of each rail located at one end of the straight track and two interfitting female connections 62 in a shape corresponding to a recessed tenon comprising the ends of each rail located at the opposite end of the track . the straight track is free of end boards as an element thereof removing an obstruction associated with prior art 23 . the obstruction hinders entering or dismounting a track or traversing two connected tracks . fig2 b shows a perspective view of a rectangular rail 31 . each rail comprises step insertion elements 63 located in whole or part at the interior side of the rail 32 . an element 63 may accommodate the insertion of a step 70 into or through the interior side of the rail 32 , the top side of the rail 33 , or the exterior side of the rail 34 . the drawing depicts a single row of square shaped rung insertion elements 64 that accommodate rungs 71 with squared closures 75 . said elements 64 bore through the rail from the exterior side 34 to the interior side 32 . the ends of each rectangular rail 36 are comprised of an interfitting male connection 61 in the shape of a tenon and an interfitting female connection 62 in a shape corresponding to a recessed tenon . these elements are used to effect connections with contiguous rails of tracks , straight 30 , arced 40 , or curved 50 , or to a contiguous distinct end coupler 90 , thereby bridging the non - contiguous rails of tracks . the surface of the top side of a rectangular rail 33 may be may be smooth or semi - rough . an anti - slide element 67 is affixed to the bottom side of the rail 35 . fig3 a shows a topside view of an arced track 40 . said arced track comprises two oblong , rigid , arced rails each rail 41 of substantially equal height and width joined together by readily detachable steps 70 . each rail 41 comprises step insertion elements 63 located in whole or part at the interior side 42 of a rail into which a step 70 is inserted . an element 63 may accommodate the insertion of a step 70 into or through the interior side of the rail 42 , the top side of the rail 43 , or the exterior side of the rail 44 . the drawing depicts an arced track 40 comprising two rigid , arced rails 41 joined together by readily detachable rungs 71 , a type of step 70 . each rail 41 comprises square shaped rung insertion elements 64 into which a rungs 71 with squared rung closures 75 are inserted . the elements 64 bore through each rail 41 from the exterior side 44 to the interior side 42 . the arced track comprises elements 60 used to effect connections to a contiguous track or tracks , straight 30 , arced 40 , or curved 50 , or to a distinct end coupler 90 , thereby bridging the non - contiguous ends of tracks . the drawing depicts two interfitting male connections 61 in the shape of a tenon comprising the ends of each rail located at one end of the arced track and two interfitting female connections 62 in a shape corresponding to a recessed tenon comprising the ends of each rail located at the opposite end of the track . the arced track is free of end boards as an element thereof removing an obstruction associated with prior art 23 . the obstruction hinders entering or dismounting a track or traversing two connected tracks . fig3 b shows a perspective view of an arced rail 41 . each rail comprises step insertion elements 63 located in whole or part at the interior side of the rail 42 . an element 63 may accommodate the insertion of a step 70 into or through the interior side of the rail 42 , the top side of the rail 43 , or the exterior side of the rail 44 . the drawing depicts a single row of square shaped rung insertion elements 64 that accommodate rungs 71 with squared closures 75 . said elements 64 bore through the rail from the exterior side 44 to the interior side 42 . the ends of each arced rail 46 are comprised of an interfitting male connection 61 in the shape of a tenon and an interfitting female connection 62 in a shape corresponding to a recessed tenon . these elements are used to effect connections with contiguous rails of tracks , straight 30 , arced 40 , or curved 50 , or to a contiguous distinct end coupler 90 , thereby bridging the non - contiguous rails of tracks . the surface of the top side of an arced rail 43 may be smooth or semi - rough . an anti - slide element 67 is affixed to the bottom side of the arced rail 45 . fig4 a shows a topside view of a curved track 50 . said curved track comprises two oblong , rigid , curved rails each rail 51 of substantially equal height and width joined together by readily detachable steps 70 . each rail 51 comprises step insertion elements 63 located in whole or part at the interior side 52 of a rail into which a step 70 is inserted . an element 63 may accommodate the insertion of a step 70 into or through the interior side of the rail 52 , the top side of the rail 53 , or the exterior side of the rail 54 . the drawing depicts a curved track 50 comprising two rigid , curved rails 51 joined together by readily detachable rungs 71 , a type of step 70 . each rail 51 comprises square shaped rung insertion elements 64 into which a rungs 71 with squared closures 75 are inserted . the elements 64 bore through each rail 51 from the exterior side 54 to the interior side 52 . the curved track comprises elements 60 used to effect connections to a contiguous track or tracks , straight 30 , arced 40 , curved 50 , or to a distinct end coupler 90 , thereby bridging the non - contiguous ends of tracks . the drawing depicts two interfitting male connections 61 in the shape of a tenon comprising the ends of each rail located at one end of the curved track and two interfitting female connections 62 in a shape corresponding to a recessed tenon comprising the ends of each rail located at the opposite end of the track . the curved track is free of end boards as an element thereof removing an obstruction associated with prior art 23 . the obstruction hinders entering or dismounting a track or traversing two connected tracks . fig4 b shows a perspective view of a curved rail 51 . each rail comprises step insertion elements 63 located in whole or part at the interior side of the rail 52 . an element 63 may accommodate the insertion of a step 70 into or through the interior side of the rail 52 , the top side of the rail 53 , or the exterior side of the rail 54 . the drawing depicts a single row of square shaped rung insertion elements 64 that accommodate rungs 71 with squared closures 75 . said elements 64 bore through the rail from the exterior side 54 to the interior side 52 . the ends of each curved rail 56 are comprised of an interfitting male connection 61 in the shape of a tenon and an interfitting female connection 62 in a shape corresponding to a recessed tenon . these elements are used to effect connections with contiguous rails of tracks , straight 30 , arced 40 , or curved 50 , or to a contiguous distinct end coupler 90 , thereby bridging the non - contiguous rails of tracks . the surface of the top side of a curved rail 53 may be smooth or semi - rough . an anti - slide element 67 is affixed to the bottom side of the curved rail 55 . fig5 a , 5 b , and 5 c show perspective views of rungs 71 , a type of step 70 , with oval 77 , rectangular 78 , and triangular 79 shaped colored footings , respectively . each rung comprises an affixed flange 72 on the end of a first squared rung closure 73 , a geometrically shaped footing 74 , a second squared rung closure with a threaded female fastener 75 , and a threaded male flanged fastener 76 that is screwed into the second squared rung closure 75 . each rung 71 is of substantially equal length and , when secured to the rails , of substantially equal height . the preferred embodiment of the invention further includes additional features described below . each additional feature is represented in a dependent claim identified in claims 2 through 8 and shown in fig2 c , 3 c , 4 c , 6 a , 7 a , 7 b , 7 c , 8 , 9 , 10 , 11 , or 12 . fig2 c shows a perspective view of a rectangular rail 31 wherein said rectangular rail comprises step insertion elements 63 located in whole or part at the interior side of the rail 32 in a pattern that permits the steps to be varied in height . an element 63 may accommodate the insertion of a step 70 into the interior side of the rail 32 , the top side of the rail 33 , or the exterior side of the rail 34 . the drawing depicts two rows of square shaped rung insertion elements 64 that accommodate rungs 71 with squared closures 75 . the upper row of elements 65 is located directly over the lower row of elements 66 . insertion of a rung 71 into an element 64 located on either the upper 65 or lower 66 row and into the corresponding element 64 of the opposing rail results in the height of the rungs being varied . said elements 64 bore through the rail from the exterior side 34 to the interior side 32 . in all other respects , this rectangular rail is identical to the rectangular rail shown in fig2 b . fig3 c shows a perspective view of an arced rail 41 wherein said arced rail comprises step insertion elements 63 located in whole or part at the interior side of the rail 42 in a pattern that permits the steps to be varied in height . an element 63 may accommodate the insertion of a step 70 into the interior side of the rail 42 , the top side of the rail 43 , or the exterior side of the rail 44 . the drawing depicts two rows of square shaped rung insertion elements 64 that accommodate rungs 71 with squared closures 75 . the upper row of elements 65 is located directly over the lower row of elements 66 . insertion of a rung 71 into an element 64 located on either the upper 65 or lower 66 row and into the corresponding element 64 of the opposing rail results in the height of the rungs being varied . said elements 64 bore through the rail from the exterior side 44 to the interior side 42 . in all other respects , this arced rail is identical to the arced rail shown in fig3 b . fig4 c shows a perspective view of a curved rail 51 wherein said curved rail comprises step insertion elements 63 located in whole or part at the interior side of the rail 52 in a pattern that permits the steps to be varied in height . an element 63 may accommodate the insertion of a step 70 into the interior side of the rail 52 , the top side of the rail 53 , or the exterior side of the rail 54 . the drawing depicts two rows of square shaped rung insertion elements 64 that accommodate rungs 71 with squared closures 75 . the upper row of elements 65 is located directly over the lower row of elements 66 . insertion of a rung 71 into an element 64 located on either the upper 65 or lower 66 row and into the corresponding element 64 of the opposing rail results in the height of the rungs being varied . said elements 64 bore through the rail from the exterior side 54 to the interior side 52 . in all other respects , this curved rail is identical to the curved rail shown in fig4 b . the preferred embodiment of the invention further includes an anti - tip device 80 for use with a straight track 30 . fig6 a shows a perspective view of said anti - tip device . the anti - tip device comprises an elongated , rectangular shaped planar surface 81 and two work holder areas 82 . each work holder area is in the shape of a rectangular rail 31 and bordered by two raised elongated work stop abutments , a tall exterior work stop abutment 84 comprising step insertion elements 86 and a shorter interior work stop abutment 85 . the drawing depicts square shaped rung insertion elements 87 . the anti - tip element 83 is comprised of the portions of the planar surface 81 extending out from each exterior work stop abutment 84 . an anti - slide element 67 is affixed to the bottom side of the anti - tip device . the preferred embodiment of the invention further includes a geometrically shaped distinct end coupler 90 . fig7 a shows a perspective view of a diamond shaped distinct end coupler 95 . fig7 b shows a perspective view of an octagon shaped distinct end coupler 96 . fig7 c shows a perspective view of a rectangular shaped distinct end coupler 97 . each distinct end coupler 90 comprises a planar surface 91 comprising elongated stripes 94 connecting the non - contiguous ends of two tracks in a visual sense . each side of a distinct end coupler comprises either two interfitting male connections 92 in the shape of a tenon or two interfitting female connections 93 in a shape corresponding to a recessed tenon . these elements are used to effect connections with one or more contiguous tracks , straight 30 , arced 40 , or curved 50 , thereby bridging non - contiguous tracks . an anti - slide element 67 is affixed to the bottom side of each distinct end coupler . the preferred embodiment of the invention further includes various design apparatuses each apparatus traversed horizontally by a human . said apparatuses are shown in fig8 , 9 , 10 , 11 , and 12 . each apparatus comprises a straight track 30 or tracks , an arced track 40 or tracks , or a curved track 50 or tracks , or a combination thereof . each track comprising an apparatus is connected to one or more contiguous tracks or to a distinct end coupler 90 , thereby bridging the non - contiguous ends of tracks . fig8 shows a topside view of the preferred embodiment of the invention in the design of a figure eight lying on its side . the apparatus is comprised of tracks contiguously connected and a diamond shaped distinct end coupler 95 used as a bridge to connect the non - contiguous ends of tracks . the distinct end coupler is located at the center of the apparatus . fig9 shows a topside view of the preferred embodiment of the invention in the design of a figure eight lying on its side . the apparatus is comprised of tracks contiguously connected and an octagon shaped distinct end coupler 96 used as a bridge to connect the non - contiguous ends of tracks . the distinct end coupler is located at the center of the apparatus . fig1 shows a topside view of the second embodiment of the invention in the design of a figure eight lying on its side longitudinally intersected at its center by a column of straight tracks . the apparatus is comprised of tracks contiguously connected and an octagon shaped distinct end coupler 96 used as a bridge to connect the non - contiguous ends of tracks , including the column of straight tracks 130 . the distinct end coupler is located at the center of the apparatus . fig1 shows a topside view of the second embodiment of the invention in the design of a figure eight lying on its side longitudinally and laterally intersected at its center by a column and row of straight tracks . the apparatus is comprised of tracks contiguously connected and an octagon shaped distinct end coupler 96 used as a bridge to connect the non - contiguous ends of tracks , including the column and row of straight tracks 130 . the distinct end coupler is located at the center of the apparatus . fig1 shows a topside view of the preferred embodiment of an apparatus in the design of a circle enclosing a plus sign . each arced track 40 comprising the circle is connected to one or more contiguous arced tracks or connected to one or more tracks , straight or arced , with the aid of a rectangular shaped distinct end coupler 97 . each straight track 30 comprising the plus sign is connected to one or more contiguous straight tracks or connected to one or more tracks , straight or arced , with the aid of a rectangular shaped distinct end coupler 97 . a distinct end coupler 97 is located at the center of the plus sign bridging the non - contiguous ends of four straight tracks . four distinct end couplers 97 are located at the ends of the plus sign each distinct end coupler intersecting and connecting with the circle of arced tracks bridging the non - contiguous ends of straight and arced tracks . the preferred embodiment of the invention is an article of educational equipment horizontally traversed by a human . the invention comprises tracks , straight 30 , arced 40 , or curved 50 . a single track may be traversed . a track may be connected to a contiguous track or tracks , straight , arced , or curved , and the combination of tracks traversed . a track may be connected to a contiguous distinct end coupler 90 bridging one end of the track to the end of a non - contiguous track or tracks , straight , arced , or curved . the combination of tracks and the distinct end coupler are then traversed . contiguous tracks and tracks with the aid of one or more distinct end couplers may be joined together to create an apparatus in a design shown in fig8 , 9 , 10 , 11 , or 12 . the apparatus is then traversed . a human may traverse the geometrically shaped colored footings of the steps 70 of a track , straight , arced , or , curved , or walk upon the top side of either rail using the rail as a balance beam . the distance between the steps 70 may be adjusted to accommodate the stride of a human . the height of each step 70 is substantially the same if the rails comprising the track comprise level step insertion elements 63 . the height of each step may vary if the rails comprising the track comprise step insertion elements 63 that are not level . the ability to adjust the height of the steps 70 increases the level of difficulty associated with traversing a track . an anti - slide element 67 is affixed to the bottom sides of each rail , distinct end coupler 90 , and anti - tip device 80 preventing a track from shifting while under foot . in addition to bridging the non - contiguous ends of tracks , a distinct end coupler 90 is used as an agent to traverse from one track to another . the planar surface 91 comprises elongated stripes 94 visually connecting non - contiguous ends of tracks thereby assisting a traversing human . a distinct end coupler is also used as a station on which a human stands while receiving instructions prior to traversing a track or apparatus . an anti - tip device 80 may be employed to prevent tipping of a straight track 30 while under foot . an anti - tip device provides protection in two ways . first , an anti - tip element 83 is comprised of the portions of the elongated , rectangular planar surface 81 that extend out from each exterior work stop abutment 84 . second , the sides of each rectangular rail 31 lie adjacent to the exterior 84 and interior 85 work stop abutments gaining support . additionally , each rail may be attached to the exterior work stop abutment 84 if the steps 70 are inserted through step insertion elements 86 comprising the abutment 84 . a track , straight 30 , arced 40 , or curved 50 , is assembled by placing the bottom side of each rail on a flat surface directly opposite one another . to join the rails , readily detachable steps 70 are inserted into opposing step insertion elements 63 located in whole or part at the interior side of each rail . each drawing in fig2 a , 3 a , and 4 a depicts a track , straight 30 , arced 40 , or curved 50 , comprising two rails joined together by readily detachable rungs 71 . each drawing in fig2 b , 3 b , and 4 b depicts a rail , rectangular 31 , arced 41 , or curved 51 , comprising a single row of square shaped rung insertion elements 64 located in whole or part at the interior side of each rail that accommodate rungs 71 with squared closures 75 . a rung 71 is inserted into the exterior side of a rail and pushed through the rail exiting its interior side and subsequently inserted into the opposite rail at its interior side and pushed through the rail exiting its exterior side whereupon the rung is secured by means of a threaded male flanged fastener 76 screwed into the squared rung closure 75 . each drawing in fig2 c , 3 c , and 4 c depicts a rail comprising two rows of square shaped rung insertion elements 64 located in whole or part at the interior side of each rail that accommodate rungs 71 with squared closures 75 . the upper row of elements 65 is directly over the lower row 66 . a rung is perpendicularly inserted into or through an element 64 located on either the upper row 65 or lower row 66 of a rail and subsequently inserted into the corresponding row of the opposing rail . the height of the rung steps may be varied . otherwise , the method of installing or removing rungs is the same as that described in the above paragraph for a rail with a single row of elements 64 . after the steps 70 are secured and the track assembled , the steps are positioned length - wise in a perpendicular or diametrical relationship to each rail , are incapable of rotating or shifting horizontally , and serve to hold the rails in a fixed equidistant relationship to each other . each readily detachable step 70 may be installed or removed without the necessity of dismantling a track . a straight track may also be assembled with the aid of an anti - tip device 80 . refer to fig6 b . the anti - tip device is positioned on a flat surface . each rectangular rail 31 of a straight track is positioned upon the anti - tip device , within each work holder area 82 , and directly opposite one another . each work holder area is bordered by an exterior 84 and interior 85 work stop abutment . the exterior work stop abutments 84 are each comprised of two rows of step insertion elements 86 into which steps 70 are inserted . the drawing depicts exterior work stop abutments 84 comprised of square shaped rung insertion elements 87 . the drawing also depicts a readily detachable rung 71 with a squared rung closure 75 which is inserted through the square shaped rung insertion element 87 comprising one of the exterior work stop abutments 84 , through the square shaped rung insertion elements 64 comprising each rail , and finally through the square shaped rung insertion element 87 comprising the other exterior work stop abutment . assembly of the track is complete when the rungs are fastened joining the opposing rails together in a fixed parallel relationship . the ends of each track , straight 30 , arced 40 , or curved 50 , are either comprised of two interfitting male connections 61 in a shape of a tenon or two interfitting female connections 62 corresponding to a recessed tenon . the assembled tracks are positioned on a flat surface . the act of connecting contiguous tracks is accomplished by lifting a track , straight , arced , or curved , and positioning the tenons 61 of the lifted track into corresponding tenon shaped recesses 62 of a contiguous track . a track may also be connected to a contiguous distinct end coupler 90 . each side of a distinct end coupler comprises two matching elements used to effect connections to a contiguous track . the two matching elements are two interfitting male connections in a shape of a tenon 91 or two interfitting female connections in a shape corresponding to a recessed tenon 92 . the assembled track and distinct end coupler are positioned on a flat surface . the act of connecting the track and the distinct end coupler is accomplished by lifting the track and positioning the tenons 61 of the lifted track into corresponding tenon shaped recesses 92 of the distinct end coupler or placing the tenon shaped recesses 62 of the lifted track around the tenons 91 of the distinct end coupler . each apparatus arranged in the designs shown in fig8 , 9 , 10 , 11 , and 12 is assembled by connecting contiguous tracks and one or more distinct end coupler as described above . description — second embodiment — fig1 , 14 , 15 , 16 a , 16 b , and 16 c the second embodiment of the invention comprises straight 30 , arced 40 , and curved 50 tracks , each track comprising two rails joined together by affixed steps with geometrically shaped colored footings 170 and comprising a means 60 to connect to other tracks . said second embodiment is described below and claimed in independent claim 9 . fig1 shows a perspective view of a straight track 130 . said straight track comprises two rigid , rectangular rails each rail 131 of substantially equal dimensions joined together by affixed , colored steps 170 . the drawing depicts affixed , colored rungs 171 comprising geometrically shaped footings 174 . each rung 171 is of substantially equal length and affixed perpendicularly at the interior side of each rectangular rail 131 serving to hold the rails in a parallel relationship to each other . the straight track comprises elements 60 used to effect connections to a contiguous track or tracks , straight 130 , arced 140 , or curved 150 , or to a distinct end coupler 90 , thereby bridging the non - contiguous ends of tracks . the drawing depicts two interfitting male connections 61 in the shape of a tenon located at one end of the straight track and two interfitting female connections 62 in a shape corresponding to a recessed tenon located at the opposite end of the track . the surface of the top side of the elongated rail 131 may be smooth or semi - rough . an anti - slide element 67 is affixed to the bottom side of the elongated rail . the straight track is free of end boards as an element thereof removing an obstruction associated with prior art 23 . the obstruction hinders entering or dismounting a track or traversing two connected tracks . fig1 shows a perspective view of an arced track 140 . said arced track comprises two oblong , rigid , arced rails each rail 141 of substantially equal height and width joined together by affixed , colored steps 170 . the drawing depicts affixed , colored rungs 171 comprising geometrically shaped footings 174 . each rung 171 is of substantially equal length and diametrically affixed length - wise at the interior side of each arced rail serving to hold the directly opposing rails in an equidistant relationship to each other . the arced track comprises elements 60 used to effect connections to a contiguous track or tracks , straight 130 , arced 140 , or curved 150 , or to a distinct end coupler 90 , thereby bridging the ends of tracks . the drawing depicts two interfitting male connections 61 in the shape of a tenon located at one end of the arced track and two interfitting female connections 62 in a shape corresponding to a recessed tenon located at the opposite end of the track . the surface of the top side of the arced rail 141 may be smooth or semi - rough . an anti - slide element 67 is affixed to the bottom side of the arced rail . the arced track is free of end boards as an element thereof removing an obstruction associated with prior art 23 . the obstruction hinders entering or dismounting a track or traversing two connected tracks . fig1 shows a perspective view of a curved track 150 . said curved track comprises two curved , oblong , rigid rails each rail 151 of substantially equal height and width joined together by affixed , colored steps 170 . the drawing depicts affixed , colored rungs 171 comprising geometrically shaped footings 174 . each rung 171 is of substantially equal length and diametrically or otherwise affixed length - wise at the interior side of each curved rail serving to hold the directly opposing rails in an equidistant relationship to each other . the curved track comprises elements 60 used to effect connections to a contiguous track or tracks , straight 130 , arced 140 , or curved 150 , or to a distinct end coupler 90 , thereby bridging the ends of tracks . the drawing depicts two interfitting male connections 61 in the shape of a tenon located at one end of the arced track and two interfitting female connections 62 in a shape corresponding to a recessed tenon located at the opposite end of the track . the surface of the top side of the curved rail 151 may be smooth or semi - rough . an anti - slide element 67 is affixed to the bottom side of the curved rail . the curved track is free of end boards as an element thereof removing an obstruction associated with prior art 23 . the obstruction hinders entering or dismounting a track or traversing two connected tracks . fig1 a , 16 b , and 16 c show perspective cross - section views of affixed rungs 171 , a type of step 170 , with oval 177 , rectangular 178 , and triangular 179 shaped colored footings , respectively . a rectangular rail 131 is used as a backdrop although an arced or curved rail may have been depicted . each rung is affixed length - wise at the interior side of each rail serving to hold the directly opposing rails in a fixed relationship to one another . the second embodiment of the invention further includes additional features described below . each additional feature is represented in a dependent claim identified in claims 10 through 15 and is depicted in fig6 a , 7 a , 7 b , 7 c , 8 , 9 , 10 , 11 , or 12 . the second embodiment of the invention further includes an anti - tip device 80 for use with a straight track 130 . fig6 a shows a perspective view of said anti - tip device . the anti - tip device comprises an elongated , rectangular shaped planar surface 81 and two work holder areas 82 . each work holder area is in the shape of a rectangular rail 31 and bordered by two raised elongated work stop abutments , a tall exterior work stop abutment 84 and a shorter interior work stop abutment 85 . the drawing depicts rectangular shaped rung insertion elements 87 , which are not used in this embodiment of the invention . the anti - tip element 83 is comprised of the portions of the planar surface 81 extending out from each exterior work stop abutment 84 . an anti - slide element 67 is affixed to the bottom side of the anti - tip device . the second embodiment of the invention further includes a geometrically shaped distinct end coupler 90 . fig7 a shows a perspective view of a diamond shaped distinct end coupler 95 . fig7 b shows a perspective view of an octagon shaped distinct end coupler 96 . fig7 c shows a perspective view of a rectangular shaped distinct end coupler 97 . each distinct end coupler 90 comprises a planar surface 91 comprising elongated stripes 94 connecting the non - contiguous ends of two tracks in a visual sense . each side of a distinct end coupler comprises either two interfitting male connections 92 in the shape of a tenon or two interfitting female connections 93 in a shape corresponding to a recessed tenon . these elements are used to effect connections with one or more contiguous tracks , straight 130 , arced 140 , or curved 150 , thereby bridging non - contiguous tracks . an anti - slide element 67 is affixed to the bottom side of each distinct end coupler . the second embodiment of the invention further includes various design apparatuses each apparatus traversed horizontally by a human . said apparatuses are shown in fig8 , 9 , 10 , 11 , and 12 . each apparatus comprises a straight track 130 or tracks , an arced track 140 or tracks , or a curved track 150 or tracks , or a combination thereof each track is connected to one or more contiguous tracks or to a distinct end coupler 90 , thereby bridging non - contiguous ends of tracks . fig8 shows a topside view of the second embodiment of the invention in the design of a figure eight lying on its side . the apparatus is comprised of tracks contiguously connected and a diamond shaped distinct end coupler 95 used as a bridge to connect the non - contiguous ends of tracks . the distinct end coupler is located at the center of the apparatus . fig9 shows a topside view of the second embodiment of the invention in the design of a figure eight lying on its side . the apparatus is comprised of tracks contiguously connected and an octagon shaped distinct end coupler 96 used as a bridge to connect the non - contiguous ends of tracks . the distinct end coupler is located at the center of the apparatus . fig1 shows a topside view of the preferred embodiment of the invention in the design of a figure eight lying on its side longitudinally intersected at its center by a column of straight tracks . the apparatus is comprised of tracks contiguously connected and an octagon shaped end coupler 96 used as a bridge to connect the non - contiguous ends of tracks , including the column of straight tracks 30 . the distinct end coupler is located at the center of the apparatus . fig1 shows a topside view of the preferred embodiment of the invention in the design of a figure eight lying on its side longitudinally and laterally intersected at its center by a column and row of straight tracks . the apparatus is comprised of tracks contiguously connected and an octagon shaped distinct end coupler 96 used as a bridge to connect the non - contiguous ends of tracks , including the column and row of straight tracks 30 . the distinct end coupler is located at the center of the apparatus . fig1 shows a topside view of the second embodiment of the invention in the design of a circle enclosing a plus sign . each arced track 140 comprising the circle is connected to one or more contiguous arced tracks or connected to one or more tracks , straight or arced , with the aid of a rectangular shaped distinct end coupler 97 . each straight track 130 comprising the plus sign is connected to one or more contiguous straight tracks or connected to one or more tracks , straight or arced , with the aid of a contiguous rectangular shaped distinct end coupler 97 . a distinct end coupler 97 is located at the center of the plus sign bridging the non - contiguous ends of four straight tracks . four distinct end couplers 97 are located at the ends of the plus sign each distinct end coupler intersecting and connecting with the circle of arced tracks bridging the non - contiguous ends of straight and arced tracks . the second embodiment of the invention is an article of educational equipment horizontally traversed by a human . the invention comprises tracks , straight 130 , arced 140 , or curved 150 . a single track may be traversed . a track may be connected to a contiguous track or tracks , straight , arced , or curved , and the combination of tracks traversed . a track may be connected to a contiguous distinct end coupler 90 bridging one end of the track to the end of a non - contiguous track or tracks , straight , arced , or curved . the combination of tracks and the distinct end coupler are then traversed . contiguous tracks and tracks with the aid of one or more distinct end couplers may be joined together to create an apparatus in a design shown in fig8 , 9 , 10 , 11 , or 12 . the apparatus is then traversed . a human may traverse geometrically shaped colored footings of the steps 170 of a track or walk upon the top side of either rail using the rail as a balance beam the height of each step 170 is substantially the same . an anti - slide element 67 is affixed to the bottom sides of each rail distinct end coupler 90 , and anti - tip device 80 preventing a track from shifting while being traversed . in addition to bridging the non - contiguous ends of tracks , a distinct end coupler 90 is an agent used to traverse from one track to another . the planar surface 91 comprises elongated stripes 94 visually connecting non - contiguous ends of tracks thereby assisting a walking human . a distinct end coupler is also used as a station on which a human stands while receiving instructions prior to traversing a track or apparatus . an anti - tip device 80 may be employed to prevent tipping of a straight track 30 while under foot . an anti - tip device provides protection in two ways . first , an anti - tip element 83 is comprised of the portions of the elongated , rectangular planar surface 81 that extend out from each exterior work stop abutment 84 . second , the sides of each rectangular rail 31 lie adjacent to the exterior 84 and interior 85 work stop abutments gaining support . the ends of each track , straight 130 , arced 140 , or curved 150 , are either comprised of two interfitting male connections 61 in a shape of a tenon or two interfitting female connections 62 corresponding to a recessed tenon . the tracks are positioned on a flat surface . the act of connecting contiguous tracks is accomplished by lifting a track , straight , arced , or curved , and positioning the tenons 61 of the lifted track into corresponding tenon shaped recesses 62 of a contiguous track . a track may also be connected to a contiguous distinct end coupler 90 . each side of a distinct end coupler comprises two matching elements used to effect connections to a contiguous track . the two matching elements are two interfitting male connections in a shape of a tenon 91 or two interfitting female connections in a shape corresponding to a recessed tenon 92 . the track and distinct end coupler are positioned on a flat surface . the act of connecting the track and the distinct end coupler is accomplished by lifting the track and positioning the tenons 61 of the lifted track into corresponding tenon shaped recesses 92 of the distinct end coupler or placing the tenon shaped recesses 62 of the lifted track around the tenons 91 of the distinct end coupler . each apparatus arranged in the designs shown in fig8 , 9 , 10 , 11 , and 12 is assembled by connecting contiguous tracks and one or more distinct end coupler as described above . description — third embodiment — fig1 , 18 , 19 , 16 a , 16 b , and 16 c the third embodiment of the present invention comprises straight 230 , arced 240 , and curved 250 tracks , each track comprising two rails joined together by affixed steps with geometrically shaped colored footings 170 . said third embodiment is described immediately below and claimed in independent claim 16 . fig1 shows a topside view of a straight track 230 . said straight track comprises two rigid , rectangular rails each rail 231 of substantially equal dimensions joined together by affixed , colored steps 170 . the drawing depicts affixed , colored rungs 171 comprising geometrically shaped footings 174 . each rung 171 is of substantially equal length and perpendicularly affixed at the interior side of each rectangular rail serving to hold the rails in a parallel relationship to each other . the surface of the top side of the rectangular rail 231 may be smooth or semi - rough . the straight track is free of end boards as an element thereof removing an obstruction associated with prior art 23 . the obstruction hinders entering or dismounting a track or traversing two connected tracks . fig1 shows a topside view of an arced track 240 . said arced track comprises two oblong , rigid , arced rails each rail 241 of substantially equal height and width joined together by affixed , colored steps 170 . the drawing depicts affixed , colored rungs 171 comprising geometrically shaped footings 174 . each rung 171 is of substantially equal length and diametrically affixed length - wise at the interior side of each arced rail serving to hold the directly opposing rails in an equidistant relationship to each other . the surface of the top side of the arced rail 241 may be smooth or semi - rough . the arced track is free of end boards as an element thereof removing an obstruction associated with prior art 23 . the obstruction hinders entering or dismounting a track or traversing two connected tracks . fig1 shows a topside view of a curved track 250 . said curved track comprises two curved , oblong , rigid rails each rail 251 of substantially equal height and width joined together by affixed , colored steps 170 . the drawing depicts affixed , colored rungs 171 comprising geometrically shaped footings 174 . each rung 171 is of substantially equal length and diametrically or otherwise affixed length - wise at the interior side of each curved rail serving to hold the directly opposing rails in an equidistant relationship to each other . the surface of the top side of the curved rail 251 may be smooth or semi - rough . the curved track is free of end boards as an element thereof removing an obstruction associated with prior art 23 . the obstruction hinders entering or dismounting a track or traversing two connected tracks . fig1 a , 16 b , and 16 c show perspective cross - section views of affixed rungs 171 , a type of step 170 , with oval 177 , rectangular 178 , and triangular 179 shaped colored footings , respectively . a rectangular rail 231 is used as a backdrop although an arced or curved rail may have been depicted . each rung is affixed length - wise at the interior side of each rail serving to hold the directly opposing rails in a fixed relationship to one another . the third embodiment of the invention further includes additional features described below . each additional feature is represented in a dependent claim identified in claims 17 through 20 and is depicted in fig2 , 21 , 22 , and 23 . the third embodiment of the invention further includes various design apparatuses each apparatus traversed horizontally by a walking human . said apparatuses are shown in fig2 , 21 , 22 , and 23 . each apparatus comprises a straight track or tracks 230 , an arced track or tracks 240 , or a curved track or tracks 250 , or a combination thereof fig2 shows a topside view of the third embodiment of the invention in the design of a figure eight lying on its side . the apparatus is comprised of one or more straight , arced , or curved tracks . fig2 shows a topside view of the third embodiment of the invention in the design of two non - contiguous sets of connected arced and curved tracks each in the shape of a horseshoe located on the left and right sides of the design the open ends of each horseshoe shaped set of tracks directly opposite and laterally positioned to one another and two non - continuous straight tracks centrally located on the upper and lower sides of the design directly opposite and longitudinally positioned to one another , all of the horseshoe shaped sets of tracks and straight tracks border an octagon shaped open area in the middle of the design . the apparatus is comprised of one or more straight , arced , or curved tracks . fig2 shows a topside view of the third embodiment of the invention in the design of two non - contiguous sets of connected arced and curved tracks each in the shape of a horseshoe located on the left and right sides of the design , within each of which a straight track is laterally and centrally positioned the ends of the each straight track abutting or lying at the interior sides of the horseshoe shaped set of tracks , the open ends of each horseshoe shaped set of tracks directly opposite and laterally positioned to one another and two non - continuous straight tracks centrally located on the upper and lower sides of the design directly opposite and longitudinally positioned to one another , all of the horseshoe shaped sets of tracks , inclusive of the partially enclosed laterally positioned straight tracks , and the longitudinally positioned straight tracks border an octagon shaped open area in the middle of the design . the apparatus is comprised of one or more straight , arced , or curved tracks . fig2 shows a topside view of the third embodiment of the invention in the design of a circle enclosing a plus sign . the circle is comprised of one or more arced tracks 240 . the plus sign is comprised of two or more straight tracks 230 . the arced and straight tracks may be connected to one another . the third embodiment of the invention is an article of educational equipment horizontally traversed by a walking human . the invention comprises tracks , straight 230 , arced 240 , or curved 250 . a single track may be traversed . a track may be joined to one or more tracks , straight , arced , or curved , and the combination of tracks traversed . tracks may be joined together to create an apparatus in a design shown in fig2 , 21 , 22 , or 23 . the apparatus is then traversed . a human may traverse the colored , geometrically shaped step 170 of a track or walk upon the top side of either rail using the rail as a balance beam . the height of each step 170 is substantially the same . from the descriptions above , a number of advantages of the embodiments of the invention over prior art become apparent : each track of the preferred embodiment comprises two rails that are joined together by readily detachable steps . one or more steps may be removed without the necessity of dismantling the track . the steps may be adjusted to accommodate the stride of a walking human . if the rails of a track comprise step insertion elements that are not level , the height of the rungs may be varied increasing the traversing challenge . each embodiment comprises steps with colored footings that are oval , rectangular , or triangular shaped . each track of the preferred and second embodiments comprise track connecting elements used to effect connections with one or more contiguous tracks or a contiguous distinct end coupler . each embodiment comprises tracks that are free of end boards removing an obstruction associated with prior art . the obstruction would otherwise hinder entering or dismounting a track or traversing two connected tracks . as regards the preferred embodiment , the removal of the end boards also increases versatility as the rails of a straight track may be widened or narrowed to accommodate teaching methods and traversing alternatives , such as by wheelchair . the preferred and seconds embodiments further include an anti - tip device used with a straight track that prevents tipping of the track while being traversed . in the preferred embodiment , the anti - tip device is also used as an aid in the assembly of a straight track . the preferred and second embodiments further include a geometrically distinct end coupler , an intermediate structure that bridges the non - contiguous ends of two or more tracks , straight , arced , or curved . in addition to bridging the ends of tracks , a distinct end coupler is used as an agent to traverse from one track to another as a station on which a human stands while receiving instructions prior to traversing a track or tracks . the preferred and second embodiments further include a number of apparatuses using the design of a figure eight lying on its side . the apparatuses are comprised of tracks , straight , arced , or curved , contiguously connected and a distinct end coupler used as a bridge to connect the non - contiguous ends of tracks . the apparatuses described in the third embodiment comprise tracks but not a distinct end coupler . a human traverses the steps or rung footings or a rail , using the rail as a balance beam , performing specific routines that are intended to increase learning capabilities . the functions of these design apparatuses are in addition to those functions that are accomplished with tracks , straight , arced , or curved , not used in combination . for example , a human traverses the apparatuses forming the letters of the alphabet , and , as a result , the brain is imprinted with the letters of the alphabet . the preferred and second embodiments further include an apparatus in the design of a circle enclosing a plus sign . the apparatus is comprised of tracks , arced and straight , contiguously connected and a distinct end coupler used as a bridge to connect the non - contiguous ends of tracks . the apparatus described in the third embodiment comprise tracks but not a distinct end coupler . a walking human traverses the steps or rung footings or a rail , using the rail as a balance beam , performing specific routines that are intended to increase learning capabilities . the functions of the design apparatus are in addition to those functions that are accomplished with tracks , straight , arced , or curved , not in combination . for example , a walking human traverses the circle as if it was a timepiece or map . accordingly , the invention is a significant improvement over prior art promoting , fostering , and facilitating the learning process . the invention comprises tracks , straight , arced , and curved , and design apparatuses comprising tracks . the tracks comprise unique elements . each rail comprises elements used to effect connections to other tracks and elements into or through which readily detachable rungs are inserted . the invention also comprises distinct end couplers used to connect non - contiguous tracks and an anti - tip device used with a straight track to avoid tipping . based upon brain research findings that supports the link of movement to learning , the result achieved by a human traversing a track or an apparatus , comprising the tracks , is increased sensory motor development , longer focus and attention , coordination of motor skills , better balance in the vestibular system , awareness of basic rhythmic patterns , and improved learning readiness . the basic design of the tracks , including the shapes and colors of the rungs , and the designs of the apparatuses provide the framework for the development of academic concepts including , but not limited to , color , shape , and number recognition , basic math operations , early literacy , reading readiness , handwriting skills , map skills , time concepts , and other basic early childhood curriculum . because the tracks are traversed while practicing academic concepts , the learning is anchored in the brain for better memory retention and retrieval as a human has combined physical and cognitive domains . if humans jointly participate in a track activity including the assembly of a track , building an apparatus of tracks , traversing a track or an apparatus , or disassembly of a track or an apparatus , team concepts , peer help , and cooperation skills are developed resulting in better social behavior and life skills . the material used to manufacture a rail , a distinct end coupler , and an anti - tip device must be sturdy , durable , color - safe , and weather resistant . an assembled track should be light in weight making the track easy to assemble and dismantle , connect to other tracks or couplers , transport , and store . however , a track must be of a sufficient weight to avoid shifting while under foot . the material used to manufacture a rung must also be sturdy , durable , color - safe , and weather resistant . a step or rung must be capable of withstanding a considerable weight . if the tracks are used outdoors , the material used to manufacture the rails , steps , and rungs must be heavier and rust resistant . although the description above contains much specificity , it should not be construed as limiting the scope of the invention but merely providing illustrations of some of the embodiments of this invention . for example , the shapes of rails and the shape and location of the elements comprising rails including the step insertion and track connecting elements , the shapes of steps , the shapes of distinct end couplers and the elements comprising a coupler , and the designs of the apparatuses are not limited to the shapes , locations , and designs shown in the drawings . the methods used to install readily detachable steps or connect tracks are not limited to those shown or described . thus the scope of the invention should be determined by the appended claims and their legal equivalents , rather than by the examples given .

an educational apparatus is traversed horizontally for the purpose of increasing learning capabilities is pictured . the apparatus is in the design of a figure eight lying on its side longitudinally and laterally intersected at its center by a column and row of straight tracks 30 . the apparatus is comprised of tracks , straight 30 , arced 40 , and curved 50 , contiguously connected to one another and an octagon shaped distinct end coupler 96 used as a bridge to connect the non - contiguous ends of tracks , straight 30 , arced 40 , and curved 50 . the distinct end coupler 96 is located in the center of the apparatus . the distinct end coupler 96 is not only a structure used to connect the non - contiguous ends of tracks but also a station from which a human receives instruction prior to traversing the apparatus and a portal used by a walking human to traverse from track to track in the proper direction and sequence , important for basic brain processing methods . the apparatus is designed to be traversed by a human in specific patterns in order to promote , foster , and facilitate the development of brain functions controlling balance , coordination , spatial awareness , and vestibular function thereby increasing learning capabilities . as a result of traversing the apparatus in specific patterns , the human brain will process alphabetic and numeric symbols more efficiently . this is especially important in the development of early childhood learners . the educational importance for the invention is based upon brain research findings that support the link of sensory motor development and increased learning capacity .

the heating device shown in fig1 , 2 and 3 comprises a lid 21 which can be coupled to a pan 18 . the lid 21 is rotatably mounted in a cover 5 and is provided to this end at its circumference with a bearing ring 16 which can rotate in the cover 5 about a rotation axis 19 and which is positioned inside the cover 5 in the axial direction by , inter alia , an edge 17 . the edge 17 protects the underside of the lid 21 , preventing a user from accidentally touching the hot parts of the lid 21 . six springs 30 are provided on the lid 21 for coupling the pan 18 to the lid 21 , which springs are provided , at their loose ends with a hook 29 which can grip around an upper edge of the pan 18 ( in fig1 , the springs 30 on the left - hand side of the figure have been drawn in a position which is rotated about thirty degrees for the sake of clarity ). as the lid 21 is pressed onto the pan 18 , the upper edge of the pan 18 presses the hooks aside until these hooks 29 fall around the upper edge and grip the pan 18 securely in such a manner that the pan 18 and the lid 21 are coupled . a resilient ring 20 is placed between the pan 18 and the lid 21 as a seal . this resilient ring 20 and the springs 30 are designed such that the hooks 29 can engage with the upper edge when the ring 20 is pressed , following which the ring 20 presses the upper edge downward in such a manner that the latter is pressed down against the hook 29 . on that side of the lid 21 which faces the pan 18 , a coiled heating element 23 is arranged , as well as a fan 24 . the fan 24 is attached to a shaft 25 of a motor 7 . a grid 22 is arranged on the underside of the lid 21 on order to protect the heating element 23 and the fan 24 . this grid 22 preferably consists of small - meshed gauze made of thin metal wire , so that a good permeability is ensured for the infra - red radiation emanating from the heating element 23 . the grid 22 can be detached from the lid 21 for ease of cleaning . in the embodiment shown , the lid 21 is made of metal , but it is likewise possible to use other materials . during switching on of the heating element 23 the lid 21 heats up , resulting in an increase in its diameter . an expansion rim 15 is provided between the part of the lid 21 which becomes hot and the bearing ring 16 which can absorb the increase in diameter of the heated part of the lid 21 so that the bearing play between the bearing ring 16 and the cover 5 does not become too small . before the pan 18 can be detached from the lid 21 , the six hooks 29 have to be moved outwards simultaneously . in order to achieve this , a ring 14 rests on the springs 30 , the springs 30 being shaped in such a manner that the hooks 29 move outwards when the ring 14 is pressed downwards . the springs 30 and the ring 14 rotate with the lid 21 . the ring 14 has a flat top surface which moves under push - buttons 1 when the lid 21 rotates . by means of the push - buttons 1 , the ring 14 can be pushed down as a result of which the hooks 29 move outwards and the pan 18 is detached from the lid 21 and the lid 21 , together with the cover 5 can be lifted off the pan 18 . the push - buttons 1 are pushed upwards by the springs 30 and the ring 14 . the upward movement of the push - button 1 in the cover 5 is limited by a pin 2 . handles 33 are arranged in the cover 5 for easy operation of the push - buttons 1 . the motor 7 can rotate with respect to the lid 21 , for which purpose a bearing ring 26 is incorporated in the lid 21 , enabling this rotation . the motor 7 is clamped inside a holder 8 by means of a clamp 34 . the holder 8 is coupled to the cover 5 by supports 4 . the heating element 23 is fastened to the underside of the motor 7 and a supply lead 10 for the heating element 23 runs to a switch 13 via the underside of the motor 7 . a supply lead 9 for the motor 7 also runs to the switch 13 . the motor 7 is also used for rotating the lid 21 inside the cover 5 . to this end , a pulley 6 is arranged on the shaft 25 at the top of the motor 7 . a drive belt 3 is tensioned around the pulley 6 and also runs around a disc 36 . the disc 36 is mounted on a shaft 31 which can rotate at the top in a bearing ( not shown ) mounted in the cover 5 . at its bottom , the shaft 31 is provided with a drive roll 37 which is pressed against the bearing ring 16 by a spring 32 . by selecting the diameters of the pulley 6 , the disc 36 and the drive roll 37 , the speed of rotation of the lid 12 and thus of the pan 18 can be selected . the cover 5 is provided with two supports 28 which are dimensioned such that there is a distance a between the supports and a table when the rotation axis 19 is vertical and the pan 18 is on the table and clamped securely by the hooks 29 . after tilting , when a rotation axis 19 of the pan 18 is horizontal , the supports 28 rest on the table by means of a support plate 27 and a support plate 38 and the pan 18 can rotate freely . in order to facilitate the tilting , a handle 35 is provided on the cover 5 . it will be clear that it is also possible to have embodiments where the supports 28 and the support plates 27 and 38 are designed in such a manner that the rotation axis 18 is not at an angle of ninety degrees to the vertical when the support plates 27 and 38 rest on the table , but are at another angle , different from zero . a sensor 11 is arranged in the cover 5 for detecting this tilted position in which the pan 18 can rotate freely . when the sensor 11 detects the tilted position , the heating element 23 , the fan 24 and thus the rotational drive of the pan 18 can be switched on . in use , the pan 18 described above is filled with food to be heated , coupled to the lid 21 , and subsequently the pan 18 is tilted . then , the heating element 23 , the fan 24 and the drive of the lid 21 are switched on and the food is heated . after a few minutes , when the food is cooked , the heating element 23 , the fan 24 and the drive of the lid 21 are switched off , the pan 18 is put on the table . subsequently , the push - buttons 1 are pushed in , as a result of which the hooks 29 move outwards and the cover 5 can be lifted from the pan 18 . the heated food can then be taken out of the pan 18 . it has been assumed in the embodiment shown that the pan 18 rotates continuously in the same direction . in a situation where the direction of rotation of the pan 18 vary and the rotation in one direction is in each case limited , the motor 7 can be securely mounted in the lid 21 , while the supply leads 9 and 10 can run directly to the motor . in this case , however , a sensor and / or switch in order to limit the rotation is required . one possible embodiment may feature a reverse clutch between a motor and the pan 18 , the sensor switching the reverse clutch and thereby reversing the rotational direction of the pan 18 . optionally , the drive for the pan 18 and the fan 24 are designed as separate units and there are two motors which can be operated independently . as a result , the use of the pulley 6 , the disc 36 and the drive belt 3 is redundant , resulting in fewer failures . the pan 18 may have a diameter of between 20 and 60 cm and a depth of 15 to 30 cm . the speed of rotation of the pan 18 is approximately 10 revolutions per minute , if desired between 5 and 15 revolutions per minute . optionally , the supports 28 of the device are designed such that , during the heating , the pan rotates about an axis which is at an angle to the horizontal plane , for example an angle of thirty degrees , so that the food partially rests against the side wall and on the bottom of the pan 18 during heating . the pan 18 may be made of heat - resistant glass . the surface of the glass is preferably metallized or the glass is made to be reflective in another way , so that the infra - red radiation from the heating element 23 reflects on the pan 18 and further heats the food present in the pan 18 . other embodiments are likewise possible , such as a metal pan or also a basket . in one embodiment , the pan 18 or basket , respectively , may be provided with partitions , which may be removable , if desired . in that case , different kinds of food are placed in the various compartments of the pan 18 , which can be heated separately . indentations 12 may be provided in order to be able to pick up the pan easily . these indentations may also be useful for moving the food in the pan 18 , as these indentations interrupt any possible sliding of the food , so that it starts to “ roll ” and is better heated on all sides . in the embodiment shown , a simple switch 13 is shown for operating the device . obviously , the device may also be provided with features which prevent overheating of the heating element 23 and it is also possible to design the device to have a programmable controller , a timer and other features known for the use of the device in the preparation of meals . it will be clear to those skilled in the art , that the abovementioned cover 5 may be moved by a manipulator which , for example , forms part of a machine for heating food , rather than by a cook . once the food has been place in the pan 18 , if desired automatically , the cover 5 and the pan 18 are coupled by the manipulator and subsequently also tilted . after heating , the pan 18 and the cover 5 are uncoupled by displacing the ring 14 using a drive fitted into the cover 5 for this purpose . the pan 18 is removed and automatically emptied , if desired , into a small tray which can be taken out of the machine . the machine may be provided with a payment system with selection means , so that an individual may , after payment , have a portion of food heated in the machine , with the machine carrying out the heating in the manner described above . fig4 shows a second embodiment of the heating device , in which most components are more or less identical to the components of the first exemplary embodiment . in the second embodiment , the cover 5 is pivotably attached between two supporting legs 43 by means of , inter alia , a hinge 40 . the supporting legs 43 are attached to a baseplate 45 which may be placed on a worktop , for example . a fastening eye 41 is fixed to the cover 5 and a fastening eye 44 is fixed to the baseplate 45 . a spring 42 is arranged between the fastening eyes 41 and 44 , which spring is designed such that the cover 5 with all the components attached to it , and the pan 18 are tilted upwards by the effect of the spring force of the spring 42 , in such a manner that the rotation axis 19 of the pan is at an angle with the vertical , as indicated in fig4 . positioning projections 46 are fitted on the baseplate 45 into which the pan 18 ′, indicated in fig4 by a broken line , can be placed . when using the heating device according to fig4 , the pan 18 , which is filled with the foodstuffs to be heated , is placed on the baseplate 45 between the positioning projections 46 . by pulling the handle 35 , the cover 5 is pressed downwards until the hooks 29 grip around the rim of the pan 18 and the pan 18 is coupled to the cover 5 . the force of the spring 42 lifts the pan 18 up until the rotation axis 19 of the pan is at an angle to the vertical . then , the heating device is switched on , as described above . once the foodstuffs are sufficiently heated , the pan is pressed between the positioning projections 46 again and the hooks are pressed outwards by pressing the buttons 1 , causing the pan 18 to be detached from the cover 5 . the cover 5 can now move upwards again and the pan 18 with the heated foodstuffs can be removed . it will be clear to those skilled in the art , that the hooks 29 , the positioning projections 46 and the other components are designed such that the cover 5 is able to make this tilting movement . if desired , the pan can slide over the baseplate 45 during the movement or the hinge 40 is designed such that restricted horizontal movements of the cover 5 are possible .

the invention relates to a device for heating food comprising a frame , a pan or basket having an opening into which the food to be heated can be placed , which pan or basket can be coupled to the frame by means of coupling means and in which the frame comprises a heating element and a fan for circulating heated air in the pan or basket , and a drive for rotating the pan or basket about a non - vertical rotation axis during the heating of food in a heating position of the frame . the frame is designed such that the pan or basket can be coupled to the frame while the pan or basket is on a supporting surface with its opening directed upwards . the invention also comprises a method for heating food .

referring firstly to fig1 to 3 , there are shown a magnetic member ( 10 ) and a housing ( 20 ) which , when assembled together , form a first preferred embodiment of the present invention of a magnetic buckle . the magnetic member ( 10 ) is the source of the magnetic coupling force for engaging with a counterpart magnetic buckle . preferably , this magnetic member includes a permanent magnet in the form of a magnetic slab made of a strong magnetic substance or alloy in order to provide a large magnetic force - to - volume ratio essential for a compact buckle design . with the current magnetic technology , a pair of complementary magnetic slabs having a diameter of 1 cm and a thickness of about 1 mm and with an appropriate design as mentioned herein can produce a magnetic coupling force of up to 20 - 30 n . in the present preferred example , the magnetic slab is substantially circular or cylindrical with a diameter of about 12 mm and a thickness of less than 1 mm . to provide a maximum magnetic coupling area , the two opposite magnetic poles are preferably disposed on the two opposing planes ( 11 , 12 ) of the magnetic slab so that the north pole is on one of the planar surfaces while the south pole is on the other with a perimeter wall ( 12 a ) therebetween . to increase the magnetic flux intensity on the coupling surface , the magnet member is preferable embedded within a casing made of a magnetic material , such as an iron , steel or other ferromagnetic casing , with one of the magnetic coupling surface exposed . with such an embedment of a strong magnet on a ferro - magnetic casing , the magnetic strength of the exposed coupling surface is considerably strengthened by concentration . of course , magnetic members of other shapes and thickness can equally be used without loss of generality . for example , the magnetic member can be made into a rectangular , polygonal , trapezoidal or even irregular or non - geometric cross - section . in addition , a ring - or toroidal shaped magnetic member can also be utilized . the housing includes a holder portion ( 21 ) or receptacle for receiving the magnetic member and a strap receiving portion ( 25 ) for anchoring a flexible end of a strap for releasable engagement with a counter - part magnetic buckle . the magnetic member holder portion includes a base portion ( 22 ) which preferably conforms closely to the base dimensions of the magnetic member and an upstanding fencing wall ( 23 ) which extends upwardly along the perimeter of the base portion . the combined structure of the base portion together and the peripheral fencing wall provides a cavity casing within which the magnetic member is received with the magnetic coupling surface ( 11 ) exposed and unobstructed . the cavity casing , which includes the base portion ( 22 ) and the upwardly extending parametric peripheral wall ( 23 ), is preferably made of a magnetic material , for example , a ferro - magnetic substance such as chromium or nickel plated steel . the magnetic member can be glued to the cavity housing or retained by other means , including mechanical retention or embedment . when the magnetic member is enclosed by a magnetic material and with an exposed surface , the magnetic strength of the exposed magnetic surface will be reinforced and maximized , and the magnetic coupling forces , when coupled with the opposite magnetic surface ( 10 ) of a similarly designed counterpart magnetic buckle , will be greatly enhanced when compared to magnetic members not so encased . with such a design , a more compact buckle with a strong magnetic strength can be provided . the strap receiving portion ( 25 ) includes a means ( 24 ) for receiving or otherwise connecting to the flexible end of a flexible strap . to enhance secured retention of the strap , the receiving portion may include a serrated slot or notch . the strap receiving portion ( 25 ) includes a means ( 24 ) for receiving the flexible end of a flexible strap in order to form a strap with a buckled end . to improve better retention of the strap end , the receiving portion may include a serrated slot or notch . in order to provide a low - profile buckle design , the strap receiving portion is relatively thin with a thickness which is preferably equal to or less than that of the peripheral wall of magnetic member . in addition , the strap receiving portion is preferably formed by placing it adjacent to the peripheral edge joining the magnetic polar surfaces rather than extending from either polar surfaces so that an over - all low - profile structure can be obtained . in the present embodiment , the strap receiving portion contains a rigid bridging portion which extends away from the cavity casing in a lateral or radial manner . in this arrangement , the strap receiving portion is substantially equi - distant from both polar surfaces and is joined to the cavity casing by the rigid bridging portion ( 27 ). the bridging portion ( 27 ) preferably includes a ribbon - shaped plate member with its wide surfaces substantially parallel to the magnetic coupling surfaces ( 11 , 12 ). of course , instead of ribbon shaped member , a thin shaft member may be used to join the strap receiving portion and the cavity casing . in any event , the portion of the housing which extends away from the cavity casing should be of a slim design so that an overall low - profile design can be achieved . for example and as shown in the figures , a substantial portion of that extension is preferably flat and the whole portion should be kept within the height of the peripheral wall of the magnetic member ( 10 ). alternatively , the strap - receiving means may be formed proximate and adjacent to the peripheral wall joining the polar surfaces ( 11 , 12 ) so that it is substantially equi - distant from both polar surfaces ( 11 , 12 ). forming the strap - receiving means sidewise of the polar surfaces will always provide a desirable low - profile structure . referring now to fig4 in which there are shown a pair of complementary counterpart magnetic buckles in magnetic engagement , it can be seen that the magnetic coupling surfaces of the counterpart buckles a and b with magnetic coupling surfaces ( 11 ) of the opposite magnetic polarities are in physical contact . it should be noted that while it is preferable that both of the complementary buckles are of the same structural design as mentioned herein , a buckle of a different design but of a complementary nature can be used as a counterpart buckle or fastener . as can be seen from this figure , the laterally or radially extending strap receiving portions help to reduce the overall thickness of the engaged buckle pair , making the assembly particularly suitable for use in circumstances , for example in lingerie and brassiere applications , where a thin assembly is desirable . furthermore , in order to alleviate the risks of undesirable or accidental disengagement of the magnetically coupled buckle pairs , the portion of the peripheral wall at the end of the cavity casing directly opposing the strap receiving portion is made with a small projection or with an elevated teeth ( 26 ) resembling portion . the protruding portion ( 26 ) of the buckle is formed on the cavity wall ( 23 ) and extends beyond the surface of its magnetic coupling surface ( 11 ). this projection ( 26 ) will become a barrier member to the magnetic member ( 10 ) of the counterpart buckle by extending also beyond the magnetic coupling surface ( 11 ) of the counterpart buckle . with the elevated portion engaging with the edge of the magnetic member of the corresponding counterpart buckle , undesirable lateral slippage in both the left and right directions , i . e ., directions along both strap receiving portions can be greatly alleviated . when the buckles are to be uncoupled , a user only needs to slightly lift one of the buckles , for example , by pivoting against the counterpart buckle and then separating the buckles . to ensure sufficient space for accommodating the protruding member ( 26 ) without having to press against the bridging portion , a slight indentation corresponding to the location of the protruding portion is preferably provided so that the teeth ( 26 ) can rest above and away from the bridging portion . this slight indentation may also be accompanied by a discontinuation of the perimetric wall at the corresponding position to allow engagement of the teeth member . as shown in the figures , the indentation is formed at the intersection or junction between the bridging portion and the cavity housing . in the present specific example , the housing is integrally formed of a magnetic material so that one of the magnetic surfaces is in contact with the base portion while the peripheral wall of the magnetic member is enclosed within the cavity housing , leaving the magnetic coupling surface exposed . where a ring - or toroidal - shaped magnet member is used , the cavity housing may have a hollow base portion . to provide a decoration or an aesthetic design , the buckle may be enclosed within a thin magnetic permeable enclosure made , for example of , pvc , synthetic resins , rubber , nylon or the like material . furthermore , while the permanent magnet ( 10 ) is held by a holder portion which is made preferably of a magnetic material in order to strengthen and concentrate the magnetic force on the exposed polar surface of the permanent magnet , it should be appreciated that the present invention can be made by having a magnetic enclosed within a housing which does not have the effect of concentrating the magnetic strength on a particular polar surface as long as there is provided a strap receiving means transverse or side - wise to the magnetic axis of the permanent magnet . in another embodiment of the present invention as shown in fig5 a to 5 b , a strap fastener ( 50 ) contains a housing ( 52 ) and a magnetic member ( 56 ) similar to the one described in the previous embodiment including strap receiving portion ( 54 ) and receptacle ( 52 c ). receptacle ( 52 c ) contains a base portion ( 52 a ) and side wall ( 52 b ). in this embodiment , the base portion ( 52 a ) is circular in shape with one side ( 54 a ) extending outwards to connect with the strap receiving portion ( 54 ). a magnet ( 56 ) of the same dimension as the base portion ( 52 a ) is provided for attachment into the receptacle ( 52 c ). in this embodiment , another strap fastener ( 60 ) having a housing portion ( 62 ) with a strap receiving portion ( 64 ) is provided to engage the first fastener ( 50 ) for proper functioning of this pair of fasteners . the base portion ( 62 a ) of the second fastener ( 60 ) is larger in diameter compared to the base portion ( 52 a ) of the first fastener ( 50 ). another magnet ( 66 ) larger in diameter than the first magnet ( 56 ) is provided for attachment into the receptacle area ( 62 c ) of the larger fastener ( 60 ). the perimeter wall ( 62 b ) of the larger fastener ( 60 ) is higher than the height of the attached magnet ( 66 ) as shown in fig5 b . as in the smaller fastener , the base portion ( 62 a ) of the larger fastener ( 60 ) is connected to the strap receiving portion ( 64 ) via an extended side ( 64 a ). during operation , the smaller fastener ( 50 ) is attached to the larger fastener ( 60 ) as shown in fig5 d . as the side wall ( 62 b ) of larger fastener ( 60 ) is higher than the magnet ( 66 ) attached , the smaller strap fastener ( 50 ) will engage larger fastener ( 60 ) in a manner such that the extended portion of the side wall ( 62 b ) will act as a stopping mechanism to prevent lateral movement between smaller fastener ( 50 ) and larger fastener ( 60 ). to disengage the two fasteners , a twisting force or pulling force in a direction substantially parallel to the magnetic axis ( 70 ) may be used in a single action . no further action is required to disengage the stopping mechanism . as can be seen by the previous discussion , the phrase “ substantially parallel to the magnetic axis ” is meant for ease of understanding and includes a twisting action to pull a pair of magnetic fasteners apart . in another embodiment shown in fig6 a to 6 e , the strap fastener ( 82 ) according to another embodiment of the present invention has a housing containing a receptacle ( 80 ) and a strap fastening portion ( 84 ) similar to the previous embodiments . the main difference in this embodiment is that the peripheral wall ( 82 b ) that is attached to the circular base portion ( 82 a ) of the receptacle ( 80 ) of the strap fastener ( 82 ) is bevelled with a tall end ( 82 d ) and a short end ( 82 e ). the tall and short ends are preferably on opposite sides of the circularly shaped base portion ( 82 a ) with the short side ( 82 e ) adjacent the strap fastening portion ( 84 ). the magnet ( 86 ) has a thickness that is shorter than the tall end ( 82 d ) of the peripheral wall , but approximately the same height as the short end ( 82 e ) as shown in fig6 b . as in the other embodiments , a connecting area ( 84 a ) connects the strap fastening portion ( 84 ) to the receptacle ( 82 ). the connecting portion ( 84 a ) is extending outwards from the base portion as shown in fig6 b and fig6 c . during fastening engagement , as shown in fig6 d , two bevelled fasteners with facing magnetic poles attracting each other according to the present embodiment may be engaged in facing directions with the tall end of the wall ( 82 d ) coupled to the short end ( 82 e ) of the wall . in the preferred embodiment , the tall end ( 82 d ) is tall enough to extend within the extended portion ( 84 a ). it is clear from the description above that lateral movements parallel to the strap fastener portion and perpendicular to the magnetic axis ( 89 ) is restricted as the engagement of the tall end with the short end together with the bracing action of the strap fastening portion acts as the stopping mechanism in the present embodiment . the advantage of this embodiment is that lateral rotational movement between the two engaged fasteners is minimized due to the restrictions engaged by the two bevelled walls when they are functionally engaged . while the magnet in the above description is described as being disc - shaped , it is clear that any magnetic element that can function within the receptacle and contains the features as claimed in the following claims would fall within the scope of the present invention . as shown in fig7 a to 7 e , the magnet according to the present invention may also be of a ring shape as shown by reference numeral 80 of fig7 c . a base plate ( 82 ), preferably with a raised internal circular portion ( 82 b ), is preferably provided for attachment onto the magnetic ring ( 80 ). the entire magnetic element ( including plate ( 82 ) and ring ( 80 )) can then be used like a magnet for attachment to the receptacle in the fastening . for example , the magnet shown in reference numerals 86 , 56 and 66 may actually consist of a magnetic ring and a metallic disk as shown in fig7 b . the advantage of such a magnetic set is that expensive magnetic material may be reduced due to the hole in the centre of the ring . this , however , does not substantially reduce the magnetism of the magnet set because the base plate may be made of a ferro - magnetic substance such as chromium or of nickel plated steel that can concentrate the magnet along magnetic axis ( 88 ) and in the direction unshielded by the base plate . the base plate is the side of the magnetic set that is attached to and adjacent the base portion of the previous - described fasteners while the magnetic ring is exposed for interaction with another magnetic attached to a matching fastener . while the present invention has been explained by reference to the preferred embodiments above , it should be appreciated that the embodiments are provided for illustration and assisting understanding only and do not intend to limit or restrict the scope of the present invention . for ease of description , the polarity of the magnetic members of each of the fasteners have not been specifically stated . it is however clear for one of ordinary skilled in the art that for a pair of fasteners to work according to the present invention , each pair of functionally engaged fasteners would have magnetic members of opposite polarity facing each other in the two matching fasteners .

a strap fastener comprising a pair of engageable magnetic fasteners of opposite polarity to each other engageable or a common axis , a strap engagement portion connected to each magnetic fastener and extending transverse to said common axis of engagement of said magnetic fasteners ; and at least one protrusion to reside against a perimeter of an opposed magnetic fastener to resist movement of one magnetic fastener with respect to the other transverse to said common axis on which they engage .

tapentadol , i . e . (−)-( 1r , 2r )- 3 -( 3 - dimethylamino - 1 - ethyl - 2 - methyl - propyl )- phenol , is a synthetic , centrally acting analgesic which is effective in the treatment of moderate to severe , acute or chronic pain . it has surprisingly been found that the enantiomer of tapentadol , ( 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol ) has a unique bioavailability . ( 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol ) has a potency similar to that of fentanyl , and it has been shown that this compound induces antinociceptive effects after local injection into the spinal cord in an animal model of acute pain ( see example 2 ). however , it has surprisingly been found that 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methyl - propyl ] phenol has no relevant oral bioavailability or intravenous bioavailability in humans because the compound is rapidly metabolized in the blood of humans by very rapid uptake and sulphation that occurs in blood thrombocytes . this unique bioavailability provides useful characteristics in a variety of clinical situations . in particular , this compound is useful for treating subjects who are not able to take oral opioids , and require intrathecal or epidural opioid administration . for example , during childbirth , women often receive epidural or intrathecal opioids alone , or in combination with a local anesthetic . opioids administered this way can inadvertently be absorbed systemically through the incorrect placement of the epidural catheter , or by using lipid soluble opioids like fentanyl or sufentanil that are more prone to leak into the maternal systemic circulation and can thus be transferred trans - placentally to the infant during delivery . in rare cases , this can lead to respiratory depression in the infant , which requires resuscitation of the infant . another example of a clinical situation in which this unique bioavailability would be useful is in subjects receiving opioid treatments through epidural catheters or implanted intrathecal pumps for severe chronic pain or cancer pain . subjects receiving this type of treatment are typically thus treated to decrease the incidence of peripherally or supraspinally mediated opioid side effects such as obstipation , gi dysfunction , components of nausea and vomiting , potentially components of urinary retention etc . by using the compound of the present invention , the side effects resulting from the opioid entering the blood stream would be mitigated or eliminated entirely . once the compound enters the blood stream , the compound is rapidly sulphated by thrombocytes and is therefore inactivated . because the cerebrospinal fluid ( csf ) and the epidural space are free of thrombocytes , the compound remains available for action in these spaces . suitable for the administration of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methyl - propyl ] phenol are also spaces with no or minor metabolism by thrombocytes . accordingly , the different embodiments of the invention as described herein also relate to the use of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methyl - propyl ] phenol or a physiologically acceptable salt thereof in spaces with no or minor metabolism by thrombocytes . until now , no existing opioid has been reported that is thus restricted after local administration to the epidural or intrathecal space . in summary , local epidural or intrathecal administration together with lack of systemic bioavailability offer the option of effective pain treatment without typical systemic , peripherally or supraspinally mediated , opioid side effects such as respiratory depression , addiction , dependency , nausea , vomitus , constipation / obstipation , and urinary retention . in addition , the method offers a treatment option with no trans - placentally exposure during delivery and ensures safety of the newborn child . 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol , can be made using the method described in u . s . pat . no . 6 , 248 , 737 , the entire disclosure of which is hereby incorporated by reference . the pharmaceutical composition of the present invention can be formulated for administration to a subject via various routes . the term “ subject ” as used herein can be a mammal , for example a human , or a patient . the term “ subject in need thereof ”, as used herein , is for example a mammal in need of pain relief , a human in need of pain relief , or a patient in need of pain relief . the pharmaceutical composition of the present invention can be formulated for administration to a subject via any route that introduces the composition into a space void of thrombocytes . for example , administration can be made in the intrathecal , epidural or intracerebroventricular spaces . the pharmaceutical composition of the present invention can be administered intrathecally by continuous infusion such as with a catheter , or a pump , or intrathecally by a single bolus injection or by intermittent bolus injection . additionally , the pharmaceutical composition of the present invention can be administered epidurally by continuous infusion such as with a catheter , or a pump , or by a single bolus injection or by intermittent bolus injection . as used herein , the terms “ intermittent bolus injection ” or “ intermittent bolus dose ” include , for example , the administration of the pharmaceutical composition to the subject more than one time but not continuously . this intermittent administration can be for example , administration of the pharmaceutical composition every thirty minutes , every hour , every few hours , every several hours , every day , or every couple of days , or combinations thereof . when the pharmaceutical composition of the present invention is administered by continuous infusion , implantable delivery devices , such as an implantable pump may be employed . examples of delivery devices that can be used within the scope of the invention include devices which can be implanted subcutaneously in the body or on the cranium , and provides an access port through which therapeutic agents may be delivered to the nerves or brain . delivery occurs through an implanted catheter . the infusion pump may be an intrathecal pump , an epidural delivery infusion pump , or a patient control analgesia pump . the pharmaceutical composition of the present invention is advantageously administered in the form of a substantially pure stereoisomer , in particular , enantiomer or diastereomer , or in the form of a mixture of the stereoisomers containing predominantly the 1s , 2s enantiomers or diastereomers . depending upon the formulation , the pharmaceutical composition of the invention preferably contains suitable additives and / or excipients . suitable additives and / or excipients for the purpose of the invention include all such substances for the preparation of galenic formulations known to persons skilled in the art . the selection of these excipients and the amounts to be used depend upon how the pharmaceutical composition is to be administered , as well as on the weight and condition of the subject and can readily be determined by a person of ordinary skill by routine experimentation . examples of suitable additives and / or excipients include water , buffered saline , ethanol , polyol ( for example , glycerol , propylene glycol , liquid polyethylene glycol and the like ), dimethyl sulfoxide ( dmso ), oils , injectable organic esters , such as ethyl oleate , detergents , preservatives , wetting agents , emulsifying agents , dispersing agents , suspending agents or suitable mixtures thereof . furthermore , this compound can be administered in combination with local anesthetics or other analgesics suitable for administration in the epidural or intrathecal space . the amount of active ingredient to be administered to the subject varies depending on the weight of the subject , on the type of administration , the indication being treated , and on the severity of the pain . the active ingredient can be formulated for administration in a one dose bolus injection , in a continuous infusion , or as a single dose to be intermittently administered throughout the course of treatment . methods of determining the most effective means and dosage of administration are well known to those of skill in the art and vary with the composition used for therapy , the purpose of the therapy , and the subject being treated . single or multiple administrations are carried out with the dose level and pattern being selected by the treating physician . when the active ingredient is formulated for administration in a single dose , i . e ., a bolus injection , or as a dose to be administered intermittently throughout the course of treatment , normally less than 1 mg , preferably less than 500 μg , and particularly preferably less than 250 μg of the active ingredient is administered per kg of subject body weight . when the active ingredient is formulated for administration as a continuous infusion , normally less than 250 μg per kg of subject body weight is administered per hour , more preferably , less than 125 μg per kg of subject body weight is administered per hour , and even more preferably , less than 75 μg per kg of subject body weight is administered per hour . the following examples are provided in order to demonstrate and further illustrate certain preferred embodiments and aspects of the present invention and are not to be construed as limiting the scope thereof . the probability of different routes of metabolic clearance in vivo can be investigated by estimating the rates of the underlying oxidation or conjugation reactions in vitro using sub - cellular fractions such as hepatic microsomes . because the rate of microsomal oxidation of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol could be shown to be very low , it was considered that oxidative metabolism was unlikely to be a significant metabolic clearance route for this molecule . a similarly low rate of microsomal oxidation was also demonstrated for the enantiomeric antipode of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol ( hereinafter 3 -[( 1r , 2r )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol ). the principal route of metabolic clearance of 3 -[( 1r , 2r )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol in most species , including humans , is glucuronidation , and this route was therefore considered to be very likely to be dominant for 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol as well . indeed , in vitro investigations showed that the rates of glucuronidation of the two enantiomers were very similar . consequently , as the oral bioavailability of 3 -[( 1r , 2r )- 3 -( dimethylamino )- 1 - ethyl - 2 - methyl - propyl ] phenol in humans was known to be ca . 33 %, it was expected that the oral bioavailability of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol in humans would be similar . surprisingly , the oral bioavailability of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol was effectively zero . on examination of the pharmacokinetics of the two compounds after intravenous administration , it became clear that the rate of elimination of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol was much higher than that of 3 -[( 1r , 2r )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol , and higher even than could be explained on clearance of the total hepatic blood flow . the elimination halftime of 3 -[( 1r , 2r )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol in humans is ca . 3 . 2 h ; if the clearance of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol was limited by the liver blood flow , an elimination halftime of 2 . 2 h would be expected . in fact , the elimination halftime of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol was ca . 0 . 75 h . after intravenous administrations of equal doses , the initial plasma concentrations of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol and 3 -[( 1r , 2r )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol are essentially identical , proving that the two enantiomers distribute similarly . consequently , the short elimination halftime of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol can be explained only if its clearance occurs at 5 - fold the hepatic blood flow , indicating that supplementary , presumably non - hepatic , clearance route ( s ) are involved . clearances of the order of cardiac output could result from extensive metabolism in the lung as the complete cardiac output passes this organ . however , as there are no known lung - specific metabolic clearance routes which could be expected to apply more to 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol than to 3 -[( 1r , 2r )- 3 -( dimethylamino )- 1 - ethyl - 2 - methyl - propyl ] phenol , this appeared to be an unlikely explanation . the remaining possibility was that the high clearance was due to a stereo - selective biochemical process occurring in blood itself . if true , then it would be expected that 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol , but not 3 -[( 1r , 2r )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol , would be metabolised in a time -, concentration -, and temperature - dependent manner by whole human blood . to test the hypothesis , blood was withdrawn from healthy volunteers , heparinised ( final heparin concentration , 15 u / ml ), and spiked with 1 μm 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol or 3 -[( 1r , 2r )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol . it was mixed on a rotary mixer at 37 ° c . in closed test - tubes . the rate of loss of the added compounds was determined by taking aliquots at regular intervals , centrifuging at 5000 g for 5 minutes , and analysing the supernatant . supernatants were alkalinized by addition of aqueous 25 % ammonia ( 50 μl / ml plasma ), spiked with an internal standard , and extracted twice with tertiary butyl methyl ether ( 2 ml per ml plasma ). the ether layers were combined and dried in a stream of nitrogen before being reconstituted in 150 μl chromatography buffer ( see below ). all assay supernatants were analysed by reversed - phase hplc on a inertsil 5 ods 2 column ( 250 × 4 . 6 mm ). the hplc system consisted of equipment from dionex or gynkotek . the auto - sampler was a gina 50t unit ( gynkotek ); the pump system was type p580a lpg ( gynkotek ); the column was thermostatted at 30 ° c . using a sht 585 unit ( gynkotek ). effluents were generally monitored for fluorescence emission at 300 nm after excitation at 215 nm using a rf 2000 detector ( dionex ); the wavelengths for excitation and emission were chosen to be optimal for 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol or 3 -[( 1r , 2r )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ]- phenol . chromatograms were evaluated using chromeleon software version 6 . 11 ( dionex ). generally , the samples were eluted using an isocratic solvent mixture . sodium pentane - sulphonate was dissolved at 1 . 92 g / l ( 10 mm )= pss ; perchloric acid ( pa ) was 60 % w / v . a mixture containing 900 ml pss , 210 ml methanol , 80 ml tetrahydrofuran , and 0 . 1 ml pa was made , allowed to stand overnight , and degassed prior to passage over the column . the effluent was passed first through the uv detector , and then into the fluorescence detector . no loss of 3 -[( 1r , 2r )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol was observed . in contrast , a linear loss of 35 % of the added 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol was observed over the course of one hour . this value is very close to the supplementary loss of 50 %/ h ( in addition to the expected glucuronidation rate ) needed to explain the human in vivo clearance . when the same experiment was conducted at room temperature ( 24 ° c . ), a loss of only 7 % was observed ; and at 6 ° c ., no loss was observed . evidently the involved process was temperature - dependent . at concentrations in excess of 1 μm 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol , net losses in whole blood were sub - linear , suggesting that the clearance process was enzymatic and evidently saturable at concentrations above 2 μm — though not at pharmacologically relevant concentrations (& lt ; 1 μm ). blood consists of plasma , plasma enzymes , and various blood cell types ( erythrocytes , leukocytes , thrombocytes etc ). 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol was expected , and proven , to be stable to plasma . of the blood cell types , thrombocytes ( platelets ) were expected to have the highest relevant enzymatic activity in sult1a3 , a sulphotransferase . thrombocyte ( platelet -) enriched plasma can be prepared by centrifuging blood at 400 g for 10 minutes as this precipitates larger cells ( erythrocytes , leukocytes ). incubation in the thrombocyte - enriched plasma won from a given volume of blood was able to cause the loss of an amount of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol ( but not of 3 -[( 1r , 2r )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol ) equivalent to that observed on incubation in the original volume of whole blood in a time -, concentration -, and temperature - dependent fashion , suggesting that the losses were caused by thrombocytes only . from the concentration dependency of the reaction rate , the km of the process was estimated to be 3 . 5 μm . after incubation of 14c - 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol with whole blood or thrombocyte - enriched plasma , only a single reaction product was observed , and this eluted identically on hlpc to synthetic 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol - sulphate . thrombocyte sulphotransferase sult1a3 conjugates and thereby inactivates systemic biogenic amines ( dopamine , noradrenaline , serotonin ). these biogenic amines are transported into the thrombocytes by specific transporters which can be inhibited by a variety of compounds . it was shown that the rate of conjugation of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol was influenced neither by inhibitors of dopamine transport ( cocaine , 10 μm ; nomifensin , 10 μm ; amphetamine , 100 μm ) nor inhibitors of noradrenaline transport ( fluoxetine , 10 μm ), nor inhibitors of serotonin transport ( desipramine , 100 μm ). in addition , no accumulation of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol - sulphate was observed in pelleted thrombocytes under any condition . consequently , import of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol into the cells , nor export of the conjugated metabolite , appears to require the assistance of any of these transporters . as no accumulation of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol - sulphate was observed in thrombocytes , it is unlikely that it could affect thrombocyte function . as the km of the reaction ( 3 . 5 μm ) is well above physiologically relevant concentrations (& lt ; 1 μm ), the rate of sulphation will be linearly related to the 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol concentration . in addition , it will be proportional to the thrombocyte count in blood . this is typically 1 . 5 - 3 . 0 * 10 5 cells / μl , but may be reduced 10 - fold in thrombocytopenia ; this can occur in bone - marrow diseases , after cytostatic or radio - therapy , or on treatment with diuretics , penicillins or streptomycin . in subjects with extreme thrombopenia , it can be assumed that metabolic clearance of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ]- phenol will occur predominantly by glucuronidation at a rate equivalent to that observed for 3 -[( 1r , 2r )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol , increasing the halftime of elimination from 0 . 75 h to ca . 3 h . in conclusion , 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol is cleared by a novel route , sulphation by thrombocytes . this guarantees that its rate of clearance is very high , which would prevent it accumulating systemically to concentrations at which it could evoke general central pharmacological effects . thus if applied locally , especially in at a low dose rate , it is likely that only local pharmacological effects will occur . efficacy of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol after intrathecal drug administration in an animal model for acute nociceptive pain antinociceptive effects of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ]- phenol were evaluated in the low intensity tail - flick test after local drug application into the spinal cord of rats . 160 male sprague dawley rats ( 200 to 260 g body weight ) from a commercial breeder ( janvier , le genest st isle , france ) were housed under standardized conditions : light / dark rhythm ( 06 . 00 - 18 . 00 h light , 18 . 00 - 06 . 00 h dark ); room temperature 20 - 24 ° c . ; relative air humidity 35 - 70 %; 15 air changes per hour , air movement & lt ; 0 . 2 m / sec . the animals were given water and feedstuff designed for rats / mice / hamsters from nohrlin ( bad salzuflen , frg ) ad libitum . they were kept in groups of six in makrolon cages type 4 . there were at least 5 days between the day of delivery and the day of testing . the experiments were performed using a tail - flick device from rhema - labortechnik ( hofheim / ts ., frg ). before and after drug application , a radiant heat beam was focused onto the dorsal surface of the rat &# 39 ; s tail about 2 to 4 cm apart from the root . during the test , the animals were restrained . the latency from switching on the lamp to tail withdrawal was measured . the intensity of the radiant heat beam was adjusted to 40 % of the maximum value so that a mean pre - test value of 4 . 5 - 9 sec was obtained for each animal group . only animals which showed both pre - test latencies of 15 sec or lower , and whose pre - test values did not differ by more than 2 sec , were used for testing . to avoid tissue damage , the radiant heat beam was switched off at the latest after 30 sec if the tail was not withdrawn . the animals were tested 10 , 20 , 30 , 60 , 90 and 120 min p . appl . intrathecal administrations of 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol were performed under light ether anesthesia , by injecting between l1 and l3 . a control group was treated with 0 . 9 % saline . the individual latencies were calculated as the percentage of the maximum possible effect (% mpe ) according to the following formula : after intrathecal ( i . t .) administration of 3 . 15 μg / animal , 3 -[( 1s , 2s )- 3 -( dimethylamino )- 1 - ethyl - 2 - methylpropyl ] phenol induced an antinociceptive effect which was long - lasting and reached a maximum of 59 . 71 ± 2 . 94 % mpe 20 min p . appl . as shown in fig1 . tail withdrawal latencies are expressed as percentage of maximum possible effect (% mpe ). control animals were injected i . t . with saline . data are expressed as mean ± s . e . m . ( n = 10 ). 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 described 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 within the scope of the appended claims and equivalents thereof .

the present invention relates to a method of providing pain management in a subject wherein the administration of the composition does not result in any non - central nervous system mediated systemic effect in the subject . in particular , the present invention relates to a method of administering 3 -- 3 -- 1 - ethyl - 2 - methyl - propyl ]- phenol in a space that is void of thrombocytes .

the polypeptide of this invention can be isolated and purified by conventional methods applied for peptides , e . g ., extraction with solvents and low - or high - performance liquid chromatography . the polypeptide of this invention can be synthesized by a solid phase peptide synthesizer . a silkworm is an industrially valuable silk - producing insect . to efficiently produce eggs of silkworms and to preserve the eggs in safety are very important in the production of silk . the diapause hormone will positively be used for preservation and stable supply of the silkworm &# 39 ; s eggs , because the eggs are diapaused and kept at an early stage by the hormone , which enables stable supply of silkworm &# 39 ; s larvae . in the meantime , some kinds of insects are harmful mainly at their growing stage on agriculture , forestry , and hygiene . the diapause hormone can positively diapause the harmful insects at the actively feeding stage and control them . as described above , an elucidation of the diapause hormone has been desired for preservation and stable supply of the silkworm &# 39 ; s eggs and control of the harmful insects . subaesophageal ganglia , which are diapause hormone - secreting organs , were excised with the first thoracic ganglia in insect physiological saline ( 0 . 75 % nacl ) from about one hundred thousand silkworm ( bombyx mori ) pupae immediately after the transformation to a pupa under an anatomy microscope to yield about 5 g of them . the obtained organs were put into 100 % ethanol immediately after the excision , and then frozen and preserved at - 20 ° c . the ganglions were recovered by low - speed centrifugation , and then triturated in 100 % ethanol . the resultant was centrifuged at low speed to obtain a precipitate . the precipitate was washed with ethanol three times , and then extracted with 150 ml of methanol - dichloromethane ( 1 : 1 ) three times to obtain a precipitate . the obtained precipitate was washed with 150 ml of 50 % 2 - propanol three times and with 150 ml of 80 % ethanol three times . to the resulting precipitate 150 ml of distilled water was added , heated in boiling water for 10 minutes , cooled on ice , and then centrifuged at 12 , 000 g for 20 minutes to obtain a supernatant . a remaining precipitate was extracted with water in the same manner as described above , and a resulting supernatant was added to the previously obtained supernatant . the extraction with hot water was effective for abolishing the activity of many proteases as well as for extracting the hormone . the extract with hot water was evaporated to dryness under reduced pressure at 35 ° c . and dissolved in 1 ml of distilled water , and then insoluble material was filtered off with a filter paper whose pore size was 4 . 5 μm . the filtrate was applied on reversed phase high - performance liquid chromatography under the following condition . the column was equilibrated with solvent a for 30 minutes . on the column 200 μl of the above - obtained specimen was loaded five times , followed by washing the column with water for 15 minutes . then , the column was put to gradient elution so that solvent b reached 7 % in 10 minutes and 13 % in 60 minutes to eliminate impurities . furthermore , the elution was carried out with 13 % solvent b for 80 minutes . then , it was continued so that solvent b reached 35 % in 60 minutes , the status was remained for 30 minutes , and finally the column was washed with 100 % solvent b to be regenerated . detector : 875 type uv absorption type detector ( nihon bunkohsya ). the detection was carried out at 210 and 280 nm . the diapause hormone was eluted 100 to 120 minutes after the iniation of the gradient elution . the obtained hormone - activity was reseparated by reversed phase high - performance liquid chromatography conducted under the following condition . after the column was equilibrated with solvent a for 30 minutes , 200 μl of the specimen was loaded on the column five times , followed by washing the column with solvent a for 15 minutes . then , the column was put to gradient elution so that solvent b reached 50 % in 120 minutes . finally , the column was washed with 100 % solvent b to be regenerated . a detector and condition of the detection were the same as above . a bioassay was carried out on a lot of peaks of the chromatogram . as a result , only the sharp peak with retention time of about 50 minutes showed the hormonal activity and was identified as a diapause hormone . a yield of the hormone was about 1 μg . using 500 ng of the isolated diapause hormone , structure of the hormone was analyzed by an automatic gas phase peptide sequencer ( model 477a / 120a protein / peptide sequencer pht analyzer ; applied biosystems ). as a result , the structure of the diapause hormone was determined as follows : ## str4 ## wherein x is cys ( seq id no : 1 ) or trp ( seq id no : 2 ). furthermore , after the hormone was cleaved with endoprotease glu - c ( protease v8 : specific to the c terminus of glu ), the cleavage products were separated by a conventional method using hplc , and each product was sequenced by an gas phase peptide sequencer . as a result , though a part of the amino acid sequence could not be identified because of a very small amount of the specimen , an amino acid sequence of the longest peptide among the cleavage products was identical with that from position 15 to 24 of the above - established amino acid sequence of the diapause hormone . this result made the above hormonal structure confirmative . molecular weight of the hormone which was calculated from this structure agreed with 2 , 500 of molecular weight deduced from a gel filtration analysis ( column ; tskgel 2000sw , tosoh co ., developing solvent ; 0 . 05 % trifluoroacetic acid ). the fact that the diapause hormone had retention time of about 50 minutes on reversed phase high - performance liquid chromatograph analysis ( tskgel octadecyl - 4pw column , tosoh co ., 0 . 05 % trifluoroacetic acid - 2 - propanol system gradient elution , the same condition as that of the above purification in second step .) showed character of the molecule of the present hormone . there exists a strain of a silkworm which does not diapause , called non - diapause strain , e . g ., n 4 line . the hormonal activity was confirmed by the following method : the specimen is injected into the 4 days - age pupa of non - diapause strain . after the pupa transforms into a imago , copulates , and lays eggs , it is investigated whether or not the eggs diapause without embryogenesis . if the specimen does not have diapause activity , the laid eggs hatch out to larvae in about 10 days . in case that the specimen has the hormonal activity , the color of the eggs becomes blackish - brown which is not observed in non - diapausing eggs . the embryogenesis is terminated in the colored eggs , which do not hatch out to larvae . the hormonal activity is determined by calculating what percentage of the eggs laid by one imago diapauses . one diapause hormone unit is the amount of the hormone which make 50 % of the laid eggs diapause . in this invention , the isolated diapause hormone was 0 . 1 ng / unit . two kinds of diapause hormones consisting of the following amino acid sequence , in which the amino acid 19 is cys ( seq id no : 1 ) or trp ( seq id no : 2 ), are synthesized : ## str5 ## wherein x is cys or trp . amino acids protected by protecting groups including t - boc are condensed by dicyclohexylcarbodiimide on p - methyl - benzhydrylamine resin in order of the above amino acid sequence to obtain a protected crude peptide . the t - boc groups are removed by trifluoroacetic acid ( tfa ) and the protecting groups other than t - boc groups are by hydrogen fluoride ( hf ) from the protected crude peptide , which is eluted with 60 % acetonitrile - water ( 0 . 1 % tfa ) to obtain a crude peptide . the peptide is isolated by use of ods ( octadecyl silan ) column with 0 % to 60 % acetonitril - water ( 0 . 1 % tfa ) gradient system . in the case of trp 19 , the formyl group has yet bound at the n - position of trp . in order to remove the formyl group from the trp - n - formyl peptide , the peptide is dissolved in 20 mm piperidine solution and reacted until an absorption at 310 nm disappears and shifts to 280 nm . the resulting peptide is purified by ods type hplc to obtain a pure peptide . both of these synthesized peptides in which the amino acid 19 is cys and trp also have diapause activity like diapause hormone obtained from silkworm pupas . __________________________________________________________________________sequence listing ( 1 ) general information :( iii ) number of sequences : 2 ( 2 ) information for seq id no : 1 :( i ) sequence characteristics :( a ) length : 24 amino acids ( b ) type : amino acid ( d ) topology : linear ( ii ) molecule type : protein ( iii ) hypothetical : no ( vi ) original source :( a ) organism : bombyx mori ( d ) developmental stage : pupa ( f ) tissue type : subesophagus , thoracic cavity ( g ) cell type : ganglion ( xi ) sequence description : seq id no : 1 : thraspmetlysaspgluseraspargglyalahissergluarggly1510 15alaleucyspheglyproargleu20 ( 2 ) information for seq id no : 2 :( i ) sequence characteristics :( a ) length : 24 amino acids ( b ) type : amino acid ( d ) topology : linear ( ii ) molecule type : protein ( iii ) hypothetical : no ( vi ) original source :( a ) organism : bombyx mori ( d ) developmental stage : pupa ( f ) tissue type : subesophagus , thoracic cavity ( g ) cell type : ganglion ( xi ) sequence description : seq id no : 2 : thraspmetlysaspgluseraspargglyalahissergluarggly1510 15alaleutrppheglyproargleu20

this invention relates to a diapause hormone , a novel polypeptide , comprising 24 amino acids residues designated by the following amino acid sequence : ## str1 ## wherein x is cys or trp and r is oh or nh 2 .

for purposes of description herein , the terms “ upper ”, “ lower ”, “ right ”, “ left ”, “ rear ”, “ front ”, “ vertical ”, “ horizontal ” and derivatives thereof shall relate to the invention as oriented in fig1 . however , it is to be understood that the invention may assume various alternative orientations and step sequences , except where expressly specified to the contrary . it is also to be understood that the specific devices and processes illustrated in the attached drawings , and described in the following specification , are simply exemplary embodiments of the inventive concepts defined in the appended claims . hence , specific dimensions and other physical characteristics relating to the embodiments disclosed herein are not to be considered as limiting , unless the claims expressly state otherwise . the first illustrated embodiment of the device 1 according to the present invention for holding a coolant is shown in fig1 - 7 , and consists of a breathable polyurethane foil with an initial size of approximately 100 cm × 50 cm . this foil is arranged in two layers , resulting in a flat square plan shape , with the dimensions of approximately 50 cm × 50 cm . the folded over or bending edge of the foil is referred to by the reference numeral 2 . in the region of the three other edges , the foil boundaries are welded together , and the two parallel foil boundaries are referred to by the reference numerals 3 and 4 , and the foil boundary running parallel to the bending edge 2 is referred to by the reference numeral 5 . this results in a closed pad volume with the pad main faces 6 and 7 arranged between the bending edge 2 and the foil boundaries 3 - 5 , wherein the pad main face 6 faces the body part to be cooled during use , and the pad main face 7 faces away from the body part to be cooled during use of the pad . the two pad main faces 6 and 7 are interconnected by a plurality of spot welds , specifically with a point grid with thirty - six welding spots 8 for connecting the pad main faces 6 and 7 , wherein six rows of respectively six welding spots 8 are formed . the point grid formed by the thirty - six welding spots 8 has the outer contour of a square which runs symmetrically with respect to the outer contour of the pad . as a result of the various welding spots 8 , the interior volume of the device 1 or the pad is subdivided into a plurality or multiplicity of chambers 9 , as can be seen from the various sectional illustrations in accordance with fig2 - 5 . in these sectional illustrations , the device 1 with coolant 10 contained therein is shown . in this case , this is a mixture of water , e . g ., an amount of two to three liters of water , and a superabsorber , e . g ., ten to twelve grams of the superabsorber . thus , in this case the coolant 10 presents itself as a gel - like mass which can easily be displaced within the pad , in particular displaced between the chambers 9 , as a result of pressure acting on the pad main faces 6 and 7 . a sealable inlet valve 11 is provided for filling the pad 1 . the device 1 is delivered filled only with the superabsorber . the user then fills the device 1 with water through the sealable inlet valve 11 . after sealing the inlet valve 11 , the pad 1 is placed in a refrigerator or transport cold box and is stored at approximately + 5 ° celsius . hence , the pad is always ready for use at the mentioned temperature and then only has to be removed from the refrigerator or the transport cold box . the pad 1 has various attachment mechanisms for positioning it on a body part , particularly a human body part . a first attachment element 12 is , for example , designed as a hook and loop fastener , and has a fleece strap 13 connected to the foil boundary 3 in the region of the bending edge 2 , and a hook strap 14 connected to the foil boundary 4 in the region of the bending edge 2 . the fleece strap 13 and hook strap 14 can have various lengths . these two straps 13 and 14 run along and parallel with the longitudinal extent of the bending edge 2 in a loosely laid out state . a second attachment element 15 , which likewise is a hook and loop fastener , is connected to the pad 1 in the region of the foil boundary 5 . the second attachment element 15 has three hook straps 16 which are arranged parallel to the foil boundary 3 , approximately in the region of the third of the pad associated with this foil boundary 3 , and extend over approximately a third of the length of the foil boundary 3 . hence , these three hook straps 16 are connected to the pad main face 7 , as can be seen in particular in fig6 . three fleece straps 17 are attached to the pad main face 7 adjacent to the foil boundary 3 and in the third of the pad 1 adjacent to the foil boundary 3 . the ends of fleece straps 17 protrude over the foil boundary 5 in the initial planar condition of the pad 1 , and are oriented parallel to the foil boundaries 3 and 4 . the pad 1 can now be placed in the style of a bandana around the head 22 of a patient , as illustrated in fig7 . fig7 discloses that , with respect to the orientation of the pad according to fig1 , the lower half of the pad rests on the back of the head and to the side of the back of the head . the head hood formed in this fashion is closed in the region of the neck by the fleece strap 13 and the hook strap 14 , while the right and left halves of the upper half of the pad 1 are pulled into an overlapping arrangement , as a result of which the hook straps 16 and the fleece straps 17 reach a virtually aligned arrangement with respect to one another . consequently , the hood 18 can be closed in the region of the cranium by means of the hook straps 16 and the fleece straps 17 . compared to the embodiment according to fig1 to 7 , fig8 shows a slightly modified design of the pad 1 . it only differs in that , in the region of the foil boundary 5 , provision is made in the pad for a single slit 19 , which extends toward the bending edge 2 , and two slits 20 extending toward the foil boundary 5 . slits 20 extend inwardly from the bending edge 2 , and are not arranged centrally , like the slit 19 , but rather on the outside portions of the pad 1 , adjacent to the respective foil boundaries 3 or 4 . the respective slits 19 and 20 are produced by areal welding of the two pad main faces 6 and 7 in the region of the slits . the respective welding boundaries are noted by the reference numeral 21 . the slit 19 permits a particularly precise resting of the pad 1 in the region of the upper cranium of the patient because the regions of the pad adjacent to the slit 19 can be brought into an overlapping arrangement particularly easily , and can be attached by means of the hook strap 16 and the fleece strap 17 . the slits 20 are used for uncovering the neck of the patient in an uncomplicated fashion , in particular for applying an external vein access . the device 1 can additionally be provided with temperature sensors for detecting or acquiring the surface temperature of the pad , specifically the temperature of the pad main face 6 which rests on the body part . if the pad 1 is used as a head hood 18 , additional receptacles can be provided in the pad main face 6 for the insertion of ear protectors in order to avoid too much cooling of the ears of the patient . in the foregoing description , it will be readily appreciated by those skilled in the art that modifications may be made to the invention without departing from the concepts disclosed herein . such modifications are to be considered as included in the following claims , unless these claims by their language expressly state otherwise .

an apparatus for cooling a body part includes a flat and flexible closed container defining an interior volume with a plurality of interconnected chambers . an attachment member is connected with the container and is configured for removably attaching the apparatus to a body part . a superabsorber is disposed in the chambers , and the chambers are shaped to be filled with water .

the present invention overcomes many of the prior art problems associated with distributing compressed air foam ( caf ) and the like for fire suppression and other applications . the advantages , and other features of the technology disclosed herein , will become more readily apparent to those having ordinary skill in the art from the following detailed description of certain preferred embodiments taken in conjunction with the drawings which set forth representative embodiments of the present invention . the illustrated embodiments can be understood as providing exemplary features of varying detail of certain embodiments , and therefore , unless otherwise specified , features , components , modules , elements , and / or aspects of the illustrations can be otherwise combined , interconnected , sequenced , separated , interchanged , positioned , and / or rearranged without materially departing from the disclosed systems or methods . additionally , the shapes and sizes of components are illustrative and exemplary , and unless otherwise specified , can be altered without materially affecting or limiting the disclosed technology . all relative descriptions herein such as left , right , up , and down are with reference to the figures , and not meant in a limiting sense . now referring to fig1 , a perspective view of a fire suppression nozzle assembly 100 particularly well - suited for distributing compressed air foam ( caf ) in accordance with the subject technology is shown . the fire suppression nozzle assembly 100 may be utilized in a wide variety of applications such as those shown and discussed in u . s . pat . no . 7 , 712 , 542 . the fire suppression nozzle assembly 100 includes a manifold body 102 for distributing a flow of caf to a plurality of angled nozzles 104 and a central nozzle 118 . the angled nozzles 104 are arranged to create a large circular spray pattern while the central nozzle 118 creates a smaller centralized circular spray pattern to yield caf dispersed evenly in the entire spray pattern . in the design of fire suppression systems , different spray patterns are often required to spray onto , around and under objects that may be protected or present an obstruction to the spray . by increasing or decreasing the number of nozzles 104 and / or by changing the orientation of the body 100 , different spray patterns may be created . referring now to fig2 and 2a , top and cross - sectional views of the manifold body 102 for the fire suppression nozzle assembly 100 are shown . the manifold body 102 defines a central inlet 106 at a proximal end 114 . the central inlet 106 forms a central passageway 112 along a central axis a that provides fluid to a plurality of angled outlets 108 in a distal end 110 . the changes in bore size of the central inlet 106 are made with sweeping smooth surfaces to minimize and avoid destruction of caf quality . the angled outlets 108 are arranged along an acute axis b at an angle α with respect to the central axis a . typical angles α are between 30 and 60 degrees . in one embodiment , the angle α is 45 degrees . the manifold body 102 also forms an axis c parallel to the axis a . the angled outlets 108 terminate in planar surfaces that contain an axis d . the angle δ formed between axis c and axis d helps determine the resulting spray pattern . typical angles δ are between 10 and 50 degrees . in one embodiment , the angle δ is 35 degrees . in another embodiment , the angle δ is 30 degrees . the manifold body 102 also forms a central outlet 116 axially aligned with the central inlet 106 along axis a and in fluid communication with the central inlet 106 . in the embodiment shown , the six angled outlets 108 are arranged in a circular or hexagonal pattern around the central outlet 116 as best seen fig2 . the angled outlets 108 are also evenly distributed about the central nozzle 118 . in an alternative embodiment , the angled outlets 108 could be unevenly clustered , a different number , or arranged in a different pattern such as an octagon , septagon , pentagon , square , a rectangle , a trapezoid , a triangle and the like to form a desired spray pattern . referring now to fig3 and 3a , perspective and cross - sectional views of an open spray nozzle 104 for a fire suppression nozzle assembly 100 in accordance with the subject technology is shown . these angled nozzles 104 provide directional spray and can be sized to meet various design requirements . the open spray nozzle 104 has a threaded frame 120 that defines a central bore 122 . fluid enters and exits the central bore 122 to impinge against a splitter 124 and defector 126 , which are held onto the frame 120 by a fastener 128 . the configuration of the angled nozzles 104 can be modified to create a desired solid uniform cone spray . referring now to fig4 , a perspective view of a spiral configuration central nozzle 118 for a fire suppression nozzle assembly 100 in accordance with the subject technology is shown . the central nozzle 118 also has a threaded frame 130 that defines a central bore 132 . fluid enters and exits the central bore 132 exit by flowing through a corkscrew end 134 . the central nozzle 118 can also be modified to create a desired solid cone shaped spray pattern with a round impact area . referring now to fig5 , a perspective view of a flat fan spray nozzle 140 for a fire suppression nozzle assembly in accordance with the subject technology is shown . the flat fan spray nozzle 118 also has a threaded frame 142 that defines a central bore 134 . fluid enters and exits the central bore 142 to impinge upon a distal head portion 144 . the distal head portion 144 has an arcuate surface 146 to create a wide angle flat fan spray pattern with uniform distributin and medium impact . the flat fan spray nozzle 140 can also be modified to create a desired spray pattern to yield an overall desired pattern once placed in a fire suppression nozzle assembly . as can be seen , various types , combinations , and arrangements of nozzles may be used on variously configured manifold bodies to create a desired spray pattern . now referring to fig6 , a top view of another manifold body 202 for a fire suppression nozzle assembly in accordance with the subject technology is shown . as will be appreciated by those of ordinary skill in the pertinent art , the manifold body 202 utilizes similar principles to the manifold body 102 described above . accordingly , like reference numerals preceded by the numeral “ 2 ” instead of the numeral “ 1 ”, are used to indicate like elements . the primary difference of the manifold body 202 in comparison to the manifold body 102 is that only four angled outlets 208 are formed in the distal end 210 . as a result , the spray pattern changes . it is envisioned that any arrangement and number of angled outlets 208 may be utilized . referring now to fig7 a - 7e , various views of still another fire suppression nozzle assembly 300 particularly well - suited for distributing caf in accordance with the subject technology is shown . as will be appreciated by those of ordinary skill in the pertinent art , the nozzle assembly 300 utilizes similar principles to the nozzle assembly 100 described above . accordingly , like reference numerals preceded by the numeral “ 3 ” instead of the numeral “ 1 ”, are used to indicate like elements . the nozzle assembly 300 includes a central inlet 306 that feeds a first central outlet 316 a axially aligned with the central inlet 306 . a sideways portion 330 extends substantially perpendicularly from the central inlet 306 and the first central outlet 316 . the sideways portion has a plurality of angled outlets 308 in fluid communication with the central inlet and spaced about a second central outlet 316 b , which is also in fluid communication with the central inlet 306 . a plurality of open nozzles 304 couple to the plurality of angled outlets 308 for directing caf . a spiral nozzle 318 couples to each of the first and second central outlets 316 a , 316 b for directing caf . in another embodiment , the manifold body 302 includes a second sideways portion that minors the first sideways portion to yield a substantially rectangular 32 × 10 foot spray pattern . it is envisioned that any arrangement and number of sideways portions , angled outlets , and central outlets may be utilized to accomplish a desired spray pattern . while the invention has been described with respect to preferred embodiments , those skilled in the art will readily appreciate that various changes and / or modifications can be made to the invention without departing from the spirit or scope of the invention . for example , aqueous film forming foam , halogen and the like may be delivered by systems in accordance with the subject technology as would be appreciated by those of ordinary skill in the pertinent art based upon review of the subject disclosure .

a fire extinguishing device for the uniform distribution of compressed air foam for fire suppression , connected to a piping network of a caf system . multiple nozzles of different types are connected to a single body , set at specific angles both horizontally and vertically . each nozzle is selected to provide a set discharge spray angle and positioned in the body of the device to provide the proper distribution . the device body has a female thread at the inlet for connection to the caf system in addition to female outlets at the discharge for connection of spray nozzles . the device may be used to create a 360 ° spray pattern or a 120 ° spray pattern depending on the application .

in the embodiment of fig1 - 8 , a cooker 18 for broiling food items 20 , such as hamburger patties ( fig1 - 16 ), has a kettle 22 supported by legs 24 and carrying a cover 26 through use of hinges 28 . after the items 20 enter one end of the kettle 22 , they are advanced continuously by intermittent pulses along a u - shaped path and before emerging from the same end of the kettle 22 , they are broiled on both sides as the result of being continuously subjected to heat thereabove emanating from electric heaters 30 carried by the cover 26 therewithin . flipover of the items 20 midway their travel ( fig1 - 16 ) occurs automatically as hereinafter explained . a primary , stationary grid 32 has a u - shaped configuration to present a first elongated leg 34 which receive the items 20 exteriorly of the kettle 22 for advancement through an opening 36 in one end 38 of the kettle 22 . the grid 32 has a semi - circular bight 40 at the opposite end 42 of the kettle 22 , made up of a first quadrant 44 , as a continuation of the leg 34 , and a second quadrant 46 from which a second leg 48 extends , terminating outside the kettle 22 after passing through the opening 36 , rendering the cooked items 20 accessible . the leg 48 is a continuation of the quadrant 46 and is disposed in spaced parallelism to the leg 34 . the leg 34 and its quadrant 44 slope upwardly as the end 38 of the kettle 22 is approached whereas the leg 48 and its quadrant 46 slope upwardly as the end 38 of the kettle 22 is approached , with the two u - shaped heaters 30 sloping accordingly ( fig1 ). the straight terminal ends of the quadrants 44 and 46 extend radially inwardly of the u - shaped end 42 with such end of the quadrant 44 spaced above the end of the quadrant 46 ( fig1 - 16 ). the grid 32 is removably supported by the kettle 22 through use of open top , notched lugs 50 rigid to the kettle 22 and by an upstanding tubular assembly 52 extending through the bottom of the kettle 22 at the axe 22 at the axis of the bight 40 . each leg 34 , 48 has a plurality of spaced , longitudinal rod elements 54 rigidly interconnected by cross bars 56 , the latter of which rest in the lugs 50 . the quadrant sections 44 and 46 have arcuate rod elements 58 joined by cross bars 60 at the terminal ends thereof , the bars 60 being supported by lugs 50 at the center of the wall 42 and by the assembly 52 . a u - shaped secondary grid 62 , shiftable up and down intermittently relative to the grid 32 is provided with sloping legs 64 and 66 corresponding to the legs 34 and 48 respectively and a bight 68 corresponding to the bight 40 . and , as in the case of the grid 32 , the bight 40 has a pair of sloping sections 70 , 72 in the form of quadrants corresponding to the quadrants 44 and 46 respectively . once again , as shown , the removable legs 64 , 66 have straight , spaced , parallel rod elements secured to cross bars , and the removable quadrants have arcuate rod elements secured to cross bars . however , each leg 64 , 66 has a pair of separate , end - to - end parts , and the quadrants 70 , 72 are separate from each other and from the legs 64 , 66 . each leg 64 , 66 is supported by a pair of elongated , inclined , spaced , walking beams 74 extending from the exterior of the kettle 22 and through the opening 36 , terminating adjacent the assembly 52 . the upper edges of the beams 74 are notched to receive the cross bars of the legs 64 , 66 and each beam 74 has a pair of spaced supporting members 76 depending therefrom . a motor 78 has a driveshaft 80 rotatably suspended from the bottom of the kettle 22 and provided with a pair of bevel gears 82 . each of the four driven eccentric shafts 84 , rotatably suspended from the bottom of the kettle 22 and corresponding with the members 76 , is provided with a bevel gear 86 . two of the eccentric shafts 84 radiate from the shaft 80 in one direction and have their gears 86 in mesh with corresponding gears 82 , whereas another pair of the eccentric shafts 84 radiate in the opposite direction from the shaft 80 and also have their gears 86 in mesh with corresponding gears 82 . thus , the eccentric shafts 84 on one side of the shaft 80 are rotated in one direction and the opposite pair of eccentric shafts 84 are driven in the opposite direction by the shaft 80 during operation of the motor 78 . each member 76 has a circular hole rotatably receiving eccentric portion 87 of the shaft 84 ( fig1 ). accordingly , the beams 74 and their legs 64 , 66 travel through essentially circular paths . the leg 64 rises , progresses toward the quadrant 44 , descends and regresses toward the end 38 during each cycle . simultaneously , the leg 66 rises , progresses toward the end 38 , descends and regresses toward the quadrant 46 . the rods of the legs of the grid 62 interleave with the rods 54 of the legs 34 , 48 such that , during each cycle , the legs of the grid 62 rise above the legs 34 , 48 to raise the items 20 off the legs 34 , 48 . after the items 20 on the leg 34 are raised they are advanced toward the quadrant 44 and then set back onto the leg 34 . conversely , after the items 20 on the leg 48 are raised they are advanced toward the end 38 and then set back onto the leg 48 . manifestly , such intermittent movement of the items 20 toward and away from the bight 40 takes place during each cycle of the beams 74 . incidentally , slots 88 in the bottom of the kettle 22 for clearing the members 76 are best shown in fig1 and 3 , and slots 90 ( fig4 ) in the end 38 clear the beams 74 . not shown are two brackets which extend upwardly from the bottom of the kettle 22 for supporting the two lugs 50 shown in fig2 between the legs 34 and 48 . referring now in more detail to the assembly 52 , especially fig5 - 8 , there is provided an outer , upright tube 92 , open at both ends and extending through the bottom of the kettle 22 , to which the tube 92 is firmly attached . bearings 94 in the tube 92 surround a vertically reciprocable , inner tube 96 which is oscillatory about its upright axis of reciprocation . the tube 96 is so moved by the continuation of shaft 80 passing through diametrically opposed clearance openings 100 in the tube 92 . the tube 96 has an oblong hole 102 with its major axis disposed vertically and an opposed , oblong hole 104 having its major axis disposed horizontally . a rotor 106 engaging the tube 96 in the hole 102 is eccentric to and rigid to the shaft 80 , and a rotor 108 engaging the tube 96 in the hole 104 is eccentric to and also rigid to the shaft 80 . a third tube 110 is an upper continuation of the tube 96 , although separate therefrom , and a fourth tube 112 is surrounded by the tubes 96 and 110 . a fifth tube 114 is disposed in the tube 110 at the upper end of the latter . a knurled cap 116 has an inner flange 118 loosely fitted into the tube 114 and a bolt 120 rigid thereto and threaded into a bar 122 extending across the tube 112 and notched at its ends into the tubes 96 and 112 . fasteners 124 attach a closure plate 126 for the bottom of the tube 112 to the bar 122 . notches are illustrated in fig5 - 7 for releasably receiving certain components of the grid assemblies 32 and 62 . the tube 112 has a number of such notches 128 at its upper edge for receiving the cross bars of the quadrant 72 which are , in turn , cleared by notches 130 in the tube 110 . the tube 110 is also provided with notches 132 in its upper edge which correspond to notches 133 in tube 114 for receiving the cross bar at the terminal end of the quadrant 70 . the outer tube 92 has notches 134 and 135 at its upper end which receive the proximal bars 56 and 60 respectively of the leg 34 whereas the cross bar 56 of the leg 48 is received in a long notch 136 in the tube 92 . therefore , the grids 32 and 62 may be removed from the kettle 22 by first turning the cap 116 to release the bolt 120 from the bar 122 . then , by slipping the tube 114 from within the tube 110 , the quadrant 70 is released from the notches 132 and 133 . next , the tube 110 may be slipped off the tube 112 to clear the notches 128 and 130 such as to release the quadrant 72 , and the leg 34 as well as the quadrant 48 can be readily removed from the notches 134 and 136 . the legs 34 and 48 are simply lifted out of the lugs 50 and the legs 64 and 66 are lifted off the beams 74 . a predetermined , elevated temperature is produced in the cooker 18 by use of a suitable control for the heaters 30 , and a desired speed of rotation of the shaft 80 is selected by a suitable control for the motor 78 . the food items 20 placed on the leg 34 of the grid 32 exteriorly of the cooker 18 , are advanced through the opening 36 of the kettle 22 , and cooking continues until they exit through the opening 36 on the leg 48 outside the wall 38 . rotation of the shaft 80 causes the shafts to rotate through the gears 82 and 86 causing rotation of all four eccentric shafts 84 in their corresponding members 76 . each time the leg 64 rises and progresses toward the quadrant 70 , the items 20 are raised off the leg 34 and advanced toward the end 42 of the kettle 22 . simultaneously , each time the leg 66 rises and progresses away from the quadrant 72 the items 20 are raised off the leg and advanced toward the end 38 of the kettle 42 . all the while , the shaft 80 rotates the rotors 106 and 108 continuously to oscillate and raise and lower the tube 96 as well as all parts carried thereby . this causes the quadrant 70 to raise the items 20 ( received from the leg 64 ) and carry the items 20 along an arcuate path toward the quadrant 72 . as demonstrated by fig1 - 16 , when the items 20 arrive at the discharge end of the quadrant 70 ( such end extending radially inwardly from the end 42 of the kettle 22 toward the assembly 52 ), they tilt downwardly and then fall upside down onto the lower quadrant 72 as shown by the arrows . immediately , the inverse side of the items 20 begin to cook , such cooking continuing throughout the arcuate movement along the quadrant 72 and the leg 66 . manifestly , the movement of the inverted items 20 along the quadrant 72 until delivered to the leg 66 also results from the rise and fall of the tube 96 by action of the rotor 108 and oscillation of the tube 96 during rotation of the rotor 106 . the up and down and arcuate movement is imparted from the assembly 52 to the quadrants 70 and 72 simultaneously with the quadrant 70 moving arcuately away from the leg 64 and the quadrant 72 moving arcuately toward the leg 66 during travel of the items along the bight 68 . as in the case of the action imparted to the legs 64 and 66 by the beams 74 , the assembly 52 causes the quadrants 70 and 72 to descend below the quadrants 44 and 46 and regress toward the leg 64 and away from the leg 66 during each cycle , depositing the items 20 back onto the quadrants 44 and 46 each time the quadrants 70 and 72 pass beneath the upper surfaces of the quadrants 44 and 46 . during the successive , intermittent advancements of the items 20 along the leg 34 , thence along the bight 40 and finally along the leg 48 , they are continuously cooked on both sides to the extent desired by adjustment of the heaters 30 and / or the speed of the motor 78 prior to successive emergence of the items 20 from the end 38 of the kettle 22 . while conveyance of the items 20 is not continual , there is no pause except somewhat momentarily each time the items come to rest on the grid 32 . a cooker 138 as shown in fig9 - 11 , differs from the cooker 18 of fig1 - 8 only with respect to the nature of the two legs of the stationary grid and of the movable grid . therefore , the same numerals are used with respect to components which are the same in both cookers 18 and 138 . legs 140 and 142 of the stationary grid have rods 144 and 146 rigidly secured to the kettle 22 and extending inwardly from corresponding sides of the kettle 22 . the spaced rods 144 continue from the exterior of the end wall 38 to the quadrant 44 and the spaced rods 146 continue from the quadrant 46 to and through the opening 36 . on the other hand , legs 148 and 150 of the movable grid each have a series of rods 152 and 154 extending toward the sides of the kettle 22 . once again the rods 152 continue through the opening 36 to the quadrant 70 and the rods 154 extend from the quadrant 72 , terminating beyond the end wall 38 . the inner ends of the rods 152 and 154 are secured to corresponding beams 74 carried by members 76 actuated by the motor 78 as above explained . while the cookers 18 and 138 as described above contemplate a stationary grid , e . g . the primary grid 32 and a movable grid , e . g . the secondary grid 62 , it is contemplated that both grids be movable if such is to be desired . it has been fully illustrated and carefully explained above how the grid 62 is caused to be moved in relation to the grid 32 . as an additional embodiment , i contemplate that the grid 32 be moved in the same manner and through use of the same structural components as employed in connection with the grid 62 , and duplication of such components for the grid 32 has not , therefore , been included in the drawings . it is but necessary to further explain that the two movable grids would move alternately such that one would arrive at its greatest height as the other grid arrives at its lowermost position . each grid would advance the product the same distance during each cycle of movement . hence , the speed of advancement of each product would be doubled and , if as such result , the products are not sufficiently cooked by the time they emerge from the cookers 18 or 138 , one need merely reduce the speed of motor 98 . a cooker 156 as shown in fig1 - 19 is similar to the cooker 138 except that radially and inwardly extending rods are substituted for quadrants 70 and 72 and rods which cyclically and successively raise , advance , lower and recede are substituted for quadrants 44 and 46 . therefore , the same numerals are used with respect to components which are the same as in cookers 18 and 138 . as in fig9 - 11 , cooker 156 has legs 140 and 142 with corresponding spaced , stationary rods 144 and 146 , and legs 148 and 150 of the movable grid with corresponding rods 152 and 154 secured to corresponding beam 74 and carried by member 76 . however , in cooker 156 , separate hinged covers 160 and 162 are pivotally mounted to kettle 158 by hinges 28 . covers 160 and 162 each carry heating elements 30 in the stationary rods 144 and leg 140 and stationary rods 146 and leg 142 are respectively mounted thereto . the covers 160 and 162 meet at junction 164 when in the closed , cooking position . the cooker 156 also differs from cooker 138 with respect to the means for advancing the patties 20 through bight 40 . the series of spaced , radially inwardly directed stationary rods 166 and 168 are mounted to arcuate legs 170 and 172 which are in turn mounted to covers 160 and 162 respectively . the leg 170 is a continuation of leg 148 and extends to junction 164 and corresponds to quadrant 70 of fig9 - 11 . leg 172 corresponds to quadrant 72 in fig9 - 11 and extends from junction 164 to leg 150 . stationary rods 168 are in a vertically lower plane than the plane defined by rods 166 and correspond to quadrant 72 in fig9 - 11 . the stationary rods 166 and 168 extend inwardly in the manner of spokes toward assembly 52 . orbiting rods 174 , 176 corresponding respectively to quadrants 44 , 46 in fig9 - 11 , are interleaved between stationary rods 166 , 168 and extend radially outwardly from inner tube 96 of assembly 52 . as in the previous embodiments , inner tube 96 is engaged by rotor 106 to oscillate and thereby raise , advance , lower and recede orbiting rods 174 and 176 mounted to the tube 96 with respect to stationary rods 166 , 168 . orbiting rods 174 , 176 are removably mounted to brackets 178 carried by tube 96 , by threaded ends on the rods , by pins or collars , or other conventional means . fig8 shows a similar arrangement of rods , with quadrant 72 attached to tubes 110 and 96 ( below tube 110 ); and in cooker 156 the number of rods 174 , 176 are preferably greater than the radially extending rods comprising quadrant 72 in fig8 . the manner of operation of cooker 156 is similar to cookers 18 and 138 , in that the food items 20 placed on leg 34 of the grill are advanced as rods 152 move in an orbital and surrounding manner about adjacent stationary rods 144 . in this manner , the food items 20 are successively &# 34 ; walked &# 34 ; along stationary rods 144 by successive lifting and advancing by rods 152 until the food items 20 have traveled the distance from end 38 to leg 170 . as is shown by fig1 , food items 20 also move upward on an incline and receive heat from element 30 . upon reaching leg 170 , the food items 20 continue in an arcuate , counterclockwise path along bight 40 . tube 96 moves in an oscillatory manner while driven by rotors 106 , 108 . each orbiting rod 174 , 176 moves in unison with rods 152 and 154 , and encircles respective adjacent stationary rod 166 , 168 in surrounding relationship . thus , when food item 20 is received from legs 140 , 148 , it is carried and advanced in a curved path in the counterclockwise direction as shown in fig1 . the orbiting rods 174 , 176 receive the food item 20 from legs 140 , 148 and continue their successive and cyclical motion of raising , advancing , lowering and receding in surrounding relationship to stationary rods 166 , 168 located adjacent thereto . the food item 20 is deposited and remains on the next forward stationary rods 166 as the orbiting rod 172 moves beneath and rearwardly its adjacent stationary rod 16 before moving upward to carry another food item 20 forward . rods 166 and 174 are disposed in the first portion of bight 40 corresponding to leg 170 , with the last rod 166 and first rod 168 of leg 174 being superposed in a vertical plane opposite junction 166 . when a food item reaches the last rod 166 , it falls downward and simultanteously turns over when the last orbiting rod 174 engages the food item 20 on an upward movement . this turning - over process is shown in fig1 - 16 and has been previously described . in the present embodiment , orbiting rods 174 correspond to quadrant 44 while stationary rods 166 correspond to quadrant 70 of fig1 - 16 . similarly , orbiting rods 176 correspond to quadrant 46 and stationary rods 168 correspond to quandrant 72 of fig1 - 16 . as food item 20 engages the first of rods 166 of leg 170 , the first of the orbiting rods 176 begin to successively advance the food item 20 until it reaches leg 142 . the food item 20 then advances along leg 42 by successive oscillations of rod 154 until the food items 20 exit the cooker 158 through opening 36 . the embodiment of fig1 - 19 is especially useful when it is desired to clean the cooker 158 . as shown in fig1 , because legs 140 and 170 are mounted to cover 160 , and legs 142 and 172 are mounted to cover 162 , the interior of the cooker 58 is easily accessible during cleaning .

a continuous conveying mechanism especially adapted as the cooker for continuous grilling of hamburger patties and the like uses a shiftable grid which intermittently lifts the patties off a stationary grid and effects advancement after each lift - off until a u - shaped path is traversed extending initially through and terminating beyond one end of the cooker exteriorly thereof . the patties initially travel upwardly along a straight line with respect to the first pair of legs of the grids and then upwardly and arcuately along interleaved , radially extending rods , whereupon they invert and drop such as to travel upwardly and arcuately with respect to a second set of radially extending interleaved rods . finally , the patties travel upwardly along a straight line with respect to a pair of legs of the grids forming the final stretch of travel .

in the following description , all those parts of the bracelet that are well known to those skilled in the art in this technical field will be explained only in a simplified manner . fig1 shows a particular embodiment of bracelet 1 according to the present invention . this bracelet 1 has first 2 and second 3 bracelet strands intended to be removably attached via a clasp 1 a . clasp 1 a , shown in fig3 , includes a support 4 and an unfolding buckle 4 a . unfolding buckle 4 a includes a base 5 at the ends of which are pivotably mounted two side portions 6 a , 6 b , which are preferably of similar length . this base 5 further includes male fastening members whose purpose is to cooperate with a female fastening member located on side portions 6 a , 6 b . this allows unfolding buckle 4 a to be closed and locked while tightening bracelet 1 . the first side portion 6 a of unfolding buckle 4 a is also pivotably mounted on support 4 , whereas the second side portion 6 b is pivotably mounted on second strand 3 . second side portion 6 b can be mounted on second strand 3 via a pin 7 . indeed , so that bracelet 1 is more comfortable for the person wearing it , unfolding buckle 4 is made to be curved to follow the shape of bracelet 1 or to partly follow the shape of the user &# 39 ; s wrist . to achieve this , base 5 of unfolding buckle 4 a is curved such that , when bracelet 1 is being worn by the user , base 5 wholly or partly matches the shape of the user &# 39 ; s wrist . side portions 6 a , 6 b are also curved so that , when unfolding buckle 4 a is closed , side portions 6 a , 6 b can be integrated into or at least match the shape of base 5 , as shown in fig1 and 2 . support 4 is pivotably mounted on first side portion 6 a and includes a fastening device 13 . support 4 is thus used to attach bracelet 1 via engagement of first strand 2 in support 4 . to achieve this , support 4 , shown in fig3 and 4 , takes the form of a generally rectangular buckle in which strand 2 of bracelet 1 is engaged . this buckle 4 is formed of two parallel lateral arms 8 , each pierced with a hole . the arms are then arranged to face each other so that an arbour 10 can be arranged transversely thereto . this arbour 10 is for mounting second side portion 6 b of unfolding buckle 4 a on which the female fastening member of side portion 6 b is mounted . arms 8 are also connected to each other by a crosspiece 9 located at one end of the arms and by a support element 12 , located opposite said crosspiece 9 . this transverse support element 12 takes the form of a plate and is used for cooperating with fastening device 13 of clasp 1 a . the function of buckle 4 a , apart from closing bracelet 1 , is to act as guide means . indeed , first strand 2 engages in buckle 4 to be removably attached to second strand 3 ? via a fastening device 13 . when engaging in buckle 4 , first strand 2 is inserted between the two lateral arms 8 of buckle 4 as shown in fig1 and 4 , with the result that the transverse movements of first strand 2 in the buckle are limited by these two arms 8 . fastening device 13 attaches first strand 2 to buckle 4 and here includes a tongue 13 a . in fact , tongue 13 a is a pin , pivotably mounted via an arbour 11 mounted between the two lateral arms 8 of buckle 4 . this tongue 13 a abuts support element 12 and is used for joining the two strands 2 , 3 to each other , while allowing the size of bracelet 1 to be selected . to achieve this , holes 14 are arranged in first strand 2 which engages in buckle 4 . thus , when first strand 2 engages in buckle 4 , tongue 13 a can be inserted in one of holes 14 , thus blocking strand 2 in buckle 4 . of course , it will be clear that tongue 13 a may take other forms such as a finger arranged directly on support element 12 . for the assembly of first strand 2 in buckle 4 , said strand 2 is engaged in buckle 4 as shown in fig4 . preferably , strand 2 is engaged by entering buckle 4 on the side where support element 12 is located . of course , the position of buckle 4 could be reversed . afterwards , bracelet strand 2 will rest on arbours 10 , 11 where first side portion 6 a and tongue 13 a are pivotably mounted , then emerge on the side of crosspiece 9 . once strand 2 is engaged , it need only be attached to buckle 4 . to achieve this , strand 2 is moved longitudinally such that one of holes 14 in said strand 2 is placed in proximity to tongue 13 a so that the tongue engages therein , thus longitudinally locking first strand 2 . next , to tighten bracelet 1 , and to enable the user to wear said bracelet , unfolding buckle 4 must be closed . to achieve this , the two side portions 6 a , 6 b are folded down towards base 5 such that the female locking members of side portions 6 a , 6 b cooperate with the male locking members of base 5 . of course , engagement of the female locking members in the male locking members can be achieved using different systems . indeed , it is possible to use means that operate by pressure or by using push - buttons 15 acting on hooks that grip the male locking members of base 5 . evidently , each side portion 6 a , 6 b could also have a different system , for example using pressure on one portion and push - buttons 15 on the other . generally , the second bracelet strand 3 has a ring 16 made of leather , or another material , fixed to said bracelet strand 3 close to the end thereof . this ring 16 is arranged so that the end of first strand 2 can be engaged in said ring 16 , allowing the two strands 2 , 3 to be pressed against each other as efficiently as possible . moreover , bracelet clasp 1 a according to the present invention can be provided with additional elements . for example , support 4 can be fitted with additional guide means to further limit the movements of first strand 2 when it is engaged in said support 4 . this additional guide means can take the form of one or more eyes located at one or both ends of support 4 . the eyes have an opening allowing just enough space for the first strand 2 to be able to engage therein . thus , the eyes limit the movements of said strand 2 , by limiting the clearance of said strand . preferably , this additional guide means is located in proximity to crosspiece 9 . however , the guide means and leather ring 16 are not infallible , and , under some stress , it may happen that first strand 2 of bracelet 1 becomes so loose that it causes bracelet 1 to open . to avoid this happening , support 4 is provided with a safety device 17 for preventing this type of nuisance . safety device 17 takes the form of a part mounted on support 4 , as shown in fig1 to 4 , and it is generally made of the same material as the support . this device 17 is then temporarily attached inside said support 4 so as to clamp first strand 2 tightly . this therefore presses said strand 2 preventing any clearance against clasp 1 a and thus limits the movements of said strand 2 still further . advantageously , according to the invention , it is thus clear that safety device 17 does not need to be opened for the timepiece to be put on . indeed , the use of unfolding buckle 4 a allows the assembly comprising fastening device 13 and safety device 17 to be fixedly adjusted in accordance with the size of the user &# 39 ; s wrist . in a particular embodiment shown in the figures , the part 22 used to clamp first strand 2 against the clasp , takes the form of an approximately u - shaped part 22 as shown in fig5 . this part 22 includes a generally flat base 22 a , for clamping the entire width of strand 2 in a uniform manner , at the ends of which are two arms 22 b mounted at right angles relative to base 22 a . at the end of one of the two arms 22 b , perpendicular to base 22 a , there is a raised portion 18 in the form of a hook . this hook 18 is used for temporarily attaching u - shaped part 22 to said support 4 . at a second end of said part 22 an eye 19 is arranged for permanently attaching said u - shaped part 22 to said support 4 . this eye is used for rotatably mounting said u - shaped part 22 on the support . to assemble said approximately u - shaped part 22 on support 4 , one of side arms 8 is provided with means for temporarily attaching part 22 and the other arm 8 is provided with means for permanently attaching said part 22 . thus , on one of arms 8 there is a permanent attachment recess 21 in which eye 19 of u - shaped part 22 is inserted , as shown in fig7 . each flank of this recess is pierced with a hole 21 a enabling a pin to be inserted therein such that said u - shaped part 22 is pivotably mounted . whereas the other side arm 8 of the support is provided with a temporary attachment recess 20 located opposite the assembly recess for part 22 . when the user wishes to lock clasp 1 a , he or she will fold part 22 down onto the clasp , thereby clamping first strand 2 , and such that hook 18 of part 22 engages in its recess 20 . of course , it is possible for this attachment to be mounted in a different manner , such as using a slide - block . moreover , it is possible for the clasp to have several safety devices 17 as described above , and , in such case , several series of recesses 20 , 21 are arranged on said support 4 . in a preferred variant shown in fig6 , safety device 17 may take the form of two u - shaped parts 22 that are integral with each other . this variant has the advantage of increasing the clamping surface and the actual clamping efficiency by distributing stress . indeed , with a single u - shaped part 22 , clamping is optimal when base 22 a of u - shaped part 22 is opposite arbours 10 , 11 where said first strand 2 abuts . whereas , with a safety device 17 that includes two u - shaped parts 22 integral with each other , it is possible to position part 22 such that the part of first strand 2 opposite arbours 10 , 11 is surrounded , for more efficient clamping . first bracelet strand 2 undergoes stress distributed over four surfaces , i . e . the two bases 22 a , and arbours 10 , 11 . these two u - shaped parts can also be made integral with each other to make the assembly attractive . if the variant of safety device 17 with two u - shaped parts is used , it is clear that temporary attachment recesses 20 and permanent attachment recesses 21 enabling said device to be pivotably mounted on said support 4 , are doubled . fig8 shows , in a simplified manner , arms 8 seen from the side along arrow a of fig7 for recesses 21 and along arrow a ′ for recesses 20 . this variant also protects push - button 15 of unfolding buckle 4 a . indeed , in this variant , safety device 17 is arranged such that the two u - shaped parts 22 surround said push - button 15 as shown in fig1 to 4 , which protects the latter from any shocks that it might be subjected to , but also from accidental opening . in another variant , safety device 17 could be not integral with support 4 . in such case , the ends of the u - shaped part ( s ) are only provided with hooks 18 . consequently , the recesses of each of arms 8 are temporary attachment recesses 20 in which said u - shaped parts are attached . of course , it is easily understood that the bracelet 1 described above is not limited simply to the characteristics described . for example , bracelet 1 may use not a clasp with an unfolding buckle 4 as above , but a conventional clasp . this clasp is arranged such that support 4 is pivotably mounted directly on second bracelet strand 3 by replacing arbour 10 with pin 7 . it will be clear that various alterations and / or improvements and / or combinations that are evident to those skilled in the art may be made to the various embodiments of the invention set out above without departing from the scope of the invention defined by the annexed claims .

the invention concerns a strap or bracelet including a first strand and a second strand . the second strand is connected to a clasp that includes a fastening device . the fastening device joins the strands to each other . the invention is characterized in that the clasp further includes a safety device for better joining the first strand to the clasp by pressing the former onto the latter .

turning now to fig1 , the s - icd of the present invention is illustrated . the s - icd consists of an electrically active canister 11 and a subcutaneous electrode 13 attached to the canister . the canister has an electrically active surface 15 that is electrically insulated from the electrode connector block 17 and the canister housing 16 via insulating area 14 . the canister can be similar to numerous electrically active canisters commercially available in that the canister will contain a battery supply , capacitor and operational circuitry . alternatively , the canister can be thin and elongated to conform to the intercostal space . the circuitry will be able to monitor cardiac rhythms for tachycardia and fibrillation , and if detected , will initiate charging the capacitor and then delivering cardioversion / defibrillation energy through the active surface of the housing and to the subcutaneous electrode . examples of such circuitry are described in u . s . pat . nos . 4 , 693 , 253 and 5 , 105 , 810 , the entire disclosures of which are herein incorporated by reference . the canister circuitry can provide cardioversion / defibrillation energy in different types of waveforms . in one embodiment , a 100 uf biphasic waveform is used of approximately 10 - 20 ms total duration and with the initial phase containing approximately ⅔ of the energy , however , any type of waveform can be utilized such as monophasic , biphasic , multiphasic or alternative waveforms as is known in the art . in addition to providing cardioversion / defibrillation energy , the circuitry can also provide transthoracic cardiac pacing energy . the optional circuitry will be able to monitor the heart for bradycardia and / or tachycardia rhythms . once a bradycardia or tachycardia rhythm is detected , the circuitry can then deliver appropriate pacing energy at appropriate intervals through the active surface and the subcutaneous electrode . pacing stimuli can be biphasic in one embodiment and similar in pulse amplitude to that used for conventional transthoracic pacing . this same circuitry can also be used to deliver low amplitude shocks on the t - wave for induction of ventricular fibrillation for testing s - icd performance in treating v - fib as is described in u . s . pat . no . 5 , 129 , 392 , the entire disclosure of which is hereby incorporated by reference . also the circuitry can be provided with rapid induction of ventricular fibrillation or ventricular tachycardia using rapid ventricular pacing . another optional way for inducing ventricular fibrillation would be to provide a continuous low voltage , i . e ., about 3 volts , across the heart during the entire cardiac cycle . another optional aspect of the present invention is that the operational circuitry can detect the presence of atrial fibrillation as described in olson , w . et al . “ onset and stability for ventricular tachyarrhythmia detection in an implantable cardioverter and defibrillator ,” computers in cardiology ( 1986 ) pp . 167 - 170 . detection can be provided via r - r cycle length instability detection algorithms . once atrial fibrillation has been detected , the operational circuitry will then provide qrs synchronized atrial defibrillation / cardioversion using the same shock energy and waveshape characteristics used for ventricular defibrillation / cardioversion . the sensing circuitry will utilize the electronic signals generated from the heart and will primarily detect qrs waves . in one embodiment , the circuitry will be programmed to detect only ventricular tachycardias or fibrillations . the detection circuitry will utilize in its most direct form , a rate detection algorithm that triggers charging of the capacitor once the ventricular rate exceeds some predetermined level for a fixed period of time : for example , if the ventricular rate exceeds 240 bpm on average for more than 4 seconds . once the capacitor is charged , a confirmatory rhythm check would ensure that the rate persists for at least another 1 second before discharge . similarly , termination algorithms could be instituted that ensure that a rhythm less than 240 bpm persisting for at least 4 seconds before the capacitor charge is drained to an internal resistor . detection , confirmation and termination algorithms as are described above and in the art can be modulated to increase sensitivity and specificity by examining qrs beat - to - beat uniformity , qrs signal frequency content , r - r interval stability data , and signal amplitude characteristics all or part of which can be used to increase or decrease both sensitivity and specificity of s - icd arrhythmia detection function . in addition to use of the sense circuitry for detection of v - fib or v - tach by examining the qrs waves , the sense circuitry can check for the presence or the absence of respiration . the respiration rate can be detected by monitoring the impedance across the thorax using subthreshold currents delivered across the active can and the high voltage subcutaneous lead electrode and monitoring the frequency in undulation in the waveform that results from the undulations of transthoracic impedance during the respiratory cycle . if there is no undulation , then the patent is not respiring and this lack of respiration can be used to confirm the qrs findings of cardiac arrest . the same technique can be used to provide information about the respiratory rate or estimate cardiac output as described in u . s . pat . nos . 6 , 095 , 987 ; 5 , 423 , 326 ; and 4 , 450 , 527 , the entire disclosures of which are incorporated herein by reference . the canister of the present invention can be made out of titanium alloy or other presently preferred electrically active canister designs . however , it is contemplated that a malleable canister that can conform to the curvature of the patient &# 39 ; s chest will be preferred . in this way the patient can have a comfortable canister that conforms to the shape of the patient &# 39 ; s rib cage . examples of conforming canisters are provided in u . s . pat . no . 5 , 645 , 586 , the entire disclosure of which is herein incorporated by reference . therefore , the canister can be made out of numerous materials such as medical grade plastics , metals , and alloys . in the preferred embodiment , the canister is smaller than 60 cc volume having a weight of less than 100 gms for long term wearability , especially in children . the canister and the lead of the s - icd can also use fractal or wrinkled surfaces to increase surface area to improve defibrillation capability . because of the primary prevention role of the therapy and the likely need to reach energies over 40 joules , a feature of one embodiment is that the charge time for the therapy , is intentionally left relatively long to allow capacitor charging within the limitations of device size . examples of small icd housings are disclosed in u . s . pat . nos . 5 , 597 , 956 and 5 , 405 , 363 , the entire disclosures of which are incorporated herein by reference . different subcutaneous electrodes 13 of the present invention are illustrated in fig1 - 3 . turning to fig1 , the lead 21 for the subcutaneous electrode is preferably composed of silicone or polyurethane insulation . the electrode is connected to the canister at its proximal end via connection port 19 which is located on an electrically insulated area 17 of the canister . the electrode illustrated is a composite electrode with three different electrodes attached to the lead . in the embodiment illustrated , an optional anchor segment 52 is attached at the most distal end of the subcutaneous electrode for anchoring the electrode into soft tissue such that the electrode does not dislodge after implantation . the most distal electrode on the composite subcutaneous electrode is a coil electrode 27 that is used for delivering the high voltage cardioversion / defibrillation energy across the heart . the coil cardioversion / defibrillation electrode is about 5 - 10 cm in length . proximal to the coil electrode are two sense electrodes , a first sense electrode 25 is located proximally to the coil electrode and a second sense electrode 23 is located proximally to the first sense electrode . the sense electrodes are spaced far enough apart to be able to have good qrs detection . this spacing can range from 1 to 10 cm with 4 cm being presently preferred . the electrodes may or may not be circumferential with the preferred embodiment . having the electrodes non - circumferential and positioned outward , toward the skin surface , is a means to minimize muscle artifact and enhance qrs signal quality . the sensing electrodes are electrically isolated from the cardioversion / defibrillation electrode via insulating areas 29 . similar types of cardioversion / defibrillation electrodes are currently commercially available in a transvenous configuration . for example , u . s . pat . no . 5 , 534 , 022 , the entire disclosure of which is herein incorporated by reference , discloses a composite electrode with a coil cardioversion / defibrillation electrode and sense electrodes . modifications to this arrangement are contemplated within the scope of the invention . one such modification is illustrated in fig2 where the two sensing electrodes 25 and 23 are non - circumferential sensing electrodes and one is located at the distal end , the other is located proximal thereto with the coil electrode located in between the two sensing electrodes . in this embodiment the sense electrodes are spaced about 6 to about 12 cm apart depending on the length of the coil electrode used . fig3 illustrates yet a further embodiment where the two sensing electrodes are located at the distal end to the composite electrode with the coil electrode located proximally thereto . other possibilities exist and are contemplated within the present invention . for example , having only one sensing electrode , either proximal or distal to the coil cardioversion / defibrillation electrode , with the coil serving as both a sensing electrode and a cardioversion / defibrillation electrode . it is also contemplated within the scope of the invention that the sensing of qrs waves ( and transthoracic impedance ) can be carried out via sense electrodes on the canister housing or in combination with the cardioversion / defibrillation coil electrode and / or the subcutaneous lead sensing electrode ( s ). in this way , sensing could be performed via the one coil electrode located on the subcutaneous electrode and the active surface on the canister housing . another possibility would be to have only one sense electrode located on the subcutaneous electrode and the sensing would be performed by that one electrode and either the coil electrode on the subcutaneous electrode or by the active surface of the canister . the use of sensing electrodes on the canister would eliminate the need for sensing electrodes on the subcutaneous electrode . it is also contemplated that the subcutaneous electrode would be provided with at least one sense electrode , the canister with at least one sense electrode , and if multiple sense electrodes are used on either the subcutaneous electrode and / or the canister , that the best qrs wave detection combination will be identified when the s - icd is implanted and this combination can be selected , activating the best sensing arrangement from all the existing sensing possibilities . turning again to fig2 , two sensing electrodes 26 and 28 are located on the electrically active surface 15 with electrical insulator rings 30 placed between the sense electrodes and the active surface . these canister sense electrodes could be switched off and electrically insulated during and shortly after defibrillation / cardioversion shock delivery . the canister sense electrodes may also be placed on the electrically inactive surface of the canister . in the embodiment of fig2 , there are actually four sensing electrodes , two on the subcutaneous lead and two on the canister . in the preferred embodiment , the ability to change which electrodes are used for sensing would be a programmable feature of the s - icd to adapt to changes in the patient physiology and size ( in the case of children ) over time . the programming could be done via the use of physical switches on the canister , or as presently preferred , via the use of a programming wand or via a wireless connection to program the circuitry within the canister . the canister could be employed as either a cathode or an anode of the s - icd cardioversion / defibrillation system . if the canister is the cathode , then the subcutaneous coil electrode would be the anode . likewise , if the canister is the anode , then the subcutaneous electrode would be the cathode . the active canister housing will provide energy and voltage intermediate to that available with icds and most aeds . the typical maximum voltage necessary for icds using most biphasic waveforms is approximately 750 volts with an associated maximum energy of approximately 40 joules . the typical maximum voltage necessary for aeds is approximately 2000 - 5000 volts with an associated maximum energy of approximately 200 - 360 joules depending upon the model and waveform used . the s - icd and the us - icd of the present invention uses maximum voltages in the range of about 50 to about 3500 volts and is associated with energies of about 0 . 5 to about 350 joules . the capacitance of the devices can range from about 25 to about 200 micro farads . in another embodiment , the s - icd and us - icd devices provide energy with a pulse width of approximately one millisecond to approximately 40 milliseconds . the devices can provide pacing current of approximately one milliamp to approximately 250 milliamps . the sense circuitry contained within the canister is highly sensitive and specific for the presence or absence of life threatening ventricular arrhythmias . features of the detection algorithm are programmable and the algorithm is focused on the detection of v - fib and high rate v - tach (& gt ; 240 bpm ). although the s - icd of the present invention may rarely be used for an actual life - threatening event , the simplicity of design and implementation allows it to be employed in large populations of patients at modest risk with modest cost by non - cardiac electrophysiologists . consequently , the s - icd of the present invention focuses mostly on the detection and therapy of the most malignant rhythm disorders . as part of the detection algorithm &# 39 ; s applicability to children , the upper rate range is programmable upward for use in children , known to have rapid supraventricular tachycardias and more rapid ventricular fibrillation . energy levels also are programmable downward in order to allow treatment of neonates and infants . turning now to fig4 , the optimal subcutaneous placement of the s - icd of the present invention is illustrated . as would be evidence to a person skilled in the art , the actual location of the s - icd is in a subcutaneous space that is developed during the implantation process . the heart is not exposed during this process and the heart is schematically illustrated in the figures only for help in understanding where the canister and coil electrode are three dimensionally located in the left mid - clavicular line approximately at the level of the inframammary crease at approximately the 5th rib . the lead 21 of the subcutaneous electrode traverses in a subcutaneous path around the thorax terminating with its distal electrode end at the posterior axillary line ideally just lateral to the left scapula . this way the canister and subcutaneous cardioversion / defibrillation electrode provide a reasonably good pathway for current delivery to the majority of the ventricular myocardium . fig5 illustrates a different placement of the present invention . the s - icd canister with the active housing is located in the left posterior axillary line approximately lateral to the tip of the inferior portion of the scapula . this location is especially useful in children . the lead 21 of the subcutaneous electrode traverses in a subcutaneous path around the thorax terminating with its distal electrode end at the anterior precordial region , ideally in the inframammary crease . fig6 illustrates the embodiment of fig1 subcutaneously implanted in the thorax with the proximal sense electrodes 23 and 25 located at approximately the left axillary line with the cardioversion / defibrillation electrode just lateral to the tip of the inferior portion of the scapula . fig7 schematically illustrates the method for implanting the s - icd of the present invention . an incision 31 is made in the left anterior axillary line approximately at the level of the cardiac apex . this incision location is distinct from that chosen for s - icd placement and is selected specifically to allow both canister location more medially in the left inframammary crease and lead positioning more posteriorly via the introducer set ( described below ) around to the left posterior axillary line lateral to the left scapula . that said , the incision can be anywhere on the thorax deemed reasonably by the implanting physician although in the preferred embodiment , the s - icd of the present invention will be applied in this region . a subcutaneous pathway 33 is then created medially to the inframammary crease for the canister and posteriorly to the left posterior axillary line lateral to the left scapula for the lead . the s - icd canister 11 is then placed subcutaneously at the location of the incision or medially at the subcutaneous region at the left inframammary crease . the subcutaneous electrode 13 is placed with a specially designed curved introducer set 40 ( see fig8 ). the introducer set comprises a curved trocar 42 and a stiff curved peel away sheath 44 . the peel away sheath is curved to allow for placement around the rib cage of the patient in the subcutaneous space created by the trocar . the sheath has to be stiff enough to allow for the placement of the electrodes without the sheath collapsing or bending . preferably the sheath is made out of a biocompatible plastic material and is perforated along its axial length to allow for it to split apart into two sections . the trocar has a proximal handle 41 and a curved shaft 43 . the distal end 45 of the trocar is tapered to allow for dissection of a subcutaneous path 33 in the patient . preferably , the trocar is cannulated having a central lumen 46 and terminating in an opening 48 at the distal end . local anesthetic such as lidocaine can be delivered , if necessary , through the lumen or through a curved and elongated needle designed to anesthetize the path to be used for trocar insertion should general anesthesia not be employed . the curved peel away sheath 44 has a proximal pull tab 49 for breaking the sheath into two halves along its axial shaft 47 . the sheath is placed over a guidewire inserted through the trocar after the subcutaneous path has been created . the subcutaneous pathway is then developed until it terminates subcutaneously at a location that , if a straight line were drawn from the canister location to the path termination point the line would intersect a substantial portion of the left ventricular mass of the patient . the guidewire is then removed leaving the peel away sheath . the subcutaneous lead system is then inserted through the sheath until it is in the proper location . once the subcutaneous lead system is in the proper location , the sheath is split in half using the pull tab 49 and removed . if more than one subcutaneous electrode is being used , a new curved peel away sheath can be used for each subcutaneous electrode . the s - icd will have prophylactic use in adults where chronic transvenous / epicardial icd lead systems pose excessive risk or have already resulted in difficulty , such as sepsis or lead fractures . it is also contemplated that a major use of the s - icd system of the present invention will be for prophylactic use in children who are at risk for having fatal arrhythmias , where chronic transvenous lead systems pose significant management problems . additionally , with the use of standard transvenous icds in children , problems develop during patient growth in that the lead system does not accommodate the growth . fig9 illustrates the placement of the s - icd subcutaneous lead system such that he problem that growth presents to the lead system is overcome . the distal end of the subcutaneous electrode is placed in the same location as described above providing a good location for the coil cardioversion / defibrillation electrode 27 and the sensing electrodes 23 and 25 . the insulated lead 21 , however , is no longer placed in a taut configuration . instead , the lead is serpiginously placed with a specially designed introducer trocar and sheath such that it has numerous waves or bends . as the child grows , the waves or bends will straighten out lengthening the lead system while maintaining proper electrode placement . although it is expected that fibrous scarring especially around the defibrillation coil will help anchor it into position to maintain its posterior position during growth , a lead system with a distal tine or screw electrode anchoring system 52 can also be incorporated into the distal tip of the lead to facilitate lead stability ( see fig1 ). other anchoring systems can also be used such as hooks , sutures , or the like . fig1 and 11 illustrate another embodiment of the present s - icd invention . in this embodiment there are two subcutaneous electrodes 13 and 13 ′ of opposite polarity to the canister . the additional subcutaneous electrode 13 ′ is essentially identical to the previously described electrode . in this embodiment the cardioversion / defibrillation energy is delivered between the active surface of the canister and the two coil electrodes 27 and 27 ′. additionally , provided in the canister is means for selecting the optimum sensing arrangement between the four sense electrodes 23 , 23 ′, 25 , and 25 ′. the two electrodes are subcutaneously placed on the same side of the heart . as illustrated in fig6 , one subcutaneous electrode 13 is placed inferiorly and the other electrode 13 ′ is placed superiorly . it is also contemplated with this dual subcutaneous electrode system that the canister and one subcutaneous electrode are the same polarity and the other subcutaneous electrode is the opposite polarity . turning now to fig1 and 13 , further embodiments are illustrated where the canister 11 of the s - icd of the present invention is shaped to be particularly useful in placing subcutaneously adjacent and parallel to a rib of a patient . the canister is long , thin , and curved to conform to the shape of the patient &# 39 ; s rib . in the embodiment illustrated in fig1 , the canister has a diameter ranging from about 0 . 5 cm to about 2 cm without 1 cm being presently preferred . alternatively , instead of having a circular cross sectional area , the canister could have a rectangular or square cross sectional area as illustrated in fig1 without falling outside of the scope of the present invention . the length of the canister can vary depending on the size of the patient &# 39 ; s thorax . in an embodiment , the canister is about 5 cm to about 40 cm long . the canister is curved to conform to the curvature of the ribs of the thorax . the radius of the curvature will vary depending on the size of the patient , with smaller radiuses for smaller patients and larger radiuses for larger patients . the radius of the curvature can range from about 5 cm to about 35 cm depending on the size of the patient . additionally , the radius of the curvature need not be uniform throughout the canister such that it can be shaped closer to the shape of the ribs . the canister has an active surface , 15 that is located on the interior ( concave ) portion of the curvature and an inactive surface 16 that is located on the exterior ( convex ) portion of the curvature . the leads of these embodiments , which are not illustrated except for the attachment port 19 and the proximal end of the lead 21 , can be any of the leads previously described above , with the lead illustrated in fig1 being presently preferred . the circuitry of this canister is similar to the circuitry described above . additionally , the canister can optionally have at least one sense electrode located on either the active surface of the inactive surface and the circuitry within the canister can be programmable as described above to allow for the selection of the best sense electrodes . it is presently preferred that the canister have two sense electrodes 26 and 28 located on the inactive surface of the canisters as illustrated , where the electrodes are spaced from about 1 to about 10 cm apart with a spacing of about 3 cm being presently preferred . however , the sense electrodes can be located on the active surface as described above . it is envisioned that the embodiment of fig1 will be subcutaneously implanted adjacent and parallel to the left anterior 5th rib , either between the 4th and 5th ribs or between the 5th and 6th ribs . however other locations can be used . another component of the s - icd of the present invention is a cutaneous test electrode system designed to simulate the subcutaneous high voltage shock electrode system as well as the qrs cardiac rhythm detection system . this test electrode system is comprised of a cutaneous patch electrode of similar surface area and impedance to that of the s - icd canister itself together with a cutaneous strip electrode comprising a defibrillation strip as well as two button electrodes for sensing of the qrs . several cutaneous strip electrodes are available to allow for testing various bipole spacings to optimize signal detection comparable to the implantable system . fig1 to 18 depict particular us - icd embodiments of the present invention . the various sensing , shocking and pacing circuitry , described in detail above with respect to the s - icd embodiments , may additionally be incorporated into the following us - icd embodiments . furthermore , particular aspects of any individual s - icd embodiment discussed above may be incorporated , in whole or in part , into the us - icd embodiments depicted in the following figures . turning now to fig1 , the us - icd of the present invention is illustrated . the us - icd consists of a curved housing 1211 with a first and second end . the first end 1413 is thicker than the second end 1215 . this thicker area houses a battery supply , capacitor and operational circuitry for the us - icd . the circuitry will be able to monitor cardiac rhythms for tachycardia and fibrillation , and if detected , will initiate charging the capacitor and then delivering cardioversion / defibrillation energy through the two cardioversion / defibrillating electrodes 1417 and 1219 located on the outer surface of the two ends of the housing . the circuitry can provide cardioversion / defibrillation energy in different types of waveforms . in one embodiment , a 100 uf biphasic waveform is used of approximately 10 - 20 ms total duration and with the initial phase containing approximately ⅔ of the energy , however , any type of waveform can be utilized such as monophasic , biphasic , multiphasic or alternative waveforms as is known in the art . the housing of the present invention can be made out of titanium alloy or other presently preferred icd designs . it is contemplated that the housing is also made out of biocompatible plastic materials that electronically insulate the electrodes from each other . however , it is contemplated that a malleable canister that can conform to the curvature of the patient &# 39 ; s chest will be preferred . in this way the patient can have a comfortable canister that conforms to the unique shape of the patient &# 39 ; s rib cage . examples of conforming icd housings are provided in u . s . pat . no . 5 , 645 , 586 , the entire disclosure of which is herein incorporated by reference . in the preferred embodiment , the housing is curved in the shape of a 5 th rib of a person . because there are many different sizes of people , the housing will come in different incremental sizes to allow a good match between the size of the rib cage and the size of the us - icd . the length of the us - icd will range from about 15 to about 50 cm . because of the primary preventative role of the therapy and the need to reach energies over 40 joules , a feature of the preferred embodiment is that the charge time for the therapy , intentionally be relatively long to allow capacitor charging within the limitations of device size . the thick end of the housing is currently needed to allow for the placement of the battery supply , operational circuitry , and capacitors . it is contemplated that the thick end will be about 0 . 5 cm to about 2 cm wide with about 1 cm being presently preferred . as microtechnology advances , the thickness of the housing will become smaller . the two cardioversion / defibrillation electrodes on the housing are used for delivering the high voltage cardioversion / defibrillation energy across the heart . in the preferred embodiment , the cardioversion / defibrillation electrodes are coil electrodes , however , other cardioversion / defibrillation electrodes could be used such as having electrically isolated active surfaces or platinum alloy electrodes . the coil cardioversion / defibrillation electrodes are about 5 - 10 cm in length . located on the housing between the two cardioversion / defibrillation electrodes are two sense electrodes 1425 and 1427 . the sense electrodes are spaced far enough apart to be able to have good qrs detection . this spacing can range from 1 to 10 cm with 4 cm being presently preferred . the electrodes may or may not be circumferential with the preferred embodiment . having the electrodes non - circumferential and positioned outward , toward the skin surface , is a means to minimize muscle artifact and enhance qrs signal quality . the sensing electrodes are electrically isolated from the cardioversion / defibrillation electrode via insulating areas 1423 . analogous types of cardioversion / defibrillation electrodes are currently commercially available in a transvenous configuration . for example , u . s . pat . no . 5 , 534 , 022 , the entire disclosure of which is herein incorporated by reference , discloses a composite electrode with a coil cardioversion / defibrillation electrode and sense electrodes . modifications to this arrangement are contemplated within the scope of the invention . one such modification is to have the sense electrodes at the two ends of the housing and have the cardioversion / defibrillation electrodes located in between the sense electrodes . another modification is to have three or more sense electrodes spaced throughout the housing and allow for the selection of the two best sensing electrodes . if three or more sensing electrodes are used , then the ability to change which electrodes are used for sensing would be a programmable feature of the us - icd to adapt to changes in the patient physiology and size over time . the programming could be done via the use of physical switches on the canister , or as presently preferred , via the use of a programming wand or via a wireless connection to program the circuitry within the canister . turning now to fig1 , the optimal subcutaneous placement of the us - icd of the present invention is illustrated . as would be evident to a person skilled in the art , the actual location of the us - icd is in a subcutaneous space that is developed during the implantation process . the heart is not exposed during this process and the heart is schematically illustrated in the figures only for help in understanding where the device and its various electrodes are three - dimensionally located in the thorax of the patient . the us - icd is located between the left mid - clavicular line approximately at the level of the inframammary crease at approximately the 5 th rib and the posterior axillary line , ideally just lateral to the left scapula . this way the us - icd provides a reasonably good pathway for current delivery to the majority of the ventricular myocardium . fig1 schematically illustrates the method for implanting the us - icd of the present invention . an incision 1631 is made in the left anterior axillary line approximately at the level of the cardiac apex . a subcutaneous pathway is then created that extends posteriorly to allow placement of the us - icd . the incision can be anywhere on the thorax deemed reasonable by the implanting physician although in the preferred embodiment , the us - icd of the present invention will be applied in this region . the subcutaneous pathway is created medially to the inframammary crease and extends posteriorly to the left posterior axillary line . the pathway is developed with a specially designed curved introducer 1742 ( see fig1 ). the trocar has a proximal handle 1641 and a curved shaft 1643 . the distal end 1745 of the trocar is tapered to allow for dissection of a subcutaneous path in the patient . preferably , the trocar is cannulated having a central lumen 1746 and terminating in an opening 1748 at the distal end . local anesthetic such as lidocaine can be delivered , if necessary , through the lumen or through a curved and elongated needle designed to anesthetize the path to be used for trocar insertion should general anesthesia not be employed . once the subcutaneous pathway is developed , the us - icd is implanted in the subcutaneous space , the skin incision is closed using standard techniques . as described previously , the us - icds of the present invention vary in length and curvature . the us - icds are provided in incremental sizes for subcutaneous implantation in different sized patients . turning now to fig1 , a different embodiment is schematically illustrated in exploded view which provides different sized us - icds that are easier to manufacture . the different sized us - icds will all have the same sized and shaped thick end 1413 . the thick end is hollow inside allowing for the insertion of a core operational member 1853 . the core member comprises a housing 1857 which contains the battery supply , capacitor and operational circuitry for the us - icd . the proximal end of the core member has a plurality of electronic plug connectors . plug connectors 1861 and 1863 are electronically connected to the sense electrodes via pressure fit connectors ( not illustrated ) inside the thick end , which are standard in the art . plug connectors 1865 and 1867 are also electronically connected to the cardioverter / defibrillator electrodes via pressure fit connectors inside the thick end . the distal end of the core member comprises an end cap 1855 , and a ribbed fitting 1859 which creates a water - tight seal when the core member is inserted into opening 1851 of the thick end of the us - icd . the s - icd and us - icd , in alternative embodiments , have the ability to detect and treat atrial rhythm disorders , including atrial fibrillation . the s - icd and us - icd have two or more electrodes that provide a far - field view of cardiac electrical activity that includes the ability to record the p - wave of the electrocardiogram as well as the qrs . one can detect the onset and offset of atrial fibrillation by referencing to the p - wave recorded during normal sinus rhythm and monitoring for its change in rate , morphology , amplitude and frequency content . for example , a well - defined p - wave that abruptly disappeared and was replaced by a low - amplitude , variable morphology signal would be a strong indication of the absence of sinus rhythm and the onset of atrial fibrillation . in an alternative embodiment of a detection algorithm , the ventricular detection rate could be monitored for stability of the r - r coupling interval . in the examination of the r - r interval sequence , atrial fibrillation can be recognized by providing a near constant irregularly irregular coupling interval on a beat - by - beat basis . an r - r interval plot during af appears “ cloudlike ” in appearance when several hundred or thousands of r - r intervals are plotted over time when compared to sinus rhythm or other supraventricular arrhythmias . moreover , a distinguishing feature compared to other rhythms that are irregularly irregular , is that the qrs morphology is similar on a beat - by - beat basis despite the irregularity in the r - r coupling interval . this is a distinguishing feature of atrial fibrillation compared to ventricular fibrillation where the qrs morphology varies on a beat - by - beat basis . in yet another embodiment , atrial fibrillation may be detected by seeking to compare the timing and amplitude relationship of the detected p - wave of the electrocardiogram to the detected qrs ( r - wave ) of the electrocardiogram . normal sinus rhythm has a fixed relationship that can be placed into a template matching algorithm that can be used as a reference point should the relationship change . in other aspects of the atrial fibrillation detection process , one may include alternative electrodes that may be brought to bear in the s - icd or us - icd systems either by placing them in the detection algorithm circuitry through a programming maneuver or by manually adding such additional electrode systems to the s - icd or us - icd at the time of implant or at the time of follow - up evaluation . one may also use electrodes for the detection of atrial fibrillation that may or may not also be used for the detection of ventricular arrhythmias given the different anatomic locations of the atria and ventricles with respect to the s - icd or us - icd housing and surgical implant sites . once atrial fibrillation is detected , the arrhythmia can be treated by delivery of a synchronized shock using energy levels up to the maximum output of the device therapy for terminating atrial fibrillation or for other supraventricular arrhythmias . the s - icd or us - icd electrode system can be used to treat both atrial and ventricular arrhythmias not only with shock therapy but also with pacing therapy . in a further embodiment of the treatment of atrial fibrillation or other atrial arrhythmias , one may be able to use different electrode systems than what is used to treat ventricular arrhythmias . another embodiment would be to allow for different types of therapies ( amplitude , waveform , capacitance , etc .) for atrial arrhythmias compared to ventricular arrhythmias . the core member of the different sized and shaped us - icd will all be the same size and shape . that way , during an implantation procedure , multiple sized us - icds can be available for implantation , each one without a core member . once the implantation procedure is being performed , then the correct sized us - icd can be selected and the core member can be inserted into the us - icd and then programmed as described above . another advantage of this configuration is when the battery within the core member needs replacing it can be done without removing the entire us - icd . to ensure adequate pacing capture of the heart through an s - icd having a subcutaneous only lead system , pacing therapy needs to be considerably enhanced by using a biphasic rather than the conventional monophasic waveform for pacing . in addition , to further compensate for the lack of direct contact with the heart , the subcutaneous electrode system , especially the anterior thoracic electrode system , that will be delivering the atp stimuli should result in as high as a current density as possible in order to activate the cardiac tissues . this can be facilitated by using a small electrode as close to the sternum as possible in the tissues overlying the right ventricle , the cardiac chamber closest to the anterior subcutaneous space where the s - icd of the present invention will lie . fig1 is a graph that shows an embodiment of the example of a biphasic waveform for use in anti - tachycardia pacing applications in subcutaneous implantable cardioverter - defibrillators (“ s - icd ”) in an embodiment of the present invention . as shown in fig1 , the biphasic waveform is plotted as a function of current versus time . in an embodiment , the biphasic waveform 1902 comprises a positive portion 1904 , a negative portion 1906 and a transition portion 1908 . in an embodiment , both the positive portion 1904 and the negative portion 1906 are substantially rectangular in shape . the positive portion 1904 of the biphasic waveform 1902 comprises an initial positive current 1910 , a positive fixed current 1912 and a final positive current 1914 . the negative portion 1906 of the biphasic waveform 1902 comprises an initial negative current 1916 , a negative fixed current 1918 and a final negative current 1920 . in an embodiment , the polarities of the biphasic waveform 1902 can be reversed such that the negative portion 1906 precedes the positive portion 1904 in time . as shown in fig1 , the biphasic waveform 1902 is initially at zero current . upon commencement of the anti - tachycardia pacing , a current of positive polarity is provided and the biphasic waveform 1902 rises to the initial positive current 1910 . next , the current of the biphasic waveform 1902 remains at a constant level along the positive fixed current 1912 . the positive portion 1904 of the biphasic waveform 1902 is then truncated and a negative current is provided . the biphasic waveform 1902 then undergoes a relatively short transition portion 1908 where the current is approximately zero . next , the biphasic waveform 1902 is increased ( in absolute value ) in the opposite ( negative ) polarity to the initial negative current 1916 . after reaching its maximum negative current ( in absolute value ), the current of the biphasic waveform 1902 remains at a constant level along the negative fixed current 1918 . after the negative portion 1906 of the biphasic waveform 1902 is truncated at the final negative current 1914 , the biphasic waveform 1902 returns to zero . the total amount of time that the biphasic waveform 1902 comprises is known as the “ pulse width .” in an embodiment , the pulse width of the biphasic waveform can range from approximately 1 millisecond to approximately 40 milliseconds . the total amount of energy delivered is a function of the pulse width and the absolute value of the current . an example of one embodiment of the biphasic waveform 1902 will now be described . in this embodiment , the amplitude of the initial positive current 1910 can range from approximately one to approximately 250 milliamps . similarly , the amplitude of the initial negative current 1916 can range from approximately one to approximately 250 milliamps . in the example , the pulse width of the biphasic waveform 1902 can range from approximately 1 millisecond to approximately 40 milliseconds . in addition , the implantable cardioverter - defibrillator employs biphasic anti - tachycardia pacing at rates of approximately 20 to approximately 120 stimuli / minute for severe bradycardia episodes , although programming of higher pacing rates up to 120 stimuli / minute is also possible . fig2 is a graph that shows an embodiment of the example of a monophasic waveform for use in anti - tachycardia pacing applications in subcutaneous implantable cardioverter - defibrillators (“ s - icd ”) in an embodiment of the present invention . as shown in fig2 , the monophasic waveform is plotted as a function of current versus time . in an embodiment , the monophasic waveform 2002 comprises an initial positive current 2004 , a positive fixed current 2006 and a final positive current 2008 . in an embodiment , the monophasic waveform 2002 is substantially rectangular in shape . in an embodiment , the polarities of the monophasic waveform 2002 can be reversed such that the waveform 2002 is negative in polarity . as shown in fig2 , the monophasic waveform 2002 is initially at zero current . upon commencement of the anti - tachycardia pacing , a current of positive polarity is provided and the monophasic waveform 2002 rises to the initial positive current 2004 . next , the current of the monophasic waveform 2002 remains at a constant level along the positive fixed current 1906 . the monophasic waveform 2002 is then truncated . an example of one embodiment of the monophasic waveform 2002 will now be described . in this embodiment , the amplitude of the initial positive current 2004 can range from approximately one to approximately 250 milliamps . in an embodiment , the pulse width of the biphasic waveform 2002 can range from approximately 1 millisecond to approximately 40 milliseconds . in addition , the implantable cardioverter - defibrillator employs anti - tachycardia pacing at rates of approximately 100 to approximately 350 stimuli / minute for ventricular tachycardia episodes . in addition , up to 30 atp stimuli for any single attempt could be allowed and as many as 15 atp attempts could be allowed for any effort to terminate a single episode of vt . one might also allow for different atp methods to be employed for vts of different rates or ecg characteristics . moreover , the device may be allowed to auto - select the method of atp to be used based upon the device &# 39 ; s and / or the physician &# 39 ; s experience with previous episodes of vt or with the patient &# 39 ; s underlying cardiac condition . in order to maintain these rates , in one embodiment of the invention , the power supply continues to operate to maintain a sufficient voltage to deliver a constant current . although it possible for the present invention to provide standard atp at predetermined or preprogrammed rates for monomorphic vt , the use of an s - icd may also be employed for the treatment of other arrhythmias such as atria tachyarrhythmias . in another embodiment , the invention can provide atp in response to a certain activity , respiration , pressure or oxygenation sensor as coupled to arrhythmia characteristics . the s - icd and us - icd devices and methods of the present invention may be embodied in other specific forms without departing from the teachings or essential characteristics of the invention . the described 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 by the foregoing description , and all changes which come within the meaning and range of equivalency of the claims are therefore to be embraced therein .

a power supply for an implantable cardioverter - defibrillator for subcutaneous positioning between the third rib and the twelfth rib and using a lead system that does not directly contact a patient &# 39 ; s heart or reside in the intrathoracic blood vessels and for providing anti - tachycardia pacing energy to the heart , comprising a capacitor subsystem for storing the anti - tachycardia pacing energy for delivery to the patient &# 39 ; s heart ; and a battery subsystem electrically coupled to the capacitor subsystem for providing the anti - tachycardia pacing energy to the capacitor subsystem .

a hand tool may be used to clean material from gaps between planking . fig1 shows a side view of a deck tool 100 having a blade portion 110 and a handle portion 120 . blade and handle portions 110 and 120 may primarily consist of a single core of sheet metal or other material thin enough to fit in a gap between planks , e . g ., less than about ¼ inch thick , and of sufficient strength to withstand the mechanical operations described further below . for many applications , the overall length of tool 100 and the core of tool 100 may be between about 10 and 40 inches with blade portion 110 being about 6 to 24 inches long and handle portion 120 being about 4 to 12 inches long . in one specific implementation , the core may be steel or galvanized steel about 1 / 16 inch thick and between about 1 and 4 inches wide . for example , the core of tool 100 may be made of a tempered or tool grade steel such as employed in handsaws so that blade portion 110 may flex without causing a permanent deformation of tool 100 . blade portion 110 of tool 100 may have one or both edges patterned to create a series of unsharpened bumps , which may be used for a back - and - forth or up - and - down action as described further below . a unsharpened bumps may be created , as shown in fig1 , by having a pattern of rounded peaks and valleys with edges that are blunt or dull . further , edge 112 may be without any set , i . e ., without bending the bumps sideways away from the plane of the major surface of blade 110 . in one specific implementation , each bump on edge 112 may be about 1 to 2 inches long , and the depth from peak to valley may be about ¼ to ½ inch . many other edge patterns could be employed in other implementations to provide dull or unsharpened bumps . fig1 shows blade portion 110 with both edges having the same pattern . alternatively , the two edges of blade portion 110 may have different patterns , e . g ., a smaller or more abrasive pattern on one side . one or both edges of the blade portion 110 may include a projection 116 that is near an end of blade portion 110 . projection 116 may be formed in blade portion 110 by cutting a notch 114 that is a deeper or more aggressive than pattern 112 so that projection 116 can better hook or catch material . in the implementation of fig1 , blade portion 110 has only one projection 116 , and a saw - tooth notch 114 creates a projection 116 that extends sideward no further than the peaks in pattern 112 . projection 116 may still be able to hook and drag material that is in a gap between planks . alternatively , pattern 112 may not include a notch , and instead , projection 116 may extend laterally from blade 110 further than the remainder of pattern 112 . projection 116 may further include a scraping feature 118 , e . g ., a tip that may be wider than the thickness of blade portion 110 . for example , scraping feature 118 may include a carbide tip or a metal crosspiece that is attached at the end of projection 116 . scraping feature 116 may be blunt but provide a width suitable for scraping or dragging material that may be caught in the gap between planks or on a surface of a joist or other support structure underlying the planks . alternatively , no scraping feature is added , and the shape and thickness of projection 116 allows for scraping as described herein . handle portion 120 may include a covering 122 over a portion of the core of tool 100 . covering 122 may be made , for example , using rubber , tape , plastic , metal , or any material that can that provides a suitable length , thickness , and texture for gripping with one or two hands . in some implementations , the pattern on the edge or edges of blade portion 110 continues to the edge or edges of handle portion 120 and provide a contour for gripping by hand . handle portion 120 may additionally include an extension attachment feature 124 that facilitates connecting an extension handle to the handle 122 of tool 100 . for example , attachment feature 124 may be threaded to receive a threaded broom handle or an extension handle of a type commonly used for painting . fig2 shows an implementation of a deck tool 200 that includes a blade portion 210 having an edge pattern 212 created with straight line cuts forming a shallow and unsharpened zigzag pattern . for example , edge pattern 212 may have peaks and valleys with angles greater than 120 ° so that a back - and - forth or sawing movement of edge pattern 212 may abrade or cut into dirt or debris trapped in a gap between planks , but pattern 212 will not significantly cut into wood or other deck material . cuts to form pattern 212 ( and the resulting edges ) may be at 90 ° to the surface of blade portion 210 so that no sharp edges are created . tool 200 also includes a notches 214 that create two projection 216 on opposite edges of blade portion 210 . in tool 200 , projections 216 rely on the shape and the thickness of the core material to hook , catch , or scrape debris . neither projection 216 uses an added tip , but the tip may be shaped or may be at a non - zero angle with the length of blade 210 to better scrape or hook material in a gap between planks . a handle portion 120 of tool 200 may be the same as handle portion 120 of tool 100 , which is described above . fig3 shows an implementation of a deck tool 300 that includes a blade portion 310 having an edge pattern 312 created with straight line cuts forming a series of plateaus . in particular , edge pattern 312 may have flat peaks and flat valleys connected by angled slops so that a back - and - forth or sawing movement of edge pattern 312 may abrade or cut into dirt or debris trapped in a gap between planks , but pattern 312 will not significantly cut into wood or other deck material . opposite edges 312 of blade portion 310 may be offset so that peaks on one edge 312 are opposite valleys on the other edge 312 . the offset pattern may allow for more uniform strength along the length of blade portion 310 and more efficient use of sheet metal from which the core of tool 300 may be cut . cuts to form patterned edges 312 may be at 90 ° to the surface of blade portion 310 so that no sharp edges are created . tool 300 also includes a notch 314 that create a projection 316 on one edge of blade portion 310 . a handle portion 120 of tool 300 may be the same as handle portion 120 of tool 100 , which is described above . fig4 a , 4b , and 4c illustrate a process for using a tool 400 to clean a gap between planks 430 on a support structure including joists 440 . tool 400 may be substantially the same as tool 100 or 200 described above with reference to fig1 and 2 . as shown in fig4 a , a blade 410 of tool 400 fits within the gap between planks 430 and extends so that a portion of blade 410 is below plank 430 . a user can work tool 400 up and down ( with an edge perpendicular or at any angle to the gap ) while moving tool 400 along the gap , e . g ., from one joist 440 to the next joist 440 as illustrated in fig4 b . if both edges of blade 410 are patterned , a user may move in either direction along the gap while working blade up and down and may reverse direction without removing blade 410 from the gap being cleaned . in general , the up - and - down movement of tool 400 will push some debris down out of the gap and pull some debris up out of the gap . any dislodged debris can then be easily vacuumed or otherwise removed from the top surface of planks 430 . in some configurations of tool 400 , the edge pattern of tool 400 provides bidirectional sawing so that both upward and downward movement of tool 400 dislodges debris from the gap with nearly equal efficiency . alternative , an asymmetric pattern on the edge of tool 400 , e . g ., a saw - tooth pattern , may more efficiently remove debris when moved in one direction , e . g ., when pulled up or when pushed down . whether the pattern is symmetric or asymmetric , the edge of blade 410 may be unsharpened so that when the edge of tool 400 encounters a joist 440 up and down motion does not easily saw into the joist 410 . fig4 c illustrates how when tool 400 reaches a joist 440 a projection 416 on the end of blade 410 can be positioned on the top edge or surface of the joist 440 and dragged across the top of the joist 440 to scrape away debris . the scraped debris may be caught on projection 416 and pulled up and out of the gap or pulled past joist 440 and pushed down and out of the gap . the removal of debris can prevent retention of moisture and prevent rotting , which may occur when joists 440 are wood . projection 416 can be similarly used to hook material that may be too hard to easily removed from the gap by the sawing motion of tool 400 illustrated in fig4 b . for example , projection 416 may be slid under a hard object such as a rock , screw , or nail that may have become wedge in a gap , so that a user can hook and pull the object up out of the gap . removal of iron items such as nails or screws may be important to prevent rust stains on planks 430 or support structure 440 . fig5 shows an end view of one implementation of a tool 100 having a handle 120 with an attachment feature 124 . attachment feature 124 includes an openings with threads into which a handle extension 620 may be threaded as shown in fig6 . with handle extension 620 , a user 650 may stand upright while using a tool to clean the gap between planks 430 . alternatively , a long tool may incorporate an extended handle 620 that is permanently attached to a blade portion 110 that is similar or identical to the blades disclosed above . a detachable handle extension may , however , have the advantage of allowing removal of handle extension 620 when the available working space makes a long handle tool cumbersome . for example , handle extension may be removed when cleaning gaps between planks on stairways or narrow sections of a deck . although particular implementations have been disclosed , these implementations are only examples and should not be taken as limitations . various adaptations and combinations of features of the implementations disclosed are within the scope of the following claims .

a deck tool has a blade edge with unsharpened bumps and an end projection . the blade fits into a gap between planks , where the unsharpened bumps permit sawing of soft gap - clogging material but do not damage structural members . the projection can hook material so that the material may be pulled from the gap or can scrape material from the top of a supporting structure . a handle of the tool may be directly held in hand and may include a feature for attachment of an extension that permits a user to stand upright while using the tool on a plank floor .

turning now to the embodiment illustrated in fig1 , a player first engages a program to play a game . the game may be downloaded to the players mobile computing device 10 , such as a personal digital assistant , laptop computer or similar device . in some preferred embodiments , the player &# 39 ; s mobile computing device may be connected to a heads - up display 12 for the purposes of displaying the game action , objects in the game , other players , scores , remote sensing features and the like . in some preferred embodiments , the user determines the location of a target object 14 , such as another player . in particular , the user determines the location of the target object relative to the user &# 39 ; s location . the target object may be another player , a physical object such as a tree , a water source or rock , or merely a selected location in physical space which may be used to correspond to a virtual location in the game . the distance between the user and a target object is determined using a ranging device 16 . appropriate ranging devices include , without limitation , a device having an element that determines the distance or range to a target based on the eye positions of the user ( e . g ., using a cross - hairs element in the heads - up display ); an infrared pointer device ; an ultrasonic device ; or any other ranging device . preferably , the player &# 39 ; s mobile computing device 10 also carries a locating element , such as a gps ( global positioning system ) locator 20 in communication with global positioning system 21 , that provides the user &# 39 ; s location , as well as the orientation of the user ( i . e ., the direction in which the user is facing ). the user &# 39 ; s location and orientation , together with the location of the target object relative to the user , thus can be used to determine the location of the target object . once the location of the target object has been determined , this location is transmitted to a central location 22 , in particular to a central computer . in particular embodiments , the information is transmitted via a wide - area network , such as the internet , using a device 24 carried by the user , such as , but not limited to , a personal data manager , a cellular telephone having internet accessibility , etc . when the central location is provided with the location of the target object , the central location searches for one or more data files pertaining to an object at that location . such data files can include , without limitation , text files , photographic files , video files , audio files , or dynamically changing data associated with the target object . in some preferred embodiments , such as when the target object is one or more other players , the data regarding the location ( s ) of the other player ( s ) may be updated dynamically with new information regarding the present location of the other player ( s ) in physical space being supplied by one or more devices , such as gps location devices 20 . in one preferred embodiment , two players are each equipped with wireless computers capable of detecting their physical locations and transmitting the locations via a wide area network to a gaming computer at central location 22 , which coordinates the location of the players with each other and virtual objects generated by the gaming program . the program then generates game object ( i . e ., virtual object ) 24 data , including perspective , size , etc ., to the players so that the objects appearing in the heads - up displays 12 of the players appear to realistically change their appearance in relation to the location of the players . for example , if the players are fifty feet apart and across from each other in a large grassy meadow of a park , in some embodiments , the gaming computer would transmit data corresponding to a game object of a dinosaur presented in the heads - up display of the players in proper proportion to appear to be between the players . as the players move , for example , circling the area corresponding to the computer - generated location of the dinosaur game object , the players would receive in their displays a rapidly updated depiction of the game object corresponding to the views one would see if one were traversing around a real object . see fig2 a - b . in some embodiments , a physical game tool or utensil 26 is also equipped with a location sensing and transmitting means 28 . in some embodiments the game tool is a sword which contains gps location sensing and transmission capability . by the use of such additional devices which can report their location coordinates to the game computer , players may use such utensils in the game . for example , a player might appear to strike the aforesaid virtual dinosaur with the player &# 39 ; s sword utensil . in some particular embodiments , the locations of the players and their actions are incorporated into the game , interact in real time with virtual game objects , such as computer generated dinosaurs , and such interactions and other game objects are displayed in a semitransparent heads - up display 12 which enables the real world to be the backdrop for the game . in other particular embodiments , the player could play against one or more physical players viewed directly via such semi - transparent heads - up displays , but who appear to be mixed into or otherwise superimposed upon the computer - generated game environments which are transmitted to the players &# 39 ; computers for display via their heads - up displays . the wireless computers may be capable of receiving voice commands via microphones attached to the heads - up displays . in one embodiment , the players could request to play a game in which voice commands are used exclusively . gaming object data as described above include video data , such as perspectives , sizes and the like . further embodiments of the inventive method include additional gaming object data such as audio , tactile and olfactory information . in specific embodiments , one or more scent reservoirs , which are carried , for example , in a headset or other apparatus worn by a player , can be triggered in response to gaming object data generated by the gaming program .

a method of location - based gaming includes the steps of engaging a program to play a game , determining the location of a target object , providing the location of the target object to a central location , obtaining a data file pertaining to an object at the location of the target object , and generating gaming object data relative to the location of the target object .

a currently preferred embodiment of the invention is described by means of fig1 to 8 . a cassette 2 according to the embodiment is composed of a lower part 5 and an upper part 7 which are connected to each other by means of snap elements 9 and 13 , and 11 and 15 , respectively . the upper part is made of a transparent material . besides , as can be seen from the figures , the cassette 2 is provided approximately in the form of a rectangle having two arms 35 a , 35 b . the lower part 5 as well as the upper part 7 of the cassette 2 comprises a window 17 in a central area of the rectangle . moreover , in the upper part 7 , two bars 3 a , 3 b are formed to be used as positioning means according to the invention . the bars 3 a , 3 b extend along a partial section of a product - conveying path 1 . a channel - type passage 1 is formed as product - conveying path 1 in the lower part 5 . the passage 1 is divided into two sections 1 a and 1 b . at one edge of the lower part 5 opposite the arms 35 a , 35 b , two tube clamps 19 a , 19 b are integrated into the lower part 5 . a tube ( not shown in the figures ) provided with a blood bag , a filter and a product bag is laid in the product - conveying path 1 such that the tube is conducted from the blood bag disposed between the arms 35 a , 35 b to the first section 1 a , along the bar 3 a , through the tube clamp 19 a arranged in the first section 1 a further to the arm 35 a . the tube then emerges from the arm 35 a , leads to the filter , and enters via the second arm 35 b the second section 1 b of the passage 1 . then , the tube is led along the bar 3 b , through the tube clamp 19 b and again the arm 35 b , in order to emerge from the same towards the product bag . at each of its arms 35 a , 35 b , the cassette 2 comprises a projection 21 a , 21 b disposed inside , which is used to detachably fix the cassette to a non - represented cartridge similar to the one in documents de 10 2007 000 308 a1 , de 10 2007 000 309 a1 and de 10 2007 000 310 a1 . the blood bag , the filter and the product bag are then accommodated in appropriate chambers of the cartridge . the cassette 2 replaces a cover in the said applications . together with the cassette 2 , the loaded cartridge is inserted into a system component 4 that is arranged in a centrifuge . an elevation 25 in which two grooves are formed is provided in a section of the system component 4 . photosensitive sensors 23 a , 23 b are inserted into the inner walls of each groove . if the cassette 2 is disposed in the system component 4 , the elevation 25 is engaged in a form - fit connection with the window 17 , and the bars 3 a and 3 b with the grooves formed in the elevation 25 . the sections of the tube extending along the bars 3 a , 3 b are disposed directly below the bars 3 a , 3 b , whereby the contents of the tube can be exactly registered by the photosensitive sensors 23 a , 23 b . the first photosensitive sensor 23 a is assigned to the first section 1 a of the product - conveying path 1 , whereas the second photosensitive sensor 23 b is assigned to the second section 1 b of the product - conveying path 1 . the optical axes of the photosensitive sensors 23 a and 23 b substantially intersect the central axis of the product conveying path ( the tube ) at a right angle . since the tube does not have to be inserted into the cassette 2 any more , but the cassette is already delivered together with the readily laid tube including blood bag , filter and product bag , a faulty insertion of the tube or a displacement of the tube that would lead to a faulty registration by the sensors can be reliably excluded . thus , it is possible , due to the interaction of the cassette according to the invention with the system component , to obtain a blood product by means of the method disclosed in document de 10 2007 000 309 a . according to the embodiment , the rotor of the centrifuge is designed for six system components 4 having one cartridge each . after all cartridges loaded with cassettes 2 have been inserted , the centrifuge is started . by means of the centrifugal force , the desired separation of the blood components is effected . since the “ buffy coat ” diluted by an additive solution is in the blood bag , the lighter components of it will remain radially inside , whereas its heavier components , i . e . the red blood cells , collect outside . in order to transport the desired blood component — according to the embodiment , these are the platelets ( thrombocytes )— in high quality , i . e . without the admixture of other blood cells , from the blood bag , the separation of the components will be followed by a slight pressure being applied onto the blood bag by means of a pressure pad , so that , after the previously closed tube clamps 19 a , 19 b have been opened , the solution rich in platelets begins to rise into the tube disposed in the passage 1 . the solution rich in platelets is led through the tube into the filter designed as a leukocyte filter , and is further conducted therethrough . in the leukocyte filter , the undesired leukocytes , i . e . the white blood cells , are removed . due to the arrangement of the tube with the filter , the filtration is effected against the centrifugal force . thus , heavier blood components , such as unintentionally transported red blood cells , are trapped in a filter - inlet chamber positioned radially outside . after having passed the leukocyte filter , the solution rich in platelets continues flowing through the tube laid in the second section 1 b of the passage 1 into a product bag , in which it is collected . preferably , the product bag is already formed as final storage bag for the product . in order to remove any air that might be present in the filter , the flow speed is kept low for a certain volume quantity at the beginning of the product transfer , thereby enabling the filter to fill with the blood product reliably and completely . after the transfer of this specific volume quantity , the conveying speed for a specific second volume quantity is increased by means of an appropriate control of the pressure pad . while this second volume is transported , there is hardly any risk that red blood cells contaminate the blood product ( here : the thrombocyte concentrate ). should this nevertheless happen , this small number of red blood cells are collected in the lower and outer area of the filter , due to the tube being guided from radially outside and below into the filter , and due to the effect of the centrifugal force . after the second volume has been transferred , the first photosensor 23 a is activated and the flow speed of the blood product in the tube is reduced . when the first photosensor 23 a detects a predetermined proportion of red blood cells in the thrombocyte - rich solution , it outputs a signal by means of which the flow speed is again reduced . furthermore , the second photosensor 23 b disposed behind the filter is activated . during this phase , also a rather large number of red blood cells can enter the filter and even pass therethrough until the second photosensor 23 b detects a predetermined proportion of red blood cells in the blood product and outputs a signal for terminating the cell separation process . by this signal , the tube clamps 19 a , 19 b are closed by operation of the ends 29 a , 29 b of a long lever 29 by means of pistons 31 a , 31 b , so that the red blood cells in the filter are reliably separated from the thrombocyte concentrate in the product bag . as an alternative to the termination by the second photosensor 23 b , the cell separation process can also be terminated after a certain period of time has elapsed after the activation of the second photosensor 23 b . in the embodiment , altogether six cartridges are provided in the centrifuge . the above - described control of the cell separation process in a cartridge 1 by means of a pressure pad , the opening and closing of the tube clamps 19 a , 19 b , and the process control by means of the two photosensors 23 a , 23 b enables a continued cell separation in the cartridges of the other system components , since the described process control takes place individually for each combination of cartridge and system component . the control of the process is effected by a microprocessor provided in the system component , said microprocessor processing the detection / registration results of the sensors 23 a , 23 b and accordingly controlling the opening and closing of the tube clamps 19 a , 19 b by operating the levers 31 a , 31 b and 33 a , 33 b , respectively . besides , the microprocessor is connected to a microprocessor arranged in the hub of the rotor for controlling the centrifuge and monitoring the microprocessors in the individual system components . when the above - mentioned process is carried out , a precise operation of the tube clamps 19 a , 19 b is required for ensuring an optimum yield while simultaneously avoiding a contamination of the product . for operating the tube clamps 19 a and 19 b integrated in the lower part 5 of the cassette 2 , the invention provides , in the system component , an arrangement having a centrally arranged long lever 29 and l - shaped , short levers 27 a , 27 b arranged at the two ends 29 a and 29 b of the long lever 29 . the ends 29 a , 29 b of the long lever are disposed between a leg of the short lever 27 a , 27 b and a closing arm 191 of the tube clamp 19 a and 19 b , respectively . at its central section , the long lever 29 is fixed to the system component 4 . the short levers 27 a , 27 b are pivotally supported around the intersection of the two legs of the “ l ”. the entire lever arrangement is disposed along the edge of the cassette 2 , on which the tube clamps 19 a , 19 b are arranged when the cassette is inserted into the system component . pistons 31 a , 31 b , 33 a , 33 b , which are suitably arranged in the system component 4 , are used for operating the levers 27 a , 27 b and 29 . the pistons 31 a , 31 b directly act on the respective end 29 a , 29 b of the long lever . the pistons 33 a , 33 b directly act on a leg of the short levers 27 a and 27 b , respectively , said leg being disposed between the pistons 33 a and 33 b and the respective ends 29 a , 29 b of the long lever 29 . since the ends 29 a , 29 b of the long lever 29 are disposed directly opposite the closing arm 191 of the tube clamps 19 a and 19 b when the cassette is inserted , an operation of the piston 31 a or 31 b leads to the closing of the respective tube clamp 19 a or 19 b . since , in turn , an operation of the pistons 33 a , 33 b acts on the one leg of the rotatably supported , short levers 27 a and 27 b , respectively , this operation leads to a twisting of the levers 27 a and 27 b , respectively . the leg disposed between the pistons 33 a and 33 b acts on the end 29 a or 29 b of the long lever 29 , whereas the other leg of the short lever 27 a or 27 b acts on an opening arm 192 of the tube clamp 19 a or 19 b , thereby opening the same . the indirect operation of the ends 29 a , 29 b of the long lever serves to exclude that the tube clamp bursts open too suddenly or too wide , so that problems e . g . due to the tube clamps getting jammed can be avoided . the invention has been described by means of a currently preferred embodiment , but is not restricted thereto in any way , but only defined by the scope of the claims attached .

the invention pertains to a cassette comprising a product conveying path and a positioning means engageable with a counter - piece on a centrifuge having a rotor for separating blood components or on a system component arranged in a centrifuge . the positioning is effected such that a section of the product conveying path is aligned with a section of the centrifuge or the system component arranged in the centrifuge . furthermore , a tube connected with bags is accommodated in the product conveying path .

embodiments of the presently disclosed defibrillator electrode delivery system will now be described in detail with reference to the drawing figures wherein like reference numerals identify similar or identical elements . as illustrated in fig1 , a defibrillator electrode delivery system , according to an embodiment of the present disclosure , is generally designated as 100 . defibrillator electrode delivery system 100 includes an automatic external defibrillator ( aed ) 102 defining a surface 140 configured to store or retain a pair of electrode pads 10 , 20 . electrode pads 10 , 20 are electrically connectable to or pre - connected to aed 102 via respective lead wires 12 , 22 joined at a connector 30 . surface 140 is coated with a release material to selectively adhere electrode pads 10 , 20 thereto and to facilitate the removal of electrode pads 10 , 20 therefrom when needed . for example , the release material may be teflon , silicone , and combinations thereof . in this configuration , a gel layer of each electrode pad 10 , 20 has a reduced tendency to dry - out . due to the adherence of the electrode pads 10 , 20 to surface 140 of aed 102 , no special packaging is required that reduces a moisture vapor transmission rate ( mvtr ) of the electrode pads 10 , 20 . as illustrated in fig2 , a defibrillator electrode delivery system , according to another embodiment of the present disclosure , is generally designated as 200 . defibrillator electrode delivery system 200 includes an automatic external defibrillator ( aed ) 202 having a pair of spaced apart brackets 212 , 214 supported on a surface thereof . defibrillator electrode delivery system 200 is configured to store or retain a pair of electrode pads 10 , 20 that are supported on a release liner 250 . brackets 212 , 214 are spaced apart an amount sufficient to engage , capture and / or lock down on release liner 250 to thereby maintain electrode pads 10 , 20 secured to aed 202 . electrode pads 10 , 20 are electrically connected to aed 202 via respective lead wires ( not shown ) joined at a connector ( not shown ). in this configuration , a gel layer of each electrode pad 10 , 20 has a reduced tendency to dry - out . due to the adherence of the electrode pads 10 , 20 to release liner 250 , no special packaging is required that reduces a moisture vapor transmission rate ( mvtr ) of the electrode pads 10 , 20 . as illustrated in fig3 a and 3b , a defibrillator electrode delivery system , according to a further embodiment of the present disclosure , is generally designated as 300 . defibrillator electrode delivery system 300 includes an automatic external defibrillator ( aed ) 302 having a carrier flap or page 360 hingedly connected thereto via a hinge member 362 . defibrillator electrode delivery system 300 is configured to store or retain a pair of electrode pads 10 , 20 that are supported on a front side , a back side and / or on opposed sides 360 a , 360 b of flap 360 ( as shown in fig3 a and 3b ). as shown in fig3 b , each electrode pad 10 , 20 may include a respective pull tab 11 , 21 to facilitate the removal of electrode pads 10 , 20 from flap 360 . electrode pads 10 , 20 are electrically connectable to or pre - connected to aed 302 via respective lead wires 12 , 22 joined at a connector 30 . in this configuration , a gel layer of each electrode pad 10 , 20 has a reduced tendency to dry - out . due to the adherence of the electrode pads 10 , 20 to flap 360 , no special packaging is required that reduces a moisture vapor transmission rate ( mvtr ) of the electrode pads 10 , 20 . as illustrated in fig4 , a defibrillator electrode delivery system , according to still another embodiment of the present disclosure , is generally designated as 400 . defibrillator electrode delivery system 400 includes an automatic external defibrillator ( aed ) 402 having a two - part fastener member 470 associated therewith for selectively securing a pair of electrode pads thereto ( only one electrode pad 10 being shown ). two - part fastener member 470 includes a first part 470 a secured to aed 402 and a second part 470 b secured to a backing layer 10 a of electrode pad 10 . electrode 10 includes a conductive and / or non - conductive substrate 10 b overlying backing layer 10 a , on a side opposite the second part 470 b of the two - part fastener member 470 . electrode 10 further includes a gel or hydrogel layer 10 c overlying substrate 10 b , and a liner 10 d overlying gel or hydrogel layer 10 c . two - part fastener member 470 may be in the form of a hook and loop type fastener where one of the first part 470 a and the second part 470 b is the hook portion and the other of the first part 470 a and the second part 470 b is the loop portion . it is contemplated that the two - part fastener member 470 may include double - sided tape or the like . in this configuration , a gel or hydrogel layer 10 e of electrode pad 10 has a reduced tendency to dry - out . due to the securement of the electrode pad 10 to aed 402 and to the provision of a liner 10 d overlying gel or hydrogel layer 10 c , no special packaging is required that reduces a moisture vapor transmission rate ( mvtr ) of the electrode pads . as illustrated in fig5 , a defibrillator electrode delivery system , according to another embodiment of the present disclosure , is generally designated as 500 . defibrillator electrode delivery system 500 includes an automatic external defibrillator ( aed ) 502 having a release liner 580 secured to a surface thereof via a clamp 582 . defibrillator electrode delivery system 500 is configured to store or retain at least one electrode pad 10 on a front side 580 a of release liner 580 . as shown in fig5 , electrode pad 10 may include a pull tab 11 to facilitate the removal of electrode pad 10 from release liner 580 . in this configuration , a gel layer of electrode pad 10 has a reduced tendency to dry - out . due to the adherence of the electrode pad 10 to release liner 580 , no special packaging is required that reduces a moisture vapor transmission rate ( mvtr ) of the electrode pads 10 , 20 . as illustrated in fig6 , a defibrillator electrode delivery system , according to yet another embodiment of the present disclosure , is generally designated as 600 . defibrillator electrode delivery system 600 includes an automatic external defibrillator ( aed ) 602 including a pair of electrical contact points or pads 690 , 692 disposed in a surface thereof . defibrillator electrode delivery system 600 includes a pair of electrode pads 10 , 20 electrically connectable to or pre - connected to aed 602 via respective lead wires 12 , 22 joined at a connector 30 . electrode pads 10 , 20 are also in contact with respective contact pads 690 , 692 . each electrical contact pad 690 , 692 is electrically connected to a respective electrical connector 690 a , 692 a which electrically interconnected to respective lead wires 12 , 22 by way of connector 30 . in this manner , a first electrical circuit is defined which includes contact pad 690 , a respective electrical connector 690 a , connector 30 , lead wire 12 and electrode pad 10 . also , a second electrical circuit is defined which includes contact pad 692 , a respective electrical connector 692 a , connector 30 , lead wire 22 and electrode pad 20 . aed 602 , as schematically shown in fig6 , includes a battery “ b ” and high voltage circuitry “ c ” disposed in a housing 602 a thereof . the battery and the high voltage circuitry are electrically connected to connector 30 and / or electrical connectors 690 a , 690 b . it is contemplated that as electrode pads 10 , 20 are lifted or separated from aed 602 , that electrode pads 10 , 20 separate from contact pads 690 , 692 , altering an impedance or breaking a respective circuit therebetween , and thereby causing aed 602 to automatically begin to power - up or initialize ( i . e ., run an automated set - up process with readies aed 602 prior to use in a cardiac emergency ). it is further contemplated that aed 602 is automatically powered - up upon a separation of any one of electrode pads 10 , 20 from contact pads 690 , 692 of aed 602 . alternatively , or in addition to the automated set - up process , as so configured , an impedance check may be performed across each electrode pad 10 , 20 to check an impedance of each electrode pad 10 , 20 and determine if a moisture content of a gel layer of each electrode pad 10 , 20 is acceptable for use thereof . as illustrated in fig7 , a defibrillator electrode delivery system , according to still another embodiment of the present disclosure , is generally designated as 700 . defibrillator electrode delivery system 700 includes an automatic external defibrillator ( aed ) 702 including a pair of electrode pads , an apex electrode pad 10 and a sternum electrode pad 20 . electrode pads 10 , 20 are electrically connectable to or pre - connected to aed 702 via respective lead wires 12 , 22 . apex electrode pad 10 includes a pull tab 13 that projects from or extends from a perimeter of a box or liner 704 disposed on aed 702 , which retains electrode pads 10 , 20 . electrode pads 10 , 20 are arranged on box or liner 704 such that , as apex electrode pad 10 is peeled off of box or liner 704 , liner 704 rolls forward and exposes a pull tab 23 of sternum electrode pad 20 so that the sternum electrode pad 20 is ready to be removed from liner 704 after placement of apex electrode pad 10 is placed against the patient . in accordance with any of the embodiments of the present disclosure described above , it is contemplated that as electrode pads 10 , 20 are removed from or separated from the surface of the aed , that the aed may automatically begin to power - up . electrode pads configured for use with any of the electrode delivery systems disclosed herein are shown and described in international patent application serial no . pct / us2007 / 010060 , filed apr . 27 , 2007 , in u . s . patent application ser . no . 12 / 237 , 803 , filed on sep . 25 , 2008 , and u . s . patent application publication no . 2009 / 0227857 , filed on mar . 6 , 2008 , the entire content of each of which being incorporated herein by reference . an example of a suitable polymer which may be utilized in the electrode pads disclosed herein includes rg - 63b hydrogel , commercially available from tyco healthcare group d / b / a / covidien . other suitable hydrogels include those disclosed in u . s . patent application publication no . 2009 / 0270709 , filed on oct . 30 , 2009 , and u . s . patent application publication no . 2009 / 0270710 , filed on oct . 30 , 2009 , the entire disclosures of each of which are incorporated by reference herein for all purposed . it is to be understood that the foregoing description is merely a disclosure of particular embodiments and is in no way intended to limit the scope of the disclosure . other possible modifications will be apparent to those skilled in the art and are intended to be within the scope of the present disclosure .

an automatic external defibrillator configured to deliver electrical pulses and / or shocks to a heart of a patient during a cardiac emergency includes a housing supporting an electrical connector ; a defibrillator electrode delivery system supported on the housing and a pair of defibrillation electrode pads supported by the defibrillator electrode delivery system . each of the pair of defibrillation electrode pads is pre - connected to the electrical connector of the housing . a hydrogel layer of each defibrillation electrode pad is retained by the defibrillator electrode delivery system in such a manner so as to reduce a moisture vapor transmission rate thereof .

a device of the present invention includes a miniature precision reciprocating displacement pump driven by a shape memory alloy wire linear actuator and controlled by a programmable pulse generating circuit . for purposes of description , the device is divided into three subcomponents , a precision miniature reciprocating displacement pump head , a shape memory alloy linear actuator , and a programmable pulse generating circuit . each subcomponent is comprised of multiple elements . a schematic representation of a most general embodiment of the invention is shown in fig1 a and is described below . the miniature precision pump head is comprised of the following elements : a rigid substrate 101 to which other components may be attached so as to fix their orientation and position relative to one another , a fluid reservoir 102 for storing the fluid to be pumped 103 and a small cavity , henceforth referred to as the displacement cavity 104 , whose volume can be varied between precisely defined limits . the limit corresponding to a state of maximum volume for the displacement cavity 104 is defined as the first limit 105 and the limit corresponding to a state of minimum volume for the displacement cavity 104 is defined as the second limit 106 . an inlet conduit 107 connects the displacement cavity 104 to the fluid reservoir 102 and thus permits fluid flow between the two . an inlet check valve 108 is situated within the inlet conduit 107 such that fluid flow is restricted to flowing from the fluid reservoir 102 to the displacement cavity 104 . an outlet conduit 109 connects the displacement cavity 104 to some point 111 to which it is desired to deliver the fluid . an outlet check valve 110 is situated within the outlet conduit 109 such that fluid flow is restricted to flowing from the displacement cavity 104 to the point 111 to which it is desired to deliver the fluid . the shape memory alloy actuator is comprised of a shape memory allow material , such as a nickel - titanium alloy material , sometimes referred to as “ nitinol .” the shape memory alloy material is sensitive to temperature or heat . for example , the material temporarily shrinks at a certain temperature , or shrinkage temperature , such as about 70 ° c . above ambient temperature for nitinol , and expands at a relatively lower temperature to return to its original condition . in response to being heated to the above - described shrinkage temperature , the shape memory alloy undergoes a dimensional change , such as a change in its length . in this way , a wire composed of a material such as nitinol , can undergo a change in length and a return toward its original length one or more times via temperature treatment or repeated temperature cycling . it is contemplated that a material that expands by going through a phase transition at a certain temperature and shrinks at a different temperature to return toward its original condition could be used . in the process of undergoing a dimensional change , as described above , the shape alloy material goes through a reversible phase transition or transformation , or a reversible structural phase transition , upon a change in temperature . generally , such a transition represents a change in the material from one solid phase of the material to another , for example , by virtue of a change in the crystal structure of the material or by virtue of a reordering of the material at a molecular level . in the case of nitinol , for example , the superelastic alloy has a low temperature phase , or martensitic phase , and a high temperature phase , or austenitic phase . these phases can also be referred to in terms of a stiff phase and a soft and malleable phase , or responsive phase . the particular phase transition associated with a particular alloy material may vary . the shape memory alloy actuator is also comprised of the following elements . a movable member is referred to as a plunger 112 and is fixed by a rigid restraint 113 such that it is constrained to a periodic motion of precisely fixed limits . the plunger 112 is situated in relation to and / or attached to the displacement cavity 104 such that movement of the plunger 112 within the limits of its constrained motion will cause the volume of the displacement cavity 104 to be varied between its limits 105 , 106 . a biasing spring 115 is situated relative to the rigid restraint 113 and the plunger 112 such that at equilibrium , the biasing spring 115 exerts a force on the plunger 112 whose direction is that which would induce the displacement cavity 104 toward a state of minimum volume , i . e ., toward its second limit 106 . a length of shape memory alloy wire 114 is connected at one end to the plunger 112 and at another end to the rigid substrate 101 . the shape memory alloy wire 114 is situated such that its dimensional change will give rise to motion of the plunger 112 . the shape memory alloy wire 114 and the biasing spring 115 are both of sufficient dimension such that when the shape memory alloy wire 114 is heated so as to induce phase transition and associated dimensional change , the wire will move the plunger 112 against the force of the biasing spring 115 “ in one generally uninterrupted motion ” to its second limit 105 so as to create a state of maximum volume within the displacement cavity 104 , whereas when the shape memory alloy is allowed to cool to ambient temperature , the force imparted by the biasing spring 115 will stretch the shape memory alloy wire 114 until the point where the displacement cavity 104 is in a state of minimum volume . the programmable pulse generating circuit is comprised of a source of electric power 116 , an electrical connection 117 from the source of electric power 116 to each end of the shape memory alloy wire 114 and a programmable pulse generating circuit 118 situated along the electrical connection 117 such that pulses of electricity from the electric power source 116 may be applied to the shape memory alloy wire 114 automatically in a preset regular periodic manner . operation of the device proceeds in a cyclic manner . for purposes of description the beginning of the cycle is defined as the following state . all void space within the fluid reservoir 102 , inlet 107 and outlet 109 conduit , inlet 108 and outlet 110 check valves and displacement cavity 104 are completely filled with the fluid 103 to be pumped . the shape memory alloy wire 114 is at ambient temperature and thus in a state of maximum length . correspondingly , the position of the plunger 112 is such that the volume of the displacement chamber 104 is at its minimum value . the biasing spring 115 is in a compressed state such that it exerts a force on the plunger 112 consistent with a state of minimum volume of the displacement cavity 104 . operation of the device involves first a heating of the shape memory alloy wire 114 to a temperature and for a period of time sufficient to induce phase transition and an associated dimensional change . heating of the shape memory alloy wire 114 is accomplished by passing an electric current though it . the duration of the electric heating period is preset and is controlled by the timing and switching circuit 118 . the dimensional change of the shape memory alloy wire 114 will result in the movement of the plunger 112 against the opposing force of biasing spring 115 so as to vary the volume of the displacement chamber 104 toward its first limit 105 and a state of maximum volume . as the volume of the displacement cavity 104 is increased , fluid 103 is drawn into the displacement cavity 104 from the fluid reservoir 102 through the inlet conduit 107 and inlet check valve 108 . fluid 103 is not drawn into the displacement cavity 104 through the outlet conduit 109 due to the one - way flow restriction of the outlet check valve 110 . after the preset duration , the current is then switched off by the timing and switching circuit 118 allowing the shape memory alloy wire 114 to cool below its phase transition temperature . cooling proceeds via natural convection to the ambient environment . when the shape memory alloy wire 114 cools below its phase transition temperature , the force exerted by the biasing spring 115 stretches the shape memory alloy wire 114 to its original maximum length . this allows the movement of the plunger 112 so as to vary the volume of the displacement cavity 104 toward its second limit 106 and a state of minimum volume . as the volume of the displacement cavity 104 is decreased , fluid 103 is pushed out of the displacement cavity 104 through the outlet conduit 109 and outlet check valve 110 . fluid 103 is not pushed out of the displacement cavity 104 through the inlet conduit 107 due to the one - way flow restriction of the inlet check valve 108 . thus one complete heating and cooling cycle of the shape memory alloy wire 114 results in the delivery of a volume of fluid 103 from the fluid reservoir 102 to the end of the outlet conduit 111 . the volume of fluid delivered with each cycle is precisely equal to the difference between the maximum and minimum volumes of the displacement cavity 104 as determined by the precisely defined limits 105 , 106 . the overall rate of fluid delivery is controlled by varying the period of time between actuations of the shape memory alloy actuator 104 . a schematic representation of an alternative general embodiment of the invention is shown in fig1 b . the alternative general embodiment includes all of the same components and elements as the general embodiment shown in fig1 a with the following exceptions . in this embodiment of the invention , heating of the shape memory alloy material 114 so as to cause a phase transition associated shortening of its length results in a minimum volume condition for the displacement cavity 104 . this may be achieved , for example , through the use of a pivoting linkage assembly 119 connecting the biasing spring 115 to the plunger 112 . as stated previously , it is an intention of the present invention that it be sufficiently small and sufficiently inexpensive to be practically used as both a portable device and as a disposable device . for example , a device that can be comfortably worn on the skin as an adhesive patch and can be disposed of and replaced after 3 days of use . a preferred embodiment of the invention includes specific embodiments of the various elements and components of the general embodiment that are consistent with this intention . a preferred embodiment of the invention is diagrammed schematically in fig2 a , 2 b and 2 c and is comprised of all of the same elements and components of the general embodiment of the invention shown in fig1 a and 1b with the following exceptions . in a preferred embodiment of the invention the displacement cavity is comprised of an elastomeric diaphragm pump head 201 . an enlarged view of the details of the diaphragm pump head 201 is shown by fig2 b with pump head 201 in a state of minimum volume and by fig2 c with pump head 201 in a state of maximum volume . the diaphragm pump head is comprised of an elastomeric diaphragm 202 set adjacent to a rigid substrate 203 and scaled about a perimeter of the elastomeric diaphragm 202 . the displacement cavity 204 is then comprised of the volume in between the adjacent surfaces of the rigid substrate 203 and the elastomeric diaphragm 202 within the sealed perimeter . separate inlet 205 and outlet 206 conduits within the rigid substrate 203 access the displacement volume of the elastomeric diaphragm pump head 201 with the inlet conduit 205 connecting the displacement cavity 204 with a fluid reservoir 207 and the outlet conduit 206 connecting the displacement cavity 204 to the point to which it is desired to deliver fluid 208 . an inlet check valve 209 and an outlet check valve 210 are situated within the inlet conduit 205 and outlet conduit 206 respectively , oriented such that the net direction of flow is from the fluid reservoir 207 to the point to which it is desired to deliver fluid 208 . the plunger 211 is comprised of a cylindrical length of rigid dielectric material . the plunger 211 is situated within a cylindrical bore 212 of a rigid restraint 213 such that the axis of the plunger 211 is oriented normal to surface of the elastomeric diaphragm 202 . the flat head of the plunger 211 is functionally attached to the non - wetted surface of elastomeric diaphragm 202 opposite the displacement cavity 204 such that movement of the plunger 211 along a line of motion coincident with its axis will cause the concomitant variation in the volume of the displacement cavity 204 . the biasing spring 214 is situated within the cylindrical bore 212 of the rigid restraint 213 , coaxial with the plunger 211 . the relative positions and dimensions of the plunger 211 , the rigid restraint 213 and the biasing spring 214 are such that at equilibrium the biasing spring 214 exerts a force on the plunger 211 along a line coincident with its axis such that the displacement cavity 204 is in a state of minimum volume ( fig2 a ). a straight length of shape memory alloy wire 215 is situated in a position coincident with the axis of the plunger 211 . one end of the shape memory alloy wire 215 is fixed to the rigid restraint 203 and electrically connected by connection 216 to the programmable pulse generating circuit 217 and the electric power source 218 . the other end of the shape memory alloy wire 215 along with an electrical connection 219 to that end is connected to the end of the plunger 211 . the shape memory alloy wire 215 and the biasing spring 214 are both of sufficient dimension such that when the shape memory alloy wire 215 is heated so as to induce phase transition and associated dimensional change , it will pull the plunger 211 against the force of the biasing spring 214 so as to create a state of maximum volume within the displacement cavity 204 , whereas when the shape memory alloy is allowed to cool to ambient temperature , the force imparted by biasing spring 214 will stretch the shape memory alloy wire 215 until the point where the displacement cavity 204 is in a state of minimum volume . a preferred embodiment of an inlet and outlet check valve is shown in cross - section in fig3 and is comprised of a molded one - piece elastomeric valve which can be press - fit into the inlet or outlet conduit . an important feature for a check valve appropriate for use in the present invention is that it possesses a low cracking pressure and provides a tight seal in the absence of any back pressure . a preferred embodiment of such a check valve is comprised of a thin - walled elastomeric dome 301 situated on top of a thick elastomeric flange 302 . the top of the dome has a small slit 303 cut through it that is normally closed . a fluid pressure gradient directed toward the concave side 304 of the dome will induce an expansion of the dome 301 forcing the slit 303 open so as to allow fluid to flow through the valve in this direction . a fluid pressure gradient directed toward the convex side 305 of the dome will induce a contraction of the dome 301 forcing the slit 303 shut so as to prohibit fluid to flow through the valve in this direction . a preferred embodiment of a pulse generating circuit is shown in fig4 and is comprised of a 200 milliamp - hour , lithium - manganese oxide primary battery 401 , a high capacitance , low - equivalent series resistance ( esr ) electrochemical capacitor 402 , a programmable digital timing circuit 403 , and a low - resistance field effect transistor switch 404 . the shape memory alloy wire is indicated in fig4 symbolically as a resistor 405 . the battery 401 and electrochemical capacitor 402 are electrically connected to each other in parallel and are connected to the shape memory alloy wire 405 through the transistor switch 404 . the programmable timing circuit 403 , also powered by the battery 401 , sends a gating signal to the transistor switch 404 , as programmed by the user in accordance with the user &# 39 ; s pumping requirements . during the period of time for which the transistor switch 404 is open , the battery 401 will keep the electrochemical capacitor 402 at a state of full charge . during the period of time for which the transistor switch 404 is closed , power will be delivered to the shape memory alloy wire 405 , primarily from the electrochemical capacitor 402 rather than from the battery 401 , owing to the substantially lower esr associated with the electrochemical capacitor 402 . as such , the battery 401 is substantially isolated from the high current draw associated with the low resistance of the shape memory alloy wire 405 and the useful life of the battery 401 is significantly extended . a preferred embodiment of a fluid reservoir 207 appropriate for use with the present invention is one for which the volume of the fluid reservoir diminishes concomitantly as fluid is withdrawn such that it is not necessary to replace the volume of the withdrawn fluid with air or any other substance . a preferred embodiment of a fluid reservoir 207 might comprise a cylindrical bore fitted with a movable piston , for example , a syringe , or a balloon constructed of a resilient material . operation of the preferred embodiment of the invention proceeds in a manner analogous to that described for the most general embodiment . in addition to its simplicity , the preferred embodiment has the advantage of physically blocking any fluid flow from the fluid reservoir to the point to which it is desired to deliver the fluid when there is no power being supplied to the system . this provides additional protection against an overdose caused by fluid expanding or being siphoned through the check valves when the system is inactive . a functional model of a preferred embodiment of the invention has been constructed and its performance has been characterized . the functional model is similar in appearance to the preferred embodiment of the invention shown in fig2 , 3 and 4 and is described in more detail below . the fixed rigid components of the pump including the rigid restraint and the rigid substrate of the diaphragm pump head are each machined from a monolithic block of acetal . inlet and outlet conduits are additionally machined out of the same block . check valves are commercially available one - piece elastomeric valves ( for example , check valve , part # va4914 , available from vernay laboratories inc . of yellow springs , ohio ). a length of shape memory alloy actuator is 40 mm long and 125 μm in diameter ( for example , shape memory alloy wire , flexinol 125 lt , available from mondo - tronics , inc . of san rafael , calif .). electrical connections to the ends of the shape memory alloy actuator are made with 30 awg copper wire . the copper wire is twisted to the shape memory alloy wire to effect a good electrical connection . a plunger is machined out of acetal and has an overall length of 10 . 0 mm and a shaft diameter of 3 . 2 mm . an elastomer diaphragm is comprised of 0 . 025 mm thick silicon rubber film ( for example , silicon rubber film , cat . # 86435k31 , available from mcmaster carr , of los angeles , calif .). the flat head of the plunger is secured to the elastomer diaphragm with epoxy ( for example , epoxy , stock # 14250 , available from itw devcon , of danvers , mass .). the ends of the shape memory alloy wire - copper conductor assembly are connected to the plunger and to the rigid restraint with epoxy . a stainless steel biasing spring has an overall length of 12 . 7 mm , an outside diameter of 3 . 0 mm , a wire diameter of 0 . 35 mm and a spring constant of 0 . 9 n / mm ( for example , biasing spring , cat . # c0120 - 014 - 0500 , available from associated spring , of dallas , tex .). a pulse generating circuit is comprised of an adjustable analog timing circuit based on a 556 dual timing integrated circuit ( for example , 556 dual timing circuit , part # ts3v556 , available from st microelectronics , of san jose , calif .). power is supplied by a 3 v lithium - manganese dioxide primary cell ( for example , li / mgo 2 battery , part # dl2032 , available from duracell , of bethel , conn .). power load leveling is facilitated by the use of an electrochemical supercapacitor ( for example , electrochemical supercapacitor , part # b0810 , available from powerstor inc ., of dublin , calif .) in parallel with the battery . high - power switching is achieved with a field effect transistor ( for example , field effect transistor switch , part # irlz24n , available from international rectifier , of el segundo , calif .). the functional model was characterized with respect to reproducibility , insulin stability and energy consumption . the model was operated by heating the shape memory alloy wire with a short pulse of current and then allowing the shape memory alloy wire to cool . each heating pulse and subsequent cooling period comprised a single actuation cycle . a device that is used to automatically deliver a drug to an individual over an extended period of time should do so with extreme precision . this is particularly critical when the drug being delivered is one that might have dangerous health consequences associated with an inappropriate dose . insulin is one such drug . an excessive dose of insulin can result in dangerously low blood glucose level , which in turn can lead to coma and death . thus any device to be used for automatically delivering insulin to a diabetic person must be able to demonstrate a very high level of precision . to characterize the precision with which the invention can deliver insulin , the functional model was repeatedly cycled at a constant period of actuation and the total quantity of liquid delivered was measured as a function of the number of actuation cycles . fig5 shows typical results . the data in fig5 were obtained with an actuation period of 28 seconds and a pulse duration of 0 . 15 seconds . in fig5 markers show actual data points and the line represents a least squares fit of the data points . data were collected over 8500 cycles at which point the measurement was stopped . the fit to the data has a slope of 1 . 997 mg / cycle and a linear correlation coefficient of 0 . 999 indicating that the functional model delivered extremely consistent volumes of liquid with each actuation over the course of the measurement . another important requirement for any medical device that handles insulin is that the device does not damage the insulin . insulin is a large and delicate biomolecule that can readily be damaged by the mechanical action ( e . g ., shear stress ) of a pumping device . three common modes of insulin destruction which result in a loss of bioactivity are aggregation , where individual insulin molecules bond together to form various polymer structures , degradation , where individual insulin molecules are broken apart , and denaturing , where individual molecules remain intact but lose their characteristic conformation . all three modes of insulin destruction are exacerbated by elevated temperatures . thus , in the development of a practical insulin pumping device , preferably , it should be demonstrated that the device does not damage insulin . to characterize the insulin stability associated with the invention , a quantity of insulin ( insulin , humalog u100 , available from eli lilly , of indianapolis , ind .) was set up to recycle continuously through the functional model over the course of several days at 37 ° c . samples of the insulin were collected each day for evaluation . this resulted in a series of pumped insulin samples with an increasing amount of pump stress . the insulin samples were then analyzed by reverse - phase high performance liquid chromatography . the chromatography indicated a 2 % loss of insulin concentration after a single pass through the pump and a further loss of another 5 % of the insulin concentration after 3 days of recycling . it is desirable for a small and inexpensive insulin delivery device to be able to execute its maximum intended term of use with the energy from a single small inexpensive primary battery . based on a 0 . 1 unit dose size and a maximum insulin consumption of 100 units per day for 3 days , a maximum term of use for the inventive device might be considered to be 3000 cycles . to characterize the energy consumption of the invention , the functional model was operated continuously for several days at an actuation period of 85 seconds while the voltage of a 200 milliamp - hour , 2032 lithium / manganese dioxide battery was monitored . fig6 shows typical results . a typical voltage vs . capacity curve for the lithium / manganese dioxide battery is characterized by an initial drop in voltage from about 3 . 2 v to a plateau voltage of about 2 . 8 v . the voltage of the battery remains at this plateau level for the duration of its useful life . the battery voltage will then drop precipitously to a value below 2 v when its capacity expires . the data in fig6 indicate that the battery is still at its plateau voltage after 4000 pump cycles and thus the 200 milliamp - hour , lithium / manganese dioxide battery is more than adequate to power the device of the present invention for its intended term of use . a first alternative embodiment of the invention is diagrammed schematically in fig7 and is comprised of all of the same subcomponents and elements of the most general embodiment of the invention shown in fig1 with the following exceptions . in a first alternative embodiment of the invention , the displacement cavity , as well as the inlet and outlet conduit , are all comprised of a single length of small - diameter flexible and resilient tubing 701 . the tubing 701 is situated within a restraining fixture 702 secured to a rigid base 703 so as to fix the position and orientation of the tubing 701 relative to the other elements of the device . inlet 704 and outlet 705 check valves are located within the bore of the tubing 701 such that they have a common orientation for flow direction and such that a length of empty tubing 701 exists in between the two check valves 704 , 705 . the volume within the inner diameter of the tubing 701 and in between the two check valves 704 , 705 comprises a displacement cavity 706 . the volume of the displacement cavity 706 is varied by compressing the resilient tubing 701 with a plunger 707 ( described below ) at a position midway between the two check valves 704 , 705 . the volume within the inner diameter of the tubing 701 and in between the two check valves 704 , 705 when the tubing 701 is uncompressed defines the maximum volume of displacement cavity 706 . the volume within the inner diameter of the tubing 701 and in between the two check valves 703 , 704 when the tubing 701 is fully compressed by the plunger 707 defines the minimum volume of the displacement cavity 705 . the plunger 707 is comprised of a cylindrical length of rigid dielectric material and includes a flange 708 and a tapered end 709 . the plunger 707 is situated within a cylindrical bore 710 of a rigid restraint 711 such that the axis of the plunger 707 is oriented normal to the axis of the resilient tubing 701 and such that the tapered head 709 of the plunger 707 may be alternately pressed against the resilient tubing 701 and removed from contact with the resilient tubing 701 with movement of the plunger 707 along a line of motion coincident with the its axis . a biasing spring 712 is fitted around the shaft of the plunger 707 in between the rigid restraint 711 and the plunger flange 708 . the relative positions and dimensions of the plunger 707 , the rigid restraint 711 and the biasing spring 712 are such that at equilibrium the biasing spring 712 exerts a force on the plunger 707 along a line coincident with its axis that is sufficient to fully collapse the resilient tubing 701 and thus create a state of minimum volume of the displacement cavity 706 . a straight length of shape memory alloy wire 713 is situated in a position coincident with the axis of the plunger 707 . one end of the shape memory alloy wire 713 is attached to the rigid base 703 and electrically connected by connection 716 to the pulse generating circuit 714 and the electric power source 715 . the other end of the shape memory alloy wire 713 along with an electrical connection 717 to that end is attached to the shaft of the plunger 707 . the shape memory alloy wire 713 is of sufficient length and strength that when heated so as to induce phase transition and associated dimensional change it will pull the plunger 707 away from contact with the resilient tubing 701 against the opposing force of the biasing spring 713 . a second alternative embodiment of the invention is diagrammed schematically in fig8 and is comprised of all of the same subcomponents and elements of the most general embodiment of the invention shown in fig1 with the following exceptions . a displacement cavity 801 is comprised of a cylindrical shell 802 and tube 803 arrangement where the tube 803 is coaxial with the shell 802 and can move freely within the shell 802 along a line coincident with that axis . the volume of the displacement cavity 801 is varied by moving the tube 803 relative to the shell 802 . movement of the tube 803 into the shell 802 reduces the volume of the displacement cavity 801 whereas movement of the tube out of the shell increases the volume of the displacement cavity 801 . a dynamic seal 804 , for example and elastomer o - ring , seals the displacement cavity 801 while not interfering adversely with the relative motion of the shell 802 and tube 803 . outlet 805 and inlet 806 conduits access the displacement cavity 801 through the ends of the shell 802 and tube 803 respectively . outlet 807 and inlet 808 check valves are situated within the shell 802 and tube 803 respectively . a biasing spring 809 is situated within the displacement cavity 801 so as to resist the motion of the displacement cavity 801 toward a state of reduced volume . a shape memory alloy wire 810 is attached between the shell 802 and the tube 803 along the outside of the assembly such that when the shape memory alloy wire 810 is heated so as to induce phase transition and associated dimensional change it will incline the displacement cavity 801 toward a state of reduced volume . the shape memory alloy wire 810 is electrically connected by connector 811 to a programmable pulse generating circuit 812 and a source of electric power 813 . hard stops ( not shown ) on the limits of the relative positions of the shell 802 and tube 803 define the maximum and minimum volumes of the displacement volume 801 . operation of both the first and second alternative embodiments of the invention proceed in a manner analogous to that described for the most general embodiment and preferred embodiment of the invention . in all of the embodiments described above , a shape memory alloy wire acts as an actuator to drive a movable member to increase or decrease the fluid volume in the pump head , and once the wire cools a spring is used to return the movable member back to its original position . those of reasonable skill in this field will appreciate that a multitude of other biasing means exist , one or more of which can be used in place of or in addition to the spring . in fact , a shape memory alloy can be constructed in such a way that it drives the movable member in both directions to act as both an actuator and a return biasing element . for example , the shape memory alloy can be coiled much like a spring to drive the movable member in one direction when heated and in the other direction when cooled . a first alternative embodiment of a pulse generating circuit is diagrammed schematically in fig9 and is comprised of a 200 milliamp - hour lithium - manganese dioxide primary battery 901 , a dc to dc converter 902 , a capacitor 903 , a low - resistance field effect transistor switch 904 , a programmable digital timing circuit 905 , an inductor 906 and a diode 908 . the shape memory alloy wire is indicated in fig9 symbolically as a resistor 907 . the objective of this embodiment of a pulse generating circuit is that the pulses of power delivered to the shape memory alloy wire 907 can be of a higher voltage , and thus higher current , than that associated with the preferred embodiment of a pulse generating circuit diagrammed in fig4 and described previously . a high voltage , high current power pulse has the advantage that it can actuate the circuit in a shorter more efficient time period . additionally , the alternative embodiment of a pulse generating circuit allows the useful life of the battery 901 to be extended to a lower voltage and can prevent other circuitry powered by the battery from resetting when the battery voltage droops as is likely to happen in the preferred embodiment . the battery 901 and capacitor 903 are electrically connected to each other in parallel through the dc to dc converter 902 . the capacitor 903 is further connected to the shape memory alloy wire 907 through the transistor switch 904 . the programmable timing circuit 905 , also powered by the battery 901 sends a gating signal to the transistor switch 904 as programmed by the user in accordance with their pumping requirements . during the period for which the transistor switch 904 is open , the dc to dc converter 902 draws energy from the battery 901 and stores it in the capacitor 903 . use of the dc to dc converter 902 allows the voltage of the capacitor 903 to be charged to a significantly higher value than that associated with the battery 901 and to be charged to the same voltage throughout the life of the battery 901 regardless of the battery voltage . it is intended that the transistor switch 904 may be modulated to send an overall energy pulse as a single pulse or as a sequence of discrete smaller pulses . it is intended that these smaller pulses may be sequenced so as to tailor a custom profile for the overall energy pulse . the custom profile would ensure optimal energy delivery to the shape memory alloy without exceeding its fusing characteristics . the inclusion of the inductor 906 and diode 908 allows current to continue to flow through the shape memory alloy wire 907 after the transistor switch 904 is opened when the pulse is modulated . this allows further control of the energy delivered to the shape memory alloy . various references , publications , provisional and non - provisional united states patent applications , and / or united states patents , have been identified herein , each of which is incorporated herein in its entirety by this reference . various aspects and features of the present invention have been explained or described in relation to beliefs or theories or underlying assumptions , although it will be understood that the invention is not bound to any particular belief or theory or underlying assumption . various modifications , processes , as well as numerous structures to which the present invention may be applicable will be readily apparent to those of skill in the art to which the present invention is directed , upon review of the specification . although the various aspects and features of the present invention have been described with respect to various embodiments and specific examples herein , it will be understood that the invention is entitled to protection within the full scope of the appended claims .

a system for the metering and delivery of small discrete volumes of liquid is comprised of a small or minimal number of inexpensive components . one such component is a movable member , such as a miniature precision reciprocating displacement pump head , which is driven by an actuator that comprises a shape memory alloy material . the operating mechanism of the system is of little or minimal complexity . the system facilitates the precise metering and delivery of the small discrete volumes of liquid . potential applications for the system include subcutaneous , long - term , automated drug delivery , for example , the delivery of insulin to a person with diabetes . in such an application , the small , simple and inexpensive nature of the invention would allow for its use as both a portable and a disposable system .

the following description is of the best mode presently contemplated for carrying out the invention . this description is not to be taken in a limiting sense , but is made merely for the purpose of describing the general principles of the invention . the scope of the invention should be determined with reference to the claims . a representative ics that may be used with the present invention is disclosed in u . s . pat . no . 5 , 522 , 865 , incorporated herein by reference . a representative fitting system , or fitting tool , that may be used in lieu of , or as a supplement to , the present invention is disclosed in u . s . patent application ser . no . 08 / 456 , 141 , filed may 31 , 1995 , also incorporated herein by reference . a representative electrode array that may be used with the ics is shown in u . s . pat . no . 4 , 819 , 647 , which patent is likewise incorporated herein by reference . bi - phasic pulse : a balanced stimulation pulse delivered in the cochlea from the implant . balanced indicates that an equal amount of charge is delivered positively as is delivered negatively in order to eliminate any dc component . blanking amplifier : an amplifier that gates off coincident with the delivery of an electrical stimulation pulse generated by the cochlear prosthesis so that stimulus - induced artifacts may be canceled out , allowing lower level signals to not be lost . channel : a selected pair of electrodes capable of applying a given stimulus to a desired location within the cochlea . see &# 34 ; ics .&# 34 ; clinician &# 39 ; s computer : a computer used by the clinician or audiologist that presents a display of the fitting process and allows parameters to modified to optimize fitting . closed - loop system : a system that uses feedback to &# 34 ; zero - in &# 34 ; on a specified output . comfort level : an electrical stimulation level on a single channel that is perceived as comfortably loud to the patient . compound action potential ( cap ): an electrical potential recordable in tissues surrounding neurons resulting from recruitment of large numbers of neurons acting synchronously in response to electrical stimulation applied by a cochlear stimulator . dynamic range : electrical dynamic range is the range between electrical threshold and comfort level . sound intensity dynamic range is the range in which input sound intensities are mapped into the electrical dynamic range . evoked potential : measured localized central nervous system potentials correlated with an external sensory event . evoked potential signals tend to be very noisy due to surface ( non - direct ) electrode placement and other bodily electrical activities . as a result , evoked potentials are best identified by correlation with an external trigger . electrical threshold : for purposes of this application , the minimum electrical stimulation level that can be perceived by the patient in a given channel of the ics . electromyogram ( emg ): the electrical activity that accompanies the muscle contractions . emg is generally recorded as a broadband , amplitude - modulated ac signal whose general amplitude or envelope corresponds to the strength of the command ( neural ) signals from the brain . fitting : the process of customizing a cochlear prosthesis to a patient by setting the appropriate psychophysical parameters . ics : an implantable cochlear stimulator , including an electrode array having spaced - apart electrodes adapted for insertion into the cochlea . the ics typically includes multiple channels , each of which may provide stimuli to a selected pair of the spaced - apart electrodes ( bipolar stimulation ), and / or to a selected one of the spaced - apart electrodes and a reference electrode ( monopolar stimulation ). each channel thus effectively delivers a stimulus to a different section or location of the cochlea . impedance bridge : a standard audiometric instrument which , for this application , measures middle ear compliance for different pressures and measures the stimulation evoked stapedius reflex . ipsilateral : on the same side of the head , in this case on the same side as the implant . middle ear compliance : a measure of the ability of the middle ear to transmit energy . mismatched negativity : an evoked potential that is created by introducing an &# 34 ; odd - ball &# 34 ; or &# 34 ; deviant &# 34 ; stimulus into a regular stimulus pattern . middle ear reflex ( mer ): mechanical tension produced by the stapedius and tensor tympani , two muscles of the middle ear , in response to neural signals received from the brain . mer may be measured by comparing the amplitude of the meg envelope with and without stimulation . most comfortable level ( mcl ): the level of stimulation at which a middle ear reflex first appears . myogenic noise : muscle noise , usually electrical noise . for purposes of the present invention , the patient is sedated in order to reduce muscle noise when evoked potentials are being recorded . speech processor ( sp ): a device used with an ics that senses audio sounds , converts such sounds to electrical signals , and processes the electrical signals in accordance with a prescribed speech processing strategy to produce stimulation control signals . the stimulation control signals , in turn , are used by the ics to stimulate the cochlea . somatic events : muscular contractions caused by accidental electrical stimulation of the facial nerve . stapedius reflex response : contraction of the stapedius muscle . such response occurs when the patient is exposed to an electrical stimulation level of between about 70 - 100 db equivalent sensation level . for purposes of the present invention , this response is used to estimate comfortably loud levels for the patient . threshold of hearing ( t ): the level of stimulation which can be perceived or heard , corresponding generally to the level of stimulation at which a cap can first be recorded , or a small fixed value above that level . tri - phasic pulse : a balanced stimulation pulse delivered in the cochlea from the implant . see &# 34 ; bi - phasic &# 34 ;. a tri - phasic pulse better models spiral ganglion firing , assisting in the recovery of neurons and possibly reducing unwanted stimulation artifacts . referring first to fig1 there is shown a simplified functional block diagram of a preferred implanted self - fitting or self - adjusting cochlear implant system 46 made in accordance with the present invention . it is to be emphasized that which is shown in fig1 is greatly simplified in order to depict the basic functions that are carried out by the implanted and external portions of the system 46 as the present invention is carried out . as seen in fig1 the system 46 includes an implanted portion 50 ( referred to hereafter as the implant 50 ) and an external ( or non - implanted ) portion 53 . the external portion , in turn , is usually made up of a microcontroller ( μc ) 52 coupled to a clinician &# 39 ; s computer 16 . the μc 52 may be realized using a conventional speech processor ( sp ) with a special interface which allows it to be connected directly to the clinician &# 39 ; s computer 16 , as is known in the art . a much more detailed description of a preferred cochlear implant 50 may be found , e . g ., in the previously referenced u . s . pat . no . 5 , 522 , 865 . as indicated , the implant 50 includes , or is coupled to , a suitable microcontroller ( μc ) 52 . it is noted that for some embodiments of the implant 50 , the μc 52 may comprise part of an external speech processor . for other embodiments of the invention , however , the μc 52 may comprise part of an internal or implanted speech processor . regardless of its location , it is the μc 52 that provides the necessary control signals to control the operation of the implant 50 . hence , the μc 52 comprises a main component of the stimulation system . in a conventional cochlear implant , the control signals from the μc 52 ( which are digital signals ) are converted to analog signals by a suitable digital - to - analog ( d / a ) converter 46 &# 39 ;. the resulting analog signals output from the d / a converter 46 &# 39 ; are then applied to a suitable driver circuit 44 for application to a cochlear electrode array 56 . of course , much additional circuitry is used to carry out these basic functions , such as modulating the control signals to inductively couple them through the skin of the patient to an implanted unit ( when required ), demodulating the received signals , decoding the control signals to extrapolate the control information contained therein , generating the appropriate stimulus signals , and applying such stimulus signals to the designated electrode pair or channel of the electrode array . however , for purposes of the present invention , it is sufficient to consider the conventional cochlear implant circuitry as that which performs the two basic functions shown within the dotted line 42 of fig1 coupled to a suitable μc 52 and electrode array 56 . as indicated above , these two basic functions are represented by the d / a converter 46 , which converts the stimulation control signals obtained from the μc 52 to analog signals , and then applies such converted signals to a selected electrode 48 of the cochlear electrode array 56 through the electrode driver 44 . in addition to the basic cochlear implant functions described above , the self - adjusting cochlear implant 50 of the present invention includes at least one additional electrode not typically found within a cochlear implant unit . that is , a specialized electrode 54 is placed near the stapedius or tensor tympani muscle . second , a separate electrode 59 , which may comprise one of the electrodes of the electrode array 56 , is placed in or near the cochlea . the separate electrode 59 may comprise part of the electrode array 56 , or may be separate from the array 56 . the stapedius / tensor tympani electrode 54 is connected to a suitable amplifier 64 , the output of which is filtered by a bandpass filter 66 . the output of the filter 66 is then converted to an appropriate digital signal by analog - to - digital circuit 68 , which digital signal is then directed to a digital signal processor ( dsp ) 57 , and then coupled to the μc 52 . in operation , the stapedius / tensor tympani electrode 54 , which may include any suitable transducer that converts mechanical motion to an electrical signal , such as a small piezoelectric element , senses movement of the stapedius muscle and generates an electrical signal as a function of such sensed movement . alternatively , the electrode 54 may be positioned to best sense the emg . the signal sensed by electrode 54 , which represents a measured response of the stapedius muscle or the mer , is then amplified , filtered and digitized by the amplifier 64 , filter 66 , a / d converter 68 , and dsp 57 , and presented to the μc 52 as a digital signal through bidirectional telemetry . still referring to fig1 the evoked potential electrode 59 is similarly connected to an amplifier 58 , an adjustable bandpass filter 60 , an analog - to - digital converter 62 , and the dsp 57 . evoked potentials sensed through the electrode 59 are thus amplified by the amplifier 58 , filtered by the filter 60 , digitized by the a / d converter 62 , processed by the dsp 57 , and presented to the μc 52 as a digital signal . advantageously , the amplifier 58 comprises a blanking amplifier . such blanking amplifier may , for example , be blanked off at all times except during a narrow window of time during which the evoked response , e . g ., the cap , if present , will appear , thereby blocking myogenic and other noise from being processed by the evoked response circuitry at times other than the narrow window detection time . more importantly , the blanking amplifier 58 may be blanked coincident with the application of a stimulus signal to the cochlear electrode array , thereby preventing any stimulus - created artifacts from being sensed through the amplifier 58 . such blanking action thus makes it easier to sense the evoked potentials because such evoked potentials might otherwise be masked out by the usually much larger stimulus - induced artifacts . further illustrated in fig1 is a graphical depiction of a tri - phasic pulse 70 . it is important that the electrical stimulus which is applied to the electrodes of the electrode array 56 be charged - balanced , meaning that such stimulus should have positive components that are equal to its negative components . the tri - phasic pulse 70 achieves this goal by having the sum of its respective leading and trailing small positive portions be substantially equal to one larger negative middle portion . in contrast to the implantable self - adjusting cochlear prosthesis system shown in fig1 a block diagram of an external self - fitting cochlear prosthesis system is shown in fig2 . as needed or desired , the external system may be used to supplement or complement that which is achieved using the implant system 46 shown in fig1 . in fig2 as with fig1 it is assumed that a patient 12 has an ics implanted in or near at least one of his or her ears . a fitting device 14 sends stimulation control signals , or &# 34 ; input &# 34 ; signals , to the ics through a first wire 20 . typically , the wire 20 is connected to a headpiece 26 which is magnetically held over the ics , and which headpiece inductively couples the stimulation control signals into the ics , as is known in the art . to this end , the fitting device 14 includes a speech processor ( sp ) 30 coupled to a microcontroller ( μc ) or microprocessor ( μp ) 38 . the μc 38 controls the sp 30 so that the appropriate stimulation control signals are generated . the fitting device 14 further includes an evoked potential blanking amplifier 32 connected to a bandpass filter ( bpf ) 34 . the bpf 34 , in turn , is connected to an analog - to - digital ( a / d ) converter 36 , the output of which is connected to the μc 38 . the input of the blanking amplifier 32 is connected by way of wire 26 to an earlobe electrode 28 . evoked potentials sensed through the earlobe electrode 28 are thus amplified by the amplifier 32 , filtered by the bpf 34 , converted to a digital value by the a / d converter 36 , and presented to the μc 38 as a digital value . still with reference to fig2 a conventional impedance bridge 18 is coupled to the middle ear of the patient 12 by way of cable 22 , which cable 22 includes sufficient conductors to enable the impedance bridge 18 to measure the compliance of the patient &# 39 ; s middle ear . such compliance may be measured in conventional manner . the impedance bridge 18 typically employs a standard rs - 232 serial interface , or equivalent data interface , through which data may be sent to the fitting device 14 , thus allowing compliance data measured within the patient &# 39 ; s middle ear to be provided to the μc 38 through the connecting cable 24 . a clinician &# 39 ; s computer 16 may also be coupled to the μc 38 of the fitting device 14 by way of cable 40 , connected to either a serial or parallel port . use of the computer 16 allows the user of the computer , i . e ., the clinician and / or audiologist , to track and control the activities being carried out by the fitting device 14 . the computer 16 is especially helpful in that it typically includes a suitable display screen , or other output device , on which graphs , tables , reports and other useful information associated with the fitting process may be displayed and / or printed . the self - fitting cochlear prosthesis system shown in fig2 determines the thresholds of the patient 12 for each channel of his or her ics by providing a known input signal to the ics from the sp 30 over the signal line 20 and measuring the resulting output stapedius reflex response ( using the impedance bridge 18 ) and / or the measured output evoked potentials ( using the blanking amplifier 32 , filter 34 , and a / d converter 36 ). more particularly , as described more fully below in conjunction with the flow chart shown in fig3 a , 3b , and 3c , the self - fitting system of the invention zeros - in on the needed threshold information by first using the stapedius reflex response to determine a coarse threshold level , which stapedius reflex response can be obtained relatively quickly ; and then uses such coarse threshold level as the starting point for a more precise hunt for a fine threshold level using the measured evoked response . turning next to fig3 a , 3b and 3c , a flow chart is shown that illustrates the self - fitting method used by the present invention to determine the patient thresholds for each channel of an ics . each main step of the self - fitting method or process is depicted as a &# 34 ; block &# 34 ; or &# 34 ; box &# 34 ;, each of which has a reference numeral assigned thereto to aid in the description that follows . while various portions of the method are depicted in each of fig3 a , 3b or 3c , it comprises a single flow chart , and reference may hereafter be made collectively to fig3 a , 3b and 3c as simply &# 34 ; fig3 &# 34 ;. the method shown in fig3 a - 3c is directed to the method used with the external self - fitting cochlear prosthesis system shown in fig2 . however , the same basic method is followed when using the implanted system of fig1 with the exceptions indicated . turning first then to fig3 a , it is seen that a first step of the method involves verifying the patient is sufficiently sedated , or otherwise at rest ( block 102 ). such step assures that the method may be carried out without interfering myogenic or other noise . once the patient is sufficiently sedated , then the necessary equipment , e . g ., the impedance bridge 18 and the fitting device 14 , as shown in fig2 is set - up and connected to the patient ( block 104 ). with the equipment connected as illustrated in fig1 the impedance bridge is calibrated by determining and setting that pressure value ( loudness ) at which maximum middle ear compliance occurs ( block 106 ). such pressure value may thereafter serve as a &# 34 ; threshold &# 34 ; value for detecting when a given sound &# 34 ; input &# 34 ; to the patient &# 39 ; s ear causes a stapedius reflex to occur on a given channel . the process of detecting the stapedius reflex on each channel includes selecting a first channel ( block 108 ), and the then stimulating the patient on the selected channel with a specified bi - phasic or tri - phasic pulse at a specified stimulation level ( block 110 ). for example , the specified bi - phasic or tri - phasic pulse may have a width of from 75 to 150 μsec , and the specified stimulation level may initially range from 6 dbu to 30 dbu . a determination is then made as to whether the applied stimulus caused a stapedius reflex ( block 112 ). if not ( no branch of block 112 ), then the stimulation level is raised by a prescribed amount , e . g ., 6 dbu ( block 114 ), and a check is made as to whether the raised stimulation level exceeds a maximum stimulation level ( block 116 ). the maximum stimulation level is typically 60 dbu or other specified fda charge limits . if the maximum limit has not been reached ( no branch of block 116 ), then a tri - phasic or bi - phasic pulse of the raised stimulation level is applied to the patient and the process repeats ( blocks 110 , 112 , 114 ). if the maximum limit has been reached ( yes branch of block 116 ), then that means a stapedius reflex is not detectable on the specified channel ( block 122 ). when a stapedius reflex is detected ( yes branch of clock 112 ) in response to the applied stimulus of the specified intensity level , then the stapedius reflex growth function is determined by varying the amplitude above and below the intensity level at which the stapedius reflex response was first detected . knowing the growth function allows one to predict how the stapedius reflex grows ( changes ) when subjected to stimuli near the threshold , and helps determine the threshold through extrapolation . once the stapedius reflex of the first channel has been determined ( or a determination has been made that the stapedius reflex is not detectable on the first channel ), then a determination is made as to whether there are any more channels for which the stapedius reflex measurement needs to be determined ( block 120 ). if so ( yes branch of block 120 ), then the next channel is selected ( block 124 ), and the stimulation intensity level is returned to its specified initial value . then the process repeats for the newly selected channel ( blocks 110 through 118 ). if all of the channels have been stimulated in an effort to determine the point at which a stapedius reflex occurs ( no branch of block 120 ), then the stapedius threshold is extrapolated or estimated for each channel ( block 130 , fig3 b ). if stapedius data was obtained ( as determined , e . g ., at blocks 110 , 112 , 118 ), then such data is used to extrapolate the threshold . if no stapedius data was detectable for a given channel ( see , e . g ., block 122 ), then the threshold is estimated to be 6 dbu . advantageously , the stapedius thresholds determined as described above , by extrapolation and / or estimation , represent a coarse , or rough , determination of the desired stimulation thresholds to be used by the ics . in order to further &# 34 ; zero - in &# 34 ; on the such threshold , the present invention uses an evoked response measurement . more particularly , as shown in fig3 b , a first channel is selected ( block 132 ). an initial stimulus amplitude is then set at a value near the previously - determined stapedius threshold for the selected channel , and an appropriate adjustment interval , δ int , is specified ( block 134 ). one of the drawbacks of using evoked potentials for determining the appropriate stimulation threshold is that a rather large sample of evoked potentials must be obtained in order to assure a statistically valid measurement . for example , evoked potentials may require from 32 to 1000 samples using the external system of fig1 . one of the advantages of the implanted system of fig2 over the external system of fig1 is that the number of samples required for the implanted system is usually reduced by a factor of at least 2 . in view of the above , a first determination at the beginning of the loop in which the evoked potential measurements are made is to determine whether sufficient evoked potential samples have been obtained to produce a statistically valid indication of threshold ( block 136 ). if not ( no branch of block 136 ), which will always be the case when the evoked potential test is first started , then a stimulus is applied that has a specified starting intensity ( block 138 ), i . e ., an intensity near that of the stapedius reflex determination . a determination is then made as to whether such applied stimulus evoked a response ( block 140 ). if not ( no branch of block 140 ), then the stimulus intensity is increased by the specified adjustment interval δ ( block 142 ). if so ( yes branch of block 140 ), then the stimulus intensity is decreased by the specified adjustment interval δ ( block 144 ). the size of the adjustment interval δ ( for use during the next pass through the loop ) is then decreased ( block 146 ). the adjusted stimulus ( which is either increased or decreased over the prior stimulus , depending upon whether an evoked response was observed or not ) is then used for a next pass through the evoked potential loop ( blocks 136 through 146 ). this process continues , with repeated passes through the evoked potential loop continuing until a sufficient number of evoked potentials have been obtained ( yes branch of block 136 ), with each pass using a decreased or smaller δ , in order to zero - in on the evoked potential threshold . after sufficient samples of evoked potential have been obtained for the first channel , the process repeats for the other channels . that is , once the evoked potential data has been obtained for one channel ( yes branch of block 136 ), a determination is made as to whether there are any more channels ( block 148 ). if so ( yes branch of block 148 ), then the next channel is selected ( block 150 ), and the initial stimulus intensity is set to an initial value for that channel based on the stapedius threshold of that channel and based on the evoked potential threshold of one or more previous channels ( block 152 ). further , the value of the adjustment interval δ is reset to δ int ( block 154 ), and the evoked potential for the newly - selected channel is determined as previously described ( blocks 136 through 154 ). once all of the channels have been subjected to the evoked - potential - determining loop ( no branch of block 148 ), then a determination is made as to whether a perceivable loudness resolution test is to be performed ( block 160 , fig3 c ). the performance of such a test is preferably an option that may be selected by the clinician . if such a test is not to be performed ( no branch of block 160 ), then the self - fitting method is completed ( block 174 ). if such a test is to be performed ( yes branch of block 162 ), then the channel on which the test is to be performed is selected ( block 162 ). the selected channel is then stimulated with a train of pulses of constant amplitude intermixed with pulses of raised or lowered amplitudes ( a stimulation pattern known as an &# 34 ; odd - ball &# 34 ; or &# 34 ; deviant &# 34 ; paradigm ). based on the applied stimulation from such odd - ball or deviant paradigm pulse train , a determination is made as to whether there is any increased cortical activity that is synchronized with the odd - ball / deviant amplitude ( block 166 ). if so ( yes branch of block 168 ), then that indicates that the patient recognizes amplitude differences corresponding to the odd - ball / deviant amplitude channel ( block 168 ). if there is no increased cortical activity synchronized with the odd - ball / deviant amplitude ( no branch of block 166 ), then that indicates the contrary result , i . e ., the patient does not recognize amplitude differences corresponding to the odd - ball / deviant amplitude . once a first channel has been subjected to the perceivable loudness resolution test as described above , then a determination is made as to whether additional channels remain which need to be subjected to the same test . if so ( yes branch of block 170 ), then a next channel is selected ( block 172 ), and the perceivable loudness resolution test is repeated for the selected channel ( blocks 164 through 168 ). if not ( no branch of block 170 ), then the fitting is completed ( block 174 ). when the implanted fitting system is used ( fig1 ) instead of the external system ( fig2 ), then essentially the same method described in fig3 a - 3c is used to zero - in on the appropriate threshold settings , with some modification . in particular , the principal modification required by the implanted system -- and , indeed , an advantage of the implanted system -- is to remove the step of using the impedance bridge to determine the stapedius reflex threshold . rather , the stapedius reflex electrode 54 ( fig1 ) provides a quantitative measure of the stapedius reflex response , which measure may be logged and / or analyzed by the μc 52 in order to determine whether a particular stapedius reflex response is to be deemed a stapedius reflex detection ( block 112 , fig3 a ). it is thus seen that by using the external fitting system shown in fig2 or the internal system shown in fig1 and through the use of a fitting method substantially as shown in fig3 a through 3c , that the present invention provides a self - fitting ics that is readily fitted to a particular patient without the necessity of relying on subjective feedback from the patient as the fitting process is carried out . it is further seen that the invention provides a closed - loop fitting procedure that advantageously zeros - in on the needed threshold value ( s ) by using a stapedius reflex response to determine a coarse threshold value ( s ), and evoked potentials to refine the coarse threshold value ( s ) to a fine threshold value ( s ). moreover , when the implanted fitting system is employed ( fig1 ), it is seen that the invention provides a self - fitting ics that does not rely on the integrity of the middle ear , and which avoids the use of surface electrodes when measuring evoked potentials . turning next to fig4 a flow chart is shown that depicts a preferred fitting session that may be used to determine the threshold of hearing ( t ) and the most comfortable level ( mcl ) settings for an ics using the implanted system ( fig1 ). as seen in fig4 once the fitting session begins ( i . e ., once the configuration shown in fig1 has been set up ), the stimulus level s is set to a minimum value ( block 180 ). then , a corresponding cap min level is recorded ( block 182 ), as is a corresponding mer min level ( block 184 ). once the cap min and mer min levels have been recorded , then the stimulus level is incremented by a prescribed amount , and a corresponding cap s level is measured ( block 186 ). a determination is then made as to whether cap s is greater than cap min ( block 188 ). if not ( no branch of block 188 ), then s is again incremented and a new cap s is measured ( block 186 ) and the determination is again made ( block 188 ). if so ( yes branch of block 188 ), then the threshold of hearing ( t ) is set as being equal to the most recent value of s ( i . e ., that value of stimulus s which produces a cap s greater than cap min ) less a prescribed small value , k t ( block 190 ). once t has been determined ( at block 190 ), the stimulus value s is again incremented ( block 192 ) by a prescribed increment , and a corresponding measure of the mer is made , mer s ( block 192 ). a determination is then made as to whether mer s is greater than mer min ( block 194 ). if not ( no branch of block 194 ), then a determination is made as to whether any form of behavioral distress is noted ( block 196 ). if so , the fitting session is stopped and the results evaluated ( block 199 ). if not ( no branch of block 196 ), then s is again incremented and a corresponding value of mer s is again measured ( block 192 ), and a new determination is made as to whether mer s is greater than mer min ( block 194 ). if mer s is greater than mer min , then the setting for the mcl is determined as the most recent value of s plus a prescribed small value , k m ( block 198 ). thus , as seen in fig4 a method of fitting is presented wherein the dynamic range of electrical stimulation desirable to be applied by an ics is determined by : ( 1 ) determining the low end of the dynamic range by searching for and finding cap s , the electrical stimulation that produces a compound action potential as sensed electronically from the cochlea , and ( 2 ) determining the high end of the dynamic range by searching for and finding mer s , the intensity of the electrical stimulation that produces a middle ear reflex . turning next to fig5 a simplified flow chart is presented that shows one technique for automatically adjusting the loudness after every stimulus cycle during use of the ics . such method or technique may be used with the implant 50 shown in fig1 when coupled to an appropriate speech processor , or μc 52 . in carrying out the method shown in fig5 it is assumed that the stimulus level may be increased or decreased in programmable increments , and that the current stimulus level is l . thus , if l is set to be equal to l = l - 1 , then that means the stimulus level is decreased by a prescribed increment ; and if l is set to be equal to l = l + 1 , then that means the stimulus level is increased by a prescribed increment . at the beginning of each stimulation cycle , a first step involves measuring the mer ( block 202 ) corresponding to the current stimulus level l by monitoring the signal sensed at the stapedius or tensor tympani electrode 54 . a determination is then made as to whether the monitored mer is greater than mer min ( block 204 ). if so ( yes branch of block 204 ), then that means the stimulus level should be decreased slightly from its current value , so the next stimulus is set to a value that is one increment lower ( l - 1 ) than the current value ( block 212 ). if , on the other hand , the monitored mer is less than mer min ( no branch of block 204 ), then that means there is still some room to increase the stimulus level above its current value . such increase is made over a prescribed number of stimulation cycles under control of a cycle counter which can reach a maximum value n . for each stimulation cycle during which no adjustment is made to the stimulus level , the count is incremented ( block 206 ), and a determination is then made ( after incrementing the count ) as to whether the stimulus count has reached its maximum value ( block 208 ). in this way , so long as the stimulus level produces an mer less than mer min , it takes n passes , or n stimulation cycles , before an adjustment to the stimuluous level is made . the parameter n thus serves as a programmable means for adjusting how quickly or rapidly the stimulous value is increased . once the value of n is reached ( yes branch of block 208 ), then the stimulous value is increased one increment to l + 1 ( block 210 ), and the cycle counter is reset ( block 214 ). similarly , the cycle counter is reset whenever the stimulous level is decreased one increment ( block 212 ). thus , each time an adjustment is made to the stimuluous level , the cycle counter is reset , and the process repeats . it is thus seen that by using the automatic adjustment process shown in fig5 the presence or absence of the middle ear reflex is used to automatically and continuously adjust the intensity of the electrical stimulation provided to the patient , thereby providing a type of automatic gain control ( agc ) based on middle ear reflexes . the patient is thus relieved of the slow and tedious process of making frequent manual adjustments of the loudness control on the speech processor . while the invention herein disclosed has been described by means of specific embodiments and applications thereof , numerous modifications and variations could be made thereto by those skilled in the art without departing from the scope of the invention set forth in the claims .

a self - adjusting implantable cochlear implant system includes an implant portion and an external portion . the system provides a device and a way to objectively determine selected psychophysical parameters , such as stimulation threshold , comfort level and loudness resolution , used by the implant portion , which includes an implantable cochlear stimulator , as it carries out its stimulation function . the input to the system is an electrical stimulation . the outputs of the system include a middle ear reflex and evoked potentials , such as a compound action potential along the auditory / cerebral pathways , both of which are sensed using objective measurement techniques and tools . in accordance with one embodiment , the adjustment process uses the mer for determining a coarse threshold value , and then uses evoked potentials to determine a more precise o fine threshold value , thereby zeroing in on a desired threshold . such zeroing - in method is preferably carried out using implanted circuitry , which implanted circuitry uses an implanted middle ear electrode and a cochlear electrode , along with appropriate amplification , filtering and processing circuitry , to respectively determine the mer response and evoked potentials . another embodiment uses the presence or absence of the mer to adjust the intensity of electrical stimulation continuously and automatically , thereby relieving the patient from having to perform slow and tedious manual adjustments of the loudness control of a speech processor used with the ics .

example embodiments will now be described more fully with reference to the accompanying drawings . example embodiments are provided so that this disclosure will be thorough , and will fully convey the scope to those who are skilled in the art . numerous specific details are set forth such as examples of specific components , devices , and methods , to provide a thorough understanding of embodiments of the present disclosure . it will be apparent to those skilled in the art that specific details need not be employed , that example embodiments may be embodied in many different forms and that neither should be construed to limit the scope of the disclosure . in some example embodiments , well - known processes , well - known device structures , and well - known technologies are not described in detail . the terminology used herein is for the purpose of describing particular example embodiments only and is not intended to be limiting . as used herein , the singular forms “ a ,” “ an ” and “ the ” may be intended to include the plural forms as well , unless the context clearly indicates otherwise . the terms “ comprises ,” “ comprising ,” “ including ,” and “ having ,” are inclusive and therefore specify the presence of stated features , integers , steps , operations , elements , and / or components , but do not preclude the presence or addition of one or more other features , integers , steps , operations , elements , components , and / or groups thereof . the method steps , processes , and operations described herein are not to be construed as necessarily requiring their performance in the particular order discussed or illustrated , unless specifically identified as an order of performance . it is also to be understood that additional or alternative steps may be employed . when an element or layer is referred to as being “ on ”, “ engaged to ”, “ connected to ” or “ coupled to ” another element or layer , it may be directly on , engaged , connected or coupled to the other element or layer , or intervening elements or layers may be present . in contrast , when an element is referred to as being “ directly on ,” “ directly engaged to ,” “ directly connected to ” or “ directly coupled to ” another element or layer , there may be no intervening elements or layers present . other words used to describe the relationship between elements should be interpreted in a like fashion ( e . g ., “ between ” versus “ directly between ,” “ adjacent ” versus “ directly adjacent ,” etc .). as used herein , the term “ and / or ” includes any and all combinations of one or more of the associated listed items . although the terms first , second , third , etc . may be used herein to describe various elements , components , regions , layers and / or sections , these elements , components , regions , layers and / or sections should not be limited by these terms . these terms may be only used to distinguish one element , component , region , layer or section from another region , layer or section . terms such as “ first ,” “ second ,” and other numerical terms when used herein do not imply a sequence or order unless clearly indicated by the context . thus , a first element , component , region , layer or section discussed below could be termed a second element , component , region , layer or section without departing from the teachings of the example embodiments . spatially relative terms , such as “ inner ,” “ outer ,” “ beneath ”, “ below ,” “ lower ,” “ above ,” “ upper ” and the like , may be used herein for ease of description to describe one element or feature &# 39 ; s relationship to another element ( s ) or feature ( s ) as illustrated in the figures . spatially relative terms may be intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures . for example , if the device in the figures is turned over , elements described as “ below ” or “ beneath ” other elements or features would then be oriented “ above ” the other elements or features . thus , the example term “ below ” can encompass both an orientation of above and below . the device may be otherwise oriented ( rotated 90 degrees or at other orientations ) and the spatially relative descriptors used herein interpreted accordingly . with initial reference to fig1 , a proximal interphalangeal (“ pip ”) joint implant assembly according to the present teachings is illustrated at reference numeral 10 . the implant assembly 10 is shown implanted in a human finger to repair the pip joint , which is located between the proximal phalanx bone and the middle phalanx bone . the implant assembly 10 can provide semi - constrained articulation between the proximal and middle phalanx bones . with additional reference to fig2 - 4 , the implant assembly 10 generally includes a distal stem 12 , a distal semi - constrained articulation 14 , a proximal stem 16 , and a proximal semi - constrained articulation 18 . the distal stem 12 includes an elongated base portion , or post , 20 , a flange 22 , and an interlocking detail 24 . the elongated base portion 20 is generally conical and tapered from a first end that is proximate to the flange 22 to a second end that is distal to the flange 22 and terminates at a distal tip 25 . the elongated base portion 20 can include a porous coating 26 and / or include regenerex ® porous titanium construct to promote bone in - growth , which enhances fixation to the proximal phalanx . regenerex ® is offered by biomet of warsaw , ind . a longitudinal axis a of the post 20 extends through the distal tip 25 , through the flange 22 , and through the interlocking detail 24 . the flange 22 includes a planar bone engagement surface 28 and a planar articulation support surface 30 , which is opposite to the bone engagement surface 28 . the planar articulation support surface 30 extends across a plane that is perpendicular to the longitudinal axis a . the elongated base portion 20 extends from the bone engagement surface 28 . the interlocking detail 24 is at the planar articulation support surface 30 . the bone engagement surface 28 can include the porous coating 26 and / or regenerex ® to enhance fixation between the flange 22 and the proximal phalanx . the interlocking detail 24 includes a t - shaped rail having a base portion 32 and a connecting flange 34 that each extend across at least a portion of the support surface 30 . the connecting flange 34 is mounted to the base portion 32 and is spaced apart from the planar articulation support surface 30 to define a gap 36 there between . the connecting flange 34 defines a bore 38 configured to receive a fastener , as further described herein . the distal semi - constrained articulation 14 generally includes an articulating surface 40 and a stem engaging surface 42 . the stem engaging surface 42 is opposite to the articulating surface 40 . as illustrated in fig1 - 3 , the articulating surface 40 includes a raised center portion 43 that is between , and stands proud of , a pair of side surfaces 45 that generally slope away from the center portion 43 and are shaped to articulate with the proximal articulation 18 . the articulation 14 defines a locking mechanism 44 with an opening 46 that extends from the stem engaging surface 42 to a side of the articulation surface 40 . the opening 46 transitions to a locking recess 48 defined within the articulation 14 . the locking recess 48 has a generally rectangular shape that is sized to receive the connecting flange 34 . a bore 50 extends from an exterior of the articulation 14 to the locking recess 48 and is configured to receive a suitable fastener 52 , such as a pin or screw for example . as illustrated in fig3 c , with the interlocking detail 24 seated within the locking recess 48 , the fastener 52 is inserted through the bore 50 to engage the bore 38 of the connecting flange 34 and secure the distal stem 12 to the articulation 14 . with additional reference to fig4 , the proximal stem 16 is substantially similar to the distal stem 12 , but has a slightly longer length and / or larger diameter base portion 20 ′. therefore , similar features are designated with the same reference numbers ; the reference numbers of the proximal stem 16 include the prime (′) symbol . with respect to the similar features , the description of the distal stem 12 is sufficient to describe the proximal stem 16 as well . the semi - constrained proximal articulation 18 generally includes an articulating surface 60 and a stem engaging surface 62 that is opposite to the articulating surface 60 . the articulating surface 60 includes a pair of spaced apart lobes 63 that are each generally hemispherical and concave with respect to the stem engaging surface 62 and shaped to articulate with one of the side surfaces 45 of the distal articulation 14 . between the lobes 63 is a recessed surface 65 that is sized and shaped to articulate with the center portion 43 of the distal articulation 14 . the proximal articulation 18 further includes a locking mechanism 64 that is substantially similar to the locking mechanism 44 of the distal articulation 14 . to attach the proximal articulation 18 to the proximal stem 16 the interlocking detail 24 ′ is mated with the locking mechanism 64 and a fastener 66 is inserted through a bore 68 of the articulation 18 and secured in the bore 38 ′ of the interlocking detail 24 ′. the distal semi - constrained articulation 14 and the proximal semi - constrained articulation 18 can each be made of any suitable material . the articulations 14 and 18 can include similar or different materials in similar or different compositions . for example , each articulation can include a metal , a polymer , or combinations thereof . suitable metals include , for example , cocr , titanium , and combinations thereof . suitable polymers include one or more of ultra - high molecular weight polyethylene , pyrocarbon , silicone , polyether ether ketone (“ peek ”), carbon fiber reinforced peek ( such as peek - optima ® from invibio , ltd . of the united kingdom ), and / or vitamin e stabilized highly crosslinked polyethylene ( hxlpe ), such as is disclosed in u . s . patent application ser . no . 10 / 757 , 551 by muratoglu et al ., which was filed on jan . 15 , 2004 and issued as u . s . pat . no . 7 , 431 , 874 on oct . 7 , 2008 . u . s . pat . no . 7 , 431 , 874 and application ser . no . 10 / 757 , 551 are incorporated by reference herein , as well as are all patent applications and issued patents that rely thereon for priority including the following u . s . patent application ser . no . 11 / 104 , 580 filed on apr . 13 , 2005 ; ser . no . 11 / 104 , 582 filed on apr . 13 , 2005 ; ser . no . 11 / 564 , 594 filed on nov . 29 , 2006 ; ser . no . 11 / 948 , 393 filed on nov . 30 , 2007 ; and ser . no . 12 / 464 , 235 filed on may 12 , 2009 . an exemplary vitamin e stabilized hxlpe that may be used includes e - poly ™ offered by biomet orthopedics , inc . of warsaw , ind . any suitable manner of interconnecting the stems 12 and 16 with the respective articulations 14 and 18 can be used . for example and with reference to fig5 a and 5b , the distal stem 12 can include an interlocking flange 100 extending from a side of the flange 22 opposite to the elongated base portion 20 . the flange 100 defines an annular recess 102 in which an annular ring 104 is seated . the annular ring 104 can be made out of any suitable material , such as a metal or a polymer . the articulation 14 defines a cavity 106 that is shaped and sized to receive the flange 100 . the cavity 106 defines an annular seat 108 . as illustrated in fig5 b , to lock the distal articulation 14 to the distal stem 12 , the distal articulation 14 is pressed onto the distal stem 12 so that the flange 100 is seated within the annular seat 108 and the annular ring 104 compresses and then snaps into the annular seat 108 . this same interlocking arrangement can also be used to attach the proximal semi - constrained articulation 18 to the proximal stem 16 . with additional reference to fig6 a and 6b , the distal stem 12 can define a locking receptacle 110 within the flange 22 and a locking flange 112 . the distal semi - constrained articulation 14 can include flexible locking tabs 114 extending from the stem engaging surface 42 . the locking tabs 114 are snapped into the locking receptacle 110 to secure the distal semi - constrained articulation 14 to the distal stem 12 . this same interlocking arrangement can also be used to attach the proximal semi - constrained articulation 18 to the proximal stem 16 . with additional reference to fig7 a and 7b , the distal stem 12 can include a truncated conical locking protrusion 120 extending from the articulation support surface 30 of the flange 22 . the distal semi - constrained articulation 14 can define a conical recess 122 within the stem engaging surface 42 that is sized and shaped to receive the truncated conical locking protrusion 120 . the surfaces of the locking protrusion 120 and the conical recess 122 are angled to provide a morse taper lock there between . thus , to secure the distal semi - constrained articulation 14 to the distal stem 12 , the articulation 14 is seated on the flange 22 so that protrusion 120 mates with the conical recess 122 to form a morse taper lock . this same interlocking arrangement can also be used to attach the proximal semi - constrained articulation 18 to the proximal stem 16 . with additional reference to fig8 a and 8b , the distal stem 12 can include a dovetail locking taper 130 extending from the articulation support surface 30 of the flange 22 . the taper 130 can include a pair of stem protuberances 134 a and 134 b that extend respectively from tapered surfaces 136 a and 136 b of the dovetail locking taper 130 . the stem protuberances 134 a and 134 b each span a distance of approximately one - half a length of the tapered surfaces 136 a and 136 b respectively . the stem protuberances 134 a and 134 b are rigid . the distal semi - constrained articulation 14 can define a dovetail shaped recess 132 sized and shaped to securely receive the dovetail locking taper 130 . the recess 132 can include a pair of recess protuberances 138 a and 138 b . the recess protuberances 138 a and 138 b include a compressible material such that they can pass by the stem protuberances 134 a and 134 b as part of a locking mechanism . the recess protuberances 138 a and 138 b span about one - half a length of the recess 132 . the other half of the recess 132 defines concavities 140 a and 140 b that are sized and shaped to receive the stem protuberances 134 a and 134 b . to mount the articulation 14 to the distal stem 12 , the articulation 14 is slid over the dovetail locking taper 130 such that the stem protuberances 134 a and 134 b pass over the compressible recess protuberances 138 a and 138 b . after the stem protuberances 134 a and 134 b completely pass over the recess protuberances 138 a and 138 b , the stem protuberances 134 a and 134 b can lock into the pair of concavities 140 a and 140 b respectively . the concavities 140 a and 140 b are configured in dimension to inversely match the stem protuberances 134 a and 134 b such that locking occurs . this same interlocking arrangement can also be used to attach the proximal semi - constrained articulation 18 to the proximal stem 16 . the various features described above for coupling the stems 12 and 16 to their respective articulations 14 and 18 include the interlocking details 24 and 24 ′ as part of the stems 12 and 16 and various different interlocking features provided on and defined by the articulations 14 and 18 . however , this arrangement can be reversed such that the interlocking details 24 and 24 ′ are at the articulations 14 and 18 and the various other interlocking features of the articulations 14 and 18 are provided on the stems 12 and 16 . furthermore , the interlocking details 24 and 24 ′ are generally described as male members protruding from the respective flanges 22 and 22 ′ and the various interlocking features of the articulations 14 and 18 are generally described as female members recessed within and defined by the articulations 14 and 18 . however , this arrangement can be reversed such that the interlocking details 24 and 24 ′ are formed as female members recessed within and defined by the flanges 22 and 22 ′ and the various interlocking features of the articulations 14 and 18 are male members extending from the stem engaging surfaces 42 and 62 and configured to mate with the female interlocking details 24 and 24 ′. with additional reference to fig9 , the implant assembly 10 can be reversed such that the distal semi - constrained articulation 14 is mounted to the proximal stem 16 and the proximal semi - constrained articulation 18 is mounted to the distal stem 12 . with additional reference to fig1 a and 10b , an additional pip joint implant assembly according to the present teachings is illustrated at reference numeral 200 . the implant assembly 200 can provide constrained articulation between the proximal and middle phalanx bones . with additional reference to fig1 a and 11b , the implant assembly 200 generally includes the same distal stem 12 and the same proximal stem 16 described herein in the context of the implant assembly 10 . however , in place of the semi - constrained articulations 14 and 18 , a distal constrained articulation 202 and a proximal constrained articulation 204 are provided and mounted to the distal stem 12 and the proximal stem 16 respectively . the distal constrained articulation 202 includes an articulation base 206 having a stem engaging surface 208 and an articulation flange or hinge 210 . the stem engaging surface 208 is generally planar and is on a first side of the articulation base 206 . the articulation flange 210 extends from a second side of the articulation base 206 that is opposite to the stem engaging surface 208 . the articulation flange 210 is offset from a center of the articulation base 206 . the articulation flange 210 defines a through bore 212 having a longitudinal axis that is 90 ° degrees relative to an axis extending through the center of the articulation base 206 . the articulation base 206 further defines a locking mechanism 214 that is similar to the locking mechanism 44 of the distal articulation 14 . the locking mechanism 214 defines a cavity 216 that is shaped and sized to securely receive the interlocking detail 24 . with the interlocking detail 24 seated within the cavity 216 , a suitable fastener 218 , such as a pin or screw , can be inserted through a bore 220 of the articulation base 206 and into engagement with the bore 38 of the interlocking detail 24 to secure the distal articulation 202 to the distal stem 12 . the proximal constrained articulation 204 is substantially similar to the distal constrained articulation 202 . therefore , similar features are designated with the same reference numbers ; the reference numbers of the proximal stem 16 and the proximal articulation 204 include the prime (′) symbol . with respect to the similar features , the description of the distal articulation 202 is sufficient to describe the proximal articulation 204 as well . as illustrated in fig1 , a difference between the distal articulation 202 and the proximal articulation 204 is that the flange 210 of the distal articulation 202 is offset from the flange 210 ′ of the proximal articulation 204 so that the axes of the through bores 212 and 212 ′ align and permit the insertion of a suitable connection device 222 , such as a pin , through the bores 212 and 212 ′ to connect the distal articulation 202 to the proximal articulation 204 and allow the articulations 202 and 204 to pivot in a hinge - like manner about the connection device 222 . in place of the locking mechanisms 214 and 214 ′, the distal and proximal articulations 202 and 204 , along with the corresponding stems 12 and 16 , can include any suitable coupling features , such as those described herein and illustrated in fig5 - 8 . the articulations 202 and 204 , as well as the connection device 222 , can include any suitable biocompatible materials , such as the metal and polymeric materials set forth above in the description of the articulations 14 and 18 . the articulations 202 and 204 and the connection device 222 can include the same composition or different compositions . for example , either of the articulations 202 and 204 , as well as the connection device 222 , can be a metal , a polymer , or combinations thereof . with additional reference to fig1 , the distal stems 12 , the proximal stems 16 , the distal semi - constrained articulations 14 , the proximal semi - constrained articulations 18 , the distal constrained articulations 202 , and the proximal constrained articulations 204 can each be provided in various different sizes and configurations , and grouped together in a kit 300 . the various features of the distal stems 12 and the proximal stems 16 can vary in size and shape in any suitable manner . for example , the elongated base portions 20 and 20 ′ can vary in length and diameter , the flanges 22 and 22 ′ can vary in surface area and thickness , and the interlocking details 24 and 24 ′ can have varying dimensions . the distal articulations 14 and 202 and the proximal articulations 18 and 204 can also vary in size and shape in any suitable manner to accommodate the stems 12 and 14 that the articulations 14 , 18 , 202 , 204 are connected to and to accommodate various pip joints of different sizes . the kit 300 can also include the fastener 52 and the connection device 222 . thus , the present teachings provide for stems 12 and 16 to which either semi - constrained articulations 14 and 18 or constrained articulations 202 and 204 can be mounted to . this allows for conversion between a semi - constrained pip implant and a constrained pip implant , such as during a revision procedure or trialing , without having to replace the stems 12 and 16 , which are secured within bone in any suitable manner , such as by using bone cement or a press - fit . the implant assemblies 10 and 200 can also be provided with different sized articulations 14 , 18 , 202 , and 204 without having to replace the stems 12 and 16 after they are implanted in bone . further , the connection device 222 can be replaced without having to replace portions of the remainder of the implant assembly 200 . the present teachings are not limited to application in a pip implant . the present teachings also apply to a variety of other types of joint replacement implants to provide modular implants having stems that can interchangeably connect to a variety of articulations having different sizes and that provide for varying degrees of constraint . for example , the present teachings also apply to metacarpophalangeal ( mcp ) joint implants , distal interphalangeal joint ( dip ) implants , carpometacarpal ( cmc ) joints , and other small joints , such as finger or toe joints . the present teachings apply to both total joint replacement and hemi joint replacement as well . the foregoing description of the embodiments has been provided for purposes of illustration and description . it is not intended to be exhaustive or to limit the disclosure . individual elements or features of a particular embodiment are generally not limited to that particular embodiment , but , where applicable , are interchangeable and can be used in a selected embodiment , even if not specifically shown or described . the same may also be varied in many ways . such variations are not to be regarded as a departure from the disclosure , and all such modifications are intended to be included within the scope of the disclosure .

a method for replacing a proximal interphalangeal joint with a modular implant assembly is provided . during a first surgical procedure , a first stem component of the implant assembly having a first articulation component removably attached thereto is implanted in a proximal phalanx bone . a second stem component of the implant assembly having a second articulation component removably attached thereto is implanted in a middle phalanx bone . during a second surgical procedure performed after the first surgical procedure , the first articulation component is removed from the first stem component and the second articulation component is removed from the second stem component . a third articulation component is attached to the first stem component and a fourth articulation component is attached to the second stem component . the second surgical procedure is performed without removing the first stem component from the first bone and without removing the second stem component from the second bone .

a first arrangement of the parts of the invention is shown in fig1 a , and 4 , as attached to an office desk 3 of the type in which the underface 3 &# 39 ; is very close to floor 16 . an upright cylindrical post 2 , preferably made of steel and preferably hollow , is adapted for detachable attachment to desk 3 and is provided with an attachment assembly therefor . the latter consists of a generally triangular lower clamping plate member 4 having a similarly - shaped notch 4 &# 39 ;. the latter is for a leg 5 of desk 3 to fit thereinto . plate 4 is also provided with a vertically - oriented open - ended sleeve 6 at its apex , sleeve 6 slidably receiving the lower end of post 1 . the primary locking means for clamping plate 4 consists of a first set - screw 7 threadedly engaged in sleeve 6 . the attachment assembly further consists of another generally triangular , upper clamping plate 8 , which does not have a notch . member 8 , like member 4 , has a sleeve 9 provided with a second set - screw 10 by which member 8 can be secured to post 1 , screw 10 constituting the other part of the primary locking means . a secondary locking means is further provided in association with upper member 8 . the means comprises : a small rectangular flat plate 11 having glued or otherwise secured to its underside a compressible pad 12 . plate 11 has a pair of spaced - apart guide pins 13 , which are insertable into corresponding guide pin holes ( not seen ) made in the underside of plate member 8 . the latter has three threaded perforations 14 in registry with three shallow notches 15 provided in the top face of flat plate 11 . perforations 14 have threadedly - engaged secondary set - screws 17 . the installation of post 1 adjacent desk 3 is accomplished simply . firstly , the post is inserted into lower clamping plate 4 , so that it contacts the floor 16 either directly or with the intermediary of a floor pad 16a . lower clamping plate 4 is then adjusted upwardly along post 1 until it presses against desk underface or under edge 3 , and is then locked into place by means of set - secrew 7 . it is essential that post 1 be in floor - engaging relation for firm and strong support . then upper clamping plate 8 is placed over the top surface 3 of desk 3 and locked into place by the second set - screw 10 . vise action is effected by screwing the secondary set - screws 17 into the respective shallow notches 15 of flat plate 11 , thereby forcing plate 11 downwardly and compressing pad 12 , since triangular plate 8 is held in locked position by the primary locking means . in order to prevent post 1 from slipping against floor 16 , pad l6a as well as the lower surface of plate member 4 are desirably provided with material known under the trademark & lt ; velcro & gt ;, if floor 16 is covered with a rug , or with rubber if the floor is made of tile or linoleum . it should be noted that , if desk underface 3 &# 39 ; leaves rest directly on the floor and suitable shims inserted between plate 4 and surface 3 &# 39 ;. fig1 and fig1 a advantageously show two vertically - spaced support tables 18 and 19 , one above and one below upper plate 8 . the tables are rectangular , horizontal and made of agglomerated woodchips covered with melamine . for instance , upper table 18 measures 16 &# 34 ;× 20 &# 34 ;, while lower table 19 measures 10 &# 39 ; by 20 &# 39 ; to support a computer video display and keyboard , respectively . each table 18 , 19 is fixed to an underlying support plate 20 , 21 , respectively , and each plate 20 , 21 has a centrally - located , downwardly projecting pin 23 , 24 , respectively . tables 18 and 19 are mounted each on one of two identical arms 25 , 26 . these arms are characterized by eyes 27 , 27 &# 39 ;, 28 , 28 &# 39 ;, respectively at both their opposite ends . the outer eyes 27 , 28 receive pins 23 , 24 , respectively , while the other two inner eyes 27 &# 39 ;, 28 &# 39 ; are slidably mounted on post 1 . both arms ar provided with vertical position lock means consisting of collars 29 , 30 having set - screws 31 . both pins 23 , 24 have a small threaded bore 23a , 24a adapted to receive capped bolts 32 , 33 , respectively , each cap having integrally - formed ears 32 &# 39 ;, 33 &# 39 ; to render the rotation of the caps easier . thus , as suggested in fig3 tables 18 , 19 are adapted to be selectively rotated to any desired position and releasably locked thereat by the locking caps . tables 18 , 19 are also free to pivot bodily with their respective arms about the axis of post 1 . referring now to fig2 a , and 5 , there is depicted a second arrangement of the same parts of the accessory table . such embodiment is suitable for a desk or work table 34 having a side 35 and laterally projecting edge 36 . as shown in the figures , all the elements described above are utilized in the second arrangement with the following exceptions : a special floor - engaging base is provided , since lower plate 4 is inverted and located under edge 36 so that plate 11 can exert vise action on the latter , as in the first arrangement . the base is comprised of a small disk 37 having an upper sleeve portion 37 &# 39 ;; a threaded stud 38 is rigidly centrally secured inside sleeve portion 37 &# 39 ;. the lower end portion of post 1 has a complementary threaded bore 39 adapted to receive stud 38 . thus , base 37 can be unscrewed to firmly contact floor 16 after lower clamping plate 4 has been secured to post 2 . base 37 is installed in the arrangement of fig1 whenever there is a sufficient gap between floor 6 and desk underface 3 &# 39 ;. the assembly is preferably provided with an aesthetic finish sheath consisting of a plurality of doughnut - shaped sections 40 inserted around post 1 . sections 40 are preferably made of polyurethane foam . this sheath can be entire lengths of single - piece sleeves cut to size . an uppermost closure cap 41 may be provided . ideally , post 1 will be located no more than approximately six inches from the side of a desk , table or other article . it is to be noted that the two support tables can carry up to 200 pounds of equipment . it is to be further noted that the attachment assembly will not release accidentally and that no damage to the article of furniture is possible with pad 12 . moreover , the attachment assembly will fit any furniture , having an intermediately - located bottom surface ( between the floor and the top surface of the furniture article ).

an accessory table adapted for detachable attachment to an article of furniture , such as a desk , is disclosed . the accessory table comprises a rigid floor supported post and an attachment assembly for the post , exerting vise action on the top and bottom surfaces of the desk . the post carries at least one table at the outer end of an arm , the latter being pivotable through a full circle . the table is also rotatable about its central vertical axis at the end of the arm . the post is hidden by an aesthetic sheath .

introduced below are methods , apparatuses , and systems ( collectively herein referred to as “ technology ”) related to dynamically and automatically sorting , moving , and racking weights based on various techniques . the technology is capable of detecting a weight &# 39 ; s ( e . g ., a dumbbell &# 39 ; s ) characteristics ( e . g ., type , weight , material , brand , age , preferred use , dimensions , etc . ), transporting the weight from a drop - off location to a desired weight location on a rack for easy access by a user . the technology can reduce time and energy exerted by gym staff ( and / or members ) who must otherwise manually locate , lift and sort weights into a proper orientation / position on a rack . in one or more embodiments , the technology is an automated dumbbell racking system that includes various functions implemented into one or more weight rack mechanisms , linear rail mechanisms , transport mechanisms , loading mechanisms , and / or other mechanisms . each “ mechanism ” includes technology and functionality that can be implemented separately and couple to technology and functionality implemented by other mechanisms , and / or a single mechanism can implement the technology and functionality of one or more of the individual mechanisms . gym members leave weights at one or more drop - off locations of the loading mechanism . in various embodiments , the loading mechanism , transport mechanism , and / or conveyor is configured with technology for identifying dumbbell characteristics for determining a type , size , configuration and / or weight of a dumbbell , for example . various techniques are implemented by the technology for determining weight characteristics , such as one or more loading cells , scales or scanners ( e . g ., bar - code , qr - code , rf - id detectors , etc .). weight characteristics are stored ( e . g ., in ram , a database , file or other means to store information ), in some embodiments , for use by other mechanisms of the technology . the loading mechanism includes a feed assembly ( e . g ., a conveyor ) with compartments for holding dumbbells while the feed assembly sequentially delivers dumbbells from the compartments to a transport mechanism . for example , after determining one or more characteristics ( e . g ., that a weight is a 15 pound dumbbell ), the technology moves and releases ( e . g ., drops / pushes / releases / etc .) a dumbbell onto the loading mechanism and / or conveyor , which moves ( e . g ., in a forward / backward direction ) one or more dumbbells to the transport mechanism ( e . g ., by allowing gravity to drop the dumbbell onto the transport mechanism after the dumbbell reaches the end of the conveyor ). the transport mechanism , in various embodiments , includes a load cell ( e . g ., a strain gage ), lift and conveyor . the transport mechanism is configured to travel about a rail ( discussed below ) for moving dumbbells to dumbbell holders of a weight rack mechanism . dumbbells are received at the transport mechanism &# 39 ; s conveyor , which is configured to hold and move a dumbbell from a first end ( i . e ., a “ receiving end ”) of the conveyor to a second end ( i . e ., a “ delivery end ”) of the conveyor . the delivery end of the conveyor is positionable about a back end of a dumbbell holder of the weight rack mechanism , such that one or more dumbbells move on the conveyor from the delivery end of the conveyor onto the back end of the dumbbell holders ( e . g ., the conveyor can release , drop , push and / or otherwise reposition the dumbbell ). in some embodiments , a lift is coupled to the transport mechanism and is configured to move dumbbells between an upper and a lower position of the transport mechanism for releasing weights at corresponding upper or lower levels shelves of dumbbell holders at the weight rack mechanism . in some embodiments , the transport mechanism is equipped with technology for causing the transport mechanism to move to one or more assigned dumbbell holders based at least on one or more dumbbell characteristics . for example , the transport mechanism can independently move between various dumbbell holder locations via one or more motorized devices ( e . g ., a computer configured to operate a motor to move , via wheels or tracks , between one or more dumbbell holder locations ). in some embodiments , the transport mechanism is configured to operate with a belt drive assembly of a rail ( e . g ., a guide rail system ) that moves the transport mechanism about the length of the weight rack . in operation , in one or more embodiments , a dumbbell rests on the conveyor &# 39 ; s transport mechanism as the transport mechanism moves ( e . g ., via the rail ) a dumbbell to a location of the rack assigned to the dumbbell . the rail mechanism can include one or more rails ( e . g ., linear guide rails ) to directly or indirectly couple to the weight rack mechanism . when the transport mechanism reaches a desired location ( e . g ., a position on the rail that is in back of a dumbbell holder location ), the technology automatically initiates operation of the transport mechanism &# 39 ; s conveyor to transport the dumbbell from the transport mechanism into the designated dumbbell holder . if the dumbbell holder is at a lower / higher shelf than the conveyor is currently positioned , the technology , in one or more embodiments , automatically initiates operation of the lift to , for example , cause the actuator to move the conveyor to the lower / higher position . in various embodiments , when a rack is configured to use only a single shelf , the transport mechanism can be implemented without a lift . the transport mechanism , in some embodiments , can retrieve dumbbells from a dumbbell holder by reversing the conveyor in a direction opposite the direction used to move the dumbbell into a holder , for example , to move and / or resort dumbbells to new / different locations according to a schema based and / or dumbbell availability . the weight rack mechanism , in some embodiments , is a stationary or semi - stationary weight rack that includes one or more dumbbell holders configured to store at least one dumbbell for manual retrieval by a user in a similar manner as weights are retrieved from traditional weight racks . as mentioned above , the weight rack mechanism can include one or more racks configured to be stacked on top and / or side - by - side other weight racks . this is useful because it allows a facility to custom configure racks based on the facilities &# 39 ; particular requirements ( e . g ., a weight rack mechanism with two levels of racks versus two single shelf racks configured in a side - by - side configuration ). each rack includes one or more dumbbell holder that is configured to receive one or more dumbbells from the transport mechanism ( as described above ). dumbbell holders can be uniform in dimensions or be sized in accordance with a particular dumbbell configuration . for example , to maximize efficient use of space , in various embodiments , dumbbell holders are manually or automatically sized to store different types of dumbbells by , for example , automatically or manually moving dumbbell holder dividers closer together ( e . g ., for the 5 lb . dumbbell ) or further apart ( e . g ., for the 85 lb . dumbbell ). a dumbbell holder can be predefined to store dumbbells based on one or more of dumbbell characteristics . for example , in a given row of dumbbell holders , each of several sets of holders can be configured to store progressively higher weight dumbbells ( e . g ., a set of two 5 lb . dumbbell holders , next to a set of two 10 lb . dumbbell holders , and up to , e . g ., a set of two 85 lb . dumbbell holders .). additionally and / or alternatively , dumbbell holders can store random dumbbells based on , for example , whether the dumbbell holder is a spare , not designated for a particular dumbbell , or designated for storing ‘ random ’ dumbbells . for example , each dumbbell holder can be assigned an address ( e . g ., a unique id ) which can be mapped to one or more dumbbell characteristics . for example , a dumbbell holder having an address of rack 1 , shelf 2 , location 4 of 10 ( r1s2l4 ) can be assigned to store only 15 lb ., unpadded dumbbells that are less than 2 years old . or , for example , a dumbbell holder ( e . g ., r2s2l9 ) can have a blank address or be assigned to hold ‘ random ’ dumbbells to indicate that the dumbbell holder can store more than one type of dumbbell ( e . g ., both 45 lb . and 50 lb . dumbbells ). simple or complex mappings can be created by a user or dynamically determined by the technology to , e . g ., partition portions of one or more racks to store newer / older weights , weights of a certain masses / sizes , padded / unpadded weights , gender - preferred weights , weights of the same brand , and / or other characteristics ( e . g ., color ). mappings can be manually or automatically programmed ( e . g ., via a computing device ) and stored for retrieval by the technology for configuring new or modified rack layout schemas . in some embodiments , the technology can identify particular dumbbell holders ( e . g ., empty versus occupied dumbbell holders ) using a variety of identification techniques , such as optical scanning ( e . g ., led , laser , or other light - based techniques ), weight ( e . g ., an actuator and / or scale in the dumbbell holder configured to indicate whether the location is occupied ), history ( e . g ., a log that stores present and past dumbbell placements ), transducers ( e . g ., hall effect sensors ), electrical switches ( e . g ., reed switches ) and / or other detection / identification technologies and / or methodologies . certain details are set forth in the following description and in fig1 - 8 to provide a thorough understanding of various embodiments of the disclosure . other well - known structures , systems and mechanisms often associated with traditional weight racks have not been shown or described in detail below to avoid unnecessarily obscuring the descriptions of the various embodiments of the disclosure . additionally , a person of ordinary skill in the relevant art will understand that the disclosure may have additional embodiments that may be practiced without several of the details described below . in other instances , those of ordinary skill in the relevant art will appreciate that the methods and systems described can include additional details without departing from the spirit or scope of the disclosed embodiments . many of the details , dimensions , functions and other features shown and described in conjunction with the figures are merely illustrative of particular embodiments of the disclosure . accordingly , other embodiments can have other details , dimensions , functions and features without departing from the spirit or scope of the present disclosure . in addition , those of ordinary skill in the art will appreciate that further embodiments of the disclosure can be practiced without several of the details described below . the terminology used in the description presented below is intended to be interpreted in its broadest reasonable manner , even though it is being used in conjunction with a detailed description of certain specific embodiments of the described technology . certain terms may even be emphasized below ; however , any terminology intended to be interpreted in any restricted manner will be overtly and specifically defined as such in this detailed description section . some techniques introduced below can be implemented by programmable circuitry programmed or configured by software and / or firmware , or entirely by special - purpose circuitry , or in a combination of such forms . such special - purpose circuitry ( if any ) can be in the form of , for example , one or more application - specific integrated circuits ( asics ), programmable logic devices ( plds ), programmable logic controllers ( plcs ), logic boards , field - programmable gate arrays ( fpgas ), etc . fig1 and the following discussion provide a brief general description of a suitable computing environment ( e . g ., a logic board ) in which aspects of the technology can be implemented . although not required , aspects of the technology may be described herein in the general context of computer - executable instructions , such as routines executed by a general - or special - purpose data processing device . aspects of the technology described herein may be stored or distributed on tangible computer - readable media , including magnetically or optically readable computer discs , hard - wired or preprogrammed chips ( e . g ., eeprom semiconductor chips ), nanotechnology memory , or other data storage media . alternatively , computer - implemented instructions , data structures , screen displays , and other data related to the described technology may be distributed over the internet or over other networks ( including wireless networks ) on a propagated signal on a propagation medium ( e . g ., an electromagnetic wave , a sound wave , etc .) over a period of time . in some implementations , the data may be provided on any analog or digital network ( packet switched , circuit switched , or other scheme ). referring to fig1 , the described technology employs a computer 100 , such as a pcb having one or more processors 101 coupled to one or more input devices 102 and data storage devices 104 . the computer 100 is also coupled to at least one output device such as a display device 106 and one or more optional additional output devices 108 ( e . g ., printer , plotter , speakers , tactile or olfactory output devices , etc .). the computer 100 may be coupled to external computers , such as via an optional network connection , a wireless transceiver , or both . the input devices 102 may include a keyboard , a microphone , a sensor , a pointing device such as a mouse , and described technology for receiving human voice , touch , and / or sight ( e . g ., a microphone , a touch screen , and / or smart glasses ). other input devices are possible such as a joystick , pen , game pad , scanner , digital camera , video camera , and the like . the data storage devices 104 may include any type of computer - readable media that can store data accessible by the computer 100 , such as magnetic hard and floppy disk drives , optical disk drives , magnetic cassettes , tape drives , flash memory cards , digital video disks ( dvds ), bernoulli cartridges , rams , roms , smart cards , etc . indeed , any medium for storing or transmitting computer - readable instructions and data may be employed , including a connection port to or node on a network , such as a lan , wan , or the internet ( not shown in fig1 ). fig2 a is a block diagram of an automated dumbbell racking system that includes various mechanisms 300 , 400 , 500 and 600 which can function independently and / or in combination to implement various aspects of the technology . as described above and further described below , loading mechanism 400 is configured to receive dumbbells ( e . g ., via a user ) and to deliver the dumbbells to a transport mechanism 500 that , in various embodiments , moves along a rail mechanism 600 to reach and deliver a dumbbell to a dumbbell holder of a weight rack mechanism 300 . fig2 b - 2g are various perspectives of one or more embodiments of the automated dumbbell racking system 200 depicted in fig2 a . fig2 b - 2g include a weight rack mechanism 300 for at least providing dumbbells to users , a loading mechanism 400 for receiving and loading one or more dumbbells 203 a dropped off by a user , and transport mechanism 500 that , in some embodiments , is configured to deliver , via rail mechanism 600 , dumbbells to the weight rack mechanism 300 . fig2 b is a top - front perspective of an embodiment of the technology in a loading configuration ; fig2 c is a top - back perspective of an embodiment of the technology in a loading configuration ; fig2 d is a top - back perspective of an embodiment of the technology in a delivery configuration ; fig2 e is a top perspective of an embodiment of the technology in a loading configuration ; fig2 f is a side perspective of an embodiment of the technology in a loading configuration ; and fig2 g is a side perspective of an embodiment of the technology indicating a delivery configuration 204 b for delivering a dumbbells to the weight rack mechanism 300 . fig3 a - 3c depict exemplary views of one or more embodiments of the weight rack mechanism 300 that includes one or more weight racks 302 a - 302 n , which can include one or more shelves 304 a - 304 n having one or more dumbbell holders 308 a - 308 n supported by legs 306 . dumbbell holders 308 a - 308 n are configured to hold one or more dumbbells 203 a - 203 n . each dumbbell holder 308 a - 308 n has an end for receiving a dumbbell ( a “ receiving end ”) 310 b via the transport mechanism 500 and an end accessible to a user for removing a dumbbell ( a “ user end ”) 310 a . in some embodiments , a single dumbbell holder 308 a - 308 n can hold two or more dumbbells ( not shown ), such that when a front dumbbell is removed a next dumbbell is revealed and ready to be removed by a user . for simplicity and not by limitation , the following figures depict embodiments that support a single dumbbell ( e . g ., 203 a ) per dumbbell holder ( e . g ., 308 a - 308 n ). fig4 a - 4c depict exemplary views of an embodiment of the loading mechanism 400 , which in one or more embodiments , includes a loading conveyor 404 connected together via stabilizers 406 and an optional loading cell 403 , in addition to or as an alternative to a load cell associated with the transport mechanism 500 ( as described below ). fig4 a is a side perspective of the loading mechanism 400 ; fig4 b is a top - front perspective of the loading mechanism 400 for transporting a dumbbell 203 a down the loading conveyor 404 ; and fig4 c is a side perspective of the loading mechanism 400 in approximation to the weight rack mechanism 300 , transport mechanism 500 and rail system 600 . the loading mechanism 400 is configured to receive one or more dumbbells 203 a - 203 n from gym members and / or staff . in some embodiments , the loading mechanism 400 includes one or more dumbbell templates 405 for orientating dumbbells into a proper position for inserting the dumbbell into the loading mechanism 400 . the optional loading cell 403 or other component of the loading mechanism 400 ( e . g ., or the conveyor ), in various embodiments , includes technology for determining various characteristics of the dumbbell for use in determining which of several dumbbell holders to store the dumbbell . dumbbell characteristics describe features of a particular dumbbell and / or dumbbell class , such as a size , shape , weight , material , color , brand , age , preferred use , preferred storage location , id , group id or other feature . for example , the loading cell 403 ( or conveyor ) can include technology for determining one or more characteristics for use in determining where to rack the dumbbell , such as a scale for measuring weight and / or optics for scanning one or more features of the dumbbell or a dumbbell id ( e . g ., a bar code , qr code or other identifier ) attached the dumbbell . the dumbbell id can be a unique identification such that when scanned it can be used for triggering the technology to reference stored data that describes attributes previously defined for a particular dumbbell ( e . g ., an unpadded 50 lb dumbbell made by manufacturer ‘ a ’ and in service in the gym facilities for 3 . 5 years ). based on one or more of the characteristics , the technology can determine ( e . g ., based on a desired layout for the rack ) a dumbbell holder for storing that dumbbell . the loading conveyor 404 includes dumbbell positions 409 a - 409 n that hold one or more dumbbells as the loading conveyor 404 moves dumbbells from a first position ( e . g ., a loading position ) 408 a to a second position ( e . g ., a delivery position ) 408 b for delivering the dumbbell to transport mechanism 500 . fig5 a - 5c depicts exemplary views of the transport mechanism 500 which receives dumbbells from the loading mechanism 400 , transports dumbbells , via a rail mechanism 600 , to a position in back of the dumbbell holders 308 a - 308 n and delivers the dumbbells to the dumbbell holders 308 a - 308 n for pickup by a user . fig5 a depicts a front - side perspective of the transport mechanism 500 ; fig5 b depicts a top side perspective of the transport mechanism 500 in approximation to the weight rack mechanism 300 and rail system 600 ; and fig5 c depicts a backside perspective of the loading mechanism 500 . transport mechanism 500 , in various embodiments , includes a delivery conveyor 503 , stabilizers 506 and , in one or more embodiments , a lift / actuator 504 . the transport mechanism 500 is configured to receive , at the delivery conveyor 503 , one or more dumbbells 203 a - 203 n from the loading mechanism 400 and further configured to transport the dumbbell 203 to a location in the back of a dumbbell holder 308 a - 308 n . the loading mechanism 500 , in one or more embodiments , has technology ( e . g ., a motor ) ( see , fig8 a - 8e ) for moving itself about the weight rack mechanism 300 to a determined dumbbell holder 308 a - 308 n . in some embodiments , the transport mechanism 500 is moved by an external force such as a rail mechanism 600 and is not required to have its own motor . when the transport mechanism 500 moves to the correct location of the weight rack mechanism 300 , the delivery conveyor 503 is configured to activate and move the dumbbell 203 toward and into the dumbbell holder 308 a - 308 n . the actuator 504 , such as a vertical linear actuator , raises and lowers the delivery conveyor 503 for reaching shelves of dumbbell holders at different heights ( e . g ., when racks are vertically stacked ). the actuator 504 can automatically activate when the technology determines that a dumbbell is at a higher / lower shelf than the current position of the delivery conveyer 503 . a loading cell ( not shown ) is couplable to the transport mechanism 500 for determining various dumbbell characteristics ( e . g ., mass ), as detailed above and further below . fig6 a - 6c depicts exemplary views of a rail mechanism 600 that , in various embodiments , guides the transport mechanism 500 to and from various dumbbell holders 308 a - 308 n of the weight rack mechanism 300 . fig6 a and fig6 b depict front - side perspectives of the rail mechanism 600 and fig6 c depicts a front side perspective of the rail mechanism 600 in approximation to the weight rack mechanism 300 . the rail mechanism 600 includes , in one or more embodiments , an actuator 604 ( e . g ., a belt actuator , linear rail drive / actuator , pneumatic actuator , etc .) for moving the transport mechanism 500 along one or more rails 606 attached via support stabilizers 602 . in operation , the actuator 604 is configured to receive and guide ( e . g ., push / pull ) the transport mechanism 500 into a position for delivering a dumbbell to the weight rack mechanism &# 39 ; s dumbbell holders 308 a - 308 n . fig7 is a flow diagram 700 depicting one or more features of the technology . flow diagram 700 depicts an example sequence of steps 702 - 716 for moving a dumbbell into a dumbbell holder . the flow diagram 700 starts at step 701 and , at step 702 , a dumbbell is received at the loading mechanism 400 . at step 704 , the loading mechanism 400 and / or transport mechanism 500 an determine one or more characteristics , such as the weight of the dumbbell . at step 706 , the technology determines if the dumbbell is assigned a predefined dumbbell holder ( e . g ., based on querying a database inventory of dumbbells ). if there is not a predefined dumbbell holder , at step 708 , a new dumbbell holder is identified for storing the dumbbell . for example , the technology may determine one or more unoccupied dumbbell holders that can store the dumbbell . at step 710 , the transport mechanism 500 moves the dumbbell along the rail mechanism 600 to a position approximate to the weight rack mechanism 300 and , at step 712 , delivers the dumbbell to the appropriate dumbbell holder ( e . g ., by moving the dumbbell down the delivery conveyor ). at step 714 , the location of the delivered dumbbell is optionally recorded ( e . g ., in a file , database and / or other recording means ) and inventoried for reference by the technology in determining one or more other dumbbell holders for other dumbbells . the flow ends at step 716 . fig8 a - 8e depict embodiments that utilize , among other things , a horizontal loading conveyor 802 , in opposed to the angled loading conveyor 404 in fig4 a - 4c . fig8 a is a front side perspective of the technology , fig8 b is a back side perspective of the technology , fig8 c is a side perspective of the technology , fig8 d is a top perspective of the technology and fig8 e is a left side perspective of the technology . referring to fig8 a , the horizontal loading conveyor 802 includes optional weight separators 804 for partitioning weights ( e . g ., dumbbells ) for transport , via motor 805 , along the horizontal loading conveyor 802 to the delivery conveyor 808 ( similar to delivery conveyor 503 ) of transport mechanism 806 ( similar to transport mechanism 500 ). in one or more embodiments and as described above , transport mechanism 806 vertically rises , via motor 814 , to accept one or more weights ( e . g ., dumbbells ) from the horizontal loading conveyor 802 onto the delivery conveyor 808 . in some embodiments , delivery conveyor 808 can simultaneously hold multiple weights ( e . g ., dumbbells ) that are positioned side - by - side , top - on - top and / or lengthwise front - to - back , etc . this allows the delivery conveyor 808 to automatically and simultaneously move , position and / or sort multiple weights to various positions within the weight rack mechanism 810 . weight rack mechanism 810 is similar to weight rack mechanism 300 , however , weight rack mechanism 810 optionally does not include partitioning ( e . g ., horizontal dividers ) between its dumbbell holder positions 812 as depicted between dumbbell holder positions 308 a - 308 n in fig3 a and 3b . fig8 b depicts features discussed above for fig8 a ( e . g ., elements 802 , 804 , 805 , 806 , 808 , 810 , 812 and 814 ) from a backside perspective . fig8 c is a front side perspective of the technology which depicts , among features discussed above for fig8 a ( e . g ., elements 802 , 805 , 806 , 810 and 814 ) and , in addition , a loading cell ( e . g ., strain gauge ) 816 ( similar to loading cell 403 ). the loading cell 816 , in some embodiments , is located at a position beneath the transport mechanism 806 and / or delivery conveyor 808 ( not shown ) for determining a weight &# 39 ; s mass by measuring the strain caused by , e . g ., a dumbbell positioned on the transport mechanism 806 . as discussed above , determining a weight &# 39 ; s mass at the loading cell 816 is useful when determining which of the dumbbell holders 812 of the weight rack mechanism 810 to reposition each respective dumbbell . fig8 d depicts a top view of the technology that includes elements described above for fig8 a - 8c ( e . g ., elements 802 , 804 , 806 , 808 810 and 812 ) and fig8 e depicts a left side view of the technology that includes elements described above for fig8 a - 8d ( e . g ., elements 802 , 806 , 810 and 814 ). in general , the detailed description of embodiments of the described technology is not intended to be exhaustive or to limit the described technology to the precise form disclosed above . while specific embodiments of , and examples for , the described technology are described above for illustrative purposes , various equivalent modifications are possible within the scope of the described technology , as those skilled in the relevant art will recognize . for example , while processes or blocks are presented in a given order , alternative embodiments may perform routines having steps , or employ systems having blocks , in a different order , and some processes or blocks may be deleted , moved , added , subdivided , combined , and / or modified . each of these processes or blocks may be implemented in a variety of different ways . also , while processes or blocks are at times shown as being performed in series , these processes or blocks may instead be performed in parallel , or may be performed at different times . the teachings of the described technology provided herein can be applied to other systems , not necessarily the system described herein . the elements and acts of the various embodiments described herein can be combined to provide further embodiments . the techniques introduced above can be implemented by programmable circuitry programmed or configured by software and / or firmware , or entirely by special - purpose circuitry , or in a combination of such forms . such special - purpose circuitry ( if any ) can be in the form of , for example , one or more application - specific integrated circuits ( asics ), programmable logic devices ( plds ), programmable logic devices ( plcs ), field - programmable gate arrays ( fpgas ), etc . software or firmware for implementing the techniques introduced here may be stored on a machine - readable storage medium and may be executed by one or more general - purpose or special - purpose programmable microprocessors . a “ machine - readable medium ,” as the term is used herein , includes any mechanism that can store information in a form accessible by a machine ( a machine may be , for example , a computer , network device , cellular phone , personal digital assistant ( pda ), manufacturing tool , any device with one or more processors , etc .). for example , a machine - accessible medium includes recordable / non - recordable media ( e . g ., read - only memory ( rom )); random access memory ( ram ); magnetic disk storage media ; optical storage media ; flash memory devices ; etc .). the term “ logic ,” as used herein , can include , for example , special - purpose hardwired circuitry , software and / or firmware in conjunction with programmable circuitry , or a combination thereof . these and other changes can be made to the described technology in light of the above detailed description . while the above description details certain embodiments of the described technology and describes the best mode contemplated , no matter how detailed the above appears in text , the described technology can be practiced in many ways . the described technology may vary considerably in its implementation details , while still being encompassed by the described technology disclosed herein . as noted above , particular terminology used when describing certain features or aspects of the described technology should not be taken to imply that the terminology is being redefined herein to be restricted to any specific characteristics , features , or aspects of the described technology with which that terminology is associated . in general , the terms used in the following claims should not be construed to limit the described technology to the specific embodiments disclosed in the specification , unless the above detailed description section explicitly defines such terms . accordingly , the actual scope of the described technology encompasses not only the disclosed embodiments , but also all equivalent ways of practicing or implementing the described technology . to reduce the number of claims , certain aspects of the described technology are presented below in certain claim forms , but the applicant contemplates the various aspects of the described technology in any number of claim forms . for example , while only one aspect of the described technology is recited as a means - plus - function claim under 35 u . s . c § 112 , 16 , other aspects may likewise be embodied as a means - plus - function claim , or in other forms , such as being embodied in a computer - readable medium . ( any claims intended to be treated under 35 u . s . c . § 112 , 6 will begin with the words “ means for ,” but use of the term “ for ” in any other context is not intended to invoke treatment under 35 u . s . c . § 112 , 6 .) accordingly , the applicant reserves the right to pursue additional claims after filing this application to pursue such additional claim forms , in either this application or in a continuing application .

automated gym equipment sorting technology is presented for receiving , measuring , sorting , delivering and inventorying weights used in a gym facility . various mechanisms are employed for efficiently replacing weights on a rack accessible to gym members . weights are randomly dropped off at and dynamically sorted by the technology based on dumbbell characteristics and an optional schema so that members can more efficiently find desired weights .

the food release film may comprise one or more layers , preferably at least 3 layers . a multilayered food release film may include one or more of each of : a can - side or inside layer ( i . e ., heat seal layer ), a food or outside layer , a coated layer which effects release of food there could also be multiple core layers between the heat sealant layer and the coating layer that effect barrier properties such as oxygen and moisture . this coating is in direct contact with the food in the can . the starch is dissolved in a water / alkaline solution . the starch can also be heated in a water solution to dissolve the starch , but this creates an unwanted increase in viscosity . besides keeping the viscosity low , alkaline treatment also creates carboxyl groups which are beneficial to crosslinking . crosslinking increases the cohesiveness of the starch coating and prevents the coating from being removed from the polyester film prematurely during the can lamination stage . it is hypothesized that once the film is laminated to the can , the coating behaves as a sacrificial layer that bonds to the meat protein during the retort process and is removed with the meat protein preventing the meat protein from attaching to the polyester film . the food and drug administration ( fda ) data standards council is standardizing vocabulary across the fda . therefore , the wording in some terms below may change slightly in the future . biotechnology — refers to techniques used by scientists to modify deoxyribonucleic acid ( dna ) or the genetic material of a microorganism , plant , or animal in order to achieve a desired trait . in the case of foods , genetically engineered plant foods are produced from crops whose genetic makeup has been altered through a process called recombinant dna , or gene splicing , to give the plant desired traits . genetically engineered foods are also known as biotech , bioengineered , and genetically modified , although “ genetically modified ” can also refer to foods from plants altered through methods such as conventional breeding . while in a broad sense biotechnology refers to technological applications of biology , common use in the u . s . has narrowed the definition to foods produced using recombinant dna . for additional information , see the biotechnology program on the cfsan internet . cedi / adi database — for a large number of food contact substances , cfsan maintains a database of cumulative estimated daily intakes ( cedis ) and acceptable daily intakes ( adis ). the cedis and adis are based on currently available information and may be revised when information is submitted or made available . the cedi / adi database is updated approximately twice annually . the cedis and adis are based on currently available information and may be subject to revision on the basis of new information as it is submitted or made available to ofas . color additive — a color additive is a dye , pigment or other substance , which is capable of imparting color when added or applied to a food , drug , cosmetic , or to the human body . the legal definition can be found in section 201 ( t ) of the federal food , drug , and cosmetic act ( fd & amp ; c act ) and provides exclusions as well . color additives for use in food , drugs , and cosmetics require premarket approval . color additives for use in or on a medical device are subject to premarket approval , if the color additive comes in direct contact with the body for a significant period of time . for additional information , consult the color additive program on the cfsan internet . colorant — a colorant is a dye , pigment , or other substance that is used to impart color to or to alter the color of a food - contact material , but that does not migrate to food in amounts that will contribute to that food any color apparent to the naked eye . the term ‘ colorant ’ includes substances such as optical brighteners and fluorescent whiteners , which may not themselves be colored , but whose use is intended to affect the color of a food - contact material . ( 21 cfr 178 . 3297 ( a )). eafus — the “ everything added to food in the united states ” ( eafus ) database is an informational database maintained by cfsan under an ongoing program known as the priority - based assessment of food additives ( pafa ). pafa contains administrative , chemical and toxicological information on over 2000 substances directly added to food , including substances regulated by the fda as a direct food additive , secondary direct food additive , color additive , gras and prior - sanctioned substance . in addition , the database contains only administrative and chemical information on approximately 1000 such substances . information about the more than 3000 total substances comprise eafus . for a complete listing of eafus substances , see the eafus list . food additive — a food additive is defined in section 201 ( s ) of the fd & amp ; c act as any substance the intended use of which results or may reasonably be expected to result , directly or indirectly , in its becoming a component or otherwise affecting the characteristic of any food ( including any substance intended for use in producing , manufacturing , packing , processing , preparing , treating , packaging , transporting , or holding food ; and including any source of radiation intended for any such use ); if such substance is not gras or sanctioned prior to 1958 1 or otherwise excluded from the definition of food additives . food contact substance ( fcs )— section 409 of the fd & amp ; c act defines an fcs as any substance that is intended for use as a component of materials used in manufacturing , packing , packaging , transporting , or holding food if such use of the substance is not intended to have any technical effect in such food . additional information can be found on the food contact substances notification program page . there is a hierarchy from food contact substance ( fcs ) through food contact material ( fcm ) to food contact article ( fca ). the food contact substance ( the subject of an fcn ) is a single substance , such as a polymer or an antioxidant in a polymer . as a substance , it is reasonably pure ( the chemist &# 39 ; s definition of substance ). even though a polymer may be composed of several monomers , it still has a well - defined composition . food contact material ( fcm ) is made with the fcs and ( usually ) other substances . it is often ( but not necessarily ) a mixture , such as an antioxidant in a polymer . the composition may be variable . the food contact article is the finished film , bottle , dough hook , tray , or whatever that is formed out of the fcm . gras —“ gras ” is an acronym for the phrase generally recognized as safe . under sections 201 ( s ) and 409 of the fd & amp ; c act , any substance that is intentionally added to food is a food additive , that is subject to premarket review and approval by fda , unless the substance is generally recognized , among qualified experts , as having been adequately shown to be safe under the conditions of its intended use , or unless the use of the substance is otherwise excluded from the definition of a food additive . gras substances are distinguished from food additives by the type of information that supports the gras determination , that it is publicly available and generally accepted by the scientific community , but should be the same quantity and quality of information that would support the safety of a food additive . additional information on gras can be found on the gras notification program page . guidance document — guidance documents are documents prepared for fda staff , applicants / sponsors , and the public that describe the agency &# 39 ; s interpretation of or policy on a regulatory issue . guidance documents include , but are not limited to , documents that relate to the design , production , labeling , promotion , manufacturing , and testing of regulated products ; the processing , content , and evaluation or approval of submissions ; and inspection and enforcement policies . guidance documents do not legally bind the public or fda or establish legally enforceable rights or responsibilities . they represent the agency &# 39 ; s current thinking ( 21 cfr 10 . 115 ). a complete listing of cfsan &# 39 ; s guidance documents is available on the internet . indirect food additive — in general , these are food additives that come into contact with food as part of packaging , holding , or processing , but are not intended to be added directly to , become a component , or have a technical effect in or on the food . indirect food additives mentioned in title 21 of the u . s . code of federal regulations ( 21 cfr ) used in food - contact articles , include adhesives and components of coatings ( part 175 ), paper and paperboard components ( part 176 ), polymers ( part 177 ), and adjuvants and production aids ( part 178 ). currently , additional indirect food additives are authorized through the food contact notification program . in addition , indirect food additives may be authorized through 21 cfr 170 . 39 . pafa — the priority based assessment of food additive ( pafa ) database is a database that serves as cfsan &# 39 ; s institutional memory for the toxicological effects of food ingredients known to be used in the united states . currently , pafa contains oral toxicology information on over 2100 of approximately 3300 direct food ingredients used in food in the us . pafa also contains minimal information on over 3200 indirect additives including the names , cas number and regulatory information of the indirect additives in the code of federal regulations . the eafus list and the indirect additive list on the cfsan internet consist of selected fields of information generated from pafa . prior sanctioned substance — a substance whose use in or on food is the subject of a letter issued by fda or usda offering no objection to a specific use . the prior sanction exists only for a specific use of a substance in food delineating level ( s ), condition ( s ) and product ( s ) set forth by explicit approval by fda or usda prior to sep . 6 , 1958 . some prior sanctioned substances are codified in 21 cfr part 181 . scogs report —“ scogs ” is the acronym for the select committee on gras substances . beginning in 1972 , under a contract with fda , the life sciences research office of the federation of american societies for experimental biology convened the select committee , which independently undertook a comprehensive review of the safety and health aspects of gras food substances on the fda &# 39 ; s then proposed gras list . the select committee published its evaluations in a series of reports known as the scogs reports . a listing of opinions and conclusions from 115 scogs reports published between 1972 and 1980 is available on the cfsan internet . secondary direct food additive — this term is in the title of 21 cfr 173 , which was created during recodification of the food additive regulations in 1977 . a secondary direct food additive has a technical effect in food during processing but not in the finished food ( e . g ., processing aid ). some secondary direct food additives also meet the definition of a food contact substance . for more on food contact substances , consult the food contact substance notification program . threshold of regulation ( tor ) exemption — a substance used in a food contact article may be exempted from the requirement of a food additive listing regulation if the use in question has been shown to meet the requirements in 21 cfr 170 . 39 . for details , see 21 cfr 170 . 39 . for a complete listing of the tor exemptions , consult the threshold of regulation inventory on the cfsan internet . the present invention comprises a polyester film which can be laminated to a metal plate for canning which is typically made of tin - free steel , with a dimensional change of not more than 2 . 0 % after a heat treatment of 210 ° c . the film is biaxially oriented and has at least two layer structure a / b , wherein a is a layer made from polyester having a melting point of 200 - 235 ° c . referred to as amorphous polyester ( apet ) which is laminated to the metal plate and b which has a melting point of 240 - 260 ° c . referred to as crystalized polyester ( cpet ) the above mentioned film also has a release coating which is applied inline to the cpet side of the film during the film making process . preferably the pet film suitable for use in the embodiments herein is biaxially oriented prior to laminating it to the metal substrate . the films are biaxially oriented by conventional methods . typically , a raw material pet resin is supplied in solid form to a melt processing device , preferably a continuous screw extruder . the heating of the melt processor is controlled to maintain the pet resin above its melting point but below polymer degradation temperature . pet molten resin is extruded from an appropriately shaped die to form a thin , flat ribbon of polymer melt . the polymer ribbon is quenched in air and or on a chilled roll to form a solid , self - supporting film . the film is taken up by sets of rollers turning at different rotation speeds that stretch the film in the direction of continuous forward motion , referred to as the machine direction (“ md ”). the stretching can be accompanied by heating of the film to establish crystal orientation in the md . the mono - directionally oriented film is clamped at its opposite edges in and stretched in the transverse machine direction (“ td ”) laterally perpendicular to the md in a tenter oven . the tenter oven is heated to temperatures operative to establish crystal orientation in the td thus forming a biaxially oriented pet film . preferably biaxially oriented pet film for use in the embodiments herein is stretched about 100 %- 400 % in the md and 100 %- 600 % in the td . the biaxially oriented film can be heat set at temperatures can be preferably between about 300 ° f . and about 490 ° f ., more preferably about 350 ° f . to about 460 f . the coating is applied after the md stretch and is stretched in the td direction along with the film and must be compatable with the thermal conditions necessary to heat set the film as mentioned above . a food release coating that contains an effective amount one or more agents . the coating is typically applied to cpet side of the film — the food side . the coating ingredients must be able to survive though the film making conditions , and also avoid transferring to the non - food side of the film with an agent that may reduce the adhesion of the apet , heat extrusion or adhesive layer that will be coated or extruded on the non - food side . the coating that we used in our product adhered well to the cpet polyester film . modified starches provide a solution for a wide variety of papermaking applications such as sizing , retention , strength , film - forming and coating . starches are also used in adhesives used for corrugated boxes , multiwall bag . the textile industry relies on starches for sizing and finished fabrics . it is also used as natural binder systems for granular and fibrous applications for many different building products . ceiling tiles , wallboard , paint and building adhesives are several examples . starch can help optimize mining and drilling operations with natural binders and recovery aids . acid - treated starch , also called thin boiling starch , is prepared by treating starch or starch granules with inorganic acids , e . g . hydrochloric acid breaking down the starch molecule and thus reducing the viscosity . dextrin roasted starch with hydrochloric acid alkaline - modified starch with sodium hydroxide or potassium hydroxide bleached starch with hydrogen peroxide oxidized starch with sodium hypochlorite , breaking down viscosity enzyme - treated starch maltodextrin , cyclodextrin monostarch phosphate with phosphorous acid or the salts sodium phosphate , potassium phosphate , or sodium triphosphate to reduce retrogradation distarch phosphate by esterification with for example sodium trimetaphosphate , crosslinked starch modifying the rheology , the texture acetylated starch esterification with acetic anhydride hydroxypropylated starch , starch ether , with propylene oxide , increasing viscosity stability hydroxyethyl starch , with ethylene oxide starch sodium octenyl succinate starch used as emulsifier adding hydrophobicity starch aluminium octenyl succinate cationic starch , adding positive electrical charge to starch carboxymethylated starch with monochloroacetic acid adding negative charge and combined modifications such as phosphated distarch phosphate acetylated distarch phosphate acetylated distarch adipate hydroxypropyl distarch phosphate acetylated oxidized starch oxidation of starch mainly causes the scission of the glucosidic linkages and oxidation of hydroxyl groups to carbonyl and carboxyl groups . the scission of the glucosidic linkage results in depolymerization of amylose and amylopectin , hence decreases swelling power and paste viscosity . formation of the carbonyl and carboxyl groups discontinuously along the chains reduces gelatinization temperature , increases solubility , and decreases gelation . it is believed that after oxidation with naoh to control the viscosity , the main functional group would still be the hydroxyl groups . berrcet 2040 was chosen because it is a highly effective insolubilizing and crosslinking agent based on dialdehyde chemistry . bercet 2040 ′ s reactivity is greatly accelerated during the drying cycle which results in higher wet rub and wet pick resistance . it also crosslinks all normally used synthetic and natural binders in pigmented or non - pigmented systems as well as reacting with the hydroxyl or amino group containing coating binders . in regards to food contact , bercet 2040 is fda compliant , subject to the provisions of : title 21 cfr 176 . 180 without limitations , and title 21 cfr 176 . 170 , when used as an insolubilizing agent in starch and protein based coatings that contact foods . in order to screen and test coating for release , a 5 % gelatin solution was used as a substitute to a meat product . the gelatin was dissolved in boiling water and applied to the coated substrate while hot and left to dry overnight . as the gelatin cooled , it solidified on the surface with varying levels of release from the coating . a rating of 1 indicates complete release from the coating . 2 partial and 3 no release . after drying , 3m 810 tape is applied to the coating surface with heavy finger pressure . the tape is then pulled off at a 45 degree angle as quickly as possible . the area under the tape was given a subjective rating from 1 - 3 based on how much of the coating has been pulled away from the surface . 1 being no coating removal , 2 being ˜ 20 % and 3 being greater than 30 % removal . this test is a measure how well the coating is adheres to the polyester film a food mixture of egg / beef / flour at a ratio of 3 / 2 / 1 was prepared . the coated film was placed in a 8 oz glass canning jar with the coated layer facing the interior of the jar . if the laminated can is being tested a circular metal disk which has been laminated with coated polyester in a previous step is placed at the bottom of the jar . the meat mixture was placed in the jar against the coated side of the polyester . the jar is sealed , placed in a pressure cooker with water and heated to boiling on a hot . as used in relation to this invention , the term “ retort process ” means a procedure in which the inside or outside of a metal container with a wall composed of a composite of a metal substrate having a polymer film laminated onto the inside , the outside or both sides of the substrate is treated with live steam for a period of time . “ live steam ” means that steam directly contacts the surface of the container . the steam is usually superheated , i . e ., above the boiling point of water . a nominal retort process calls for exposure to steam at temperature of 260 ° f . for 90 minutes . the temperature and duration of exposure of the retort process can vary to provide an approximately equivalent sterilization and food pasteurization effectiveness . for example , the temperature might be higher for a shorter duration or lower for a longer duration . the jars were removed after 90 minutes and left to cool . the jars are tipped over and were rated with a percentage of how much food mixture easily fell off the film or laminated can . the term “ substantially all food contacting the bopet during the retort test is released ” means that the percent release in the retort test before and after can lamination is greater than 80 percent , preferably at least 85 percent . starch granules are insoluble in cold water . when starch is heated in water , granules absorb water and swell . the absorption of water by amorphous regions within the granules destabilizes their crystalline structure . upon continuous heating , granules tend to swell to greater extents , and the crystallites melt , resulting in increased molecular motion that eventually leads to complete separation of amylose and amylopectin . the typical way to dissolve starch in water is by heating to160 - 180 f . for 10 min . this method leads to an unwanted increase in viscosity which would limit the amount of solids that can be used in a coating recipe . using a brookfield viscosity ( spindle # 2 @ 100rpm ) the viscosity using this method is ˜ 100 cps . a preferred method of dissolving starch in water is to use an alkali to depolymerize the amylose and amylopectin , which decreases the swelling power of the starch . the viscosity using this method is ˜ 10 cps . the invention is better understood with reference to the following examples ( ex .) and comparative ( c . ex .) to illustrate specific embodiments within the overall scope of the invention . acrylic emulsion , neocryl a1095 , was diluted to 8 % solids with water and 4 % wax emulsion was added and coated with a # 3 mayer rod . after stretching 400 % this gives an effective dry coat weight of 0 . 11 gsm . this film passes the retort and gelatin test but an acrylic polymeric binder would be not be favorable as a food additive . 9 % starch , purecoat b792 from gpc , is dispersed in water and then 2 % solution of 10 % sodium hydroxide solution is mixed in . this does not have a wax additive . this passes the gelatin , retort and tape release tests and does not interfere or detract from food taste . 9 % starch , purecoat b790 from gpc , is dispersed in water and a 2 % solution of 10 % sodium hydroxide solution is added . a 1 % solution of wax emulsion syncera cw1245 fom paramelt is also added . this passes the gelatin , tape and retort test and is the preferred example to pass both can lamination and the retort test the polyester film without the release coat does not pass the retort and gelatin tests . 100 % canauba wax only . release is good with the retort test before lamination but fails the retort test after lamination . this shows that the wax is sacrificial and is lost or reduced during the can lamination process . starch that is hydrated under normal thermal conditions with no naoh and wax additives does not have high enough release properties after retort . starch oxidized with higher amount of naoh showed poor release on the retort tests . it is hypothesized the higher ph degrades the proteins in the starch as opposed to creating crosslinking sites . ideally naoh addition should be 2 - 4 % of the coating . 8 % starch , purecoat b792 by gpc was dissolved by the standard thermal method of heating in water for 10 minutes . a wax additive , syncera cw 1245 , carnuba wax , was mixed into this solution . this did not pass the gelatin test and did not have the best adhesion before or after the retort test . the viscosity of this solution was 100 cps . table 1 shows data on composition and test results of examples and comparative examples .

an embodiment relates to a multi - layer , biaxially oriented polyester film comprising a food contact substance , wherein the bopet has a percent release in a retort test after can lamination such that substantially all food contacting the bopet during the retort test is released . another embodiment relates to a method comprising applying a food contact material comprising a food contact substance to a multi - layer , biaxially oriented polyester film , wherein the food contact material is prepared at around room temperature without heating .

this disclosure describes surgical methods for drying an osteochondral defect . the surgical methods include using a suction swab to dry the osteochondral defect . in some embodiments , the suction swab suctions moisture away from the osteochondral defect to dry the defect . in other embodiments , the suction swab communicates a gas to the osteochondral defect to dry the defect . the suction swab may be used to dry the osteochondral defect during microfracture surgeries or other osteochondral defect repairs . these and other features are described in greater detail in the following paragraphs of this disclosure . fig1 and 3 illustrate a suction swab 10 . the suction swab 10 includes a tube 12 that extends along a longitudinal axis a between a distal end 14 and a proximal end 16 . a swab tip 18 is disposed at the distal end 14 , and an adaptor 20 is disposed at the proximal end 16 . in one embodiment , the distal end 14 of the tube 12 is received within the swab tip 18 , and the proximal end 16 of the tube 12 is received within the adaptor 20 . the tube 12 may be cannulated such that a passage 22 extends through its body . the passage 22 is disposed about the longitudinal axis a and may extend from the distal end 14 to the proximal end 16 . the distal end 14 of the tube 12 may include a plurality of openings 24 , or fenestrations , formed through the tube 12 . the openings 24 are in fluid communication with the passage 22 . in one non - limiting embodiment , the tube 12 is made of polystyrene . however , the tube 12 may be constructed of other similar materials within the scope of this disclosure . the swab tip 18 is received over the distal end 14 of the tube 12 . in one embodiment , the swab tip 18 is received over the distal end 14 of the tube 12 such that the openings 24 are positioned inside the swab tip 18 . the swab tip 18 may be made of a wicking and / or moisture absorbing material . cotton and foam are non - limiting examples of such materials . in one non - limiting embodiment , the swab tip 18 is capable of absorbing fluids including but not limited to arthroscopy fluid , synovial fluid , blood , bone marrow , etc . the adaptor 20 of the suction swab 10 is configured for connection to a power device ( not shown ), such as a suction or gas device . in one embodiment , the adaptor 20 is a barbed adaptor ( see fig1 ). in another embodiment , the adaptor 20 is a luer type adaptor or a tapered adaptor ( see fig3 ). other adaptor configurations are also contemplated . the suction swab 10 can be used during surgical procedures to dry an osteochondral defect 30 . the osteochondral defect 30 includes localized , damaged areas of articular cartridge and adjacent subchondral bone within a joint space , such as a knee , hip , ankle or shoulder joint space . the suction swab 10 can also be used to perform fluid management within the joint space during a surgical procedure . for example , as shown in fig4 , moisture m ( which could include arthroscopy fluid , synovial fluid , blood , bone marrow , etc .) that has pooled on the osteochondral defect 30 may be absorbed by the swab tip 18 of the suction swab 10 . the moisture m is suctioned through the openings 24 of the tube 12 and then through the passage 22 to remove the moisture m and dry the osteochondral defect 30 . in an alternative embodiment , shown in fig5 , the suction swab 10 can be used to communicate a gas g to dry moisture m that has accumulated at the osteochondral defect 30 . the gas g may be communicated through the passage 22 of the tube 12 , then through the openings 24 , and then through the swab tip 18 to dry the osteochondral defect 30 . in one embodiment , the gas g is an inert gas , such as compressed air or nitrogen . in yet another embodiment , the suction swab 10 can be used to dry the osteochondral defect 30 by both suctioning moisture from the osteochondral defect 30 and communicating the gas g to the osteochondral defect 30 . fig4 and 5 are not necessarily drawn to scale and may be exaggerated to better illustrate the features of the suction swab 10 . fig6 - 11 , with continued reference to fig1 - 5 , schematically illustrate a method of using the suction swab 10 to prepare an osteochondral defect 30 for a subsequent surgical procedure . the method is illustrated and described as an arthroscopic method ; however , the suction swab 10 could also be used in open procedures to dry defects . in one non - limiting embodiment , the suction swab 10 is used to dry the osteochondral defect 30 to prepare a joint space 32 for receiving a repair material . although the joint space 32 of fig6 - 11 is illustrated as a knee joint , the suction swab 10 of this disclosure could be used to dry osteochondral defects located anywhere within the human body . referring first to fig6 , after the surgeon has identified the osteochondral defect 30 within the joint space 32 , the osteochondral defect 30 is debrided to a stable border having perpendicular margins . tools , such as a curette 40 and an elevator 42 , can be used to create the vertical margins and debride the calcified cartilage layer at the base of the osteochondral defect 30 . next , as shown in fig7 , a microfracture procedure may be performed to obtain a microfracture site 44 . during the microfracture surgery , the surgeon creates multiple perforations 46 in the subchondral bone 48 that extends beneath the articular cartilage 49 located near the osteochondral defect 30 of the joint space 32 . in one embodiment , the microfracture procedure is performed using a tool 53 , such as arthrex &# 39 ; s powerpick ™, to form the perforations 46 of the microfracture site 44 . the formation of the perforations 46 creates a bleeding bone bed that stimulates bone marrow seepage into the microfracture site 44 . after creating the microfracture site 44 , the osteochondral defect 30 is dried to remove excess moisture that could interfere with implantation of a repair material . as shown in fig8 , the osteochondral defect 30 is dried using the suction swab 10 . the suction swab 10 is positioned within the joint space 32 , and the swab tip 18 of the suction swab 10 may be positioned at the microfracture site 44 to begin wicking and / or absorbing any excess moisture . the moisture may be dried by suctioning the moisture out of the osteochondral defect 30 through the suction swab 10 or by introducing a gas to the osteochondral defect 30 through the suction swab 10 . it should be understood that the suction swab 10 of this disclosure is not limited to uses associated with microfracture surgeries . for example , in another non - limiting embodiment , the curette 40 shown in fig6 could be used to create the bleeding bone bed within the joint space 32 . the bleeding bone bed can then be dried as necessary using the suction swab 10 to prepare the osteochondral defect 30 for receiving a repair material or graft . referring to fig9 , a cannula 50 can be utilized in an arthroscopic portal that resides over the osteochondral defect 30 . distraction is applied with the cannula 50 to improve visualization of the osteochondral defect 30 . a repair material 52 can then be applied over the osteochondral defect 30 using a delivery needle 54 . in one non - limiting embodiment , the repair material 52 is an allograft mixture . the repair material 52 may include allograft cartilage in the form of micronized cartilage particulates which may be cartilage delivered in its native form , dehydrated via lyophilization , dehydrated via desiccation , or dehydrated by any other method . one non - limiting example of a suitable repair material 52 is arthrex &# 39 ; s biocartilage ®, which is a micronized cartilage matrix . the repair material 52 serves as a scaffold over the osteochondral defect 30 and provides a tissue network that can potentially signal autologous cellular interactions and improve the degree and quality of tissue healing within the osteochondral defect 30 . the repair material 52 can be smoothed within the osteochondral defect 30 so that it remains slightly recessed to the surrounding cartilage ( see fig1 ). a layer of fibrin 60 may be applied over the repair material 52 via an applicator 62 ( see fig1 ). after letting the fibrin 60 and the repair material 52 sit for a predefined amount of time , such as approximately five minutes , the joint space 32 may be gently ranged before closure to assure adherence of the repair material 52 and completion of the final repair 70 ( see fig1 ). although the different non - limiting embodiments are illustrated as having specific components , the embodiments of this disclosure are not limited to those particular combinations . it is possible to use some of the components or features from any of the non - limiting embodiments in combination with features or components from any of the other non - limiting embodiments . it should be understood that like reference numerals identify corresponding or similar elements throughout the several drawings . it should also be understood that although a particular component arrangement is disclosed and illustrated in these exemplary embodiments , other arrangements could also benefit from the teachings of this disclosure . the foregoing description shall be interpreted as illustrative and not in any limiting sense . a worker of ordinary skill in the art would understand that certain modifications could come within the scope of this disclosure . for these reasons , the following claims should be studied to determine the true scope and content of this disclosure .

a surgical method according to an exemplary aspect of the present disclosure includes , among other things , drying an osteochondral defect using a suction swab . the drying step includes suctioning moisture from the osteochondral defect through the suction swab or communicating a gas to the osteochondral defect through the suction swab .

fig1 . discloses in block diagram format an improved bier vessel 10 according to the present invention . the bier vessel 10 comprises a first chamber 12 typically employed as a vaporization chamber and a second chamber 14 typically employed as a test chamber . in this example the chambers 12 and 14 are of similar size , however their sizes can be varied to accommodate individual needs . a plurality of test chambers 16 attach to the vaporization chamber 12 . these test chambers 16 are much smaller in size then the vaporization chamber 12 whereby upon placing the test chamber 16 into communication with the vaporization chamber 12 the conditions of the vaporization chamber 12 are quickly established within the test chamber 16 to provide an accurate starting point for a test . the most desirable starting point in a test would have the concentration of vaporized sterilant in the test chamber 16 change instantaneously from zero to the desired test concentration . a conduit 18 connects the first chamber 12 and second chamber 14 and incorporates an isolation valve 20 to separate the first chamber 12 from the second chamber 14 . similarly , each of the test chambers 16 are isolated from the first chamber 12 by an isolation valve 22 . monitoring of conditions within the bier vessel system 10 helps assure that the process is proceeding as desired . a separate pressure monitor 24 , temperature sensor 26 and sterilant concentration monitor 28 is provided for each of the first chamber 12 , second chamber 14 and test chambers 16 . sterilant monitors for hydrogen peroxide preferably employ light absorption techniques , such as described in the prieve et al . u . s . pat . no . 6 , 269 , 680 , incorporated herein by reference . a vacuum system 30 comprises vacuum pump 32 and vacuum lines 34 from the vacuum pump 32 to the first and second chambers 12 and 14 and vacuum lines 36 serving the smaller test chambers 16 . vacuum vent valves 38 and 40 on the first chamber and second chamber 12 and 14 , respectively isolate these chambers from the vacuum line 34 and vacuum vent valves 42 isolate the smaller test chambers 16 from the vacuum lines 36 . the volume of the vacuum lines 36 exceeds the volume of their associated test chamber 16 such that upon opening the vent valves 42 contents of the test chamber 16 are quickly evacuated . when this occurs at the end of an exposure period to a sterilant , the concentration of sterilant in the test chamber 16 is quickly diminished so as to provide a controllable end point the exposure period . similar to the starting point , the most desirable end point would have the sterilant concentration drop from the desired testing concentration to zero instantaneously . a plasma generator 44 connects to electrodes 46 in the first and second chambers 12 and 14 provide the capability of driving the gases therein into the plasma state . the electrodes 46 are isolated from their respective chambers 12 and 14 and the plasma generator 44 applies an electrical potential between the electrode 46 and the respective test chamber 12 or 14 . examples of appropriate plasma generation systems are described in u . s . pat . nos . 4 , 801 , 421 , 5 , 656 , 238 and 6 , 447 , 719 , incorporated herein by reference . a control system 48 interconnects to the various sensors 24 , 26 , 28 , valves 20 , 22 , 38 , 40 , 42 , the plasma generator 44 and the vacuum system 30 and other equipment as may be needed or desired to affect control over the process of the bier vessel 10 . preferably , the control system includes data storage and networking capabilities for easy handling of the test data . vent valves 50 are provided on each of the chambers , 12 , 14 and 16 to allow venting of the chamber to atmospheric pressure or a target pressure below atmospheric . these vent valves 50 are also connected to , and are under the control of the control system 48 . preferably they comprise a dual valve couple , one being larger than the other , to provide quick venting of large volumes and fine tuning of desired pressure . they are cycled open and closed until the target pressure is reached . a separate injector 52 is provided for first chamber 12 and second chamber 14 , through which a pre - measured quantity of liquid sterilant solution can be injected via a syringe through a septum and then vaporized into the chamber 12 or 14 . fig2 shows in perspective view the bier vessel 10 depicted in block diagram form in fig1 . each of chambers 12 and 14 has a large door 60 having a floating hinge mechanism 62 and interlocking latch 64 . the latch 64 is connected to the control system 48 and plasma generator 44 to extinguish the plasma if the door 60 is opened during the cycle when there is plasma present or when the concentration of sterilant is too high . as also seen in fig3 , a pneumatic piston 65 , under control of the control system 48 , extends over the latch 64 to prevent opening of the latch during unsafe conditions . fig4 shows the hinge mechanism 62 which comprises a hinge 66 attached to the door 60 and slideably attached to the outer wall of the chamber 12 or 14 . the hinge 66 is trapped between an outer plate 68 and an inner plate 70 ′ while retaining freedom to slide therebetween . preferably , the plates 68 and 70 are formed out of or coated with a low friction substance such as polytetrafluoroethylene ( ptfe ). a spring 72 biases the hinge toward the chamber 12 or 14 . when the door 60 is closed , the spring normalizes the forces applied at the top and bottom of the chamber 12 or 14 . fig5 to 7 show an alternative version hinge mechanism 74 . a hinge mounting bracket 76 affixes to a chamber 78 . two mounting plates 80 connect to the bracket 76 via screws 82 passing through elongated slots 84 in the mounting plate 80 so as to provide a limited degree of lateral movement of the plate 80 relative to the bracket 76 . the screws 82 comprise an unthreaded shoulder 85 between machine threads 86 and a head 88 to allow easy movement of the shoulder 85 within the slots 84 . a spring 90 biases the mounting plate 80 away from a door 92 . two hinges 94 attach to the door 92 and have connectors 96 extending therefrom toward the mounting plates 80 . a clip plate 98 attaches to each mounting plate 80 and has rear notches 100 and front notches 102 into which snap respectively a proximal pin 104 and distal catch 106 on the connectors 96 thus allowing easy attachment and detachment of the door 92 . a latch 108 is provided on a side of the door 92 opposite the hinges 94 . a seal 109 about an , opening 111 into the chamber 78 and between the door 92 and the chamber 78 helps preserve a vacuum in the chamber 78 . although the hinges 94 are shown slidably attached to the chamber 78 , one of skill in the art would see that their design could be modified to slidably attach the hinges 94 to the door 92 . further , rather than allow movement at the hinges to normalize forces on the door seal 109 , movement could instead be provided at the latch 108 or at both the latch 108 and the hinges 94 . test racks for holding biological indicators are helpful in getting even distribution of the indicators within the test chambers 14 and 16 . fig8 shows a rack 110 suitable for holding twenty flat test packs ( not shown ), each containing a biological indicator , for use within the large test chamber 14 . fig9 shows a rack 112 suitable for holding four biological indicators within the cylindrical test chamber 16 . an open circular ring 114 having evenly spaced holder 116 about its circumference fits snugly within the test chamber 16 . each holder 116 has a pair of end flanges 118 between which can be placed a biological indicator . a typical cycle in the bier vessel 10 comprises the following . heat all portions of the bier vessel 10 to 50 ° c . optionally : heat the vaporizer chamber 12 to 65 ° c ., the large test chamber 14 to 50 ° c ., and the small test chambers or ports 16 to 45 ° c . the temperature differentials cause small pressure gradients in the gas which can be manipulated to help control gas flow . evacuate all portions of the bier vessel to 0 . 2 torr and light a plasma . the vacuum and plasma both aid in eliminating any possible residuals , such as water or sterilant from a prior cycle , in the vessel . as plasma energy creates heat , the pressure may rise . the 0 . 2 torr pressure can be maintained with the throttling valves 50 that opens and closes to raise or lower pressure . vent all chambers 12 , 14 and 16 to atmospheric pressure and load samples . samples are preferably positioned within all portions of the chamber 14 so that when sterilant is introduced into the portions , it exposes all samples equally . evacuate all portions of the bier vessel 10 to 0 . 2 torr . the vacuum enhances sterilant vaporization and diffusion . optionally : plasma may be introduced to condition / heat the samples / load . stop the plasma at the end of the conditioning time . close respective valves to isolate all portions of the bier vessel 10 at the 0 . 2 torr pressure . introduce sterilant , such as 59 % hydrogen peroxide solution , into the vaporizer chamber 12 until the desired concentration is reached , as detected by the sterilant monitor 28 therein . if too much is accidentally introduced , a small portion can be evacuated out . the addition and removal of sterilant can be manipulated until the desired sterilant concentration and pressure is achieved . the sterilant in the vaporizer chamber 12 will cause the pressure to rise higher than the other portions of the vessel that are currently at 0 . 2 torr . once the valves 20 or 22 isolating the other portions of the vessel are opened , the pressure ( and temperature ) differentials will immediately force the sterilant into the other portions of the vessel . optionally : the valves 22 do not have to be opened or closed simultaneously , allowing for different exposure times for different samples . at the end of the desired exposure time , evacuate the vessel portions to 0 . 2 torr to remove the remaining sterilant before opening the doors to remove the samples . the evacuation time will be less than 30 seconds for the chambers and less than 5 seconds for the ports . optionally , plasma may be introduced to enhance the removal of sterilant residual . quickly vent the portions of the vessel to allow the filtered air rushing in to “ scrub ” the surfaces , freeing sterilant that was being held by other materials , and remove the samples / load . test the biological indicators . although described above in connection with particular embodiments of the present invention , it should be understood the descriptions of the embodiments are illustrative of the invention and are not intended to be limiting . various modifications and applications may occur to those skilled in the art without departing from the true spirit and scope of the invention as defined in the appended claims .

a biological indicator evaluator resistometer provides enhancements in controlling the start and end points of exposure to a sterilant gas . the end point control employs a large volume relative to the test chamber volume upon which is drawn a deep vacuum and then exposed to the test chamber to quickly exhaust the sterilant gas from the test chamber .

one of the objectives of the present invention is a method to obtain aggregated antigenic structures of a higher immunogenicity than the antigens originating them . said method includes the following steps : b ) addition of one or several antigens of the mixture in a medium favoring the aggregation process , said medium may consist in chemical agents , oxidizing agents or other components with aggregating capacity . d ) selection of the particle aggregate with a size between 30 and 500 nm by a process allowing the retention of these molecular sizes , such as molecular exclusion chromatography , diafiltration and dialysis . e ) preparation of the formulations by mixing the selected antigenic structures in step ( c ) through the addition of the adjuvant of election and also the potential addition of other antigens , stabilizers and preservatives . several aggregates that only contain the surface antigen of the hbv may be obtained by the present invention method , including also combinations of the surface antigen and other lipoprotein , lipopeptide or lipidic homologous or heterologous antigens from any viral , bacterial , unicellular or multicellular pathogen . according to the invention method the antigens that are part of the structures obtained in the step ( b ) may be added to the surface antigen of the hepatitis b virus by hydrophobic , electrostatic or covalent interactions , generating aggregates of different sizes . the method to obtain antigenic structures allows the aggregation of the hepatitis b , c or hiv nucleocapsid antigens to the hepatitis b virus surface antigen , also antigens from virus and bacteria such as inactivated virus or outer membrane proteins of bacterial pathogens like neisseria meningitidis , may be aggregated . to obtain the aggregated antigenic structures β - cyclodextrins may be used as chemical agent favoring delipidation , membrane association and aggregation of the present particles , other chemical agents are ammonia salts at concentrations between 10 and 50 mm , potentiated by metal salts of copper and iron and others permitting aggregation . other components of the method presenting spontaneous aggregating activity that may be used together or alone for this purpose are the homologous or heterologous antigens that evidenced aggregating activity on hbsag , among them the viral nucleocapsid antigens and also bacterial outer membrane derivatives or viral envelopes of lipoprotein or hydrophobic nature . it was also found that adjuvants of the same nature favored hbsag aggregation and that of hbsag with themselves . in general the present invention method allows hbsag aggregation or the hbsag aggregation with other antigens or adjuvants through the development of hydrophobic interactions , electrostatic or covalent linkages , with incubation periods ranking from 10 minutes to one week , depending on the selected constituents . the aggregates separation is achieved by molecular size exclusion methods , among them molecular exclusion chromatography , dialysis , diafiltration or other method permitting the retention of molecular sizes between 30 and 500 nm . we have also shown that although it is possible to generate aggregates of around 1 micrometer of size by non denaturing methods ( maximum temperature 28 ° c . ), similar to those obtained by schirmbeck ( schirmbeck , r . et al . 1995 . j immunol 155 : 4676 - 4684 ), these continue to be less immunogenic when evaluating the humoral response and dth . only those particle aggregates of a size between 30 and 500 nm , adjuvanted with alum , have demonstrated the generation of igg levels significantly higher than the native antigen control , showing additionally a significant increase of the dth and igg2a responses . all this evidences the importance of the later selection of the antigen by molecular exclusion chromatography . the cause of this performance may be given by the different presentation and or processing of the antigen or antigens of interest . moreover the present invention method foresees the adsorption of the resulting structures to such adjuvants as alum or calcium salts , oily or other commercially used adjuvant . it may be also added to the final formulation other antigens and stabilizing and preserving substances . another object of the present invention is the aggregated antigenic structure obtained according to the previously described method , which favors an increase in the immunogenicity of the resulting formulation and a differential recognition by the immune system of the involved epitopes . said aggregated antigenic structures are characterized by the presence of the hepatitis b virus surface antigen , alone or in combination with other antigens forming the aggregate . these other antigens are lipoproteins or hydrophobic , among them hbcag , possessing additionally the intrinsic property of favoring the aggregation state between them by hydrophobic linkages . other hydrophobic viral capsid and lipoprotein antigens have shown this capacity , among them the nucleocapsid antigen of the hepatitis c virus , the human papilloma virus and hiv 1 and 2 , besides the outer membrane of n . meningitidis in proteolyposome vesicles and some viral envelope antigens . among the antigenic structures object of the present invention the associations of hbsag with hydrophobic adjuvants are included which may be part of the aggregate by the same previously described method . in general the antigenic structures object of the present invention may be obtained by aggregation of at least one , two or more hydrophobic particles according to the described method and at least one of particulate character , and should be visible by electron microscopy as described in the examples . the aggregation of these structures favors the immune modulation , differential recognition and immunogenicity enhancement in a general fashion . taking into account these characteristics of the antigenic structures object of the present invention , it is possible the use them for the rational design of preventive and therapeutic human and veterinary vaccines , through the systemic or mucosal routes and their use in diagnostic systems . among the advantages of the new preparations resulting from the use of the method for obtaining this type of antigens the following are found : increase of immunogenicity , co - trapping capacity for new adjuvants , immunomodulators and antigens during the aggregation . the preparations resulting from the present invention method , depending on the inoculation route and species to be immunized may be used in volumes of 0 . 01 up to 10 ml and the antigen doses may vary between 0 . 001 and 1 mg in the final vaccine formulation . preparation of vaccine formulations of aggregated of surface antigen of the hepatitis b virus obtained by the cyclodextrins use the particles were obtained from the 22 nm native antigen by the controlled treatment of the antigen with chemical compounds with lipid subtracting activity from the particle , in this case cyclodextrins were used in concentrations higher than 1 mg / ml . depending on its concentration the incubation time varied from 24 hours to 7 days . the incubation temperature used in this assay was of 28 degrees centigrade although it has been observed that at higher and lower temperatures it is also possible to obtain aggregates . the temperature is a factor favoring the partial delipidation process though oxidation and lipids subtraction . later the different aggregates were analyzed by gel filtration and electron microscopy , finding sizes which varied from tenths nanometers up to particles that precipitated due to their huge size . after centrifugation to eliminate precipitated residues , the antigen was selected depending on its size for immunochemical analyses , which demonstrated a decreased level of lipids regarding the proteins level . it has been shown by hplc that these aggregates have a high stability during the storage time . the controlled treatment of the antigen with β - cyclodextrins , between 5 - 100 mg / ml during 1 - 240 hours , at temperatures ranging from 20 to 37 ° c ., allow to obtain a size range that made possible the later election of the elution time for immunochemical analysis . afterwards the aggregated antigen was adsorbed to alum at a final concentration between 0 . 002 and 0 . 1 mg / ml and was used for immunogenicity assays . one incubation variant with cyclodextrins at different times and temperatures involved the addition of immunomodulating compounds such as lypo - polysaccharides and saponins , that are part of the final aggregate adsorbed to alum to produce the final vaccine formulation . preparation of vaccine formulations of surface antigen of hepatitis b virus aggregates using oxidizing agents with the addition of oxidizing chemical substances to the normal antigen it was possible the delipidation in controlled time , temperature and concentration conditions in the same way that with cyclodextrins . salts as ammonium peroxi - disulfate between 9 and 44 mm , permitted the generation of the delipidated antigen starting from the 22 nm antigen particles , to produce size increase by particle fusion . the optimal sizes were selected by gel filtration . la adjuvant adsorption was achieved on alum . in the same way that in the example 1 , it was possible to include in the aggregate different quantities of other adjuvants and immunomodulators during the incubation . preparation of vaccine formulations of over - particulate chemical structures , obtained by modification of the incubation conditions of the yeast the particles were obtained naturally from the picchia pastoris yeast strain , the antigen was selected during the purification process by its physical chemical characteristics . the antigen production process is submitted to long lasting culture time , higher than 100 hours and oxidative stressing conditions . this process makes possible that a part of the antigen remains in its 22 nm particle size native state but an important moiety gets aggregated and delipidated by the increase of the intracellular oxidative conditions , as demonstrated by the lipid and protein analyses done to samples of the different peaks from gel filtration . finally the fraction is separated by hplc gel filtration in tsk g5000 columns . this material reaches up to 10 % of total the antigen which is actually discarded . alum adjuvant adsorption is achieved in similar conditions as for the normal antigen . the analysis of both antigens demonstrated that hbsag gets aggregated in a process that involves a significant loss of lipids of all types which is shown for phospholipids of both antigens in the following table : with this example it is evidenced that a new over - particulated antigen may be obtained after a natural oxidizing and delipidating process . the stability of these aggregates would be based on the aggregation processes that may occur during the elimination of lipids from the particles that could expose hydrophobic regions and by protein polymerizations between particles when sulphydril groups are exposed . with the objective of evaluating the immunogenicity of the aggregated hbsag resulting from the example 3 , adsorbed in alum or in pbs for mucosal route , an immunization schedule was carried out with inoculations the days 0 , 14 and 28 and retro - orbital blood extractions the day 42 and female balb / c mice of 10 to 15 weeks old were immunized by intranasal and intramuscular routes . the doses per mouse are presented in the table at the end of this example , and the results are shown in fig1 a , and the hbsag aggregate are shown in fig1 b . the statistical analysis of results was performed by the student test and p & lt ; 0 . 05 was considered a significant difference . from this experiment it was demonstrated that it is possible to generate a higher anti hbsag igg response when immunizing by mucosal or systemic routes , regarding the normal antigen , in equal conditions . in the same figure it is represented the comparison of this effect for the dth response ( bars ), which also resulted significantly higher for the aggregated variant . with the objective of studying the kinetics of the anti - hbsag igg response 10 groups of female 10 - 15 weeks old balb / c mice were immunized . the schedule used was : inoculation the weeks 0 , 2 and 18 and extractions pre immune at 4 , 6 , 8 , 10 , 12 , 14 , 16 y 20 weeks . the groups tested are described in the following table : the antigens of the groups 5 and 6 , 7 and 8 , and 9 and 10 were obtained by incubating at different times and concentrations of cyclodextrins obtaining different degrees of aggregation . for the dth experiment , the measurements were performed the days : 1 ( 1 , 3 ), 2 ( 1 ′, 3 ′), 3 ( 1 ″, 3 ″) and 5 ( 1 ′″, 3 ′″) the statistical analysis of results was performed by the student test : p & lt ; 0 . 05 se was considered a significant difference . in this experiment it was corroborated that the delipidated hbsag , with different degrees of aggregation , have immunological characteristics that distinguished each one . the larger immunogenicity and dth response did not corresponded to the larger antigen size but to intermediate antigen sizes although according to the performance of the antibody appearance kinetics at the end of the experiment the larger immunogenicity corresponded to the variant with a higher degree of aggregation . however it was observed a significant increase of the dth response in the groups immunized with alum adjuvant as compared to those immunized with the antigen in pbs , the group of aggregated antigen with an intermediate size generated the larger increases with arrived to be significant the day 56 . in fig2 a the individual titers the day 56 are represented for all immunized groups . in this figure are also represented the results of the dth experiment performed during 5 days of the week 22 , using 20 μg of hbsag in the right leg and pbs in the left leg in an inoculation volume of 20 μl . all resting groups also had a significantly lower response regarding the difference in diameter between the right and left legs as compared to group 3 , which was inoculated with alum adjuvanted hbsag with an intermediate aggregation level , obtained as described in example 3 . it is worth to take into account that in the later examples it is demonstrated that the recognition in the case of over - particulated structures is wider regarding the epitopes recognized in the hbsag , which indicates a better performance for this type of structure . although from group 5 to group 10 , the anti native hbsag reactivity is similar to that obtained immunizing with native hbsag during a major part of the time , a strong response is also obtained against other epitopes present in the aggregated antigen , see example 8 , fig4 . with the objective of studying if a variation in the igg1 / igg2a ratio existed due to the its linkage between the th1 / th2 response , the sera of the d and e groups of the immunization schedule of example 4 , were tested for anti igg 1 and igg2a antibody levels . this analysis was performed for the sera of the day 42 extraction . the igg2a antibody levels increased significantly in the group immunized with the over - particulated antigen ( 50 - 500 nm ) up to attaining an igg1 / igg2a ratio closer to 1 as compared to the normal hbsag also adjuvanted in alum ( fig4 ). the igg1 / 2a ratio for the normal hbsag group immunized with alum was 6 . 2 times higher to that found for the delipidated hbsag group of intermediate size . from this experiment it could be concluded that the different presentation of the surface antigen not only generates a quantitative but also a qualitative change regarding the igg type which is potentiated and the correlation of these variations in the igg subclass pattern with an enhancement of the cellular response , corroborating the dth assessment findings . study of the anti - native hbsag reactivity of the sera of mice immunized with different antigenic variants after the immunization of mice with the delipidated antigens obtained according to examples 1 , 2 and 3 , the reactivity of their sera was compared to that of the sera from the mice immunized with the normal antigen . as a result of this experiment it was observed that the immune response generated in the sera from the mice immunized with the different variants had a different reactivity against the normal hbsag ( 22 nm ), the major reactivity was exhibited by the sera from mice immunized with the normal antigen , while for the different degrees of delipidation the reactivity against hbsag was also different . even existing high titers against their own immunogens the sera from mice immunized with immunized with highly oxidized variants did not recognized hbsag , evidencing a different recognition of the generated antibodies with the different immunogens and demonstrating the different antigenic nature of the newly generated structures . therefore the results of example 5 must be analyzed taking into account that although for the last three aggregated antigen variants similar anti native hbsag responses are obtained , a response is also present against other hbsag protein epitopes not recognized by immunizing with native hbsag . recognition of lineal epitopes by the sera from mice immunized with different antigen variants with the objective of comparing the recognition of the antibodies generated by an over - particulated hbsag obtained by the oxidation variant described in example 2 , a mapping was performed on cellulose membrane containing linear hbsag sequences ( s region ), 37 peptides of 12 aminoacids were synthesized each one overlapped in 6 until completing the whole protein sequence . the epitopic mapping on cellulose membrane was performed according to ronald frank ( frank , r . 1992 tetrahedron 48 : 9217 - 9232 ). the serum samples were assayed at a 1 / 100 dilution . results of facing the sera from the mice inoculated with the normal antigen and the different aggregated variants of the same antigen , evidenced that there is no a similar linear recognition pattern between both antigens , which leads to the conclusion that a different presentation is produced for the b epitopes present on the surface of hbsag and its aggregated variants ( fig4 ). equal volumes of two preparations containing 0 . 1 mg / ml hbsag and hbcag were incubated at 4 ° c . overnight and afterwards aggregates were obtained by hplc tsk g6000 molecular exclusion chromatography . a sample of these aggregates was processed for electron microscopy visualization techniques , the other sample was used for its immunological evaluation with an immunization schedule in balb / c mice by intranasal inoculation , with both antigens separately and with the aggregate verified by electron microscopy ( fig5 a ). results evidenced that the mixture of both aggregated antigens by intranasal route allowed the potentiation of the response against the hbsag ( fig5 b ). the groups of the figure are represented in the following table : similar results were obtained when other viral capsid antigens such as hepatitis c and hiv were used to prepare the mixture . ( a ) three dose schedule ( 0 , 2 y 4 weeks ). the extractions were performed the week 6 . the three first groups were inoculated with 50 μl by intranasal route . the two remaining groups were inoculated by intramuscular route in alum with 100 μl . three dose schedule ( 0 , 2 y 18 weeks ). all groups were inoculated by intramuscular route with a volume of 100 μl . the antibody values correspond to the week 8 ( fig2 a ). during the week 22 se the dth test was performed . fig2 b represents the dth value for groups 1 and 3 during 5 days . fig2 c represents the kinetics of increase of titers during the schedule . the same 3 doses schedule ( 0 , 2 y 4 weeks ) of fig1 . analysis of groups d and e sera from the week 6 extraction . both groups were inoculated by intramuscular route in alum with 100 μl , group d with delipidated hbsag ( 50 - 500 nm ) and group e with normal hbsag with the same doses . in the graph it is represented the geometric mean value and interval of the igg1 / igg2a ratio for each mouse of both groups . mapping of overlapping peptides ( seq . id . nos : 1 - 37 ) of the s region of hbsag on cellulose membrane containing linear sequences . 1 / 100 dilutions of sera pools were analyzed : 1 , hbsag ( normal ): 2 , hbsag ( aggregated ): ( 3 - 5 : monoclonal antibodies ( mabs ) obtained immunizing with aggregated antigens ; 3 , clone 6 ; 4 , clone 7 ; 5 , clone 8 ); 6 , non related serum ; 7 , mab ( hep 1 ). four color intensities represent the response against the peptides . blank : negative response , clear gray : slightly positive response , dark gray : positive response , black : very positive response . ( a ) electron microscopy of hbsag aggregates and hbcag , the higher electron - dense particles in the center mayor corresponds to hbcag , the other are hbsag . ( b ) 2 dose schedule ( 0 , 14 days ). analysis of sera the day 26 .

the invention relates to a method for obtaining aggregated antigenic structures that are capable of enhancing an immune response to aggregate antigens administered systemically and / or mucosally generating powerful immune response and to the chemical structures resulting from the application of said method , to the formulations obtained from such structures and their use . the method describes the obtention of novel aggregate antigenic structures by using aggregating , delipidating or oxidating agents or compounds enabling the release of lipids from the particles and their heterogeneous aggregation , wherein aggregates with particle sizes of between 30 and 500 nm are subsequently selected by means of a molecular exclusion process . the aggregation state can also be provoket inside the yeast by changing incubation conditions . the resulting structures can be used conveniently adjuvated or in a formulation in which several antigens can be introduced , wherein synergism between said components is found with respect to the immunogenicity of the response obtained . the preparation may also contain stabilizers and preservatives . the resulting antigenic structures can be used in the pharmaceutical industry as preventive or therapeutic vaccine formulation both for human and veterinary use and as part of diagnostic system .

the skin - cosmetic composition of the present invention which contains , as the active ingredient , a compound of the formula ( i ) has a significant effect of propagating epidermal keratinocytes and also a significant effect of curing skin disorders induced by 12 - o - tetradecanoyl phorbol - 13 - acetate ( tpa ) and therefore is effective for preventing the skin from being roughened , chapped , cracked or inflamed , or from aging . it is said that tpa causes skin disorders such as erythema , exfoliation , proliferative hyperacanthosis , etc . and that the symptoms of such disorders are similar to those of dermatokeratonosis as caused by surfactants . in the above - mentioned formula ( i ), the alkyl group having from 1 to 10 carbon atoms may be either straight or branched chain and includes , for example , methyl , ethyl , n - propyl , isopropyl , n - butyl , isobutyl , sec - butyl , n - pentyl , isopentyl , neopentyl , n - hexyl and isohexyl groups ; the alkenyl group having from 2 to 6 carbon atoms includes , for example , vinyl , allyl , 2 - butenyl and 3 - pentenyl groups ; and the cycloalkyl group having from 3 to 7 carbon atoms includes , for example , cyclopropyl , cyclopentyl and cyclohexyl groups . the alkyl group is preferably an isopropyl group . specific examples of the compounds of formula ( i ) are mentioned below , which , however , are not limitative . table 1______________________________________in the formula ( i ): ## str3 ## ( i ) data ofno . r . sup . 1 xr . sup . 2 physical properties______________________________________1 ch . sub . 3 och . sub . 3 m . p . 125 - 129 ° c . 2 i - c . sub . 3 h . sub . 7 o - i - c . sub . 3 h . sub . 7 m . p . 59 - 60 ° c . 3 i - c . sub . 3 h . sub . 7 oc . sub . 2 h . sub . 5 m . p . 54 ° c . 4 i - c . sub . 3 h . sub . 7 ## str4 ## m . p . 69 ° c . 5 i - c . sub . 3 h . sub . 7 o - n - c . sub . 6 h . sub . 13 m . p . 40 ° c . 6 i - c . sub . 3 h . sub . 7 och . sub . 2 chch . sub . 2 m . p . 48 ° c . 7 i - c . sub . 3 h . sub . 7 ## str5 ## m . p . 70 - 72 ° c . 8 i - c . sub . 3 h . sub . 7 nh - n - c . sub . 6 h . sub . 13 n . sub . d . sup . 23 1 . 57289 ch . sub . 3 o - i - c . sub . 4 h . sub . 9 n . sub . d . sup . 20 1 . 592810 c . sub . 2 h . sub . 5 oc . sub . 2 h . sub . 5 m . p . 113 ° c . 11 i - c . sub . 4 h . sub . 9 o - i - c . sub . 4 h . sub . 9 m . p . 76 - 78 ° c . 12 i - c . sub . 5 h . sub . 11 o - i - c . sub . 5 h . sub . 11 m . p . 55 - 56 ° c . 13 n - c . sub . 3 h . sub . 7 o - n - c . sub . 3 h . sub . 7 m . p . 73 - 75 ° c . 14 n - c . sub . 4 h . sub . 9 o - n - c . sub . 4 h . sub . 9 m . p . 74 - 75 ° c . 15 s - c . sub . 4 h . sub . 9 o - s - c . sub . 4 h . sub . 9 m . p . 63 - 65 ° c . 16 n - c . sub . 5 h . sub . 11 o - n - c . sub . 5 h . sub . 11 m . p . 70 - 70 . 5 ° c . ______________________________________ the skin - cosmetic composition of the present invention may be mixed with the compound of the formula ( i ) and a base for external use to prepare skin - cosmetic preparations such as skin - emulsions , creams , lotions , powders , agents for pack , cosmetic , liquid , etc . the content of the active ingredient of the formula ( i ) in skin - cosmetic preparation may be selected generally from a range of between 0 . 0001 % and 20 % relative to the base in the preparation , preferably from a range of between 0 . 05 % and 5 % relative to the same , especially preferably from a range of between 0 . 01 % and 3 % relative to the same . the skin - cosmetic composition of the present invention may optionally contain , in addition to the above - mentioned essential components , various additives which are commonly added to ordinary skin - cosmetic preparations , for example , aqueous components which are commonly added to ordinary skin - cosmetic preparations ; powdery components such as titanium dioxide , mica , talc , etc . ; nonionic surfactants such as polyoxyethylene glycol monooleate , polyoxyethylene alkyl ether , etc . ; cationic surfactants such as stearyltrimethylammonium chloride , etc . ; anionic surfactants such as sodium palmitate , sodium laurate , alkylsulfate triethanolamine ether , etc . ; ampholytic surfactants ; humectants such as hyaluronic acid , muco - polysaccharides , glycerin , 1 , 3 - butylene glycol , etc . ; higher alcohols such as capryl alcohol , lauryl alcohol , myristyl alcohol , cetyl alcohol ; ph - adjustor ; thickners such as methyl cellulose , ethyl cellulose , arabic gum , polyvinyl alcohol , montmorillonite , etc . ; antimicrobial preservatives such as benzoic acid , salicylic acid , sorbic acid , ethylparaben , butylparaben , hexachlorophene , etc . ; higher fatty acids such as capric acid , lauric acid , linolic acid , linolenic acid , etc . ; perfumes ; oils ; dyes ; etc . in addition , the skin - cosmetic composition of the present invention may further contain , if desired , antioxidants such as vitamin e , bht ( dibutylhydroxytoluene ), bha ( butylhydroxyanisole ), tocopherol , phytic acid , etc . ; ultraviolet absorbers such as amyl salicylate , octyl cinnamate , 2 , 4 - dihydroxybenzophenone , etc . ; skin - whitening agents such as ascorbic acid derivatives , hydroquinone derivatives , pyrrones , extracts from bovine placentae , etc . ; cell activation promoters such as allantoin and its derivatives , deproteinized bovine blood , kojic acid and its derivatives , adenosine triphosphate , adenosine diphosphate , adenosine monophosphate , succinic acid and its derivatives , extracts from lithospermum roots , extracts from ginsengs , extracts from placentae , etc . examples of the present invention are mentioned below , which , however , are not intended to restrict the scope of the present invention . in the examples , all parts are parts by weight . ______________________________________compound of the invention 0 . 5 partstearic acid 0 . 8 partpolyoxyethylenemonooleate ( 20 e . o .) 1 . 0 partbees wax 2 . 0 partsdisodium edetate 0 . 02 partbentonite 0 . 3 partconcentrated glycerin 5 . 0 partsmethyl parahydroxybenzoate 0 . 15 partperfume ad lib . pure water balance______________________________________ the above - mentioned components were mixed by an ordinary method to prepare an emulsion . ______________________________________compound of the invention 0 . 1 partstearyl alcohol 5 . 0 partscetanol 5 . 0 partsmiddle - chain fatty acid 10 . 0 partstriglycerideisopropyl myristate 5 . 0 partspolysorbate 60 4 . 0 partssorbitan monostearate 1 . 0 partmethyl parahydroxybenzoate 0 . 14 partpropyl parahydroxybenzoate 0 . 06 partdibutylhydroxytoluene 0 . 02 partpure water balance______________________________________ the above - mentioned components were mixed by an ordinary method to prepare a cream . normal human epidermal keratinocytes ( produced by kurabo biomedical business ) were cultured in keratinocyte growth medium ( k - gm produced by kurabo biomedical business ; this comprises , as the basal medium , modified mcbd153 and contains epidermal growth factor , bovine pituitary extract , insulin , hydrocortisone , gentamicin and amphotericin b ) in humidified atmosphere of 5 % co 2 and 95 % air for 48 hours at at 37 ° c . the compound no . 2 of the present invention dissolved in dimethyl sulfoxide ( dmso ) was added to keratinocyte basal medium ( k - bm ) at 0 . 01 μm , in which the concentration of dmso was 0 . 1 % of the medium . the number of keratinocytes incubated in the medium containing 0 . 1 % dmso or 0 . 01 μm of the compound in the same condition for one day or for 5 days were counted on a hemocytometer . the results are shown in fig1 . the results show that the growth of the cells incubated in the medium containing 0 . 01 μm of the compound of the invention was significantly increased as compared with that of the cells incubated in the medium containing dmso . effect of the compound on the growth of human epidermal keratinocytes in the logarithmic growth phase normal human epidermal keratinocytes suspended in k - gm were seeded in a 12 - well culture plate ( costar , 3512 ) at a concentration of 5 × 10 4 cells / ml / well and cultured in humidified atmosphere of 5 % co 2 and 95 % air for 48 hours at 37 ° c . the compound no . 2 of the invention dissolved in dmso was added to the medium to make a concentration of 0 , 0 . 001 , 0 . 01 , 0 . 1 , 1 , 10 or 100 μm . the concentration of the respective dmso was 0 . 1 % of the medium and 0 μm of the compound ( 0 . 1 % dmso only ) was regarded as the control . the cells were incubated in the medium containing various concentrations of the compound of the invention in the same condition for 24 hours and followed by further incubation in the presence of 2μ ci of [ methyl - 3 h ]- thymidine ( nen , specific activity of 20 . 0μ ci / mmol ) for 2 hours . after the incubation , 10 μl of 1 % nan 3 were added to each culture and cooled with ice , by which the reaction was stopped . the culture was washed two times with a phosphate buffered saline ( pbs ) containing 1 mm non - ratio labeled thymidine and 0 . 01 % nan 3 , and 1 . 0 ml of 0 . 2n naoh was added thereto to lyse the cells . the lysate - containing liquid was taken into a tube and neutralized with 0 . 2 ml of 1n hcl , and 150 μl of 50 % trichloroacetic acid ( tca ) solution cooled with ice were added thereto . then , this was allowed to stand at 4 ° c . for one full day to form a precipitate therein . the supernatant was removed by centrifugation ( at 15000 rpm for 10 minutes ), the precipitate was washed two times with a 5 % tca solution , again dissolved in 0 . 2 ml of 0 . 2n naoh and then neutralized with 0 . 2 ml of 0 . 2n hcl . the resulting solution ( 0 . 2 ml ) was put in a vial containing 4 . 0 ml of a scintillant ( ready protein + ), and its radioactivity was measured a liquid scintillation counting . the incorporation of h - thymidine into the dna in the cells was represented as a relative value based on the count ( 100 %) per mg of the protein in the cells ( or per well ) of the control group ( 0 . 1 % dmso - added group ). each test was carried out in triplicate , and the average results are shown in fig2 . as compared with control group , the thymidine uptake in the cells of the test group was increased by about 43 % in the presence of 0 . 01 μm of the compound of the invention and by about 30 % in the presence of 0 . 1 μm of the same . however , no change in the thymidine incorporation in the cells was observed in the presence of 0 . 001 μm or 1 μm of the compound of the invention , while the growth of the cells was oppositely retarded in the presence of the compound of the invention at 10 μm or more . influence of the compound of the invention on the growth of epidermal keratinocytes in the stationary phase epidermal keratinocytes suspended in k - gm were seeded in a 12 - well culture plate ( costar , 3512 ) at a concentration of 6 × 10 4 cells / ml / well and cultured in humidified atmosphere of 5 % co 2 and 95 % air for 48 hours at 37 ° c . the cells were washed four times with a phosphate buffered saline and then cultured in keratinocyte basal medium ( k - bm ) at the same condition for 24 , 48 or 72 hours . the compound no . 2 of the present invention dissolved in dmso was added to k - bm to make a concentration of 0 , 0 . 01 , 0 . 1 , 1 , 10 or 100 μm , in which dmso concentration in the medium was 0 . 1 %, and 0 μm of the compound ( 0 . 1m dmso only ) was regarded as the dmso control . the cells were incubated in the medium containing various concentrations of the compound in the same condition for 24 hours and followed by further incubation in the presence of 2μ ci of [ methyl - 3 h ]- thymidine ( nen , specific activity of 20 . 0μ ci / mmol ) for 2 hours . after the incubation , the radioactivity of thymidine in the cells was measured in the same manner as in test example 2 . during the incubation , each well was observed with a phase contrast microscope ( olympus , imt - 2 , phase contrast ulwcd 0 . 30 ) at intervals of 24 hours . at the end of the incubation , the total protein content in each well was measured by using a protein - measuring kit ( micro bca protein assay reagent , pierce ), and the cells in each well were considered to be in the stationary phase at the first point at which the total protein content increased no more . each test was carried out in triplicate , and the average results are shown in table 2 below , in which the 3 h - thymidine incorporation was represented in terms of dpm / well ( mean ± s . e .) and the protein content was in terms of μg / well ( mean ± s . e .). the statistical analysis of the average values in each group was assessed by student &# 39 ; s t - test . the results are shown in table 2 . table 2______________________________________ concentration of incorporation the compounds of of amount ofincubation the invention in . sup . 3 h - thymidine proteinon k - bm the medium ( μm ) (× 10 . sup . 5 dpm / well ) ( μg / well ) ______________________________________24 h + ( 26 h ) non - treated 16 . 9 ± 0 . 6 1905 ± 46 control 0 . 1 % dmso 16 . 7 ± 0 . 1 1892 ± 29 control 0 . 001 16 . 3 ± 0 . 2 1888 ± 31 0 . 01 (*) 17 . 9 ± 0 . 4 1900 ± 54 0 . 1 (*) 14 . 9 ± 0 . 5 1845 ± 29 1 . 0 14 . 7 ± 1 . 1 1870 ± 62 10 (*) 15 . 0 ± 0 . 5 1909 ± 36 100 (*) 15 . 4 ± 0 . 4 1868 ± 8048 h + ( 26 h ) non - treated control 6 . 6 ± 0 . 1 2442 ± 53 0 . 1 % dmso control 6 . 6 ± 0 . 4 2382 ± 45 0 . 001 6 . 8 ± 0 . 2 2444 ± 26 0 . 01 6 . 5 ± 0 . 2 2391 ± 49 0 . 1 7 . 2 ± 0 . 6 2351 ± 139 1 . 0 6 . 1 ± 0 . 4 2403 ± 44 10 6 . 0 ± 0 . 4 2337 ± 37 100 (***) 1 . 2 ± 0 . 0 2121 ± 1272 h + ( 26 h ) non - treated 4 . 5 ± 0 . 1 2493 ± 45 control 0 . 1 % dmso 4 . 5 ± 0 . 0 2400 ± 80 control 0 . 001 4 . 4 ± 0 . 1 2427 ± 51 0 . 01 4 . 4 ± 0 . 1 2456 ± 6 0 . 1 4 . 4 ± 0 . 1 2450 ± 92 1 . 0 4 . 5 ± 0 . 1 2510 ± 84 10 (*) 3 . 8 ± 0 . 2 2318 ± 20 100 (***) 1 . 3 ± 0 . 0 2367 ± 83______________________________________ * p & lt ; 0 . 05 *** p & lt ; 0 . 001 vs . 0 . 1 % dmso control in each incubation the cells in the non - treated control group and those in the 0 . 1 % dmso control were determined as confluent at 72 hours after the incubation based on microscopic observation of the cells and no increase in protein content after 48 hours (+ 26 hours ) incubation . even though the compound of the invention was added to the cells after 72 hours (+ 26 hours ) incubation , the incorporation of 3 h - thymidine in the cells was not increased . from these facts , it is considered that the compound of the invention does not promote the growth of epidermal keratinocytes which have been in the confluent phase . in general , the cells which have been in the confluent phase and have been completely surrounded with other cells in vitro lose their mobility to be in the g 0 phase , and their growth is temporarily stopped . as opposed to these , the growth of transformed cells is not hindered by the contact with other cells while their mobility is not changed , and their dividing ability is not decreased even though the cell density is increased . it is known that cancer cells are not in a single layer but are in aggregate while continuously growing and propagating to have a cell density of several times as large as normal cells . when the compound of the invention is added to epidermal keratinocytes , the cells grow and propagate while they are in the logarithmic growth phase [ see table 2 , 24 h (+ 26 h )] but the compound added does not affect the confluent phase of the cells while the cells grow under the density - dependent control of themselves . for these reasons , it is presumed that the compound of the invention will not promote unlimitedly the growth and the propagation of epidermal keratinocytes . the hair on the back of each of male c3h mice was shaved . one mm of tpa was dissolved in 70 % ethanol , and 0 . 1 ml / mouse of the resulting solution was topically applied to the thus - shaven back of each mouse twice a week , totaling four times , at which time , the back exhibited erythema , exfoliation and proliferative hyperacanthosis . compound no . 2 of the invention was dissolved in 70 % ethanol at 1 % ( w / v ), and 0 . 1 ml / mouse of the resulting solution was topically applied to the back of each mouse daily ( 6 days / week ). 12 days and 15 days after the application , the outward appearance of the skin of each mouse was observed , which revealed that the erythema , exfoliation , etc . of the mice in the test group were relieved as compared with those of the mice in the control group and that the degree of the hyperacanthosis of the mice in the test group was histologically light . as has been described in detail hereinabove , the active ingredient to be contained in the skin - cosmetic compotion of the present invention has a cell - activation - promoting effect and is characterized in that it acts to promote the growth of cells in the growing phase but does not act on cells in the stationary phase . in addition , the active ingredients act to retard the growth of cells when the cells begin to propagate abnormally or differentiate into different cells . therefore , the characteristics of the skin - cosmetic composition of the present invention are such that it acts as a promoter to promote the curing , of the skin when the skin needs curing while it acts as an inhibitor to inhibit the abnormal reaction of the skin when some abnormal reaction of the skin is to be inhibited . accordingly , the skin - cosmetic composition of the present invention is useful as a preventive or remedial agent for preventing the skin from aging or roughened and also for curing roughened skin , such as chapped , cracked or inflamed skin . while the invention has been described in detail and with reference to specific embodiments thereof , it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope thereof .

disclosed is a skin - food cosmetic composition containing , as the active ingredient , at least one compound of the formula : ## str1 ## r 1 represents an alkyl group having 1 to 10 carbon atoms ; r 2 represents an alkyl group having 1 to 10 carbon atoms , an alkenyl group having 2 to 6 carbon atoms , or a cycloalkyl cycloalkyl group having 3 to 7 carbon atoms ; and x represents -- o -- or -- nh --. this is useful for preventing the skin from being roughened , chapped or cracked , or from being aged .

in the present context , terms such as upper , lower , inner , outer , convex , concave , etc . refer , unless otherwise defined , to the intentional orientation of a nasal dilator to be applied and fixated straddling the nose of a user . in the following description , primed reference numerals correspond to identical or similar parts . fig1 is a perspective view of a side or an elevated side of a nasal dilator 10 according to the present invention . the dilator according to the present invention is seen to have a shape resembling a butterfly , with a long central , resilient , beam - shaped element 12 and two wing - like ends 14 , 16 for attachment to a user &# 39 ; s nose . the nasal dilator is symmetrical relative to a plane perpendicular to the longitudinal axis of the beam - shaped element and not symmetrical relative to a longitudinal plane with respect to the beam - like element . the dilator is shaped in such a manner that the central , beam - shaped region 12 is elevated on one side , and consequently thicker than the regions 14 , 16 at the wing - like ends , which can better be seen in fig2 . from a geometrical point of view , the shape of the nasal dilator may be described as the non - superposed part of a first circle intersecting two closely neighbouring circles which are coaxial with the first circle and do not intersect each other , one having a radius being substantially equal to the radius of the first circle , the other having a radius substantially larger , the angles resulting from the intersection being rounded . in fig2 a cross - section along the axis ii -- ii of fig1 is shown , disclosing that that the nasal dilator 10 has a smooth or a plane side 11 , which is the side facing or contacting the skin of the user &# 39 ; s nose , and another side 18 being elevated in the central , beam - shaped element 12 , and that the transition between the central , elevated part and the margins of the attachment element is gradual , with a very low inclination . the large area of the margins 14 and 16 , their particular shape comprising unequal wing tips 13 , 15 and 2 , 4 , respectively , of which the most prominent , 15 and 4 , respectively , in use face downwards toward the bridge of the nose , their relative thinness and consequently their higher flexibility and capacity to adapt to the shape of the wings of the nose 34 and 36 , and the slight inclination between the elevated part 12 and the thinner parts 14 and 16 ensure good transfer and distribution of the tensile and shearing forces appearing when bending the dilator and attaching it to the nose . in fig2 an adhesive coating 20 is shown applied to the plane side 21 of the wing region 14 and covered by a release paper 24 , i . e . before the dilator is attached to the nose . the figure shows the ratio between the thickness of the elevated region 18 and the thickness of the thin layer 14 . in practice , the thickness of the elevated region 18 is approx . 1 . 2 - 1 . 5 mm , typically 1 . 3 - 1 . 35 mm , and the thickness of the attachment elements 14 and 16 is approx . 0 . 3 mm , the thickness ratio being of the order of magnitude of 4 - 5 . fig3 is a perspective view of the nasal dilator 10 according to the invention , seen from the skin - contacting side or the plane side 11 which are covered at their outermost or broad ends on the plane end regions 21 , 23 by the adhesive coatings 20 , 22 which are further covered by pieces of non - adhesive foil or release paper 24 , 26 , respectively . the extent of the adhesive coatings on the plane side can be seen in the figure . fig4 is a perspective view corresponding to the view of fig3 showing the nasal dilator 10 according to the invention , seen from the skin - contacting side or the plane side 11 , with the non - adhesive foil 24 removed from one end and slightly lifted from the other side . the removed foil reveals the adhesive coating 22 , 20 on the attachment ends . in this embodiment , a skin - friendly , non - aggressive , diffusion - tight adhesive is preferably used , allowing athletes , in particular , to carry the nasal dilator according to the invention without the dilator losing its adhesive properties due to moisture or sebum . fig5 is a schematical front view of a user 30 having the nostrils 34 , 36 in a normal , non - dilated state defined by the distance a 1 , between the nostrils , without the application of the nasal dilator 10 . fig6 is a schematical front view of the user with a nasal dilator 10 for improving breathing through the nose by dilating the user &# 39 ; s nostrils 34 , 36 . it appears from the figure that the use of the nasal dilator 10 leads to a larger distance between the nostrils a 2 & gt ; a 1 . a clearer view of the placement of the dilator on the nose is given in fig7 where it can be seen that the most prominent tip 15 of the wing area 14 in use points downwards towards the bridge of the nose and follows the curvature of the wing of the nose , ensuring a larger adhesive area and better adhesion between the plane attaching element 21 and the wing of the nose 34 . fig8 shows a plastic bar 42 seen from its elevated side and showing the desired profile according to one of the alternative embodiments of the invention , i . e . a smooth side and an elevated side with sharp separation lines between the respective areas . the plastic bar 42 is extruded by means of an extrusion tool 40 and has a central , elevated part 48 , two inclined transitional regions 46 and 50 , and two marginal regions 44 and 52 . the central part 48 is separated from the transitional regions 46 and 50 by separation lines 47 and 49 , respectively , and the marginal regions 44 and 52 are separated from the transitional regions 46 and 50 by separation lines 45 and 51 , respectively . fig9 is a schematical , perspective view of a preferred method of producing a nasal dilator according to the present invention . a rotary punching tool 74 is shown with protruding punching profiles 76 matching perfectly the shape of the nasal dilator 10 , an extruded plastic bar 42 produced by means of the extrusion tool 40 , two double adhesive tapes 54 , 56 originating from two adhesive tape rolls 58 , 60 , two respective paper bands 62 , 64 with the same breadth as the adhesive tape rolls 58 , 60 and originating from two paper band rolls 70 , 72 , and two respective rolls 60 , 68 . to produce the nasal dilator 10 &# 39 ; the adhesive tape rolls 58 , 60 are rolled on the plane side 11 &# 39 ; along the margins of the plastic bar 42 , and on top of them the paper band rolls 70 , 72 are rolled by means of the rolls 60 and 68 which press the paper band rolls 70 , 72 against the plane side of the plastic bar 42 so that the paper band rolls 70 , 72 perfectly overlap the adhesive coating on the plane side 10 &# 39 ;. the rotary punching tool 74 is thereafter rolled along the length of the plane side 10 &# 39 ; and its profiles cut out in the plastic bar 48 the nasal dilators 10 &# 39 ; in their finished shape , with double adhesive tape adhered to the plane side 11 &# 39 ; and covered by paper foil . fig1 is a perspective view of a nasal dilator 10 &# 39 ; according to the present invention , produced by punching a profiled plastic band 42 . fig1 shows that the transitional region between the central part 18 &# 39 ; and the end parts 14 and 16 is plane , and that the connection between the plane transitional region 19 and the central part 12 and the end part 14 , respectively , is not rounded , but forms straight separation lines 5 and 7 , respectively . the same applies for the symmetrical half of the nasal dilator , where the separation lines between the plane transitional area 17 and the the central part 12 and the end part 16 , respectively , forms sharp separation lines 6 and 8 , respectively . fig1 is a perspective view of the nasal dilator of fig1 seen from the skin - contacting side , i . e . the plane side 19 , having applied on the adhesive coatings 20 and 22 the release paper foils 24 and 26 , respectively . the release paper foil 26 entirely covers the adhesive coating 22 , whereas the release paper foil 24 is shown slightly lifted , allowing visual inspection of the adhesive coating 20 . fig1 is a perspective view similar to the view of fig1 of a nasal dilator 10 &# 34 ; according to the present invention also produced by punching a profiled plastic band 42 as illustrated in fig9 . the nasal dilator 10 &# 34 ; basically constitutes a structure similar to the structure of fig1 , however , differing from the structure of fig1 in that the nasal dilator of fig1 is a generally curved structure , whereas the nasal dilator of fig1 is a generally plane structure . the end parts 14 and 16 of the nasal dilator 10 &# 34 ; are interconnected through the central part 18 &# 34 ; which is curved as compared to the substantially planar central part 18 &# 39 ; of the nasal dilator 10 &# 39 ; illustrated in fig1 . the nasal dilator 10 &# 34 ; further differs from the nasal dilator 10 &# 39 ; illustrated in fig1 in that the plane transition areas 17 &# 39 ; and 18 &# 39 ; delimited between the straight separation lines 6 , 8 and 5 , 7 , respectively , are somewhat narrower as compared to the transition areas 17 and 19 , respectively , illustrated in fig1 . fig1 is a perspective view of the nasal dilator of fig1 seen from the skin - contacting side , i . e . the lower curved side . in fig1 , the adhesive coating 20 is partly exposed , whereas the adhesive coating 22 is covered by the release paper foil 26 . fig1 and 15 are perspective views similar to the view of fig1 illustrating a further modified embodiment of the nasal dilator according to the present invention as compared to the nasal dilator 10 &# 39 ; illustrated in fig1 . the further modified nasal dilator illustrated in fig1 and 15 is designated the reference numeral 10 &# 39 ;&# 34 ; and differs from the above described embodiment 10 &# 34 ; in that the end parts 14 and 16 of the dilator 10 &# 34 ; are cut into two parts 14 &# 39 ;, 14 &# 34 ; and 16 &# 39 ;, 16 &# 34 ;, respectively , through separation lines or cuts 27 and 25 , respectively . by separating the end parts 14 and 16 of the dilator 10 &# 34 ; illustrated in fig1 into segmented end parts 14 &# 39 ;, 14 &# 34 ; and 16 &# 39 ;, 16 &# 34 ;, respectively , the end parts of the overall structure are allowed to flex and adopt a configuration as illustrated in fig1 , allowing the end parts of the dilator 10 &# 39 ;&# 34 ; to readily conform to the configuration of the nose of the user as the outer contour of the nose of the user seldom constitutes two opposite plane surfaces but more often defines bends or cracks on the side surfaces of the nose to which bend the nasal dilator 10 &# 39 ;&# 34 ; readily adopts its shape through the provision of cuts or slits 25 and 27 . the nasal dilator can be produced in several different dimensions and it presents certain ratios between the dimensions thereof ; the dilator has in its largest version a maximum length ( l ) of between 50 and 75 mm , preferably 60 mm , a maximum breadth ( b ) of between 16 and 25 mm , preferably 20 mm , and the breadth of the central narrowing ( b ) is between 4 and 6 mm , preferably 5 mm . thus , the following dimensional ratios in relation to the preferred embodiment are achieved : l / b = 60 / 20 = 3 , l / b = 60 / 5 = 12 . the dilator is provided in a cross - section along its longer axis with a thickness of the elevated part ( t ) of 1 . 3 - 1 . 35 mm and a thickness of the flat end part ( t ) of approx . 0 . 3 mm . in the smallest version , designed for children , the ratios between the maximum length , the maximum breadth and the breadth of the central narrowing are retained so that the maximum length l is between 40 and 55 mm , preferably 48 mm , the maximum breadth b between 13 and 18 mm , preferably 16 mm , and the breadth of the central narrowing b between 3 and 5 mm , preferably 4 mm , i . e . l / b = 48 / 16 = 3 , l / b = 48 / 4 = 12 . the nasal dilator according to the present invention is preferably made from plastic material , such as polyethylene , polypropylene , polyvinylchloride or similar plastic materials or mixtures thereof . the presently preferred embodiments of the nasal dilator according to the present invention as illustrated in fig1 , 11 , 12 , 13 , 14 and 15 are preferably made from low - density polyethylene , such as ldpe of the type ncpe 6600 supplied by the company borealis polymers oy , finland , or the type le 6600 supplied by the same company . the adhesive coating applied to the lower side of the nasal dilator may constitute any skin - compatible adhesive , such as a medical grade adhesive generally used within the field of bandages , plaster structures , etc . the adhesive coating may be applied directly to the end parts 14 , 16 or may alternatively be presented through a double adhesive tape applied to the end parts 14 , 16 . examples of relevant double adhesive tape are tesa 4962 ™ supplied by the company beiersdorf a / s , denmark or fixomull ® stretch tape supplied by the same company . an alternative example of an adhesive material is an adhesive which allows the nasal dilator to be removed from its position straddling the nose of the user and to be repositioned on the nose without ruining the adhesive material and deteriorating the fixture of the nasal dilator as compared to the first or original fixation of the nasal dilator on the nose of the user .

a nasal dilator for placing on a user &# 39 ; s nose and for improving respiration through the nose by dilation of the user &# 39 ; s nostrils comprises a central , resilient , beam - shaped element and two attaching elements placed at respective ends of the beam - shaped element for attachment to respective sides of the user &# 39 ; s nose . the beam - shaped element extends in use from one side of the user &# 39 ; s nose across the bridge of the user &# 39 ; s nose to the other side of the user &# 39 ; s nose and the central , resilient , beam - shaped element and the two attaching elements are integrally made of plastic . the nasal dilator constitutes a configuration which is symmetrical relative to a central plane perpendicular to the longitudinal axis of the beam - shaped element and preferably constitutes an overall curved structure or alternatively a substantially plane structure . the central , resilient , beam - shaped element exhibits a rigidity increasing from the central plane towards the two attaching elements and the two attaching elements constitute substantially , plane , flat - shaped elements constituting extensions of the central , resilient , beam - shaped element to which attaching elements a skin - compatible adhesive is applied .

fig1 shows an embodiment of an assembly 30 according to the invention fitted with a shoe 1 with a device 2 , wherein the shaped piece 3 has the form of a semi - open , rigid clip . the foot is shown in a state inverted in relation to the lower leg 8 , a state which is a combination of plantar flexion , supination and adduction . this state is one of the most common dislocation states . the open side of the clip 3 is located at the front of the lower leg 8 above the instep part of the shoe 19 . the clip 3 rests with support parts 24 , 25 on the rear of the lateral malleolus 17 and medial malleolus 18 respectively . it is also possible that the support parts 24 , 25 clasp around the malleoli 17 , 18 . on the back of the clip 3 is a cavity 23 to provide freedom of movement for the achilles &# 39 ; tendon or tendo calcaneus . near the instep part of the shoe 19 on the outside 15 of the shoe is mounted a fixing ring 20 . through the fixing ring 20 runs a connecting means 12 in the form of a strap 21 which connects the support parts 24 , 25 together and to the shoe . an instep part 21 b of the strap 21 then lies between the fixing ring 20 and support part 25 , an outer part 21 a of the strap 21 lies between the fixing ring 20 and support part 24 . the fixing ring 20 can also be produced with the shoe 1 as an integral component , for example an injection moulding . the inversion movement is countered because the outside 15 of the shoe 1 moves with the fixing ring 20 away from the support parts 24 and 25 , exerting a tensile force on the strap 21 . the strap 21 acts as a type of external ligament and offers resistance to the tensile force exerted . this prevents injury to the ankle ligaments or other parts of the foot . it is important that the part of the outside 15 of the shoe 1 which lies in the extension of the strap parts 21 a , 21 b is formed sufficiently rigid . the resistance offered by the strap 21 can be made adjustable , for example by means of a rotation wheel or by pulling the strap 21 with a fastening on the clip 3 or shoe 1 so that the ratio between firstly the freedom of movement and secondly protection against dislocation is controllable . because the clip 3 is preferably reinforced at the back of the cavity 23 , it is also prevented that on an inversion movement , the clip 3 is drawn over the malleoli 17 , 18 by the band 21 , whereby the assembly remains stable . fig2 a shows the shoe 1 with the clip 3 from fig2 wherein the foot is standing flat on the ground . it is also shown that on the outside 15 of the shoe 1 is attached a further strap 21 ′ between the fixing ring 20 and the sole 5 below the strap 21 . the strap 21 ′ serves as extra reinforcement for the exterior of the shoe 1 . the strap 21 ′ has a hook part 21 ′ b which extends between the fixing ring 20 and the sole 5 / heel 7 , and an upper part 21 ′ a which extends between the fixing ring 20 and the sole 5 of the upper 6 . on an extreme inversion movement , the strap 21 ′ provides extra resistance to tensile forces . because no extra reinforcement is necessary in the shoe 1 at the site of the strap 21 ′, particularly between strap parts 21 ′ a and 21 ′ b , the freedom of movement of the bone parts and / or joints present on the outside of the foot is increased , in particular the proximally protruding part of the metatarsus , whereby the user will experience a higher comfort . it is possible that the strap 21 ′ continues into the sole and is attached hereon . it is furthermore possible that the strap 21 ′ is located fully inside the shoe and is attached to the insole . fig2 b shows the embodiment of the shoe 1 with clip 3 of fig1 and 2 a but on the inside of the foot . fig2 b also shows how the strap 21 is connected with the support part 25 . it can also be seen that the support part 25 has a rounded form to increase the wearing comfort in the region around the medial malleolus 18 , in particular when relatively great forces are exerted . the addition of padding increases the comfort further and improves the distribution of forces . fig3 a shows a side view from the outside of a foot with the embodiment of the clip 3 of fig1 a and 2 b , wherein the forces occurring on inversion are shown . fig3 a shows the three force vectors f 21b , f 21 ′ and f lm , wherein f 21b is the force on the fixing ring 20 which is exerted on inversion by strap part 21 b , f 21 ′ is the force exerted on the fixing ring 20 by strap 21 ′ or the shoe 1 , and f lm is the reaction force exerted by the lateral malleolus 17 on the clip 3 . fig3 b shows a top view of the foot in fig3 a with an embodiment of the clip 3 of fig1 a and 2 b , wherein again the forces occurring on inversion are shown . on inversion , strap 21 ′ exerts a force f 21 ′ on the fixing ring 20 which transmits this force via strap parts 21 a and 21 b to the clip 3 . because the clip 3 rests via support parts 24 , 25 on malleoli 17 , 18 , this force is transferred to these malleoli 17 , 18 . thus reaction forces f lm and f mm occur from the malleoli 17 , 18 . furthermore fig3 b shows how the clip 3 surrounds the malleoli 17 , 18 . it is also shown how the cavity 23 leaves room for the achilles &# 39 ; tendon such that the freedom of movement of this tendon and thus the foot is increased . fig4 shows an embodiment of the connecting means 12 for mutual connection of the clip and the shoe , or assembling the assembly from fig2 a . the connecting means 12 comprises a patch 22 with first and second parts 22 a , 22 b . the first part 22 a and the second part 22 b extend from each other at an angle of between greater than or equal to 0 ° and 180 ° so as to form a capital lambda ( λ ) shape , a boomerang shape or an inverted v shape , wherein the enclosed angle is preferably between 90 ° and 120 °. the patch 22 furthermore comprises a fixing means 13 , in fig4 and 5 in the form of engaging means for engaging the strap 21 of the clip 3 . the engaging means can be designed in the form of a hook . it is also possible that the fixing means is designed as an integral passage or ring for the strap 21 in the patch 22 . fig5 shows the patch 22 in the shape of a capital lambda ( λ ) which is attached to a shoe . the patch 22 has a first leg 22 a which extends from the fixing means 13 in the direction of the sole 5 near the upper 6 , and a second leg 22 b which extends from the fixing means 13 in the direction of the sole 5 near the heel 7 . the first and second legs 22 a , 22 b extend over part of the outside 15 of the shoe but do not touch the sole 5 . the patch 22 is attached to the outside of the shoe with stitching but can also be attached by an adhesive . it is also possible to integrate the patch in the shoe . the patch can also be attached to or integrated into the inside 14 of the shoe depending on the desired reinforcement of the ankle .

an assembly includes a shoe and a device connected with the shoe to support the ankle , wherein the device includes a shaped piece which surrounds the ankle at least at the rear and is formed corresponding to the malleoli of the ankle . a shaped piece and a shoe suitable for use in the assembly and a set of the shaped piece and a fixing element for attachment to a shoe are also described .

referring first to fig1 and 2 , there is shown a first embodiment of the present invention . there is shown a doll 2 holding a futuristic weapon 1 in the form of a gun in its hand . the interior of the weapon 1 includes a smoke generator within the weapon housing 3 which includes a smoke chamber 4 containing a heating coil in the form of a high resistance wire 5 therein . an oil soaked wick 6 is disposed in a compartment 7 of the housing 3 , an end of the wick being wrapped around the coil or wire 5 whereby , when the coil is sufficiently hot , it causes the oil in the wick in contact therewith to smoke . as oil at the coil is decomposed pyrolitically , the wicking action causes other oil in the wick and / or compartment 7 to travel to the coil for further decomposition thereof when the coil is sufficiently hot . the coil 5 is heated by current provided from a battery disposed in a battery pack 8 which is snapped onto the back of the doll 2 by means of snaps 70 , only one of which is shown in fig1 . the snaps 70 are composed of a pair of resilient fingers 71 , integral with the pack 8 , which bend toward each other due to the camming action on the snaps , whereby the snaps enter and are locked in the interior of the doll . affixed to the bottom of the battery pack 8 is a pump 9 which comprises a cylinder 10 and a piston 11 biased out of the pack by a spring 25 . at the opposite end of the battery pack 8 is a push button switch 12 having a bar 13 affixed thereto which , when depressed , lowers the battery contacts 14 and 15 to simultaneously touch both of the upper terminals of the batteries 16 and 17 . this completes a circuit with the lower battery contact 18 and the electric wires 19 and 20 which extend from the battery pack to the heating coil 5 . in operation , both push button 12 and piston 11 are operated simultaneously , for example , by placing the thumb of the right hand on the piston 11 and the index finger on the push button 12 . by compressing both push button 12 and piston 11 simultaneously , electrical contact is made to close the electrical circuit to the coil as the air in the cylinder 10 is discharged . since the outward bias on the push button 12 requires less pressure and operates over a shorter distance than the piston 11 , the heater coil 5 is energized at the start of the piston stroke . the smoke generated in the smoke chamber 4 ahead of the air stream generated by the cylinder is then blown out of the gun barrel 21 by the compressed air delivered from the piston 11 and cylinder 10 via the flexible tube 22 to the nozzle 23 of the weapon 1 . the wires 19 and 20 and the flexible tube 22 may be bound together at intervals by bands 24 as shown . the compression spring 25 returns the piston to its original position and the resiliency of contacts 14 and 15 returns the push button 12 to the open switch position as shown in fig1 . it is therefore apparent that the blowing action requires no battery power and the smoke generation requires only intermittent battery operation . the pump 9 consisting of the cylinder 10 and the piston 11 may be replaced by a bellows . referring now to fig3 and 4 , there is shown a second embodiment of the invention which is depicted in accordance with a monster figure wherein the smoke is designed to emanate from the mouth , for example , of the monster . in this embodiment the smoke generator is entirely incorporated within the body 2 &# 39 ; with the battery pack being external thereto only if the body is too small to contain it . the smoke generator comprises a smoke chamber 26 having a heating coil 27 therein and a long oil soaked wick 28 confined in compartment 29 with a portion of the wick wrapped around the coil 27 . the pump 30 comprises a cylinder 31 and a piston 32 , the pump incorporating therein the electrical switch which allows the coil 27 to be heated by the current flowing thereto from the battery ( not shown ). the switch comprises a contact 33 affixed to the piston in any well known manner and two electrical contacts 34 and 35 . the compression spring 38 returns the piston and switch to their original position . the tube 39 emanating from the smoke chamber 26 is centrally located in the neck and rotatably connected to the tube 40 leading to the doll &# 39 ; s mouth . in this manner , the doll &# 39 ; s head can be rotated while maintaining the exhaust path for the smoke . the batteries 41 and 42 for the embodiment of fig3 and 4 are shown in fig5 ( a ) and 5 ( b ) in a battery pack 8 &# 39 ; fastened to the back of the doll by means of the contact pins 43 and 44 that fit snugly into the pin sockets 45 and 46 and serve both to fasten the battery pack to the doll and conduct electricity to pin sockets 45 and 46 . the pin 47 , slidably mounted within the battery pack , serves to operate the piston 32 while keeping the length of the piston rod that extends from the doll body to a minimum . the current path is apparent and is traced from the positive contact 48 of the battery 41 through the pin 43 and socket 45 through the wire 36 to the rivet contact 34 , across the moving contact 33 to the rivet contact 35 , then through the wire 37 to the heating coil lead 49 and then through the heating coil 27 to the coil lead 50 and then through the wire 51 to the socket 46 and pin 44 to the negative contact 52 of the battery 42 , the batteries 41 and 42 being connected by the contact strip 53 . it is apparent that the switch contained within the cylinder as shown in fig3 may also be incorporated into the cylinder shown in fig1 thus eliminating the separate push button switch . the need to actuate the piston repetitively to obtain the air stream in order to pump the smoke out of the generator is advantageous because it causes the intermittent operation of the switch and thereby limits the drain on the batteries . as stated hereinabove , smoke generators have traditionally utilized a coil of very fine high resistance wire of the type normally used in a light bulb as shown in fig6 ( a ). the handling and mounting of such a delicate heating element comprising a coil 53 and means to fasten leads 54 and 55 to the coil such as the crimped fasteners 56 and 57 are not desirable . the problem is compounded when the wick must be placed securely in contact with the coil . accordingly , it has been determined that solid resistors 58 as shown in fig6 ( b ), such as carbon or metal film resistors , can be used in this unusual manner as heaters and have the advantage of attached leads 59 and 60 . these solid resistors are particularly advantageous when tying or wrapping the wick 61 around the body of the resistor as shown in fig6 ( b ). as stated above , smoke generators utilizing heaters of the type described in fig6 ( b ) can perform several hundred smoke generating operations when operated intermittently in the manner described hereinabove . resistor values of approximately 2 to 4 ohms operating with a battery source of two c or d cells are satisfactory and afford the advantages stated above . though the invention has been shown with respect to specific preferred embodiments thereof , many variations and modifications will immediately become apparent to those skilled in the art . it is therefore the intention that the appended claims be interpreted as broadly as possible in view of the prior art to include all such variations and modifications .

the disclosure relates to a smoke generator for a toy , primarily passive toys , which the blower for blowing smoke out of the smoke generating chamber operates intermittently and mechanically , simultaneously with the generation of the smoke , so that the operation of the battery used for smoke generation is also intermittent , thereby prolonging battery life . also disclosed is a smoke generator wherein a metal film or carbon resistor is utilized to heat an oil containing wick to produce the smoke .

referring now to the drawings , fig1 illustrates a radiation therapy machine 10 suitable for use with the present invention . the radiation therapy machine 10 preferably includes a radiotranslucent table 12 having a cantilevered top 14 . the table top 14 is received within a bore 18 of an annular housing 20 of the radiation therapy machine 10 with movement of the table 12 along tracks 16 extending along a longitudinal axis , such as the z - axis of a cartesian coordinate system 22 . the table 12 is preferably disposed along a translation axis and may slide along that axis through the bore 18 passing first the front surface and then the rear surface . the table 12 is preferably supported along the guide tracks 16 and moved by a motorized drive , such as is well known in the art , so that its position may be controlled by a computer as will be described . the table 12 also preferably includes an internal track assembly and elevator ( not shown ) to allow adjustment of the table top 14 in a lateral horizontal position ( indicated by the x - axis of the coordinate system 22 ) and a vertically ( indicated by the y - axis of the coordinate system 22 ). motion in the lateral ( x ) and vertical ( y ) directions are limited by the diameter of the bore 18 . a rotating gantry 24 , coaxial with the bore 18 and positioned within the housing 20 , supports an x - ray source 26 and a high energy radiation source 28 on its inner surface . the x - ray source 26 and the radiation source 28 rotate with the gantry 24 about a center of rotation near the top of the patient table 12 when the table top 14 is positioned within the bore 18 . the x - ray source 26 is collimated to produce a fan beam 30 lying generally within the x - y plane and crossing the bore 18 and thus the table top 14 when the table top is positioned within the bore 18 . the fan beam 30 diverges about a central axis whose angle is controlled by the position of the gantry 24 . after exiting the table top 14 , the fan beam 30 is received by a linear array detector 32 positioned diametrically across from the x - ray source 26 . thus , the rotating gantry 24 permits fan beam radiographic projections of a patient on the table top 14 to be acquired at a variety of angles about the patient during the treatment process . the radiation source 28 is mounted so as to project a fan beam of high energy radiation 34 , similar to the fan beam 30 , but crossing fan beam 30 at right angles so as to be received on the other side of the gantry 24 by a radiation detector and stop 36 . therefore , the x - ray can be taken of a region prior to application of radiation . the radiation source 28 has a collimator 38 mounted in front of it to divide the fan beam of high energy radiation 34 into multiple adjacent rays whose intensity may be individually controlled to adjust the fluence of radiation . the location of the radiation source 28 and x - ray source 26 are precisely characterized so that images obtained from the x - ray source 26 may be used to aim the radiation source 28 . the radiation therapy machine 10 further includes a computer 40 having a display screen 42 and user entry input devices 44 , well known in the art , that is connected to the radiation therapy machine 10 to control motion of the table 12 and to coordinate operation of the gantry 24 together with the radiation source 28 and x - ray source 26 and to collect data from the linear array detector 32 during a scan of a patient according to methods well known in the art . the present invention provides radiographic indexing marker embedded or inlaid in the patient treatment table . the radiographic indexing markers are preferably used for positional calibration of the patient treatment table . the present invention comprises a patient treatment table having at least one radiological marker or indexing matrix embedded or inlaid into the patient treatment table of a radiation therapy system . the radiological marker or indexing matrix may be placed and spaced in any configuration in the table . the inlaid radiological marker or indexing matrix may be actual material or voids that provide contrasting densities in the treatment table that are detectable . the marker or indexing matrix is comprised of contrasting high or low density material in the form of solids ( e . g . wire , pellets , balls , paste , etc . ), liquids ( e . g . column of water , bubble - level , etc . ), disjoint - solids ( e . g . strings of marker beads , etc .) that are inlaid into or fixed onto the sides , top or bottom of the patient treatment table . these density markers can either be actual objects or the absence or objects ( e . g . voids ). the present invention includes various styles and forms of radiological markers and in various configurations . fig2 is a perspective view and detail of an embodiment of a radiographic marker indexing grid 50 embedded or inlaid into the patient table top 52 of the radiation therapy system . the present invention preferably provides a high density material contrasted with the typical low density patient table top . in this embodiment , a wire inlay crosses latitudinally and longitudinally forming a matrix grid 54 across the patient table top 52 . fig2 shows a basic indexing grid , but the grid of the present invention is preferably significantly more complex to achieve accurate resolution in three dimensional space . the matrix grid 54 of radiological material inlaid or embedded in the table top 52 is preferably a three - dimensional material inlaid or embedded into the table top 52 that would allow for table indexing . for example , the detail shown in fig2 shows a three - dimensional cross - hair 56 as part of the matrix grid of marker material inlaid or embedded in the table top 52 . the wire inlays are shown as crossing at right angles . the wire inlays may also cross at other angles , such as forming a v - grid across the patient table . this allows for the imaging system of the radiation therapy system to detect the distances between markers and reference the patient table position . in a preferred embodiment , the marker material may be tungsten wire crisscrossed latitudinally and longitudinally across the patient table top 52 . in addition , other more complex matrix grids or reference points may be inlaid or embedded into the table top 52 for more accuracy and precision of table top calibration and positioning . fig3 is a top plan view and detail of another embodiment of a radiographic marker indexing grid 60 embedded or inlaid into the patient table top 62 of the radiation therapy system . in this embodiment , a plurality of contrasting density material 64 is embedded or inlaid in the patient table top 62 forming a matrix grid 66 across and / or through the patient table top 62 . the matrix grid 66 of radiological material 64 inlaid or embedded in the table top 62 is preferably a three - dimensional material inlaid or embedded into the table top 62 that would allow for table indexing . for example , the detail shown in fig3 shows a three - dimensional layer 68 of marker material inlaid or embedded in the table top 62 . the4 three - dimensional layer 68 of marker material , may be a high density wire inlay , which when imaged , contrasts with the scanned body structure of a patient laying on the table top 62 . in addition , other more complex matrix grids or reference points may be inlaid or embedded into the table top 62 for more accuracy and precision of table top calibration and positioning . fig4 is a cross - sectional view and detail of the patient table top 62 of fig3 taken along line 4 - 4 showing a three - dimensional layer 68 of marker material inlaid or embedded in the table top 62 of the patient treatment table . for example , the three - dimensional layer of marker material may be an embedded tungsten radiographic marker . in another embodiment , the markers are protrusions from the table , allowing for patient fixation devices to be connected to the protrusions . in another embodiment , the markers are flush with the sides or surfaces of the table . in yet another embodiment , the markers are indentations or grooves in the table . in still another embodiment , the markers are embedded at a depth into the table . the markers may be individual markers or may be arranged in sets of two or three , or more , and potentially utilize the sides and / or surfaces of the treatment table . the markers may also be permanently fixed or removable from the treatment table , to minimize interference with dose delivery . the markers may also be interchangeable with different sets or subsets utilized for different objectives . in another embodiment , the markers are magnetic , or include magnets or sensors that are used for positioning patients and / or fixation devices on the treatment table . in still another embodiment , the markers emit radio frequency ( rf ) signals which are detected using rf sensitive detection devices . the markers of the present invention may also be rf detectors for detecting rf signals . in yet another embodiment , the markers include lasers that can be used for any of the above purposes , including the positioning of patients and / or fixation devices on the table , avoidance of table collisions , system setup and calibration , etc . the markers , including lasers , may send and / or receive signals with other fixtures in the room to detect changes in table height or deformations in the table , such as sagging . this information can be used to automatically , semi - automatically , or manually adjust the table position before or during treatment procedures . the markers can also include tlds , mosfets , diodes , or other dosimetric devices used to measure dose during the treatment or scan procedures . use of these devices can be integrated into qa , dose reconstruction , treatment planning , or other related applications . the markers may also be used for calibration and verification of table speed , table position and of the virtual isocenter . treatment accuracy is maintained by aligning the linear accelerator &# 39 ; s isocenter to a precise point within the patient . the isocenter is a single reference point in the x - y - z planes which serves to orient the radiation beams to the proper coordinates of the slices of the tumor in the patient . in addition to the embodiments shown , the present invention comprises radiographic plugs that are inserted into the table that are used for calibrating the imaging system . the plugs would preferably have a density different than bone , tissue or water . the radiographic plugs would preferably be inserted into a row of cylindrical holes at the ends of the table . the plugs would generally be used to calibrate the imaging system . you would take an image of the table and make sure that you see the plugs where you expect to see them . the plugs are preferably used for density or imaging calibration . the plugs may be the same or a different density from the table material . the plugs are generally available from such manufacturers as standard imaging or gammex . in another embodiment , either contrast inserts or resolution inserts would be inserted into the openings described above . in an alternative embodiment , the contrast inserts or resolution inserts could also be embedded or molded into the table . the resolution inserts would preferably be a set of wires or openings based on some even or uneven spacing . these inserts would be used for calibrating the imaging system , and possibly positioning of the patient on the table . in another embodiment , the present invention comprises a substantially flat member that includes radiographic indexing markers and is placed on and / or attaches to the patient treatment table for positional calibration of the treatment table . the markers of the present invention may interact with markers in or on the patient , or characteristics of the patient , to determine the patient position relative to the couch . this includes , but is not limited to , magnetic , rf , laser , and / or light signals . while the invention has been described with reference to preferred embodiments , those skilled in the art will appreciate that certain substitutions , alterations and omissions may be made to the embodiments without departing from the spirit of the invention . accordingly , the foregoing description is meant to be exemplary only , and should not limit the scope of the invention as set forth in the following claims .

a system and method for calibrating and positioning a radiation therapy treatment table with a high degree of precision and accuracy . the system and method comprising a treatment table for use with a radiation therapy system with radiographic indexing markers embedded or inlaid in the patient treatment table . the radiographic indexing markers having a density different from density of the table material , or a radio - frequency or magnetic contrasting matter , something that the imaging system and detector of the radiation therapy system can detect , so that when scanned , with or without a patient or phantom on the table , the precise location of the patient treatment table in the x , y and z planes is known . the radiographic indexing markers may also have the ability to be visually seen by the technician , doctor , physicist or other health care provider conducting the procedure . this is important so that the table may be reconstructed , alone or with a phantom on it , by the radiation therapy system software , providing a very good indication of where the table top is prior to treatment .

the present invention lies in the discovery that a distinct improvement is realized when teeth are remineralized or desensitized by the application of certain soluble salts yielding ions which will react to form a desirable remineralizing or desensitizing precipitate . the improvement in the application comprises the simultaneous use of a water - soluble salt of a divalent metal compound , other than calcium , which is admixed with the reactant paste , gel or solution of soluble salts which are placed in contact with the tooth surface . in this reaction selected cations and anions diffuse through the tooth surface to its demineralized subsurface . however , the additional divalent metal cations contained in the reactant paste , gel or solution stabilize the system from rapidly precipitating the calcium cations and the phosphate anions . the remineralizing cations and anions can then diffuse through the tooth surface to the demineralized subsurface without rapidly forming the precipitate which is bound to the tooth structure . as a result , the tooth &# 39 ; s subsurface is more effectively remineralized or desensitized when an effective amount of the divalent metal cations is utilized . by &# 34 ; effective amount of remineralizing system or agent &# 34 ; is meant an amount when used in accordance with this invention will bring about the remineralizing of teeth having carious lesions , or the mineralizing of normal teeth to prevent caries from forming and to inhibit hypersensitivity by utilizing a toothpaste , gel , or mouthwash having the various components in the amounts set forth below . concentrations of the cationic calcium and anionic phosphate soluble salts are from about 0 . 05 to 15 . 0 % or the limit of solubility of the salt . excess salt can be present , if desired . concentrations from about 0 . 10 % to 10 . 0 % are preferred . the concentrations of the soluble salts containing the desired remineralizing anions are essentially the same as those for the water - soluble salts containing the desired cations . concentrations of the soluble , non - toxic divalent metal salts ( other than calcium ) are greater than about 0 . 001 %, preferably between about 0 . 001 % to 2 . 0 %, with concentrations of about 0 . 01 % to 1 . 0 % being most preferred . although many precipitates are within the broad scope of this invention , by depositing a precipitate less soluble than the original enamel , the remineralized subsurface can be made to be more resistant to demineralization than was the original enamel . if a fluoride ion is utilized , the remineralized enamel is more resistant to demineralization than was the original enamel . the concentration of salt containing fluoride ion in the solution may be from about 0 . 01 % to 5 . 0 %, but from about 0 . 02 % to 2 . 0 % is preferred . in order to effect remineralization of the dental enamel , an effective amount of the desired cations and anions must be employed in the oral cavity . the amount of solution generated in the mouth must contain at least 100 ppm of desired cations and 100 ppm of desired anions and preferably contains more than 1 , 000 ppm of desired cations and 1 , 000 ppm of desired anions . the solution must contain at least 10 ppm of divalent metal ions other than calcium and , preferably contains more than 100 ppm thereof . it is preferred to provide a level of fluoride ions between about 20 ppm to 5 , 000 ppm in the oral cavity from the dentifrice or professionally applied or prescribed gel . while the length of time of contact between the dissolved calcium and phosphate salts and the tooth &# 39 ; s surface is not critical , it is necessary for the length of time to be great enough to allow diffusion of the ions through the tooth &# 39 ; s surface to the demineralized subsurface . it is submitted that at least ten seconds is required for this diffusion and preferably it should be greater than thirty seconds and even longer if possible . the desired extended time for such diffusion is a benefit acruing from the use of the divalent metal salts of this invention . upon preparation with water or upon use in the oral cavity with saliva any solution should have a ph of from about 4 . 0 to 7 . 0 and preferably between about 5 . 0 and 5 . 75 before and after the precipitation reaction , and be otherwise compatible in the oral environment . the ions must not combine prematurely in the solution to form a precipitate , but must be able to diffuse through the surface of the tooth to a demineralized subsurface area and be able to form an insoluble salt with ions of the other solution . the solutions and the insoluble precipitates must have acceptable levels of toxicity ( i . e ., the particular ions , in the amounts used in the remineralization process , must be non - toxic ). in a preferred embodiment of the invention the demineralizing composition is a stable , one - part dry - mix . such dry - mix contains from about 1 . 0 % to 80 . 0 % of at least one calcium salt , from about 1 . 0 % to 80 . 0 % of at least one phosphate salt , from about 0 . 1 % to 20 . 0 % of at least one water - soluble divalent metal salt wherein the metal in other than calcium , from about 0 . 1 % to 20 . 0 % of flavor , from about 0 . 1 % to 30 . 0 % of sweetener , from 0 to about 10 . 0 % of a fluoride salt , and from 0 to about 5 . 0 % of surfactant . the flavor is preferably provided as a spray dried powder . in another preferred embodiment of the present invention , the remineralizing cationic phase of a dentifrice composition contains about 0 . 05 % to 15 . 0 %, preferably about 0 . 10 % to 10 %, of at least one soluble calcium salt yielding calcium ions and greater than about 0 . 001 %, preferably from 0 . 001 % to 2 . 0 %, most preferably from about 0 . 01 % to 1 . 0 %, of at least one water - soluble divalent metal salt selected from the group consisting of magnesium , strontium , tin and zinc , with magnesium being preferred . the remineralizing anionic phase contains from about 0 . 05 % to 15 . 0 %, preferably about 0 . 10 % to 10 . 0 %, of dissolved phosphate salt yielding phosphate ions and from about 0 . 01 % to 5 . 0 %, preferably from about 0 . 02 % to 2 . 0 %, of a soluble fluoride salt yielding fluoride ions . the resulting precipitate is a calcium phosphate or hydroxyapatite , the natural constituent of tooth enamel , with incorporated fluoride ions . not only does this improved process result in remineralized enamel , but the remineralized enamel may be more resistant to subsequent demineralization than was the original enamel . as the calcium compound it is , in principle , possible to employ , in the preparations of the invention , any water - soluble toxicologically harmless calcium compound . a compound is considered to be water - soluble when at least 0 . 25 gram thereof dissolves in 100 ml of h 2 o at 20 ° c . suitable water - soluble calcium compounds are , for example , calcium chloride , calcium bromide , calcium nitrate , calcium acetate , calcium gluconate , calcium benzoate , calcium glycerophosphate , calcium formate , calcium fumarate , calcium lactate , calcium butyrate and calcium isobutyrate , calcium malate , calcium maleate , calcium propionate , or mixtures of water - soluble calcium compounds . calcium nitrate is preferred . in the compositions of the invention for the remineralization of human dental enamel , at least about 100 ppm and perferably at least about 1000 ppm of calcium ions should be present ; the upper limit is about 35 , 000 ppm of calcium ions . suitable water - soluble inorganic phosphates within the scope of the present invention are , for example , alkali salts and ammonium salts of orthophosphoric acid , such as potassium , sodium or ammonium orthophosphate , monopotassium phosphate , dipotasium phosphate , tripotassium phosphate , monosodium phosphate , disodium phosphate and trisodium phosphate . the concentration of the phosphate ions is at least about 100 ppm , and preferably at least about 1000 ppm to 40 , 000 ppm . solubility in water is defined as in the case of the calcium compounds . if desired , water - soluble salts yielding both calcium and phosphate ions , such as monobasic - calcium orthophosphate , may be employed . as the stabilizing divalent metal compound it is also , in principle , possible to employ any water - soluble , non - toxic divalent metal compound which will stabilize the calcium and phosphate ions so that they do not rapidly or prematurely precipitate before diffusing into the teeth . in practice , however , it has been found that at least one member selected from the group consisting of magnesium , strontium , tin , and zinc , with magnesium being preferred , are the most effective in stabilizing the system . suitable magnesium compounds are , for example , magnesium acetate , magnesium ammonium sulfate , magnesium benzoate , magnesium bromide , magnesium borate , magnesium citrate , magnesium chloride , magnesium gluconate , magnesium glycerophosphate , magnesium hydroxide , magnesium iodide , magnesium oxide , magnesium propionate , magnesium d - lactate , magnesium dl - lactate , magnesium orthosphosphate , magnesium phenolsulfonate , magnesium pyrophosphate , magnesium sulfate , magnesium nitrate , and magnesium tartrate . preferred magnesium compounds are magnesium chloride , magnesium acetate and magnesium oxide . suitable strontium compounds are , for example , strontium acetate , strontium ammonium sulfate , strontium benzoate , strontium bromide , strontium borate , strontium caprylate , strontium carbonate , strontium citrate , strontium chloride , strontium gluconate , strontium glycerophosphate , strontium hydroxide , strontium iodide , strontium oxide , strontium propionate , strontium d - lactate , strontium dl - lactate , strontium pyrophosphate , strontium sulfate , strontium nitrate , and strontium tartrate . preferred strontium compounds are strontium acetate , strontium chloride , strontium nitrate . suitable tin compounds are , for example , stannous acetate , stannous ammonium sulfate , stannous benzoate , stannous bromide , stannous borate , stannous carbonate , stannous citrate , stannous chloride , stannous gluconate , stannous glycerophosphate , stannous hydroxide , stannous iodide , stannous oxide , stannous propionate , stannous d - lactate , stannous dl - lactate , stannous orthosphosphate , stannous pyrophosphate , stannous sulfate , stannous nitrate , and stannous tartrate . a preferred tin compound is stannous chloride . suitable zinc compounds are , for example , zinc acetate , zinc ammonium sulfate , zinc benzoate , zinc bromide , zinc borate , zinc titrate , zinc chloride , zinc gluconate , zinc glycerophosphate , zinc hydroxide , zinc iodide , zinc oxide , zinc propionate , zinc d - lactate , zinc dl - lactate , zinc pyrophosphate , zinc sulfate , zinc nitrate , and zinc tartrate . preferred zinc compounds are zinc acetate , zinc chloride , zinc sulfate , and zinc nitrate . the concentration of divalent metal ions is at least about 10 ppm , and preferably at least about 100 ppm , with about 20 , 000 ppm or more being the upper limit . solubility in water is , again , as defined as in the case of calcium and phosphate compounds . the compositions of the invention for the remineralization or prevention of demineralization of human teeth may also contain water - soluble fluoride compounds , the caries - prophylactic activity of which has for a long time been considered to be established . when two phase systems are employed these compounds are preferably present in the phase containing phosphate in order to avoid the formation of sparingly soluble calcium fluoride . suitable fluoride compounds are the alkali fluorides such as sodium , potassium , lithium or ammonium fluoride , tin fluoride , indium fluoride , zirconium fluoride , copper fluoride , nickel fluoride , palladium fluoride , fluorozirconates such as sodium , potassium or ammonium fluorozirconate or tin fluorozirconate , fluorosilicates , fluoroborates , fluorostannites . organic fluorides , such as the known amine fluorides are also suitable for use in the compositions of the invention . water - soluble alkali metal monofluorophosphates such as sodium monofluorophosphate , lithium monofluorophosphate and potassium monofluorophosphate , preferably , sodium monofluorophosphate may be employed . in addition other water - soluble monofluorophosphate salts may be employed including ammonium monofluorophosphate aluminum monofluorophosphate , and the like . if monofluorophosphate salts are used as the fluoride source in two component systems , they could be present in the first component along with the calcium cations without departing from the present invention . however , this is less desirable due to the potential loss of fluoride . suitable toothpastes and gels can be made by employing , in addition to the remineralizing agents of the invention , from about 0 . 5 % to 65 %, preferably from about 5 % to 40 %, of an abrasive , from about 0 . 2 % to 5 % of a sudsing agent , from about 0 . 1 % to 5 % of a binding agent , from 0 % to 50 % of a humectant , and the balance , water and minors . from about 1 . 0 % to 10 . 0 % of an inorganic thickener such as hydrated silica may be added . in the case of two separate components , the ph of a component of such toothpaste or gel comprised of the active cationic or anionic ingredients each has a ph of more than about 3 . the mixture of the two portions which is placed in the mouth , however , must have a ph between about 4 . 0 and 7 . 0 and , preferably , between about 5 . 0 and 5 . 75 . the ph &# 39 ; s of the cationic portion and the anionic portion can be adjusted so long as the above ph parameters are not exceeded . suitable abrasives include silica xerogels . other conventional toothpaste abrasives can be used in the compositions of this invention , and include beta - phase calcium pyrophosphate , dicalcium phosphate dihydrate , anhydrous calcium phosphate , calcium carbonate , zironium silicate , and thermosetting polymerized resins . silica aerogels and the insoluble metaphosphates such as insoluble sodium metaphosphate can be used . mixtures of abrasives can be also be used . silica xerogel abrasives are preferred . suitable sudsing agents are those which are reasonably stable and form suds throughout the period of application . preferably , non - soap anionic or nonionic organic synthetic detergents are employed . examples of such agents are water - soluble salts of alkyl sulfate having from 10 to 18 carbon atoms in the alkyl radical , such as sodium lauryl sulfate , water - soluble salts of sulfonated monoglycerides of fatty acids having from 10 to 18 carbon atoms , such as sodium monoglyceride sulfonate , salts of c 10 - c 18 fatty acid amides of taurine , such as sodium n - methyl taurate , salts of c 10 - c 18 fatty acid esters of isethionic acid , and substantially saturated aliphatic acyl amides of saturated monoaminocarboxylic acids having 2 to 6 carbon atoms , and in which the acyl radical contains 12 to 16 carbon atoms , such as sodium - n - lauryl sarcoside . mixtures of two or more sudsing agents can be used . a binding material is added to thicken and provide a desirable consistency for the present compositions . suitable thickening agents are water - soluble salts of cellulose ethers , such as sodium carboxymethyl cellulose , hydroxypropyl cellulose , and hydroxyethyl cellulose . natural gums such as gum karaya , gum arabic , carrageenan and gum tragacanth , can also be used . colloidal magnesium aluminum silicate , silica aerogels , silica xerogels , fumed silica , or other finely divided silica can be used as part of the thickening agent for further improved texture . a preferred thickening agent is xanthan gum . it is also desirable to include some humectant material in a toothpaste or gel to keep it from hardening . suitable humectants include glycerine , sorbitol , polyethylene glycol , propylene glycol , and other edible polyhydric alcohols as well as mixtures thereof . toothpaste or gel compositions may also contain flavoring agents such as oil of wintergreen , oil of pepperment , oil of spearmint , oil of sassafras , and oil of clove . toothpaste or gel compositions may also contain sweetening agents such as saccharin , dextrose , levulose , sodium cyclamate , and aspartame mixtures of sugar with a sweetner , e . g ., sucralose , are contemplated . it is also possible to manufacture the dentifrice product in the form of a transparent or transluent gel . this is accomplished by matching the refractive index of the water - humectant system with the abrasives and inorganic thickeners if used . professional gels can be formulated similar to dentifrices but with higher fluoride contents . since these products are not designed for cleaning but only as a fluoride application , abrasives and other cleaning agents need not be included in the formulation . the remineralizing systems herein can also be provided in the form of a mouthwash product . both the cationic and anionic parts of mouthwashes can be made in accordance with the following . mouthwashes generally comprise an aqueous solution of ethyl alcohol and flavoring materials . the alcohol provides an antibacterial effect , solubilizes the flavoring materials and provides a pleasant mouth feeling . alcohol - free mouthwashes are now , however , gaining in popularity . optionally , mouthwashes also contain additional antibacterial agents and humectants such as glycerine and sorbitol which give a moist feeling to the mouth . in addition to the remineralizing agents of the invention , typical mouthwashes contain about 0 to 30 %, preferably about 0 to 20 %, ethyl alcohol ; about 30 % to 90 % water ; about 0 to 20 % glycerine or other humectant ; about 0 to 0 . 1 % of an antibacterial agent ; about 0 to 0 . 2 % of a soluble fluoride source , about 0 . 01 % to 0 . 5 % of a sweetening agent , about 0 . 01 % to 2 . 0 % of a flavoring agent , and from about 0 . 1 % to 1 % of an emulsifier - surfactant . examples of suitable flavoring agents include heliotropyl nitrile , wintergreen oil ( methyl salicylate ), oil of peppermint , oil of assia , oil of anise , oil of cinnamon , and mixtures thereof . suitable sweetening agents include saccharin , glycerine , sorbitol , levulose , and 6 -( trifluoromethyl )- tryptophane and aspartyl phenylalanine methyl ester . the products of the present invention can be prepared as single solutions , as two separate solutions , in a single solid powdered , gel for paste form , or a solid powder , gel or paste comprised of two separate components . in accordance with this invention a single solution comprised of the ingredients set forth below is prepared as follows . the product is prepared by dissolving at least one water - soluble calcium salt in a concentration of from 0 . 05 % to 15 . 0 %. at least one water - soluble divalent metal salt , other than a calcium salt , is added in a concentration greater than about 0 . 001 % and preferably from about 0 . 001 % to 2 . 0 %. a second solution containing at least one water - soluble phosphate salt at a concentration of from about 0 . 05 % to 15 . 0 % is also prepared . if desired , at least one water - soluble fluoride releasing compound may be added to the phosphate containing solution at a concentration of from about 0 . 01 % to 5 . 0 %. the ph of each solution is adjusted so that upon mixing the final total solution ph will be between about 4 . 0 and 7 . 0 , preferably between about 5 . 0 to 5 . 75 . the two solutions are then mixed to produce a stable supersaturated or nearly supersaturated solution of calcium phosphate . in this preferred embodiment of the invention it is preferable to use sodium monofluorophosphate as the fluoride source . this keeps the fluoride in solution even in the presence of high concentrations of calcium and allows the supersaturated calcium phosphate solutions to remain stable for longer periods . when the total concentration of calcium ions and phosphate ions is such that the mixing results in a metastable solution , i . e ., one that eventually precipitations calcium phosphate on standing , the two solutions are kept separately until it is desired to use the admixed product and obtain the advantage of the stabilizing divalent metal ions of the present invention . in another embodiment of this invention there is provided a product for remineralizing dental enamel comprising : ( i ) a first component comprising from about 0 . 05 % to 15 . 0 %, preferably about 0 . 10 % to 10 %, of at least one water - soluble calcium salt together with from about 0 . 001 % to 2 . 0 %, preferably about 0 . 01 % to 1 . 0 % of at least one water - soluble , non - toxic divalent metal salt other than a calcium salt ; ( ii ) a second component comprising from about 0 . 05 % to 15 . 0 %, preferably about 0 . 10 % to 10 % of at least one water - soluble phosphate salt , and if desired , from about 0 . 01 % to 5 . 0 % and , preferably from about 0 . 02 % to 2 . 0 % of at least one fluoride releasing agent , ( iii ) a dispensing container comprising at least two discrete compartments each with an outlet end , the first compartment storing the first component which includes soluble calcium salt together with soluble divalent metal salt and the second compartment storing the second component which includes soluble phosphate salt and , if desired , together with the fluoride source , ( iv ) a closure mechanism for closing the compartments ; and ( v ) wherein when the two components are mixed the ph in between about 4 . 5 and 7 . 0 and preferably between about 5 . 0 and 5 . 75 . a plurality of packaging methods may be employed in order to separately contain or store the two components and provide effective dispensing thereof into the oral cavity . thus , the two components of a toothpaste , gel , cream , or the like , may be simultaneously dispensed from separate collapsible tubes preferably made of plastic , a plastic and metal laminate , etc . for convenience and in order to aid in dispensing substantially equal amounts of the components , the tubes may be held together by banding or cementing , preferably along the corresponding ventral sides of the tubes . in another embodiment the two tubes may be constructed to have abutting , preferably flat , sidewall portions . in the forgoing embodiments the mouths of the tubes are usually sufficiently close so that sufficient quantities of the components of the toothpaste or gel may be simultaneously dispensed directly on the toothbrush with the tubes the being capped separately . alternatively , another packaging method comprises loading each component of the paste or gel into separate compartments of the same collapsible composite tube , joined by a common orifice . such composite tube has compartments separated by a divider which is firmly attached along substantially diametrically opposed portions of the sidewall , and corresponding portions of the head structure of the tube . the divider may be glued or welded to the sidewall and head structure of the tube during manufacture of the latter . the divider is preferably provided with a protruding portion which extends into the mouth of the tube until its edge is substantially flush with the rim of the mouth . thus , a divider forms with the sidewall two separate compartments of substantially the same volume for storage of the cationic and aniomic components , respectively . in another alternative packaging method , the two tubes are &# 34 ; concentric &# 34 ;. an inner tube lies within and parallel with an outer tube . the mouths of the tubes abut at the same point . protrusions or the like are inserted between the inner and outer tubes so that the component contained in the outer tube can pass through an available space between the mouth of outer tube and the mouth of the inner tube . the closures of this tube - within - a - tube , ( which can screw on the outer tube or simply be held by pressure ), may , but does not have to be , equipped with an interior protrusion to fit in the inner tube in order to prevent premature intermixing of the two components at the mouth of the tube . the tubes of all the above embodiments are usually filled from the bottom and are subsequently sealed together by conventional techniques . another alternative packaging arrangement comprises of a pressurized container which is provided with two compartments and two spouts . the internal pressure of the compartments is maintained by a pressurized gas , i . e ., nitrogen , at the bottom of each compartment . operation of a mechanical actuator actuates valves which release the contents of the compartments through the spouts causing discharge of the paste or gel components onto a brush . the mouthwash or rinse and similar liquid embodiments are maintained in a manner similar to the pastes or gels in that during storage , each of the components are maintained separate from one another to prevent premature reaction . upon dispensing , the components mix and react in the oral cavity to effect remineralization of dental enamel . the liquid components can therefore be stored each in separate compartments of a dual - compartment dispenser . the dispenser usually includes a closure system comprising for example , an inclined crown portion , at least two pouring spouts extending upwardly from an upper surface of the crown portion and a cover for securement to the crown portion . the cover is provided with closure means , for example , depending plugs , to close the closure . each pouring spout is preferably provided with a vent opening in addition to product orifices in the spouts . the orifices can be positioned close together on the crown , all of which assists in achieving control over pouring . transparent containers have proven to be the most satisfactory . transparency aids a person &# 39 ; s ability to accurately and controllably dispense relatively equal volumes from a dual - compartment dispenser . transparent walled containers also serve as a window function for gauging the amounts of liquid remaining in the dispenser . the walls of the containers can be scribed or otherwise calibrated to assist in dispensing the correct remineralizing amount of product . while applicants do not wish the scope of the present invention to be limited by theory , it is believed that the calcium , phosphate , and , optionally , the fluoride ions diffuse through the tooth surface to the demineralized subsurface and precipitate in the demineralized subsurface where they remineralize the tooth structure . this is attainable because sufficient calcium , phosphate , and fluoride ions remain soluble for a period of time sufficient to permit their diffusion into the demineralized subsurface of the dental enamel . this is accomplished by the use of the divalent metal cations of this invention and in the instance of two component systems combining the particular ions just prior to their application to the tooth in a solution having a ph of about 4 . 0 to 7 . 0 and preferably from about 5 . 0 to 5 . 75 at which ph enough of the calcium , phosphate , and fluoride ions remain soluble for the period of time required to remineralize the lesions of the dental enamel . chemically equivalent concentrations of the first and second solutions are not necessary as long as the molar ratio of calcium and phosphate ions in the mixture is from about 0 . 01 to up to 100 to 1 . it is preferred that the ratio is from about 0 . 2 to 1 to 5 to 1 , and it is most preferred that the ratio is from about 1 : 1 to 1 . 67 to 1 , the ratio of calcium to phosphate in the range of the various less soluble calcium phosphate salts . while completely aqueous solutions are preferred in the present invention , non - aqueous solvents may be employed in combination with water . for example , suitable nonaqueous solvents include ethyl alcohol , glycerine and propylene glycol . solvent systems suitable for use in the present invention are those which are capable of dissolving the salts employed in the invention and which are safe for use in the mouth . with regard to the period of time of exposure of the solutions to the teeth , it is necessary that the length of time be great enough to allow diffusion of the ions into the demineralized subsurface . at least about ten seconds are required for this diffusion . the solution is preferably applied to the teeth for from about 10 seconds to about 15 minutes . the ph of the solution remains relatively constant after its introduction into the oral cavity . under some conditions calcium phosphate readily precipitates at this ph , but most surprisingly while some of the precipitation may occur immediately and some small amount even before application to the teeth , substantially greater amounts of calcium , phosphate and fluoride ions remain in solution to diffuse into the teeth and remineralize the demineralized dental enamel due to the presence of the divalent metal cations hereinbefore described . it is believed that the ability of the solutions to provide ions for remineralization is greatest upon their first introduction into the oral cavity , thereafter decreasing , but at a rate less than that encountered when not employing the instant divalent metal cations . when using two component systems the time period between the mixing of the first and second solutions and the application of the mixture to the teeth should not exceed 1 minute , and preferably is less than 1 minute . with a toothpaste , gel , and the like , mixing is achieved on the surface to the teeth while brushing . the essence of the present invention lies in the mixing of components and the quick and timely application of the resulting solution which will precipitate calcium phosphate , calcium fluoride , and calcium fluoro - apatite in the subsurface enamel of the teeth . before such precipitation occurs , the mixture comprising the solution must quickly be applied to the teeth . surprisingly , the solution can have a ph of about 4 . 0 to 7 . 0 , but preferably about 5 . 0 to 5 . 75 to achieve this result . at a ph below about 3 , demineralization occurs rapidly . a ph below 2 . 5 is generally undesirable from a safety standpoint . the ph of the solutions of the present invention may be adjusted to the ph desired by methods well known in the art . the ph may be lowered by the addition of any acid which is safe for use in the oral cavity and which yields the desired ph at the amount employed . examples of suitable acids are acetic acid , phosphoric acid , hydrochloric acid , citric acid and malic acid . the following examples illustrate the invention : in the examples and elsewhere herein parts and percent are by weight unless otherwise stated . artificial lesions , about 50 u deep , were formed in one surface of bovine enamel chips using a demineralizing carbopol gel , which was used to treat the specimens for 72 hours . the surface hardness of the surface to be treated was then measured . the regimen cycle consisted of a 30 minute demineralization in a standard demineralizing solution followed by a 5 minute treatment of the test products diluted 1 part product to two parts human saliva , followed by a 60 minute remineralization in human saliva . overnight , which was every fifth cycle , the specimens were kept with a layer of saliva and stored in a cold room . the test ran for three days , from a total 15 demineralization : treatment : remineralization cycles . for the treatment cycle , the two parts of the remineralizing test agents of the example were separately diluted 1 part product to 2 parts saliva and mixed together immediately before immersion of the enamel specimens . __________________________________________________________________________ control a example 1 example 2 example 3 part a part b part a part b part a part b part a part b__________________________________________________________________________calcium nitrate 3 . 00 0 . 00 3 . 0 0 . 00 3 . 0 0 . 00 3 . 00 0 . 00magnesium chloride 0 . 00 0 . 00 0 . 4 0 . 00 0 . 8 0 . 00 0 . 8 0 . 00monopotassium phosphate 0 . 00 2 . 00 0 . 0 2 . 10 0 . 0 2 . 10 0 . 0 2 . 40dipotassium phosphate 0 . 00 0 . 70 0 . 0 0 . 60 0 . 0 0 . 60 0 . 2 0 . 20sodium fluoride 0 . 00 0 . 50 0 . 0 0 . 50 0 . 0 0 . 50 0 . 0 0 . 00sodium mfp 0 . 00 0 . 00 0 . 0 0 . 00 0 . 0 0 . 00 0 . 0 1 . 80glycerine 24 . 00 22 . 85 24 . 0 22 . 85 24 . 0 22 . 85 24 . 0 22 . 85water 73 . 00 73 . 95 72 . 6 73 . 95 72 . 2 73 . 95 72 . 2 72 . 75__________________________________________________________________________the ph of each after mixing the two parts was approximately 5 . 5 . crest control a example 1 example 2 example 3__________________________________________________________________________hardness increase 16 20 . 0 62 49 . 0 21 . 0__________________________________________________________________________ the results show that examples 1 and 2 containing sodium fluoride and magnesium chloride significantly outperform control a and crest which do not contain magnesium chloride . example 3 containing sodium monofluorophosphate and magnesium chloride performed equal to control a and better than crest . this is surprising since sodium monofluorophosphate is generally less effective at promoting remineralization than sodium fluoride . ______________________________________ example 4 control b * part a part b part a part b______________________________________calcium nitrate 3 . 0 0 . 0 0 . 0 0 . 0magnesium chloride 0 . 8 0 . 0 0 . 0 0 . 0monopotassium phosphate 0 . 0 0 . 6 0 . 0 0 . 0dipotassium phosphate 0 . 0 2 . 1 0 . 0 0 . 0glycerine 24 . 0 22 . 85 50 . 0 50 . 0water 72 . 2 74 . 45 50 . 0 50 . 0______________________________________ * the ph of the control was adjusted to 5 . 5 . a similar treatment regimen was performed as for examples 1 - 3 except that in test 1 the treatment time was 15 minutes using the formulation of example 4 . in test ii , and control test iii the first cycle of the day wa a 5 minute treatment with crest and cycles 2 , 3 , 4 , and 5 were a 15 minut treatment with the formulation of example 4 or control b respectively . th 15 minute treatment time was chosen to replicate what might happen if thi formulation was released from a produce where the treatment time might be extended to 15 minutes . the three tests were also compared with a standar crest treatment in which crest treatment was applied 5 times per day for minutes . the test was run for 3 days for a total of 15 cycles . __________________________________________________________________________ test ii control test iii example 4 control b test i 4 cycles / day 4 cycles / day example 4 crest crest crest 5 cycles / day 1 cycle / day 1 cycle / day 5 cycles / day__________________________________________________________________________hardness increase 10 . 0 13 6 . 0 16__________________________________________________________________________ the results show that treatments with the nonfluoride containing remineralizing formulation was effective in remineralizing teeth . test i illustrates it was slightly less effective on a one to one treatment basi with crest . however , test ii compared to control test iii illustrates it was more effective than crest on a five to one treatment basis than crest when used with the fluoride toothpaste the remineralizing treatments had an additive remineralizing effect . this demonstrates the likely positive effects of a nonfluoride product , i . e ., a lozenge or candy containing the remineralizing ingredients if repeated several times a day e . g . after eating . examples 5 - 7 illustrate various embodiments of remineralizing formulation of the invention . a two part oral remineralizing mouthwash and a two part remineralizing toothpaste and a one phase toothpaste are prepared as follows . ______________________________________ example 5 example 6 mouthrinse toothpaste example 7 a b a b toothpaste______________________________________water 73 . 8 75 . 9 21 . 7 21 . 5 0 . 0sorbitol 40 . 0 40 . 0 0 . 0glycerine 20 . 0 20 . 0 10 . 0 10 . 0 69 . 69silica abrasive 15 . 0 15 . 0 12 . 0silica thickener 6 . 0 6 . 0 4 . 0cmc 1 . 0 1 . 0 0 . 0carbowax 8000 5 . 0sodium lauryl sulfate 1 . 5 1 . 5 1 . 5calcium nitrate 4 . 5 0 . 0 3 . 0 0 . 0tetrahydratecalcium chloride 3 . 0anhydrousdipotassium phosphate 0 . 5 0 . 2 0 . 0monopotassium phosphate 3 . 0 2 . 3 3 . 0magnesium chloride 1 . 2 0 . 0 0 . 8 0 . 0hexahydratemagnesium oxide 0 . 4sodium 0 . 0 0 . 0 1 . 5 0 . 0monofluorophosphatesodium fluoride 0 . 1 0 . 24flavor 0 . 4 0 . 4 0 . 8 0 . 8 0 . 9saccharin 0 . 1 0 . 1 0 . 2 0 . 2 0 . 3______________________________________ to further demonstrate the beneficial effects of magnesium , strontium , zinc and stannous ions in stabilizing supersaturated solutions of calcium phosphate , the following examples and controls were prepared . ______________________________________ example example example control 8 9 10 c______________________________________ part a part a part a part a______________________________________calcium nitrate 1 . 44 1 . 44 1 . 44 1 . 44zinc chloride 0 . 015 0 . 00 0 . 00 0 . 00stannous chloride 0 . 00 0 . 01 0 . 00 0 . 00strontium chloride 0 . 00 0 . 00 0 . 30 0 . 00water 73 . 545 73 . 55 73 . 26 73 . 56______________________________________ part b part b part b part b______________________________________monopotassium 0 . 37 0 . 42 0 . 42 0 . 42phosphatedipotassium phosphate 0 . 14 0 . 07 0 . 07 0 . 07water 74 . 49 74 . 51 74 . 51 74 . 51the two parts of each example were mixed and the time takenfor the solutions to become cloudy was measured with thefollowing results . after mixingph start 5 . 6 5 . 45 5 . 54 5 . 60minutes before 10 10 9 6becoming cloudy______________________________________ the results show that the three examples of the invention remained stable for longer than the control product which did not contain a divalent meta salt . the addition of the divalent metal thus allows more time for penetration into the tooth before precipitation occurs . ______________________________________ example 11 example 12 control______________________________________ part a part a part a______________________________________calcium nitrate 1 . 28 2 . 01 1 . 28magnesium chloride 0 . 10 0 . 01 0 . 00stannous chloride 0 . 00 0 . 01 0 . 00water 73 . 545 73 . 55 73 . 72______________________________________ part b part b part b______________________________________monopotassium phosphate 0 . 91 1 . 02 0 . 91dipotassium phosphate 0 . 12 0 . 08 0 . 12sodium 0 . 43 0 . 43 0 . 43monofluorophosphatewater 74 . 49 73 . 47 73 . 55ph start 5 . 64 5 . 45 5 . 69minutes before becoming 7 . 5 10 2 . 5cloudy______________________________________ the magnesium chloride and stannous chloride , stabilized the solutions from early precipitation of calcium phosphate even in the presence of mfp as shown by the longer times before the solutions became cloudy . the above examples show how divalent metals of the invention sucessfully retard the precipitation of calcium phosphates . examples of suitable mouthwashes and toothpastes are shown below in examples 13 - 15 . ______________________________________ example 13 professional example 14 gel mouthwash example 15 part a part b part a part b toothpaste______________________________________water 28 . 3 30 . 9 73 . 6 75 . 8glycerine 10 . 0 10 . 0 10 . 0 10 . 0 64 . 06sorbitol 40 . 0 40 . 0 10 . 0 10 . 0silica abrasive 15 . 0silica thickener 12 . 0 12 . 0 5 . 0xanthan gum 0 . 9 0 . 9sodium lauryl 1 . 5sulfatecalcium nitrate 7 . 5 0 . 0 5 . 5 0 5 . 0stannous chloride 0 . 1 0 . 0zinc chloride 0 . 1 0strontium 0 . 2chloridedipot . phosphate 0 . 0 0 . 2 0 0 . 2 0 . 3monopot . 0 . 0 4 . 2 0 3 . 2 3 . 2phosphatesodium mfp 0 . 76sodium fluoride 0 . 0 1 . 0flavor 0 . 5 0 . 5 0 . 5 0 . 5 0 . 7saccharin 0 . 3 0 . 3 0 . 3 0 . 3 0 . 4carbowax 8000 2 . 0______________________________________ examples 16 - 17 illustrate dry - mix formulations which are employed when added to and mixed with water . ______________________________________ example 16______________________________________calcium gluconate 65 . 0magnesium chloride 10 . 0monosodium phosphate 12 . 5disodium phosphate 2 . 5stannous fluoride 2 . 5flavor 5 . 0saccharin 2 . 5usage concentration 1 . 2 g per oz______________________________________ ______________________________________ example 17______________________________________encapsulated * calcium nitrate 97 % 36 . 0monopotassium phosphate 30 . 0malic acid 11 . 0magnesium chloride 5 . 0sodium bicarbonate 10 . 0sodium fluoride 2 . 0flavor 4 . 0saccharin 2 . 0usage concentration 5 . 0 g per oz______________________________________ * calcium nitrate encapsulated with water soluble ethyl cellulose encapsulent

the present invention relates to remineralization , without demineralization , by applying to the teeth a composition which is present in either one or in two phases and which does not react to any large extent until introduced into the oral cavity and upon such introduction does not rapidly precipitate . one phase systems contain at least one water - soluble calcium compound , at least one other water - soluble , non - toxic compound containing a divalent metal different from calcium , and at least one water - soluble inorganic phosphate compound . if desired at least one water - soluble fluorine compound may be added to the system . in two phase systems one phase contains the calcium and the divalent metal compounds and the other the phosphate and optionally , the fluoride compound . in this way the ions which effect remineralization can be absorbed by the dental enamel and their subsequent , but controlled , reaction causes rehardening of demineralized areas in the dental enamel .

reference will now be made in detail to the present exemplary embodiments , examples of which are illustrated in the accompanying drawings . wherever possible , the same reference numbers will be used throughout the drawings to refer to the same or like parts . blood flow can be blocked from interfering with an ablation procedure by maintaining a seal that completely or substantially occludes blood flow through an anatomic passageway , such as a pulmonary vein . in one embodiment described herein , the occlusion seal is formed by placing an expandable device within the ostia region of the pulmonary vein . proper positioning of the expandable device and / or formation of a seal can be confirmed by monitoring the relative pressure on each side of the seal . this allows a clinician to remedy any break in the occlusion seal and can permit formation of a more uniform circumferential lesion without the need to repeat the procedure or perform a time - consuming point - to - point ablation . while cryoablation in the pulmonary vein is described specifically herein , one skilled in the art will appreciate that the methods and device provide can be adapted for use in , or proximate to , other anatomic or non - anatomic structures . moreover , the devices described herein need not perform cryoablation . while cryoablation is described in detail , other ablation procedures , such as for example , radio - frequency and microwave - type ablation could be used with the expandable device . further , ablation devices could be additionally or alternatively located on a device or system separate from the occluding devices illustrated herein and / or the devices described herein could be used in procedures that do not include an ablation step . fig1 is an exemplary side view of a device 10 for performing a cryoablation procedure in accordance with one embodiment . generally , device 10 includes an elongate body 105 ( also referred to herein as a catheter body ) extending between a proximal end 141 and a distal end 142 . the elongate body 105 can include an expandable member 138 for at least partially occluding an anatomic structure . in one aspect , expandable member 138 is positioned proximate to the distal end of elongate body 105 . expandable member 138 can include a variety of structures configured to expand in cross - section from a first insertion configuration to a second , larger , occluding configuration . during insertion of device 10 , expandable member 138 can have a first size and shape that allows insertion through vasculature . upon reaching a target tissue location , the expandable member can be expanded to seat the device at a desired location relative to the target tissue . in one aspect , expandable member 138 is an inflatable device that can be expanded , for example , by infusion with a fluid . the expandable member 138 can be formed from a variety of flexible , deformable , and / or stretchable materials that permit expansion , including , for example , medical grade polymers and elastomers . however , the expandable member need not be stretchable . for instance , the expandable member can be folded and can unfold to expand and increase in size . in use , the materials forming the expandable member can limit or control maximum expansion and reduce the chance of applying excessive pressure on sensitive tissue surfaces . alternatively , the expandable member can be a balloon - like structure that stretches or deforms to permit volume expansion . regardless of the materials used to form the expandable member 138 , the expandable member 138 can be defined by one or more bodies ( having the same , similar , or different properties ) and can include one or more chambers . in one aspect , the expandable member can include a first and second chamber defined by first and second expandable bodies . in particular , one of the chambers can receive a cryo - fluid while the other chamber expands to occlude a vessel and / or to position the first chamber . examples include concentrically arranged and side - by - side expandable bodies . in addition , multiple ablation chambers can be positioned within the expandable member to permit patterning or segmented ablation . in still another aspect , multiple expandable members can be used with the systems and device described herein . one skilled in the art will appreciate that a variety of expandable member structures are contemplated and the expandable member can be varied depending , for example , on the type of ablation and / or target tissue location . the expandable member 138 can also comprise a balloon structure . the balloon can have a substantially circularly shaped cross - section in a plane substantially orthogonal to the longitudinal axis of the balloon catheter . however , the balloon shape can vary to accommodate the target tissue area . the balloon can also be compliant such that when the balloon contacts the target tissue structure , the tissue surface can shape the balloon into a corresponding configuration . in addition , or alternatively , the balloon can compress or deflect tissue to change the shape of the target tissue . in addition to the above inflatable members , other expandable member 138 structures are also contemplated . for example , mechanically expandable structures can be used in association with the methods described herein . one such example is the use of mechanical arms to drive expansion of an expandable structure . in another aspect , flaps positioned around elongate body 105 can be pivoted or rotated into position to mate device 10 with tissue and / or occlude a vessel . regardless of the configuration of the expandable structure 138 , the size and shape of expanded structure can correspond in side and / or shape to a target tissue region . thus , a variety of expanded shapes and sizes are contemplated depending on the use of device 10 . in one aspect , the expandable structure has a generally spherical shape . however , a variety of other geometric or irregular shapes could be substituted . in one embodiment , the expandable body is mated with a distal portion of the catheter body and the catheter body can house at least one lumen for the delivery of an inflation medium to the expandable body . however , the expandable body and catheter body need not be fixedly mated and in one aspect , the expandable body can be inserted separately from the catheter . for example , the expandable body can be inserted through a catheter body and expanded through an opening in the catheter body . regardless , the catheter body can be associated with more than one expandable member and / or an expandable member can be associated with multiple catheter bodies . catheter body 105 includes at least one lumen or channel , and can include two , three or more separate channels that extend over all or a portion of the length of the catheter . in one aspect , the catheter body can include one or more lumens or channels that define fluid pathways , house wires for transmitting / receiving signals , and / or include actuating mechanisms for controlling movement of a portion of the catheter . in the illustrated embodiment , the expandable member 138 is mated with the catheter body 105 proximal to the distal - most end of the catheter such that the expandable member expands radially from the longitudinal axis of the catheter . alternatively , multiple expandable members could be positioned around the catheter body and / or an expandable member could be expanded from one side of the catheter body . in other words , the expandable body and catheter need not have a concentric or coaxial configuration . the distal tip of the catheter can include a blunt surface to assist with insertion of device 10 and to minimize tissue trauma . in addition , or alternatively , the tip , or a portion of the catheter proximate to the distal tip can include an opening for the delivery of a therapeutic substance and / or medical instrument . the size and shape of catheter body 105 can be chosen based on the intended use of device 10 . where device 10 is used for cardiac ablation , catheter 105 can be sized and shaped for insertion through a vascular lumen . in addition , the materials and structure of catheter can be chosen to provide a flexible elongate body . one skilled in the art will appreciate that body 105 can represent the variety of catheter structure commonly known in the art for a vascular approach . the proximal end of device 10 can include a user interface or handle that permits a clinician to grasp device 10 . the handle can have a variety of forms depending on the intended use of device 10 and / or the environment in which device 10 is used . in one aspect , the handle can include one or more sources of liquid or gas for expanding expandable member 138 . the liquid can be a cryo - fluid or volume displacement fluid . controls for governing the delivery of the liquid or gas can , in one aspect , also be located on the handle . alternatively , or additionally , the proximal portion of catheter 105 can be configured to mate with one or more sources of liquid . in one embodiment , the fluid source includes a cryo - fluid and / or volume displacement fluid and can further include a mechanism for regulating and controlling expansion of expandable member 138 via delivery of fluid . in yet another aspect , the catheter body can include one or port ports for receiving or removing fluid , biological samples , therapeutic agents , instruments , and / or other related devices and materials . after the expandable member 138 is successfully placed within the anatomic structure , cryoablation can be performed . in one embodiment , such as in fig1 , expandable structure 138 is cooled to a temperature that destroys cells along the walls of an anatomic passageway , such as pulmonary vein 148 , to some depth . the balloon 138 may be filled with an ablation fluid ( e . g ., a gas or fluid ) including the variety of known substances for cryoablation procedures , examples of which include saline solution , perfluorocarbon , nitrous oxide , and combinations thereof . typically , the ablation fluid is cryofluid or coolant . the cryofluid can be introduced into the balloon from the proximal side of the catheter in one implementation . in one embodiment , the coolant is used to inflate the expandable body at least in part . a lumen can also be provided to expel used coolant and / or create a flow of cooling fluid through the expandable member . alternatively , the expandable member 138 may be heated to a temperature that kills surrounding cells . in a heat - based embodiment , the expandable member 138 can surround a heat source positioned within the expandable member 138 and / or a heating fluid can be delivered into device 10 . in addition , the heating can be effectuated by radiation or conduction from a point inside the expandable member 138 . a separate radiation member can be located inside the balloon 138 . the expandable member 138 can be used to control the shape of the radiation or conduction . consequently , the balloon 138 may come in a variety of shapes depending on the exact procedure being performed and the ablation shape and / or pattern required . the cryo - catheter can include a supply lumen for delivery of ablation fluid to the expandable member . in one implementation , a return tube is positioned inside the lumen of the cryo - catheter to establish a return line . in this way , the ablation fluid may be provided through the supply lumen and , after the substance has been used , returned through the supply tube . in one embodiment , a supply of hot or cold ablation fluid is circulated through the expandable member , and stirring may be provided . a supply tube need not be directed through the interior of the catheter in one embodiment . for example , some other path to the site of the procedure is possible . likewise , the return tube is not directed through the interior of the catheter in all embodiments . with reference to fig1 , the catheter body can be defined by one or more segments fixedly , movably , and / or detachable mated within one another . in one aspect , an outer sheath 130 extends along at least a portion of the outer surface of an inner sheath 110 containing a coolant supply lumen . the sheath 130 can inhibit unintended freezing of any tissue , blood , and / or other biological substance contacted by the cryo - catheter and / or supply lumen during distribution of the coolant . in one aspect , the expandable member can be movably mated with catheter 105 . for example , the system can include a slidable part , such as a cylindrical - shaped sleeve , for use in positioning a balloon at the treatment site . in greater detail , the expandable member can be mounted on the sleeve . the sleeve may then be mounted over the cryo - catheter or some other guide wire that leads to the desired site of the procedure . the system further can include a fill tube attached to the sleeve to fluidly communicate with the expandable member . in another embodiment , the expandable member is separate from the ablating structure . for example , expandable structure 138 can act as an occluding device while a different structure effects ablation . in one such embodiment , a cryoablation member positioned distally to the expandable member sprays a liquid coolant directly onto the walls of the anatomic passageway . in one aspect , the cryoablation member can be delivered through a lumen defined by catheter 105 . alternatively , the cryoablation member can be mated with catheter 105 and cryo - fluid can be delivered through catheter 105 to the cryoablation member . in any embodiment , occlusion can facilitate the formation of a uniform circumferential lesion . as shown in fig1 , an occlusion seal 158 is formed when the pulmonary vein is sealed with the expandable member . the seal helps ensure that the circumferential lesion caused by cryoablation is uniform , and properly blocks problematic electrical impulses from passing to the atrium . for example , if the expandable member 138 is responsible for ablating the tissue , an unclosed gap between the expandable member 138 and tissue ( e . g ., tissue region 150 or 155 ) can result in a non - uniform circumferential lesion because of non - uniform heat or energy transfer between the expandable member and tissue . turning to fig2 , a gap 210 is illustrated between tissue surface 215 and balloon 138 . because the balloon 138 is pressed firmly against tissue surface 220 , the ablation procedure can destroy tissue at 220 more effectively than at 215 . the gap and / or blood flowing through gap 210 can insulate tissue 215 and interfere with effective heat transfer between balloon 138 and tissue 215 . for example , the blood flow can counteract the heating or cooling of the tissue 215 by absorbing the heat or cooling effect as it washes past surface 215 . gap 210 may be acceptable or have minimal impact on the ablation procedure . for example , an ice layer ( e . g ., ice ball ) may form on the outside of the balloon 138 that effectively fills the gap 210 . in this way , even though separation exists between the balloon 138 and the tissue 220 , the pulmonary vein can remain completely occluded . as described in more detail below , the device and systems described herein can , in one aspect , detect if the gap 210 is filled with ice sealing the pulmonary vein . in general , however , the presence of gap 210 can hinder the ablation procedure , and result in a shallower lesion or non - uniform circumferential lesion in the pulmonary vein . a non - uniform lesion might not block impulses from passing into the atrium , and consequently the procedure fails to prevent future atrial fibrillations . in some instances , it is difficult to determine the long - term effectiveness of the lesion until after the cryoablation procedure is complete . therefore , it is helpful if the occlusion is as complete as possible during ablation to help ensure that the lesion is uniform . the presence of a seal in the anatomic passageway ( or lack thereof ) can be detected by measuring a pressure drop at spaced proximal and distal locations . in one embodiment , pressure is measured on either side of the expected location of seal 158 . a first pressure can be detected at a location proximate to a distal surface of expandable structure 138 and inside the pulmonary vein . the first pressure is compared to a second pressure detected proximate to a proximal surface of expandable structure 138 located inside the atria . in one embodiment , the first and second pressures are measured at locations that can detect the pressure drop from the pulmonary vein to the atrium . stated another way , the first and second sensors can measure pressure on either side of the location at which the expandable member contacts tissue . the first pressure can be measured distal to the contact area and the second pressure can be measured proximal to the contact area . in one aspect , sensors positioned in a proximal portion of catheter body 105 can sense pressure distal to the expandable member . in fig2 , a hollow lumen 255 contains an opening 250 on the distal side of balloon 138 . a sensor 162 located within lumen 255 at the proximal side of balloon 138 can measure the pressure on the distal side of balloon 138 . measuring a distal pressure with sensor 162 located at the proximal side of balloon 138 can reduce bulkiness at the distal end 252 of the medical device . fig3 depicts an exemplary longitudinal , cross - sectional view of a medical device including a lumen 510 defined by the inner sheath 110 . the inner sheath 110 can be a catheter in one embodiment . lumen 510 can extend between a proximal end 141 of device 10 and opening 520 distal to the distal side of balloon 138 . lumen 510 can be fluidly sealed from the surrounding environment proximal to balloon 138 such that the pressure at the proximal end of lumen 510 equalizes with pressure in the anatomic chamber distal to balloon 138 . thus , the distal pressure can be measured at the proximal side of the balloon 138 via first sensor 162 . a second sensor 160 can measure the pressure proximal to balloon 138 . in one aspect , a channel 530 is defined by a space between the outer surface of inner sheath 110 and the inner surface of outer sheath 130 . the second sensor 160 can sense pressure proximal to the location where balloon 138 contacts tissue and / or proximal to the proximal surface of balloon 138 . as illustrated in fig3 , an opening 140 at the distal end of channel 530 allows second sensor 160 to measure pressure proximate to balloon 138 from a proximally spaced location . in another embodiment , the second pressure sensor 160 is located outside the medical device and measures the fluid column pressure of lumen 530 from outside the patient . in one aspect , the second pressure sensor 160 may provide a pressure value against which the first pressure sensor value can be measured . for example , the second differential pressure sensor may be calibrated to output a pressure relative to ambient atmosphere pressure . in one such embodiment , the pressure difference is therefore the pulmonary vein pressure , as sensed by the first sensor relative to the pressure value of the second sensor . while fig1 and 3 illustrate device 10 having concentric sheaths 110 , 130 , a variety of alternative configurations are contemplated . for example , parallel lumens could extend to openings 520 and 140 , respectively . in yet another embodiment , an example of which is shown in fig4 , first pressure sensor 162 is positioned on the distal side 120 of balloon 138 , while second pressure sensor 160 is positioned on the proximal side 115 of the balloon 138 . in this embodiment , the lumen or catheter 610 may contain conductive paths 620 and 630 for receiving signals from pressure sensors 162 and 160 , respectively . conductive paths 620 and 630 can be in communication with sensors 162 and 160 and with logic 170 for analyzing the detected pressure differences . fig5 is an exemplary illustration of still another embodiment , wherein a catheter 705 incorporates a single differential sensor 710 to measure the pressure difference between the proximal 115 and distal 120 sides of balloon 138 . in this embodiment , differential sensor 710 is positioned between paths 720 and 730 . path 720 can extend to an opening beyond balloon 138 , while path 730 can extend to an opening proximal to balloon 138 . the differential pressure measured via sensor 710 can be communicated to logic 170 and / or output as a visual and / or aural response to the user through output 720 . regardless of the pressure sensor configuration , the first pressure can be compared to the second pressure based on signals received from pressure sensors . in one aspect , two or more pressure readings are displayed for a user and the user can compare the sensor readings to confirm proper placement of the expandable structure and that a seals has been established . alternatively , a differential pressure circuitry 170 can compare pressure readings . in one embodiment , the pressure sensing circuitry 170 incorporates digital circuitry for analyzing the pressure difference . the digital circuitry can incorporate logic gates and / or a microprocessor . in another embodiment , the pressure - sensing circuitry 170 includes analog components . an amplifier may be used to amplify the pressure signal ( s ) for analysis purposes , and other circuitry may be used to communicate the pressure drop ( or lack thereof ) to a user , as discussed below . in one embodiment , the differential pressure circuitry 170 is incorporated into the medical device 105 . for example , the circuitry can be mounted within a housing or handle . in one embodiment , the differential pressure circuitry 170 remains external to the patient , and can even be external to the catheter in one aspect . for example , wires may connect the differential pressure circuitry 170 to the catheter . in another embodiment , a wireless transmission between the catheter and the differential pressure circuitry may occur . pressure differential can be displayed in a variety of ways . in one embodiment , as shown in fig6 , the pressure differences are plotted on a display as a graph 305 of pressure difference 310 versus time 320 . in this example , the pressure indicates that a complete occlusion ( i . e ., seal ) exists when the pressure is within a predetermined range 330 . between time 0 and time 2 , a seal is present . but at time 2 , the seal is lost and is not regained until time 5 . as illustrated , in one embodiment the pressure difference does not instantaneously fall into the predetermined range 300 upon occlusion , but instead first ramps up towards the predetermined range 330 . an embodiment that graphs the pressure difference can also provide historical data for gauging the success of an ablation procedure . for instance , the physician or surgeon may be shown the length of time that passed during which the occlusion was incomplete , and adjust the ablation procedure accordingly . the display screen can also include other readings , such as a pressure reading inside the balloon . tracking additional readings along with the pressure drop across the balloon 138 could help the user understand why complete occlusion was lost , and make appropriate adjustments . in another embodiment , the output 720 includes an aural component , such as an alarm , that alerts the user when pressure readings indicate that the seal is broken . when the seal is reformed , the alarm stops sounding in one embodiment . in one instance , the alarm is a human voice that warns that the seal is broken and / or notifies the user when the seal is complete . the aural component may aid the user in quickly fixing the incomplete occlusion , such as when the user is not looking at the display 180 ( fig1 ). additionally , or alternatively , notification of when occlusion is complete can help the user initially form the seal in the anatomic passageway . when the user hears the aural indicator , the user may then begin the ablation procedure , knowing that a seal is in place . the aural indicator may also have a pitch or loudness that varies proportional to the pressure difference across the balloon . a pressure difference of approximately zero between the proximal and distal sides of balloon 138 indicates that the anatomic passageway is not occluded , and the seal is not present . in this case , the user should adjust the balloon 138 to reform the seal in order to ensure a successful ablation procedure , such as by adding additional inflation fluid . adjustment may be performed , for example , by repositioning the balloon and / or adjusting the pressure inside the balloon ( e . g ., by further inflating the balloon ) until the occlusion is once again complete . the differential pressure range representative of a complete occlusion can vary depending on the placement of the sensors and / or the anatomic passageway being occluded , the expected or measured blood pressure adjacent to the location of the implanted expandable structure , and / or the need to form an absolute occlusion . in the case of a pulmonary vein , the pressure difference indicative of a complete occlusion can be between about 10 mm hg to about 50 mm hg . in another embodiment , the difference is between about 30 mm hg to about 40 mm hg . however , this range can vary depending on the characteristics of the individual heart . as is shown in fig6 , the pressure can vary upwards and downwards within the range 330 that indicates complete occlusion . this variance can be caused , for example , by the beating of the heart . additionally , the heart rate and forcefulness of heart contractions can affect the pressure drop . other physiological activity , such as breathing or muscle movement , can also produce slight variation in the pressure readings . in addition , when graphing the pressure difference versus time , a slight delay in actual versus sensed pressure can exist , depending on the length and mechanical compliance of the catheter tubing ( e . g ., lumens ). as a result of the compliance , a pressure change at the distal end of the catheter might not be immediately apparent at the proximal end of the catheter . however , the time delay , if present , can be indicated to the user or its impact reduce with a predictive algorithm in one embodiment . in one embodiment a user can program the threshold range at which the device will notifies the user that occlusion is complete and / or that no seal is present . this allows the user , such as a physician , to set the range specifically for an individual patient , particularly patients whose pressure characteristics at complete occlusion do not fall within the typical pressure range . in one embodiment , the user can program an upper and lower pressure threshold . a differential pressure above the upper threshold indicates the existence of a seal . after a seal is present , the pressure must drop below the lower threshold before a break in the seal is indicated in that embodiment . in some embodiments , the lower threshold is near zero mm hg . however , the pressure range might be influenced by factors already mentioned , including the size of the heart and / or pulmonary vein . in addition , an indication of occlusion in other anatomic passageways might involve widely different pressure drops across the balloon , for which programming may be needed . as another option , the physician can set a time offset before the aural component alerts the physician regarding a break in the seal in an embodiment . this offset can help eliminate unwarranted alarms when the pressure momentarily dips below or rises above the pressure thresholds as a natural occurrence not indicative of an incomplete occlusion . these settings and features can be accessed and adjusted through an input interface in one embodiment . the interface can include a mouse , keyboard , voice recognition program , or any other known method of inputting electronic data . the display can include a computer , with an input interface and output interface such as a monitor and / or speakers . in one embodiment , the display components 180 include a microprocessor and a memory . the memory can hold instructions for execution by the microprocessor , which cause the computer to perform the executed stages . in another embodiment , the display components include a hardware interface that is installed within one or more computers capable of running software for displaying the pressure drop on a screen . the pressure - sensing device may be an accessory device that is separate from the catheter device to which it attaches in one embodiment . for example , turning to fig1 , the device 10 may include sensor components 160 and 162 for connecting to lumens 110 and 130 of an existing catheter 105 via ports in the lumens . this may facilitate use of an add - on device with existing catheters . in addition , this embodiment would potentially allow the pressure - sensing device to be used with a disposable catheter . for example , a single device ( comprising sensors 160 and 162 and differential pressure circuitry 170 ) can mate with ports 161 and 163 of a disposable catheter . the sensor components 160 and 162 can include pressure sensors in one embodiment , and also can also include connectors for attaching to the lumen ports . for example , in one embodiment , the sensor components may comprise additional tubing that connects to the ports and leads to differential pressure circuitry 170 , where a pressure transducer makes the pressure reading . in one embodiment , the differential pressure circuit 170 and / or sensor components 160 , 162 wirelessly transmit the pressure difference and / or sensed values to the output circuitry . in another embodiment , the catheter includes the pressure - sensing components as a single pre - manufactured device . the catheter may already include pressure sensors within two separate lumen . however , this embodiment may still employ differential pressure circuitry and output circuitry that is maintained exterior from the patient , and kept in communication with the catheter through either conductive wires or a wireless technology . for example , the catheter may include a transmitter that transmits encrypted signals to a receiver kept external to the patient , the receiver being coupled to the differential pressure circuitry . the above embodiments can be used with any elongate structure that delivers a balloon into a patient , including , but not limited to , any lumen , catheter , tool , tubing , pin or specialized medical device . a method for using a medical device consistent with an embodiment herein has already been described , but for the sake of clarity , various exemplary stages of use are presented in an exemplary flow chart in fig7 . at stage 405 , the expandable member 138 , such as a balloon , is positioned within an anatomic passageway 148 , such as the pulmonary vein . positioning the balloon requires making at least one small incision in the patient , through which the balloon is fed . in one embodiment , the balloon is part of a catheter that is fed into the pulmonary vein from within smaller veins that connect to the pulmonary vein . a guide wire can be used to navigate the balloon into place . in some embodiments , a lens lumen or catheter - mounted camera eye , such as an endoscope , is used to effectively navigate the balloon into position . in other embodiments and procedures , the balloon can be placed by making an incision in proximity to the final destination of the balloon , and directly placing the balloon in position . at stage 410 , the balloon is inflated with an ablation fluid and / or an inflation fluid that can comprise one or more fluids including a cryo - fluid . in general , if the balloon is heated or cooled to perform the ablation , the ablation fluid can include at least the variety of known liquid and / or gas ablation fluids already discussed . at stage 415 , the position of the balloon and / or inflation of the balloon is adjusted until the pressure difference between the proximal and distal sides of the balloon falls within the range indicative of the desired degree of occlusion . in some embodiments , aural feedback is provided to the user . in another embodiment , the user monitors the pressure levels on a display to assure a satisfactory the pressure difference in some embodiments , positioning the balloon includes inflating the balloon and / or moving the balloon . positioning the balloon can include the process of stages 425 and 430 , which can be iterative . stage 425 includes checking whether the differential pressure is approximately zero mm hg . this step can be performed through out the therapeutic procedure and / or ablation step to reduce the likelihood of incomplete occlusion . in another embodiment , the user monitors a visual display , such as a pressure versus time graph , to determine if the occlusion is no longer complete . at stage 430 , if a break in the occlusion seal is detected , the balloon is repositioned as in step 415 until the pressure difference varies in a range indicative of complete occlusion . as previously stated , for most patients , a complete occlusion of the pulmonary vein will result in a pressure difference in the range of about 30 mm hg to about 40 mm hg . once the balloon is positioned and occlusion is present , the cryoablation temperature is applied at stage 420 . in one embodiment , this includes cooling the inner substance of the balloon to a temperature capable of killing tissue in contact with the balloon . in another embodiment , a separate cryoablation member is cooled to a level capable of destroying the tissue . step 420 can include additional filling if the balloon ( or other expandable member ) was not completely filled in step 410 or if inner fluid is cycled through the balloon as a method of applying the temperature to the tissue . similarly , step 420 may include filling a separate chamber with cryo - fluid ( i . e ., and ablation fluid ) in one embodiment . consequently , some embodiments perform step 420 simultaneously with step 410 , while other embodiments do not . at stage 427 , the treatment continues for a desired amount of time . during this time , the pressure difference across the balloon can be monitored to ensure a uniform ablation . if the occlusion becomes incomplete during the process , the iterative process of stages 425 and 430 can be followed to regain a seal . the seal is maintained for a predetermined amount of time while heat is transferred from device 10 to the anatomic tissue or heat is transferred from the tissue to device 10 . once that predetermined amount of time has elapsed , the ablation procedure is completed at stage 440 . although several embodiments refer to a balloon , the expandable member , as previously explained , is broader than just the balloon embodiment . therefore , alternative embodiments exist for all embodiments using described herein as using a balloon . in the alternate embodiments , a different expandable member is used . other embodiments will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein . it is intended that the specification and examples be considered as exemplary only , with a true scope and spirit of the invention being indicated by the following claims .

a method , system , and device for detecting whether an expandable member completely occludes an anatomic passageway allows a user , such as a physician , clinician , or surgeon , to perform a medical procedure more efficiently and increases the procedure &# 39 ; s chances of success . an incomplete occlusion can be immediately detected by monitoring the pressure difference across the expandable member . through this method , a user can quickly diagnose the problem and reposition the expandable member in the anatomic passageway . in particular , in a cryoablation procedure , devices incorporating this method can help ensure a uniform and complete lesion in the pulmonary vein to electrically isolate the pulmonary vein from the atrium , thus preventing atrial fibrillation .

referring now to the drawings in greater detail , fig1 shows the face paint dispenser 1 of the present invention . it should be noted that the face paint in the dispenser of the present invention is designed to provide sport fans with a safe , non - toxic face paint in their teams colors in a convenient , easy to use packaging . the face paint will come in a variety of colors and can comprise any type of conventional face paint . as shown in fig1 the dispenser 1 of the present invention comprises a container 2 which has a quantity of face paint 7 contained therein . one end of the container has a operating wheel 3 which is secured to a conventional worm gear 4 which has threads 5 around the circumference of the gear 4 . at the top of the gear 4 is a pushing platform 6 , which will engage the bottom surface of the face paint 7 and push it out of the container 2 when the wheel 3 is turned . this mechanism is similar to the mechanism disclosed in u . s . pat . no . 2 , 284 , 218 to livingston , which is hereby incorporated by reference . the open end of the container ( the end that the face paint comes out of ) has a groove 8 closely adjacent the top . the cap 9 will fit over the open end of the container 2 and will have an o - ring 10 secured to an internal surface thereof in any conventional manner . when the cap 9 is placed on the container 2 , the o - ring 10 will snap into the groove 8 which will serve two purposes . first , it will secure the cap 9 to the container 2 to prevent loss of the cap and to prevent contaminants from deteriorating the face paint 7 . second , it will seal the interior of the container 2 to prevent the face paint from drying out . if the paint dries out it will not be usable to apply a covering of paint to a user &# 39 ; s face . [ 0022 ] fig2 shows a second embodiment of the present invention which comprises a jar 11 which contains the face paint and a cap 12 which operates similar to the cap 9 of the fig1 embodiment . [ 0023 ] fig3 and 4 show another embodiment of the present invention which comprises a rectangular container 13 , a wheel 14 similar to the wheel 3 of the fig1 embodiment , and a cap 15 similar to the cap 9 of fig1 . the internal mechanism and the locking groove have not been shown for clarity . [ 0024 ] fig5 and 6 show another embodiment of the present invention which comprises a circular container 17 , a wheel 18 similar to the wheel 3 of the fig1 embodiment , and a cap 16 similar to the cap 9 of fig1 . the internal mechanism and the locking groove have not been shown for clarity . [ 0025 ] fig7 shows another embodiment of the present invention which comprises a circular container 19 and a wheel 20 similar to the wheel 3 of the fig1 embodiment . the operating wheel 20 is positioned away from the end of the container 19 . this allows two different colors of face paint to be placed in the same container . when the wheel 20 is turned in one direction , one color of face paint will be dispensed from one end of the container 19 . when the wheel 20 is turned in the opposite direction , another color of face paint will be dispensed from the opposite end of the container 19 . in this manner , a sports fan will have two team colors in the same container , which can be easily dispensed from the same container . in the fig7 embodiment , two caps , similar to the cap 9 of fig1 will be used to seal the opposite ends of the container 19 . the internal mechanism , the caps , and the locking groove have not been shown for clarity . although the sportpaint and the method of using the same according to the present invention has been described in the foregoing specification with considerable details , it is to be understood that modifications may be made to the invention which do not exceed the scope of the appended claims and modified forms of the present invention done by others skilled in the art to which the invention pertains will be considered infringements of this invention when those modified forms fall within the claimed scope of this invention .

a dispensing container which has an operating mechanism for dispensing a product in the container , and which has a cap which locks onto the container and which seals the product within the container .

the present invention is generally directed to a drug delivery arrangement that improves the performance of implantable fusion pumps , catheter systems and other drug delivery devices . in one example embodiment , the present invention prevents blood coagulation at a distal end of a drug delivery system by preventing the blood from flowing back into the tubing of the drug delivery system . in an example application , the present invention facilitates the treatment of atrial fibrillation and atrial flutter through pharmaceutical therapies , as an alternative to electrical cardioversion therapy . while the present invention is not necessarily limited to such an application , the invention will be better appreciated using a discussion of example embodiments in such a specific context . according to an embodiment of the present invention , an implantable drug delivery device includes a drug reservoir having movable surfaces or plates at a drug delivery end or wall portion . the movable plates have two surfaces overlapping each other when the drug delivery device is in an off state , so that , while in the off state , the drug remains inside the drug reservoir . however , when in an on state , the drug is able to flow out of the reservoir in a controllable displacement or flow via apertures disposed in the movable plates that become exposed in response to relative movement of the movable surfaces . the motion of the movable plates results from elongation of the plate material upon receiving heat generated from an electrical source ( current or voltage ), a magnetic source or a thermal source . the plate material includes shape memory alloys responsive to various external stimuli . the shape memory alloy used is configurable to include apertures that open and close as the material elongates and contracts in response to the external stimulation , as described below . [ 0019 ] fig1 a illustrates a drug delivery device according to an illustrative embodiment of the present invention . as illustrated in fig1 a , a drug delivery device 100 according the present invention delivers a drug 102 stored within a drug reservoir 104 to an internal body tissue or organ 106 through apertures of a bottom side 108 of the drug delivery device 100 . the drug delivery device 100 includes a top side 105 , along with a first wall member 114 and a second wall member 116 that form the drug reservoir 104 . in particular , first wall member 114 includes a first side wall 118 integral with a first plate 110 that extends the entire length of bottom side 108 when drug delivery device is in an off state , illustrated in fig1 a . second wall member 116 includes a second side wall 120 integral with a second plate 112 having a length shorter than first plate 110 and slideably positioned over first plate 110 . first side wall 118 extends horizontally between an outer side 119 and an inner side 121 and second side wall 120 extends horizontally between an outer side 123 and an inner side 125 . the drug delivery device 100 is located proximate to body tissue 106 to maximize drug delivery through the bottom side 108 of drug delivery device 100 . drug 102 is released through bottom side 108 and into body tissue 106 upon receipt of an external stimulus at wall member 114 and wall member 116 . in this example , an electrical circuit 119 , located external to or within drug delivery device 100 , such as a pump system , or within an implantable pulse generator , such as a pacemaker , cardiac defibrillator / cardioverter , provides the external stimulus to wall member 114 and wall member 116 . the external stimulus , which can either be electrical , magnetic or thermal , physically reconfigures the relative position of first plate 110 and second plate 112 forming bottom side 108 so that drug 102 is released through bottom side 108 and into body tissue or organ 106 , as described below . [ 0021 ] fig1 b illustrates a detailed view of a bottom side of the drug delivery device of fig1 a according to an illustrative embodiment of the invention . as illustrated in fig1 b , wall portion 108 is formed by overlapping plates 110 and 112 made of a shape memory alloy , with plate 110 extending from a first end 120 , at which a series of one or more apertures 110 a are positioned , to a second end 122 , and plate 112 extending from a first end 124 , at which a series of one or more apertures 112 a are positioned , to a second end 126 . according to the present invention , when the drug delivery device is in an off state , plates 110 and 112 are relatively positioned so that plate 112 is positioned over apertures 110 a so that drug is prevented from passing through bottom side 108 via apertures 110 a of plate 110 , and plate 110 is positioned over apertures 112 a so that drug is prevented from passing through bottom side 108 via apertures 112 a of plate 112 . on the other hand , apertures 110 a and 112 a of plates 110 and 112 , respectively , allow drug 102 of fig1 a to flow outward from drug reservoir 104 to body tissue 106 when plates 110 and 112 are positioned in an on state , illustrated in fig1 b . in particular , when plates 110 and 112 are positioned in the off state , second end 126 of plate 112 is positioned to cover apertures 110 a of plate 110 and second end 122 of plate 110 is positioned to cover apertures 112 a of plate 112 to prevent flow of drug 102 outward from drug reservoir 104 . as wall members 114 and 116 are electrically stimulated by circuit 120 , plates 110 and 112 begin to elongate and expose apertures 110 a and 112 a such that drug 102 is released through one or more of apertures 110 a and 112 a into body tissue 106 of fig1 a . the relative movement of plates 110 and 112 results from elongation of the plate material upon receiving heat generated from an electrical source ( current or voltage ). in this example embodiment , the plates are made from a nitinol - based shape memory alloy that is a { fraction ( 50 / 50 )} mix of titanium nitinol , for example . the choice of the type of shape memory alloy used in the various embodiments of bottom portion 108 depends on where the movable plate arrangement will be used and the acceptable range of electrical , thermal or magnetic parameters . the distribution and size of the apertures in the movable plates are designed according to particular parameters for the flow rate and drug dosage requirements of an individual patient or condition to be treated . the quantity of displacement of the movable plates can be controlled by the source providing the stimulus to the plates . according to an embodiment of the present invention , apertures 110 a and 112 a may be positioned so as to be offset relative to each other in such a way as to minimize the distance that plates 110 and 112 are required to advance relative to each other in order to enable drug 102 to flow outward from drug reservoir 104 . it is understood that while the drug delivery device 100 described in reference to fig1 a and 1b includes one or more apertures 110 a and 112 a located along both plates 110 and 112 , the present invention is intended to include other combinations of apertures and movable plates . for example , according to an alternate embodiment of the present invention , one or more apertures are positioned along only one of plates 110 and 112 , and / or only one of plates 110 and 112 moves in response to the electrical stimulation from circuit 119 . according to yet another embodiment of the present invention , apertures are included only along first plate 110 , and are in direct opposition to second plate 112 when delivery device 100 is in the closed state preventing flow of drug 102 from drug reservoir 104 . the external stimulus is received at plate 110 and top side 105 , so that only top side 105 and plate 110 are physically reconfigured , while second plate 112 remains at a fixed position . when top side 105 and plate 110 expand , the apertures positioned along plate 110 move relative to fixed plate 112 to become exposed , enabling flow of drug 102 through the apertures . the magnitude of the physical reconfiguration of plate 110 is controlled via pressure feedback to meet a desired flow rate . [ 0026 ] fig2 illustrates a drug delivery system according to an alternate embodiment of the present invention . as illustrated in fig2 a drug delivery system 200 according to an alternate embodiment of the present invention includes a valve arrangement 201 for connecting to an implantable infusion pump 210 . valve 201 includes an outer sleeve member 202 and an inner sleeve member 204 , having a diameter less than the outer sleeve member 202 so as to be insertable within the outer sleeve member 202 , with one or more apertures 206 positioned along inner sleeve member 204 . a medicinal fluid 208 flows within an interior 207 of inner sleeve 204 , in the direction of dashed arrow 208 a . when in an off state , inner sleeve member 204 is positioned relative to outer sleeve member 202 so that apertures 206 are covered by outer sleeve member 202 , preventing fluid 208 from exiting from inner sleeve member 204 via apertures 206 . on the other hand , when in an on state , inner sleeve member 204 is positioned relative to outer sleeve member 202 so that apertures 206 are not covered by outer sleeve member 202 , enabling fluid 208 to exit from inner sleeve member 204 via apertures 206 . fluid 208 exits inner sleeve 204 through apertures 206 , as indicated by directional arrow 208 b , flowing into a patient . fluid 208 is pumped out of a drug reservoir 209 by infusion pump 210 , infusion pump 210 drawing suction from reservoir 209 and discharging into inner sleeve 204 . medicinal fluid 208 flows to the patient after valve 201 opens as a result of stimulating inner sleeve member 204 . in one example implementation , inner sleeve member 204 is stimulated directly with an electrical current from a wire 214 disposed within sleeve member 204 provided by an electrical circuit 212 . the electrical stimulation of inner sleeve member 204 causes inner sleeve member 204 to elongate and expose apertures 206 thereby allowing medicinal fluid 208 to flow to the patient . inner sleeve member 204 elongation results in relative motion of portions of inner sleeve member 204 with respect to outer sleeve member 202 , as indicated by directional arrow 220 . in another example implementation , an electrical current through wire 214 indirectly stimulates inner sleeve member 204 , the electrical current causing a heating element 222 to generate heat , and the heat causing member 204 to elongate , and expose apertures 206 . medicinal fluid flow can cease before infusion pump 210 stops by closing valve 201 via a reconfiguration of inner sleeve member 204 , for example by stimulating member 204 using reverse polarity current , or by curtailing electrical current flow thereby cooling heating element 222 respectively . this approach allows better control of the flow rate of the medicinal fluid stream through the apertures . providing movable surfaces in valve 201 for use with infusion pump 210 improves drug flow and pump efficiency . for a more detailed discussion of implantable infusion pumps , reference is made to u . s . pat . no . 5 , 820 , 589 to torgerson , et al ., which is assigned to the assignee of the present invention and is incorporated herein by reference in its entirety . the present invention addresses certain difficulties that currently exist in known valve designs , such as controlling the flow rate of the medicinal fluid , high resistance from the surrounding blood or bodily fluids to introduction of the drug , and limited pressure generated from the infusion pump 210 . in particular , the present invention utilizes the reconfiguration properties of the shape memory alloy in inner sleeve member 204 so that the internal pressure generated by infusion pump 210 enables medicinal fluid 208 to flow outside valve 201 more easily when the valve 201 is open , and will prevent blood from refluxing into apertures 206 . system 200 has low resistance , and the pressure generated from infusion pump 210 only needs to be slightly greater than that of the blood or surrounding bodily fluid to move medicinal fluid 208 out of valve 201 . once the fluid 208 is delivered , valve 201 is closed completely with an additional electrical stimulus . the drug flow rate from valve 201 can be more easily controlled by infusion pump 210 , circuit 212 , and the design of inner sleeve member 204 according to the present invention . the present invention improves the control of fully turning on or off valve 201 to prevent drug leakage . the drug dosage and speed of delivery is also controlled more precisely . according to a further example embodiment of the present invention , fluid 208 is pumped out of a drug reservoir 209 by infusion pump 210 , pump 210 drawing suction from reservoir 209 and discharging fluid 208 into inner sleeve 204 through pressure sensor 216 . pressure sensor 216 detects pressure of the flow of medicinal fluid 208 at a selected location between infusion pump 210 and a point at which the medicinal fluid 208 exits through apertures 206 . as discussed above , the elongation of inner member 204 , and the relative movement of portions of member 204 with respect to outer member 202 , is proportional to the amount of stimulation experienced by member 204 . therefore , the quantity of apertures 206 exposed through which fluid can flow , the flow rate and pressure of medicinal fluid through apertures 206 , are also controlled by the amount of stimulation experienced by member 204 . as more apertures are exposed , pump 210 backpressure decreases and flow rate increases , but at a lower fluid pressure as sensed by pressure sensor 216 . the rate and pressure of fluid delivery to the patient is thereby proportional to the stimulation to inner member 204 . in order for medicinal fluid to exit apertures 206 , the pressure of fluid flow through apertures 206 must be greater than a predetermined threshold , such as the patient &# 39 ; s blood pressure for example . if medicinal fluid pressure is too low , bodily fluid will flow into the interior of inner member through exposed apertures 206 . unnecessarily exposing too many apertures 206 reduces medicinal fluid delivery pressure . additionally , exposing apertures 206 to bodily fluids ( e . g ., blood cells and proteins ) subjects the apertures to buildup of blockage elements . conversely , an excessive medicinal fluid pressure through apertures 206 resulting from exposing too few apertures , may be detrimental to pump 210 , and / or the patient . according to one aspect , stimulation of inner member 204 is controlled to limit the quantity of exposed apertures 206 , while providing medicinal fluid flow through the apertures 206 at a pressure not to exceed a selected maximum threshold . a closed loop feedback path 218 communicatively couples pressure sensor 216 with the inner sleeve elongation control mechanism , circuit 212 for example . as pressure increases , and is detected by sensor 216 , sensor 216 electrically communicates a feedback signal to circuit 212 via feedback path 218 . circuit 212 stimulates inner sleeve 204 responsive to the feedback signal thereby causing additional apertures 206 to be exposed and mitigating the detected pressure increase . the quantity of exposed apertures is controlled to maintain fluid pressure according to a selected flow rate , not to exceed a selected maximum pressure , 250 mm hg for example . for example , the inner sleeve member 204 is initially stimulated to cause a limited number of apertures 206 to be exposed . if fluid pressure is subsequently sensed to be too high , a pressure feedback signal causes further stimulation of inner sleeve member 204 resulting in more of apertures 206 to be exposed . [ 0034 ] fig3 a illustrates a drug delivery system 300 that includes a drug delivery device 308 according to another example embodiment of the invention . in particular , drug delivery system 300 includes a catheter 301 having a catheter body 302 and a catheter tip 304 with a pair of tines 306 for anchoring catheter 301 to body tissue . drug delivery system 300 further includes drug delivery device 308 that is mounted between catheter body 302 and catheter tip 304 for local delivery of medication . the medication can be in the form of a fluid or a solid that can travel within catheter 301 . [ 0035 ] fig3 b illustrates an exploded view of drug delivery device 308 of fig3 a according to another example embodiment of the invention . drug delivery device 308 includes an outer sleeve member 310 and an inner sleeve member 312 having a plurality of apertures 314 . a drug 316 elutes out of inner sleeve member 312 via apertures 314 once drug delivery device 308 is in an on position in response to an electrical stimulation of inner sleeve member 312 . in the on state , the electrical stimulation of inner sleeve member 312 causes inner sleeve member 312 to elongate and expose apertures 314 , thereby allowing drug 316 to elute or flow into the patient in a controlled manner . in an off state , drug flow is cease by closing apertures 314 via a reconfiguration of sleeve member 312 upon receiving the electrical stimulus so that apertures 314 are covered by outer sleeve member 310 . this approach allows better control of the flow rate of a drug , with or without a particulate substance , to the patient . in another embodiment , drug delivery arrangement 300 is incorporated into a pacing / sensing electrode lead head member that is implantable in a patient &# 39 ; s heart . in this embodiment , drug delivery device 308 is disposed within the electrode lead head member and opens via an electrical stimulus received from the electrode lead body . this approach to drug delivery can replace a monolithic controlled release ( mcr ) device normally incorporated into electrode leads . mcr devices typically include a small sponge disposed at the end of the electrode lead that elutes a steroid to inhibit implant rejection . the use of drug delivery device 308 provides the capability of inhibiting tissue inflammation , thereby delaying or preventing the onset of implant rejection , by controlling the elution rate , quantity and release time of the steroid . device 308 can be intermittently stimulated to open and close , thereby locally releasing the desired drug in a controlled manner . in related embodiment , the electrode lead head member of drug delivery arrangement 300 can be similarly formed from a shape memory alloy with a series of apertures . similar to the embodiment illustrated in fig3 a and 3b , the electrode lead head member would include outer sleeve member 310 and an inner sleeve member 312 having apertures 314 . drug 316 elutes out of inner sleeve member 312 via apertures 314 once drug delivery device 308 is in an on position in response to an electrical stimulation of inner sleeve member 312 . in the on state , the electrical stimulation of inner sleeve member 312 causes inner sleeve member 312 to elongate and expose apertures 314 , thereby allowing drug 316 to elute or flow into the patient in a controlled manner . in an off state , drug flow is cease by closing apertures 314 via a reconfiguration of sleeve member 312 upon receiving the electrical stimulus so that apertures 314 are covered by outer sleeve member 310 . according to an alternate embodiment , both inner sleeve member 312 and outer sleeve member 310 include apertures not directly opposed . when in the on state , outer sleeve member 310 is physically reconfigured by the stimulus so that the apertures positioned along inner sleeve member 312 become aligned with the apertures positioned along outer sleeve member 310 , enabling flow of the drug outward from the electrode head member . when in the off state , the apertures positioned along outer sleeve member 310 are covered by a portion of inner sleeve member 312 not having apertures and the apertures positioned along inner sleeve member 312 are covered by a portion of outer sleeve member 310 not having apertures , preventing flow of the drug outward from the electrode head member . upon stimulating the electrode head member , the head member elongates and exposes the apertures , thereby releasing the drug stored within the head member . this approach prevents the formation of fibrosis around the apertures by intermittently releasing a steroid that inhibits tissue inflammation . the electrode head member can be easily placed against the surface of an internal body tissue , such as the myocardium of the heart , to increase the penetration of drug delivery to the body tissue . with this approach the drug is not diluted by local bodily fluids , because the drug is delivered directly to the body tissue or organ . according to an embodiment of the present invention , the drug delivery system may include more than one valve arrangement as described above , so that two or more sets of apertures are positioned along various portions of the inner and outer sleeve members , longitudinally displaced relative to one another along a length of the inner and outer sleeve members , to form multiple sleeve valves that may act as surrogate valves in the case a primary valve becomes occluded . various modifications , equivalent processes , as well as numerous structures to which the present invention may be applicable will be readily apparent to those of skill in the art to which the present invention is directed upon review of the present specification . the claims are intended to cover such modifications and devices .

a medical delivery system for delivering a fluid to a desired location within a body that includes a first member having an aperture , and a second member adapted to be positioned over the first member . the fluid to be delivered is contained within a fluid storage device , formed by at least one of the first member and the second member . the medical delivery system includes means for repositioning the first member relative to the second member between a first state preventing passage of the fluid through the aperture and a second state enabling passage of the fluid outward from the fluid storage device through the aperture .

a system for measuring the signature of a localized superparamagnetic particles within the body according to the present invention generally comprises means for generating an induction field , means for inducing a magnetization induced flux change , and means for measuring a magnetization flux change as described herein . such a system should be both stable and sensitive . while the physical parameters to be measured with such as system are necessarily design dependent , the system can be simulated as described below and the problems inherent in the design of this type of measurement can be solved in a straightforward manner . development of a magnetic body scanner according to the present invention involves simulating the physical parameters involved in order to obtain an accurate assessment of signal of the superparamagnetic inclusion , signal of diamagnetic background of the body , and optimization of the geometry of the measuring device . the magnetic nanoparticles employed are preferably superparamagnetic ( sp ) particles . in magnetite and maghemite this phase occurs for particle sizes less then 25 nm . similar to single domain ( sd ) particles , sp particles have a net spontaneous magnetic moment ; however , unlike sd particles the strength on the volume dependent anisotropy constant is small enough so that it can be overcome by thermal fluctuations . in this state , the particle magnetization instantaneously aligns in the magnetic field . for example , we have performed ac - susceptibility measurements of 20 nm sized maghemite particles ( e . g ., miltenyi microbeads in solution ), in a quantum design squid magnetometer , and have found effectively perfect alignment of the magnetization ( constant in - phase susceptibility and zero out - of - phase susceptibility ) with the field for field frequencies up to 1 khz . this is well above the preferred frequency range measured with the present invention and we can neglect any sample magnetization time dependences ( remanences ). initial simulations were performed to identify theoretical limitations and determine the physical parameters under which a squid coupled sensing device could obtain a signal from superparamagnetic inclusion located in the body . to do this , we developed a brute force three - dimensional simulation of the body , superparamagnetic inclusion , applied magnetic field , and squid sensing coils . by necessity , a scanner design must be chosen and a particular protocol simulated . referring to fig2 in our simulations we chose a scanner 10 which incorporates a dc superconducting induction field ( low noise and highly stable ) and uses motion of the patient to produce a flux change in the pick up coils . this design is simple , cost effective and flexible . the phantom torso ( body ) in our simulations was modeled as an ellipsoid filled with water . the molar diamagnetic susceptibility of water is − 13 × 10 − 6 ( emu ). this approximation was used to determine the maximum absolute contribution of a large slowly varying diamagnetic background ( of approximate torso dimensions ) with rapidly varying edges . there are clearly limitations on the information that can be obtained from this simple model , but the model is useful for determining theoretical limits of the technique . a three dimensional rectangle 12 was formed with dimensions of 120 cm in length , 20 cm in width and 20 cm in thickness . the dimensions of the rectangle were then divided into mm 3 cubes , with the magnetization from each cube contributing to the measured signal . the torso was modeled in the rectangular box as an elongated ellipsoid 14 with the same maximum dimensions as the rectangle 12 . the scan covered the upper positive quadrant of the three dimensional rectangle and hence the upper quadrant of the ellipsoid . the rectangle and ellipsoid were shifted by 10 cm from the x - y plane for mathematical simplicity ( all positions in this quadrant are positive definite ). the pickup coils , located in the scanner 10 , were located 1 cm above the top of the rectangle . the magnetic field was in a “ racetrack ” configuration centered around the scanner platform as shown in fig3 . during the summing of the magnetic field contributions of the magnetization , it was found that cubes located outside the ellipsoid produced no contribution to the field at the sensing coils . on the other hand , cubes located inside the ellipsoid had a diamagnetic response to the applied field and produced a corresponding contribution to the field at the squid sensing coil . the tumor 16 was modeled as a paramagnetic inclusion located at various positions within the ellipsoid 14 . in the mm representation , the tumor with magnetic particles was represented as a 1 cm × 1 cm × 1 cm cube containing 1000 mm 3 cubes . these “ tumor ” cubes had both a diamagnetic contribution and a paramagnetic contribution due to the magnetic nanoparticles . the paramagnetic contribution was calculated using the parameters given in shen et . al ., who studied the behavior of magnetic nanoparticles uptake by mouse brain tumors as a contrast agent for mri . see , shen et al ., monocrystalline iron oxide nanocompounds ( mions ) physicochemical properties , magn . reson . med 31 , 599 - 604 ( 1994 ). using a value of ( 100 ng of iron )/( 1 million tumor cells ) and taking the average diameter of a tumor cell to be 20 μm , we estimated that a 1 cm 3 tumor to contain 12 . 5 μg of fe . from the graph of the magnetization vs . field in shen et al . we took the magnetic susceptibility for fields less then 2 kg to be 2 . 2 × 10 − 2 emu / gm ( fe ). the magnetic field was modeled as a “ racetrack ” geometry extending across the width of the body . fig3 is top plan schematic illustration of a squid scanner 20 modeled in simulations . the scanner comprises an array of ten first order gradiometrer pickup coils 22 located to the interior of and on the same platform 24 as a superconducting solenoid 26 . fig4 shows the configuration of one of the pickup coils 22 . preferably , the centers of loops 28 a , 28 b that make up an individual pickup coil 22 are separated by 2 cm as shown . in the simulations , the long sides 30 a , 30 b of the “ racetrack ” shaped solenoid are separated by 10 cm . the value of the magnetic field is the field generated at the midpoint of a set of coils of a pickup coil . this is also defined as the scan point 32 . neglecting end effects ( extending the magnet well past the width of the body ), the magnetic field was modeled as a contribution from the two wires separated by 10 cm , each wire located 5 cm on opposite sides of the scan point . the magnetic field located at a distance r from the wire has a magnitude equal to b ( r )= c / r where c is a constant determined by the magnetic field at 1 cm . this field was taken to be 5000 g , producing a total magnetic field of 2 kg at the central scan point . the field is a vector quantity radiating tangentially from a circle or radius r centered on the wire . the field due to the second wire circulates in the opposite direction giving a significant cancellation of the x components near the vertical line passing through the scan point . the y - components of the magnetic fields located near the same vertical line add , producing strong vertical polarization of the diamagnetic ellipsoid and the magnetically enhanced tumor . by knowing the direction of the magnetic field and magnetic susceptibility at any point in the matrix , the magnetization vector can be calculated . treating the magnetization of a mm 3 cube as a magnetic dipole we calculated the magnetic field produced by the sample magnetization at the position of the pick up coils . to minimize ambient noise and the background signal , the pickup coils were modeled in a planar first - order gradiometer configuration ( see , ketchen m . b ., “ design of improved integrated thin - film planar dc squid gradiometers ”, j . appl . phys , 58 , 11 1985 , incorporated herein by reference ) with each of the counter wound pickup coils having an area of 1 cm 2 and each coil located along the length - axis with the center of the coils displaced 2 cm on either side of the scan point . the magnetic field signal due to the inclusion and / or a background cube was calculated at a point at the center of each coil . the coils were assumed to be 1 cm 2 each and the field was assumed to be uniform over the area of the coil . the scan covered the upper positive quadrant of the three dimensional rectangle and hence the upper quadrant of the ellipsoid . the rectangle and ellipsoid were shifted by 10 cm from the x - y plane to allow for a scan across the full width of the body . in general the pickup coils were placed 1 cm from the top of the ellipsoid . a scan at any one scan point included a scan volume of 100 mm along the length , 200 mm along the width and 100 mm of thickness and the magnetic field was calculated at each of the two counterwound pickup coils for each of the ten scan elements . the 100 mm length of the scan volume had the effect of clipping the generated signal at distances greater then or equal to 5 cm from the tumor along the length axis . as the scanner was moved the length of the body , six hundred of these scan volumes were included in the total scan . we estimated that the total ten squid simulation included approximately 1 × 10 11 calculations and takes approximately 6 . 5 hours on a 960 mhz pentium iii pc . even so the mm 3 grain size appeared as rapid jumps in the background contribution as the mm 3 grains were limited by the smooth ellipsoidal function . exploratory phase measurement with phantom tumors can be performed in an electromagnetically shielded screened room . by developing experiments in a screened room , much of the electromagnetic noise is eliminated which may otherwise hinder the ability to accurately determine the signal to noise ratio of the design and characterize the signal induced by the phantom tumors . a commercially built ( lindgren and associates inc .) screened room is covered in bronze mesh providing 120 db of screening above 10 khz and greater then 30 db of magnetic screening . with such a screen room , we expect to achieve at least 10 db reduction in electric field noise and greater then 5 db noise reduction in field due to magnetic dipoles in the lower frequency range of interest ( 0 . 1 hz to 40 hz ). since we are performing an effectively dc experiment , we do not expect to induce a significant noise contribution from the screening material . the interior dimensions are 3 m × 3 m × 2 . 5 m , leading to lowest order waveguide modes above 100 mhz well above our region of interest . several modifications need to be made to the room . one noise issue is the noise generated by the control and data acquisition computer . this can be addressed by placing the scanner and computer at opposite ends of the room , by placing the computer in a secondary screened volume , or by moving the computer completely outside of the screened room and filtering the computer lines going into the screened room . we have performed a set of computer simulations to determine the feasibility of measuring and mapping the magnetic fields produced by superparamagnetic nanoparticles which have been aligned by an external magnetic field . simulations were constructed using values for the concentration of iron in nanoparticles associated with tumors in an in vivo mouse model . an induction field polarizes the nanoparticles magnetic moment . as a patient is transported past the scanner , the aligned magnetic moments produce magnetic flux changes in a planar first order gradiometer coil . the generated signals by a 1 cm 3 tumor , at a distance of 10 cm , are of sufficient strength to be detected with a dc squid amplifier . these simulations allow determination of physical parameters important to the development of this type of magnetic scanning technology and the simulations demonstrate the feasibility of using squid magnetometry for in vivo detection of magnetic labels targeted to specific structures . [ 0059 ] fig5 shows the absolute magnetic field generated by a 1 cm 3 tumor at various distances from the squid scanner , ranging from 1 cm to 10 cm . edge effects of the signal are due to a finite scan width and accentuated by the log scale . the magnetic field applied was 0 . 2 t ( 2000 g ) at the scanner . in this range , it appears that the signals are well above detection limits but in practical applications detection limits of small signals are generally determined by the ambient magnetic noise . noise reductions of two to four orders of magnitude can be achieved with a well - balanced gradiometer configuration for the pick - up coils . while the differential magnetic field detected by gradiometer configurations is smaller then the absolute magnetic field , this difference is more then compensated for by the reduction ( cancellation ) in ambient noise . the data presented below are from a first gradiometer pick - up coil with center to center coil distance of 4 cm . as such the signal measured is a differential magnetic field . [ 0060 ] fig6 and fig7 show the signals generated from the tumor located 5 cm from the central pickup coil . fig6 shows the spatial distribution of the signals at the various pickup coils in the scanner for the following parameters : no background or continuous background ( rectangular box filled with water ); tumor is located at x = 10 cm ( 100 mm ) y = 6 cm ( 5 cm from pickup coils ) and z = 10 cm ( center of the ellipsoid ); scan produced by 10 squid scanner ; and maximum amplitude scan located at scanner with coordinates x = 10 cm , y = 11 cm and z = 10 cm . in fig7 the signals from the different pickup coils in the scanner are superimposed to aid the eye in the reading of the actual signals . as the scanner moves across the length of the scan rectangle the pickup coil on the near side begins to pickup the signal . the signal then maximizes close to the point where the pickup coil is positioned vertically over the tumor . the signal then goes to zero when the scan point is directly over the tumor and then goes negative as the other counterwound coil passes over the tumor . the maximum signal is close to 1 × 10 − 9 tesla well within the limits of this type of scanner technology . the key to using this technology is that the pickup coils will need to be able to sense at 10 cm . approximating the thickness of the body to be 20 cm ( for a patient lying on a flat table ), a complete body scan can be accomplished by having the patient scanned both over the front and the back of the body . fig8 shows the raw signal for the tumor located 10 cm from the pickup coils . fig9 is a plot of the maximum differential signal ( signal from the pickup coil ) from the tumor as a function of distance of the tumor from the scan point of the detector . the theoretical signal produced by the first order gradiometer pickup coils for an isolated 1 cm 3 tumor drops off rapidly as a function of distance from the scanner but is still theoretically within squid resolution even at a distance of 11 cm from the scanner . the signal from the tumor located at 10 cm from the pickup coil is interesting for two reasons . first the magnitude of the signal is still larger then the technique resolution in an unscreened environment . however the signal to noise ratio is not adequate for realistic and reproducible detection considering an expected ambient noise of order 10 − 12 tesla . the second interesting feature is that the structure of the signal is different from the 5 cm scan . this adds a second dimension to the analysis opening the possibility of obtaining depth information from the form of the signal . [ 0064 ] fig1 shows the variation of absolute magnetization inflection point versus distance from scanner . the inflection point corresponds to a peak in the in the differential magnetic field signal . while the signal is an order of magnitude greater than a minimal signal , a signal to noise ratio of 10 to 1 is not optimal strongly enhancing the need to increase the magnetization on the tumor . this can be achieved by increasing the applied magnetic at 10 cm , increasing the number of magnetic particles per tumor , finding particles with a larger magnetic susceptibility , or a combination of all three . [ 0065 ] fig1 is a plot of the differential magnetization field at the squid scanner as a function of the applied magnetic field as defined above for this geometry . the signal being amplified by the squid is a linear function of the applied field . for an applied field of 2 - tesla the actual induction field at the tumor 10 cm from the pickup coils is 1800 gauss , still within the linear region of the susceptibility . therefore with application of a 2 - tesla field , the signal can be increased by an order of magnitude . an increase in the dc field will however , make the system even more sensitive to vibrational noise . we next simulated the effects of the diamagnetic background of the body . fig1 shows the differential magnetic field scan ( output from first order pickup coil subtraction ) as a function of scan distance for a 1 cm 3 tumor located 100 mm from the y - axis and located at a distance of 5 cm from the central scan point and a depth of 4 cm below the surface of the diamagnetic ellipsoidal background . simulated signal generated by 10 squid scanners scanning the width of the ellipsoid . the noise on the background is an artifact of discontinuities caused by the mm 3 cubes bumping up against the boundary of the continuous ellipsoid . the magnetic induction field applied was 0 . 2 t ( 2000 g ) at the scanner . the signal from the tumor at a depth of 5 cm depth can easily be observed against the diamagnetic background signal . at larger depths (& gt ; 6 cm distance for scanner ) the signal is difficult to discern due to the large artificial noise component in the simulation . it can be observed that the tumor at 5 cm has a signal approximately equal to the maximum signal of the diamagnetic background and can therefore be resolved . it can also be observed that the background has a noise associated with it , which appears as ripples . these “ ripples ” are an artifact of the algorithm . the body is simulated as an ellipsoidal function . when the mm sized cubes , which are being summed over , bump up against the continuous ellipsoidal function we get a staircase like pattern in the cubes producing a discontinuous signal . this artificial noise is more then an order of magnitude larger then the signal of the tumor at 10 cm and therefore the tumor cannot be resolved against this background . to further follow up on the discussion of background signal , we investigated the effects of a uniform background signal and a tumor located in say a large organ . moore et al . who studied the uptake of long circulating dextran - coated iron oxide nanoparticles ( lcdio ) by 9l gliosarcoma brain tumors in a rodent model raise this issue . see , moore a ., marecos e ., bogdanov a . and r . weissleder , “ timoral distribution of long - circulating dextran - coated iron - oxide nanoparticles in a rodent model ”, radiology 2000 ; 214 : 568 - 574 . these vary small particles show minimized uptake by the reticuloendothelial system and uptake by tumor vasculature . in this sense these particles are not specifically targeted to the tumor with a targeting molecule such as a monoclonal antibody . in this study they found that tumor uptake by the brain tumor was approximately 0 . 11 % of injected dose . they also found that the surrounding healthy brain tissue lcdio concentration was approximately 10 % of the tumors concentration . the effect of this type of background signal was investigated in fig1 . a fictitious organ was modeled around a tumor that is located 5 cm from the scanner . the organ was modeled as a rectangular box with thickness 2 . 5 cm on either side of the tumor , width 5 cm on either side of the tumor and length 5 cm on either side of the tumor in the direction of the scan length . the organ was given an iron oxide concentration of 1 % of the tumor concentration . the diamagnetic background of the body was included . the scan in fig1 shows that a 1 % organ background produces a signal comparable to the signal due to the tumor . at 1 % the signal due to the tumor is still resolvable . simulations were also done with a 10 % background tumor . in these simulations the background completely overwhelmed the tumor signal . this provides limits on contributions due to surrounding tissue . on the other hand for intravenously administered targeted iron oxide particles conjugated with monoclonal antibodies it was found that tissue surrounding the tumor had “ modest ” uptake but no evidence of the presence of monoclonal antibodies . this suggests that well constructed magnetic label - target specific vector conjugate will provide the best system for maximizing tumor uptake while minimizing background . in terms of the physical parameters analyzed in this simple model , values of magnetization in realistic magnetic induction fields are measurable with squid technology . theoretical signal to noise ratios of between one hundred and eight hundred are predicted for an 1 cm 3 tumor located 6 cm to 8 cm from the scanner , in a reasonably quiet environment . the diamagnetic signals from the body volume have signals on the same order as the tumor at 5 cm . while it may be possible to eliminate much of the background signal by surrounding the body with water the volume contribution of organs , bones etc . must also be accounted for . we also analyzed a 1 cm 3 tumor at 5 cm within a simulated organ of thickness , width and length , 5 cm × 10 cm × 10 cm consisting of a diamagnetic water concentration and a 1 % of tumor concentration superparamagnetic contribution . the organ contribution was as large as the tumor signal suggesting the need for efficient targeting . there are several variables that can be potentially modified to enhance the signals generated using this technique . we focused on the signal due to a paramagnetic inclusion located 10 cm from the detector . the signal is directly proportional to the amount of fe in the tumor . the most promising method for enhancing the signal is optimization of the nanoparticles magnetization and size . while larger fields may be employed to increase the tumor signal , larger fields will also increase the background signal and the inherent noise in the system . theoretically the magnitude of the signal of a 1 cm 3 tumor at distances of 10 , 11 or even 12 cm from the scanner ( pickup coils ) are accessible by squid technology in a low noise environment . to achieve this level of sensitivity , the configuration and spacing of the pickup coils should be optimized . in this regard , there are two factors that come in to play in consideration of the pickup coils . the first factor is to maximize the magnetic sensitivity by varying the pickup coil configuration , ( i . e . dipole loop , 1 st order gradiometer , second order gradiometer etc .). the second factor is optimization of the spatial configuration of multiple pickup coil - squid system to maximize spatial resolution of the entire scanner . methods for significantly reducing the background include surrounding the body with water to produce a more uniform background and eliminate contributions from air pockets and edge effects . it is clear from the simulations that measurement of the localized moment will require the most sensitive type of squid magnetometry ; namely dc squid magnetometry . it will be appreciated that the theory of imaging magnetic sources at a distance from a scanner is quite well developed . a scanner that comprises scanning elements located across the width and scanned lengthways over the length of the body produces at minimum enough information for a two dimensional magnetic image . correlations of signal structure with depth have shown evidence for identifying the depth of the tumor and hence giving a third dimension of information . in a preferred embodiment of the invention , a model 601 lts dc squid scanner available from tristan technologies inc . of san diego is modified as described below . tristan currently builds squid scanner systems for measuring hepatic liver stores and for magnetocardiography . as far as we are aware , tristan technologies inc . is the only company that produces commercially available dc squid scanners . modifying a commercial squid scanning device built for design flexibility eliminates many of the technical issues involved with setting up a squid system and allows for tapping into the expertise of several experts in this field . with 1 cm pickup coils tristan reports that sensitivities approaching 10 ft per square root hertz are possible . some of the technological difficulties involved with building a useful squid scanner include minimization of the dewar wall between the sensor and target , rigidity of field coils with respect to the pickup coils and electronics design . we preferably use a he cooled cryostat and the pickup coils will be positioned above the target as require by this type of cryostat . tristan currently produces a dewar that at the scan face goes from 4 . 2k to 300k in & lt ; 5 mm . this feature is essential as the simulations show the signal decreases rapidly as a function of distance . the squid signal is preferably filtered and processed through an analog - to - digital converter ( adc ) connected to a personal computer ( pc ) or the like . the pc preferably includes software to control both a transport mechanism and the data acquisition . by sampling data at a reasonably fast rate compared to the transport velocity signal , averaging can be employed to improve the signal to noise ratio . the final array of scan data will have a spatial resolution of greater then 1 mm . the line scan is preferably stored as a linear array , as a function of scan distance . [ 0075 ] fig1 schematically shows the configuration of a squid dewar , scanner , and proximity transport system 40 configured for use in the present invention . the liquid he dewar 42 is preferably fixed in an aluminum collar ( not shown ) located near the top of the dewar . the collar is preferably supported by a - frame aluminum legs ( not shown ). the transport device 44 , such as a transport table / belt or the like , conveys a sample 46 past the squid sensors 48 along the x - axis as shown . the squid sensors are positioned above the sample at a height h . in the embodiment illustrated , the superconducting magnet coils 50 and second derivative gradiometer detection coil 52 are shown for reference . the transport device 44 is preferably located between , but not in contact with , the a - frame legs . both the stand ( not shown ) for the dewar and the transport table should be independently bolted to a solid stable floor structure ( e . g ., concrete ) under the screen room ( not shown ). low frequency vibrational damping can be added as required . screening preferably will be accomplished at these floor contact sites by bolting through an eighth inch copper plate ( not shown ). analog and stepping motors should be electromagnetically screened . note that scanners built by tristan use wire wound pickup coils with the counterwound coils wound at different positions along the y - axis as shown in fig1 . while a second - order gradiometer geometry gives better noise cancellation and is preferred , first - order gradiometer coils are much less sensitive as a function of distance . referring again to fig4 the pickup coils are preferably fabricated in a planar geometry ( without integrated squid ) using thin film technology and optical lithography techniques . these techniques allow for minimizing area differences between the coils down to the μm 2 scale . the pickup coils are preferably deposited on si as a 500 nm film of nb and patterned as shown in fig4 . this is a simple design , requiring only a single deposition and a single lithographic step . using optical lithography and a chromium mask , estimates of pickup coil balance of greater than one ppm are achievable . most of the balance error will come from the attached leads . this can be minimized by ultrasonically “ drilling ” two holes in the si substrate . nbti wire fed through the holes can be attached to the film pad by ultrasonic bonding . it will be appreciated that these pickup chips can be fabricated with various characteristics . for example , the chip shown in fig4 will have high signal resolution but low spatial resolution . an alternative embodiment with dimensions approximately a factor of ten smaller than the chip of fig4 will have good spatial resolution but less signal resolution due to the smaller pickup coil area . this smaller chip will also have better signal to noise ratio and better background subtraction . [ 0079 ] fig1 schematically shows an interchangeable solenoid and pickup coil platform 60 according to the present invention . the nbti leads 62 are twisted and epoxied to a g10 rod 64 extending from the back of the pickup coil chip 66 ( e . g ., chip 22 shown in fig3 and fig4 ) up to the entrance to the dc squid . the leads ends attached to the pickup coil pads 68 a , 68 b will thread through the holes 70 a , 70 b in the si and converge , epoxied to the backside , where twining begins . to maximize vibrational stability , all components of the platform will be embedded in stycast epoxy ( e . g ., g10 ). thus each pickup coil will have its own dedicated g10 platform 72 and solenoid 74 . preferably , the magnetic field solenoid 74 is fabricated from nbti ( 52 %/ 48 %) wire . the wire preferably has a diameter of 2 . 8 × 10 − 3 cm . in order to produce a 1t field ( at the scan point ) at 5a current approximately four layers of windings are required . upon completion of winding , the solenoid is embedded in the stycast epoxy and a persistent switch is constructed at the top of the platform . the magnet can be powered by any conventional power supply . referring again to fig1 , the transport device 44 for a human body scanner should be designed to minimize magnetic and vibrational contributions . the transport device preferably comprises four sections , all isolated from contact with the scanner as discussed above . two sections of the transport device effectively comprise a table on either side of the scanner . two physically independent but electrically connected rotating belts on each table will provide the transport mechanism . the proximity of the belts to the scanner obviate the need for care to be taken to only use belt materials with small and small homogenous magnetic susceptibilities as would be the case with phantom samples . the table preferably have sides approximately 30 cm high to help support the sides of the body chamber . referring to fig1 , the chamber 80 that the patient will be transported in preferably comprises a thin walled flexible plastic . the transport chamber preferably has walls approximately 20 cm high and sealed at the top and the bottom . the chamber has a foam body cavity 82 in which the human body is placed for scanning , and the chamber preferably comprises water filled foam 84 to decrease the background signal of the diamagnetic contribution of the body . transport velocities preferably range from approximately 2 cm / sec to approximately 20 cm / second . this will provide a comfortable scan speed for the patient and allow for rapid scanning taking approximately 10 s to 20 s per full body scan . this speed will also provide a magnetization change through the pick up coils at large enough frequency to minimize the low frequency noise inherent in squids . stepping motors used for driving the device should have both stepping and analog modes for optimization of the transport technique . standard magnetometers that operate on the principle of faraday &# 39 ; s law produce a signal that is proportional to the time derivative of the change in magnetic flux ( faster flux change gives a larger signal ). the superconducting pickup coil loop integrates the signal making rapid scanning unnecessary . instead , scanning rates are determined by optimization of squid signal bandwidth , patient comfort and efficiency . it may also be necessary to cycle all or a small part of the patient over the scanner to average the signal and increase signal to noise ratio . although the description above contains many specificities , these should not be construed as limiting the scope of the invention but as merely providing illustrations of some of the presently preferred embodiments of this invention . therefore , it will be appreciated that the scope of the present invention fully encompasses other embodiments which may become obvious to those skilled in the art , and that the scope of the present invention is accordingly to be limited by nothing other than the appended claims , in which reference to an element in the singular is not intended to mean “ one and only one ” unless explicitly so stated , but rather “ one or more .” all structural , chemical , and functional equivalents to the elements of the above - described preferred embodiment that are known to those of ordinary skill in the art are expressly incorporated herein by reference and are intended to be encompassed by the present claims . moreover , it is not necessary for a device or method to address each and every problem sought to be solved by the present invention , for it to be encompassed by the present claims . furthermore , no element , component , or method step in the present disclosure is intended to be dedicated to the public regardless of whether the element , component , or method step is explicitly recited in the claims . no claim element herein is to be construed under the provisions of 35 u . s . c . 112 , sixth paragraph , unless the element is expressly recited using the phrase “ means for .”

a magnetic body scanning method and apparatus for scanning the entire body for a magnetic signature of a cluster of ferromagnetic nanoparticles in relation to the diamagnetic signature of the body .

the common view of the preferred embodiment of the present invention is shown in fig1 . fig2 represents the preferred embodiment as a body comprising five parts : two identical half - cylindrical external walls [ 001 ], the central core [ 002 ], the entrance cover [ 003 ] and the mouthpiece [ 004 ]. fig2 shows the drawings of the side half - wall [ 001 ] of the invented cigarette holder in details . as one can see , this part is made of an aluminum half - cylinder ( although steel , brass , bronze , cooper , silver , gold , platinum and their alloys with high heat and thermal conductivity can be used ). a rectangular piece of the material is cut out off of said half - cylinder , so that inside it there the symmetric flat rectangular central notch [ 005 ] all along said half - cylinder is made . on the center of sides of said rectangular central notch [ 005 ] there are made other , smaller and shorter , flat side rectangular notches [ 006 ]. the one half - cylindrical external wall [ 005 ] can be attached to the second half - cylindrical external wall [ 001 ] so that the obtained body will represent a cylindrical carcass of the invented cigarette holder : the cylindrical tube having a rectangular hole [ 011 ] all along it with two doubled side rectangular notches [ 012 ] inside , as it is shown in fig2 . the bottom and top surfaces of said rectangular central hole that are actually assembled of two half - cylindrical external walls [ 001 ] are modified with the dense triangular lattice of the segmental dimples . fig3 shows the schematics of the central core [ 002 ] of the invented cigarette holder in details . the central core [ 002 ] of the invented cigarette holder is a body , which has a rectangle normal cross - section in every point along its length , and is made of the aluminum ( although steel , brass , bronze , cooper , silver , gold , platinum and their alloys with high heat and thermal conductivity can be used ). said core can be considered as body having three parts : central part and two identical strictly rectangular “ wings ” [ 007 ]: one from the left side of said central part and another one from the right side of said central part . the dimensions of said “ wings ” should be chosen to make each “ wing ”, being entirely placed in the doubled side rectangular notch of the described cylindrical carcass of the invented cigarette holder , to completely fill said side rectangular notch . the wide of the central part of the core [ 002 ] should be chosen to provide reliable contact with the half - cylindrical external walls [ 001 ] of the described cylindrical carcass of the invented cigarette holder in every point of the side surfaces of the core . core [ 002 ] begins with a rounded “ nose ” [ 008 ] and ends with gradually decreasing “ tail ” [ 009 ] that is providing a low turbulization of the stream of smoke at the streamlined core . the top and bottom surfaces of said central part of the core are modified with the dense triangular lattice of the segmental dimples [ 010 ]. the height of the central core [ 002 ] should be chosen to provide free flat channel of such height h between said core and walls of the described cylindrical carcass of the invented cigarette holder , which guarantees existence in said channel of a well - developed vortical boiling regime of flow of the smoke at smoking . fig4 shows the schematics of the dense triangular lattice of segmental dimples . signature feature of such lattices is the fact that the parameter of it is a = 3 1 / 2 r . it is important to maintain right orientation of lattice in regard to stream of fluid : just as it is shown in fig4 . fig5 shows an example of a well - developed vortical boiling regime of flow over a surface that is modified with the dense triangular lattice of segmental dimples . generally said regime strongly depends on geometry of the channel , thermal characteristics of its walls and speed of smoke &# 39 ; s flow . particularly , it is recommended to make each dimple as a segment of some imaginary sphere of radii r = 1 . 61 mm and with its own radii r = 1 . 2 mm and depth h = 0 . 54 mm . all such dimples should be put in a dense triangular lattice with parameter of lattice a = 2 . 08 mm . at the proper rate of flow of the streamlined flux of smoke over such lattice generates a coherent pattern of vortical jets between neighboring dimples , as it is shown in fig5 . this flow provides the ultimately low pressure drop and ultimately high index of heat exchange between the smoke and walls of the channel . as a result of said features the present invention provides full recuperation of the inhaled smoke up to the normal temperature of the smoker &# 39 ; s body . said recuperation is achieved due to usage of materials for the cigarette holder that have high thermal conductivity and high heat capacity ( aluminum , cooper , silver , gold , etc .). during the smoking and pauses between two consecutive smoking events , the heat accumulated by the cigarette holder is quickly delivered to the external surface of said cigarette holder due to high thermal conductivity of the used materials , so that the cigarette holder can be easily chilled by the natural convection with the ambient environment . fig6 shows the schematics of the entrance cover [ 003 ] of the invented cigarette holder . fig7 shows the schematics of the mouthpiece [ 004 ] of the invented cigarette holder . these two parts , being screwed on the ends of the described cylindrical carcass of the invented cigarette holder , are keeping entire construction in the reliable strength state , in one hand , and do provide a quick and easy disassembling of the entire construction in case of the need to clean of its inside surfaces . fig8 shows the schematics of the multichannel cigarette holder , when the idea of an insider core , like [ 002 ], is used for creation of multitude parallel channels for a smoke . the foregoing descriptions of specific embodiments of the invention are presented for purposes of illustration and description . they are not intended to be exhaustive or to limit the invention to precise forms disclosed and , obviously , many modifications and variations are possible in light of the above teaching . the embodiments are chosen and described in order to best explain principles of the invention and its practical application , to thereby enable others skilled in the art to best utilize the invention and its various embodiments with various modifications best fit to the particular use contemplated . it is intended that a scope of the invention be defined broadly by the drawings and specification appended hereto and to their equivalents . therefore , the scope of the invention is in no way to be limited only by the following exemplary claims nor by any possible , adverse inference under the rulings of warner - jenkins company , v . hilton davis chemical , 520 us 17 ( 1997 ) or festo corp . v . shoketsu kinzoku kogyo kabushiki co ., 535 u . s . 722 ( 2002 ), or other similar case of law or subsequent precedent should not be made if such claims are amended subsequent to this utility patent application .

the present invention describes the cigarette holder with advanced smoking effect . the invented cigarette holder offers the means for making a full draw of the low temperature smoke into the lungs using minimal suction effort .

some of the preferred embodiments are described with reference to the figures . with reference to fig1 , a three way connector 1 mates three members 3 of a frame at three or four positions on the top of the device forming a substantially square or rectangular shape . a two way connector 2 mates two members 3 of a frame at three or four positions on the bottom of the device forming a substantially square or rectangular shape . thereby a scaffolding , frame or base is formed . wheels 4 are mounted onto the scaffolding , frame or base to provide a means for easy movement . pouches 5 are found present in a netting 6 to serve as a target for collecting a ball . the netting may be permanently affixed to the scaffolding , frame or base or temporarily affixed thereto , such as , for instance draped over or encasing the scaffolding , frame or base . with reference to fig2 , a three way connector 1 mates three members 3 of a frame at three or four positions on the top of the device forming a substantially square or rectangular shape . a two way connector 2 mates two members 3 of a frame at three or four positions on the bottom of the device forming a substantially square or rectangular shape . thereby a scaffolding , frame or base is formed . wheels 4 are mounted onto the scaffolding , frame or base to provide a means for easy movement . pouches 5 are found present in a mesh or fabric 6 to serve as a target for collecting a ball . the mesh or fabric may be permanently affixed to the scaffolding , frame or base or temporarily affixed thereto , such as , for instance draped over or encasing the scaffolding , frame or base . the rear extent or surface of the pouches 7 may define a substantially arc shaped aperture to allow passage of a ball from one pouch to another or to a bottom surface for easy collection . with reference to fig3 b , a three way connector 1 mates three members 3 of a frame at three or four positions on the top of the device forming a substantially square or rectangular shape . with reference to fig3 a a two way connector 2 , or optionally a second three way connector 1 , mates two members 3 of a frame at three or four positions on the bottom of the device forming a substantially square or rectangular shape . with reference to fig4 , wheels 4 are mounted onto the scaffolding , frame or base to provide a means for easy movement . a wheel 4 may be attached to , connected to or affixed to members 3 of a frame at three or four positions on the bottom of the device . optionally , the wheel 4 may be attached to , connected to or affixed to a member 3 of a frame at three or four positions on the bottom of the device . optionally , the wheel 4 may be attached to , connected to or affixed to a three way connector 1 or a two way connector 2 . the wheel 4 may engage the scaffolding , frame or base by a connecting means such as a u bolt 10 that may engage a base 11 via a connecting member 9 . the assembly of the connecting means such as a u bolt 10 engaging a base 11 via a connecting member 9 may be secured by a securing means such as a bolt 12 . with reference to fig5 a a side view and 5 b a front or rear view , the wheels 4 are engaged with or connected to a base 11 , such as with the assembly depicted in fig4 . with reference to fig6 , a pouch 13 is formed . the rear extent or surface 7 of the pouch 5 may define a substantially arc shaped aperture to allow passage of a ball from one pouch to another or to a bottom surface for easy collection . the pouch 5 may be supported by a cross bar 13 made of aluminum , plastic or any suitable material for the scaffold , frame or base . the cross bar 13 may engage , be connected to or continuous with the members 3 of the scaffold , frame or base . the pouch 5 may be adapted so as to extend around , encase or rely upon the crossbar 13 for support . as best seen in reference to fig1 and 2 , a free - standing scaffolding , frame or base forming a goal is illustrated . the scaffolding , frame or base may be constructed of a plurality of frame members in the form of pipes or tubing . the frame members can be provided from a variety of materials and may include materials such as aluminum , plastic , plastic metal , wood , fiberglass , or composite materials . such materials may be provided in a variety of shapes . for instance , the frame elements may be selected from the above materials and have a structural shape of a rectangular , triangular , square , round , or other design or combinations of structural designs and which offer sufficient strength , durability , resilience , and desired weight . the horizontal scaffolding , frame or base members 3 are combined to form a substantially square or rectangular top which is positioned parallel to and above a substantially square or rectangular bottom . two , three or four horizontal scaffolding , frame or base members 3 may define the bottom of the scaffolding , frame or base . the top and bottom are connected by at least three , preferably four and in some embodiments more than four vertical scaffolding , frame or base members 3 . as seen in reference to fig1 and 2 , the horizontal scaffolding , frame or base members 3 are joined at substantially right angles to corresponding vertical scaffolding , frame or base members 3 . as seen in reference to fig1 , and 6 , a mesh or fabric covering 6 , preferably in the form of a conventional net material such as a nylon or synthetic netting commonly employed in a conventional soccer goals or driving ranges is attached to or suspended over or substantially encases the scaffolding , frame or base . the mesh or fabric covering 6 may be permanently or temporarily attached to or affixed to the scaffolding , frame or base , such as with a fastening means or with stitches or it may be sewn in such a shape as to be readily draped over the scaffolding , frame or base . in some embodiments , the mesh or fabric 6 may be attached by hook - and loop - type fabric strips , snaps , or tied with string or tie - wraps or the like . in preferred embodiments , it is sewn in such a fashion that allows removing the top scaffolding , frame or base members 3 so that the mesh or fabric may then be secured around the vertical scaffolding , frame or base members 3 . the top scaffolding , frame or base members 3 may then be placed through a corresponding pocket of the mesh or fabric on the top of the device and secured into the appropriate two way connectors 2 or three way connectors 1 . in such embodiments , in preferred embodiments one or more cross bars 13 may be secured by attachment to one or more vertical scaffolding , frame or base members 3 to support one or more pouches 5 . the cross bars 13 are preferably placed on a front surface of the scaffolding , frame or base . the mesh or fabric covering 6 is preferably presewn as one piece designed to affix to or drape over the scaffolding , frame or base . the pouches 5 are preferably sewn , glued or affixed such as , for example , by a snap or fastener , to the mesh or fabric covering and form a part thereof . the mesh or fabric covering 6 may be formed of any suitable commercially available mesh material , such as , for instance , those appropriate for soccer goals or driving ranges . in some embodiments , the open spaces of the mesh are about ¼ ″, ½ ″, ¾ ″, ⅞ ″, 1 ″, 1¼ ″, 1½ ″, 1¾ ″, 2 ″ or 2½ ″ in size . especially preferred is about ⅞ ″ to about 1¾ ″ in size . the mesh or fabric may be made of any suitable material such as , for instance , nylon , rayon , cotton , fiber , hemp , polypropylene or wool . the resulting elastic properties of the mesh or fabric 6 provide for a resiliency to the pouches 5 which facilitates the retention of balls within the pouches 5 . in some embodiments , fasteners such as in the form of a stake or in the form of a suction cup may be used to secure the scaffolding , frame or base to the ground or a floor . alternatively , the scaffolding , frame or base may be supported by wheels 4 which may in some embodiments be retractable or lockable suitable for facilitating movement of the scaffolding , frame or base . additionally , it is envisioned that in some embodiments , the scaffolding , frame or base may be readily disassembled into smaller component parts or constructed in a manner which folds into a more compact shape for storage or transportation . the number of pouches 5 may be provided as is deemed appropriate to the primary goal of using the device . a plurality of pouches 5 may be equally spaced and formed on the mesh or fabric 6 . each pouch 5 may be designed so as to affix to a cross bar 13 on a back surface of the device . the number of pouches may vary according to the preferred size of the aperture allowing passage of the ball into the pouch 5 or according to the intended use of the device . for instance , there may be only 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , or 10 or more pouches 5 . a substantially arc surface of the back surface of the pouches 7 may be present on the pouch 5 so as to connect to or affix to a back surface of the device . the substantially arc surface 7 is of an appropriate size so as to define an aperture in the pouch so that a ball of the desired size , such as , for instance , 1 ″, 2 ″, 3 ″, 4 ″, 5 ″, 6 ″, or even 12 ″ or 18 ″ or 24 ″ in diameter may pass through thereby allowing a ball to descend from one pouch 5 to another pouch 5 until it reaches the bottom of the mesh or fabric 6 . the bottom of the mesh or fabric 6 in turn defines a substantially solid piece without a substantially arc surface 7 thereby preventing further movement of a ball to the floor or ground . as a result , a ball may be easily retrieved from the device . the mesh or fabric 6 can optionally have a strike zone or target woven into the mesh or fabric 6 within a pouch 5 . bright or colored materials that contrast with the mesh or fabric 6 and background can be used . the present invention provides a device having several unique uses . the device may be used by an individual or a team . the device provides a useful training tool where a soccer player may practice precise placement of kicks within the various pouches 5 defined by the mesh or fabric 6 and the device . likewise , the device provides a useful training tool where a baseball or softball player may practice throwing or batting a ball within the various pouches 5 defined by the mesh or fabric 6 and the device . similarly , the device provides a useful training tool where a football player may practice throwing or kicking a ball within the various pouches 5 defined by the mesh or fabric 6 and the device . the device may be used by having players either kick , throw , bat , propel by stick or bounce a ball with the aim of trying to have the ball captured in one of the pouches 5 . the shape and dimensions of the device and mesh or fabric 6 may be varied depending upon the particular ball game it is designed for , the available playing space as well as variations in size to accommodate variations in the ages and skill levels of players . for instance , a smaller size which may include a fewer number of pouches 5 may be developed for use in a garage or small gymnasium . larger sizes may be used with more spacious indoor arrangements or use in a larger playing field or stadium . accordingly , the present invention envisions that differences in relative sizes , number of pouches 5 , and dimensions may be used in keeping with the present invention . additionally , the device may be constructed to allow for disassembly or folding to assist in transportation and storage . in some embodiments , the device is at least about 4 ′ tall , 5 ′ tall , 6 ′ tall , 7 ′ tall , 8 ′ tall , 9 ′ tall , 10 ′ tall or even 15 ′ or 20 ′ tall if desired . especially preferred are devices in the 7 ′- 9 ′ tall range . in some embodiments , the device is at least about 1 ′ wide , 2 ′ wide , 3 ′ wide , 4 ′ wide , 5 ′ wide , 6 ′ wide , 10 ′ wide or even 15 ′ or 20 ′ wide if desired . especially preferred are devices in the 2 ′- 3 ′ wide range . one or more additional transverse supports may be provided for the horizontal or vertical scaffolding , frame or base members 3 . the transverse support may be provided in back , on one or more sides , on the top or on the bottom of the device . the scaffolding , frame or base is preferably formed of relatively light - weight aluminum or plastic plumbing - type materials . the parts are preferably press fit together so that they form a stable rigid framework that can be removed for compact and easy shipment . select fittings may be chemically welded to the linear supports .

the present invention provides a device designed to increase the accuracy of both the throwing , bouncing , propelling by stick and kicking of a baseball , football , lacrosse ball or soccer ball . the apparatus is constructed of a frame , for example of aluminum tubing . a net is attached to or hung over the aluminum tubing to provide a series of pouches aligned horizontally at various heights . these pouches provide target areas for a ball . the pouches may be designed to allow the ball to drop from a pouch it enters into a second pouch or to the bottom of the device for easy removal . the device is held by a base that may have wheels and may be steadied by one or more transverse supports running across the bottom or the back of the base .

referring to fig1 , there is shown in perspective assembly format a first example of the parts of the invention in which frame 1 provides the support base for the rotating and synchronizing components of the machine . right and left pedal crank assemblies 2 and 3 are each rotatably mounted on axels 20 extending from frame crossbar 22 and supported by diagonal uprights 24 and 26 . each assembly consists of a rotatable pedal support member 28 having , at the opposite end of the axel mount , a pedal mount 4 having axel 30 which is rotatably mounted in hub 32 . pedal mount 4 is attached to a timing belt sprocket 34 which rotates on pedal mount axel 30 . at the opposite end of support member 28 , a second timing belt sprocket 7 is attached to axel 20 . timing belt sprockets 7 and 34 are linked by timing belt 9 . fig7 illustrates a suitable pedal 38 attachable to pedal mount 4 . as both the right and left pedal crank assemblies 2 and 3 rotate about axels 20 , timing belts 9 will also rotate resulting in the rotation of timing belt sprockets 34 ( one turn per the revolution of each crank ) which will in turn result in the upper surface 36 of the pedal 38 always remaining in a horizontal plane . the pedal assemblies are linked together so as to provide coordinated motion of the users legs when operating the machine . two examples of such linkage arrangements are illustrated herein . the first is shown in fig1 and the additional views of the same structure in fig2 - 6 illustrating perspective , front , back , top , and side views of the entire machine ; and the second as depicted in fig7 and 8 . referring again to fig1 , left pedal crank assembly 3 is coaxially connected to sprocket gear 40 and upon rotation simultaneously turns gear 40 which is engaged with roller chain 42 which in turn engages sprocket 44 similarly connected to the right pedal crank assembly 2 . each combination sprocket gear and crank assembly , i . e ., crank 3 and gear 40 and crank 4 and gear 44 thereby function and rotate together as synchronized units . chain tensioner 5 provides an automatic adjustment for variations in the slack in chain 42 . this combination establishes the synchronization of the left and right pedal cranks additionally , sprocket 46 is coaxially mounted with and fixed to sprocket gear 44 and functions to drive roller chain 18 , which in turn rotates sprocket 16 mounted on frame 1 by shaft 13 . sprocket 48 is coaxially mounted with and fixed to sprocket gear 17 which engages and drives roller chain 50 . chain 50 engages sprocket 52 and in turn drives generator / flywheel 6 providing power for electrical displays and calculations of operational parameters as well as enhancing the smooth running of the machine . fig7 and 8 show a second structure for providing the linkage and auxiliary functions described above . in this approach , the pedal crank assemblies 56 and 58 are mounted directly on synchronizing gears 60 and 62 , which mesh thereby turning together to provide the linking function . these gears and their associated pedal crank assemblies are mounted on and directly rotate about axles 64 . the timing belt arrangement for pedal orientation operates in the same manner as that previously shown . idler gear 66 is fixed to idler shaft 68 and engages with and is rotated by meshed gears 60 and 62 . the consequent rotation of shaft 9 may be arranged to operate a generator and or flywheel , shown schematically , or any other appropriate device similar to the configuration illustrated in fig1 .

an improved structure for an exercise device having dual pedals wherein each pedal operates in a rotary manner in a vertical plane parallel to the bilateral axis of the user with each of the user &# 39 ; s feet disposed , respectively , on a different one of the dual pedals .

the above general description and the following detailed description are merely illustrative of the subject invention and additional modes , advantages and particulars of this invention will be readily suggested to those skilled in the art without departing from the spirit and scope of the invention . referring now to the figures , there is depicted a weighted exercise pant 10 having a waist section 12 , lumbar section 14 , left leg panel section 28 , right leg panel section 30 , central expansion section 16 and weights pockets 40 , 50 . the lumbar section 14 has a lumbar section right side seam 14 a , lumbar section left side seam 14 b , lumbar section upper edge 14 c , lumbar section lower edge 14 d , lumbar section outer layer 14 e , lumbar section inner layer 14 f , and a padding layer 15 a between the lumbar section outer and inner layers 14 e and 14 f . the lumbar section 14 connects at its right and left seams 14 a , 14 b to the right and left portions of the waist section 12 . the waist section , along with the lumbar section , provide the user with comfort and support . the inner and outer layers 14 f , 14 e of the lumbar section 14 are preferably constructed of a durable fabric , such as nylon , or a 2 - ply nylon . the foam layer 15 a is made of suitable foam padding materials , such as neoprene - type materials . the thickness of the foam layer 15 a can be varied , for example , one embodiment uses foam ranging between ¼ ″ to 1 ″ in thickness . preferably , the waist section 12 is also provided with an internal foam layer much like with the lumbar section 14 . the waist section 12 can be constructed of similar materials as with the lumbar section 14 . the weighted exercise pant 10 can also employ a belt 24 ( of any desired variety and width ) that can be secured to the waist / lumbar section via one or more belt loops 22 . the belt loops 22 can be sewn directly to the waist / lumbar sections , or along its lower seam 22 a ( attachment point ). the belt 24 can be tightened and secured with any suitable belt buckle or clasp 26 , such as side release buckles , contoured molding plastic buckles , tongue buckles , cam buckles , backpack buckles , strap adjuster buckles , spring buckles , d - rings , o - rings , triangle rings , triglides , tension locks , in metal or plastic . the belt 24 ( which can be of any suitable material , such as leather , nylon , polypropylene , or other durable webbing strap material , and the like ) can assist in securing support for the user around the waist and lumbar regions . in the embodiment shown , the belt 24 is depicted as an independent belt , sitting within belt loops 22 , but in other embodiments , the belt could be integral with the waist section 12 , or built into the waist section . the waist section 12 and lumbar section 14 are connected to the lower section ( leg panels 28 , 30 ) at the waist seam 32 . the waist / lumber sections 12 , 14 provide support for the pants as well by securing the pants to the user so that the weight of the pants is transferred to the hip region of the user . the exercise pants further comprise a left leg panel section 28 and a right leg panel section 30 joined together medially by a central expansion section 16 . preferably , the leg panels 28 , 30 , are constructed of a durable , light - weight fabric such as 2 - ply nylon . to permit some flexibility in the design , the central expansion section is preferably constructed of a stretch - type material or fabric , such as spandex , or the “ lycra ” brand of stretch material . the central expansion section 16 comprises a central expansion section left seam front top 16 a , a central expansion section right seam front top 16 b , a central expansion section left seam rear top 16 c , a central expansion section right seam rear top 16 d , a central expansion section left seam 16 e , a central expansion section right seam 16 f , a central expansion section crotch section 16 g , a central expansion section front top edge 16 h and a central expansion section rear top edge 16 i . the central expansion section right seam 18 and central expansion section left seam 20 connect the central expansion section 16 to the respective right and left leg panels 30 , 28 . in one embodiment , the central expansion section front top edge 16 h ( the distance between seam tops 16 a and 16 b ) is narrower than the central expansion section rear top edge 16 i ( the distance between seam tops 16 c and 16 d . in the embodiment shown in fig1 , the waist section 12 terminates above the respective central expansion section left seam front top 16 a and right seam front top 16 b , thereby leaving a gap in the waist section above the central expansion section front top edge . in other embodiments , the waist section 12 could extend across the top of central expansion section front top edge . the left leg panel 28 may be of unitary construction or constructed from a number of separate panels or sections joined by left leg panel seams 29 . similarly , the right leg panel 30 may be of unitary construction or constructed from a number of separate panels or sections joined by right leg panel seams 31 . the right leg panel lower edge 33 and left leg panel lower edge 34 can be modified to include additional elastic or stretch material , or otherwise be a hemmed edge . it is preferred that the length of the leg panels are such that edges 33 and 34 fall above the user &# 39 ; s knees . each leg panel is further equipped with a permanently attached weight pocket . more particularly , the right side leg panel 30 further comprises a right side weights pocket 40 having a plurality of weight sleeves 44 integral to the right side weights pocket 40 . a right side pocket sleeve seam 40 e may be employed to separate adjacent sleeves 44 . at the top of each sleeve 44 is an opening capable 44 a of receiving one or more weights 60 . above the openings is a right side weight pocket flap 42 having a right side weight pocket flap upper edge seam 42 a , a right side weight pocket flap front inside edge 42 b , a right side weight pocket flap rear inside edge 42 c , and a right side weight pocket flap lower edge 42 d . the right side weights pocket 40 also has a right side pocket upper edge 40 a , right side pocket front inner edge 40 b , right side pocket rear inner edge 40 c , right side pocket lower edge 40 d , and right side pocket sleeve seam 40 e . similarly , the left side leg panel 28 further comprises a left side weights pocket 50 having a plurality of weight sleeves 54 integral to the left side weights pocket 50 . a left side pocket sleeve seam 50 e may be employed to separate adjacent sleeves 54 . at the top of each sleeve 54 is an opening 54 a capable of receiving one or more weights 60 . above the openings 54 a is a left side weight pocket flap 52 having a left side weight pocket flap upper edge seam 52 a , a left side weight pocket flap front inside edge 52 b , a left side weight pocket flap rear inside edge 52 c , and a left side weight pocket flap lower edge 52 d . the left side weights pocket 50 also has a left side pocket upper edge 50 a , left side pocket front inner edge 50 b , left side pocket rear inner edge 50 c , left side pocket lower edge 50 d , and left side pocket sleeve seam 50 e . in a preferred embodiment , the weight pockets 40 , 50 contain a layer of padding 15 b to serve as a cushion or shock absorber between the user &# 39 ; s legs and the weights 60 . the pocket padding 15 b can also serve to provide some stability to the weight pockets 40 , 50 and to provide increased comfort to the user . the pocket construction can be varied . for example , referring to fig9 , the pocket member contains a pocket backing material 43 that is sewn on or otherwise fixably attached to the pants leg panel . in one embodiment , foam padding 15 a is placed between the pocket backing material and the pants panel , and then the pocket backing is sewn or fixably attached to the pant leg . in another embodiment , such as shown in fig8 , the foam padding 15 a could be attached in its own enclosure 43 a to the back of the pocket backing material 43 prior to the pocket being attached to the pant leg panel . in another embodiment , shown in fig1 , a weight pocket design 70 is shown employing a plurality of weight sleeves 74 separated by seams 70 e . each weight sleeve 74 comprises a stretchable fabric tube containing a slit 72 capable of receiving into it one or more weights 60 . the weights , once inserted through the slits 72 , sit within the interior tube space 71 . this weight pocket design 70 could be employed on the weighted exercise pants device 10 discloses herein by affixing the plurality of weight sleeves 74 onto the face of the pant leg panels so that the slits 72 fact outward to permit the user to add or subtract weights from the exercise pants without the need to remove them . the various seams , 50 c , 50 d , 50 e can be single stitched , but are preferably double stitched for added strength . the weights 60 used in connection with the present disclosure can be any suitable weight . in a preferred embodiment , the weights 60 comprise small bags filled with dense granular material such as steel shot or sand , in amounts of desired weight , such as 1 lb or 2 lb bags . in another embodiment , the weights could be rubber coated iron ( or other metal ) bars . in yet another embodiment , the weights could be a flexible , dense weight bar material such as that described above by cook . in one embodiment , the exercise pants are outfitted with 6 weight sleeves , with each sleeve capable of receiving up to 2 lbs of weight , but other variations are possible . additionally , the weight pocket flaps 42 , 52 may be outfitted with various enclosures ( not shown ), if desired , to secure the flap down over the top of the weight sleeve openings . for example , various enclosure devices could be used , such as , a hook and loop fastener ( such as sold under the “ velcro ” trademark ), a snap , a zipper , a clasp , a button , or other suitable fastener . in a preferred embodiment , the weight pockets 40 , 50 extend around approximately ¾ of the circumference of each respective pant leg panel 30 , 28 , respectively , so that there are no weights protruding in the zone between adjacent legs beneath the central expansion section crotch region 16 g . with this design , there is sufficient space between , e . g ., the right side pocket flap inner edges 40 b and 40 c , and the left side pocket flap inner edges 50 b and 50 c to reduce the potential for chafing caused by weights from opposite legs rubbing against each other . additionally , the hockey pants structures described herein could be modified to advantage by adding weight pocket members , such as those disclosed herein , to the external surface of such hockey pants . these modified hockey pants could be further modified to remove impact protection pads . the adjustable weight exercise pants of the present disclosure can be used by any person , regardless of whether the person is at a beginner , intermediate , or advanced workout or fitness level . the exercise pants can be used in any level of physical activity ranging from walking to sprinting , specific sports practices ( such as , for example , basketball , football , hockey , tennis , volleyball , baseball , cycling , soccer ), hiking , skating , biking , skating , stationary biking , treadmill workouts , stair or stepper workouts , core workouts , etc . the ability to easily adjust the amount of weight carried in the exercise pants provides great flexibility in tailoring the exercise pants to the desired level of weight . the desired level of weight can depend on any number of factors , including , the level of fitness of the person using the pants and the type of workout desired , and can be easily increased or decreased during use . additionally , the added weight increases the work intensity and resistance therefore burning more calories even while walking or doing simple household chores . the comfortable and fitted design makes it easy to wear and the increased weight helps tone and sculpt core muscles as well as legs and buttocks . the exercise pants can be used while engaging in regular workouts ( squats , leg lifts , push - ups ) as well as , spinning and running . the unique sleek design of the exercise pants can also assist in correcting a person &# 39 ; s running form . this specification is to be construed as illustrative only and is for the purpose of teaching those skilled in the art the manner of carrying out the invention . it is to be understood that the forms of the invention herein shown and described are to be taken as the presently preferred embodiments . as already stated , various changes may be made in the shape , size and arrangement of components or adjustments made in the steps of the method without departing from the scope of this invention . for example , equivalent elements may be substituted for those illustrated and described herein and certain features of the invention may be utilized independently of the use of other features , all as would be apparent to one skilled in the art after having the benefit of this description of the invention . further modifications and alternative embodiments of this invention will be apparent to those skilled in the art in view of this specification .

the present disclosure pertains generally to exercise clothing , and more specifically , to weighted exercise pants . a weighted exercise pants system is disclosed employing weighted leg panels joined by a stretch fabric central expansion section . the weight pocket systems employ a plurality of weight sleeves capable of removably receiving one or more weights . the weighted exercise pants of the present disclosure can be used for strengthening muscles in a manner specific to the way the muscles are used in a particular sport , for other types of exercise , or for strength development , speed training , over - speed training and plyometric training .

the following is a detailed description of the preferred embodiments of the present invention . the description is meant to describe preferred embodiments , and is not meant to limit the invention in any way . various stent types and stent constructions may be employed in the invention . among the various stents useful include , without limitation , self - expanding stents and balloon expandable extents . the stents may be capable of radially contracting , as well , and in this sense can best be described as radially distensible or deformable . self - expanding stents include those that have a spring - like action which causes the stent to radially expand , or stents which expand due to the memory properties of the stent material for a particular configuration at a certain temperature . nitinol is one material which has the ability to perform well while both in spring - like mode , as well as in a memory mode based on temperature . other materials are of course contemplated , such as stainless steel , platinum , gold , titanium and other biocompatible metals , as well as polymeric stents . the configuration of the stent may also be chosen from a host of geometries . for example , wire stents can be fastened into a continuous helical pattern , with or without a wave - like or zig - zag in the wire , to form a radially deformable stent . individual rings or circular members can be linked together such as by struts , sutures , welding or interlacing or locking of the rings to form a tubular stent . tubular stents useful in the present invention also include those formed by etching or cutting a pattern from a tube . such stents are often referred to as slotted stents . furthermore , stents may be formed by etching a pattern into a material or mold and depositing stent material in the pattern , such as by chemical vapor deposition or the like . the present invention provides a stent / graft composite endoluminal prostheses 22 shown in fig5 including a stent 2 of the type shown in fig1 secured to a tubular graft 16 of the type shown in fig4 . an improved method of forming such composite structure in accordance with the present invention includes providing a an adhesive bond between stent 2 and graft 16 by use of a polymeric coating 14 on stent 2 as shown in fig2 . referring specifically to fig1 and 2 of the drawings , one type of stent which may be included in the composite endoluminal prosthesis of the present invention is shown . stent 2 is formed from an elongate wire 4 which is helically wound with a plurality of longitudinally spaced turns into an open tubular configuration . stent 2 is an expandable tubular member which may be either of the balloon - expandable or self - expandable type . as previously discussed , one type of self - expanding stent may be formed of a shaped memory material such as nitinol . the elongate helically wound wire 4 forming stent 2 defines successive upper wave - like peaks 10 and lower wave - like peaks 12 . wire 4 is wound into a specific configuration where upper peaks 10 are placed adjacent to lower peaks 12 of the next adjacent winding . in order to effectively form the composite endoluminal prosthesis of the present invention , stent 2 is coated with polymeric coating 14 . polymeric coating 14 is a biocompatible material , desirably ptfe . polymeric coatings useful in the present invention include those biocompatible materials which are capable of adhering to ptfe grafts and desirably eptfe grafts . among those coatings contemplated are polytetrafluoroethylene ( ptfe ), expanded ptfe ( eptfe ), polyurethane , fluorinated ethylene propylene ( fep ), silicone , polyurethane - acrylate , silicone - acrylate , urethanesilicone , and the like . combinations of these polymers may also be useful . portions of the stent may also be coated with different polymers . one particularly desirable form of polymer coating is one formed by polymeric particles or powder . ptfe powder coatings have been found to be especially useful in the present invention since these coatings bond well under heat and pressure to eptfe tubular grafts . other coatings are contemplated , however , and can include those which can flow into the porous structure of the graft or which are capable of bonding to ptfe or eptfe . the polymeric coating may be applied to stent 2 using a number of different techniques . two preferred examples of application of coating 14 include spraying the stent with a spray of ptfe particles or dip coating the stent in a mixture containing ptfe particles . powder coating generally refers to a variety of methods employing powdered plastics and resins which are used commercially to apply coatings to various articles . these methods include fluidized bed , electrostatic spray , electrostatic fluidized bed , plasma spray , and hot flocking , as well as combinations and variants of these methods . in the electrostatic spray process , a coating powder is withdrawn from a reservoir in an air stream and electrostatically charged in the high voltage corona field of a spray gun . the charged particles are attracted to the grounded metal object to be coated and adhere to it by electrostatic attraction . the coated substrate is then placed in an oven and the coating is fused to form a substantially continuous film . the discrete ptfe particles form a connected path around the stent . the relatively high viscosity of the ptfe melt serves to effectuate a superior coating . if the powder is sprayed on a preheated article , the powder melts and fuses directly on the hot surface ; further heating to fuse or cure the coating may be required , depending upon the type of coating powder . plasma coating is a method comprising establishing a hot temperature plasma in an inert gas such as nitrogen , and the coating powder is introduced at the periphery of the plasma . the particles melt and are propelled at high velocity to the substrate , where they form a film . in hot flocking techniques , powders are usually dispersed in air and sprayed or blown onto the preheated substrate , where they melt and form a coating . in a variant of this process , small parts are preheated and dropped into a bed of powder kept in a mobile state by vibration . in this method , the parts are completely coated with an unfused layer of powder on the surface . another method for coating the stent is to suspend stent 2 in the air , such as , on a hook , and spray the polymeric coating onto the stent according to the electrostatic spray method mentioned above . an advantage of applying the powder coating in this manner , is that it would sufficiently coat the stent in its entirety , and thus provide improved adhesion at its mating surface to the graft . referring to fig3 a desirable method for applying coating 14 to stent 6 is shown . stent 6 is shown in an expanded state , and may be supported on a mandrel 8 . mandrel 8 is a rod - like stainless steel member of diameter approximately equal to that of the expanded stent . once positioned on mandrel 8 , stent 6 is polymeric coated with coating 14 . ptfe polymeric coating 14 desirably forms a thin film on the wire . the thickness of the ptfe coating generally ranges from about 1 to about 100 microns . coated stent 6 can then be removed from mandrel 8 tubular graft 16 to form the composite structure , or left on mandrel 8 and tubular graft 16 placed thereover . assembly of the stent / graft prosthesis includes the steps to positioning the graft either on the outside or the inside of the stent and using the combination of heat and pressure sufficient to adheringly assemble the components together . tubular graft material can be used on both the interior and exterior of the tubular stent , as well . the graft may be a continuous tube , or may be formed with discontinuous sections . tubular wrapping in a helical pattern is also contemplated . as shown in fig2 the entire stent may be coated with polymeric coating 14 . it is further contemplated , however , that the stent may be partially coated with the polymeric coating at selected regions ( fig6 ) for purposes which will be described in detail hereinbelow . referring now to fig4 graft 16 is a tubular structure of conventional construction formed of eptfe . graft 16 may be extruded as a tube or may be formed from an extruded sheet which is subsequently formed into a tubular structure . textile or fabric constructions formed of ptfe or eptfe yams , filaments or mesh may also be employed . fig5 shows a perspective of a composite endoluminal prosthesis 22 comprised of stent 6 with polymeric coating 14 , which circumferentially encloses eptfe graft 16 . the ptfe polymeric coating provides a bonding interface between the stent wire and the graft 16 . the coated stent 6 is bonded to graft 16 by sintering the composite structure over a suitable mandrel such as , for example , mandrel 8 ( fig3 ). it is further contemplated that this bonding interface may be enhanced by first coating the stent with the ptfe polymeric coating , then less than fully sintering the ptfe coating on stent 6 . by sintering stent 6 less than fully , i . e . only partially sintering , the stent can then be placed on the eptfe tubular graft 16 and sintered again over the mandrel . the subsequent sintering of the partially sintered coating 14 on graft 16 serves to increase bonded interface between graft 16 and stent 6 . referring to fig6 a further embodiment of the present invention is shown . a composite intraluminal prosthesis 24 is shown including an eptfe graft 16 , circumferentially enclosed by a partially coated polymeric stent 26 . the composite structure may be assembled as described above . in this embodiment of the present invention , stent 26 is partially coated with ptfe coating 14 at areas intermediate of the undulations in the stent . by partially coating stent 6 , the upper and lower wave - like peaks 10 , and 12 respectively , are subsequently left exteriorly exposed without ptfe coating . this embodiment provides the composite graft with increased flexibility as the unexposed peaks do not readily bond to the graft . this provides multiple points of flexure throughout the length of the composite prosthesis 22 . the particular wire stent 6 of fig1 - 6 is shown as merely one example . other stent configurations , as discussed above , may be employed . for example , fig7 shows another stent configuration which may be used in the present invention is shown . stent 30 may be the type more fully described in u . s . pat . no . 4 , 733 , 665 , and is herein incorporated by reference . stent 30 is an expandable and deformable tubular structure including a plurality of longitudinally extending parallel struts 31 connected to one another by transverse tabs 34 . the struts 31 and tabs 34 define slots 32 which define open spaces 35 through the tube . this stent construction not only ensures patency and flexibility with the slotted configuration , but the configuration of slots and tabs would allow for a partially covered polymeric coating with increased flexibility as shown in fig6 . stent 30 fully or partially coated as described above is subsequently bound to a tubular graft 16 ( fig4 ) in a manner described above to form a composite endoluminal prosthesis 22 . various modifications and changes may be made without departing from the spirit and intent of the invention and all such changes are intended to be included in the following claims .

a tubular intraluminal prosthesis includes a ptfe or eptfe tubular structure such as a graft , and a tubular diametrically deformable stent circumferentially surrounding the tubular structure . the diametrically deformable stent includes a polymeric coating which allows for attachment to the tubular graft structure and enhances the biocompatibility and integrity of the composite prosthesis .

referring now to the drawings , and in particular fig1 a preferred embodiment of the free - standing rack assembly of the present invention is generally indicated at 10 . the free - standing rack assembly 10 includes a plurality of divider members 12 . each divider member 12 has a first end 14 and a second end 16 . the divider members 12 , preferably , are disposed in a parallel orientation . as shown more clearly in fig2 each divider member 12 includes a first horizontally extending portion 18 adjacent the first end 14 , a first generally vertically extending portion 20 adjacent the first horizontally extending portion 18 , a second generally horizontally extending portion 22 adjacent the first generally vertically extending portion 20 , and a second generally vertically extending portion 24 adjacent the second generally horizontally extending portion 22 and adjacent the second end 16 . in an alternate embodiment a stabilizing member 25 shown in phantom lines extends between the second end 16 and the corresponding first horizontally extending portion 18 of each divider member 12 . referring back to fig1 the free - standing rack assembly 10 includes a base member 26 which is connected to the first end 14 of each divider member 12 . a base member 28 is connected to the second end 16 of each divider member 12 and extends parallel to the base member 26 . in addition , the base member 26 and the base member 28 extend perpendicular to a plane defined by each divider member 12 . a support member 30 is connected to each divider member 12 at a point 31 that is intermediate of the first end 14 and the second end 16 thereof . as shown more clearly in fig2 the support member 30 is connected to each divider member 12 at a point 31 which coincides with the juncture of the second generally horizontally extending portion 22 and the second generally vertically extending portion 24 . also , the support member 30 extends perpendicular to the plane of each divider member 12 and parallel to both the base member 26 and the base member 28 . in addition , a plane defined by the support member 30 and the base member 28 extends perpendicular to the plane of each divider member 12 . moreover , the plane defined by the support member 30 and the base member 28 is perpendicular to a plane defined by the base member 28 and the first horizontally extending portion 18 of each divider member 12 . as shown in fig2 the base member 26 is connected to the first end 14 of each divider member 12 so that the base member 26 is offset from the plane defined by the base member 28 and the first horizontally extending portion 18 of each divider member 12 by the thickness of the base member 26 . in addition , a plane defined by the base member 26 and the base member 28 is disposed at an obtuse angle to the plane defined by the support member 30 and the base member 28 . accordingly , and as shown in fig2 when placed on a shelf 38 having a front edge 40 , the base member 26 rests against the front edge 40 of the shelf 38 and the first horizontally extending portion 18 and second end 16 of each divider member 12 , as well as the base member 28 rest upon the surface of the shelf 38 . the base member 26 forms the leading edge of the free - standing rack assembly 10 and is flush with the level of the shelf 38 . the base member 26 also forms a lip over the front edge 40 of the shelf 38 . in this manner , the base member 26 does not interfere with the removal or insertion of items supported by the free standing rack assembly 10 . as shown more clearly in fig1 the support member 30 and the base member 28 define a back 46 and serve to limit the degree to which a book or chart 48 ( shown in phantom ) can be inserted within the free - standing rack assembly 10 . since the base member 26 is flush with the level of the shelf 38 , the shelf 38 entirely supports the weight of the supported items and the free - standing rack assembly 10 functions to maintain the supported items in an upright manner . by forming a lip over the front edge 40 of the shelf 38 , the base member 26 prevents the free standing rack assembly 10 from being dislodged from its position on the shelf 38 when a book or chart 48 is forced against the back 46 defined by the support member 30 and the base member 28 . preferably , the books or charts 48 supported by the free - standing rack assembly 10 when forced against the back of the rack 10 extend beyond the front edge 40 of the shelf 38 and beyond the base member 26 . in this manner , the weight of the supported books or charts 48 prevents the base member 26 from moving upwardly during use and dislodging the free - standing rack assembly 10 from its position on the shelf 38 . as shown in fig1 the free - standing rack assembly 10 may be assembled to yield a left assembly 32 , a middle assembly 34 , and a right assembly 36 . according to the left assembly 32 , one end of the base member 26 , the base member 28 , and the support member 30 is flush with the divider member 12 disposed at the left end of the left assembly 32 while the other end of the base member 26 , the base member 28 , and the support member 30 extends beyond the divider member 12 disposed at the right end of the left assembly 32 . according to the middle assembly 34 , both ends of the base member 26 , the base member 28 and the support member 30 extend beyond the divider member 12 located at either end of the middle assembly 34 . according to the right assembly 36 , one end of the base member 26 , the base member 28 , and support member 30 is flush with the divider member 12 disposed at the right end of the right assembly 36 while the other end of the base member 26 , the base member 28 , and the support member 30 extends beyond the divider member 12 disposed at the left end of the right assembly 36 . in this manner , and as shown in fig1 the free - standing rack assembly 10 is modularized and adapted for placement on shelves of varying length . as shown in fig3 the free - standing rack assembly 10 may be used to support books , charts , files and the like on a shelf 38 having a groove 42 which registers with the base member 26 . preferably , the base member 26 is registered within groove 42 so that the base member 26 is flush with the surface of the shelf 38 . in this manner , the first end 14 of each divider member 12 is recessed from the front edge 40 of the shelf 38 . this arrangement makes the free standing rack assembly 10 particularly adapted for use in closable cabinets . as shown in fig4 the free - standing rack assembly 10 is adapted for use on a shelf 38 which also supports a spacer 44 . the spacer 44 , preferably , has a thickness equal to the diameter or thickness of the base member 26 . in addition , the spacer 44 has a width substantially equal to the distance between the base member 26 and the second end 16 of each divider member 12 . in this manner , the shelf 38 is contacted by and supports the base member 26 , the second end 16 of each divider member 12 and the base member 28 . the books , files , charts or the like supported by the free - standing rack assembly 10 rest on the spacer 44 . the base member 26 hangs over the front edge 50 of the spacer 44 to prevent the free - standing rack assembly 10 from moving in relation to the spacer 44 when books , files , charts or the like are inserted into the free - standing rack assembly 10 and against support member 30 . it will be recognized by those of ordinary skill in the art that in the various embodiments of the free - standing rack assembly 10 of the present invention , the divider members 12 , the base member 26 , the base member 28 , the support member 30 and the stabilizing member 31 may be formed of any suitable rigid material including , but not limited to , metal wire stock , plastic or wood . for purposes of this application , the term rigid shall be understood to mean rigid and semi - rigid . it will also be recognized by those cf ordinary skill in the art that in the various embodiments of the free - standing rack assembly 10 of the present invention , the divider members 12 , the base member 26 , the base member 28 , the support member 30 and the stabilizing member 31 may be connected in the described manner by any conventional technique including , but not limited to , welding , brazing , gluing , soldering , and riveting . finally , it will be recognized by those of ordinary skill in the art that the distance between the first horizontally extending portion 18 and the second end 16 of each divider member 12 may be varied so the free - standing rack assembly 10 may be adapted to support in an upright manner books , files , charts and the like of differing sizes . while the present invention has been described in detail and with reference to specific examples thereof , it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope thereof .

a free - standing rack assembly including a plurality of dividers which is useful for supporting books , charts , files , or the like . the assembly may be placed upon an open shelf or cabinet with the shelf or cabinet bearing the weight of the supported items and the rack assembly maintaining the supported items in an upright manner .

the present invention provides methods and use of two classes of compounds having dopamine receptor activities for the treatment of rls . one class of compounds useful for treating rls in the present invention are those compounds , or pharmaceutically acceptable salts thereof , disclosed generically or specifically in u . s . pat . nos . 5 , 273 , 975 and 5 , 436 , 240 . these compounds are generically referred to as heterocyclic amines and are structurally represented by formula i , wherein : r 1 , r 2 , and r 3 are independently c ) c 3 - 7 cycloalkyl , c 4 - 10 cycloalkyl - or phenyl - substituted c 1 - 6 alkyl , or d ) r 1 and r 2 are joined to form a c 3 - 7 cyclic amine which can contain additional heteroatoms and / or unsaturation ; a ) ch , ch 2 , ch - halogen , chch 3 , c ═ o , c ═ s , c — sch 3 , c ═ nh , c — nh 2 , c — nhch 3 , c — nhcooch 3 , or c — nhcn ; illustrative preferred compounds of formula i for use in the present invention include the compound wherein d is n or nh , and n is 0 ; the compound wherein a is ch , ch 2 , chch 3 , c ═ o , c ═ s , c — sch 3 , c ═ nh , c — nh 2 , c — nhch 3 , c — nhcooch 3 , or c — nhcn ; and the compound wherein a is ch or c ═ o . an especially suitable compound of formula i in the present invention is a compound of formula ia , the name of the compound of formula ia is ( r )- 5 , 6 - dihydro - 5 -( methylamino )- 4h - imidazo [ 4 , 5 , 1 - ij ]- quinolin - 2 ( 1h )- one ( uninverted cas name ) or ( 5r )- 5 -( methylamino )- 5 , 6 - dihydro - 4h - imidazo [ 4 , 5 , 1 - ij ] quinolin - 2 ( 1h )- one ( generated by acd / name software ). another especially suitable compound of formula i in the present invention is the maleate salt of the compound of formula ia , and is represented by formula ib : the name of the compound of formula ib is ( r )- 5 , 6 - dihydro - 5 -( methylamino )- 4h - imidazo [ 4 , 5 , 1 - ij ]- quinolin - 2 ( 1h ) one ( z )- 2 - butenedioate ( 1 : 1 ) or ( 5r )- 5 -( methyamino )- 5 , 6 - dihydro - 4h - imidazo [ 4 , 5 , 1 - ij ] quinolin - 2 ( 1h )- one maleate . another group of compounds within the generic formula i shown above are selected heterocyclic amine compounds wherein a is c ═ s ; the most preferred being , ( 5r )- 5 -( methylamino )- 5 , 6 - dihydro - 4h - imidazo [ 4 , 5 , 1 - ij ] quinoline - 2 ( 1h )- thione , a compound of the formula ic below , also referred to herein as the compound of formula viii . and pharmaceutically acceptable salts thereof . it is preferred that ( 5r )- 5 -( methylamino )- 5 , 6 - dihydro - 4h - imidazo [ 4 , 5 , 1 - ij ] quinoline - 2 ( 1h )- thione ( ix ) be present as a pharmaceutically acceptable salt . the pharmaceutically acceptable salts are preferred over the corresponding free amines since they are more water soluble and more crystalline . pharmaceutically acceptable salts include salts of both inorganic and organic acids . the preferred pharmaceutically acceptable salts include salts of the following acids hydrochloric , hydrobromic , sulfuric , phosphoric , nitric , citric , methanesulfonic ch 3 —( ch 2 ) n1 — cooh where n 1 is 0 thru 4 , hooc —( ch 2 ) n 1 - cooh where n is as defined above , hooc — ch ═ ch — cooh , φ - cooh . for other acceptable salts , see int . j . pharm ., 33 , 201 - 217 ( 1986 ). it is more preferred that ( 5r )- 5 -( methylamino )- 5 , 6 - dihydro - 4h - imidazo [ 4 , 5 , 1 - ij ] quinoline - 2 ( 1h )- thione be present as the maleate salt , which is ( 5r )- 5 -( methylamino )- 5 , 6 - dihydro - 4h - imidazo [ 4 , 5 , 1 - ij ] quinoline - 2 ( 1h )- thione maleate . the maleate salt is shown below as formula id or formula ix . the heterocyclic amines , processes for making them , and methods for preparing medicaments from them are disclosed in u . s . pat . nos . 5 , 273 , 975 and 5 , 436 , 240 , herein incorporated by reference . while u . s . pat . no . 5 , 273 , 975 generically discloses and claims ( 5r )- 5 -( methylamino )- 5 , 6 - dihydro - 4h - imidazo [ 4 , 5 , 1 - ij ] quinoline - 2 ( 1h )- thione , it neither contains an example of nor specifically mentions this compound . ( 5r )- 5 -( methylamino )- 5 , 6 - dihydro - 4h - imidazo [ 4 , 5 , 1 - ij ] quinoline - 2 ( 1h )- thione ( viii ) is preferably made from the corresponding non - thio analog , ( 5r )-( methylamino )- 5 , 6 - dihydro - 4h - imidao ( 4 , 5 , 1 - ij ) quinolin -( 2h )- one ( vii ). a preferred process of making ( 5r )-( methylamino )- 5 , 6 - dihydro - 4h - imidao ( 4 , 5 , 1 - ij ) quinolin -( 2h )- one ( vii ) is illustrated in preparation 1 and examples 1 - 6 , and is schematically shown in chart a . a preferred method of transforming ( 5r )-( methylamino )- 5 , 6 - dihydro - 4h - imidao ( 4 , 5 , 1 - ij ) quinolin -( 2h )- one ( vii ) into ( 5r )- 5 -( methylamino )- 5 , 6 - dihydro - 4h - imidazo [ 4 , 5 , 1 - ij ] quinoline - 2 ( 1h )- thione ( vii ) is set forth in example 7 . a preferred method of transforming ( 5r )- 5 -( methylamino )- 5 , 6 - dihydro - 4h - imidazo [ 4 , 5 , 1 - ij ] quinoline - 2 ( 1h )- thione ( viii ) into ( 5r )- 5 -( methylamino )- 5 , 6 - dihydro - 4h - imidazo [ 4 , 5 , 1 - ij ] quinoline - 2 ( 1h )- thione maleate ( ix ) is set forth in example 8 . another class of compounds useful in the present invention are those compounds , or pharmaceutically acceptable salts thereof , disclosed generically or specifically in u . s . pat . nos . 5 , 594 , 024 and 5 , 462 , 947 , both incorporated by reference herein . these compounds are generically referred to as substituted phenylazacycloalkanes and are structurally represented by formula ii , wherein : r 1 and r 2 are independently h ( provided only one is h at the same time ), — oh ( provided r 4 is other than hydrogen ), cn , ch 2 cn , 2 - or 4 - cf 3 , ch 2 cf 3 , ch 2 chf 2 , ch ═ cf 2 , ( ch 2 ) 2 cf 3 , ethenyl , 2 - propenyl , oso 2 ch 3 , oso 2 cf 3 , sso 2 cf 3 , cor 4 , coor 4 , con ( r 4 ) 2 , so x ch 3 ( where , x is 0 - 2 ), so x cf 3 , o ( ch 2 ) x cf 3 , so 2 n ( r 4 ) 2 , ch ═ nor 4 , cocoor 4 , cocoon ( r 4 ) 2 , c 1 - 8 alkyls , c 3 - 8 cycloalkyls , ch 2 or 4 , ch 2 ( r 4 ) 2 , nr 4 so 2 cf 3 , no 2 , halogen , a phenyl at positions 2 , 3 or 4 , thienyl , furyl , pyrrole , oxazole , thiazole , n - pyrroline , triazole , tetrazole or pyridine ; r 3 is hydrogen , cf 3 , ch 2 cf 3 , c 1 - c 8 alkyl , c 3 - c 8 cycloalkyl , c 4 - c 9 cycloalkyl - methyl , c 2 - c 8 alkenyl , c 2 - c 8 alkynyl , 3 , 3 , 3 - trifluoropropyl , 4 , 4 , 4 - trifluorobutyl , —( ch 2 ) m — r ( where m is 1 - 8 ), ch 2 sch 3 or a c 4 - c 8 alkyl bonded to said nitrogen and one of its adjacent carbon atoms inclusive to form a cyclic structure ; r 4 is independently hydrogen , cf 3 , ch 2 cf 3 , c 1 - c 8 alkyl , c 3 - c 8 cycloalkyl , c 4 - c 9 cycloalkyl - methyl , c 2 - c 8 alkenyl , c 2 - c 8 alkynyl , 3 , 3 , 3 - trifluoropropyl , 4 , 4 , 4 - trifluorobutyl , —( ch 2 ) m — r 5 where m is 1 - 8 ; r 5 is phenyl , phenyl ( substituted with a cn , cf 3 , ch 2 cf 3 , c 1 - c 8 alkyl , c 3 - c 8 cycloalkyl , c 4 - c 9 cycloalkyl - methyl , c 2 - c 8 alkenyl , c 2 - c 8 alkynyl ), 2 - thiophenyl , 3 - thiophenyl , — nr 6 conr 6 r 7 , or — conr 6 r 7 ; r 6 and r 7 are independently hydrogen , c 1 - c 8 alkyl , c 3 - c 8 cycloalkyl , c 4 - c 9 cycloalkylmethyl , c 2 - c 8 alkenyl or c 2 - c 8 alkynyl ; and with the proviso that when r 1 is 2 - cn or 4 - cn , r 2 is h , r 3 is n - pr and n is 1 or 3 then such compound is a pure enantiomer . also useful in the present invention are the pharmaceutically acceptable salts of compounds of formula ii above . preferred compounds of formula ii for use in the present invention include : the compound wherein said r 1 is cn ; the compound wherein r 2 is h and r 3 is n - propyl ; the compound wherein said r 1 is an — oso 2 cf 3 ; the compound wherein r1 is so 2 ch 3 ; the compound wherein r 2 is h and r 3 is a c 1 - 8 alkyl ; the compound wherein said n is 2 ; the compound wherein r 1 is 3 - oh , r 2 is h , r 3 is n - propyl and r 4 is a c 1 - 8 alkyl ; and the compound wherein n is 0 . a particularly suitable compound of formula ii in the present invention is ( 3s )- 3 -[ 3 -( methylsulfonyl ) phenyl ]- 1 - propylpiperidine hydrochloride ( uninverted cas name ) or osu 6162 or ( 3s )- 3 -[ 3 -( methylsulfonyl ) phenyl ]- 1 - propylpiperidine hydrochloride ( generated by acd / name software ), and is represented by formula iia : another particularly suitable compound of formula ii in the present invention is ( 3s )- 3 -[ 3 -( methylsulfonyl ) phenyl ]- 1 - propylpiperidine hydrobromide ( uninverted cas name ) or ( 3s )- 3 -[ 3 -( methylsulfonyl ) phenyl ]- 1 - propylpiperidine hydrobromide ( generated by acd / name software ), and is represented by formula iib : yet another particularly suitable compound of formula ii in the present invention is ( 3s )- 3 -[ 3 - methylsulfonyl ) phenyl ]- 1 - propylpiperidine ( 2e )- 2 - butenedioate ( 1 : 1 ) ( uninverted cas name ) or ( s )- osu6162 , and is represented by formula iic : the substituted phenylazacycloalkanes , processes for making them and methods for preparing medicaments from them are disclosed in u . s . pat . nos . 5 , 462 , 947 and 5 , 594 , 024 , herein incorporated by reference . conventional pharmaceutical preparations of the heterocyclic amines and of the substituted phenylazacycloalkanes can be used , e . g ., consisting essentially of an inert pharmaceutical carrier and an effective dose of the active substance ; e . g ., plain or coated tablets , capsules , lozenges , powders , solutions , suspensions , emulsions , syrups , suppositories , transdermal patch , etc . tablets are preferred . the effective dose range for the compounds of formula i is about 0 . 1 to 50 mg / day . more specifically , the effective dose range for compounds of formula i wherein a is c ═ o is 1 to 50 mg / day , and often more than 1 mg will be administered to a patient per administration and per day , and preferably between 4 to 10 mg / day . for compounds of formula i wherein a is c ═ s , the effective dose range is 0 . 4 to 10 mg / day and often more than 0 . 4 will be administered to a patient per administration and per day , and preferably between 1 . 6 to 10 mg / day . the effective dose range for the compounds of formula ii is about 10 to 100 mg / day and often more than 10 mg will be administered to a patient per administration and per day , and preferably between 15 to 40 mg / day and most preferably 20 to 30 mg / day . while the above dosage levels for the heterocyclic amines compounds and for the substituted phenylazacycloalkanes indicate mg / day , and typically they may be given once or twice a day , surprisingly , they may be given in these dosages on a less than daily basis . while the drugs may be given once a day or twice a day , they might only be given three times a week , two times a week or even once a week for some patients . for less than daily dosing the tablet size or amount of administration of drug can vary and the mg of drug administered per patient may in fact be the mg / day dose suggested above . when given on a daily or less frequent schedule , the daily dosages mentioned here would be given only for the day of administration . patients with milder forms of the disease would be expected to need less drug . patients with more severe forms of the disease and those who have been treated with other dopaminergic agents may be expected to need more drug . providing patients do not experience intolerable side effects , the dosage should be titrated to achieve a maximal therapeutic effect . dosages should be increased gradually . the precise dosage for the heterocyclic amines compounds and for phenylazacycloalkanes would be determined by the treating physician evaluating such factors as the progression of the state of the disease , the weight and age of the patient , whether and what extent other drugs such as l - dopa or levodopa were administered , and other such factors as are typically evaluated by a physician before determining the dosage of a cns drug to be administered to a patient . the definitions and explanations below are for the terms as used throughout this entire document including both the specification and the claims . chromatography ( column and flash chromatography ) refers to purification / separation of compounds expressed as ( support , eluent ). it is understood that the appropriate fractions are pooled and concentrated to give the desired compound ( s ). cmr refers to c - 13 magnetic resonance spectroscopy , chemical shifts are reported in ppm ( δ ) downfield from tms . ms refers to mass spectrometry expressed as m / e , m / z or mass / charge unit . [ m + h ] + refers to the positive ion of a parent plus a hydrogen atom . ei refers to electron impact . ci refers to chemical ionization . fab refers to fast atom bombardment . nmr refers to nuclear ( proton ) magnetic resonance spectroscopy , chemical shifts are reported in ppm ( δ ) downfield from tetramethylsilane . pharmaceutically acceptable refers to those properties and / or substances which are acceptable to the patient from a pharmacological / toxicological point of view and to the manufacturing pharmaceutical chemist from a physical / chemical point of view regarding composition , formulation , stability , patient acceptance and bioavailability . solubility of a solid in a solvent , the ratio of the solid to the solvent is weight / volume ( wt / v ). [ α ] d 25 refers to the angle of rotation of plane polarized light ( specific optical rotation ) at 25 ° with the sodium d line ( 589a ). without further elaboration , one skilled in the art can , using the preceding description , practice the present invention to its fullest extent . the following detailed examples and chart a describe how to prepare the various compounds and / or perform the various processes of the invention and are to be construed as merely illustrative , and not limitations of the preceding disclosure in any way whatsoever . those skilled in the art will promptly recognize appropriate variations from the procedures both as to reactants and as to reaction conditions and techniques . r - naproxen ( can . j . chem ., 72 ( 1 ), 142 - 5 ( 1994 ), 260 g ), methylene chloride ( 3 . 33 kg ) and dmf ( 8 . 2 ml ) are added to a reactor . oxalyl chloride ( 191 . 8 g ) is slowly added to this mixture . after addition of the oxalyl chloride , the slurry is stirred at 5 to 10 ° and then slowly warmed to 20 - 25 °. the resulting mixture is concentrated to remove the methylene chloride , branched octane is added to the concentrate and the mixture is again concentrated . more branched octane is added to the concentrate and the mixture is cooled to 0 ° and stirred to crystallize . the crystal slurry is filtered , the crystal cake is washed with octane and dried at 20 - 25 ° to obtain the title compound . the filtrate from the first crop is concentrated , branched octane is added and the mixture is cooled and stirred to obtain a second crop of the title compound . the slurry is filtered , the crystal cake is washed with branched octane and dried at 20 - 25 °. a mixture of 4h - imidazo [ 4 , 5 , 1 - ij ] quinolin - 2 ( 1h )- one ( i , j . heterocyclic chem ., 19 , 837 - 49 ( 1982 ), 1 . 0 g , 5 . 8 mmol ) in dmf ( 10 ml ) is cooled to 0 ° and treated with potassium t - butoxide in thf ( 1 . 98 m , 3 . 2 ml , 6 . 3 mmol ) maintaining the reaction temperature at 0 °. the resulting mixture is stirred at 0 ° for 10 minutes . benzyl bromide ( 0 . 73 ml , 6 . 1 mmol ) is then added while maintaining the reaction temperature at 0 °. after 1 hour , the mixture is partitioned with methyl t - butyl ether ( mtbe ) from water followed by several water washes . the mtbe phase is concentrated under reduced pressure . the concentrate is cooled to 0 °, filtered and washed two times with 0 ° mtbe . the product is dried at 50 ° under reduced pressure with a nitrogen purge to give the title compound , cmr ( cdcl 3 , 100 mhz ) 153 . 78 , 136 . 44 , 128 . 69 , 127 . 67 , 127 . 60 , 126 . 73 , 125 . 86 , 122 . 90 , 122 . 78 , 121 . 28 , 116 . 92 , 116 . 17 , 108 . 36 , 44 . 95 and 42 . 37 δ . 1 - benzyl - 4h - imidazo [ 4 , 5 , 1 - ij ] quinolin - 2 ( 1h )- one ( ii , example 1 , 240 g ), acetonitrile ( 1 . 086 kg ), water ( 227 ml ) and fluoboric acid ( 48 . 5 %, 13 . 4 g ) are mixed and cooled to 0 to 5 °. dibromantin ( 163 . 5 g ) is slurried into acetonitrile and is added to the reaction mixture . the reaction is carried out for about 3 hr at 0 to 5 °. after the reaction is complete , methyl t - butyl ether is added over about 45 minutes keeping the reaction temperature in the pot below 10 °. the slurry is cooled to − 10 to − 15 °, stirred for an hour and then filtered . the product is washed with precooled methyl t - butyl ether , dried with 40 ° nitrogen to give the title compound , cmr ( cdcl 3 ) 156 . 0 , 137 . 8 , 130 . 5 , 129 . 6 , 129 . 3 , 129 . 1 , 126 . 6 , 123 . 6 , 122 . 5 , 119 . 6 , 110 . 4 , 69 . 9 , 49 . 6 , 47 . 7 , 46 . 9 and 43 . 8 δ . ( 5r , 6r )- 1 - benzyl - 5 - bromo - 6 - hydroxy - 5 , 6 - dihydro - 4h - imidazo [ 4 , 5 , 1 - ij ] quinolin - 2 ( 1h )- one ( iii , example 2 , 143 g ), methylene chloride ( 3 , 136 g ), n - methyl morpholine ( 100 . 2 g ) and 4 - dimethylaminopyridine ( 497 mg ) are added to the reactor and the mixture is cooled to 0 to 5 °. ( r )- naproxen chloride ( preparation 1 , 118 . 5 g ) dissolved in methylene chloride ( 694 ml ) is added to the reactor over about 1 hr and the mixture is stirred at 0 to 5 ° to complete the reaction . if necessary , additional naproxen chloride is added to complete the reaction . potassium carbonate solution diluted with water is added to the mixture . the aqueous phase is extracted with methylene chloride and the combined methylene chloride phase is washed with water . the washed mixture is concentrated by vacuum distillation and solvent exchange with ethyl acetate is performed . the concentrate is cooled to − 10 ° and stirred . the crystal slurry is filtered and the crystal cake is washed with precooled methyl t - butyl ether and dried at 50 ° to give the title compound in solid form , ( 5s , 6s )- 1 - benzyl - 5 - bromo - 2 - oxo - 1 , 2 , 5 , 6 - tetrahydro - 4h - imidazo [ 4 , 5 , 1 - ij ] quinolin - 6 - yl ( 2r )- 2 -( 6 - methoxy - 2 - naphthyl ) propanoate ( iva ), cmr ( cdcl 3 ) δ 173 . 2 , 157 . 8 , 153 . 4 , 136 . 1 , 134 . 6 , 133 . 7 , 129 . 2 , 128 . 8 , 127 . 8 , 127 . 8 , 127 . 6 , 127 . 2 , 125 . 9 , 125 . 9 , 125 . 6 , 121 . 5 , 121 . 4 , 119 . 1 , 113 . 2 , 109 . 0 , 105 , 105 . 6 , 69 . 2 , 55 . 3 , 45 . 4 , 45 . 2 , 42 . 5 , 41 . 7 and 18 . 3 . ( 5s , 6s )- 1 - benzyl - 5 - bromo - 2 - oxo - 1 , 2 , 5 , 6 - tetrahydro - 4h - imidazo [ 4 , 5 , 1 - ij ] quinolin - 6 - yl ( 2r )- 2 -( 6 - methoxy - 2 - naphthyl ) propanoate ( iva , example 3 , 110 g ) is slurried in acetonitrile ( 1 , 297 g ). after adding aqueous methylamine ( 40 wt %, 327 g ) the reaction is carried out for about 12 hr at about 30 °. after the reaction is complete , the mixture is concentrated and ethyl acetate is added . dilute hydrochloric acid is added to make the water - soluble salt of the title compound . the byproduct ( r - naproxen methylamide impurity ) is insoluble in water and stays in the ethyl acetate phase . further extractions and washes are carried out for better separation of the ( naproxen acetamide ) impurity with minimum loss of the desired product . then a sodium hydroxide solution is added to the aqueous phase and the hydrochloride salt of the title compound is converted to the free base . the free base is less soluble in water and is extracted into ethyl acetate . the product mixture is concentrated and solvent exchanged with ethyl acetate to remove water . crystallization is performed by adding branched chain octane and cooling the mixture . the resulting slurry is filtered , washed and dried at 50 ° to give the title compound , cmr ( cdcl 3 ) δ 153 . 7 , 136 . 3 , 128 . 7 , 127 . 8 , 127 . 7 , 125 . 7 , 121 . 3 , 119 . 9 , 118 . 6 , 107 . 5 , 66 . 2 , 60 . 1 , 45 . 1 , 42 . 6 and 34 . 0 . ( 5r , 6r )- 1 - benzyl - 5 - hydroxy - 6 -( methylamino )- 5 , 6 - dihydro - 4h - imidazo [ 4 , 5 , 1 - ij ] quinolin - 2 ( 1h )- one ( v , example 4 , 70 g ) and thf ( 1 , 389 g ) is concentrated to remove any moisture by distillation as a precaution due to reactivity of n - butyllithium towards water . the mixture is cooled to about − 10 ° and n - butyllithium is added to make the lithium salt of the starting material with formation of n - butane byproduct in an exothermic reaction . benzenesulfonyl chloride is added slowly to make benzenesulfonate in an exothermic reaction . the reaction mixture is warmed to 20 - 25 ° to complete the reaction . agueous potassium carbonate solution is added to scavenge the benzenesulfonic acid and the mixture is stirred to allow crystallization . water is added to complete crystallization , the slurry is stirred , cooled and filtered . the crystal cake is washed with water followed by branched chain octane and dried at 40 to 50 ° to give the title compound , cmr ( cdcl 3 ) δ 154 . 1 , 136 . 3 , 128 . 6 , 127 . 9 , 127 . 6 , 124 . 3 , 120 . 7 , 119 . 7 , 107 . 4 , 46 . 7 , 44 . 9 , 40 . 7 , 38 . 1 and 37 . 6 . a mixture of ( 7as , 8ar )- 4 - benzyl - 8 - methyl - 7 , 7a , 8 , 8a - tetrahydroazireno [ 2 , 3 - c ] imidazo [ 4 , 5 , 1 - ij ] quinolin - 5 ( 4h )- one ( vi , example 5 , 40 g ) t - amyl alcohol ( 42 . 4 g ) and anhydrous ammonia ( 1 , 200 g ) is treated with lithium at − 33 °. after the lithium addition is complete , the reaction mixture changes from a yellow slurry to a dark blue mixture . this dark blue mixture is stirred for 30 - 60 minutes and then quenched with the addition of water . the cooling water is removed from the condenser and the ammonia is allowed to evaporate . the residue is dissolved in methanol . this mixture is then concentrated to dryness to give the title compound , which is carried on directly to the next step without isolation . a mixture of ( 5r )-( methylamino )- 5 , 6 - dihydro - 4h - imidazo [ 4 , 5 , 1 - ij ] quinolin - 2 ( 1h )- one ( vii , example 6 , 15 . 0 g , 73 . 8 mmol ) and tetraphosphorus decasulfide ( 36 . 1 g , 81 . 2 mmol ) in pyridine ( 300 ml ) is heated in a 125 ° oil bath under nitrogen . the reaction is stirred for 5 hr . the mixture is cooled to 20 - 25 ° and the pyridine is removed under reduced pressure . sodium hydroxide ( 2 . 2 n , 200 ml ) is added and a vigorous reaction ensues . additional sodium hydroxide ( 1 n ) is added until a solution is formed . the solution is saturated with sodium chloride and extracted with methylene chloride ( 2 . 5 l , in portions ). the organic phase is absorbed onto silicon dioxide ( 40 g ) and purified via column chromatography ( silicon dioxide , 225 g ; methanol / methylene chloride , 3 . 5 - 5 . 0 / 96 . 5 - 95 ). the appropriate fractions are pooled and concentrated . the material is recrystallized from methanol / ethyl acetate / hexanes to give the title compound , mp = 210 - 213 °; ir ( drift ) 2940 , 2907 , 2884 , 1483 , 1458 , 1391 , 1366 , 1354 , 1254 , 1239 , 1229 , 895 , 762 , 734 and 630 cm − 1 ; nmr ( 300 mhz , cdcl 3 ) δ 7 . 12 , 7 . 03 , 7 . 00 , 4 . 30 , 3 . 96 , 3 . 30 - 3 . 50 , 3 . 15 , 2 . 88 and 2 . 57 ; ms ( ei ) m / z 219 ( m + ), 190 , 189 , 187 , 186 , 164 , 163 , 155 , 145 ; hrms ( fab ) calculated for c 11 h 13 n 3 s ( mh + )= 220 . 0908 , found = 220 . 0904 . a solution of maleic acid ( 0 . 317 g , 2 . 36 mmol ) in a minimal amount of methanol (˜ 1 ml ) is added to a mixture of ( sr )- 5 -( methylamino )- 5 , 6 - dihydro - 4h - imidazo [ 4 , 5 , 1 - ij ] quinoline - 2 ( 1h )- thione ( viii , example 7 , 0 . 493 g , 2 . 25 mmol ) in methylene chloride . the resulting solid is collected by filtration to give the title compound ; mp = 195 - 196 °; [ α ] 25 d =− 60 ° ( c 0 . 93 , methanol ); ir ( drift ) 3140 , 3112 , 3060 , 2969 , 1627 , 1619 , 1568 , 1481 , 1455 , 1398 , 1389 , 1361 , 1220 , 868 and 747 cm − 1 ; nmr ( 300 mhz , cd 3 od ) δ 7 . 20 - 7 . 30 , 7 . 10 - 7 . 20 , 6 . 26 , 4 . 49 , 4 . 31 , 4 . 05 - 4 . 20 , 3 . 28 and 2 . 83 ; cmr ( 100 mhz , dmso - d 6 + cd 3 od ) δ 170 . 4 , 169 . 4 , 136 . 6 , 131 . 1 , 130 . 9 , 125 . 1 , 122 . 1 , 116 . 2 , 109 . 6 , 53 . 9 , 43 . 1 , 31 . 9 and 27 . 2 ; ms ( esi ) m / z = 220 . 1 ( mh + ).

the invention provides methods and use of heterocyclic amines , and phenylazacycloalkane compounds , and their pharmacologically acceptable salts for the treatment of restless legs syndrome .

the present invention relates to foaming liquids and powders that can be used to prepare foaming liquids . an example of a foaming liquid according to the invention is a beverage such as coffee . instant coffee powder is well known for the preparation of a coffee beverage and is an example of a powder that can be used to prepare a foaming liquid according to the invention . a coffee beverage or instant coffee powder is produced from a coffee extract . a foaming liquid is produced by introducing gas into a liquid to produce a sufficient amount of bubbles to form a foam on the top of the liquid . the foam may be produced directly in the liquid , e . g . in the case of a coffee beverage just before consumption of the coffee beverage , by introducing gas bubbles into the liquid , e . g . by agitating or stirring the liquid manually or by a suitable machine . foam may also be produced by a dried soluble powder , e . g . in the form of a soluble , or instant , coffee beverage powder , which is porous and contains gas that is released in the form of bubbles when the powder is dissolved . such a powder may be produced by drying a liquid , e . g . a liquid coffee extract , so as to form a dried porous soluble powder . when reconstituted , e . g . in the case of a soluble coffee powder with hot or cold water or milk to form a coffee beverage , the gas entrapped in the pores of the powder will be released into the liquid and forms a foam on the surface . by unroasted coffee solids are meant coffee solids that have not been subjected to a roasting process . coffee solids according to the invention are any compounds derived from a coffee plant , excluding water . coffee solids according to the invention are preferably derived from coffee beans . roasting of coffee solids are normally performed on the raw green coffee beans before grinding and extraction of the beans , but may also be performed on the ground beans or on an extract of soluble coffee solids that has been dried . by roasting is meant a dry , or almost dry , heat treatment of the coffee beans or coffee extract as opposed to e . g . steaming or cooking of coffee beans in water , e . g . under pressure . during roasting of coffee beans drying takes place . the green beans will usually comprise about 12 - 16 % water before roasting , and as a result of the roasting the moisture level will be reduced , e . g . to about 2 %. roasting is thus different from a heat treatment in water or with steam . the purpose of roasting of coffee is usually to develop the specific flavour notes characteristic of roasted coffee . these flavours result from processes such as e . g . pyrolisation of coffee solids and maillard reactions . in one embodiment of the invention , roasting means a heat treatment at a temperature above 200 ° c . at a moisture level below 4 % ( by weight ), preferably below 3 %. the moisture level is understood as the proportion of water contained in the coffee beans or coffee extract being roasted . as explained above , the moisture level at the beginning of the roasting may be higher than 4 %, but during roasting the moisture level is reduced to below 4 %, preferably below 3 %. the unroasted coffee solids of the invention may be obtained by any suitable method . in a preferred embodiment unroasted coffee solids originate from extraction of raw , also called green , coffee beans . the green coffee beans may be whole or ground when extracted . the green coffee beans are preferably extracted with water , preferably without use of an organic solvent . green coffee beans may be extracted with water in any suitable manner . methods for water extraction of green and / or roasted coffee beans are well known in the art . e . g . u . s . pat . no . 5 , 972 , 409 , which is incorporated herein by reference , discloses suitable methods for extraction of green coffee beans . green coffee beans are preferably extracted with water at a temperature above 130 ° c ., such as above 140 ° c ., or above 150 ° c . extraction may be performed in one or more stages at different temperatures , e . g . a first stage at less than 120 ° c . and a second stage at above 140 ° c . a product of the invention preferably comprises at least 1 g of unroasted coffee solids per 100 g of total coffee solids in the product , such as at least 2 g or at least 5 g of unroasted coffee solids per 100 g of total coffee solids . if desired all coffee solids of the product may be unroasted coffee solids , but in a preferred embodiment of the invention a product comprises between 1 g and 90 g of unroasted coffee solids per 100 g of total coffee solids , more preferred between 5 g and 80 g of unroasted coffee solids per 100 g of total coffee solids , even more preferred between 10 g and 70 g of unroasted coffee solids per 100 g of total coffee solids , or between 20 g and 50 g of unroasted coffee solids per 100 g of total coffee solids . by a dried soluble powder is meant a powder consisting of particles that are soluble in a liquid , preferably in water . the powders are dried meaning that they comprise no or minor amounts of water , so that they appear in a solid state . in one aspect the invention relates to a dried soluble powder comprising unroasted coffee solids and with a foaming porosity of at least 20 %, preferably at least 30 %, more preferably at least 35 %, and most preferably at least 40 %. foaming porosity is a measure of the porosity which contributes to foaming and characterises the potential foaming ability of the powder of the invention . indeed , open pores will not contribute to the foaming as much , or even in some cases not at all compared to closed pores . pores with opening diameter of less than 2 micrometres may also contribute to foam since the capillary pressure in these pores is greater than the ambient pressure and this may enable foam formation . in the present invention , the foaming porosity is obtained by including closed pores and open pores having an opening diameter of less than 2 micrometres . thus , for the purpose of measuring the foaming porosity , only closed pores as well as open pores having an opening diameter of less than 2 micrometres are taken into account as these are considered to contribute to foaming . the foaming porosity is obtained by the ratio of the volume of pores contributing to foaming over the volume of the aggregate excluding the volume of open pores having an opening diameter above 2 micrometres . this can be measured by mercury porosimetry or x - ray tomography . the foaming porosity of conventional non - foaming coffee powders is normally found to be less than 15 %. the soluble powder particles of the invention preferably have a total porosity of at least 40 %, preferably at least 55 %, even more preferably at least 70 %. in a preferred embodiment , the powder particle total porosity is between 65 and 85 %, more preferably between 65 and 80 %, even more preferably between 70 and 80 %, most preferably between 70 and 75 %. total porosity can be measured by means known in the art . for instance , the total porosity can be calculated by the following equation : ( vp − vcm )/ vp 100 , wherein vp is the total volume of the particle and vcm is the volume of the matrix in the particle . these values may be determined by standard measurements such as mercury porosimetry or also by x - ray tomographic technique . the powder of the invention is therefore characterised by its high porosity which allows an increased amount of crema to be formed upon reconstitution of the powder . the pores of the present powder may have an average diameter d 50 of less than 80 microns , preferably less than 60 microns , more preferably less than 40 microns , most preferably less than 25 microns . the pore size distribution in the particles can be measured by x - ray tomography . wherein d 90 , d 10 and d 50 represents the diameters where 90 %, 10 % and 50 %, respectively , of the pore volume is in pores with a size below this value . thus , a distribution span factor ( n ) of less than 4 , preferably less than 3 , more preferably less than 2 , most preferably less than 1 . 5 characterises the pores of the powder according to the invention . the lower the span factor ( n ), the more uniform and sharp is the size distribution . the particle size of the powder particles may e . g . be characterised by the median particle diameter ( volume distribution ), x50 . x50 is preferably in the range between 50 and 500 microns , such as e . g . between 100 and 300 microns , or between 150 and 250 microns . the dried soluble powder of the invention is preferably a food or beverage powder . a food powder may e . g . be a dried soup or condiment powder . a dried soluble beverage powder may e . g . be a dried soluble instant beverage powder , such as e . g . a dried soluble coffee powder , a dried soluble cocoa powder , or a dried soluble malt extract powder . in another aspect the invention relates to a method of producing a dried soluble coffee product comprising : a ) providing a liquid coffee extract comprising unroasted coffee solids ; and b ) injecting gas into said liquid coffee extract ; and c ) drying said liquid coffee extract . the gas to be injected into the liquid may be any suitable gas such as e . g . atmospheric air , nitrogen , carbon dioxide , nitrous oxide , or argon . the gas may be injected into the liquid coffee extract in any suitable way , e . g . by sparging the gas into the liquid coffee extract through a nozzle designed to form small bubbles . in a preferred embodiment the liquid coffee extract is subjected to pressure during or after the injection of the gas , e . g . to a pressure between 50 and 400 bar , preferably between 150 and 350 bar . the pressure may e . g . be created by passing the liquid coffee extract through a high pressure pump , the gas being injected into the liquid coffee extract before or after the high pressure pump . the gas injection may be performed in a way so that the gas is entirely solubilised in the coffee extract , or it may be present in the extract as gas bubbles , e . g . with a size of 1 - 10 microns . the liquid coffee extract may he homogenised after injection of the gas to reduce the size of the gas bubbles before drying . in a preferred embodiment , the liquid coffee extract has a dry matter content of 35 to 70 % when the gas is injected . the temperature of the liquid coffee extract when the gas is injected is preferably between 10 ° c . and 70 ° c ., more preferably between 30 ° c . and 70 ° c . it may be advantageous to keep the oil content of the coffee extract low . the liquid extract is dried after gas has been injected . drying may be performed by any suitable method ensuring the required properties of the dry soluble coffee powder . in a preferred embodiment the liquid coffee extract is spray dried . methods for spray drying of coffee extracts are well known in the art . if the injected gas is completely dissolved in the liquid coffee extract , the amount should be sufficient to ensure that it forms gas bubbles in the sprayed droplets due to the rapid pressure drop at the atomisation nozzle . the spray drying tower temperature during spray drying may e . g . be between 70 ° c . and 115 ° c . the presence of gas bubbles ensures the formation of the required porous structure of the dried particles . in another preferred embodiment the liquid coffee extract is subjected to spray - freezing after injection of the gas . spray freezing consists in spraying a liquid into droplets and simultaneously freezing said droplets . the temperature of the extract should preferably be brought to between 0 ° c . and 60 ° c ., preferably between 0 ° c . to 30 ° c ., such as between 10 ° c . and 25 ° c . or between 15 ° c . and 30 ° c . the foamed extract may enter a high pressure pump or homogeniser , and the pressure may e . g . be increased to 65 to 400 bar , preferably 85 to 250 bar . the coffee extract to be spray frozen preferably has a solids content above 40 %, more preferably above 50 %. the extract may be pumped to the top of a spray - freezing tower where the extract is atomised . the spray - freezing process may be carried out by means of direct or indirect contact with cryogenic fluids such as liquid nitrogen , cold air , and liquid carbon dioxide . a suitable freeze spraying process is e . g . disclosed in wo 2009 / 080596 ( nestec s . a .). the resulting porous spray - frozen powder may be freeze - dried to yield a porous soluble coffee product of the invention . suitable methods for injecting gas into a liquid coffee extract and drying it to produce a dried soluble coffee product are e . g . the methods disclosed in wo 2009 / 040249 ( nestec s . a .) and u . s . pat . no . 5 , 882 , 717 ( kraft foods inc .). a soluble coffee product powder may be an agglomerated powder . methods for agglomeration of spray frozen powders , e . g . coffee powders , are well known in the art . an agglomerated powder may e . g . be produced by sintering of e . g . a spray dried or a spray frozen powder , e . g . as disclosed in wo 2009 / 059938 ( nestec s . a .) or wo 2009 / 080596 ( nestec s . a .). in one embodiment the invention relates to a method of producing a foamed coffee beverage , comprising a ) providing a liquid coffee extract comprising unroasted coffee solids ; and b ) introducing gas bubbles into the liquid coffee extract to create a foam . gas bubbles may be introduced into the liquid in any suitable way , e . g . by agitating or stirring the liquid manually or by a suitable machine , and / or by sparging gas into the liquid coffee extract . sparging is the process of injecting gas directly into the liquid through a nozzle or other suitable equipment . the gas introduced into the liquid may be any suitable gas , e . g . atmospheric air , steam , nitrogen , and / or carbon dioxide . autopore iv 9520 was used for the structure evaluation ( micromeritics inc . norcross , ga ., usa ). the operation pressure for hg intrusion was from 0 . 4 psia to 9000 psia ( with low pressure from 0 . 4 psia to 40 psia and high pressure port from 20 to 9000 psia ). the pore diameter under this pressure is ranged from 500 to 0 . 01 μm . the data reported was volume ( ml / g ) at different pore diameter ( μm ). about 0 . 1 to 0 . 4 g of samples was precisely weighted and packed in a penetrometer ( volume 3 . 5 ml , neck or capillary stem diameter 0 . 3 mm and stem volume of 0 . 5 ml ). after the penetrometer was inserted to the lower pressure port , sample was evacuated at 1 . 1 psia / min , then switch to a medium rate at 0 . 5 psia and a fast rate at 900 μm hg . the evacuating target was 60 μm hg . after reaching the target , the evacuation was continued for 5 min before hg is filled in . the measurement was conducted in set - time equilibration . that is , the pressure points at which data are to be taken and the elapsed time at that pressure in the set - time equilibration ( 10 sec ) mode . roughly 140 data points were collected at the pressure ranges . the bulk volume of the granulate was obtained from the initial volume of mercury and the sample holder . the volume of the open pores with opening diameter greater than 2 micrometers ( 3 ) was obtained after intrusion with mercury up to a diameter of 2 micrometer . subtraction of this volume from the bulk volume of the granulate gave the new volume of the granulate which comprises the closed pores ( 2 ), open pores with opening diameters less than 2 micrometers ( 4 ) and the volume of the coffee matrix . the volume of the closed pores , open pores with opening larger than 2 micrometers in the granulate was obtained by subtracting the volume of the coffee matrix from the new volume of the granulate . the volume of the coffee matrix was obtained from the weight of the sample and coffee matrix density . the foaming porosity is the ratio of the volume of closed pores and open pores having an opening diameter of less than 2 micrometer over the new volume of the granulate . the total particle porosity may be measures using the method as described in u . s . 60 / 976 , 229 . roasted coffee extracts and green coffee extract were dissolved in milliq water at 75 ° c . in different ratios as described in the table below to reach a total solids concentrations of 2 %. 83 ml of each solution was passed through a whipping device ( 15000 rpm for 20 s ) and the foamed liquid was recovered in a volumetric cylinder . the foam volume was recorded every 30 s up to 360 s . the initial foam volume and foam decay ( 0 - 120 s ) are extrapolated from the foam curve using a logarithmic model . 4 g of powdered roasted coffee extract and powdered green coffee extract in different ratios as described in the table below , were added in a simple device consisting of a reconstitution vessel connected to a water reservoir , which initially was blocked off with a valve . after reconstitution of the powder mixture with 200 ml of water at 85 ° c ., the reconstituted vessel was closed with a special lid that ended in a scaled capillary . the valve between the reconstitution vessel and the water reservoir was then open and the water ( standard tap water at any temperature ) pushed the reconstituted beverage upwards into the capillary , thus facilitating the reading of the crema volume . a roasted coffee powder was produced by extracting ground roasted coffee with water using conventional technology for coffee extraction for the production of soluble coffee . liquid nitrogen was injected into the liquid coffee extract following the method disclosed in wo 2009 / 040249 ( nestec s . a .) and the extract was spray dried to produce a foaming dried soluble coffee product of the invention . this method was found to produce dried soluble coffee powders with a foaming porosity as defined herein of at least 40 %. a green ( unroasted ) coffee powder was produced from whole green coffee beans with water in the same way as described above for roasted coffee beans . the initial foam volume produced upon reconstitution of the coffee powder with water was measured as described above for roasted coffee powder , green coffee powder and mixtures thereof . the results are given in table 1 below . to determine the stability of the foam , the same samples of coffee powders were reconstituted in water in cups by dissolving 1 g of coffee extract in the ratios as described above with 50 ml milliq - water and the cups were photographed from above immediately after reconstitution ( 0 min ), and 2 min , 5 min , 10 min and 15 min after reconstitution . the photographs are shown in fig1 .

the present invention relates to improvements of foaming properties achieved by using unroasted coffee solids . specifically the invention relates to dried soluble powders with improved foaming properties upon dissolution . the products have a foaming particle porosity of at least 20 %.

referring to fig1 a - 5c the above described problem can be solved in the cervical , thoracic and lumbar spine by insertion into the denuded intervertebral disc space a bidirectional fixating transvertebral ( bdft ) screw or ( ubs ) screws 100 . fig1 a through 1c illustrate three - dimensional views of the ubs / bdft screw 100 . all its inner components are in the gear box casing 101 . the internal mechanisms are illustrated in fig2 - 5c . fig1 a illustrates the isometric view of the ubs 100 showing the outer gear box 101 containing the external mechanism , with superior screw 102 and inferior screw 103 extended . there are serrations 104 on the superior and inferior surfaces of the box 101 intended to integrate with the surface of the superior and inferior vertebral body surfaces . the gear box 101 which is made either of peek ( polyethylene - ketol ) or titanium acts as a column preventing subsidence of the disc space . also seen are the surface of the worm drive screw 105 , and the horizontal mini - plate screw insert 106 for capping the horizontal mini - plate to the gear box &# 39 ; s 101 surface ( fig1 a - c and 6 a - c ). fig1 - 4 illustrate the inner components of the bdft / ubs 100 without the enclosing gear box 101 . the inner components include a single wormed drive screw 105 , a drive spindle 201 , a spur gear 202 , superior screw 102 and inferior screw 103 with superior and inferior screw spindles 205 , 206 ( fig1 - 4 ). the mechanism of operation is thus : the wormed drive screw 105 is rotated clockwise . this rotation in turn rotates the spur gear 202 . the spur gear 202 interdigitates with the superior screw 102 on one side and the inferior screw 103 on the other side . rotation of the spur gear 202 leads to simultaneous rotation of the superior and inferior screws 102 , 103 in equal and opposite directions . the spindles in the wormed drive screw 105 and the superior and inferior screws 102 , 103 maintain the axis of screw orientation . the screws 102 , 103 are self drilling and hence there is no need for bony preparation . fig5 a and 5b illustrate in perspective and cross - sectional views the detailed elements of the superior and inferior screws 102 , 103 . these figures illustrate the external threading 501 , the internal threading 502 , the spindle socket and the spur gear teeth 503 which interdigitate with the spur gear 202 . the screws 102 , 103 are self drilling as noted . fig5 c illustrates the details of the spindle including its base 505 , its rod 506 and its threaded segment 507 . fig6 a - 6c illustrate the two - in - one design concept . this design concept includes two ubs / bdft screws 100 a , 100 b which are placed in the left and right portions of the intervertebral disc space , which are then capped by a horizontal mini - plate 600 . note how the mini - plate has four perforations . there are two perforations 601 , 602 , one on each side to allow entry of the wormed screw drive into the gear box . there are an additional two perforations 603 , 604 , one on each side , to secure the plate to the two ubs boxes 100 a , 100 b with plate screw caps 605 , 606 . fig6 c demonstrates the position of the two - in - one system with respect to the vertebral body 610 . in between the two bdft / ubs screws 100 a , 100 b , bone fusion material is inserted . the horizontal mini - plate 600 prevents the bone from growing into the nerves above it . with this system it is also possible to place a third screw inferior and in the middle of the two other ubs screws 100 a , 100 b thereby providing additional screw intervertebaral fixation . fig7 a through 7c illustrate the three - in - one design otherwise known as the ibfd . this device consists of five components . three ubs / bdft screws 100 a , 100 b , 100 c , a superior and an inferior enclosure 701 , 702 . the enclosures 701 , 702 are attached to the ubs / bdft screws 100 a , 100 b , 100 c . a screw driver 705 is used to actuate the screws 100 a , 100 b , 100 c . there are also slots 703 , 704 for bone fusion material . this device is only for anterior insertion into the spine , and it covers the entire cross - sectional area of the interspace , and is thus a total ibfd . the enclosures can be made out of peek , titanium , cobalt chromium or any other similar substance . the structure of the device provides significant three column stability and prevents subsidence of the construct . fig8 a and 8b illustrate the individual components of the facet joint staple gun 800 . it consists of a remote action mechanism which includes grip handles 801 , transmission linkages 802 , a drive rod 803 , a cylinder 804 . the drive rod 803 has a force end 805 and an action end 806 . fig9 a and 9b illustrate the details of the facet joint stapler . the staple 900 has superior and inferior staple segments 901 , 902 . these segments 901 , 902 are joined by a teethed unidirectional locking mechanism 903 having right triangular teeth 910 , and a spring washer 904 . the inferior surfaces 905 , 906 of each staple segment 901 , 902 are serrated to facilitate bony integration , and each segment has two bone piercing elements 907 with a base 908 . fig1 illustrates the staple 900 in the staple gun 800 , in the opened position engaging the facet joints , prior to penetration and stapling . fig1 - 13 illustrate the different components of the staple gun 800 and staple 900 in a detailed manner . the mechanism of action of the staple gun 800 includes engaging the staple 900 in the action end 806 of the drive rod 803 and resting in the staple guide chamfers 1201 ( fig1 a - 13 ). when the staple 900 is thus engaged in the staple gun 800 , the grip handles 801 are squeezed together , bringing the linkages 802 together ( fig1 - 12c ). this action is transmitted to the force end 805 of the driving rod 803 which moves upwards . this leads to upward movement of the action end 806 of the drive rod 803 in which the staple 900 is nestled , leading to the opposition of the superior and inferior segments 901 , 902 of the staple , 900 and the penetration of the pins 907 into the bone . the distance of bone penetration is modulated by the pressure put on the hand grips 801 . hence graded facet joint opposition leading to different degrees of opposition and hence rigidity can be accomplished . the greater the force the greater the opposition . thus this is a modulated not a static stapling mechanism . the surgical steps necessary to practice the present invention will now be described . the posterior lumbar spine implantation of the bdft ( ubs ) screws 100 , horizontal mini - plate 600 and ibfd 100 a , 100 b , 100 c can be implanted via previously described posterior lumbar interbody fusion ( plif ) or posterior transforaminal lumbar interbody fusion ( tlif ) procedures . the procedure can be performed open , microscopic , closed , tubular or endoscopic . fluoroscopic guidance can be used with any of these procedures . after the adequate induction of anesthesia , the patient is placed in the prone position . a midline incision is made for a plif , and one or two parallel paramedian incisions or a midline incision is made for a tlif . for the plif a unilateral or bilateral facet sparing hemi - laminotomy is created to introduce the bdft ( ubs ) screws 100 , into the disc space after it is adequately prepared . for the tlif procedure , after a unilateral dissection and drilling of the inferior articulating surface and the medial superior articulating facet , the far lateral disc space is entered and a circumferential discectomy is performed . the disc space is prepared and the endplates exposed . there are then multiple embodiments to choose from for an intervertebral body fusion . with the first and simplest choice , under direct or endoscopic guidance one . two or three bdft screws 100 can be placed . if two screws 100 are placed . one is placed on the right , and one on the left . if three are placed , the additional one can be placed more anterior and midline , such that the three screws 100 a , 100 b , 100 c form a triangulation encompassing the anterior and middle columns of the vertebral bodies ( fig6 b and 6c ). once the screws 100 are placed into the desirable intervertebral body positions , the worm drive screws 105 are turned clockwise which leads to the penetration and engagement of the superior and inferior bidirectional screws 102 , 103 into the vertebral bodies above and below . bdft screws can also be placed in angled positions if desirable ( not illustrated ). bone material or alternative intervertebral fusion material can then be packed into the disc space around the bdfts 100 . the casing gear box 101 of the screws prevents subsidence of the vertebral bodies ( fig1 a - c ). an additional option in the posterior lumbar spine is to place a horizontal mini - plate 600 underneath the thecal sac to prevent bone migration into the nerves . this plate 600 ( fig6 a - c ) can be slid underneath the thecal sac , and secured to the right and left bdft ( ubs ) screws 100 . once set , the plate 600 can be locked down with plate screw caps 606 thereby preventing movement ( fig6 a - c ). if further posterior column stability or rigidity is required , unilateral or bilateral , single level or multiple level facet screw stapling 900 can be performed under open , microscopic flouroscopic or endoscopic vision . radiographic confirmation of staple position is obtained . calibrated stapling leads to opposition of the facet joints 1000 with incremental degrees of joint opposition . this can lead to variable degrees of posterior column rigidity and / or flexibility ( fig8 - 13 ). the anterior cervical , thoracic and lumbar spine implantation of one , two or three ubs ( bdft ) screws 100 can be performed in a similar manner to posterior application . likewise a horizontal mini - plate 600 can be used to cap two bdft screws 100 . anterior placement of the three - in - one device ( ibfd ) 100 a , 100 b , 100 c into the l4 / 5 and l5 / s1 interspaces can be performed on the supine anesthetized patient via previously described open micropscopic or endoscopic techniques . once the disc space is exposed and discectomy and space preparation is performed , placement of one , two or three bdft screws 100 with or without a mini - plate 600 , or placement of the ibfd 100 a , 100 b , 100 c is identical to that performed for the posterior approach . the posterior placement of the bdft screws 100 alone or combined with horizontal mini - plates ( two - in - one ) 600 or with ibfd 100 a , 100 b , 100 c into the thoracic spine can be performed via previously described transpedicular approaches ; open or endoscopic . the anterior placement of the ibfd ( three - in - one ) into the thoracic spine can be accomplished via a trans - thoracic approach . once disc space exposure is obtained via either approach , all of the above mentioned embodiments can be inserted . engagement of the devices is identical to what was mentioned above . for anterior placement of the cervical embodiments of the bdft screw ( s ) 100 with or without the horizontal cervical mini - plate 600 , and the ibfd 100 a , 100 b , 100 c embodiment , the anterior spine is exposed in the anesthetized patient as previously described for anterior cervical discectomies . once the disc space is identified , discectomy is performed and the disc space prepared . implantation and engagement of all devices is identical to that described for the anterior lumbar and thoracic spines . the present invention may provide an effective and safe technique that overcomes the problems associated with current tanspedicular - based thoracic and lumbar fusion technology , and with current vertical cervical plating technology , and for many degenerative stable and unstable spine diseases , and could replace many pedicle screw - based and anterior vertical - plate based instrumentation in many but not all degenerative spinal conditions . calibrated facet joint screw staples 900 can facilitate flexible fusions and could replace current static trans - facet screws . to our knowledge there has not been any other previously described bidirectional screw 100 for use in the spine , other joints , or for any commercial or carpentry application . the bidirectional screw 100 described herein may indeed have applications in general commercial , industrial and carpentry industries . to our knowledge the description of zero to subzero profile anterior or posterior horizontal spinal plates which traverse the diameter of the disc space has not been previously described . to our knowledge an intervertebral three - in - one construct 100 a , 100 b , 100 c has not been previously reported . to our knowledge calibrated facet joint staples 900 have not been previously described .

an apparatus and method for joining members together using a self - drilling screw apparatus or stapling apparatus are disclosed . the screw apparatus includes a worm drive screw , a spur gear and superior and inferior screws which turn simultaneously in a bi - directional manner . a rotating mechanism drives the first and second screw members in opposite directions and causes the screw members to embed themselves in the members to be joined . the screw apparatus can be used to join members such as bones , portions of the spinal column , vertebral bodies , wood , building materials , metals , masonry , or plastics . a device employing two screws can be combined with a capping horizontal mini - plate . a device employing three screws can be combined in enclosures . the stapling apparatus includes grip handles , transmission linkages , a drive rod a fulcrum and a cylinder . the staple has superior and inferior segments with serrated interfaces , a teethed unidirectional locking mechanism and four facet piercing elements . the staples can be also be used to join members such as bones , portions of the spinal column , or vertebral bodies .

fig1 shows a prosthesis of the invention placed between two cervical vertebrae ; fig2 is an exploded view of an embodiment of a prosthesis in accordance with the invention ; fig3 is a view of the fig2 prosthesis when closed and held compressed by a severable tie ; fig5 shows a variant embodiment of the compressible cushion of the preceding figure ; fig6 shows the cushion of the preceding figure folded in half ; fig7 shows a variant embodiment of a compressible cushion ; and fig8 is an exploded view of a variant embodiment of the prosthesis of the invention . fig1 shows two successive cervical vertebrae 1 and 2 , each having a vertebral body 1 a and 2 a , and a posterior articular surface 3 . between the vertebral bodies , there is shown in diagrammatic manner a prosthesis 4 comprising two end plates 5 and 6 together with an intermediate body 7 in the form of a compressible cushion that is wedge - shaped with the tip or vertex ( thin end ) in the posterior position , the right - hand portion of the figure representing the anterior zone of the spine . the end plates 5 and 6 of the prosthesis are in contact with the vertebral bodies 1 a and 2 a via surfaces of said bodies that have received prior preparation after removal of the damaged natural disk . the outside surfaces of these plates may include anchor means , e . g . portions in relief , in order to improve bone fixing ; they may also make use of screws or any other equivalent element . the spine is shown presenting lordosis through an angle a that imposes on the prosthesis the relative orientation of these two vertebrae . in fig2 , it can be seen that each of the plates 5 and 6 possesses an inside surface 5 a , 6 a , drawn as plane , but that could possibly have a substantially spherical or cylindrical concave shape . the compressible cushion 7 is fastened to the plate . this cushion is enclosed in a contention membrane 8 that biologically isolates the cushion from the remainder of the patient &# 39 ; s body . the membrane is fastened to the remainder of the prosthesis by any appropriate means . by way of example , mention can be made of a “ cylindrical ” membrane fastened to the edge of each plate ( in particular by crimping ); the membrane may also be such that its edge is sandwiched between the inside face of each plate and a backing plate fitted thereto , e . g . by riveting . the membrane may also be in the form of a completely closed bag with the plates being stuck thereto . fig3 shows the prosthesis in its state ready for being inserted between two vertebrae , this state corresponding to the compressible cushion 7 being held in a compressed state by a tie 10 disposed on the anterior face of the prosthesis 4 and that is suitable for being ruptured after the prosthesis has been put into place between the vertebral bodies 1 a and 2 a . the tie may also be placed in such a manner as to surround the entire prosthesis so that it can be ruptured and removed after being cut , when necessary , by the surgeon acting via a posterior approach . in this figure , it can be seen that the plates 5 and 6 are of dimensions such that , in the posterior portion of the prosthesis , they are set back from the cushion which projects beyond the plates via a portion 9 beside the tip of the wedge . fig4 , as a detail corresponding to the preceding figures , shows an elastically compressible cushion 7 that is folded in half , having two portions 7 a and 7 b folded one onto the other about a portion 7 c that constitutes a thin zone forming a folding hinge that becomes the posterior end of the wedge . the prosthesis is thus subdivided into two units that co - operate with each other via complementary contact surfaces , here represented diagrammatically as being plane surfaces . in fig5 , the cushion 11 shown likewise possesses two membranes 11 a and 11 b that can be folded one onto the other about a thin zone 11 c acting as a folding hinge , such that , as shown in fig6 , indentations 12 can interpenetrate when the two portions are folded one against the other . it can be understood that the contact surface via which the two units of the prosthesis co - operate is complex in this embodiment : it comprises the flanks of interpenetrating teeth . on fabrication , it is possible to select the angle of inclination of the indentations 12 , the number of indentations , their profile , . . . as a function of the elastic characteristics and of the behavior desired for the cushion . in a variant ( not shown ) the indentations are curved , e . g . in circular arcs centered beside the hinge . in another variant ( not shown ) the two portions 11 a and 11 b can be separate ( the hinge being omitted ) and merely superposed with their indentations interleaved . in fig7 , the cushion 13 as shown constitutes a kind of resilient capsule for a gel core 14 that can deform depending on the extent to which the cushion is compressed during intervertebral movements . in this embodiment , the prosthesis likewise satisfies the general definition of the invention , i . e . the lens of gel subdivides the prosthesis into two units possessing surfaces that co - operate with each other via a gel . in other words , the functional complementarity of the surfaces is provided by the gel lens . finally , fig8 shows a variant embodiment of the prosthesis reproducing most of the elements described above and given the same references . inside the membrane ( not shown ), this variant embodiment has two slide tabs 15 and 16 situated in the vicinity of one of the plates , between the cushion and that plate . the subdivision of the prosthesis into two units is performed in this embodiment outside the cushion , the complementary surfaces being slide planes with surface states prepared so as to correspond with desired behavior . the cushion is shown as being a single piece . it could also be made as two portions folded one on the other , with the ability to slide being in additional to the performance of the prosthesis that results from it being separated into two units as described above . advantageously , at least one of the plates 5 and 6 , and preferably both of them , is dimensioned in such a manner that the prosthesis has a cushion that projects beyond the plates , behind them , so as to leave a space adjacent to the posterior portion of the spine in which there is no metal element , with this being done for two purposes : limiting the artifact ( degraded imagery ) concerning this posterior portion of the spine by keeping the metal portion constituted by the plate away therefrom ; and facilitating decompression ( resection of the posterior wedges of the vertebral plates ). finally , it should be mentioned that the above - described prosthesis corresponds to a single - piece prosthesis that is put into place using an anterior approach . in an embodiment adapted to be put into place via a posterior approach , it would comprise two half - prostheses that are put into place via lateral approaches so as to be placed on either side of the remaining portion ( nucleus pulposus ) of the natural disk . the shape of each half - prosthesis should then be adapted to the morphology that is encountered , e . g . by being kidney - bean shaped , when seen from above . each half - prosthesis should be subdivided into two units using the various above - described variants .

an intervertebral disk prosthesis , comprising : a rigid top plate ; a rigid bottom plate ; and an elastically - compressible intermediate cushion received between the two inside surfaces of the plates ; remarkable in that the assembly is subdivided in the thickness direction into two units resting one on the other via complementary contact surfaces .

fig1 is a perspective view of the four main elements that embody the patent application showing how they relate to each other by using a human character , a putter , golf balls , and a putting surface . the three target ball catch ( fig1 a ) shows the game part of the adjustable pendulum golf putting trainer ( fig1 ). a successful putt is trapped in one of the three catch areas not allowing the ball to enter adjacent catch areas and not allowing the ball to scatter out of the general area selected for playing the putting game . unsuccessful putts that hit the wood outside of the cutouts on the front of the triple target ( 1 ) generally stay nearby because of the dampening effect of the soft wooden material . the sound of the ball hitting pine wood combined with the ball &# 39 ; s stopping distance from the pine wood give feedback for judging a ball &# 39 ; s likely travel distance . the three target ball catch ( fig1 a ), is placed on a putting surface at an optional distance from the other three elements of the embodiment , fig1 b , fig1 c and fig1 d . after putting a quantity of balls , the three target ball catch ( fig1 a ) can be used to drag ( i . e ., rake ) the putted balls back to the starting point for another putting sequence . as alternatives , the three target ball catch ( fig1 a ) can be picked up and placed on the opposite end of the designated putting surface without relocating the ball supply , or additional three target ball catch &# 39 ; s ( fig1 a ) can be placed at other locations on the designated putting area to provide multi - hole putting games . the three target ball catch ( fig1 a ) is assembled into a single unit by attaching the triple target ( 1 ) to four of the ball catch separators ( 2 ) using eight wood screws ( 4 ). the ball catch stopper ( 3 ) is then fastened to the ball catch separators ( 2 ) using eight wood screws ( 4 ). the adjustable pendulum ( fig1 b ) shows the adjustable pendulum element of the adjustable pendulum golf putting trainer ( fig1 ). the adjustable pendulum ( fig1 b ) is used to train children and adults to duplicate the natural motion of a swinging pendulum . the individual may use any putter model with the adjustable pendulum ( fig1 b ). the adjustable pendulum &# 39 ; s ( fig1 b ) mounting height and vertical length can be adjusted to accommodate an individual &# 39 ; s height . the adjustable pendulum ( fig1 b ) can also be slid toward and away from an individual &# 39 ; s head and chest to accommodate differing training routines . the following items are press - fit into the upper pendulum section ( 7 ); the nylar threaded accessory mount ( 10 ) with its screwed - on head position sensor accessory ( 9 ); and the press fit pendulum rotation sleeve ( 6 ). the putter head contact ( 12 ) and the twist - lock mechanism ( 11 ) are press - fit into the lower pendulum telescoping section ( 8 ). the adjustable pendulum ( fig1 b ) is assembled into a single unit by sliding the upper pendulum section ( 7 ) into the lower pendulum telescoping section ( 8 ) and locking them together with the twist - lock mechanism ( 11 ). the pendulum support structure ( fig1 c ) is the weight - supporting structure for the adjustable pendulum ( fig1 b ) and the adjustable pendulum holder ( fig1 d ). the pendulum support structure ( fig1 c ) provides a stable platform to align , support and counter balance the adjustable pendulum ( fig1 b ) while static and in motion . the slot in the upper support ( 17 ) enables an individual to vary the adjustable pendulum holder &# 39 ; s ( fig1 d ) height . the pendulum arc simulator ( 16 ) provides a path for the putter head to follow that simulates the arc path of the bottom of the pendulum . the pendulum support structure ( fig1 c ) is assembled by joining the upper support ( 17 ) and the lower support ( 13 ) with two wood screws ( 18 ). two upper braces ( 19 ) and the lower support ( 13 ) are joined using one carriage bolt ( 14 ) and the lower front brace ( 22 ) is joined to the lower support ( 13 ) using one carriage bolt ( 14 ). two upper braces ( 19 ) are now joined with the lower aft brace ( 20 ) and lower front brace ( 22 ) using four wood screws ( 18 ). the pendulum arc simulator ( 16 ) is attached to the lower front brace ( 22 ) using four finishing nails ( 15 ) while keeping the pendulum arc simulator ( 16 ) and lower front brace ( 22 ) bottoms flush . leveling screws ( 21 ), 2 each , are located on the bottom of the lower aft brace ( 20 ) and the lower front brace ( 22 ). the adjustable pendulum holder ( fig1 d ) is used to mount the adjustable pendulum ( fig1 b ) to the pendulum support structure ( fig1 c ). as previously described , the slot in the upper support ( 17 ) enables adjusting the pendulum holder ( fig1 d ) height to suit a particular individual . selection of an individual &# 39 ; s height location must enable the individual to touch their chest to the coil spring end cap ( 24 ) and their nose to the head position sensor accessory ( 9 ). an individual slides the adjustable pendulum ( fig1 b ) toward or away from the pendulum &# 39 ; s upper support ( 17 ) to align their eyes with plane of the swinging pendulum . after eye alignment is completed , the pendulum location clip lock ( 28 ) is snapped in place against the threads of the carriage bolt to keep it from moving . to give a more compatible location for a particular individual , the carriage rod ( 26 ) that holds the adjustable pendulum ( fig1 b ) is moved vertically by loosening the wing nuts ; sliding the carriage rod up or down ; and tightening the wing nuts at the new location . after the new carriage rod ( 26 ) location is set , the adjustable pendulum &# 39 ; s ( fig1 b ) length is adjusted using the twist - lock mechanism ( 11 ). final adjustments are described with fig1 d . the adjustable pendulum holder ( fig1 d ) is assembled by rotating the coil spring ( 25 ) onto the threads at the end of the carriage rod ( 26 ) and then pressing the coil spring end cap ( 24 ) onto the coil spring ( 25 ). the first wing nut ( 27 ) and washer ( 23 ) are located approximately 2 inches from the left end of the carriage rod ( 26 ). the second wing nut ( 27 ) and washer ( 23 ) are temporarily located near the left end of the carriage rod ( 26 ). the pendulum location clip lock ( 28 ) is temporarily snapped onto the carriage rod ( 26 ). pendulum support structure ( fig1 c ) and adjustable pendulum ( fig1 b ) are assembled by inserting the carriage rod ( 26 ) of the adjustable pendulum holder ( fig1 d ) through the press fit pendulum rotation sleeve ( 6 ) of the adjustable pendulum ( fig1 b ) and the slot in the upper support ( 17 ). the second wing nut ( 27 ) and washer ( 23 ) are tightened on to the carriage rod ( 26 ) at a height selected for individual comfort . final adjustments of the pendulum &# 39 ; s extension length , mounting height and distance away from the upper support ( 17 ) are made to accommodate each individual &# 39 ; s posture so the eyes are over the line of the ball , the nose contacts the head position sensor accessory ( 9 ) and the chest touches the coil spring end cap ( 24 ). the pendulum location clip lock ( 28 ) is relocated into the slot in the press fit pendulum rotation sleeve ( 6 ). six training routines have been designed to separate and practice critical elements of a putting stroke . the training routines defined below give putting instructions of how to incrementally practice putter - body synchronization , arc path tracking , tempo , timing , direction , distance and putting to a image . the six training routines are : push the pendulum into motion using your hand , then place your putter adjacent to the pendulum and practice swinging the putter until you can synchronize your putting motion exactly with the pendulum as it slowly comes to rest . practice with the putter several times making 10 to 50 strokes synchronizing with the motion of the decelerating pendulum . while practicing , keep the putter head within ¼ to ½ inch of the pendulum &# 39 ; s moving bottom tip . adjust the pendulum and putter as follows : a ) release the pendulum location locking clip ( 28 ) and slide the adjustable pendulum ( fig1 b ) toward the pendulum support structure ( fig1 c ) until the pendulum &# 39 ; s bottom is about one and one half inches away from the lower front brace ( 22 ). b ) place putter head in front of the pendulum with the putter &# 39 ; s bottom touching the top side of the pendulum arc simulator ( 16 ) and the putter &# 39 ; s outer tip touching the lower front brace ( 22 ). c ) make slight adjustments of the pendulum as necessary so the back center of the putter can swing the pendulum aft without jamming . d ) push the pendulum aft with the putter head about eight inches as the putter head follows the path provided by the pendulum arc simulator ( 16 ) and pause for two seconds . after the 2 seconds , let the down and forward motion of the pendulum pace the putter on the forward stroke . pause again for two seconds at the end of the forward stroke and observe the putter position . the putter should stay about ⅛ inch from the pendulum arc simulator ( 16 ) and the lower front brace ( 22 ) without touching during repeated pauses and strokes . keep the putter and pendulum synchronized throughout the fore and aft putting motion while varying the stroke length from several inches up to approximately 30 inches . this training routine is difficult and will require a great deal of practice and patience before the individual becomes comfortable with the tempo and accuracy of the stroke . this training routine focuses on the swing plane and swing arc . to set up for this training routine , release the location retention clip and move the pendulum toward the vertical support until it hangs over the center line of the putter head while the putter &# 39 ; s outer tip is not touching either the pendulum arc simulator ( 16 ) or the lower front brace ( 22 ). the pendulum &# 39 ; s length is now adjusted to accommodate the particular putter design being used by the individual so the rear of the putter head can freely push the pendulum &# 39 ; s bottom tip aft and then stay in touch and synchronized with the pendulum &# 39 ; s bottom tip without jamming as the putter controls the entire stroke of the pendulum . a ball is now placed about one half inch in front of the center of the putter head . balls are now putted toward the three target ball catch ( fig1 a ) until a consistent direction is accomplished . an opening in the three target ball catch ( fig1 a ) is then moved in alignment with the observed direction . training should continue until the results show improvement and understanding of the pendulum - emulating putting swing . practice putting 50 to 100 balls before moving on to the next training routine . be sure that the shoulders rotate with the pendulum staying perpendicular to the pendulum and that the wrists maintain a constant angle with the arms and the wrists maintain at a constant distance from the lower pendulum telescoping section ( 8 ) as the pendulum and writs rotate . this training routine focuses on using the senses of sight , sound and touch to provide real time feedback to learn to avoid moving the head and the body except for the rotation of the shoulder area until after ball - putter impact . the training routine uses the eyes to watch and select the length of the putting stroke to control ball travel distance . this routine changes the pendulum setup so the ball , the putter and the pendulum tip are now far enough away from the pendulum arc simulator ( 16 ) and the lower front brace ( 22 ) so there can be no contact with the pendulum arc simulator ( 16 ) and the lower front brace ( 22 ) during the putting stroke . the pendulum &# 39 ; s length should also be readjusted for the particular putter head design to avoid jamming during the putting stroke . these additional items should be accomplished in the setup : the nose should touch the head position sensor accessory ( 9 ), the chest should touch the coil spring end cap ( 24 ) and the feet should be placed shoulder width apart , perpendicular to and at the same distance from the lower front brace ( 22 ). the individual must keep their head and the center of their upper chest still until after the sound of the ball - putter impact is heard . the critical lesson learned with this training routine is the awareness of the motion of the head position sensor accessory ( 9 ) as it moves away from the touch of the nose and then moves back to touch the nose at exactly the sound of ball - putter impact , while the coil spring end cap ( 24 ) is remaining still and in continuous contact with the chest at the center point of shoulder rotation . also , the individual is made to recognize that the putter continues to follow the pendulum tip &# 39 ; s direction and arc as the putter and pendulum move aft and forward , pausing at each end and then being in contact with each other at the sound of ball - putter impact . and lastly , the individual is made to watch the length of the putting arc relative to the ball distance traveled by pausing at the end of the back swing and seeing the relative location of the pendulum and putter to both the aft and forward ends of the lower front brace ( 22 ) during the putting stroke . this training routine embodies all of the previous training routines with the addition of establishing and maintaining a mental image of the real target in their mind during the back half of the putting stroke . the individual trains themselves to capture a target image on their last look at the target . the target &# 39 ; s yellow center marking is retained as a mind &# 39 ; s image on the target while the eyes focus on the ball and the putter until after the sound of ball - putter impact is heard . this practice routine is a mind - controlling practice of putting to an imagined target until it becomes easy and repeatable . this final training routine embodies the prior training concepts but without any contact of the putter with the pendulum as golf balls are putted . the golf ball location , body posture , head and eye position and body alignment are established adjacent to the adjustable pendulum ( fig1 b ) so the pendulum swing path does not interfere with the newly acquired putting stroke . the pendulum is put into motion by using the individual &# 39 ; s hand . the individual selects a putter start location somewhere on the pendulum &# 39 ; s swing path that represents a putting distance and then holds the putter static in this location until the pendulum backward swing decelerates to match the static putter location . the individual then emulates the pendulum &# 39 ; s arc motion with the putter to strike the ball . the individual must remember to use the mental target image and the ball - impact sound before any movement of the head and the shoulder rotation point on the chest is allowed . the adjustable pendulum golf putting trainer ( fig1 ) enables individuals of all ages to learn to improve their putting skill while enjoying the social aspects of the putting game . this embodiment is an assembly of simple materials and parts that are readily available at any large home building supply store . this embodiment is accomplished without the use any electronic counting , sensing or aiming devices , and uses no lighting or electric power source . as a result , it can be easily setup and stored . it can be used in many different locations . the putting game can be used in an area as small as 4 × 4 ft or as large as a gymnasium provided the ball rolling surface is acceptable . the end result from using the adjustable pendulum golfing putting trainer ( fig1 ) should be improved putting skills for every individual who has used the training routines that are enabled by the adjustable pendulum golf putting trainer ( fig1 ). the putting training routines previously described are listed below : the same embodiment can be used as a chipping trainer if the individual uses the same stroke for chipping as for putting which is recommended by some golf professionals . however , some slight body position setup changes may be required to account for the differing angular relationship of the golf club heads and shafts as well as differing shaft lengths . several three target ball catches ( fig1 a ) can be arranged to create putting and chipping games similar to croquet and shuffle board . in the putting game , balls passing through the triple target and closest to , but not hitting , the ball catch stopper are winners . although this putting trainer is shown for learning to square the putter head and move it like a pendulum , a slightly off square putting motion can be incorporated by changing the geometry of the pendulum arc simulator ( 16 ). this trainer embodiment can be used without any modifications to teach putting on a natural putting green so the reading of putting green shape , slope , grain , speed or other conditions affecting a natural putting green become part of the training routines . a ) change the putter head contact ( 12 ) to make it into a variable weight accessory to change the weight of the pendulum thereby enabling individuals to vary the pendulum &# 39 ; s tempo to one that is more compatible with their natural tempo . b ) replace the 3 to 6 ft adjustable pendulum ( fig1 b ) used for this embodiment with an optional 2 to 4 ft adjustable pendulum to make the embodiment more compatible with individuals of shorter height . c ) add a shoulder rotation guide on the pendulum &# 39 ; s nylar threaded accessory mount ( 10 ) to enable a new training routine for separately teaching shoulder rotation that emulates the pendulum &# 39 ; s arc path . the pendulum support structure ( fig1 c ) and the adjustable pendulum holder ( fig1 d ) can be used without the adjustable pendulum ( fig1 b ) to provide a training routine for hitting full shots using any club . the coil spring end cap would remain in contact with the chest during the back swing to help detect any chest movement occurring until after ball - club impact sound . a slightly longer carriage rod may be required so the clubs clear the pendulum support structure ( fig1 c ) when using a full swing . the reference arc path provided by the pendulum and support structure provide real time visibility for the putter head to trace a pendulum - shaped arc path without connecting to any other mechanisms . emulating the freely singing pendulum &# 39 ; s natural motion with a freely swinging putter as the pendulum &# 39 ; s travel decelerates to zero to teach putting with an arc motion , putting for distance control , putting for swing tempo and putting for synchronization of the hands , arms and shoulders with the pendulum &# 39 ; s motion . the freely swinging putter motion teaches the individual to eliminate any jerkiness in the putting stroke and to emulate the natural downward acceleration and resulting velocity that is provided by the effects of gravity . touching of the nose with the pendulum tip and the chest with the spring cap at start of the putting stroke and assuring the pendulum tip moves forward from the nose and returns to touch nose at the moment of putter - ball impact gives real time sound and feel feedback to easily discern whether the individual is allowing premature motion of the head or chest area . the dimensions for parts fabrication are shown in fig2 ( 3 parts ). the pendulum is purchased and modified as shown in fig2 . the other materials are purchased in bulk and cut to the dimensions shown in fig2 . fasteners are purchased in bulk . fig2 is located in the appendix . fig1 , 1 a , 1 b , 1 c , 1 d , and 2 and tables 1 and 2 are included in the appendix .

two devices , an adjustable pendulum golf putting trainer device and a golf ball target device are useful to teach individuals to emulate the natural swing of a pendulum with their putter . the devices are used when practicing and playing competitive putting games . the pendulum golf putting device is vertically adjustable in three ways , adjusting the vertical support for the pendulum , adjusting the telescoping pendulum to reach the back side of the putter head and moving the pendulum toward and away from the individual . the ball capturing device is independent of the golf putting trainer device and is made of soft wood . it is independently positioned and provides three different sized targets with separated ball catch areas that earn 1 , 2 , or 3 points for successful putts . the pendulum putting trainer can be used inside or outside in areas as small as 4 × 4 square feet or as large as a family room , basement , garage , gymnasium or back yard provided the areas have an acceptable putting surface . the pendulum putting trainer can be adjusted to teach individuals of all sizes to putt with the motion and tempo of a pendulum . by using multiple ball capturing devices , various mini - putting indoor or outdoor games can be arranged since no mechanical , electronic or electrical power connections are required to use the device . incrementally described training routines are designed to teach individuals to use their natural sense of sight , sound and touch as they are learning the pendulum putting stroke . no attachments constrain the putter or the individual &# 39 ; s arms during the putting stroke which is the case with many other putting trainers .

the above described drawing figures illustrate the invention , an apparatus for soccer training 5 . as shown in fig1 the apparatus consists of a user attachment means 10 attached to a ball holding means 100 by an elastic tether line 60 . as shown in fig1 the user attachment means 10 is preferably a flexible belt that encircles a waist 30 of a user . the belt 10 preferably is made of neoprene to provide flexibility and some elasticity . the belt 10 preferably includes a fixing means 40 , such as a hook and loop type fastener , for fixing the belt 10 to the user . such a fixing means 40 , in conjunction with the neoprene material , is adjustable so as to accommodate and snugly adapt to a variety of waist sizes . a first attachment means 50 , preferably a spring - loaded clip , extends from the belt 10 away from the user . as shown in fig1 a tether line 60 is made of an elastic material that lengthens under tensile forces on the line 60 , and thereafter contracts due to elastic resilience of the material . the line 60 is preferably a flat braided elastic cord that stretches out approximately 200 %. the line 60 includes a second attachment means 70 and a third attachment means 80 fixed at opposing ends of the line 60 . the second attachment means 70 cooperates with the first attachment means 50 of the belt . for example , in the embodiment wherein the first attachment means 50 is a spring - loaded clip , the second attachment means 70 is a plastic loop that engages the spring - loaded clip . the spring - loaded clip 50 allows the user to easily attach and remove the line 60 from the belt 10 . the spring - loaded clip 50 is preferably swivel - mounted to prevent the tether line 60 from becoming twisted during use . clearly , other alternate cooperative attachment means 50 , 70 may be readily used by those skilled in the art . further , the tether line 60 preferably includes a length adjustment means 62 , such as a triglide buckle arrangement that allows the tether line 60 to be set at various lengths , preferably between 3 - 6 feet in length , depending on the skills being developed . a ball holding means 100 is preferably made of a ball cradle 110 , shown in fig2 that engages a plurality of locking arms 120 , shown in fig3 to completely encircle the ball 130 so as to secure the ball 130 within the combination of the ball cradle 110 and the locking arms 120 . as shown in fig2 the ball cradle 110 has at least three , and preferably four , cradle arms 110 a . the ball cradle 110 and the cradle arms 110 a are preferably made of neoprene to provide flexibility and some limited elasticity . it is important that the ball cradle 110 is made of a single piece of material without any holes in the material . this allows the ball cradle 110 and the cradle arms 110 a to snugly fit partially around the ball 130 , but the material is not elastic enough to allow the ball 130 to slip out of the ball cradle 110 . each of the cradle arms 110 a is attached to , and terminates at , a fastening means 140 . the fastening means 140 is preferably a hook type fastener material which is flexible but inelastic , the material being sewn onto each of the cradle arms 110 a . in its preferred embodiment , four locking arms 120 which match the four cradle arms 110 a are formed by crossing two strips of a loop type fastener material and fixing the strips in place by sewing them securely together at their overlap portion 120 a . the ball cradle 110 is wrapped around the ball 130 and the hook type fastener material of each of the fastening means 140 removable engages its complimentary locking arm 120 , snugly locking the ball 130 between the ball cradle 110 and the locking arms 120 . the shape of the ball holding means 100 improves the holding power of the apparatus for soccer training 5 . since the locking arms 120 only cover a portion of the ball 130 , most of the ball 130 is left exposed for the user to kick . furthermore , since the locking arms 120 are inelastic and the ball cradle 110 is of only limited elasticity , it is very difficult for the ball 130 to slip out from between the ball cradle 110 and the locking arms 120 . as shown in fig3 a fourth attachment means 160 extends away from the locking arms 120 . the fourth attachment means 160 is preferably a strip of 3 inch webbing material sewn in two places to the overlap portion 120 a , forming a loop . the third attachment means 80 is preferably a loop formed by sewing the line 60 opposite the second attachment means 70 to another portion of the line 60 . by passing the line 60 through both the third and fourth attachment means 80 and 160 , a slip knot is formed which removably attaches the line 60 to the four locking arms 120 . in another embodiment , the line 60 is simply sewn directly to the overlap portion 120 a . the specific nature of this connection is not critical to the inventive nature of this invention , and those skilled in the art could devise many other attachment means equivalent to this invention . in use , as shown in fig1 the first attachment means 50 of the belt 10 is attached to the second attachment means 70 of the tether line 60 , and the third attachment means 80 of the tether line 60 is attached to the fourth attachment means 160 of the girdle 100 . the belt 10 is fixed around the waist 30 of the user . the ball 130 is positioned in front of the user for receiving kicking blows by the user , whereupon the ball 120 is propelled away from the user . since the ball cradle 110 and the four locking arms 120 only cover a relatively small portion of the surface of the ball 130 , the ball &# 39 ; s surface usually receives the kicking blows rather than the invention , providing the user a more realistic tactile feedback when kicking the ball 130 . the belt 10 and the fixing means 40 are strong enough to transmit the tension in the tether line 60 to the waist 30 of the user without stretching or breaking . the natural resiliency of the tether line 60 returns the ball 130 to the front of the user in each case for cyclic , repetitive practice in kicking the ball 130 by the user . the connection between the ball cradle 110 and the four locking arms 120 can easily be adjusted to form a ball holding means 100 to securely hold a ball 130 of a wide range of sizes and shapes . the present invention , while having been described for use with a soccer ball and for providing training for skills associated with the game of soccer , may certainly be readily adapted to other sports by those skilled in the art . such other sports might include tennis or other racquet sports , volleyball , american football , and the like . clearly , many types of sports require endurance and quick reflexes , and the present invention is particularly well suited for training in these areas . the present invention can be readily adapted for use with many other types of physically manipulated sporting equipment , such as volleyballs , tennis balls , footballs , badminton birdies , and the like . while the invention has been described with reference to at least one preferred embodiment , it is to be clearly understood by those skilled in the art that the invention is not limited thereto . the scope of this invention includes all structures equivalent to the preferred embodiments described in this specification .

a sports ball is held in a novel manner within a cradle having multiple arms encircling the ball and attached by velcro ® to a set of strips attached to a flexible tether line fastened to a person &# 39 ; s waist . the ball is able to be kicked or punched and return to the striker in each cycle .

the embodiment of electrode cable 10 according to the invention shown in the figure , is a multipolar electrode cable , having four individual , electrically insulated conductors 12 , 14 , 16 and 18 , which are bundled and enclosed in an outer sleeve 20 made of e . g . silicone rubber . more or fewer conductors can be used and extend axially in the longitudinal direction of the cable 10 . these conductors extend straight or can be intertwined . alternatively , the conductors can be helically coiled in the conventional manner , particularly at the distal end section of the electrode cable in order permit the formation there of a j - shaped electrode for fixing in the atrium . a combination of helically coiled and straight or twisted conductors is also possible . according to the present invention , a thin , soft , tubular element 22 , made of biodegradable , biocompatible polymer material extending axially along the entire length of the electrode 10 , from a proximal end to a distal end thereof , is attached to the exterior of the sleeve 20 . the tubular element 22 forms a channel 24 for a stylet ( not shown ) which is to be inserted into the channel 24 upon the introduction of the electrode cable 10 into a vein and on to the heart to stiffen the cable 10 to the desired degree and to guide it to the desired fixing site in the heart . since the tubular element 22 no longer has any purpose after the electrode cable 10 has been implanted , according to the present invention the tubular element is made of a material which is biodegradable or which dissolves , through contact with blood , within an appropriate period of time . the electrode cable accordingly can be slimmer and more flexible than a conventional cable , thereby providing more space for e . g . the implantation of more electrode cables , if desired . a biodegradable polymer material can e . g . be selected from the groups of proteins / amino acid polymers , polyhydroxycarboxyl acids and / or carbohydrate polymers . the proteins / amino acid 20 polymers group may contain gelatin , collagen , polyserine , polythreonine , polyphenylalanine or the like . the polyhydroxycarboxyl acids group may contain e . g . polylactides and / or polyglycolides . the carbohydrate polymer group may contain dextran , starch , hyaluronic acid , cellulose or the like . the breakdown or degradation time for the tubular element 22 should exceed at least one hour but can range from one or more days up to several months . although modifications and changes may be suggested by those skilled in the art , it is the intention of the inventor to embody within the patent warranted hereon all changes and modifications as reasonably and properly come within the scope of his contribution to the art .

an electrode cable for implantation in a body cavity has a tube made of a biodegradable , biocompatible polymer material attached to the exterior of the cable , the tube forming a channel for a stylet .

with reference to fig1 and 2 , the present disclosure relates to a package 10 for holding any suitable medical item such as an orthopaedic medical implant i . package 10 is part of a packaging assembly 100 and generally includes a sleeve 12 , a substantially rigid base or tray 14 , a skin pack film or lid 16 , and a collar 15 . base 14 defines a cavity 17 and may be wholly or partly made of a rigid polymer . cavity 17 is dimensioned to receive medical implant i contained inside sleeve 12 . sleeve 12 defines an opening 61 ( see fig8 ) extending therethrough and prevents , or at least hinders , skin pack lid 16 from wrapping medical implant i too tightly . opening 61 of sleeve 12 is adapted to receive medical implant i . in some embodiments , sleeve 12 is wholly or partly made of glycol - modified polyethylene terephthalate (“ petg ”) or any other suitable thermoplastic . in certain embodiments , the shape of sleeve 12 is substantially similar to the shape of medical implant i . consequently , when medical implant i is positioned inside sleeve 12 , sleeve 12 substantially envelopes medical implant i . during assembly , a sleeve 12 containing medical implant i is positioned within cavity 17 of base 14 . skin pack lid 16 is sealed over collar 15 and base 14 to enclose and secure sleeve 12 inside cavity 17 . skin pack lid 16 is then vacuum formed over sleeve 12 . as a consequence , skin pack lid 16 attains a geometry that substantially conforms to the shape of sleeve 12 . although skin pack lid 16 is sealed over base 14 , skin pack lid 16 is actually adhered to collar 15 , which surrounds a periphery of base 14 . referring to fig3 and 4 , base 14 has a first end portion 25 , a second end portion 26 , and a central portion 27 located between first and second end portions 25 , 26 and incorporates an exterior wall 22 , a cavity 17 located within the confines of exterior wall 22 , a rim 18 surrounding a periphery of the base 14 , a supporting surface 28 for supporting sleeve 12 , and means for retaining or locating sleeve 12 relative to base 14 , as discussed in detail below . exterior wall 22 encloses cavity 17 and includes a first end 23 and a second end 24 . in some embodiments , exterior wall 22 has six sides joined by six rounded corners . in other embodiments , exterior wall has a substantially oblong shape . however , exterior wall 22 may have any suitable shape or configuration . rim 18 is positioned around first end 23 of exterior wall 22 and extends outwardly from exterior wall 22 . supporting surface 28 is oriented substantially parallel to rim 18 and is located adjacent to first end 23 of exterior wall 22 . in use , sleeve 12 ( fig2 ) is placed on supporting surface 28 . sleeve 12 is in turn secured to base 14 by any suitable structure or means , as will be discussed below . in some embodiments , the means for retaining or locating sleeve 12 relative to base 14 includes first and second inner walls 29 , 30 extending from supporting surface 28 . first inner wall 29 is located adjacent to first end portion 25 of base 14 , whereas second inner wall 30 is positioned adjacent to second end portion 26 of base 14 . when sleeve 17 is placed on supporting surface 28 , first and second inner walls 29 , 30 limit the motion of sleeve 12 during shipping of package 10 . the means for retaining or locating sleeve 12 relative to base 14 may ( additionally or alternatively ) include a pin 19 for engaging one or more holes in sleeve 12 ( see e . g ., holes 49 and 50 in fig9 ). in some embodiments , pin 19 extends from second inner wall 30 past beyond second end 24 of exterior wall 22 , as seen in fig3 . as discussed in detail below , sleeve 12 has a hole dimensioned to securely receive pin 19 . when pin 19 engages the hole of sleeve 12 , sleeve 12 is secured to base 14 , thereby maintaining the location of sleeve 12 with respect to cavity 17 . moreover , the means for retaining or locating sleeve 12 relative to base 14 may ( additionally or alternatively ) include at least one ridge ( 31 or 32 ) formed on supporting surface 28 . in the embodiment depicted in fig4 , base 14 includes first and second ridges 31 , 32 for increasing the friction between sleeve 12 and supporting surface 28 when sleeve 12 is placed in base 14 . first ridge 31 has a twisted configuration and extends from a location adjacent to first inner wall 29 to central portion 27 of base 14 . second ridge 32 also has a twisted configuration and extends from second end portion 26 of base 14 toward central portion 27 of base 14 . at least a portion of second ridge 32 is located adjacent to second inner wall 30 . in certain embodiments , base 14 incorporates at least one rib 21 for limiting the movement of sleeve 12 inside cavity 17 . in the embodiment shown in fig4 , base 14 includes two ribs 21 formed on supporting surface 28 at central portion 27 of base 14 . although both ribs 21 are positioned in central portion 27 , ribs 21 are located on opposite sides of external wall 22 . on the side of supporting surface 28 facing cavity 17 , both ribs 21 have a raised profile configured to engage sleeve 12 . on the side of supporting surface 28 facing away from cavity 17 , each rib 21 defines a void adapted to receive a user &# 39 ; s fingers . in use , the end user can place the fingers in these voids to grab base 14 and then separate base 14 from skin pack lid 16 . with reference to fig5 and 6 , package 10 further includes a collar 15 configured to be positioned around a periphery of base 14 . collar 15 defines a central opening 37 and includes an exterior wall 33 surrounding central opening 37 . central opening is configured to receive base 14 . external wall 33 includes a first end 34 and a second end 35 and has a shape substantially similar to the shape of exterior wall 22 of base 14 . consequently , collar 15 is adapted to form around a periphery of base 14 . a flange 36 extends outwardly from second end 35 of external wall 33 . flange 36 has a generally planar shape . in several embodiments , collar 15 has six sides joined by six rounded corners . collar 15 , however , may have any suitable shape or configuration so long as it fits around the periphery of base 14 . when package 10 is assembled , skin pack film or lid 16 is adhered to flange 36 of collar 15 rather than base 14 . as a result , an end user can separate base 14 from skin pack film or lid 16 without cutting package 10 . fig7 - 9 show an embodiment of sleeve 12 . this embodiment of sleeve 12 includes first and second sides 38 , 39 coupled to each other and is made wholly or partly of a biocompatible flexible material . in one embodiment , sleeve 12 is made wholly or partly of a biocompatible polyurethane . the precise shape of sleeve 12 depends on the implant to be packed inside said sleeve 12 . for example , sleeve 12 can be designed to accommodate hip femoral implants , shoulder humeral implants , and other implants with a general oblong shape . in any event , sleeve has a shape substantially similar to the shape of medical implant i or any other suitable implant . in the embodiment shown in fig7 - 9 , first and second sides 38 , 39 have substantially similar shapes . first side 38 can be bent and sealed over second side 39 and vice - versa . in some embodiments , a living hinge 40 or any suitable structure or means connects first side 38 to second side 39 . in these embodiments , first side 38 can be bent over second side 39 along living hinge 40 . first side 38 includes an elongate portion 41 having a substantially triangular shape and a flange 42 extending from elongate portion 41 . elongate portion 41 of first side 38 has a first end 43 and a second end 44 and includes a sealing area 51 extending between first and second ends 43 , 44 . in use , elongate portion 41 covers an elongate portion of medical implant i , such as the stem of a hip femoral implant . first and second sides 38 , 39 may be heat sealed along sealing areas 51 , 52 , which are located along the borders of elongate portions 41 , 45 . flange 42 is connected to second end 44 of elongate portion 41 and has a hole 50 adapted to securely receive pin 19 ( fig4 ) of base 14 . the secure engagement between pin 19 and hole 50 helps limit the motion of sleeve 12 within cavity 17 of base 14 . at least a portion of flange 42 has a rounded profile . the rounded profile of flange 42 assists in covering rounded features of medical implant i . second side 39 also has an elongate portion 45 having a substantially triangular shape and a flange 46 extending from elongate portion 45 . elongate portion 45 has a first end 47 and a second end 48 and includes a sealing area 52 extending between first and second ends 47 , 48 . sealing area 52 is positioned along a border of elongate portion 45 . as discussed above , the first and second sides 38 , 39 may be heat sealed along sealing areas 51 , 52 when first and second sides 38 , 39 are bent over each other . flange 46 is connected to second end 48 of elongate portion 45 and has a hole 49 adapted to securely receive pin 19 of base 14 . the secure engagement between pin 19 and hole 49 helps hinder the motion of sleeve 12 within cavity 17 of base 14 . hole 49 is substantially aligned with hole 50 of first side 38 when first side 38 is bent over second side 39 . at least a section of flange 46 has a rounded profile , which assists in covering rounded features of medical implant i . when first side 38 is bent over second side 39 , sleeve 12 defines an opening 61 extending therethrough . opening 61 is sized to receive medical implant i . when medical implant i is positioned in opening 61 of a sealed sleeve 12 , elongate portions 41 , 45 of first and second sides 38 , 39 can collectively envelop a portion of medical implant i , such as a stem of a hip femoral implant , and flanges 42 , 46 can together enclose a portion of medical implant i , such as the cup and ball of a hip femoral implant . referring to fig1 - 12 , another embodiment of the sleeve is generally designated with reference number 112 . the structure and operation of sleeve 112 are similar to the structure and operation of sleeve 12 . however , the shape of flange 142 of first side 138 is different from the shape of flange 146 of second side 139 . in addition , flange 146 of second side 139 has a hole 149 adapted to securely receive pin 19 of base 14 , while flange 142 of first side 138 does not have a hole . moreover , flange 146 is larger than flange 142 . second side 139 further includes another bendable axis or ridge 148 formed on its outer surface . ridge 148 extends along the entire length of the second side 139 . fig1 - 15 illustrate another embodiment of sleeve 212 . sleeve 212 is substantially similar to sleeve 112 but does not include ridge 148 . returning to fig1 and 2 , during assembly , a skin packing machine is loaded with a roll or sheet of lidstock 53 and a roll of flexible seal material , which eventually turns into skin pack lid 16 . in an exemplary method , the manufacturers utilize an asp series skin packing machine sold by starview packaging machinery , inc . under the trademark starview . lidstock 53 is made of any suitable medical grade packaging material . in one embodiment , lidstock 53 is made of the nonwoven material comprising of spunbond olefin fiber , which is sold by dupont under the trademark tyvek . base 14 is placed on a sheet of lidstock material 53 in a designated location . medical implant i is inserted inside opening 61 of a sealed sleeve ( 12 , 112 , or 212 ). alternatively , medical implant i is placed on one side ( e . g ., 38 or 39 ) of sleeve 12 ( or any other sleeve described above ) and then one side is sealed over the other side of sleeve 12 to enclose medical implant i within sleeve 12 . once medical implant i has been enveloped by sleeve 12 , sleeve 12 ( along with medical implant i ) is placed in cavity 17 of base 14 . to secure sleeve 12 to base 14 , pin 19 of base 14 can be introduced through holes ( e . g ., 49 and 50 ) of sleeve 12 . before or after placing medical implant i inside base 308 , collar 15 is positioned around base 308 . next , a piece of the flexible seal material is sealed over base 14 to form skin pack film or lid 16 . in some embodiments , the flexible seal material is wholly or partly made of a resin . regardless of the particular material employed , the flexible seal material is placed over base 14 and sealed to collar 14 using a skin packing process . in one exemplary method , the skin packing process involves heating the flexible seal material to soften it . once softened , the flexible film material can be stretched and placed over base 14 to cover the opening leading to cavity 17 . the flexible seal material , however , is adhered to collar 15 , which is positioned around base 14 . after placing the flexible film material over base 14 , a manufacturer employs vacuum forming to shape the flexible seal material and , therefore , form skin pack film or lid 16 . in one exemplary method , vacuum forming involves applying a vacuum between base 14 and the flexible seal material to mold the shape of the flexible seal material . as a result of this process , the flexible seal material forms a skin pack film or lid 16 having a geometry that substantially conforms to the shape of the sleeve 12 containing medical implant i . then , skin pack film or lid 16 is adhered to collar 15 . since skin pack lid 16 is adhered to collar 15 rather than base 14 , an end user can separate base 14 from skin pack film or lid 16 without cutting package 10 . lidstock 53 is also adhered to collar 15 . subsequently , a radiation or sterilization indicator 55 may be attached to an outer surface of skin pack lid 16 . indicator 55 has a signal response to sterile processing conditions experienced by medical implant i and includes an ink having color - change response to exposure to sterilization processing to signal a history of sterile processing . in some embodiments , the ink is responsive to exposure to radiation or a sterilizing gas such as ethylene oxide . in certain embodiments , the ink is responsive to sterilizing steam or vapor , or organic agents such as formaldehyde . following the assembly of package 10 , package 10 is positioned in an outer blister or tray 56 . outer blister 56 is sealed with another lidstock 57 . like lidstock 53 , lidstock 57 is made of any suitable medical grade packaging material . in one embodiment , lidstock 57 is made of the nonwoven material comprising of spunbond olefin fiber , which is sold by dupont under the trademark tyvek . a label 58 is then attached to the outer surface of lidstock 57 . once package 10 has been shipped to the end user , patient information may be printed on label 58 . a package insert 59 may be attached to the outer surface of label 59 . usually , package insert 59 contains information required by regulatory agencies . the sealed outer blister 56 is then placed inside a box 60 . after closing box 60 , shrink wrap may be applied over box 60 to protect its contents . with reference to fig1 - 18 , a package 300 is designed for holding generally hemispherical or spherical shaped implant y . for illustration purposes only , the drawings shows a hip acetabular shell , but package 300 can retain many other kinds of implants such as knee femoral implants , knee tibial implants , hip acetabular heads , shoulder head implants , among others . package 300 includes a base or tray 308 , a flexible cover 302 , a flexible pad 304 , a collar 312 , and a skin pack film or lid 306 . base 308 is made wholly or partly of a substantially rigid material , such as a rigid plastic , and has a cavity 310 dimensioned to receive medical implant y . one side of base 308 has a supporting surface adapted to support medical implant y , and another side of base 308 has an opening leading to cavity 310 . a collar 312 is positioned around the periphery of base 308 . specifically , collar 312 surrounds an external wall of base 308 . accordingly , the shape of collar 312 is substantially similar to the shape of the external wall of base 308 . package 300 may additionally include a structure or means for securing medical implant y ( along with flexible pad 304 and flexible cover 302 ) to base 308 . this means or structure may be substantially similar to the means for securing sleeve 12 to base 14 described above . during assembly , a skin pack film or lid 306 is sealed over base 308 and adhered to collar 312 after positioning medical implant i , flexible pad 304 , and flexible cover 302 inside cavity 310 . flexible pad 304 and flexible cover 302 prevent , or at least inhibit , skin pack lid 306 from wrapping medical implant y too tightly , preventing easy removal of medical implant y . this arrangement allows the end user to separate skin pack film or lid 306 from base 308 without cutting package 300 . as seen in fig1 , flexible pad 304 includes at least one slit 326 extending from an exterior edge 314 to a central portion 320 thereof . slit 326 enhances the flexibility of flexible pad 304 . in the depicted embodiment , flexible pad 304 features a circular shape and has six slits 326 spread around its superficial area . nonetheless , flexible pad 304 may have any other suitable shape and may include more or fewer slits 326 . irrespective of the specific number of slits 326 , flexible pad 304 is configured to wrap an inner surface of medical implant y . flexible cover 302 is substantially similar to flexible pad 304 but may have a different size than flexible pad 304 , as shown in fig1 and 17 . in the depicted embodiment , flexible cover 302 is smaller than flexible pad 304 . the sizes of flexible cover 302 and flexible pad 304 would ultimately depend on the medical implant y to be packed . flexible cover 302 also has at least one slit 326 for enhancing its flexibility . slit 326 extends from an outer edge 322 to a central portion 324 of flexible cover 302 . while fig1 shows flexible cover 302 with six slits 326 and featuring a circular superficial area , flexible cover 302 may include more or fewer slits 326 and may have other suitable shapes and configurations . in any case , flexible cover 302 is configured to wrap an external surface of medical implant y . it is envisioned that flexible cover 302 and flexible pad 304 can be monolithically formed . alternatively , flexible cover 302 and flexible pad 304 can be separate components . in any event , flexible cover 302 and flexible pad 304 collectively wrap around medical implant y and maintain a sterile barrier around medical implant y . during assembly , a skin packing machine is loaded with a roll of lidstock 318 and a roll of flexible seal material . lidstock 318 is made of any suitable medical grade packaging material . in one embodiment , lidstock 318 is made of the nonwoven material comprising of spunbond olefin fiber sold by dupont under the trademark tyvek . base 308 is placed on a sheet of lidstock material 318 in a designated location . medical implant y is centered on flexible pad 304 . then , the shape of flexible pad 304 is substantially conformed to the shape of an inner surface of medical implant y . at this point , flexible pad 304 covers ( entirely or substantially ) the inner surface of medical implant y . flexible cover 302 is subsequently placed over medical implant y to cover ( entirely or substantially ) the outer surface of medical implant y . once medical implant y has been enveloped by flexible cover 302 and flexible pad 304 , medical implant y ( along with flexible cover 302 and flexible pad 304 ) is placed in cavity 310 of base 308 , with flexible pad 304 abutting the supporting surface of base 308 . before or after placing medical implant y inside base 308 , collar 312 is positioned around base 308 . next , a flexible seal material is sealed over base 308 to form skin pack film or lid 306 . in some embodiments , the flexible seal material is made of resin . regardless of the particular material employed , the flexible seal material is sealed over base 308 and adhered to collar 312 using a skin packing process . in one exemplary method , the skin packing process involves heating the flexible seal material to soften it . once softened , the flexible seal material can be stretched and placed over base 308 to cover the opening leading to cavity 310 of base 308 . the flexible seal material , however , is adhered to collar 312 , which is positioned around base 308 . after placing the flexible seal material over base 308 , a manufacturer employs vacuum forming to shape the flexible seal material and , therefore , form skin pack film or lid 306 . in one exemplary method , vacuum forming involves applying a vacuum between base 308 and the flexible seal material to mold the shape of the flexible seal material . as a result of this process , the flexible seal material forms a skin pack film or lid 306 having a geometry that substantially conforms to the shape of the medical implant y enveloped by flexible pad 304 and flexible cover 302 . then , skin pack film or lid 306 is adhered to collar 312 . since skin pack film or lid 306 is attached to collar 312 rather than base 308 , an end user can separate base 308 from skin pack film or lid 306 without cutting package 300 . lidstock 318 is also adhered to collar 312 . package 300 can also be contained in outer blister 56 and the packed in box 60 . in use , an end user may remove the implant from package ( 10 or 300 ) without contacting the implant surfaces . first , the user opens box 60 and removes outer blister 56 from box 60 . then , the user peels back lidstock 57 from outer blister 56 to access package 10 or 300 . to remove the implant from either package 10 or 300 , the end user peels back sheet of lidstock 23 or 318 adhered to collar 15 or 312 . subsequently , the end user separates base 14 or 308 from skin pack lid 16 or 306 . while separating base 14 or 308 from skin pack lid 16 or 306 , the end user should maintain a gentle grip on the implant through sleeve 12 or cover 302 . then , the end user removes the implant from package ( 10 or 300 ). during removal and afterwards , the end user grabs the implant through sleeve 12 or cover 302 and pad 304 , without contacting the implant surface . no tool is required to remove the implant from the package ( 10 or 300 ). once the end user has removed the implant from package ( 10 or 300 ), an insertion instrument can be attached to the implant without removing the implant from sleeve 12 or cover 302 and pad 304 . the processes described above results in substantially advantages over other known packaging processes . in particular , the use of sleeve 12 or cover 302 in conjunction with skin packaging greatly reduces the volume of package waste generated when an implant is consumed . fewer components are required to package the implants , and the implant can be packed in multiples . sleeve 12 allows the end user to grasp the sterile implant firmly without contacting the implant surface . instruments required to place the implant in a patient body can be attached while the implant is being held by sleeve 12 , reducing the risk of premature contact with fluids . in addition , the skin package eliminates , or at least minimizes , motion within the packages ( 10 or 300 ). neither sleeve 12 nor cover 302 and pad 304 substantially compress the implant , keeping the implant firmly positioned until opened by the end user . moreover , sleeve 12 or cover 302 and pad 304 protect implant coatings and surface finish from damage . in turn , skin pack lid ( 16 or 306 ) is protected from implant coatings and sharp features . additionally , sleeve 12 and cover 302 allow the end user to handle the implant without actually contacting the implant surface . sleeve 12 and cover 302 also provide packages ( 10 or 300 ) with sleeker inner package profiles as compared with other implant packages . further , the skin packing process described above results in substantial cost savings . since the presently disclosed skin packaging processes do not entail the use of foams , the manufacturer may save time by using sleeves 12 or covers 302 and pads 304 , as opposed to foams . for example , the void - filling packaging approach , which entails the use of foam , typically requires manual packing . the use of sleeves 12 or covers 302 and pads 304 in a skin packing process , on the other hand , can be performed automatically by machines . thus , the skin packing process allows the manufacturer to package the medical implant quicker than if foams were employed . although the invention herein has been described with reference to particular embodiments , it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention . it is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the appended claims .

a system for packaging a medical implant may include a sleeve for housing the implant within a cavity in the sleeve , with at least a portion of the cavity conforming to the shape of the implant . a flexible material film may cover and substantially conform to the shape of the sleeve so as to aid in stabilizing the sleeve and implant within an outer package . an insertion instrument for inserting the implant within the body of a patient may also be provided with the system . in some embodiments , the sleeve , with the implant inserted in the cavity of the sleeve , is configured for manipulation by a user without contacting the implant , and the implant is connectable to the insertion instrument while in the sleeve .

the present invention comprises the application of s - aba or its salts to red grape grapevines to modify development of grape berry and wine sensory characteristics . s - aba or a salt of s - aba is applied to the grapevines as a foliar spray to the grape berries and leaves , by application to the roots of the grapevine through irrigation or fertigation methods , or by injection into the grapevine . abscisic acid ( s - aba ; aba ; s -(+)- abscisic acid ; +- aba , (+)-( s )- cis , trans - abscisic acid , (+)-( s )- cis , trans - aba ; s - aba ; ( s )- 5 -( 1 - hydroxy - 2 , 6 , 6 ,- trimethyl - 4 - oxo - 2 - cyclohexen - 1 - yl )- 3 - methyl -( 2z , 4e )- pentadienoic acid ; cas registry no . [ 21293 - 29 - 8 ]) is available from lomon biotechnology co ., ltd . ( shichuan , china ). suitable salts of s - aba include , but are not limited to sodium , potassium , calcium , ammonium , magnesium and amine salts . s - aba or its salts is applied to the grapevines after berry set to achieve the desired effect on the sensory characteristics of the grape berries and wine . the presently preferred timing of the s - aba application is during the period of pre - veraison ( approximately 3 weeks before veraison , where veraison is defined as berry softening ) through the post - veraison period ( when sugar levels in berries measure approximately 18 - 20 ° brix ( 10 - 11 baume )). water is used as the carrier solvent for the applications . in the present invention , surfactants can be added to the chemical solution to improve the performance of the s - aba or its salts , particularly for the foliar application . the water solution may contain between 0 . 01 % to 0 . 5 % v / v of a surfactant , such as tween 20 ( available from sigma - aldrich , st . louis , mo .). the presently preferred surfactant for s - aba or s - aba salt performance is brij 98 ( polyoxyethylene ( 20 ) oleyl ether ) available from uniqema ( castle , del .). other surfactants are also useful in the present invention , including but not limited to , other surfactants in the brij family ( polyoxyethylene fatty alcohol ether ) available from uniqema ( castle , del . ), surfactants in the tween family ( polyoxyethylene sorbitan ester ) available from uniqema ( castle , del . ), the silwet family ( organosilicone ) available from momentive performance materials ( wilton , conn . ), the triton family ( octylphenol ethoxylate ) available from the dow chemical company ( midland , mich . ), the tomadol family ( ethoxylated linear alcohol ) available from tomah3 products , inc . ( milton , wis . ), the myrj family ( polyoxyethylene ( poe ) fatty acid ester ) available from uniqema ( castle , del . ), the span family ( sorbitan ester ) available from uniqema ( castle , del . ), and the trylox family ( ethoxylated sorbitol and ethoxylated sorbitol ester ) available from cognis corporation ( cincinnati , ohio ) as well as commercial surfactants such as latron b - 1956 ( 77 . 0 % modified phthalic / glycerol alkyl resin and 23 . 0 % butyl alcohol ) available from dow agrosciences llc ( indianapolis , ind . ), capsil ( blend of polyether - polymethylsiloxanecopolymer and nonionic surfactant ) available from aquatrols ( paulsboro , n . j . ), agral 90 ( nonyl phenol ethoxylate ) available from norac concept . inc . ( orleans , ontario , canada ), kinetic ( 99 . 00 % proprietary blend of polyalkyleneoxide modified polydimethylsiloxane and nonionic surfactants ) available from setre chemical company ( memphis , tenn . ), and regulaid ( 90 . 6 % 2 - butoxyethanol , poloxalene , monopropylene glycol ) available from kalo , inc . ( overland park , kans .). other additives are also useful in the present invention including , but not limited to , urea , nitrate salts such as ammonium nitrate , salts such as calcium chloride , humectants such as poly ( ethylene glycol ), and vegetable oils such as soybean oil , corn oil , cotton oil , and palm oil . the effective concentration range of the active ingredient s - aba varies depending on the water volume applied as well as other factors such as the plant variety , height , age , desired duration of effect and application method . the s - aba concentration range is from about 1 - about 10 , 000 ppm s - aba . the preferred s - aba concentration range for foliar applications is about 50 - about 500 ppm . the preferred application volume for foliar applications is about 25 - about 300 gallons / a . foliar spray applications are directed at the grape bunches to achieve complete coverage of the grapes bunches and to maximize the effect of the s - aba application . soil applications are directed towards the rooting zone . application methods include , but are not limited to application through irrigation / fertigation dripper line - or application of s - aba formulations or solutions to the soil at the base of the vine , followed by application of water to the soil to transport the s - aba to the roots of the vine . the following examples illustrate that application of s - aba to red grapes alters wine sensory characteristics . s - aba ( 200 ppm ) was applied by foliar spray using a standard vineyard airblast sprayer at 2000 l / ha to commercially grown shiraz grapes approximately 3 weeks prior to initiation of veraison . the spray mix contained the surfactant / wetter agral at 10 ml / 100 l . results reported are means of 4 replicates ( grapes ) and 3 replicates ( wines ) per treatment . winemaking followed a standard small lot fermentation protocol with each replicate wine being made from 50 kg of harvested grapes . table 1 shows that s - aba does not affect at - harvest grape sugar , ph , or total acidity or wine ph . however , at - harvest grape anthocyanin and wine color density and total phenolics are increased by s - aba . table 2 shows the sensory profile as determined by 10 experienced sensory assessors . shiraz wine made from s - aba - treated fruit were described as have a more intense berry aroma and a more fruity , more acidic taste . using a nine - point hedonic scale rating ( dislike = 1 to like = 9 ) the sensors judged wine from the s - aba treatment higher than the untreated ( 6 . 2 vs . 5 . 0 , respectively ) and thus a technically better wine . s - aba ( 200 ppm ) was applied by foliar spray to cabernet sauvignon grapes when sugar levels were approximately 11 be using a standard vineyard airblast sprayer at approximately 2000 l / ha . the spray mix contained the surfactant / wetter agral at 10 ml / 100 l . wine was prepared from the treated and untreated grapes . table 3 shows that s - aba did not affect sugar , ph , total acidity , and anthocyanins of grapes at harvest and did not affect the alcohol , ph , wine color density , wine hue , and total phenolics of the wine . although s - aba did not affect sugar , total acidity , and anthocyanin / color of grapes at harvest or wine , an experienced sensory panel judged cabernet sauvignon wine from the s - aba treatment as having a longer finish , increased aroma , and greater color intensity than the untreated wine ( table 4 ). s - aba ( 0 . 4 grams per vine ) was applied to commercially grown shiraz grapes through the drip irrigation system at approximately 3 weeks prior to initiation of veraison . no surfactant was added to the irrigation water . results reported are means of 3 replicates . winemaking followed a standard small lot fermentation protocol with each replicate wine being made from 50 kg of harvested grapes . table 5 illustrates that s - aba increased anthocyanin and phenolics of grape / juice at crush and wine color density and total phenolics and reduced wine hue . s - aba had no effect on sugar , ph , or total acidity of grapes / juice at crush or on alcohol or ph of wine . wine made from s - aba treated shiraz berries produced a wine that had more intense fruit and was less acidic based on the judging of 6 experienced wine sensory assessors . s - aba ( 200 ppm ) was applied by foliar spray at veraison to commercially grown shiraz grapes through standard agricultural spray equipment on 12 jan . 2007 . kendeen 20 ( tween 20 ) was added to the spray mix at 50 ml / 100 l . reported results are means of 3 replicates . winemaking followed a standard small lot fermentation protocol with each replicate wine being made from 50 kg of harvested grapes . table 6 shows that s - aba did not affect sugar , ph , total acidity , anthocyanins , or phenolics of grapes / juice at crush . s - aba increased color density and total phenolics , but did not affect alcohol , ph , or wine hue . however , wine made from s - aba treated shiraz berries produced a wine that had more intense fruit , spice and herbaceous flavors and more tannin based on the judging of 6 experienced wine sensory assessors . thus , regardless of the effect of s - aba on sugar , acidity , anthocyanin / color or phenolics of red grapes at harvest or the subsequent wine made from these berries , these examples illustrate that s - aba consistently alters the sensory characteristics of the wine such as aroma and flavor .

this invention describes the use of s - abscisic acid to modify sensory characteristics such as aroma , bouquet , flavor , mouthfeel , astringency , balance , complexity or finish of red grapes and red wine .

the present invention is a new and distinct variety of peppermint plant having the following characteristics that , in combination , are not exhibited in other peppermint plants : 4 . oil profile that shows little variability based on plant maturity . 5 . improved resistance to mint rust ( puccinia menthe pers ); 6 . improved resistance to verticillium wilt ( verticillium dahliae and v . albo - atrum ). mckenzie is an herbaceous perennial with an upright shrubby growth habit . this facilitates harvesting and thereby reduces costs . numerous branching stems are produced each year with an eventual height between 70 - 90 cm . when compared to black mitcham , the industry standard , mckenzie is more upright in its growth habit , taller with thicker stems ( due to a large extent to the highly lignified stems which reduces lodging ), larger leaves and a lighter green color with less anthocyanin pigment development under similar growing conditions . based on flowering mckenzie matures at approximately the same time as black mitcham . mckenzie also features the additional benefit of vigorous and abundant root growth , which results in more rapid acreage expansion and reduction in planting costs . in botanical terms , mckenzie has a distinct flower spike that is quite elongated as compared to other peppermints and can be up to 30 cm long under some growing conditions when measured from the lowermost verticillaster to the tip . the number of paired flower whorls , or verticillasters , can vary from 8 to 20 . the first internode between verticiels varies from 1 . 8 to 4 . 0 cm . flower petal color is much lighter than black mitcham . the petals are mostly white , but have a very slight lavender cast to them . the leaves halfway up the main stem are approximately 7 . 5 cm long by 2 . 4 cm wide and have an ovate shape with a serrate margin . the oil produced by mckenzie is of a typical peppermint type . in contrast to black mitcham , the oil profile of the mckenzie varies little with plant maturity . this feature allows for increased yield due to flexible harvest timing during a single season without significant changes occurring to its oil profile . mckenzie has been grown and observed under 3 different field conditions as well as under greenhouse conditions . as with all plants , the traits have varied depending on location . these differences can be attributed to varying climates , soils , fertilizers and water regimes . however , mckenzie remains distinct from other peppermint plants in its characteristics . the resistance to the diseases identified above is presented in table i . the results were gathered from a study performed in western oregon and show the comparison of mckenzie to black mitcham according to the mean number of rust pustules per leaf , mean number of verticillium strikes per plot and mean number of spider mites per leaf during three years of analysis . table i mean number of mean number mean number of rust pustules of verticillium spider mites per variety per leaf strikes per plot leaf aug . 15 , 1999 mckenzie 0 . 00 0 . 00 0 . 75 black mitcham 40 . 30 9 . 25 8 . 25 aug . 22 , 2000 mckenzie 0 . 00 0 . 75 0 . 58 black mitcham 183 . 25 17 . 00 10 . 00 aug . 26 , 2001 mckenzie 0 . 25 1 . 75 0 . 25 black mitcham 81 . 25 30 . 50 11 . 25 as illustrated by table i , mckenzie is significantly more resistant to the diseases shown . for example , although the incidence of mint rust varied overall according to the three years shown due to differences in annual growing conditions , mckenzie consistently showed much greater resistance to puccinia menthe pers when compared to the mean number of rust pustules per leaf . in fact , mint rust was almost eliminated . similarly , the number of mean strikes per plot for verticillium dahliae and verticillium albo - atrum was markedly reduced by mckenzie when compared to black mitcham . in the case of tetranychus urticae , the man number of spider mites per leaf was , again , almost eliminated in comparison to black mitcham . while the plant identified in the present invention has been described as it relates to a specific embodiment , it is understood that this application is intended to cover other variations , uses and adaptations that may arise under different environmental conditions .

a new and distinct peppermint plant ‘ mckenzie ’ characterized by its upright growth habit , vigorous and abundant root growth , resistance to spider mites , mint rust , mint wilt , and a distinct flower spike with mostly white petals and consistent oil quality throughout its phases of maturity .