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fig1 a and 1b are completed and partially - exploded perspective views respectively of the bowling practice device 10 of the invention . the device 10 comprises a generally - cylindrical hollow body whose shaped is bounded by an outer wall 12 and a cylindrical inner wall 14 . the outer wall 12 is joined to the cylindrical inner wall 14 by means of tapered end pieces 16 , 18 to complete the generally - cylindrical shape of the hollow body that comprises the bowling practice device 10 . as will be described below , the device 10 includes features that enable a bowler to develop a consistent arm swing or stroke away from the bowling alley . it includes a number of features , including an aerodynamic design and finger holds that contribute to the exercise and evaluation of stroke consistency . the device 10 allows repetition of motions ( at home ) that result in the development of muscle memory ( grooving ) in regard to the bowler &# 39 ; s personal stroke . such development of muscle memory is readily transferred to the bowling ball and bowling alley . finger holes are provided for emulating the finger holes of a bowling ball . two sets of finger holes are provided on the device . a first set or pair of rather small and relatively closely - spaced finger holes 20 , 22 is provided primarily for children and others who may not require the type of personalized fitting that an experienced bowler ( who may have a bowling ball that is fitted to his hand and finger span ) may require for optimum benefit . a second pair of finger holes 24 , 26 is provided that may be fitted to the hand of the bowler . the detailed structure and operation of the elements associated with the adjustable finger holes 24 , 26 is described below with particular reference to fig4 a , 4 b and the associated portions of the specification . longitudinal stripes 28 are painted or otherwise imprinted upon the outer wall 12 of the device 10 . such stripes enable the bowler to evaluate the correctness of his posture when first addressing the ball ( i . e . prior to the backswing ). it is during this portion of the stroke that the bowler initially locks his or her wrist and is critical to the success or the entire stroke . by providing visible longitudinal stipes 28 that are parallel to the imaginary line that connects the centers of the finger holes , the bowler is able to observe when he or she has aligned the “ ball ” precisely correctly during the addressing phase of the stroke . additional details of the structure of the device 10 are illustrated by the partially - exploded perspective view of fig1 b . as can be seen , the device 10 comprises a collapsible structure for facilitating transport . in this way , one may store it in a suitcase , for example . this permits reassembly for use in a hotel room during a business or other trip . the outer wall 12 is formed of a plurality of cover sections 32 . each cover section is , in turn , comprised of an intermediate piece 34 joined ( by gluing , for example ) at its opposed ends to end pieces 36 and 38 . each of the end pieces is aerodynamically tapered to join a bottom board 40 which is , in turn , glued to the bottom of the cover section 32 . each of the cover sections 32 comprises a rugged piece capable of absorbing the shock of collision with a wall when used and is preferably of foam - like composition . such cover sections 32 are preferably of injection - molded foam rubber , ethylene - vinyl acetate foam or polyethylene foam composition . the curved inner ( bottom ) surfaces of the bottom boards , when joined together , form the cylindrical inner wall 14 of the device 10 . pedestals 42 , 44 are provided adjacent opposed ends of the bottom board 40 having apertures ( a central aperture 46 and outer apertures 48 , 50 ) that serve as female elements for receiving corresponding male members affixed to an assembly ring 52 , 54 . the assembly rings 52 , 54 provide a frame onto which the elements of the cowl - like device 10 are fixed . pairs of barbed inserts 56 and 58 interlock with outer apertures 50 of the pedestal to secure the composite of cover panel 32 and bottom board 40 to the assembly ring 54 while a like arrangement secures the opposed end of the composite to the assembly ring 52 . similarly , other segments of the device 10 are engaged and fixed at their opposed ends to the assembly rings 52 , 54 by the interactions of like elements ( i . e . a pedestal fixed to a bottom board with apertures aligned to lockingly receive pairs of barbed inserts fixed to an underlying segments of the assembly rings 52 and 54 ). additionally , a vertical dowel 60 is fixed to the assembly ring 54 intermediate the pairs of barbed inserts 56 and 58 . the dowel 60 is aligned with and received within the central aperture 46 of the pedestal 44 . such member provides additional strength to the structure of the device 10 which may be subjected to significant forces and shock when contacting , e . g . a wall in a room of a house during use . fig2 is a view of the device of the invention as gripped for use . as can be seen , fingers 62 , 64 of the bowler &# 39 ; s hand are received in finger holes of the device 10 in like manner and configuration to a bowling ball . the device 10 is preferably about 8 . 25 ″ in length , 8 . 25 ″ in diameter and weighs between 3 oz . and 12 oz . to provide aerodynamic performance while giving the user the “ feel ” of a bowling ball . while a finger hole is not provided for the bowler &# 39 ; s thumb 66 , this in no way compromises the effectiveness of the device 10 as a training tool as the role of the thumb 66 is limited to gripping the bowling ball while the fingers 62 , 64 impart the spin or rotation to the ball upon release that results in “ hooking ” or curving of the path of travel the bowling ball . fig3 a and 3b illustrate the invention in use for emulating the address and a portion of the stroke and release of a bowling ball respectively . as discussed above , the longitudinal stripes 28 of the device 10 ( aligned parallel with an imaginary line between the centers of the finger holes ) enable the user to check for proper wrist alignment prior to the inception of initial stride and backstroke motion by posing as illustrated in fig3 a front of a mirror . the completion of the stroke and release of the device 10 are illustrated in fig3 b . as can be seen , proper technique requires a snapping of the wrist ( or other action to rotate the palm of one &# 39 ; s hand from a horizontal to a vertical attitude ) of the bowler as the device 10 ( emulating a bowling ball ) is released ( i . e . as the device is swung between positions 68 and 70 .) unlike practice with a spherical ball , the device 10 enables one to observe the degree of consistency of the stroke itself and without the influence of such factors as lane conditions . further , its relatively light weight allows the user to release and direct the device 10 at a target . by consistent contacting of the target , the bowler may gain assurance that , through muscle memory , he or she has effectively grooved his or her stroke . fig4 a and 4b are detailed exploded perspective and sectional views ( taken at line 4 b - 4 b of fig1 a ) for illustrating the arrangement for personalizing the grip of the bowling practice device 10 . personalizing the device 10 to the user &# 39 ; s grip ( i . e . adjusting the distance between finger holes for the natural spread of the user &# 39 ; s hand ) will , in many cases , mimic the manner in which the finger holes of the users bowling ball have been drilled to fit his or her hand . in the invention , this is accomplished through selective rotation of finger plugs 72 and 74 that are fitted within apertures 76 and 78 respectively of a cover section 80 . offset interior channels 81 , 82 within the finger plugs 72 and 74 respectively provide finger holes for the user . a receptacle , such as receptacle 84 is formed in the upper surface of the bottom board 86 that underlies the cover panel 80 and is aligned with an overlying finger hole 78 . the interior or the receptacle is serrated , having a plurality of inwardly - directed teeth 88 which surround a central aperture 90 . each finger plug 74 forms part of a three - piece unit ( the three pieces being glued together ) that includes an underlying finger panel 92 and a finger ring 94 . the finger panel 92 includes a split top surface 96 , each side of which includes an upstanding dowel 98 for fitting and being glued with a corresponding hole on the bottom of the finger plug 74 . an axial , downwardly - directed shaft 100 at the opposed surface of the panel 96 is aligned with , and glued to , a central aperture 102 of the finger ring 94 . radially - directed nipples 104 , 106 are aligned and directed outwardly from the periphery of the finger ring 94 . referring to fig4 b , one may see that the bottom of the shaft 100 is barbed . it thereby holds down the finger panel 92 , causing the finger panel 92 to exert a downward - acting force against the bottom board 86 . such downward - acting force causes the finger ring 94 ( and the opposed nipples 104 and 106 of the ring 94 ) that is glued to the finger panel 92 to exert a downwardly - acting force that causes the nipples 104 , 106 to become locked in position with respect to the inwardly - directed teeth 88 of the receptacle 84 . such locking of the position of the nipples 104 , 106 with respect to the teeth 88 of the receptacle 84 serves to lock the angular position of the de - centered vertical channel 82 that passes through the interior of the finger plug 74 as the finger plug 74 , the finger panel 92 and the finger ring 94 are glued together to form an integral unit . the two integral units comprising the finger plugs 72 , 74 with de - centered vertical channels 80 and 82 are rotated within the finger holes 76 and 78 respectively so that the radially - directed nipples of the associated finger rings are independently ratcheted through angular positions with respect to the inner - directed teeth of the underlying receptacles of the bottom board 86 . when the two plugs 72 and 74 ( and associated finger panels and finger rings ) have been rotated to such positions that the distances between the de - centered vertical channels define an appropriate spread or distance therebetween ( based , of course , upon the user &# 39 ; s preference ), downward pressure is applied to the tops of the plugs 72 and 74 to cause the barbed end of the shaft at the bottom of each finger panel to protrude through the aperture at the center of the underlying receptacle of the bottom board and thereby become engaged in the manner illustrated in fig4 b . thus , the finger holes are adjusted to the user . thus it is seen that the present invention provides a practice device for a bowler . by applying the teachings of the invention , one is able to realize the advantages of sustained practice at home . the device of the invention provides a number of features that permit the bowler to both analyze his technique and to recognize his progress while practicing in front of a mirror , in a hotel room , bedroom or other convenient location . while the invention has been described with reference to its presently - preferred embodiment , it is not limited thereto . rather , the invention is limited only insofar as it is defined by the following set of patent claims and includes within its scope all equivalents thereof .

a bowling practice device for regularizing and perfecting bowling technique . an aerodynamically designed hollow body includes an outer wall and a cylindrical inner wall . the opposed ends of the outer wall taper to meet the cylindrical inner wall . the outer wall preferably comprises a plurality of foam panels , one of which includes at least two finger holes suitable for personalization to the hand of the bowler .

as pointed out above , the present invention provides an enhancement to use of a chemostimulant to stimulate nociceptor ( irritant ) and c - fibre receptors in the patient &# 39 ; s throat as described in the above - referenced &# 39 ; 404 application , by coupling the delivery port of the chemostimulant nebulizer with a throat insertable conduit . this serves to achieve focused delivery of the chemostimulant to that region of the patient &# 39 ; s throat ( the mucosa of the laryngeal vestibule ) being visualized by a device such as a laryngoscope , and allows a medical practitioner to visually monitor the functioning of the patient &# 39 ; s airway in the course of determining whether the patient is at risk to one or more abnormal physiological conditions , such as oral or pharyngeal dysphagia , and pneumonia . in accordance with a non - limiting embodiment the laryngoscope - associated , focused chemostimulant delivery process of the invention , diagrammatically illustrated in fig2 the patient 10 may wear a nose clip 12 , as in the inhalation cough test of fig1 described above . the nebulizer , shown at 20 , may comprise a standard pneumatically controlled atomizer device , that is supplied with an aerosol chemostimulant , such as a solution of twenty percent concentration by volume of tartrate mixed with saline , described in the &# 39 ; 533 patent . as pointed out above , this solution has been demonstrated to stimulate a cough one - hundred percent of the time in normal individuals ; also tartrate is considered safe , does not cause pain or discomfort , and has not been shown to cause bronchoconstriction or complications in asthmatics when inhaled in an aerosol form . to control its operation , the nebulizer 20 is coupled via a pneumatic control input line 22 to a pulse atomizing pneumatic source ( not shown ). in accordance with the invention , nebulizer 20 has its output port 23 fitted with a length of relatively narrow chemostimulant delivery conduit 25 . the conduit 25 may comprise a section of flexible tubing of the type used for airway - invasive procedures , so that it may be readily fed through the patient &# 39 ; s airway , such as the patient &# 39 ; s nasal cavity 31 , with a distal end 27 of the conduit 25 placed adjacent to a targeted and visually observable region of the patient &# 39 ; s throat 33 . to facilitate its use with a laryngoscope , shown at 40 , the chemostimulant - delivery tube 25 may be physically coupled with an associated length of the laryngoscope &# 39 ; s observation tube 42 , as by means of a flexible adhesive or other attachment medium , so that both tubes may be simultaneously inserted into the patient &# 39 ; s airway and fed to a desired observation , chemostimulation region ( shown as being in proximity of the patient &# 39 ; s vocal cords 51 and laryngeal vestibule 53 ). alternatively , the chemostimulant - delivery tube 25 may be fed separately of the laryngoscope tubing 42 to the region of interest . in either case , the chemostimulant delivery tube 25 is fed into the patient &# 39 ; s airway such that the distal end 27 of the tube is positioned adjacent to the distal end 44 of the laryngoscope &# 39 ; s tube 42 . this ensures that delivery of the chemostimulant to the target region of the patient &# 39 ; s throat , such the laryngeal vestibule 53 , may be directly observed through the laryngoscope 40 during inhalation and / or the laryngeal cough reflex , and enable the practitioner to determine whether the patient &# 39 ; s larynx is functioning normally or abnormally . similar to the inhalation test performed in accordance with the methodology described in the &# 39 ; 533 patent , controlled pulsing of the nebulizer 20 causes a prescribed quantity of atomized chemostimulant to be injected ( through the delivery conduit 25 ) into the patient &# 39 ; s airway . however , unlike the mouth - based injection scheme of the &# 39 ; 533 patent , the use of the conduit 25 at the output of the nebulizer 20 provides for ‘ focused ’ delivery of the chemostimulant directly to the region of the patient &# 39 ; s throat to be stimulated . being coupled with and terminated at the distal end 44 of the laryngoscope observation tubing 42 enables the chemostimulant delivery conduit 25 to target the atomized spray within a confined region being visualized through the laryngoscope 40 , and thereby allows the medical practitioner to visually monitor the functioning of the patient &# 39 ; s airway ( e . g ., laryngeal vestibule ). again , the patient may be tested a prescribed number of times at different stimulant strengths until a cough is elicited . during successive chemostimulant injections , the patient may receive progressively increasing concentrations of the chemostimulant within the aerosol mixture , using successively increasing percentage concentrations ( e . g . 20 , 50 and 80 percent ) of chemostimulant . once a cough is elicited from the patient as a result of the inhaled aerosol mixture , the patient &# 39 ; s response to the inhalation test may be graded , as in the patient evaluation process detailed in the &# 39 ; 533 patent . as will be appreciated from the foregoing description , coupling the delivery port to a chemostimulant nebulizer with a throat insertable conduit not only enables focused delivery of the chemostimulant to a targeted region of the patient &# 39 ; s throat ( e . g ., the mucosa of the laryngeal vestibule ) but , when coupled with the observation tubing of a monitoring device such as a laryngoscope , allows a medical practitioner to visually monitor the functioning of the patient &# 39 ; s airway during chemostimulant injection . while we have shown and described an embodiment in accordance with the present invention , it is to be understood that the same is not limited thereto but is susceptible to numerous changes and modifications as known to a person skilled in the art . we therefore do not wish to be limited to the details shown and described herein , but intend to cover all such changes and modifications as are obvious to one of ordinary skill in the art .

a laryngoscope - associated arrangement provides for focused delivery of a chemostimulant from a nebulizer through a delivery conduit to a patient &# 39 ; s larynx to allow a practitioner to directly observe the function of the patient &# 39 ; s larynx during the course of delivery of the chemostimulant . this not only provides the practitioner with a visualization of whether the patient &# 39 ; s laryngeal vestibule is functioning properly , but allows the practitioner to be satisfied that the chemostimulant is accurately delivered to the intended region of interest .

next , examples of the present invention will be explained based on the attached drawings . fig1 is a perspective view of a skin adhering charge carrying pad of an electrotherapy device according to example 1 of the present invention . this skin adhering charge carrying pad is obtained by using a silicone rubber ( plastic insulating substance ) as a binder , mixing a fine powder of charcoal into this , and mixing well to disperse the powder in it . for sale , it is shaped into the sheet like kneaded material 1 shown in fig1 which is used by treating it into suitable sizes . in the middle of the kneading , the static electricity generated by the friction of the kneading is discharged . the front and reverse of the sheet like kneading material 1 shaped into a thin sheet are covered by insulating films 2a and 2b with perforations for division . note that it is also possible to use latex or another vulcanized rubber as the binder . the type of the power of charcoal mixed together with the silicone rubber ( rtvke45 made by shinetsu kagaku kogyo inc .) is selected from carbon black , oak charcoal , bamboo charcoal , and mugwort charcoal . consideration is given to the relationship between the time elapsed from a reference point of 10 hours after the end of the kneading and the potential difference due to the charging . the time 10 hours after the end of the kneading is used as a reference point because the charge carried is too strong directly after kneading and measurement ends up becoming impossible or unstable . for the measurement , use is made of a millivolt potential difference meter , that is , a d - 13 type measurer made by horiba seisakusho ( glass electrode orp meter ). as shown in the graph of fig2 the residual charge potential difference ( mv ) of carbon black follows substantially the same trend as the case of just silicone rubber ( rtvke45 ) and ends up attenuating down to 1 / 10 after the elapse of one day . with oak charcoal , bamboo charcoal , and mugwort charcoal , however , there is no sudden attenuation and a gradual attenuation is followed so a sustainability of charge of several months is observed . in particular , with mugwort charcoal , the rate of attenuation is extremely low . it is learned that it has the greatest sustainability of charge among all plant charcoal . further , consideration was given to the dependency of the charge carried on the charcoal powder content . fig2 shows the charge potential difference at the point of time 10 hours after the end of kneading with respect to the percent weight of fine powder charcoal mixed into the silicone rubber ( rtvke45 made by shinetsu kagaku kogyo inc .). in the case of all of the charcoal powder , it was learned that the charge carrying property was saturated at about 5 wt %. among these , the charge carrying property was highest in the case of mugwort charcoal . therefore , as the skin adhering charge carrying pad , it is desirable to mix in 5 wt % of charcoal powder . in this experiment , the amount mixed in was stopped at 30 wt %. if the ratio is increased , probably the charge carrying property will conversely deteriorate since the conductivity is increased . the sheet like kneading material 1 using mugwort charcoal is torn into a suitable size and adhered by sticky plaster etc . to the treated area ( diseased areas or pressure point ) shown in fig4 in accordance with the symptoms . it may be directly brought into contact with the skin as well . further , it may be adhered through gauze , nonwoven fabric , paper , etc . it may be affixed using adhesive tape etc . when clinical experiments were performed , many reports were obtained of good effects regarding various symptoms . examples of the reports are given below . table 1______________________________________ ( runny nose ) adheredpatient symptoms position results______________________________________a1 runny nose due 1 stopped immediately to colda2 suffered from 1 stopped immediately constant runny ( started again after nose removal ) a3 suffered from 1 stopped immediately runny nose during tripa4 runny nose due 1 stopped immediately to colda5 runny nose 1 stopped when adhered , but appeared when removed______________________________________ table 2______________________________________ ( coughs ) adheredpatient symptoms position results______________________________________b1 suffered from 6 stopped when adhered cough due to coldb2 suffered from 6 no more coughing night time coughing , and insufficient sleep due to coldb3 suffered from 6 coughing stopped . night time started again when coughing due to removed in morning coldb4 coughing when 6 no more coughing even talking if talkingb5 suffered from 6 no more coughing , coughing when phone calls possible talking on phone______________________________________ table 3______________________________________ ( sore throat ) adheredpatient symptoms position results______________________________________c1 coughing and 6 sore throat relieved sore throat due slightly earlier to coldc2 coughing and 6 sore throat relieved sore throat due slightly earlier to coldc3 coughing and 6 sore throat appeared to sore throat due be relieved slightly to cold earlierc4 coughing and 6 coughing relieved sore throat due earlier . sore throat to cold when relieved______________________________________ table 4______________________________________ ( aching shoulders ) adheredpatient symptoms position results______________________________________d1 aching shoulders 3 appears to have due to simple worked . eased when fatigue reattachedd2 aching shoulders 3 no more need for due to simple shoulder massage fatigued3 aching shoulders 3 eased , so adhered due to simple continuously every day fatigued4 aching shoulders 3 became easier in about due to simple three hours after being fatigue , widely adhered physically well fleshedd5 aching shoulders 3 became easier due to simple fatigue , physically well fleshedd6 aching shoulders 3 and 8 shoulders became due to office lighter in about 40 work minutesd7 aching shoulders 3 and 8 aching shoulders due to office became no longer work noticeabled8 aching shoulders 3 adhered for about one due to simple hour , then ache no fatigue longer noticeabled9 baker 3 worked on one shoulder . became better when reattached______________________________________ table 5______________________________________ ( headache ) adheredpatient symptoms position results______________________________________e1 could not sleep 2 appears to have due to headache worked in about 30 minutes . learned when waking up in morninge2 took pain 2 relief obtained in 20 to reliever every 30 minutes daye3 took pain 2 and 3 believed to have come reliever every from shoulders . when day attached to 3 in addition to 2 , ache relieved in about 30 minutese4 head suddenly 2 immediately cured began aching______________________________________ table 6______________________________________ ( knee pain ) adheredpatient symptoms position results______________________________________f1 pain starting five 7 pain relieved over years ago nightf2 pain in right 7 pain immediately knee relievedf3 pain in left knee 7 pain relieved and could not sleep at nightf4 pain in both 7 pain relieved in one knees , day hospitalizationf5 pain in right 7 pain relieved in one knee dayf6 over weight , 7 pain relieved in about knee pain when two days , work possible workingf7 both knees 7 pain disappeared when injured in waking up , could sit accident five cross - legged years agof8 ankles painful 10 and 11 no fatigue next day , for long period work possible______________________________________ table 7______________________________________ ( backache ) adheredpatient symptoms position results______________________________________g1 hospitalization 9 backache relieved , for hernia seven numbing weakened years ago , backache , numbing of left leg______________________________________ table 8______________________________________ ( others ) adheredpatient symptoms position results______________________________________h1 upset stomach 4 symptoms relieved and vomiting after about 20 minutes feeling after mealsh2 acute stomach 5 returned to normal ache after about 30 minutes and able to eat . h3 suffered from ear lobe complete relieved in 30 ear ache minutes . h4 constipated and 5 medicine became ingested unnecessary and bowel medicine daily movement became dailyh5 diarrhea 5 diarrhea conditions conditions disappeared continuedh6 constipation 5 no change______________________________________ fig5 ( a ) is a partial plane view of a band with skin adhering charge carrying pads according to example 2 of the present invention , fig5 ( b ) is a cutaway view showing the state cut along the line b -- b in fig5 ( a ), and fig6 is a back view of the human body with a band with skin adhering charge carrying pads attached . the band 10 with skin adhering charge carrying pads of this example uses substantially round skin adhering charge carrying pads 5 ( 5a to 5i ) obtained by dividing the sheet like kneading material 1 according to example 1 into suitable sizes . that is , the band 10 with skin adhering charge carrying pads it comprised of a flexible attachment band 6 able to be wrapped around the waist , a thin layer like conductive wiring 7 laid around one side ( reverse side ) of the attachment band 6 , skin adhering charge carrying pads 5a to 5i attached at separate locations at predetermined portions of the conductive wiring 7 , and a protective fabric 8 covering the charge carrying pads 5a to 5i and the conductive wiring 7 . the charge carrying pads 5a to 5i are arranged at locations corresponding to the pressure points of the waist . the conductive wiring 7 is power wiring for replenishing the charge of the charge carrying pads 5a to 5i . rivet shaped power terminals 9 are provided at parts of the same . such a band 10 with skin adhering charge carrying pads is wrapped around the waist so that the charge carrying pads 5a to 5i correspond to the pressure points of the waist . the charge carrying pads 5a to 5i carry a charge , so the charge due to the electrostatic induction collects locally at the skin of the adhered portions , so the electrostatic field penetrates deep below the skin directly beneath the same . when the attachment time becomes longer , the charge carrying pads 5a to 5i lose the charge and the electrostatic field gradually weakens . in such a case , the electrostatic field can be sustained by bringing a negative electrode of a charging device into contact with the power terminal 9 and injecting a negative charge to replenish the charge of the charge carrying pads 5a to 5i . the charging device , when a commercial power supply is used , may be comprised of a rectifier diode circuit ( for example , a diode bridge circuit ) and a smoothing capacitor . a battery and capacitor are also acceptable . the charge carrying pad 5 and the skin where it is adhered constitute a type of capacitor , so it may also be constituted by a piezoelectric element and rectifier diode rectifying the pulse current . the band 10 with skin adhering charge carrying pads of this example , as shown in fig7 ( a ), is structured with the engagement projections 7a of the conductive wiring 7 fit in the engagement holes 6a of the flexible attachment belt 6 . charge carrying pads 6 of unnecessary locations on the conductive wiring 7 may be removed . further , the number of charge carrying pads 5 may be increased as well . the invention is not limited to this structure . as shown in fig7 ( b ), it may be a sandwiched layer structure comprised of a conductive wiring 7 covered by an attachment belt 16 and 16 on the two sides , wherein the engagement projections 15a of the charge carrying pads 15 are fit with the engagement holes 16a . note that the invention is not limited to just the above charge carrying pads . for example , it is possible to use an electrotherapy device to which magnetic pads ( magnetic granules ) are attached as well . as explained above , the present invention is characterized by using a skin adhering charge carrying pad as a new electrotherapy device and using a kneading material such as a soft material or elastic material comprised of a plastic insulating substance in which a powder of charcoal is dispersed as a skin adhering charge carrying pad . the following distinctive effects were exhibited . ( 1 ) it is possible to continuously adhere pads to suitable locations on the body according to the symptoms and possible to expect an excellent result effective against various symptoms due to the local action of the charge carrying pads . it is possible to provide a handy , user friendly electrotherapy device . further , it is possible to realize a reduction in the treatment costs . in particular , since a kneading material such as a soft material or elastic material using a plastic insulating material as a binder is used as the skin adhering charge carrying pad , it is possible to eliminate the discomfort at the time of adhesion to the skin . ( 2 ) if plant charcoal is used as the powder of charcoal , the sustainability of the charge becomes longer . ( 3 ) in particular , with mugwort charcoal , the charge carrying pad has a high charge and high sustainability . ( 4 ) if a silicone rubber plastic insulating substance is used as a binder , the viscoelasticity and kneadability can be maintained as they are . rekneading becomes possible at any time by the fingers etc . a large amount of static electricity is generated by he friction at the time of kneading , so easy recharging of the charge carrying pads is possible and repeated use becomes possible . ( 5 ) if more than 5 wt % of charcoal powder is intermixed , the chargeability becomes higher . ( 6 ) by attaching the band with skin adhering charge carrying pads to the body , it is possible to apply an electrostatic field to a plurality if locations of diseased areas or pressure points and improve the ease of use . further , if a charge is applied to the power terminals , it is possible to replenish the charge carried by the charge carrying pads through the conductive wiring and possible to achieve sustainability of the electrostatic field . ( 7 ) by using a charging device for replenishing the charge carried by the skin adhering charge carrying pads , it is possible to achieve easy replenishing of the charges .

to provide a user friendly electrotherapy device not large in space taken and not requiring a human operator or special treatment time , the electrotherapy device uses as a skin adhering charge carrying pad a soft kneaded material comprising a silicone rubber as a binder in which a fine powder of mugwort charcoal etc . is mixed and kneaded well . the ratio of mixture of the powder of charcoal with respect to the silicone rubber is preferably at least 5 wt %. this skin adhering charge carrying pad is superior in the sustainability of the charge . many reports of good results have been obtained by just continuously adhering pads to suitable locations of the body in accordance with the symptoms .

the present invention is a beauty mask which uses natural material , like coconut milk , royal jelly , vegetable enzymes , aloe and loofah , placed on a mask body made of natural material , so that facial skin is not harmed , while a whitening , anti - wrinkle and moisturizing effect is achieved without further additives . furthermore , the present invention is directly frozen , without adding antiseptic agents and antioxidants , allowing for storage over extended periods . in the following , a detailed description is given . coconut milk is used to a fraction of 70 %- 99 % and is the cleanest natural juice found in the world , since palm trees filter out germs in several layers . coconut milk contains vitamin c , fat , proteins , fructose and glucose and is recognized as a mild , germ - free , fever - preventing liquid which is applicable to human skin and easily absorbed there , without invoking allergies . the ingredients of coconut milk have a whitening , anti - wrinkle and moisturizing effect . soap made of palm oil is environmentally friendly and can be washed off by water , while a pleasant natural scent remains , so that no essences need to be added . royal jelly is used to a fraction of 0 . 1 %- 10 % and has in japan used as a beauty agent for a long time . components of royal jelly are active proteins and 10 - hydroxy - decenoic acid ( 10 - hda ), which is naturally effective against germs , several vitamins , including a , c , e , b1 , b2 , b6 , b12 , which are beneficial to the skin , and various organic acids , including pantothenic acid , eolic acid , inoshol and acetyl cholne . in japan , royal jelly has a reputation of being valuable and a symbol of beauty , providing the skin with shine and brilliance . vegetable enzymes are used to a fraction of 0 . 1 %- 5 % and soften horny skin by furthering metabolism with the help of papayase and other enzymes . papayase quickly enters the skin and , in both an acid and alkaline environment , dissolves hair follicles , eliminates dirt and reduces pimples . aloe is used to a fraction of 0 . 1 %- 5 % and strengthens body immunity and helps healing of wounds . the present invention uses aloe arborescens , alow vera , aloe ferox and alow perryi . loofah is used to a fraction of 0 . 1 %- 5 % and helps to reduce swellings and pimples . the mask of the present invention has a mask body made of nonwoven fabric with high absorption for accommodating beauty agents and having properties that do not change after prolonged exposure to freezing temperatures . by employing coconut milk , royal jelly , vegetable enzymes , aloe and loofah , the mask of the present invention contains no substances that are harmful to human skin . the mask of the present invention is directly frozen , without adding antiseptic agents and antioxidants , and then stored at a temperature of approximately − 20 ° c ., allowing for unlimited storage . effects for beauty are : moisturizing and reducing wrinkles by coconut milk and aloe , beautifying and preventing infection by royal jelly , refining and whitening by vegetable enzymes , which all in a short time inter depths of the skin , dissolving hair follicles and fat and giving the skin a healthy , shining appearance . the method for manufacturing of beauty masks of the present invention comprises the steps of : ( 1 ) mixing coconut milk to a fraction of 70 %- 99 %, royal jelly to a fraction of 0 . 1 %- 10 %, vegetable enzymes to a fraction of 0 . 1 %- 5 %, aloe to a fraction of 0 . 1 %- 5 %, and loofah to a fraction of 0 . 1 %- 5 %, forming a liquid beauty agent , keeping the beauty agent at a temperature of 5 ° c . to 10 ° c . ; ( 2 ) filtering the beauty agent at a temperature of 5 ° c . to 10 ° c . ; ( 3 ) soaking a beauty mask body in the beauty agent , so that a beauty mask is generated . for manufacturing beauty masks according to the present invention , it has to be considered that coconut milk is a seasonal product . for avoiding infection with germs , coconut milk used outside harvesting seasons preferably is after harvesting kept at a temperature of approximately − 40 ° c . royal jelly is preferably cleaned of herbicides and pesticides before usage . papayase is preferably prepared by collecting and exposing to ultraviolet light juice of the papaya fruit , so as to kill germs . aloe is peeled , mixed with coconut milk , filtered and exposed to ultraviolet light . loofah is preferably exposed to ultraviolet light , as well . referring to fig2 , the method of the present invention comprises the steps of ( 1 ) cutting openings of certain sizes at certain positions into a separating foil ; ( 3 ) placing the beauty mask on the separating foil , tucking jutting out parts thereof into the openings ; ( 4 ) packing the beauty mask and the separating foil in a bag ; ( 6 ) freezing the bag at a temperature of approximately − 20 ° c . for storage . by storing beauty masks at freezing temperatures , effectivity and freshness thereof are maintained , quality is not impaired , and unlimited storage is possible , without usage of antiseptic agents and antioxidants . the beauty mask of the present invention is during summer after storage at freezing temperatures directly applicable to the skin , providing a pleasant cool and fresh feeling . should the beauty mask feel too cold , storage at room temperature for a couple of minutes before applying is preferred . if applied at cool temperatures , the beauty mask of the present invention tightens the skin effectively and allows for relativiely good absorption of agents . using alcohol , as in conventional beauty masks , leads to a fresh feeling , but is harmful to the skin . for transporting and storing the beauty mask of the present invention , insolating boxes , e . g ., styrofoam boxes , are preferably used . referring to fig2 - 5 , the beauty mask storing and dispensing device of the present invention comprises a bag 10 , a plurality of separating foils 20 , and a plurality of beauty masks 30 . the plurality of separating foils 20 and the plurality of beauty masks 30 are placed in the bag 10 . the bag 10 provides space for accommodating the plurality of separating foils 20 and the plurality of beauty masks 30 . each of the plurality of separating foils 20 is shaped like a rectangle , made of environmentally friendly material , e . g ., pet , which is light and heat - resistant , and has several openings 21 for fastening one of the plurality of beauty masks 30 . each of the plurality of beauty masks 30 is laid on one of the plurality of separating foils 20 , with parts that jut out bent rearward and tucked into the openings 21 thereof . thereby , the plurality of beauty masks 30 are respectively fastened to the plurality of separating foils 20 and , when stacked on each other and placed in the bag 10 , thereby separated from each other and prevented from sticking to each other . dispensing single beauty masks 30 is readily done , without any need to separate single beauty masks 30 from each other , thus avoiding a risk of contamination thereof . in contrast thereto , conventional beauty masks are usually folded and the packed to reduce volume , so that conventional beauty masks are not easily dispensed and a risk of contamination thereof is increased . while a preferred embodiment of the invention have been set forth for the purpose of disclosure , modifications of the disclosed embodiments of the invention as well as other embodiments thereof may occur to those skilled in the art . accordingly , the appended claims are intended to cover all embodiments which do not depart from the spirit and scope of the invention .

a beauty mask uses natural material , like coconut milk , royal jelly , vegetable enzymes , aloe and loofah , for achieving a whitening , anti - wrinkle and moisturizing effect without further additives , thereby avoiding skin injuries , and which can be stored for a long time ; furthermore a method for packing and storing beauty masks , by inserting separating foils between beauty masks and comprising steps of packing , sealing and freezing , prevents beauty masks from sticking together , so that beauty masks are storable for a long time and easily dispensable .

the basic anatomy of the lacrimal fluid drainage system of the human eye 10 is illustrated in fig1 . tears flow into small openings called punctal located in the lids of the eye . both upper punctum 12 and lower punctum 13 lead to corresponding upper canaliculus 14 and lower canaliculus 15 . the upper canaliculus 14 and lower canaliculus 15 merge into the lacrimal sac 16 from which tears travel into the nasal lacrimal duct and drain into the nose . the majority of tears drain through the lower punctum 13 via the canaliculus into the nasal passage . in accordance with features of the invention , a gel plug may be inserted through either punctal into its corresponding canaliculus . the typical punctal can be opened easily to 0 . 5 millimeter diameter . however , for insertion of the silicone elastomer punctal plug 31 and canalicular plug 41 shown in fig3 and 4 , the punctal opening is sometimes stretched to 1 millimeter and beyond to accommodate the largest dimensions of these plugs . each of the punctal openings has a sphincter muscle 32 , 42 formed around it , and excessive stretching of the punctal opening can lead to tearing of this muscle . from the punctal openings 12 , 13 the upper and lower canaliculus 14 , 15 runs vertically for about 2 millimeters and then horizontally for another 8 to 10 millimeters to the lacrimal sac . at its narrowest portion the canaliculus measures about 0 . 5 millimeter in diameter . a gel is defined as a material that is sufficiently soft and pliable as to acquire the shape of the container or structure that it is placed in . it is distinguished from a viscous solution in that it does not dissolve in fluids . a gel plug incorporating features of the invention when placed in the canaliculus will conform to the inside walls of the canaliculus without distorting the walls or changing the volume of the void being filled and completely block passage of fluid through the canaliculus . soft and pliable gels , which are stiff in their dry state , can be formed from a variety of natural and synthetic materials . in general , as the water content of such hydrophilic materials is increased , the material transitions from a rigid or semi - rigid ( stiff ) state at or near zero percent water ; to a more flexible state at moderate percent water contents ; and finally to a soft and pliable gel at high to very high water contents . the transition to a soft and pliable gel typically occurs above about 80 % water content . in contrast , hydrophilic materials , which are usually classified as hydrogels , are composed of polymers that have been modified by cross - linking to covert them from a viscous solution to a gel which swells in the presence of water rather than dissolving . hydrogel can be made by polymerizing hydrophilic monomers in the presence of crosslinkers or by cross - linking the polymers post polymerization . hydrophilic gels can be composed of natural or synthetic polymers . examples of natural gels , derived from natural polymers , include crosslinked polysaccharides like dextran or crosslinked cellulosic polymers like hydroxypropylmethyl cellulose ( hpmc ), methyl cellulose ( mc ) or carboxymethyl cellulose ( cmc ). an example of a synthetic gels is crosslinked polyvinyl alcohol ( pva ). the following monomers may be used by themselves or in combinations with other monomers in varying amounts to obtain polymers that can swell sufficiently in water to form a gel . these monomers can be either neutral , anionic , or cationic . examples of the neutral monomers include hydroxyethyl methacrylate ( hema ), glyceryl methacrylate , propyleneglycol methacrylate , polyethyleneglycol methacrylate , acrylamide and its derivatives , polyvinyl alcohol , and hydrolyzed polyacrylonitrile , and n - vinyl pyrrlidinone ( nvp ). examples of anionic monomers include acrylic or methacrylic acid , crotonic acid , and styrene sulfonate . examples of cationic monomers include aminoethyl methacrylate and its derivatives , and vinyl pyridene . examples of cross - linkers include ethyleneglycol dimethacrylate ( egdma ), polyethyleneglycol dimethacrylate , and methelene - bis - acrylamide . one can also affect cross - linking by adding small amount of hydrophobic monomers to the polymerizing mixture to create hydrophobic domains that can cause a hydrophilic polymer to form gels in the presence of an aqueous media . at high percent water contents , gels formed from all of these materials become soft , pliable , and tissue like . while hydrophilic materials can be produced to absorb a wide range of fluid concentrations , once formed into a shape that shape is generally fixed and swells in all directions maintaining that shape . hydrogels when swollen will not assume the shape of the space in which they are placed . in fact swollen hydrogels can be used to dilate the space in which they are placed . a particularly preferred combination comprises a cross - linked gel prepared from n - vinyl pyrrolidinone ( nvp ) and a difunctional monomer such as , for example , polyethylene dimethacrylate ( peg200 ), ethylene dimethacrylate or propylene dimethacrylate and a free radical initiator such as , for example , azo - bis - isobutrylnitrile or dimethyl - 2 , 2 ′- azobisisobutyrate . a hydrophobic monomer like methyl methacrylate ( mma ), or other esters of methacrylic acid ( e . g . ethyl , butyl , or hexyl , etc .) or n - vinyl phthalimide , or styrene or acrylonitrile can be added to aid in stablizing or firming the gel to give it sufficient body to have the gel characteristics without disintegrating when placed in water . the objective is to produce a cross - linked gel which at hydration equilibrium contains from about 80 % to about 97 % water . below 80 % the swollen gel will maintain its shape and will not readily deform to take the shape of the space that it is confined within . for canaliculus blocking , it is important to fill the space without deforming and not cause irritation or adverse reactions . at very high water content the gel no longer can be kept together in water and behaves as a viscous fluid which eventually dissolves and dilutes indefinitely . the gel materials used in accordance with the present invention are preferably biologically inert , biocompatible , and non - immunogenic . no acute physiological activity or response occurs due to the presence of the gel in the canaliculus . further , the high water content associated with these materials should enable the transport of nutrients and gases to and from the tissues of the canaliculus that the gel is in contact with . this can prevent the eventual denaturation of cells in long term contact with the gel . fig5 shows a first embodiment of a gel plug 61 in accordance to the present invention . the gel plug 61 in its dry state has a diameter appropriate for insertion through the punctum , generally less than about 1 millimeter and preferably less than about 0 . 5 millimeter , and a length of less than about 6 millimeters and preferably less than about 3 millimeters . the plug 61 is formed by either casting the material into molds having the desired geometry , by extrusion of rods which are cut to the desired length , or by coring , cutting , or machining bulk pieces of the material into the desired shape . although other shapes of the dry plug can be made , when the material swells to become a gel , it looses its dry shape and takes on the configuration of the canaliculus where it is placed . the preferred shape is cylindrical for ease of insertion through the punctal opening . the end of the dry plug 52 can be pointed , rounded or made conical to further ease its insertion through the punctum . fig2 shows a prior available resorbable collagen plug 21 inserted into the canaliculus 23 . the plug is made by cutting a twisted catgut suture of 0 . 3 millimeter to 0 . 5 millimeter diameter to the desired length of approximately 2 millimeters . the plug 21 is inserted through the punctal opening into the canaliculus 23 using needle - nose forceps . the end of the collagen plug is held by the forceps and pushed through the punctal opening . the tip of the forceps are then used to push the plug into the vertical portion of the canaliculus . the collagen resorbable plug absorbs tear fluid and expands without substantial change in shape , thus fixating the plug 21 in place until it is degraded by the enzymes in the tear fluid . as shown in fig6 a gel plug 61 in its dry state , having dimensions approximately the same as the resorbable collagen plug 21 , is inserted into the canaliculus 62 ( which is the same as upper canal 14 an lower canal 16 of fig1 ) in a similar manner to the prior art resorbable collagen plug . when the gel plug is in its dry state , it is rigid or semi - rigid ( stiff ) depending on the material and the amount of water in the material . the end of the gel plug can be gripped with forceps 63 and pushed through the punctal opening 64 ( which is the same as punctum openings 12 , 13 of fig1 ). this is performed in a rapid manner as the gel plug may quickly absorb fluids and swell to become a gel . alternatively , as shown in fig7 , the gel plug 61 in its dry state can be placed inside a thin - walled tube 80 such as those formed of polyimide plastic having a wall thickness of approximately 0 . 02 millimeter . the tip 82 of the tube would be placed through the punctal opening 12 , 13 . using a plunger 84 , the gel plug 61 is then pushed from the inside of the tube 80 into the canaliculus 62 . this method of insertion will allow the tube containing the dry plug to be placed through the punctal open without possible hydration and softening of the gel plug until it is pushed from the tube 80 . inside the canaliculus 62 the dry gel plug 61 absorbs lacrimal and other fluids and swells to become a gel . a hydrophilic material having an 80 % water content would swell in volume by 5 times . this represent an increase in diameter and length of 1 . 7 times . ( the cube root of 5 ). similarly a hydrophilic material having a 95 % water content would swell in volume by 20 times . this represents an increase in diameter and length of 2 . 7 times . such a gel plug measuring 0 . 5 millimeter in diameter by 3 . 0 millimeters long in its dry state would swell to be nearly 1 . 5 millimeters in diameter and 9 millimeters long . as illustrated in fig8 , this swollen gel plug 71 would conform to the inside of the canaliculus 62 after it swells , thereby forming an effective blockage of lacrimal fluid flow from the eye . a soft and pliable gel plug would remain in the canaliculus 62 permanently , unless it was intentionally removed by the physician . to remove it , the physician flushes the gel plug out of the canaliculus and into the nasal cavity utilizing a syringe of physiological solution such as saline . a cannula on the end of the syringe is placed through the punctual opening and the physiological solution is injected into the canaliculus . the pressure of the solution expands and lubricates the canaliculus causing the gel plug 61 to be flushed through the canaliculus by the pressure of the solution . at very high water contents , gels are some - what fragile . in some cases the gel plug may be fractured by the solution and flushed out of the canaliculus in several pieces . in order that the present invention may be more fully understood , the following examples and other comparative results are given by way of illustration only and are not intended to be limiting . monomers and initiator were mixed , then filtered through a 0 . 45 micron nylon filter into polypropylene vials ( about 4 ml ) and capped under a nitrogen atmosphere . the mixture was cured at 40 ° c . for one day , then post cured at 80 ° c . to obtain cylinders of a dry gel about 25 millimeters diameter by 10 millimeters thick . the cylinders were cored with an appropriately sized cannula to produce rods measuring approximately 0 . 4 millimeter diameter . these rods were cut into 3 millimeter long gel plugs . this gel formulation following hydration under equilibrium conditions in physiological saline , had a 94 % hydration . the dry gel plugs swelled to 16 times their original volume . the linear dimensions of the gel plugs increased 2 . 5 times to 1 millimeter diameter by 7 . 5 millimeters long . the resultant hydrated gel plug was extremely soft and pliable . monomer mixture from example 1 was filled into polypropylene molds having multiple cavities measuring approximately 0 . 4 millimeter diameter by 3 millimeters deep and the molds were cured as above . the gel plug rods were removed from the molds and extracted with a 50 / 50 mixture of heptane and acetone to remove unreacted monomers , then dried at 50 ° c . the dried gel plug rods were placed in pouches and sterilized by gamma irradiation . toxicological testing showed the above gel plugs to be non - toxic and biocompatible . gel plugs were inserted into the canaliculi of beagle dogs and the flow of lacrimal fluids through the canaliculi was effectively blocked . after a period of time , the gel plugs were removed from the canaliculus by flushing the canaliculi with a syringe filled with saline . the gel plugs were successfully removed from all the canaliculi and flow through the canaliculi was resumed . as an alternative the gel plug 61 may be partially or fully hydrated before insertion into the canaliculus . in such instance the partially or fully hydrated plug is inserted through the punctum using a tubular device such as shown in fig7 . the gel plug can be first hydrated and then drawn into the tubular delivery device or hydrated after placement in the tube of the delivery device by immersing the open end of the tubular delivery device , with gel plug therein , in a container holding the hydration liquid . also it is possible that hydration can be provided in whole or in part after insertion into the canaliculus by also introducing a hydration fluid from an external source . in describing the invention , reference has been made to preferred embodiments . those skilled in the art , and familiar with the disclosure of the subject invention , may recognize additions , deletions , modifications , substitutions , and / or changes which will fall within the purview of the invention as designated in the following claims .

a cylindrical plug for insertion through the punctum and into the canaliculus to block the flow of tears therethrough comprises an insert of a gelatinous material which when hydrated expands and changes shape , conforming at least to a portion of the canaliculus crossection and contacting the walls of the canaliculus , thus blocking flow . the gel plug can be inserted in a dry state and hydrating in situ or hydrated , either partially or fully , prior to insertion .

the compounds of the formula i can be prepared by methods disclosed in u . s . pat . no . 4 , 250 , 094 , issued feb . 10 , 1981 . acid addition salts of compounds of the formula i can be prepared by neutralization of the free base with the appropriate amount of an inorganic or organic acid , examples of which are hydrochloric , hydrobromic , sulfuric , nitric , phosphoric , acetic , lactic , benzoic , salicylic , glycolic , succinic , tartaric , maleic , malic , pamoic , cyclohexanesulfamic , citric and methanesulfonic acids , and like acids . the neutralization can be carried out by a variety of procedures known to the art to be generally useful for the preparation of amine acid addition salts . the choice of the most suitable procedure will depend on a variety of factors including convenience of operation , economic consideration , and particularly the solubility characteristics of the particular free base , the acid , and the acid addition salt . if the acid is soluble in water , the free base can be dissolved in water containing an equivalent amount of the acid , and thereafter , the water can be removed by evaporation ; in some instances , the salt precipitates from the aqueous solution , particularly when cooled , and evaporation is not necessary . if the acid is soluble in a relatively nonpolar solvent , for example , diethyl ether or diisopropyl ether , separate solutions of acid and free base in such a solvent can be mixed in equivalent amounts , whereupon the acid addition salt will usually precipitate because of its relatively low solubility in the nonpolar solvent . alternatively , the free base can be mixed with an equivalent amount of the acid in the presence of a solvent of moderate polarity , for example , a lower alkanol , a lower alkanone , or a loweralkyl ester of a lower alkanoic acid . examples of these solvents are ethanol , acetone , and ethyl acetate , respectively . subsequent admixture of the resulting solution of acid adddition salt with a solvent of relatively low polarity , for example , diethyl ether or hexane , will usually cause precipitation of the acid addition salt . these acid addition salts are useful for upgrading the free bases . the compositions of the present invention are presented for administration to humans in unit dosage forms , such as tablets , capsules , pills , powders , granules , sterile parenteral solutions or suspensions , and oral solutions or suspensions , and oil in water and water in oil emulsions containing suitable quantities of the compound of formula i . for oral administration either solid or fluid unit dosage forms can be prepared . for preparing solid compositions such as tablets , the compound of formula i is mixed with conventional ingredients such as talc , magnesium stearate , dicalcium phosphate , magnesium aluminum silicate , calcium sulfate , starch , lactose , acacia , methylcellulose , and functionally similar materials as pharmaceutical diluents or carriers . wafers are prepared in the same manner as tablets , differing only in shape and the inclusion of sucrose or other sweetener and flavor . in their simplest embodiment , capsules , like tablets , are prepared by mixing the compound with an inert pharmaceutical diluent and filling the mixture into a hard gelatin capsule of appropriate size . soft gelatin capsules are prepared by machine encapsulation of a slurry of the compound with an acceptable vegetable oil , light liquid petrolatum or other inert oil . fluid unit dosage forms for oral administration such as syrups , elixirs , and suspensions can be prepared . the water - soluble forms can be dissolved in an aqueous vehicle together with sugar , aromatic flavoring agents and preservatives to form a syrup . an elixir is prepared by using a hydro - alcoholic ( ethanol ) vehicle with suitable sweeteners such as sugar and saccharin , together with an aromatic flavoring agent . suspensions can be prepared with a syrup vehicle with the aid of a suspending agent such as acacia , tragacanth , methylcellulose and the like . for parenteral administration , fluid unit dosage forms are prepared utilizing the compound and a sterile vehicle , water being preferred . the compound , depending on the vehicle and concentration used , can be either suspended or dissolved in the vehicle . in preparing solutions the compound can be dissolved in water for injection and filter sterilized before filling into a suitable vial or ampul and sealing . advantageously , adjuvants such as a local anesthetic , preservative and buffering agents can be dissolved in the vehicle . to enhance the stability , the composition can be frozen after filling into the vial and the water removed under vacuum . the dry lyophilized powder is then sealed in the vial and an accompanying vial of water for injection is supplied to reconstitute the liquid prior to use . parenteral suspensions are prepared in substantially the same manner except that the compound is suspended in the vehicle instead of being dissolved and sterilization cannot be accomplished by filtration . the compound can be sterilized by exposure to ethylene oxide before suspending in the sterile vehicle . advantageously , a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound . the term unit dosage form as used in the specification and claims refers to physically discrete units suitable as unitary dosages for human subjects and animals , each unit containing a predetermined quantity of a active material calculated to prevent panic atacks or treat panic disorders in association with the required pharmaceutical diluent , carrier or vehicle . the specifications for the novel unit dosage forms of this invention are dictated by and directly dependent on ( a ) the unique characteristics of the active material and the particular effect to be achieved , and ( b ) the limitations inherent in the art of compounding such an active material for use in humans and animals , as disclosed in detail in this specification , these being features of the present invention . examples of suitable unit dosage forms in accord with this invention are tablets , capsules , pills , suppositories , powder packets , granules , wafers , cachets , teaspoonfuls , tablespoonfuls , dropperfuls , ampuls , vials , segregated multiples of any of the foregoing , and other forms as herein described . the dosage of the compound for treatment depends on route of administration ; the age , weight , and condition of the patient . a dosage schedule of from about 5 to 50 mg / day in a single or divided dose , embraces the effective range for treating panic disorders for which the compositions are effective . the dosage to be administered is calculated on the basis of from about 0 . 05 to about 2 mg / kg by weight of subject per day . the compound is compounded with a suitable pharmaceutical carrier in unit dosage form for convenient and effective administration . in the preferred embodiments of this invention , the dosage units contain the compound in : 5 , 10 , 20 and 50 mg amount for systemic treatment ; and 0 . 1 % to 1 % w / v for parenteral treatment . the compositions are useful in preventing and treating panic attacks in adults ( age fifteen years or more ), agoraphobia , and phobic anxiety . the following examples are illustrative of the best mode contemplated by the inventor for carrying out his invention and are not to be construed as limiting . a lot of 10 , 000 tablets , each containing 5 mg of 8 - chloro - 1 -[( dimethylamino )- methyl ]- 6 - phenyl - 4h - s - triazolo [ 4 , 3 - a ][ 1 , 4 ] benzodiazepine methanesulfonate is prepared from the following types and amounts of ingredients : the compound and dicalcium phosphate are mixed well , granulated with 7 . 5 percent solution of methylcellulose in water , passed through a no . 8 screen and dried carefully . the dried granules are passed through a no . 12 screen , mixed thoroughly with the talc , starch and stearate , and compressed into tablets . these tablets are useful in preventing panic attacks at a dose of 1 tablet 4 times a day . one thousand two - piece hard gelatin capsules , each containing 10 mg of 8 - chloro - 1 -[( dimethylamino )- methyl ]- 6 - phenyl - 4h - s - triazolo [ 4 , 3 - a ][ 1 , 4 ] benzodiazepine methanesulfonate are prepared from the following types and amounts of ingredients : the ingredients are mixed well and filled into capsules of the proper size . capsules so prepared are useful to prevent panic attacks at a dose of one capsule four times a day . one thousand tablets for sublinqual use are prepared from the following ingredients : the ingredients are mixed well and compressed into sublingual - type tablets weighing 245 mg . these tablets placed under the tongue are useful in treating panic attacks at a dose of 1 tablet . soft gelatin capsules for oral use , each containing 20 mg of 8 - chloro - 1 -[( dimethylamino )- methyl ]- 6 - phenyl - 4h - s - triazolo [ 4 , 3 - a ][ 1 , 4 ] benzodiazepine methanesulfonate are prepared by first dispersing the micronized compound in corn oil to render the material capsulatable and then encapsulating in the usual manner . one thousand tablets , each containing 50 mg . of 8 - chloro - 1 -[( dimethylamino )- methyl ]- 6 - phenyl - 4h - s - triazolo [ 4 , 3 - a ][ 1 , 4 ] benzodiazepine methanesulfonate are made from the following types and amounts of ingredients : the ingredients are screened and blended together and pressed into 500 mg tablets . the tablets are useful to prevent panic attacks at a dose of one tablet twice a day . a sterile preparation suitable for intramuscular injection and containing 10 mg of 8 - chloro - 1 -[( dimethylamino )- methyl ]- 6 - phenyl - 4h - s - triazolo [ 4 , 3 - a ][ 1 , 4 ] benzodiazepine methanesulfonate in each milliliter is prepared from the following ingredients : one milliliter of this sterile preparation is injected to treat panic attack . following the procedure of the preceding example 1 to 6 , inclusive , compositions are similarly prepared and administered substituting one equal amount of the free base , n - oxide , or hydrochloride salt of the active compound of the example .

therapeutic process for treating panic disorders in humans comprising , the systemic administration of a 8 - chloro - 1 -- methyl ]- 6 - phenyl - 4h - s - triazolobenzodiazepine including the n - oxides and pharmacologically acceptable acid addition salts thereof in combination with a pharmaceutical carrier .

with reference now to the drawings , and in particular to fig1 through 6 thereof , a new spice dispensing device embodying the principles and concepts of the present invention and generally designated by the reference numeral 10 will be described . as best illustrated in fig1 through 6 , the spice dispensing device 10 generally comprises a container including a pair of side members 11 , 17 detachably attached to one another . the side members 11 , 17 are made of permeable material and are generally concave and are mirrored halves with each of the side members 11 , 17 including a curved side wall 12 , 18 having an outer edge 13 , 19 , and also includes an open side , a top end 14 , 20 , and a flat bottom end 15 , 21 for resting upon a surface . each of the side members 11 , 17 also has a slot 16 , 22 being disposed in a respective outer edge 13 , 19 and in a respective top end 14 , 20 thereof . the slots 16 , 22 are mated to form an opening in the container when the side members 11 , 17 are closed upon one another . the spice dispensing device 10 also comprises a means for attaching the side members 11 , 17 together . the means for attaching the side members 11 , 17 together includes a hinge member 23 being conventionally attached along portions of the outer edges 13 , 19 of the side members 11 , 17 , and also includes a lid 24 having an edge hingedly attached along an edge of the slot 16 of one of the side members 11 . the lid 24 also has a latch member 25 for fastening to the other of the side members 17 . the lid 24 further is removably closed over the opening . a funnel 26 is removably disposed in the container for filling the container with selected spices . the funnel 26 is removably extended through the opening into the container for filling the container with the selected spices with the funnel 26 being tapered from a top to a bottom . in use , the user opens the lid 24 and puts selected spices in the container and then closes the lid 24 , and places the spice dispensing device 10 in with the food such as a pot which is cooking the food upon which the food would be flavored with the flavoring from the spices permeating through the side walls 11 , 17 of the container without the spices actually coming into contact with the food . as to a further discussion of the manner of usage and operation of the present invention , the same should be apparent from the above description . accordingly , no further discussion relating to the manner of usage and operation will be provided . with respect to the above description then , it is to be realized that the optimum dimensional relationships for the parts of the invention , to include variations in size , materials , shape , form , function and manner of operation , assembly and use , are deemed readily apparent and obvious to one skilled in the art , and all equivalent relationships to those illustrated in the drawings and described in the specification are intended to be encompassed by the present invention . therefore , the foregoing is considered as illustrative only of the principles of the invention . further , since numerous modifications and changes will readily occur to those skilled in the art , it is not desired to limit the invention to the exact construction and operation shown and described , and accordingly , all suitable modifications and equivalents may be resorted to , falling within the scope of the invention .

a spice dispensing device for seasoning food and regulating the proper amounts of spices being used to season the food . the spice dispensing device includes a container including a pair of side members detachably attached to one another ; and also includes a funnel being removably disposed in the container for filling the container with selected spices .

the baler 10 is provided with ground wheels 12 adapting the same for movement across a field , a fore - and - aft extending tongue 14 adapted at its forwardmost end for attachment to a towing vehicle ( not shown ), a pickup 16 for lifting windrowed crop materials off the ground as the baler 10 advances , and a bale chamber 18 disposed upwardly and rearwardly from the pickup 16 for receiving crop material from the latter . the chamber 18 is partially defined by belts 20 and 22 that cooperate to roll the incoming crop material into a bale until the latter reaches final size such as represented by the bale 24 in fig1 . when the bale 24 reaches its final size , advancement of the baler 10 is halted , but the belts 20 , 22 continue to be driven in direction that will cause bale 24 to continue spinning within the chamber 18 about the longitudinal axis of the cylindrical bale . at this time , a suitable wrapping element ( herein illustrated and described as being twine although other suitable materials could likewise be utilized ) is dispensed to the bale 24 progressively along the length thereof so that the bale 24 wraps itself with the element to preserve its integrity upon discharge from the baler 10 . to this end , the baler 10 is provided with twine - dispensing mechanism broadly denoted by the numeral 26 , said mechanism 26 including a generally l - shaped dispensing tube 28 having an upturned end 30 pivotally coupled via a pivot 32 to a transverse structural member 34 for swinging movement about the axis of the upright pivot 32 . although in practice a pair of such tubes 28 may be utilized , for clarity only a single tube 28 has been illustrated and will be described herein . the tube 28 includes an outermost sleeve end 36 that is operably coupled with power apparatus for effecting swinging of the tube 28 about the pivot 32 , said apparatus taking any suitable form . for example , a hydraulic piston and cylinder assembly 38 has been shown schematically in fig8 . the assembly 38 is operable to swing the tube 28 between its home or standby position as illustrated in fig1 , 9 , 14 and 15 , and a remote , operated position approximately 90 ° from the home position . as illustrated in fig2 twine 40 may be fed from a source of supply within a twine box 42 on the outside of the baler 10 . the twine 40 passes through a suitable tensioning device 44 on its way to the tube 28 , such tensioning device 44 being shown more completely in fig3 as including a plate 46 biased by springs 48 and 50 toward the proximal sidewall 10a of the baler 10 so as to yieldably clamp the twine 40 against the sidewall 10a . the degree of clamping pressure applied by the springs 48 , 50 may be adjusted through nuts 52 and 54 threaded onto the outer ends of studs 56 and 58 , such nuts 52 , 54 serving to trap the respective springs 48 , 50 in place about their corresponding studs 56 , 58 against the plate 46 . the twine 40 enters the tube 28 via the upturned end 30 thereof and leaves the same via the sleeve end 36 thereof . a cutter 60 is mounted on the inside surface of the sidewall 10a in a position slightly rearwardly of and slightly below the structural member 34 . the cutter 60 includes a faceplate 62 rigidly secured by means not shown in a flat relationship against the sidewall 10a to provide supporting assistance for the remaining components of the cutter 60 . a knife 64 in the form of a generally flat plate has a tubular boss 66 adjacent one end thereof which rotatably receives a pivot bolt 68 which in turn attaches the knife 64 to the faceplate 62 adjacent the upper region thereof . bolt 68 adapts the knife 64 for depending , swinging movement about an axis disposed in transverse relationship to the path of travel of the baler 10 and likewise in transverse relationship to the path of travel of the tube 28 in the vicinity of the standby position of the latter . the lowermost edge of the knife 64 is sharpened so as to present a knife edge 70 extending parallel to the axis and swinging movement of the knife 64 , and an upwardly projecting ear 72 on the boss 66 is adapted to receive one end of a tension spring 74 which extends in a generally vertical direction upwardly from the axis defined by the bolt 68 to be attached at its upper end to an inwardly projecting lug 76 on the sidewall 10a as illustrated in fig7 . consequently , the spring 74 yieldably biases the knife 64 to an essentially vertically oriented position which is illustrated , for example , in fig9 and which may hereinafter be referred to as the cutting position of the knife 64 . the cutter 60 also includes a second member or lever 78 of generally l - shaped configuration having a relatively long flat leg 80 and a relatively short upturned leg 82 . the lever 78 has a tubular boss 84 affixed transversely to the backside thereof between the opposite ends 86 and 88 , said boss 84 rotatably receiving a pivot bolt 90 attaching the lever 78 to the faceplate 62 for rocking movement about an axis transverse to the path of travel of the baler 10 and to the path of travel of the twine tube 28 as the latter moves in the vicinity of its home position . the pivot bolt 90 is substantially directly below the pivot bolt 68 for the knife 64 and is disposed in parallelism therewith . the short leg 82 of lever 78 has a depending lug 92 to which is attached one end of a tension spring 94 , the opposite end of the spring 94 being suitably secured to a transverse structural member 96 or the like of the baler 10 as illustrated in fig7 such that the spring 94 yieldably biases the lever 78 in a clockwise direction viewing fig4 to rock the long leg 80 upwardly toward the knife 64 and the short leg 82 downwardly away from the knife 64 . the knife 64 and the lever 78 are disposed in vertical alignment with each other transversely of the baler 10 , and the long leg 80 is of such length that it is disposed to engage the boss 66 associated with knife 64 when the lever 78 is rocked to the position of fig4 the boss 66 thereby serving as a limit stop for the biasing action of the spring 94 against the lever 78 . as illustrated herein , the end 88 of the lever 78 is preferably sharpened , although such is not an absolute requirement insofar as proper functioning of the cutter 60 is concerned . in this regard , as will hereinafter become apparent , the main role of the end 88 of lever 78 is to serve as a transverse guide across which the twine 40 is drawn during the cutting sequence , the primary severing action being obtained at the knife edge 70 of the knife 64 . however , having the end 88 of lever 78 sharpened does provide a source of backup or auxiliary severing ability if , for any reason , such should become necessary during the twine - cutting sequence . in use , the piston and cylinder assembly 38 maintains the twine tube 28 in its home or standby position of fig1 and 9 throughout the time that the bale 24 is forming within the chamber 18 . at such time , the condition of the knife 64 and lever 78 is as shown in fig9 wherein the tube 28 is located forwardly beyond the depending knife 64 in the sense of the direction of travel of the baler 10 and maintains the lever 78 rocked to a position wherein the long leg 80 is almost horizontal , and the upturned , short leg 82 is slightly past vertical . the knife 64 hangs essentially vertically at this time , aided by the spring 74 . a portion of the twine 40 dangles from the end of the tube 28 from the previous wrapping and cutting cycles . upon actuation of the piston and cylinder assembly 38 , the twine tube 28 swings rearwardly into engagement with the front side of the knife 64 as shown in fig1 and deflects the knife 64 out of the way . such movement of the tube 28 permits the spring 94 to rock the lever 78 in a clockwise direction from its fig9 position until the long leg 80 abuts the stop defined by the boss 66 associated with the knife 64 . further rearward movement of the twine tube 28 causes the latter to clear the knife 64 and permit the latter to swing back to its vertically depending position as illustrated in fig1 , for example . when the twine tube 28 has swung sufficiently far rearwardly for the dangling twine 40 to be caught up in new crop material being delivered to the chamber 18 by the pickup 16 , the twine 40 will commence wrapping around the bale 24 as the tube 28 continues to be swung essentially along the length of the bale 24 toward an extreme remote position approximately 90 ° from that shown in fig8 . the operator will normally terminate further advancement of the baler 10 at this time such that no new material is picked up , although the belts 20 , 22 continue to be operated so that the bale 24 continues to spin within the chamber 18 , the twine 40 thereby being coiled helically around and along the length of the bale 24 as the tube 28 swings back and forth between its two extreme positions . fig1 shows the twine tube 28 returning home toward the cutter 60 near the end of the wrapping cycle . as the tube 28 then makes contacting engagement with the depending knife 64 as illustrated in fig1 , the tube 28 begins to swing and deflect the knife 64 out of its way so that the tube 28 can reach its home , standby position . pressure is simultaneously transmitted to the long leg 80 of the lever 78 so as to likewise rock the latter in a counterclockwise direction to move it out of the way of the tube 28 as well . this action continues as illustrated in fig1 as the tube 28 continues to approach its standby position and moves between the pivoting axes of the knife 64 and the lever 78 . finally , as shown in fig1 , the tube 28 reaches its standby position , at which point the tube 28 releases the knife 64 and bears directly against the leg 80 of lever 78 to rock the same to its counterclockwisemost position corresponding to that of fig9 . note that by the time the tube 28 reaches the position of fig1 , the twine 40 has been drawn between the knife 64 and the lever 78 and across the guide defined by the end 88 of lever 78 . a stretch 40a of the twine 40 is thus presented between the guide end 88 of the lever 78 and the tube 28 at this time , and it should be remembered that such stretch 40a is fairly taut because of the fact that the spinning bale 24 is pulling on one end of the twine 40 while the opposite end of the twine 40 is being resistively paid out by the tube 28 and the tensioning device 44 of fig2 and 3 . the stretch 40a is also moving rather rapidly at this time in a linear sense rearwardly toward the bale 24 . such linear movement of the twine 40 , coupled with the force of gravity and the return spring 74 , causes the knife 64 to be returned quickly back to its essentially vertical position of fig1 as the knife edge 70 of knife 64 comes into contacting engagement with the stretch 40a . the distance from the pivot bolt 68 to the knife edge 70 exceeds the perpendicular distance between the bolt 68 and a straight line drawn between the tube 28 and the guide end 88 of lever 78 such that , as the knife 64 returns to its fig1 position with the knife edge 70 engaging the stretch 40a , the latter is deflected and depressed downwardly toward the lever 78 and out of a straight - line configuration such that the edge 70 and guide end 88 cooperate to provide a serpentine restriction and resistance to further pay out of the twine 40 to bale 24 . this places great stress upon the stretch 40a at the points where it moves across the edge 70 and the guide end 88 . continued linear movement of the twine 40 toward the bale 24 simply increases the intensity of the restrictive forces and the stress on the stretch 40a across these two strategic points as the twine stretch 40a drags the knife edge 70 closer and closer to guide end 88 , until at a certain instant the serpentined stretch 40a can no longer withstand such forces and the twine 40 severs itself against the knife edge 70 . it has been found that the knife 64 is normally rotated in a slightly more counterclockwise position from that illustrated in fig1 at the precise moment of severance . upon severance the knife 64 returns to the extent necessary to its vertically depending position controlled by the spring 74 such as illustrated in fig9 and the lever 78 remains in the position held by the tube 28 as also shown in that figure . the above - described cycle is then ready to be repeated after the next bale has been completely formed . hence , it will be seen that the twine 40 itself determines the precise point in time that severance will occur . only after the moving twine 40 has pulled the knife 64 so far toward the guide end 88 that the stretch 40a is too severely crimped , tensioned and otherwise stressed to withstand the shearing action of the knife edge 70 will the twine 40 indeed be severed . consequently , it will be recognized that the twine 40 itself does indeed actuate the cutter 60 to carry out the severance in contra distinction to prior devices wherein severance was totally controlled by the twine - dispensing tube and its position relative to other components of the baler . furthermore , it is noteworthy that any crop material which might tend to become accumulated on the lever 78 during the bale - forming cycle is dumped from the lever 78 at the beginning of the wrapping cycle as the lever 78 swings quickly upwardly to its fig1 and fig1 position . even if a small amount of material should happen to accumulate on the lever 78 during the short interval that the bale is being wrapped , such accumulated material will pose no problem insofar as proper cutting action of the knife 64 is concerned because such material can only lie beneath the twine stretch 40a as the lever 78 rocks rearwardly to its positions of fig1 and 15 . consequently , the accumulated material is not between the stretch 40a and the knife edge 70 but rather is in a backing - up position on the far side of the stretch 40a to , if anything , actually assist in proper severance rather than detract therefrom .

as the twine dispensing tube swingably approaches its home or standby position , the tube strikes one leg of an l - shaped , pivoting lever of the cutter to swing the opposite leg thereof up into edgewise engagement with the underside of the twine such that the latter is stretched between the raised leg and the end of the tube . a depending , swingable knife of the cutter which has been momentarily pushed by the tube out of its path of travel returns with its sharp edge engaging the twine stretch and depresses the latter out of a straight - line relationship between the tube and the raised leg of the lever such that , as the tension and stress in the moving twine stretch increase due to its deflected , serpentine condition around said knife edge and the lever and the opposite pulling forces exerted by the tube and the bale , the twine severs itself against the sharp edge of the knife .

with respect to fig1 there is illustrated one embodiment of a fire suppression system 100 comprising an electronic system having electric circuits for detecting , identifying , and recording the presence of persons 112 within a monitored area 113 . fire suppression system 100 includes a fire detector 105 , electronic id readers or detectors 103 , 104 , rfid detector 110 , an audible and visible alarm 119 , fire suppressant containers 108 , 109 , fire suppressant tank outlets 116 , 117 , all electrically connected to fire control processing system 106 over communication channel 107 . a person 111 not within monitored area 113 enters monitored area 113 through entry / exit points 101 , 102 . similarly , a person 112 within monitored area 113 exits monitored area 113 through entry / exit points 101 , 102 . fire suppressant tanks 114 , 115 for flooding monitored area 113 are connected to fire suppressant tank outlets 116 , 117 , respectively , via pipes 118 . electronic id readers or detectors 103 , 104 may be deployed at each entry / exit point 101 , 102 for detecting entry and exit by persons into and out of monitored area 113 . such devices may comprise employee badge readers , which can be card - based magnetic strip reading devices or bar code reading devices ; text input devices such as keypads or other input devices for inputting id numbers or names ; radio frequency identification ( rfid ) reading devices which comprise circuitry for detecting an rfid source worn or carried by an employee , worker or other person ; a facial imaging and recognition device which includes a digital camera for capturing an image of a person &# 39 ; s face and facial recognition programming for identifying the person based on the captured facial image ; a retinal imaging and recognition device which captures an image of a portion of a person &# 39 ; s eye for identifying the person based on retinal patterns ; a voice recognition device for receiving a voice sample from a person in order to identify the person based on voice characteristics ; a fingerprint reader ; a hand print reader ; or any combination thereof . the id readers or detectors 103 , 104 are placed at each entry / exit point 101 , 102 and contain electric circuits for detecting and reading id information from each person entering and exiting monitored area 113 . the id information so detected is electronically stored in electronic memory of fire control processing system 106 or in memory that is accessible by fire control processing system 106 . instead of , or in combination with , the readers and detectors just described , an rfid detection system may be deployed within monitored area 113 to track personnel that are present within monitored area 113 by detecting rfid devices worn or carried by personnel within monitored area 113 . persons entering within range of rfid detector 110 are detected , identified , and recorded as being present in monitored area 113 . conversely , persons that depart monitored area 113 are detected , identified , and recorded as being no longer present in range of rfid detector 110 in monitored area 113 . such detection systems , as described herein , can be used to store the detected identification data and used in conjunction with , for example , an employee database that may be part of a standard security system employed by a company for controlling entry to monitored areas 113 of work sites by authorized personnel . the fire control processing system 106 may be configured to have access to such a security system database . each electronic id reader or detector 103 , 104 , or the personnel id data generated thereby , is accessible by fire control processing system 106 for determining , at any time , the presence of persons within monitored area 113 . fire control processing system 106 can be configured to be connected to , or part of , such a standard security system for tracking personnel that enter and exit monitored area 113 . databases utilized for tracking such personnel can be electrically connected to fire control processing system 106 such that fire control processing system 106 can freely access such data to determine whether there are persons who have entered but not exited the monitored area 113 via the entry / exit points 101 , 102 . in the embodiment shown in fig1 , the fire control processing system 106 directly manages and is directly connected to the electronic id readers and detectors 103 , 104 using communication channel 107 . in the embodiment shown in fig1 , fire control processing system 106 comprises a processor and memory for managing personnel id data and for storing and executing programs according to the algorithms described herein . the fire control processing system 106 can be located proximate to or remote from monitored area 113 . communication channel 107 represents either a wired communication channel 107 or a wireless communication channel . wired communication channel 107 can be implemented as a networked communication channel , such as an ethernet or usb communication channel , or a privately designed communication channel . similarly , the communication channel implemented as a wireless communication channel can be implemented as a wifi , cellular , or a privately designed wireless communication channel . fire control processing system 106 may comprise a microcontroller , memory , and electric circuits for executing a stored computer program triggered by reception of the fire condition signal from fire detector 105 . fire control processing system 106 may be embodied in an application executed on a general purpose processing system such as a pc or laptop , a site wide server , or a network - based system remotely located from monitored area 113 and communicating , over communication channel 107 implemented as an internet connection , with fire detector 105 or other detection devices proximate to monitored area 113 . in one embodiment , communication channel 107 may comprise , in various combinations , an internet connection , a cellular network connection , a wired network connection and a wifi connection interoperating to maintain communication between detection devices proximate to monitored area 113 and fire control processing system 106 connected remotely to such devices . in one embodiment , electronic id readers and detectors 103 , 104 are not configured to identify each person entering and exiting monitored area 113 . rather , the electronic id readers and detectors 103 , 104 track persons who enter and exit monitored area 113 without identifying such persons and merely keep track of a total count of persons entering and exiting monitored area 113 . such devices can comprise one or more of the readers and detectors described above and can further include other means for tracking entry and exit of persons from monitored area 113 , such as turnstiles , infrared detectors , and light beam detectors , for example . an rfid detection system using rfid detector 110 can anonymously detect persons carrying or wearing generic rfid tags . rfid detector 110 can be replaced or used together with a motion detector or infrared detector for determining that one or more persons are present or not present within monitored area 113 . any such detection devices communicate detection data to fire control processing system 106 as described above to indicate whether detection data indicates the presence of one or more persons within monitored area 113 . detected motion by a motion detector , or a total entry count higher than an exit count at entry / exit points 101 , 102 are further examples of data indicating the presence of persons in monitored area 113 . the fire suppressant container 109 is designated to store a human - safe fire suppressant , and container 108 is designated to store a carbon dioxide - based fire suppressant , wherein each container is connected to fire control processing system 106 using communication channel 107 . each of fire suppressant containers 108 , 109 comprise an electrically actuable valve for releasing its contents under pressure upon receiving an electric signal from fire control processing system 106 over communication channel 107 to open its valve . similarly , the valves in fire suppressant containers 108 , 109 close in response to receiving a second electric signal from fire control processing system 106 over communication channel 107 for terminating release of fire suppressant . the fire suppression system 100 is automated and is programmed to constantly monitor an area 113 such as a region on a factory floor , or other commercial or private premises wherein various personnel may enter and exit via one or more entry / exit points 101 , 102 . the premises may be occupied by at least one person intermittently , during scheduled times , or at all times . a programmed operation of fire suppression system 100 is triggered upon receiving a signal at fire control processing system 106 from fire detector 105 that a fire condition has been detected , as described below . in one embodiment , one or more fire detectors such as fire detector 105 is powered via battery power or permanent site power supply , and constantly monitors area 113 . upon detecting a fire condition , fire detector 105 issues an electric signal to fire control processing system 106 over communication channel 107 . fire detector 105 may comprise any conventional fire detection means such as a smoke detector or a heat detector . in one embodiment , a smoke detector may comprise a photodetector that monitors clarity of the air within smoke detector and is triggered when fire generated smoke particles affect transmissivity of the air within the detector above or below a preset threshold . in another embodiment , a smoke detector may comprise a ionization detector that monitors the air within the smoke detector and is triggered when fire generated smoke particles affect conductivity of ionized air within the smoke detector above a certain preset threshold . the fire detector 105 may also comprise a combination of the above types of smoke detectors . in another embodiment , fire detector 105 may be a heat detector , such as a temperature reading electronic heat detector , or an eutectic alloy ( melting switch ) heat detector , or a rate - of - rise heat detector , or a combination of the above . in one embodiment , the fire detection mechanism may be powered by connecting it to a permanent building power supply ( mains ), a battery , or capacitor - based power supply , or in any combination thereof , and using any combination thereof as a backup power supply . the preceding examples of fire detection mechanisms are not to be interpreted in a limiting sense , and are described herein as exemplary detection mechanisms useable with embodiments of the present invention . any other type of fire detection device used in fire suppression system 100 is contemplated as an embodiment of the present invention . the human - safe fire suppressant in fire suppressant container 109 may include a dry chemical powder ( dcp ) fire extinguishing agent , or another fire suppressant that is safe for humans , to be used when one or more persons are detected inside monitored area 113 during a fire condition . fire suppressant container 109 using a dcp fire suppressant is available in portable cylinders pressurized with nitrogen . similarly , fire suppressant container 108 using a carbon dioxide - based fire suppressant is available in portable pressurized cylinders . in one embodiment , large fire suppressant tanks 114 , 115 are connected with piping system 118 to fire suppressant tank outlets 116 , 117 respectively . the outlets are capable of selectively flooding monitored area 113 under control of an electric signal from fire control processing system 106 over communication channel 107 to either or both of fire suppressant tank outlets 116 , 117 . in this embodiment , fire suppressant tank 114 comprises a carbon dioxide - based fire suppressant in sufficient quantities for flooding monitored area 113 , while fire suppressant tank 115 comprises a fire suppressant safe for humans in sufficient quantities for flooding monitored area 113 , such as the dcp described above . both fire suppressant tank outlets 116 , 117 comprise valves selectively electrically actuable , individually or together , under control from an electric signal received from fire control processing system 106 over communication channel 107 to open and release fire suppressant from the fire suppressant tanks 114 , 115 , respectively , through a corresponding pipe 118 and through fire suppressant tank outlets 116 , 117 for flooding monitored area 113 . similarly , the valves in fire suppressant tank outlets 116 , 117 are selectively electrically actuable to close , for terminating the release of fire suppressant into monitored area 113 upon receiving a second signal from fire control processing system 106 . the dcp in fire suppressant container 109 and in fire suppressant tank 115 may comprise monoammonium phosphate . monoammonium phosphate is a well - known fire suppressant and is non - toxic to human beings . in the event that carbon dioxide has been released , or carbon dioxide is otherwise present , and a person is in , or enters , the monitored area 113 during a fire condition state , the dcp from fire suppressant container 109 or from fire suppressant tank 115 may be released into monitored area 113 as described below . with reference to fig2 , there is illustrated a fire control processing system algorithm 200 performed by fire control processing system 106 according to a program stored in a memory of fire control processing system 106 . as described above , fire detector 105 constantly monitors area 113 for a fire condition . when fire detector 105 detects a fire condition , it transmits an electric signal over communication channel 107 to fire control processing system 106 which interprets the signal as a fire condition detected signal at step 201 . at step 202 , fire control processing system 106 triggers an audible and visible alarm 119 in monitored area 113 by sending an electrical signal to alarm 119 over communication channel 107 . at step 203 , fire control processing system 106 determines if one or more people are present in monitored area 113 as described above . for example , fire control processing system can access an id information database to determine that people who have entered monitored area 113 have not yet exited , that a total entry count is less than a total exit count , that rfid detector 110 is currently detecting rfid tags in monitored area 113 , or that a motion detector is currently detecting motion in monitored area 113 . if fire control processing system 106 determines that one or more people are present in monitored area 113 , then at step 204 fire control processing system 106 sends an electric signal over communication channel 107 to human - safe fire suppressant container 109 , or to human - safe fire suppressant tank outlet 117 , or both , which causes corresponding valves to open and release human - safe fire suppressant from container 109 into monitored area 113 , and / or from tank 115 through fire suppressant tank outlet 117 for flooding monitored area 113 . a programmed delay occurs at step 205 for a preselected duration to allow time for people present in monitored area 113 to evacuate . at step 206 , fire control processing system 106 checks to determines if people are present in monitored area 113 . if fire control processing system 106 determines that people are still present in monitored area 113 then the human - safe fire suppressant continues to be released at step 204 until it is depleted , manually shut off , or the fire control processing system no longer detects a fire condition . if fire control processing system 106 determines at step 206 that people are no longer present in monitored area 113 , then the fire control processing system 106 sends an electric signal over communication channel 107 to carbon dioxide - based fire suppressant container 108 , or to carbon dioxide - based fire suppressant tank outlet 116 , or both , which causes the corresponding valves to open and release carbon dioxide - based fire suppressant from container 108 into monitored area 113 , and / or from fire suppressant tank 114 for flooding monitored area 113 through fire suppressant tank outlet 116 . the release of carbon dioxide - based fire suppressant at step 207 , following decision step 206 , may include fire control processing system 106 sending a second electric signal over communication channel 107 to fire suppressant container 109 , or to fire suppressant tank outlet 117 , or both , to close their valves and terminate release of the human - safe fire suppressant , or the human - safe fire suppressant can continue to be released together with the carbon dioxide - based fire suppressant . after step 207 , at step 206 , fire control processing system 106 determines if people are present in monitored area 113 . if fire control processing system 106 determines that people are still no longer present in monitored area 113 then the carbon dioxide - based fire suppressant continues to be released at step 207 until it is depleted , manually shut off , the fire control processing system no longer detects a fire condition , or until fire control processing system 106 detects that people are present at step 206 . if fire control processing system 106 determines at step 206 that people are present in monitored area 113 after a release of carbon dioxide - based fire suppressant at step 207 , then , at step 208 the fire control processing system 106 sends a second electric signal over communication channel 107 to carbon dioxide - based fire suppressant container 108 , or to carbon dioxide - based fire suppressant tank outlet 116 , or both , which causes the corresponding valves to close and terminate release of the carbon dioxide - based fire suppressant from container 108 and / or from fire suppressant tank 114 into monitored area 113 . at step 204 , if the human - safe fire suppressant container 109 and / or fire suppressant tank outlet 117 was not closed , the human - safe fire suppressant continues to be released until it is depleted , manually shut off , or the fire control processing system no longer detects a fire condition . if the human - safe fire suppressant container 109 and fire suppressant tank outlet 117 were closed , then fire control processing system 106 again sends an electric signal over communication channel 107 to human - safe fire suppressant container 109 , or to human - safe fire suppressant tank outlet 117 , or both , which causes corresponding valves to open and again release human - safe fire suppressant from container 109 into monitored area 113 , and / or from tank 115 through fire suppressant tank outlet 117 for flooding monitored area 113 . the fire control processing system algorithm 200 then continues through to step 206 as described above . returning back to step 203 , if , after receiving a fire condition detected signal at step 201 and triggering the alarm at step 202 , fire control processing system 106 determines that no people are present in monitored area 113 , then at step 207 the fire control processing system 106 sends an electric signal over communication channel 107 to carbon dioxide - based fire suppressant container 108 , or to carbon dioxide - based fire suppressant tank outlet 116 , or both , which causes the corresponding valves to open and release carbon dioxide - based fire suppressant from container 108 into monitored area 113 , and / or from fire suppressant tank 114 for flooding monitored area 113 through fire suppressant tank outlet 116 . in one embodiment , the release of carbon dioxide - based fire suppressant at step 207 may include fire control processing system 106 also sending an electric signal over communication channel 107 to fire suppressant container 109 , or to fire suppressant tank outlet 117 , or both , to simultaneously release the human - safe fire suppressant into monitored area 113 together with the carbon dioxide - based fire suppressant . after step 207 , at step 206 , fire control processing system 106 determines if people are present in monitored area 113 , and the algorithm continues as described above . in view of the foregoing , embodiments of the invention provide an automatic fire suppressant release system designed to protect people in the vicinity of the fire from hazardous fire suppressants . a technical effect is to automate the fire suppressant system without requiring manual mechanical shut off of fire suppressants that are hazardous to people . as will be appreciated by one skilled in the art , aspects of the present invention may be embodied as a system , method , or computer program product . accordingly , aspects of the present invention may take the form of an entirely hardware embodiment , an entirely software embodiment ( including firmware , resident software , micro - code , etc . ), or an embodiment combining software and hardware aspects that may all generally be referred to herein as a “ service ,” “ circuit ,” “ circuitry ,” “ module ,” and / or “ system .” furthermore , aspects of the present invention may take the form of a computer program product embodied in one or more computer readable medium ( s ) having computer readable program code embodied thereon . any combination of one or more computer readable medium ( s ) may be utilized . the computer readable medium may be a computer readable signal medium or a computer readable storage medium . a computer readable storage medium may be , for example , but not limited to , an electronic , magnetic , optical , electromagnetic , infrared , or semiconductor system , apparatus , or device , or any suitable combination of the foregoing . more specific examples ( a non - exhaustive list ) of the computer readable storage medium would include the following : an electrical connection having one or more wires , a portable computer diskette , a hard disk , a random access memory ( ram ), a read - only memory ( rom ), an erasable programmable read - only memory ( eprom or flash memory ), an optical fiber , a portable compact disc read - only memory ( cd - rom ), an optical storage device , a magnetic storage device , or any suitable combination of the foregoing . in the context of this document , a computer readable storage medium may be any tangible medium that can contain , or store a program for use by or in connection with an instruction execution system , apparatus , or device . program code and / or executable instructions embodied on a computer readable medium may be transmitted using any appropriate medium , including but not limited to wireless , wireline , optical fiber cable , rf , etc ., or any suitable combination of the foregoing . computer program code for carrying out operations for aspects of the present invention may be written in any combination of one or more programming languages , including an object oriented programming language such as java , smalltalk , c ++ or the like and conventional procedural programming languages , such as the “ c ” programming language or similar programming languages . the program code may execute entirely on the user &# 39 ; s computer ( device ), partly on the user &# 39 ; s computer , as a stand - alone software package , partly on the user &# 39 ; s computer and partly on a remote computer or entirely on the remote computer or server . in the latter scenario , the remote computer may be connected to the user &# 39 ; s computer through any type of network , including a local area network ( lan ) or a wide area network ( wan ), or the connection may be made to an external computer ( for example , through the internet using an internet service provider ). aspects of the present invention are described herein with reference to flowchart illustrations and / or block diagrams of methods , apparatus ( systems ) and computer program products according to embodiments of the invention . it will be understood that each block of the flowchart illustrations and / or block diagrams , and combinations of blocks in the flowchart illustrations and / or block diagrams , can be implemented by computer program instructions . these computer program instructions may be provided to a processor of a general purpose computer , special purpose computer , or other programmable data processing apparatus to produce a machine , such that the instructions , which execute via the processor of the computer or other programmable data processing apparatus , create means for implementing the functions / acts specified in the flowchart and / or block diagram block or blocks . these computer program instructions may also be stored in a computer readable medium that can direct a computer , other programmable data processing apparatus , or other devices to function in a particular manner , such that the instructions stored in the computer readable medium produce an article of manufacture including instructions which implement the function / act specified in the flowchart and / or block diagram block or blocks . the computer program instructions may also be loaded onto a computer , other programmable data processing apparatus , or other devices to cause a series of operational steps to be performed on the computer , other programmable apparatus or other devices to produce a computer implemented process such that the instructions which execute on the computer or other programmable apparatus provide processes for implementing the functions / acts specified in the flowchart and / or block diagram block or blocks . this written description uses examples to disclose the invention , including the best mode , and also to enable any person skilled in the art to practice the invention , including making and using any devices or systems and performing any incorporated methods . the patentable scope of the invention is defined by the claims , and may include other examples that occur to those skilled in the art . such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims , or if they include equivalent structural elements with insubstantial differences from the literal language of the claims .

a system and method for fire suppression proactively identifies persons present , during a fire , in a fire suppressant release area . the persons are identified using an electronic monitoring system . an fire suppression system using a suppressant that is effective but unsafe for humans is put into service only if no person is detected . in situations where a person is present , an alternate fire suppressant is released that is safe for humans .

now referring to the drawings in fig1 - 6 , wherein similar components are identified by like reference numerals , there is seen in fig1 the device 10 configured to an assembled configuration and ready for use as a portable back rest . in the depicted mode of fig1 , the device 10 includes a solid or hollow tubular frame 12 , which may be formed from a single member which is bent at two corners , or otherwise formed of segments which are operatively engaged at corners . in this assembled configuration , the frame 12 is substantially a u - shape and has opposing and coplanar opposing vertical segments 22 which support a horizontal segment 22 a distance above the ground or soil . by substantially u - shaped is meant that the vertical segments 22 can be parallel and engaged at a substantially right angle with the horizontal segment 22 , or may run at an angle toward or away from each other in the direction toward their respective intersection or engagement with the horizontal segment 22 . as noted this angle of engagement can be between 80 to 110 degrees . the horizontal segment 20 and the opposing vertical segments 22 with the frame 12 when formed to an assembled or as - used mode , such as in fig1 a , and 3 - 4 are all preferably all coplanar to allow for proper positioning and support of the towel or blanket or other flexible sheet over the horizontal segment 22 where it may be supported thereby or may be held in position by an engagement surface 21 positioned on the horizontal segment 22 . such an engagement surface for example can be hooked fabric or a gnarled surface on the horizontal segment to resist slippage of the fabric support 16 . in all preferred modes of the device 10 , the vertical segments 22 have distal ends which are pointed or have a point 23 thereon , either formed or engaged , to allow for easy penetration thereof into loose soil or sand 18 . the frame 12 in current preferred modes has a substantially uniform outer diameter of between 0 . 125 and 1 inches . it may be formed with circular or rectangular or geometrical cross sections . additionally , the vertical segments 22 , may be between 10 to 48 inches in total length from points 23 to engagement with the horizontal segment 20 , and the horizontal segments 20 , 3 to 36 inches in length . a currently preferred angle between each of the vertical segments 22 at their respective intersection with the horizontal segment 20 , thereby forming the u - shaped frame 14 , is between 80 and 110 degrees . when using fittings for a removable engagement therebetween , a substantially 90 degree angle has been found to form a strong and stable structure when engaged to sand or soil . by substantially 90 degrees is meant exactly 90 degrees or plus or minus 5 degree from 90 degrees . each vertical segment 22 preferably includes between 1 and 5 stabilization fins 14 positioned at or adjacent the distal ends of the vertical segments 22 where the points 23 are positioned . the fins 14 provided for increased resistance to disengagement from the soil or sand while supporting a user and help prevent the vertical segments from tipping when the user leans upon the towel or fabric support 16 . the stabilization fins 14 in a current preferred mode are of a length of 0 . 25 and 5 inches , extend radially from the center axis and exterior surface of the vertical segments 22 of the formed tubular frame 12 . the fins 14 may be positioned at or adjacent the distal ends of the vertical segments 22 as noted , or in an adjustable mode , using removably engageable fins 14 such as in fig5 , which allow for adjusting the fin 14 distance from the points 23 , to adjust for harder or softer dirt or sand and adjust the depth of insertion of the ends of the vertical segments . further , it is preferred that the fins 14 extend a distance from the vertical segment 22 with a fin edge 15 ( fig5 ) that runs perpendicular or at a slight incline to the axis of the vertical segment 22 . the forms the fin edge 15 to define a foot - engagement surface , so the user may step upon the fin edge 15 during engagement of the points 23 , fins 14 and vertical segment 22 in the soil or sand . as noted below , the fins 14 can also be engaged adjustably , to allow for more or less penetration into the soil or sand , which allows for a spacing of the fins 14 from the pint 23 and a more secure support resistant to tilting . to employ the device 10 herein , a user will force the vertical segments 22 downward thereby piercing the loose ground 18 with the points 23 positioned at the distal ends of the vertical segments 22 . the distal ends are forced below ground lever until the stabilization fins 14 are partially or preferably fully buried . as noted , the fin edge 15 of each fin 14 can also allow for a foot engagement to help force the vertical segments 22 into the sand or soil . for a device 10 configured without a permanent or removably engaged flexible fabric support 16 , the user will position a fabric support 16 such as a towel or blanket or similar planar flexible support surface held over or upon over the horizontal segment 20 of the frame 12 . the towel or blanket ends may be draped down and over or in - between the vertical segments 22 , and onto the loose ground 18 . thereafter a user sitting on the two ends of the towel 18 or blanket providing the fabric support 16 , will secure them to the ground and leaning thereon creates a taught backrest to allow the user to lounge in comfort . in addition to , or in place of the towel 18 or blanket , the user may choose to employ one or a combination of soft collapsible and portable items including but not limited to : cloths , clothing , bags , sheets or nets . in another preferred mode of the device 10 , per fig2 , the tubular frame 12 can be formed of the vertical segments 22 and a horizontal segment 20 which are disengageable for easy packing and transportation . in this mode , the device 10 should contain one or a combination of rigid , temporary segment coupling means such as mating threads , pins , spring pins , slots , interference fits , snaps , clasps , bands , ties or slidably engageable fittings at the corners 29 . or the corners 29 may be portions of either the ends of the horizontal segment 20 or the upper ends of the vertical segments 22 which are bent to a curve forming the engageable corner 29 . in all modes the adjacent vertical segment 22 and horizontal segment 20 will be formed to connect in a removable engagement as noted . to prevent segment loss in a disassembled mode of the frame 12 , optionally a flexible and preferably elastic joining member 24 may be employed which is axially threaded through the continuous axial passageway formed between all the connecting components . this joining member 24 can be engaged for instance to a point 23 component such as in fig6 , which will connect to the ends of the joining member 24 by crimping thereto , or engaging it with knots to an aperture in the point 23 component . if the length of an elastic joining member 24 is less than that of the axial passageway through the formed and assembled frame 12 , it will impart a biasing force to the assembled components of the formed frame 12 to help hold it assembled . as shown in fig3 , a permanent or removable horizontal splat 26 may be engaged to the vertical segments 22 . as depicted a collar is formed on both ends of the splat 26 through which vertical segments 22 are inserted . in fig4 is shown a mode of the device 10 employing clips 28 positioned on the formed frame 12 such may also be employed to temporarily affix a towel 18 or blanket or the like to the device 10 . as noted , fig5 depicts an adjustably positionable fin component 31 which is slidably engageable in position upon the vertical segments 22 . the fins 14 extend radially around a collar 33 sized to slidably engage upon the exterior of the vertical segments 22 . the fin component 31 and fins 14 may be slid closer to or further from the points 23 to allow for a deeper or shallower positioning of the fins 14 in the soil or sand . a releasable connector 35 , such as a set screw or an aperture which will engage depressible balls on each vertical segment 22 , allows the collar 33 to be positioned , and then held in that position by setting the connector 35 such as a set screw . fig6 depicts points 23 which may be operatively engaged with the distal ends of both vertical members 22 and showing a flexible elastic member 24 connected thereto by a connector such as a crimp 37 . a recess 39 in the exterior circumference would be sided for slidable engagement within the axial passage at the distal ends of the vertical members 22 . as noted , the frame 12 should preferably be composed of a durable , lightweight material such as aluminum , but can alternatively be made of one or a combination of materials in a list including but not limited to : wood , steel , carbon fiber , fiberglass , resin or plastic . in either a single pieced component or formed of multiple components , an axial passage running the length of the frame 12 will allow for communication of the flexible member 24 therethrough and if elastic , a biased compressive engagement of multiple components if so formed . as noted , any of the different configurations and components can be employed with any other configuration or component shown and described herein . additionally , while the present invention has been described herein with reference to particular embodiments thereof and steps in the method of production , a latitude of modifications , various changes and substitutions are intended in the foregoing disclosures , it will be appreciated that in some instance some features , or configurations , or steps in formation of the invention could be employed without a corresponding use of other features without departing from the scope of the invention as set forth in the following claims . all such changes , alternations and modifications as would occur to those skilled in the art are considered to be within the scope of this invention as broadly defined in the appended claims . further , the purpose of any abstract of this specification is to enable the u . s . patent and trademark office , the public generally , and especially the scientists , engineers , and practitioners in the art who are not familiar with patent or legal terms or phraseology , to determine quickly from a cursory inspection the nature and essence of the technical disclosure of the application . any such abstract is neither intended to define the invention of the application , which is measured by the claims , nor is it intended to be limiting , as to the scope of the invention in any way .

a portable back rest is provided having a u - shaped frame formed from two vertical segments joined with a horizontal segment . points on the end of each vertical segment are adapted to pierce and become submerged in soil or sand and hold the frame upright where the horizontal segment will support fabric such as a towel as a back support . fins may be positioned adjacent the points on the ends of the vertical segments to further stabilize their engagement with soil or sand and provide a contact point for a foot during insertion .

referring now to the drawings , fig1 shows my new and improved step like climbing device or climbing device or tree step 4 . the climbing device 4 includes an elongated threaded attaching structure or attaching structure 6 for attaching the climbing device to a vertical structure 2 to be climbed such as a tree 3 and a pole ( not specifically shown ). excellent results are obtained when the attaching structure 6 comprises an elongated threaded screw like structure as shown in fig1 . however , alternative embodiments of my invention may employ a nail like structure 40 , a removable bolt like structure 42 or a removable belt like structure 44 , as shown respectively in fig7 and 9 , and still remain within the disclosed and claimed scope of my invention . a surface engageable portion 8 is connected to the attaching structure 6 and extends perpendicularly in a downward direction therefrom . a step 10 is connected to the surface engaging portion and extends perpendicularly thereto in a direction away from the attaching structure 6 . an upturned outer end or outer end 12 is connected to the step and extends perpendicularly thereto . next , there is a chamber 14 located at the outer end 12 . the chamber is sized to house a luminescent material 24 . the luminescent material provides radiating light therefrom . excellent results are obtained when the luminescent material comprises a powder ( to be mixed with some other material to protect it from the environment ) and the luminescent material is self regenerating through exposure to a member from the group consisting of natural light and artificial light . at present , it is contemplated that the luminescent material be that sold under the trademark &# 34 ; luminova &# 34 ;(™) by nemoto company of tokyo , japan , which is distributed in the u . s . by united mineral and chemical company of n . j . an annular lip 16 of opaque material encircles the luminescent material . the lip serves to limit the radiating light to a substantially vertical direction of travel away from the chamber . the feature of limiting the light radiating from the luminescent material ( obtainable through the lip 16 and other structure as discussed in detail hereafter ) is critical to the practice of my invention . in particular , the light is intended to be viewable only from a position over looking the climbing device where the radiating light essentially just glows by radiating light only a very short distance which does not illuminate other structures such as tree branches and the like located above the attached climbing device . also in this way , other individuals on the ground cannot readily see the climbing device . then , a cover structure 22 covers the chamber 14 and protects the luminescent material from an outside environment , such as weather elements and ones foot that steps onto the climbing device when being used . in the preferred embodiment of my invention as shown in fig1 a rubber like coating 30 covers a substantial portion of the climbing device 4 . further excellent results are obtained when the attaching structure 6 , the surface engageable portion 8 , the step 10 and the outer end 12 are all integrally constructed of a solid rod shaped hardened metal and the luminescent material is permanently housed in the chamber , thereby providing an integrally connected climbing device 4 . additionally , excellent results are obtained when the luminescent material is encapsulated in a rigid transparent shell 26 . in particular , this shell 26 includes a top portion 28 , the cover structure 22 is rigid and transparent and comprises the top portion of the shell . further , the shell completely encapsulates the luminescent material in a continuous layer of clear plastic resin like material thereby forming the shell and the cover structure as one integrally connected layer encapsulating the luminescent material . at present , it is preferred that the clear plastic resin be that sold under the trademark &# 34 ; castolite - ac &# 34 ;( tm ) by castolite company of woodstock , ill ., and known as clear casting plastic . in alternative embodiments of my invention shown in fig5 through 6 inclusive , it is preferred that the climbing device 4 comprising the attaching structure 6 , the surface engageable portion 8 , the step 10 and the outer end 12 are all integrally constructed of a solid rod shaped hardened metal material . additionally , it is preferred that a rubber like coating 30 cover a substantial portion of the climbing device to provide a non - slip surface to at least the step of the climbing device . as shown in fig5 through 6 inclusive , a chamber housing 32 can be removably mounted in a secure relationship to the outer end 12 of the climbing device ( preferably utilizing an existing climbing device , such as those shown in the prior art cited herein , thus eliminating the need for any structural modification before being equipped with means for luminating the existing climbing device ), where the chamber 14 is located in the chamber housing . further for these embodiments the chamber housing 32 is preferably constructed of an opaque material from the group consisting of metal , plastic and synthetic plastic . then , the chamber 14 includes a bottom 34 , a top 36 , and a perimeter wall 3 8 extending between the bottom and the top where the opaque material provides the perimeter wall and the bottom with an opaque characteristic that completely prevents the radiant light from passing through the perimeter wall and the bottom to the outside environment . in further alternative embodiments of my invention shown in fig7 through 9 inclusive , it is preferred that the climbing device 4 comprising the attaching structure 6 , the surface engageable portion 8 , the step 10 and the outer end 12 are all integrally constructed of a rigid material , namely , an opaque material from the group consisting of metal , plastic and synthetic plastic . additionally , it is preferred that a tread 46 cover a substantial portion of the step of the climbing device to provide a non - slip surface . as shown in phantom in fig7 ( and applicable though not specifically shown in fig8 and 9 ), the chamber 14 includes a bottom 34 , a top 36 , and a perimeter wall 38 extending between the bottom and the top . here , the opaque material provides the perimeter wall and the bottom with an opaque characteristic that completely prevents the radiant light from passing through the perimeter wall and the bottom to the outside environment . at the present time the preferable way to construct my invention comprises the following steps . first , providing an existing climbing device or tree step 4 . then , sizing a chamber 14 in the outer end 12 by appropriate means known in the prior art , such as boring with a drill bit . third , one should mixing a clear plastic resin or clear casting compound with a powered luminescent material ( to protect it from the environment ). next , this mixture is dripped into the chamber , where the climbing device must be maintained in an upright position until the construction process is complete . fifth , the mixture is allowed a sufficient time to cure in the chamber thereby effectively permanently securing the shell and luminescent material in the chamber . further , during the curing step the luminescent powder automatically collects in the center of the mixture leaving a rigid transparent continuous layer of clear plastic resin shell surrounding the luminescent material . although at the present time the preferable way to construct my invention comprises the above steps , it is contemplated that in a large scale manufacturing setting it will be preferable to make the climbing device 4 comprising the attaching structure 6 , the surface engageable portion 8 , the step 10 , the chamber 14 and the chamber housing 32 from raw materials . thereafter , mixing the clear plastic resin or clear casting compound with a powered luminescent material and continuing with the applicable steps to complete the construction of my invention . it should be understood that other structures have been experimented with to provide the lumination or illumination for my invention here , such as battery operated lighting or a treatium light source . however , testing and experimentation has proven these to be near inoperable and vastly inferior to the operation of my invention disclosed and claimed here . this does not mean , however , that despite these inferior results such other structures could be utilized with my invention and they would fall outside the scope of my invention . rather , it is contemplated that such other structures utilized with my invention would fall within the broad scope of my invention , though the other structures may embody additional improvements that go beyond the scope of my invention . as various possible embodiments may be made in the above invention for use for different purposes and as various changes might be made in the embodiments and method above set forth , it is understood that all of the above matters here set forth or shown in the accompanying drawings are to be interpreted as illustrative and not in a limiting sense .

a tree step for climbing a vertical structure such as a tree and a pole in a relatively enlightened environment and then descending the vertical structure in a relatively darkened environment . the tree step comprising an attaching structure . a surface engageable portion connected to the attaching structure . a step connected to the surface engageable portion . the step having an outer end with an upwardly facing surface . a luminescent member for radiating light upwardly from the upwardly facing surface only in a substantially vertical direction . a semi - rigid , semi - transparent cover structure protecting the luminescent member from an outside environment .

embodiments of the present disclosure provide non - invasive optical tomography imaging modalities that can be used to detect and monitor peripheral arterial disease ( pad ) in the lower extremities . the imaging of peripheral hemodynamics in the lower extremities can efficiently diagnose lead regardless of compressibility of the arteries , making it ideal for diabetic patients . optical tomography can also be used to image vascular dynamics and blood flow patterns . since in breast cancer and arthritis vascular changes are secondary effects , whereas in pad changes in the vasculature are primary effects , the disclosed optical tomography imaging modalities can be used to diagnose and monitor vascular diseases . the breast imaging systems can be used to gather preliminary data on diabetic patients with pad . differences between healthy and diabetic pad patients could be observed using these preliminary images . fig1 a illustrates an optical tomography imaging system 100 used in one embodiment . frequency domain optical tomography ( fdot ) system : this frequency domain instrument is based on the picostar hr imager ( la vision gmbh ). the light sources consist of laser diodes ( picoquant gmbh ) that are modulated by a signal generator ( aeroflex intl . ltd .) at frequencies up to 1 ghz . the laser light is coupled to an optical switch that demultiplexes the light into various optical fibers which deliver the light to different positions on an imaging geometry . inside the imaging geometry resides the target to be imaged which will attenuate the light and induce a phase shift based on its optical properties . detector optical fibers collect light exiting the imaging geometry and deliver the light to the picostar imager . the detected light is incident on an image intensifier ( kentech instruments ltd .) that is also modulated by a signal generator at frequencies up to 1 ghz in order to demodulate the detected light . the demodulated detected light is measured by a ccd camera . by using a ccd camera , light can is measured in parallel from all detector fibers . by inducing phase shift between the modulating action of the laser and the demodulating action of the intensifier , one can use the measure light at the respective phase shifts in order to calculate the attenuation and phase shift induced by the imaged target . the measured attenuation and phase shift at several frequencies between dc and 1 ghz , is input to a frequency domain optical tomography reconstruction code in order to reconstruct the optical properties of the target . this system is currently being integrated with the mri machine ( see 5 ) to allow for simultaneous optical and mr imaging of small animals . the system 100 can include a laser source ld 1 , such as , but not limited to a laser diode , a laser diode driver 2 , a signal generator 3 and 7 , a body part ( finger , foot , breast , etc .) placement area 4 for surface scan as well as trans - illuminating imaging , one or more lenses 5 , an iccd camera , a high frequency imager 8 , and a computer processing system 9 to image body parts to produce cross section or volumetric images or raw transmission data . the data may relate , for example , to the volume or flow of blood through the major arteries of the body part , such as , feet , fingers , or other extremities . in operation , the body part 4 is scanned simultaneously with light from the laser diode ld 1 and a second diode ld 2 ( not shown ). both laser diodes can be mounted on the same or separate scanning mechanisms , such as a gear - wheel , for example , so that slight movements of the scanning mechanisms move the laser spot on the body part 4 to be imaged . in embodiments the laser may scan a line to acquire the surface geometry as explained below . light from the same or a second diode ld 1 may be transmitted through the body part 4 and the detected light intensity which is transmitted through the body part 4 captured by the camera 6 . the background may serve as calibration of the camera coordinate system . the 3d surface coordinates are subsequently used to generate a 3d finite element mesh . this mesh together with the light transmission measurements from the light detectors are input to an image reconstruction algorithm that generates the cross - sections through the imaged body part . fig1 b illustrates a frequency modulated optical tomographic system 200 that can also be used to generate tomographic images of a body part 4 . the frequency modulated tomography system 200 includes two laser diodes 201 , 202 , generating light at two different wavelengths . both laser diodes 201 and 202 are driven by modulated laser drivers and both are connected through optical fibers to a 2 × 32 fiber optic switch 203 . both source and detection fibers interface with the imaging geometry ( e . g ., measuring module ) 204 in which the body part is placed . detection fibers 221 that deliver light from the measuring module 204 have their respective tips of the fibers connected to the ccd camera 205 . the camera images the fiber ends arrayed by the image intensifier 206 . the image intensifier may or may not be used . each laser diode 201 and 202 can be modulated at a different frequency by signal generators 207 and 208 . the signal generators may be used to modulate the laser diodes 201 , 202 as well as a photocathode of the image intensifier 206 . the parameters of the generated signals ( amplitude , frequency , phase , etc .) can be controlled by a computer processor cpu 209 . the fiber optics switch 203 redirects the light from the two laser diodes 201 , 202 in succession to the array of source optical fibers that deliver the light to fixed locations positioned around the measuring module . the light transmitted through the body part is carried by the detection optical fibers into the image intensifier 206 . the source optical fibers 222 are optically coupled in pairs at different positions around the measuring module 204 to sample the body part at two different frequencies . a reference fiber 223 is also connected between the fiber switch 203 and the image intensifier 206 . the signal from one of the signal generators 207 is input to both of the modulated laser diodes 201 and 202 , whereas the input from the second signal generator is input only to the image intensifier 206 . the frequency of the second signal generator 208 can be the same as the first signal generator 207 and the phase differences resulting between the two signals can be adjusted by the cpu 209 . using this set - up , the signals in respective pixels of the ccd depend on the phase difference . the source fibers serially illuminate the body part at discrete phase offsets . fig1 c illustrates a continuous wave tomography system 300 includes two laser diodes 301 , 302 , generating light at two different wavelengths . both laser diodes 301 , 302 are connected through optical fibers to a fiber optic switch 303 . both source and detection fibers interface with the imaging geometry ( e . g ., the measuring module ) 304 in which the body part is placed . detection fibers 321 that deliver light from the measuring module 304 have their respective tips of the fibers directed to the ccd camera 305 by the image array 307 which supports the fibers in known positions so their respective signals can be demultiplexed from the image of the camera . the parameters of the generated signals can be controlled by a computer processor cpu 314 . the fiber optics switch 303 redirects the light from the two laser diodes 301 , 302 in succession to the array of source optical fibers 322 that deliver the light to fixed locations positioned around the imaging geometry 304 . the source optical fibers 322 are coupled in pairs at different positions around the imaging geometry 304 to sample the body part . the light transmitted through the body part is carried by the detection optical fibers to image array 307 . the imaging systems 100 - 300 can include various types of measuring module for bringing the illuminating light source such as a fiber into contact with the body part to be imaged ( or projecting light onto the surface of a body part ), and then bringing the detected light from the body part to the camera 6 or other photo detector . this may be accomplished with optical fibers , which either make direct contact with the body part , or are brought close to the body part in a simple , fixed geometry . in the case that the optical fibers do not make direct contact with the body part , an optical matching fluid ( such as intralipid ) may be used to direct the light from the fiber tip to the surface of the body part . in order to create full 3d images of the entire imaged body part , the source optical fibers and the detection optical fibers that deliver and collect light from the entire body part are positioned around the body part , so that the tips of the source optical fibers and the tips of the detection optical fibers are adjacent to and are surrounding the body part . the light is effectively scanned over the body part by sequentially emitting light from one light source at the time and detecting the light intensity which is transmitted through the body part by the light detectors . one emitter may operate at a given time while all the receivers receive light scattered from the emitter . then another emitter may be activated and so on . the light of different frequencies ( color ) may be injected simultaneously and demultiplexed to provide higher temporal resolution . acquired or predicted 3d surface coordinates are used to generate a 3d finite element mesh . this mesh together with the light transmission measurements from the light detectors are input to an image reconstruction algorithm that generates the cross - sections through the imaged body part . in the embodiment of fig2 , a measuring module 30 is used to image a finger 31 ( not shown ). the measuring module 30 includes a cylindrical body 32 into which the finger can comfortably slide and which acts to stabilize the finger throughout the imaging process . the measuring module 30 encircles a portion of the cylindrical body 32 so that the actual finger can be positioned inside the measuring module 30 . a plurality of source and detection optical fibers 33 positioned in two separate rows are detachable attached to the measuring module 30 around the perimeter of the imaging module 30 . each row can include up to 24 optical fibers . the size of the measuring module 30 can be changed to accommodate fingers of various shapes and sizes . nir light is delivered to the surface of the finger 31 through one fiber at the time ( i . e ., source optical fiber ) and the transmitted light intensities are measured by all other optical fibers ( i . e ., detection optical fibers ). the captured transmission data is delivered to the photodetector for further processing . using image reconstruction software , the detected transmitted light data can be used to generate three - dimensional cross sectional images of the body part . a measuring module 11 is shown in fig3 . in this embodiment , the body part that is being imaged is the lower part of a leg 20 . the measuring module 11 can be a cuff - shaped device that rises a few inches above the ankle and is configured to accommodate various leg 20 sizes while still keeping the relative source - detector fiber 13 positions constant . the measuring module 11 includes a plurality of source optical fibers 13 and detection optical fibers 13 detachably attached to the cuff - like device and arranged in at least two layers around the cuff - like device 11 so as to encircle the lower part of the leg 12 and so that when in use , the source and detector fibers 13 deliver near - infrared ( nir ) light to the major arteries of the leg 12 , and deliver the light transmitted through the major arteries of the leg 12 to the photodetector . each source and detector fiber 13 can be connected to a light conduit 14 to deliver light from the laser source of an optical tomography systems 28 , which could be any one of systems 100 - 300 , for example , to the body part 12 and to deliver transmitted light from the body part 12 to the photodetector of the optical tomography system 28 , which can be any one of the optical tomography systems 100 - 300 . the measuring module 11 is configured to be variable in size so that any size leg 12 can be comfortably fitted inside the measuring module 11 . the measuring module 11 can target the response around the dorsalis pedis artery , the response of the posterior tibial artery , as well as the response across the calf to measure the perfusion at an elevated location on the lower extremities . the source optical fibers and the detection optical fibers in the measuring module 11 can be positioned so as to surround a major artery of the lower leg 12 . in operation , after the patient places a leg 12 inside the measuring module 11 , the module 11 can be filled with a matching liquid to overcome the gap between the foot 12 and the source and detection optical fibers 13 . the matching liquid can help to overcome mismatches between the measuring module 11 , and the leg 12 being imaged . visible and near - infrared ( nir ) light is guided through the optical fiber conduits 14 to the surface of the leg 12 under investigation . each of the source optical fibers 13 sequentially delivers light to the major arteries in the leg 12 while each of the detection optical fibers 13 capture the light transmitted through the arteries at various locations . the specific geometry between the source optical fibers and the detection optical fibers allows the detection optical fibers to capture reflected and transmitted light through the major arteries of the leg 12 . the captured transmission data is then delivered to the photodetector for further processing . using image reconstruction software , the detected transmitted light data can be used to generate three - dimensional cross sectional images of the body part . in order to determine whether there are any changes in the vasculature of the body part imaged or in the oxy and deoxy - hemoglobin or in the main protein in blood , a second set of transmission data and corresponding second set of images are generated after an external stimulus is applied to the imaged body part . the stimulus can be generated by applying an external pressure on the body part using a pressurizing device , such as but not limited to , a sphygmomanometer cuff 18 placed around the body part 12 . after the application of the stimulus , a second set of transmission data are taken and a second set of tomographic images are reconstructed using the same imaging and reconstruction methods as used for the generating of the first set of data and images . the cuff 18 is activated to exert pressure on the leg 12 by a cuff actuator 42 . the amount of pressure exerted by the cuff 18 , as well as the timing of sequential release of pressure is controlled by a controller 40 . the controller is operatively connected to the cuff actuator 42 as well as the system 28 . each set of transmission data and reconstructed images include information regarding optical properties ( reflection , absorption , scattering ) of the imaged body part . from these optical properties , parameters such as perfusion rates , oxy and deoxy hemoglobin concentrations , as well as blood volume can also be determined . by comparing the transmission data and the images in the first set with corresponding transmission data and images in the second set , biomarkers such as , but not limited to , distribution of optical properties , perfusion rates , and differences in oxy and deoxy hemoglobin concentrations can be ascertained . these biomarkers can then be used to differentiate between a sick and a healthy patient . the optical tomography system 28 may have a controller 40 which operates the cuff and ot system to perform an end to end diagnostic sequence . in the embodiment of fig4 , a cuff - like measuring module 20 is shown . the cuff - like measuring module 20 can include a plurality ( three shown ) of adjustable rings 22 - 24 , each including a plurality of source optical fibers and detection optical fibers positioned around a surface of the ring . the cuff - like measuring module 20 is adjustable in diameter in order to accommodate various leg sizes and can open similar to a handcuff for easy attachment and detachment . each of the rings includes two separate parts linked together using bracket type connecting members 27 , which when positioned in a first locked position , securely lock the rings 22 - 24 together , and when in a second unlocked position , the rings may be moved in the axial ( z axis ) direction relative to each other to change the mutual spacing of the rings . the rings can also be opened by means of a clasp 29 . the brackets may include a plurality of engaging surfaces , to act as stops , positioned along the length of the brackets 27 to allow the rings to be securely positioned in different positions along the length of the bracket when in the desired position . the rings 22 - 24 are detachably attached to the brackets 22 to render a boot - like device 20 . each ring 22 - 24 can be placed strategically around the lower extremity of the leg 12 to encircle the major arteries in the desired portion of the leg 12 . the width of the measuring module 20 as well as the measuring rings 22 - 24 can be adjusted to accommodate different leg sizes . the rings 22 - 24 can be placed around the metatarsals and the ankle as well as the calf to obtain the hemodynamic response in the major arteries and its surroundings and that of a higher portion of the lower extremity . the rings 22 - 24 can also move in a vertical direction z so as to be able to be positioned at any desired height on the measuring module 20 and around the body part 12 . the rings 22 - 24 with the optical fibers distributed around the ring detect the transmission and reflectance of light through the arteries of the leg 12 . this design may employ an optical spacer but may also instead allow the optical fibers to make direct contact with the skin and still maintain constant source - detector fiber positions . in case the design does not have a constant geometry , a robust image reconstruction technique called the normalized differentiation method ( ndm ) can be used to reconstruct the images . this reconstruction algorithm can take the difference between a baseline optical measurement and the optical response measurement relative to a stimulus . this method can reconstruct the difference / relative optical properties instead of absolute optical properties and is therefore not nearly as dependent on the boundary conditions and the source detector optical fiber positions . the measuring modules 11 and 20 can target the response around the dorsalis pedis artery , the response of the posterior tibial artery , as well as the response across the calf to measure the perfusion at an elevated location on the lower extremities . the source optical fibers and the detection optical fibers in both measuring modules 11 and 20 can be positioned so as to surround a major artery of the lower leg 12 . in operation , after the patient places a leg 12 inside the boot 11 or 20 , the boot can be filled with a matching liquid to overcome the gap between the foot 12 and the source and detection optical fibers 13 . the matching liquid can help to overcome mismatches between the measuring module 11 , 20 , and the leg 12 being imaged . visible and near - infrared ( nir ) light is guided through the optical fiber conduits 14 to the surface of the leg 12 under investigation . each of the source optical fibers 13 sequentially delivers light to the major arteries in the leg 12 while each of the detection optical fibers 13 capture the light transmitted through the arteries at various locations . the specific geometry between the source optical fibers and the detection optical fibers allows the detection optical fibers to capture reflected and transmitted light through the major arteries of the leg 12 . the captured transmission data is then delivered to the photodetector for further processing . using image reconstruction software , the detected transmitted light data can be used to generate three - dimensional cross sectional images of the body part . the constant geometry of the source fibers and detection fibers around the measuring modules may facilitate reconstruction of these optical images , because of the precise locations of the source and detection fibers are known along the boundaries of the measuring modules 11 and 30 . various reconstruction algorithms can be used to generate the images , such as , but not limited to model based iterative image reconstruction algorithms , diffusion - based algorithms , and transport theory reconstruction algorithms . fig5 shows an optical interface module that can be opened and closed about a foot 340 , for example the metatarsal region thereof , with a flat portion 352 , which acts as a base upon which the patient can stand . the optical interface modules also have an arching portion 344 . both the base 352 and arching portion 344 support fibers ( locations thereof indicated at 346 and 350 ) for transmitting and receiving light signals . the fiber supports may support fibers for contact or non - contact arrangement over the body part . the arching portion may be attached by a hinge 345 to allow the arching portion 344 to be positioned over the foot . a latch 348 to hold the arching portion 344 firmly , once closed , may be provided . a cuff 342 may be provided for provoking the vasculature of the foot . fig6 shows a single fiber support 362 , 368 and an associated linear actuator 364 configured to move the end of the fiber 366 to known position in contact or non - contact relation to a body part . the feature of fig6 is applicable to any of the embodiments disclosed . a controller as in any of the embodiments described herein may be used to position each of the fiber ends to a desired position automatically based on acquired or predicted surface geometry as described elsewhere herein . by knowing the precise position of the actuator and the support , the position of the fiber end may be known . even if the fiber end , in contact with the skin , obscures the body part , the shape of the anatomy may be inferred by knowing the precise position of the fiber end if it is assumed the skin conforms to it . such actuators may be provided , for example , in the apparatus of fig5 or any others compatible devices . in alternative embodiments , the linear actuator may be replaced by a movable support with a spring that permits the light guide to move passively therewithin . the support may further include an encoder to indicate a position of the light guide relative to the support . the information from the encoder may be used to form the mesh . referring now to fig7 and 10 , in a relevant embodiment , at s 10 a body part such as a foot is surface scanned , imaged ( photographed from multiple angles , for example ) to derive raw data from which a 3 surface model can be generated . alternatively a predicted surface is used , for example , by drawing from a library of stored template for different anatomical archetypes . to obtain the geometry for image reconstructions , a photograph of the foot or a laser scan surface geometry acquisition system may be used . adjacent objects may be provided to give a reference to obtain precise absolute dimensional data . the surface geometry information may be used to create a boundary and locate the sources and detectors . in embodiments in which one or more actuators position the fiber ends into known positions in contact with the body part , the known positions and sizes of the fiber ends are used in determining the surface geometry . the process is illustrated figuratively in fig1 where a camera 272 images a foot 270 which is scanned by a laser 268 to acquire the surface geometry indicated at 282 . at s 14 the body part is positioned in the imaging device ( 283 of fig1 ). alternatively , the body part may already be positioned in the imaging device if concurrent surface geometry acquisition is done while positioned therein . the latter may be the case where a device such as non - contact imaging is done or where the positions of the fibers in contact with the body can be obtained directly such as with the actuator of fig6 . optical transmission measurements on the body part , such as the foot , are begun at s 16 . in embodiments , these may be performed with a digital near - infrared optical tomography imager . in that case , a combined optical beam consisting of two laser diodes ( wavelength λ ,= 765 nm and 830 nm ) may act as illuminating sources . the sources may be sequentially coupled into different 1 mm multimode fiber bundles that distribute light to multiple areas along the measurement probe . the measurement probe may have any number of fiber supports that hold optical fibers close to or in contact with the surface of the body part such as a foot . for example , the device of fig5 may be used . the current of each laser diode may be modulated to a distinct amplitude and frequency . in this way , multiple wavelengths may be illuminated simultaneously , and their respective amplitude and phase contribution on the attenuated detected signal can be extracted using synchronous detection techniques . the total power incident on the target may be , for example , about 30 mw . once the light is attenuated as it propagates through the body part , it then exits the probe and is collected by the various fiber bundles positioned around the target for a fiber multiplexing scheme . as described here and elsewhere other schemes for optical tomography transmission measurements are also possible , for example , non - contact using imaging as in fig1 , without the use of fiber multiplexing . in an exemplary embodiment , a total of 34 fibers may be brought in contact with the foot with 14 serving as light sources and 20 as detection fibers . at s 12 , in parallel or series with other steps , a mesh may be generated using the data from the surface geometry 282 and or a priori information of anatomy ( or patient - specific documentation such as medical imaging studies ). for example , a two dimensional mesh of a foot ( fig1 , 308 ) may be generated . alternatively a three - dimension mesh may be generated . at s 17 , a provocation is induced in the body part . for example , the flow through the vasculature may be modified using a pressure cuff that is applied proximally of the imaging module , for example , to the upper thigh . initially , a baseline measurement may be taken , for example , for an interval of approximately 1 minute and data recorded for the generation of multiple image frames , for example , 400 frames . next , the pressure cuff may be inflated to a first pressure , for example to produce a venous occlusion ( for example , 60 mmhg )/ the pressure may be maintained for an interval while data is acquired continuously ( for example , 1 . 5 minutes ) at which point the pressure may be released to generate a rest interval during which data is also recorded . as indicated at s 18 , a number of additional provocations may be induced with continuous data acquisition for the generation of time series imaging ( or non - imaging ) data during each and in the interval between . for example , an increased pressure of 120 mmhg for arterial occlusion may be applied to a proximal cuff with a following rest period , the intervals being the same as for the venous occlusion . the provocations may be repeated multiple times , for example three times , to confirm repeatability , for statistical analysis or for merging data for random error filtering . at s 20 the data are processed by system ( fig1 , 284 ) for display . for example , to generate two - dimensional reconstructions of the optical properties of a body part such as the foot , a transport - theory - based pde - constrained multispectral image reconstruction scheme may be used to reconstruct the spatial distributions of the oxy and deoxy - hemoglobin concentrations in the foot . for this purpose , the differences in h1b021 and [ hb ] obtained through reconstruction is relative to baseline which may be assumed to be given by h1b021 = 23 . 4306 μm1 and [ hb ]= 14 . 6874 μm1 , throughout the body part . a radial basis function ( rbf )- type regularization scheme may be employed to obtain quality images by reducing noise and artifacts near the foot surface . in an actual example , the observed signal changes corresponded to understandable physiologic responses in a foot and finger . fig8 a through 9b show the temporal response of multiple detector intensities at the finger ( fig8 a and 8b ) and foot ( fig9 a and 9b ) for a healthy person ( fig8 a and 9a ) and a diabetic person with peripheral vascular disease ( fig8 b and 9b ). the traces 301 depict the transmission profiles over respective detector channels for a single illumination position at one wavelength each . the responses are plotted as a change in intensity versus time ( minutes ) and are normalized to a rest period prior to provocation of the vasculature . when the first pressure cuff (@ 60 mmhg ) is applied to a healthy volunteer , venous return is inhibited while arterial supply is still active , causing blood to pool in the leg . as a result , the optical attenuation absorption increases causing a decline in transmitted intensities . subsequent to the pressure being released , the accumulated blood volume begins to diminish , at first rapidly , due to the elevated pressure gradient in the vascular system , and then more gradually as the gradient eases toward equilibrium and the optical signal returns towards baseline . when the cuff is reapplied ( e . g ., at 120 mmhg ) the signal magnitude drops even further relative to the initial value , indicating a more complete venous occlusion . the time traces of patients with pad show significantly different behaviors from those of a healthy volunteer . while in all the cases a drop in transmitted intensities is observed upon application of the pressure cuff , the drops of the pad patients are much smaller in magnitude (˜ 15 %) than the healthy volunteer . in addition , in both pad cases the occlusion and recovery rate appear to be almost linear , however the healthy volunteer &# 39 ; s rates show a more exponential profile . in an example embodiment , the transmission and surface data may be processed to reconstruct and display 304 a section view 306 of the body part in which the concentration or volumes of interest are suitably highlighted 307 . for example , the hbt concentrations in the arteries of the foot may be shown with a color or luminance channel indicating the amount or properties of blood ( e . g ., oxygenation ). in an embodiment , the display interface may permit the selection of a particular part ( e . g ., a pixel ) for which selected part the time trace of the target property may be displayed as indicated at 306 in display 302 . for example , a cursor 309 may be provided for this purpose . a reference 308 trace ( healthy ) may be superimposed on the measured trace 311 ( pad ) for comparison . the reference trace may be selected from a library and may represent statistics of classes of pathology or other groups . the finger results above are from a study in which an arm cuff was used to provoke the finger vasculature . actual observations by the inventors show that the ankle brachial index ( abi ) can easily distinguish between the healthy subjects and pad patient but in some cases the differences are not clear . a healthy volunteer and a patient with both diabetes and pad can have very similar abi measurements . yet the optical transmission traces clearly show a compromised vasculature in the observed cases , indicating that optical methods may provide a more reliable test for pad in patients with diabetes than abi . model based iterative algorithms ( mobir ) typically include three elements , such as a forward model , an objective function , and an updating scheme . the forward model can give a numerical solution of the light distribution inside the object ω and predicts the measurements ( energy radiance ψ d ) on the boundary ∂ ω . to predict these measurement one can provide the source strength s ( r s ), the source positions r s and an initial guess of the optical biomarkers μ 0 =[ μ s , 0 ( r ), μ a , 0 ( r )]. a given set of measurements m on the boundary ∂ ω can then be compared with the set of the predicted radiances ψ d ( μ 0 ) by defining an objective function φ . a simple example can include the least square error norm between measured and predicted data given by an updating scheme can be employed that provides a new guess of optical biomarkers μ 0 + δμ , which reduce the value of the objective function φ . a new forward calculation can be performed based on the new set of optical biomarkers μ 0 + δμ . the iteration process can be finished when the minimum of the objective function is reached within a specified error . at this point the predicted detector readings can be identical to the measured detector readings within a given tolerance . the optical biomarkers , μ , can be mapped into a two or three - dimensional image . algorithms differ in the way updates are obtained , how the objective function is defined and what forward model is used . while changing the updating scheme can affect the convergence speed of a code , changing the objective function or the forward model can affect the accuracy of the reconstruction result . as a forward model most groups use the diffusion equation given by using finite - difference , finite - element , or analytical solution , predictions of the fluence ( energy per unit area ) on the surface of the medium are made . the diffusion based algorithm can be an approximation of the more generally applicable integro - differential equation of radiative transfer ( ert ), given by in cases where the diffusion approximation is not valid , using this approximation can lead to erroneous prediction of the measurements . diffusion - based calculations can predict an almost constant fluence rate in the area of the fluid . the calculations based on the theory of radiative transport can predict a different distribution of light within the medium . the differences in the forward model can directly influence the accuracy of the reconstruction . for example , if for a given distribution of optical properties , the diffusion model predicts a higher signal at a detector than actually measured , the reconstruction scheme can lower absorption and / or scattering coefficients in certain areas . in general the diffusion approximation is not as accurate when small sample geometries are considered in which source - detector separations are small and boundaries effects are dominant . the transport theory can be more accurate when the medium contains regions in which the absorption coefficient is not much smaller than the scattering coefficient or when regions are considered in which the scattering and absorption are very low ( so - called void - like regions ), such as cerebrospinal - fluid - filled spaces in the brain , or the synovial - fluid - filled space in joints . in order to determine whether there are any changes in the vasculature of the body part imaged or in the oxy and deoxy - hemoglobin or in the main protein in blood , a second set of transmission data and corresponding second set of images are generated after an external stimulus is applied to the imaged body part . the stimulus can be generated by applying an external pressure on the body part using a pressurizing device , such as but not limited to , a sphygmomanometer cuff placed around the body part . after the application of the stimulus , a second set of transmission data are taken and a second set of tomographic images are reconstructed using the same imaging and reconstruction methods as used for the generating of the first set of data and images . each set of transmission data and reconstructed images include information regarding optical properties ( reflection , absorption , scattering ) of the imaged body part . from these optical properties , parameters such as perfusion rates , oxy and deoxy hemoglobin concentrations , as well as blood volume can also be determined . by comparing the transmission data and the images in the first set with corresponding transmission data and images in the second set , biomarkers such as , but not limited to , distribution of optical properties , perfusion rates , and differences in oxy and deoxy hemoglobin concentrations can be ascertained . these biomarkers can then be used to differentiate between a sick and a healthy patient . multiple response characteristics can be defined that serve to discriminate healthy tissue from diseased tissue . for example , the minimum and maximum absorption coefficients , the ratio between the minimum and maximum absorption coefficients , the smallest and largest absorption and scattering coefficients , the ratios of these coefficients , and the variance of the absorption and scattering coefficients . differences in these optically derived biomarkers can all be used individually or in combination to classify and monitor patients . for example , the absorption coefficient ( μa ) decreases in patients with lead because of the decreased amount of blood flowing in the arteries , and thus the magnitude in the decrease of ( μa ) may be proportional to the degree of the patient &# 39 ; s lead . further , the oxygenated hemoglobin trace may recover at a slower rate in patients with lead because the arteries may not be able to supply the oxygenated blood as quickly as patients with no occlusions in their arteries . the total hemoglobin concentration and total blood volume may also decrease for patients with lead because of the decrease in blood flowing through the arteries of the sick patients . therefore , monitoring these biomarkers can enable the physicians to accurately diagnose the degree of pad or lead by detecting the physiological change in the hemoglobin and the change in the optical properties of the vasculature with respect to the stimulus . the image based biomarkers extracted from the first and second sets of optical tomography images can be used individually and in combination with other biomarkers to further increase the accuracy of the system in determining whether a patient is healthy or has pad or lead . in addition , the results obtained using the tomographic imaging modalities as described above can also be used together with results obtained using other existing technologies to allow earlier and more appropriate intervention to treat this debilitating condition . for example , results obtained using ankle - brachial index ( abi ) as well as that of duplex ultrasound scans , which are considered the standard techniques , can be used together with the results obtained using the tomographic imaging modality described above . the data can also be reconstructed in order to obtain the differences in the metabolic activity in the joints , for example . by using data obtained using two wavelengths , the fluctuation in the oxygenated and deoxygenated hemoglobin concentrations for the finger joints can also be obtained . the spatial distribution of the f11b 021 , [ hb ] and [ mt ] in finger joints of healthy patients and patients with rheumatoid arthritis are markedly different . a ring structure is evident a healthy patient , a void - like center region shrinks until it is completely lost and the entire joint cavity is inflamed . a high metabolic rate activity can also be seen . since the total hemoglobin concentration can be directly proportional to blood volume , this data can also be used to determine blood volume . a similar protocol can be used to study the feet . patients can have their abi measured first , which is the ratio of the systolic pressure measured at the dorsalis pedis or posterior tibial artery to that of the brachial systolic pressure . patients can place their foot inside the measuring module to target the major arteries of the foot . then a pressure cuff can be placed around the patient &# 39 ; s thigh . a baseline measurement can be taken and then pressure can be applied to the thigh until it constricts the venous return , while arteries can still be flowing blood to the lower extremities . the pressure can then be released for a rest period and then the cuff reapplied with stronger force to shut off both venous return and arterial supply . during the measurements , the patients can have multiple cuffs around their legs to compress the arteries . the temporal response of the detector intensities can be used to reconstruct the data to obtain the spatial maps of the hemoglobin response of the foot cross sections that contain the dorsalis pedis and the posterior tibial artery . the same exemplary experiment can be repeated with a heated pad added at the measuring site in order to induce vasodilatation . the difference in the responses to the various stimuli can be used as signatures to diagnose lead in both diabetics and non - diabetic patients . the absorption coefficient ( μa ) may decrease in patients with lead because of the decreased amount of blood flowing in the arteries . the magnitude in the decrease of ( μa ) can be proportional to the degree of the patient &# 39 ; s lead and these findings can be validated with the abi measurements and ultrasound scan . the total hemoglobin concentration and total blood volume may also decrease for patients with lead because of the decrease in blood flowing through the arteries of the sick patients . an alternative system that can be used is a frequency domain optical tomography system . this optical tomography system is capable of using high modulation frequencies up to 1 ghz , which allow for better separation of absorption and scattering and more accurate reconstructions . to characterize the efficacy of optical tomography in identifying lead the sensitivity and specificity can also be determined . the results obtained can be compared with those of the ankle - brachial index ( abi ) as well as that of duplex ultrasound . these are non - invasive diagnostic techniques that are currently used on patients suspected to have lead , before resorting to digital subtraction angiography . these diagnostic techniques can be used as standards , and differences in mean values and standard deviation of various optically derived classifiers that can be used to distinguish between diseased and healthy vasculature can be sought . the abi is a quantitative method for detecting lower extremity arterial disease . the optical images show different stages of lead . table 1 shows the abi measurements associated with mild , moderate and severe lead as well as those for patients with non - compressible arteries and healthy patients . one of the key advantages of optical tomography is that it is capable of imaging calcified arteries which are not diagnosable with abi measurements . the other imaging modality that can be considered for comparison with optical tomography is duplex ultrasound . duplex ultrasound is commonly used in clinical settings to detect lead . ultrasound however has a lot of operator dependent variables that affect its efficacy at detecting lead . in addition , ultrasound cannot provide reliable imaging if there are poor acoustic windows ( e . g ., bowel gas attenuation , diffuse vascular calcification , or metallic stents ) or poor intrinsic echogenicity of the tissues . the ultrasound also only provides qualitative measurements which could vary in interpretation depending on the physician making the diagnosis . the ultrasound measurements can be grouped into 4 categories similar to the abi measurements : healthy control , mild lead , moderate lead and severe lead . they can be compared with the optical tomography images of the same patients to determine the optical tomography imaging modality &# 39 ; s sensitivity and specificity . several biomarkers can be acquired from optical tomography images taken during the clinical study and each parameter can be used individually and in combination with other biomarkers to determine if the patient has lead . to combine these biomarkers an analysis under a vector quantization based classification called self - organizing mapping ( som ) can be used . som is an unsupervised learning method , with the purpose of transforming a feature vector of arbitrary dimension drawn from the given feature space into simplified generally 2d discrete maps . this method can allow producing multivariate receiver operating characteristic ( roc ) curves from which sensitivity and specificities can be determined . parameter combinations can lead to higher sensitivities when compared to single parameter classifications . the data can also be separated for patients with lead and those with lead and diabetes in order to examine if the biomarkers that maximize the accuracy of the diagnosis as defined by sensitivity and specificity . fig1 shows an example of a computer processing system that can be used to implement the optical tomographic imaging methods described herein . for example , the imaging methods can be performed by a processing arrangement and / or a computing arrangement 101 . such processing / computing arrangement 101 can be , e . g ., entirely or a part of , or include , but not limited to , a computer / processor 102 that can include , e . g ., one or more microprocessors , and use instructions stored on a computer - accessible medium ( e . g ., ram , rom , hard drive , or other storage device ). a computer - accessible medium 103 ( e . g ., as described herein above , a storage device such as a hard disk , floppy disk , memory stick , cd - rom , ram , rom , etc ., or a collection thereof ) can also be provided ( e . g ., in communication with the processing arrangement ). the computer - accessible medium 103 can contain executable instructions 104 thereon . in addition or alternatively , a storage arrangement 105 can be provided separately from the computer - accessible medium 103 , which can provide the instructions to the processing arrangement 101 so as to configure the processing arrangement to execute certain exemplary procedures , processes and methods , as described hereinabove , for example . further , the exemplary processing arrangement 101 can be provided with or include an input / output arrangement 106 , which can include , e . g ., a wired network , a wireless network , the internet , an intranet , a data collection probe , a sensor , etc . the exemplary processing arrangement 101 can be in communication with an exemplary display arrangement 107 , which , according to certain exemplary embodiments of the present disclosure , can be a touch - screen configured for inputting information to the processing arrangement in addition to outputting information from the processing arrangement , for example . further , the display and / or a storage arrangement can be used to display and / or store data in a user - accessible format and / or user - readable format . of special interest are the blood constituents oxy - hemoglobin ( hb02 ) and deoxy hemoglobin ( hb ), which have distinctly different absorption spectra in the visible and near - infrared wavelength region . by performing measurements at multiple wavelengths , concentrations of these chromophores as well as parameters such as total hemoglobin 11 − 1bt1 = 11 − 1b021 +[ hb ] or oxygensaturation st02 = 11 − 1b021 / 1hbt1 can be derived . using advanced tomographic image reconstruction codes 2 - and 3 - dimensional maps of these and other parameters , such as blood volume , can be generated . the foregoing merely illustrates the principles of the disclosure . various modifications and alterations to the described embodiments will be apparent to those skilled in the art in view of the teachings herein . it will thus be appreciated that those skilled in the art will be able to devise numerous systems , arrangements , and procedures which , although not explicitly shown or described herein , embody the principles of the disclosure and can be thus within the spirit and scope of the disclosure . in addition , all publications and references referred to can be incorporated herein by reference in their entireties . it should be understood that the exemplary procedures described herein can be stored on any computer accessible medium , including a hard drive , ram , rom , removable disks , cd - rom , memory sticks , etc ., and executed by a processing arrangement and / or computing arrangement which can be and / or include a hardware processors , microprocessor , mini , macro , mainframe , etc ., including a plurality and / or combination thereof . in addition , certain terms used in the present disclosure , including the specification , drawings and claims thereof , can be used synonymously in certain instances , including , but not limited to , e . g ., data and information . it should be understood that , while these words , and / or other words that can be synonymous to one another , can be used synonymously herein , that there can be instances when such words can be intended to not be used synonymously . further , to the extent that the prior art knowledge has not been explicitly incorporated by reference herein , it can be explicitly being incorporated herein in its entirety . all publications referenced can be incorporated herein by reference in their entireties . many alternatives , modifications , and variations are enabled by the present disclosure . features of the disclosed embodiments can be combined , rearranged , omitted , etc . within the scope of the invention to produce additional embodiments . furthermore , certain features of the disclosed embodiments may sometimes be used to advantage without a corresponding use of other features . accordingly , applicants intend to embrace all such alternatives , modifications , equivalents , and variations that are within the spirit and scope of the present disclosure . while embodiments and applications of this invention have been shown and described , it would be apparent to those skilled in the art that many more modifications are possible without departing from the inventive concepts herein . the invention is not limited to the description of the embodiments contained herein , but rather is defined by the claims appended hereto and their equivalents . for example , the disclosed subject matter includes various structures and methods as applied principally to the problem of diagnosing or screening for vascular disease . however , the same may be applied to other types of diagnostic problems and / or body parts with relatively minor modification or no modification at all .

the disclosed subject matter includes optical tomographic systems for acquiring and displaying dynamic data representing changes in a target tissue sample to external provocation . for example , the disclosed devices , methods and systems may be used for quantifying dynamic vascular changes caused by imposed blood pressure changes for diagnosing peripheral artery disease .

the aim of the present invention is to overcome the above disadvantages by providing an apparatus for attaching the front end of a boot to a ski , particularly a cross - country ski , specifically adapted for a ski whose upper surface has a longitudinal rib bordered by two longitudinal strips . to this end , the apparatus according to the invention is defined in a manner to be herein described . a support is adapted to be pivotably mounted around a transverse axis on the ski and carries , towards the rear , a retention apparatus of the front end of the boot . elastic bias means biases the support towards the rear and the bottom of the ski for rotation around the transverse axis . the elastic bias means comprises two elastically flexible longitudinal tongues , each positioned on opposite sides of the rib and having a rear end affixed to the support and a front end adapted to be supported on the bottom of the ski . the tongues are capable of free longitudinal displacement with respect to the ski , at least over a portion of the path of rotation of the support . this solution makes it possible to considerably reduce the obstruction of the elastic bias means , with respect to the ski , in the direction of the height by carefully exploiting the space exposed by the difference in level between the longitudinal rib and the two longitudinal strips which border it . these elastic bias means thus become less vulnerable to shock and their presence near the edges of the ski translates into a lifting of the lower edges which is less than the lifting which these edges have when the elastic bias means are situated at a level above that of the rib . this results in less uptake of snow . the transverse axis around which the support is journalled to the ski can be positioned above the longitudinal rib . by positioning the journal axis either at the level of the longitudinal rib or beneath it , the advantage of reducing the obstruction of the assembly is further increased . for any of the alternative positions adopted for the axis , the support can be pivotably mounted around this axis directly on the ski , or one can provide an intermediate mounting element adapted to be fixed to the upper surface of the ski while straddling the rib , in which case the support is pivotably mounted around the axis on this intermediate element . as will become clear below , different embodiments for supporting the tongues on the bottom of the ski , either prestressed or not , can be provided to cause the support to rotate in the direction of elastic bias towards the rear and bottom of the ski as a function of the effective angular position of the support with respect to the ski , around the transverse axis of their mutual journal . similarly , one can provide relative abutment means of the front ends of the tongues in at least a longitudinal direction with respect to the ski to impose a limit to the free longitudinal displacement of the front ends of the tongues in a longitudinal direction corresponding to the direction of movement of the support towards the rear and bottom of the ski or in a reverse longitudinal direction or in the two longitudinal directions , which causes a different manner of flexion of the tongues and of elastic bias of the support when this limit is reached . in other words , by virtue of an appropriate choice of the embodiment of support of the tongues with respect to the ski , one can provide that as the support pivots upwardly and towards the front with respect to the ski , around their mutual transverse journal axis , the elastic bias means oppose an increasing force , or decreasing force , or constant force , or are further variable in a manner selected freely , to such a pivoting . according to a preferred embodiment of the apparatus according to the invention , the tongues are formed of an elastically flexible material integral with the support . in the mid - section of each tongue , a zone of reduced thickness defines a preferred elastic flexion zone of the tongue . thus , the front end of each tongue can be without any elastic flexibility and can be dimensioned so as to have a rigidity such that it does not deform when the tongue flexes . the rigidity of the tongue in the zone in which it receives the downward support forces makes it possible to more easily provide the elastic flexion characteristic of the tongue , to calculate it more easily , and furthermore increases the durability of the tongue . depending upon the particular embodiment , one can provide a direct support of the front end of each tongue on the ski , which makes it possible to provide a simple and economical structure of the apparatus . when there is provided an intermediate mounting element of the support on the ski , the front ends of the tongues are supported on the ski by means of this intermediate mounting element . this makes it possible to benefit from the advantages of the apparatus according to the invention on a ski whose upper surface has insufficient resistance to abrasion under the effect of a longitudinal displacement of the front ends of the tongues with respect to it , or which has a coefficient of friction which is too great to permit longitudinal translation of the tongues . referring to fig1 - 4 , there is illustrated a central portion of a cross - country ski 1 , which carries an apparatus according to the invention 2 , adapted to assure the attachment of the front end 3 of boot 4 with the ski 1 and to permit relative pivoting around a transverse axis 5 of ski 1 and boot 4 with respect to a longitudinal median plane 6 of the ski 1 . for reasons of simplicity , plane 6 will be assumed to be vertical in the description which follows , axis 5 thus being positioned horizontally , and it will be assumed that ski 1 itself is horizontal and placed in a normal position of use . in particular , it will be considered that a longitudinal direction 7 constituting the normal direction of displacement of the ski is horizontal . naturally , the references to orientation and level which follow from the description should only be taken as being indications of relative positioning , without implying limitation as to the conditions of use of the apparatus according to the invention . it is the same for the other embodiments of the apparatus according to the invention , likewise described in a normal position of use of the ski , which is assumed to be horizontal . ski 1 which is illustrated is of the &# 34 ; edged &# 34 ; type and comprises in its longitudinal median zone , a longitudinal bottom surface 8 , perpendicular to plane 6 , two edge surfaces 9 and 10 likewise longitudinal and both positioned parallel to one another and to plane 6 , and an upper surface 11 . surfaces of sides 9 and 10 connect upper surface 11 to bottom surface 8 . in a characteristic manner , the upper surface 11 of ski 1 has two longitudinal strips 12 and 13 which are positioned at the junction of upper surface 11 and sides 9 , 10 and are generally parallel to bottom surface 8 . these two strips 12 and 13 of upper surface 11 border a longitudinal rib 14 of the ski 1 . rib 14 is positioned longitudinally with respect to the ski and has a crosssection of isosceles trapezoid configuration . this crosssection is defined by an upper longitudinal surface 15 offset upwardly with respect to strips 12 and 13 and by two planar side surfaces 16 and 17 connecting surface 15 to strips 12 and 13 , respectively . surfaces 16 , 17 are positioned symmetrically to one another with respect to plane 6 , and converging mutually upwardly . the shape of upper surface 11 of ski 1 is only one non - limiting example and one can construct rib 14 unsymmetrical with respect to plane 6 and / or that strips 12 and 13 be mutually unsymmetrical with respect to this plane , and / or that rib 14 has a different cross - section than that of an isosceles trapezoid , for example , a triangular cross - section , in which case its upper surface 15 will be reduced to a junction edge between its side surfaces 16 and 17 . one of ordinary skill in the art will be able to modify without difficulty and without going beyond the scope of the present invention the apparatus according to the invention 2 which will be described at this time as a function of these possible differences of shape of the upper surface 11 of ski 1 . in its embodiment illustrated particularly in fig1 - 4 , the apparatus 2 according to the invention comprises an intermediate mounting element 18 , to be affixed to the upper surface 11 of the ski and having a shape adapted to surface 11 to better mate with it , by straddling rib 14 and covering the two longitudinal strips 12 and 13 in the longitudinal central zone of the ski . the attachment of the intermediate mounting element 18 with the upper surface 11 of the ski can be performed by any appropriate means , known to one of skill in the art , for example , by screwing or gluing in a localized manner or distributed over as large a surface as possible . the intermediate mounting element 18 has an omega - shaped cross - section defined by five generally planar longitudinal surfaces : lower surfaces , 19 , 20 , 21 , 22 , 23 which are tightly complementary and mate with strip 12 of side 16 , upper surface 15 , side surface 17 and strip 13 , respectively ; two edge surfaces 24 and 25 which are generally planar , parallel and symmetrical to one another extend upwardly from the surface of edge 9 and the surface of edge 10 , respectively , connected to surface 19 of element 18 and to surface 23 thereof ; five upper planar surfaces , i . e ., two surfaces 26 and 27 respectively adjacent to vertical edge surfaces 24 and 25 , positioned perpendicularly to plane 6 and parallel to direction 7 , two surfaces 28 and 29 symmetrical to one another with respect to plane 6 and parallel thereto in being turned in the direction of a distancing with respect thereto , and a surface 30 parallel and upwardly offset with respect to surfaces 26 and 27 connected by surfaces 28 and 29 ; the surfaces 26 and 27 define with surfaces 19 and 23 , respectively , two zones 31 and 32 for covering longitudinal strips 12 and 13 of the upper surface 11 of ski 1 by intermediate element 18 , while surfaces 28 , 30 , 29 define with surfaces 20 , 21 , 22 a zone 33 straddling rib 14 by means of element 18 . towards the front and rear , with reference to direction 7 , element 18 is defined by two planar transverse surfaces 34 and 35 perpendicular to direction 7 which connect the longitudinal surfaces of intermediate mounting element 18 . in a zone closer to the transverse rear surface 35 than to the front transverse surface 34 , upper surface 30 of element 18 carries in an affixed manner , in upward projection , a localized protuberance 36 spaced with respect to plane 6 by coplanar localized extensions of surfaces 28 and 29 ; along axis 5 , situated above the upper surface 15 of rib 14 , the localized protuberance 36 is bored on both sides , i . e ., from the surface 28 to the surface 29 perpendicular to axis 6 , with a cylindrical bore 37 around axis 5 having a diameter that is not secant to surface 21 of intermediate element 18 . to this end , this diameter is less than double the distance separating axis 5 from surface 21 perpendicular to the latter . in an alternative embodiment illustrated in fig2 a and 3a in which the same elements are shown as in fig2 and 3 , utilizing the same reference numerals , differing in that the transverse journal axis of zone 3 of the front end of boot 4 on ski 1 intersects the ski 1 at the level of rib 14 , such a position of this axis being shown at 5 &# 39 ; in fig2 a and 3a . in this case , surface 30 can be without protuberance 36 and bore 37 is replaced by two bores 37 &# 39 ; and 37 &# 34 ; which are cylinders of revolution around axis 5 &# 39 ;, respectively , between surfaces 28 and 20 and between surfaces 22 and 29 , with identical diameters and such that these bores are integrally situated between surface 21 and surfaces 26 and 27 , respectively . in particular , these diameters are less than the distance separating surface 21 from surfaces 26 and 27 and less than double of the smaller of the distances separating axis 5 &# 39 ; from surface 21 and from surfaces 26 and 27 . the axis 5 &# 39 ; of bores 37 &# 39 ; and 37 &# 34 ; extend coaxially , in rib 14 , through a bore 37 &# 39 ;&# 34 ; of identical diameter , that is , non - secant to the upper surface 15 of rib 14 . bore 37 of fig3 or the assembly formed by the coaxial bores 37 &# 39 ;, 37 &# 34 ;, 37 &# 39 ;&# 34 ; of fig3 a receives a coaxial pivot 38 of the general shape of a cylinder of revolution around axis 5 or 5 &# 39 ; with a diameter substantially identical to the diameter of bore 37 or to the diameters of bores 37 &# 39 ;, 37 &# 34 ;, 37 &# 39 ;&# 34 ;. one can either provide an immobilization of pivot 38 against a rotation around axis 5 or 5 &# 39 ; or against a translation parallel to this axis 5 or 5 &# 39 ; by any appropriate means in bore 37 or in bores 37 &# 39 ;, 37 &# 34 ;, 37 &# 39 ;&# 34 ;. in an alternative embodiment discussed below , free sliding occurs between pivot 38 and bore 37 or bores 37 &# 39 ;, 37 &# 34 ;, 37 &# 39 ;&# 34 ;. along axis 5 or 5 &# 39 ;, pivot 38 has a length greater than the distance separating surfaces 28 and 29 of the intermediate mounting element so that , when it is placed symmetrical with respect to plane 6 , this pivot 38 forms a projection with respect to two surfaces 28 and 29 , respectively above the surface 26 of surface 27 . for example , pivot 38 is defined by end surfaces 39 and 40 , is perpendicular to axis 5 or 5 &# 39 ;, and surfaces 39 and 40 are coplanar and equidistant from surfaces 24 and 25 , respectively , when pivot 38 is placed symmetrical to plane 6 . pivot 38 serves as a guide , for rotation around axis 5 or 5 &# 39 ; with respect to element 18 without any possibility of relative displacement , of substantially rigid zone 42 , of a support 41 having further , at the rear of zone 42 and in at least approximately rigid attachment with zone 42 , a zone 43 in which this support 41 carries a retention apparatus 44 for the front end 3 of boot 4 . this apparatus can be of any type which is known in itself , adapted to be affixed with zone 43 of support 41 of zone 3 of the front end of boot 4 or , as desired , to free the boot 4 with respect to support 41 . by way of non - limiting example , a retention apparatus 44 has been illustrated of the type described in french patent applications nos . 2 447 731 and 2 537 011 which have been referenced above . preferably formed of a single element , zones 42 and 43 of support 41 have a shape adapted to straddle element 18 , by surfaces 28 , 29 , 30 including the localized protuberance 36 , if desired , from in front of axis 5 or 5 &# 39 ; up to the rear transverse surface 35 . more specifically zone 43 straddles rib 14 at surfaces 15 , 16 and 17 at the rear of the rear transverse surface 35 of element 18 . zones 42 and 43 of support 41 thus have , as will become clear from fig3 with respect to zone 42 , the shape of an inverted u when they are viewed in cross - section through a plane perpendicular to direction 7 . considered in their entirety , zones 42 and 43 have two wings 45 and 46 , one positioned on either side of element 18 facing surfaces 26 and 28 of element 18 and facing surfaces 27 and 29 thereof . these two wings 45 and 46 are both connected , above the upper surface 30 of element 18 as well as below the localized protuberance 36 of this surface 30 , by a core plate 47 . towards each other , wings 45 and 46 have planar facing surfaces 28 and 29 of element 18 , planar surfaces 48 and 49 which are parallel and symmetrical with respect to one another and to plane 6 and equidistant therefrom . this distance is substantially equal to the distance separating surfaces 28 and 29 of element 18 , with which surfaces 48 and 49 are in contact , respectively , with a possibility of mutual sliding . surfaces 48 and 49 thus defined extend upwardly until connecting to a lower surface 50 of core 47 , which surface 50 is positioned facing localized protuberance 36 , as well as facing surface 30 of element 18 at the rear of localized protuberance 36 and facing upper surface 15 and of rib 14 at the rear of transverse rear surface 35 of element 18 , providing for a continuous clearance 52 of approximately constant thickness if one refers to the position of support 41 illustrated in fig2 . above the optional localized protuberance 36 , surface 50 is interrupted towards the front to be connected to a transverse front surface 51 of core 47 , which is planar and oriented perpendicularly to plane 6 while ascending towards the rear if one refers to fig2 or 2a . towards the rear , surface 50 is connected , as are surfaces 48 and 49 , to a planar surface 53 , perpendicular to plane 6 and ascending towards the front in the position illustrated in fig2 or 2a , which planar surface constitutes for front end zone 3 of boot 4 an abutment surface towards the front and towards the bottom as is clear from the french patent application nos . 2 447 731 and 2 537 011 and u . s . pat . nos . 4 , 382 , 611 and 4 , 484 , 762 to which reference has been made . towards the top and front , abutment surface 53 is connected to surface 51 by an upper surface 54 of core 47 . surface 54 carries in an affixed fashion , in upward projection and towards the rear a support element 55 receiving the front and top for zone 3 of the front end of boot 4 , as was described in french application nos . 2 447 731 and 2 537 011 and u . s . pat . nos . 4 , 382 , 611 and 4 , 484 , 762 . support element 41 and abutment surface 53 form an integral portion of retention apparatus 44 and will not be further described herein . towards the bottom , the two surfaces 48 and 49 connect two respective lower surfaces 56 and 57 of wings 45 and 46 . surfaces 56 and 57 are perpendicular to plane 6 and symmetrical with respect to one another . in zone 42 , surfaces 56 and 57 are coplanar and positioned parallel to surfaces 26 and 27 of intermediate element 18 , providing for a clearance 58 , 59 if one refers to the position illustrated in fig2 or fig2 a . at the transverse level of rear surface 35 of element 18 , surfaces 56 and 57 flex downwardly , so that surfaces 56 , 57 form planar zones resting flat against strips 12 and 13 respectively , of upper surface 11 of the ski 1 in the position illustrated in fig2 or 2a . towards the rear , these planar zones of surfaces 56 and 57 are connected to an abutment surface 53 along the length of a cut edge . in the direction of a spacing with respect to plane 6 , wings 45 and 46 of support 41 are defined by planar surfaces 60 and 61 , respectively , which are mutually parallel and symmetrical to one another with respect to plane 6 and preferably coplanar with surfaces 9 and 24 and surfaces 10 and 25 , respectively . surface 60 thus connects surfaces 56 , 53 , 54 , 51 , while surface 61 connects surfaces 57 , 53 , 54 , and 51 . the height of surfaces 56 and 57 , particularly when the support 41 occupies its position illustrated in fig2 or 2a , is intermediate between the lower level of bore 37 or bores 37 &# 39 ;, 37 &# 34 ;, 37 &# 39 ;&# 34 ;, i . e ., the lower level of pivot 38 in its zones projecting respectively on both sides of element 18 , and the level of surfaces 26 and 27 of zones 31 and 32 covering strips 12 and 13 of upper surface 11 of the ski . thus , axis 5 or 5 &# 39 ; cuts wings 45 and 46 which are both bored along this axis , between surfaces 48 and 60 and between the surfaces 49 and 61 , respectively , with respective bores 62 and 63 for receiving pivot 38 . the two bores 62 and 63 are cylinders of revolution around axis 5 or 5 &# 39 ; with a diameter substantially identical to that of pivot 38 so as to assure by means of pivot 38 a guidance of support 41 in rotation around axis 5 or 5 &# 39 ; with respect to element 18 without other possibility of relative movement . if pivot 38 is free to rotate in bore 37 or in bores 37 &# 39 ;, 37 &# 34 ;, 37 &# 39 ;&# 34 ;, it is affixed by any mean with support 41 in bores 62 and 63 . if on the other hand pivot 38 is immobilized within bore 37 or bores 37 &# 39 ;, 37 &# 34 ;, 37 &# 39 ;&# 34 ;, it is free to rotate around axis 5 or 5 &# 39 ; in bores 62 and 63 . thus , support 41 can occupy the position illustrated in fig2 or 2a as well as fig1 and 3 or 3a , in which surfaces 56 and 57 rest against strips 12 and 13 at the rear of element 18 . boot 4 can optionally be affixed by retention apparatus 44 with zone 43 of support 41 resting on the upper surface 11 by mating this surface with a longitudinal groove of sole 64 . additional positions such as the position illustrated in fig4 can be assumed and in which , by an ascending of the heel of the boot and a pivoting of the support 41 around axis 5 or 5 &# 39 ; with respect to element 18 in a direction 65 extending longitudinally towards the front above axis 5 or 5 &# 39 ;, the zones of surfaces 56 and 57 initially resting on strips 12 and 13 of surface 11 of the ski are offset upwardly with respect to strips 12 and 13 . the position of the support 41 illustrated in fig1 or 2a , 3 or 3a is the position support 41 assumes when it is not biased in the direction 65 by boot 4 . elastic return means of support 41 in a direction 66 opposite to direction 65 , tend to elastically press support 41 by means of surfaces 56 and 57 against strips 12 and 13 at the rear of element 18 . according to the present invention these elastic bias means of support 41 comprise two longitudinal tongues 67 and 8 which are elastically flexible , and positioned respectively on both sides of rib 14 , more specifically , on both sides of zone 33 of element 18 . each tongue has a respective rear end 69 , 70 affixed to support 41 in front of zone 42 and axis 5 or 5 &# 39 ; for journalling on element 18 , front end 71 , 72 which is supported on its bottom on surface 26 , 27 respectively capable of free longitudinal displacement relative to element 18 and ski 1 by sliding on surface 26 , 27 . the figure shows each tongue prestressed ; however , it is within the scope of the invention to provide tongues which are not prestressed . according to one embodiment not shown , tongues 67 and 68 can be in the form of elastically flexible elements , applied to support 41 which is rigid , forming zones 42 and 43 . however , as it is shown , one can preferably make it possible to form tongues 67 and 68 out of a single element with support 41 , grouping zones 42 and 43 by selecting as a material for this single element an elastically flexible or rigid material depending upon whether it is in the form of a plate or comparatively thin bar , or in the form of a comparatively compact block . for example , one can select amongst known materials under the marks &# 34 ; arnytel &# 34 ; or &# 34 ; hytrel &# 34 ;, which are polyamides , other materials possessing such a property being known to one of ordinary skill in the art and which can be selected without going beyond the scope of the present invention . thus , in the example illustrated , tongues 67 and 68 are formed in a single element with support 41 comprising zones 42 and 43 . coplanar surfaces 48 , 49 face each other and plane 6 while coplanar surfaces 60 , 61 face away from each other and are directed away from plane 6 . the two tongues 67 and 68 are symmetrical to one another with respect to plane 6 and are furthermore each defined by an edge surface , 73 , 74 . edge surfaces 73 , 74 are defined by rectilinear generating lines perpendicular to plane 6 resulting in a shape which , at the rear ends 69 and 70 through which tongues 67 and 68 are connected to zone 42 of support 41 immediately in front of axis 5 or 5 &# 39 ;. fig2 and 2a illustrate the tongues flexed upwardly from surface 56 of wing 45 and from surface 57 of wing 46 while resting at a level lower than that of axis 5 or 5 &# 39 ;, then flexed downwardly and towards the front , with a concave shape , up to front end 71 , 72 where the edge 73 , 74 has a convex semi - cylindrical shape of revolution around an axis perpendicular to plane 6 by flexing first upwardly and then frontwardly then upwardly and towards the rear . towards the top , from this semi - cylindrical zone , each of the edges 73 and 74 has a convex shape , with zones being approximately parallel to each other to the concave zone which it has towards the bottom as was previously stated , until adjacent the rear respective end 69 or 70 , where the edge 73 or 74 is situated at a level above that of axis 5 or 5 &# 39 ; and connects to the lower portion of surface 51 of zone 42 of support 41 by means of a respective cutout 75 , 76 oriented perpendicular to plane 6 and extending respectively from surface 67 to surface 48 and from surface 49 to surface 68 to define at the level of the rear end 69 , 70 of each tongue 67 , 68 a localized thinning in the direction of height , defining a preferred elastic flexion zone of the tongue 67 , 68 in the direction of height , to its connection with support 41 which is itself rigid in the position of support 41 illustrated in fig2 or 2a , tongues 67 and 68 are prestressed so as to firmly apply support 41 , by means of the respective zones of surfaces 56 and 57 situated at the rear of element 18 , against strips 12 and 13 of upper surface 11 of the ski 1 . the cutouts 75 and 76 , located at the connection of the rear ends 69 and 70 of tongues 67 and 68 with support 41 , have dimensions such that the average level of tongues 67 and 68 at their rear ends 69 and 70 is greater than the level of the axis 5 or 5 &# 39 ;. the cutouts further cause support 41 to pivot in the direction 65 around axis 5 or 5 &# 39 ; with respect to element 18 , as is shown in fig4 . the two tongues 67 and 68 flex identically by sliding towards the front , by means of their respective front ends 71 and 72 , against upper respective surfaces 26 and 27 of zones 31 and 32 of covering of strips 12 and 13 . when support 41 pivots to its biased position of direction 66 , front ends 71 and 72 of tongues 67 and 68 slide towards the rear on surfaces 26 and 27 . alternatively , tongues 67 and 68 can be connected to support 41 at an average level lower than the level of axis 5 or 5 &# 39 ;, such that the pivoting of support 41 in the direction 65 results in a sliding of front ends 71 and 72 of tongues 67 and 68 towards the rear , and that pivoting in the return in the direction of 66 translates into a sliding of front ends 71 and 72 of tongues 67 and 68 towards the front . the more the flexion of tongues 67 and 68 increases with respect to their initial flexion corresponding to the position of support 41 illustrated in fig2 or 2a , the more tongues 67 and 68 oppose resistance as a result of the pivoting of support 41 in direction 65 , and tend to bias support 41 elastically to its return position illustrated in fig2 or 2a . it is possible to affect the elastic return force imposed on support 41 by tongues 67 and 68 by forming surfaces 26 and 27 of zones 31 and 32 of element 18 , at the support of front ends 71 and 72 of tongues 67 and 68 . to this end , rather than providing an element 18 of a different shape to obtain a different elastic return effect , removable and replaceable wedges are adapted to be mounted on zones 31 and 32 of element 18 . thus , in fig5 - 7 in which the same reference numerals are used as in the elements appearing in fig2 or 2a , a removable plate is mounted on planar surface 27 . the plate has a lower planar surface 78 mounted on surface 27 of zone 32 , an upper planar surface 79 , parallel to surface 78 , and slidably supporting front end 72 of tongue 68 . an identical plate is , similarly , removably mounted on upper surface 26 of zone 31 to serve as a slidable support to the front end 73 of tongue 67 . the support surfaces such as surface 79 of these two plates 77 are of constant level with respect to surfaces 26 and 27 of element 18 , and the support of front ends 71 and 72 of tongues 67 and 68 on these plates instead of a direct support on surfaces 26 and 27 corresponds to an increased rigidity of tongues 66 and 67 opposing a pivoting of support 51 in the direction 65 with respect to element 18 . fig8 shows one type of connection for plate 83 . by way of removable mounting of plate 77 on zone 32 of element 18 , fig8 illustrates the use of a hollowed cutout 80 in surface 27 of zone 32 , perpendicular to surface 27 , with a localized narrowing in the immediate vicinity of surface 27 , to receive a bulbous projection 82 force - fit therein and provided to project under surface 78 of plate 77 , perpendicular to surface 78 . other means can be utilized for this purpose , and one can , for example , provide that instead of a blind bore , cutout 80 extends completely through zone 32 of element 18 and extends into ski 1 through a blind bore in which bulbous projection 82 is immobilized by traversing zone 32 of element 18 . naturally , the plate associated in a removable manner with zone 31 of element 18 can be affixed in the same manner . fig6 illustrates the removable mounting , on surface 27 of zone 32 of element 18 illustrated in fig8 having a lower planar surface 84 flattened against surface 27 of zone 32 , and an upper surface 85 which is planar and defined by generating lines perpendicular to plane 6 , and rising towards the front with respect to lower surface 84 or surface 27 for downward support , under constraint of the front end 72 of tongue 68 , in the form of a cam . an identical plate ( not shown ) is mounted on surface 26 of zone 31 of element 18 for supporting front end 73 of tongue 67 . by virtue of such a mounting , one obtains a progressive increase in the elastic resistance opposed by tongues 67 and 68 to pivoting of element 61 in direction 65 , i . e ., a return that increases , in the direction 66 , the more that the angular offset of support 41 with respect to its position illustrated in fig2 is substantial , in the case where the front ends 71 and 72 of tongues 67 and 68 are displaced frontwardly when support 41 pivots in direction 65 . in fig7 the mounting has been illustrated on surface 27 of zone 32 of element 18 , of a cam plate 87 having a lower planar surface 86 glued to surface 27 and an upper surface likewise planar 88 , defined by generating lines perpendicular to plane 6 and converging towards the front with respect to surfaces 86 and 27 . an identical cam plate is located on surface 26 of zone 31 of element 18 . the connection is , for example , formed by means of the type illustrated in fig8 . where the pivoting of support 41 in direction 65 is accompanied by a displacement of the front ends 71 and 72 of tongues 67 and 68 towards the front , such a pivoting is accompanied likewise by a descending movement of these front ends 71 and 72 and , if the slope of surface 88 with respect to surface 87 is selected in an appropriate manner , easily determinable by one of ordinary skill in the art , this progressive descent can translate into a progressive reduction of elastic resistance opposed by tongues 67 and 68 to the pivoting of support 41 in the direction 65 , i . e ., by a progressive reduction of the elastic return of this support 41 in direction 66 . instead of being planar , the support surfaces 85 ascending towards the front and 88 descending towards the front can have a curvilinear shape , defined by generating lines perpendicular to plane 6 . furthermore , where support 41 pivots in a direction 65 , as illustrated in fig2 or 2a , resulting in movement of front ends 71 and 72 of tongues 67 and 68 towards the rear , the desired effects described with reference to fig6 and 7 will be obtained by providing either a cam plate having a support surface rising towards the rear or a cam plate having a support surface descending towards the rear . it will be noted that the intermediate mounting element 18 is not necessary when the desired position of the journal axis of the front end 3 of boot 4 cuts the ski at the level of the rib of the upper surface thereof , as is illustrated at 5 &# 39 ;, or below this rib . fig9 - 15 illustrate an alternative embodiment according to the invention which is analogous to that described with reference to fig1 - 8 , 2a and 3a , with the only modification being that the support carries , towards the rear the retention apparatus of the front end of the boot and pivots directly on the ski , around an axis cutting the latter at the level of the rib of its upper surface . similarly , fig1 - 18 illustrate an apparatus according to the invention whose support pivots directly on the ski , around an axis cutting the latter beneath the rib , this apparatus also being analogous to that which has been described with reference to fig1 - 8 . in fig1 - 14 the elements described have the reference numerals corresponding to the reference numerals of fig1 - 8 , 2a and 3a , increased by 100 which are identical to elements of fig1 - 8 , 2a and 3a or including modifications which will be described below . similarly , the embodiment of fig1 - 18 has reference numerals of fig1 , 2a and 3a increased by 200 which are identical to elements of fig1 - 8 , 2a and 3a or having modifications which will be described below . only elements corresponding to elements 5 , 18 - 36 , 37 , 37 &# 39 ;, 37 &# 34 ; of fig1 - 8 , 2a and 3a are missing from the embodiments illustrated respectively in fig9 - 15 and fig1 - 18 . reference will be made now more particularly to fig9 - 15 to explain the differences between the embodiment of the apparatus according to the invention 102 illustrated in these figures , and the apparatus 2 illustrated in fig1 - 8 and 2a , 3a . as is seen more particularly in fig1 , the side surfaces 116 and 117 of longitudinal rib 114 have , in the central zone thereof receiving the apparatus according to the invention 102 , respective hollows 191 and 192 defined towards the bottom by extensions of strips 112 and 113 in the direction of the longitudinal median plane 106 of the ski and , towards plane 106 , by respective planar surfaces 189 and 190 which are mutually parallel , symmetrical to one another with respect to plane 106 and turned in the direction of a distancing with respect thereto . these surfaces 189 and 190 connect the respective extensions of strips 112 and 113 to the upper surface 115 of rib 114 thereof , and connect surfaces 116 , 117 to surface 115 along the length of rectilinear extensions of junctions with surface 115 . as a result , the pivot 138 has , along axis 105 &# 39 ; as was said with respect to pivot 38 , a length corresponding to the mutual spacing between the surfaces of sides 109 and 110 of ski 101 formed a protection on both sides of rib 114 , with respect to surfaces 189 and 190 of hollows 191 and 192 engaging bores 138 and 139 of wings 146 and 147 of support 141 in zone 142 thereof . in order to prevent movement of support 141 along axis 105 &# 39 ; of ski 101 , surfaces 148 and 149 of the support 141 , facing each other , are planar and parallel , symmetrical to one another with respect to plane 106 as was said with respect to surfaces 48 and 49 , and their relative spacing is substantially identical to the relative spacing of surfaces 189 and 190 perpendicular to plane 106 , such that surface 148 is flattened against surface 189 and surface 149 is flattened against surface 190 , in both cases permitting relative sliding . furthermore , in the absence of the intermediate mounting element corresponding to element 18 , surface 150 of support 141 has a planar shape adapted to mate , given a continuous clearance 152 of constant thickness , the surface 115 of rib 114 of ski 101 in the position of support 141 illustrated in fig9 and 10 , in which this support 141 rests flat , by rear respective zones of lower surfaces 156 and 157 of wings 145 and 146 , respectively against strip 112 and against strip 113 of the upper surface 111 of ski 101 , at the rear of axis 105 &# 39 ;. to this end , as was illustrated in fig9 with respect to hollow 192 , the two hollows 191 and 192 extend towards the rear beyond respective connections of surfaces 156 and 157 with surface 153 of support 141 , or the surface such as 190 of hollow 192 connects to the corresponding side surface 117 of rib 114 by a transverse planar surface 193 turned towards the front . in the absence of element 18 , the clearances 158 and 159 are adapted to facilitate a pivoting of support 141 in a direction 165 corresponding to a lifting of the zones of this support situated at the rear of axis 105 &# 39 ;, as illustrated in fig1 , are positioned between a front zone of surface 156 and strip 112 , and between a front zone of surface 157 and strip 113 . rather than sliding during pivoting in the opposite direction 166 on zones of an intermediate mounting element such as 18 , the respective front ends 172 , of elastically flexible tongues 167 , 168 slide directly on longitudinal strips 113 of upper surface 111 of ski 101 , towards the front or towards the rear along the direction of pivoting or the level to which the tongues 167 , 168 are connected to support 141 , as was discussed with respect to tongues 67 and 68 and of support 41 above . as with tongues 67 and 68 , tongues 167 , 168 are defined towards plane 106 by respective coplanar extensions of surfaces 148 and 149 . to allow for their support against strips 112 and 113 , surfaces 189 and 190 of hollows 191 and 192 extend beyond the front extreme position of the front ends such as 172 of the elastically flexible tongues 167 , 168 , as was illustrated with respect to hollow 192 , by providing a front extreme transverse surface 194 which is planar , connecting its surface 190 to side surface 117 of rib 114 of ski 101 . with reference to the above , it is noted that a second tongue 167 , not shown , similar to tongue 67 of fig1 - 8 and its corresponding elements is symmetrical to tongue 168 . rather than providing a direct sliding of the front respective ends 172 of the elastically flexible tongues 167 , 168 on the longitudinal strips 112 and 113 of the upper surface 111 of ski 101 , one can provide such a sliding by means of plates applied respectively on strips 112 and 113 , which are preferably removable , to protect these strips 112 and 113 from abrasion by sliding . these plates affect the elastic rigidity opposed by the tongues 168 to a pivoting of support 161 in direction 165 , that is , on the elastic return in direction 166 exerted by these tongues such as 168 , as a function of the angular position of support 141 with respect to ski 101 . as illustrated in fig1 - 14 plates 177 , 183 , 186 having lower respective surfaces 178 , 184 , 187 which are planar and adapted to be applied flat against strips 113 of the upper surface 111 of the ski , and upper respective surfaces 179 , 185 , 188 which are planar or which may be curved if desired , defined by generating lines perpendicular to plane 106 . these plates define for the front respective ends 172 of elastically flexible tongues 168 the support surfaces respectively as being of constant level with respect to the strip 113 ( surface 179 of plate 177 of fig1 ); rising towards the front with respect to the strip 113 ( surface 185 of plate 183 of fig1 ) or descending towards the front with respect to the strip 113 ( surface 188 of plate 186 of fig1 ). as was said above with respect to plates 77 , 83 , 86 and as is illustrated in fig1 with respect to wedge 177 , one can , for example assure a removable affixation of each plate 177 with the corresponding strip such as 113 of ski 101 by force - fitting a bulbous projection such as 182 of the lower surface such as 178 of the plate 177 in a blind bore such as 180 provided in the strip such as 113 of ski 101 and having a narrowing at its opening in this strip such as 113 . other means whose realization is within the skill of one of ordinary skill in the art can likewise be selected to attach , in a removable and easily interchangeable manner , the plates with strips 112 and 113 of ski 101 . if one refers to fig1 - 18 it is seen that rib 214 of ski 201 has a shape which is completely identical to that of rib 14 of ski 1 and that hollows 291 and 292 are provided in the ski respectively at the junction of strip 212 with the edge surface 209 and at the junction of strip 213 with the edge surface 210 , in a zone localized around axis 205 &# 39 ; positioned between surface 208 of the ski , and the strips 212 and 213 of the upper surface 211 thereof . more precisely , each of hollows 291 and 292 is defined towards plane 206 by a planar surface , respectively 289 , 290 parallel to this plane 206 and turned in the direction of a distancing with respect thereto . the two surfaces 289 and 290 are symmetrical to one another with respect to plane 206 and connect on top to strip 212 and 213 , for example approximately half - way between corresponding edge surface 209 or 210 of ski 201 and the corresponding side surface 216 or 217 of rib 214 of ski 201 . naturally , surfaces 289 and 290 continue downwardly past axis 205 &# 39 ;, at a distance therefrom , without reaching bottom surface 208 of ski 201 . openings 291 and 292 are defined by concave surfaces , turned upwardly 293 and 294 , defined by generators perpendicular to plane 206 and connecting surface 289 to surface 209 and surface 290 to surface 210 , respectively . towards the front and rear , surfaces 293 and 294 are connected on top to strips 212 and 213 of the upper surface 211 of ski 201 . at the front , between the rear end support limit of the respective front ends 272 of the elastically flexible tongues 268 on strips 212 and 213 and axis 205 &# 39 ;, and at the rear between the axis 205 &# 39 ; and the position occupied by the rear respective zones of surfaces 256 and 257 of wings 245 and 246 of support 241 when it occupies its position illustrated in fig1 , i . e ., its limit of movement position in the direction 266 with respect to ski 201 , to then allow for a support which is as extended as possible of these rear zones respectively on strip 212 and strip 213 . in a corresponding fashion , wings 245 and 246 of support 241 extend downwardly , at their surfaces 248 and 249 , until they cut axis 205 &# 39 ;, and surfaces 293 and 294 extend around the bottom of the zones of pivot 238 projecting with respect to surfaces 289 and 290 , while allowing for a relative spacing such as exists , between the lower surfaces 256 and 257 of wings 145 and 146 and surfaces 293 and 294 , of clearances 256 and 257 allowing for a free pivoting of support 241 in direction 265 from the position illustrated in fig1 , and a free pivoting in return in the opposite direction 266 . furthermore , as is seen in fig1 , surfaces 248 and 249 define symmetrical wings 245 and 246 towards plane 206 , in positions parallel to plane 206 and spaced by a distance corresponding to the distance separating surfaces 289 and 290 , to rest against these surfaces and be capable of sliding . surface 250 , which can maintain a planar shape as in the case of the embodiment illustrated in fig9 - 15 , is superimposed in this case not only to surface 215 of rib 214 , providing a clearance 252 , but likewise to side surfaces 216 and 217 of rib 214 and to respective zones of strips 212 and 213 situated between these side surfaces of the rib and , respectively , the surfaces 289 and 290 of hollows 291 and 292 . preferably , the elastically flexible tongues 268 are likewise defined towards plane 206 , by coplanar extensions of surfaces 248 and 249 . they are supported on strips 212 , 213 by their front ends 272 , with prestress in the non - limiting example illustrated and capable of longitudinal sliding , either directly as is illustrated in fig1 - 18 , or by means of wedges at all points identical to those which were described with reference to fig1 - 14 , for example mounted as is indicated with reference to fig1 . it will be noted that , even though a direct mounting of support 241 on ski 201 is preferred when axis 205 cuts ski 201 beneath rib 214 of upper surface 211 thereof , one can alternatively provide for a mounting by means of an intermdiate mounting element analogous to element 18 of fig1 - 8 . this may be accomplished by providing in the zones 31 and 32 of this element cavities adapted to receive , at the level of axis 205 &# 39 ;, the respective zones of wings 245 and 246 of support 241 having bores 262 and 263 for receiving pivot 238 . with respect to the different embodiments which have just been described , with reference respectively to fig1 - 8 and 2a , 3a , 9 - 15 and 16 - 18 , the possibility of affecting the rigidity of the elastically flexible tongues as a function of the angular position of the support with respect to the ski has been discussed in the form of applying plates of appropriate shape either directly on the ski ( fig1 - 15 ), or on an intermediate mounting element of the apparatus according to the invention on the ski ( the case of fig5 - 8 ). however , in addition to or in place of these plates , one can likewise act to this end by forming in an appropriate fashion the front ends by means of which the tongues rest for example in prestress either directly on the strips bordering the longitudinal rib of the upper surface of the ski , or on the zones of the intermediate mounting element covering these strips , and this whatever the position of the pivot axis of the support with respect to the ski . thus , there is illustrated in fig1 and 20 an apparatus which is identical at every point to that which was described with reference to fig1 - 4 and 2a , 3a , in the case of an axis cutting the ski at the level of the rib . the only difference between this embodiment and that of fig1 - 4 and 2a , 3a , resides in the contour of the elastically flexible tongues . as a result , fig1 and 20 have the same reference numerals as fig1 - 4 and 2a , 3a , to designate the same elements . the flexible tongue of the alternate embodiment has a designation of reference 74 &# 39 ; to the edge of the elastically flexible tongue 68 . as in the previous embodiment , it will be noted that even though this single tongue 68 is visible in fig1 and 20 , support 41 likewise carries in this case a second elastically flexible tongue symmetric to tongue 68 with respect to the longitudinal median plan of the ski . in the case of the embodiment of fig1 and 20 , edge 74 &# 39 ; of the elastically flexible tongue 68 presents successively , from its rear end such as 70 which connects with the wing such as 46 of support 41 and core 47 thereof , an approximately planar and horizontal zone 95 turned downwardly and situated both at a level above that of axis 5 &# 39 ; and directly beneath the cutout 76 of the tongue 68 to define the localized thinning referred to above , then a zone 96 which is likewise turned downwardly but having a convex profile adapted to be supported by a rectilinear generating line , perpendicular to the longitudinal median plane of the ski , on the surface 27 of the covering zone 32 of the longitudinal strip 113 by the intermediate mounting element 18 . towards the front , the zone 96 of edge 74 &# 39 ; connects to a zone 97 which is planar , perpendicular to the longitudinal median plane of the ski and rising towards the front , which zone 97 connects on top to a convex zone 98 turned upwardly , and assuring the connection of zone 97 to the cutout 76 of the rear end 70 of the tongue 68 . when , as was illustrated in fig2 , support 41 pivots in direction 65 , around axis 5 &# 39 ;, with respect to the intermediate mounting element 18 and with respect to ski 1 , the front end 72 of the elastic tongue 68 tends to longitudinally displace towards the front due to the level of connection of the rear end 70 of the tongue 68 to the support 41 but , by an appropriate choice of the shape of the zone 96 , within the skill of one of ordinary skill in the art , one can provide either a constant longitudinal distance between the support of this zone 96 on the surface 27 of the covering zone 32 , or a variation of this distance in the direction of increase or reduction . in practice , when such a pivoting occurs in direction 65 , zone 96 comes into contact with the surface such as 27 of the covering zone 32 by means of generating lines situated toward the rear on zone 96 , i . e ., closer to zone 95 , resulting in a pivoting of the tongue assembly 68 with respect to support 1 around the thinned localized zone defined by zone 95 and cutout 75 . an arrangement can be adopted such that the journal axis of the support on the intermediate mounting element 18 occurs at the level of the rib as illustrated in fig1 and 20 or that it is located above this rib as illustrated in fig1 - 4 , or furthermore beneath this rib , in the position illustrated in fig1 - 18 , assuming that on intermediate mounting element is employed . in the absence of such an element , whether the axis is positioned at the level of the rib or below it , one can , however , likewise adapt the shape of the front end of the tongue described with reference to fig1 and 20 . thus , by way of non - limiting example , fig2 and 22 have been limited to an apparatus which is identical at every point to that which is illustrated in fig9 - 11 , such that one has preserved in fig2 and 22 the same references as fig9 - 11 , with the only exception that the front end zone 172 of each tongue 168 is directly supported on the strip 113 associated with the upper surface 111 of ski 101 through a zone 196 of its edge 174 . zone 196 has a shape which is identical at every point to the shape described with respect to zone 96 in the embodiment of fig1 and 20 , with the same effects . more precisely , one finds in fig2 and 22 respectively under references 195 , 196 , 197 , 198 , elements identical to those which were described under the references 95 , 96 , 97 , 98 , respectively , with respect to the embodiment of fig1 and 20 . in the embodiment illustrated in fig2 and 22 as in the embodiment illustrated in fig1 and 20 , zones 96 and 196 are shaped , in a manner which can easily be determined by one of ordinary skill in the art , as a function of the desired effect for the angular position of support 41 or 141 with respect to ski 1 or 101 . this will affect the resistance of tongues 68 and 168 to a pivoting of the support in direction 65 or 165 , and also the elastic return exerted by the tongues in the opposite direction 66 or 166 . in all of the embodiments of the invention which have been described , the prestressing of support of the tongues downwardly with respect to the ski , implies the application to support 41 , 141 , 241 of a return torque in direction 66 , 166 , 266 whatever the angular position of this support with respect to the ski . one will not go beyond the scope of the present invention by shaping the tongues so as to eliminate this prestress , either such that the resting of the support downwardly and rearwardly on the ski preserves a direct or indirect downward contact of the front ends of the tongues to assure a return torque as soon as the support is spaced from the support position by pivoting in direction 65 , 165 , 265 . alternatively , the tongues may be shaped such that the resting of the support downwardly and rearwardly on the ski causes a spacing of the front ends of the tongues upwardly with respect a direct or indirect contact position of these front ends downwardly with the ski so as to assure the application of a return torque only when the support is spaced by a predetermined angle from this support position by pivoting in direction 65 , 165 , 265 . such a configuration is well within the skill of one of ordinary skill in the art . the different embodiments which have just been described assume a direct support of the front ends of the tongues either on an intermediate mounting element locally covering the ski or directly on the ski . one can provide , however , other modes of cooperation between the respective front ends of the tongues and the ski or , preferably , an intermediate mounting element of the apparatus according to the invention on the ski , as is specifically illustrated in fig2 - 26 to which reference will now be made . referring first to fig2 and 24 , where there has been illustrated an apparatus according to the invention 302 which , with the exception of the method of support , in prestress in the non - limiting example illustrated of the front ends of the tongues with respect to the ski , and more precisely with respect to the intermediate mounting element , is in every other respect , the same as the apparatus illustrated in fig1 - 4 such that one finds under the same reference numerals , incremented by 300 , the elements described with reference to fig1 - 4 , identical or including modifications which will be now described . in the case of the embodiment of fig2 and 24 , the upper surface 330 of the intermediate mounting element 318 , furthermore identical to the intermediate mounting element 18 described with reference to fig1 - 4 , has in a front zone i . e ., adjacent to the front end surface 334 of element 318 , a localized protuberance 389 which extends in the form of a coplanar extension upwardly , from the surface of element 318 which corresponds to surface 28 of support 18 to a coplanar extension , towards the top , of the surface 329 corresponding to surface 29 . furthermore , surface 330 has in a rear zone a localized protuberance 336 corresponding to protuberance 36 , to receive pivot 338 for guidance of support 341 to rotate with respect to element 318 around axis 305 situated above rib 314 of the ski . however , as is the case with the embodiment of fig2 a and 3a , one can provide a mutual journal around axis 305 &# 39 ; which is itself secant to rib 314 of the ski , which implies the absence of the protuberance 336 , or even around an axis situated beneath the rib of the ski resulting in an appropriate modification of element 318 , as was explained with respect to the embodiment of fig1 - 18 . within the localized protuberance 389 is hollowed out a logitudinal slot 390 , positioned towards the bottom by a planar surface 393 parallel to surface 321 through which element 318 applies itself against upper surface 315 of rib 314 , such that this surface 393 is parallel to surface 315 as to the longitudinal strips such as 313 bordering rib 314 respectively on both sides . slot 390 extends thus from the surface of element 318 corresponding to the surface 28 to surface 329 and receives therein , with a longitudinal clearance allowing for a longitudinal relative sliding , a rectilinear pin 391 , perpendicular to the longitudinal median plane of the ski , i . e ., to the axis 305 or 305 &# 39 ;, which pin constitutes a rigid transverse member rigidly affixed to front ends 372 of the elastically flexible tongues 368 . in every other aspect , tongues 368 are furthermore at every point analogous to tongues 67 and 68 described with reference to fig1 - 4 . to this end , in each of the tongues 368 , the pin 391 engages in a transverse bore 392 , in which it is immobilized by any appropriate means , easily within the skill of one of ordinary skill in the art . the bores such as 392 are situated , on the tongues 368 , such that the engagement of pin 391 in slot 390 prevents a contact of the front end zone 372 of each tongue with the surface 327 of the covering zone 363 with which it is respectively associated , by applying , to the two tongues a downward support , in prestress against the intermediate mounting element 318 , by support of pin 391 downwardly against surface 393 of slot 390 . it is easily seen that , in the case of the embodiment of fig2 and 24 as in the case of the embodiment of fig1 - 4 , a pivoting of support 341 in direction 365 corresponding to the direction 65 or in the direction 366 corresponding to direction 66 is accompanied by a longitudinal displacement of the front respective ends of the supported tongues 368 with respect to element 318 . support of the tongues is formed by pin 391 downwardly supported on surface 393 of slot 390 , and , respectively , an increase or a reduction of elastic stress of the elastically flexible tongues such as 368 . in order to modify the bias in a predetermined manner , the elastic resistance that the tongues 368 oppose to a pivoting of support 341 in direction 365 , and on the effect of the elastic return of support 341 in direction 366 , lower surface 393 of longitudinal slot 390 may not be positioned so that it is not parallel to surface 321 of element 318 , or to surface 315 of rib 314 and to the strips 313 but rather , oblique with respect to these reference surfaces . thus , in fig2 and 27 , embodiments have been illustrated which are the same at every point to those of fig2 and 24 , with the exception that slot 390 is replaced by slots 390 &# 39 ; and 390 &# 34 ; defined on the bottom by respective surfaces 393 &# 39 ; and 393 &# 34 ;; slot 390 &# 39 ; supports pin 391 &# 39 ; descending towards the front with respect to surface 321 of fig2 and rising towards the front with respect to this surface of fig2 . seen in cross - section through the longitudinal median plane of the ski or through a plane parallel thereto , the lower respective surfaces 393 , 393 &# 39 ;, 393 &# 34 ; of slots 390 , 390 &# 39 ;, 390 &# 34 ; have a general rectilinear shape but one can likewise give them a curvilinear shape in such a plane , in a manner which can be easily determined by one of ordinary skill in the art as a function of the effect sought to be achieved of the influence of the tongues such as 368 on rotation of support 341 . in a manner illustrated in fig3 , one can superimpose in element 318 , which is appropriately dimensioned , a plurality of longitudinal slots 390 , 390 &# 39 ;, 390 &# 34 ;, adapted to receive pin 391 , to provide the user the option of selecting the elastic resistance effect or elastic return of the tongues 368 with respect to rotation of support 41 in direction 365 or in direction 366 . fig3 a illustrates pin 392 as engaging slot 390 &# 39 ;, but it could alternately be positioned in either of slots 390 or 390 &# 34 ;. this effect may also be achieved as illustrated in fig2 . in that embodiment , front end 372 of tongues 368 is provided with a plurality of bores 392 &# 39 ;, 392 &# 34 ;, 392 &# 39 ;&# 34 ; distributed in a predetermined fashion and adapted to receive pin 391 which is itself engaged in slot 390 &# 39 ; or 390 &# 34 ;, ( not shown in fig2 ) or in one of the slots thus superimposed to be supported against element 318 , in prestress of the tongues 368 , through the lower surface of the slot , while providing a longitudinal clearance therein . fig2 and 29 illustrate apparatus 402 according to the invention constituting another alternative embodiment described with reference to fig2 and 24 . fig2 and 29 are similar to the embodiment of the apparatus illustrated in the fig2 and 24 . the same reference numerals are used in fig2 and 29 as in fig2 and 24 , incremented by 100 . only those elements which differ from the elements described with reference to fig2 and 24 will be explained below . the embodiment of fig2 and 29 has an axis 405 situated above the upper surface 415 of rib 414 or an axis 405 &# 39 ; cutting the ski at the level of rib 414 , or axis situated below rib 414 . these variations provide an adaptation of the configuration of intermediate mounting element 418 . protuberance 489 is positioned in a front zone of the upper surface 430 of the intermediate mounting element 418 is bored not with a slot but with transverse bore 492 perpendicular to the longitudinal median plane of the ski . this bore 492 , extends from the surface of element 418 corresponding to surface 28 of element 18 to surface 429 corresponding to surface 29 of this element , receives an affixed transverse member preferably constituted by a pin 491 which is rectilinear and rigid and projects with respect to the surfaces 428 , 429 . preferably , a plurality of longitudinally offset bores 492 are thus provided , as is schematically shown at 492 &# 39 ; and 492 &# 34 ;, and , if desired , in the direction of the height of protuberance 489 , to receive selectively pin 491 . additionally , in each of elastically flexible tongues 468 a longitudinal slot 490 is provided transversely on both sides of the tongue and having an upper surface 493 whose shape , in any cross sectional plane parallel to the longitudinal median plane of the ski , is rectilinear as is illustrated in fig2 and 29 , or is curvilinear ( not shown ). by way of a non - limiting example , slots 490 of the tongues 468 receive pin 491 which projects onto surfaces 428 , 429 of the intermediate mounting element 418 and permits relative longitudinal sliding of the tongues and the intermediate mounting element to define , by means of surface 493 , a lower support of prestressed tongue 468 on pin 491 and by means thereof on intermediate mounting element 418 . in such a mounting , pivoting of support 441 in the direction 465 going to the front above axis 405 or 405 &# 39 ;, is accompanied by an increase of the elastic stress of the tongues 468 accompanied by an increase of the resistance which they oppose such a pivoting as well as the elastic bias which they apply to support 441 in opposite direction 466 . by an average orientation and a shape chosen from slots such as 490 and by choosing in an appropriately shaped slot 492 , 492 &# 39 ;, 492 &# 34 ;, and receiving pin 491 , one can modulate these effects as a function of the angular position of support 441 with respect to intermediate mounting element 418 , in a fashion easily determined by one of ordinary skill in the art . one of ordinary skill in the art will easily understand that instead of being situated above rib 414 of upper surface 411 of ski 401 as is illustrated , the transverse member constituted by pin 491 can likewise be situated at a level such that it is secant to rib 414 . in this case , it can be mounted as described with respect to axis 5 &# 39 ; with reference to fig2 a and 3a , or further be carried in an affixed manner directly by rib 414 by forming a projection respectively on both sides thereof , as is described with respect to axis 105 &# 39 ; with reference to fig9 - 11 , i . e ., be carried by the ski without use of element 418 . this element 418 can then be totally omitted if one chooses an axis 405 &# 39 ; which is secant to the ski for journalling of the support 441 and mounted as axis 105 &# 39 ; described with reference to fig9 - 11 . preferably , the option remains of choosing the positioning of pin 491 by providing a plurality of bores comparable to bores 492 , 492 &# 39 ;, 492 &# 34 ; to receive the pin . one of ordinary skill in the art will understand furthermore easily that instead of resting downwardly with respect to the ski , by means of a pre - stress , when support 341 or 441 is itself resting against the bottom and towards the rear with respect to the ski , the front ends of the tongues such as 368 and 468 can be such as to being not pre - stressed , or further , be pre - stressed by pressing upwardly with respect to the ski , in which case they would elastically bias support 341 or 441 for pivoting in direction 365 or 465 while the support would occupy such a support position as well as any intermediate angular position between this support position and a pre - determined angular position corresponding to a zero stress of the tongues , while the crossing by the support of this pre - determined angular position in direction 365 or 465 will cause the application to the support of an elastic return in the opposite direction 366 or 466 . the realization of such alternatives is within the normal aptitude of one of ordinary skill in the art . furthermore , even though different embodiments of the invention which have been described assume the possibility of free longitudinal displacement of the front ends of the tongues with respect to the ski in the range of angular positions of the support with respect to the ski accessible under normal conditions of use , one would not go beyond the scope of the present invention by providing abutment means imposing on the front ends of the tongues a longitudinal displacement limit with respect to the ski either in the direction 7 , 107 , 207 , 307 , 407 , or in the opposite direction , or further in one of the other of these directions , of which each corresponds respectively to a direction of rotation of the support with respect to the ski . thus , in fig2 in which front ends 71 and 72 of tongues 67 and 68 are displaced in direction 7 when support 41 pivots in direction 65 , there has been illustrated at 99 a pin extending through rib 14 and intermediate mounting element 18 on both sides along a direction perpendicular to plane 6 , in the manner described with respect to pivot 38 , with reference to fig2 a and 3a , to form a projection with respect to surfaces 28 and 29 of element 18 , above surfaces 26 and 27 of zones 31 and 32 thereof , beneath its surface 30 , in front of the front ends 71 and 72 of tongues 67 and 68 with reference to direction 7 . pin 99 occupies a predetermined position such that after a pivoting of a predetermined amplitude of support 41 in direction 65 from its position illustrated in fig2 by means of a flexion of tongues 67 and 68 , the front ends 71 and 72 of the latter abut frontwardly against pin 99 which prevents them from pursuing their displacement in direction 7 . preferably , this abutment occurs by engagement of pin 99 in a cutout such as 100 , open towards the front , which is preferably provided in edge 73 , 74 of each tongue 67 , 68 , on the front end thereof . if the pivoting of support 41 in direction 65 continues after coming into abutment , it imposes on tongues 67 and 68 a longitudinal compression and a manner of flexion , by buckling , different from their mode of flexion during the free longitudinal displacement of their front ends resting downwardly on surfaces 26 and 27 , with generally a more energetic elastic return of support 41 in direction 66 . a plurality of bores perpendicular to plane 6 , offset mutually particularly along a longitudinal direction , can be provided in element 18 and in rib 14 , in a manner not shown , to receive as desired the pin 99 . such an alternative embodiment can be applied to all of the embodiments of the invention illustrated in fig1 - 22 . likewise , in the case of the embodiments illustrated in fig2 - 27 and 28 , 29 , one can provide that one of the ends of slots 390 , 390 &# 39 ;, 390 &# 34 ;, 490 constitutes an abutment limiting the longitudinal relative displacement of this slot and of pin 391 , 491 in a direction , and / or that the other of these ends constitutes an abutment limiting the longitudinal relative displacement of the slot and of the pin in the other direction . one can likewise constitute such an abutment by means allowing for an adjustment of the longitudinal position thereof , for example , in the form of a transverse end of a longitudinal brake - screw 333 forming a longitudinal projection within the slot as illustrated in fig2 where the abutment 399 is constituted by the rear transverse end of a longitudinal screw which can be screwed more or less in a longitudinal tapping of the intermediate mounting element 318 , from the front surface 334 thereof and along the longitudinal median plane of the ski , to oppose an adjustable abutment to the displacement of pin 391 towards the front from a predetermined angular position of support 341 in its rotation in direction 365 such that the continuation of this rotation causes tongues 367 and 368 to compress and to buckle , with an increased elastic return . an analogous adjustable abutment can be provided to limit the displacement of pin 391 towards the rear in slot 390 such that support 341 tends to naturally occupy an angularly offset position for example , of 20 ° in the direction 365 with respect its position illustrated in fig2 , and that its passage to the position illustrated in fig2 , and that its passage to the position illustrated in fig2 necessitates an extension of tongues 367 and 368 by continuation of rotation of support 341 in direction 366 after contact of the pin with this abutment . analogous means can naturally be provided in the case of oblique slots 390 &# 39 ; and 390 &# 34 ;, as well as in the case of each of slots 490 , in each tongue such as 468 . when a relative abutment must be established in the two longitudinal directions , one can preferably replace the single pin 391 , 491 by two pins perpendicular to plane 306 , 406 , mounted as was said with respect to pin 391 or 491 and mutually longitudinally offset . in a general fashion , the embodiments of the invention which have been described are given by way of non - limiting example only , with respect to which one can provide numerous alternatives without going beyond the scope of the present invention . in particular , even in the case of the use of an intermediate mounting element to assure the guidance of the support to pivoting with respect to the ski as is illustrated in fig1 - 4 , 2a and 3a , 19 and 20 , one can provide a support of the front end zones of the tongues without using such an element as is illustrated in fig9 - 18 , 21 and 22 . likewise , during a direct journal of the support on the ski as illustrated in fig9 - 11 , 16 - 18 , 21 and 22 , one can provide support of the front end zones of the tongues according to the embodiments illustrated in fig1 - 8 , 2a and 3a , 19 and 20 , 23 - 29 , i . e ., by means of a piece straddling the rib of the ski in the manner of the intermediate mounting element described with reference to fig1 - 8 , 2a and 3 a , 19 and 20 , 23 - 29 . it should be understood that although the invention has been described with respect to particular means and embodiments , the invention is not limited thereto but extends to all equivalents within the scope of the claims .

an apparatus for attaching a front end of a ski boot to a ski , particularly for a cross - county ski , comprising a support pivotably mounted about an axis transverse to the longitudinal axis of the ski and retaining the front end of the boot on the ski . the apparatus further elastically biasing the support toward the rear of the ski . the biasing device being fixedly attached to the support which pivots about a fixed axis and is longitudinally displaceable with respect to the ski . the biasing device comprising at least one longitudinal tongue . the apparatus comprising a longitudinal rib adapted to be positioned on the ski surface and having at least one tongue attached to the support and being guided by the longitudinal rib .

preferred embodiments of the presently disclosed tagging device will now be described in detail with reference to the drawings , in which like reference numerals designate identical or corresponding elements in each of the several views . one embodiment of the presently disclosed tagging device will now be described with reference to fig1 - 13 . in fig1 and 2 , tagging device 10 generally includes a body 20 formed of first and second body halves 22 , 24 , an elongated tube 26 extending distally from the body 20 , an anchoring assembly 12 supported on the elongated tube 26 , and an actuator assembly 34 operably associated with the anchor assembly 12 . referring to fig3 ( also shown in fig8 and 9 ) the body 20 defines a stepped throughbore 50 having a first diameter portion 52 and a second smaller diameter portion 54 . the first diameter portion 52 opens onto a rear face of the body 22 , 24 . the second diameter portion 54 is connected to the proximal end of the first diameter portion 52 , and opens onto a distal face of the body 20 . the body 20 is flared outwardly at its distal end , and includes a pair of sidewalls 25 , 27 having spaced vertical ridges 29 formed thereon . the flared distal end and the spaced vertical ridges 29 facilitate grasping and actuation of the device . the actuator assembly 34 includes an actuator knob 40 , an actuator piston 42 , and an actuator plunger 38 . the actuator piston 42 is configured to be slidably positioned within the first diameter portion 52 of the throughbore 50 . a proximal end of the piston 42 extends from the throughbore 50 and is connected to the actuator knob 40 . the actuator plunger 38 has a proximal end 39 fastened to the distal end of the piston 42 , and a distally extending body portion 41 . the distally extending body portion 41 passes through the second diameter portion 54 of the throughbore 50 into the elongated tube 26 . referring to fig4 - 7 , the proximal end of the elongated tube 26 is secured within the smaller diameter portion 54 of the throughbore 50 . the distally extending body portion of the plunger 38 extends from within the throughbore 50 into the elongated tube 26 and can be reciprocated therein by pressing on the actuator knob 40 . to prevent inadvertent proximal movement of the actuator assembly 34 and possible disengagement from the body 20 , the actuator piston 42 has a resilient latch member 58 cantilevered thereto positioned to be engaged in an opening 56 formed in the body 24 . the latch member 58 includes a free end 60 that projects into the opening 56 when the actuator assembly 34 is in a retracted position . proximal movement of the actuator 34 beyond the fully retracted position is prevented by engagement between the free end 60 of the latch member 58 and an inner surface 62 of the opening 56 . distal movement of the actuator piston 42 causes a sidewall of the latch member 58 to engage another wall of opening 56 to bias the latch member 58 from within the opening 56 and permit distal movement of the actuator assembly 34 . referring temporarily back to fig3 the first diameter portion 52 of the throughbore 50 has a planar wall 59 . the actuator piston 42 also includes a planar wall 61 configured to slidably engage the planar wall 59 of the throughbore 50 to prevent relative rotation therebetween . referring again to fig4 to 7 , anchoring assembly 12 includes an anchor 14 , an elongated member 16 , for example , wire and a guide member 18 . the anchor 14 is configured to be positioned in the distal end of the elongated tube 26 , and includes an intermediate opening 64 to facilitate attachment to one end of the elongated member 16 . the proximal end of the elongated member 16 is fastened to the guide member 18 which is formed with a cylindrical longitudinal throughbore 45 configured to permit the guide member 18 to be slidably received about the elongated tube 26 . a slot 32 is formed in the distal end of the elongated needle 26 to permit the elongated member 16 to communicate directly with the anchor 14 . the proximal end of the elongated tube 26 includes a section 63 of increased diameter . the guide member 18 is slidably positioned about the section 63 of increased diameter to increase the frictional fit between the two members . the distal end of the plunger 38 includes an angled surface 44 that engages the proximal end of the anchor 14 when the plunger is moved distally , and is positioned to pivot the distal end of the anchor 14 about the proximal end of the anchor 14 . in use , as shown in fig8 - 13 , elongated tube 26 is positioned to locate a breast lesion , as shown in fig1 , by inserting the tagging device 10 as indicated by arrow &# 34 ; a &# 34 ;. the location is preferably confirmed using known techniques such as mammographics , stereotactics or x - ray . as shown in fig8 - 9 and 11 , the tagging device 10 is actuated by grasping the body 20 and pressing down on the actuator knob 40 to move the actuator piston 42 and plunger 38 distally , as indicated by arrows &# 34 ; b &# 34 ; in fig8 and 11 , into engagement with the anchor 14 . as the anchor 14 is pushed distally , elongated member 16 also travels distally . the guide member 18 is thus pulled distally by elongated member 16 . however , guide member 18 is positioned on increased diameter portion 63 of the elongated tube 26 , and its movement therealong is retarded by friction . thus , anchor 14 traverses an arcuate path in the direction of arrow &# 34 ; c &# 34 ; in fig8 and 11 as plunger 38 moves distally . the anchor 14 is pushed completely from the distal end of the elongated tube 26 and will continue to pivot about the distal tip of the angled surface 44 . at this point , the anchor 14 will have been rotated approximately ninety degrees and will be anchored in position marking the lesion site . as illustrated in fig1 and 13 , the guide member 18 can be removed as indicated by arrow &# 34 ; e &# 34 ; in fig1 from the elongated tube 26 after the anchor 14 has been ejected . the guide member 18 can be slid from the elongated tube 26 easily because the diameter of the elongated tube 26 is not increased towards the distal end of the tube 26 . a further embodiment of the presently disclosed tagging device will now be described with reference to fig1 to 24 . in fig1 and 15 , tagging device 100 includes a body 120 having first and second body halves 122 , 124 defining a stepped throughbore 150 having a first diameter portion 152 and a second diameter portion 154 . the throughbore 150 is configured to slidably receive a piston 142 and a plunger 138 of an actuation assembly 134 . an elongated tube 126 is fastened within the stepped throughbore 150 and extends distally from the body 122 , 124 . the proximal end of the actuator assembly 134 includes an actuator knob 140 which can be pressed to move the plunger 138 distally within the tube 126 . all of the above features have been discussed with reference to the first embodiment and will not be discussed in detail herein . referring to fig1 to 20 , an anchor assembly 112 includes an arcuate anchor 114 and an elongated member 116 fastened to a central portion of the anchor 114 at an attachment point 117 . the anchor 114 slopes upwardly from the attachment point 117 in the proximal and distal directions along its longitudinal axis . the anchor 114 is formed with a distal end having a tapered surface with an edge 119 and a proximal end having a tail 121 which extends along a curved surface 127 to a position substantially perpendicular to the upwardly sloping proximal end of the anchor 114 . the anchor 114 is positioned in the distal end of the tube 126 and the elongated member 116 extends from the attachment point 117 of anchor 114 proximally within the tube 126 . as shown in fig1 and 20 , the plunger 138 is formed from a tube which has a proximal end 129 fastened to the actuator piston 142 via a pin 125 and a distal end 131 positioned to engage the tail 121 of the anchor 114 . the anchor 114 is configured to be slidably positioned within the distal end of the tube 126 . the tapered surface 119 , the curved surface 127 and the attachment point 117 of the anchor frictionally engage inner surfaces of the tube 126 to retain the anchor 114 within the tube 126 . the distal ends of the tube 126 and the tubular plunger 138 comprise hollow slots 132 and 133 , respectively . each slot 132 , 133 is dimensioned to allow passage of the wire 116 but prevent passage of the anchor 114 . in use , as shown in fig2 to 24 , tube 126 is positioned to locate a breast lesion by inserting the tagging device 100 into body tissue 160 adjacent suspect tissue . the location is preferably confirmed using known techniques such as mammographics , stereotactics or x - ray . the tagging device 100 is actuated by pressing down on the actuator knob 140 to move the actuator piston 142 and plunger 138 distally into engagement with the tail 121 of the anchor 114 . because of the angle of the tail 121 with respect to the plunger 138 , the anchor 114 is pivoted , as indicated by arrow &# 34 ; f &# 34 ; in fig2 to 23 , until the curved surface 127 of the anchor 114 is positioned within the distal end of the plunger 138 . at this point , the anchor 114 will have been rotated to a position substantially perpendicular to the elongated member 116 marking the lesion site . since the anchor 114 is no longer frictionally held within the tube 126 , the tube 126 can be easily separated from the elongated member 116 as shown in fig2 leaving the end of the elongated member 116 extending from the body . turning to the alternative embodiment of fig2 - 28 , tissue marking assembly 200 includes first handle 202 , second handle 204 , first elongated member 206 , second elongated member 208 and anchor 210 . the materials of construction of the various components of tissue marking assembly 200 are preferably as described herein for the other embodiments . first elongated member 206 is fixedly attached to first handle 202 , while second elongated member 208 is fixedly attached to second handle 204 . both first and second elongated members 206 , 208 are fixedly attached to anchor 210 in a spaced relation , as shown . referring to the partial sectional views of fig2 and 28 , both first and second handles 202 , 204 include an internal passage ( passages 212 and 214 , respectively ) which are sized to receive an appropriate structure , e . g ., a needle , for introducing the anchor to the target tissue . thus , internal passages 212 , 214 are in axial alignment to facilitate passage of the introducing structure therethrough . first handle 202 is movable with respect to second handle 204 , thereby allowing the user to remotely rotate anchor 210 thorough at least 90 °. the degree to which anchor 210 may be remotely rotated may be modified by increasing the degree to which first and second handles 202 , 204 are relatively movable . first handle 202 includes an outwardly directed flange 216 which is sized to engage inwardly directed stop 218 on second handle 204 , as shown in fig2 . abutment of flange 216 with stop 218 limits the relative movement of first handle 202 relative to second handle 204 . in a preferred embodiment , travel of first handle 202 relative to second handle 204 from the position shown in fig2 and 26 to the position shown in fig2 and 28 effects a 90 ° rotation of anchor 210 . second handle 204 preferably includes finger grips 220 on a distal face thereof , and first handle 202 preferably defines a finger loop 222 . finger grips 220 and finger loop 222 facilitate movement of first handle 202 relative to second handle 204 to effect rotation of anchor 210 . as shown in fig2 and 26 , first handle 202 is in its distal - most position relative to second handle 204 . thus , the operative length of first elongated member 206 , which is the length of first elongated member 206 from the finger grips of second handle 204 to anchor 210 , is roughly equal to the corresponding operative length of second elongated member 208 . accordingly , anchor 210 is oriented transverse to the longitudinal axis of elongated members 206 , 208 . as shown in fig2 and 28 , however , first handle 202 is in its proximal - most position relative to second handle 204 . in this position , the operative length of first elongated member 206 is substantially less than the operative length of second elongated member 208 , thereby effecting rotation of anchor 210 into substantial alignment with the longitudinal axis of elongated members 206 , 208 . in use , first and second handles 202 , 204 may be repeatedly moved between the relative positions of fig2 , 26 and fig2 , 28 , as desired , so as to move anchor 210 between its transverse and longitudinal orientations . in this way , anchor 210 may be introduced ( longitudinal orientation ), deployed in target tissue ( transverse orientation ), undeployed ( longitudinal orientation ) and removed , if desired , or redeployed in the same or a different location ( transverse orientation ). the ability to deploy and redeploy anchor 210 provides the user with increased flexibility and advantageously improves the user &# 39 ; s ability to position anchor 210 in the appropriate tissue . it will be understood that various modifications may be made to the embodiments disclosed herein . for example , the elongated member need not be made from wire but rather could be made from another strand , fiber , or filament of natural or manufactured material . therefore , the above description should not be construed as limiting , but merely as exemplifications of preferred embodiments . those skilled in the art will envision other modifications within the scope and spirit of the claims appended hereto .

a tagging device for marking the location of lesions within the body prior to a surgical procedure such as excision or biopsy . the device includes an elongated tube having one end supported on a housing and a second end extending distally therefrom . an anchor is positioned within the distal end of the elongated tube and has an elongated member extending proximally therefrom . an actuation assembly including a plunger is movable within the tube to engage and push the anchor from the distal end of the tube . the anchor and the actuation assembly are positioned and configured such that the anchor is pivoted from a position parallel to the longitudinal axis of the tube to a position perpendicular to the longitudinal axis of the tube as it as being pushed from the tube .

fig1 a discloses a syringe 80 having a proximal end 82 and a distal end 84 . the syringe has a cylinder cover 86 over the distal end 84 . the proximal end 82 is open and is sealed by a plug 101 which had a body portion 88 formed about an axis 114 . in fig1 b , an optional bulge 90 is shown . fig1 a and 1b , which is the preferred embodiment , shows a cross - section through a plug 101 , which is arranged in a barrel 102 . plug 101 consists of a core 103 , which has three notches 105 on plug cylinder edge 104 , which have the shape of a partial circle . notches 105 do not directly abut one another , but are connected by webs 106 , which directly adjoin inside wall 107 of the cylinder . then below , i . e ., facing toward the medium and away from the plunger , there are two sealing lips 108 and 109 , which are arranged behind one another . proximal sealing lip 108 forms an orthogonal triangle , whereby side 111 that is adjacent to the acute angle , which is proximal , is formed by cylinder wall 110 of plug 101 , opposite side 112 is formed by a radially projecting side , and hypotenuse 113 is formed by a side that faces plug axis 114 obliquely . hypotenuse 113 adjoins cylinder inside wall 107 only in a small area , which adjoins opposite side 112 . distal sealing lip 109 has a triangular shape , whereby base 115 provides a root of the sealing lip which is arranged obliquely to plug axis 114 and extends at an obtuse angle with respect to the axis . two almost identical legs 116 and 117 emerge from base 115 and extend at acute angles with respect to the axis 114 so that the sealing lip 109 extends obliquely with respect to the axis 114 . only the leg 117 that has a surface 117a which faces away from plug axis 114 touches cylinder inside wall 107 . because of the material , two sealing lips 108 and 109 are elastic ; they also press lightly on cylinder inside wall 107 in the at - rest position . fig2 shows the main force ratio in a plug 201 according to the invention . it is a cross - section through plug 201 , which is arranged in a barrel 202 . plug 201 consists of a core 203 , which has two notches 205 , which are rectangular , at plug cylinder edge 204 . notches 205 do not directly adjoin one another , but are connected by a web 206 , which directly adjoins cylinder inside wall 207 . sealing lip 209 has an almost triangular shape , whereby base 215 is arranged obliquely to plug axis 214 . two almost identical legs 216 and 217 emerge from base 215 , whereby only the leg that faces away from plug axis 214 touches cylinder inside wall 207 . because of the material , sealing lip 209 is elastic ; it also presses lightly on cylinder inside wall 207 in the at - rest position . the forces on sealing lip 209 are designed differently in the dynamic and static states . the dynamic state exists if pressure is exerted on the plunger , so that plug 201 is pressed in the distal direction . in this case , the syringe internal pressure of the medium is increased . in a static state , neither the medium nor the plunger exerts pressure on the plug , which is in equilibrium . if the coefficient of friction were infinitely small , the plunger , if no forces acted on it , would be free in this position . sealing lip 209 has a light prestressing ; it thus easily adjoins cylinder inside wall 207 . since the contact pressure surface is very small , the surface pressing power is still relatively high . in the static state , plug 201 thus adequately seals the interior space of barrel 202 . in this case , small forces are used . small forces also mean , however , that the cold - flow behavior of the polytetrafluoroethylene is not stressed . such a syringe can be stored for a long time without the material of plug 201 being noticeably deformed by cold flow . in the dynamic state , plug 201 is pressed in the distal direction , and pressure builds up in the medium . the latter presses on leg 216 that faces inward , thereby forcing the mass of sealing lip 209 outward . on the one hand , the force is caught by base 215 , and , on the other hand , by the front part of outside leg 217 . especially the last - mentioned part has the effect that the pressure of lip 209 on cylinder inside wall 207 is very high per unit of surface area . in this case , the surface area is large enough to successfully prevent the medium from overflowing from the lumen of the syringe into the ambient space . since webs 206 are not basically sealing , atmospheric pressure , which differs from the internal pressure of the syringe , is exerted on leg 217 that faces outward . fig3 shows a cross - section through a plug 301 , which is arranged in a barrel 302 . plug 301 consists of a core 303 , which has three notches 305 , which are rectangular , on syringe cylinder edge 304 . notches 305 do not directly adjoin one another , but are connected by webs 306 , which directly adjoin cylinder inside wall 307 . then there are two sealing lips 308 and 309 that are distal , i . e ., facing toward the medium and away from the plunger and which are arranged behind one another . these two sealing lips 308 and 309 form an orthogonal triangle , whereby sides 311 that are adjacent to the acute angle , which faces proximally , are formed by cylinder wall 310 of plug 301 , opposite sides 312 are formed by a radially projecting side , and hypotenuses 313 are formed by a side that faces obliquely toward plug axis 314 . hypotenuses 313 adjoin cylinder inside wall 307 only in a small area , which adjoins opposite side 312 . fig4 shows , in a different way , a sealing lip 409 , which has a convex shape both in outside leg 417 and in inside leg 416 . fig5 shows three sealing lips , one which with two legs 516 and 517 faces distally , and one which with two legs 516 &# 39 ; and 517 &# 39 ; faces proximally . in between the two there is a dovetail - shaped web , which also exerts a sealing action when there is dynamic movement of plug 501 since , owing to elastic base 515 &# 34 ;, it buckles lightly against the direction of movement and is pressed by its contact area , facing in the direction of movement , against cylinder inside wall 507 . fig6 a shows a seal according to the prior art . in this connection , the spatial distribution of the webs relative to the surface pressure at certain points of the web at the cylinder inside wall is represented . as is seen in fig6 b , the surface pressure is distributed over a sizeable area , and in this case has a point pressure that is relatively low . fig7 a shows a sealing lip 709 according to the invention , which owing to its shape has only a small contact surface with cylinder inside wall 707 . as is seen in fig7 b , relatively great pressure is exerted at certain points , but in this case the entire surface that adjoins cylinder inside wall 707 is smaller . the dotted surfaces in fig6 and 7 should be equally large relative to the integral . the basic difference is that in fig7 the surface application force is greater than in fig6 . in addition , and this is the most important point , this pressure - surface area diagram shows only the static state . in the dynamic state , whereby the medium is compressed in the syringe , considerably higher values occur in fig7 ; conversely the values in fig6 remain the same quantitatively , and at most move proximally in their position . fig8 shows a cross - section through a plug 801 with a sealing lip 809 , which adjoins cylinder inside wall 807 . sealing lip 809 does not end with an acute taper , but has a thickening 820 . in addition , the elasticity zone and plasticity zone 821 , which is between sealing lip projection point or base 822 and contact surface 823 between sealing lip 809 and cylinder inside wall 807 , can be clearly seen from fig8 . in addition , the elasticity zone and plasticity zone 821 are arranged between sealing lip projection point or base 822 and thickening 820 . in the area of the elasticity zone , there are a compressing zone 824 and a pulling zone 825 , which both run approximately parallel to plug axis 814 . in addition , it can be seen that elasticity zone 821 is not on the perpendicular lines to cylinder inside wall 807 ; said perpendicular lines pass through contact surface 823 simultaneously . plasticity zone 821 plays a role when a constant pressure or thermal stress acts on sealing lip 809 , as occurs especially in autoclaving . this area exhibits flow behavior , without sacrificing the entire elasticity of the sealing lip at the same time . the balanced relationship between plasticity and elasticity in this area 821 is essential to successfully seal the plug . the forces and changes that arise in this case can be easily checked by one skilled in the art by tests . the sealing lip 809 has a first surface 830 which includes an arcuate surface 832 which curves outwardly at 833 , inwardly at 834 and outwardly again at 835 as it progresses from the base 822 to the contact surface 823 . the contact surface 823 forms an axially extending portion of a second surface 840 which is joined to the base 822 by a connecting surface 842 .

a medicinal syringe includes a cylinder with a proximal and distal end , and an outlet . the syringe contains , or is adapted to receive , a medicine or a diagnostic agent , and includes a plug . the surfaces of plug which touch the inside wall of the cylinder are preferably made of polytetrafluoroethylene . the material for the cylinder inside wall directly adjoins the surfaces of the plug , which touch the inside wall of the cylinder . the plug has at least one sealing lip and the mass - resultant of the sealing lip forms an acute angle with the axis of the syringe in that distal direction .

the nanoparticles described herein or their derivatives can be formulated in pharmaceutical compositions , and administered to patients in a variety of forms , in particular to treat conditions ameliorated by the administration of the ligand . by way of example , this may occur as the ligand blocks a carbohydrate mediated interaction that would otherwise tend to lead to a pathology . thus , the nanoparticles may be used as medicament for modulating leukocyte - endothelial cell adhesion , carbohydrate - antibody interactions , carbohydrate - protein bacterial and viral infection , immunological recognition of tumour cells , the inhibition of metastatis and foreign tissue and cell recognition . pharmaceutical compositions for oral administration may be in tablet , capsule , powder or liquid form . a tablet may include a solid carrier such as gelatin or an adjuvant or an inert diluent . liquid pharmaceutical compositions generally include a liquid carrier such as water , petroleum , animal or vegetable oils , mineral oil or synthetic oil . physiological saline solution , or glycols such as ethylene glycol , propylene glycol or polyethylene glycol may be included . such compositions and preparations generally contain at least 0 . 1 wt % of the compound . parenteral administration includes administration by the following routes : intravenous , cutaneous or subcutaneous , nasal , intramuscular , intraocular , transepithelial , intraperitoneal and topical ( including dermal , ocular , rectal , nasal , inhalation and aerosol ), and rectal systemic routes . for intravenous , cutaneous or subcutaneous injection , or injection at the site of affliction , the active ingredient will be in the form of a parenterally acceptable aqueous solution which is pyrogen - free and has suitable ph , isotonicity and stability . those of relevant skill in the art are well able to prepare suitable solutions using , for example , solutions of the compounds or a derivative thereof , e . g . in physiological saline , a dispersion prepared with glycerol , liquid polyethylene glycol or oils . in addition to one or more of the compounds , optionally in combination with other active ingredient , the compositions can comprise one or more of a pharmaceutically acceptable excipient , carrier , buffer , stabiliser , isotonicizing agent , preservative or anti - oxidant or other materials well known to those skilled in the art . such materials should be non - toxic and should not interfere with the efficacy of the active ingredient . the precise nature of the carrier or other material may depend on the route of administration , e . g . orally or parenterally . liquid pharmaceutical compositions are typically formulated to have a ph between about 3 . 0 and 9 . 0 , more preferably between about 4 . 5 and 8 . 5 and still more preferably between about 5 . 0 and 8 . 0 . the ph of a composition can be maintained by the use of a buffer such as acetate , citrate , phosphate , succinate , tris or histidine , typically employed in the range from about 1 mm to 50 mm . the ph of compositions can otherwise be adjusted by using physiologically acceptable acids or bases . preservatives are generally included in pharmaceutical compositions to retard microbial growth , extending the shelf life of the compositions and allowing multiple use packaging . examples of preservatives include phenol , meta - cresol , benzyl alcohol , para - hydroxybenzoic acid and its esters , methyl paraben , propyl paraben , benzalconium chloride and benzethonium chloride . preservatives are typically employed in the range of about 0 . 1 to 1 . 0 % ( w / v ). preferably , the pharmaceutically compositions are given to an individual in a “ prophylactically effective amount ” or a “ therapeutically effective amount ” ( as the case may be , although prophylaxis may be considered therapy ), this being sufficient to show benefit to the individual . typically , this will be to cause a therapeutically useful activity providing benefit to the individual . the actual amount of the compounds administered , and rate and time - course of administration , will depend on the nature and severity of the condition being treated . prescription of treatment , e . g . decisions on dosage etc , is within the responsibility of general practitioners and other medical doctors , and typically takes account of the disorder to be treated , the condition of the individual patient , the site of delivery , the method of administration and other factors known to practitioners . examples of the techniques and protocols mentioned above can be found in remington &# 39 ; s pharmaceutical sciences , 16th edition , osol , a . ( ed ), 1980 . by way of example , and the compositions are preferably administered to patients in dosages of between about 0 . 01 and 100 mg of active compound per kg of body weight , and more preferably between about 0 . 5 and 10 mg / kg of body weight . the nanoparticles may be used as carriers for raising antibody responses against the carbohydrate containing ligands linked to the core particles . these antibodies can be modified using techniques which are standard in the art . antibodies similar to those exemplified for the first time here can also be produced using the teaching herein in conjunction with known methods . these methods of producing antibodies include immunising a mammal ( e . g . mouse , rat , rabbit , horse , goat , sheep or monkey ) with the nanoparticle ( s ). antibodies may be obtained from immunised animals using any of a variety of techniques known in the art , and screened , preferably using binding of antibody to antigen of interest . isolation of antibodies and / or antibody - producing cells from an animal may be accompanied by a step of sacrificing the animal . as an alternative or supplement to immunising a mammal with a nanoparticle , an antibody specific for the ligand and / or nanoparticle may be obtained from a recombinantly produced library of expressed immunoglobulin variable domains , e . g . using lambda bacteriophage or filamentous bacteriophage which display functional immunoglobulin binding domains on their surfaces ; for instance see wo92 / 01047 . the library may be naive , that is constructed from sequences obtained from an organism which has not been immunised with any of the nanoparticles , or may be one constructed using sequences obtained from an organism which has been exposed to the antigen of interest . the term “ monoclonal antibody ” as used herein refers to an antibody obtained from a substantially homogenous population of antibodies , i . e . the individual antibodies comprising the population are identical apart from possible naturally occurring mutations that may be present in minor amounts . monoclonal antibodies can be produced by the method first described by kohler and milstein , nature , 256 : 495 , 1975 or may be made by recombinant methods , see cabilly et al , u . s . pat . no . 4 , 816 , 567 , or mage and lamoyl in monoclonal antibody production techniques and applications , pages 79 - 97 , marcel dekker inc , new york , 1987 . in the hybridoma method , a mouse or other appropriate host animal is immunised with the antigen by subcutaneous , intraperitoneal , or intramuscular routes to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the nanoparticles used for immunisation . alternatively , lymphocytes may be immunised in vitro . lymphocytes then are fused with myeloma cells using a suitable fusing agent , such as polyethylene glycol , to form a hybridoma cell , see goding , monoclonal antibodies : principles and practice , pp . 59 - 103 ( academic press , 1986 ). the hybridoma cells thus prepared can be seeded and grown in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused , parental myeloma cells . for example , if the parental myeloma cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase ( hgprt or hprt ), the culture medium for the hybridomas typically will include hypoxanthine , aminopterin , and thymidine ( hat medium ), which substances prevent the growth of hgprt - deficient cells . preferred myeloma cells are those that fuse efficiently , support stable high level expression of antibody by the selected antibody producing cells , and are sensitive to a medium such as hat medium . culture medium in which hybridoma cells are growing is assayed for production of monoclonal antibodies directed against the nanoparticles / ligands . preferably , the binding specificity is determined by enzyme - linked immunoabsorbance assay ( elisa ). the monoclonal antibodies of the invention are those that specifically bind to the nanoparticles / ligands . in a preferred embodiment of the invention , the monoclonal antibody will have an affinity which is greater than micromolar or greater affinity ( i . e . an affinity greater than 10 − 6 mol ) as determined , for example , by scatchard analysis , see munson & amp ; pollard , anal . biochem ., 107 : 220 , 1980 . after hybridoma cells are identified that produce neutralising antibodies of the desired specificity and affinity , the clones can be subcloned by limiting dilution procedures and grown by standard methods . suitable culture media for this purpose include dulbecco &# 39 ; s modified eagle &# 39 ; s medium or rpml - 1640 medium . in addition , the hybridoma cells may be grown in vivo as ascites tumours in an animal . the monoclonal antibodies secreted by the subclones are suitably separated from the culture medium , ascites fluid , or serum by conventional immunoglobulin purification procedures such as , for example , protein a - sepharose , hydroxylapatite chromatography , gel electrophoresis , dialysis , or affinity chromatography . nucleic acid encoding the monoclonal antibodies of the invention is readily isolated and sequenced using procedures well known in the art , e . g . by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies . the hybridoma cells of the invention are a preferred source of nucleic acid encoding the antibodies or fragments thereof . once isolated , the nucleic acid is ligated into expression or cloning vectors , which are then transfected into host cells , which can be cultured so that the monoclonal antibodies are produced in the recombinant host cell culture . hybridomas capable of producing antibody with desired binding characteristics are within the scope of the present invention , as are host cells containing nucleic acid encoding antibodies ( including antibody fragments ) and capable of their expression . the invention also provides methods of production of the antibodies including growing a cell capable of producing the antibody under conditions in which the antibody is produced and preferably secreted . antibodies according to the present invention may be modified in a number of ways . indeed the term “ antibody ” should be construed as covering any binding substance having a binding domain with the required specificity . thus , the invention covers antibody fragments , derivatives , functional equivalents and homologues of antibodies , including synthetic molecules and molecules whose shape mimics that of an antibody enabling it to bind an antigen or epitope , here a carbohydrate ligand as defined herein . examples of antibody fragments , capable of binding an antigen or other binding partner , are the fab fragment consisting of the vl , vh , cl and ch1 domains ; the fd fragment consisting of the vh and ch1 domains ; the fv fragment consisting of the vl and vh domains of a single arm of an antibody ; the dab fragment which consists of a vh domain ; isolated cdr regions and f ( ab ′) 2 fragments , a bivalent fragment including two fab fragments linked by a disulphide bridge at the hinge region . single chain fv fragments are also included . a hybridoma producing a monoclonal antibody according to the present invention may be subject to genetic mutation or other changes . it will further be understood by those skilled in the art that a monoclonal antibody can be subjected to the techniques of recombinant dna technology to produce other antibodies , humanised antibodies or chimeric molecules which retain the specificity of the original antibody . such techniques may involve introducing dna encoding the immunoglobulin variable region , or the complementarity determining regions ( cdrs ), of an antibody to the constant regions , or constant regions plus framework regions , of a different immunoglobulin . see , for instance , ep 0 184 187 a , gb 2 188 638 a or sp 0 239 400 a . cloning and expression of chimeric antibodies are described in ep 0 120 694 a and ep 0 125 023 a . as strategy for tailoring polyvalent carbohydrate surfaces with globular shapes to investigate in solution carbohydrate - to - carbohydrate recognition , an approach was devised by which carbohydrates are linked to gold nanoparticles [ 7 ] . by way of example , the preparation , characterisation and preliminary interaction studies of sugar functionalized monolayer and water soluble gold nanoclusters is disclosed below . thiol derivatised neoglycoconjugates of two biological significant oligosaccharides , the lactose disaccharide ( galβ ( 1 - 4 ) glcβl - or ) 1 and 2 and of the trisaccharide le x antigen : the trisaccharide le x and the disaccharide lactose build up the glycosphingolipid ( gsl ) le x antigen : which have been proposed to mediate formula compaction and metastasis in healthy and carcinoma mouse cells respectively , via a homotypic carbohydrate - to - carbohydrate interaction . [ 8 ] the lacto and le x protected glyconanoparticles provide a glycocalyx - like surface with chemically well defined synthetic matrix and globular shape . moreover , this approach opens the way to tailor glyconanoparticles containing a variety of carbohydrate ligands as well as different surface density providing an under - control model for structure - function studies and for investigating carbohydrate clustering [ 9 ] and orientation effects at a surface . [ 10 ] the lacto - and le x functionalised nanoparticles will be our polyvalent model system to mimic gsl clustering in plasma membrane [ 11 ] and to investigate in solution the attractive and repulsive forces involved in cell aggregation via carbohydrate - to - carbohydrate interactions . previous studies using synthetic receptors provided first solid evidence that stabilising interactions between lipophilic carbohydrate surfaces exist in water . [ 12 ] the synthesis of the disulfides 1 , 2 and 3 was carried out by glycosidation of the conveniently protected lactose and le x derivative with 11 - thioacetate - 3 , 6 , 9 - trioxa - undecanol ( for 1 ) and 11 - thioacetate undecanol ( for 2 and 3 ) using the trichloroacetimidate method , see fig1 . [ 13 ] compounds 1 , 2 and 3 were isolated as disulfide forms , and in this form used for the formation of the gold protected glyconanoparticles . the water soluble glyconanoparticles 1 - au , 2 - au and 3 - au were obtained in methanol following the procedure of brust et al for the synthesis of monolayer protected gold nanoclusters . [ 7a ] a series of gold protected nanoparticles , all of them soluble in organic solvents , have recently been prepared for different purposes . [ 14 ] the lacto - au and le x - au glyconanoparticles are water soluble , stable and can be manipulated as a water soluble biological macromolecules . they have been purified by dialysis and characterised by 1 h - nmr , uv and transmission electron microscopy ( tem ). synthesis of glyconanoparticles : a solution of disulphide 1 , 2 , or 3 ( 0 . 012m , 5 . 5 eq ) in meoh was added to a solution of tetrachloroauric acid ( 0 . 025m , 1 eq ) in water . nabh 4 ( 1m , 22 eq ) in water was added in small portions with rapid stirring . the black suspension that was formed was stirred for additional 2 hours and the solvent was then removed under vacuum . the crude of the reaction was washed with meoh and was centrifuged for 10 minutes . the methanol was removed and the process was repeated several times until the starting material was not detected by tlc . the glyco - nanoparticles are completely insoluble in meoh but quite soluble in water . they were purified by dialysis : 50 mg of crude product was dissolved in 10 ml of water ( nanopure ). this solution was loaded into 10 cm segments of cellulose ester dialysis membrane ( sigma , mwco = 12400 ) and placed in 4 l of water ( nanopure ). the dark glyconanoparticles solution was collected from the dialysis segments and lyophilized . the products obtained were free of salts and starting material ( absence of signals due to disulphide and na + in nmr ). transmission electron microscopy ( tem ) examination of the samples was carried out with a philips cm200 microscope working at 200 kv . a single drop of a 0 . 1 mg / ml aqueous solution of the gold glyconanoparticles was placed onto a copper grid coated with a carbon film . the grid was left to dry in air for several hours at room temperature . particle size distribution of the au clusters were evaluated from several micrographs using an automatic image analyser . the number of particles selected for consideration was around 400 , which resulted in stable size distribution statistic . fig2 shows tem images and core size distribution histograms for the 2 - au and 3 - au gold glyconanoparticles . the gold particles stabilized with the lactose show a narrower and more homogeneous particle size distribution than the particles stabilized with the le x conjugate . a mean diameter of 1 . 8 nm was found in both samples for the gold core of the functionalized nanoparticles . such a mean particle size corresponds , according to previous work , [ 15 ] to an average number of gold atoms per particles of ca . 200 and 70 protecting alkanethiolate glycoconjugates . the aqueous solutions of the nanoparticles were stable during months and no agglomeration was detected by tem . the presentation of the carbohydrate molecules at the nanoparticles surface was then investigated . the molecular properties of the neoglycoconjugates 1 , 2 and 3 suffer a differential change after attaching them to the gold surface . for example , the lacto derivative 2 , which is soluble in methanol and insoluble in water , gives glyconanoparticles 2 - au insoluble in methanol but with good solubility in water . the le x derivative 3 is soluble in methanol and water , its nanoparticle 3 - au , however , is insoluble in methanol and very soluble in water . these differences in solubility can be used to purify the glyconanoparticles from the non - reacted disulfides by washing them with methanol . however , the most significant fact in these changes is that they reveal the influence of clustering at the surface on the carbohydrate presentation to the surrounding . the 1 h - nmr spectra of the glyconanoparticles show clearly these differences ( fig3 ). the spectra of the lacto - nanoparticles 1 - au and 2 - au in d 2 o differ strongly from those of the lacto - disulfides 1 and 2 ( fig3 a spectrum of 1 not shown ) showing the line broadening of slowly rotating macromolecules in solution . the signal of the methylenes closest to the thiolate / au interface completely disappears , as it occurs in the alkanethiol monolayer - protected gold nanoclusters . in contrast , these differences are not founded in the case of the 3 - au nanoparticles . the 1 h - nmr spectra in d 2 o of both 3 and 3 - au show similar broadening for all signals ( fig3 b , a , b ), indicating an intramolecular aggregation already present in the le x disulfide 3 . this self - interaction persists even at highly diluted water solution and is abolished by addition to the d 2 o solution of 3 of increasing amounts of cd 3 od . some well - resolved signals appear in cd 3 od / d 2 o ( 1 : 1 ) solution and in 70 % cd 3 od / d 2 o solution all signal are well - resolved in the spectrum ( fig3 b , c ). the tendency of the le x disulfide 3 to self - assemble in water cannot exclusively be attributed to the hydrophobicity of the aliphatic chain , but rather to the specific partaking of the carbohydrate moiety in this aggregation , as point out the lack of aggregation in water observed in the 1 h - nmr of the lacto - disulfides 1 and 2 ( fig3 a ). the self - aggregation ability will have consequences in the organisation and clustering of le x - containing gsls , as claimed by some authors [ 16 ] and contrary to the proposal of others that the carbohydrate head group plays an insignificant role in formation of glycolipid - enriched microdomains in the plasma membrane . [ 17 ] the steric crowding of the carbohydrate moiety at the nanoparticle surfaces is also shown by the different behaviour of 1 and 2 and their corresponding nanoclusters 1 - au and 2 - au with β - glycosidases . the β - galactosidase of e . coli processes 1 and 2 at a level comparable to lactose itself ( 5 - 10 % relative to the specific activity of gonp ), while the hydrolysis by the enzyme under the same conditions of 1 - au and 2 - au nanoparticles was barely detected (& lt ; 3 % relative to the enzymatic activity with the free ligands 1 and 2 ). these experiments demonstrate that it is possible to use nanoparticles to produce tailored globular carbohydrate models mimicking gsl - clusters in plasma membrane , allowing for the first time investigations to be carried out in solution of a novel mechanism of cell adhesion via carbohydrate - to - carbohydrate interactions . the glyconanoparticle approach described herein provides a strategy to prepare , in a simple way , a great variety of globular carbohydrate arrays that can advantageously compete with other spherical ( dendrimers , liposome ) or linear carbohydrate displays . the lacto - and le x - nanoparticles may be considered appropriate models to intervene in cell - cell adhesion and recognition processes . a ) g . i . bell , m . dembo , p . bongrand , biophys . j . 1984 , 45 , 1051 - 1064 ; b ) a . frey , k . t . giannasca , r . weltzin , p . j . giannasca , h . reggio , w . i . lencer , m . r . neutra , j . exp . med . 1996 , 184 , 1045 - 1059 . [ 2 ] w . i . weis , k . drickamer , annu . rev . biochem . 1996 , 65 , 441 - 73 . [ 3 ] a ) s . hakomori , pure & amp ; appl . chem . 1991 , 63 , 473 - 482 ; b ) g . n . misevic , microsc . res . tech . 1999 , 44 , 304 - 309 and references therein . [ 4 ] m . mammen , s . choi , g . m . whitesides , angew . chem . int . ed . 1998 , 37 , 2754 - 2794 . [ 5 ] a ) l . kiessling , n . l . pohl , chemistry & amp ; biology 1996 , 3 , 71 - 77 ; b ) k . j . yarema , c . r . bertozzi , curr . opin . chem . biol . 1998 , 2 , 62 - 66 ; c ) p . i . kitov , j . m . sadowska , g . mulvey , g . d . armstrong , h . ling , n . s . pannus , r . j . read , d . r . bundle , nature 2000 , 403 , 669 - 672 . [ 6 ] a ) b . t . houseman , m . mrksich , angew . chem . int . ed . 1999 , 38 , 782 - 785 ; b ) n . horan , l . yan , h . isobe , g . m . whitesides , d . kahne , proc . natl . acad . sci . usa 1999 , 96 , 11782 - 11786 . [ 7 ] a ) m . brust , j . fink , d . bethell , d . j . schiffrin , c . kiely , j . chem . soc ., chem . commun . 1995 , 1655 - 1656 ; b ) a . c . templeton , w . p . wuelfing , r . w . murray , acc . chem . res . 2000 , 33 , 27 - 36 ; c ) j . j . storhoff , c . a . mirkin , chem . rev . 1999 , 99 , 1849 - 1862 . [ 8 ] i . eggens , b . fenderson , t . toyokuni , b . dean , m . stroud , s . hakomori , j . biol . chem . 1989 , 264 , 9476 - 9484 . [ 9 ] a ) p . h . weigel , r . l . schnaar , m . s . kuhlenschmidt , e . schmell , r . t . lee , y . c . lee , s . roseman , j . biol . chem . 1979 , 254 , 10830 - 10838 ; b ) r . liang , j . loebach , n . horan , m . ge . c . thompson , l . yan , d . kahne , proc . natl . acad . sci . usa 1997 , 94 , 10554 - 10559 . [ 10 ] n . strömberg , p .- g . nyholm , i . pascher , s , normark , proc . natl . acad . sci . usa 1991 , 88 , 9340 - 9344 . [ 11 ] s . hakomori , k . handa , k . iwabuchi , s . yamamura , a . prinetti , glycobiology 1998 , 8 , xi - xix . [ 12 ] a ) j . m . coterón , c . vicent , c . bosso , s . penadés , j . am . chem . soc . 1993 , 115 , 10066 - 10076 ; b ) j . jiménezbarbero , e . junquera , m . martin - pastor , s . sharma , c . vicent , s . penadés , j . am . chem . soc . 1995 , 117 , 11198 - 11204 ; c ) j . c . morales , d . zurita , s . penadés , j . org . chem . 1998 , 63 , 9212 - 9222 . [ 13 ] r . r . schmidt , k .- h . jung in preparative carbohydrate chemistry , ( ed . stephen hanessian ), marcel dekker inc . 1997 , pp 283 - 312 . the synthesis of the neoglycoconjugates 1 , 2 and 3 will be published elsewhere . [ 14 ] a ) d . fitzmaurice , s , nagaraja rao , j . a . preece , j . f . stoddart , s . wenger , n . zaccheroni , angew . chem . int . ed . 1999 , 38 , 1147 - 1150 ; b ) j . liu , s . mendoza , s . román , m . j . lynn , r . xu , a . e . kaifer , j . am . chem . soc . 1999 , 121 , 4304 - 4305 ; c ) a . k . boal , f . iihan , j . e . derouchey , t . thurn - albrecht , t . p . russell , v . m . rotello , nature 2000 , 404 , 746 - 748 . [ 15 ] a . c . templeton , s . chen , s . m . gross , r . w . murray , langmuir 1999 , 15 , 66 - 76 . [ 16 ] k . simon , e . ikonen , nature 1997 , 387 , 569 - 572 . [ 17 ] d . a . brown , e . london , biochem . biophys . res . commun . 1997 , 240 , 1 - 7 . [ 18 ] taton et al , science , 289 : 1757 - 1760 , 2000 . [ 19 ] g . ada , n . engl . j . med ., 345 ( 14 ), 1042 - 1053 , 2001 . [ 20 ] e . klarreich , nature , 413 , 450 - 452 , 2001 .

materials and methods for studying and modulating the interaction of carbohydrate - containing moieties with other species are described , in particular , small particles , e . g . clusters of metal or semiconductor atoms , which can be employed as a substrate for immobilising a plurality of ligands comprising carbohydrate groups . these “ nanoparticles ” can then be used to study carbohydrate mediated interactions , e . g . with other carbohydrates or proteins , and as therapeutics and diagnostic reagents .

referring to the figures , there are shown several , but not the only , embodiments of the invented prosthetic attachment system . in this description and the claims , the term “ proximal ” means toward the center / torso of the body , and so toward the top / upper end of the liner and prosthetic device . thus , in the case of a prosthetic device for a person &# 39 ; s leg , “ proximal ” would mean nearer or toward the upper thigh and trunk . “ distal ” means away from the center / torso of the body , and so the regions of the liner or prosthetic device farther out from the trunk , and farther out on the leg . referring to fig1 - 12b , buckle 26 includes base 10 , which is mounted on the external surface of the hard socket 12 by means of a rivet 20 , glue or other fastener , or it may even be molded integrally with the socket 12 . the buckle 26 is positioned proximally higher up the socket than conventional “ distal ” locks that are mounted near the distal end of the socket , typically at the bottom of the inside “ well ” of the hard socket 12 . connected to base 10 are a lever 11 and pin 11 ′ with e - clips 11 ″, which together create a biased system for receiving and capturing strap 22 , as seen in fig8 and 12b . strap 22 , as discussed below , is preferably secured to the liner 16 , by means of a umbrella 18 ( see fig1 a ), and is long enough to comfortably and conveniently extend from the middle to upper region of the side of the liner to reach the lower region of the liner ( see fig2 ). liner 16 may be a custom or a pre - manufactured liner as described in the related art section above . examples of currently - available conventional liners are iceross , alpha , luxury liner , alps , silipos ( all trademarks ). modern urethane liners are especially preferred . as is well - known in this field , the currently - available liners listed above are examples of interface liners that are positioned between a residual limb and a prosthetic socket and are frequently called “ suction liners ,” “ gel liners ,” or “ roll - on liners .” these liners typically are rolled - onto the residual limb for a suction , slight compression , and / or gripping connection of the inner gel layer of the liner to the skin of the residual limb . the liner - covered limb is then inserted into the prosthetic socket , and the outer surface / layer of the liner preferably forms a suction , grip , or other interference fit to the socket to interfere with the socket falling off the limb . the liners called by these names (“ suction liners ,” “ gel liners ,” or “ roll - on liners ”) include the modern “ second generation ” liners currently preferred by most wearers of prosthetics , which include a textile / fabric outer layer , as well as the older , “ first generation ” liners that typically did not have a textile / fabric outer layer . the term “ suction liner ” is still used by many manufacturers , prosthetic technicians , insurance and medicare / medicaid entities , and wearers of prosthetics , even though the modern liners , with their textile / fabric outer layers , do not form what would be called “ true ” or “ pure ” suction with the socket . see , for example , discussion of suction liners in janusson , et al . ( u . s . pat . no . 6 , 706 , 364 ) and janusson , et al . ( u . s . pat . no . 6 , 626 , 952 ). strap 22 is connected at its proximal end to liner 16 , preferably by an umbrella 18 or other fixture or bracket . the umbrella 18 may be glued to the liner , as seen in fig2 . umbrella 18 , as shown in fig1 a , is preferably an aluminum plate structure of approximately ¾ ″ in diameter and ¼ ″ thick , with preferably a slightly - concave inner surface for contacting the glue , and with apertures at various locations on the umbrella to assist in receiving and better gripping of the glue that connects the umbrella 18 to the liner &# 39 ; s 16 outside side surface . however , umbrella 18 may also be sewn onto or into liner 16 , or it may be formed integrally with liner 16 . also , alternatively , other shapes of an attachment plates or other attachment means may be used instead of the umbrella , as long as preferably they are thin and easily slide / fit into the socket . the strap 22 is attached to the umbrella 18 , for example , with a 10 / 24 - spanner bolt or screw . the screw is then tightened down to the umbrella 18 , rather than allowing the strap 22 to pivot around the screw . this results in the strap 22 being adjustable , allowing the user or prosthetist to move the strap 22 and then lock it into the optimum position , even if the strap 22 or lock mechanism have been attached to their respective structures in less - than - perfect position or location . when hard socket 12 is installed on the residual limb , it extends up over and around liner 16 and umbrella 18 , as shown in fig1 . strap 22 extends from umbrella 18 on liner 16 a short distance on the inside of socket 12 through an aperture 15 in socket 12 to the external surface of socket 12 ( see fig2 and 3 ). there , the strap 22 continues to extend to and through the preferred buckle 26 attached on the outside surface of the socket 12 , as shown in fig4 . the buckle 26 adjustably receives the distal end of the strap 22 , by means of the strap 22 extending through the buckle 26 between the base 10 and the lever 11 . the strap 22 is pushed / pulled through the buckle 26 to the point where the hard socket 12 is securely , but comfortably secured around and connected to liner 16 via the strap 22 and umbrella 18 combination . this way , the advantages of the invention are realized . strap 22 is preferably sufficiently rigid , sufficiently long , and is positioned so that , upon the limb / liner being inserted into the socket , the strap naturally tends to slide to and through the aperture 15 , to the buckle 26 , and through the buckle 26 with little or no need for the user to thread or pull the strap 22 through the aperture 15 or buckle 26 . a prosthetist will be able to adjust the strap and / or buckle locations and aperture size to enable this smooth movement and latching of the strap in the buckle . optionally , the socket wall surface , on the interior or exterior , may be contoured to facilitate and direct the strap . the release button of the buckle 26 is buckle lever 11 , which features sharp edge 13 , as shown in fig7 . the top surface of base 10 ramps up in thickness in the distal direction . this provides for easier strap 22 entry into the buckle - style latch mechanism , and increasing pressure on the strap 22 when engaged by means of the buckle lever 11 pressing / ratcheting against the strap 22 . edge 13 engages the sharp “ ratchet teeth ” of strap 22 , extending into the transverse detents 17 and abutting against the teeth walls upending from the strap top surface ( see fig1 b ). any pull on the strap 22 in the proximal direction is resisted by the engagement of edge 13 in detents 17 and the pressure of lever 11 against c - clips 11 ″. the attachment system may be placed in a position on the liner and socket that the prosthetist deems most advantageous and convenient for the patient . the mechanism is attached to the exterior of the socket at a location determined by test socket fitting , but in any event , not at the distal end of the socket . typically , when a single attachment system is employed , it will placed in a lateral position so that the user may reach it by reaching toward the outside of his limb . after mounting of the base 10 of the buckle 26 onto the socket 12 , the umbrella 18 onto the liner 16 , and strap onto the umbrella 18 , the roll - on prosthetic liner 16 of choice is applied to the patient . the patient can then step into the hard socket 12 and engage the attachment system , by inserting the strap 22 through the aperture 15 and into the buckle 26 . this procedure may be used in the retrofitting of the attachment system to an existing prosthetic . if a new prosthetic is being created , the liner 16 is applied to the patient , and the ideal location for the umbrella 18 is marked on liner 16 . a mold over the patient &# 39 ; s limb and liner 16 is then taken . after the mold and liner 16 are removed , the umbrella 18 is then attached to the liner 16 in the location marked . from the mold the hard socket 12 is created , and the base 10 of the lock mechanism is attached in the proper location on the outside of hard socket 12 , and then the aperture 15 is created in hard socket 12 as above . the aperture 15 or any other opening through the socket preferably may be easily sealed by a gel suction wrap / cover , or other air - tight wrap or plug that preferably encases the lock mechanism and aperture . this allows and maintains a “ suction ” fit between the socket and the liner that improves the function of the prosthetic . as shown to best advantage in fig2 - 5 , after donning of the prosthetic , the roll - on liner proximal wall extends generally parallel to the socket proximal wall , and the liner extends above the upper extremity edge of the socket while the strap at its attachment to the liner proximal wall is inside the socket . the above attachment system was fit to three test patients . all three of these patients utilized alpha ™ liners in a normal manner . the locking tab was attached to the alpha ™ liners in a normal manner . two of these patients were unilateral transtibial amputees , and one patient was a unilateral congenital above - knee amputee . the above - knee amputee was a congenital amputation resulting from pffd , and his amputation level was consistent with a knee disarticulation level . all three of these patients either demonstrated problems with conventional distal pin - lock systems , or , in the case of the transfemoral amputee , did not have sufficient room to install any of the distal locking mechanisms currently on the market . these patients were using the prosthetic lock suspension according to the present invention on their prosthesis on a daily basis . these patients were all experimentally fit in june of 2000 and no problems were encountered with mechanical failures or with patient acceptance or satisfaction . we continue to monitor these patients at 2 - 3 week intervals . one may see , after reviewing the disclosure of this description and the drawings , that the invented attachment system tends to prevent rotation of the prosthesis on its longitudinal axis ( axis extending between its proximal end and distal end ) relative to the amputated limb . by providing one of the invented side - located , “ proximally - located ” attachment systems , such rotation is limited or prevented . this is because the strap extends from a fixed anchor location on the side of the liner / limb to a fixed anchor location on the side of the socket , thus connecting those two fixed locations together at substantially a fixed distance apart , thereby not allowing the anchor location on the socket to rotate any significant distance away from the anchor location on the liner . although one of the invented attachment systems is preferred , more than one may possibly be used , for example , at two positions around the side of the limb / socket , as described below . other benefits of the attachment system include comfort and ease of use . the preferred attachment system is simple to use , each to reach , and requires a minimum of dexterity . the externally - mounted lock mechanism eliminates the jamming of conventional distal locks often caused by a sock worn over the roll - on liner . while a ratchet - style buckle and strap combination is preferred , other releasable attachments and fasteners may be used . for example , extension members other than a flat strap with detents may be used , such as a cord ( s ), loop ( s ), tab ( s ), or other rigid or flexible extension members . latch mechanisms other than a buckle may be used , such as a hook ( s ), clip ( s ), snap ( s ), or other devices that adjustably or non - adjustably grip the extension member . the connection between the extension member and the latch mechanism is preferably , but not necessarily , adjustable . this permits the user or the prosthetist to manipulate the connection for optimum use and comfort , either by lengthening or shortening the connection or by pivoting or otherwise moving the location of the extension member or latch mechanism . in the description and claims , the term “ lateral ” means on / toward the outer surface or region of the body , and therefore , on / toward the outer surface or region of the apparatus that is installed on the human body . thus , a lateral surface of the liner or socket is an outer side surface , away from the inner or medial plane of the body . see lateral surfaces 101 , 101 ′ of the liner and socket , respectively , in fig1 and 14 , wherein the apparatus is on the left leg and fig1 is a ventral ( front ) view . the term “ medial ” means on / toward the inside or medial plane of the body . thus , a medial surface of the liner or socket is an inner side surface , away from the outside of the body . see medial surfaces 102 , 102 ′ of the liner and the socket , respectively , in fig1 , wherein the apparatus is on the left leg . referring to fig1 - 17 , attachment systems are shown with improved straps and latch mechanisms that make donning and doffing the prosthesis more convenient and comfortable . the embodiment of fig1 - 17 comprises two straps 122 , one attached to the lateral surface 101 of the liner 16 and one attached to the medial surface 102 of the liner 16 , as shown in fig1 . these two straps are secured to the liner by means of an umbrella 18 described above and shown in fig1 - 12b . the especially preferred strap 122 has a “ nipple ” shaped tab extension 114 , or other tapered , narrow tip , at its distal end . the extension 114 preferably has a width less than half of the width of the strap 122 . the extension facilitates the strap 122 from the inside of the socket 12 to the socket &# 39 ; s external surface and through the buckle 126 ( see fig1 ). the bottom surface 123 of the especially preferred strap 122 may have a longitudinal channel 124 , or other grove or ramp - like shape at the distal end , to prevent the strap 122 from “ catching ” on the rivet 20 in the base 110 of the buckle 126 . the thinness ( from top surface to bottom surface ) of the central region of the distal end , caused by the channel 124 , aids in smooth insertion of the strap 122 into the buckle 126 , and allows the distal end to slide over the rivet 20 . this way , the rivet 20 need not be lowered or countersunk into the base 110 . alternatively , the entire bottom surface of the distal end of the strap may be slanted / thinned , but this would result in a weaker distal end . in order to install the socket 12 on the residual limb , the user places the two straps 122 inside the socket 12 and then feeds them through two apertures 115 located medially and laterally in the socket &# 39 ; s 12 side wall , as seen in fig1 and 16 . once the tabs 114 of the straps 122 exit the apertures 115 to the external surface of the socket 12 , they feed into two buckles 126 , distal from the apertures 115 , on the medial and lateral surface of the socket 12 ( see fig1 and 17 ). preferred buckle 126 may include a spring - biased member with one or more sharp edges 113 , that frictionally engage transverse detents 17 located between transverse raised ridges on the strap &# 39 ; s surface . connected to each base 110 of the buckles 126 , are a lever 111 , pivot axle pin 111 ′, and e - clips 111 ″ or other biasing spring or member , which together create a biased system for receiving and capturing the straps 122 . the top surface of each base 110 ramps up towards the distal end of the buckle 126 , allowing easy insertion of the straps 122 , as shown in fig1 . as the distal end of each strap 122 moves into the proximal end of each buckle 126 , the sharp edge or edges 113 of the buckles 126 engage the transverse detents 17 of the straps 122 ( see fig1 ). the channel 124 , on each strap 122 , bypasses the rivet 20 in base 110 of its respective buckle 126 , allowing the distal end strap 122 to exit the distal end of the buckle 126 , in turn securing the socket 12 to the residual limb ( see fig1 ). the preferred method for releasing the straps 122 from the buckles 126 , is for the user to pull up on the distal end of each lever 111 to pivot the lever 111 into a raised position as shown in fig1 a , which corresponds to pivoting the distal end of the lever 111 away from the socket . this , in turn , disengages the sharp edge or edges 113 of each buckle 126 from the transverse detents 17 of each strap 122 ( see fig1 and 19 ). the user is then able to remove the socket 12 from the residual limb by holding on to each lever 111 and pulling the socket 12 off the liner and also by maneuvering his / her residual limb out of the socket . having a plurality of attachment systems for a single prosthetic device may improve stability and comfort for the user . by utilizing lateral and medial strap and buckle combinations , rotation of the prosthetic device relative to the user &# 39 ; s residual limb is minimized , if not prevented . further , the levers of the lateral and medial buckles provide a hand - hold for the user , especially during removal of the socket from the liner - covered residual limb . the lift - to - release buckle levers may be easier to operate and may provide a better hand - grip for the user , compared to the embodiment of fig1 - 12b which requires that the user push and hold down the levers of the buckles during removal of the prosthesis . the buckles illustrated in fig1 are depicted to be quite large and to protrude significantly from the socket , but the buckles may be made to small and low - profile , so that the strap and buckle combination is discreet when covered by clothing and comfortable for walking without the buckle catching on the other leg or clothing . alternative buckles may be made to be small and / or low - profile , so that the strap and buckle combination is discreet when covered by clothing and comfortable for walking without the buckle catching on the other leg or clothing . one way of establishing a low - profile system is to locate at least a part of a buckle / latch mechanism ( s ) inside the socket wall , rather than on the socket wall . for example , a portion of the buckle may be recessed into the socket wall from the outer surface , but , more preferably , at least a portion of the buckle extends through the socket wall from at or near an internal surface of the socket . either way , the buckle is , in effect , “ sunk ” into the socket rather than resting on the outer surface of the socket , so that the strap enters the buckle closer to the outer surface of the socket and the buckle protrudes from the socket to a lesser amount . the preferred buckle has only about 25 - 50 %, and more preferably about 25 %, of its thickness above the plane of the outer surface . referring to the embodiment shown in fig2 - 27 , one or buckles 226 are mounted in the socket by inserting the buckle 226 through an opening in the socket wall . the buckle extends through the wall to protrude slightly beyond the external surface of the socket . strap 222 may enter the buckle at or near the plane of the external surface of the socket ; and the buckle may protrude minimally from the socket , so that it tends not to catch on the user &# 39 ; s clothing or other leg , and tends to be less noticeable . preferably , two straps 222 and two buckles 226 are used . the straps 222 are attached to the lateral surface 101 and medial surface 102 of the liner 16 , respectively , as shown in fig2 a and 22 , by an “ umbrella ” or other attachment . the buckles 226 extend through the wall of the socket , with the bottom surface 250 of the buckle preferably being coplanar with the inside surface 103 . top surface 260 of the buckle , which is configured for receiving the strap , is preferably approximately coplanar with the lateral or medial outside surfaces 101 ′, 102 ′ of the socket near the buckle . one may understand that , due to the typically generally - cylindrical shape of the inner and outer surfaces of the sides of the socket , neither the inner or outer surfaces are expected to be exactly planar in the region of the buckle . however , given the relatively small size of the preferred buckles ( less than about 1 . 5 inches in width transverse to the length of the socket ), one may still say that the bottom surface 250 of the buckle is generally parallel to the plane of the inner surface 103 of the socket , and one may still say that the top surface 260 ( which is typically planar but slanted / ramped ) is generally parallel to the plane of the outer surface 101 ′, 102 ′. in this discussion , “ top ” is used to refer to the surface 260 across which the strap slides or otherwise moves , and “ bottom ” is used to refer to the opposing surface , as this is convenient in view of the orientation of the buckle 226 when it is set , for example , on a table prior to installation . this terminology is not intended to limit the orientation of the buckle when installed in the prosthetic system , however . buckle 226 preferably comprises base 210 having a flange 230 around at least part of the base . the flange 230 is thinner than the main body of the base 210 and thinner than the thickness of the socket wall . this way , the flange lies within the wall of the socket but does not extend all the way through the wall , so that a portion of the socket wall ( such as lip 270 ) extends over the flange to help prevent the buckle from being pulled out of the socket wall from the outside of the socket . connected to the base 210 are a lever 211 and pin 211 ′ with resilient e - clips 211 ″, which together create a bias system generally located over , and cooperating with , top surface 260 to retain strap 222 in the buckle . as shown to best advantage in fig2 and 24 , the top surface 260 of the base 210 ramps up slightly in thickness in the distal direction . proximal end 260 ′ of the top surface is at or slightly below the plane of the outer surface of the socket wall , to assist in easy sliding of the strap into the buckle from the distal region of the socket . distal end 260 ″ of the top surface is farther out from said plane for better clamping of the strap between the top surface 260 and the bias system and for placing the end of the strap slightly distanced from the outside of the socket in a position that is easily reachable by the user ( fig2 ). the lever 211 acts as both the securement device for fastening the strap 222 in the buckle 226 , as well as the release button to allow release the strap 222 from the buckle 226 . the lever 211 preferably comprises a generally sharp edge 213 at its distal end . the edge 213 engages the “ ratchet teeth ” of strap 222 by extending into the transverse detents 17 and abutting against the teeth walls upending from the strap top surface . a pull on the strap 222 in the proximal direction is resisted by the engagement of edge 213 in detents 17 and the pressure and bias of lever 211 against e - clips 211 ″. the preferred , but not the only , method of installing buckles 226 through the wall of the socket 12 is as follows . the socket 12 is molded with a dummy piece in the place where the buckle 226 will be inserted , wherein the dummy piece will typically be about the width and length of the base without its flange . this typically results in the space for the buckle substantially being “ reserved ” so that the laminate materials used to make the socket do not fill said space . a thin layer or layers of laminate over the outer surface of the dummy piece may form and remain after the molding , which layer / layers may be drilled or cut away so that the dummy piece may be “ popped out ” the exterior of the socket . after the dummy piece is removed , the wall around the dummy - created hole is modified to receive the flange , that is , so that the wall has step or lip 270 extending over the hole at the outer perimeter of at least some areas of the hole . this way , the buckle base may be inserted into the stepped hole , with the flange retained by the lip 270 and with the ramped top surface being exposed on / near the outside of the socket and the bias system protruding from the socket . at least a portion of the base is adhered to the interior surface 103 of the socket , for example , the flange 230 is preferably adhered to the lip 270 by glue , other adhesive , or other securement means . a rivet , screw , or other fastener may be used to secure various embodiments of the buckle in the wall of the socket , for example , a rivet through the flange 230 and t - rough the lip 270 . instead of such hardware , however , it is preferred that the dimensions of the buckle be formed to make it unlikely that it will be pulled out of the socket by the strap and that adhesive further ensures this and also keeps the buckle in place in the wall when there is no force being applied to the buckle by the strap . strap 222 is preferably sufficiently rigid , sufficiently long , and is positioned so that , upon the limb / liner being inserted into the socket , the strap naturally tends to slide to and through the aperture 215 in the socket , to the buckle 226 , and through the buckle 226 with little or no need for the user to thread or pull the strap 222 through the aperture 215 or buckle 226 . strap 222 optionally may have a tapered , narrow , or otherwise specially - shaped tip or extension at its distal end , to assist in the strap 222 easily moving through the aperture 215 , and along the buckle ; this is not known in fig2 - 27 , but one embodiment is shown in fig1 - 20 . such a tip or extension facilitates the strap from the inside of the socket 12 to the outside of the socket and through the buckle because the tip / extension tends to center the strap as the tip / extension enters the aperture or buckle . also in a similar manner as described for the strap shown in fig1 - 20 , the bottom surface of strap 222 may have a longitudinal channel , or other grove or ramp - like shape especially at the distal end , to prevent the strap 222 from “ catching ” in the base 210 of the buckle 126 . this may be helpful , especially in the case of the buckle comprising a rivet or other fastener that might get in the way of the strap 222 , but , for the preferred low - profile buckle with proximal surface 260 ′ being recessed relative to the surrounding outer surface of the socket , the channel or grove in the bottom surface of the strap is typically not as necessary . in order to install the socket 12 on the residual limb , the user places the two straps 222 inside the socket 12 and then feeds them through two apertures 215 located medially and laterally in the socket &# 39 ; s 12 side wall , as illustrated by fig2 and 22 . once the ends of the straps 222 exit the apertures 215 to the external surface of the socket 12 , they tend to automatically feed into two buckles 226 , distal from the apertures 215 , on the medial and lateral surfaces of the socket 12 ( see fig2 and 22 ). the preferred method for releasing straps 222 from the buckles 226 , is for the user to push down on the proximal end of each lever 211 to pivot the lever 211 from the “ lowered position ” of fig2 into the “ raised position ” as shown in fig2 , which corresponds to pivoting the distal end of the lever 211 away from the socket 12 . this , in turn , disengages the sharp edge or edges 213 of each buckle lever 211 from the transverse detents 17 . the user is then able to remove the socket 12 from the residual limb , preferably by continuing to keep the buckles unlatched by pushing on the proximal end of the lever 211 , by pushing the socket 12 off the liner 16 , and also by maneuvering his / her residual limb out of the socket 12 . alternatively , lift - to - release buckle levers , for example , as illustrated in fig1 - 18 , may be easier to operate than push - to - release levers for some users and may provide a better hand - grip for some users . the inventors envision that both styles may be used in embodiments of low profile buckles . while lateral and medial positions for two strap and buckle combinations are preferred , a single strap and buckle combination may add prosthetic stability and operability for many users . alternatively , other numbers and arrangements of straps and buckles / latch mechanisms may be effective . preferred levers 11 , 111 , and 211 are deemed to be convenient and reliable for latching and unlatching their respective buckles , and preferably , each lever is biased into the latched position and requires positive action by the user or prosthetist to unlatch it . however , other styles of latch mechanisms may be used , such as other pivotal arms or hooks , snaps , clips , loops , ties , or other releasable locks and latches . preferably , the prosthesis attachment system comprises the invented extension member and latch system , with or without the aid of suction between the liner and the socket , but no other straps or attachments . preferably , there is no belt or strap extending to encircle part of the user &# 39 ; s body , and preferably no attachment between the distal end of the limb / liner and the bottom of the well of the socket . although this invention has been described above with reference to particular means , materials and embodiments , it is to be understood that the invention is not limited to these disclosed particulars , but extends instead to all equivalents within the broad scope of this disclosure and the following claims .

an attachment system secures a residual limb to an artificial limb in a comfortable and substantially non - rotational manner . the attachment system offers proximal anchoring of the residual limb in a hard socket , by connecting a side surface of a residual limb liner to the side surface of the socket . preferably , this connection is accomplished using an extension member extending from the liner through a portion of the socket interior , through the socket wall , and attaching to a latch mechanism . the preferred attachment system requires no clearance in the bottom of the socket well because neither the extension member nor the latch mechanism is located between the distal end of the residual limb / liner and the bottom of the well . the attachment system is preferably disposed entirely along the side of the limb and the side of the socket .

according to one embodiment which carries the inventive idea into effect , the drive element is formed as a rod coupled at one end to the base of the piston and connected at its other end by way of a coupling with an actuating element formed as a double ring which engages in two mutually opposed slits arranged at the lower end of the shell , and an abutment is provided at the periphery of the double ring . very desirably the double ring together with the double coupled rod and the piston acting as holding means is formed as one - piece injection moulding . also the shell with the mutually opposed slits is formed as a one - piece injection moulding , and thus both mouldings can be produced from the same plastics material , such as polypropylene , thereby facilitating the disposal of waste and scrap . assembly is effected in that the injection moulding comprising the flexible double ring serving as actuating element , the double coupled rod and the piston , can be inserted into the slit shell directly from above and thus snaps into the slits . the principle of the piston connecting rod drive also enables e . g . transverse sections of elliptical form of the outer shell , which has the advantage that deformation of the double ring during insertion is lessened . moreover , the ring then protrudes less from the edge of the shell . additionally , the elliptical stick shape has the advantage for the user that depending upon the way the stick is held , a thin or a wide trace of glue can be produced at will . the required diameter of the double ring depends on the desired length of stroke of the stick , i . e . on the length of the glue stick in question . this embodiment will be explained more fully with reference to fig1 to 3 . the piston ( 1 ) has an anchorage element ( 7 ) for the glue substance ( 100 ) and a sealing lip ( 4 ). to the piston is coupled by way of the coupling ( 2a ), preferably centrally , the rod ( 2 ) which acts in the manner of a piston connecting rod and which is connected at its opposite end by way of a coupling ( 2b ) with the double wheel ( 3 ) acting as drive element . the double wheel ( 3 ) has an abutment ( 9 ) on its periphery at the apex of its starting position , so that actuation can only be in the direction of the arrow . also , the double wheel ( 3 ) has strengthening ribs ( 6 ). it engages in the slits ( 5a , 5b ) of the outer shell ( 5 ), which at its open end has a cap closure that protects the stick substance from drying out and is preferably formed as a push - on cap ( 10 ). the double ring ( 3 ) is provided with transverse serrations ( 8 ) along its periphery and the notches formed by this serve as a non - return means since the upper edge of the two apertures ( 5a , 5b ) engages with the nearest notch as shown in fig3 by the detail y . the anchorage element ( 7 ) of the piston ( 1 ) is very desirably formed in the nature of a little basket with projections and / or retaining grooves ( 7a ), thereby ensuring good anchorage with the fill of glue substance after it has cooled and set . fig2 shows the section a -- a of an elliptically formed stick where the mutually opposed slits ( 5a , 5b ) are advantageously disposed in the position of the major axis of the ellipse . in fig2 the broken line indicates the section of a stick of circular cross section . according to a further preferred embodiment the drive element is formed as a flexible band which at on end is coupled to the base of the piston and at the other end is coupled , by an arrangement so that it can be wound thereon , to an actuating element made in the form of a double ring which engages in two mutually opposed slits disposed at the lower end of the shell . very desirably , the double ring together with the double coupled flexible band and the piston is formed as a one - piece injection moulding . also with this embodiment , the injection moulding can be assembled with the slit shell by inserting it from above or , in the case of a different embodiment , from below . the shell can be of circular or preferably elliptical cross section . an elliptical shape of the shell yields the advantages already mentioned above with regard to particularly easy assembly and the practical application of the glue stick . forming the drive element as a flexible ban moreover brings the advantage that the diameter of the double ring does not depend on the required piston stroke so that the ring diameter can be less than when the drive element is constructed as a rod . moreover , the double ring can be carried in axial bearings . this embodiment will be explained more fully with reference to fig4 to 9 . in the embodiment of fig4 the shell receiving the drive element is formed as one piece . in the embodiment of fig5 a separate base part ( 5c ) is provided which takes care of guiding the band . here , for assembly , the one - piece injection moulding is appropriately inserted in the shell from below , following which the base part with the band guide is inserted . the piston ( 1 ) again has an anchorage element ( 7 ) for the glue substance which is preferably formed in the nature of a little basket with projections and / or retaining grooves ( 7a ). to the piston ( 1 ) there is coupled with inclined lead - in ( cp . fig5 e ) the flexible band ( 2c ) which at its other end is secured to the double ring ( 3 ) so that it can be wound thereon , the double ring engaging in the mutually opposed slots ( 5a , 5b ) of the shell ( 5 ). the double wheel has transverse serrations ( 5 ) along its periphery in whose notches the upper edges of the apertures ( 5a , 5b ) engage , as shown by the detail y enlarged in fig7 . this constitutes a nonreturn means for the actuating element ( 3 ). upon rotation to propel the glue stick , the flexible band ( 2c ) is supported against the wall of the shell ( 5 ) as shown in fig5 whereby it is stiffened . the slitting from one side of the band ( 2d and 2f ) reproduced in fig8 and 9 limits excessive bulging of the band , in case it flips over , as can be seen from fig4 and fig8 . thus , the flexible band is self stiffening . the fully assembled and filled stick is closed at the open end of the shell by a cap , which desirably is formed as a push - on cap ( 10 ). according to a third embodiment the drive element is formed as rod coupled at one end to the piston and having a toggle joint at its other end whose arm engages by way of a transverse axle in a bearing provided at the closed end of the shell , the toggle joint also acting as actuating element . in this embodiment the shell is desirably of domed form at its closed end and has , extending from its apex , a slot or slit into which the toggle joint movably engages , and the shell is provided at the other open end with a screw - on or push - on closure . the drive element , the actuating element ( toggle joint ) and the piston can desirably be produced in the form a one - piece injection moulding which can be pushed into the shell from its open end . an entry aid in the nature of a slotted guide on the inner wall of the shell helps to guide the transverse axle of the drive element so that it snaps reliably into the bearing provided in the wall of the shell . flutes are provided in the arm of the toggle joint which engage with nodules on the inner wall of the slot or slit of the shell , whereby a forward travel snap action means and a non - return means are realized . the shell can be made circular or elliptical , the elliptical form having the advantages already mentioned above . this third embodiment will be explained more fully with reference to fig1 to 16 : the drive element ( 18 ) is coupled at one end of the rod ( 18a ) to the piston ( 1 ) which is provided with a sealing lip ( 4 ) and has an anchorage element ( cp fig1 and 11a ). the rod ( 18a ) merges at its opposite end into a toggle joint , whose second arm ( 17 ) is connected with a transverse axle ( 16 ). the rod ( 18a ) and the toggle joint arm ( 17 ) have flutes ( 21 ) as appears from fig1 a and 13b . the outer edge of the toggle joint arm ( 17 ) can have serrations which facilitates actuation by the hand . fig1 explains the position and form of the slot ( 24 ) in the shell ( 5 ) in which the drive and actuating element engages , wherein the nodules ( 22 ) upon movement of the toggle joint engage in the flutes ( 21 ) which are there provided . fig1 and 16 explain the operation of the entry aid ( 23 ) formed in the nature of a slotted guide , which serves to lead the transverse axle ( 16 ) securely to the bearing ( 25 ). after the fully assembled device has been filled with glue substance , the shell ( 5 ) is provided at its open end with a screw - on or push - on closure ( 26 ). according to a fourth embodiment the drive element is formed as a rod coupled at one end to the piston and coupled at its other end to the tip of a double wheel which to one side is formed tongue shaped and which by way of a transverse axle engages in a bearing provided at the closed end of the shell , the double wheel also serving as actuating element . in this embodiment the shell is preferably of domed form at its closed end and has extending from its apex a slot not which the double wheel movably engages , a screw - on or push - on closure being provided at the open end of the shell . the rod with the coupled piston and the coupled double wheel including its transverse axle , desirably form a one - piece injection moulding , which again is pushed into the shell from its open end , wherein an entry aid in the nature of a slotted guide on the inner wall of the shell takes care of guiding the transverse axle until it snaps into the bearing provided in the shell wall . transverse serrations are provided along at least half the periphery of the double wheel , which facilitates actuation of the wheel by the hand and at the same time acts as non - return means by snap engagement of the edge of the shell in the notches of the serrations . moreover , an abutment is provided on the periphery of the double wheel so that the starting position after filling with the glue substance is fixed and rotation is only possible in the direction indicated by the arrow in fig1 . the shell can be made circular or elliptical , the elliptical form having the advantages already indicated above . this embodiment will be more fully explained with reference to fig1 to 25 . the drive rod ( 3 ) is coupled at one end to the piston ( 1 ) which is provided with a sealing lip ( 4 ) and has anchorage elements ( cp fig1 and 18a ). at its other end the drive rod ( 30 ) is coupled to the tip ( 31 ) of the double wheel ( 32 ) which to one side is formed tongue shaped and which by way of the transverse axle ( 33 ) engages in the bearing ( 34 ) of the shell ( 5 ). just as in the third embodiment of fig1 to 16 , an entry aid ( 36 ) in the nature of a slotted guide on the inner wall of the shell ( 5 ) serves to guide the transverse axle ( 33 ) to the bearing ( 34 ) without tilting ( cp fig2 and 24 ). transverse serrations ( 38 ) are provided along at least half the periphery of the double wheel ( 32 ), which facilitates actuation by the hand and moreover forms notches in which the edge of the shell can snap as shown in the enlargement of fig2 , thus forming a non - return means . moreover an abutment ( 37 ) is provided on the periphery of the double wheel , which fixes the starting position of the wheel so that , after filling of the stick , rotation is possible only in the direction of the arrow ( cp fig1 ). after filling , the open she . 11 component is provided with a closure ( 39 ). according to a further embodiment , which largely corresponds to the foregoing ( cp fig1 to 25 ), the actuating wheel is a round circle and preferably carried in an axial bearing . the drive element is again formed as rod coupled at one end to the piston and coupled at its other end to the periphery of an actuating element formed as a wheel which by way of a transverse axle engages in a bearing provided at the closed end of the shell . since the actuating wheel is preferably carried in an axial bearing , it need not be largely surrounded by the shell and this presents advantages for handling of the wheel . moreover it can be formed as a simple solid wheel . also in this embodiment the rod together with the coupled piston and the coupled wheel including its transverse axle , advantageously forms a one - piece injection moulding , which is pushed in to the shell from its open end , wherein an entry aid in the nature of a slotted guide on the inner wall of the shell takes over the guidance of the transverse axle until it snaps into the bearing provided in the shell wall . extending from the apex of the shell to both sides is a slit in which the wheel engages . transverse serrations are desirably provided on the periphery of the wheel , which at the same time act as a non - return means as already described above in relation to fig1 to 25 . moreover , the wheel has an enlargement on its periphery which acts as an abutment , so that the wheel can be turned in only one direction . the shell itself can be made circular or elliptical , the elliptical form being preferred . this embodiment will be more fully explained in the following by fig2 to 34 . the drive rod ( 40 ) is coupled at one end to the piston ( 1 ) which is provided with a sealing lip ( 4 ) and has anchorage elements ( cp fig2 and 27a ). at its other end the drive rod ( 4 ) is coupled to the periphery of the actuating wheel ( 41 ) which engages in the bearing ( 45 ) in the shell ( 5 ) by way of the transverse axle ( 42 ). just as in the embodiment of fig1 to 25 , an entry aid ( 43 ) in the nature of a slotted guide on the inner wall of the shell ( 5 ) serves to guide the transverse axle ( 42 ) to the bearing ( 45 ) ( cp fig3 and 33 ). the shell has a slit ( 44 ) into which the wheel ( 41 ) engages . the wheel ( 41 ) has transverse serrations ( 46 ), where the notches between the serrations serve as a snap provision into which the upper edge of the shell ( 5 ) can snap , as depicted enlarged in fig3 in the detail y of fig2 . the abutment ( 47 ) is formed by a corresponding enlargement on the wheel periphery ( cp also fig3 which reproduces a section through the wheel in the middle of the axle ). after filling with the stick substance , the open shell component is provided with a closure ( 48 ). finally , it is envisaged in a further construction of the invention to form the actuating element as a non - deformable partial or solid wheel , which however requires a different method of assembly . in this embodiment the shell is formed in two components , where one shell component is closed at one side and at the closed end has a slot or slit extending to both sides of the apex , while the other shell component is open at both sides . the two components each have one open end formed so that it can be united with the other . a rod acting as drive element is coupled at one end to the solid wheel and at its other end to the piston , the solid wheel having a transverse axle for engagement in a bearing provided in the closed shell component . the combination of the rod with the coupled piston and coupled solid wheel including its transverse axle is advantageously formed as a one - piece injection moulding . upon assembly , such a moulding is first pushed in to the shell component which is closed at one side , until the transverse axle snaps into the bearing , an entry aid in the shell inner wall constructed in the nature of a slotted guide guiding the transverse axle to the bearing . subsequently , the shell end which his open at both sides is united with the other shell component , for example by a snap or screw connection or also by a welded joint . the solid wheel is preferably formed as a fluted wheel and has transverse serrations at it periphery . nodules are provided on the inner wall of the slit or slot of the shell component that is closed at one side , the nodules engaging in flutes of the drive rod . in the case of a fluted wheeled , the nodules also engage in the wavy upper surface of the wheel and thus form a non - return means . this embodiment will be more fully explained by reference to fig3 to 42 : the drive element ( 52 ) is at one end coupled to the piston ( 1 ) which has a sealing lip ( 4 ) and an anchorage element for the stick substance preferably formed in the manner of a little basket with thread projections and / or retaining grooves . at the other end the rod ( 52 ) is coupled to a semi - circular fluted wheel ( 53 ), whose axle ( 54 ) snaps into a bearing ( 56a ) in the wall of the shell component ( 55a ), wherein the axle is secured against tendency to topple over by the entry aid ( 56b ) ( cp fig4 and 41 ). the rod ( 52 ) desirably has flutes ( 6 ) ( cp fig3 b and 38 ). if an axle bearing is provided for the wheel ( 53 ), as in the case of the embodiment shown , the drive rod must have a corresponding recess ( 52a ). transverse serrations ( 58 ) are provided on the periphery of the wheel . the wheel is movably mounted in the slit ( 57 ) by way of the transverse axle ( 54 ) and the bearing ( 56a ), the slit ( 57 ) extending to one side into the shell component ( 55b ) which is open at both sides . by means of the nodules ( 59 ) provided on the inner wall of the slit , engagement in the flutes ( 60 ) of the drive rod ( 52 ) is made possible , whereby a non - return means is created . the length of stroke corresponds to the diameter of the wheel ( 53 ). in this embodiment too , the cross section of the shell can be made circular or elliptical . after filling the fully assembled device with glue substance , the open end ( 55c ) of the shell is closed by a cap ( 61 ).

a glue stick with a piston supporting the stick substance and a shell surrounding the stick substance is disclosed . a drive mechanism for up and down movement of the stick substance is formed in the nature of a piston connecting rod coupled to the piston , which at the other end is coupled to an actuating element which can be actuated from outside the shell . the drive element can be formed as a rod or as a flexible band . the actuating element can be formed as a double ring , as a toggle joint , as a tongue shaped double wheel , as a wheel , or as a semi - circular solid wheel . preferably formed as a one - piece injection moulding . for assembly of the glue stick is pushed in to the shell from the open side , and then the glue stick substance is poured from above into the hollow space of the shell , becoming anchored on or in the piston when it set .

referring to the drawings and particularly fig1 to 7 , and referring initially to fig1 , a programmable robotic swing training system is illustrated depicted generally by the reference numeral 10 , and is seen generally to include an upper arm portion assembly 11 and a lower arm portion assembly 12 connected together at an elbow hinge 14 . a servo motor assembly 15 guides the pivotal movement of the lower arm assembly 12 with respect to the upper arm assembly 11 . an optical encoder 16 is driven by the servo motor 15 and provides signals to an onboard microprocessor 18 to guide the golfer &# 39 ; s lower arm movement with respect to his upper arm movement throughout the golf swing . a pair of velcro upper arm straps 22 and 23 , which are maintained in position by integral loops on the upper arm assembly 11 and a single wide lower arm velcro strap 24 , which is supported on integral loops on the lower arm assembly 12 , all hold the programmable robotic swing training system 10 in position on the golfer &# 39 ; s trailing arm as shown in fig2 . the swing training system 10 is illustrated in dynamic positions on an actual golfer in fig2 to 7 , as well as in fig2 . this sequence of pictures in fig2 to 7 is intended to replicate the golf swing of professional golfer padriq harrington with the robotic swing training system 10 in position . fig2 and 3 depict the address position of the swing trainer and at address the swing trainer senses the actual take away of the golfer &# 39 ; s swing , ignoring preliminary waggles , to begin the cycle of the swing training system 10 . at the top of the swing illustrated in fig4 and 5 , the swing training system senses when the golfer is approaching or reaching the top of the golf swing to initiate the timing cycle of the downswing . if during the downswing cycle the golfer begins to extend his trailing arm 26 , the training system 10 will block or brake the extension of the trailing arm 26 to maintain its approximate right angle position illustrated in fig4 and 5 . when the golfer reaches the just prior to release position in fig6 and 7 , which is achieved when the bicep 27 nears the golfer &# 39 ; s right side and is approximately in the vertical position pointing toward the ground , the servo motor 15 releases the lower arm brace assembly 12 from the upper arm brace assembly 11 permitting the golfer to release the lower trailing arm from the upper trailing arm in the golfer &# 39 ; s position of fig6 and 7 , which is what initiates the release of the golfer &# 39 ; s wrist 29 and the club head 30 at high speed into the golf ball . an important aspect of the present invention is that it keys on the release of the trailing lower arm 28 from the upper arm 27 and that in fact is what initiates the release of the wrists 29 and the club head 30 into the golf ball . as seen in fig1 , the upper arm assembly 11 includes a flanged plastic beam 32 that carries the velcro straps 22 and 23 and an aluminum pivot frame 34 that has a planar central section 35 , an arcuate peripheral rib 36 , a pivot boss 37 , and a fastener receiving bore 38 that receives a fastener 39 connecting the aluminum pivot frame 34 to the flanged plastic beam 32 . plastic beam 32 has an arcuate arm 32 a that wraps around the bicep to hold the brace 11 against the bicep ( see fig1 , 8 and 9 ). the frame 34 wraps around the flanged plastic beam 32 so that there is no relative pivotal movement there - between and they are held rigidly together . as seen in fig1 , the aluminum frame 34 supports and is fixed to a pivot shaft 40 controlled by the servo motor 10 . the lower arm brace assembly 12 is depicted in fragmentary form in fig1 and 17 and is seen to include a flanged plastic frame portion 42 fixed to an aluminum frame member 44 , also depicted in fig1 , that has a pair of apertures 45 therein that receive fasteners to connect the pivot frame 44 to the plastic frame portion 42 . an arcuate arm 45 a projects from frame portion 42 and wraps around the golfer &# 39 ; s forearm to hold the system 10 in position with the aid of the velcro straps ( see fig8 ). frame 44 has a aperture 46 therein that also receives , rotatably , servo motor shaft 40 as seen in fig1 . as seen in fig1 and 11 , the frame 44 carries a circular plate 48 that is fastened to lower circular base 49 of the servo motor that receives fasteners through apertures 50 therein that are equally spaced around the plate 48 and the base 49 , not shown in complete detail in fig1 for the sake of brevity . as seen in fig1 , the upper arm assembly 11 has integral loops 51 and 52 to receive the straps 22 and 23 respectively , and while not shown clearly in the drawings , the lower frame assembly 18 has similar loops for receiving the velcro strap 24 . viewing fig1 , for a description of servo motor 10 , it should be understood that the servo motor contemplated by the present invention can either be a servo motor that controls the release of the club head in the golfer &# 39 ; s downswing , or it can continuously control movement of the golfer &# 39 ; s lower arm 28 with respect to his upper arm 27 throughout the golf swing , but the servo motor specifically depicted in fig1 functions : a ) to brake the golfer &# 39 ; s extension of the lower arm 28 with respect to the upper arm 27 during the downswing so that the golfer maintains the trailing arm in approximately a 90 degree position between the top of the swing depicted in fig4 and 5 , and the true release position in fig6 and 7 when the golfer &# 39 ; s upper arm is vertical . viewing fig1 , the servo motor includes spaced annular housing walls 54 and 55 integrally extending upwardly from base plate 49 and housing there - between an annular electromagnetic coil 56 powered through a conductor assembly 57 a , which is connected to one of the outputs of the microprocessor 18 . conductor assembly 57 a is powered by a 24 - volt backpack carried on the golfer &# 39 ; s waist . the housing assembly of the servo motor has a stator plate 57 enclosing the coil assembly 56 that cooperates with an armature assembly 58 fixed to the servo motor shaft 11 . the armature assembly 58 includes an armature frame 58 a consisting of a plate portion 59 and a reduced annular boss portion 60 that is keyed at 61 to the servo motor shaft 40 . the plate portion 59 carries an axially movable annular armature plate 62 that is mounted on the plate portion 59 by a plurality of pins 63 that permit axial movement between the armature plate 62 and the plate portion 59 . a plate spring assembly 65 forces the armature plate 62 against the bottom surface of the plate portion 59 but permits relative movement there - between as the armature coil 56 attracts the armature plate 62 into engagement with the stator 57 locking plate 62 to stator plate 57 . both the lower surface of the armature plate 62 and the upper surface of the stator plate 57 have a plurality of interengaging radial teeth 67 depicted in fig1 and 12 a . the outer peripheries of the teeth 67 , as shown at 68 , are square - shaped while the inner ends 69 of the teeth come to a point to accommodate the difference in diameter between the outer diameter of the armature plate 70 and the inner diameter 71 . the innerengagement of the teeth 67 on the armature plate 62 and the stator plate 57 substantially increases the braking force of the servo motor 10 and is an important aspect of the present invention . the servo motor 10 is similar to the electromagnetic brake manufactured by lenze ag located in germany , model magneta no . 14 . 110 and 14 . 100 , size 05 , 24 - volt dc flanged mounted with 12 mm . central bore . the encoder 16 provides square wave signals illustrated in fig2 to the microprocessor 18 illustrated in block diagram form in fig1 to provide angle data and direction of rotation data to the microprocessor so that the microprocessor 18 may control the braking function of the servo motor 10 at appropriate times . the encoder 16 , as seen in fig1 , is supported on the servo motor housing by four brackets 71 a fastened to servo motor housing wall 54 . one encoder that has been found suitable for this use is manufactured by us digital corporation entitled “ optical kit encoder ”, model no . e3 , codes 472 , of e3 - 500 - 472 - 10 - pkg3 . the encoder 16 is an optical encoder and includes a thin plastic annular disc 72 that has a plurality of optical apertures therein through which led light is projected by an optical circuit assembly 74 that generates a plurality of pulses and signal conditioning including the pulses a and b from the encoder illustrated in fig2 to the microprocessor 18 . this encoder generates 360 pulses per revolution , and it generates one series of pulses a for counter - clockwise revolution , and one series of pulses b for clockwise revolution and also generates a reference signal at a certes a plurality of pulses and signal conditioning including the pulses a and b from the encoder illustrated in fig2 to the microprocessor 18 . this encoder generates 360 pulses per revolution , and it generates one series of pulses a for counter - clockwise revolution , and one series of pulses b for clockwise revolution and also generates a reference signal at a certain angular relationship between the upper arm assembly 11 and the lower arm assembly 12 so that there are at least three signals going from the encoder 16 to the microprocessor 18 . in fig1 , the software for the microprocessor 18 is illustrated , and as shown it has a reset function and a function that determines whether the swing has begun or not . this function is necessary to prevent the cycle from being started if the golfer is simply waggling the golf club and moving his arms back and forth in waggle fashion , and this is determined by sensing the degree of pivot of the lower arm 28 with respect to the upper arm as shown at 76 and 77 . after the swing has actually begun , the microprocessor begins counting the swing angles at 78 and determines the top of the swing at 79 by determining when either the a signal changes to the b signal from the encoder as shown at 80 when the downswing begins at 80 , the clock starts at 82 in the block diagram of fig1 so that it begins developing a window of 30 to 600 milliseconds that can be varied at 81 to the individual golfer &# 39 ; s swing speed 1 . the brake can be applied any time during this variable downswing window if the b pulse count illustrated at 81 is greater than a predetermined value which can be varied to the golfer , and if less than that value , the brake will not be applied . after the variable window has expired at 83 , the brake will be released and the golfer can begin his release from the fig6 and 7 position . 1 . golfer peter jacobson &# 39 ; s downswing has been timed at 570 ms . it should be understood that certain variations of the software in fig1 are within the scope of the present invention . for example , one variable would be to always engage the brake at the top of the backswing regardless of whether the golfer begins casting or extending his lower arm from his upper arm . requiring somewhat similar software . the block diagram in fig1 is a representation of the microprocessor function as programmed by the software in fig1 . at 86 , the microprocessor senses an ab reversal at the top of the backswing at 87 and an alternate function can be achieved where the top of the backswing is sensed by a diminution of the rate of the a signal from the optical encoder 18 . lights 88 , 89 and 90 , which can be carried by the onboard microprocessor 18 , or by a remote wireless receiver , can be utilized by the instructor to vary the parameters of the training system 10 to accommodate the specific golfer &# 39 ; s swing speed and habits . the top of swing sensor is variable as indicated at 89 a . the clock counter 90 a and the begin b count function 91 , which is variable at 92 , determines the window at 80 shown in fig1 and the brake is actuated when the b count exceeds a value within the window determined at 81 in fig1 . the entire system is a 24 - volt system as indicated with a 5 - volt dc converter 93 to drive the encoder and also supplies 24 - volts to the coil 56 . the arm positions are illustrated sequentially at 94 in fig2 , and at 95 indicates that when count b is more than 12 pulses , in this case indicating a 12 degree extension of the lower arm relative to the other arm , then clamping occurs but this is a variable . fig2 represents a clamping line 96 and an unclamping at line 97 .

a golf swing training system that straps to the rear or trailing arm of the golfer and guides movement of that arm to correctly delay release of the golf club on the downswing until the trailing arm bicep is approximately pointing toward the ground . a servo motor locks the trailing arm at the elbow from extension near the top of the backswing as the trailing arm reaches its fully bent position preventing premature club release during the initial downswing , and releases the elbow when the upper arm reaches a near vertical position on the downswing . the entire system is controlled by an on - board microprocessor encoded by input angle signals of the trailing arm bending movement adapted to the swing cycle of the individual golfer under study .

fig1 depicts an embodiment of the instant device . a clip 100 has a single piece u - shaped body 102 consisting of two oppositely aligned gripping sections 106 and 108 . the body is fabricated from semi - rigid materials such as plastic , rubber or hard foam , such that the clip can easily be opened , even by a child . in alternate embodiments , the body can be made of wood , metal , cardboard or any other material known or convenient . the clamping force exerted by the u - shaped body 102 should be such that the clip will return to a closed position when opened , but will not clamp down suddenly on fingers . the clamping force should be sufficient enough to secure a paper napkin , yet the clip should be able to easily open wide enough to accommodate and secure thicker cloth napkins . the edges and corners of the body 102 are rounded to provide safety . in alternate embodiments , the body 102 may be coated in a soft covering to further aid in safety . fig2 and fig3 show an alternate embodiment of the device featuring gripping components 202 a and 202 b located on the inner surfaces of gripping sections 106 and 108 . these components may be constructed from soft materials such as rubber or felt to permit easy attachment and removal of articles . with these gripping elements , the gripping sections do not need to assert much force in securing the napkin . the napkin may simply be secured by friction from the gripping components 202 a and 202 b acting on the napkin . in alternate embodiments , the gripping components 202 a and 202 b may have patterns that aid in gripping , such as small ridges or teeth . fig4 depicts one such embodiment in phantom view , having gripping components 201 a ( not shown ) and 202 b with integral rows of ridges 401 . these patterns may differ in size and shape in alternate embodiments . fig5 and fig5 a demonstrate the attachment of a paper or cloth dining napkin 501 to an article of clothing 502 . to use the device , the clip 100 is opened and one gripping surface tucked inside the waistband 503 or side pocket 504 of the child &# 39 ; s pants , shorts or dress . ( fig5 a depicts the inner gripping surface that is tucked inside the article of clothing 502 .) the dining napkin 501 can then be slid between the second gripping section facing outwards and the article of clothing , thereby securing the napkin to the article of clothing . the napkin is meant to be placed across the lap of the child ( see fig5 ), just like grown - ups . alternatively , the clip may be also be used to secure a napkin to clothing of the upper body for eating foods that may create a mess . a dining napkin may be gripped by the clip and remain secured to an article of clothing , as long as the child does not exhibit excessive movements during the meal . it is not an object of the invention to provide a gripping force that can withstand such movements , but rather aid the child in developing proper eating manners and napkin usage by reinforcement . if the napkin does slip from the clip , the child can be informed gently that he is not behaving properly at the dining table , such as not staying still , letting his legs slip off the chair , or generally not maintaining a good sitting posture . in a further embodiment depicted in fig6 , the clip 600 comprises a top half 601 and a bottom half 602 connected by spring means 603 . the spring means assert pressure on the halves to keep the clip in a closed position , as depicted in fig6 b . a slight pressure is applied by a user &# 39 ; s fingers to tabs 601 a and 602 a aft of the spring means 603 to open the clip . while the clip is in its open position , it can be clamped onto an article of clothing and a dining napkin in a similar manner as discussed above . the spring means exert just enough pressure to hold a dining napkin to the article of clothing when the clip returns to its closed position , as depicted in fig6 b . this ensures that a child will not be injured by the clip suddenly snapping or clamping down on the child &# 39 ; s extremities . further , this embodiment has a rounded shape with no sharp corners , and is preferably made of a soft and pliant material for increased safety for use around children . although the invention has been described in conjunction with specific embodiments thereof , it is evident that many alternatives , modifications and variations will be apparent to those skilled in the art . accordingly , the invention as described and hereinafter claimed is intended to embrace all such alternatives , modifications and variations that fall within the spirit and broad scope of the appended claims .

a device for securing a napkin to a child &# 39 ; s clothing is disclosed . the device is an teaching aid used to teach a child how to behave at the dining table like grown - ups . it helps in establishing correct eating manners , encourage proper posture during the meal , and teaches the proper usage of dining napkins .

the present invention relates to a topical multiphase cosmetic composition comprising a gel phase and an emulsion phase wherein the composition provides the beneficial effects of both phases in a single application . as used herein , the term “ outer surface ” of the composition means the outer surface of the composition as present in the package and that is exposed to the atmosphere and visible to the human eye when the composition is dispensed from the nozzle / tip of the container . it is to be understood that this outer surface is a function of the shape and geometry of the dispensing tip / nozzle of the container , which is generally circular or square . this shape and geometry has no bearing on the invention . it is also to be understood that the external appearance of the composition after dispensing by extrusion from such containers is similar to the bulk of the composition filled in the container . the term “ co - extensive ” means that the two phases extend over the entire length of the container and are capable of being extruded uniformly and simultaneously from the container and can be applied to the substrate in a single application . in order to enhance the effectiveness of the composition in providing that the user first experiences the effect of the gel phase to a substantial extent before the effect of the emulsion phase , it is preferred that the gel phase forms greater than 80 % of the outer surface of the composition . it is further preferred that the gel phase forms the entire outer surface of the composition . more preferably the emulsion phase is coaxially disposed within the gel phase , i . e . the longitudinal axis of emulsion phase is the longitudinal axis of the gel phase when the composition is dispensed from the container and also when the composition is stored within the container . alternatively or additionally , a preferred aspect provides for the longitudinal axis of the emulsion phase to be parallel to the longitudinal axis of the gel phase . the emulsion and gel phases can be present in a percentage volume ratio of 10 : 90 to 90 : 10 , preferably from 30 : 70 to 70 : 30 and most preferably from 40 : 60 to 60 : 40 . in a preferred embodiment , the emulsion and gel phase each form 50 % by volume of the composition . it is preferred that the composition has an oil - in - water emulsion constituting the emulsion phase and a hydrophilic gel forming the gel phase . in an alternative embodiment the emulsion phase is a water - in - oil emulsion and the gel phase is a hydrophobic gel . the term “ multiphase ” means that the composition has at least two different phases , an emulsion phase and a gel phase . the emulsion and gel phases can be disposed in various spatial geometric patterns in the composition , while ensuring that the phases have at least one common interface and the gel phase forms greater than 50 % of the outer surface of the composition . non - limiting examples of such patterns are illustrated in the drawings . fig1 to 9 represent the transverse cross sectional view of the composition of the invention on extrusion from a tube or package having a dispensing nozzle of circular cross section . it would be apparent that various other cross - sections can be obtained by selecting a package of appropriate nozzle shape such as square , rectangle , hexagon and oval shape . fig1 shows an embodiment in which the emulsion phase forms a circular core e , which is surrounded by the shell of the gel phase g . fig2 shows another embodiment of a core - shell type configuration where the circular core e extends further towards the periphery of the circle defined by the gel phase g . fig3 and 5 represents another embodiment of a core - shell type configuration where the core of the emulsion phase e is star shaped or cross - shaped in cross - section respectively . fig6 represents an embodiment in which the oval shaped core of the emulsion phase e is offset or eccentrically located within the gel phase g . fig8 represents an embodiment in which the core of emulsion phases e is shaped in the form of a band . it is also possible to have more than one distinct region of the emulsion or gel phases in the cosmetic composition . fig4 shows such an embodiment having diamond shaped regions e 1 e 2 , e 3 and e 4 of the emulsion phase within the gel phase g . alternative such embodiments are depicted in fig7 and 9 having respectively multiple hexagonal regions e 1 , e 2 , e 3 , e 4 , e 5 and e 6 within gel phase g and multiple streaks e 1 , e 2 , e 3 and e 4 within gel phase g . gel - based cosmetics are known in the art . they are generally formulated using an appropriate base , hydrophilic or hydrophobic , such as water or oil , and by adding suitable gel - forming materials , commonly referred to as thickeners . gels are generally formulated as low solids compositions as they contain a high proportion of the base material . hydrophilic gels usually produce an intense cooling sensation on the skin and provide a high degree of moisturization . they can also be used to deliver high levels of hydrophilic actives . hydrophobic gels can be used as delivery vehicles for oil - soluble actives . the gel phase used for this invention can be hydrophilic or hydrophobic in nature , but is preferably hydrophilic . the gel phase can comprise from about 50 to 90 %, preferably 60 to 95 % and more preferably 80 to 90 % by weight carrier . a hydrophilic gel phase is defined for the purpose of this invention as a gel wherein the carrier is hydrophilic . the carrier is preferably selected from one of more of water , ethyl alcohol and isopropyl alcohol . the most preferred carrier is water . “ hydrophobic gels ” for the purpose of this invention are defined as gels in which the carrier is hydrophobic in nature . preferred hydrophobic carriers are oils , thickened oils , silicone oils and mixtures thereof . the gel phase has at least one thickening or gelling agent which can be selected from the group consisting of starch , modified starches , cellulose gum , modified cellulose gums , xanthan gum , modified xanthan gums , guar gum , modified guar gums , inorganic thickeners , silica based thickeners , acrylic polymers and mixtures thereof . it is preferable to have inorganic thickeners as the thickening agent . the thickening or gelling agent is present from 0 . 01 to 10 %, preferably 0 . 5 to 5 % and more preferably 0 . 5 to 1 % by weight of the gel phase . high levels of thickeners may lead to a sticky and tacky gel and may also adversely affect its transparency . the gel phase can be transparent or translucent . it can contain one or more agents selected from silica and polyols ( such as glycerine , sorbitol and / or propylene glycol ). it is preferable to have a transparent gel phase . the gel phase can also be suitably colored by incorporating coloring agents . optionally the gel phase can have cosmetic adjunct materials such as emollients , preservatives , perfumes , rheology modifiers , humectants , moisturizing agents , skin lightening agents and others generally known in the art . the viscosity of the gel phase can range from 0 . 4 to 1 . 0 , preferably 0 . 6 to 0 . 9 and more preferably from 0 . 7 to 0 . 8 pa · s at a shear rate of 1000 per second and a temperature of 20 ° c . emulsions are heterogeneous systems of liquids such as oil and water and are generally binary , i . e . two component systems . in these systems , droplets of one liquid are homogenized and stabilized into the other using surface - active agents , which are also called “ emulsifiers ”. these agents are added to reduce the interfacial tension between the two phases . emulsions are generally of two types , oil - in - water and water - in - oil . as the name suggests oil - in - water emulsions are ones in which a continuous aqueous phase has droplets of oil / oily material dispersed therein . water - in - oil emulsions , on the other hand , have a continuous phase of oil / oily material with droplets of an aqueous medium dispersed and stabilized therein . “ vanishing creams ” and “ moisturizing creams ” are two of the several classes of oil - in - water emulsions that are commonly used in cosmetics . as the name suggests , vanishing creams are designed to spread easily on the skin and then rapidly vanish into it . such creams are formulated using oils that melt above the normal temperature of the body . these creams are also an effective vehicle for delivery of benefit agents onto the skin and are used to provide a soft matty and draggy feel while and after application . “ cold - creams ” form one sub - class of water - in - oil emulsions , used in cosmetics . as the name suggests , these types of emulsions are intended to be used during winter . these creams prevent the skin from becoming dry , patchy and flaky during winter by depositing a thin layer of oil on the skin . the emulsion phase of the present invention can be an oil - in - water or water - in - oil emulsion , preferably an oil - in - water emulsion . the oil - in - water emulsion preferably has 20 to 85 % by weight water , 10 to 70 % by weight oil and 0 . 1 to 5 % by weight emulsifier . the term oil includes oils such as castor oil , coconut oil , soyabean oil , olive oil , thickened oils and oily substances such as long chain ( c 8 - c 20 ) fatty acids and alcohols . it is preferred that the oil phase comprises mono carboxylic fatty acids with a carbon number from c 8 to c 22 , preferably c 10 to c 18 and more preferably from c 14 to c 18 . it is highly preferred that from about 10 % to 25 % of the total fatty acid is neutralized with a suitable base such as sodium hydroxide or potassium hydroxide . such compositions are referred to in the art as “ vanishing creams ”. the emulsion phase can be advantageously used to provide skin lightening benefits by including suitable skin lightening agents including , for example , one or more of niacinamide , kojic acid , 4 - ethyl resorcinol , hydroquinone , tridecyl salicylate and others known in the art . the amount of skin lightening agent can range from 0 . 01 to 5 %, preferably 0 . 1 to 3 %, and more preferably 0 . 5 to 2 % by weight of the emulsion phase . niacinamide is the most preferred skin lightening agent . the viscosity of the emulsion phase can range from 0 . 1 to 0 . 3 , preferably 0 . 15 to 0 . 25 and more preferably 0 . 2 pa · s at a shear rate of 1000 per second and a temperature of 20 ° c . the emulsifier is selected from the group of anionic , cationic , nonionic , amphoteric and zwitterionic surfactants generally known in the art . it is preferred that the emulsifier is an anionic surfactant and more preferably a soap , that is , sodium or potassium salt of fatty acid . the individual phases may additionally comprise materials commonly employed in skin care products such as liquid or solid emollients , silicone oils , emulsifiers , solvents , humectants , polymeric or inorganic thickeners , powders , organic or inorganic sunscreens , skin lightening agents , skin conditioners , optical brighteners , propellants , healing agents ( e . g . allantoin ), cooling agents ( e . g . urea , menthol , menthyl lactate , frescolate ), antiseptic agents and other specific skin - benefit actives . the vehicle may also further include adjuncts such as antioxidants , perfumes , opacifiers , preservatives , colorants and buffers . a safe and effective amount of sunscreen may be used in the compositions of the subject invention . the composition preferably comprises from 0 . 1 % to 10 %, more preferably from 0 . 1 % to 5 % by weight of the composition of a sunscreen agent . the sunscreen agent may comprise either organic or inorganic sunscreen or combinations thereof . the organic sunscreens are preferably chosen from 4 - tertiary butyl - 4 ′- methoxy dibenzoylmethane , available under the trade name parsol ™- 1789 ( givaudan ) or 2 - ethyl hexyl methoxy cinnamate , available under the trade name parsol ™- mcx ( givaudan ) or mixtures of the two sunscreen compounds . inorganic sunscreens , which may be employed , include titanium dioxide , zinc oxide or silica ( such as fumed silica ) and mixtures thereof . these inorganic sunscreens are preferably in micronized form . ultrafine titanium dioxide in either of its two forms , namely water - dispersible titanium dioxide and oil - dispersible titanium dioxide , is particularly suitable for the invention . water - dispersible titanium dioxide is ultra - fine titanium dioxide , the particles of which are non - coated or which are coated with a material to impart a hydrophilic surface property to the particles . examples of such materials include aluminium oxide and aluminium silicate . oil - dispersible titanium dioxide is ultrafine titanium dioxide , the particles of which exhibit a hydrophobic surface property , and which , for this purpose , can be coated with metal soaps such as aluminium stearate , aluminium laurate or zinc stearate , or with organosilicone compounds . by “ ultrafine or micronized form ” is meant particles of inorganic sunscreens having an average particle size of less than 100 nm , preferably 70 nm or less , more preferably less than 40 nm and most preferably from 15 nm to 25 nm . vitamins , which act as skin - lightening ingredients can be advantageously included in the composition to provide for additional skin lightening effects . these include vitamin b6 , vitamin c , vitamin a or their precursors and cosmetically acceptable derivatives . mixtures of the vitamins can also be employed in the composition of the invention . when present , these vitamins are used in the range of 0 . 01 to 10 . 0 % by weight of said composition . emollients which may be employed include one or more of stearyl alcohol , glyceryl monoricinoleate , mink oil , cetyl alcohol , isopropyl isostearate , stearic acid , isobutyl palmitate , isocetyl stearate , oleyl alcohol , isopropyl laurate , hexyl laurate , decyl oleate , octadecan - 2 - ol , isocetyl alcohol , eicosanyl alcohol , behenyl alcohol , cetyl palpitate , silicone oils ( such as dimethylpolysiloxane ), di - n - butyl sebacate , isopropyl myristate , isopropyl palmitate , isopropyl stearate , butyl stearate , polyethylene glycol , triethylene glycol , lanolin , cocoa butter , corn oil , cotton seed oil , olive oil , palm kernel oil , rape seed oil , safflower seed oil , evening primrose oil , soybean oil , sunflower seed oil , avocado oil , sesame seed oil , coconut oil , arachis oil , castor oil , acetylated lanolin alcohols , petroleum jelly , mineral oil , butyl myristate , isostearic acid , palmitic acid , isopropyl linoleate , lauryl lactate , myristyl lactate , decyl oleate and myristyl myristate . propellants may also be employed with the composition and include propane , butane , isobutane , dimethyl ether , carbon dioxide , nitrous oxide and mixtures thereof . solvents include ethyl alcohol , isopropanol , acetone / ethylene glycol monoethyl ether , diethylene glycol monobutyl ether , diethylene glycol monoethyl ether and mixtures thereof . powders include chalk , talc , fullers earth , kaolin , starch , gums , colloidal silica sodium polyacrylate , tetra alkyl and / or trialkyl aryl ammonium smectites , chemically modified magnesium aluminium silicate , organically modified montmorillonite clay , hydrated aluminium silicate , fumed silica , carboxyvinyl polymer , sodium carboxymethyl cellulose , ethylene glycol monostearate and mixtures thereof . plant extracts include those from genus rubia , symplocus , curcuma and mixtures thereof . perfume / fragrance ingredients may also be included in the composition at ranges from 0 . 001 to 40 . 0 % by weight of the composition . the term “ topical cosmetic composition ” as used throughout the specification means cosmetics which are intended to be used on the skin , which includes the face , neck region , legs and hands . more preferably the product is a leave - on product ( a product to be applied to the skin without a deliberate rinsing step soon after its application to the skin ). the composition can be packed in suitable squeezable tubular packs with a dispensing opening ( nozzle ) through which the product can be extruded . alternatively the product can be packed in hand actuated dispensing pumps or flexible pouches with a closure . such packs are generally known in the art as form - fill - seal packages . the invention will now be described with the help of the following examples . a core and sheath type of cosmetic composition as depicted in fig2 was prepared as described hereunder by using ingredients listed in table 1 below . 0 . 6 g aristoflex ™ and 0 . 25 g laponite ™ were dispersed in 20 ml water under overhead stirring . 0 . 6 g glycerin and 2 . 5 g propylene glycol were added to this dispersion . preservatives were dissolved in 10 ml water and this solution was added to the dispersion . niacinamide and urea were dissolved in separate portions of water ( 7 ml each ) and added to the above dispersion . the mixture was stirred and deaerated under vacuum to remove entrapped bubbles of air . glycerin , niacinamide and potassium hydroxide were mixed with water and this solution was heated to 80 ° c . in another container , the oil - soluble ingredients ( stearic acid , oil - soluble preservatives , cetyl alcohol , dc - 200 ™, etc ) were heated to 80 ° c . the oil phase was then added to the water phase to form an oil - water phase . parsol ™ mcx and parsol ™ 1789 were then warmed and titanium dioxide ( mt 100z ™— size 15 nm , supplied by tayka corporation , japan ) dispersed therein to form a sunscreen mix . the sunscreen mix was then added to the above oil - water phase . perfume and coloring matter were added finally . the composition was filled into tubes using a co - extrusion machine . the gel phase and cream phase were stored in separate pots , which were each connected to the filling nozzle of the co - extrusion machine . the nozzle diameter was chosen such that the tubes fitted snugly into it . the cohesive value , viscosity , bulk density of the gel and emulsion as well as the pump setting and flow rate were suitably adjusted such that the two phases co - extruded as desired and were filled in the tubes after proper weight adjustment . samples of the above composition filled in tubes as described above were stored at 45 ° c . and room temperature (˜ 20 ° c .) for six weeks . after this storage it was observed that the gel and emulsion phases still retained their gloss and overall stability ( integrity on visual observation ). a core and sheath type of cosmetic composition as depicted in fig2 was prepared by using the ingredients listed in table 2 in a similar way to that used for the preparation of the composition of example 1 . the gel phase and the cream phase were present in amounts of 50 % and 50 % with respect to the weight of composition . an 8 week clinical study was conducted in india on 35 men to assess the skin lightening efficacy of the composition . the study was done on the lateral and volar forearm and the composition was randomized on both of the arms to the same extent . 20 mg of the composition was applied twice daily at least six hours apart , each application consisting of 10 rubs . hands were washed prior to each application . the initial skin color of the inner side of their forearms was determined visually by a trained expert and was allotted a score between 1 ( very fair ) to 10 ( very dark ). at the end of the trial the change in skin color of the treated sites was recorded again by the same trained expert . the difference between the initial skin colour score and the final score is indicative of the efficacy of the formulation . a negative value indicates skin lightening and a positive value indicates skin darkening with respect to the initial skin color . the more negative the skin lightening efficacy , the better the skin lightening efficacy . statistically significant skin lightening was observed only four weeks after the composition was first applied . a natural context product test was carried out with 440 consumers in two cities in india over a ten day test . the results of the study indicated significantly better scores on cooling , freshness , fairness , visual appearance , and uniqueness for the composition than a conventional skin lightening cream ( fair & amp ; lovely multivitamin fairness cream available from hindustan lever limited ). an anti - tanning study was also conducted to assess the tan protection index ( tpi ) {[ grade of tan level on untreated site − grade of tan level on treated site ]/ grade of tan level on untreated site ) of the product . the tan protection efficacy is largely a result of the uv - a component of sunscreens . the study was a double blind design in which both study personnel and study subjects did not know which composition was thre test composition . both forearms ( area from elbow to wrist ) were were used as treatment sites . sites were exposed to the mid - day sun for 30 minutes and clinically / visually evaluated prior to application and immediately after exposure to the sun on the first day of the study . the evaluation was performed by expert graders using a tanning scale from 0 ( no difference ) to 8 ( extremely dark with peeling ). the application and sun exposure continued for 3 consecutive days . as melanogenesis usually peaks around 5 - 7 days following exposure , the sites were visually evaluated for tan up to 10 days . on the tenth day , the tpi was calculated . the greater the tpi value , the better the tan protection ( i . e , less tanning is observed ). product tpi day 5 tpi day 8 tpi day 10 example 2 51 52 57 the composition showed statistically significant anti - tanning efficacy on day 8 and 10 .

a topical multiphase cosmetic composition is provided comprising co - extensive emulsion and gel phases . the phases have at least one common interface and are disposed such that the gel phase forms greater than 50 % of the outer surface of the composition . the composition provides a combination of the unique sensory and delivery properties of gel and emulsion based cosmetics and allows for their contact with the skin at selected time intervals during application .

the crisis response kit of this invention is specially designed for use during building emergencies , critical incidents , or for training and practice of situational response drills . it is usable by businesses , schools and colleges , institutions , hospitals , day and elder care facilities , police , fire and emergency responders . the kits are intended be placed throughout the facility in key locations as determined by security directors , managers , or site based safety and security committees . fig1 shows a rigid case embodiment of a crisis response kit 10 having exterior visible surfaces 12 that preferably have reflective decals 13 affixed on one or more of the exterior walls of the case 14 that holds all components of the kit . the case 14 shown in fig1 is a molded plastic box . in the preferred embodiment shown in fig1 , the reflective decals are positioned as follows : front facing —“ crisis management kit ” 13 ; remainder of decals not shown , left side —“ telephone ” symbol ; right side —“ first aid symbol ; rear —“ safety first ” crisis management kit . additionally , the kit preferably includes two highly reflective door knob placards 18 and 20 , one colored red with a white reflective “ x ”, and another , colored green with the letters “ ok ” in white reflective material . fig2 shows the case in top plan view with the lid 21 opened . the crisis response kit 10 contains a molded plastic separation unit 23 to compartmentalize space required for binders labeled “ crisis management plan ” 22 , “ evacuation guidelines ” 24 and , “ student facility management ” 26 . this binder is referred to elsewhere as personnel management compilation . it is understood that these binders 22 , 24 , 26 can carry any alternative titles as appropriate so long as they have contents sufficient to provide the critical information necessary in an emergency . additionally , the contents of each of the indicated binders could be combined into one or more binders as the particular application dictates . the separation unit 23 is adjusted in dimension accordingly . in addition important response and communication devises are also included in the kits 10 and 11 . these include a first aid kit 28 which is held in the first aid aperture 29 . the first aid kit should include barrier protection . a flashlight 30 with charge indicator is held in a flashlight aperture 31 formed by the separation unit 23 , and a 911 - capable , aaa battery adaptable cell phone 32 , held in a cell phone aperture 33 . additional items can be added to the crisis response kit to customize its application to the needs of the specific facility . fig3 illustrates an embodiment of the crisis response kit 11 which utilizes a soft sided case 15 which has partitions built in comparable to the separation unit 23 but not shown which separates the components . this separation unit may be fabric partitions attached to the case 15 . other components are identical to the fig1 embodiment and are identified with the same reference numbers . fig4 shows a flip chart 34 designed to attach the building keys 36 to a convenient small summary chart of highlights of the plan . the flip chart has attached to it a ring key holder 38 which holds office , schoolroom or workplace room keys needed in an emergency to access particular areas . the flip chart is also provided with a page attachment device 39 which is this embodiment is the same ring structure to which the key is attached , and is adapted for keeping the pages together but allowing for periodic replacement of individual pages as updating of information is required . the compact color coded content summary sheet 40 of the emergency plans set forth on the pages of the flip chart allows rapid access to site - specific protocols and procedures that address particular emergencies such as fire 42 , lock downs 44 , chemical / hazmat emergencies 46 , shelter - in - place protocols 48 , hurricane , tornado and other severe weather emergencies 50 . it also includes key contact names and telephone numbers for emergency responders and other community based resources 52 . the key holder is adapted to receive one or more room keys 54 . in the context of a school environment , one of the flip charts is intended to be available to the teacher in charge of each classroom in the school with the room key for that room attached to the flip chart . it is designed to be portable and provides a quickly accessible overview of what is in the full kit with checklists for easy reference for each type of emergency . the printed pages of the flip chart are small enough to fit in pocket or pocketbook and contains a summary of the most important information from the binders of the crisis response kit including simplified protocols and procedures for the various types of emergencies along with lists of contact numbers for emergency agencies to be contacted in each type of emergency . the preparation and assembly of site specific portable crisis response kit and crisis quick response miniaturized flip chart are useful as a focus point for end users in preparing for possible emergency situations . testing the kits through use of contained catalogued materials allows for specific customization and addresses the site based needs of each facility . each site based safety and security team works with their constituents to assemble the kits and insure distribution throughout the organization . kits should be inspected and updated at least once every six months to insure populated information is complete and correct . the plurality of binders 22 , 24 , 26 in the kit contain important information . by way of example , the following recommendations for compiled listings and procedures for inclusion in the crisis response kit binders include : ( a ) a complete , up to date , copy of the crisis management plan ( b ) tabulated checklists for handling common emergency events such as bomb threats , fires , lockdowns , weather related events , and other emergencies . ( b ) multiple copies of simplified building and floor plans showing evacuation routes , assembly areas , designated receiving areas for building occupants , parents ( in the case of schools or day care facilities ), public information officer , and members of the press . ( c ) site maps and location of potential threat areas ( chemistry labs , shops , flammable storage areas ). ( f ) information about how to enable or disable electricity , gas , phone and other utilities at the school and a list of individuals who have been trained to do so . ( g ) exact meeting points for identified staff members and emergency response personnel . ( a ) a list of people normally on site in the building . for example , in a school setting , the staff , students , teachers . for each person , names , addresses , and contact details , including known medical conditions of students and staff and the availability of medications during a lockdown or extended shelter - in - place event . ( g ) list of contact details for emergency response team , school crisis team , and school administration . a duplicate copy of the crisis response kit should also be kept off - site ; preferably at the home ( district ) office , state and / or local police , area fire department , town / city / state / federal offices of emergency management . although this invention has been shown and described with respect to the detailed embodiments thereof , it will be understood by those of skill in the art that various changes may be made and equivalents may be substituted for elements and steps thereof without departing from the scope of the invention . in addition , modifications may be made to adapt a particular situation to the teachings of the invention without departing from the essential scope thereof . therefore , it is intended that the invention not be limited to the particular embodiments disclosed in the above detailed description , but that the invention will include all embodiments falling within the scope of the above description .

a method of preparing for emergencies in a building setting such as a school and using the method to create to a comprehensive crisis resource kit including evacuation plan , contact numbers , master contingency plan , flashlight , cell phone and first aid kit for use in a variety of emergency situations .

the invention to be protected consists of a synergic composition to be used in the prevention and treatment of neurodegenerative diseases such as alzheimer and other dementias associated to aging . the composition contains shilajit extract , folic acid , vitamin b 6 and b 12 . shilajit is a millenary sacred plant with a large quantity of healing properties , it is very effective in reducing fatigue and works as a natural energizer . this herb growing in the himalayas mountains contains fulvic acid and humic acid , natural antioxidant substances that help to delay cell aging , they attack tumor generation , help to neutralize toxins and to improve the availability of minerals in the body making them bioactive and bioavailable for our body . we have recently found this plant in the andean sector of the north of chile ( andean shilajit ). shilajit contains roughly 85 types of minerals in their ionic form which are vital to maintain energetic metabolism balanced in the body . shilajit &# 39 ; s minerals are not similar to the ones normally sold in the market as food supplements because these have ionic form and have been previously absorbed by plants and have returned to the soil , so they are easily absorbed by human cells . a few patents exist associated to the shilajit nutraceutic around the world vindicating the advantages and qualities of the individual product . u . s . pat . no . 5 , 405 , 613 refers to the use of shilajit or its extracts in vitamin or mineral compositions and methods to restore the energetic balance or to increase the bioenergetic field in mammals . inventors found that shilajit ,“ has a vibrational field substantially stronger than that of any other vitamin , mineral , alimentary substance or herb ”. they also discovered that when adding small quantities of shilajit to a vitamin or mineral formulation the energetic properties increased . u . s . pat . no . 6 , 440 , 436 describes a shilajit composition having an abundance of bioactive components useful for countering toxic agents , as well as for personal , pharmaceutical and nutritional care . below is a description of the main characteristics and attributes of the components of this invention using andean shilajit in addition to other food supplements : fulvic acid . it is a shilajit component , a completely natural and organic extract rising from the deposit of a plant 75 million years ago and corresponding to the higher cretaceous period . it contains a large quantity of photochemicals , biochemicals , antioxidants , free radicals suppressors , nutrient substances , enzymes , hormones , aminoacids , antibiotics , antivirals , antimycotic substances , among other elements . fulvic acid contains about 74 essential organic and mineral compounds dissolved with 42 % of solid acid food . it improves mineral availability in the body , regenerates and extends residence time of essential nutrients in the cells , diminishes the damage produced by toxic compounds , heavy metals , free radicals and its consumption improves permeability for the digestive and circulatory systems and cell membranes . in the 15 th century , during the ming dinasty , li shi zhen registered , in the pharmacologic abridgement of medical matters , the incidents of the use of “ wujinsan ” ( golden medicine ) which contained fulvic acid as an active ingredient in the treatment of infectious ulcerous diseases , thus involving fulvic acid as an agent for anti - inflammatory coagulation and for efficient blood . before 1978 , fulvic acid had been used in hospitals and on population in general to treat successfully a wide range of diseases ; nonetheless , there was very scarce research on its therapeutic mechanism . due to lack of clinical data and absence of clinical trials , there were still doubts as to the therapeutic use of fulvic acid . from that time onwards , a group of medical schools and hospitals in china have begun to carry out comprehensive studies on the toxicology and pathology of fulvic acid and its clinical uses . hundreds of studies have been published in china , some of them appearing in international newspapers , in addition to some reports presented in various meetings outside china . the pharmaceutic companies in the hands of dr . shanxi in gongxian , henan and in kunming , yunnan produced the fulvic acid that was then approved by the chinese drug administration due to its non - toxicity , for oral as well as external uses . the pharmaceutic use of fulvic acid has been approved by the provincial drug administration on the basis of its efficacy and safety , both internally and externally . at present , it is recognized that fulvic acid acts as an important protective agent and a powerful natural electrolyte that can restore the electric balance of damaged cells , neutralize toxins and eliminate food intoxication in a matter of minutes . it is created in the soil by microorganisms with the aim of transporting minerals and nutrients from there to the plants . then , complex photosynthesis reactions produce the components from different zones of the plant . sugars coming from complex carbohydrates flow along the whole plant for nutrition . some return to the roots where microorganisms are fed , producing fulvic acids as a complex with minerals and nutrients , and the cycle begins again . in plants , fulvic acid stimulates metabolism , provides breathing , increases proteins and the activity of multiple enzymes , improves permeability of cell membranes , their division and elongation , it facilitates chlorophyl synthesis , drought tolerance , protects soil ph and from microbe attacks , contributes to electrochemical balance as a donor or acceptor , disintegrates silicone in order to release essential nutrient substances , detoxificates contaminants such as pesticides and herbicides . when minerals contact with fulvic acid , in an aqueous environment , they dissolve naturally in an ionic manner and , literally , they become a part of it . once minerals are in the fulvic acid complex , they become bioactive , bioavailable and organic . for that reason , when elemental minerals are transformed into an organic state through a natural chemical process implying fulvic acid and photosynthesis , they are safe to be used both in human beings and animals . fulvic acid is found and extracted , preferentially , in the himalayas , but it was recently discovered in the northern region of chile ( andean shilajit ). the latter is richer in fulvic acid than the shilajit from the himalayas . it has been scientifically demonstrated that among its multiple benefits it helps human tissue to grow and regenerate , it lowers strain , stress , general weakness and fatigue , acting as an antioxidant . its use as medication helps to slow down cell aging . another important aspect of the use of fulvic acid consists in a general health improvement through the fight against several diseases associated to mineral deficiency in the body . organic fulvic acids are created precisely by microorganisms in the soil with the goal of transporting minerals and nutrients from the soil up to the plant , which would help to perform the same function in the human body . in ancestral medicine it was considered a panacea and used to increase sexual and spiritual energy , the same vigor that tension and anxiety wither . in india the indigenous medicine system uses it to combat various illnesses such as : kidney and bladder affections , anaemia , asthma , chronic bronchitis , nervous weakness , diabetes , fermentative dyspepsia , hepatosplenomegaly , hysteria , sexual neurasthenia , digestive disorders , etc . 1 . as an antiinflammatory agent : the efficacy of hydrogenated cortisone with respect to fulvic acid changes according to the site of its origin and the extraction method used . ( i ) fulvic acid inhibits an enzyme discharged in the infected area and moreover regulates the zinc and copper levels of the trace elements , thus activating the dismutase that contain zinc and copper . 2 . stimulates blood circulation and enhances coagulation : many diseases are caused by the malfunctioning of circulation in the blood &# 39 ; s capillary system . the therapeutical effect of fulvic acid is a result of its capacity to restore and improve circulation in the blood &# 39 ; s capillary system . on the other hand , fulvic acid also serves as a blood coagulant when there is tapping or blood filtrating from the vascular layer . 3 . digestive ulcers : the healing effects of fulvic acid are the result of its capacity to stimulate blood circulation in the stomach wall and its ability to inhibit the secretion of acid - producing cells . it also stimulates the secretion of glands that have the capacity to protect the stomach &# 39 ; s inner wall , thus preventing ulcers . 4 . immune system : there is reason to believe that if fulvic acid is injected in the abdominal area , the size of the thymus increases in animals under testing , together with the augmentation of macrophage activity . a dosification of 5 mg / kg of weight injected in the abdominal area is beneficial . nonetheless , doses over 50 mg / kg showed the opposite effect , that is , the size of the thymus is reduced . 5 . endocrine system : fulvic acid regulates the abnormal secretion of the thyroid hormone as a result of its power to regulate cyclic at the cell level . 6 . cancer : fulvic acid , in general , does not kill tumor cells ; nonetheless , it serves as a regulator agent in the immune system and can be used jointly with other antineoplastic medicines . 1 . antiinflammatory and blood coagulant : in many clinical cases infections were accompanied by blood filtering into the area or bleeding ulcers . fulvic acid moderates ulcerous conditions on the basis of its antiinflammatory nature , acting at the coagulation level and the whole body . 2 . infection of the cornea : fifty - three cases were studied and treated with fulvic acid eye drops and intramuscular injections , obtaining a rate of success of 94 . 2 %. the study was carried out in an eye clinic at the shaoxin hospital , zhejiang province , china . 3 . acute gastrointestinal hemorraghe : 160 cases were studied and treated with fulvic acid in oral and injectable form , with a rate of success of 95 . 6 %. the studies were carried out at internal medicine at the tongren hospital , beijing , china . 4 . skin ulcers : fifty - one cases were studied and treated with a fulvic acid bath and minerals with a rate of success of 92 . 2 %. the studies were carried out at internal medicine at the tongren hospital , beijing , china . 5 . rheumatoid arthritis : a large number of cases were studied and treated with the fulvic acid bath mixed with minerals and in oral form ( capsules ), with a rate of success of 92 %. de éxito . the studies were carried out at the haidian hospital , beijing , china . 6 . hemorrhoids : several thousands of cases were studied and treated with the fulvic acid preparation . the rate of success was so high that the chinese medical authorities developed an over - the - counter ( otc ) medicine for its national distribution . the studies were carried out at the hospitals of erlonglu in beijing and kunming in yunnan , china . 7 . esophageal cancer : disease &# 39 ; s incubation period : 27 cases were studied and treated using a solution of fulvic acid in water during two years . the hit rate was 100 % in the progression of the prevention of the tumor in its cancerous state . the studies were carried out by hongji xie , et al . 8 . overactive thyroid : 33 cases studied and treated during 6 months with fulvic acid in oral form ( capsules ) with a rate of success of 0 . 9 %. the studies were carried out at the tongren hospital , beijing , china . in short , as a result of common efforts contributed by researchers and their basic clinical studies on science , the fulvic acid component , originating from humic acid , has proven to be an effective and safe remedy for a wide variety of illnesses . this contribution has raised the curiosity and interest of foreign scientists , as stated in “ the recent progress in chinese medicine ” published in singapore and in “ fulvic acid ” published in germany . discovered in the 1940 &# 39 ; s , folic acid ( b9 ) is considered a water - soluble vitamin pertaining to the b complex . it is also known as folacin or folate whose etymology comes from the latin “ folium ” meaning leaf . the vitamin is essential to achieve all of our body &# 39 ; s functions . its great importance lies in the fact that folic acid is fundamental at the cell level to synthetize dna ( deoxyribonucleic acid ), responsible for the transmittal of the 11 genetic characters and also to synthetize rna ( ribonucleic acid ), required to form the body &# 39 ; s proteins and tissues and other cell processes . therefore , the presence of folic acid in our body is indispensable for the correct cell division and duplication . folates work together with vitamin b 12 and vitamin c in the use of proteins . it is important to point out that folic acid is basic in the formation of the hemo group ( part of hemoglobin containing iron ), that is why it is related to the formation of red blood cells . folic acid also benefits the cardiovascular system , the nervous system and the neurological fetal formation , among others . given its great importance for human beings , much of the foodstuff we consume nowadays is enriched with folic acid . this acid is formed in the intestine from our colonic flora . it is absorbed mainly in the small intestine ( jejunum ), then it is distributed in the tissues via blood circulation and is stored in the liver and is excreted through urine and feces . a large number of research studies have permitted to observe that folic acid is necessary in the formation of red blood cells , it reduces the risk of the appearance of defects in the neural tube of the fetus , such as spina bifida and anencephaly , diminishes the occurrence of cardiovascular diseases , prevents some types of cancer , helps to increase appetite and stimulates the formation of digestive acids . vitamin b 6 is a water - soluble vitamin , this implies that it is eliminated through the urine and therefore must be replaced daily with the diet . vitamin b 6 is in fact a group of three chemical compounds called pyridoxine ( or pyridoxol ), pyridoxal and pyridoxamine . the phosphorylated derivatives of pyridoxal and pyridoxine , that is , pyridoxal phosphate ( plp ) and pyridoxamine phosphate ( pmp ) perform coenzyme functions . they participate in many enzymatic reactions of the metabolism of aminoacids and their main function is the transfer of amino groups ; therefore , they are transaminase coenzymes , enzymes that catalyze the transfer of amino groups among aminoacids . those coenzymes act as temporary carriers of amino groups . this vitamin is often known popularly as the “ women &# 39 ; s vitamin ” since it has been sustained that it contributed to relieve premenstrual syndrome ( irritability , downheartedness , etc .). scientific studies carried out on this matter have not achieved clear and conclusive results . vitamin b 6 intervenes in the elaboration of brain substances regulating the mood such as serotonine , being able in some cases to help some people suffering from depression , stress and sleep disorders . this vitamin is very popular among sportsmen and sportswomen because it increases muscular performance and energy production . the latter is due to the fact that when there is the need to make a greater effort it favors the release of glycogen stored in the liver and muscles . it can also contribute to lose weight because it helps our body to obtain energy from accumulated fat . it is known that our body requires vitamin b 6 to adequately synthesize antibodies and erythrocytes , it is very important for an adequate absorption of vitamin b 12 and magnesium . it also helps in cases of a tendency to have night - time muscular spasms , leg cramps and dead limbs , it favors iron absorption and intervenes in myeline formation . in addition it can help reduce mouth dryness caused by medication ( specially by some antidepressants ). gestational and nursing diabetes have been linked to a vitamin b 6 deficiency that would bring about a low level of insulin and thus would hinder the entrance of carbohydrates in cells . diabetics often observe they need less insulin if they take vitamin b 6 , so they must supervise their glucose levels and adapt the insulin dose . vitamin b 6 is found in wheat germ , meat and vegetables , food rich in refined sugars , additives and natural dyes . this is a complex b water - soluble vitamin , important for metabolism , it helps to form blood red cells and to maintain the central nervous system . it is found in eggs , beef , chicken meat , seafood , and also in milk and its by - products . low levels of vitamin b 12 may cause anaemia , numbness or tingling sensation in arms and legs , weakness and loss of balance . additionally , people who have undergone surgery in specific parts of the small intestine or stomach are also subject to present a deficiency if they do not take supplements of this vitamin . surprisingly and unexpectedly we have observed that the mixture of shilajit and folic acid , together with small quantities of vitamins b 6 and b 12 generate beneficial effects as an antioxidant agent and cell protector , especially in nerve cells . these effects are much greater than the individual effects of the agents forming the mixture . this strongly suggests the use of this composition in neurodegenerative diseases such as alzheimer . these synergetic effects are observed presumably due to shilajit &# 39 ; s neuroprotector characteristics , in addition to the homocysteinemic activity of the mixture between folic acid and vitamin b 12 , which , together with vitamin b 6 &# 39 ; s antidepressant and antistress effect generates a new nutraceutic product with great strength as a neuroprotector to prevent and treat neurodegenerative disorders . the composition is appropriate for direct oral human consumption , either in solid form or in a solution to be added to food or as a nutraceutic agent ; it can be an ingredient of energizing beverages or can be formulated as a medication together with authorized excipientes . folic acid : 200 μg vitamin b 12 : 4 μg vitamin b 6 : 200 μg shilajit : 250 mg and excipients : c . s . p . 350 mg for the production of one 350 mg capsule of our medication we proceed in the following way : the components of the composition illustrated above are mixed in the previously described proportions and in a random mode . then the composition is mixed with corn maltodextrin in enough quantity for a 350 mg powder capsule . the capsule may be administered in the following diseases and in the indicated dosage : a . alzheimer disease : 1 every 12 hours b . senile dementia , mild or moderate : 1 every 12 hours . c . mild cognitive impairments ( mci ): 1 every 12 hours . d . memory disorders associated to aging : 1 every 24 hours . the toxicity of the composition &# 39 ; s main component was determined , whose toxicity in nerve cells was unknown up to now . this study consisted in the application of concentrations ranging from 10 to 50 mg / ml to a culture of neuroblastoma cells ( n - 115 cell line ) ( mtt assay ) and subsequent observation of neuronal death through fluorescent microscopy using the calcein - am method that determines the morphologic integrity . the experiment &# 39 ; s results are shown in table 1 . results show a very low neuronal death , even at high concentrations of purified shilajit in the culture , which indicates a very low or even null product toxicity . experiments were carried out to determine shilajit &# 39 ; s antioxidant capacity versus known products evaluated through the determination of the absorption capacity of oxygen reactive species ( orac ) using for that fluorescein as a fluorescent probe and employing peroxyl radical as an instrument of evidence . trolox was used as a comparison standard , a vitamin e analogue in a water - based solution , with which the respective calibration curves were made . the results obtained can be seen in table 2 . for this analysis primary cultures were used of rats &# 39 ; hypocampus cells placed in plate culture and incubated under standard conditions with substrata . the results of the morphometric analysis can be seen in table 3 . it can be inferred from the experiment that the invention &# 39 ; s formulation shows clear advantages over shilajit only with respect to control , proving , therefore , a therapeutic efficacy analyzed on the basis of the morphometric characteristics of neuronal cells . r . b . maccioni & amp ; g . perry ( 2009 ) “ current hypotheses and research milestones in alzheimer &# 39 ; s disease ”. springer , new york , 296 pp . r . b . maccioni , j . fernandez , l . rojo and r . kuljis ( 2009 ) “ neuroimmunomodulation in alzheimer &# 39 ; s disease ”. ann new york acad . sci . 1153 : 240 - 247 . j . fernandez , l . rojo , r . o . kuljis and r . b . maccioni ( 2008 ) “ the damage signals hypothesis of alzheimer &# 39 ; s disease pathogenesis ”. j . alz . disease v . 14 : 329 - 333 . dubois b ., feldman h ., jacova c . ( 2007 ). research criteria for the diagnosis of alzheimer &# 39 ; s disease : revising the nincds - adrda criteria . lancet neurol . 6 : 734 - 46 . green r . c ., cupples l . a ., go r ., benke k . s ., edeki t ., griffith p . a ., williams m ., hipps y ., graff - radford n ., bachman d ., farrer l . a . ( 2002 ). mirage study group . risk of dementia among white and african american relatives of patients with alzheimer disease . jama . 287 ( 3 ): 329 - 36 . kurt m . a ., davies d . c ., kidd m . ( 1997 ). paired helical filament morphology varies with intracellular location in alzheimer &# 39 ; s disease brain . neurosci lett . 239 ( 1 ): 41 - 4 . maccioni r . b ., farias g . a ., rojo l . e ., sekler m . a . and kuljis r . o . ( 2008a ). what have we learned from the tau hypothesis ? in : hypotheses and research milestones in alzheimer &# 39 ; s disease ( r . b . maccioni & amp ; g . perry , eds .). springer - verlag , new york - heidelberg . maccioni r . b ., lavados m ., maccioni c . b . and mendoza a . ( 2004 ). biological markers of alzheimer &# 39 ; s disease and mild cognitive impairment . current alzheimer research . 1 : 307 - 314 . maccioni c ., arzola m . e ., mujica l . and maccioni r . b . ( 2003 ). new paradigms in the study of the pathogenesis of alzheimer &# 39 ; s disease . rev chil neuro - psiquiatr . 41 ( 2 ): 33 - 46 . maccioni , r . b ., barbeito l ., and munoz j . p . ( 2001 ). the molecular bases of alzheimer &# 39 ; s disease and other neurodegenerative disorders . arch . medical research . 32 : 367 - 381 . mattson m . ( 2004 ). pathways towards and away from alzheimer disease . nature . 430 ( 7000 ): 631 - 9 . review . rojo l . e ., fernández j . a ., maccioni a . a ., jimenez j . m ., maccioni r . b . ( 2008 ). neuroinflammation : implications for the pathogenesis and molecular diagnosis of alzheimer &# 39 ; s disease . arch med res . 39 ( 1 ): 1 - 16 . wimp a ., winblad b . ( 2001 ). health economical aspects of alzheimer disease and its treatment . psychogeriatrics . 1 : 189 - 93 . winblad b . ( 2001 ). maintaining functional and behavioral abilities in alzheimer disease . alzheimer dis assoc disord . 1 : s34 - 40 . zambrano c a , egaña j t , núñez m t , maccioni r b , gonzález - billault c . ( 2004 ). oxidative stress promotes tau dephosphorylation in neuronal cells : the roles of cdk5 and pp1 . free radic biol . med . 36 ( 11 ): 1393 - 402 .

the present invention relates to a potent antioxidant neuroprotective nutraceutical composition that comprises blending extract of shilajit and folic acid , together with small amounts of vitamins b6 and b12 consumed per day . this composition can be used to prevent and to treat neurodegenerative diseases or episodes of cognitive deterioration arising from various pathological conditions . the use thereof is indicated in the treatment of alzheimer &# 39 ; s disease and senile dementia as the pathological conditions preferably to be treated . the composition is suitable for direct human consumption by mouth , either in solid form as a powder or as a suspension of the extract , as a food additive or as a nutraceutical agent . it may be formulated as a nutraceutical agent to be included as an ingredient in beverages or as a drug in conjunction with permitted excipients .

the present invention is specifically explained below with references to examples which are made for merely illustrative purpose , and the invention is not limited to these examples . the present invention ( nahco 3 ) was demonstrated using rice . absorbent cotton was spread on a 4 . 5 cm dish , and thereto was added 10 ml of a test solution . seeds ( 10 seeds ) were added thereto , grown at 23 ° c . for 4 days in the dark , and thereafter cultured at 23 ° c . for 3 days in the light ( about 3000 lux ). each figure illustrates for nahco 3 used as a principal active ingredient showing from the left : control ( nahco 3 concentration of 0 %), 1 % ( 1 / 10 dilution of a stock solution of an aqueous saturated solution of 10 %), 0 . 3 %, 0 . 1 %, 0 . 03 %, 0 . 01 %, and 0 . 003 %. fig1 is a drawing illustrating the state of seeds within each of the dishes . fig2 is a drawing comparing the length of each shoot and the length of each root . the shoots have the length of 5 . 3 ± 0 . 3 mm , 3 . 3 ± 0 . 3 mm , 7 . 3 ± 1 . 5 mm , 13 . 3 ± 0 . 9 mm , 15 . 0 ± 1 . 0 mm , 10 . 0 ± 0 mm , 11 . 0 ± 1 . 0 mm , respectively . the length of the roots is 10 . 3 ± 1 . 8 mm , 0 ± 0 mm , 2 . 3 ± 0 . 3 mm , 20 . 7 ± 2 . 3 mm , 23 . 7 ± 0 . 9 mm , 18 . 0 ± 9 . 7 mm , 32 . 0 ± 9 . 3 mm , respectively . for reference , the length of the label is 5 mm . as is clear from fig1 and fig2 as well as the length of each shoot and root , it is revealed that the growth is suppressed when the concentration is high , whilst the growth is accelerated when the concentration is low . the present invention ( nahco 3 ) was demonstrated using tomato . fig3 is a drawing illustrating the state of germination within each of the dishes similarly to fig1 . fig4 is a drawing comparing the length of each embryonic axis ( shoot ) and that of each root similarly to fig2 . the shoots have the length of 22 . 7 ± 1 . 5 mm , 0 ± 0 mm , 14 . 7 ± 0 . 3 mm , 41 . 3 ± 1 . 9 mm , 46 . 0 ± 1 . 5 mm , 39 . 3 ± 1 . 5 mm , 30 . 0 ± 1 . 7 mm , respectively . the length of the roots is 55 . 0 ± 1 . 2 mm , 0 ± 0 mm , 1 . 3 ± 0 . 3 mm , 29 . 3 ± 1 . 8 mm , 60 . 7 ± 8 . 1 mm , 26 . 3 ± 3 . 7 mm , 17 . 0 ± 1 . 5 mm , respectively . for reference , the length of the label is 5 mm . as is clear from fig3 and fig4 as well as the length of each shoot and root , it is revealed that the growth is suppressed or the germination does not occur when the concentration is high , whilst the growth is accelerated when the concentration is 0 . 1 % or less . the present invention ( nahco 3 ) was demonstrated using lettuce . fig5 is a drawing illustrating the state of germination within each of the dishes similarly to fig1 . fig6 is a drawing comparing the length of each shoot and that of each root similarly to fig2 . the shoots have the length of 17 . 3 ± 0 . 3 mm , 0 ± 0 mm , 6 . 7 ± 0 . 3 mm , 15 . 7 ± 0 . 3 mm , 24 . 3 ± 0 . 3 mm , 24 . 3 ± 0 . 9 mm , 14 . 0 ± 0 . 6 mm , respectively . the length of the roots is 21 . 3 ± 0 . 7 mm , 0 ± 0 mm , 3 . 7 ± 0 . 3 mm , 11 . 0 ± 0 . 6 mm , 14 . 3 ± 1 . 9 mm , 21 . 0 ± 0 . 6 mm , 18 . 7 ± 4 . 7 mm respectively . for reference , the length of the label is 5 mm . as is clear from fig5 and fig6 as well as the length of each shoot and root , it is revealed that the growth is suppressed or the germination does not occur when the concentration is high , whilst the growth is accelerated when the concentration is low . the present invention ( nahco 3 ) was demonstrated using perennial ryegrass . fig7 is a drawing illustrating the state of seeds within each of the dishes similarly to fig1 . fig8 is a drawing comparing the length of each shoot and that of each root similarly to fig2 . the shoots have the length of 25 . 3 ± 0 . 9 mm , 0 ± 0 mm , 19 . 0 ± 0 . 6 mm , 55 . 7 ± 0 . 7 mm , 44 . 3 ± 1 . 5 mm , 42 . 0 ± 0 . 6 mm , 24 . 7 ± 0 . 3 mm , respectively . the length of the roots is 29 . 7 ± 0 . 3 mm , 0 ± 0 mm , 4 . 7 ± 0 . 3 mm , 28 . 0 ± 1 . 5 mm , 26 . 0 ± 0 . 6 mm , 27 . 3 ± 1 . 5 mm , 25 . 3 ± 0 . 9 mm , respectively . for reference , the length of the label is 5 mm . as is clear from fig7 and fig8 as well as the length of each shoot and root , it is revealed that the growth is suppressed or the germination does not occur when the concentration is high , whilst the growth is accelerated when the concentration is low . the present invention ( nahco 3 ) was demonstrated using radish . fig9 is a drawing comparing the length of each embryonic axis ( shoot ) and that of each root similarly to fig2 . the shoots have the length of 60 . 3 ± 1 . 9 mm , 0 ± 0 mm , 19 . 3 ± 0 . 7 mm , 66 . 7 ± 3 . 4 mm , 60 . 0 ± 3 . 1 mm , 74 . 0 ± 1 . 5 mm , 66 . 3 ± 4 . 1 mm , respectively . the length of the roots is 33 . 7 ± 4 . 2 mm , 0 ± 0 mm , 7 . 3 ± 1 . 3 mm , 22 . 0 ± 1 . 5 mm , 80 . 7 ± 5 . 9 mm , 71 . 3 ± 1 . 9 mm , 37 . 0 ± 1 . 5 mm , respectively . for reference , the length of the label is 5 mm . as is clear from fig9 as well as the length of each shoot and root , it is revealed that the growth is suppressed or the germination does not occur when the concentration is high , whilst the growth is accelerated when the concentration is low . ( 2 ) effect of khco 3 and nahco 3 used in combination the present invention ( nahco 3 + khco 3 ) was demonstrated using veronica persica poir . fig1 is a drawing illustrating the state of seeds within each of the dishes similarly to fig1 , and each control is shown . the figure illustrates for nahco 3 used as a principal active ingredient showing from the left : 0 %, 10 %, 3 %, 1 %, 0 . 3 %, and 0 . 1 %. in addition , the lengths of each embryonic axis shoots and root are indicated . experiments were conducted with varying concentrations of khco 3 for each concentration of nahco 3 shown in fig1 . although not shown in the figure , when the concentration of khco 3 was varied at 0 % of nahco 3 , the length of the shoot and root was 0 mm at 1 % of khco 3 ( the germination did not occur ), but became 7 mm and 10 mm respectively at 0 . 1 %, which were approximately identical to the values for 0 . 1 % of nahco 3 . next , the experiments were conducted with varying concentrations of khco 3 ( 0 . 1 to 10 %) when the concentration of nahco 3 was 10 %, 3 %, 1 % and 0 . 3 %. thus resulting length of the shoot and root was 0 mm ( the germination did not occur ). moreover , when similar tests were carried out for 0 . 1 % of nahco 3 , the development of the shoot and root was not found at 10 to 1 % of khco 3 ( the germination did not occur ), however , at 0 . 1 % of khco 3 , the length of the shoot became 10 mm and the length of the root became 18 mm . these results suggest that more remarkable growth was achieved than the control ( fig1 ) for 0 . 1 % of nahco 3 ( shoot : 8 mm , root : 9 mm ) and for 0 . 1 % of khco 3 ( shoot : 7 mm , root : 10 mm ). accordingly , the effects by combined use of both compounds were demonstrated . the present invention ( nahco 3 + khco 3 ) was demonstrated using tomato . fig1 is a drawing illustrating the state of seeds within each of the dishes similarly to fig1 , and each control is shown . the figure illustrates for nahco 3 used as a principal active ingredient showing from the left : 0 %, 10 %, 3 %, 1 %, 0 . 3 %, and 0 . 1 %. in addition , the lengths of each shoot and root are presented . in addition , it is revealed that the germination does not occur at 10 % and 3 %. experiments were conducted with varying concentrations of khco 3 for each concentration of nahco 3 shown in fig1 . although not shown in the figure , when the concentration of khco 3 was varied at 0 % of nahco 3 , the length of the shoot and root was 0 mm at 1 % of khco 3 ( the germination did not occur ), became 40 mm and 62 mm respectively at 0 . 1 %, which revealed greater effects than those suggested by the values for 0 . 1 % of nahco 3 . next , the experiments were conducted with varying concentrations of khco 3 ( 0 . 1 to 10 %) when the concentration of nahco 3 was 10 % and 3 %. thus resulting length of the shoot and root was 0 mm ( the germination did not occur ). moreover , when similar tests were carried out for 1 % of nahco 3 , the development of the shoot and root was not found at 10 % or 0 . 1 % of khco 3 , however , at 1 % of khco 3 , the length of the shoot became 11 mm and the length of the root became 5 mm . these reveal greater effects than the control ( fig1 ) for 1 % of nahco 3 ( shoot : 5 mm , root : 1 mm ). in addition , when khco 3 was used at 10 % for 0 . 1 % of nahco 3 , the development of the shoot and root was 0 mm ( the germination did not occur ). however , at 1 % of khco 3 , the length of the shoot was 2 mm , and , at 0 . 1 % of khco 3 the length of the shoot was 50 mm and the length of the root was 45 mm . accordingly , the effects by combined use of both compounds are remarkable . the present invention ( auxin used in combination ) was demonstrated using tomato . indole - 3 - acetate ( iaa ) was used as the auxin . when iaa was used at 10 − 4 to 10 − 5 m , although not shown in the figures , the length of each shoot was 20 mm , 23 mm , and the length of each root was 30 mm , 41 mm , respectively . thus , when the cases of use in combination with nahco 3 were examined , as is shown in fig1 , in the instances of 10 % or 3 % of nahco 3 and 10 − 3 to 10 − 5 m of iaa were used , any of the length of the shoot and root was 0 mm ( the germination did not occur ). fig1 is a photograph illustrating the instances where 1 % or 0 . 3 % of nahco 3 and 10 − 3 to 10 − 5 m of iaa were used . moreover , fig1 is a photograph illustrating the instances where 0 . 1 % of nahco 3 and 10 − 3 to 10 − 5 m of iaa were used . according to these figures , it was revealed that when both compounds were used at a predetermined ratio , the root especially became strong . as the foregoing , when nahco 3 and iaa were used in combination , the effects of the combined use are prominent , including the inhibition of the growth and the acceleration of the growth of the plant . in particular , it is proven that when nahco 3 was used at 0 . 1 %, iaa at the concentration of approximately 10 − 4 to 10 − 6 m greatly contributes to the growth of the plant . the present invention ( auxin used in combination ) was demonstrated using veronica persica poir . indole - 3 - acetate ( iaa ) was used as the auxin . when iaa was used at 10 − 4 to 10 − 5 m , although not shown in the figures , the length of each shoot was 8 mm , 13 mm , and the length of each root was 11 mm , 22 mm , respectively . thus , when the cases of use in combination with nahco 3 were examined , in the instances of 10 % or 3 % of nahco 3 and 10 − 3 to 10 − 5 m of iaa were used , any of the length of the shoot and root was 0 mm ( the germination did not occur ). fig1 is a photograph illustrating the instances where 1 % or 0 . 3 % of nahco 3 and 10 − 3 to 10 − 5 m of iaa were used . moreover , fig1 is a photograph illustrating the instances where 0 . 1 % of nahco 3 and 10 − 3 to 10 − 5 m of iaa were used . according to these figures , it is proven that when nahco 3 and iaa were used in combination , the effects of the combined use are prominent including the inhibition of the growth and the acceleration of the growth of the plant . nahco 3 was blended in volcanic ash ( originated in hokkaido , chitose ), and the germination of lettuce was thereby accelerated . for control 1 , absorbent cotton was spread on a 4 . 5 cm dish , and thereto was added 10 ml of water . seeds ( 10 seeds ) were added thereto , grown at 23 ° c . for 4 days in the dark , and thereafter cultured at 23 ° c . for 3 days in the light ( about 3000 lux ). the length of the shoot and root was as shown in fig1 . control was for water alone , resulting in the length of the shoot and root of 24 . 1 ± 1 . 1 mm and 26 . 9 ± 1 . 5 mm . additionally , when the lettuce seeds were seeded to the soil which was prepared by adding water to the volcanic ash ( volcanic ash : 100 g and water : 28 g ), the length of the shoot and root was 23 . 7 ± 2 . 9 mm and 17 . 1 ± 2 . 6 mm . however , for the soil including the volcanic ash + 10 % nahco 3 ( volcanic acid : 100 g and saturated sodium bicarbonate solution : 28 g ), the development of the shoot and root was 0 mm . moreover , for the soil including the volcanic ash + 1 % nahco 3 ( volcanic acid : 100 g and 1 % nahco 3 solution : 28 g ), the length of the shoot and root was 26 . 0 ± 1 . 5 mm and 5 . 4 ± 1 . 1 mm . further , for the soil including the volcanic ash + 0 . 1 % nahco 3 ( volcanic acid : 100 g and 0 . 1 % nahco 3 solution : 28 g ), the development of the shoot and root was 33 . 4 ± 1 . 1 mm and 21 . 0 ± 0 . 8 mm . according to these results , adding nahco 3 to the soil contributes to the growth of a plant . thus , the modification of volcanic ash such as whitebait , and red soil was enabled . of course , it goes without mentioning that modification of soil can be practiced by use of nahco 3 alone , and use thereof in combination with khco 3 , as well as use in combination with a plant hormone . the plant growth regulator of the present invention exerts dramatic effects as described herein above , and is readily available . furthermore , the plant growth regulator of the invention is characterized by not adversely affecting the soil and being friendly to the environment , and thus the usefulness thereof is eminent .

the present invention relates to plant growth regulators and processes for regulating plant growth , and more particularly , relates to a technique to regulate the growth of a plant using a substance which is friendly to the global environment . a growth regulator of a plant comprising nahco 3 and / or khco 3 as a principal active ingredient is provided .

in general , in order to move a piston holder forward and backward , the above - described drive mechanism of the automatic injection device converts the rotational movement of a motor into a linear movement by using a ball screw and the like , as described by reference to fig9 . hence , backward - moving prohibition mechanism can be provided in any portion of a transfer route from the motor to the piston holder . that is , depending on the specific embodiment of the invention , the backward - moving prohibition mechanism can be constituted such that either the rotation is prohibited or the linear movement is prohibited . referring to a double head type chemical solution injection device mountable with two syringes , a description will be made below . as shown in fig9 , the syringe for a contrast medium is mounted on one side of a head a and the syringe for a physiological saline solution is mounted on the other side of a head b . in the same drawings described below , though only the head at the side of the physiological saline solution ( at the side of the head b ) will be shown , the head at the side of the contrast medium can be constituted similarly to the head at the side of the contrast medium as shown in fig9 . in this case , the head a corresponds to the first head , and the head b corresponds to the second head . the head at the side of the contrast medium may also be provided with the backward - moving prohibition mechanism if necessary . an example using an electromagnetic brake as backward - moving prohibition mechanism will be described below with reference to fig1 . in this example , the main body of the electromagnetic brake 11 is fixed to a frame unit 10 , while the axis ( to which a screw gear 7 b is fixed ) of a ball screw 8 b is fixed to an armature side of the electromagnetic brake . linking and separation between the main body and the armature is performed by controlling the coil inside the electromagnetic brake . when a syringe piston at the side of the head b is moved forward of backward , the main body and the armature are separated each other ( i . e . contact is released ), thereby the ball screw 8 b can rotate freely by receiving the rotation of a motor 4 b . when the electromagnetic brake is turned on , the main body and the armature is linked ( i . e . contact is attained ), thereby the rotation of the axis of the ball screw 8 b is fixed . hence , if the electromagnetic brake is turned on when the syringe piston at the side of head b is in a stopped state and the syringe piston at the side of the head a is allowed to act , the syringe piston at the side of the head b does not move and there is no risk of sucking the contrast medium . an example using a disc brake as backward - moving prohibition mechanism will be described below with reference to fig2 . the disc brake 12 has a disc 13 and pads 14 , which stops the rotation of the disc by holding the disc 13 between the pads 14 . when the piston syringe at the head b is moved forward and backward , the space between the disc 13 and the pads 14 is left open so that the motor gear 6 b can freely rotate . when the backward - moving of the syringe piston at the head b is desired to be prohibited , the disc 13 may be clamped by the pads 14 by electrically controlling the disc brake . in this example , though the disc 13 is fixed to the motor gear 6 b , it may be fixed to the screw gear 7 b or fixed to any place of the axis of rotation . in the above - described embodiments 1 and 2 , though a method of using the brake was described , other types of brakes other than the electromagnetic brake and the disc brake may be used if the movement in the backward direction can be prevented . moreover , though the embodiments 1 and 2 are constituted such that the rotation is stopped , they may be also constituted such that the linear movement is stopped . an example using a ratchet mechanism as the backward - moving prohibition mechanism will be described below with reference to fig3 . as shown in fig3 ( a ), a ratchet 15 is provided on a cylinder portion 19 of a ball nut unit 9 b and fitted into a ratchet claw of a ratchet pole 16 , making it possible to move forward the syringe piston and prohibit the backward - moving thereof . that is , when at least the motor at the side of the head b is stopped and the ratchet is allowed to engage with the ratchet claw , there is no backward - moving of the syringe piston nor a backward flow . when the syringe piston allows to move backward , a rotary solenoid 17 is electrically controlled so as to rotate the ratchet pole 16 , and the engagement of the ratchet and the ratchet claw is released . in fig3 ( b ) ( cross - sectional view at line a - a in fig3 ( a )), a state of the ratchet being engaged with the ratchet claw and a physical relationship of the rotary solenoid 17 are shown . the place where the ratchet is provided is not limited to this example , and if it is provided on the member which makes reciprocating movement together with the syringe piston , such construction functions similarly to this example . in the embodiment 3 , the example using the linear type ratchet was shown , but in the embodiment 4 , a wheel type ratchet 21 as shown in fig5 is used . as shown in fig4 , the wheel type ratchet 21 is fixed to a screw gear 7 b and is engaged with the ratchet pole 16 . engagement and release of the ratchet is controlled by the rotary solenoid 17 . in this example , the wheel type ratchet is fixed on the axis of a ball screw 8 b and prevents the ball screw 8 b from rotating in the backward direction when the syringe piston at the side of the head b is in a stopped state . however , the ratchet may be fixed on the axis of the motor 4 b . in the devices of the embodiments 1 to 4 , examples were shown wherein the rotational transmission route itself from the motor to the ball screw is the same as the conventional route shown in fig9 and provided additionally with the backward - moving prohibition mechanism . in the embodiment 5 , the improvement was placed in the rotational transmission route ; that is , the transmission is made only in one way from the motor to the ball screw . that is , the transfer route is constituted such that the rotation ( both forward and backward directions ) of the motor is transferred to the ball screw , on the other hand , even if a force to rotate the ball screw is applied , the force does not incur the rotation of the motor axis . in an example as shown in fig6 , a worm reduction gear 22 using a worm gear is linked to the motor 4 b and reduces the rotation of the motor , at the same time the axis of motor is arranged such that it is not rotated by the rotational force from the side of the ball screw . inside the worm reduction gear 22 , a cylindrical worm gear 25 comprising a cylindrical worm 23 and a worm wheel 24 is provided as shown in fig7 , and the axis of motor is linked to the axis of the cylindrical worm 23 , and the central axis of the worm wheel 24 is linked to the axis of the motor gear 6 b . in this constitution , the rotation of the cylindrical worm 23 is transferred to the worm wheel 24 due to the characteristic of the cylindrical worm gear , but it is not possible to rotate the cylindrical worm 23 even if the wheel worm tries to rotate . the constitution of the worm gear is not limited to this example . for example , the axis of the worm wheel 24 may be joined to the axis of the ball screw 8 b so as to be rotated by the cylindrical worm 23 . as described above , according to the present invention , an automatic injection device mountable with a plurality of syringes can be provided wherein , when at least one head is in an injecting state and at least one head is in a stopped state , the backward - moving of the syringe piston of the stopped head is prevented so as to prevent liquid from being undesirably mixed and the injection amount thereof from becoming less accurate .

an automatic injection device has piston holders holding cylinder pistons and plural systems of heads having a drive mechanism for moving the piston holders forward and backward so that the device can hold a plurality of syringes and operates injection or suction in each syringe independently . this device also has a mechanism for prohibiting the backward - moving of the piston holder of a second head when the piston holder of a first head is in a forward - moving state and the piston holder of the second head is in a stopped state . this structure effectively prevents liquid from being undesirably mixed and the injection amount thereof from becoming less accurate .

turning now to the drawings , and referring first to fig1 , a planter 10 is shown , having a seed drive system 12 . the planter is designed to be towed behind a work vehicle , such as tractor ( not shown ). as will be appreciated by those skilled in the art , the seed drive system is coupled to a power supply and a control system , represented as a block diagram for the sake of simplicity . the power supply and control system are used to regulate the seed drive system to attain desired seed spacing as well as to account for overall speed of the implement . the power supply will generally include a hydraulic power supply ( not separately shown ) that provides a flow of pressurized hydraulic fluid for driving parts of the seed drive system , as described below . the hydraulic power supply itself may be driven by a motor ( not shown ) or by the tractor itself ( e . g ., by a power takeoff shaft ), or may be part of the tractor hydraulic system . the planter 10 consists of a frame , designated generally by reference numeral 14 , which may be made of any suitable material , such as structural steel . the frame 14 further includes a tool bar 16 secured generally transverse to a tow bar 18 . the tow bar 18 of the frame 14 forms a fore - end - aft longitudinal beam designed to be connected to the towing work vehicle . in the present embodiment , the tool bar 16 includes a center section 20 which is coupled to the tow bar 14 and supports central components of the planter such as seed tanks . planter 10 is generally symmetrical about centerline 22 , with wings on each side of the tow bar . centerline 22 generally runs in the same direction as the implement in towed , above the tow bar 18 . the wings may be folded forward , generally depicted by arrows 24 , during road transport of the planter , thereby reducing the width of the implement . as shown in somewhat greater detail in fig2 , the view of a central portion of the planter shows the seed drive system components of the present embodiment , including hydraulic motor 26 connected to a coupling 28 . as will be appreciated by those skilled in the art , hoppers and other components of the row units are removed to enhance clarity . the coupling 28 is attached to jackshaft 30 , shown here as a shaft with a hexagon cross - section . in the present embodiment , other components of the mechanism include inner hex shaft 32 , which is flexibly coupled to outer hex shaft 34 by universal joint 36 . the drive shafts may be made of any suitable material , such as rolled steel . as those skilled in the art will appreciate , the geometric shape of the drive shafts may be varied to meet particular application and manufacturing requirements . the universal joint 36 is connected alongside tool bar pivot 38 , both of which allow the outer portions of tool bar 16 to change in elevation as the row units and wheeled supports 40 travel along the contours of the soil . the hydraulic power supply is connected to hydraulic flow control valve 42 , which regulates the speed of hydraulic motor 26 , thereby controlling seed distribution . fig3 shows a detailed view of the direct seed drive system . components of the drive shafts are mounted and aligned using bearings , designated generally by reference numeral 44 . bracket 46 may couple bearings 44 to the center section of the toolbar . in the embodiment , the motor 26 may be mechanically supported by bearings 44 , coupling 28 and jackshaft 30 . the jackshaft is connected via chain and sprocket 48 to a secondary parallel shaft 50 . central row units 52 and their seed systems are driven by parallel shaft 50 . in this embodiment , the central row units 52 are set back on the rear portion of the frame to allow folding of the tool bar wings and to allow space for other components such as seed tanks and the seed distribution system . as will be appreciated by those skilled in the art , the row units may serve various functions , depending upon the design , the nature of the field to be planted ( e . g ., tilled or untilled ), the particular seeds to be planted , and so forth . structures of each row unit may typically include an opener disc , a metering system , a covering disc , a firming wheel , and so forth . for the sake of clarity , many components of the row units are not pictured . accommodations may be made for fertilizers , dispensing of fertilizers , chemical distribution , and the like . the row units are spaced apart and staggered along the frame and tool bar to provide the desired spacing of rows of crops after seeding . the figure also shows a paddle coupling 54 , which allows the seed drive system to connect to the wing row units , continuing in a direction designated generally by arrow 56 . moreover , the flexibility in the seed drive system 12 provided by the paddle coupling 54 allows the wings that comprise each side of tool bar 16 to fold for transport without any adjustment to the drive mechanism . that is , the paddles 54 and the drive mechanism do not require any alteration when the planter &# 39 ; s wings are folded to a transport position . this is due to the fact that the paddles 54 allow for complete separation of the drive mechanism when the wings are folded . the folding of the wings for transport and the wing movement due to changes in elevation may be described as flexing movement . an isolated view of the seed drive system 12 is illustrated by fig4 . hydraulic motor 26 , coupling 28 , and hex shaft 32 are shown . bearings 44 provide mounting locations and alignment for components of the seed drive system . in the present embodiment , the hydraulic motor 26 is suspended by the coupling 28 and is prevented from rotation about the drive shaft axis by anti - rotation member 58 . this anti - rotation feature is shown in more detail in fig5 , which is a view along the axis of jackshaft 30 . as will be appreciated by those skilled in the art , a seed drive system 12 may be displaced on each of the two wings that comprise the tool bar 16 . that is , two seed drive systems 12 are typically placed on a planter , one on each wing of tool bar 12 , located on either side of tow bar 18 . further , the components of the drive mechanism are variable , depending upon many factors , including planter configuration and size . while only certain features of the invention have been illustrated and described herein , many modifications and changes will occur to those skilled in the art . it is , therefore , to be understood that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the invention .

the invention provides an innovative yet straightforward approach to driving the seed distribution system in planters which feature hinged winged extensions . the flexibility of the hinged winged extensions may allow the planter to adjust to the contours of a field and to fold to facilitate transport of the planter . in one embodiment , for example , the invention may provide a mechanical coupling between several sections of a seed drive shaft which may support and be driven by a hydraulic motor for each of the winged sections . the seed drive system may also be coupled to row units to synchronize and power the distribution of seeds by the planter .

the object of the game is to accumulate $ 300 , 000 cash . money is earned by successfully bidding on construction jobs and then satisfying the terms of the contract in order to receive payment , including profit . as a minimum , two players are required for the game , but up to six players may participate . the playing board for the game is illustrated in fig1 and 2 . the rules of the road for movement of playing pieces in the game will now be explained by reference to fig2 . as shown in fig2 , there is a simulated roadway for movement around the board , in both directions , shown with arrows on two continuous paths around the board . address spaces on the board are located on both sides of the roadway , and designated by a street number and corresponding street name . located at the four corners of the board are the four store spaces , where players must land their simulated vehicles in order to purchase the four different types of materials . located on the roadway are eight of each of the two types of card spaces , called “ bid ” and “ life .” playing pieces ( simulated trucks ) must travel on the roadway , in either direction , and can stop , or “ land ” on store and address spaces . the game begins by naming one player , or a separate person who is not a player , to be the banker . each player selects a color and starts with two trucks 108 . each player selects a home address on the game board and places his / her trucks 108 there . the players may select any address space on the board for their home address . each player starts with $ 50 , 000 in the following denominations : one ( 1 ) $ 20 , 000 . 00 bill , two ( 2 ) $ 10 , 000 . 00 bills , one ( 1 ) $ 5 , 000 . 00 bill and five ( 5 ) $ 1 , 000 . 00 bills . during the game , players must keep their cash exposed to the view of the other players . at any time in the game , any player may ask another what their total cash amount is and that player must answer honestly . each player has a bid board 110 . each player rolls one die and the player with the highest roll goes first . play then rotates to the left . the players must remember which player went first as the remaining players get one last turn when a player achieves $ 300 , 000 . the player rolls as many dice as he / she owns trucks 108 . players are allowed to make transactions at any time during their turn , including before they roll the dice , after rolling the dice but before moving any trucks 108 , after moving any and all of the dice amounts , and at the end of their turn . the player &# 39 ; s turn is over when all dice have been used and the player states that he / she wishes to make no more transactions . for example , a player may use one die to move a truck 108 to land on a space marked bid on the board 108 , at which time bids will be taken , and then proceed to use another die , and so on . six dice are provided and the player rolls the appropriate number of dice one time at the start of a turn . there is no need to roll the dice more than once on any given turn . as shown in fig1 , trucks 108 must travel on the right side of the road . the trucks 108 may cross dotted lines but never solid lines . no more than two trucks 108 may occupy a road space at any one time . if a player lands on a road space already occupied by two trucks 108 , his / her truck 108 must land on the next road space directly ahead . each die rolled can be used by the player to move any truck 108 . for example , a player with three trucks 108 can move each truck 108 one die amount , or one truck 108 one die amount and one truck 108 two dice amounts , or one truck 108 all three dice amounts . die amounts must be used as whole and can never be split . exact rolls of the dice are not required to land on a store or address space on the board 10 . for example , if a roll of three is required to reach such a destination , and a five is rolled , that truck 108 may proceed to that destination and “ land ”, or stop , there . however , the remaining amount from that die is forfeited and cannot be used for any other purpose . any truck 108 that reaches a store or address space ‘ lands ’ there . at no time can a player use a store or address space as an interim space in a move . the players may only land on address spaces for which they have a contract , or on their selected home address . exact rolls are required to land on bid or card spaces . when a truck 108 moves two dice amounts without stopping , the player does not ‘ land ’ on the space that is the first die amount , he / she only ‘ lands ’ on the final space . purchasing additional trucks 108 : the players may purchase additional new trucks 108 at a cost of $ 25 , 000 . the maximum number of trucks 108 that each player may own is six . to purchase a new truck 108 , a player pays the bank $ 25 , 000 and the truck 108 is placed at his / her home address . purchasing materials : a player must land on the appropriate store in order to purchase materials . the various materials 100 , 102 , 104 , 106 are illustrated in fig3 , 5 and 6 . fig3 illustrates plumbing materials 100 . fig4 illustrates electrical materials 102 . fig5 illustrates concrete 104 . fig6 illustrates lumber 106 . each truck 108 can carry a maximum of twenty units of material . each unit of material costs $ 1 , 000 . when ten units are purchased at one time , a 10 % discount applies and the player pays $ 9 , 000 for the ten units . when a player lands on a store space , he / she does not have to purchase materials at that time . the players may purchase materials during any turn when the player &# 39 ; s truck 108 resides on that store space . the player then places the materials on that truck . 108 delivering materials : when a player lands on an address space for which he / she has a contract , that player may immediately unload the materials needed for the contract . fulfilling a contract : a contract is defined as fulfilled when all of the materials listed on the contract , or bid card , are delivered to the address on the contract , or bid card . as soon as all the materials listed on the contract are delivered by the player to the contract address , the contract is turned into the bank . the bank verifies that the contract is filled , and pays the player the bid amount . the materials accumulated by the player for that job are then returned to the store stocks . bids : when a player lands on a bid space on the board shown in fig1 , the top bid card is turned over for all players to see . the bid cards 110 a through 110 vv are illustrated in fig9 a through 9 vv . each bid card has a base amount , a list of required materials , and an address . the base amount is the total cost of the materials . materials are listed as whole numbers of units , and each unit costs $ 1 , 000 . each player must decide , in complete secret , what he / she will bid for this job and write that amount on his / her bid board . the bid amount is the amount that the job would be contracted for . all bid amounts must be in whole thousands of dollars . when all players have written their amounts , all players simultaneously expose their bid amounts for all to see . as an alternative , the players may opt to use a timer if they want to limit bidding time . the lowest bidder is awarded the job at his / her bid amount . the bid amount is attached to the bid card , thus forming a contract which is given to that player . bid amounts are attached to bid cards by using bid tabs , or clips . these are just solid paper clips with numbers on them , allowing for the various amounts to be physically attached to the bid card . bid cards with such attached amounts are then referred to as contracts . this player must then deliver all the materials listed on the contract to the address on the contract . when he / she completes delivery , he / she is awarded the contract amount , or the amount he / she bid on the job . a player must have at least the base amount of money on the bid card in his / her possession in order to bid . if he / she does not , he / she cannot bid on that job . players with at least the base amount of cash on hand must bid . the maximum allowable bid is three times the base amount . the minimum allowable bid is equal to the base amount . however , it would not be wise to bid at the base amount because the player would have to do all the work to fulfill the contract and would then receive the same amount he / she spends on materials . thus , the player would make no profit for all his / her work on the job . in rare cases where a player holds discount cards or has leftover materials , he / she may wish to bid the minimum allowable bid amount . the average bid is two times the base amount . for example , for a job with a $ 50 , 000 base amount , the average bid is $ 100 , 000 . this represents a reasonable profit for purchasing all the materials and providing all the labor to deliver them to the job site and fulfill the contract . no player can ever share his / her bid , or in any way indicate his / her bid , to any other player before all the bids are simultaneously exposed . this would be considered cheating and is absolutely forbidden . the maximum number of contracts any player may possess at one time is three . when a player possesses three contracts , he / she may not bid on any new jobs . in the case of a tie for the lowest bid , each tied player rolls one die and the highest die wins the contract at the amount he / she bid . cards : when a player lands on a card space , labeled “ life ” in fig1 and 2 , he / she must turn over the top card and immediately do whatever the card says . the card is then placed on the bottom of the deck , except discount cards . the cards , 112 a to 112 dd , are illustrated in fig1 a through 10 dd . discount cards : discount cards are retained by the player who draws them , for his / her use at any subsequent material purchase transaction . these cards can only be used for one purchase . in the case where a discount amounts to an amount that is not in whole thousands of dollars , that discount figure is rounded down to the nearest whole thousand amount . for example , a 50 % discount applied to a $ 5 , 000 purchase results in a $ 2 , 000 discount for a final cost of $ 3 , 000 . discount material offers come with free delivery . to use a discount card a player purchases the desired material amount by paying the bank , the materials are then placed at the address space the player wishes , and the card is returned to the bottom of the deck . note that the free delivery is to one address space only . if a player wishes to apply the discount to additional materials for other locations at the time of his / her purchase , he / she must first land his / her trucks 108 to be loaded at the store space . the discount is then applied to the whole purchase and materials are placed at the one address space and in the trucks 108 at the store , accordingly . if a player lands on a card space and the card tells him / her to pay an amount and he / she does not have enough cash , that player must pay the bank what he / she has , bringing his / her cash total to zero , and can continue to play . winning the game : the first player to possess $ 300 , 000 cash is the winner . when a player achieves this amount , and there are players whose turns came after that player in the first round of the game , those remaining players get one last turn . for example , if the player who went first originally achieves $ 300 , 000 , all remaining players get one last turn . if a player in a game of four who went third in the original round achieves $ 300 , 000 , then only the fourth player gets one more turn . if any other players achieve $ 300 , 000 on their last turn , players count their money and the player with the highest total amount is declared the winner and game is over . those of ordinary skill in the art will recognize that the embodiments just described merely illustrate the principles of the present invention . many modifications may be made thereto without departing from the spirit and scope of the invention as set forth in the following claims .

a business method game for bidding on and fulfilling construction contracts is disclosed . the method is implemented through a board game with various implements such as dice , playing cards , vehicles and script money .

the instant invention provides a method whereby a polyurethane mix can be applied directly on a polycarbonate surface where it foams and adheres without additional surface coatings . another aspect of the instant invention provides articles comprising polycarbonate foamed with polyurethane foam . the manufacture of polycarbonate is well known in the art . there is no limit on the polycarbonate that can be employed in the instant invention . appropriate polycarbonates for use in the instant invention include those materials that comprise structural units of the formula ## str1 ## wherein r 1 is a divalent organic radical . suitable r 1 values include ethylene , propylene , trimethylene , tetramethylene , hexamethylene , dodecamethylene , 1 , 4 -( 2 - butenylene ), 1 , 10 -( 2 - ethyldecylene ), 1 , 3 - cyclopentylene , 1 , 3 - cyclohexylene , 1 , 4 - cyclohexylene , m - phenylene , p - phenylene , 4 , 4 &# 39 ;- biphenylene , 2 , 2 - bis ( 4 - phenylene ) propane , benzene - 1 , 4 - dimethylene and similar radicals such as those which correspond to the dihydroxy compounds disclosed by name or formula ( generic or specific ) in u . s . pat . no . 4 , 217 , 438 , the disclosure of which is incorporated by reference herein . also included are radicals containing non - hydrocarbon moieties . these may be substituents such as chloro , nitro , alkoxy and the like , and linking radicals such as thio , sulfoxy , sulfone , ester , amide , ether and carbonyl . most often , however , all r 1 radicals are hydrocarbon radicals . preferably r 1 is aromatic . more preferably , the aromatic r 1 radicals have the formula wherein each of a 1 and a 2 is a monocyclic divalent aromatic radical and y is a bridging radical in which one or two atoms separate a 1 from a 2 . the free valence bonds in formula ii are usually in the meta or para positions of a 1 and a 2 in relation to y . in formula ii , the a 1 and a 2 values may be unsubstituted phenylene or substituted derivatives thereof , illustrative substituents ( one or more ) being alkyl , alkenyl , halo ( especially chloro and / or bromo ), nitro , alkoxy and the like . unsubstituted phenylene radicals are preferred . both a 1 and a 2 are preferably p - phenylene , although both may be o - or m - phenylene or one o - or m - phenylene and the other p - phenylene . the bridging radical , y , is one in which one or two atoms , preferably one , separate a 1 from a 2 . it is most often a hydrocarbon radical and particularly a saturated radical such as methylene , cyclohexylmethylene , 2 - 2 . 2 . 1 !- bicycloheptylmethylene , ethylene , isopropylidene , neopentylidene , cyclohexylidene , cyclopentadecylidene , cyclododecylidene or adamantylidene , especially a gem - alkylene ( alkylidene ) radical . also included , however , are unsaturated radicals and radicals that contain atoms other than carbon and hydrogen ; for example , 2 , 2 - dichloroethylidene , carbonyl , phthalidylidene , oxy , thio , sulfoxy and sulfone . for reasons of availability and particular suitability for the purposes of this invention , the preferred radical of formula ii is the 2 , 2 - bis ( 4 - phenylene ) propane radical , which is derived from bisphenol a and in which y is isopropylidene and a 1 and a 2 are each p - phenylene . for use in the instant invention , the polycarbonate must have at least one type of nucleophilic reactive radical on its surface . any nucleophile capable of reacting with the diisocyanate of the polyurethane mix can be provided on the polycarbonate surface as a nucleophilic reactive radical . suitable nucleophilic reactive radicals include , but are not limited to , amino , hydroxyl , amide , and thiol groups . preferably , the nucleophilic reactive radical is a hydroxyl group . the nucleophilic reactive radicals can be provided by processing as the polycarbonate is manufactured . nucleophilic reactive radicals can be formed on the polycarbonate during polymerization . for example , bisphenol a polycarbonate that has been produced by a melt transesterification process contains hydroxyl nucleophilic reactive radicals . a polycarbonate that has nucleophilic reactive radicals can be blended with an inertly capped polycarbonate , which does not include any nucleophilic reactive radicals . it is not necessary that all of the polycarbonate in a blend possess nucleophilic reactive radicals . it is also possible to obtain nucleophilic reactive radicals by treating the polycarbonate after it is polymerized . for example , surface hydroxyl radicals can be formed on inertly capped polycarbonate by hydrolysis . the polycarbonate surface can be treated with an alkaline reagent , such as koh , to generate nucleophilic reactive radicals . after polymerization , polycarbonate can also be subjected to processes such as reactive extrusion . during reactive extrusion , nucleophilic materials with nucleophilic reactive radicals , such as hydroxy groups , can be added to polycarbonate as it is extruded . during extrusion , the nucleophilic materials react with the polycarbonate , generating surface nucleophilic reactive radicals on the extruded polycarbonate . polycarbonate that has undergone a redistribution process after polymerization , such as that described in u . s . pat . no . 5 , 414 , 057 , can be provided with nucleophilic reactive radicals . redistribution is a process whereby a polycarbonate having an initial weight average molecular weight is reformed into a redistributed polycarbonate composition having a weight average molecular weight which is different from the initial molecular weight . this can be accomplished by melt equilibrating a polycarbonate in the presence of a carbonate redistribution catalyst . polyurethane foam is generally produced by methods well known in the art . typically , a polyurethane mix is generated by combining at least one polyol , typically a poly ( oxyalkylene ) polyol , and at least one diisocyanate , such as toluene diisocyanate or 4 , 4 &# 39 ;- diphenylmethane diisocyanate , commonly known as methylene diphenyl diisocyanate , in proportions effective to generate the desired product . also , catalysts , surfactants and blowing agents are typically present in the polyurethane mix . for use in the present invention , the polyol and diisocyanate must be mixed in a proportion such that the isocyanate index is greater than 82 . more preferably , the isocyanate index is 90 to 110 . the polyurethane mix can be applied to a surface of the polycarbonate by any means well known in the art , such as pouring and spraying . the polyurethane mix then reacts to produce polyurethane foam . as the mix foams , it adheres itself to the polycarbonate . the necessary reaction conditions , such as time and temperature , are well known to those skilled in the art . a skin can then be applied to the foam surface so that the foam surface is entirely covered . this skin can comprise materials such as polyvinyl chloride . this skin can be attached to the foam by methods well known in the art . adhesion of polyurethane foam to two grades of bisphenol a polycarbonate ( polycarbonate ) was evaluated . one grade is a low molecular weight ( low mw ) grade ; the other is a high molecular weight ( high mw ) grade . the results are described in the following table . in each case , the polyurethane mix , from textron automotive interiors of farmington , n . h ., which comprised uf1010b polyol and p100 diisocyanate , was poured onto the polycarbonate and allowed to foam . the resulting polyurethane foam had a density of approximately 6 lb / ft 3 . the foam was then peeled from the polycarbonate surface . the polycarbonate / foam adhesion was rated qualitatively from &# 34 ; 5 &# 34 ;, which indicates good adhesion , to &# 34 ; 0 &# 34 ;, which indicates that no adhesion existed between the polycarbonate and foam . the results clearly indicated that the adhesion depended on the concentration of nucleophilic reactive radicals on the polycarbonate surface and on the ratio of reagents in the foam mix . under the standard foaming condition ( isocyanate index of 92 ), the inertly capped polycarbonate ( lexan ® 121 polycarbonate and lexan 101 polycarbonate , products of general electric plastics , pittsfield , mass .) showed little adhesion to the foam . only the hydroxyl nucleophilic reactive radical -- enriched lexan lx x28 polycarbonate had sufficient adhesion to the foam to qualify as a &# 34 ; pass &# 34 ;. the lexan lx x32 polycarbonate , which had fewer hydroxyl end groups than the lx x28 polycarbonate , showed marginal adhesion to the foam . thus , under the standard foaming condition ( isocyanate index of 92 ), only polycarbonate with nucleophilic reactive radicals showed any adhesion to the polyurethane foam . however , once the isocyanate index was increased , the polycarbonate / foam adhesion improved drastically . while all four materials showed improved adhesion , particularly at an isocyanate index of 120 , the lx materials with their nucleophilic reactive radicals demonstrated better adhesion than the inertly capped materials at the higher isocyanate index of 105 . polycarbonate with nucleophilic reactive radicals can provide better adhesion than inertly capped polycarbonate to polyurethane foams with isocyanate indices of 92 and 105 , which are , respectively , the same as and slightly higher than the standard indices currently used by the automotive industry . ______________________________________ isocyanate index 120 105 92 82______________________________________lexan 121 0 % oh , pass ( 5 ) pass ( 4 ) fail ( 1 ) fail ( 0 )( control ) low mwlexan lx x32 16 % oh , pass ( 5 ) pass ( 5 ) marginal ( 2 ) fail ( 0 ) low mwlexan 101 0 % oh , pass ( 5 ) pass ( 4 ) fail ( 1 ) fail ( 0 )( control ) high mwlexan lx x28 23 % oh , pass ( 5 ) pass ( 5 ) pass ( 4 ) fail ( 0 ) high mw______________________________________

a method improves the adhesion of polyurethane foam to polycarbonate by providing reactive groups on the polycarbonate surface . the adhesion is further improved by utilizing a polyurethane mix with an isocyanate index greater than 82 . articles comprising polycarbonate and polyurethane foam adhered to the polycarbonate by the method of the instant invention , such as automobile dashboards , are also provided .

fig1 is a perspective view of the first embodiment of this apparatus of this invention , 10 . the apparatus has an upper body 11 a and a lower body , 11 b . the upper body will be described first . the apparatus 10 has a pair of spaced side walls 15 a and 15 b , the back wall 25 is seen in fig2 , a top wall 13 is hingedly connected to the back wall by hinges 23 . a front wall 17 is spaced from the back wall and is connected between the two side walls 15 a and 15 b . optional round corner bracing can be employed for both strength and aesthetics at all four corners where the front and rear panels meet the sides . the lower body 11 b has spaced side walls 21 a and 21 b of spacing equal to that of the upper body side walls 11 a & amp ; 11 b and each lower body sidewall may be integrally formed with the upper body side wall as may be desired . as can be seen from fig2 , the back wall extends the full length of both the upper and lower bodies . the front wall 22 is seen in both fig1 and 17 and it is connected at the front edge of said lower side walls to both of the spaced lower body side walls . note that the lower body side walls extend forwardly of the side walls of the upper body . an access shelf 19 extends forwardly from the base of the front of the upper body to the top edge of the front of the lower body . the access shelf 19 is coextensive with the side walls of the apparatus laterally . a pair of spaced preferably round cutouts 20 provide access to both a water bowl and a feed bowl , both of which will be discussed infra . the discussion now turns to fig3 , which is a top perspective view of the interior of the upper body of this embodiment . as can be seen the space between the two side walls 15 a & amp ; b is divided into three major sections of about the same size from left to right . the middle section is divided in half . the left section is laterally defined by the left side wall 15 a and the left stabilizer - divider , hereinafter to abbreviated as ( s - d ), here ( s - d ) 27 l . a spaced ( s - d ) is disposed inwardly an equal amount from right side wall 15 b to define the right chamber . that ( s - d ) is designated 27 r . while the ( s - d ) that extends downwardly vertically part way toward the lower body that is in the middle is designated 27 c for central . the upper edge of each of the outer ( s - ds ) is the upper edge of the front and rear walls , while the center stabilizer - divider commences spaced down from the top edges of the front and rear walls of the upper body . each of the two outer ( s - d ) s extend downwardly to an impact shelf 33 that is part of the assembly 35 . the impact shelf is disposed normal to the ( s - d ) and butts up to it when the vessels with the first wicking means defined as a wick and attached to a weight , have water or other fluid such as milk therein . see fig3 . the movement of and structure of the first retainer assembly 35 will be discussed infra in the discussion of fig6 . note that the ( s - d ) s 27 l and 27 r terminate just above the impact shelf 33 , which extends outwardly beneath said respective ( s - d ) to be designated element 37 . the overall designation is food hopper 30 . lateral dividers 29 c and 9 cc normally bifurcate the central areas between the left and right ( s - d ) s . these lateral dividers preferably commence at an elevation equal to that of the ( s - d ) 27 c lateral dividers 29 l and 29 r are each spaced down even further from the top edge of the apparatus 10 , and also extend laterally between their respective stabilizer - divider and a side wall to divide the outer areas into two chambers . in three of the four central zones 28 that lie between the ( s - d ) 27 l and 27 r , an incline plane 31 diverges downwardly from the middle stabilizer - divider 27 c . the incline plane of the left front zone 28 , defined by 27 l , 27 c , 29 c and the front wall 17 has had the incline plane 31 removed to reveal the space below each of the inclined planes 31 . the space or opening that is visible in fig3 is designated 34 . in each of the outer four chambers there is disposed a retainer assembly 35 one of which is seen up close in fig6 . further discussion on the retainer assembly 35 will follow infra . in each first and second retainer assembly sits a water vessel 80 having content markings 82 scrawled or etched into the side wall . see fig4 specifically . a simple plastic beaker wider at the top than at the bottom will suffice for each water vessel . each of the two left vessels each carry a weight 82 such as a stainless steel or brass nut 82 to which is tied a cotton or other suitable material wick of a predetermined size . more on the sizing of the first and second wicking means infra . the reader should also note that the vessels on the right side of the apparatus specifically have a wick extending therefrom but are not seen in this view . suffice it to say that the first wicking means are associated with the first vessels for food delivery and the second wicking means are for fluid or water delivery for drinking by the animal . in fig5 , one of the vessels 80 a used in the right side of the apparatus is shown . this vessel 80 a also has volume markings thereon designated 82 . in the base of the vessel , while here again can be a conventional polyethylene plastic beaker , a series of apertures 84 are seen . these permit any fluid placed in the vessel 80 to slowly drain out the bottom of the vessel . due to cost considerations to drill tiny predefined apertures on a repetitive basis for commercial product quantities , the use of the wick as the fluid draining means is preferred here as well . the reader is now referred to fig6 , where the front left section is seen , and specifically the first retainer assembly , 35 . the first retainer assembly comprises a flat piece of wood , metal or plastic , a plate 37 , which serves as a counterweight to the retainer ring 40 , when said ring carries a vessel , which plate has a front face 37 f and a pair of opposed pins 38 which are designated pivot points . an interrupted ring 40 having two points 40 p are engaged by friction or retained by adhesive into bores not seen in face 37 f . as mentioned supra , plate 37 acts as a counter weight to loaded ring 40 . note the position of ring 40 in fig3 , it has swung upward since no vessel 80 or 80 a is present . contrast the position in fig6 with the position of the ring 40 in fig3 . a view of fig2 will show that the points 40 p of ring 40 while directed straight into the face 37 f of the plate 37 , the rest of the ring 40 is canted . this plate 37 is seen to exist on both sides of the outer stabilizer divers 27 a and 27 c . the portion of plate 37 that serves as the impact shelf for food falling down is designated 33 and is disposed on the interior side of ( s - d ) 27 l . reference is made to the imaginary line 90 in fig2 . this explains why the impact shelf which was discussed previously has a lower designator number ; namely , 33 . see fig7 wherein the plate in the three areas where vessels are present . here the left front vessel is missing and the impact shelf 33 is seen to have relocated downwardly due to the absence of vessel 80 . reinforcement of these points may be gleaned from fig8 where the impact shelf 33 portion of pivot bar 37 is seen on both sides of stabilizer divider 27 l . fig8 also shows the corner brace 43 that can be employed for both aesthetic and structural integrity purposes , rather than having a butt joint of two sheets of wood or plastic or metal at the corner of the apparatus . reference is again made to fig7 for space 34 which is the space below each of the incline planes 31 . space 34 is also seen in fig9 since the counterweight has repositioned itself in the absence of a loaded vessel . wall 58 is a vertical wall disposed spaced from outside wall 15 a and which may serve as a rest for vessel 80 when a vessel is disposed in ring 40 . this wall 58 may be seen in fig6 , 9 , and 22 among others . it can be held in place by any conventional construction means . wall 58 also serves to direct pellet animal feed into food receivers 16 . wall 58 commences from beneath lateral divider 29 l and is normally disposed . wall 58 terminates just above receivers 29 as per fig1 and 17 . the discussion now moves to the exterior of the apparatus . thus , reference is made to fig1 . here the access shelf 19 is seen normally disposed relative to lower front wall 22 . a pair of circular cutouts 20 communicate indirectly with food dish and water bowl 36 . the indirect communication will be discussed infra with respect to the elements beneath access shelf 19 . front wall 17 is seen to have a pair of spaced cutouts 17 c , to accommodate the shape of quoit shaped annular members 16 which communicate with food receiver 42 and water receiver 42 respectively . these annular receivers 16 will be discussed relative to figure . also seen in fig1 are food pellets 120 and liquid such as milk or water 121 in respective separate bowls . as can be seen , a portion of one quoit - shaped receiver overlies part of the respective cutout 20 which permits access by the animal to the food or liquid . fig1 , 12 & amp ; 16 should all be viewed together . in fig1 , a top perspective view of the interior of the lower body , as well as in fig1 a side perspective , one can see the “ guts ” of this apparatus which is designated as base 12 seen in fig1 among others . base 12 has front , rear and spaced side walls , open at the bottom and has a top surface 19 with a pair of cutouts 20 therein . disposed beneath the base is a tray 14 , which is a conventional plastic or metal painting tray with upstanding walls . tray 14 is seen also in fig1 wherein the ridged upper inclined surface 24 is seen , which surface leads to a lower planar horizontal section . a pair of spaced side by side bowl like elements each support one of the quoit - shaped annular members 16 thereon . these bowl - like elements have a central opening 16 c through which food and water flow respectively from up in the apparatus down to the respective food and water receiver 42 disposed beneath the member 16 f . food receiver 42 l has an interrupted side wall where the bowl - like receiver 42 intersects dish 36 which also has an interrupted sidewall . due to the interruptions , food can fall from the receiver 42 into the bowl 36 . see also fig1 . on the fluid side , only the wall of the annular member 16 l , wherein l is for liquid , is interrupted as can be seen in fig1 . the bowl like receiver 42 r for the fluid has its side wall intact , but for the bores 50 which communicate with liquid bowl 26 l . see fig1 . surround 18 , seen in fig2 and elsewhere is part of the support 51 . the surround 18 , is a planar member that is disposed beneath the access shelf 19 has similar cutouts 20 ′ which are sized and shaped similar to the cutouts 20 with which they communicate . that is openings 20 are respectively above openings 20 ′ because the surround 18 is disposed directly beneath the access shelf 19 . the support 51 comprises the surround 18 which is supported by a w - shaped inside framework having a pair of spaced opposed sides 52 — fig1 , a front or base member 54 ,— fig1 and a center support frame member 56 , whose edge is seen also in fig1 . as can be seen the w - shaped frame , unnumbered since never shown as an entity in the figures , rests within the tray 14 to support surround 18 , which optionally may be attached thereto by nails , staples , screws etc . the width of surround 18 is equal to the width of tray 14 . the planar surround , 18 , while having outer edges that are normal to its base , includes a pair of opposed mirror image leading arcuate edges 18 c and a central section 26 with a pair of arcuate edges 18 cc . the curvature of the arcuate edges 18 c and 18 cc is mated to the curvature of the quoit - like annular members 16 and serve as an alignment surface for the placement of the annular members 16 to butt up against . thus it is seen that as food drops down from the top , it enters receiver 42 f through the annular member 16 disposed on top of the receiver and since the surface 24 of tray 14 slopes forwardly , the receivers therefore are disposed at an incline rather than flat . thus the food pellets fall forwardly from the receiver 42 f for food , into the bowl 36 adjacent thereto by gravity as well . fluid takes a similar path . it enters through opening 16 c into the annular member 16 to reach its receiver 42 l for liquid , which is also inclined due to the inclination of surface 24 upon which it rests . the fluid then flows through bores 50 into the liquid bowl 36 l . see fig2 as well which shows the pellets flowing into the food bowl and the fluid coming through the bores 50 . fig1 is a top view of the center of this apparatus . the four zones 28 have previously been defined . this view being a bit close up shows the open space 34 below the impact plane 31 missing from the front left zone . fig1 , fig1 , fig1 and 22 should all be considered together , in order to understand the path that the food pellets traverse on the way down to annular member 16 and from there to end up in the bowl 36 as noted supra . in fig1 the upper housing is seen removed from the tray 14 which is seen in the background . the rear wall 25 is seen connected to the upper and lower side walls and the braces 43 are also seen in this figure . internal wall 58 is seen to terminate prior to the bottom of the rear wall as per fig1 . this is because of the elevation of the annular member 16 to which internal wall 58 leads and because the purpose of wall 58 is to direct food into the annular member 16 directly below . the small food director 47 is a planar member connected to internal wall 58 , rear wall 25 , and large food director 45 . its purpose is to receive food pellets that fall through space 34 when the impact shelf is down due to no fluid in the vessel 80 . food pellets impact the food director 45 and fall into annular member 16 . see fig2 where the left rear first retainer assembly has been removed for ease of understanding of the travel path of the food pellets . small food director 47 is mounted at about a 45 - degree angle forwardly down . large food director 45 is disposed between the front and rear walls at a leftwardly 45 - degree angle downward . its lower edge between the front and rear walls terminates at about the same elevation as small food director 47 . a gap 49 between the two food directors aforementioned is where the food pellets descend . large food director 45 commences immediately beneath right stabilizer divider 27 r , and serves to receive food pellets from the right two zones 28 , denoted in fig3 & amp ; 22 and works in conjunction with the small food director 45 to deliver food pellets to the annular member 16 . the reader should again note fig1 wherein only the four zones 28 are seen . while not specifically defined separately , it is readily understood that they are left front , left rear , right front and right rear . front is the direction of the forward extension of the lower body that holds the two bowls . from fig1 , 14 and 17 it can be seen that the path of the food pellets is not the same for each of the four zones . one can envision the placement of the annular receiver 16 substantially directly below the front - left zone per fig1 . food pellets from the front left zone 28 after impacting the inclined plane 31 , then the pivot bar 37 , fall into space 34 and then drop directly down into annular member 16 through the gap seen in fig1 and 17 , which gap is in front of small food director 47 . food pellets from the left rear zone after impacting elements 31 and 33 would fall onto small food director 47 and be directed forwardly into annular member 16 . food pellets from the right rear zone 28 would , after impacting elements 31 and 33 , are angularly directed to the large food director 45 and then into annular member 16 . food pellets from the right front zone , after impacting elements 31 and 33 fall through the respective space 34 onto large food director 45 and then into the annular member 16 . the discussion now moves to the filling of the fluid bowl 36 l . as may have been mentioned , the path into the bowl 36 for fluid is the same as for pellets in part . when the fluid falls it enters into annular member 16 , through opening 16 c for delivery into receiver 42 siting on an incline on tray 14 , and flows through the bores 50 into the bowl 36 l by gravity . one should remember that fluid can leave the vessel for the watering side of the apparatus through the use of gravity fed apertures as discussed above or by use of a wick also discussed above . now the discussion relates to getting the liquid to the annular member 16 . as can be seen from fig5 & amp ; 14 , and fig1 & amp ; fig1 , the vessel 80 has bores or holes 84 in the base thereof such that water placed in the vessel will eventually but slowly drip through the series of holes 84 and fall directly downwardly into annular member 16 below . thus the placement of the annular member and the receiver 42 must be coordinated to ensure that the gravity flow of fluid goes directly into the annular member 16 . wick placement may be less precise but should be net . from fig3 , 4 , 8 , and 23 it is noted that the weight , which can be a ½ inch stainless steel or brass nut to avoid water corrosion , has a wick 83 secured thereto . the wicks employed here may be cotton , polyester or a cotton blend among other fabrics and usually of a length about eight to ten inches long . wicking action is well known and need not be discussed in detail . in any event , by placement of the end of the wick below the bottom of the respective vessel 80 , fluid will flow along the wick and drop down onto the plastic tray 14 for temporary storage until disposed of . since the food receiver 42 and the food bowl are made from materials that are water impervious , the food pellets will not be made soggy . provision can be made for fluid to enter into the rear of the fluid receiver 42 by appropriate through bores , such that wick water can be delivered for addition to the fluid bowl 36 . by careful selection of the wick as to the material chosen and the number of strands and their diameter , time can be adjusted as to when the vessel will be emptied by wicking action . the wick in this application means the total number of strings used as described below . volume control is one reason for the measurement indicia 81 on the side of vessel 80 . the combination of water volume and the size of the wick , and material of the wick control the time for depletion of the water from vessels 80 . thus it is seen to be beneficial to have two different combinations of water volume and wick size and / material , in order to permit sequential addition of food to the food bowl . i have found that by using a finite number of ounces of water and a wick having a specific number of strands , and each wick is of a specific gauge or size in diameter that one can control the number of hours to drain the vessel . this time period can range from 4 hours , to 1 day to 4 days or more as may be desired . for each extra ounce of water added , the additional time to complete drainage is hours . by adding or removing strands to or from the wick , as well as the volume of water utilized , the time of water depletion can be controlled as well . the apparatus of this invention is assembled and disassembled quite easily . the entire body of the apparatus can be seen in fig1 & amp ; 17 . the body is merely lifted vertically from the base 12 which is seen in fig1 & amp ; 12 . the support 51 described supra is readily removable from the tray 14 such that the tray can be cleaned as may be necessary due to the presence of dried fluid other than water such as milk when used as the fluid for the animal . the quoit like annular member 16 is removable from its respective receiver for easy cleaning . when and as the apparatus owner desires to go away for an extended period , he / she places the assembled apparatus at the desired location in the kitchen bath or elsewhere in the household . he / she then places the four vessels 80 and 80 a in their respective assembly receivers 35 and fills the leftwardly ones with water to a desired fullness level as set forth by the indicia 81 on the vessel . a wick 83 chosen specifically for the desired time period , — fig2 — is attached to a nut 82 and placed in each of the two left side vessels with the wick 83 dangling down out of the vessel , as is known to the art . the two filled vessels cause their respective assembly first retainer &# 39 ; s ring to rest horizontally with their respective impact bar 33 up in touch with their respective inclined plane 31 , thereby not creating a space 34 . food pellets 120 are placed into the front and rear left zones 28 . of course food may be placed directly into the food bowl 36 as may be desired for immediate access by the animal . liquid such as water may be placed directly in the liquid bowl 36 l if desired . vessels 80 a are placed in position in their second retainers assemblies 35 , and filled with fluid , usually water . the fluid will immediately commence to drain through the apertures 84 in the bottom of the vessels 80 a downwardly toward the quoit like annular member 16 and proceed downwardly into the bowl 36 l as described supra . meantime back at the food , the water will drain downwardly into the tray 14 and cause the vessels 80 on the left side to drain , which when that condition is reached the impact bar raises creating space 34 such that the stored food pellets can fall downwardly to impact the respective food director ( s ) 47 and the food diverter 45 as discussed above on the way to the food bowl 36 . see also fig1 and 17 . the discussion now moves to the second embodiment , which operates in the same manner using the same principles as the first embodiment . the primary difference is that many of the components of version 2 are molded plastic thus lending itself more to commercial large scale production at reasonable cost . turning now to fig2 one sees a more streamlined structure that falls with in the metes and bounds of this invention . in this second embodiment , rather than employ a wire assembly 35 to hold a separate water vessel 80 , a molded water vessel 180 with an integral or adhesed impact shelf 133 is employed . see fig2 where this sub - combination is illustrated . it is noted that in the second embodiment like elements are designated with like numbers but in the 100 series . thus the designation 180 for the vessel . reference is now made to the engineering drawing of fig2 wherein the operating principle of this invention is illustrated . reference should also be made simultaneously to fig2 , a top perspective view . in fig2 , vessels 180 are seen to be a molded part having a series of spaced raised linear bosses 201 with a channel 202 between each boss . these channels are intended to receive the wick strings previously described to keep them neat and to make sure that they terminate below the vessel without curling upwardly . these vessels include a built in hinge 138 and an impact shelf 133 . the vessel 180 l is seen to contain fluid as designated by the wavy line at the top of the water . for this reason the impact shelf fits tight against the hopper . on the right side for vessel 180 r , the water has drained and thus the pivot member by gravity has swung down . the wicks are not shown in this figure for ease of understanding of the figure . the food delivery element 160 seen in its entirety in fig2 is a funnel having 3 vertical sides normal to each other and the 4 th side while normal to two of the sides to present a rectangular cross section , is an inclined plane 161 . wall or side 161 serves the same function as food diverter 45 and food director 47 in fig1 , and also fig2 . the food delivery element serves the same function as the combination of parts 45 and 47 ; namely to deliver food to the annular ring 15 as seen in fig2 . part 161 is a slot used during assembly of a totally or substantially totally plastic apparatus of the second embodiment and is non - functional with respect to usage and operation . the reader &# 39 ; s attention is directed to fig2 wherein the vessel 180 in the lower right corner of the figure is being held by a person &# 39 ; s finger to simulate the location of the vessel 180 r if it had no water therein as in fig2 . all of the other 3 vessels 180 are in a position similar to 180 l though no water is actually present . thus one cn see the gap between members 131 an 133 as per fig2 . fig2 is a bottom plan view of the tray 114 showing the built in dimples 114 d , or feet for raising the tray off the ground . i have found that by the careful selection of the material for the wicks and the number and size of the wicks , that i can predetermine when the desired amount of water will have exited the vessel 80 and the pivot bar will move too permit food to be delivered vertically . the wicks can be made of silk , nylon , polyester or cotton fibers , but i prefer cotton . # 1 i used increments of 3 strings , ie . 3 , 6 , 9 , and 12 strings of 1 / 16th polyester cord made by wrights , about 18 inches long to control delivery of a 32 ounce cup of food for a large dog . # 2 for a collie who only needed 16 ounce cups of food , and which i refer to as a medium dog , i used size 3 mercerized cotton string also about 18 inches long . the more strings i used , the quicker the water was drained out of the container . 12 strings caused food drop in 1 day , 6 strings 2 days and 3 strings 4 days . it is within the skill of the art based on the information provided to select the thread and number of strings needed for the particular animal and time frame . # 3 for a small dog like a basset , cocker spaniel , who need less food , perhaps 8 oz , the number of strings can be determined . thus 12 strings would drop 8 oz in day and 6 strings in a single day . it is seen that doubling of the number of strings reduces the time frame by 50 %. i found that the ideal string is size 10 mercerized cotton crochet thread made by jp coates . it appears that cotton is a slower to operate wick than is polyester . when placing the string in the water for wicking to transpire , it is important that the length of the string must end below the bottom of the container 80 , otherwise the container will not fully drain . it is also seen that mathematically , that reduction of the water volume will also affect the time frame for food to drop . a 50 % reduction in water volume will reduce the time for a given amount of strings by ½ . it is also within the skill of the art to determine the combination of the number of apertures and the diameter thereof to permit drainage by gravity for any predefined time period . one big problem with using the aperture method of water delivery to the trough for the animal , especially in those situations where the elapsed time is to be relatively long , and the aperture ( s ) are quite narrow , is the presence of calcium and other minerals in the water . the minerals cn precipitate out and clog the apertures , thus leaving the animal thirsty . one can draw the analogy to mineral deposits on the shower door . the high cost of precision drilling , also bears consideration when doing an analysis of cost of production versus marketing price point of the apparatus . it is seen that i have created an animal feeder and waterer , ie , water delivery unit , that can be set to deliver food and fluid to the animal at precise future times by picking the number of strands and fabric of the wicks for vessels 80 for the food , and the diameter of and number of apertures of the vessels 80 a for the delivery of fluid . this apparatus permits the user to go away for a weekend or a brief vacation and know that the cat or dog will be fed , without worrying about batteries wearing out or a power failure taking place . thus it is seen that the release of water by wicking action , from each of the fluid containing vessels causes the respective vessel to lose content mass , ie water . for food delivery , at a critical point in time upon the loss of a finite amount of fluid , the respective second retainer assembly which holds each vessel 80 , for the vessels that serve as timing devices for food delivery , and which retainer assembly is also attached to an impact shelf 33 , actually moves from a first position to a second position , upward of the first position , which movement causes the attached impact shelf to move from a first position which closes off a food bin to a second position downwardly , to provide a gap between the previously touching impact shelf 33 and an adjacent inclined plane 31 to permit food pellets to fall through to the respective gap onto the food diverter 45 or the food director 47 ; and then ultimately through the annular member 16 for delivery to food dish 36 l . water for the water bowl flows in a more direct path . the wicking action removes water from the water from the water vessels and delivers it down to the tray 24 , fig1 for entry through communication bores 50 to the water bowl 36 r . since certain changes may be made in the described apparatus without departing from the scope of the invention herein involved , it is intended that all matter contained in the above description and shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense

a plural day gravity fed animal feeding and watering apparatus . the non - electric apparatus has compartments for food and water . a timer that uses the principle of wicking action permits food and water to enter respective dishes . alternatively , mass reduction via disposition of water in a bored container can deliver water to the water bowl . the mass of water disposed in a container is to be reduced by the wicking action to reduce fluid mass . for food delivery , the mass of water holds an impact plate upward but when the mass is reduced by the wicking action , the weight will discontinue hold up the impact plate and a gap opens thereby allowing food to exit through the apparatus into the food dish . selection of wicks controls the time period before the gap opens . each distinct areas for dispensing food or drink can be controlled separately by the proper choice of wick .

this invention will now be described in detail with the help of non - limiting examples showing several embodiments . naturally one can make either a sheet of biomaterial which will then be cut out according to the desired patch dimensions and shape , or directly a biomaterial having the shapes and dimensions of the patch . the following examples relate to the latter possibility , with the desired patch being selected as rectangular and having dimensions of about 5 × 7 × 0 . 08 cm . starting from an acid type i , iii , or i + iii collagen solution one makes a precipitation , preferably with the help of sodium phosphate . the precipitate is then frozen and freeze - dried . the obtained compress is then packed down so as to make the fibrous layer which then has the appearance of a thin dehydrated sheet of neutral ph , porous and very dense . as a variant , starting from a neutral type iv collagen solution which may contain a curing agent such as collagen oxided with periodic acid and possibly glycerin , one freezes and freeze - dries , then packs down the obtained compress so as to obtain the fibrous layer . 1 volume na 2 hpo 4 ( 0 . 2m , ph 7 . 5 ) is mixed with 9 volumes of an acid iii + i collagen solution ( collagen iii + i prepared according to the process described in french patent application no 2 597 499 ) at a concentration of 0 . 125 % in distilled water at 20 ° c . a precipitation follows . the precipitation lasts between 4 - 15 hours and the precipitate is collected by centrifugation . the precipitate is then adjusted to a concentration of 0 . 5 - 3 % collagen and 0 . 5 - 3 % glycerin before being frozen and freeze - dried . the obtained compress ( dimensions 5 × 7 × 0 . 8 cm ) is packed down to yield a fibrous , scarcely hydrophilic sheet ( dimensions 5 × 7 × 0 . 08 cm ). into an acid iii + i collagen solution ( collagen iii + i prepared according to the process described in french patent application no 2 597 499 ) at a concentration of 0 . 125 % in distilled water at 20 ° c ., is added , with shaking , a periodic acid solution so as to obtain a final concentration of 0 . 002m . after shaking for 2 hours at room temperature na 2 hpo 4 ( 0 . 2m , ph 7 . 5 ) is added in an amount of 9 volumes of iii + i collagen for 1 volume of na 2 hpo 4 . a precipitation follows . the precipitation lasts between 4 - 15 hours and the precipitate is collected on nylon cloth or by centrifugation . a further step for washing the precipitate may be added after this step . this relates to bovine type i collagen . one resumes example 1 . this relates to bovine type i collagen as cured by periodic oxidation . one resumes example 2 . one starts from a neutral aqueous solution containing 2 % glycerin and 2 % non - oxided human type iv collagen . one freezes and freeze - dries , then packs down the obtained compress . one starts from an aqueous solution containing 2 % glycerin and 2 % collagen , that is to say 8 volumes non - oxided human type iv collagen for 2 volumes oxided human type iv collagen . one freezes and freeze - dries , then packs down the obtained compress . one starts from an aqueous collagen solution obtained from a 1 % oxided human type iv collagen solution to which human type i + iii collagen has been mixed , in the form of fibrils or particles , at a concentration of 10 - 30 mg / ml . one freezes and freeze - dries , then packs down the obtained compress . onto a very dense collagen sheet , cured or non - cured , described above , are cast : 2 - 10 ml of a mixture of an aqueous human collagen iv solution at a concentration which may reach 5 % weight / volume , and another oxided human collagen iv solution ( oxided collagen according to the process described in french patent application no 2 601 371 ) in the respective proportions of 0 to 100 % after dehydration under a sterile laminar flow hood , a biomaterial made up of collagen only is obtained ; this biomaterial is then sterilized ; these dehydration and sterilization steps will not be repeated in the following examples ; they will be understood . in the following examples , the smallest concentrations ( 0 . 2 - 1 %) are preferred for cold collagen solutions and the highest concentrations ( 1 - 5 %) may be used for tepid gelatin solutions . 2 - 10 ml of a non - oxided human collagen iv solution at a concentration of 0 . 2 - 5 %; 2 - 10 ml of an oxided human collagen at a concentration of 0 . 2 - 5 %; 2 - 10 ml of a solution containing 60 - 95 % ( volume / volume ) human iii + i collagen at a concentration of 1 % and 40 - 5 % ( volume / volume ) oxided human collagen iv ; 2 - 10 ml of a human iii + i collagen solution at a concentration of 0 . 2 - 5 %; 10 ml of an oxided human iii + i collagen solution ( collagen oxided according to the process described in french patent application no 2 601 371 ) at a concentration of 0 . 2 - 5 %; 10 ml of a bovine type i collagen solution , as blended , or not , in the proportions of example 8 with oxided human collagen iv or oxided bovine collagen i ; this process including casting a collagen or gelatin solution onto a dehydrated fibrous structure allows one to obtain some impregnation of said solution in the fibrous structure , which yields , after dehydration of the whole , to a mechanically very resistant inter - layer linkage . the obtained dehydrated and sterilized biomaterial may whenever needed be rehydrated in a physiological fluid . this rehydration does not entail the loss of its mechanical resistance nor of its inter - layer cohesion . the obtained biomaterial is very flexible and can completely adapt to any contour . various uses of the collagen patch in visceral surgery will now be described in detail . i . use of the collagen patch for the prevention and treatment of post - operative digestive fistulae anastomotic separations as a consequence of a lack of healing between two viscerae represent the main source of mortality , morbidity and excess costs in digestive surgery . in other words a process that could prevent the appearance of a post - operative anastomotic separation would represent a notable advance . a ). a study of the healing of an intestinal loss of substance in a favorable context for the healing process after the occurrence of a 1 cm diameter loss of substance in the front face of the caecum of 56 male wistar rats each loss of substance is sealed off with the help of a collagen iv patch of human origin , obtained by cutting out a biomaterial sheet so as to form 1 . 5 cm diameter disks , the collagen patch being linked to the rims of the loss of substance with a biological glue which is applied onto the fibrouss layer . the animals were killed in series of 8 at days 5 , 10 , 15 , 20 , 30 , 40 and 60 post - operation and have been studied macroscopically for adhesions and a possible retraction , and have also been studied with an optical microscope and a scanning microscope . mortality and morbidity attributable to the surgical technique were zero . on day 5 after operation the collagen patch is well fastened onto the caecum and seals off the breach perfectly . from day 5 to day 20 the intestinal loss of substance heals by degrees whereas the patch is partially resorbed or eliminated in the caecum lumen . on day 20 after operation the mucous membrane seems to be restored . healing of the muscles begins on day 30 and on day 40 healing is completed . this first experimental step allows one to assert that the collagen patch allows the healing of a healthy non - suturated loss of digestive substance . because healing problems generally appear under unfavorable general and local conditions the next step was to study the healing potential of the collagen patch after creation of a digestive fistula causing a severe denutrition and a local inflammatory response hardly susceptible to primary healing . a open colonic fistula is created on 106 wistar rats . each colonic fistula is closed in the third week with a patch of collagen iv of human origin , in the shape of a 1 . 5 cm diameter disk obtained as above . as a glue one uses a biological glue . samples are taken sequentially on days 5 , 10 , 15 , 20 , 30 , 40 and 60 after operation . some animals die within 48 hours after the second operation because of the important denutrition generated by the fistula . none of the deaths could be attributed to a lysis of the patch . healing is the same as that observed in case of a loss of healthy substance , but it is delayed . reepithelialization is completed on day 30 only , and muscular healing is obtained on day 60 only . c ). a study of the healing of an intestinal anastomosis as protected by a patch in a septic local - regional context anastomosis in a septic environment is considered as a hazardous suture , and is therefore condemned by a majority of authors whose recommendation is to refrain from making a suture in a first step . 112 rats are distributed into two groups , with control group 1 benefiting from a suture 12 hours after a peritonitis is created , and group 2 benefiting from a suture which is protected by a collagen patch according to the invention . biliary leakage and stenosis are the main complications to be feared after opening of the main biliary tract . to avoid the hazard of a premature biliary leakage which can lead to a biliary peritonitis one proceeds to make an external drain after every opening of the main biliary duct requiring a secondary suture . this technique is a demanding and prolonged one because it requires a 14 - day treatment in hospital , the drain being removed on day 12 only , while causing pain to the patient . a ). an in vitro study : the physical resistance of the collagen patch to biliary aggression collagen patch samples are incubated in human bile at 37 ° c . during 20 days . the study of physical resistance is appreciated by a surface study with a scanning electron microscope , and with mechanical tests relating to the breakage strength and the distorsion of the sample when placed in an extensometer . the surface study did not show any structural change on days 5 , 7 and 20 after incubation . mechanical tests did not show any alteration after incubation in bile . b ). use of the collagen patch in the healing of a non suturated bile duct injury in the dog 10 dogs are subjected to a 1 cm longitudinal incision of the bile duct , 2 cm away from the upper limit of the first duodenum . this opening is not suturated but simply sealed off by sticking a collagen patch directly made wit the appropriate shape and dimensions . the dogs are killed on day 30 after operation after intravenous cholangiography . a sample is taken from the zone which has been stuck and each sample taken is studied macroscopically , with an optical microscope and with a scanning electron microscope . one can thus show that this biomaterial allows one to guarantee bilistasis , avoiding any post - operative bile leakage , and leads to bile duct healing without parietal ischemia . the technique of hepatectomy is not without complications such as haemorrhages , bile leakages and subphrenic abscesses . the test protocol relates to male wistar rats . each rat is subjected to an hepatic section on a lobe and a selective ligature of the left hepatic duct . in the first , or control , group the slice of the left hepatic section is protected with biological glue , without any other measure being taken so as to cause hemostasis or bilistasis . in a second group the slice of the hepatic section is protected with a collagen patch , stuck with biological glue . each series includes 40 animals which are sequentially killed on days 5 , 10 , 20 and 30 after operation , at a rate of 10 animals per period . each piece of hepatectomy is studied macroscopically , with an optical microscope and with a scanning electron microscope , so as to study the integration of the patch as well as the progress of healing . contrary to what can be observed in the first group the second group has no bile or blood leakage . the healing of bile ducts which were cut at the section slice is perfect .

a patch for visceral surgery is made from a biomaterial consisting of two layers of collagen superimposed and closely combined , namely a porous adhesive layer of fibrous collagen and a film of collagen and / or gelatin .

this invention has not been observed under all possible environmental conditions . the phenotype may vary with variations in growing environment , without , however , any variations in genotype . ‘ abmtf ’ is currently being grown in fields adjacent to 6327 hwy . 20 , loganville , walton county , ga . this particular area of walton county has a clay loam soil type located in usda zone 7 and has an average rainfall of 30 - 60 inches annually . the following is a detailed description of ‘ abmtf ’ trident maple at age seven with color terminology in accordance with the royal horticulture society ( r . h . s .) colour chart , except where the context indicates a term having its ordinary dictionary meaning . parentage : chance seedling random open - pollinated trident maple parentage purchased from supplier in florida . propagation : genetically stable characteristics reproduced through asexual , vegetative softwood cuttings . locality where grown and observed : city of loganville , county of walton , state of ga . size and growth rate : at time of transplant , the new tree was five years old and measured 5 . 5 ″ caliper at 12 inches above the ground . the height was 21 feet and the width was 13 feet , thus providing a height to width ratio of 1 . 61 . prior to transplanting , the tree had an average growth rate of 1 . 25 ″ caliper per year . this same rate of growth has been evident in the progeny . vigor : in field test on liner stock , my tree , ‘ abmtf ,’ was grown next to ‘ abtir ’ and seedling material . with the same environmental conditions ‘ abmtf ’ was 30 % larger than the seedlings and 10 % larger than ‘ abtir .’ tree shape .— upright oval with very dense foliage . trunk .— smooth and unfluted with minimal exfoliation . some stripe detail is evident which causes the coloring to vary between greyed - green ( rhs 197a ) and greyed - brown ( rhs 199d ). branching habit : more dense than species , primary lower branching emerges at about 10 to 15 degree angle with 20 % of branch end curving upward . branching toward the top third of the tree has 50 to 60 degree angles . branches : hardwood branching has a greyed - green ( rhs 197b ) coloring while soft wood branching is yellow - green ( 146c ). wood is rigid but smooth , with small greyed - white lenticels . foliage : mature leaves are semi - gloss tri - lobed with each lobe being triangular . width between outer lobes averages two to three inches . distance from base of leaf to middle lobe is also two to three inches . margin of leaf in lobe section tends to be slightly serrate . the color of the leaf front is a dark green ( rhs 139a ) while the backside is a greyed - green ( rhs 189a ). as new growth emerges , the coloring is a greyed - red ( rhs 178a ). during the fall , foliage is varied between yellow - orange ( rhs 20b ) through a greyed - red of ( rhs 179b ). the petiole is a yellow - green ( rhs 146c ), measures about two inches and is smooth . buds .— conical , reddish - brown ( rhs 176c ), ¼ inch long and pyramid . stems .— slender , grayed - brown ( rhs 199d ) with pubescence . flower .— small , greenish - yellow ( rhs 145b ) in slightly rounded clusters during mid - spring . fruit .— yellowed - green ( rhs 144c ) double samaras ¾ inch to one inch long and ¼ inch wide , formed in autumn . disease and pest .— during the evaluation period , i have not seen disease or pest damage on the parent or the progeny . hardiness .— usda hardiness zone 5 - 8 .

a trident maple tree named ‘ abmtf ’ having an upright oval canopy , dense branching , smooth bark that has minimal exfoliation , and vigorous growth rate , and is capable of being reproduced reliably from vegetative cuttings .

the present invention provides an apparatus , generally shown at 10 in the figures , for improved collection and sanitary disposal of excretory waste from a bedridden individual . preferably , the apparatus is a bedpan 10 including a vessel , generally indicated at 12 and an absorption mechanism generally indicated at 14 . the vessel includes side walls 16 , inner lips 18 for preventing liquid spill over , a bottom wall 22 , and optionally , a seating surface 17 . the absorption mechanism 14 is disposed on the bottom wall 22 of the vessel 12 and is secured thereto through attachment mechanisms 24 . the absorption mechanism 14 optionally includes a super - absorbing material 20 either concentrated in the center of the absorption mechanism 14 as illustrated in fig2 or dispersed and impregnated throughout the absorption mechanism 14 as illustrated in fig3 . the apparatus 10 is either disposable or reusable and varies in sizes and shapes . the terms “ bedpan ” 10 and “ apparatus ” 10 as used herein are meant to include , but are not limited to , a vessel used by a bedridden person for collection of excretory waste such as urine and feces . bedpans are generally known in the art and vary in size , shape , and volume capacity . preferably , the present invention is an oval - shaped receptacle with a seating surface 17 . the term “ vessel ” 12 as used herein is meant to include , but is not limited to , a concave structure designed to hold and retain liquids . generally , the vessel has side walls 16 , inner lips 18 , and a bottom wall 22 that are all impervious to liquids . the vessel 12 has a large opening 26 for receiving excrement and optionally , a seating surface 17 surrounding the opening 26 . optionally , the vessel 12 forms an inner chamber 25 for placement of the absorption mechanism 14 therein . the vessel 12 is made from materials including , but not limited to , plastic , polyurethane , metal , glass , polymers , and other similar liquid impervious materials known to those of skill in the art . the term “ absorption mechanism ” 14 or “ absorbent layer material ” 14 as used herein is a layer of material that is absorbent to various liquids . specifically , the absorption mechanism 14 is made of materials including , but not limited to , artificial and natural fibers , paper materials , sponge , cloth , cotton , and any other similar liquid absorbing materials known to those of skill in the art . the absorption mechanism 14 optionally has a super - absorbing material 20 that has increased liquid absorbency . the term “ super - absorbing material ” 20 as used herein is meant to include , but is not limited to , a gel , silica , resins such as hydrolyzed starch - acrylonitrile graft polymers or neutralized starch - acrylic acid graft polymer , absorbent powders , desiccating agents , chemical compounds such as polyacylamide , polyacrylate , or potassium , crystals , and other similar liquid absorbing substances or materials known to those of skill in the art . the super - absorbing material 20 is concentrated within the center of the absorption mechanism 14 ( fig2 ), or the absorption mechanism 14 is impregnated with the super - absorbing material 20 ( fig3 ). the term “ deodorizer ” as used herein is meant to include , but is not limited to , any odor reducing substance known to those of skill in the art . the deodorizer is either placed on or within the absorption mechanism 14 , super - absorbing material 20 , or both . the term “ disinfectant material ” as used herein is meant to include , but is not limited to , any antiseptic , germicide , anti - viral , antibacterial substance and any similar substance known to those of skill in the art . the disinfectant material is either placed on or within the absorption mechanism 14 , super - absorbing material 20 , or both . the term “ attachment mechanism ” 24 as used herein is meant to include , but is not limited to , velcro , snaps , buttons , string , glue , tape , adhesives , elastic , fasteners , and any other affixing devices known to those of skill in the art . the attachment mechanism 24 is used to attach the absorbent layer material 14 to an interior or exterior portion of the vessel . the attachment mechanism 24 can be placed on any location of the absorption mechanism 14 . the term “ excrement ” as used herein is meant to include , but is not limited to , urine , solid feces , liquid feces , water , stool , body fluids , vomit , and any substance cast out as waste from the body . the present invention is applicable for use in any setting including , but not limited to , hospitals , assisted living homes , medical offices ,. patient homes , emergency rooms , public and private facilities , and any other similar settings where the device is needed by an individual . there are several embodiments of the present invention . all of the embodiments are well suited for use in the collection of human excrement , especially urine , from individuals . in one embodiment , the present invention is a vessel 12 including a large opening 26 for receiving excretory waste , side walls 16 , inner lips 18 for retaining spill over of liquids , and a bottom wall 22 . another embodiment of the present invention is the absorption mechanism 14 itself , whereby the absorption mechanism 14 is placed within a disposable or reusable bedpan 10 . if the present invention is placed within a disposable bedpan 10 , then the bedpan 10 and the absorption mechanism 14 can be entirely disposed of in the appropriate repository . however , if the present invention is placed within a reusable bedpan , then the absorption mechanism 14 can be solely removed from the reusable bedpan 10 and be disposed of thereafter in the appropriate repository . the absorption mechanism 14 collects and retains liquids including urine , water , liquid fecal matter , and other similar body fluids . the absorption mechanism is either laid in the bottom inner surface 28 , connected to the inner surface 28 of the bottom wall 22 through attachment mechanisms 24 , connected to the inner surface 30 of the side walls 16 through attachment mechanisms 24 , or connected to both the inner surface 30 of the side walls 16 and the inner surface 30 of the bottom wall 22 through attachment mechanisms 24 . the absorption mechanism 14 can be placed in a disposable bedpan 10 or be placed in a reusable bedpan 10 . additionally , the absorption mechanism 14 can be retrofitted onto any currently existing bedpans 10 and can either be permanently or removably attached to the bedpan 10 . the absorption mechanism 14 optionally includes super - absorbing material 20 concentrated in the center of the absorption mechanism 14 as generally shown in fig2 . alternatively , super - absorbing material 20 is dispersed or coated throughout the absorption mechanism 14 as generally shown in fig3 . a deodorizer is impregnated into absorption mechanism 14 , super - absorbing material 20 , or both . additionally , a disinfectant is placed onto the absorption mechanism 14 , super - absorbing material 20 , or both . in another embodiment of the present invention , there is provided a single , disposable unit comprising an external standard bedpan - shaped vessel 12 including the absorption mechanism 14 and super - absorptive material 20 . in the preferred embodiment , the absorption mechanism 14 is attached to both the inner surface 30 of the vessel 12 through attaching mechanisms 24 . the present invention is capable of separating liquid waste , such as urine , from solid waste , such as feces . thus , the present invention is well suited for weighing and measuring liquid waste weight and volume . easy and safe measurement of patients &# 39 ; urine output is computed by first determining the weight of an unused bedpan 10 including the absorption mechanism 14 . then , after collecting both solid and liquid waste , the solid waste is scraped out and removed from the bedpan 10 . next , the used bedpan 10 is subsequently weighed to determine liquid output . alternatively , urine output is computed by just weighing the absorption mechanism 14 . first , the unused absorption mechanism 14 is weighed . then , the absorption mechanism 14 is placed and secured to the vessel 12 of the bedpan 10 . after the bedpan 10 is used , the solid waste is scraped out and removed from the bedpan 10 . next , the absorption mechanism 14 is detached from the vessel 12 of the bedpan 10 . finally , the absorption mechanism 14 containing the absorbed liquids is weighed and the liquid output is determined . subsequently , the bedpan 10 is reused for additional collection of excrement from patients . another embodiment of the present invention provides using the absorption mechanism 14 as an integrated part with a conventional bedpan . the absorption mechanism 14 is easily adaptable for placement onto or over a conventional bedpan 10 . various attaching mechanisms 24 known to those of skill in the art are utilized to secure the absorption mechanism 14 to the bedpan . fig2 and fig3 show an insertable unit including the absorption mechanism 14 and super - absorbing material 20 for placement and attachment within a commonly used bedpan 10 . in operation , the present invention includes the steps of positioning the bedpan 10 including the vessel 12 having the inner surface 30 , and absorption mechanism 14 disposed on the inner surface 30 of the vessel 12 . then , solid and liquid waste are collected with the liquid waste being separated from the solid waste by absorption of the liquid waste in the absorption mechanism 14 and super - absorbing mechanism 20 , or both . finally , the bedpan is disposed of in the appropriate waste repository . additionally , the operation of the present invention includes a further step of collecting liquid and solid waste , but only measuring the amount of captured liquids . thus , a determination of the amount of liquids excreted by an individual is accurately determined . throughout this application , various publications , including united states patents , are referenced by author and year and patents by number . full citations for the publications are listed below . the disclosures of these publications and patents in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains . the invention has been described in an illustrative manner , and it is to be understood that the terminology that has been used is intended to be in the nature of words of description rather than of limitation . obviously , many modifications and variations of the present invention are possible in light of the above teachings . it is , therefore , to be understood that within the scope of the appended claims , the invention may be practiced otherwise than as specifically described .

according to the present invention , there is provided an apparatus for collecting , disposing , and measuring liquids including a vessel with an inner surface and an absorption mechanism disposed on the inner surface of the vessel for absorbing and collecting liquids within the vessel . the present invention additionally provides for an absorption mechanism disposed on an inner surface of a vessel for preventing the spillage of any liquids , particularly those associated with excretory waste . finally , the present invention provides for a method of using the apparatus claimed herein to collect , dispose , and measure liquid output from a bedridden individual .

[ 0044 ] fig2 a to 2 d illustrate an injection mold for the injection molding of the bladder . fig2 a , and 2 b illustrate the top , 2 c and 2 d illustrate the bottom . the mold top 202 , seen from the side , and the bottom mold - cavity side 2 a , and 2 b , respectively . the top of the molding tool 201 is shown with top portion of a molding cavity 205 . the molding cavity comprises a main mold cavity 207 , flow conduits 209 for flow of uncured elastomeric resin into the mold , inlet conduit . the bottom 204 , seen from the side , the top mold - cavity side , and the end , in fig2 c , and 2 d , respectively , includes bottom portion of the main mold cavity 207 , with appropriate flow conduits 209 , an inlet conduit or injection port 211 , and outlet conduit or vacuum port 213 . an o - ring groove is provided to accommodate an o - ring to provide a vacuum seal between the top and bottom of the mold during the molding process . the cross - sectional view in fig3 a , which is a cross - section through a - a in fig2 c , shows the o - ring groove 215 and flow conduit 209 . the cross - sectional view in fig3 b , which is a cross - section of top mold , b - b in fig2 c , shows the flow conduits 209 and threaded connector rod 223 . the cross - sectional view in fig3 c , which is a cross - sectional view through the bottom of the mold , c - c in fig2 c , show the o - ring grooves , the lower half of the main mold cavity 207 . the bladder as molded is generally tubular , which is accomplished by placing a mandrel 217 that extends through the center of the main mold cavity 207 a . the mandrel is illustrated in fig4 and 5 . for the molding process , a threaded connector rod 223 is attached to the proximal end 235 of the mandrel 217 . the connector rod 223 comprises an adjustment nut 225 screwed on threads 227 of the connector rod . the connector rod 223 is attached to the proximal end 235 of the mandrel 217 by a threaded end 229 screwed into a threaded hole 231 . referring to also to fig5 which is a detail view of the ends of the bottom of the mold in fig2 d , the mandrel 217 is placed in the bottom portion of the mold . the distal end of the mandrel 219 is clamped by screw clamps 221 and the adjustment nut 225 is placed in a nut cavity 233 . the mandrel is tensioned by turning of the adjustment nut 225 , which is retained in the nut cavity 233 . the tensioning of the mandrel 217 maintains the mandrel along the central axis 236 of the main mold cavity 207 , so that the finished bladder will be radially symmetrical . after the mandrel 217 is clamped and tensioned in the bottom portion 204 of the mold , and o - ring is placed in the o - ring grooves 215 , the mold is closed by aligning and closing the top mold half 204 over the bottom mold half 202 , using aligning pins 237 and aligning holes 239 . before closing the mandrel 217 and the mold cavities 207 , 209 are preferably coated with an appropriate release agent , such as boron nitride . referring to fig6 which is a schematic of the bladder molding apparatus 251 , the mold 201 is placed vertically , with the injection port 211 down , to prevent the weight of the mandrel from displacing it from the center . the mold is clamped closed against the molding pressure by any suitable clamping system , such as a “ fire - hose ” clamp 253 as illustrated . the mold is degassed through the vacuum port 213 , using a vacuum pump 256 applied through vacuum line 258 . an injection pump 255 of conventional design is used to inject a curable liquid polymeric thermosetting resin though injection line 257 , which fills the cavities of the mold . any suitable injection pump may be used , such as , for example , floware ™ model rtm - 2100 available from radius engineering , salt lake city , utah . a suitable injection pressure is about 120 psig . the injection is continued until the mold is filled and the resin begins to leave the mold through vacuum port 213 , which is then clamped . the mold is then heated at a sufficient temperature and period of time to cure the resin . the cured resin is elastomeric and preferably has heat resistant properties , so that when it is used in the shaft molding process it will retain its integrity and be used more than once . a suitable resin is rtv silicone , such rodorsil 1556 ™, and is cured at about 200 ° f . for about one hour . before injection the resin is mixed with a suitable catalyst . for rotorsil , a suitable catalyst is mixed at a ratio of resin to catalyst of 10 : 1 . the mold 201 is allowed to cool , the mold unclamped and removed from the molding apparatus . the tension on the mandrel is released by unclamping the distal end of the mandrel from the clamp 221 . the mandrel 217 covered by the cured bladder 260 is then demolded from the mold 201 . the bladder mandrel 217 is then removed from the bladder 260 . the mandrel 217 is tapered from the proximal end to the distal end to aid in removal . referring to fig7 which is a cross - section of the bladder 260 , the bladder is generally tubular with a proximate end 262 , distal end 264 , and bladder wall 266 surrounding an internal cavity 268 . the internal dimension , i . e ., the thickness of the wall and the outer dimensions of the bladder , is determined by the dimensions of the mold cavity and bladder mandrel , which varies along the length of the bladder . the dimensions of the bladder are described in greater detail below . since bladder as molded is tubular in nature with an opening at each end , to create an inflatable bladder with only one opening for inflation the opening at the distal end 264 is sealed by seal 270 . referring to fig8 showing the seal 270 the bladder at the distal end 264 has distal opening 265 into the bladder cavity 268 . the opening is sealed by a steel sleeve 272 over the distal end 264 of the bladder 260 with a tapered screw 274 the screws into the cavity opening 265 . as the screw is turned into the cavity opening 265 , the taper of the thread clamps the walls of the bladder against the inner surface of the sleeve 276 , thereby , sealing the end of the bladder 264 . referring to fig9 a rolling mandrel 278 , which is similar to the mandrel 217 used to form the bladder 260 , the dimensions being slightly smaller to account for shrinkage , is used to roll an uncured fiber - reinforced material ( prepreg ) 280 over the bladder . the rolling mandrel 278 is inserted into the cavity of the bladder 268 , and air trapped in the bladder gently squeezed out . prepreg material 280 is then wrapped around the bladder 260 using a heated table to keep the prepreg flexible . suitable prepreg materials include any suitable thermosetting and thermoplastic materials used for forming fiber - reinforced composites . the prepreg is rolled over the mandrel / bladder 278 , 280 assembly by any suitable method , such as rolling tables , or heating tables , or the like . as an example , a heating of neoprene rubber covered with silicone rubber , and is set at a temperature of 110 ° f . may be used . the table may be contoured to match the profile of the mandrel , i . e ., padded up at the waist , to assist the rolling . before the plies are rolled upon the bladder , the bladder is treated with a suitable rubber shield protectant , such as mclube 1929 ™ from mcgee industries or zyvax rubbashield ™, to prevent resin from adhering to the bladder . the first ply 101 , which is rolled first does not extend the full length of the shaft , and essentially provides tip reinforcement with plies at 0 ° to the axis of the shaft . referring to fig1 , which shows the reference for wrapping the plies , the plies are wrapped in the positive direction , as shown by arrow . the first ply , illustrated flat as 101 in fig1 is placed on the table and the starting point ( the 0 ° reference point ) of the first ply is marked on the bladder for the reference . the second ply 102 extends the full length of the part , and has fiber orientation 0 °. using the marked reference the second ply is started at − 45 ° ( behind the start of the first ply ). the third ply 103 is actually a double ply . the third ply 103 is prepared by placing ply 103 a over ply 103 b in an overlapping configuration as shown . the combined third ply 103 is then rolled over the first and second ply , starting at the 0 ° reference . the two components of the third ply 103 a and 103 b have a fiber orientation of + 45 ° and − 45 °, respectively . the forth ply 104 with a fiber orientation of 0 ° is rolled over the preceding plies staring at 135 °. the plies are shaped and dimensioned such that they will wrap around the bladder twice , although more layers can be laid by making the plies wider and wrapping more than one circumference , or one layer or less than one layer by narrowing the plies . a wide range of shapes and rolling sequences can be used . fig1 shows a shaft cross - section with the plies separated to better illustrate the wrapping arrangement . shown are plies 101 , 102 , 103 a , 103 b , and 104 . the shapes are also adjusted to allow the plies to wrap smoothly , to “ tuck ” at the tapers and the transitions of the part . for example , the bottom edge of ply 103 b is not perfectly straight but is slightly concave . other ply arrangements and fiber orientations are also contemplated to achieve a shaft that is essentially radially symmetric in properties . after the plies have been wrapped , the mandrel 278 in the bladder 260 is removed and the assembly of the bladder 260 and the prepreg preform 282 is placed in mold bottom half 204 . alternately , the assembly may be stored and an inventory built up before the curing step . referring to fig1 , showing the end of the bladder / mandrel assembly in cross - section , before the ply is cured , a polytetrfluroethylene ( teflon ™) sleeve 284 is placed over the steel sleeve 272 of the tip seal 270 at the distal end 264 of the bladder 260 to prevent the molded part from adhering to the steel sleeve 272 . referring to fig1 a to 14 d , the mold 301 , which is of a suitable material , such as steel or aluminum , comprises a top mold half 303 ( fig1 a - b ) and a bottom mold half 305 ( fig1 c - d ). in the top section 303 , is half of the main cavity 307 and connecting cavities 309 to a vacuum port 311 connected to a vacuum line 313 . referring also to the cross - sectional view in fig1 b , the top section 303 includes , channels 315 in the outer surface to accommodate water cooling tubes 317 and heating rods 319 . the cooling tubes 317 are copper tubes conveying cooling water . the heating rods 319 are conventional resistance heating rods for heating the mold . the bottom section 305 comprises bottom portion of main cavity 307 , flash cavity 323 , and o - ring groove 325 . the bottom section also includes a bladder pressurizing port 321 , bladder pressurizing line 322 , and barb connector 323 for connection to a bladder . suitable cavities 327 are provided to accommodate the pressure port and connector 321 , 323 . referring also to the cross - section in fig1 a , the bottom section also comprises cooling tubes 317 and heating bars 319 . the bladder pressurizing line 322 is pressure sealed to the mold bottom 305 with a compression type fitting 328 . referring to fig1 , the assembly of prepreg and bladder is placed into the mold bottom section 305 , the teflon sleeve is placed at the distal end of the mold , and the proximate end of the bladder is fitted over a barbed fitting 323 which communicates with the pressure port 321 by a conduit 322 . at the proximal end of the bladder where it fits over the barbed fitting 323 is a silicone tape ring 261 that serves provide local clamping of the bladder 260 onto the barbed fitting . the mold is placed in a molding apparatus 332 . known molding systems are suitable . such an apparatus 332 is shown schematically in fig1 . the apparatus 332 comprises a clamping system , to hold the mold halves together against pressurization of the bladder , a control system which provides power for the heaters , vacuum for the mold cavity , bladder pressurization lines , and water for mold cooling . the mold apparatus 332 shown uses a pneumatically actuated clamping system comprising a pressurizable “ fire ” hose 336 , which is inflated to squeeze the mold halves together . the mold water cooling lines 338 , mold electrical heating rod lines 340 , mold cavity vacuum line 342 , bladder pressurization line 344 , are connected to the control system . referring to fig1 , which is a profile graph of the cure conditions and is mostly self explanatory . the bladder was pressurized by first pulsing the bladder and then maintaining the pressure at a fixed pressure . after the mold is unclamped the assembly of the cured part 346 and the bladder 260 is removed , by removing the top of the mold 303 and disconnecting the bladder 260 at the barbed fitting 323 . the teflon sleeve 284 is removed and the bladder 260 removed by pulling it out through the proximal end of the cured part 348 . fig1 shows a cross - section of the cured part . the part is round , but varies in diameter along its length . referring to fig2 to 22 , showing the cross - sections of the rolling mandrel 278 , the bladder 260 and the finished part 249 , as in fig9 , and 19 , respectively , but with the radial dimension expanded by a factor of 10 to more clearly show the variations in the diameter . the mandrel 278 , with outer dimensions the essentially as the inner diameter of the bladder 260 , maintains the shape of the bladder during the wrapping of the plies 280 . the inner dimensions of the bladder 350 and taper of the mandrel are also designed to enable removal of the mandrel after wrapping , i . e ., with the taper from a large diameter at the proximal end 352 to the small diameter at the distal end 354 . the outer dimensions of the bladder 356 correspond generally to the final inside dimensions of the part 358 . basically , the outer dimensions of the bladder 356 are as close to the inner dimensions of the part 358 as is practical , considering that the bladder 260 is wrapped as tightly as possible before the cure , and the assembly of the bladder 260 and prepreg preform must be placed in the mold 301 , allowing closure of the mold 301 without pinching any of the plies 280 between the mold halves 301 . in general practice , for shafts with having a wall thickness of about 30 to 40 thousands of an inch , the outer dimensions of the bladder are about ⅓or 10 to 20 thousands of an inch less than the final inner dimensions of the shaft . the finished part can then be trimmed to suitable length ( between 0 . 25 and 1 . 5 inches ) at the ends and fitted with suitable grips and club heads in a conventional manner to make a golf shaft . in the illustrated example in fig1 and 22 , the shaft starts with a grip section of a constant diameter at the grip end of about 0 . 585 inches , tapers down in a first body section to about 0 . 490 inches to form a waist , tapers in a second body section to a larger diameter of 0 . 585 , and tapers to 0 . 336 in a tip section . the lengths of the grip , first , second , third , and tip sections are about 10 , 7 . 5 , 7 . 5 , and 20 inches , respectively . while this invention has been described with reference to certain specific embodiments and examples , it will be recognized by those skilled in the art that many variations are possible without departing from the scope and spirit of this invention , and that the invention , as described by the claims , is intended to cover all changes and modifications of the invention which do not depart from the spirit of the invention .

a pressurizable bladder for the manufacture of a composite shaft manufactured from a flexible elastomeric material and adapted for supporting at least one layer of fiber impregnated with resin has an opening for pressurization of the bladder to compress the impregnated fiber against female tooling while the tooling is heated to cure the resin . the bladder has a wall of variable thickness to permit outer contours of the bladder to conform to inner contours of the female tooling .

the following description includes the best presently contemplated mode of carrying out the invention . this description is made for the purpose of illustrating the general principles of the invention and should not be taken in a limiting sense . the novel methods of the present invention involve the generation of necessary internal voltages for bridging callus or new bone between two ( or more ) fragments . unlike other methods and devices in prior art , the claimed methods are site - specific allowing new bone to be regenerated where it has the most structural significance . importantly , this model for enhancing fracture healing more nearly imitates nature than do the prior art external voltage techniques thereby resulting in more efficient bone healing . the method by which bone healing can be accelerated , and the degree of bone healing determined , involves resonant frequency determination for assessing degree of healing . as described in more detail below , for fracture healing acceleration , resonant frequency of the fractured bone is first determined , followed by mechanical stimulation at the resonant frequency of the fractured bone plus a small excess , for a &# 34 ; donkey and carrot &# 34 ; effect . in one embodiment , resonant frequency determination of the present invention requires a variable frequency generator such as a standard generator or a fast fourier transformer ( fft ) as a part of a digital signaling process , sensor signal conditioners ( preferably two ), a computer , amplifiers , shaker or transducer with projecting probe , accelerometer , and an impulse force test hammer . resonant frequency of a bone containing a partially healed fracture is lower than that of an intact , uninjured bone . the healing process is marked by serial increases in resonant frequency . thus , the diagnostic aspect of this device provides objective evidence of the amount and degree of bone healing as opposed to the reading of a radiograph that is an essentially subjective evaluation . the determination of the resonant frequency of a bone may be used for assessing individual testing and for application during the course of therapy to measure changes in resonance during treatment . individual testing requires the use of an impact hammer , and application of resonant frequency during therapy is accomplished using either an fft or a signal generator to resonate a probe at a required frequency . individual testing involves the striking of a bone with an impact hammer that creates a resonance measurement from the accelerometer . the accelerometer is held non - invasively against the skin above the bone , through the fft analyzer . a typical test result is the average of five impacts . the impact hammer and the accelerometer may be connected through individual signal conditioners to the fft and the computer and the resonance is read on the computer screen . resonance may be read as either force or displacement . typical readings in the therapy model are read as force . use of resonant frequency determination during the course of therapy involves sending an impact signal through a transducer probe during the course of treatment . the transducer probe thus replaces the impact hammer as the source of the initial signal input . the signal may be a random burst , sine wave , or chirp and is established as periodic intervals by a computer software program especially designed to calculate the approximate signal . the impact signal is read by the accelerometer and the passes through the fft digital signal analyzer to the computer screen . the result is the same value that would have been created by the use of the impact hammer , but there is no interruption in the therapy by virtue of using the same probe that is applying therapy . according to the novel methods of the present invention , acceleration or induction of rapid healing of bone fractures involves stimulation of the partially healed bone at its current resonant frequency plus a small , ( 1 - 15 hz ) lead factor ( donkey - carrot analogy ). therefore , if the resonant frequency of a fractured bone is determined to be approximately 45 hz , then according to the present invention , bone healing therapy using mechanical stimulation comprises initial mechanical stimulation at a frequency slightly above 45 hz , for example , 47 - 57 hz . subsequent mechanical stimulation involves a progressive and gradual increase in the frequency applied until the frequency of the bone is close to , or equivalent to , that of intact bone . bone as a living tissue will adapt and conform to external physical stimuli . for example , if 130 hz represents 50 % healing in a fractured tibia , then stimulation at an unvarying 130 hz would in all likelihood preserve the 50 % healing but would not promote further progression of the healing process . as was suprisingly discovered , if the stimulating frequency is slowly advanced to maintain an approximately 1 - 15 hz margin above resonant frequency , then the fractured bone will continue to adapt to the new increasing frequency environment resulting in acceleration of healing . most importantly , the bone tissue begins to heal as it adapts to the increase in frequency . accordingly , the novel methods of the present invention involve determination of the resonant frequency of a fractured bone and application of frequency stimulation to maintain a margin above the resonant frequency until the bone is healed . only at , or very close to , the resonant frequency of a partially healed fracture , is there a strong focusing of vibratory energy at the fracture site ( weakest part of the bone ). in a feedback mechanism it is observed that the weakest ( least rigid ) area is subjected to the greatest elastic deformation at its resonant frequency , leading to the greatest piezoelectric voltage generation and further leading to the greatest speed in new bone deposition at the fracture site . the method and device of the present invention are therefore directed to promoting and accelerating bone healing by mechanical stimulation , namely resonant frequency stimulation , at a frequency range that is slightly above that of the broken bone and then subsequently modifying the frequency stimulation to accommodate and optimize bone tissue healing . the methods of the present invention may also be used to prevent bone loss and reduce bone deterioration associated with bone - related disorders such as osteoporosis and osteopenia . in addition the methods may be used for promoting bone tissue re - growth and for maintaining bone mass . acceleration of bone healing and therapeutic intervention for bone - related disorders may be effectively accomplished non - invasively by resonant frequency application according to the methods of the present invention . in the preferred embodiment of the present invention , the principal components , required for measuring resonant frequency ( as shown in greater detail in fig1 ) include an impact hammer hooked to a fast fourier transformer analyzer card ( fft ) via an input channel , an accelerometer also hooked to the fft via a separate input channel , signal conditioners ( separately connected to the impact hammer and accelerometer and also connected to the fft ) and a computer . the fft is configured so that it attaches to a computer port . the same components are required for application of resonance frequency , however , the impact hammer is replaced by a transducer and amplifier ( as shown in fig2 ). alternatively , resonance frequency may be applied as shown in fig3 wherein one part of a transducer ( or shaker ) with a projecting probe , is held against the skin near to the broken bone , and wherein another part of the transducer is connected to an amplifier which in turn is connected to a frequency generator and a power source . one preferred generator is the bk precision , model number 3022 . the fft is a mechanism for receiving or transmitting signals . it is capable of both measuring resonance frequency or driving a transducer at a predetermined frequency for therapy . a preferred fft is manufactured by data physics and has the model number dp104 . the transducer supplies resonant frequency through the skin to the fractured bone . an important feature of the transducer is that it can be used non - invasively , i . e . it is simply held against the skin and no incision is necessary . a preferred transducer according to the present invention is custom made by modifying a speaker with a nylon probe attached to the voice coil . although the steps of the present invention may be conducted individually , and each of the measurements made manually , the entire procedure may be automated by use of appropriate computer software . in a preferred embodiment of the present invention , software enables the computer to receive and record input from the impact hammer via the fft , and subsequently calculate and generate the appropriate therapeutic frequency for promoting bone repair according to the methods of the present invention through the fft and transducer , for a predetermined period of time . at the end of resonant frequency application , the computer directs the fft to send a burst , chirp or actual hammer signal through the probe . the accelerometer then measures the resonance frequency and , in a feedback arrangement , causes adjustment of the applied resonance accordingly . in summary , the software optimizes resonance therapy management , recording of resonance measurements , resetting and adjustment of resonance therapy based upon correct ( intact bone ) measurement and may further alert a technician to any anomalies that may occur during the measurement or therapy phase . in addition , the program output can also be utilized to provide a database of information concerning the patient , fracture type , original resonance management , original resonance therapy setting , duration of therapy , subsequent resonance measurements , modifications in therapy , and physician / technician notes . the database may be centralized and made available to relevant parties by various sources such as the internet . theoretical calculations suggest that the four to six month time frame for fully healing a major long bone fracture might be compressed to 40 - 50 hours of active treatment using methods of the presently claimed invention . under normal fracture healing conditions a piezoelectric event might be produced by movement of a limb , muscle contraction , muscle spasm or a local systolic pulse . with resonant frequency stimulation a piezoelectric event would be a single hertz component of that stimulating frequency . the most frequent piezoelectric event in the normal healing category is the systolic pulse 72 / min . the average frequency of resonant frequency stimulation could be in the range of 100 - 500 hertz . applied &# 34 ; micromotion &# 34 ; dynamic axial loading ( dynamization ), and decreasing rigidity of fixation as fractures heal ( progressive destabilization ) are all techniques which have been shown to enhance healing and are incorporated in various fracture treatment devices and techniques . this invention is further illustrated by the following examples , which are not to be construed in any way as imposing limitations upon the scope thereof . on the contrary , it is to be clearly understood that resort may be had to various other embodiments , modifications , and equivalents thereof , which , after reading the description herein , may suggest themselves to those skilled in the art without departing from the spirit of the present invention . the following experiment was conducted to assess the effect of resonant frequency on bone fractures . specifically , the effect of resonant frequency was studied with respect to healing tissue and bone composition . the subject of this study was a one year old walker hound dog . a surgical fracture of the ulna was performed ( partial fracture osteotomy ) on the dog . subsequently , twenty hours of resonant frequency stimulation was applied to the fractured ulna using a transducer modified loud speaker with a probe , an audioamplifier and a signal generator . histopathological studies were conducted by decalcifying samples in rapid acting decal according to methods well known in the art . samples studied included ulna sections . the degree of healing was surprisingly high at 12 days post osteotomy . there was active remodeling in the adjacent cortex . the amount of fibrous tissue and trabecular bone formation in the osteotomy site had progressed in the correct physiological manner . there may be some increase in the amount and irregularity of spicules in the marrow cavity . there was also more tangential or parallel orientation of external callus than the radial pattern than would be expected . section a : section a is a section through the cortex of the ulna that showed a gap filled with fibrous connective tissue with small islands and fine trabeculae of woven bone . there was abundant bony callus on one surface beneath an active layer of periosteal osteoblasts . the direction of the callus bone was generally perpendicular to the cortical surface . on the opposite surface ( the surface with complete osteotomy ) there was also abundant trabeculae of woven bone being formed . some cartilage was present at the periphery on the one side . the orientation of this bone was generally parallel to the cortical surface rather than perpendicular . in the deeper portion of section a there was an increased amount of periosteal callus and islands of cartilage were found on both surfaces . some debris was present in the defect at its base . there was active remodeling in the adjacent cortex . the area of empty osteocyte lacunae back from the osteotomy site was judged to be about normal ( that is normal extent of osteocyte death ). there was active osteoclastic remodeling on the osteotomy margins and active woven bone formation in the depth of the defect . section b is another section of cortex and contains callus adjacent to the defect site . there was an abundance of woven bone callus at the site . there was some fragmented debris in the cortical remnant . at this level there was trabeculae of woven bone occupying approximately 70 % of the cortex on its inner surface . there was also increased woven bone formation throughout the marrow cavity . in the section through what is presumably the facing cortex there was a second defect seen with new bone formation on the surface ( possible nutrient canal being remodeled ). the defect site was filled with fibrous connective tissue and woven bone spicules . the woven bone spicules occupied approximately 50 % of the defect between the ends of the cortex . fragments of mineralized debris were encased in fibrous tissue in the marrow cavity . there was excessive formation of woven bone in the marrow cavity . effect of resonant frequency on healing bone fractures using &# 34 ; donkey - carrot &# 34 ; approach on human tibia this study is concerned with the use of resonant frequency mechanical stimulation of fractured bone such as human tibia for both therapeutic and diagnostic purposes . this study also explores the interaction of resonance with another significant natural force , namely the piezoelectric effect in which strain and elastic deformation of certain crystalline substances ( including bone ) generate small voltages ( approximately 1 - 15 millivolts ) which propagate and control the healing process . eight patients with simple isolated , closed fractures of their tibia or ulna ( mid - diaphyseal location ) that are amenable to closed treatment are eligible for the study . criteria for entry into the study includes patients who are non - smokers with no medical conditions and / or taking medications which might alter normal fracture healing ( e . g . renal osteodystrophy , cancer , epileptics taking anticonvulsants , alcoholism , nutritional deficiencies , etc .). the patients are adults ( over 18 years of age ) and agree to participate fully until healing of the fracture is complete or the study is discontinued at the discretion of the study investigators . conditions for discontinuation include conditions that are harmful to the patient , or compromise study validity like delayed healing ( healing time greater than two standard deviations from mean normal range ), illness , equipment failure , non - compliance , adverse effects . after initial fracture , management - closed reduction of displaced fractures and immobilization ( in cast , splint or brace ), the patients follow routine orthopedic procedures . at 1 to 3 weeks when initial healing callus is evident , the patients are asked to participate in the study . four patients who are willing to participate in the treatment ` arm ` of the study receive resonant frequency stimulation treatments . healing of all patients is measured by resonant frequency analysis and radiographs as well as by clinical examination . treatment is given five days a week , four hours per day for a total of 40 hours or less if fracture union is achieved earlier . in this study a variable audio frequency , or fft generator ranging from 50 to 500 hz , is used . the output is fed to an audio amplifier which in turn drives the transducer whose output probe is placed approximate to the bone at an accessible subcutaneous location and coupled to it through the skin for measurement purposes . the resonant vibration is detected by accelerometer created by an impact hammer or through the transducer . analysis by microcomputer with fast fourier transform ( ftt ) yields a spectrum of pure frequencies and their amplitudes . the highest resonance frequency in this spectrum represents the first bending mode , which is a property of bone stiffness and is used as a measure of fracture healing . there should be no pain or discomfort with the use of the resonant frequency stimulation ( rfs ) therapy device . should there be any discomfort , the gain ( strength level ) can be instantly reduced . the subject may or may not feel a mild vibration sensation . no difficulty has been encountered to date with skin irritation . precautionary measures are routinely used , namely the use of moleskin and or tincture of benzoin or both to lower the likelihood of any skin problems . the use of an impact hammer for measurement may produce mild soreness ; however , there are few measurements in the course of treatment . the ` control arm ` of the study measures resonant frequency response in healing fractures of four patients who are not participating in resonant frequency stimulation treatment . this provides a control group of patients with fractures that heal normally ( without enhancement ). it also provides for comparison of resonant frequency response method of determining stage of fracture healing versus radiographs . the initial 8 patients in this study constitute a pilot group that utilizes similar fractures treated conventionally , as described above , as the control . after the first 8 patients , a single blind placebo control is implemented if it proves feasible and compatible with the operation of the electronic equipment . it should be understood that the foregoing relates only to preferred embodiments of the present invention , and that numerous modifications or alterations may be made therein without departing from the spirit and the scope of the invention as set forth in the appended claims . the references cited throughout are hereby incorporated by reference in their entireties .

methods for healing bone fractures are provided . the methods as provided herein involve the application of resonant frequency stimulation to promote fracture healing and also to diagnose status of fracture healing . the methods of the present invention are particularly desirable because they are site - specific , non - invasive and require a minimum amount of early healing or callus formation .

as a preliminary matter , it will readily be understood by one having ordinary skill in the relevant art (“ ordinary artisan ”) that the present invention has broad utility and application . as should be understood , any embodiment may incorporate only one or a plurality of the above - disclosed aspects of the invention and may further incorporate only one or a plurality of the above - disclosed features . furthermore , any embodiment discussed and identified as being “ preferred ” is considered to be part of a best mode contemplated for carrying out the present invention . other embodiments also may be discussed for additional illustrative purposes in providing a full and enabling disclosure of the present invention . as should be understood , any embodiment may incorporate only one or a plurality of the above - disclosed aspects of the invention and may further incorporate only one or a plurality of the above - disclosed features . moreover , many embodiments , such as adaptations , variations , modifications , and equivalent arrangements , will be implicitly disclosed by the embodiments described herein and fall within the scope of the present invention . accordingly , while the present invention is described herein in detail in relation to one or more embodiments , it is to be understood that this disclosure is illustrative and exemplary of the present invention , and is made merely for the purposes of providing a full and enabling disclosure of the present invention . the detailed disclosure herein of one or more embodiments is not intended , nor is to be construed , to limit the scope of patent protection afforded the present invention , which scope is to be defined by the claims and the equivalents thereof . it is not intended that the scope of patent protection afforded the present invention be defined by reading into any claim a limitation found herein that does not explicitly appear in the claim itself . thus , for example , any sequence ( s ) and / or temporal order of steps of various processes or methods that are described herein are illustrative and not restrictive . accordingly , it should be understood that , although steps of various processes or methods may be shown and described as being in a sequence or temporal order , the steps of any such processes or methods are not limited to being carried out in any particular sequence or order , absent an indication otherwise . indeed , the steps in such processes or methods generally may be carried out in various different sequences and orders while still falling within the scope of the present invention . accordingly , it is intended that the scope of patent protection afforded the present invention is to be defined by the appended claims rather than the description set forth herein . additionally , it is important to note that each term used herein refers to that which the ordinary artisan would understand such term to mean based on the contextual use of such term herein . to the extent that the meaning of a term used herein — as understood by the ordinary artisan based on the contextual use of such term — differs in any way from any particular dictionary definition of such term , it is intended that the meaning of the term as understood by the ordinary artisan should prevail . regarding applicability of 35 u . s . c . § 112 , ¶ 6 , no claim element is intended to be read in accordance with this statutory provision unless the explicit phrase “ means for ” or “ step for ” is actually used in such claim element , whereupon this statutory provision is intended to apply in the interpretation of such claim element . furthermore , it is important to note that , as used herein , “ a ” and “ an ” each generally denotes “ at least one ,” but does not exclude a plurality unless the contextual use dictates otherwise . thus , reference to “ a picnic basket having an apple ” describes “ a picnic basket having at least one apple ” as well as “ a picnic basket having apples .” in contrast , reference to “ a picnic basket having a single apple ” describes “ a picnic basket having only one apple .” when used herein to join a list of items , “ or ” denotes “ at least one of the items ,” but does not exclude a plurality of items of the list . thus , reference to “ a picnic basket having cheese or crackers ” describes “ a picnic basket having cheese without crackers ”, “ a picnic basket having crackers without cheese ”, and “ a picnic basket having both cheese and crackers .” finally , when used herein to join a list of items , “ and ” denotes “ all of the items of the list .” thus , reference to “ a picnic basket having cheese and crackers ” describes “ a picnic basket having cheese , wherein the picnic basket further has crackers ,” as well as describes “ a picnic basket having crackers , wherein the picnic basket further has cheese .” referring now to the drawings , one or more preferred embodiments of the present invention are next described . the following description of one or more preferred embodiments is merely exemplary in nature and is in no way intended to limit the invention , its implementations , or uses . in particular , a preferred cleaning apparatus 10 for lifting , removing and extracting a spill or stain in accordance with one or more aspects and features of the present invention is shown in fig1 . fig2 - 5 are side elevational views of apparatus 10 , fig6 is a plan view of a top of apparatus 10 , and fig7 is a plan view of a bottom of the apparatus 10 . a similar apparatus 20 having transparent outer wall 14 ′ is shown in fig8 , and the follow description of apparatus 10 is equally applicable to apparatus 20 . cleaning apparatus 10 is hand transportable and hand operable , and includes a handle 12 ; an outer wall 14 ; a base 16 ; and an applicator 18 . as shown in fig8 , the handle 12 is attached to a piston 11 and includes a head 13 . the piston 11 and head 13 are disposed within cylinder 15 . the piston head 13 is disk - shaped and creates an airtight seal with the interior wall of the cylinder 15 against which it moves , and against standing pipes 36 , 38 of the pump , which are described in greater detail below . in this respect , the head 13 defines openings through which the standing pipes 36 , 38 extend during movement of the head 13 within the cylinder 15 . movement of the handle 12 up and down relative to the outer wall 14 and base 16 causes the head 13 of the piston 11 to move back and forth within the cylinder 15 and displace the air within the cylinder 15 . the handle 12 ; piston 11 ; cylinder 15 ; and standing pipes 36 , 38 all form part of a manually operated pump , the operation of which is described in greater detail below . the outer wall 14 of the apparatus 10 defines , in part , the outer walls of two interior chambers , including a cleansing fluid chamber 22 , and a waste fluid chamber 2 , which are perhaps best seen in fig8 with reference to apparatus 20 . an interior wall 17 of the apparatus defines the interior walls of the respective chambers 22 , 24 . the interior wall 17 also defines the cylinder 15 within which the piston 11 moves and head 13 resides . each chamber includes an opening through which liquid is poured . with respect to the cleansing fluid chamber 22 , a cap 6 covers the opening ; and with respect to waste fluid chamber 24 , a cap 8 covers that opening . a cleaning fluid to be used to cleanse an area is poured through the opening into the cleansing fluid chamber 22 in preparation for cleaning , and waste fluid suctioned from the area is poured from the waste fluid chamber 24 after cleaning . in the apparatus 10 , the interior wall 17 generally divides the apparatus in half and separates the cleansing fluid from any waste fluid in the respective chambers 22 , 24 . the applicator 18 is located on the bottom of the apparatus 10 , and is used to cover an area to be cleaned . specifically , when the apparatus 10 is positioned over the area to be cleaned and the apparatus 10 is pressed , the applicator 18 encompasses the area and creates at least a partial seal surrounding the area by engagement of a rim 19 of the applicator 18 with a surrounding perimeter of the area . the rim 19 is perhaps best seen in fig1 , 13 and 19 . fig9 is a perspective view of various components of cleaning apparatus 10 , including base 16 , piston 11 and head 15 , and standing pipes 30 , 32 , 34 , 36 , 38 . air flows through standing pipe 30 into the cleansing fluid chamber 22 ; waste fluid suctioned from an area being cleaned flows through standing pipe 32 into waste fluid chamber 24 ; and air flows from waste fluid chamber 24 through standing pipe 34 . part of the air from the waste fluid chamber 24 travels to one area of the pump through standing pipe 36 , and then travels from that side through standing pipe 38 . the standing pipes 30 , 32 , 34 , 36 , 38 are in parallel relation to each other and to the cylinder 15 in which the piston head 113 moves . one - way valve 40 is also visible in part in fig9 , through which the other part of the air from the waste fluid chamber 24 travels to the other area of the pump . fig1 is a plan view of components of fig9 . sold arrows indicate flow of fluid and , in particular , flow of waste fluid through standing pipe 32 into waste fluid chamber 24 , and flow of cleansing fluid from cleansing fluid chamber 22 through opening 50 defined in the base 18 for travel to applicator 18 . open arrows indicate the flow of air and , in particular , flow of air from the waste fluid chamber 22 into and down standing pipe 34 toward the pump , and flow of air from the pump up through standing pipe 30 into the cleansing fluid chamber 22 . fig1 is the same view as fig1 . fig1 is a cross - sectional view of the components of fig1 taken along the line 11 - 11 . the split of air flow through the pump is perhaps best seen in fig1 taken in conjunction with fig1 . the complete flow of air from the waste fluid chamber 24 travels through standing pipe 34 and take either one of two paths depending on the direction of travel of the piston 11 within the cylinder 15 . when the piston is traveling upwardly ( due to the handle 12 being pulled away from the base 16 ), air flows through umbrella valve 42 up through standing pipe 36 into a first piston area . this path is indicated by open arrows shown adjacent the numeral ‘ 1 ’. on the other hand , when the piston is traveling downwardly ( due to the handle 12 being pushed toward the base 16 ), air flows through umbrella valve 40 into a second piston area . this path is indicated by open arrows shown adjacent the numeral ‘ 2 ’. fig1 also shows waste fluid flow away from the applicator 18 , through standing pipe 32 , into waste fluid chamber 24 . a one - way valve 44 is provided in order to inhibit reverse flow of the waste fluid back toward applicator 18 , which would be undesirable . fig1 is a cross - sectional view of the components of fig1 taken along the line 13 - 13 . the split air flow path through the pump , discussed above , is recombined on the other side of the pump as shown in fig1 . in particular , the air from the first piston area travels down standing pipe 38 and through umbrella valve 46 , whereat air flow from the second piston area also travels through umbrella valve 48 . air flow from both of the one - way valves 46 , 48 then travels through one - way valve 50 and travels up through standing pipe 30 into the cleansing fluid chamber 22 . the air flow path from the first piston area is indicated by open arrows shown adjacent the numeral ‘ 1 ’, and the air flow path from the second piston area is indicated by open arrows shown adjacent the numeral ‘ 2 ’. the piston areas are located on opposite sides of the piston head . as will be appreciated , movement of the piston head within the cylinder changes the volume of space in the first and second piston areas , wherein one increases as the other decreases , and vice - versa . this results in air being drawn into one of the piston areas concurrently with air being expelled from the other of the piston areas , and provide a dual - action pump whereby continuous pumping of air is provided during both forward and back ( or up and down ) strokes of the piston . fig1 and 15 further illustrate the standing pipes and one - way valves , and further schematically illustrate the defines recesses and resulting intermediate compartments that are defined thereby on the underside of the base 16 when the base 16 and applicator 18 are attached . further in this respect , fig1 shows the recessed spaces defined on the bottom of the base . the top of the applicator 18 includes corresponding walls for engaging the base when the two components are secured together . the intermediate compartments include the locations at which the air flow is split and then later recombined , as discussed above . specifically , the space 45 shown in fig1 forms the compartment in which the airflow is split , and the space 47 shown in fig1 forms the compartment where the airflow is recombined . fig1 shows a bottom of the applicator body , which includes two openings 52 , 54 . cleansing fluid for applying to the area to be cleaned travels through opening 52 onto a distribution plate 60 , and waste fluid suctioned from the area through a suction port 62 of the distribution plate 60 travels through opening 54 . a bottom plan view of the distribution plate 60 is shown in fig1 and shows the suction port 62 . moreover , a plurality of dispensing opening 64 are arranged about the suction port 62 . the cleansing fluid flowing onto the top side of the distribution plate 60 travels to one of the dispensing openings 64 and is dispensed therethrough onto the area being cleaned . it will be appreciated that flow through the area being cleaned , which area is at least partially sealed by the rim 19 of the applicator body 18 , travels generally from the dispensing openings 64 arranged about the suction port 62 in a radial toward the suction port 62 , as shown by the arrows in fig1 . the general flow of the cleaning apparatus 10 is shown in fig2 . specifically , air is pumped into the cleansing fluid chamber of the cleaning apparatus ; cleansing fluid is thereby expelled from the cleansing fluid chamber to the applicator , where it is applied to the area being cleaned ; waste fluid is suctioned from the area being cleaned into the waste fluid chamber ; and air is drawn from the waste fluid chamber to the pump for delivery to the cleaning fluid chamber via the pump . it will be appreciated that the withdrawal of the air form the waste fluid chamber results in a low pressure that , in turn , results in the air flow and suctioning of the waste fluid from the applicator to the waster fluid chamber . it will thus be appreciated that air is transferred through the pump from the waste fluid chamber to the cleansing fluid chamber as cleansing fluid is transferred through the applicator from the cleansing fluid chamber to the waste fluid chamber and waste fluid is transferred from the area being cleaned to the waste fluid chamber . in use of the cleaning apparatus 10 , the cleansing fluid chamber is filled with a cleansing fluid . water may be used , or a solution including a solvent or other chemical may be used . the apparatus is next positioned over the area to be cleaned . while pressing the apparatus , the pump is manually actuated by moving the handle and piston up and down . this results in the flow represented in fig2 , wherein cleansing fluid is applied to the area and waste fluid is suctioned from the area . additionally , the application of the cleansing fluid concurrently with the suctioning of the waste fluid is continuous since the pump is a dual action pump , driving the flow in both up and down strokes . if the interior of the cleansing fluid chamber is visible from an exterior of the apparatus , the extent to which the cleansing fluid has been used can be monitored by a person using the apparatus . once the cleansing fluid is exhausted , the cleaning process is stopped and the waste fluid is disposed of . if needed , the cleaning operation can be repeated once additional cleansing fluid has been added to the cleaning fluid chamber . fig2 is a perspective view of another preferred cleaning apparatus 100 for lifting , removing and extracting a spill or stain in accordance with one or more aspects and features of the present invention . fig2 is a similar view to that of fig2 , with the omission of some components in order to reveal the tops of the standing pipes and tops of the chambers and cylinder . additionally , fig2 is a perspective view including a top side of an applicator body of the apparatus of fig2 ; fig2 is a perspective view including a bottom side of the applicator body of the apparatus of fig2 ; and fig2 is a perspective view including a bottom side of the container walls forming the chambers and cylinder of the apparatus of fig2 . the apparatus 100 includes structure and operates in accordance with the same theory as apparatus 10 and 20 discussed above , and like those other embodiments , it includes a handle 112 ; outer wall 114 ; base 116 ; and applicator 118 . the outer wall 114 , together with an inner wall , define the cleansing fluid chamber 122 and waste fluid chamber 124 . a cap covers 106 an opening to the cleansing fluid chamber 122 ; and a cap 108 covers an opening to the waste fluid chamber 124 . in one difference , the cylinder 115 of the pump is disposed in part on the outside and is defined by both the inner and outer walls . the piston 111 and piston head 113 are located within the cylinder , as shown , and two standing pipes 136 , 138 are also included as before for flow to and from the first piston area 172 . the second piston area 174 is located on the opposite side of the piston head 113 , which seals off the two areas from each other . also , unlike the prior apparatus 10 , 20 , the cleaning apparatus 100 includes only three standing pipes instead of five . the standing pipes for flow of the waste fluid into the waste fluid chamber 124 , and flow of the air into the cleaning fluid chamber 122 , may be omitted as shown . in alternatives , one or both of these omitted standing pipes are included . as before , the movement of the piston 111 and piston head 113 within the cylinder 115 results in the pumping of air into the cleansing fluid chamber 122 regardless of the direction of movement of the piston 111 within the cylinder 115 . yet additional embodiments of cleaning apparatus in accordance with one or more aspects of the present invention are disclosed in the incorporated appendix . based on the foregoing description , it will be readily understood by those persons skilled in the art that the present invention is susceptible of broad utility and application . many embodiments and adaptations of the present invention other than those specifically described herein , as well as many variations , modifications , and equivalent arrangements , will be apparent from or reasonably suggested by the present invention and the foregoing descriptions thereof , without departing from the substance or scope of the present invention . accordingly , while the present invention has been described herein in detail in relation to one or more preferred embodiments , it is to be understood that this disclosure is only illustrative and exemplary of the present invention and is made merely for the purpose of providing a full and enabling disclosure of the invention . the foregoing disclosure is not intended to be construed to limit the present invention or otherwise exclude any such other embodiments , adaptations , variations , modifications or equivalent arrangements , the present invention being limited only by the claims appended hereto and the equivalents thereof .

a hand carried , manually operated apparatus for cleaning flooring , carpet , upholstery , and the like includes a cleansing fluid chamber , a waste fluid chamber , a pump and an applicator . a first fluid passageway connects the pump and cleansing fluid chamber , a second passageway connects the cleansing fluid chamber and applicator , a third passageway connects the applicator and waste fluid chamber , and a fourth passageway connects the waste fluid chamber and pump . a first one - way valve permits flow from the pump to the cleansing fluid chamber but inhibits reverse flow ; and a second one - way valve permits flow from the applicator to the waste fluid chamber but inhibits reverse flow . air is transferred through the pump from the waste fluid chamber to the cleansing fluid chamber as cleansing fluid is transferred to the applicator from the cleansing fluid chamber and waste fluid is transferred from the applicator to the waste fluid chamber .

the intervertebral implant 1 shown in the drawing includes three parts , namely a platelike upper part 2 , a platelike lower part 3 , and a substantially platelike pivot insert 4 . the upper part 2 is embodied flat on its top , thus creating a support face 5 , on which various kinds of protrusions 6 , 7 are disposed which serve the purpose of anchoring the upper part 2 in a vertebra that rests , with its end face toward an intervertebral space , on the support face . the upper part 2 is substantially rectangular in cross section ; in the exemplary embodiment shown , a longitudinal edge 8 curves outward . on the two short sides of this rectangle , the thickness of the platelike upper part 2 is less than in the central region , so that along the short sides of the upper part 2 , downward - pointing recesses 9 each extending parallel to these edges are formed that are open toward the outside . the central region of the upper part 2 is located between the two recesses 9 and thus has a greater thickness or height and thus forms a downward - pointing protrusion 10 embodied between the two recesses 9 . this protrusion is defined by an underside 11 , which extends substantially parallel to the support face 5 and in which there is a spherical indentation 12 , which forms a bearing plate for the pivot insert 4 . the lower part 3 of the intervertebral implant 1 is also platelike in embodiment and on its underside has a flat support face 13 with protrusions 14 and 15 , which correspond to the protrusions 6 and 7 of the support face 5 . on the side remote from the support face 13 , the thickness of the lower part 3 is less in the central region than in an outer region . this outer region of greater thickness has the form of a u , with two parallel legs 16 , 17 , which extend parallel to the short edges of the lower part 3 , which in cross section is embodied similarly to the upper part 2 , and with a crosspiece 18 that connects the two legs 16 and 17 on one end . the region enclosed by the legs 16 and 17 and the crosspiece 18 forms a central indentation 19 , whose area is substantially equivalent to the area of the central protrusion 10 of the upper part 2 , while the disposition and length of the legs 16 and 17 correspond essentially to the disposition and length of the recesses 9 on the upper part 2 . as a result , it is possible to place the upper 2 and lower part 3 on one another in such a way that the central protrusion 10 of the upper 2 dips into the central indentation 19 , while the legs 16 and 17 of the lower part 3 dip into the recesses 9 of the upper part 2 ( fig4 ); in this position , the upper part 2 and lower part 3 have maximum proximity to one another and a minimal structural height . the dimensions are selected such that the various recesses are essentially filled completely by the protrusions dipping into them . blind bores 20 and 21 are machined into the two legs 16 and 17 of the lower part 3 , extending parallel to these legs 16 , 17 from their free ends ; the diameter of these bores is relatively great in proportion to the height of the legs 16 , 17 , and this diameter is in fact greater than the thickness or height of the lower part 3 in the region of the central indentation 19 . blind bores 22 and 23 , which extend parallel to the blind bores 20 and 21 in the lower part 3 , are machined into the central protrusion 10 of the upper part 2 , in the vicinity of its side edges . these blind bores 22 and 23 again have a relatively great diameter , which corresponds to a substantial portion of the height of the protrusion 10 and is greater than the thickness of the upper part 2 in the region of the recesses 9 . when the upper part 2 and lower part 3 rest tightly against one another in the manner described , the blind bores 20 and 21 of the lower part 3 and the blind bores 22 and 23 of the upper part 2 overlap at least partly in the direction of the height of the intervertebral implant 1 , as is clearly shown in fig4 and 5 . the blind bores 20 , 21 , 22 and 23 serve as receptacles for pinlike extensions of a manipulation instrument , not shown in the drawing , and thus form engagement elements for this manipulation instrument , which in this way separately engages the upper part 2 and the lower part 3 . with this manipulation instrument , it is possible to introduce the upper part 2 and the lower part 3 of the intervertebral implant 1 into an intervertebral space ; the very low structural height of the intervertebral implant 1 facilitates this introduction , which can be done essentially without major widening of the intervertebral space . after the introduction of the upper part 2 and lower part 3 in this way , the two parts of the intervertebral implant 1 can be spread apart ; that is , their spacing is increased , for instance with the aid of the manipulation instrument that is holding the upper 2 and the lower part 3 . in this spread - open position of the upper part 2 and lower part 3 , it is possible to thrust the pivot insert 4 between the upper part 2 and the lower part 3 . this pivot insert is constructed essentially in the shape of a plate , which has a flat underside 24 and a spherically upward - curved top side 25 . the outer dimensions of the platelike pivot insert correspond to those of the central indentation 19 in the lower part 3 , so that the pivot insert 4 can be thrust into this indentation , filling it up , specifically from the side toward which the blind bores 20 , 21 , 22 , 23 open . guide strips 26 on the side edges of the pivot insert 4 engage corresponding guide grooves 27 in the legs 16 , 17 , so that an insertion guide for the pivot insert 4 is formed that fixes it in the lower part 3 after its insertion . the inserted pivot insert 4 , after insertion , fills up the indentation 19 and protrudes with its spherically curved top side 25 upward past the top side of the lower part 3 ; the spherical top side 25 dips in complimentary fashion into the spherically curved indentation 12 on the underside of the protrusion 10 , where with the upper part 2 it forms a ball joint , which enables a certain pivotability of the upper part 2 relative to the lower part 3 ( fig7 ). the pivot insert 4 can have a detent protrusion 28 on its flat underside 24 ; when the pivot insert 4 is inserted into the lower part 3 , this protrusion locks elastically into a detent recess 29 that is located on the bottom of the indentation 19 ; as a result , the pivot insert 4 is also fixed in the insertion direction in the indentation 19 . the upper part 2 and lower part 3 are preferably made of physiologically safe metal , such as titanium , while the pivot insert 4 preferably comprises a likewise physiologically safe plastic material , such as polyethylene . these support faces 5 and 13 can be embodied in an especially bone - compatible way ; for instance , this surface can be roughened by a coating , so that optimal anchoring to the adjacent bone material is obtained . the invention may also be described as follows , which description is the full equivalent of the preceding discussion . an upper part 2 has an upper surface 5 for engaging a vertebrae and a lower surface which comprises a downward pointing protrusion 10 between side recesses 9 and a rounded portion , preferably in the form of a concave spherical indentation 12 . a lower part 3 has a lower surface 13 for engaging a vertebrae . a pivot insert 4 , when joined to the lower part 3 , as shown for example in fig3 , provides a convex upper surface portion 25 , preferably spherical , in operational engagement with the rounded portion 12 of the upper part . the lower part 3 and pivot insert 4 may , taken together , be described as a lower part formed in two pieces , namely the elements 3 and 4 , wherein the element 3 may be referred to as a lower piece and the element 4 may be referred to as an upper piece . the upper and lower parts include on their upper surface and lower surface , respectively , protrusions 7 and 14 which may also be referred to as anchors , which anchor the upper and lower parts , respectively , into the adjacent vertebrae that form the intervertebral space and rest against the respective upper and lower surfaces . as shown in the figures , the anchors 6 and 14 each have a zigzag edge which comprise teeth . as best shown in fig7 , anchor 6 is greater in height than the remainder of the upper part 2 , i . e ., from surface 5 to the bottom of protrusion 10 . similarly , anchor 14 is greater in height than the remainder of the lower part 3 , i . e ., from lower surface 13 to the top of walls 16 , 17 and 18 . as also shown in the figures , in the preferred embodiment , the length of the anchors 6 and 14 , i . e ., in the direction from the anterior to the posterior thereof , is greater than one half of the overall dimension of its respective part from its anterior to its posterior , passing through that anchor . the lower part comprises three walls including parallel side walls 16 and 17 and a rear wall 18 . these walls form between them a central indentation 19 which comprises a recess with a generally flat surface . the fourth side of the recess is open . the pivot insert 4 has a detent 28 that snap - fits into a detent recess 29 formed in the generally flat surface of recess 19 . as best shown in fig2 , 4 and 5 , in the absence of pivot insert 4 , the protrusion 10 of upper part 2 can fit down between walls 16 , 17 and 18 of the lower part 2 . this fitting of protrusion 10 within the recess 19 , surrounded by walls 16 , 17 and 18 may be referred to as “ nesting ” since the protrusion 10 essentially “ nests ” within recess 19 . with the upper and lower parts in this nested condition , as shown in fig4 and 5 , the combined height of the upper and lower parts 2 and 3 , i . e ., the height from surface 13 to surface 5 , is less than the total additive height of the upper and lower parts , taken separately , i . e ., less than the total of the height from surface 13 to the top of walls 16 , 17 and 18 plus the height from surface 5 to the bottom of protrusion 10 . to reach its final destination within an intervertebral space , the implant must of course be moved along a path from outside of the patient , into the patient , and then into the intervertebral space . in the illustrated embodiment , as described above , instruments would engage apertures 20 , 21 , 22 and 23 to move the implant along a path . the anchors 6 and 14 are parallel to this path . as a point of reference , lateral planes parallel to the direction of this path pass through opposed side surfaces of the parts . thus , in the illustrated embodiment , the path would be parallel to the front to rear ( anterior to posterior ) direction , wherein , during insertion , the rear ( posterior ) of the implant would constitute the lead end and the front ( anterior ) thereof would constitute the trailing end . although the invention has been described in detail with respect to preferred embodiments thereof , it will be apparent that the invention is capable of numerous modifications and variations , apparent to those skilled in the art , without departing from the spirit and scope of the invention .

an intervertebral implant comprises first and second parts having outer surfaces engaging adjacent vertebral surfaces . an insert between these parts provides relative movement therebetween . the first and / or second parts may have engagement means in the form of apertures for engagement with insertion instruments . the first and second parts may nest together , in the absence of the insert , for insertion into the intervertebral space . the boundaries of the implant may form a working space which would include insertion instruments therein . a detent and detent recess may be provided for engagement of the insert and one of said first and second parts .

the present invention provides a stent comprising a stable nuclide element that may be externally activated by thermal neutrons , thereby providing localized neutron capture therapy in the vicinity of the vessel around the stent . since radiation is applied by an external source , therapy may be delivered at any time after placement of the stent and easily may be repeated . furthermore , unlike other known radiation techniques , the present invention ensures that neutron capture therapy is only provided to patients where radiation exposure is expected to provide therapeutic benefit . in accordance with the principles of the present invention , a stent is constructed including a material having a high neutron capture cross - section , for example , greater than 10 3 barns , and that provides a high quality of radiation emission . as will of course be apparent , the irradiation dose provided by the stent after irradiation by an external source also depends upon the amount of stable nuclide element that is incorporated into the stent . preferred stable nuclides suitable for use in a stent constructed in accordance with the present invention are listed below with their corresponding thermal neutron capture cross - sections . atomic element cross - section ( barn ) 157 gd 254000 155 gd 60900 149 sm 40140 113 cd 20600 151 eu 5900 bulk materials with which these nuclide elements may be combined to form a stent or other interventional device for neutron capture therapy are provided below , again with corresponding thermal neutron capture cross - sections . preferably , the bulk materials have significantly lower neutron cross - sections compared to the elements employed for neutron capture , generally less than 10 2 barns . atomic element cross - section ( barn ) 198 au 98 59 co 20 48 ti 7 . 8 109 ag 4 . 5 107 ag 3 . 0 56 fe 2 . 6 while these bulk materials may produce a small amount of ionization radiation when subjected to thermal neutron radiation , the contribution of this ionization radiation to a composite absorbed dose is negligible . in a preferred embodiment , a stent for neutron capture therapy comprises gadolinium as the stable nuclide . gadolinium is a trivalent metallic element and is a member of the rare earth group . its atomic number is 64 , and it has a relative atomic mass of 157 . 25 . gadolinium has the largest known thermal neutron capture cross - section ( 254000 barn ) of any element . the most frequent stable gadolinium nuclide is denoted as gd - 157 . gd - 157 makes up 15 . 65 % of all gadolinium , and it primarily radiates energy in the form of high - energy gamma radiation . a previously known stent , for example , such as depicted in fig1 typically may weigh on the order of 40 mg . the amount of stable nuclide incorporated into such a stent in accordance with the principles of the present invention may be chosen based upon a variety of design considerations . for the purposes of illustration , assume an enriched target of n atoms of gd - 157 and a neutron flux of n thermal neutrons / cm2 / s . the number of neutron captures per second , ac , may be computed as : ac = n · n · 2 . 54 · 10 − 9 . 1 mg of gd - 157 ( n = 3 . 8 · 10 18 atoms ), which radiates neutrons at a rate of approximately n = 10 8 neutrons / cm 2 / s , provides an ac of about 9 . 7 · 10 7 captures per second . this is equivalent to a radioactive source with a strength of 9 . 7 · 10 7 bq . from the gamma spectrum of gd - 157 , the γ - constant may be determined as 1 . 28 gy / h / m 2 , and the dose rate distribution may be determined for a point source containing the 1 mg of gd - 157 . fig2 presents this dose rate distribution in a thermal neutron field of 10 8 n / cm 2 / s . the dose obtained from this calculation reflects a kerma value rather than an actual absorbed dose . gamma energies emitted are fairly high , on the order of several mev . these energies may have build - up zones of several millimeters , as seen in fig3 . the build - up zones level out the dose close to the source and compensate for the square - law dependence at the closest distances from the stent . this is an advantage of the present invention when compared to other radiation techniques that use high - energy beta or low - energy gamma sources having negligible build - up zones . according to these illustrative calculations , a therapeutic radiation dose may be delivered within a few seconds (& lt ; 10 seconds in a distributed source ). the dose contribution of the neutrons themselves , distributed as a general background , yield a dose far below biologically dangerous levels . in this example , the dose rate is expected to be about 1 gy / second in the area closest to the source , as seen in fig2 . the required dose may then be delivered in 10 - 30 seconds , or somewhat longer ( in a couple of minutes ) if the source is extended to offer a larger area , such as stent 20 of fig4 . stent 20 is fabricated from a material incorporating stable nuclide element s . this example indicates that therapeutic dose rates may be delivered within clinically acceptable parameters . corresponding calculations according to the above example also may be performed for the other listed atomic elements . it will be apparent to those of skill in the art that the amount of stable element s may be tailored to specific patient populations . referring still to fig4 stent 20 may comprise metal wire mesh 22 that is fabricated from an alloy or mix incorporating from a few tens to a few hundreds of micrograms of the desired stable nuclide s . in another embodiment , wire mesh 22 may comprise hollow wires in which stable element s is located . wire mesh 22 is preferably coated with a biocompatible material b to prevent direct contact between body tissue and the wire mesh metal containing stable nuclide s . also , stent 20 optionally may include fabric 24 , thereby providing a continuous tubular profile to stent 20 . the % composition , as well as the nuclide or nuclides comprising stable element s , may be varied within stent 20 to obtain a differentiation of radiation along stent 20 . in some applications , creating a larger radiation dose at the ends of the stent , where restenosis may be more pronounced , is expected to be advantageous . a method of using stent 20 is now described . stent 20 is deployed at a treatment site within a patient &# 39 ; s vasculature using well known percutaneous or subcutaneous techniques . when neutron capture therapy is deemed therapeutically beneficial , the patient is subjected to external radiation near the treatment site at clinically - acceptable levels that minimize damage to biological tissue . due to its high neutron capture cross - section , stable nuclide element s preferentially absorbs and emits the radiation to tissue at the treatment site surrounding stent 20 , thereby providing localized radiation therapy in a concentrated dose . the emitted radiation acts on surrounding tissue to provide a therapeutic benefit , for example , to reduce the restenosis often encountered after angioplasty and stenting . the short half life of stable element s provides negligible radiation when not irradiated , as imposed activity decays in milliseconds after completion of thermal neutron irradiation . an advantage of the stents constructed in accordance with the present invention is that the stents may be handled without concern for radiation exposure , as they contain only stable nuclides . a still further advantage is that when using , for example , gd - 157 as the neutron capture therapy element , a stent will only produce gamma radiation when subjected to neutron irradiation , as the lifetime of the active gadolinium is very short and decays in microseconds . as already noted , the primary wire mesh metal constituent of the stent will have a very small capture cross - section for neutron irradiation , but will not produce any harmful residual activity . irradiation using the present neutron capture therapy may advantageously be limited to when restenosis is observed , and the therapy may be applied repetitively , as needed . this avoids more extensive methods involving rearrangement of existing implanted stents or introduction of new stent devices , due to restenosis . it should be noted that , although stent 20 of fig4 illustrates a device for use in connection with coronary dilatation , a general stent device according to the present invention may also be used in connection with any subcutaneous ( or percutaneous ) therapy , e . g ., in connection with treatment of a tumor . radiation sources suitable for use with the stents of the present invention are known . for example , radiation sources capable of delivering a suitable number of thermal neutrons have been developed for boron neutron capture therapy ( bnct ) and are expected to be readily applicable to neutron capture therapy in accordance with the present invention . other sources , such as accelerators and radioactive sources delivering neutrons , may also be used with embodiments of the present invention . although preferred illustrative embodiments of the present invention are described above , it will be evident to one skilled in the art that various changes and modifications may be made without departing from the invention . for example , a wide variety of stent designs are known in the art ; incorporation of stable nuclides into these designs for the purpose of neutron capture therapy falls within the present invention . it is intended in the appended claims to cover all such changes and modifications that fall within the true spirit and scope of the invention .

improved method and apparatus for neutron capture therapy are disclosed , which may beneficially be used to counteract restenosis . an improved stent and a method for manufacturing the stent are also presented . the stent comprises a stable nuclide having a large neutron capture cross - section . when a clinical need exists for radiation therapy , the stent is irradiated with thermal neutrons , thereby giving rise to radiation in the proximity of the stent to a therapeutic benefit . since radiation is applied by an external source , it can be delivered at any time after placement of the stent and easily can be repeated . the stent only contains stable nuclides and therefore can be handled without the precautions needed when handling radioactive matter .

the hair treatment preparations of the invention comprise an agent or payload in permanent or semi - permanent intimate relationship with a polymeric nanostructure , the polymeric nanostructure being reactive to ( such as by covalent bonding ) or capable of being immobilized onto or in hair . in one embodiment , the polymeric nanostructure may include hair - reactive functional groups for binding or attachment of the nanostructure to the hair to be treated . by “ intimate relationship ” is meant that the payload is surrounded by , contained within , chemically attached to or otherwise in permanent or semi - permanent relationship with the polymeric nanostructure . by “ hair - reactive ” is meant that the payload - containing nanostructure will form a covalent bond with the hair . the terms “ payload ” and “ payload agent ” as used herein refer collectively to any material or agent that would be desirable for permanent or semi - permanent attachment to or treatment of human or animal hair . it may modify a property of hair or may add new and desirable properties to the hair . the payloads are also referred to herein as “ pendant groups ”. the payload may be , but is not limited to , dyes or coloring agents , pigments , opacifying agents , scents and fragrances , drugs and pharmaceuticals , softeners , insect repellents , antibacterials and antimicrobials , and the like . while the following discussions herein are directed to certain exemplary agents , it is important to note that other materials having any desirable activity or characteristic suitable for hair treatments may also be incorporated into polymeric nanostructures according to the teachings herein and are included within the scope of this invention . by “ dye ” is meant a molecule that can absorb wavelengths in the visible or ultraviolet region of the electromagnetic spectrum . nano - technology is an emerging field of study , where the objects / structures are nanoscopic in dimension . the word “ nano ” means one - billionth . therefore , objects characterized by dimensions of 1 nanometer to 1 micron ( 1 micrometer , or 1000 nanometers ) fall within the range of nano - technology . the power of nano - technology is evidenced by its ability to allow the designed products to segregate or partition engineering requirements into different parts of the system . instead of requiring the coloring agents or their precursors to penetrate deeply into the hair shaft , the nanoscopic entities may simply be deposited on the surface of the hair strand or only partially penetrate into the interior . durability or semi - permanency may be the result of , for example , how the nanoscopic structure attaches itself to the hair or crosslinks amongst neighboring entities or crosslinks through a fixative . in the latter two versions , the nanoscopic entities do not have to form direct linkages with the hair itself . in all versions , the nanoparticles or nanoscopic networks are only carriers for the active ingredients ( e . g ., hair dye ). they themselves do not have to be colored intrinsically . their primary functions are two - fold . first , they must provide a means to anchor themselves on the surface or shallow interior of hair . second , they must encase or encapsulate the correct dosage of dyestuff ( in the case of nanospheres or nanoparticles ) or have the dyestuff linked to the carrier ( in the case of nanoscopic networks ). note that nanoparticles may assume other , non - spherical shapes , yet may be equally capable of performing the same functions . in either direct attachment or indirect anchoring , the nano - technology approach does not resort to high temperature or extreme ph or harsh chemicals , the use of which will compromise the goal of this invention . examples of attachment / anchoring are presented below . those who are skilled in the art of polymer precipitation and complexation will undoubtedly envision additional means of securing the nanospheres based on the teachings herein . these are all intended to be covered by the spirit and scope of this disclosure . the above concepts are illustrated by the examples below . first , with respect to nanospheres or nanoparticles , the payload , for example dye molecules or their aggregates ( referred to collectively herein as “ dyestuff ”), is entrapped , that is , surrounded by or contained within a polymer shell or matrix . the nanoparticle of the invention may comprise a polymeric shell surrounding the payload or it may comprise a three - dimensional polymeric network entrapping the payload , both of which are referred to herein as a “ polymer shell ”. alternatively , in the case of hair dyes , if a lighter color / shade is desired , some or most of the particles will contain blocking agents , such as colloidal white pigments ( e . g ., titanium oxide or zinc oxide ). mixed with these whitening or opacifying agents are nanoparticles containing dyestuff . the overall system yields the desired color / shade , once the mixed particles are deposited on the hair . the nanospheres may be made of non - toxic , non - allergenic polymers . many polymers have been approved by the fda for topical usage . silicones and cellulosics , among many others , are salient examples . synthetic hydrocarbon - based polymeric systems are equally suitable alternatives . proteins or synthetic peptides can also be used for this purpose . well - established encapsulation techniques exist to encase the right amount of dye in particles of controlled size distribution . literature abounds in both processing and material information to achieve this objective . however , in the present invention , the surface of the nanoparticles contain functional groups for binding or attachment to the hair , to provide permanent or semi - permanent attachment of the payload to the hair . alternatively , the surface of the nanoparticle includes functional groups that can bind to a linker molecule that will in turn bind or attach the particle to the hair . in either case , these functional groups are referred to herein as “ hair - reactive functional groups ”. the chemical linkage on the surface of the nanoparticle does not involve the molecules of the payload . the payload agents are physically entrapped within the nanoparticle , thus requiring no chemical modifications of the payload molecules themselves . the resulting encapsulated payload preparations or nanoparticles have improved retention within and on the hair structure without changing the inherent character of the payload agent . the payload - containing nanoparticles may be formed via one of several methods of encapsulation known in the art , such as interfacial polymerization , microemulsion polymerization , precipitation polymerization , and diffusion . multi - component mixture preparation followed by atomization / spraying into a drying chamber is yet another processing scheme . reactive functional groups on the polymer shell provide a means for attaching the hair treatment nanoparticles to human hair . the nanoparticles of the invention are formed by contacting a payload with a set of monomers , oligomers , or polymers ( referred to herein as a “ polymeric set ”). the monomers , oligomers , or polymers assemble around the payload and then are polymerized , with or without crosslinking , into a polymeric network or shell surrounding the payload . the polymeric set in one embodiment includes at least some components that provide reactive functional groups on the surface of the final polymeric bead , which will bind to the hairs to be treated . alternatively , a nanoparticle optionally having hair - reactive functional groups on its surface can first be prepared by polymerizing a polymeric set , after which a payload can be exposed to the bead under suitable conditions such that the payload is absorbed into and entrapped in the polymeric network or shell , to provide the hair - reactive payload nanoparticle . particular monomers , oligomers , or polymers useful in forming the nanoparticles of the present invention are those that contain amine , hydroxyl , or sulfhydryl monomers or polymers combined with amine -, hydroxyl -, or sulfhydryl - reactive monomers or polymers . along the backbone of the polymer constituting the nanospheres , hair - reactive functional groups may be introduced that may either be chemically reactive under mild conditions or be electrostatically interactive with complementary groups on the surface of the hair when the ionic strength or surfactant content of the medium is shifted by rinsing . example interactions include charge - charge , dipolar , hydrogen - bonding , hydrophobic , or dehydration interactions . the nanospheres may be made of a polyelectrolyte with an isoelectric point in the range of alkaline ph . these particles may be effectively precipitated or aggregated by using another polyelectrolyte ( linear or branched polymer fixative ) that possesses an acidic isoelectric point . when the hair is first exposed to the nanospheres and then is re - exposed to the second polyelectrolyte fixative , a complex forms in situ , coating the treated hair . another route is the use of a potent surfactant formulation to carry the payload - containing nanoparticles to the hair surface in a finely divided dispersion . once in place , the surfactant is rinsed away , leaving the nanoparticles adhering strongly to the treated hair . an example is silicone - based nanoparticles . such particles can be easily dispersed in a block or graft copolymer of poly ( dimethylsiloxane - ethylene glycol ) liquid . the latter medium may be rinsed away by water , as the component is water - soluble , leaving the insoluble nanoparticle as an adherent precipitate . functionalized siloxanes can further refine this precipitation principle by utilizing complexation as well . for example , siloxanes with carboxylate side groups may be precipitated by the dual use of removing the surfactant and adding a polyamine ( such as polyethyleneimine in the aqueous rinse solution ). conversely , amino - substituted siloxanes can form an in situ crosslinked network with the nanoparticles embedded within by the addition of polyacids ( such as polyacrylic acid or polymaleic acid or copolymers thereof ). complexation can also be induced by addition of polyvalent cations or anions , each reactive towards the complementary charged surface groups . the principle of thermodynamics - induced and complexation - induced precipitation / anchoring on hair surfaces can be equally applied to other synthetic or naturally occurring nanostructures . for example , the payload can first be chemically coupled onto a protein carrier . this protein - payload complex is dispersed in a medium , which is then applied to the hair . a change in the thermodynamic balance of the medium causes deposition of the complex on the surface of hair . the hair is thus treated . since coupling is carried out chemically outside the presence of hair , traditional chemical means can be used without fear of hair degradation or skin sensitivity . protein deposition can then be effected by simpler , milder fixative reactions . we reiterate the power of delegating different engineering requirements to different parts of the system . the color comes from the dyestuff contained within the nanoparticles . yet , the controlled degree of permanency stems from the attachment methodology . the above precipitation / complexation approach can be made difficult to reverse or it can be easily reversible . reversibility can be engineered to occur only in the presence of certain specific agents . therefore , normal hair wash or shampoo does not cause fading of the color . for example , functionalized silicones are difficult to wash away , unless specific siloxane - containing surfactants such as block or graft copolymers of siloxane - polyethylene glycol are used . equivalently , complex or precipitate dissolution may or may not occur under similarly engineered rinsing conditions . thus , the artificially - created hair color can be either preserved in a prolonged manner or reversed when desired . note that derivatized cellulosics can be made to function in a similar way . synthetic polypeptides can also be used for dyestuff encapsulation . such cellulosic or proteinaceous surfaces can be modified to exhibit varying isoelectric points , which can be exploited to tailor their precipitation / coagulation / complexation properties . nanospheres are but one geometry as a possible dye or other payload carrier . dye molecules can also be attached to linear , branched , or lightly crosslinked polymer carriers , as long as they remain soluble or dispersible in a suitable ( aqueous or mixed aqueous ) and chemically mild liquid . dye fixation onto hair is implemented through reaction / precipitation / complexation on the surface of hair via any of the above - illustrated and many other schemes . imagine the dye - attached polymer having a tree - like architecture . as long as residual functional groups exist after the dye is attached onto the tree , the whole ensemble may be deposited on the surface of hair in a subsequent operation ( removal of surfactant , addition of precipitant , introduction of coagulating or complexing agent , etc .). even if no discernible functional groups remain after the initial dye attachment , the carrier still may have great utility simply due to its ability to adhere firmly to hair as a consequence of a shift in the thermodynamic environment of the medium . one group of polymers useful as nanostructures in the present invention are the dendrimers and other highly branched polymers . dendrimers also have a high degree of symmetry . because such polymers are branched , they are compact and so good penetration , and thus permanency , into hair is expected . dendrimers and highly branched polymers can be designed to have one or more different types of functional groups on them . using these functional groups , dye molecules , alkyl or siloxane chains to add softness , or other molecules of interest can be attached to the dendrimer so that it becomes a compact carrier . the payload - containing linear , branched , or lightly crosslinked polymer carriers may be attached to the hair via a mordant or cationic fixing agent . carboxyl -, phosphate -, phosphonate -, sulfate -, and sulfonate - containing polymers can be complexed with alkaline earth metal that have very low toxicity , such as mg 2 + , ca 2 + , and sr 2 + . thus , for example , a soluble polymer that contains , for example , carboxyl groups and one or more payloads , such as dye molecules or compounds that add softness , is applied to the hair . in a next step , a soluble calcium or magnesium salt is added to the hair to precipitate the polymer on and in the hair . in short , the nanoscopic carrier approach provides a flexible , invisible system to color hair . in contrast to traditional chemical assaults , the system is gentle to the hair and the color may be long - lasting or reversed by custom - tailored means . in a manner similar to the dying process described above , the nanoscopic carriers described in this invention may also be used to deposit fragrances , uv absorbers / blockers , and other desirable agents on hair . the carriers may be particulate in shape or simply be a polymer of arbitrary architecture . the use of methods of fixation enabled through the carriers is one part of the innovation . silicones and polyolefins impart a soft hand on hair . they may be deposited on hair simply as the carrier itself in the context of this invention . the fixative step is then part of the innovation . for example , in the first rinse a cationic silicone is applied . this coating is then fixed in place in a subsequent rinse containing an anionic silicone , resulting in a complex formation that creates a silicone network on the surface of the hair . charged polyolefins can be substituted for the silicones in the above example . in certain instances , such as for example when the payload is a fragrance or a pharmaceutical agent , it is desirable for the payload to be controllably released from the nanostructure on or into the hair . nanoparticles can be designed so that the payload agent is embedded or entrapped within the polymeric shell or matrix of the nanoparticle but is also able to be released from the nanoparticle in a prolonged or otherwise controllable fashion . the release profile is programmed via the chemistry of the polymer network of the nanoparticle . the nanoparticle can be formulated with an almost infinite degree of designed characteristics via structural features , such as crosslinking density , hydrophilic - hydrophobic balance of the copolymer repeat units , and the stiffness / elasticity of the polymer network ( for example , the glass transition temperature ). in addition , erodible nanoparticles or other nanostructures can be developed to controllably release the payload . furthermore , the polymer matrix may contain components that react or respond to environmental stimuli to cause increased / decreased content release . “ smart polymers ” are polymers that can be induced to undergo a distinct thermodynamic transition by the adjustment of any of a number of environmental parameters ( e . g ., ph , temperature , ionic strength , co - solvent composition , pressure , electric field , etc .). for example , smart polymers based on the lower critical solution temperature ( lcst ) transition may cut off release when exposed to warm or to hot water during washing . when cooled back to room temperature , sustained release resumes . smart polymers may be selected from , but are not limited to , n - isopropyl acrylamide and acrylamide ; polyethylene glycol , di - acrylate and hydroxyethylmethacrylate ; octyl / decyl acrylate ; acrylated aromatic and urethane oligomers ; vinylsilicones and silicone acrylate ; polypropylene glycols , polyvinylmethyl ether ; polyvinylethyl ether ; polyvinyl alcohol ; polyvinyl acetate ; polyvinyl pyrrolidone ; polyhydroxypropyl acrylate ; ethylene , acrylate and methylmethacrylate ; nonyl phenol ; cellulose ; methyl cellulose ; hydroxyethyl cellulose ; hydroxypropyl methyl cellulose ; hydroxypropyl cellulose ; ethyl hydroxyethyl cellulose ; hydrophobically - modified cellulose ; dextran ; hydrophobically - modified dextran ; agarose ; low - gelling - temperature agarose ; and copolymers thereof . if crosslinking is desired between the polymers , multifunctional compounds such as bis - acrylamide and ethoxylated trimethylol propane triacrylate and sulfonated styrene may be employed . in presently preferred embodiments , the smart polymers comprise polyacrylamides , substituted polyacrylamides , polyvinylmethyl ethers , and modified celluloses . where it is desirable for the payload to be visible ( when it is a dye or a uv protector , for example ), the nanoparticle will be constructed of optically transparent or translucent material , allowing light to come into contact with the payload and be reflected , refracted or absorbed . the polymeric set can be chosen to give either hydrophobic or oleophilic nanoparticles , allowing a wider array of bioactive compounds or drugs to be comfortably entrapped within . where the particles are hydrophilic , they are easily dispersible in a stable aqueous suspension or emulsion by surfactants , which can subsequently be washed away without affecting the performance of the payload agent within . the inherent thermodynamic compatibility of the agents and the polymeric shell or matrix material can increase the loading level per particle . the following examples are intended to illustrate some , but not all , of the concepts described in this disclosure , and are in no way intended to limit it . one skilled in the art would also see that different ideas from different examples or from the above explanation could be combined to yield other possible ways of treating hair . one or more of the same or different dye molecules are covalently bonded , by methods known in the art , to an amine - containing polymer or oligomer such as poly ( ethylenimine ), poly ( allylamine hydrochloride ), or poly ( lysine ). ( an oligomer or polymer of arginine would be expected to behave similarly .) hair is wet with a solution containing this polymer or oligomer with dye molecules pendant on it ( a polymeric or oligomeric dye ). in some cases it may be necessary to rinse away excess material . to set or cure the amine - containing polymer , the hair is then exposed to a polymer that contains carboxyl , sulfate , sulfonate , phosphate , or phosphonate moieties . examples of such polymers include dna , poly ( acrylic acid ), poly ( itaconic acid ), poly ( maleic anhydride ), copolymers containing maleic anhydride units , a polymer with — c 6 h 5 cooh groups , poly ( methacrylic acid ), or polystyrene sulfonate , sodium salt ). excess material is then rinsed away . an electrostatic interaction holds the two polymers together , greatly decreasing the solubility of the complex . this and all other formulations and solutions mentioned in this document may additionally contain fragrances , wetting agents , oxidizing agents , antioxidants , opacifiers , thickeners , reducing agents , defoamers , surfactants ( anionic , cationic , nonionic , amphoteric , zwitterionic , or mixtures thereof ), sequestering agents , medicines ( drugs ), dispersing agents , conditioners , limited quantities of organic solvents , antibacterial agents , preserving agents , and the like , as well as mixtures thereof . one or more dye molecules are covalently bonded to a carboxyl - containing polymer or oligomer such as poly ( acrylic acid ), poly ( itaconic acid ), poly ( maleic anhydride ), a copolymer containing maleic anhydride units , a polymer with — c 6 h 5 cooh groups , or poly ( methacrylic acid ). hair is wet with a solution containing this oligomeric or polymeric dye . excess material is then rinsed away . to set this polymer , the hair is exposed to a polycation ( polymer or oligomer ), such as poly ( ethylenimine ), poly ( allylamine hydrochloride ), poly ( lysine ), poly ( arginine ), or poly ( diallyldimethylammonium chloride ). hair is exposed to a solution containing one or more polymeric or oligomeric dyes , as described in example 1 ( polycations ). it may be necessary to rinse the hair after this first treatment . the hair is then exposed to a solution that contains one or more polymeric or oligomeric dyes ( polyanions ), as described in example 2 and it is rinsed . an alkyl chain , which is defined herein as a linear or branched molecule that contains primarily c , ch , ch 2 , and ch 3 units , is tethered to an amine - containing polymer or oligomer , such as poly ( ethylenimine ), poly ( allylamine hydrochloride ), or poly ( lysine ). linear or branched siloxane chains may also be added to the amine - containing polymer or oligomer . one or more of the same or different dye molecules may also be added to the polymer , by methods known in the art . hair is then exposed to this polycation and excess reagent may be rinsed away . the hair is then exposed to a polyanion , which may have alkyl chains , siloxane chains , or dyes tethered to it . one possible polyanion , which may act as a softener , is a copolymer of maleic anhydride and a vinyl ether of the form : ch 2 ═ cho ( ch 2 ) n ch 3 , where n is at least 2 , and is preferably greater than 4 . an amine - containing dye is reacted with benzoquinone , naphthoquinone , anthraquinone or a derivative thereof to form a polymeric or oligomeric dye . the following are three of the numerous possible adducts . an amine - containing dye is reacted with a dye that contains one or more reactive groups such as acid chlorides (— c ( o ) cl ), sulfonyl chlorides (— so 2 cl ), vinyl sulfones (— so 2 ch ═ ch 2 ), or an active derivative of cyanuric chloride . examples of each of these four possible linking chemistries for dyes and polymers is shown below . any other amine - reactive functional groups that may appear on a reactive dye molecule , such as epoxides or acid anhydrides , could be used as well . a polyelectrolyte containing pendant groups , which modify a property of hair or which add new and desirable properties , is deposited on hair . an oppositely charged polyelectrolyte , which also may contain one or more pendant groups that modify a property of hair or that add a desirable property to hair , is added to the hair , condensing with the first polymer to immobilize it . a polymer or oligomer that contains one or more pendant groups , which modify one or more properties of hair or which add one or more desirable properties , is deposited on hair . excess reagent may be washed away from the hair . a mordant , which we define as a species that contains a metal atom with an oxidation number of 2 or higher , is added to the deposited polymer , immobilizing the polymer . a mordant is deposited on hair . excess reagent may be washed away from the hair . a polymer or oligomer that contains one or more pendant groups which modify one or more properties of hair or which adds one or more desirable properties is deposited on hair . the mordant complexes with the polymer to immobilize the polymer . one or more dye molecules is covalently attached to a polymer or oligomer of ethylenimine , such as triethylenetetraamine ( see reaction scheme 1 ). in addition town ethylenimine , any polymer with free amine groups may be used , including poly ( allylamine hydrochloride ) and poly ( lysine ). additional starting materials include small molecules with multiple amines , such as ethylenediamine , and large polymers of ethylenimine ( branched or linear ). amines are well know to react with a variety of dyes . for example , u . s . pat . no . 6 , 203 , 578 shows reactions of amines with benzoquinone , naphthoquinone , and anthraquinone , and some of their derivatives , as well as with dyes that have amine - reactive groups . other amine - reactive groups that are found on commercially - available reactive dyes include moieties based on vinyl sulfone and cyanuric chloride . after introduction of the dye to the polymer , a group capable of chelating a metal is introduced . one of the possible ways of doing this is by reaction of the remaining amines on the molecule with an ester of α - chloro , α - bromo , or α - iodoacetic acid . the ester is a protecting group that is removed after addition of the molecule to the polymer . thus , this triethylenetetraamine - dye adduct is then allowed to react with an ester of α - haloacetic acid ( clch 2 c ( o ) or , brch 2 c ( o ) or , ich 2 c ( o ) or ) ( see reaction scheme 1 ). the ester group is then removed by a method known in the art ( deprotection ), leaving a metal - chelating polymeric dye . methods for the introduction of the protected metal chelating group and its deprotection are known in the art ; see , u . s . pat . no . 6 , 080 , 785 . in a preferred embodiment , the ester of the α - haloacetic acid is a methyl ester . for example , clch 2 c ( o ) och 3 is an inexpensive chemical that is available in bulk quantities . note that the carboxymethyl group can be introduced by reaction of formaldehyde and hydrogen cyanide with an amine . the addition of these two reagents to ethylenediamine ( the strecker synthesis ) yields ethylenediaminetetraacetic acid ( edta ) ( see beyer and walter in handbook of organic chemistry , prentice hall , 1996 ). also note that the chelating polymeric dye shown in reaction scheme 1 is a close analog of edta and nitrilotriacetic acid ( n ( ch 2 cooh ) 3 ), both of which are effective metal chelators . this example ( see reaction scheme 2 ) demonstrates two important features of the chemistry disclosed herein . first is the ability to immobilize a polymeric dye with a mordant using groups that can chelate a metal . second is the extraction of the metal atoms from the polymer with edta or nta , which reverses the initial dyeing process . note that the exact geometry of the metal - polymer complex will vary from metal to metal . both intramolecular ( shown in reaction scheme 2 ) and intermolecular crosslinks between polymeric or oligomeric dye molecules are expected . as is the case for all of the processes shown here , the depth of penetration of the dye into the fiber could be controlled , in part , by the size of the molecule . one or more surfactants or other additives may also be present in this and other formulations ( see example 1 ). in this example ( see reaction scheme 3 ), a polymeric dye is first created , a softening agent is then added to the oligomeric or polymeric dye , and a chelating group is introduced . siloxane and alkyl chains are expected to act as softeners , but another important feature of these long chains is to reduce the solubility of the polymeric or oligomeric dye . thus , when any surfactants in the formulation are removed by rinsing , the polymeric dye may be deposited onto the hair . addition of metal ( shown in reaction scheme 4 ) would act to increase its durability . as was the case in example 11 , the process of adding a metal is reversible using edta and nta ( see reaction scheme 5 ). reaction scheme 3 shows introduction of an alkyl or siloxane chain with an epoxide group . while epoxide chemistry is a preferred embodiment of the ideas in this example , other possible reactive groups that could be used to introduce long - chain alkyl or siloxane groups by means known in the art include , but are not limited to , anhydrides , acid chlorides , carboxylic acids , sulfonyl chlorides ( to make sulfonamides ), etc . a variety of molecules that impart desirable properties to hair or to the formulation can be incorporated into reactive monomers , such as in the reaction between an amine and an acid chloride ( see reaction schemes 6 and 7 ). later it will be possible to polymerize such monomers into polymers that have desirable properties , where the level or concentration of certain groups is carefully controlled . n - isopropylacrylamide ( nipa ) ( see reaction scheme 7b ) will make a polymer thermally sensitive . in other words , at low temperatures , a polymer that has nipa ( or an analogous monomer ) will have a higher water solubility than at higher temperatures . thus , a polymer can be designed that precipitates when the hair is washed with warm or hot water . in this example ( see fig1 ), a set of molecules , which may be dyes , fragrances , softeners , medicines ( drugs ), monomers , or other molecules which modify a property of hair or which add new and desirable properties , is emulsified with a polymerizable surfactant . the resulting micelles are then polymerized into a nanoparticle , which can be applied to hair and then , depending on the head group of the surfactant , set with a mordant or a polyelectrolyte with a charge opposite that of the surfactant &# 39 ; s head groups . the head groups may be designed to be analogs of edta or nta so that the surfactant will be particularly effective in chelating a metal ion . derivatives of itaconic anhydride and maleic anhydride can be used as polymerizable surfactants ( see reaction scheme 8 ). to produce such surfactants , a fatty alcohol ( or amine , which is not shown ) can be reacted with the anhydride to produce a surfactant . a carboxyl group is the head group . in its deprotonated form , it will impart a high degree of solubility to the alkyl chain in the surfactant . this head group can be precipitated with an appropriate mordant . in some cases , it may be desirable to create an anionic surfactant by addition of ethylene oxide units to the carboxyl group of the polymerizable surfactant ( bottom four structures in reaction scheme 8 ). it is not intended that the present invention be limited to the polymerizable surfactants described in this document . a variety of other polymerizable surfactants have been developed and may be applicable to the situations described herein . a few references showing the syntheses , use , and properties of these materials include : stähler , et al ., langmuir 1998 , 14 , 4765 - 4775 ; stähler , et al ., langmuir 1999 , 15 , 7565 - 7576 ; kline , langmuir 1999 , 15 , 2726 - 2732 ; soula and guyot , langmuir 1999 , 15 , 7956 - 7962 ; shen , et al ., langmuir 2000 , 16 , 9907 - 9911 ; viitala , et al ., langmuir 2000 , 16 , 4953 - 4961 ; jung , et al ., langmuir 2000 , 16 , 4185 - 4195 ; gargallo , et al ., langmuir 1998 , 14 , 5314 - 5316 ; liu , et al ., langmuir 1997 , 13 , 4988 - 4994 ; xu , et al ., langmuir 1999 , 15 , 4812 - 4819 . a polyamine , which contains two or more amine groups ( the amines could be pendant or the spacing between the amines could be three or more carbons , although it is two in the preferred embodiment ), is reacted with one or more alkyl or siloxane chains to produce a surfactant ( see reaction scheme 9 ). the amines are then derivatized with carboxymethyl groups to form a surfactant that can chelate metals . thus , a set of dyes , fragrances , softeners , medicines ( drugs ), or other small molecules or polymers could be brought into solution with this surfactant and the resulting micelles could be precipitated onto hair by using an appropriate mordant . a particularly useful embodiment of this idea is the reaction of ethylenediamine with an oxirane ring ( epoxide ) on an alkyl or siloxane chain . carboxymethyl groups are then introduced into the resulting molecule . one or more of the carboxyl groups or the hydroxyl group may be functionalized with ethylene oxide units , as is commonly done with nonionic surfactants . a variety of molecules that add desirable properties to a polymer are added to poly ( acryloyl chloride ), which acts as a scaffold . see reaction scheme 10 for examples of a few of the many possible species ( amines and alcohols in the preferred embodiment ), which could react with poly ( acryloyl chloride ) to create a functionalized polymer with tailored properties . a variety of molecules that add desirable properties to a polymer are added to poly ( acrylic anhydride ), which acts as a scaffold . see reaction scheme 11 for examples of a few of the many possible species ( amines and alcohols in the preferred embodiment ), which could react with poly ( acrylic acid ) to create a functionalized polymer with tailored properties . copolymers of maleic anhydride would be expected to react similarly to the polymer shown in reaction scheme 11 . a fatty amine with the general formula ch 3 ( ch 2 ) n nh 2 , although branched alkyl chains are also possible , is derivatized with carboxymethyl groups according to the methods described in this document to yield a surfactant with the formula : ch 3 ( ch 2 ) n n ( ch 2 cooh ) 2 . one or both of the carboxyl groups in this surfactant can be deprotonated . a set of small molecules , which may include dyes , fragrances , softeners , medicines ( drugs ), monomers , etc ., is made soluble with this surfactant . the resulting micelles are then precipitated onto hair with a mordant . because this surfactant can be rendered insoluble by chelating it with an appropriate metal , this surfactant could be generally useful in any situation where it is desirable to remove a surfactant from a formulation . as is the case for nonionic surfactants , some ethylene oxide units may be added to this surfactant . it is expected that mordant crosslinking with chelating surfactants will be of intermediate effect in limiting the release of small molecules captured in micelles by these surfactants . thus , capture and immobilization of small molecules by this method may provide an effective means of allowing time release of certain small molecules such as fragrances and medicines ( drugs ). surfactants with different chelating powers ( note those in example 17 and reaction scheme 9 ) could be combined to fine tune properties of time - release formulations . a set of one or more surfactants is used to bring one or more insoluble or quite insoluble species , including polymers and oligomers , into aqueous solution . upon rinsing away the material , the insoluble or nearly insoluble species are deposited onto hair . a known dye molecule , including , but not limited to acid dyes , direct dyes , reactive dyes , mordant dyes , sulfur dyes , and vat dyes , is reacted with a polymer and the polymer is deposited on hair by one of the methods described in this document . a mordant dye is coupled to a polymer or oligomer and this material is deposited on hair . addition of a mordant causes crosslinking of the polymer molecules through the mordant dye pendant groups . a protein , which acts as a scaffold , is derivatized with dye molecules , softeners , a polyelectrolyte oligomer chain , carboxymethyl groups or other species that may impart a desirable property to hair . the resulting protein complex is then precipitated onto hair and immobilized to one degree or another with the methods described herein , e . g ., a polyelectrolyte or a mordant . while this invention has been particularly shown and described with references to preferred embodiments thereof , it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims .

the present invention is directed to a hair treatment preparation comprising a payload in an intimate relationship to a polymeric nanostructure , the polymeric nanostructure being reactive to hair or capable of being immobilized onto or in hair . the nanoscopic nature of the entities being engineered ensures three distinct characteristics . first , the imparted attribute can be either nearly permanent or semi - permanent , depending on the attachment chemistry . in the semi - permanent version , the intended effect can be controllably erased by removal of the nanostructure by simple chemical or physical means . second , the nanoscopic entities are invisibly small . their presence does not deteriorate the hand or feel of the hair . third , the nano - technology approach is infinitely flexible and adaptable . it can be coupled with many existing dyes , colorants , uv absorbers , fragrances , softening agents and the like for hair treatment . methods for treating hair with the hair treatment preparations of the invention are also encompassed .

as used herein , the term “ eye disease ” refers to either an acute or chronic condition , which may in some instances be a result of oxidation processes , including macular degeneration , age - related macular degeneration ; stargardt disease , best diseases , retinitis pigmentosa , and cataracts . “ visual performance ” refers to the visual performance of a subject . visual performance includes visual acuity , low contract acuity , mesopic acuity , letter contract sensitivity , grating contrast sensitivity , disability glare , intraocular stray light , and visual fields . an improvement in visual performance includes an improvement in an aspect of vision , such as an improvement in visual acuity , low contract acuity , mesopic acuity , letter contract sensitivity , grating contrast sensitivity , or visual fields or a reduction in disability glare or intraocular stray light . “ macular carotenoid formulation ” refers to a composition that includes carotenoids found in the macula of the eye , principally lutein and zeaxanthin . as used herein , the term “ therapeutically effective amount ” refers to the amount / dose of a compound or pharmaceutical composition that is sufficient to produce an effective response ( i . e ., a biological or medical response of a tissue , system , animal or human sought by a researcher , veterinarian , medical doctor or other clinician ) upon administration to a subject . the “ therapeutically effective amount ” will vary depending on inter alia the disease and its severity , and the age , weight , physical condition and responsiveness of the subject to be treated . as used herein , the terms “ treated ” and “ treating ” refers to preventing or delaying the appearance of clinical symptoms of a disease or condition in a subject that may be afflicted with or predisposed to the disease or condition , but does not yet experience or display clinical or subclinical symptoms of the disease or condition . “ treating ” also refers to inhibiting the disease or condition , i . e ., arresting or reducing its development or at least one clinical or subclinical symptom thereof . “ treating ” further refers to relieving the disease or condition , i . e ., causing regression of the disease or condition or at least one of its clinical or subclinical symptoms . the benefit to a subject to be treated is either statistically significant or at least perceptible to the subject and / or the physician . the invention provides the use as above wherein the composition is for administration as a unit dose . in another embodiment of the invention , the unit dose contains the active ingredient ( s ) in an amount from about 10 μg / kg to 10 mg / kg body weight , in another embodiment from about 25 μg / day / kg to 1 . 0 mg / day / kg , in yet another embodiment from about 0 . 1 mg / day / kg to 1 . 0 mg / day / kg body weight . in another embodiment , the unit dose is containing the active ingredient in an amount from 0 . 1 mg / day / kg to 1 . 0 mg / day / kg body weight . according to the invention , the compounds mentioned above may be administered in any suitable way e . g . orally or parenterally , and it may be presented in any suitable form for such administration , e . g . in the form of tablets , capsules , powders , syrups or solutions or dispersions for injection . in another embodiment , and in accordance with the purpose of the present invention , the compound of the invention is administered in the form of a solid pharmaceutical entity , suitably as a tablet or a capsule or in the form of a suspension , solution or dispersion for injection . the compound of the invention is most conveniently administered orally in unit dosage forms such as tablets or capsules , containing the active ingredient in an amount from about 10 μg / kg to 10 mg / kg body weight , for example 25 μg / day / kg to 1 . 0 mg / day / kg . compounds of the present invention may be administered as an oral dose form , such as a solid oral dose form , typically tablets or capsules , or as a liquid oral dose form , or may be administered in an immediate release dosage form or a controlled or sustained release dosage form . the compounds may be conveniently administered orally in unit dosage forms , such as tablets or capsules , containing the active ingredient in an amount from about 0 . 1 to about 150 mg / day , from about 0 . 2 to about 100 mg / day , from about 0 . 5 to about 50 mg / day , from about 0 . 1 to about 50 mg / day , from about 1 to about 15 mg / day , or from about 2 to about 5 mg / day . typically , the pharmaceutical composition comprises from about 0 . 5 mg to about 20 mg , such as about 0 . 5 mg , about 1 mg , about 1 . 5 mg , about 2 mg , about 2 . 5 mg , about 3 mg , about 3 . 5 mg , about 4 mg , about 4 . 5 mg , about 5 mg , about 5 . 5 mg , about 6 mg , about 6 . 5 mg , about 7 mg , about 7 . 5 mg , about 8 mg , about 8 . 5 mg , about 9 mg , about 9 . 5 mg , about 10 mg , about 10 . 5 mg , about 11 mg , about 11 . 5 mg , about 12 mg , about 12 . 5 mg , about 13 mg , about 13 . 5 mg , about 14 mg , about 14 . 5 mg , about 15 mg , about 15 . 5 mg , about 16 mg , about 16 . 5 mg , about 17 mg , about 17 . 5 mg , about 18 mg , about 18 . 5 mg , about 19 mg , about 19 . 5 mg or about 20 mg of one or more of the compounds . in one embodiment , the compound ( s ) of the present invention are administered once daily ( for example , in the morning or afternoon ) using doses of about 2 . 5 mg to about 20 mg . in another embodiment , the compound ( s ) are administered in a more prolonged and continuous release , e . g ., administration 2 - 3 times daily with low doses or a modified release formulation prepared using conventional methods known in the art , such that about 5 to about 50 mg administered to the subject per 24 hour period . according to the present invention , the compound ( s ) of the present invention or a pharmaceutically acceptable salt thereof may be administered in any suitable way , e . g ., orally or parenterally , and it may be presented in any suitable form for such administration , e . g ., in the form of tablets , capsules , powders , syrups or solutions or dispersions for injection , or as an inhalant . in another embodiment , and in accordance with the purpose of the present invention , the compound ( s ) of the present invention are administered in the form of a solid pharmaceutical entity , suitably as a tablet or a capsule or in the form of a suspension , solution or dispersion for injection . additionally , the compound ( s ) of the present invention may be administered with a pharmaceutically acceptable carrier , such as an adjuvant and / or diluent . methods for the preparation of solid or liquid pharmaceutical preparations are well known in the art . see , e . g ., remington : the science and practice of pharmacy , 21st ed ., lippincott williams & amp ; wilkins ( 2005 ). tablets may thus be prepared by mixing the active ingredients with an ordinary carrier , such as an adjuvant and / or diluent , and subsequently compressing the mixture in a tabletting machine . non - limiting examples of adjuvants and / or diluents include : corn starch , lactose , talcum , magnesium stearate , gelatine , lactose , gums , and the like . any other adjuvant or additive such as colorings , aroma , and preservatives may also be used provided that they are compatible with the active ingredients . the pharmaceutical compositions of the invention thus typically comprise an effective amount of the compound ( s ) of the present invention and a pharmaceutically acceptable carrier . the compounds may be administered systemically in a form selected from the group consisting of : an aerosol suspension of respirable particles ; a liquid or liquid suspension for administration as nose drops or nasal spray ; a nebulized liquid for administration to oral or nasopharyngeal airways ; an oral form ; an injectable form ; a suppository form ; and a transdermal patch or a transdermal pad . one such means involve an aerosol mixture of respirable particles comprised of the active compounds , which the subject inhales . the therapeutic compound is absorbed into the bloodstream via the lungs in a pharmaceutically effective amount . the respirable particles may be liquid or solid , with a particle size sufficiently small to pass through the mouth and larynx upon inhalation ; in general , particles ranging from about 1 to 10 microns , but more preferably 1 - 5 microns , in size are considered respirable . ever since its identification as a major fluorophore of ocular lipofuscin , a2e has been considered an important mediator of pathalogical processes involved in aging and retinal degenerations ( 3 - 6 ). clinically , autofluorescent compounds in the human retinal pigment epithelium increase with age when measured with autofluorescence imaging ( 17 - 18 ), and early onset macular dystrophies such as stargardt and best diseases likewise exhibit high levels of lipofuscin deposition ( 7 , 9 ). in dry age - related macular degeneration , intense autofluorescence is often seen at the border of geographic atrophy in regions in which further expansion of atrophy is likely to occur ( 19 ). increased levels of a2e have been confirmed biochemically in autopsy eyes of elderly individuals and in donor eyes from individuals with macular dystrophies ( 4 - 9 ). animal models of dominant and recessive stargardt disease have been developed that accumulate a2e such as the abca4 knockout mouse ( heterozygous and homozygous ) as well as the elov14 transgenic mouse ( 7 - 8 ). in vitro studies indicate that a2e may exert its toxic effects on the rpe through blue - light - mediated free radical generation or by induction of lysosomal dysfunction through detergent - like and ph altering effects ( 10 - 11 , 20 - 21 ). there is general consensus that limiting a2e formation is a worthwhile target for pharmacological interventions against amd and related diseases , and a number of groups in academia and industry have dedicated themselves to this task . a2e formation has been linked to intense light exposure which causes high degrees of throughput of retinoids in the visual cycle , facilitating formation of elevated amounts of various schiff base adducts of all - trans - retinal with phosphatidylethanolamine , the precursors of a2e ( 22 - 23 ). although severe light restriction inhibits a2e formation in animal models ( 22 ), this approach is probably not practical in humans . therefore , inhibitors of the visual cycle have been a primary focus . these include 13 - cis - retinoic acid , an fda approved acne medicine that inhibits dark adaptation through alcohol dehydrogenase and / or isomerase inhibition ( 24 ), fenretinide , a retinoid analogue that induces a moderate systematic deficiency of vitamin a ( 25 ), and rpe - 65 antagonists targeted to inhibit a key step of the vertebrate mechanism which isomerizes all - trans - retinoids to 11 - cis - retinoids ( 26 ). all of these agents will cause some degree of night blindness which may be uncomfortable for the patients , and retinoid - based compounds when used chronically may cause significant systemic side effects and teratogenicity . non - retinoid rpe - 65 antagonists appear to be well tolerated in animal models , but there is little , if any , human experience with these compounds . the macular carotenoids lutein and zeaxanthin have also been considered as possible antagonists against the formation and the toxic effects of a2e ( 14 ). multiple epidemiological studies have demonstrated an inverse correlation between high dietary intakes , blood levels , and macular levels of these xanthophylls and risk of amd ( 27 - 30 ), and the areds 2 study is currently evaluating their efficacy against amd in a large , randomized , placebo - controlled , prospective manner . the macular carotenoids efficiently absorb blue light , the region of the visible spectrum that is most likely to produce free radicals from a2e , and in vitro they can inhibit photo - oxidation of a2e and its precursors ( 14 ). organic solvents were hplc grade from fisher scientific ( hampton , n . h .). standards of a2e and iso - a2e were prepared and column purified in the laboratory of dr . heidi r . volmer - snarr , department of chemistry and biochemistry , brigham young university , provo , utah . they were dissolved in methanol ( meoh ) at a concentration of 1 μg / ml , stored at − 70 ° c ., and brought to room temperature before use . the concentration of the stock solution of a2e was confirmed spectroscopically [ e ( im ) at 439 nm = 36900 ] using a published extinction coefficient ( 4 ). similar standard stock solutions of lutein ( kemin health , des moines , iowa ) and zeaxanthin ( dsm , kaiseraugst , switzerland ) were prepared , and concentrations were confirmed using published extinction coefficients ( 33 ). human donor eyes were obtained from the utah lions eye bank within 24 hours after death after corneas had been harvested for transplantation . none of the donors had a known history of eye disease . tissue procurement and distribution complied with the tenets of the declaration of helsinki . the time between donor death and enucleation was not more than four hours . dissections were carried out 6 - 24 hours after donor death in a dim light environment . these data exclude older outliers of age 48 or greater who had been consuming high - dose lutein supplements regularly prior to death ( 34 ). all eyecups were visually inspected with a handheld magnifier to exclude the presence of obvious ocular pathology such as intermediate or large drusen , hemorrhages , or scars . after carefully removing adherent vitreous , macular and mid - peripheral retinal tissues were excised with an 8 - mm circular trephine . the underlying rpe / choroid layer was then carefully excised using the same trephine . diverse non - human mammalian eyes were obtained from neighboring laboratories or local slaughterhouses . since non - primate animal eyes do not have a macula , the entire retina and rpe / choroid were isolated and processed for small eyes , and the 8 - mm trephine was used in a random region for large eyes . we weights were recorded for all collected tissues after blotting excess moisture . total protein levels and protein separation patterns determined by bradford assay and by one - dimensional sds gel electrophoresis , respectively , were similar in both macular and retinal rpe / choroid punches from humans (˜ 250μ / 8 - mm of tissue ). a2e and its isomers were extracted and isolated from rpe / choroid using a previously described method ( 8 ). rpe samples were homogenized in 1 : 1 chcl 3 / meoh ( 2 ml ) and 0 . 01 m phosphate - buffered saline ( pbs ) ( 1 ml ). the homogenizer was washed with 1 : 1 chcl 3 / meoh ( 2 ml ), 0 . 01 m pbs ( 1 ml ), and then chcl 3 ( 2 ml ) and ch 2 cl 2 ( 2 ml ) were added to remove any remaining material . all solutions were combined , and the organic layer was extracted from the aqueous layer . the combined organic extracts were evaporated to dryness under vacuum at room temperature . the residue was dissolved in meoh for hplc . the vials were centrifuged at approximately 2000 g to remove the minor amounts of insoluble solid particles prior to analysis . tissues were homogenized and extracted three times with tetrahydrofuran containing 0 . 1 % butylated hydroxytoluene by sonication at 5 ° c . to 10 ° c . for 30 minutes each time . the combined organic extracts were evaporated to dryness under vacuum at room temperature . the dried residue was redissolved in one ml of hplc mobile phase and centrifuged at approximately 2000 g for 10 minutes to remove the minor amounts of insoluble solid particles prior to analysis . the majority of carotenoids in bird retinas are esterified ( 32 ), so after the initial extraction , the dried carotenoid residue was redissolved in hexane and subjected to saponification in 1 . 8 % ( w / v ) methanolic potassium hydroxide ( koh ) for two hours at room temperature . after saponification , the samples were washed with water until the samples achieved neutral ph . the vials were centrifuged at approximately 2000 g to remove the minor amounts of insoluble solid particles . the solution was evaporated to dryness on a rotary evaporator under reduced pressure at room temperature and reconstituted in the appropriate hplc solvents . hplc analysis was performed on a thermo separations ( san jose , calif .) hplc system with binary gradient pumps , a refrigerated autosampler , a uv6000 photodiode - array detector ( pda ), and an msq single quadrupole mass spectrometer . peak identities were confirmed by pda and mass spectra and by co - elution with authentic standards as necessary . calibration was by external standardization curves with authentic standards . we do not routinely use internal standards because they may interfere with low - level analytes in small biological samples ( 35 ). typical reproducibility with external standardization in our laboratory is + 5 %. a2e hplc analysis : the dried a2e samples were redissolved in 100 μl of meoh . a gradient of 84 - 100 % acetonitrile ( a ) with 0 . 05 % trifluoroacetic acid in h 2 o ( b ) over 35 minutes was used to separate a2e at a flow rate of 1 . 0 ml min − 1 on a reverse - phase c18 column ( 4 . 6 × 250 mm , phenomenex , atlanta , ga .). the column was maintained at room temperature , and the hplc pda detector was operated at 440 nm . carotenoid hplc analysis : the dried extracts were re - dissolved in 100 μl of hplc mobile phase [ hexane : dichloromethane : methanol : n , n - di - isopropylethylamine ( 80 : 19 . 2 : 0 . 7 : 0 . 1 v v − 1 )]. hplc separation was carried out at a flow rate of 1 . 0 ml min − 1 on a cyano column ( microsorb 25 cm length × 4 . 6 mm id , particle size 5 μm , rainin instrument co ., woburn , mass .). the column was maintained at room temperature , and the hplc pda detector was operated at 450 nm . ms analysis was performed using a thermo separations ( san jose , calif .) msq single quadrupole mass spectrometer , equipped with an electron spray ionization ( esi ) source and an atmospheric pressure chemical ionization ( apci ) source . a2e and carotenoids were ionized in positive ion esi and apci modes , respectively . to avoid overloading of eluted solvent molecules in the mass spectrometer and to optimize ionization conditions , 50 % of the eluate was directed to waste with the help of a diverter valve after the pda detector . the delay time from pda to ms was 0 . 13 minutes . the protonated precursor molecular ions were initially acquired in full - scan mode from 300 - 1000 da with 0 . 2 step size , revealing the molecular masses of the components . selected ion monitoring ( sim ) was performed using dwell time of 200 ms for each channel . in sim mode , the m / z channels 592 ± 3 , 608 ± 1 . 5 , 624 ± 1 . 5 , and 640 ± 1 . 5 were used for a2e and its oxidative products . typical detection conditions for a2e were : rf lens bias voltage 0 . 1v , cone voltage 80v and heater temperature 550 ° c . the ion source and tuning lens parameters were optimized automatically by infusing a2e samples via the injector . for carotenoids , the m / z channels 551 ± 0 . 7 and 569 ± 0 . 7 were used for lutein , and 569 ± 0 . 8 for zeaxanthin . typical detection conditions were : corona discharge current 5 μa , cone voltage 80v , and probe temperature 500 ° c . adult japanese quail ( coturnix japonica ) were procured from b & amp ; d farms ( harrah , okla . ), and all experiments were reviewed and approved by the university of utah &# 39 ; s institutional animal care and use committee . the birds were kept under ambient room light on a 12 - hour light - dark cycle , and they were divided into three groups of four birds : lutein supplemented , zeaxanthin supplemented , and unsupplemented . all birds were fed daily with a standard turkey diet (˜ 20 g / day ) ( purina mills , st . louis , mo .) that was low in carotenoids ( 1 . 10 ng / g ). the supplemented birds were gavaged daily with 0 . 5 ml of a microbial extract rich in lutein or zeaxanthin for 16 weeks ( 0 . 2 mg of carotenoid per bird per day ). lutein was prepared from the freshwater alga chlorella protothecoides cs 41 ( microalgae supply service , csiro , hobart australia ) under conditions described earlier ( 36 ). zeaxanthin was obtained from the non - pathogenic bacteria flavobacterium multivorum atcc 55238 grown on liquid growth medium as detailed earlier ( 37 ). after the experiments , the birds were sacrificed , and the a2e and carotenoid content of the rpe / choroid and retina , respectively , were measured as described above . reported values are mean ± standard deviation ( sd ). statistical analysis was done using microcal origin version 6 . 0 ( northampton , mass .). in most cases , a two - population ( independent ) t - test was performed with significance level set at 0 . 05 . we used photodiode array ( pda ) and mass - spectral ( ms ) detection for convenient in - line hplc quantitation and identification of a2e and its isomers from human rpe / choroid . younger human eyes (& lt ; 50 years old ; n = 22 ) always had a single major molecular ion peak for a2e and iso - a2e at m / z 592 . 6 , while eyes older than 50 ( n = 31 ) were more likely to exhibit detectable higher molecular weight ions of a2e , two of which are consistent with previously reported oxidation products at m / z 608 and 624 ( n = 24 ) ( 15 - 16 ), as well as unidentified higher m / z ions between 724 and 808 ( fig1 ). single ion monitoring ( sim ) of these ions allowed the quantification these peaks relative to the a2e peak at m / z 592 ± 3 , 608 ± 1 . 5 , and 624 ± 1 . 5 . the ratio of the m / z 608 and 624 peaks present in donors above 50 years relative to unoxidized a2e was 0 . 027 ± 0 . 008 ( n = 24 ), while these oxidized peaks were absent in the donors below age 50 . initial experiments with whole rfp / choroid from human eyes between ages 20 to 88 revealed a linear increase of a2e with age ( n = 66 , p & lt ; 0 . 0001 ) ( fig . sa ). this same significant increase with age was present in both the macula and the peripheral retina , although a2e levels were typically 4 - fold higher in the periphery ( fig2 b and 2c ). we speculated that lower levels of macular a2e might be related to higher levels of carotenoids in the overlying retina . table 1 shows that this was indeed the case with 10 - fold higher levels of total carotenoids in the macula versus the periphery and greater than 3 - fold higher levels of a2e in the periphery versus the macula in young and old eyes . retinal carotenoid levels were inversely correlated with a2e levels in the underlying rpe / choroid in both the macula ( r =− 0 . 28 ; n = 35 ; p = 0 . 10 ) and the peripheral retina ( r =− 0 . 36 ; n = 40 , p = 0 . 20 ), but only the peripheral retina reached statistical significance ( fig3 ). the human eye is not easily amenable to experimental manipulation of carotenoid and a2e levels due to the slow changes of macular carotenoid levels in response to dietary manipulations and the invasive nature of the a2e analytical measurements , so we surveyed the eyes of a variety of higher vertebrates and compared ocular carotenoid and a2e levels on a wet weight basis ( table 2 ). as expected , monkey eyes most closely resembled human eyes with respect to a2e and carotenoid content , but these laboratory animals are expensive to procure and difficult to manage and handle . young rat and mouse eyes contain barely detectable levels of carotenoids , and there is no published literature demonstrating that high - dose carotenoid supplementation can alter these very low levels . moreover , their a2e levels relative to tissue wet weight are orders of magnitude lower than the other animals listed . generally , rodents have high levels of a2e only when they are appropriately genetically modified , as in the abca4 knockout and elov14 transgenic mice ( 7 - 8 ). cows and , to a lesser extent , pigs have reasonable levels of a2e and carotenoids suitable for dietary manipulation , but these animals are quite large . the female japanese quail possesses the best combination of small size and reasonable levels of ocular a2e and carotenoids , so they were selected for further study . young adult female japanese quail were supplemented with ( 3r , 3 ′ r , 6 ′ r )- lutein or ( 3r , 3 ′ r )- zeaxanthin for a 16 - week period and compared to unsupplemented quail . as shown in fig4 and table 3 , total retinal carotenoid levels rose 1 . 6 - fold in the lutein - supplemented group and 3 . 1 - fold in the zeaxanthin supplemented group relative to baseline , while control diet birds decreased 16 %. total lutein and zeaxanthin levels increased 2 . 8 - fold in the lutein supplemented group and 8 . 1 - fold in the zeaxanthin supplemented groups relative to baseline , while control diet birds increased 6 . 5 %. all of these increases in supplemented birds were statistically significant ( p & lt ; 0 . 05 ). supplementation of lutein and zeaxanthin also led to significant increases in the levels of lutein , zeaxanthin and their carotenoid metabolites in the rpe in comparison to basal and control groups ( p & lt ; 0 . 05 ) ( table 3 ). a2e levels rose more than six - fold relative to basal levels ( p & lt ; 0 . 001 ) in the unsupplemented control group in a 16 - week period , while the lutein and zeaxanthin supplemented birds registered barely any rise from baseline levels ( p = 0 . 1 ). mass spectra of a2e from control group had higher levels of oxidation products in comparison to mass spectra from the lutein and zeaxanthin supplemented groups ( fig5 ). in this study , we first examined the relationship between retinal carotenoids and a2e in human donor eyes . we confirmed that a2e rises with age in both the macula and the peripheral retina , and that it becomes more oxidized with age . interestingly , macular a2e levels in these 8 - mm punches were about three - fold lower in the macular relative to the periphery despite its focused light exposure and high metabolic activity . in both the macula and the periphery , there was an inverse correlation between a2e levels and the total carotenoids , although statistical significance was reached only in the periphery . taken in sum , these human cadaver eye data are consistent with the hypothesis that retinal carotenoids inhibit formation and oxidation of a2e in the underlying rpe , but proof of this hypothesis requires either prospective clinical studies or appropriate animal experiments . human studies would be challenging because noninvasive quantitative a2e measurements are difficult to execute with adequate reliability , and it is not possible to measure peripheral carotenoids in living humans . therefore , we turned to animal models for further study . rodents have been used most frequently to study inhibitors of a2e formation , but their low endogenous ocular levels of a2e and carotenoids and their inability to incorporate carotenoids into the retina in response to supplementation make further study impossible . we surveyed a diverse array of other potential study animals and determined that the japanese quail was the best small nonprimate animal model to study further since it had baseline levels of carotenoids and a2e comparable to a human on a wet weight basis , and it is amendable to dietary manipulation of ocular carotenoid levels ( 31 - 32 ). our experiments demonstrated a profound inhibition of a2e formation in birds supplemented with high dose lutein or zeaxanthin relative to birds fed a control diet low in carotenoids . since the majority of carotenoids in the quail retina are sequestered as fatty acid esters in oil droplets , it is more likely that inhibition of a2e formation by ingested carotenoids is mediated by a light filtering effect rather than a direct antioxidant mechanism because although there was a significant increase in rpe carotenoids in response to supplementation , levels still remained about ten times lower than the overlying retina . our findings provide evidence for a new mechanism for the potential protective effect of lutein and zeaxanthin in degenerative eye disorders — inhibition of a2e formation and oxidation . as noninvasive quantitation of lipofuscin improves , this hypothesis can be directly tested in living humans . lutein and zeaxanthin are particularly attractive agents for clinical use as a2e formation inhibitors because , unlike the other inhibitors currently under investigation , they are already extensively used in humans as dietary supplements , and no toxicity has ever been reported . moreover , our investigations point out the value of non - rodent small animal models for testing a2e formation antagonists . at 150 - 200 grams , an adult japanese quail is the size of a rat , is easy to care for , and forms several - fold increased levels of a2e over a several month period when fed a control diet low in carotenoids . thus , rapid screening of novel pharmacological inhibitors of a2e formation should be quite feasible . the following references are incorporated herein in their entirety by this reference : 1 . rattner a , nathans j ( 2006 ) macular degeneration : recent advances and therapeutic opportunities . nat rev neurosci 7 : 860 - 872 . 2 . beatty s , koh h , phil m , henson d , boulton m ( 2000 ) the role of oxidative stress in the pathogenesis of age - related macular degeneration . surv opthalmol 45 : 1 . 15 - 134 . 3 . dorey c k , wu g , ebenstein d , garsd a , weiter j j ( 1989 ) cell loss in the aging retina . relationship to lipofuscin accumulation and macular degeneration . invest opthalmol vis sci 30 : 1691 - 4 699 . 4 . parish c a , hashimoto m , nakanishi k , dillon j , sparrow j r ( 1998 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s macular degeneration . proc natl acad sci usa 100 : 4742 - 4747 . 25 . radu r a , han y , bui t v , nusinowitz 5 , bok d , lichter j , widder k , travis gil , mata n l ( 2005 ) reductions in serum vitamin a arrest accumulation of toxic retinal fluorophores : a potential therapy for treatment of lipofuscin - based retinal diseases . invest opthalmol vis sci 46 : 4393 - 4401 . 26 . maiti p , kong j , kim s r , sparrow j r , allikmets r , rando r r ( 2006 ) small molecule rpe65 antagonists limit the visual cycle and prevent lipoftiscin formation . biochemistry 45 : 852 - 860 . 27 . eye disease case - control study group ( 1993 ) antioxidant status and neovascular age - related macular degeneration . arch opthalmol 111 : 104 - 109 . 28 . seddon j m , a . u ., sperduto r d , hiller r , blair n , burton t c , farber m d , gragoudas e s , hailer j , miller d t et a !. ; eye disease case - control study group ( 1994 ) dietary carotenoids , vitamins a , c , and e , and advanced age - related macular degeneration . jama 272 : 1413 - 1420 . 29 . sangiovanni j p , chew e y , clemons t e , ferris f l 3rd , gensler g , lindblad a s , milton r c , seddon j m , sperduto r d , age - related eye disease study research group ( 2007 ) the relationship of dietary carotenoid and vitamin a , e , and c intake with age - related macular degeneration in a case - control study : areds report no . 22 . arch opthalmol 125 : 1225 - 1232 . 30 . bernstein p s , zhao d y , wintch s w , ermakov i v , mcclane r w , gellermann w ( 2002 ) resonance raman measurement of macular carotenoids in normal subjects and in age - related macular degeneration patients . opthalmology 2002 109 : 1780 - 1787 . 31 . toyoda y , thomson l r , langner a , craft n e , garnett k m , nichols c r , cheng k m , dorey c k ( 2002 ) effect of dietary zeaxanthin on tissue distribution of zeaxanthin and lutein in quail . invest opthalmol vis sci 43 : 1210 - 1221 . 32 . bhosale p , serban b , zhao d y , bernstein p s ( 2007 ) identification and metabolic transformations of carotenoids in ocular tissues of the japanese quail coturnix japonica . biochemistry 46 : 9050 - 9057 . 33 . britton , g . ( 1995 ) uv / visible spectroscopy , in : carotenoids , eds britton g ., liaaen - jenson s , pfander h . ( birkhaeuser , basel , switzerland ) vol ib , pp 13 - 62 . 34 . bhosale p , zhao d y , bernstein p s ( 2007 ) hplc measurement of ocular carotenoid levels in human donor eyes in the lutein supplementation era . invest opthalmol vis sci 48 : 543 - 549 . 35 . bhosale p , zhao d y , serban b , bernstein p s . ( 2007 ) identification of 3 - methoxyzeaxanthin as a novel age - related carotenoid metabolite in the human macula . invest opthalmol vis sci 48 : 1435 - 1440 . 36 . bhosale p , serban b , bernstein p s ( 2006 ) production of deuterated lutein by chiorella protothecoides and its detection by mass spectrometric methods . biotechnol lett 17 : 1371 - 1375 . 37 . bhosale p , teredesai p v , lihong j , ermakov i v , gellermann w , bernstein p s ( 2005 ) production of deuterated zeaxanthin by flavobacterium multivorum and its detection by resonance raman and mass spectrometric methods . biotechnol lett 21 : 1719 - 1723 .

a method of decreasing the content of 2 -- 1e , 3e , 5e , 7e - octatetraenyl )- 1 -- 4 -- 1e , 3e , 5e - hexatrienyl - pyridinium and its isomers in a subject by administering a therapeutically effective amount of a macular carotenoid formulation .

the apparatus for installing a frame and related appurtenances of the instant invention enables a significant advance in the state of the art of basketball return devices . the preferred embodiments of the apparatus accomplish this by new and novel arrangements of elements that are configured in unique and novel ways and which demonstrate previously unavailable but preferred and desirable capabilities . the detailed description set forth below in connection with the drawings is intended merely as a description of the presently preferred embodiments of the invention , and is not intended to represent the only form in which the present invention may be constructed or utilized . the description sets forth the designs , functions , means , and methods of implementing the invention in connection with the illustrated embodiments . it is to be understood , however , that the same or equivalent functions and features may be accomplished by different embodiments that are also intended to be encompassed within the spirit and scope of the invention . with reference now to the accompanying figures and specifically to fig1 and fig2 in one of the many preferable configurations , the basketball return apparatus 100 , generally consisting of , among other elements , a resilient rebound panel 120 positioned beneath the backboard bb , a panel retainer assembly 104 adapted to flexibly and adjustably connect the upper section of the resilient rebound panel 120 to the goal assembly ga , and a panel support assembly 106 adapted to releasably and adjustably connect the lower section of the resilient rebound panel 120 to the goal assembly ga . numerous embodiments incorporate variations of the resilient rebound panel 120 , the panel retainer assembly 104 , and the panel support assembly 106 . in one of the many variations of the present invention , the resilient rebound panel 120 may include a rebound panel frame 152 upon which a resilient material 150 may be secured . additionally , the resilient material 150 may include an elasticized membrane , a plurality of interconnected elasticized cords , or any of the myriad of materials known to one skilled in the art . alternatively , the rebound panel 120 may include a non - stretch material that is connected with elastic devices to the rebound panel frame 152 . for example , but not limitation , the elastic devices connecting the frame 152 to the material may includes springs , pneumatic cylinders , hydraulic cylinders , and bands constructed of virtually any resilient material . as shown in fig2 the rebound panel frame 152 is preferably substantially rectangular and at least as wide as the backboard bb . however , the resilient rebound panel 120 , and the rebound panel frame 152 , may be of any size and shape . the present invention incorporates unique panel retainer 104 and support 106 assemblies that assist in returning a basketball to the player p at substantially the same angle with which the basketball approached the backboard bb . numerous embodiments incorporate variations of the panel retainer assembly 104 and the panel support assembly 106 . for example , as shown in fig1 and fig2 the panel retainer assembly 104 incorporates at least one upper panel elastic retainer 110 to flexibly and adjustably join the resilient rebound panel 120 with the goal assembly ga . the at least one upper panel elastic retainer 110 may be flexibly and adjustably joined to any component of the goal assembly ga . in one such variation , shown in fig1 and fig2 two upper panel elastic retainers 110 are used with each one secured to opposite ends of a rebound panel frame 152 edge and secured to a common backboard support bs . as with the panel retainer assembly 104 , numerous panel support assembly 106 variations exist . perhaps the most simple panel support assembly 106 includes at least one support brace 130 that is releasably and adjustably connected to the goal assembly ga at one end via at least one support brace goal assembly mounting device 140 , and is connected to the rebound panel 120 at the opposite end . the connection of the support brace 130 to the rebound panel 120 is generally a rotatable connection , but may be rigid or flexible . the at least one support brace goal assembly mounting device 140 may be configured in any number of ways to connect with any of the commercially available goalposts gp . for example , the mounting device 140 may be configured to mount to square , rectangular , or round goalposts gp . now referring to fig8 the unique result of this apparatus 100 may be described . for example , during the course of practicing shooting basketball players often need to practice shoots that are not directly in front of the basket , i . e . at locations other than that along the y - axis of the coordinate system cs shown in fig8 . therefore , a player p shooting at roughly a forty - five degree angle from the right side of the court , between the positive x - axis and the positive y - axis , also identified as quadrant number one q 1 , would like the basketball to return to approximately the same location from which it was released . typically a good basketball player p will be able to shoot the basketball through the rim r without the basketball hitting the rim r . when this occurs the basketball will continue to substantially follow its flight path as it passes through the basketball net n and beyond . therefore , the basketball will strike the left half of the rebound panel 120 . one unique advantage of the present invention is that when a basketball strikes the rebound panel 120 at a location other than the center of the panel 120 , the panel 120 will rotate , as shown by rotation indicator rt , and the tension in one of the upper panel elastic retainers 110 will increase while the tension in the opposite upper panel elastic retainer 110 will decrease . therefore , as the upper panel elastic retainer 110 with the increased tension quickly returns to the pre - strike tension it returns the panel 120 to the normal position thereby imparting a return angle of a substantially reciprocal direction returning the basketball to quadrant number one q 1 . conventional deflector plate type basketball return devices would typically return a ball shoot from quadrant number one q 1 to the opposite side of the court , quadrant number two q 2 . this same basic principal applies to all the embodiments described herein . additionally , the resilient rebound panel 120 may be formed in a substantially concave manner to assist in imparting the substantially reciprocal return angle . in a further variation illustrated in fig3 and fig4 the panel retainer assembly 104 may incorporate at least one retainer brace 160 having a distal end and a proximal end , at least one retainer brace goal assembly mounting device 180 , and an upper retainer cross - member 170 . the at least one retainer brace &# 39 ; s 160 distal end connects to the upper retainer cross - member 170 , and the retainer brace &# 39 ; s 160 proximal end may be releasably and adjustable joined to the at least one retainer brace goal assembly mounting device 180 . additionally , the upper retainer cross - member 170 may be flexibly and adjustably joined to the resilient rebound panel 150 with at least one upper panel elastic retainer 110 . an alternative embodiment , not shown , may not include the upper retainer cross - member 170 , and the resilient rebound panel 120 may be flexibly and adjustably attached to the at least one retainer brace 160 with at least one upper panel elastic retainer 110 . as shown in fig5 and fig6 additional variations may include alternative panel support assemblies 106 that may incorporate at least one support brace 130 having a distal end and a proximal end , at least one support brace goal assembly mounting device 140 , and a lower retainer cross - member 220 . the at least one retainer support brace &# 39 ; s 130 distal end connects to the lower retainer cross - member 220 , and the at least one support brace &# 39 ; s 130 proximal end may be releasably and adjustably joined to the support brace goal assembly mounting device 140 . additionally , the lower retainer cross - member 220 may be flexibly and adjustably joined to the resilient rebound panel 120 with at least one lower panel elastic retainer 210 . an alternative embodiment , not shown , may not include the lower retainer cross - member 220 , and the resilient rebound panel 220 may be flexible and adjustably attached to the at least one support brace 130 with at least one lower panel elastic retainer 210 . now referring to fig7 a further variation the panel support assembly 106 may include at least one panel vertical frame cross member 250 connecting the resilient rebound panel 120 to an adjustable intermediate support brace 260 , a torsion device 230 releasably and adjustably connecting the adjustable intermediate support brace 260 to at least one support brace 130 , and a support brace goal assembly mounting device 140 releasably and adjustably connecting the at least one support brace 130 to the goal assembly ga . an additional panel horizontal frame cross - member 240 may be added to increase the strength of the apparatus 100 . further , any of the preceding embodiments may include at least one articulable adjustable support brace joint 190 and at least one articulable adjustable retainer joint 200 , as shown in fig1 fig3 fig5 and fig7 . such joints would allow the rebound panel 120 to be quickly and easily positioned beneath the backboard bb , as well as quickly and easily repositioned into a “ storage position ” that is out of the playing court and does not pose a danger to players . additionally , adjustment of the articulable joints would allow the player to adjust the angle , and thereby the height , at which the ball is returned . numerous alterations , modifications , and variations of the preferred embodiments disclosed herein will be apparent to those skilled in the art and they are all anticipated and contemplated to be within the spirit and scope of the instant invention . for example , although specific embodiments have been described in detail , those with skill in the art will understand that the preceding embodiments and variations can be modified to incorporate various types of substitute and or additional or alternative materials , relative arrangement of elements , and dimensional configurations for compatibility with the plurality of commercially available basketball goals . accordingly , even though only few variations of the present invention are described herein , it is to be understood that the practice of such additional modifications and variations and the equivalents thereof , are within the spirit and scope of the invention as defined in the following claims . the corresponding structures , materials , acts , and equivalents of all means or step plus function elements in the claims below are intended to include any structure , material , or acts for performing the functions in combination with other claimed elements as specifically claimed .

a basketball return apparatus designed to return a thrown basketball substantially in the direction of the player shooting the ball is mounted beneath a basketball goal assembly and includes a resilient rebound panel , a panel retainer assembly , and a panel support assembly . the resilient rebound panel , in multiple embodiments , is provided with flexible and adjustable tensile connections to the goal assembly that allows a limited degree of rotation when the resilient rebound panel is impacted by a thrown basketball . the rotational motion of the rebound panel and the resilience of the rebound panel , combined with the tension and untensioning of the flexible and adjustable tensile connections to the goal assembly , tends to return a thrown basketball substantially back towards the player shooting the ball . the basketball return apparatus is adjustable for a plurality of heights and angles of return , and is easily removable from the field of play .

the following detailed description should be read with reference to the drawings , in which like elements in different drawings are identically numbered . the drawings , which are not necessarily to scale , depict selected preferred embodiments and are not intended to limit the scope of the invention . the detailed description illustrates by way of example , not by way of limitation , the principles of the invention . this description will clearly enable one skilled in the art to make and use the invention , and describes several embodiments , adaptations , variations , alternatives and uses of the invention , including what is presently believed to be the best mode of carrying out the invention . the present invention is directed to a catheter connector system for connecting a catheter to extracorporeal medical equipment . in the embodiments and examples that follow , reference will be made to a catheter connector for a catheter that has been trimmed proximally , following placement thereof in the body of a patient . however , it should be understood that the present invention is not limited to such uses and instead is applicable to any application that requires the connection of a catheter to separate medical equipment as would be apparent to one of skill in the art . moreover , when discussing the catheter connectors of the present invention in terms of attachment to a patient , it should be understood that attachment can be direct through suturing , medical tape , or other means , or indirect through the use of a statlock ® or other intermediary device . in one embodiment according to the present invention , a catheter connector system 100 is illustrated in fig2 - 10 . the catheter connector system 100 includes two primary components , a boot 120 and a bifurcation assembly 130 , and is configured for attachment to a catheter 110 to provide a proximal connection for the introduction and / or withdrawal of fluids thereto . the catheter connector system 100 as illustrated is configured as a two - piece system , which can be assembled by the clinician upon placement of a catheter . it should be appreciated that although the embodiments shown are directed to a dual lumen catheter , similar embodiments directed to single lumen and triple lumen catheters are contemplated ( as well as other multi - lumen catheters ). more particularly , while the catheter 110 and bifurcation assembly 130 are illustrated in a dual - lumen configuration , the present invention is equally directed to a single lumen configuration , having a single lumen catheter and assembly , and to a triple or multi - lumen configuration , having a triple or multi - lumen catheter and assembly . the catheter connector of the present invention can be used for a variety of different types of catheters , such as peripherally inserted central catheters ( piccs ), having small or large diameters . in one embodiment , catheter connector system 100 is configured for a picc , ranging from 3 fr to 7 fr in size . while certainly many different materials could be used for each of the primary components of the catheter connector system 100 and catheter 110 , examples of possible materials are polyurethane and silicone ( i . e ., a soft biocompatible elastomeric material ) for the catheter 110 and the boot 120 , and either a soft elastomeric material or a hard plastic material for the bifurcation assembly 130 . referring to fig2 , the bifurcation assembly 130 includes extension leg tubes 134 , 136 , which are in fluid communication with catheter lumens 112 , 114 ( fig3 ) when catheter connector system 100 is fully assembled . the boot 120 includes a main body portion 122 and a pair of suture wings 124 that are configured for attachment to the skin of a patient or a statlock ® or similar device to stabilize the catheter connector system 100 . as shown in the cross - sectional view in fig3 , the catheter 110 within the boot 120 has lumens 112 , 114 with a trapezoidal cross - sectional shape . while certainly other cross - sectional shapes are possible , the trapezoidal shape may be advantageous to prevent collapse due to the force exerted on the catheter 110 by the boot 120 . fig4 illustrates in partial cut - away view the boot 120 . in this isolated view of the boot 120 , a proximal coupling section 126 can be seen comprising a barbed end . of course , coupling section 126 can take on a variety of forms , depending on the form of the associated coupling section of the bifurcation assembly 130 , such that the coupling sections together provide a tight connection that will withstand forces associated with the infusion and / or withdrawal of fluid from a patient . the main body portion 122 of boot 120 is fashioned with a reverse - taper or stepped - taper , meaning that the diameter at the proximal end 121 is greater than the diameter at the distal end 123 . this is advantageous because the smaller diameter distal end 123 can be partially inserted into the venipuncture site 102 , as shown in fig2 , to achieve venipuncture tamponade and reduce site bleeding . although the taper of main body portion 122 is shown as being very slight with respect to the longitudinal axis l 120 of the boot 120 , forming an angle a 122 therewith , the preferred range is between approximately 1 to 45 degrees with larger tapers being equally within the scope of the present invention . the main body portion 122 includes a section distal the suture wings 124 , having a length 1 122 that in one embodiment is in the range of approximately 2 . 0 cm to 5 . 0 cm . the boot 120 is formed with a throughgoing lumen 128 and may have a diameter slightly smaller than the diameter of the outer wall of the catheter 110 to create an interference fit therewith . although certainly various diameters are possible for the lumen 128 and the outer wall of the catheter 110 , in one embodiment the diameter of the lumen 128 is in the range of approximately 0 . 50 mm to 4 . 0 mm , while the diameter of the outer wall of the catheter 110 is approximately 0 . 55 mm to 4 . 4 mm . the lumen 128 is also sized to receive a dilator , which is used to place the boot 120 over the catheter 110 and into the venipuncture site 102 . fig5 illustrates a dilator 140 in cross - section , the dilator 140 including a shaft 142 that has a transition section 146 at a distal end thereof , which is tapered to form a smooth transition for insertion percutaneously into the venipuncture site . in addition , the tip of the transition section 146 may be rounded ( e . g ., via radio frequency means , thermal means , etc .) the shaft 142 has an outer diameter that is larger than lumen 128 of boot 120 in order to dilate the lumen 128 and provide an interference fit for a tight , smooth transition into the venipuncture site . the dilator 140 also has a throughgoing lumen 148 , which can be slightly larger than the diameter of the outer wall of the catheter 110 to allow slideable movement therealong . in one embodiment , the dilator lumen 148 is at least 0 . 025 mm greater than the diameter of the outer wall of the catheter 110 . in addition , the dilator 140 has a handle 144 ( fig6 ) positioned at the distal end thereof , the handle 144 having a fin 143 and a base 145 , which together facilitate the handling of the dilator 140 . the fin 143 , base 145 , or both may additionally be equipped with gripping sections to further facilitate the handling of the dilator 140 . the dilator should be formed of a material exhibiting sufficient columnar and radial strength to prevent compression or time / thermal creep and allow advancement into the boot and removal therefrom ( e . g ., polyurethane , polytetrafluoroethylene ( ptfe ) and high density polyethylene ( hdpe )). in one embodiment , the outer surface of the shaft 142 is lubricated to facilitate removal from the boot 120 . fig6 - 9 illustrate , in sequence , steps according to the present invention for inserting the boot into the venipuncture site . referring to fig6 , the venipuncture site 102 has been established and the catheter 110 has been advanced to a central location , a length of the catheter 110 extending from the venipuncture site 102 . the shaft 142 of the dilator 140 has been pressed into the lumen 128 of the boot 120 ( generally performed at the place of manufacture , but can take place on site ) and the combination is slid over the catheter 110 , the lumen 148 of the dilator 140 receiving the catheter 110 therethrough . fig7 shows the next step as the boot 120 and dilator 140 are pressed into the venipuncture site 102 , with the catheter 110 extending from the proximal end of the dilator 140 . both the reverse - taper of the boot 120 and the transition section 146 of the dilator 140 enable a smooth advancement into the venipuncture site 102 . as stated above , the reverse - taper configuration of the boot shaft 122 provides a tight fit into the venipuncture site and reduces blood loss therethrough . the dilator 140 is then removed from the boot 120 , which is held in place in the venipuncture site , as depicted in fig8 . as the dilator 140 is removed from the lumen 128 of the boot 120 , the lumen 128 , which was previously expanded due to the larger diameter of the dilator shaft 142 , contracts and forms a tight fit with the catheter 110 remaining therein . thereafter , the proximal length of the catheter 110 extending from the now placed boot 120 is trimmed ( e . g ., using medical scissors , a scalpel or other cutting tool ) so that the proximal end of the trimmed catheter 110 is flush with the opening in the proximal end of the boot 120 , resulting in the entire external length of the catheter 110 being supported and protected by the boot 120 , as illustrated in fig9 . referring now to fig1 , the attachment of the bifurcation assembly 130 is described . bifurcation assembly 130 includes a coupling section 132 , which is configured for attachment to the proximal coupling section 126 of the boot 120 to provide a securing connection thereto . the coupling section 132 includes a pair of stems 137 , 139 , which are shaped and sized to fit tightly within lumens 112 , 114 of catheter 110 to provide a fluid tight connection between the boot 120 and the bifurcation assembly 130 . in one embodiment , the stems are made of metal , although certainly other non - metal materials are also possible . immediately surrounding the stems 137 , 139 is a hood 138 , which is configured and shaped to tightly receive proximal coupling section 126 of the boot 120 . surrounding both stems 137 , 139 and hood 138 is a cover 133 , which abuts a shoulder 125 at the proximal end 121 of the main body portion 122 upon assembly and has a diameter approximately the same as the diameter thereof . the stems 137 , 139 extend beyond the cover 133 to enable initial engagement with the catheter lumens 112 , 114 prior to the remainder of the coupling section 132 coming into contact with the proximal coupling section 126 . the bifurcation assembly 130 is assembled onto the boot 120 by sliding the stems 137 , 139 into the respective lumens 112 , 114 of the catheter 110 , while providing pressure to the boot 120 to ensure a stationary position . to facilitate this insertion process and prevent damage to the catheter , round - nosed obturators , which are described in more detail below , may be utilized . as the stems 137 , 139 are received into the lumens 112 , 114 , the hood 138 receives the barbed portion of the proximal coupling section 126 . the assembly is complete when the cover 133 comes into contact with the shoulder 125 and the proximal coupling section is locked within the hood 138 . the connection between the bifurcation assembly 130 and the boot 120 can be of several different varieties . in one embodiment , the pressing of the proximal coupling section 126 into the hood 138 results in both an audible and tactile indication that the connection is complete . the connection may be permanent , such as the embodiment shown in fig1 , or alternatively a releasable locking mechanism can be provided . the assembled catheter connector system 100 , as illustrated in fig2 , provides a secure , fluid - tight connection system that is streamlined and is capable of attachment to the patient . following complete assembly of the catheter connector system 100 , the catheter is flushed to assure patency and to examine the connection for leaks . finally , the suture wings 124 are secured to either the skin of the patient or a statlock ® or similar device . catheter connector system 300 is illustrated in fig1 and is similar to catheter connector system 100 . catheter connector system 300 includes a bifurcation assembly 330 having a distal coupling section 332 configured to be received within a proximal receiving portion 322 of a boot 320 . the distal coupling section 332 is comprised of an anchoring portion 334 , an enlarged head portion 334 , slots 336 and stems 338 . the slots 336 are shown as being positioned circumferentially about distal coupling section 332 in 90 ° intervals such that distal coupling section 332 comprises four slots . the slots 336 permit the head 334 to compress radially inward as the distal coupling section 332 is pressed into the proximal receiving portion 322 and begins to enter head receiving portion 324 . of course , any number of slots could be utilized ( 1 , 2 , 3 , etc . ), depending on a variety of factors ( material selection , connection configuration , etc .) in order to maximize the effectiveness of the connection . catheter connector system 300 is assembled similarly to that described above with catheter connector system 100 . catheter 110 is placed within the patient and , if necessary , may be proximally trimmed to a suitable length . with a portion of the catheter 110 extending from the proximal end of the boot 320 , the stems 338 of the bifurcation assembly 330 are pressed into lumens 112 , 114 of catheter 110 , after which the distal coupling section 332 is pressed into the proximal receiving portion 322 . when the head 334 has been fully received by head receiving portion 324 ( i . e ., has been pressed beyond shoulder 326 of head receiving portion 324 ), the geometry thereof permits head 334 to expand outward , at which point there is an audible “ click ,” effectively locking bifurcation assembly 330 to boot 320 . once assembled , the portions of the distal coupling section 332 surrounding the stems 338 act to seal the catheter 110 against the stems 338 for a fluid - tight connection . as with catheter connector system 100 , the locking connection of catheter connector system 300 may be permanent or releasable . in another embodiment of the present invention , a catheter connector system 200 is illustrated in fig1 - 12 , having a boot 210 , a bifurcation assembly 220 and a clamp 230 . the catheter connector system 200 is shown prior to attachment of the bifurcation assembly 220 , with the boot 210 slid over a catheter 202 and into the venipuncture site 102 , the catheter 110 having been trimmed at its proximal end to lie flush with the proximal end of the boot 210 . the boot 210 has incorporated in its proximal end a connector member 214 , which has a distal portion 215 with grooves to optimize locking connection with the clamp 230 , and a proximal portion 216 having an energized seal design , which in the preferred embodiment is made of a soft material ( e . g ., silicone with a durometer of 30 ). the boot 210 has a distal taper , which allows it to be slid into the venipuncture site to not only seal the site from extraneous bleeding , but also to protect the extracorporeal portion of the catheter from breakage . the bifurcation assembly 220 has a connector member 224 at the distal end thereof , having a similar configuration to that of the distal portion 215 of the connector member 214 . extending from the connector member 224 are a pair of stems 226 , which can be made of metal or other hard or hardened material , for insertion into the lumens of catheter 110 , similar to that described above in connection with catheter connector system 100 . also included in the bifurcation assembly 220 is a hub 222 and extension tubes 223 . in one embodiment , the boot body 212 and the bifurcation assembly body 222 , as well as the extension legs 223 are made of a soft elastomer material ( e . g ., medical grade polyurethanes and silicones ). certainly , however , many materials are possible and would equally be within the scope of the invention . in one embodiment , the bifurcation assembly 220 is shipped pre - assembled to the boot 210 . the clamp 230 is in a clamshell configuration having locking opposed halves 234 that are connected by a bottom hinge 232 . the interlocking halves 234 comprise teeth 236 , separated by gaps 238 , the teeth 236 on one half corresponding positionally with the gaps 238 on the opposite half when the clamp 230 is in a closed condition . the teeth 236 and gaps 238 are configured to create an interference fit ( i . e ., mechanical lock ) when in a closed position to prevent inadvertent opening under normal pressures . the interlocking halves 234 also include ring portions 237 on the inside thereof , which create axial compression upon closing around the connector members 214 , 224 and also ensure the tensile integrity of the assembly . it should be appreciated that , although the clamp 230 is shown in a particular configuration with respect to teeth 236 , ring portions 237 and gaps 238 , many other configurations would be equally within the scope of the present invention , the primary considerations being that the clamp 230 be shaped to lock around the connector members 214 , 224 of the boot 210 and bifurcation assembly 220 so that inadvertent opening is prevented and to provide a seal against the catheter within the boot connector member 214 as will be described in more detail below . also incorporated into the clamp 230 are suture wings 239 having openings adapted for attachment to a patient ( through either direct means or indirect means as discussed above ). the suture wings 239 can be integrally formed with the clamp 230 ( e . g ., via injection molding ) or alternatively may be molded over the interlocking halves 234 . in one embodiment , the interlocking halves 234 are made of a semi - rigid plastic , while the suture wings 239 are made of a soft elastomer material . as stated , assembly of the catheter connector system 200 is initiated by placing the catheter 110 within the body of a patient using traditional methods , such that a length of catheter 110 extends from the venipuncture site 102 . upon confirmation of correct catheter placement , the clinician holds the proximal end of the catheter 110 and slides the boot 210 over the catheter 110 and into the venipuncture site 102 . a dilator may be used to position the boot 210 over the catheter as described above , or other means of positioning the boot 210 over the catheter 110 may be utilized as would be known to one of skill in the art . in one embodiment , an expander is inserted / activated under the distal end of the boot 210 after it has been positioned in the venipuncture site in order to create a seal between the catheter 110 and the boot 210 to prevent blood fluids from wicking between the components and to create a friction fit between the components , which could facilitate assembly thereof . following positioning of the boot 210 over the catheter 110 , the proximal end of the catheter 110 extending from the connector member 214 of the boot 210 is trimmed , the clinician utilizing the surface of the proximal portion 216 of the connector member 214 as a guide , resulting in a flush outer surface thereof . while firmly holding the boot 210 , the bifurcation assembly 220 is then connected to the boot 210 by inserting stems 226 into the lumens of the catheter 110 until the connector members 214 , 224 meet . as with catheter connector system 100 , in the case of a single lumen catheter , only one stem would be provided ; moreover , the cross - sectional shape of the stem may correspond to the cross - sectional shape of the lumen to provide a fluid tight connection . round - nosed obturators 228 may be employed to facilitate the insertion of the stems 226 into the lumens of the catheter 110 and to prevent material damage during the insertion process , which can occur in small catheters ( e . g ., 5 fr or 6 fr ). the obturators 228 are inserted through the extension legs 223 and the lumens within the body 222 of the bifurcation assembly 220 to emerge through the stems 226 ( fig1 and 14 ). the obturators 228 can be removed after assembly , for example , by using stylets that are insert molded into the obturators 228 and extend past the luer connectors at the proximal end of each extension leg 223 . finally , the clamp 230 is oriented so that the suture wings 239 are parallel to the top and bottom surfaces of the boot 210 and the bifurcation assembly 220 ( i . e ., the bottom surface being that surface adjacent the skin of the patient ) and is closed around the connector members 214 , 224 . as the clamp 230 closes , the mating surfaces on the connector members 214 , 224 and the interlocking halves 234 interact to compress the proximal portion 216 of the connector member 214 . the incompressible nature of the material thereof causes the outer diameter of the proximal portion 216 to increase and its inner diameter to decrease . the inside surface of the clamp 230 minimizes the change in the outside diameter and maximizes the decrease in the inside diameter , which equates to a compressive force on the catheter 110 , resulting in a seal against the stems 226 inserted into the lumens thereof . following locking of the clamp , the obturators are removed and the suture wings 239 are utilized to affix the system 200 to the skin of the patient . in one variation of the catheter connector system 200 , a slightly different connector member 240 is utilized , having a collet design as shown in fig1 . the connector member 240 may be made of a semi - rigid plastic and has a distal portion 242 that is attached to the boot 210 and an insert portion 244 extending from the proximal end of the boot 210 . the bifurcation assembly connector member 224 has a receiving bore to permit entry and locking of the insert portion 244 therein . the insert portion 244 has a frustoconical shape with individual sectioned panels 246 attached to a base 248 . the sectioned panels 246 flex inward as they are received within the bore of the connector member 224 , reducing the inside diameter of the insert portion 244 and thereby creating a compressive seal on the catheter . as the insert portion 244 is received within the bore of the connector member 224 , a snap fit ( i . e ., a mechanical lock ) occurs due to the configuration of the bore as can be seen in fig1 . all other aspects of assembly of the bifurcation assembly 220 to the boot 210 are as described above . an exploded cross - sectional view of the catheter connector system 200 employing the collet design is shown in fig1 . it should be noted that more attention to detail is required in trimming the proximal end of the catheter when utilizing the collet design , as opposed to the energized seal design , as the insert portion 244 will often be made of a harder material . as a result , haphazard trimming can produce burrs on the face of the insert portion 244 , which could lead to problems . it should further be noted that unlike the energized seal design , the clamp 230 does not impact the sealing operation and instead only serves to keep the bifurcation assembly 220 and boot 210 connected . the seal is created upon insertion of the insert portion 244 into the bore of the connector member 224 . it should be appreciated that when the clamp is closed around the connector members 224 , 240 in the collet design , an external closure is provided to the mechanical lock created by the insertion of the insert portion 244 into the bore of the connector member 224 , the expected result of which is that the assembled system 200 will have a significantly higher tensile capability than the individual components . the present invention has been described above in terms of certain preferred embodiments so that an understanding of the present invention can be conveyed . however , there are many alternative arrangements for a catheter connector not specifically described herein , but with which the present invention is applicable . although specific features have been provided , the catheter connector of the present invention would equally be embodied by other configurations not specifically recited herein . the scope of the present invention should therefore not be limited by the embodiments illustrated , but rather it should be understood that the present invention has wide applicability with respect to catheter systems generally . all modifications , variations , or equivalent elements and implementations that are within the scope of the appended claims should therefore be considered within the scope of the invention .

a catheter connector system for a subcutaneously placed catheter and method of attaching a catheter to extracorporeal medical equipment . the catheter connector system and method enables proximal trimming of the placed catheter and facilitates precise positioning of both distal and proximal ends of a catheter . the method includes sliding a boot and dilator combination over a portion of a catheter extending from a venipuncture site until a distal end of the boot is positioned in the venipuncture site , removing the dilator from the boot , and trimming a portion of the catheter extending from a proximal end of the boot . a bifurcation assembly may be attached to the proximal end of the boot following trimming of the catheter .

referring to the drawings in detail , wherein like reference numerals indicate like elements , there is seen in fig1 a protective hat designated generally by the referene numeral 10 . the protective hat 10 in fig1 represents one major variation of the invention , intended for use by girls , and having decorative ruffles 12 , which are described in greater detail below . fig7 illustrates an alternative form 10 &# 39 ; of protective hat , which has a peak ( designated generally by the reference numeral 14 ) rather than the ruffles 12 , and which is more suitable for use by boys . fig8 and 9 show another form of hat , suitable for use by boys or girls . the protective hats 10 and 10 &# 39 ; comprise a head - enveloping member , designated generally by the reference numeral 16 , which in the illustrated embodiment may also be referred to as a &# 34 ; crown .&# 34 ; the head - enveloping member 16 is adapted to overlie and protect at least the sides and one other area of the head of a wearer . in the embodiments of the invention illustrated in fig1 and 7 ( and elsewhere in the drawings ), the head - enveloping number 16 overlies the sides and top of the head of the water . the head - enveloping member 16 is an arcuate member , generally u - shaped in cross - section . in conjunction with a closure member 18 , which is affixed to it in a manner described below , it forms a concavity , closed on three sides and at the top , which may be placed over the head of the wearer . the closure 18 in the illustrated form of the inventions , is a separate piece , and it is so arranged with respect to the head - enveloping member 16 that edge portions of the closure member 18 are complemental with and coupled to respective edge portions of the head - enveloping member 16 . the head - enveloping member 16 and closure member 18 of the protective hat 10 are each made up of a resilient shock absorbent core of plastic polymeric material , enclosed by a shell of textile fabric material , as is perhaps best seen in fig4 . fig2 illustrates a presently preferred form a core 20 for the head - enveloping member or crown 16 . the core 20 comprises a flat sheet of shock absorbent and thermally insulating material , which may be cut or die stamped to shape from a flat sheet of raw material . the core 20 may be perforated , as by holes 22 , to enhance the vapor permeability of the finished hat 10 , and may also be perforated , as by the holes 24 , at positions that correspond to the ears of the wearer . the edges 26 of the core 20 are bevelled , for a purpose described below , and the shape of the core 20 is such as to facilitate assembly of the head - enveloping member 16 and closure member 18 to provide the desired configuration of the protective hat 10 . similarly , referring to fig3 the core 28 of the closure member 18 may be cut or die stamped from a sheet of suitable material , preferably the same kind of material as the core 20 . like the core 20 , the core 28 may be provided with holes 30 , which serve the same purpose as the above - mentioned holes 24 . the edges 32 of the core 28 may be bevelled , as at 32 , complementally with the bevelled edge 26 of the core 20 . the core 20 is enclosed by fabric shell pieces 34 and 36 , stitched together around their peripheries and outside the periphery of the core 20 . the core 28 is preferably enclosed by similar material . thus , referring again to fig4 an outer shell piece 38 and inner shell piece 40 are associated with the core 28 . like the above - described outer and inner shell pieces 34 and 36 , the shapes of the respective shell pieces 38 and 40 approximate the shape of the core with which they are associated , the core 28 , and the outer shell piece 38 and inner shell piece 40 are stitched together around their periphery and outside the periphery of the core 28 . the material from which the shell pieces 34 , 36 , 38 and 40 are made may be any suitable fabric . in one presently preferred form of the invention , the material used for the shell pieces is a broadcloth of 65 % polyester and 35 % cotton . such a material provides a desirable degree of durability and soil resistance , as well as an acceptable feel and conventional appearance . it has been found desirable to cut the inner shell pieces 36 and 40 on the bias , whereas the outer shell pieces 34 and 36 are straight of grain . fig5 shows a construction detail of a protective hat 10 in accordance with the invention . it illustrates the relationship between the cores 20 and 28 and the shell pieces 34 and 36 and 38 and 40 , respectively , associated with them . it also illustrates the manner in which the head - enveloping member 16 and closure member 18 may be assembled . referring to fig5 it will be the outer piece 34 and inner shell peice 36 and the outer shell piece 38 and the inner shell piece 40 , when sewn together , provide a small area of selvage which facilitate their being stitched together around the edges of the head - enveloping member 16 and closure member 18 . the bevelled edges 26 and 32 of the cores 20 and 28 provide in effect , a &# 34 ; mitre &# 34 ; or right - angle corner . the cores 20 and 28 are ideally made from dimensionally stable , chemically inert , highly impact resistant material . one suitable material , which is presently preferred is sold by uniroyal , inc . under the trademark &# 34 ; ensolite &# 34 ;, type &# 34 ; aa .&# 34 ; it comprises a closed - cell foam of specially modified pvc with nitrile rubber . the material is a cross - linked polymer capable of withstanding repeated impact / recovery cycles , and has a density of between about 4 . 0 and 6 . 0 lbs ./ cu . ft ., a thermal conductivity of 0 . 26 , and a 25 % compression resistance of 5 . 0 to 7 . 0 psi . at 70 ° f . in presently preferred forms of the invention , the cores 20 and 28 have thicknesses of about 1 / 4 to 3 / 8 inches . referring now to fig4 the shell of textile fabric material which encloses the cores 20 and 28 will now be described . referring to the head - enveloping member 16 , the shell is made up of an outer shell piece 34 , which provides the outer surface of the top and sides of the protective hat 10 , and an inner shell piece 36 , which provides the inner lining of the side and top portions of the protective hat 10 . the outer and inner shell pieces 34 and 36 are cut or stamped to a shape somewhat similar to the shape of the core 20 , but somewhat larger , and they are stitched to each other around their peripheries outside the peripheral edge of the core 20 . when such stitching is completed , the outer and inner shell pieces 34 and 36 fully enclose and encapsulate the core 20 , so that the outer surfaces of the protective bonnet 10 have a conventional appearance and texture imparted by the textile fabric material of the outer and innter shell pieces 34 and 36 . as in the case of the core 20 , the core 28 is also enclosed and encapsulated in a shell of textile fabric , joined between the plane defined by the closure member 18 and the side and top walls of the hat is provided by the head - enveloping member 16 . a variety of stitching and finishing techniques may occur to those skilled in the art , but is is presently preferred that the selvage of the outer shell piece 34 and 36 and the selvage of the outer shell piece 38 and inner shell piece 40 be joined by a line of stitching 44 , and that bias tape 46 be used to &# 34 ; pipe &# 34 ; or finish the edge . referring now to fig1 the botom and front edges of the embodiment of the protective hat 10 shown in that figure are provided with the above - mentioned ruffle 12 . referring , however , to fig6 ( wherein elements corresponding to those previously described are designated by like primed (&# 39 ;) reference numerals ) the protective hat 10 &# 39 ; may be provided with a peak 14 in the following manner . in the protective hat 10 &# 39 ;, a core 48 , cut approximately to the desired shape of the peak 14 , is encased within a pair of fabric shell pieces 50 and 52 , and the assembly thus created is sewn into the seam between the outer shell piece 34 &# 39 ; and inner shell piece 36 &# 39 ; at the front of the protective hat 10 &# 39 ;. as before , bias tape 46 &# 39 ; may be used to finish the edges around the peripheries of the head - enveloping member 16 &# 39 ; and the closure member ( not seen ). in either embodiment , suitable ties 54 , 54 &# 39 ; may be used to secure the protective hat 10 , 10 &# 39 ; to the head of the user . for example , referring to fig1 in the protective hat 10 , intended for use by girls , the tie 54 may be provided with a bow 56 at this point of anchorage with the head - enveloping member 16 , and the tie itself may be of the type which is intended to be tied into a bow . on the other hand , referring to fig6 the embodiment 10 &# 39 ;, intended to be used by boys , is provided with a tie 54 &# 39 ; which has a buckle 58 . such a tie could of course be used in conjunction with the embodiment 10 if so desired . referring now to fig7 and 8 , there is seen an embodiment 10 &# 34 ; of a protective hat in which elements corresponding to those previously described are designated by like double - primed (&# 34 ;) reference numerals . in the protective hat 10 &# 34 ;, the core 20 &# 34 ; is an arcuate member which covers , in general , the head of the wearer from the top of the forehead to the nape of the neck . the remainder of the head - enveloping member 16 &# 34 ; is built around side core pieces 60 and 62 , which have bevelled edges 64 which complement bevelled edges 26 &# 34 ; of the core 20 &# 34 ;. fabric shell pieces 34 &# 34 ;, 36 &# 34 ;, 66 and 68 encapsulate the core 20 &# 34 ; and side core pieces 60 and 62 . the hat 10 &# 34 ; provides a simplified construction , suitable by reason of its shape and lack of trim , for use by boys and girls . suitable ties , not shown , may be used with the hat 10 &# 34 ;. the present invention may be embodied in other specific forms without departing from its spirit or essential attributes . accordingly , reference should be made to the appended claims rather than the foregoing specification and accompanying drawings for an indication of the scope of the invention .

protective headgear for infants and young children comprises a head - enveloping member having the appearance of a conventional hat , but constructed of a core of impact absorbent foam , encapsulated within a shell of textile fabric material , the textile fabric material providing the inner and outer surfaces of the garment .

like characters of reference designate like parts in those figures of the drawings in which they occur . the reference numeral 10 indicates the device as a whole comprising an open box - like frame 12 elongated rectangular in general configuration . by way of the example the device 10 is approximately 12 feet ( 3 . 65 m ) wide , 8 feet ( 2 . 43 m ) high and 40 feet ( 12 . 19 m ) long and formed by side members 13 and 14 interconnected in laterally spaced relation at their respective ends by end members 16 and 18 forming a rectangular horizontal base frame means 20 having an open central portion accessible from one side and both ends of the frame , as presently explained . the device 10 is generally truncated triangular shaped when viewed from one end ( fig3 ). a plurality of pairs of generally upright longitudinally spaced wall studs 24 and 26 , are respectively rigidly connected in laterally spaced relation at their depending ends with the base frame side members 13 and 14 and adjacent their upper ends by respective ends of a ceiling joist 28 . a like plurality of rafter means 30 formed by pairs of rafters 32 and 34 , interconnected at their upper ends to form an apex 36 , are connected at their respective diverging end portions with the respective studs 24 and 26 intermediate the height of the latter so that the apex 36 of the rafters project a predetermined distance above the horizontal plane defined by the joists 28 medially the framework width . a plurality of right angle frame reinforcing rails 38 extend longitudinally coextensive with the framework and are rigidly connected with the top ends of the respective studs 24 and 26 and the respective rafters 32 and 34 intermediate their height between the joists 28 and apex 36 . the rails 38 , joists 28 and rafters 32 and 34 form a rigid baled hay platform or rack 40 at the upper limit of the device 10 . a plurality of preferably sheet iron panels 42 , overlie , in edge overlapping relation with respect to each other , the studs 24 at one side of the framework to form a windbreak wall when disposed normal to the wind direction . similar panels 42 &# 39 ; overlie the upper end portion of the studs 26 at the opposite side of the frame to further insure a rigid bracing for the device and add additional shelter for livestock within the frame . the device 10 is normally disposed horizontally on substantially level soil as shown by fig1 and 3 and in this position a front - end loader , not shown , may successively hoist lq a plurality of hay bales a , b , and c on the hay rack means 40 . by positioning the bails a and b on opposing sides of the row of rafters ( fig3 ) the third bale c may be lifted to overlie the two bales a and b . the center of gravity of each of the bales a and b being inwardly of the upper limit of the respective stud 24 and 26 maintain the bales in place as shown and forms a temporary hay roof . since the bales are usually not longer than their diameter a plurality of piles of three each ( a , b and c ) of the bales may be disposed in longitudinal end - to - end relation along the rack 40 . when it is desired to feed livestock being sheltered by the device 10 , an upper most hay bale is pulled off the rack means 40 so that it falls by gravity to the surface of the earth adjacent one side of the framework 10 . this is accomplished by a bale hook 45 ( fig4 ) comprising a triangular generally planar body 46 having a pair of arcuate hooks 48 depending from its base end and an endless ring 50 secured to its apex . with one end portion of a rope 52 connected with the ring 50 the bale hook may be manually thrown up and over the topmost surface of one of the uppermost bales . with the hooks 48 engaged with the hay of a bale and the other end portion of the rope tied to a prime mover , or to the saddle horn of a saddle on a riding horse , neither being shown , the hay bale may be pulled off the hay rack in a rolling action of the bale in a manner well understood by ranchers or farmers the device 10 is rendered mobile by a tubular shaft 54 which extends transversely of the base frame side members 13 and 14 substantially medially their ends which journals a pair of crank arms 56 and 58 for vertical pivoting movement each crank arm has an axle portion journalling a pair of wheels 60 and 62 , respectively , within respective sides of the base frame . when the device is to be moved it is assumed no hay bales are on the rack means 40 , the base frame sides are lifted , as by a conventional jack , not shown , allowing the wheels 60 and 62 to remain in contact with the surface of the earth 63 . an upright strut 64 pivotally connected at one end portion with the respective axle is removably bolted at its other end portion with an adjacent stud and supports the framework for mobile movement . when the framework is parked and rests on the surface of the earth , the bolt end of the struts 64 is loosely supported by adjacent rafters a generally conventional trailer hitch 70 , a - frame in shape , and connected with one end portion of the framework 10 is connected by its ball hitch 72 with the trailer hitch ball of a pick - up truck or the like , not shown , for moving the device 10 to a new location . obviously the invention is susceptible to changes or alterations without defeating its practicability . therefore , i do not wish to be confined to the preferred embodiment shown in the drawings and described herein .

a generally rectangular elongated horizontally disposed open frame having a base frame , upright studs , joists and rafter members form an overhead round hay bale rack for supporting hay bales . one side of the frame is closed by panel members to form a windbreak for livestock which may enter both ends or the side opposite the windbreak panels for shelter . hay bales supported by the hay rack portion of the device may be rolled off the rack for access by animals as they consume the respective bale .

fig1 is a front cross - sectional view of the esophageal - gastro - intestinal tract 40 from a lower portion of the esophagus 41 to the duodenum 42 . the stomach 43 is characterized by the greater curvature 44 on the anatomical left side and the lesser curvature 45 on the anatomical right side . the tissue of the outer surfaces of those curvatures is referred to in the art as serosa tissue . as will be seen subsequently , the nature of the serosa tissue is used to advantage for its ability to bond to like serosa tissue . the fundus 46 of the greater curvature 44 forms the superior portion of the stomach 43 , and traps gas and air bubbles for burping . the esophageal tract 41 enters the stomach 43 at an esophageal orifice below the superior portion of the fundus 46 , forming a cardiac notch 47 and an acute angle with respect to the fundus 46 known as the angle of his 57 . the lower esophageal sphincter ( les ) 48 is a discriminating sphincter able to distinguish between burping gas , liquids , and solids , and works in conjunction with the fundus 46 to burp . the gastroesophageal flap valve ( gefv ) 49 includes a moveable portion and an opposing more stationary portion . the moveable portion of the gefv 49 is an approximately 180 degree , semicircular , gastroesophageal flap 50 ( alternatively referred to as a “ normal moveable flap ” or “ moveable flap ”) formed of tissue at the intersection between the esophagus 41 and the stomach 43 . the opposing more stationary portion of the gefv 49 comprises a portion of the lesser curvature 45 of the stomach 43 adjacent to its junction with the esophagus 41 . the gastroesophageal flap 50 of the gefv 49 principally comprises tissue adjacent to the fundus 46 portion of the stomach 43 . it is about 4 to 5 cm long ( 51 ) at it longest portion , and its length may taper at its anterior and posterior ends . the gastroesophageal flap 50 is partially held against the lesser curvature 45 portion of the stomach 43 by the pressure differential between the stomach 43 and the thorax , and partially by the resiliency and the anatomical structure of the gefv 49 , thus providing the valving function . the gefv 49 is similar to a flutter valve , with the gastroesophageal flap 50 being flexible and closeable against the other more stationary side . the esophageal tract is controlled by an upper esophageal sphincter ( ues ) in the neck near the mouth for swallowing , and by the les 48 and the gefv 49 at the stomach . the normal anti - reflux barrier is primarily formed by the les 48 and the gefv 49 acting in concert to allow food and liquid to enter the stomach , and to considerably resist reflux of stomach contents into the esophagus 41 past the gastroesophageal tissue junction 52 . tissue aboral of the gastroesophageal tissue junction 52 is generally considered part of the stomach because the tissue protected from stomach acid by its own protective mechanisms . tissue oral of the gastroesophageal junction 52 is generally considered part of the esophagus and it is not protected from injury by prolonged exposure to stomach acid . at the gastroesophageal junction 52 , the juncture of the stomach and esophageal tissues form a zigzag line , which is sometimes referred to as the “ z - line .” for the purposes of these specifications , including the claims , “ stomach ” means the tissue aboral of the gastroesophageal junction 52 . fig2 is a front cross - sectional view of an esophageal - gastro - intestinal tract illustrating a grade i normal appearance movable flap 50 of the gefv 49 ( shown in dashed lines ) and a deteriorated grade iii gastroesophageal flap 55 of the gefv 49 ( shown in solid lines ). as previously mentioned , a principal reason for regurgitation associated with gerd is the mechanical failure of the deteriorated ( or reflux appearance ) gastroesophageal flap 55 of the gefv 49 to close and seal against the higher pressure in the stomach . due to reasons including lifestyle , a grade i normal gastroesophageal flap 50 of the gefv 49 may deteriorate into a grade iii deteriorated gastroesophageal flap 55 . the anatomical results of the deterioration include moving a portion of the esophagus 41 that includes the gastroesophageal junction 52 and les 48 toward the mouth , straightening of the cardiac notch 47 , and increasing the angle of his 57 . this effectively reshapes the anatomy aboral of the gastroesophageal junction 52 and forms a flattened fundus 56 . the deteriorated gastroesophageal flap 55 shown in fig2 has a gastroesophageal flap valve 49 and cardiac notch 47 that are both significantly degraded . dr . hill and colleagues developed a grading system to describe the appearance of the gefv and the likelihood that a patient will experience chronic acid reflux . l . d . hill , et al ., the gastroesophageal flap valve : in vitro and in vivo observations , gastrointestinal endoscopy 1996 : 44 : 541 - 547 . under dr . hill &# 39 ; s grading system , the normal movable flap 50 of the gefv 49 illustrates a grade i flap valve that is the least likely to experience reflux . the deteriorated gastroesophageal flap 55 of the gefv 49 illustrates a grade iii ( almost grade iv ) flap valve . a grade iv flap valve is the most likely to experience reflux . grades ii and iii reflect intermediate grades of deterioration and , as in the case of iii , a high likelihood of experiencing reflux . with the deteriorated gefv represented by deteriorated gastroesophageal flap 55 and the fundus 46 moved inferior , the stomach contents are presented a funnel - like opening directing the contents into the esophagus 41 and the greatest likelihood of experiencing reflux . disclosed subsequently is a device , assembly , and method which may be employed to advantage according to an embodiment of the invention in restoring the normal gastroesophageal flap valve anatomy . referring now to fig3 , it shows a device 100 according to an embodiment of the present invention . the device 100 includes a longitudinal member 102 for transoral placement of the device 100 into the stomach . the longitudinal member 102 has a longitudinal axis 103 . the device further includes a first arm 104 , hereinafter referred to as the chassis , and a second arm 106 , hereinafter referred to as the bail . the chassis 104 and bail are hingedly coupled at 107 . the chassis 104 and bail 106 form a tissue shaper which , as described subsequently in accordance with this embodiment of the present invention , shapes tissue of the stomach into the flap of a restored gastroesophageal flap valve that is substantial parallel to the axis 103 . the chassis 104 and bail 106 are carried at the distal end of the longitudinal member 102 for placement in the stomach . the device 100 has a longitudinal passage ( not shown ) to permit an endoscope 110 to be guided through the device and into the stomach . such a passage may be seen , for example , in copending application ser . no . 11 / 172 , 427 , filed jun . 29 , 2005 , for apparatus and method for manipulating stomach tissue and treating gastroesophageal reflux disease , and which application is incorporated herein by reference . this permits the endoscope to service as a guide for guiding the device 100 through the patient &# 39 ; s throat , down the esophagus , and into the stomach . it also permits the gastroesophageal flap valve restoration procedure to be viewed at each stage of the procedure . as will be seen subsequently , to facilitate shaping of the stomach tissue , the stomach tissue is drawn in between the chassis 104 and the bail 106 . further , to enable a flap of sufficient length to be formed to function as the flap of a gastroesophageal flap valve , the stomach tissue is pulled down so that the fold line is substantially juxtaposed to the opening of the esophagus into the stomach . hence , the stomach is preferably first gripped at a point out and away from the esophagus and the grip point is pulled to almost the hinged connection 107 of the chassis 104 and bail 106 . as described in copending application ser . no . 11 / 001 , 666 , filed nov . 30 , 2004 , entitled flexible transoral endoscopic gastroesophageal flap valve restoration device and method , which application is incorporated herein by reference , the device 100 is fed down the esophagus with the bail 106 substantially in line with the chassis 104 . to negotiate the bend of the throat , and as described in the aforementioned referenced application , the chassis 104 and bail 106 are rendered flexible . the chassis 104 is rendered flexible by the slots 108 and the bail 106 is rendered flexible by the hingedly coupled links 112 . further details concerning the flexibility of the chassis 104 and the bail 106 may be found in the aforementioned referenced application . the device further includes a tissue gripper ( not shown ). the gripper , as shown and described in the aforementioned copending application ser . no . 11 / 172 , 427 , comprises a helical coil . the coil is carried at the end of a cable ( not shown ) and may be attached to the end of the cable or be formed from the cable . with continued reference to fig3 , the device 100 further comprises a fastener director 140 . the fastener director includes a plurality of fastener deployment guides 142 . each fastener deployment guide 142 takes the form of a guide lumen . the guide lumens extend through the longitudinal member 102 to the first member 104 and terminate at delivery points 144 where a fastener is driven into the molded stomach tissue . the delivery ports 144 are within a wall 143 of the first member that is transverse to the longitudinal axis 103 of the longitudinal member 102 and the fastener director lumens 142 . the device 100 further includes a window 130 within the chassis 104 . the window is formed of a transparent or semi - transparent material . this permits gastroesophageal anatomy , and more importantly the gastroesophageal junction ( z - line ) to be viewed with the endoscope . the window includes a location marker 132 which has a know position relative to the fastener delivery points 144 . hence , by aligning the marker with a known anatomical structure , the fastener will be delivered a known distance from or at a location having a predetermined relation to the marker . for example , by aligning the marker with the z - line , it will be know that the fastener will be placed aboral of the z - line and that serosa tissue will be fastened to serosa tissue . as previously mentioned , this has many attendant benefits . it may also be mentioned at this point that the device 100 further includes an invaginator 145 including a plurality of orifices 146 . these orifices 146 , which alternatively may be employed on the longitudinal member 102 , are used to pull a vacuum to cause the device 100 to grip the inner surface of the esophagus . this serves to stabilize the esophagus and maintains device positioning during the procedure . this vacuum gripping of the esophagus may also be used to particular advantage if the patient suffers from a hiatal hernia . upon being thus gripped , the esophagus may be moved downwardly with the device toward the stomach to eliminate the hiatal hernia . referring now to fig4 , it shows the device 100 forming a flap to restore a gefv from stomach tissue layers 180 and 182 . the tissue layers have been pulled in between the bail 106 and chassis 104 by the gripper and cable ( not shown ) and the bail has been rotated about pivot 107 to close on the tissue to form a flap portion from tissue layers 180 and 182 . it may be noted in fig4 that the bail 106 has a distal end 145 that includes an opening 147 . the opening permits a deployment stylet 264 , fed down the guide lumen 142 and through the delivery port 144 to pierce through both tissue layer 180 and 182 during the deployment of a fastener through tissue layers 180 and 182 . more specifically , when the bail 106 is closed on the chassis as shown in fig4 , the wall 143 and bail distal end 145 are closely adjacent . the delivery port 144 is aligned with the opening 145 and the tissue layers are bent so that the tissue layers are disposed substantially transverse to the longitudinal axis 103 and presented to the stylet path for fastener deployment . this permits the fastener director guide lumen 142 to direct a fastener along the stylet 264 in a path that is continuously substantially parallel to the longitudinal axis 103 . this is in direct contrast to prior arrangements where the guide lumen paths were bent to present a fastener substantially transverse to tissue layers which were not bent . as a result , unlike prior arrangements , the force with which a fastener may be deployed is not diminished . also , since the fastener is translated over a substantially straighter path , the fastener travel through the guide lumen is rendered much smoother . hence , with the bail 106 closed on the chassis 104 with the tissue layers 180 and 182 there between and the delivery port 144 aligned with the opening 147 , the stylet may be advanced down the guide lumen 142 , through the port 144 , through the tissue layers 180 and 182 and through the opening 147 into the distal link 109 of the ball 106 . a fastener may now be deployed to fasten the tissue layers 180 and 182 together to maintain the formed flap . fig5 and 6 illustrate a manner in which the device 100 of fig3 and 4 may deploy a fastener 200 through the layers 180 and 182 of stomach tissue . the fastener 200 generally includes a first member 202 , a second member 204 , and a connecting member 206 . as may be noted in fig6 , the first member 202 and second member 204 are substantially parallel to each other and substantially perpendicular to the connecting member 206 which connects the first member 202 to the second member 204 . the first member 202 is generally cylindrical or can be any shape . it has a channel 212 that extends therethrough . the though channel 112 is dimensioned to be slidingly received on the tissue piercing deployment wire 264 . the first member 202 includes a pointed tip 224 . the tip 224 may be conical and more particularly takes the shape of a truncated cone . the tip can also be shaped to have a cutting edge in order to reduce tissue resistance . the first member 202 also has a continuous lengthwise slit 225 . the slit 225 includes an optional slot 226 that communicates with the through channel 212 . the slot 226 has a transverse dimension for more readily enabling receipt of the tissue piercing deployment wire 264 during deployment of the fastener 200 . the fastener member 202 is preferably formed of flexible material . the slit 225 may thus be made larger through separation to allow the deployment wire to be snapped into and released from the through channel 212 . in addition to the fastener 200 and the deployment wire 264 , the assembly shown in fig5 and 6 further includes a pusher 266 and a guide tube 268 . the subassembly of the tissue piercing wire 264 , fastener 200 , and pusher 266 may be guided to its intended location relative to the tissue layers 180 and 182 by the guide tube 268 . the tissue piercing wire 264 , fastener 200 , and the pusher 266 are all initially within the guide tube 268 . the guide tube 268 is representative of the fastener deployment guide and to that end , includes the fastener deployment guide lumen 142 . the subassembly of the tissue piercing wire 264 , fastener 200 , and pusher 266 may be guided to its intended location relative to the tissue layers 180 and 182 by the guide lumen 142 . as shown in fig5 and 6 , the tissue piercing wire 264 has a tip 270 helping it pierce the tissue layers 180 and 182 that will form the restored gastroesophageal flap valve . the pusher 266 has pushed the first member 202 of the fastener 200 through the tissue layers 180 and 182 on the tissue piercing wire 264 . this may be accomplished by moving the wire 264 and the pusher 266 together . as may be further noted in fig5 , the first member 202 is clearing the wire 264 and tissue layer 182 . the tissue piercing wire 264 may now be retracted into the pusher 266 and the tissue piercing wire 264 and pusher 266 may be withdrawn . fig6 illustrates the fastener 200 in its fully deployed position . it will be noted that the fastener has returned to its original shape . the tissue layers 180 and 182 are fastened together between the first member 202 of the fastener 200 and the second member 204 of the fastener 200 . the connecting member 206 extends through the tissue layers 180 and 182 . if the additional fastener deployment guides are provided , the foregoing steps for deploying further fasteners may be repeated . to render the flap uniform about the opening of the orifice into the stomach , it may be necessary to rotate the device 100 and repeat the previously described procedure for forming a further flap portion . when the appearance of the valve flap is satisfactory as viewed through an endoscope , for example , the bail 106 may be moved to a fully opened position as seen , for example , in fig3 and the device 100 may be removed from the stomach and esophagus . this would then complete the procedure of restoring to gefv . referring now to fig7 , it shows the chassis 304 of another apparatus 300 embodying the present invention . the apparatus 300 , as in the previous embodiment , includes the fastener director 140 in the form of fastener directing guide lumens 142 . the main difference between the apparatus 300 and the apparatus previously described is that the window for observing tissue is within the wall 143 that is substantially transverse to the fastener director lumens 142 . through this window , the color of the tissue may be readily observed so that it may be known where the z line is and to make sure that the fasteners are driven into the stomach tissue aboral of the z line . fig8 shows yet another embodiment . here , the apparatus 400 includes a non - linked bail 406 hingedly coupled to its associated chassis 404 at the pivot point 407 . the apparatus also includes a fastener director 440 which , as in the previous embodiments , may be one or more fastener guide lumens 442 . here however , it will be noted that the fastener director 440 deviates from a line 446 substantially parallel to the longitudinal axis at point 448 by an angle theta ( θ ). the lumen 442 then terminates at the wall 443 which is still substantially transverse to the lumen 442 . as may be appreciated by those skilled in the art , the drive force applied to a fastener beyond point 448 will be split into two components , a longitudinal component , and a lateral component . more specifically , the lateral component will vary with the sine of theta and be equal to the total drive force ( f ) times the sine of theta ( f × sine θ ). similarly , the longitudinal component will vary with the cosine of theta and be equal to the total drive force times the cosine of theta ( f × cosine θ ). when the lateral force becomes greater than the longitudinal force , the fastener will be pushed sideways and the longitudinal force component will become relatively ineffective at driving a fastener through the tissue as required . to make sure that the longitudinal force component is always greater than the lateral force component , f × cosine θ must always be greater than f × sin θ and theta must be no greater than 45 degrees . hence , at the delivery end of lumen 442 , the deviation θ is no greater than 45 degrees . further , it is preferable the fastener director be devoid of any deviation greater than 45 degrees . while particular embodiments of the present invention have been shown and described , modifications may be made , and it is thereto intended in the appended claims to cover all such changes and modifications which fall within the true spirit and scope of the invention .

a transoral gastroesophageal flap valve restoration device presents stomach tissue for fastening . the device comprises a longitudinal member having a portion arranged for transoral placement into a stomach . a tissue shaper is carried on the distal end of the longitudinal member that shapes stomach tissue within the stomach into a gefv . the tissue shaper comprises a pair of hingedly coupled first and second arms for receiving the stomach tissue there between . the device further comprises a fastener director that directs a fastener into the stomach tissue along a path that is devoid of any deviations or bends greater than 45 degrees .

in exemplary embodiments of the inventions herein , the antimicrobial activity of air and mixtures of non - thermal ( cold ) plasmas using air with vaporized water and ethanol are demonstrated . without limiting effect , it is believed that the use of vaporized liquids within a confined plasma reactor system result in potent antimicrobial species that can be used in surface disinfection applications . in some embodiments described herein the surfaces are non - tissue or organ surface . in some embodiments , the surface may be a tissue or organ . in some embodiments , the use of ethanol vapor as an initial gaseous media source may serve as an additional source of antimicrobial species generated in the plasma vapor chamber . in some embodiments , the use of vaporized liquids in order to create plasma may result in potent antimicrobial processes within a reaction system and allow for decontamination of recalcitrant microorganisms or difficult to sanitize substrates . fig1 is an exemplary embodiment of a plasma vapor chamber 100 . plasma vapor chamber 100 includes a high voltage electrode 112 made out of a conductive material , such as , for example copper . in this exemplary embodiment , the high voltage copper electrode had an outer dimension of 38 . 1 mm and an inner dimension of 25 . 4 mm . plasma vapor chamber includes a ground electrode 109 . the high voltage electrode 112 and ground electrode 109 were configured and designed to generate a dielectric barrier discharge ( dbd ) plasma . in this exemplary embodiment , an acrylic housing 101 was used . the acrylic housing 101 had the following dimensions : height , 100 mm ; inner diameter , 41 . 28 mm , and outer diameter ; 50 . 80 mm . high voltage electrode 101 was connected to a high voltage wire 113 that went through cap 102 located on the top of the plasma vapor chamber 100 . high voltage electrode 101 may have any suitable shape to create plasma inside the plasma vapor chamber 100 . ground electrode 109 may take any suitable shape to create the desired plasma . in some embodiments , ground electrode 109 may be a mesh . in some embodiments , ground electrode 109 may be a mesh that surrounds or partially surrounds plasma vapor chamber 100 . in some embodiments , multiple ground electrodes 109 may be used . in some embodiments , the plasma 150 is created throughout the plasma vapor chamber 100 . in some embodiments , the plasma 150 is created in one or more locations within the plasma vapor chamber 100 . in some embodiments , the plasma 150 is created throughout the plasma vapor chamber 100 however it is concentrated in one or more locations . in some embodiments , the plasma 150 is created in more than about 10 % of the volume of the plasma vapor chamber 100 . in some embodiments , the plasma 150 is created in more than about 20 % of the volume of the plasma vapor chamber 100 . in some embodiments , the plasma 150 is created in more than about 30 % of the volume of the plasma vapor chamber 100 . in some embodiments , the plasma 150 is created in more than about 40 % of the volume of the plasma vapor chamber 100 . in some embodiments , the plasma 150 is created in more than about 60 % of the volume of the plasma vapor chamber 100 . in some embodiments , the plasma 150 is created in more than about 10 % of the volume of the plasma vapor chamber 100 . cap 102 was a polypropylene cap . a rubber gasket 111 was located between cap 102 and housing 101 . a dielectric barrier 114 was located on the bottom of the high voltage electrode 112 with the remaining surfaces surrounded by a non - conductive housing 116 , which in this case was ultem ™ polyetherimide resin ( sabic america , houston , tex .). the dielectric barrier 114 was quartz and had a thickness of 1 mm . the high voltage electrode 112 was connected to a microsecond pulsed power supply ( not shown ) manufactured by advanced plasma solutions , malvern pa . the operating voltage and frequency were 20 kv and 3 . 5 khz respectively . the pulse duration was set at 10 μs . the base 103 of the vapor chamber 100 was made of a teflon ® supported ground conductor 109 which was made of stainless steel electrode . the gap between the electrode 112 and the ground electrode 109 was kept maintained at 2 mm . the vapor chamber 101 was also equipped with two gas inlets 106 and two gas outlet ports 108 that allowed the introduction and exhaust of gases into the vapor chamber 100 . although particular materials , sizes and configurations are disclosed in this one embodiment , different materials , sizes , and power settings may be used . in addition , other plasma sources may be utilized in some embodiments . the following parameters and set - up ( not shown ) were used to generate vapor . bench - mounted nitrogen and oxygen gas cylinders were connected to single valve gas flow controllers with high pressure tubing . additional lines were utilized to provide gases to an air free glass bubbler . five ml of prepared ethanol / water solutions at concentrations varying from pure water to pure ethanol were introduced into the bubbler . mixtures of nitrogen with oxygen at various ratios were used to vaporize the liquid in the bubbler . an additional line was then connected from the bubbler to an inlet 106 connected to the vapor chamber 100 to allow the transport of the vaporized liquids along with their carrier gases . in the exemplary embodiments , cold plasma was generated using the following settings : 3 . 5 khz , 20 kv , 10 μs pulse duration , and a 100 % duty cycle . the total flow rate of the gases introduced into the chamber ranged from 100 - 500 standard cubic centimeters per minute ( sccm ), but was fixed at one specific flow rate for the duration of plasma generation . the average power transferred to the discharge ranged from 1 . 5 to 3 . 1 w . the power measurements were taken from an energy monitor ( watts up ™ 57777 energy monitor , think tank energy products , inc ., milton , vt .). substrates 152 were loaded , with the bacteria inoculated surface 153 facing the high voltage electrode 112 , into the vapor chamber 101 and were set on the grounded electrode 109 and the vapor chamber 100 was sealed . the vaporized liquids were introduced into the vapor chamber and allowed to saturate the vapor chamber for 1 minute prior to plasma generation for each sample . the mist was exposed to plasma for periods of time from 5 seconds to 1 minute . following treatment in the plasma vapor chamber 100 , the exposed substrates were placed into centrifuge tubes that contained sterile de - ionized water for bacterial evaluation . the following bacteria strands and media were used . e . coli atcc 35150 ( type culture collection , manassas , va .) was used in the experiments described herein . all prepared cultures were grown overnight to reach logarithmic growth phase within brain heart infusion broth ( bhib ; difco , becton dickinson , franklin lakes , n . j . ), composed of 6 . 0 g / l brain heart infusion ( from solids ), 6 . 0 g / l peptic digest of animal tissue , 5 . 0 g / l sodium chloride , 3 . 0 g / l dextrose , 14 . 5 g / l pancreatic digest of gelatin , and 2 . 5 g / l disodium phosphate at a final ph of 7 . 4 . the initial overnight bacterial cultures had an approximate concentration of 1 . 0 × 10 9 cfu ( colony formation units )/ ml . ten μl of the bacterial suspension ( in nutrient - rich bhib ) was aseptically pipetted onto the surface of sterile stainless steel disks ( 1 cm diameter ; muzeen & amp ; blythe , montreal ) or freshly obtained , washed baby spinach leaves ( 1 cm × 1 cm cut squares ). the substrates were air dried in a thermo scientific 1300 series biosafety cabinet ( pittsburgh , pa .) for 90 minutes . surviving bacteria was detected using the following procedures . bacterial viability was assessed immediately after plasma exposure . sample tubes containing plasma - exposed substrates were serially diluted in order to obtain dilutions of experimental samples and then applied to brain heart infusion agar ( bhia ) plates . liquid aliquots ( 0 . 1 ml ) for each sample at each dilution factor were pipetted aseptically on the surface of bhia plates . this method is known as the spread plate method and is commonly used for antimicrobial assessment . results are expressed through the log 10 reduction ( lr ) term which corresponds to : where a and b represent the number of viable bacterial colonies that are present before and after plasma treatment , respectively . the pour plate method was also performed in order to assess larger amounts of overall bacterial inoculum at a given time . briefly , bhia was prepared and slowly cooled to 45 ° c . the entire sample ( at a given dilution factor ) was poured into an empty , sterile , plastic petri dish ( 100 × 15 mm ). a 15 ml aliquot of the cooled agar was mixed slowly to the sample and gently swirled for 30 seconds . the plates were left undisturbed until the agar solidified . for both methods , the inoculated plates were incubated at 37 ° c . for 18 hours . bacterial cell enumeration were collected the following day with the neutec flash and grow colony counter , ( neutec , farmingdale , n . y .). data was analyzed with graphpad prism and instat graphical and statistical software ( graphpad software , inc ., la jolla , calif .). a usb4000 - uv - vis ( ocean optics , dunedin , fla .) spectrometer with a det4 - 200 - 850 detector and order - sorting filter to cover the ( 200 - 850 nm ) wavelength range was employed in order to analyze emission spectra generated with different nitrogen : oxygen gas mixtures and ethanol vapor concentrations . the spectrometer had an optical resolution of 1 . 5 nm and was equipped with a multi - band pass order - sorting filter and a 25 μm entrance slit . an optical fiber was fixed in place 5 mm beyond one of the gas outlet ports and connected back to the spectrometer . spectra were taken from a discharge gap 2 mm from the discharge to the substrate . measurements were obtained over the duration of 30 seconds of plasma exposure . oes spectra were collected by accompanied ocean optics software and analyzed using spectrum analyzer open freeware ( version 1 . 7 ). optical emission spectroscopy was employed to analyze the plasma phase and to obtain information on the presence of active species that have the potential to contribute to the antimicrobial activity of the plasma . optical emission spectra collected in the uv - vis - nir region ( 200 - 600 ) are illustrated in fig2 and 3 . the molecular nitrogen emission bands dominate the obtained spectra in gas mixtures composed of high nitrogen concentration . the spectra were collected from discharges using the following gas mixtures : 98 % n 2 : 2 % o 2 , 75 % n 2 : 25 % o 2 , 50 % n 2 : 50 % o 2 , and 25 % n 2 : 75 % o 2 . these spectra were collected from the plasma vapor chamber 100 via a port located near the bottom of the chamber . the above mentioned spectra were collected without ethanol vapor being present in the discharge . the captured spectra ( 200 - 300 ) in the ultraviolet range seen in fig2 present a series of unique peaks that can be attributed to the presence of no . the illustrated spectrum was observed in the discharge generated from gas mixtures that contained four different ratios of nitrogen and oxygen . there are a series of intense bands that range from ( 230 - 270 ) nm , particularly with 99 % n 2 : 1 % o 2 gas mixtures . these intense bands can be assigned to the noγ ( a - x ) system . it is believed that the generation of the no species is an indication of extensive o 2 and n 2 dissociation at temperatures higher that 1600 k or due to direct electron impact . the role of n 2 metastables and their collisions form no based on the following reactions are known : the role of no is critical , as its emissivity in the uv - c range of the electromagnetic spectrum contributes to the disruption of viral and bacterial membranes . uv - c light can directly attack cellular dna leading to cell death while it inhibits their ability to spread . increase of the oxygen content in mixtures presented in fig2 , demonstrated quenching of the no bands . the appearance of fewer and weaker no peaks in the ( 180 - 280 ) nm range indicate that the gas temperatures increased with increasing amount of o 2 . this is due to the fact that oxygen as an electronegative gas tends to consume free electrons towards the formation of o − and o 2 − anions . therefore , higher energy is required to sustain the discharge when the oxygen concentration is increased and results in overall higher gas temperature . however , an increase in temperature is not responsible for the antimicrobial efficacy observed in the experimental results . measurements of experimental substrates immediately after exposure indicated the samples remained at room temperature . fig3 illustrates another portion of the collected uv - vis spectrum , ranging from 200 - 300 ). the intensity of the 337 . 1 nm peak for various o 2 — n 2 concentrations represents the ( 0 - 0 ) c - b transition of n 2 in the second positive system . an increase of the oxygen concentration leads to a dramatic decrease of the intensity of this spectral line . in additional experiments , ethanol - water mixtures were vaporized and carried by a gas mixture containing 78 % nitrogen and 22 % oxygen , designed to mimic the concentrations found in room air . the concentration of ethanol vapor in the bubbler for this portion of the study was 80 % ( v / v %) in h 2 o . the limit of detection for antimicrobial efficacy was 5 . 0 logs ( 99 . 999 % reduction ). some of the objectives of these experiments were to determine optimal flow rates of gas used to carry vaporized liquid to the reaction chamber that promote antimicrobial efficacy . the experimental results demonstrated very limited antimicrobial efficacy with 5 seconds of plasma exposure across all flow rates studied . at 15 seconds of exposure , a differential trend between the flow rates was observed . there was a − 0 . 232 log reduction ( lr ), 0 . 059 lr , 0 . 484 lr , 0 . 339 lr , and 0 . 346 lr for flow rates of 100 , 200 , 300 , 400 , and 500 sccm respectively . thirty seconds of plasma exposure provided results that displayed significant difference between the total gas flow rate into the plasma vapor chamber . log reductions of 0 . 067 and 0 . 273 were associated with total flow rates of 100 and 200 sccm . when the flow rate increased to 300 sccm , a 3 . 78 lr was observed . at 400 and 500 sccm , lr values of 3 . 569 and 1 . 491 were observed . at 45 seconds , there is significant antimicrobial efficacy across all of the flow rates studied . log reductions of 3 . 615 and 4 . 234 were observed at 100 and 200 sccm . higher flow rates all displayed complete kill that reached the limit of detection . fig4 illustrates the average values for all log reductions across all flow rates . the antimicrobial efficacy was best when the flow rate was at 300 sccm for the combined gas mixture . however , 400 sccm also had similar log reduction values . as the flow rate of the gas mixture increased to 500 sccm , the efficacy dropped at lower plasma exposure durations . in this exemplary embodiment , the optimal gas flow rate appears to be between ( 300 - 400 ) sccm for this chamber configuration . it is believed that the residence time of the plasma - derived species also plays a role in this observation . it is believed that a certain flow rate needs to be applied in order to create a sufficient concentration of actives . in some embodiments , bacterial kill may be promoted through the mechanical dislodging of the bacteria from contaminated surfaces . the total flow rate of the combined nitrogen and oxygen gases was set at 300 sccm for the below experimentation with respect to plasma exposure times and various n 2 to o 2 ratios . the concentration of ethanol vapor in the bubbler for these experiments was set at 80 %. the limit of detection for antimicrobial efficacy on stainless steel coupons was 5 . 0 logs ( 99 . 999 % reduction ). as shown in fig5 , the percentage of nitrogen in oxygen was varied from 98 % to 25 %. high nitrogen content within the plasma ( 98 %) displayed the following log reduction (“ lr ”) values : 0 . 221 with 5 seconds of plasma exposure , 0 . 484 with 15 seconds of plasma exposure , 3 . 776 with 30 seconds of plasma exposure , 5 with 45 seconds of plasma exposure , and 5 with 60 seconds of plasma exposure . plasmas generated with nitrogen at overall percentages of 88 % and 78 % displayed excellent germicidal efficacy against e . coli , particularly after 45 seconds and 60 seconds of exposure . generally , log reduction values for 30 seconds and below were fairly poor with plasmas composed of less than 78 % nitrogen . however , there was a spike in antimicrobial efficacy for plasma exposure intervals 30 seconds and below for plasma discharges composed of 50 % oxygen and 75 % oxygen . the effect of vapor from various ethanol concentrations in water was also investigated . ethanol vapor was generated with the use of a bubbler system as described previously . the concentration of ethanol vapor and its effect on antimicrobial efficacy of bacteria introduced into the plasma vapor chamber is discussed below . optical emission spectra data was also collected for ethanol vapor and is shown in fig6 . initial ethanol concentrations supplied to the bubbler was varied from 0 % ( deionized water ) to 100 % ( pure ethanol ). the total flow rate of combined nitrogen and oxygen was set at 300 sccm . the composition of the combined gas mixture was 78 % nitrogen and 22 % oxygen . the spectrum collected from plasmas generated with 80 % ethanol displayed emission bands between ( 245 - 250 ) nm and 681 nm where increased nitric oxide peaks were present . the proportion of the nitrogen lines found in the ( 300 - 400 ) nm ( fig6 ) was highest in the de - ionized water spectrum . the molar concentration of ethanol , water , and nitrogen : oxygen gas vapor delivered to the plasma vapor chamber was determined for each spectral characterization . for the 80 % ethanol solution , 2 . 923 % ethanol , 2 . 374 % water , and 94 . 703 % nitrogen : oxygen gas was delivered to the chamber . for the 40 % ethanol solution , 1 . 261 % ethanol , 6 . 147 % water , and 92 . 592 % nitrogen : oxygen gas . to study the effect of vaporized ethanol plasmas on e . coli , 3 plasma exposure durations were selected : 15 seconds , 30 seconds , and 45 seconds . results from the microbial testing show that the 15 second exposure displayed relatively low antimicrobial efficacy across all ethanol vapor concentrations . thirty seconds of plasma exposure resulted in lr values & gt ; 2 ( 99 %) with 80 % and 90 % ethanol concentrations . forty - five seconds of plasma exposure resulted in lr values & gt ; 3 ( 99 . 9 %) with 40 % and 60 % ethanol concentrations . log reductions increased even further to the limit of detection , 5 logs ( 99 . 999 %), with 70 % and 80 % ethanol concentrations . the log reduction values dropped from 5 to 2 . 716 when the concentration of the ethanol delivered inside the plasma vapor chamber increased from 80 % to 90 %. furthermore , the use of 100 % ethanol resulted in very poor antimicrobial efficacy and marked a strong transition point away from previous ethanol concentration log reduction values ( fig7 ). the experiments determined that there is an optimal ethanol range that can be used in vaporized form . the reduction in antimicrobial efficacy at high ethanol vapor concentrations likely stems from oversaturation of the plasma vapor chamber with ethanol . elevated concentration of ethanol and its oxidized forms ( e . g . acetaldehyde and acetic acid ) may prevent formation of minimum threshold concentrations of ros or rns due to oversaturation . b . application of air plasmas containing ethanol vapor on spinach leaves and stainless steel the effect of the experimental substrate was also investigated . the results presented above were collected from stainless steel coupons only . the total flow rate of combined nitrogen and oxygen ( at a gas composition mixture of 78 % and 22 % respectively ) was fixed at 300 sccm . this mixture of gas was chosen in order to mimic ambient air and represent plasmas that could be generated in a more cost effective manner . the use of room air instead of defined gas canisters expands applications into more practical settings . three plasma discharge exposure durations were selected : 15 seconds , 30 seconds , and 45 seconds . fig8 a compares log reduction differences between substrates based on ethanol concentration and the substrate type : stainless steel ( ss ) or spinach leaves ( sp ). a biological substrate ( spinach ) was chosen to evaluate possible differences between abiotic and biotic substrate effects on plasma antimicrobial efficacy . log reduction values for spinach leaves are nearly half of those for stainless steel coupons across all plasma exposure groups for low concentrations of ethanol vapor ( 40 %). this observed trend continues , but is not as pronounced by the maximum plasma exposure time point of 45 seconds for substrates exposed to 60 % ethanol vapor . log reduction differences between the substrates continued to be present with 80 % ethanol vapor , but log reduction values of 1 . 799 and 3 . 765 were observed on spinach leaves after 30 and 45 seconds of exposure respectively . these values were ˜ 1 . 5 logs less than their counterparts on stainless steel coupons . the log reduction between the stainless steel and spinach can be attributed to spinach leaves being a more complex substrate . these complex substrates are rough and uneven when compared to smooth , stainless steel coupons . machined substrates are relatively consistent whereas biological samples are unique , even sample to sample . the challenge for using plasmas on biological samples or tissues is the topography of the sample , its localized environment ( soil load , liquid vs . dry , etc . ), and response to the plasma . biological samples such as leaves may also outgas in physiological response to plasmas , further affecting localized species activity generated from plasmas in the vicinity of the treated surface . fig8 b illustrates differences between biotic and abiotic surfaces and possible effects on antimicrobial effects generated by the plasma vapor system described previously . the gas composition mixture of nitrogen and oxygen was set at 78 % and 22 % respectively . an 80 % ethanol solution was provided for the vapor study . three plasma discharge exposure durations were selected : 15 seconds , 30 seconds , and 45 seconds . a flow rate of 300 sccm did not significantly differ between stainless steel coupons and spinach leaves . the lr values remained fairly consistent between the two substrates . however , when the flow rate was adjusted to 400 and 500 sccm , lr values for the stainless steel coupons were markedly different from those generated from spinach leaves . antimicrobial efficacy was investigated further with the use of the pour plate method described previously . this method was used to evaluate a higher total volume of bacterial culture and increase the limit of detection for the purpose of antimicrobial calculations and subsequently confirm previous results . in the earlier experiments , the maximum limit of detection was 5 . 0 logs , a maximum that correlated to a 99 . 999 % reduction in bacterial viability . this method increased the limit of detection by 2 additional logs , correlating to an assay of 100 × more sensitivity . a maximum measurement with this assay , correlated to a 99 . 99999 % reduction in bacterial viability . a range of nitrogen : oxygen gas flow ratios were used to transport 80 % ethanol vapor downstream into the plasma reactor chamber for plasma exposure durations of 30 and 45 seconds respectively . in both exposure groups , a consistent trend was observed . as shown in fig9 , thirty seconds of plasma exposure resulted in lr values & gt ; 2 logs ( 99 %) across all nitrogen : oxygen mixtures and reached nearly 4 logs with high nitrogen content ( 98 %). forty - five seconds resulted in lr values & gt ; 4 logs ( 99 . 99 %) across all nitrogen : oxygen mixtures are reached nearly 7 logs ( 99 . 99999 %), the limit of detection for this study , with high nitrogen content ( 98 %). experimental results indicate that there are optimal ranges for different experimental variables during the application of plasma vapor within a chamber electrode configuration . for example , the total flow rate of the combined gaseous medium should be optimized during plasma application . in these experiments , a total gas flow rate of ( 300 - 400 ) sccm resulted in the most substantial antimicrobial efficacy . the flow rate and subsequently the plasma residence time of the reactive species also likely play a role in this observation . it was discovered that the composition of the initial feed gas medium contributed significantly to the overall antimicrobial efficacy . the combination of mixtures found to be most antimicrobial were those with high nitrogen . while , low nitrogen and high oxygen did ultimately provide multi - log antimicrobial efficacy , it did so only after 60 seconds of continuous exposure . high nitrogen discharges achieved lr values of 4 + ( 99 . 99 % kill ) within half of that the time as low nitrogen discharges . it is believed that the high nitrogen compositions likely produce nitric oxide , which is a known powerful antimicrobial species . optical emission spectroscopy identified intense peaks between ( 220 - 270 ) nm that can be assigned to nitric oxide , these peaks diminish significantly as the concentration of fed nitrogen within the initial gas medium into the reactor chamber drops below 98 %. ethanol vapor delivered into the chamber also was found to have an optimal concentration gradient . fig7 illustrates that ethanol concentrations as low as 40 % can be used to generate multi - log reductions in pathogenic bacteria after 45 seconds of plasma exposure on stainless steel coupons within the plasma vapor chamber . the optimal ethanol concentration range was determined to be between about 70 to about 80 %. this concentration range showed highly significant antimicrobial efficacy after 45 seconds of continuous plasma exposure . furthermore , this ethanol concentration range also resulted in multi - log antimicrobial efficacy after just 30 seconds of plasma exposure . fig8 a illustrates that the ethanol concentration variable results in values that differ by 1 - 2 logs between stainless steel coupons and spinach leaves . the antimicrobial efficacy based on the total flow rate of the gas does not seem to differ significantly between substrates for rates less than 400 sccm . once the flow rate increases , dramatic differences between the efficacies of the two substrates as shown in fig8 b .

exemplary apparatuses and methods of killing or deactivating bacteria are disclosed herein . an exemplary apparatus for killing or deactivating bacteria includes a plasma vapor chamber . the plasma vapor chamber has a vapor inlet for allowing a vapor into the chamber , a high voltage electrode , one or more grounding electrodes . the one or more grounding electrodes at least partially surrounding the plasma vapor chamber . the plasma vapor chamber includes an outlet for allowing fluid to flow out of the chamber . when the chamber is filled with vapor for a period of time sufficient to saturate the chamber with vapor , the high voltage electrode is energized to generate plasma throughout the chamber .

in fig1 , one recognizes a device for the production of an individually fitted orthopedic aid , in this case of a prosthesis shank for a thigh . one recognizes a plurality of shaped parts 1 , 2 , 3 , 4 which are fastened by supports 5 , 6 to a base frame 7 . in their border areas , the individual shaped parts , two of which are shown in fig3 , feature oblong holes 8 , 9 which together comprise an approximate angle of 90 °. connecting screws can be threaded through paired corresponding oblong holes along the dot - dash lines as per fig3 . this construction makes it possible to shift the individual shaped parts connected to each other in all directions of a plane . the individual shaped parts are made of a deformable , thermoplastic material in particular , such as pet for instance . they are capable to be twisted and to bend etc . through exterior forces applied to them . at the same time , it is ensured that the individual shaped parts on their interior surface transition as uniformly as possible and without the formation of a possible step into an adjacent shaped part . the shaped parts described here make it possible to fit a functional form with precise contours to a thigh stump under a load deforming it and thus to simulate an interior surface of a prosthesis shank to be formed after it which eventually will correspond optimally not only to the thigh stump , but also to the prosthesis components to be adapted to the prosthesis shank . the individual shaped parts are , as shown in fig4 and 5 , connected over intermediate elements 12 to the corresponding supports 13 . the intermediate elements contain plates 12 a , 12 b , which are adjustable against each other , while being able to be fastened against each other by appropriate tensioning screws 14 or fixing devices 15 in any position to each other . it is hence possible , by means of appropriate levers 16 , 17 , as shown in fig6 , to apply forces over guide rods 18 or pressure bars 19 to push them forward or backwards , or even to rotate them around a pivot 20 or an axis 21 , thus fitting the shaped form in an optimal manner to a leg stump . the shaped form being transparent or translucent , it is possible to visually verify the fit of the stump to the surface formed by the shaped parts . the individual plates , pivots , axes etc . may also be provided with markings , scales or may be connected by sensors to electronic measuring instruments on which the adjustments that have been performed can be read or stored . in this manner , it is also possible to reproduce any adjustments , if necessary . positions , in which the person to be fitted with a prosthesis a device described here , signal a comfortable position of a shaped part , and the previously modified degrees of freedom can be fixed individually by appropriate tensioning elements 22 , 23 , 24 , 25 . over the corresponding levers 16 , 17 , it is possible to first apply transforming forces on the corresponding shaped parts and then the articulations etc . being in connection with the levers that can be fixed in the resulting position whereby the shaped parts are being maintained in their deformed position . this makes it possible to remove , from the stump , the complete functional shape resulting from several shaped parts and which is taken off an existing stump under load while retaining the last shape it received . this last conserved shape does indeed respect shape alterations of the stump based on muscle or other tissue displacements occurring on it under load . in the example represented here , the base frame 7 is additionally fastened to a base support 27 by means of a swing 26 which is part of an articulation 85 . this provides the possibility to swing said functional form into several positions , especially also by the prosthesis - wearer with his existing muscles . these positions thus correspond in particular to the most diverse positions through which a prosthesis is moved during its use . one has thus the possibility to also include muscle and bone relief changes occurring on the stump during movements in considerations for the design of the prosthesis shank this also enables the user to already test the fit and comfort as long and as often as he likes prior to the actual production of the aid . fig7 b shows that coupled to the shank suspensions 44 there are counterweights 45 which are movable over the guide rods 46 in order to thereby absorb the loads acting upon the shank suspensions resulting from the weight of the prosthesis - wearer etc ., who supports himself over his prosthesis shank on the shank suspensions . it is mentioned here in passing that a purposeful displacement of the counterweights 45 can also be used for therapy purposes to stretch the hip joint of a prosthesis - wearer . fig7 a and 7 b also show that the base support 27 is additionally provided with a seesaw 43 . on this seesaw , there are two shank suspensions 44 which are to be fastened laterally to a prosthesis shank ( not shown ) and which permit tilting of this prosthesis shank in the frontal plane . the swivel fixed pivot bracket 47 of the seesaw 43 is movable in the horizontal direction and thus able to laterally displace the swivel and center of motion of the seesaw in the space between the suspensions ( for instance in the space of the forces entering the shank ). through the lateral displacement , it is possible to localize the courses of the load lines on a stump or prosthesis shank respectively , thus permitting the orthopedic mechanic to optimally position add - on pieces on a prosthesis shank for the electronic capture of the center of gravity of the seesaw , it is necessary to install the bearing 87 of the seesaw 86 additionally on a pivot the bearing seat 88 of which is fixed by an abutment 89 , with minimal freedom of movement between sensors 90 . the sensors capture with precision the unilateral loading of the seesaw and the point of equilibrium for determining the line of force . added together , the possible adjustments comprise all essential features to simulate the prosthesis to be produced also as realistically as possible . based on the close connection addressed above of the adjacent shaped parts , any modification of a shaped parts always entails a slight modification of the other shaped parts and possibly their location relative to the stump is also slightly changed . in this way , one obtains fundamentally a fluid , optimal design of the resulting functional form . but it is especially important , to establish an appropriate prosthesis shank in the shank entrance area , on the one hand with respect to the pelvis , especially the seat bone or the ramus ossis ischii respectively (“ ramus ” in the context of this application ) and on the other hand with respect to the thigh bone , here especially to its apophyse located on the side of its condyle , called the trochanter major (“ trochanter ” in the context of this application ). for this , provisions are made for the availability of an appropriate shaped part , e . g . a ramus layout 4 and / or an appropriate trochanter socket . these are adjustable , independent of the adjacent shaped parts 1 , 2 so that a stump in the entrance area of the thigh prosthesis can be seized with great precision . a section through an appropriate ramus layout is shown in fig8 . this shaped part is essential for a thigh prosthesis as described here to be adaptable under load , with the previously adjusted ramus layout remaining unchanged . with an appropriate anatomically correctly shaped ramus layout , a stump can be seized very precisely in the shank entrance area . this provides also the well - fitted setting of the shank volume by means of a proximal / distal displacement of an individual distally placed support plate as described further below . the ramus layout shown here is being provided as a separate shaped part 4 during the acceptance of a stump shape . during the subsequent formation of the functional form , this shaped part 4 will be replaced by a component 48 that is rigidly connected with an adjacent shaped part 49 . as described further below , it is over this combination of the component 48 and the adjacent shaped part 49 that during the coating of the resulting functional shape a uniform lining of plastic material 50 is being applied . during the production of the final form , it is on this plastic lining that an industrially prefabricated shaped part 51 , 52 is applied , the shape of which matches the shaped part 4 . in this way , the plastic lining 50 is being provided with a cushion 51 , 52 . this ensures an optimal support in the area of the ramus layout that is free of any pressure points . the shaped part for this ramus layout 4 can be adjusted by means of lever 6 and 5 even during a full load which makes it possible to try out the ideal pressure application of the ramus - pelotte [ foam filling ] even in vivo . for an electronic measurement of the pressure application of this shaped part on the human body part ( ramus ) sensors 80 are mounted in the horizontal direction 84 and in the vertical direction . considering that the aforementioned modification of the frame 7 in relation to a base support 27 can also be made around several axes that are orthogonal to each other , an outward and inward sliding motion of the ramus layout generated through movement can be verified and optimized on the prosthesis wearer in a very precise and realistic manner . in principle , the ramus layout can also be provided with an adductor support 51 forming here a unit with the ramus layout and is carried along into each position and advantageously positioned . in this context , it is then essential to adapt the volume of the prosthesis stump to the volume of the loaded stump in order to achieve here a good fit . it is for this purpose , as can be seen in fig1 that at the distal end of the prosthesis stump an individually fitted support plate is positioned which is adapted in its shape to the shape of a stump as it develops under loading . this support plate is adjustable for the volume change of the prosthesis shank in proximal / distal direction . to generate this shape , a sock 29 is placed in proximal direction over a stump end . due to the traction working in proximal direction the fabric at the distal end of the sock 29 is essentially dislocated proximally while forming a build - up . at the same time a traction hose 30 is placed over the sock 29 and directed through the center hole 31 of a guide plate 32 . a tensioning device 33 serves to load the distal end of the traction hose 30 . this has the effect of seizing and compressing the build - up forming on the stump end because of the traction by the sock 29 and the netting 14 so that the distal stump end assumes an overall compact and load - bearing shape . through proper adjustments of the forces acting upon the sock 29 and the hose 30 and over the direction of the traction towards ventral / dorsal , sagittal / medial it is possible to achieve a shape that meets not only the comfort needs of a prosthesis - wearer but also the orthopedic requirements . for electronic monitoring of the stump end loading , at least three sensors 76 are placed between the support plate 34 at the distal stump end and a salient support plate 77 . this makes it possible to measure the shank tilt at the stump end as well as the determination of the total loading of the stump end . a plastic material adaptable to the shapes or additionally in osseous areas , an elastic silicone or similar can be applied to the sock 29 , over which eventually the shaped parts and the prefabricated in itself equally adjustable support plate 28 are installed . such a support plate is preferably to be used on a lower leg prosthesis but also on a thigh prosthesis . alternatively , an orthopedic technician can also manufacture an individual cup that accepts the shape of the distal stump end . such a cup is better suited for accepting heavier loads . furthermore the loading of the distal stump end can be simulated more precisely with an individual shape of the stump end cup . the resulting functional form can then be used either for the molding of a model representing for instance the form of a loaded thigh stump . alternatively , prior to the production of the functional form , a corresponding thigh stump can be beefed up with a distance piece , for instance through bands , socks or preferably netting 91 , 92 etc ., so that the resulting functional form is slightly oversized . fabric hoses 14 are generally known and serve as a place holder for subsequently introduced material for production of the shank . a material preferred for this purpose and described hereunder , as shown in fig1 , for beefing up [ the stump ] consists of individual strands and has a thickness of at least 1 mm . the strands 91 , 92 of this material run in parallel in layers and placed on top of each other with only punctual connections . during the collected bundling of the strands , this results in a minimal bundling measurement ( fig1 ) and with radial expansion in a maximal expansion measurement ( fig1 ). in the one to four superimposed layers from such strands free spaces are created which balance out every change in volume of the stump relief . the over - dimension of the functional form can then be used to be lined with a preferably thermoplastic material for the production of a rough mold . the inside of the resulting plastic material lining or rough mold respectively then corresponds to the shape of a loaded stump that is not beefed up . the plastic lining thus produced can be used as a rough shape to form itself the shank of a thigh prosthesis . a device for installing an appropriate plastic lining or rough form respectively in the functional shape formed with individual shaped parts is shown in fig1 and 12 . one identifies a threaded rod 53 which at its lower end is provided with a plate 54 which over a screw thread 55 accepts an adapter plate for the ulterior threaded joint of knee and foot part . between shaped part 1 and an elastic balloon skin 56 which is made of rubber , silicone or similar material and which is expandable by at least 100 %, a deformable thermoplastic material 62 is introduced . preferably , this plastic material has already been prefabricated in a conical shape . the balloon skin is fastened by its end that is opposite to plate 54 to a bearing disc 57 featuring a circumferential sealing groove 58 . over a threaded element 59 corresponding with the threaded bar 53 the bearing disc 57 is height - adjustable , thus making the complete length of the described device adjustable . in the bearing disc 57 , there is a valve 60 through which a pressure medium ( arrow 61 ) can be pressed into the volume limited by the balloon skin 56 . over a device as described here , the thermoplastic material is then placed which has been appropriately heated , or which is subsequently heated . the device coated with this synthetic material is introduced into the functional shape , and through the valve 60 a pressure medium is pressed into the balloon skin , whereby the thermoplastic material is being pressed towards the outside and brought into adhesion with all shaped parts 1 , 4 etc . preferably the thermoplastic material has already been prefabricated in conic form by industrial methods . the opening of the cone is compatible with the connection plate 57 of the balloon or it is hermetically screwed , as shown in fig1 , to the connection plate 58 ( without interior balloon ) with the seal 75 and the pressure plate 69 . the distal end of the cone encloses the necessary connectors 63 for a liner or the prosthesis . over the connection plate 58 the plastic cone can be heated either by streaming hot air 73 or by heating elements installed in the inner space . the plastic deformation of the heated cone occurs subsequently by incoming compressed air 61 and brings the wall of the cone , from the inside to the outside , into contact with the shaped part 66 . to prevent a thinning of the cone rim , the connecting plate 58 is being tracked distally during the deformation up to the shank rim 66 , to facilitate the shaping 67 . that is why the inner tube 72 is executed in a mobile linear form . the thermoplastic material is then cooled which makes it rigid in the shape that has been preset by the functional form . the resulting plastic part may then , as described above , be upholstered with individual silicone pads . it can be used as a rough form or even as a prosthetic shank or as the basis for a classic construction of a prosthetic shank the addition of an adapter plate for the substructures of the prosthesis is shown in fig1 . according to the invention , the connecting plate 94 is being brought from distal to proximal in a thermoplastic deformable plastic container 93 over the stump end loading plate 95 in horizontal position by a device to the shank 99 and is being fitted positively over the thermoplastic deformable rim 96 of the plastic container to the distal shank end . in a rigid screwed connection , a vertically adjustable counter plate 98 is connected to the adapter plate 94 . according to the state of the art , the hollow space inside the container 93 is being filled with poly - urethane foam and through the filling a connection is being made to the shank 99 . advantageous are here a horizontal orientation of the connecting plate 94 relative to the determined position of shank 99 in vertical and horizontal position and the shaping of the poly - urethane foam connection 97 in a sealed container . this ensures a functional position and high rigidity of the connecting plate . for the prosthesis shank a dispenser valve is used for a vacuum adaptation of the shank on a stump . for this purpose the valve seat needs to be fitted into the shank with particular precision . it is for this purpose that with a device 100 , as shown in fig1 , hot air is being conducted over an inlet channel 102 toward a circular defined area for the valve seat on the thermoplastic deformable plastic cone and along the plastic material , through ejector channels located at the valve seat . the valve seat 104 that is being used is pressed into the plastic material 103 by means of a tension shaft 107 and a locknut 105 for the shaping of the plastic material 106 . since the method described here is executed without a model , this device is necessary for a precise valve seat . besides the shank as for instance of a thigh prosthesis as it has been described so far , it is also possible in the same manner , to produce ortheses for instance , be they seat shells or even trunk ortheses . the production of load alleviating ortheses for the lower extremities is made according to the same principle with the same shaped parts from the leg prosthesis construction described here , but without a lower support plate as it was described above . primarily it is the loaded joint area that is being molded where the resulting mold can then also be used for the classic construction of an orthesis . in fig1 , it is shown for the production of a trunk orthesis that several shaped parts 35 , 36 , 37 are fastened to a base support 38 by means of support 39 . the individual shaped parts 35 , 36 , 37 and the corresponding supports 39 are interconnected by fastening elements 40 that are adjustable by levers 41 / 42 , so that the individual shaped parts 35 , 36 , 37 can be adapted to the individual requirements of a person ; resulting individual fitting shapes can then be determined by means of appropriate fixing levers , following the same principle as it was described above for a prosthesis shank . in the example of execution described here , the shaped parts are likewise made of semi - flexible plastic material which permits individual adaptation to a user .

the invention relates to a device and a method for producing a orthopaedic aid . in order to precisely adapt an orthopaedic aid , it is necessary , on the body part intended to correspond to the orthopaedic aid , to take into account , during preparation of the orthopaedic aid , the displacements of muscle and other tissue that occur when the finished aid is used under loading . to avoid the hitherto lengthy adaptation procedure , a device is proposed that has a plurality of interconnected shaped parts connected to a main frame via holders that can be fixed in their position . by means of these shaped parts , it is possible to generate a spatial supporting surface and to alter it as required in order to support a body part with realistic loading an accordingly realistic tissue displacement . the resulting shape can be utilized to produce a corresponding orthopaedic aid .

the present inventors have conceived of , isolated and applied compounds jo - 4 and jo - 4a against nucleated infectious agents comprising parasites , bacteria , and the like microorganisms . fungi and insects likewise are targeted by the instant teachings . the practice of the present invention will employ , unless otherwise indicated , conventional laboratory animal handling techniques , microbiology , parasitology , organic and medicinal chemical synthesis within the skill of the art . such techniques are explained fully in the literature . see miller , l . h . ; et al ., eds ; immunity to blood parasites of animals and man , plenum press , new york and london , 1977 ; baker , j . r . muller r , and rollinson , d . eds ., advances in parasitology vol . 43 , academic press , 1999 ; bogitsh b . j . and chen t . c . eds . human parasitology 2nd edition , academic press , 1998 ; murray , p . r et al . eds ; medical microbiology . third edition , mosby , st . louis , mo ., 1998 ; ojo - amaize , e . a . et al . plasmodium berghei sporozoites are mitogenic for murine t cells , induce interferon and activate natural killer cells , j . immunol . 1984 , 133 : 1005 - 1009 ; ojo - amaize , e . a . et al . positive correlation between degree of parasitemia , interferon titers , and natural killer cell activity in plasmodium falciparum - infected children , j . immunol . 1981 , 127 : 2296 - 2300 ; silverman , r . b ; the organic chemistry of drug design and drug action , academic press , inc . ny ( 1992 ); smith , m . b . ; organic synthesis , mcgraw hill , inc . ny , ( 1994 ); okogun , j . i . et al ., z . naturforsch , 37c : 558 - 561 , 1982 ; adesomoju , a . a . et al ., phytochemistry 22 : 2535 - 236 , 1983 . likewise , artisans will understand those conventional techniques used to practice the instant teachings . the following terminology will be used in accordance with the definitions set out below in describing the present invention . the term “ inhibiting the growth of ” is used with respect to protozoan parasites that are pathological to humans or other animals . for example , with respect to protozoan malarial parasites , “ inhibiting the growth of ” means inhibition of parasitemia as determined by decreased numbers of parasitized red cells in blood which results in alleviating the “ pathological effects ” of malaria infection and increasing the life span of infected subject . the term “ pathological effects ” as used herein is illustrated by an understanding of the life cycle of the protozoan parasite and its effects in a host . it will be understood that protozoans , including those of the genus plasmodium , trypanosoma , theileria , babesia , coccidia , amoebae and the like ciliates ( including microsporidians ), trichomonad and related forms , non - trichomonad flagellates , hemoflagellates ( such as leishmania , trypanosoma ), and other apicomplexans such as bahesia , toxoplasma , pneumocystis , cryptosporidium , cyclospora and isospora are described herein . ( bogitsh , b . j . and cheng , t . c . eds . human parasitology 2nd edition , 1998 : academic press , san diego , london , boston , new york etc .). the protozoan plasmodial parasite causes malaria , one of the most debilitating diseases afflicting humans and animals . plasmodia are nucleated coccidian or sporozoan parasites of blood cells , and as seen with other coccidia , they require two hosts : the mosquito for the sexual reproductive stages and humans and other animals for the asexual reproductive stages . human infection is initiated by the bite of an anopheles mosquito , which introduces infectious plasmodia sporozoites via its saliva into the circulatory system . the sporozoites are carried to the parenchymal cells of the liver where asexual reproduction ( schizogony ) occurs . this phase of growth is termed the exoerythrocytic cycle and lasts 8 - 25 days depending on the plasmodial species . the hepatocytes eventually rupture , liberating the plasmodia ( termed merozoites at this stage ), which in turn attach to specific receptors on the surface of erythrocytes and enter the cells , thus initiating the erythrocytic cycle . asexual replication progresses through a series of stages ( ring , trophozoite , schizont ) that culminates in the rupture of the erythrocyte , releasing merozoites , which initiates another cycle of replication by infecting other erythrocytes ( murray , p . r . et al . eds . medical microbiology 3rd edition , 1998 : mosby - year book , inc ., st . louis , mo .). pathological and clinical syndromes of malarial parasites consist , in part , of influenza - like symptoms with fever patterns , severe nausea , vomiting and diarrhea , anemia due to destruction of increased numbers of infected erythrocytes resulting in toxic cellular debris , adherence of red blood cells to vascular endothelium and to adjacent red blood cells , and formation of capillary plugging by masses of red blood cells , platelets , leukocytes , and malarial pigment . it is also known that involvement of the brain ( cerebral malaria ) is most often seen in p . falciparum infection . capillary plugging from an accumulation of malarial pigment and masses of red cells can result in coma and death . kidney damage is also associated with p . falciparum malaria resulting in an illness called blackwater fever . intravascular hemolysis with rapid destruction of red blood cells produces a marked hemoglobinuria and can result in acute renal failure , tubular necrosis , nephrotic syndrome , and death . liver involvement is characterized by abdominal pain , vomiting of bile , severe diarrhea , and rapid dehydration . although any malaria infection may be fatal , p . falciparum is the most likely to result in death if left untreated . in rodents , p . berghei , and p . chabaudi infections result in death ( miller , l . h . et al . eds . immunity to blood parasites of animals and man : advances in experimental medicine and biology , volume 93 , 1977 : plenum press , new york and london ). as used herein , the term “ alleviate ” means to mitigate , lessen or reduce or make more bearable . the term “ subject ” is taken to mean humans as well as other animals . the following materials and methods were employed in the non - limiting examples set out below , which illustrate unexpected results noted , those skilled in the art will understand use of the instant teachings with known nucleated infectious agents . p . berghei berghei ( e1 strain clone b6 of 125674 sf - 2393 ) was purchased from american type culture collection ( atcc ), rockville , md . the parasites were maintained in vivo and routinely passaged in c57bl / 6 strains of mice . animals used in this work were female c57bl / 6 mice , 6 - 8 wk old , purchased from charles river laboratories , wilmington , mass . one vial containing 0 . 5 ml of p . berghei - infected frozen mouse blood , obtained from atcc , was thawed and injected intraperitoneally ( i . p .) into a single mouse . when the mouse was sick , blood was collected by ocular venipuncture into a heparinized tube . giemsa stained thin blood film smears on glass slides were prepared to determine the level of parasitemia by light microscopy . infected blood was diluted 1 : 1000 in hbss ( hanks balanced salt solution ) and 0 . 3 ml was injected i . p . into a fresh ( uninfected ) mouse . this process was repeated serially for parasite maintenance in vivo . the level of parasitemia was determined by standard technology with thin smears of fresh blood on glass slides , fixed with absolute methanol for 5 minutes , and stained for 30 minutes with 5 % giemsa dye buffered to ph 7 . 0 to 7 . 2 ( ojo - amaize , e . a . et al . j . immunol . 1981 , 127 : 2296 - 2300 ; murray , p . r . et al . eds . medical microbiology . third edition , mosby , st . louis , mo . ; 1998 ). stained parasitized red blood cells on glass slides were viewed with 100 × 1 . 25 objective lenses in oil immersion under a light microscope ( nikon ). at least 1000 red blood cells ( rbcs ) were counted in each field and 5 fields were counted per slide . the total number of parasitized cells per 1000 rbcs per field was recorded and the average was calculated per slide and expressed in percent (%) of total rbcs . for determination of the prophylactic effect of jo - 4a on level of blood parasitemia , 5 mice were pretreated p . o . with 1 . 0 mg / kg once a day for 3 days . five control mice received vehicle ( water ) only . on the 4th day after drug pretreatment was stopped , all mice were infected i . p . with 0 . 1 ml of infected blood diluted 1 : 100 in hbss . blood samples were obtained from experimental and control mice on days 2 , 3 , 4 and 5 post infection to determine the level of blood parasitemia . for determination of mortality , there were 5 groups of 10 mice per group ( no drug control , 31 . 2 μg / kg , 62 . 5 μg / kg , 125 . 0 μg / kg and 250 μg / kg ). experimental mice received appropriate doses of jo - 4a p . o . once a day for 4 days prior to infection with p . berghei parasites on the 5th day of jo - 4a pretreatment . treatment with jo - 4a was continued for 3 more days , once daily , post infection . mortality of mice was followed daily for 24 days and recorded . while clinical data and involved mechanisms remain to be further developed it is believed those skilled in the art will readily understand that treatment by the instant compounds and methods for fungal - insect - based , and the like microbiological nucleated agent mediated insult and injury would be routine using any conventional modes of administration , comprising those falling within the scope of the instant claims and such usages and applications would not require undue experimentation to artisans . having merely described aspects of the best modes to practice those preferred embodiments which would enable artisans to fully comprehend and practice the teachings of the present invention , it is further noted that various modifications , changes , ameliorations and alterations may be effected by those skilled in the art without impacting on the scope of spirit of the instant invention as defined by the appended claims . likewise , the present inventors have used the instant compound to combat related microbiological issues and challenges . for example , it has further been hypothesized that tissues and systems insulted by fungal infestation exhibit with similarly shown improvement under jo - 4a treatment .

novel enhanced usage of hypoestoxides derivatives and agonists theeof as active agents against nucleated infectious entities including known parasites and the like microbiological insultors of living tissue , systems and organisms , known modes of administration and related compounds are used alone or in combination with the instant teachings .

reference will now be made in detail to embodiments of the present invention , examples of which are illustrated in the accompanying drawings , wherein like reference numerals refer to the like elements throughout . embodiments are described below to explain the present invention by referring to the figures . fig1 illustrates a user who wears an example apparatus 100 for enhancing muscular movement according to an embodiment of the present invention . referring to fig1 , the apparatus 100 may be used as an auxiliary artificial muscle that is formed of fibers and can thus be worn by a user . for example , the apparatus 100 may be formed into clothing wearable by a user , such as a glove , stocking , wrap , or other wearable clothing . in detail , in an embodiment a user may wear the apparatus 100 in order to supplement muscular strength . when a user who wears the apparatus 100 moves his / her left arm , as indicated by fig1 , a muscular movement sensor 110 of the apparatus 100 may sense the muscular movement of the user . then , the result of the sensing may be analyzed , and an actuator , realized using an electroactive polymer ( eap ) 130 a , may be driven according to the result of the analysis , thereby enhancing the muscular movement of the user . here , the user may feel as if he / she moved his / her muscle on his / her own without the auxiliary aid of the apparatus 100 . the operation of the apparatus 100 , according to an embodiment of the present invention , will hereinafter be described in further detail with reference to fig2 . fig2 illustrates an apparatus 100 , such as that illustrated in fig1 . referring to fig2 , the apparatus 100 may include a muscular movement sensor 110 , a movement information controller 120 , a storage module 125 , and a muscular movement actuator 130 , for example . when a user wears the apparatus 100 and causes to move a muscle that is , e . g ., fully surrounded by the apparatus 100 , the muscular movement sensor 110 may detect the movement of the muscle . a sensor using optical fibers or a bioelectric sensor may be used as the muscular movement sensor 110 . some sensing methods used by the muscular movement sensor 110 may be well known to one of ordinary skill in the art to which the present invention pertains , and thus , a detailed description thereof will be omitted . the movement information controller 120 may analyze the muscular movement , sensed by the muscular movement sensor 110 , and generate muscular movement information based on the results of the analysis , for example to control movement of the muscle . the muscular movement information may include the strength and direction of the muscular movement sensed by the muscular movement sensor 110 . the storage module 125 may store muscular movement information in a database according to a set of standards , for example . the movement information controller 120 may then control the muscular movement actuator 130 with reference to the muscular movement information stored in the storage module 125 . in an embodiment , the movement information controller 120 may supply the muscular movement actuator 130 with an input voltage having an appropriate waveform with reference to the storage module 125 . examples of the input voltage include , without limitation , voltages having various waveforms such as direct current ( dc ) voltages and alternating current ( ac ) voltages having a sinusoidal wave , a triangle wave , or a square wave . the muscular movement actuator 130 may be supplied with the input voltage , and may enhance the muscular movement of the user according to the muscular movement information provided by the movement information controller 120 , or the muscular movement information stored in the storage module 125 , for example . the muscular movement actuator 130 may thus enhance the muscular movement of the user , thereby not only providing additional strength , but also potentially weakening or decreasing the muscular movement of the user , by selectively resisting the movement of the user , for example . the storage module 125 may store muscular movement information such as the strength and direction of the muscular movement of the user by mapping the muscular movement information as a database according to a set of standards , for example , according to the gender and age of the user , part of the user &# 39 ; s body surrounded by the apparatus 100 , and corresponding muscles , and the time when the user may use the apparatus 100 . the muscular movement information stored in the storage module 125 may further be updated for each of the standards . then , when the user uses his / her muscles more intensely than he / she usually does , the muscular movement actuator 130 may reduce the strength of the muscular movement of the user according to the muscular movement information stored in the storage module 125 , for example . in addition , if a muscle movement exceeds a desired range because of weakness in a muscle , such as a weak bicep muscle , further potentially resulting in the dropping of a held item , an opposing movement force may be generated to maintain the normal holding position . as an example of increasing the strength , it may be assumed that a muscular strength of one hundred , on a hypothetical scale , is needed to lift a predetermined object . a user who can exert a muscular strength of up to eighty , on the hypothetical scale , can lift the predetermined object by making up for a deficit in muscular strength of twenty with the aid of the apparatus 100 . a user who can exert a muscular strength of up to ninety , on a hypothetical scale , can also lift the predetermined object by referencing the muscular movement information stored in the storage module 125 and making up for a deficit in muscular strength of ten , on a hypothetical scale , with the aid of the apparatus 100 . the structure of the muscular movement actuator 130 will hereinafter be described in detail . the muscular movement actuator 130 may include an eap that can be configured as fiber , e . g ., tissue resembling human muscle tissue , and include a pair of electrodes that contact the lateral sides of the eap , although other quantities of electrodes may be used , and an electric circuit that applies a voltage to the electrodes . the muscular movement actuator 130 may generate additional muscular strength or displacement for the user by responding to a signal obtained through conversion by the movement information controller 120 , and an actuator interface ( not shown ). the actuator interface ( not shown ) may be arbitrarily connected between the muscular movement actuator 130 and the movement information controller 120 , and may convert a signal generated by the movement information controller 120 into an appropriate signal for driving the muscular movement actuator 130 , for example . examples of the actuator interface may include a power amplifier , a switch , a digital - to - analog ( dac ) converter , an analog - to - digital converter ( adc ), and other components . two types of eaps and the physical characteristics of each of the two types of eaps will hereinafter be described in detail with reference to fig3 , noting that alternatives are equally available . eaps are polymers that are manufactured and processed to reflect a wide range of physical and electrical properties . when eaps are activated by applying a voltage , they display a significant size or shape distortion or deformation . the degree of deformation of eaps is dependent on the length , width , thickness , and radial direction of the material of each eap . in general , eaps are deformed by 10 - 50 % when activated . given that piezoelectric materials are generally deformed by less than 0 . 3 %, the degree of deformation of eaps is highly distinctive . eaps can also be precisely controlled using an appropriate electric system . eaps are generally small , easy to control , consume small amounts of power , achieve high response speeds , and are inexpensive . eaps are thus , hereby suggested to be widely employed in the field of artificial muscles , and research on potential applications of eaps as artificial muscles has been vigorously conducted . eaps output an electric signal when they undergo physical deformation due to external forces . thus , eaps can be used as sensors . since most eap materials generate an electrically measurable electrical potential difference , eaps can also be used as strength , location , velocity , acceleration , and pressure sensors . further , since most eaps have bidirectional properties , eaps can be used as sensors or actuators . examples of eaps may include eap gels , ionic polymer metal composites ( ipmc ), and electrostrictive polymers . the operating principles of most eap materials are based on ionic movements inside and outside a polymer network . eaps are broadly classified into dry polymers using a dielectric material and wet polymers using an ionic material . the upper view and the lower view of fig3 respectively illustrate a dry polymer and a wet polymer . referring to the upper and lower views of fig3 , each of the dry and wet polymers may be formed as a sandwich made up of a dielectric or ionic polymer 130 a and two conductive / compliant electrodes 130 b that are on the opposite sides of the dielectric or ionic polymer 130 a . when a high electric field ( e . g ., an electric field of several hundreds or thousands of volts ) generated by an electric circuit 130 c is applied , the suction force of the electrodes 130 b increases and thus presses on the dielectric or ionic polymer 130 a that is interposed between the electrodes 130 b , thereby causing a significant deformation of the dielectric or ionic eap 130 a so that the dry or wet polymer can elongate or bend in one direction . here , the degree of deformation of the dry or wet polymer may be about 50 %. referring to the upper view of fig3 , two electrodes 130 b contact an eap 130 a , having a predetermined thickness , on the opposite sides of the eap 130 a , for example . each of the electrodes 130 b is formed of a conductive polymer layer . in order for the electrodes 130 b to be deformed along with the eap 130 a , the electrodes 130 b should be compliant as well as conductive . an initial state of the eap 130 a when the electrodes 130 b are not supplied with power by an electric circuit 130 c is illustrated in the left part of the upper view of fig3 . once the electrodes 130 b are supplied with power by the electric circuit 130 c , the thickness of the eap 130 a decreases , and thus , the eap 130 a spreads wide between the electrodes 130 b , as illustrated in the right part of the upper view of fig3 . here , the electrodes 130 b that are compliant are deformed along with the eap 130 a . referring to the lower view of fig3 , two electrodes 130 b contact an eap 130 a , having a predetermined thickness , on the opposite sides of the eap 130 a , for example . each of the electrodes 130 b may be formed of a conductive polymer layer . in an embodiment , in order for the electrodes 130 b to be deformed along with the eap 130 a , the electrodes 130 b should be compliant as well as conductive . an initial state of the eap 130 a when the electrodes 130 b are not supplied with power by an electric circuit 130 c is illustrated in the left part of the lower view of fig3 . once the electrodes 130 b are supplied with power by the electric circuit 130 c , ions in the eap 130 a rush into a cathode , thereby causing a deformation of the eap 130 a so that the eap 130 a bends like a bow , as illustrated in the right part of the lower view of fig3 . here , the electrodes 130 b that are compliant bend along with the eap 130 a . the principles of realization of an actuator using the wet polymer illustrated in the lower view of fig3 will hereinafter be described in detail with reference to fig4 . referring to fig4 , an eap 130 a having a uniform curvature may be formed as a wave , for example , one of a cathode 130 b (−) and an anode 130 b (+) may be inserted into curvature portions of the eap 130 a , and an anode 130 b (+) or a cathode 130 b (−) ( whichever of the cathode 130 b (−) and the anode 130 b (+) connected to none of the curvature portions of the eap 130 a ) may be inserted into the middle of the eap 130 a . when the anode 130 b (+) and the cathode 130 b (−) are supplied with power by an electric circuit 130 c , the curvature of the eap 130 a changes in the direction of a current , and thus , the eap 130 a either contracts or elongates . examples of the action of a muscular movement actuator using an eap will hereinafter be described in detail with reference to fig5 through 7b . fig5 illustrates an explanation for the action of a muscular movement actuator according to an embodiment of the present invention . referring to fig5 , an eap 130 a may be formed as a single wavy layer having a uniform curvature , a pair of electrodes 130 b may be formed by connecting one of an anode 130 b (+) and a cathode 130 b (−) to an upper curvature portion of the eap 130 a and connecting whichever of the anode 130 (+) and the cathode 130 b (−) is left unconnected to the upper curvature portion of the eap 130 a to a lower curvature portion of the eap 130 a . when a current is applied to the electrodes 130 b by an electric circuit 130 c that is connected to a power supply , the eap 130 a bends in one direction , thereby causing a deformation of the eap 130 a so that the eap 130 a contracts . fig6 illustrates an explanation for the action of a muscular movement actuator according to another embodiment of the present invention . referring to fig6 , an eap 130 a may be formed as a double wavy layer having a uniform curvature . a pair of electrodes 130 b may be formed by connecting one of an anode 130 b (+) and a cathode 130 b (−) to both upper and lower curvature portions of the eap 130 a and connecting whichever of the anode 130 b (+) and the cathode 130 b (−) is connected to none of the upper and lower curvature portions of the eap 130 a to the interface between the upper layer and the lower layer of the eap 130 a . when a current is applied to the electrodes 130 b by an electric circuit 130 c that is connected to a power supply , the eap 130 a further bends in one direction so that the eap 130 a further contracts . fig7 a and 7b illustrate an explanation for the action of a muscular movement actuator according to another embodiment of the present invention . referring to fig7 a and 7b , an eap 130 a may be formed as a cylinder that extends longer in a longitudinal direction than in a latitudinal direction . a pair of electrodes 130 b may be formed by connecting one of an anode 130 b (+) and a cathode 130 b (−) to the outer circumferential surface of the eap 130 a and connecting whichever of the anode 130 b (+) and the cathode 130 b (−) is left unconnected to the outer circumferential surface of the eap 130 a to the inner circumferential surface of the eap 130 a which is the outer circumferential surface of a central axial member of the eap 130 a , for example . in detail , referring to fig7 a , the volume of a central portion of the eap 130 a varies , and thus , the central axial member of the eap 130 a extends . accordingly , the eap 130 a elongates . fig7 b illustrates the opposite situation to the situation illustrated in fig7 a . in other words , referring to fig7 b , the volume of an outer circumferential portion of the eap 130 a increases , and thus , the diameter of the eap 130 a increases so that the eap 130 a contracts along the longitudinal direction . the apparatus 100 may be realized as outerwear or underwear that can be worn by a user , for example . in this case , it is possible to facilitate user activities by providing a user who wears the apparatus 100 with almost the same feeling of wearing outerwear or underwear . the apparatus 100 may enhance the muscular movement of a user and may serve as auxiliary artificial muscles for a user . the apparatus for enhancing muscular movement according to the present invention may be realized , using fibers , as clothes that provide almost the same arrangement as that of the human muscles , thereby enhancing muscular movement of individuals , such as elderly people who have weak muscular strength . in addition , the apparatus for enhancing muscular movement according to the present invention may prevent excessive muscular movement of a user who has weak muscular strength by limiting the movement of the individuals and can correct posture so that a user can properly maintain a desired posture . although a few embodiments of the present invention have been shown and described , it would be appreciated by those skilled in the art that changes may be made in these embodiments without departing from the principles and spirit of the invention , the scope of which is defined in the claims and their equivalents .

an apparatus to enhance muscular movement is provided . the apparatus includes at least one muscular movement sensor to sense a result of an attempt to move a muscle , a movement information controller to analyze the sensed muscular movement , and generate muscular movement information based on the analyzed muscular movements , and a muscular movement actuator to enhance the movement of the muscle according to the generated muscular movement information by actively controlling a deformation of the muscle movement actuator over the surface of the muscle .

the following is a list of the reference characters used in this description : [ 0039 ] 10 — a object with an impression of a maze of a labyrinth on its surface ; [ 0043 ] 14 — the planes of the tracers , a set of parallel planes within which the tracers are allowed to move . [ 0044 ] 15 — the planes of the tracers , a set of intersected planes within which the tracers are allowed to move . [ 0045 ] 21 , 22 , 23 — mazes of a labyrinth game with multiple maze ; h — the distance between parallel planes of the tracers 14 ; referring now to fig1 the objective of the invention is to make solving labyrinth games more challenging by navigating set of several tracers that are correlated to each other . the pct method is equally applicable to a two or three - dimensional labyrinth games realized in hard or software . the system of a labyrinth game with the pct is comprised of : a pathway of a labyrinth 11 ( fig3 ) or 21 , 22 , and 23 of fig2 ; a set of tracers 12 , placed on the pathway ( s ) of the labyrinth 11 ; and a set of bridges 13 . the bridges 13 have a number of purposes . first , they are used to keep the tracers 12 within the pathway of the labyrinth 11 . second , they are also used to keep each tracer within its plane 14 , or 15 . third , to keep planes of the tracers parallel to each other . fourth , to keep distance ( h or ω ) between parallel planes constant ( although not necessarily equal ). fifth , to orient parallel planes perpendicular to the gdl . in computer versions of the labyrinth game with the pct , the bridges may be substituted by preprogramming conditions . to apply the pct method correctly , it is very important to know the orientation of the general direction of the labyrinth ( gdl ). every labyrinth , whether two or three - dimensional , has its gdl which is defined by positions of its ends ( a and b ). for a labyrinths , having one end on left side and the other end on right side , gdl will be horizontal , x - gdl ( fig1 b ). for a labyrinth , having one end on the top and other end on the bottom , gdl will be vertical y - gdl ( fig1 a ). for a labyrinth with one end on the top or bottom and the other end on right or left side will have two gdls : x - gdl and y - gdl ( fig1 c ). two such gdls may be substituted with a resultant single xy - gdl ( fig1 d ), which is oriented diagonally to x and y coordinate axies . finally , three - dimensional labyrinths may have a z - gdl , oriented perpendicular to both x - gdl and y - gdl . three gdls may be substituted with a single resultant xyz - gdl oriented diagonally to all three coordinate axies . once the gdl is defined , the planes of the tracers 14 or 15 , and therefore , the bridges 13 , must be oriented perpendicular to it . a labyrinth game with more than one gdl may be certainly realized in a computer game , although it can be hard to realize it in hardware . typically , therefore , games performed in hardware have a single gdl . labyrinth games made in hardware form are shown on fig3 a , b , c . all of them have a single gdl . a labyrinth game with a disk shape has a single circular gdl ( fig3 d ). as the game is played , each tracer is moved across the gdl until it aligns with a portion of the labyrinth , which is parallel to the gdl . when all of the tracers are positioned in labyrinth paths that move along the gdl , the entire set of tracers may be moved by moving the bridges along the gdl until the next lateral movement path is reached . at that point , the tracers can be moved again to the next lateral movement . these movements are repeated until the game is solved . in the case of the multiple gdl games , the tracers may be moved along either gdl as desired . thus , a player may move along a vertical gdl in one movement and then switch to a horizontal gdl in the next movement and then the player can switch back again as needed to solve the labyrinth . the only requirement is that the bridges , or the planes of the tracers , must move consistent with the gdl selected . the present disclosure should not be construed in any limited sense other than that limited by the scope of the claims having regard to the teachings herein and the prior art being apparent with the preferred form of the invention disclosed herein and which reveals details of structure of a preferred form necessary for a better understanding of the invention and may be subject to change by skilled persons within the scope of the invention without departing from the concept thereof .

a system and method of parallel correlation of tracers to enhance challenge of mastering a labyrinth or maze , where from one side the tracers are restricted in their movement by the pathway of the labyrinth ; and from the other side — by the conditions of the their mutual correlation . utilization of this method in labyrinth games makes the labyrinths more difficult and exciting .

referring to fig1 , a deep fryer is shown , and generally referred to by reference numeral 10 . deep fryer has a housing 14 and two fryer pots 15 that are each used for cooking the same or different foods . referring to fig4 , each deep fryer pot 15 has a heating element 20 proximate to its lower surface . adjacent to each heating element 20 is a temperature sensor 25 . each fryer pot 15 also has a temperature sensor 95 located on a side wall to provide temperature feedback as the fryer pot is filled . sensors 25 and 95 could also be bi - metallic switches or any other temperature sensor capable of providing temperature feedback . deep fryer 10 has a control panel 35 that is associated with each fryer pot 15 . control panel 35 is operatively connected to a controller 40 that monitors the operation of sensors and timers associated with each fryer pot 15 . controller 40 can accept various settings , such as , for example , temperature and timing settings . for example , controller is 40 is capable of counting the number of times cooking cycles processed in a fryer pot 15 . after a predetermined temperature has been sensed , and a number of cooking cycles have been counted , the automatic filtration can be initiated . alternatively , after a predetermined temperature has been sensed , the control panel 35 prompts the user with filter cycle indicator 42 , such as a lamp or an audible indicator for manual operation of the initiation of the automatic filtration cycle with or without a counted number or basket cycles . controller 35 permits user selection of either automatic or manual operation . referring to fig1 through 7 , the components of the oil filtration cycle are described in sequence . prior to commencement of a filtration cycle , a bubbling period of from approximately 5 to 15 second disturbs any debris that may have come to rest on the inner surface of fryer pot 15 . air for the bubbling period is introduced to each fryer pot 15 by return valve 90 . each fryer pot 15 has a drain valve 45 that is opened and closed by a linear actuator 50 . drain valve 45 has a diameter of approximately 1 . 25 inches in its fully open position to prevent clogging by debris formed during the cooking process . linear actuator 50 is either automatically or user activated by operation of controller 40 following prompting by filter cycle indicator lamp 42 on control panel that will commence draining of fryer pot 15 . beneath each fryer pot 15 is a drain manifold 55 that collects oil from drain valves 45 of each fryer pot 15 . manifold 55 collects oil from each drain valve 45 in deep fryer 10 . while instant deep fryer 10 shows two fryer pots 15 , there could be as many as twelve fryer pots in a deep fryer . oil passes from drain manifold 55 to crumb basket 65 , via downspout 60 . crumb basket 65 is a preliminary filter that removes large pieces of residual food product from oil . referring to fig4 and 5 , after oil passes through crumb basket 65 , it is deposited in filter pan 70 . as oil passes through filter pan 70 , it is pulled through a filter pad 72 located in the bottom of filter pan 70 . filter pad 72 has a series of ridges and grooves on the lower surface thereof to permit oil to flow around pad 72 . filter pan 70 contains a hold down ring 71 to maintain position of filter pad 72 . filter spout 75 and filter spout receiver 80 transfer filtered oil to filter pump and motor assembly 85 . filter pump and motor assembly 85 push oil through return valve 90 , when it is in an open position , to return oil to fryer pot 15 . return valve 90 is opened and closed by a linear actuator 52 . return valve 90 has a much smaller diameter of approximately 0 . 5 inches , in comparison to drain valve 45 . drain valve 45 must be able to accommodate debris from bottom of fryer pot whereas , oil entering return valve 90 would have already been filtered by crumb basket 65 and filter pad 72 . referring to fig2 through 7 , the process of filtering the oil will be described . cooking oil must be of a temperature that is warm enough to support a filtration cycle so that oil may freely flow through filtering cycle components . the oil temperature must be in a range of from 270 ° f . to 300 ° f . if oil is too cool to commence a filtration cycle , feedback from temperature sensor 25 immersed in oil prevents initiation of an automatic filtration cycle . alternatively , a user can disable the filtration cycle and warm the oil to an acceptable temperature . once the oil has reached an acceptable temperature , such as above 270 ° f ., linear actuator 50 can be actuated to open drain valve 45 and allow oil to drop into manifold 55 . the user can also initiate the filtration cycle after the acceptable temperature has been sensed , based upon the number of basket uses or if within their judgement a filtration cycle is needed . once a substantial amount of oil has drained from fryer pot 15 into filter pan 70 from manifold 55 , temperature sensor 25 in fryer pot 15 is exposed to an ambient air temperature . when temperature sensor 25 senses a 10 ° f . to 20 ° f . temperature drop below the set oil temperature , controller 40 energizes linear actuator 52 to open return valve 90 and pump and motor assembly 85 are switched on to return oil back to fryer pot 15 . sensor 25 senses a temperature of from approximately 250 ° f . to 280 ° f . the pumping action pulls the oil through filter pad 72 located in the bottom of filter pan 70 and forces clean filtered oil through return valve 90 . the temperature drop sensed by sensor 25 informs controller that oil is no longer in fryer pot 15 and that pump and motor assembly 85 can be switched on to commence filling of fryer pot 15 . were filtration system only time based , the pump and motor assembly 85 may improperly commence operation and run in the absence of oil and cause premature component failure . after filtered oil is pushed through opened return valve 90 , it is forced through a narrow slot or several slots 100 at lower edge of fryer pot 15 and sprayed over fryer pot lower surface . these slots are from 2 to 5 inches long , 0 . 05 to 0 . 10 inches in height , and from 1 to 5 in number . the force with which oil is sprayed back over lower surface of fryer pot 15 is strong enough to push remaining heavy debris that did not initially flow through drain valve 45 at commencement of filtering cycle , but not so great as to force oil to splash out of the fryer pot 15 . by having an oil flow rate of approximately 3 to 9 gallons / minute through a limited size pump and motor assembly 85 , oil is prevented from splashing out of fryer pot 15 . the sprayed oil and additional debris will then flow through drain valve 45 . the amount of time for spraying the oil from return valve 90 back and though the drain valve 45 is predetermined and set in controller 40 for a duration of 15 to 30 seconds . during this time , cooking oil is repeatedly cycled through filtration system . after 15 to 30 seconds , linear actuator 50 is activated to close drain valve 45 while pump and motor assembly 85 return oil to fryer pot 15 . the repeated or polishing cycles filters the oil to ensure that substantially all food particles have been removed from the cooking oil and the fryer pot 15 . the polishing filtration cycles eliminate the need for the cooking oil to be replaced prematurely and therefore extends the useful life of the cooking oil . further the centralized control of drain valve 45 , return valve 90 , and pump and motor assembly 85 provides sensory feedback to ensure that the filtering cycle is performed in the correct timed sequence . approximately 15 to 30 seconds after drain valve 45 is closed , heating elements 20 are automatically energized to warm cooking oil that has been returned to fryer pot 15 . after 20 to 45 more seconds , the volume of cooking oil in fryer pot 15 is great enough so that temperature sensor 95 on fryer pot wall is able to sense an increase in temperature because it is immersed . when sensor 95 senses approximately 5 to 10 seconds of rising temperature the oil is considered to be returned substantially to the pot . twenty to forty - five additional seconds of bubbling insure that the oil is completely returned to the fryer pot from filter pan 70 . at this time , pump and motor assembly 85 are de - energized and linear actuator 52 is energized to close return valve 90 . while the instant disclosure has been described to incorporate linear actuators , either hydraulic or pneumatic pistons could also be used for opening and closing the drain and return valves of the instant disclosure . the present invention having been thus described with particular reference to the preferred forms thereof , it will be obvious that various changes and modifications may be made therein without departing from the spirit and scope of the present invention as defined in the disclosure .

a deep fryer having a plurality of fryer pots disposed in the deep fryer . each of the plurality of fryer pots having a first temperature sensor , a second temperature sensor a drain valve and return valve . the system further has a controller that is pre - programmed to count a number of cooking cycles . after the first temperature sensor senses a first predetermined temperature , oil drains from the fryer pot through the drain valve and when the second temperature sensor senses a second predetermined temperature the oil has substantially returned to the fryer pot through the return valve .

generally , the present invention includes a system and method for constructing , selecting and presenting pathway ( s ) to a target location within an anatomical luminal network in a patient . the present invention is particularly , but not exclusively , suited for guiding and navigating a probe through the bronchial airways of the lungs . the present invention includes a preoperative and an operative component . the preoperative component is conducted prior to navigation and can be categorized as “ pathway planning ” the operative component is conducted during navigation and can be categorized as “ navigation .” the pathway planning phase includes three general steps , each of which is described in more detail below . the first step involves using a software graphical interface for generating and viewing a three - dimensional model of the bronchial airway tree (“ bt ”). the second step involves using the software graphical interface for selection of a pathway on the bt , either automatically , semi - automatically , or manually , if desired . the third step involves an automatic segmentation of the pathway ( s ) into a set of waypoints along the path that can be visualized on a display . it is to be understood that the airways are being used herein as an example of a branched luminal anatomical network . hence , the term “ bt ” is being used in a general sense to represent any such luminal network , and not to be construed to only refer to a bronchial tree , despite that the initials “ bt ” may not apply to other networks . referring now to fig1 , there is shown a flowchart describing the first step - using a software graphical interface for generating and viewing a bt . at 20 , the first step begins with importing ct scan images , preferably in a dicom format , into the software . the data may be imported into the software using any data transfer media , including but not limited to cds , memory cards , network connections , etc . at 22 the software processes the ct scans and assembles them into a three - dimensional ct volume by arranging the scans in the order they were taken and spacing them apart according to the setting on the ct when they were taken . the software may perform a data fill function to create a seamless three - dimensional model . at 24 , the software uses the newly - constructed ct volume to generate a three - dimensional map , or bt , of the airways . the three dimensional map can either be skeletonized , such that each airway is represented as a line , or it may be include airways having dimensions representative of their respective diameters . preferably , when the bt is being generated , the airways are marked with an airflow direction ( inhalation , exhalation , or separate arrows for each ) for later use during the pathway generation step . it is envisioned that this step is optional . the ct volume may be used as it is . at 26 , the software displays a representation of the three - dimensional map on a user interface , such as a computer monitor . referring now to fig2 , there is shown a flowchart describing the second step - using the software graphical interface for selection of a pathway on the bt . at 40 , the second step begins with a determination , by the software , of an appropriate pathway to a selected target . in one embodiment , the software includes an algorithm that does this by beginning at the selected target and following lumina back to the entry point . using the airways as an example , the target is first selected . the software then selects a point in the airways nearest the target . if the point closest to the target is in an airway segment that is between branches , the software has to choose between two directional choices . if the airways of the bt were marked with airflow direction , the software moves in the opposite direction of the arrows , thereby automatically generating a pathway to the entry point . alternatively , the pathway to the target may be determined using airway diameter . moving toward the entry point ( the trachea ) results in an increased airway diameter while moving distally results in a decreased airway diameter . hence , the software could choose to move in the direction of increased airway diameter . if the point closes to the target is in an airway segment that includes one or more branches , the choices are more numerous but the following the path of the greatest increase in airway diameter will still result in the correct path to the entry point . though unlikely , in the event that an incorrect path is taken , the software would eventually detect an inevitable decrease in diameter , if this is the case , the software would automatically abort that path and revert to the last decision - making point . the algorithm will resume , blocking off the incorrect path as an option . at 42 , after the pathway has been determined , or concurrently with the pathway determination , the suggested pathway is displayed for user review . preferably , the entire bt will be displayed with the suggested pathway highlighted in some fashion . the user will have zoom and pan functions for customizing the display . at 44 , the user is given the opportunity to edit and confirm the pathway . there may be reasons an alternative pathway is desirable . for example , though the targeted lesion is closest to a particular airway , there may be an artery or a lobe division between the selected airway and the target . hence , it is important to provide the user with editing ability . referring now to fig3 , there is shown a flowchart describing the third step — using the software to automatically generate waypoints . at 60 , the third step begins by designating each of the decision making points from 40 of step 2 as waypoints . this may happen concurrently with 40 . each time the software , while navigating backwards toward the trachea , was presented with navigational choices , the user navigating toward the target will necessarily also be presented with choices . hence , it is logical to designate those decision - making points as waypoints along the path to the target . at 62 , the waypoints appear on the suggested pathway , and may be labeled in such a way as to distinguish them from each other . for example , the waypoints may be numbered , beginning at 1 , in the order that they appear . preferably , the waypoints are positioned just downstream of each bifurcation , instead of at the bifurcation . in this way , providing navigation directions to the waypoint results in the probe being positioned in the appropriate airway once the waypoint has been reached . hence , the physician can begin navigation to the next waypoint by simply advancing the probe without being concerned about advancing down an incorrect airway . at 64 , the user is given the opportunity to edit the waypoints . it is understood that the second and third steps may occur concurrently . if the user is editing the pathway to the target , the user will also be selecting alternative waypoints , as one in the art will realize . fly - through feature in addition to the editing features described above , the software presents a “ fly - through ” feature that presents the user with the opportunity to view the user interface as it would appear from start to finish if the procedure was performed as planned . a preferred embodiment of one view the user interface is shown in fig4 . the interface 80 is divided into four quadrants , 82 , 84 , 86 and 88 . the upper - left quadrant 82 is a lateral view of the ct volume of the lungs , i . e . as though looking parallel to the spine of the patient . the lower - left quadrant 84 is a birds - eye view of the ct volume of the lungs . the upper - right quadrant 86 is a side view of the ct volume of the lungs . the lower - right quadrant 88 is a three - dimensional perspective view inside a virtual airway of the bt . cross - hairs 90 span over all of the quadrants to show the present location of the lg . the cross - hairs 90 in quadrant 88 are shown in a perspective format . the heading “ navigation ” refers to the processes occurring during the actual procedure . referring now to fig5 , there is shown a user interface 100 that assists the user in navigating to the target . this view of the user interface 100 includes four quadrants 102 , 104 , 106 , and 108 . the images shown in each quadrant are preferably customizable . hence , any of the aforementioned views from interface 80 may be displayed . however , pertinent to the navigation discussion is the view shown in the lower - right quadrant 108 . quadrant 108 is shown as displaying an lg steering indicator . the destination 110 appears as a circle which floats over the quadrant 108 and moves when the lg is turned . the destination 110 represents the next waypoint to which the user is navigating , or the final destination ( targeted lesion ) in the event that the last waypoint has been passed . when the distal tip of the lg is pointing directly at the destination 110 , the destination 110 appears in the center of the circle 112 . if the lg is not pointing directly at the destination 110 , the destination 110 is located in a representative location in or out of the circle 112 . for example , if the lg is pointing down and right of the destination 110 in the body ( in other words , the destination 110 is above and left of where the lg is pointing ), the destination 110 on the display in quadrant 108 will appear above and left of the center of the circle 112 . if the lg is deflected away from the destination 110 far enough , the destination 110 may not even appear in the quadrant 108 . for this reason , a guide arrow 114 appears somewhere on the circle 112 . the guide arrow 114 tells the user which direction the lg must be deflected to align the tip with the destination 110 . although the invention has been described in terms of particular embodiments and applications , one of ordinary skill in the art , in light of this teaching , can generate additional embodiments and modifications without departing from the spirit of or exceeding the scope of the claimed invention . accordingly , it is to be understood that the drawings and descriptions herein are proffered by way of example to facilitate comprehension of the invention and should not be construed to limit the scope thereof .

a navigation system for use in a luminal network of a patient , such as the airways , that is able to analyze a three - dimensional model of the luminal network and automatically determine a pathway from an entry point to a designated target . the system further automatically assigns waypoints along the determined pathway in order to assist a physician in navigating a probe to the designated target .

a display system of the present invention is generally indicated at 10 in fig1 - 3 . the display system 10 generally comprises a picture frame 12 , card holders 14 , a chamber 16 and a mounting structure 18 . the card holders 14 are attachable to and arranged about the picture frame 12 in viewable relation to the chamber 16 . preferably , the card holders 14 retain photographic memorabilia 20 , such as trading or collectible cards , which are associated with an object of memorabilia 22 , such as a miniature replica of a racing car , contained within the chamber 16 . the picture frame 12 includes a molding 24 , an optically clear member 26 , and a backing 28 . the backing 28 is preferably constructed of poster board and includes a decorative finish applied to a front viewable surface 30 . the card holders 14 are attached to the front viewable surface 30 of the backing 28 , either by a permanent or non - permanent adhesive . the card holders 14 are optically clear so that photographic memorabilia 20 placed within the holders 14 are easily visible . preferably , photographic memorabilia 20 is meant to include trading cards relating to a sports figure or team . examples of such trading cards include trading cards relating to nascar , national football league , national basketball association , women &# 39 ; s national basketball association , major league baseball and national hockey league . examples of such trading cards include , but are not limited to , those sold under the trademarks donruss ®, fleer ® and topps ®. however , other non - exhaustive examples of photographic memorabilia 20 include any type of trading or collectible card , photograph , lithograph , painting , sketch , or depiction which can be inserted within the card holder . the display system 10 of the present invention also includes the chamber 16 for holding the object of memorabilia 22 . the chamber 16 , or compartment , is preferably defined by an upper member 32 and a lower member 34 , and left and right sidewalls 36 and 38 , respectively . the upper and lower members 32 and 34 are preferably substantially parallel to one another , as are the left and right sidewalls 36 and 38 . however , it would be within the scope of the present invention to provide any type of chamber 16 which would support an object of memorabilia 22 . the lower member 34 of the chamber 16 acts as a platform supporting the object of memorabilia 22 placed thereon . alternatively , it would be within the scope of the present invention to fixedly secure the object of memorabilia 22 within the chamber by any suitable fastening means . the upper and lower members 32 and 34 , along with the sidewalls 36 and 38 , are positioned proximate a rear surface 40 of the backing 28 such that the chamber 16 is accessible through an aperture 42 located within the backing 28 . both the trading card holders 14 and the chamber 16 are positioned within the frame 12 , resulting in the front viewable portion of the display system being substantially flat . by substantially flat is mean that , preferably , the card holders 14 and the chamber 16 are located behind the optically clear member 26 , with only edges of the molding 24 protruding slightly past the optically clear member 26 . the trading card holders 14 and the chamber 16 are protected by the optically clear member 26 extending between and held by the molding 24 of the frame 12 . the optically clear member may also retain the object of memorabilia 22 within the chamber 16 . the optically clear member 22 is positionable over the backing 28 , and the molding 24 retains the backing 28 and the optically clear member 22 within the frame 12 . the optically clear member 22 may either be a sheet of glass or a sheet of plastic , as is well known in the art . preferably all materials used in constructing the display system 10 are acid free . as illustrated in fig3 the mounting structure 18 may be attached along the border of the frame 12 . the mounting structure 18 surrounds and protects the chamber 16 . the mounting structure 18 includes a back portion 44 and walls 46 , 48 , 50 and 52 extending from the back portion 44 of the frame 12 . the walls 46 , 48 , 50 and 52 are of a depth approximately equal to or greater than the depth of the chamber 16 . the walls 46 , 48 , 50 and 52 also provide the display system 10 with a box - like impression . preferably , the chamber may be accessed through an aperture 54 in the back portion 44 of the mounting structure 18 . the aperture 54 is positioned proximate to the chamber walls 32 , 34 , 36 and 38 , and a door 56 may be attachable to back portion 44 to retain the object of memorabilia 22 contained within the chamber 16 . alternatively , the aperture 54 of the back portion 44 may be eliminated , and access to the chamber 16 is provided by removing the optically clear member 26 from the molding 24 of the frame 12 . in the particular example illustrated in fig1 the object of memorabilia 22 is a replica of a nascar racing car driven by the driver depicted in the trading cards 20 in the holders 14 . as is easily understood , other types of sports memorabilia may be placed within the chamber 16 for display along with trading cards 20 of the particular sports figure . in addition , photographs of a particular event along with memorabilia from that event may also be displayed using the present invention . the event may be a sporting event , or a personal event . as illustrated in fig1 the card holders 14 are positioned in a selected scheme wherein the card holders 14 are positioned in a viewable relation to the chamber 16 . where each card 20 is positioned to comprise the particular scheme is not critically important , and any other scheme is included within the scope of the present invention . preferably , the optically clear member 26 defines a plane in which both the trading cards 20 and a viewable opening in the chamber 16 , defined by walls 46 , 48 , 50 and 52 , are viewable in relations to one another . alternatively , this may be defined as the chamber 16 being positioned in a recessed relationship with regard to the card holders 14 . although the present invention has been described with reference to preferred embodiments , workers skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention .

a display system having a substantially flat front portion for holding and displaying memorabilia . the display system comprises a frame , a backing supported by the frame , a plurality of cardholders for holding photographic memorabilia and a recessed chamber for holding an object of memorabilia associated with the photographic memorabilia . the cardholders retain trading cards and are attachable to the backing . the cardholders are arranged about the chamber in an aesthetic manner .

referring particularly to fig1 - 6 a hand - held portable lottery drum 10 is shown . it should be apparent that although the drum 10 is illustrated in cylindrical form it may take other forms , such as a rectangular box or an elliptical enclosure . the drum 10 is provided with a plurality of slots 12 which are offset or staggered relative to each other . it is important that the drum be provided with at least six slots about its entire periphery . within the drum 10 are a multiplicity of chips , or discs 14 , in the order of 60 or more , all of which are numbered . it has been found that the lottery drum works best when the dimensions are approximately 8 &# 34 ; in length and 4 &# 34 ; in diameter with a 3 &# 34 ; neck portion functioning as a handle . each of the slots are preferable 11 / 2 &# 34 ; long and a 1 / 4 &# 34 ; wide so that they pass only one numbered disc or chip at any given time through the slot . moreover , the slots are spaced 13 / 4 &# 34 ; apart . furthermore , the entire drum is fabricated of a opaque material such as a colored plastic , so that the discs cannot be viewed while rotating the drum . the end 16 of the drum 10 is provided with a neck portion 18 having an knurled surface 20 , functioning as a handle . the handle 20 has an internal rod 22 which passes centrally through the rotatable drum 10 and is affixed to the opposite end 19 of the drum . as clearly seen in fig3 the opposite end 19 of the drum is provided with a projecting hand - hold 24 , so that the drum can be rotated easily while holding the handle 20 in one hand and holding the hand - hold 24 with several fingers of the other hand , thus permitting the drum to be spun in the hands of a user in order to thoroughly mix and agitate the discs while causing the numbered discs to be ejected from the drum 10 individually through the offset slots 12 . as is seen in fig4 and 6 the slots 12 are offset or staggered relative to each other so that none of the slots are precisely lined up with each other whereby the entire inner surface of the drum is provided with slots to capture the discs 14 which are agitated upon rotating the drum 10 . although six offset slots about the circumference of the drum are shown in the drawings it is within the scope of the present invention to provide additional slots in some states in the united states use more than sixty numbers in their lottery . consequently , more slots are appropriate with a larger number of numbered discs or chips are utilized in the drum . in that case it may be necessary to enlarge the drum so that additional slots are also offset relative to the other slots in the periphery of the drum . in addition , it should be noted that the discs may be in the form of standard poker chips having numbers applied or can be specially manufactured discs having the numbers based thereon . since the slots 12 are such a dimension that only one disc will pass therethrough at a time the drum is rotated and agitated continually until the selected number of discs are individually dispensed through the various slots in the lottery drum . referring now to an alternate embodiment of the present invention is shown in fig7 . a base 26 is provided having an l shaped bracket 28 at one end and another l shaped bracket 30 at the other end . the bracket 28 is provided with a bearing sleeve 32 while the bracket 30 is provided with an end bearing 34 , a crank 36 passes through the bearing 32 and crank shaft 33 passes centrally through an aperture 29 in the neck portion 18 of the drum 31 and out an aperture 38 in the end 19 of the drum with the extreme end being held in the bearing 34 . the crank is operated by a crank handle 40 . thus , by rotating the crank handle 40 the drum 31 can be variously agitated so that the discs 14 therein will find their way through the various slots 14 until the required number of discs have been injected , thus representing the selected numbers for the lottery . the structure shown in fig7 is intended to be rather in the nature of a device that is supported on a table or bureau rather than being portable , as is the lottery device shown in fig1 - 6 . although the present invention has been disclosed and described with reference to two embodiments thereof , it should be apparent that other variations and modifications may be made , and it is intended that the following claims cover each said variations and modifications as follows within the true spirit and scope of the invention .

a lottery number selection device having a rotatable drum with offset or staggered slots around the periphery . the drum contains an amount of numbered chips or discs corresponding the total amount of numbers in a lottery , the chips being agitated by rotating the drum and passing individually out of the sized slots until six or more numbers for the lottery picks are selected .

the characteristic details from this novel product and process are clearly shown in the following description and the accompanying tables . the physical state of avocado powder is a porous solid and its organoleptic characteristics are a green color identical to that of avocado in its natural state . the characteristic odor of avocado is preserved in avocado powder due to the fact that the chemical compounds that confer odor are not altered , on the other hand , avocado flavor , once re - hydrated is identical to the natural flavor . in powdered avocado , the nutrient content is very similar to that of natural avocado , it can be seen that proteins , fats , carbohydrates , and fibers have a percentage similar to that of avocado in its natural state . since the treatment , which is described below , prevents that nutrients contained in avocado from being lost , this was confirmed using scientific methods . the technique that was used for protein determination was the kjeldahl method , to determine the fat content in avocado the soxhlet extraction method was used , moisture was determined using the gravimetric technique of constant weight , the amount of fiber present was determined by the crude fiber method . the powdered avocado is obtained by a process consisting of the following steps : i . avocado selection , in this step the fruits are separated depending on the industrial application pretended for avocado powder , if it is pretended for the cosmetic industry , the fruit should have a high content of fat , which is determined by performing bromatological analysis to the different avocado varieties , in addition to discarding any fruit which is damaged . the selected fruit for processing should be a ripe fruit , free of diseases and / or pests typical of avocado , because if the avocado is not ripe the flavor of the paste changes . ii . removal of pit and hull from avocado flesh , which can be done manually , or by means of automatic equipment depending on the scale in which the work is carried out . this process step is performed in order to conditioning or preparing the fruit for the next process step . iii . milling of the avocado pulp , which can be manually or automatically depending on the scale in which the work is carried out . in this step , as a result , a paste having a density of 904 g / cm 3 is obtained , with a green color that is identical to the color of natural avocado . this step is performed in order to conditioning the avocado pulp and to increase both the mass transfer area , and the heat transfer area , and in this way to obtain more efficient results , and in a lower cost en steps v and vi of the process . iv . application of avocado paste to the dehydrator vessels . the paste obtained in step iii is placed in the dehydrator vessels , taking care that the paste does not exceed a 2 centimeters thickness . this is to ensure that dehydration will be uniform throughout the paste . the time used to perform steps iii and iv should be short , e . g . less than 30 min , because if the exposition time of the avocado paste to environment increases , the paste begins to oxidize due to contact with oxygen and light . the time used in steps iii and iv could be increased to more than 2 hours if additives such as antioxidants such as : ascorbic acid , sodium ascorbate ( 0 . 01 ), citric acid ( 0 . 01 to 1 . 5 %) are added , but our goal is to obtain a natural product ; another way to reduce oxidation of the paste is performing step iii in cold conditions at temperatures from 1 ° c . to 5 ° c . v . cooling prior to dehydration , in this step a refrigeration chamber is used which must meet the requirements of temperature needed such that a proper previous cooling can be carried out . said cooling can be effected in two ways : by means of fast cooling , with liquid nitrogen , or a freezing mixture consisting of dry ice and ethanol , for 2 to 5 minutes ; or otherwise , by means of a slow cooling in a refrigeration chamber ( 1 ° c . to 5 ° for a minimum of 1 hr ): during fast cooling small ice crystals are formed within the avocado pulp matrix whereas during slow cooling large ice crystals are formed in the avocado pulp matrix . in our experiment , we use both cooling methods and we achieved excellent results . the pre - cooling should have a minimum duration that ensures water solidification , that is crystal formation from water contained in the avocado paste at a temperature that prevents the formation of eutectics which are detrimental to the process , during this period of time , the vessels should be rotated continuously in order to ensure a uniform cooling . in this step the enzymatic activity is inhibited by virtue of the low temperatures that are used , preventing , therefore , the oxidation of the avocado paste . vi . avocado paste dehydration . this step relies on the principle of sublimation , that is , having the water passing from solid state to vapor state without passing through the liquid phase , this is achieved working with low pressures and low temperatures . this kind of dehydration is carried out in a freeze dryer that works under the principle of sublimation . the vessels containing the avocado paste are placed in the dryer . during dehydration the parameters to be controlled are ; a vacuum pressure lower than atmospheric from between 450 × 10 − 3 to 50 × 10 − 3 in the freeze dryer vacuum chamber , a freeze dryer condenser temperature of − 40 ° c . as minimum . an additional parameter to be controlled is heat applied to the avocado paste - containing vessels which should be kept at a temperature close to ambient temperature , because if said temperature is lower than 20 ° c ., more time will be needed to sublimate all of the ice present in the avocado paste , if the temperature applied to the vessels containing the avocado paste is greater than 35 ° c ., the avocado &# 39 ; s nutritional and organoleptic properties are affected by the applied heat , greater then 35 ° c . the dwelling time of the avocado paste in the freeze dryer was from 1 hr to 10 hrs . said time depends on the parameters which are employed . all parameters mentioned in this step should be strictly controlled to achieve a successful dehydration . finally a porous solid having a color identical to that of avocado is obtained , with a moisture content lower than 1 %, having odor and flavor typical of avocado , and retaining the nutrients contained in avocado . the freeze drying method is used for food stuffs that are degradable or that experiences changes in their structure , texture , appearance or flavor as consequence from the high temperatures employed in the conventional drying methods , therefore , the present method was used to dehydrate avocado . in the experiments , the drying time was in different time intervals . all the obtained samples were analyzed for its nutrimental components , confirming that regardless of time the nutrients are conserved in avocado powder . said stability can be seen in the following tables ( 1 , 2 , 3 , 4 , 5 ). all the results from tables ( 1 , 2 , 3 , 4 , 5 ) are on a dry basis , these tables come from experimentation on drying which was performed in triplicate as well as the bromatological analysis . vii . finally , the dehydrated avocado is removed from the containers , pulverized and packaged . this packing should be in oxygen and light - impervious containers to avoid discoloration and rancidity of fats from avocado . the packing should be carried out in a controlled atmosphere and not under vacuum . once the above described method concludes , an amount of powdered avocado from between 30 % to 35 % relative to the mass of avocado applied is obtained ; said percentage will depend on the type of avocado which is used and on the duration of dehydration . powdered avocado allows for a reduction in transportation cost , and in storage space costs since that a lesser amount of space and power is required to store the avocado powder due to it does not contain water anymore and it does not need refrigeration , and the residence time or shelf life of powdered avocado is extended , at least 1 year , the latter due to the fact that the percentage of water in powdered avocado is less than 1 %, thereby preventing the proliferation of microorganisms ( due to the low water activity ). the avocado powder can be used in the food industry for human consumption , as raw material for the making of other food products , such as creams , shakes , ice cream base , mousse , buttermilks , jams , milk shakes , guacamoles , in the form of deep , sauces . also as a raw material in textile industry from the pigment , that is , the natural colorant obtained from powdered avocado , in the cosmetics industry as raw material using the oil contained in the avocado powder for the making of creams , exfoliating creams , shampoo , baby oil , perfumes , and in pharmaceutical industry in the extraction of active ingredients since it does not contain any additive that modifies its characteristics . to the product obtained by the present process , certain type of additive can be added , that is , it can be fortified , with vitamins , minerals , proteins , antioxidants , preservers , thickeners , colorants or any other chemical that is added to the final product . meaning that this powdered avocado is a natural product , however , the powdered avocado is ready to be added with nutritive substances based on the requirements of the companies from the food industry , which requires so . during the process of production of powdered avocado , the step of dehydration using the freeze dryer is a crucial step , the optimal dehydration times varying from 4 hrs to 6 hrs , for several reasons : first , after 6 hrs of dehydration the product becomes highly hygroscopic causing that more energy than necessary should be expended and that after the drying process this removed moisture would be recovered by the product , if left from 1 to 3 hrs , more heat will need to be applied , that is , greater than 35 ° c . which will cause damage to the nutrients and characteristic compounds from avocado .

the invention relates to avocado powder and to the method of obtaining the same . avocado powder is a novel product which enables the avocado to be preserved for an extended period of time at ambient temperature , such as to conserve the characteristic properties of the product , with the additional advantage of being 100 % natural and occupying less physical storage space , thereby eliminating the post - processing cold chain . the method of obtaining avocado powder comprises a series of operations or steps that terminate in the pulverization and packing of the end product .

the display and storage stand of this invention is illustrated , completely assembled , in fig1 and is designated generally as 10 . the stand 10 is made entirely of metal . there are three triangles , base triangle 12 , center triangle 14 and top triangle 16 . each triangle is truncated at all three its apexes . base triangle 12 has sides 18 , 20 and 22 welded to its edges , each side being perpendicular to the surface 24 of triangle 12 . additionally , base triangle 12 has web 26 welded into the corner joining side 18 and side 20 and truncation piece 28 . web 30 is welded into the corner joining side 20 and side 22 and truncation piece 32 . web 34 is welded into the corner joining side 22 and side 18 and truncation piece 36 . webs 26 , 30 and 34 are each provided with tapped holes 38 for mounting the wheels . caster wheel 40 is bolted to web 34 by means of bolts 42 . fixed wheel 44 is bolted to web 30 by means of bolts 42 , and fixed wheel 46 is bolted to web 26 by means of bolts 42 . center triangle 14 has sides 48 , 50 and 52 , each of which is perpendicular to surface 54 . truncation piece 56 joins sides 48 and 50 . the truncation pieces joining sides 50 and 52 and joining sides 52 and 48 are not shown . there is a rectangular cutout 58 in side 48 , extending part way into surface 54 . the purpose of cutout 58 is to accommodate the door hinge which will be described below . top triangle 16 has sides 60 , 62 and 64 , each of which is perpendicular to surface 66 . truncation piece 68 joins sides 60 and 62 . the truncation pieces joining sides 62 and 64 and joining sides 64 and 60 are not shown . each truncation piece is provided with two holes for assembly bolts , as illustrated in fig9 . each hole is fitted with a tapped cylinder welded to the inside surface to accommodate the assembly bolts . the location of the holes is best shown in fig2 and 3 . bar 70 is formed in the shape of an open s . in bar 70 the central element 72 is flat and straight and is provided with three pairs of assembly holes 74 . the angle between bracket element 76 and central element 72 is 150 degrees . bracket element 76 is fitted with l - shaped projections 78 for the purpose of supporting shelf brackets . element 80 of bar 70 forms an angle of 120 degrees with respect to central element 72 . element 80 has a rectangular cutout 82 near the top 84 of element 80 , and a rectangular cutout 86 near the bottom 88 of element 80 . bar 90 is a mirror image of bar 70 . in bar 90 the central element 92 is flat and straight and is provided with three pairs of assembly holes 94 . the angle between bracket element 96 96 and central element 92 is 150 degrees . bracket element 96 is fitted with l - shaped projections 98 for the purpose of supporting shelf brackets . element 100 of bar 90 forms an angle of 120 degrees with respect to central element 92 . element 100 has a rectangular cutout 102 near the top 104 of element 100 , and a rectangular cutout 106 near the bottom 108 of element 100 . bar 110 has a straight flat central element 112 which has three pairs of assembly bolt holes 114 . bracket element 116 , having l - shaped projections 118 , extends from one edge of central element 112 , and bracket element 120 , having l - shaped projections 122 extends from the other edge of central element 112 . in each case , the included angle between the bracket element and the central element is 150 degrees . basic assembly of the triangle unit is illustrated in fig2 and 5 . bar 80 is bolted to the truncation pieces between sides 20 and 22 of base triangle 12 , to the truncation pieces between sides 48 and 52 of center triangle 14 and to the truncation pieces between sides 60 and 64 of top triangle 16 . bracket element 76 of bar 70 extends perpendicularly with respect to sides 22 , 52 and 64 . bar 90 is similarly bolted to truncation pieces 28 , 56 and 68 , with bracket element 96 of bar 90 projecting perpendicularly with respect to sides 18 , 50 and 62 . bar 110 is bolted to the truncation pieces between sides 18 and 22 of base triangle 12 , between sides 50 and 52 of center triangle 14 , and between sides 62 and 64 of top triangle 16 . side panel 24 is permanently attached to sides 22 , 52 and 64 by means of self - tapping screws inserted through holes 126 into pilot holes ( not shown ) in the respective sides . side panel of 28 is permanently attached to sides 18 , 50 and 62 by means self - tapping screws inserted through holes 126 into pilot holes ( not shown ) in the respective sides . it can be seen that the interior of the triangle stand provides a considerable amount of storage volume . the storage area is accessed through a door 130 which encloses the third side of triangle stand 10 . bars 132 and 134 form the upright portions of door 130 . bar 132 straight flat portion 136 from which perpendicularly projects bracket portion 138 having l - shaped projections 140 . bar 134 is a mirror image of bar 136 and has straight flat portion 142 from which perpendicularly projects bracket portion 144 having l - shaped projections 146 . element 136 of bar 132 is welded to horizontal open - sided rectangular tubes 146 and 148 . element 142 of bar 134 is welded to rectangular tubes 150 and 152 . tube 146 is inserted into tube 150 and is welded to tube 150 . tube 148 is inserted into tube 152 and is welded to tube 152 . tubes 146 , 148 , 150 and 152 are actually c - shaped in cross - section , the open portion not being visible in fig4 and 5 . rectangular tube 154 is hinged to tube 150 at its first end , and is hinged to bar 90 at its second end . rectangular tube 156 is hinged to tube 152 at its first end , and is hinged to bar 90 at its second end . panel 158 is attached to bars 132 and 134 by means of self - tapping screws inserted through holes 160 in panel 158 which engage pilot holes ( not shown ) in bars 132 and 134 . a catch 162 is attached to bar 90 near the top of element 92 . catch 162 releasably engages clip 164 which is attached to element 144 of bar 134 on door 130 . the left side of door 130 ( as illustrated in fig5 ) is secured by means of a tab 166 which extends angularly from bar 146 , and which engages element 72 of bar 70 . a tube 168 extends downward from tube 148 . caster wheel 170 is inserted into tube 168 . door 130 is opened by releasing catch 162 and pulling bar 134 away from triangle stand 10 . the right end of door 130 swings open and tab 166 is released , allowing the door 130 to open freely , giving access to the storage space inside triangle stand 10 . stand 10 can accommodate at least four different kinds of display fixtures . rack 172 has brackets 174 and 176 which cooperate with the bracket projections 140 and 146 on bars 132 and 134 respectively . rods 178 , suitable for display of bagged or blister - packaged products , project from clips 180 which simply snap onto rack 172 . one or more such racks may be used , as illustrated in fig1 . tilted shelves 182 are supported by brackets 184 to which shelves 182 are attached . brackets 184 are designed to cooperate with any of the bracket projections . horizontal shelves 186 are supported by brackets 188 to which shelves 186 are attached . brackets 188 are designed to cooperate with any of the bracket projections . grille shelf 190 is supported by bar 192 which is attached to and supported at the outer ends of a pair of brackets 188 , and grille shelf 190 is supported at its inner side by brackets 188 as well . in fig1 , 4 , 5 and 12 it will be noted that the bracket support projections are not shown . this is because the projections are so small that the edges having projections would appear simply as broad black lines with no real definition . this specification describes , and the figures illustrate , a triangle shaped merchandise display and storage stand which can utilize several different types of shelves and display rods , and which can be moved easily to different locations within the store . while this invention is susceptible of embodiment in different forms , the drawings and the specification illustrate the preferred embodiment of the invention , with the understanding that the present disclosure is to be considered an exemplification of the principles of the invention , and the disclosure is not intended to limit the invention to the particular embodiment described .

a display and storage stand for retail stores comprises three triangular platforms , one above the other . each triangle is truncated at each apex . the triangles are joined at their truncated portions by steel bars bolted to the triangles . two sides of the stand are enclosed by panels . the third side is closed by a door . each steel bar has shelf bracket projections along each longitudinal side . shelves may be horizontal or tilted . projecting rods for bagged and blister - packed items are provided . wheels are attached to the under side of the base triangle .

the drawings depicts one exemplary embodiment of an auto - injector in accordance with the present invention . the depicted auto - injector has a casing “ c ” comprised of a front casing part 1 and a rear casing part 2 , wherein the two casing parts are joined together by a connection 3 . if the auto - injector is a refillable auto - injector , the connection 3 is releasable , for example , it may comprise a threaded connection . if , however , the auto - injector is a disposable , the connection 3 can be fixed , for example , by a fused connection , adhesive connection or latching connection . on the left in the figures , a needle protecting tube 4 can be seen which can be shifted axially in the front casing part 1 , as will be described in more detail below . a sliding sleeve 5 which can be shifted axially is guided in the needle protecting tube 4 via its front end and in the front casing part 1 via a flange 6 formed on its rear end . the sliding sleeve 5 accommodates an ampoule - like active agent container 7 , in the interior of which a piston 8 can be shifted axially with the aid of a piston rod 9 , for the purpose of delivering the active agent . at its front end , the active agent container 7 is provided with an injection needle 10 . a locking member in the form of a locking sleeve 24 is mounted externally on the sliding sleeve 5 . at least one locking tongue 25 protrudes elastically outwards from the locking sleeve 24 and in the operational state in accordance with fig1 abuts an inner heel 27 of the needle protecting tube 4 . a cavity 26 which is formed in the needle protecting tube 4 and into which the locking tongue 25 protrudes is connected to the heel 27 . the function of the locking sleeve 24 and the locking tongue 25 will be set forth further below . a guiding sleeve 11 is arranged in the rear casing part 2 , such that it can be shifted axially . a driving part 12 , which protrudes backwards out of the guiding sleeve 11 and abuts an end flange of the guiding sleeve 11 via latching projections 13 , is situated in the guiding sleeve 11 . the driving part 12 contacts the piston rod 9 and is biased against it by a driving spring 14 . in fig1 , the auto - injector is depicted in its latched position . this position is useful for the delivery , shipment , sale or storage of the auto - injector since it secured against being intentionally or unintentionally activated and is protected from contamination . a needle protecting cap 15 on the side of the injection needle 10 serves this purpose and has an outer sleeve 16 reaching over the front casing part 1 and the needle protecting tube 4 and an inner sleeve 17 reaching over the injection needle 10 and the front end of the active agent container 7 which encloses it , forming a seal , and thus ensures that the injection needle 10 is clean and sterile . in addition , the attached needle protecting cap 15 also secures the auto - injector against being intentionally or unintentionally triggered , by preventing the needle protecting tube 4 from being touched or shifted . a securing cap 18 , which comprises a securing pin 19 in its centre , is placed on the rear end of the auto - injector , on the right in the figures . the securing pin 19 protrudes between the latching projections 13 of the driving part and thus reliably prevents an injection from being triggered . in order to prepare the auto - injector for use , the needle protecting cap 15 and the securing cap are removed . it is clear that when the needle protecting cap 15 is removed , a tensile force is exerted on the active agent container 7 as a result of the static friction between the inner sleeve 17 and the active agent container 7 . consequently , the active agent container 7 must be prevented from leaving its position ( e . g ., being undesirably moved or pulled forward ) in the auto - injector when the needle protecting cap 15 is removed . for this purpose , a latching sleeve 20 is mounted in the front casing part such that it cannot move axially and at least one latching tongue 21 is arranged on the latching sleeve 20 . three latching tongues 21 are preferably provided in one embodiment , arranged or distributed symmetrically around the circumference of the latching sleeve . as fig1 clearly shows , the free end of the latching tongue 21 abuts the flange 6 of the sliding sleeve 5 and thus prevents the sliding sleeve 5 from being pulled forwards together with the active agent container 7 arranged in it . fig2 shows the auto - injector after the needle protecting cap 15 and the securing cap 18 have been removed as described above . the latching member 20 is still in the latching position and the latching tongue 21 prevents the active agent container 7 , comprising or carrying the injection needle 10 , from being slid forward . in addition , at the then open end , the needle protecting tube 4 creates a distance which prevents the injection needle 10 from being touched or at least makes it difficult to touch the injection needle 10 . the needle protecting tube 4 is held in this position by the force of a spring 22 which is clamped between the rear end of the needle protecting tube 4 and the rear casing part 2 . fig3 shows the auto - injector in a position which it assumes when it is pressed onto the skin of a patient but has not yet been triggered . the needle protecting tube 4 has been shifted backwards into the casing as compared to the position of fig2 , compressing the spring 22 , such that the tip of the injection needle 10 is then situated slightly above the skin of the patient . fig3 also shows that the needle protecting tube 4 shifted backwards has forced the latching tongue 21 outwards , which then exposes the flange 6 of the sliding sleeve 5 . as compared to fig2 , it can be seen that a flange 23 formed internally in the rear part of the needle protecting tube 4 then abuts the front facing side of the guiding sleeve 11 . it should be noted that the needle protecting tube still protrudes out of the front casing part 1 by a remaining amount at the front . however , as compared to fig1 and 2 , it should be clear that the needle protecting tube 4 has slid the locking sleeve 24 some distance backward on the sliding sleeve 5 . fig4 shows the auto - injector at the moment of triggering . proceeding from the state depicted in fig3 , the user has pressed the auto - injector slightly harder onto the skin , such that the needle protecting tube 4 has been shifted into the casing by the remaining amount mentioned above , wherein the flange 23 has shifted the guiding sleeve 11 backwards in the rear casing part 2 by the remaining amount and the latching projections 13 have been moved into the region of a triggering ring 28 arranged in the rear end of the rear casing part 2 . the triggering ring 28 has contacted and / or pressed the latching projections 13 , formed on elastic arms of the driving part , far enough against each other that they are then pulled through the end opening of the guiding sleeve 11 by the force of the driving spring 14 . the force of the driving spring 14 then acts , unobstructed , on the piston 8 via the piston rod 9 , the piston 8 in practice abruptly increasing the hydraulic pressure in the active agent container 7 . this pressure slides the active agent container forwards , such that the injection needle 10 penetrates into the skin of the patient . since the diameter of the passageway in the injection needle 10 is comparatively small , at most a very small amount of the active agent can exit the injection needle 10 in this short period of time between triggering and the injection needle 10 penetrating into the skin . the injection stroke is complete when the flange 6 of the sliding sleeve 5 abuts the end of the needle protecting tube 4 and / or the end of the locking sleeve 24 . fig5 and 6 show the auto - injector in the position in which the injection needle 10 is inserted or injected , wherein fig5 shows the operational state at the beginning of delivering the active agent and fig6 shows the state of the auto - injector after the active agent container 7 has been completely emptied . when the operational state in accordance with fig6 has been reached , the user retracts the auto - injector in order to remove the injection needle 10 from his skin . fig7 shows the operational state after the injection needle 10 has been removed from the skin of the patient . the needle protecting tube 4 was shifted back into its initial state by the force of the spring 22 as soon as the auto - injector was lifted from the skin of the patient . it then mainly serves to substantially cover the injection needle and protect the user and other persons from injuries from the injection needle 10 . consequently , the needle protecting tube 4 must be prevented from being shifted relative to the injection needle 10 such that the injection needle 10 protrudes out of the needle protecting tube 4 . this task is accomplished by the locking tongue 25 , which is formed in the locking sleeve 24 . while the needle protecting tube 4 , as mentioned , has been shifted forwards by the spring force , the locking sleeve 24 maintains its position on the sliding sleeve 5 as a result of a latch tongue 29 formed on the sliding sleeve 5 , which then protrudes into a cavity of the locking sleeve 24 in the position in accordance with fig7 and thus fixes it in place on the sliding sleeve 5 . as can clearly be seen in fig7 , the free end of the locking tongue 25 at the rear end of the needle protecting tube 4 then protrudes into its path . thus , the needle protecting tube 4 cannot be retracted without the locking sleeve 24 , the sliding sleeve 5 and the active agent container 7 together with the injection needle 10 , being shifted backwards relative to the front casing part 1 and the rear casing part 2 , against the force of the driving spring 14 . thus , the injection needle 10 maintains its relative position with respect to the needle protecting tube 4 and the injection needle 10 and is reliably prevented from being intentionally or unintentionally touched . this solution has the advantage that the axially directed force to be absorbed by the locking tongue 25 never exceeds the force of the driving spring 14 , irrespective of how hard one presses against the front end of the needle protecting tube 4 . fig8 to 11 show another embodiment of an auto - injector in accordance with the present invention . in these figures , identical elements and elements having substantially the same function are denoted using the reference numerals from fig1 to 7 . in this embodiment , the latching tongue 21 is guided by means of surfaces on the latching tongue 21 and the sliding sleeve 5 , the surfaces running or extending obliquely with respect to the longitudinal axis of the auto - injector . the latching tongue 21 for latching the active agent container or the sliding sleeve 5 and the locking tongue 25 for latching the needle protecting tube 4 are also both arranged on the latching sleeve 20 . in some preferred embodiments , the latching tongue 21 and the locking tongue 25 are formed integrally with the latching sleeve 20 . in some embodiments , multiple latching tongues 21 and locking tongues 25 can be provided on the latching sleeve 20 . fig8 shows a latching member in the form of a latching sleeve 20 which comprises a latching tongue 21 which comprises a surface 30 running or extending obliquely with respect to the longitudinal axis of the auto - injector , on its facing side . the tip of the oblique surface 30 abuts the outer side of the latching tongue 21 . the sliding sleeve 5 comprises a cavity 31 into which the latching tongue 21 protrudes in the latching position . the edge of the cavity 31 opposite the oblique surface 30 of the latching tongue 21 comprises an oblique surface 30 ′ which runs or extends generally parallel to the oblique surface 30 of the latching tongue 21 . ( in some embodiments , an oblique surface could be provided directly on the active agent container 7 , such that the sliding sleeve 5 can be omitted .) the two oblique surfaces 30 and 30 ′ come to rest on each other . the needle protecting tube 4 is at least partially arranged between the latching sleeve 20 and the sliding sleeve 5 , wherein the latching tongue 21 protrudes through a cavity in the needle protecting tube 4 into the cavity 31 of the sliding sleeve 5 . a part 32 of the needle protecting tube 4 overlaps the abutting point of the oblique surfaces 30 and 30 ′, such that the latching tongue 21 is locked in the latching , latched or lacked position . in fig8 , a locking tongue 25 is also arranged on the sliding sleeve 5 , on the side opposite the latching tongue 21 . the locking tongue 25 protrudes into a cavity opposite it , in the needle protecting tube 4 . fig9 , generally analogous to fig3 , shows the auto - injector in a release position in which the needle protecting tube 4 is slid into the casing “ c ”. in this position , the part 32 of the needle protecting tube 4 has been retracted from the overlapping area of the oblique surfaces 30 and 30 ′. the latching tongue 21 can then be moved into the cavity 31 of the needle protecting tube 4 . the movement can be caused by a bias on the elastic latching tongue 21 . in some preferred embodiments , however , the latching tongue 21 is slid outwards into the cavity by the pressure exerted by the driving spring 14 , which acts on the oblique surface 30 . fig1 , generally analogous with fig5 , shows the auto - injector in a position in which the active agent container 7 is advanced relative to the casing “ c ” and the injection needle 10 is injected into a tissue . the sliding sleeve 5 has been advanced together with the active agent container 7 in a distal direction along the latching sleeve 20 , wherein the latching tongue 21 comes to rest in the cavity 31 of the needle protecting tube 4 . fig1 , generally analogous with fig7 , shows the auto - injector in a position in which the needle protecting tube 4 surrounds the injection needle 10 after the auto - injector has been removed from the surface of the tissue . in this embodiment , the locking tongue 25 is likewise arranged on the sliding sleeve 5 . this enables a component to be omitted in the auto - injector . when the needle protecting tube 4 is advanced , the locking tongue 25 grips behind the end edge of the needle protecting tube 4 , such that the needle protecting tube 4 is secured against retracting relative to the active agent container 7 or the sliding sleeve 5 . when pressure is applied to the needle protecting tube 4 in the proximal direction , the needle protecting tube 4 shifted together with the sliding sleeve , the active agent container 7 and the injection needle 10 , relative to the casing “ c ”. in the foregoing description , 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 form disclosed . obvious modifications or variations are possible in light of the above teachings . the embodiments were chosen and described to provide the best illustration of the principals of the invention and its practical application , and to enable one of ordinary skill in the art to use the invention in various embodiments and with various modifications as are suited to a 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 .

in an elongated casing , an active agent container connected to an injection needle can be shifted axially by a spring force . auto - injectors which are sold or distributed filled and with the springs tensed have to be provided with a needle protecting cap to ensure the sterility of the injection needle . when such a needle protecting cap is removed as preparation for using the auto - injector , a tensile force can be exerted on the active agent container . therefore , the active agent container comprising the injection needle must be prevented from being undesirably pulled forwards . at least one latching tongue prevents the active agent container from being prematurely shifted with respect to the casing , by abutting a flange arranged on a sliding sleeve which accommodates the active agent container . when the auto - injector is placed onto a person &# 39 ; s skin , a needle protecting tube is shifted into the casing , forcing the latching tongue away from the flange and , thus , freeing the travel path for needle movement .

fig2 is a side view of a teeter - totter 100 in accordance with a first exemplary embodiment of the invention . the teeter - totter 100 may include an elongated plank 102 , for example a 2 × 12 × 12 ′, coupled to a base 104 . the base 104 may be in contact with , and coupled to , the middle of the plank 102 with a bolt 106 and cooperating nut 108 extending through an upper portion 132 of the base 104 . alternatively , the base 104 may be coupled to the plank 102 with any mechanical fastener , for example , a screw , without departing from the present invention . as shown in fig2 – 4 , the base 104 may include an “ l ” bracket 110 , a first leg 112 , and a second leg 114 . the “ l ” bracket 110 and the legs 112 , 114 may be made from aluminum or other materials . the legs 112 , 114 may be hollow tube stock or , alternatively , may be solid . the first leg 112 may be rotatably coupled to a lower portion 130 of the “ l ” bracket 110 with a first fastener 116 , and the second leg 114 may be rotatably coupled to the lower portion 130 of the “ l ” bracket 110 with a second fastener 118 . the first leg 112 may be disposed on a first side of the lower portion 130 and the second leg 114 may be disposed on a second side of the lower portion 130 . rotation of the first leg 112 may be restricted by a first stopper 120 and rotation of the second leg 114 may be restricted by a second stopper 122 . the stoppers 120 , 122 may be mechanically coupled to the “ l ” bracket 110 , for example , by welding , soldering , or brazing . alternatively , the stoppers may be pins inserted through the “ l ” bracket . alternatively , the legs 112 , 114 may be hinged to the upper portion 132 of the “ l ” bracket 110 ; and the stopper may be mechanically coupled to the upper portion 132 without departing from the present invention . fig3 and 5 show the teeter - totter 100 in a “ compact ” position , and fig4 and 6 show the teeter - totter in an “ extended ” position . in the “ compact ” position , an edge 140 contacts the ground 142 and the plank rotates about the edge 140 . the edge 140 is spaced from the upper portion 132 . to convert the teeter - totter 100 from the “ compact ” position to the “ extended ” position , the user rotates the legs 112 , 114 until the legs 112 , 114 contact the stoppers 120 , 122 respectively . the height from the ground 142 to the top surface of the middle of the plank 102 in the “ compact ” position is h1 , and the height from the ground 142 to the top surface of the middle of the plank 102 in the “ extended ” position is h2 . in the “ extended ” position , the legs 112 , 114 contact the ground 142 and the plank rotates about the legs 112 , 114 . when a dog 2 approaches the teeter - totter 100 , one end of the elongated plank 102 , either the near end or the far end , is in contact with the ground . the dog 2 must touch the near contact zone with at least one paw , traverse the plank 102 , and then touch the far contact zone with at least one paw before proceeding to the next obstacle . as the dog 2 traverses the teeter - totter 100 , the plank 102 rotates about the edge 140 in the “ compact ” position and the legs 112 , 114 in the “ extended ” position . during training , the user starts off with the teeter - totter 100 in the “ compact ” position , i . e ., the middle of the plank 102 is at a height h1 from the ground 142 . after the dog 2 gains sufficient confidence , the user can rotate the legs 112 , 114 into the “ extended ” position , i . e ., the middle of the plank 102 is at a height h2 from the ground 142 . it should be understood that , while the present invention has been described in detail herein , the invention can be embodied otherwise without departing from the principles thereof ; and such other embodiments are meant to come within the scope of the present invention as defined in the following claims .

a teeter - totter base for training canines may be coupled to the middle of an elongated plank . the base has a pair of legs that can be rotated in order to change the height of the plank off of a ground surface .

the eye contains round or slightly ovoid openings approximately 0 . 3 mm in size ( lacrimal punctum or punctal opening ) and surrounded by connective tissue ( sphincter ) about 1 mm in depth . each of the punctal openings leads into a vertical portion of the respective canaliculus , which is about 2 . 5 to 3 . 5 mm in length , before turning horizontally for about 8 mm to join its other canaliculus at the entrance of a lacrimal sac . referring to fig1 there is shown a representation of an apparatus 1 according to the present invention for sizing and dilating a lacrimal punctum 6 . apparatus 1 comprises a handle 4 and a tip 5 . the tip 5 has a dilator portion 3 and a gauge portion 2 . the gauge portion 2 is of cylindrical shape , has a diameter ranging from about 0 . 1 - 1 . 0 mm ( preferably from about 0 . 4 mm to about 0 . 9 mm ) and is of 0 . 5 mm to about 2 mm in length ( preferably about 2 mm ). tapered tip 11 located at the end of the gauge portion 2 facilitates the insertion of the gauge into the lacrimal punctum . the dilator portion 3 has a diameter that is about 0 . 1 mm larger than the diameter of the gauge portion 2 . this graduated system provides for actual measurement of the lacrimal punctum 6 and canaliculus 8 ( e . g ., the vertical portion of the canaliculus ) with the gauge 2 followed by insertion of the dilator 3 to provide a controlled dilation of the punctal dilation prior to insertion of a punctum plug . as previously described , in the treatment of keratoconjunctvitis sicca prevention of the drainage of lacrimal fluid from the eye may be achieved by blocking the lacrimal punctum 6 . fig2 and 4 depict a method for proper measurement of the lacrimal punctum and canaliculus , and dilation of the punctum , prior to insertion of a punctum plug . referring to fig2 which depicts proper insertion of the gauge portion 2 , e . g ., it is inserted into the lacrimal punctum 6 until the sphincter 7 seats flush around the gauge portion 2 providing a snug fit . in the preferred embodiment a series of gauge portion 2 of the tip 5 ranging from 0 . 4 to 0 . 9 mm are used to measure the lacrimal punctum 6 and canaliculus 8 . by inserting the gauge portion 2 of the tip 5 into the lacrimal punctum 6 and canaliculus 8 in a graduated fashion from the smallest gauge to the largest gauge , a snug fit can be observed and measured . the gauge size that provides the snug fit is then used to determine the correct size punctum plug to use . when performing the measurement step , it is important to observe the seating of the gauge portion 2 without advancing the tip 5 farther into the canaliculus 8 , as doing so may cause premature or over - dilation of the sphincter . referring to fig3 which depicts insertion of the tip into the lacrimal punctum 6 . when the gauge portion 2 of the tip 9 appears to enter the sphincter 7 with little or no resistance , the gauge is too small and the next largest size gauge should be used . it is recommended that the next gauge tested be about 0 . 1 mm larger than the previous gauge used . alternatively , if the gauge portion 2 offers substantial resistance when entering the lacrimal punctum 6 , it is to large . the next smallest gauge should be tested . continue insertion of the gauge portion 2 incrementally with the next gauge until the gauge portion 2 of the tip 5 fits snugly . referring to fig4 which depicts controlled punctal dilation , the dilator portion 3 of the tip 5 may be inserted in the lacrimal punctum 6 . insertion of the dilator 3 results in a controlled dilation of the sphincter 7 . once sphincter dilation is observed remove the tip 5 . insert a punctum plug into the lacrimal punctum following insertion instructions for the specific punctum plug used . insertion of the punctum plug is done as quickly as possible to ensure dilation of the sphincter . in describing the invention , reference has been made to a preferred embodiment and illustrative advantages of the invention . those skilled in the art , however , may recognize additions , deletions , modifications , substitutions and other changes which will fall within the purview of the subject invention and claims .

an apparatus for measuring a lacrimal punctum and a canaliculus is provided . the apparatus comprises a handle and a tip disposed at one end of the hand , said tip having a gauge portion of size and shape to allow measurement of the lacrimal punctum and the canaliculus . the apparatus may further comprise a dilator portion disposed between the gauge portion and handle .

an important feature of the invention is the use of a static dissipative layer ( as distinguished from a conductive layer ) in intimate contact with the skin of the person wearing the device . as is noted in the prior art , the typical prior art static draining wrist device employs a conductive material , which usually has a surface resistivity of less than 100 , 000 ohms per square . in contrast , the device of the invention includes a static dissipative layer in direct contact with the skin of the user , which layer in the preferred embodiment consists of a flexible , static dissipative polymer material having an exposed surface resistivity to a grounded snap portion , of typically between one and 10 megohms . the use of this material in place of a conductive material also obviates the need to include a conventional and bulky inline resistor in the path between skin contact and ground . the safety of the user is thereby ensured due to the resistive nature of the static dissipative strip , and without the addition of an extraneous conventiona resistor . referring now more particularly to the drawings and fig1 , 3 , 8 and 9 thereof , one embodiment of the invention consists of a flexible dielectric strap 10 formed of any suitable well known dielectric material and adapted to be worn on the wrist of user ( not shown ). the strap 10 may optionally include a wrist watch 11 of conventional well known type . if a wrist watch is provided , however , it is preferable that all exposed portions of the watch surface be formed of a dielectric insulative material , e . g ., plastic resin . the flexible dielectric strap 10 has a dielectric strip 12 thereon and in the preferred embodiment is non - porous , and located on the inside face of the strap 10 in order to be in intimate contact with the skin of the person ( not shown ) wearing the device . the strip 12 may extend any desired length along the inside face of the strap 10 , consistent with the desired static dissipative requirements and even over the rear face of the watch 11 . due to the flexible nature of the strip 12 , the strip may be formed to any desired length without discomfort to the user and remains in intimate skin contact due to its conformity to the skin surface . the longer the strip therefore , the greater skin contact and the greater the functionality of the device . the strip 12 is provided with a static dissipative layer 13 , which may consist of a polymer which has been rendered electrically conductive by the additon of activated carbon black or other suitable materials . various polyesters and vinyl acrylic materials are suitable vehicles for activated carbon black , as is well known in the art . it has been found to be particularly desirable to form the static dissipative layer by depositing an electrically conductive ink upon a textured flexible substrate layer ( including polycarbonate or polyvinylchloride ), such as by the silk screen process . a preferred ink consists of polymethacrylate of vinyl / acrylic , containing carbon black , in a slow drying solvent . the methacrylate may be deposited as a monomer , and allowed to cure on the surface of the substrate layer , such as strip 12 . the preparation and electrical characteristics of the static dissipative strip layer are more fully described in my co - pending application ser . no . 735 , 870 . the static dissipative layer 13 may be applied to the strip 12 or directly to the back of flexible strap 10 , if desired , and additionally , may be provided with a non - porous flexible coating 14 , such as teflon ® or other suitable material with low surface tension characteristics , so that the build - up of dirt , waxes , or other contaminants can be avoided thereby reducing the chance of increased surface resistivity due to contaminant build up . the static dissipative layer 13 is electrically connected to a conductive ground cord connector snap 16 through an opening in the dielectric strip 12 and the strap 10 with a metallic grommet end 15 of the snap 16 in contact with the static dissipative layer 13 . a closed end dielectric rivet 17 is engaged in the exposed open end of the connector snap 16 to provide intimate sealing contact with the layer 13 , and at the same time to insulate all portions of the conductive end 15 from direct contact with the wearer &# 39 ; s skin . this sealing feature prevents perspiration and other contaminants from contact with grommet end 15 , and shorting out the safety resistive feature of the static dissipative layer 13 . the inclusion of a non - porous flexible static dissipative strip 12 with a static dissipative layer 13 as the primary means of making skin contact is a substantial feature of the invention and a dramatic improvement over the prior art . in the prior art , as has been discussed , the wearing of the device , particularly in conjunction with a wrist watch would expose its components to perspiration which can short out a conventional resistor and make the device unsafe . in the present device , perspiration is prevented from shorting out or otherwise destroying the desired electrical resistance while at the same time improving electrical contact at the critical interface between the skin of the wearer , and the static dissipative layer of the device . in use , electrical contact is made between the static dissipative layer 13 and the conductive snap rivet 16 . the electrical charge , which is accumulated on the static dissipative layer 13 , is transferred to and collected at the conductive snap rivet 16 , to be transferred to an attachment to ground such as by an electrical cord 17 &# 39 ;, having a complementary female conductive snap 17a for attachment to the head 18 of the male snap rivet 16 . the snap 17a is attached to a length of electrical wire 20 which may be attached directly to ground by an alligator clip 21 . accordingly , when the device 10 is to used , the person wearing the device has only to connect the female snap portion 17a to achieve proper ground . when the device is not in use , the ground wire 17 &# 39 ; can be easily removed . in the embodiment described above , in which a wrist watch 11 is included as part of the device , the person may wear the device for everyday use , and has only to connect the device to ground , when arriving at the work location , by attachment of the female snap portion 17a , without the necessity of removing his or her personal watch and applying a separate wrist strap device . it is also important to note that the static dissipative layer 13 of the invention prevents the exposed head 18 of the snap 16 from presenting a hazardous condition to the user when the device is not connected to ground . this safety feature occurs because the static dissipative layer 13 is of a sufficiently high resistance that there is no need to install a separate conventional resistor to protect the user from electrical shock , should the head 18 come into contact with a source of electrical energy . referring now to fig4 another embodiment of the device 50 of the invention is illustrated which includes a watch 11 , and a flexible dielectric strap 51 similar to strap 10 , with a dielectric strip 52 on the inside face of the strap 51 and with a static dissipative layer 53 thereon similar to layer 13 , for intimate skin contact . a rivet 54 , similar to rivet 16 , is provided with a metal grommet end 55 in direct contact with the static dissipative layer 53 and with a dielectric patch 56 of well known type covering the exposed grommet end 55 in sealing relationship with the layer 53 . the rivet 54 has a plate 57 in contact with the outer face of the strap 51 and a head 58 which may be connected to ground by a ground cord 17 &# 39 ; of fig8 and 9 . in another embodiment of the invention to be described , an adaptor kit is provided for adapting a conventional wrist watch to be a static dissipative device . the adaptor kit includes a dielectric strap with a backing strip , which serves as a substrate for a static dissipative layer for intimate skin contact . the device may be looped around or attached directly to the band of a conventional wrist watch , so that the static dissipative portion of the strip of the person wearing the watch is maintained in electrical contact with the skin . referring now to fig5 and 7 , one embodiment of adaptor kit 100 is shown wherein a conventional wrist watch 110 having a band 101 is fitted with the adaptor kit . the adaptor kit includes a flexible dielectric strap 102 with an attached flexible backing strip 103 , with a static dissipative layer 104 on the surface thereof for skin contact , as described for fig1 and 3 . in this embodiment , the strap 102 of the device 100 is provided with a layer 111 of pressure sensitive adhesive of well known type , enabling the adaptor device to be wrapped around the entire watch band 101 . accordingly , when the watch is worn , the static dissipative layer 104 is maintained in intimate contact with the user &# 39 ; s skin ( not shown ). a rivet 106 is provided , similar to rivet 16 above , with a grommet end 107 in contact with layer 104 and has a plastic rivet 108 engaged thereon for sealing of rivet 106 from perspiration , as described for rivet 17 . the rivet 106 is additionally provided with a head 109 for connection to a grounding cord ( not shown ) as described for cord 17 &# 39 ; above . the device 100 may be attached to the wrist watch 110 by any suitable means , so long as the static dissipative layer 104 is maintained against the skin of the user ( not shown ) when the watch is worn . referring now to fig1 , another embodiment of static dissipative grounding device is illustrated which includes a stretch band 150 adapted to be worn on the wrist of the user ( not shown ) with a strip 151 of dielectric material thereon , which has a layer of static dissipative material 152 thereon , as described above for layer 13 , with a rivet 153 in contact therewith , and extending upwardly through the band 150 . a plate 154 is provided in contact with the outer face of the band 150 , and with a head 155 of rivet 153 in contact therewith , which head may be connected to a suitable grounding cord ( not shown ) such as cord 17 &# 39 ;. a plastic rivet 157 is provided engaged in rivet 153 as described for rivet 17 . the embodiment illustrated in fig1 is provided with an inner occlusive coating or layer 156 of latex or other suitable occlusive coatings to make the band 150 impervious to water and perspiration to thereby maintain the band as an insulative layer , with electrical contact only through the rivet 153 . referring now to fig1 , another embodiment of static dissipative grounding device 175 is illustrated which includes a band 176 of plastic , such as pleated pvc or flat ribbon elastic , being non - porous and having an outer elastic tubular band 177 engaged therewith . a layer of static dissipative material 178 is provided on the inside of band 177 , for contact with the skin of the user ( not shown ), with a rivet 179 engaged therewith extending through the bands 176 and 177 , with a plate 180 in contact with the outer face of band 176 and with a head 181 for engagement by a ground cord ( not shown ) such as ground cord 17 &# 39 ;. a plastic rivet 182 is provided , similar to rivet 17 , and engaged in rivet 179 for sealing as described for fig1 and 3 . referring now to fig1 , another embodiment of static dissipative grounding device 200 is illustrated , which includes a band 201 of non - porous dielectric material , similar to strap 10 of fig1 and 3 , and with a strip of dielectric material 202 on the inner face which has a layer 203 of static dissipative material similar to layer 13 for contact with the skin of the user ( not shown ), and with a rivet 204 extending through the band 201 as described for device 175 . in addition , a plastic sealing rivet 205 is engaged in rivet 204 as described for rivet 17 . the band 201 at one of its ends is provided with a buckle 206 of conventional type , which can be of resin plastic and which band 201 also has a strip of velcro ® 207 thereon so that the end can be threaded through buckle 206 and engaged with a complimentary strip of velcro ® 208 , to provide for adjustment of the device 200 to fit varying size wrists . the device 200 is designed so as not to expose any porous section of the fastening buckle to direct contact with the skin . this prevents perspiration from providing a direct electrical contact to the skin . referring now to fig1 , still another embodiment of static dissipative grounding device 300 is provided , which includes a non - porous dielectric band 301 , similar to band 201 with a strip of dielectric material 302 on the inside face , which has a layer of static dissipative material 303 on the inside of the strip 302 for intimate contact with the skin of the user ( not shown ), is provided with a contact rivet 304 and a sealing rivet 305 as described for device 200 above . the band 301 , at its ends , is provided with plastic rivets 306 which are each engaged with the ends of an elastic material 307 urging the ends together and providing for retention of the band 301 on the wrist of the user ( not shown ). it should be noted that for the various static dissipative straps described above , that the electrical characteristics are such that from any point on the static dissipative layer to the electrical contact on the outer part of the band , the resistance between the point and the contact is never , typically , less than one ohm or more than 10 ohms . it will , of course , be appreciated that any suitable means of attaching the adapter kit strip to the watch band , for example a hook and loop fastener , may be employed in lieu of the disclosed embodiments . it will thus be seen that a static dissipative grounding strap has been described with which the objects of the invention are achieved .

a static dissipative device is disclosed for use by persons assembling , maintaining , repairing or operating sensitive electronic equipment . the static dissipative device includes a strap having a static dissipative layer in contact with the skin of the user , which layer consists of an electrically static dissipative material of high surface resistivity , and with an electrically conductive portion in contact with the static dissipative layer for connection to ground .

referring now to fig1 - 3 , there is shown the spinal coupler seater instrument 10 of the present invention . the instrument 10 includes a main handle 12 pivotally connected to a lever handle 14 in a scissors like fashion about a pivot such as pin 16 . handle 12 includes a distal end 18 and proximal end 20 . as shown in fig1 and 2 , lever handle 14 includes a c - shaped channel 34 into which handle 12 may interfit when instrument 10 is compressed . the handles 12 and 14 include an attachment means , such as forked jaws 22 and 24 , for attachment of instrument 10 to spinal rod 26 , as shown in fig5 and 6 . jaws 22 and 24 are part of lever handle 14 and main handle 12 , respectively , and are opposed to grab opposite sides of rod 26 . each jaw 22 and 24 is forked , jaw 22 having legs 22a and 22b with jaw 24 having legs 24a and 24b . each leg of jaws 22 and 24 includes a grooved portion 28 as shown in fig3 . these grooved portions 28 on each leg are sized to correspond with the diameter of a particular spinal rod 26 ( fig5 ). each jaw 22 and 24 further includes a ramp section 30 and 32 , respectively . the angle of ramps 30 and 32 relative grooves 28 cause the rod 26 to slide into groove 28 when instrument 10 is clamped about a rod 26 . the ramps 30 and 32 permit casual attachment of instrument 10 to rod 26 while forcing instrument 10 and rod 26 into proper orientation relative to each other . moreover , instrument 10 is automatically oriented so that it is substantially normal to the axis of spinal rod 26 when clamped about rod 26 . instrument 10 is designed to attach a spinal coupler 36 over a spinal rod 26 with an interference fit . spinal coupler 36 is preferably one of a modulock ™ type design , manufactured by zimmer , inc ., warsaw , ind . a full description of the preferred spinal rod coupler 36 is found in u . s . patent application ser . no . 07 / 909 , 509 , now u . s . pat . no . 5 , 312 , 405 , assigned to the assignee of the present invention and expressly incorporated herein by reference . alternatively , other compatible spinal rod couplers maybe utilized with the present invention . spinal coupler 36 comprises a u - shaped yoke ( fig7 ) that engages directly about the spinal rod 26 and a c - shaped coupler clamp 36 that overfits and locks yoke 35 to spinal rod 26 . the coupler clamp and yoke combination permits positioning of coupler clamp 36 on spinal rod 26 at angles different than perpendicular to within plus or minus 18 °. this allows for flexibility during surgical operations . the pressing or compression means of instrument 10 for attaching coupler clamp 36 to rod 26 includes a plunger 38 preferably comprising a cylindrical rod slidably disposed within an axial passageway 40 in body handle 12 . plunger 38 is partially exposed via slot 39 in body handle 12 ( see fig3 ). during use , plunger 38 is slid axially against coupler 36 to compress the coupler into locking attachment with rod 26 . a cam handle 48 is pivotally connected to main handle 12 so that cam handle 48 pivots in the same directions as handle 12 and lever handle 14 . cam handle 48 pivots about a pivot such as pin 50 , which is located at a position offset from pivot pin 16 . as shown in fig3 cam handle 48 includes a projection such as cam blade 52 that interfits into slot 39 and into an open slot 54 in plunger 38 . cam blade 52 is oriented so as to slide plunger 38 toward distal end 18 of body handle 12 when cam handle 48 pivots toward handle 12 . when squeezed , instrument 10 operates in a two stage manner . the first stage closes the jaws 22 and 24 together when the lever handle 14 is pulled upwardly toward handle 12 . the second stage occurs as cam handle 48 is pivoted downwardly toward handle 12 thereby pushing plunger 38 and sliding it toward distal end 18 into pressing engagement with a spinal coupler 37 ( fig7 ). axial passageway 40 at proximal end 20 of body handle 12 includes an enlarged counterbored recess 42 about plunger 38 ( fig3 ). within recess 42 is located a biasing means such as a spring 44 . spring 44 is disposed around plunger 38 and retained in recess 42 by a control knob 46 threadedly attached on the proximal end of plunger 38 . the bias of spring 44 and the orientation of pivot pins 16 and 50 are such to permit one hand operation of instrument 10 . further , spring 44 is utilized to urge apart handle 12 and handle 14 when instrument 10 is not gripped about rod 26 . control knob 46 may be rotated on plunger 38 to change the bias force of spring 44 experienced by plunger 38 . control knob 46 acts as a stop to prevent over extension of plunger 38 during instrument actuation , by interfering with proximal end 20 of handle 12 . further , control knob 46 operates as a visual indicator to the user that the compression operation is complete when it engages distal end 20 of handle 12 . the bias force on plunger 38 creates a certain level of gripping tension on handle 48 . in operation , the present invention will couple a spinal coupler 36 to a rod 26 as shown in fig5 - 8 . spinal rod 26 will first be inserted into a patient , adjacent the spine . the surgeon will then fit a modulock ™ yoke 35 and coupler 36 over rod 26 into a particular position necessitated by the condition of the patient . the surgeon will then grasp instrument 10 and adjust control knob 46 to the proper location by rotating control knob 46 about plunger 38 to adjust the amount of travel of plunger 38 . rotation of control knob 46 will either compress or expand spring 44 . the surgeon will place instrument 10 into engagement with rod 26 so that rod 26 closely aligns into grooved portions 28 of jaws 22 and 24 . ramp sections 30 and 32 will assist the surgeon in guiding the rod 26 and instrument 10 into the proper position . instrument 10 engages and attaches to rod 26 on both sides of coupler 36 thereby preventing axial movement of coupler 36 on rod 26 . jaw legs 22a , 22b , 24a , and 24b surround coupler 36 and firmly engage rod 26 . as the surgeon squeezes instrument 10 like a pair of pliers , jaws 22 and 24 close together thereby positively locating the instrument 10 and coupler 36 on rod 26 . fig5 and 7 show this intermediate stage . forked jaws 22a , 22b and jaws 24a , 24b grasp rod 26 tightly when instrument 10 is squeezed . as handle 48 is further squeezed by the surgeon , it pivots about pivot pin 50 . blade 52 on cam handle 48 rotates about pivot pin 50 and engages surface 53 of opening 54 in plunger 38 , thereby axially moving plunger 38 toward coupler 36 and rod 26 until knob 46 stops against end 20 of handle 12 . fig7 and 8 show cam blade 52 having two engagement surfaces 58 and 60 . engagement surface 58 contacts with surface 53 of plunger 38 during the initial stage of the compression operation . as cam handle 48 is pivoted from its starting position , engagement surface 58 causes plunger 38 to slide toward coupler 36 . at a point during pivoting , engagement surface 60 engages plunger surface 53 changing the point of contact between cam blade 52 and plunger 38 thereby further increasing the force applied to coupler 36 . instrument 10 , as shown in fig6 and 8 , is fully actuated or closed such that plunger 38 is fully extended out of handle 12 . this extension of plunger 38 transmits a compression force from the front face 56 of plunger 38 onto coupler clamp 36 thereby connecting yoke member 35 and coupler clamp 36 to spinal rod 26 via an interference fit . as shown in fig7 yoke 35 , having internal opening 62 , is interfit or snapped over rod 26 . yoke 35 includes a pair of legs 64 having a flange 66 extending outwardly and generally perpendicular from legs 64 . c - shaped clamp member 36 includes a recess 68 having a slot 70 into which flange 66 of yoke member 35 may interfit and lock . prior to compression , clamp member engages yoke member 35 within recess 68 holding it in place on rod 26 ( fig7 ). when clamp member 36 is compressed toward rod 26 , yoke member 35 slides further into recess 68 until yoke flange 66 seats within slot 70 . this orientation compresses leg 64 about rod 26 creating an interference fit thereby securing both yoke member 35 and clamp member 36 to rod 26 . the compression coupling force utilized by the instrument originates from the hand of the surgeon and is transmitted to cam handle 48 , then to plunger 38 . this coupling force is quite strong because of the leverage created by handle 48 and the action of cam surfaces 58 and 60 . sufficient force is generated and transmitted to prevent coupler 36 from separating yoke 35 from rod 26 after assembly . plunger 38 effectively delivers a high compression force to the coupler 36 without loss of control or accuracy . instrument 10 assures that the compression force is precisely applied without coupler 36 or instrument 10 sliding along rod 26 . while this invention has been described as having a preferred design , the present invention can be further modified within the spirit and scope of this disclosure . this application is therefore intended to cover any variations , uses , or adaptations of the invention using its general principles . further , this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this invention pertains and which fall within the limits of the appended claims .

an instrument and method for locating and attaching a spinal coupler to an implanted spinal rod including body and lever handles that attach about the spinal rod . a cam handle is connected to the body handle to actuate a plunger that applies a compression force to the spinal coupler to attach it to the spinal rod by an interference fit . the body and lever handles each include a forked jaw having legs that attach to the spinal rod on each side of the spinal coupler . in one embodiment , the plunger includes a control knob to vary the instrument actuating force and prevent over extension of the plunger .

an embodiment of the present invention provides a method for treating the heart following a myocardial infarction ( mi ). electrical stimulation is provided to selected portions of the heart without regard to whether a diagnosis of any arrhythmia has been given . stimulation may be in the form of excitatory or non - excitatory pulses using cathodal , anodal , and biphasic waveforms . the portions of the heart selected for stimulation are selected based on the type of stimulation to be administered and the extent of the damage sustained by the cardiac tissue . in an exemplary embodiment , only healthy cardiac tissue is stimulated . in an exemplary embodiment of the present invention , biphasic , biventricular stimulation is directed to undamaged areas of the heart to enhance the muscular contraction of the healthy tissue thereby allowing the heart to achieve normal or near - normal functioning . the enhanced muscular contraction of the stimulated portion of the heart reduces heart loading and prevents or reduces the adverse forms of remodeling of the heart following a myocardial infarction . the biphasic , biventricular stimulation comprises continuous application of both cathodal and anodal pulses simultaneously to the right and left ventricles through electrodes that contact undamaged portions of the heart . in an embodiment of the present invention , unlike pacing that is used to control arrhythmias , the biphasic stimulation is not applied to the heart in response to sensing a cardiac signal indicative of an arrhythmia . rather , the biphasic stimulation is applied continuously to allow the heart to compensate for the cardiac tissue affected by a mi while avoiding undesirable forms of remodeling . optionally , the application of the biphasic stimulation is timed to coincide with the beginning of a depolarization wave as determined by cardiac sensors . additionally , the biphasic stimulation of the exemplary embodiment is combined with stem cell implantation at sites where the cardiac tissue has been damaged . the stem cell therapy regenerates damaged cardiac tissue so that over time , the biphasic stimulation therapy may be terminated . referring to fig1 , a diagram of the heart illustrates the four chambers : right atrium ( ra ), left atrium ( la ), right ventricle ( rv ), and left ventricle ( lv ). electrode lead 201 , connected to rv electrode group 201 a comprising individual electrodes 202 , 204 , 206 , 208 and 210 , is shown with the individual electrodes connected to multiple points on the external surfaces of the right ventricle . electrode lead 301 , connected to lv electrode group 301 a comprising individual electrodes 302 , 304 , 306 , 308 and 310 , is shown with the individual electrodes connected to multiple points on the external surfaces of the left ventricle . while rv electrode group 201 a and lv electrode group 301 a are illustrated with five electrodes per group , this is not meant as a limitation . other group sizes may be used without departing from the scope of the present invention . in alternative embodiments , the locations of the individual electrodes in fig1 ( 202 , 204 , 206 , 208 and 210 ; and 302 , 304 , 306 , 308 and 310 ) are selected to avoid stimulation of damage cardiac tissue as , for example , tissue damaged as a result of a mi . in yet another embodiment of the present invention , pulses are applied to the electrodes so as to mimic the normal physiological flow of the normal ventricular depolarization wave . in this embodiment , the areas closest to ( or at ) the a - v node are first stimulated during a given beat . in an embodiment of the present invention , atrial excitation is sensed ( p - q interval ) or ventricular excitation is sensed ( qrs interval ) and an external excitatory pulse is applied to the first electrode ( after an appropriate delay ) to coincide with the beginning of the ventricular depolarization wave . subsequent excitatory pulses are directed to areas progressively further from the a - v node . areas intermediate between these two extremes are appropriately stimulated on a scaled time basis that , again , mimics the normal intrinsic conduction paths that facilitate the most efficient cardiac contraction . in an embodiment of the present invention , the pulses are applied to healthy cardiac tissue that is unaffected the mi , thereby allowing the damaged tissue to heal and the stimulation voltage to be low . this progressive stimulation embodiment requires specific knowledge of the placement of each electrode relative to each other electrode , as well as the placement relative to the electrical conduction pathways in the heart . thus , it is appropriate to contemplate “ classes ” of electrodes , in which , for example , electrodes are identified or categorized according to when they are fired . in a simplistic five tier system , e . g ., the first tier electrodes are designated as the first to be fired ( i . e ., the electrodes closest to the a - v node ), followed successively ( and temporally progressively according to the normal conducting paths ) by the second , third , fourth , and fifth tier electrodes , where the fifth tier electrodes would be the last to be fired , and whose locations on the ventricle ( s ) would correspond to the last areas to be depolarized in the course of a normal ventricular contraction / beat . an even simpler ( i . e ., two , three or four ) tiered system may be used , or one more complex ( i . e ., one with greater than 5 tiers , or with any other basis of electrode placement , such as a honeycomb - like array in a particular area with a known or suspected pathology as to rhythmicity , reentry , conduction , contractility , etc . furthermore , multiple electrodes within a given tier may be numbered or otherwise distinctly identified so that the practitioner may test and use electrodes with respect to known locations in the heart , for example , to anticipate and / or bypass an area of electrical blockage . in this embodiment , multiple , small electrodes are pulsed with excitatory pulses in a physiologic sequential fashion . in still another embodiment of the present invention , the technique described above for stimulating the ventricles is applied to the atria . in this embodiment , electrodes are progressively placed from close to the sa node ( first to be fired ) to close to the av node ( last to be fired ), mimicking the normal intrinsic conduction paths of the atria . bypassing an area of damaged tissue is also anticipated by the present invention , and can be effected by first identifying such areas , for example , by determining myocardial resistance values between electrodes . electrical pulses then are routed to those myocardial areas with appropriately low resistances , following as closely as possible the lines of conduction of the normal intrinsic conduction paths . communication of , and control of , measurements of resistance between electrodes , as well as developing a bypass protocol for a particular patient , can be effected by an external computer . the external computer can communicate with the pacemaker by any convenient method , for example , radiotelemetry , direct coupling ( as by connecting to an external wire from the pacemaker to the surface of the skin of the patient ), etc . fig2 through 5 depict a range of biphasic stimulation protocols . these protocols have been disclosed in u . s . pat . no . 5 , 871 , 506 to mower , which is herein incorporated by reference in its entirety . fig2 depicts biphasic electrical stimulation in which a first stimulation phase comprising anodal stimulus 202 is administered with amplitude 204 and duration 206 . the first stimulation phase is followed immediately by a second stimulation phase comprising cathodal stimulus 208 , which is of equal intensity and duration to those of anodal stimulus 202 . fig3 depicts biphasic electrical stimulation wherein a first stimulation phase comprising low level , long duration anodal stimulation 302 having amplitude 304 and duration 306 is administered . this first stimulation phase is immediately followed by a second stimulation phase comprising cathodal stimulation 308 of conventional intensity and duration . in an alternative embodiment of the invention , anodal stimulation 302 is at maximum subthreshold amplitude . in yet another alternative embodiment of the invention , anodal stimulation 302 is less than three volts . in another alternative embodiment of the invention , anodal stimulation 302 is a duration of approximately two to eight milliseconds . in yet another alternative embodiment of the invention , cathodal stimulation 308 is of a short duration . in another alternative embodiment of the invention , cathodal stimulation 308 is approximately 0 . 3 to 1 . 5 milliseconds . in yet another alternative embodiment of the invention , cathodal stimulation 308 is of a high amplitude . in another alternative embodiment of the invention , cathodal stimulation 308 is in the approximate range of three to twenty volts . in yet another alternative embodiment of the present invention , cathodal stimulation 308 is of a duration less than 0 . 3 milliseconds and at a voltage greater than twenty volts . in another alternative embodiment , anodal stimulation 302 is administered over 200 milliseconds post heart beat . in the manner disclosed by these embodiments , as well as those alterations and modifications which may become obvious upon the reading of this specification , a maximum membrane potential without activation is achieved in the first phase of stimulation . fig4 depicts biphasic electrical stimulation wherein a first stimulation phase comprising anodal stimulation 402 is administered over period 404 with rising intensity level 406 . the ramp of rising intensity level 406 may be linear or non - linear , and the slope may vary . this anodal stimulation is immediately followed by a second stimulation phase comprising cathodal stimulation 408 of conventional intensity and duration . in an alternative embodiment of the invention , anodal stimulation 402 rises to a maximum subthreshold amplitude . in yet another alternative embodiment of the invention , anodal stimulation 402 rises to a maximum amplitude that is less than three volts . in another alternative embodiment of the invention , anodal stimulation 402 is a duration of approximately two to eight milliseconds . in yet another alternative embodiment of the invention , cathodal stimulation 408 is of a short duration . in another alternative embodiment of the invention , cathodal stimulation 408 is approximately 0 . 3 to 1 . 5 milliseconds . in yet another alternative embodiment of the invention , cathodal stimulation 408 is of a high amplitude . in another alternative embodiment of the invention , cathodal stimulation 408 is in the approximate range of three to twenty volts . in yet another alternative embodiment of the present invention , cathodal stimulation 408 is of a duration less than 0 . 3 milliseconds and at a voltage greater than twenty volts . in another alternative embodiment , anodal stimulation 402 is administered over 200 milliseconds post heart beat . in the manner disclosed by these embodiments as well as those alterations and modifications which may become obvious upon the reading of this specification , a maximum membrane potential without activation is achieved in the first phase of stimulation . fig5 depicts biphasic electrical stimulation wherein a first stimulation phase comprising series 502 of anodal pulses is administered at amplitude 504 . in one embodiment rest period 506 is of equal duration to stimulation period 508 and is administered at baseline amplitude . in an alternative embodiment , rest period 506 is of a differing duration than stimulation period 508 and is administered at baseline amplitude . rest period 506 occurs after each stimulation period 508 with the exception that a second stimulation phase comprising cathodal stimulation 510 of conventional intensity and duration immediately follows the completion of series 502 . in an alternative embodiment of the invention , the total charge transferred through series 502 of anodal stimulation is at the maximum subthreshold level . in yet another alternative embodiment of the invention , the first stimulation pulse of series 502 is administered over 200 milliseconds post heart beat . in another alternative embodiment of the invention , cathodal stimulation 510 is of a short duration . in yet another alternative embodiment of the invention , cathodal stimulation 510 is approximately 0 . 3 to 1 . 5 milliseconds . in another alternative embodiment of the invention , cathodal stimulation 510 is of a high amplitude . in yet another alternative embodiment of the invention , cathodal stimulation 510 is in the approximate range of three to twenty volts . in another alternative embodiment of the invention , cathodal stimulation 510 is of a duration less than 0 . 3 milliseconds and at a voltage greater than twenty volts . the individual pulses of the series of pulses may be square waves , or they may be of any other shape , for example , pulses which decay linearly or curvilinearly from an initial subthreshold amplitude , to a lower amplitude . in the biphasic stimulation protocol practiced by the present invention , the magnitude of the anodal phase does not exceed the maximum subthreshold amplitude . the anodal phase serves to precondition the stimulated myocardium , thereby lowering the excitation threshold such that a cathodal stimulation of lesser intensity than normal will produce depolarization leading to contraction . the pacing and subsequent normalizing of wall stresses promotes the implantation of stem cells in damages tissue , and guides their proper orientation during the maturation of the cells . the values of duration and amplitude will depend on factors such as the placement / position of the particular electrode ( including , e . g ., whether the electrode is in purely muscle tissue versus in specialized conducting or pacemaking tissue ), whether damaged / scarred tissue is in close vicinity to the electrode , depth of the electrode within the tissue , local tissue resistance , presence or absence of any of a large range of local pathologies , etc . nonetheless , typical anodal phase durations often fall within the range from about two milliseconds to about eight milliseconds , whereas typical cathodal durations often fall within the range from about 0 . 3 millisecond to about 1 . 5 millisecond . typical anodal phase amplitudes ( most commonly at the maximum subthreshold amplitude ) often fall within the range from about 0 . 5 volt to 3 . 5 volts , compared to typical cathodal phase amplitudes from about 3 volts to about 20 volts . because the heart is constantly stimulated , the pacing pulses are applied without the need for demand sensing . further , constant consistent pacing diminishes stress on the heart . in another embodiment of the present invention , the damaged tissue is located and treated by inserting or applying donor or “ stem ” cells . means for inserting and means for applying stem cells to damaged cardiac tissue are described in u . s . patent application no . 60 / 429 , 954 , entitled “ method and apparatus for cell and electrical therapy of living tissue ”, a utility application for which was filed on nov . 25 , 2003 , both of which applications are incorporated herein in their entirety for all purposes . in an embodiment of the present invention , the damaged tissue is treated and biventricular pacing pulsing is continuously applied to functioning portions of the heart . in one embodiment , the pacing sites are chosen to assure that the tissue treated with stem cells is not electrically stimulated . in an alternate embodiment , the pacing sites are chosen so that the tissue treated with stem cells receives electrical stimulation pulses having an amplitude below that required to excite the heart tissue . a system and method for managing detrimental cardiac remodeling following myocardial infarction have been disclosed . it will also be understood that the invention may be embodied in other specific forms without departing from the scope of the invention disclosed and that the examples and embodiments described herein are in all respects illustrative and not restrictive . those skilled in the art of the present invention will recognize that other embodiments using the concepts described herein are also possible . further , any reference to claim elements in the singular , for example , using the articles “ a ,” “ an ,” or “ the ” is not to be construed as limiting the element to the singular .

a system and method for managing and inhibiting cardiac remodeling in mi patients . bi - ventricular stimulation is constantly provided with and without sensing to encourage normal pumping of the heart on a consistent basis . pulses are administered using an anodal pulse followed by a cathodal pulse to stimulate cardiac muscle contraction . stem cells are administered to mi areas to encourage regeneration of cardiac tissue in the damaged area . stimulation may be provide to both healthy and compromised cardiac tissue .

fig1 is an exemplary system 100 including an implantable shunt apparatus 105 implanted within a hydrocephalus patient 110 . shunt apparatus 105 includes a proximal , head or ventricular catheter 115 installed in a ventricular cavity 120 of the patient 110 , and a distal , peritoneum or drainage catheter 125 disposed in the peritoneum 130 of the patient 110 . extending between the ventricular and drainage catheters 115 , 125 is a programmable valve apparatus 135 for regulating the flow of csf into and out of the ventricular cavity 120 of the patient 110 . the programmable valve apparatus 135 may be disposed anywhere along the fluid pathway of the proximal catheter 115 , the distal catheter 125 or therebetween . preferably , programmable valve apparatus 135 is located within the peritoneal cavity of the patient 110 , as illustrated in fig1 , so that size constraints for the programmable valve apparatus 135 are minimized ( e . g ., larger valves can be implanted within the peritoneum than adjacent to the skull ). one or more sensor elements 140 may be used to measure or detect a physiological characteristic of the patient . for example , the single sensor element 140 depicted in fig1 may be a volume sensor for detecting volumetric variations within the ventricular cavity or the ventricular catheter of the patient . sensor element 140 may be coupled to the programmable valve apparatus 135 , or it may be separate therefrom , as shown in fig1 . although shown positioned within the csf fluid pathway of the shunt system , sensor element 140 may be disposed outside of the csf fluid pathway while still residing within the ventricular cavity 120 of the patient 110 . furthermore , the sensor element 140 may be eliminated entirely , if desired . system 100 further includes an external controller 145 to communicate data to and from the implantable shunt apparatus 105 when the external controller is positioned proximate the patient and the shunt apparatus is energized . for example , external controller 145 may be configured to energize and receive an input signal generated from the sensor element 140 that is representative of the measured value of the physiological characteristic . in one particular aspect of the present invention , sensor element 140 is a volume sensor and the physiological characteristic is a measured volume of the ventricular cavity 120 of the patient 110 . sensor element 140 may measure the volume of fluid flowing through the shunt to monitor proper functioning of the shunt in order to detect a blockage . alternatively , sensor element 140 may be used to determine the drained volume . this determination of drained volume will disadvantageously consume a significant amount of power . external controller 145 may be configured to generate and transmit to the programmable valve apparatus 135 a control signal that commands the valve to adjust its pressure . the external controller 145 preferably communicates with the implantable shunt wirelessly , e . g ., via rf communication . implantable shunt apparatus 105 may include more than one sensor element 140 for measuring an additional physiological characteristic of the patient . for example , a second sensor 150 may be a pressure sensor for detecting the ventricular pressure of the patient . like the first sensor element 140 , additional sensor elements transmit data representing a measured or detected value of the additional physiological characteristic to the external controller 145 . as with the first sensor , any additional sensors may either be coupled to the valve 135 or be separate therefrom . implantable shunt apparatus 105 and external controller 145 of the present invention are equipped with electronic circuitry similar to those for medical telemetry systems that communicate physiological data ( e . g ., temperature , pressure , etc .) between an implant and a receiver unit . for example , sensor element 140 may be configured to generate an analog signal that is received by the implantable shunt apparatus 105 and converted electronically to a digital pulse . in turn , the digital pulse is transmitted from the implantable shunt apparatus 105 to the external controller 145 wirelessly such as by radiofrequency ( rf ) communication . alternatively , any control signal may be processed by the implantable medical device 105 itself using microprocessor 165 . one skilled in the art will recognize that these are merely examples of the forms of remote communication suitable for the present invention , and that other forms of non - invasive communication may be utilized without departing from the scope of the present invention . an illustrative example of the electronic circuitry in the implantable shunt apparatus 105 and external controller 145 in wireless communication therewith is shown in fig2 a . implantable shunt apparatus 105 has an associated secondary coil 155 , rf communication block 160 and microprocessor 165 . rf communication block 160 transmits / receives and respectively modulates / demodulates the rf data signals . internal power source 170 such as a primary battery , smart rechargeable battery or a super capacitor is used to power the implantable medical device 105 and all components and circuitry associated therewith . an analog - to - digital converter ( adc ) 175 converts the analog signal generated by the sensor element 140 to a digital signal prior to being processed by the microprocessor 165 . only a single sensor element 140 is shown , however , more than one sensor element may be employed to gather information regarding a physiological characteristic or the sensor element may be eliminated . external controller 145 includes a primary coil 180 electrically connected to an rf communication block 185 that transmits / receives and respectively modulates the rf data signals . the output of the rf communication block 185 is connected to a microprocessor 190 . all components and circuitry associated with the external controller 145 are powered by a power source 195 , e . g ., a battery or super capacitor . in a preferred embodiment , the power source 195 for powering the external device 145 and its associated circuitry and components is a secondary / rechargeable battery , most preferably a smart rechargeable battery , or a super capacitor . microprocessor 190 of external controller 145 compares the measured physiological characteristic ( e . g ., measured volume detected by sensor element 140 ) to a predetermined target or reference value ( e . g ., target or reference volume ) for the patient 110 . the predetermined target value may be ascertained through clinical assessment of the patient 110 and is therefore preferably customized for each particular patient . this target value is then preset or programmed into a memory associated with the external controller 145 . during operation , the external controller 145 energizes the implantable shunt apparatus 105 and detects the measured value of the physiological characteristic detected or measured by sensor element 140 . microprocessor 190 associated with external controller 145 determines whether the measured physiological characteristic value is higher than , lower than , or within an acceptable range of the target value . based on this assessment , the microprocessor 190 then determines whether the opening pressure and / or internal diameter or circumference of the shunt and flow rate of fluid passing therethrough should be increased , decreased or maintained accordingly in order to achieve the target ventricular volume for the patient 110 . once again , such functionality may alternatively be performed in a closed loop manner by the microprocessor 165 of the implantable medical device 105 . for instance , the rate of fluid flow or drainage is increased if the measured volume is higher than the target volume ; conversely , the flow rate and internal diameter of the shunt is decreased if the measured volume is lower than the target volume . the microprocessor 190 generates an output control signal to control the flow rate of the valve by altering the opening pressure and / or the opening , size , diameter or circumference of the shunt itself . if the measured volume is essentially the same as , or within an acceptable range of the target value , then no adjustment is made . an electrokinetic actuator 200 is used to convert electric potential to a movement or a force that may be used to adjust the valve 135 that controls the drainage rate through the shunt . a basic configuration of the electrokinetic actuator 200 is depicted in fig2 b & amp ; 2 c . electrokinetic actuator 200 has two chambers 208 , 209 separated by a porous dielectric 210 . chamber 209 is connected to one end of a bellows 211 capable of expanding and collapsing . a linearly displaceable actuator pin 212 is disposed at the opposite end of the bellows 211 . polar electrolyte 215 passes from chamber 208 to chamber 209 via the porous dielectric 210 upon the application of an electric field or potential to spaced - electrodes or electrode - arrays 220 . the porous dielectric 210 may include non - porous particles , high surface area structures fabricated within the channel , or microporous such as monolithic polymer networks . porous dielectric 210 offers at a minimum significant resistance or may prevent the polar electrolyte 215 from moving from one chamber to the other naturally in the absence of an electric field or potential . preferably , the electrokinetic actuator is biased to apply a minimum pressure or force even in the start position depicted in fig2 b . as shown in fig2 c , when an electric field or potential is applied across the electrodes 220 , the polar electrolyte 215 is driven from chamber 208 to 209 due to electro - osmotic flow . this movement of polar electrolyte 215 expands the bellows 211 attached to chamber 209 with a pressure corresponding to darcy permeability of the porous dielectric 210 and also the volume of the chamber 209 and the attached bellows 211 . the displacement of the bellows 211 and the actuator pin 212 with the associated pressure supporting it is utilized as the actuation mechanism for controlling the valve mechanism 135 that controls fluid flow in a shunt . pump performance in terms of pressure generated per volt of applied electric potential is determined by any one or more of several factors including composition of the porous dielectric material , the composition of the stationary phase and geometry as well as the properties of the electrolyte . the electrokinetic actuator 200 includes a mechanical valve actuation mechanism to titrate or adjust the pressure at which the fluid pathway will open or even the size of the fluidic pathway itself . in fig2 b and 2 c , the mechanical valve actuation mechanism is the bellows 211 and actuator pin 212 . several alternative more complex mechanical valve actuation mechanisms exhibiting rotation , translation or a combination thereof are shown in fig3 a , 3 b , 4 a , 4 b , 5 a , 5 b and 6 , however , different mechanical valve actuation mechanisms are contemplated and within the intended scope of the present invention . a brief description of each of the mechanical valve actuation mechanisms is provided below . fig3 a & amp ; 3 b shows a mechanical valve actuation mechanism including a rack - n - pinion gear in combination with a coil - spring and a linear extension or bias plate 241 . rack and pinion gear converts or translates rotation into linear motion or vice - versa . the relatively flat , toothed part is the rack 230 and the gear 235 is the pinion . rack 230 and pinion gear 235 each have formed or cut therein complementary teeth which mesh or engage with one another . the speed with which the pinion gear turns as the rack advances or retreats is determined by the diameter of the pinion gear and geometric ratios of the teeth . pinion gear 235 , in turn , is connected to one end of a coil - spring 240 while the opposite end of the coil - spring 240 is connected to a proximal end of a bias plate 241 . an opposite distal end of the bias plate 241 is affixed , fastened or secured to the valve mechanism 245 such as a ball - socket valve . bias plate 241 is supported and held fixed by a guide / fulcrum 216 . in operation , an electric field is applied via a power source 170 to electrodes 220 producing an electro - osmotic force that moves electrolyte 215 from chamber 208 towards chamber 209 thereby expanding the bellows 211 and displacing the actuator pin 212 which , in turn , pushes the proximal end of the rack 230 causing it to move to the right and rotate pinion gear 235 clock - wise ; as depicted in fig3 a . rotation of pinion gear 235 , in turn , applies tension on the coil - spring 240 causing it to apply increased pressure via the bias plate 241 on the valve mechanism 245 thereby restricting fluid flow . this increase in pressure on the valve mechanism 245 will increase the resistance on the valve mechanism opening and thereby decreasing the rate of drainage . as a corollary , one may reverse the field applied via the power source 170 to the electrodes 220 accordingly producing an electro - osmotic force that moves electrolyte 215 towards chamber 208 thereby causing the bellows 211 to collapse and move the rack 230 to the left and unwind the coil - spring 240 , as shown in fig3 b . this collapse or reverse movement will also be aided by the energy stored within the coil - spring 240 . the release in energy from the coil - spring 240 will , in turn , reduce the pressure applied by the bias plate 241 on the valve mechanism 245 decreasing the resistance at the valve mechanism opening and thereby increasing the rate of drainage . an alternative embodiment of a translational mechanical valve actuation mechanism is shown in fig4 a & amp ; 4 b wherein the bellows 211 is in contact with an actuator pin 212 which , in turn , is in contact with , a proximal end of a bias - plate 241 whereas its opposite distal end is affixed , fastened or secured to the valve mechanism 245 such as a ball - socket valve . in operation , an electric field is applied via a power source 170 to electrodes 220 producing an electro - osmotic force that moves electrolyte 215 from chamber 208 towards chamber 209 thereby expanding the bellows 211 which , in turn , displaces actuator pin 212 that pushes against a proximal end of a bias - spring 241 causing it to deflect , as depicted in fig4 b . a counterbalancing force will thereby be created on the opposite distal end of the bias - spring 241 that increases the pressure on the valve mechanism 245 correspondingly increasing the resistance to opening and thereby decreasing the rate of drainage . as a corollary , one may reverse the field applied via the power source 170 to the electrodes 220 accordingly producing an electro - osmotic force that moves electrolyte 215 from chamber 209 towards chamber 208 thereby causing the bellows 211 to collapse and displacing the actuator pin 212 to the left thereby releasing the tension on the proximal end of the bias - spring 241 . this reverse movement will also be aided by the energy stored within the bias - spring 241 . the release in energy from the bias - spring 241 will , in turn , reduce the pressure applied on the valve mechanism 245 thereby decreasing the resistance to opening of the valve mechanism 245 and increasing the rate of drainage . still another embodiment of a translational mechanical valve driving mechanism is shown in fig5 a & amp ; 5 b , wherein one end of the bellows 211 is in contact with the actuator pin 212 while the opposite end of the actuator pin is in contact with an increasing slope wedge member 255 that moves under the bias - spring 241 affixed , fastened or secured to the valve mechanism 245 such as a ball - socket valve . in operation , an electric field is applied via a power source 170 to electrodes 220 producing an electro - osmotic force that moves electrolyte 215 from chamber 208 towards chamber 209 thereby expanding the bellows 211 and displacing the actuator pin 212 and wedge 255 to the right , as shown in fig5 b . since the wedge 255 has an increasing slope with its widest part at its proximal end that is connected to the actuator pin , displacement of the wedge 255 pushes the proximal end of the bias - spring 241 upward causing the energy contained within it to increase . this increase in energy will result in increased pressure on the valve mechanism 245 and thus increase the resistance to opening ; thereby decreasing the rate of drainage . as a corollary , one may reverse the field applied via the power source 170 to the electrodes 220 accordingly producing an electro - osmotic force that moves electrolyte 215 from the chamber 209 towards chamber 208 thereby causing the bellows 211 to collapse and the wedge 255 to move to the left . this reverse movement will also be aided by the energy stored within the bias - spring 241 and , in turn , reduces the pressure applied by the bias - spring 241 on the valve mechanism 245 ; resulting in decreased resistance at the opening and thereby increasing the rate of drainage . all embodiments of the mechanical valve actuator mechanism described above may not only finely titrate the fluid flow therethrough but are also adapted to permit full fluid flow or cease or close off completely all fluid flow . in this last embodiment represented in fig6 , the flexible tubing 275 in which drainage of the fluid therethrough is to be controlled or regulated is received within a channel 243 of a constrictor block 241 . one side of constrictor block 241 is preferably connected directly to one end of the bellows 211 thereby eliminating the actuator pin 212 in order to maximize the surface area of contact . a constrictor 242 , preferably hemispherical in shape , is disposed within the channel 243 between the flexible tubing 275 and the side of the constrictor block 241 connected to the bellows 211 . the constrictor 242 and constrictor block 241 are preferably made from a magnetic resonance imaging ( mri ) compatible thermoset polymer , glass , natural stone ( e . g ., ruby ), hardened metal or alloy . materials used for the constrictor 242 and constrictor block 241 may be the same or different . constrictor 242 pushes against the flexible tubing 275 made of a biocompatible flexible and elastic material , for example , silicone or polyurethane . in operation , an electric field is applied via a power source 170 to electrodes 220 producing an electro - osmotic force that moves electrolyte 215 from chamber 208 towards chamber 209 thereby expanding the bellows 211 which , in turn , pushes the constrictor block 241 upward . the upward displacement of constrictor block 241 and constrictor 242 imposes a force against flexible tubing 275 causing it to deform and thereby restricting the cross - sectional size of the passage available for the fluid to drain therethrough . the preferred hemispherical shape of constrictor 242 distributes the pressure more gradually than a sharp edge and minimizes any damage to the flexible tubing with long - term operation . as a corollary , the electric field applied via the power source 170 to the electrodes 220 may be reversed producing an electro - osmotic force that moves electrolyte 215 from chamber 209 towards chamber 208 thereby causing the bellows 211 to collapse and reduce the pressure applied by the constrictor 242 on the flexible tubing 275 which will result in decreasing the resistance at the opening of valve member 245 and thereby increasing the rate of drainage . the embodiment depicted in fig6 of the present invention is adapted to finely titrate or full fluid flow rather than close off fluid passage completely . thus , the operation never closes off passage completely to prevent the passage of any fluid therethrough , but instead only titrates , adjusts or controls the size of the opening and rate of fluid flow by adjustment of the size , diameter or circumference of the channel 243 . flexible tube 275 is never restricted by the force imposed by constrictor 242 so as to completely close off and prevent passage of all fluid therethrough . as previously mentioned , the present inventive electrokinetic actuator is not limited to only those mechanical value actuation mechanisms expressly disclosed and illustrated herein . furthermore , the present inventive electrokinetic actuator to finely titrate fluid flow has been described with respect to a particular application of use with an externally programmable implantable shunt system for draining csf . other medical uses both implanted and external to the body as well as non - medical applications are contemplated and within the intended scope of the present invention . thus , while there have been shown , described , and pointed out fundamental novel features of the invention as applied to a preferred embodiment thereof , it will be understood that various omissions , substitutions , and changes in the form and details of the devices illustrated , and in their operation , may be made by those skilled in the art without departing from the spirit and scope of the invention . for example , it is expressly intended that all combinations of those elements and / or steps that perform substantially the same function , in substantially the same way , to achieve the same results be within the scope of the invention . substitutions of elements from one described embodiment to another are also fully intended and contemplated . it is also to be understood that the drawings are not necessarily drawn to scale , but that they are merely conceptual in nature . it is the intention , therefore , to be limited only as indicated by the scope of the claims appended hereto . every issued patent , pending patent application , publication , journal article , book or any other reference cited herein is each incorporated by reference in their entirety .

an electrokinetic actuator for fluid flow titration including two chambers separated from one another by a porous dielectric disposed therebetween . a plurality of electrodes are disposed about a perimeter of the first and second chambers . polar electrolyte disposed within the actuator is able to pass through the porous dielectric between the first and second chambers upon the application of an electric field or electric potential to the plural electrodes . a mechanical valve actuation mechanism connected to the second chamber allows for fine titration of fluid flow using electro - osmosis , including full - flow and / or complete cut - off . the polar electrolyte is isolated to prohibit intermixing with a fluid being titrated such as cerebrospinal fluid .

a first embodiment of a goods display hook according to the present invention is described below referring to fig1 - 5 of the accompanying drawings . a goods display hook 1 shown in fig1 comprises a main body 3 and a goods hanging arm ( hereinafter referred to as “ arm ”) 4 . the arm 4 has a goods hanging section 41 , a free end 41 ′ of which is slightly bent upward to prevent goods from dropping off and has an led lamp 5 at a tip thereof . the main body 3 is adapted to engage with a crossrail 2 drawn by a double - dotted imaginary line in the formed of a rectangular pipe which is assembled in a goods display furniture ( not shown ). as shown in fig3 , the main body 3 includes a bar holding section 30 which is comprised of a base plate 31 positioned on the top surface 21 of the crossrail 2 and front and rear hanging walls 32 and 32 ′ extending downwardly along the front and rear surface 22 , 23 of the crossrail 2 from the front and rear end of the base plate 31 . the crossrail 2 is held in a space 33 defined by the base plate 31 , front and real hanging walls 32 , 32 ′ of the bar holding section 30 of the main body 3 . as shown in fig3 , an arm supporting section 6 is formed above the bar holding section 30 of the main body 3 . the arm supporting section 6 comprises a pair of upright side walls 61 , 61 which are upwardly extending from the top surface of the base plate 31 of the bar holding section 30 to define a space 66 being open toward the top , front and back . a shaft 7 is connected between the upright walls 61 , 61 . a base end section 42 of the arm 4 is housed in the open space 66 and pivotally connected to the side walls 61 , 61 through the shaft 7 ( see fig1 ). the arm supporting section 6 further has an upright front short wall 34 serving as a stopper against the downward pivotal movement of the arm about the shaft 7 . when goods are hung on the goods hanging section 41 of the arm 4 , the arm 4 is held substantially in a horizontal position while resting on the upper end of the short wail 34 , and prevented from tilting down . a recess 36 is formed on the surface of the base plate 31 adjacent to the short wall 34 . the recess 36 and the short wall 34 define the housing of a coil spring 8 . the coil spring 8 is provided beneath the arm 4 at a position between a portion pivotally connected by the shaft 7 to the arm supporting section 6 of the main body 3 and the goods hanging section 41 of the arm 4 for urging to the arm 4 such that the goods hanging section 41 pivotally moves upwardly about the shaft 7 . other types of spring elements such as a flat spring may be used instead of the coil spring 8 . as shown in fig1 to 3 , a micro switch 9 is fixed to one of the side walls 61 at a position above the base end section 42 of the arm 4 . a switch button 92 projects the underside of a housing 91 of the micro switch 9 . a switch lever 93 having one end connected to the underside of the housing 91 and the other end 931 freely extending toward and coming into contact with the upper surface of an end 422 of the base end section 42 of the arm 4 which is on the opposite side of the shaft 7 to the goods hanging section 41 . the micro switch 9 is provided on the top surface of the housing 91 with electric terminals 94 which are connected through lead lines not shown to a terminal of the led lamp 5 attached to the free end 41 ′ of the goods hanging section 41 of the arm 4 and to a terminal of a battery 10 ′ described later ( see fig5 ). the embodiment described has the micro switch 9 disposed above the arm 4 on one side of the shaft 7 and the coil spring 8 disposed below the arm 4 on the other side of the shaft . the mounting layout of these elements will however not be restricted to this arrangement . the positions of the micro switch 9 and the coil spring 8 may be reversed with respect to the arm 4 and / or shaft 7 , or both the micro switch 9 and the coil spring 8 may be arranged on the same side with respect to the arm 4 and / or shaft 7 . the main body 3 is provided on the outer surface of the rear hanging wall 32 ′ with a power source box 10 containing a battery 10 ′. the power source box 10 has a terminal of the battery 10 ′ ( not shown ) on the upper surface thereof . a power switch 11 is disposed on the top surface of the power source box 10 and has a terminal ( not shown ) at the underside of its housing for electrical connection with the terminal of the battery 10 ′ and the terminal 94 of the micro switch 9 . in this embodiment , the main body 3 has the bar holding section 30 engageable with the crossrail 2 of the goods display hook and the upright side walls 61 , 61 constituting the arm supporting section 6 is made of synthetic resin and formed integrally with the bar holding section 30 of the main body 3 . however , the bar holding section 30 may be designed to be engageable with a horizontally extending material in the form of a bar , rod or wire other than the crossrail . likely , the arm supporting section 6 may be made of metal and may be formed separately from the bar holding section 30 of the main body 3 . further , in the embodiment described above , an led lamp is used for excellence in illuminance , a little power consumption , long service life as a light source , but other type of lamp including fluorescent lamp may be used . lamps with different colors including red , blue , yellow and green may be used for the goods display hooks according to the present invention to classify the goods to be hung on the hook by the different colors . this would help salespersons to find sold - out goods easily by glancing at the color of the lamp associated with the sold - out goods . then , a typical example of operation of the first embodiment according to the present invention will be explained referring to fig3 , 4 and 5 . in the state as shown in fig3 where goods 12 are hung on the arm 4 , the goods hanging section 41 of the arm 4 keeps a horizontal position while resting on the top surface of the short upright wall 34 serving as a stopper against the load of the goods 12 overcoming the resilient force of the coil spring 8 . in this state , the end 422 of the base end section 42 of the arm 4 contacts and presses the free end 931 of the switch lever 93 upward which in turn presses the switch button 92 at the intermediate portion of the lever . as apparent from the above , the button 92 and the lever 93 constitute an operating means of the micro switch 9 while the end 422 of the base end section 42 serves as an actuating means acting on the operating means of the micro switch 9 . fig5 shows an electric circuit of the goods display hook 1 in the state as shown in fig3 where goods 12 are hung on the goods hanging portion 41 of the arm 4 and the switch button 92 is pressed . in this state , as apparent from fig5 , the micro switch 9 is kept off . accordingly , as long as goods 12 are hung on the goods hanging section 41 and the switch button 92 is pressed , the micro switch 9 is not actuated even though the power source switch 11 is on , to thereby prevent the voltage of the battery 10 ′ from being applied to the led lamp 5 which is kept turned off . by changing the positional relationship between the micro switch 9 and the arm 4 , the electric circuit may be configured such that the micro switch 9 is actuated when the arm 4 is released from a load of goods hung thereon . fig4 shows the goods display hook 1 in the state where goods 12 are all removed from the goods hanging section 41 and there is no load on the arm 4 . the coil spring 8 pushes up the portion of the arm 4 between the pivoted portion 423 by the shaft 7 and the goods hanging section 41 , thereby pivotally moving the goods hanging section 41 of the arm 4 upward , in the counterclockwise direction b in the figure . at this time , since the opposite end 422 of the arm 4 is moved downward to release the force applied to the free end 931 of the lever 93 which in turn releases the pressure on the switch button 92 . in the state as shown in fig4 , the electric circuit is configured so as to turn on the micro switch 9 . if the power switch 11 is on , the voltage of the battery 10 ′ is applied to the led lamp 5 to turn on the lamp . since the lit led lamp 5 associated with the goods display hook having no goods hung on the arm can be easily found among many goods display hooks arranged on the display furniture , it is possible to replenish the hook with goods as soon as and just after the goods have been sold - out . the led lamp 5 can be set to remain lit unless the hook is replenish with goods for smooth replenishment . in the case where there is no stock for missing goods , the power source switch can be switched off to prevent power distribution to the led lamp 5 until replenishment with goods becomes possible . when the goods are delivered , switching on the power supply switch 11 and hanging the goods on the arm 4 presses the switch button 92 to prevent power distribution to the led lamp 5 , thereby turning off the led lamp 5 . a second embodiment of a goods display hook according to the present invention is described , referring to fig6 , in which a weight is used instead of the spring element 8 of the first embodiment . fig6 shows a cross - section view in the state where the hook is empty . in the second embodiment , a weight 8 ′ is attached to the lower surface of the base end section 42 of the arm 4 including an end 422 ′. the weight 8 ′ is formed separately from the base end section 42 of the embodiment , but it may be formed integrally with the arm , and may be made of metal or synthetic resin . an operation of the second embodiment of a goods display hook according to the present invention is described herein after almost the same as the first embodiment . namely , as shown in fig6 , there is no load of the goods 12 applied to the goods hanging section 41 of the arm 4 . the end 422 ′ of the base end section 42 of the arm 4 tilts down by the load of the weight 8 ′. this movement of the arm 4 releases the force applied to the free end 931 of the switch lever 93 which in turn releases the pressure applied to the switch button 92 , thereby actuating the micro switch 9 to turn on the led lamp 5 . the operation of the second embodiment in the state where goods 12 are hung on the hanging section 41 of the arm 4 is the same as that of the first embodiment and therefore omitted .

a goods display hook which enables salespersons to quickly and easily get information on the empty state of the goods display hooks . in a goods display hook comprising a main body engageable with a horizontally extending bar assembled in a goods display furniture and an arm including a base end supported by the main body and a goods hanging section extending from the base end section , the goods display hook further comprises a bias means for urging the arm in the direction that the goods hanging section tilts upwardly , the goods hanging section of the arm having a lamp at a free end thereof , the main body having a power source for the lamp , a switch device for the lamp and a shaft providing the arm with a pivotal movement , wherein the switch device is actuated by the arm to turn on the lamp when all the goods hung on the arm are removed which causes a pivotal movement of the arm in the direction that the goods hanging section tilts upwardly by the action of the bias means .

while this invention may be embodied in many different forms , there are shown in the drawings and described in detail herein specific embodiments of the invention . the present disclosure is an exemplification of the principles of the invention and is not intended to limit the invention to the particular embodiments illustrated . for the purposes of this disclosure , the term stent refers to stents , stent - grafts , grafts and other endoluminal prostheses whether self - expanding , balloon expandable , self - expanding and balloon expandable or otherwise expandable as are known in the art . in addition to the over - the - wire embodiments ( example also found in u . s . pat . no . 5 , 980 , 533 ) shown in the figures , the inventive catheter system and methods may also be provided in any catheter system , such as plain balloon angioplasty catheters and rapid - exchange configurations . examples of rapid - exchange catheters may be found in u . s . pat . no . 5 , 534 , 007 and u . s . pat . no . 5 , 833 , 706 . the inventive stent delivery systems may also be made in fixed wire form . examples of fixed - wire catheters may be found in u . s . pat . no . 5 , 702 , 364 . the system may be adapted for use with a medical device such as a stent , for example , a self - expanding , balloon expandable or combination self - expanding and balloon expandable stent . the system may also be used for delivery of other medical devices for use in the body as well including , but not limited to , ultrasonic devices , laser devices , vena cava filters , drug coated sleeves and other implantable drug delivery devices and the like . the inventive medical systems disclosed herein may also be provided with any of the features disclosed in u . s . pat . no . 6 , 096 , 056 , u . s . pat . no . 6 , 068 , 634 , u . s . pat . no . 6 , 036 , 697 , u . s . pat . no . 6 , 007 , 543 , u . s . pat . no . 5 , 968 , 069 , u . s . pat . no . 5 , 957 , 930 , u . s . pat . no . 5 , 944 , 726 , u . s . pat . no . 5 , 653 , 691 and u . s . pat . no . 5 , 534 , 007 . the stent delivery system may also comprise various coatings as are known in the art , including lubricious coatings to facilitate movement of the various parts of the system , as well as collagen - type coatings . more information concerning suitable coatings may be found in u . s . pat . no . 5 , 443 , 907 , and u . s . application ser . nos . 08 / 382 , 478 , 09 / 306 , 939 and 09 / 316 , 502 . the invention is also directed to medical device delivery systems and catheters produced using the inventive methods . for the purposes of the detailed description of the invention , figures of a portion of the distal end of a typical balloon catheter will be used . it should be understood , as mentioned above , that the present invention is applicable to other portions of the catheter as well as other medical devices , which use a constraining sleeve for bonding parts and joints together . it should also be understood that the materials used may be any of those materials known in the art where applicable . for the purposes of this disclosure , unless otherwise indicated , identical reference numerals used in different figures refer to the same component . fig1 illustrates the distal end of a typical balloon catheter 10 for delivering stent to a specific location within the body . the catheter 10 has an outer sheath 12 which extends over the body of the catheter 10 . the catheter also comprises an inner shaft 14 forming an inner lumen 18 , which allows access for a guide wire 15 . a balloon 16 is mounted on the catheter 10 at the distal end . the proximal end of the balloon 20 , in this type of catheter , is bonded to the distal end 22 of the outer sheath 12 at point 24 . in other embodiments , the proximal end of the balloon may also be bonded to the inner shaft . the catheter is typically guided through a guide catheter 53 ( shown in fig4 ). the distal end of the balloon 26 is mounted on the inner shaft 14 and will eventually be bonded to the inner shaft 14 at point 28 . there is a distal tip 30 at the distal end of the catheter , but , as will be explained later , it may not be needed due to the forming of a distal tip by the sleeve 32 ( hereafter called sleeve 32 ). marker bands 31 are also illustrated . the sleeves of the present embodiments suitably comprise non - cross linked thermoplastics , such as olefins and tecothanes , so that bonding and flowing is enhanced . the parts of the catheter to be made are held together via the sleeve 32 . as mentioned above , the sleeve 32 is heat shrunk around the parts to be permanently bonded to constrain them in place as a bonding aid . this is done typically at 200 - 250ef , however , the material dictates the temperature . in this instance , as shown in fig5 , a heating element 41 , such as a heat gun , a hot block or hot jaws , is used to apply heat to a point 43 on sleeve 32 . the heating element can be applied directly on the surface of the sleeve 32 . the heating element 41 can be then moved along the length of the sleeve 32 , as shown , causing the sleeve 32 material to shrink , and optionally flow . depending on the type of heating element used , movement may not be needed . the temperature is dictated by the material used . the heat must be sufficient to shrink the sleeve , but not so hot as to break the material down so as to destroy the integrity of the sleeve . by heating the material at or slightly above its melt temperature , the material will flow and create a fuse bond where bonds are desired . this bonding may be dictated by the part which is being made . for example , in the case of forming a stent retaining sleeve , it may be desirable to only bond a part of the sleeve , leaving the remaining portion shrunk but not bonded . this allows the stent retaining sleeve to be capable of moving relative to the balloon for effective release of the stent during delivery . complete bonding of the parts together at desired spots can be completed during the welding procedures . the moving heating element seals the sleeve 32 to the catheter , holding the parts of the catheter together . the longitudinal moving of the heating element and the flow of the sleeve 32 material stretches the material out and removes any air pockets to result in a tight , uniform fit . the shrinking of the sleeve 32 can start at one end of the sleeve 32 , proceeding to the opposite end . however , it is contemplated that the shrink may start at any place along the sleeve , gradually moving longitudinally . the bonding of the parts of the catheter is then started , suitably done by laser welding . the sleeve remains as part of the final product and in some cases can be used to hold a loaded stent in place during sterilization . in fig1 , sleeve 32 remains to form the distal tip of the catheter . in all cases , the sleeve may also act as an added protective layer and be lubricated for easy movement through body lumens . the port 34 of the inner lumen 18 may be closed due to the heat shrunk sleeve 32 until needed . if the catheter were a back loaded catheter , as shown , the guide wire 15 would pierce the closed port when needed . a sleeve 55 may also be used to secure the marker bands 31 to the inner shaft 14 during the securement of the marker bands 31 to the shaft 14 . sleeve 55 remains a part of the catheter and may be a soft protective cover over the marker band 31 to protect the balloon 16 from being damaged by the marker bands 31 . sleeve 5 may be used in any of the embodiments . in the embodiment shown in fig2 , a larger sleeve 36 is used . the word larger is used in terms of length of coverage over the catheter . in addition to the functions of sleeve 32 , as described above , sleeve 36 also forms a distal stent retaining sleeve 38 . as mentioned above , stent retaining sleeves are known . the materials and methods for applying and using the sleeve 32 are similarly applicable here . retaining sleeve 38 can aid in holding the stent 40 in place . the invention also contemplates a sleeve which may extend up the cones of the balloon , but not over the end of the stent . such a sleeve may aid in balloon rewrap as well as provide leading lubrication for the catheter to aid in trackability of the stent . the use of retaining sleeves to retain a stent on a catheter has been disclosed in a number of patents including u . s . pat . no . 4 , 950 , 227 to savin et al ., u . s . pat . no . 5 , 403 , 341 to solar and u . s . pat . no . 5 , 108 , 416 to ryan et al ., as well as u . s . pat . no . 5 , 944 , 726 and u . s . pat . no . 5 , 968 , 069 . one or more retaining sleeves typically retain the stent on the catheter when the stent is in an unexpanded state . upon expansion of the stent , the retaining sleeves release the stent . fig3 illustrates another embodiment . the method of applying the stent is the same . in this embodiment , an even larger sleeve 42 is used . in addition to the function of sleeves 32 and 36 , as described above , sleeve 42 also forms a proximal stent retaining sleeve 44 which extend down the proximal end of the balloon 16 , over the balloon waist 20 . it should be understood that , the sleeve 42 may extend further in the proximal direction to provide for bonding at point 24 . in this embodiment , sleeve 42 covers the entire balloon section , as well as the stent 40 . as described above , sleeve 42 constrains the parts of the catheter in this area until they are fully bonded , such as through laser welding . as with the other sleeves , sleeve 42 remains in place for sterilization and use . as part of the final catheter , sleeve 42 forms a distal tip 46 , a distal stent retaining sleeve 48 and a proximal stent retaining sleeve 44 . sleeve 42 also forms a tubular member 50 which surrounds the stent . this member may be used in the final product or discarded , according to the application . to allow the stent to eventually be separated from the catheter the stent retaining sleeves 44 , 48 are separated from the tubular member 50 by tear away perforations 52 . the tubular member 50 also may be drug eluting . it should be understood that an embodiment may comprise a catheter wherein the heat shrinkable sleeve covers the stent , but only provides one stent retaining portion , and therefore only one circumferential perforation . fig4 shows the embodiment of fig3 wherein the guide catheter 53 is withdrawn and the balloon 16 is expanded . as can be seen , the retaining sleeves 44 , 48 tear away , or are peeled , from the tubular member 50 and fall away from the stent 40 . the tubular member 50 must be made from a material which can expand with the stent . if the tubular member 50 is meant to be left in the body , it preferably should be biocompatible . in such a case , the stent effectively pushes it into the artery wall . biocompatible materials are well known in the art . they include , but are not limited to teflon and urethanes . the material may further include pharmaceutical agents to prevent restenosis . such agents may comprise proteins with small molecules , such as taxol - containing drugs , nucleotides and actinomycine . materials which eventually dissolves or disintegrates may also be used , such as polylactic acid . the tubular material 50 may also incorporated drugs which aid in the healing and acceptance of the stent , such as anti - thrombogenic agents . these types of agents are well known . teflon or a fluoropolymer may also be used for the tubular member 50 to protect against hyperplasia or restenosis . the member prevents the vessels from growing back in on the delivered stent . the present invention contemplates a multi - material sleeve 42 , which is pre - assembled . in such a sleeve , the retaining sleeve portions 44 , 48 may be made of a material which has less elasticity than the tubular member . the sleeve 42 may vary in other characteristics as well , such as lubricity and strength . it should be understood that the invention contemplates the use of the sleeve in any welding application . fig6 shows the process of a catheter midshaft bonding between a proximal shaft 64 and a distal shaft 62 . shaft 64 may be a metal hypotube . the ends of the shafts are fitted onto a mandrel 68 for support . in accordance with examples of the methods , a support mandrel may be used as support for other parts to be bonded together . a sleeve 66 is shrunk around the junction to be bonded . the sleeve 66 is then bonded to shafts 64 , 62 , providing a tight connection . the sleeve allows for a connection which does not require that the shafts overlap , as seen in fig1 at 24 , and thus a smooth inner transition . it should be understood that the connection at 24 may also be created by this method . fig7 - 10 illustrate the use of a sleeve 84 in connecting and sealing between a mid - shaft 72 , a distal shaft 74 and a distal inner shaft 76 , which functions as a guide wire lumen , in a rapid exchange catheter . rapid exchange catheters are well known in the art . these catheters are generally characterized in that a port 78 allows for insertion of certain parts from the outside of the catheter to the inside anywhere along the length of the catheter . in typical rapid exchange catheters , the port is for insertion of a guide wire or an inflation lumen . only the portion showing the port 78 and connection between the mid - shaft 72 , distal shaft 74 and distal inner shaft 76 is shown . fig7 shows the distal end 82 of the mid - shaft 72 inserted into the proximal end 80 of the distal shaft 74 . it should be understood that the distal shaft 74 could be inserted into the midshaft 72 in an inverted manner . a port 78 is positioned in the wall of the distal shaft 74 and / or the wall of the midshaft , depending on the port s positioning . in this particular embodiment , the port 78 opens into a guide wire lumen 76 , which is bonded to the distal shaft 74 and extends distally to the end of the catheter . a sleeve 84 is shrunk around the juncture of the shafts 72 , 74 . the shafts are then bonded together . the sleeve 84 also allows for a connection between the shafts 72 , 74 with a smooth internal transition , as shown in fig8 - 10 . in these embodiments , as with the embodiment shown in fig6 , the ends 82 , 80 of the shafts 72 , 74 are adjacent , but not overlapping . the shrunken sleeve 84 is used to connect the shafts 72 , 74 . the shafts 72 , 74 need not be bonded directly to each other . instead , the sleeve 84 may be bonded to each shaft . fig8 - 10 also show various positions of the port 78 . fig8 shows the port 78 in the proximal end 80 of the distal shaft 74 , fig9 shows the port 78 in the distal end of the midshaft and fig1 shows the port 78 being formed in the ends 80 , 82 of both shafts 74 , 72 . fig1 illustrates a further embodiment of the invention . this particular embodiment comprises a balloon 16 attached to the catheter , a proximal stent retaining sleeve 44 and a distal stent retaining sleeve 42 , an outer sheath 12 , a stent 40 and a proximal shrunken sleeve 100 and a distal shrunken sleeve 102 . the invention contemplates incorporating the proximal sleeve 100 or the distal sleeve 102 or both . as can be seen , the balloon is positioned on the catheter and then the stent retaining sleeves 108 , 110 are positioned . the stent retaining sleeves may extend beyond the ends of the balloon , as shown with sleeve 110 , to the ends of the balloon , as shown with sleeve 108 , or they may stop short of the ends of the balloons . it should be understood that the ends of the balloon 104 and the outer sheath 22 may overlap in either manner . only the manner in which the balloon end overlaps the sheath end is shown . in this particular embodiment , the shrunken sleeves 100 , 102 are shrunk down over these junctures . the bonds are then welded into place and the sleeves 100 , 102 are left in place . arrows 111 , 112 illustrate the preferred direction in which the sleeves 100 , 102 are welded . fig1 illustrates an alternative juncture configuration between the stent retaining sleeve , the balloon and the outer sheath . in this particular configuration , end of the balloon 104 does not overlap the end 22 of the outer sheath 12 . the stent retaining sleeve 108 extends beyond the end of the balloon and over or under the end of the outer sheath . the shrunken sleeve 100 is then shrunk down over the juncture and the components are then welded , as discussed above . for the examples shown , the medical balloon may be made of any suitable material including pebax . other suitable materials are disclosed in u . s . pat . no . 6 , 024 , 752 , and u . s . pat . no . 6 , 036 , 697 . for the examples shown , suitable materials for the outer sheath / shaft are well known in the art and include high density polyethylene ( hdpe ) and surlyn and those materials disclosed in u . s . pat . no . 6 , 036 , 697 and u . s . pat . no . 5 , 543 , 007 . the effectiveness of the bonding may be limited by the compatibility of the adjacent materials . adjacent materials which provide covalent bonding or molecular entanglement are examples of suitable material . for the examples shown , the inner shaft may be made of a flexible construction having any collapse strength . the inner shaft may also be made of an incompressible construction , such as a polymer encapsulated braid or coil . the flexibility of the braid / coil allows the medical device delivery system to navigate through body lumens and the incompressibility of the braid / coil aids in maintaining the integrity of the system and aids in deployment accuracy when during release of the medical device . the braid / coil may be comprised of stainless steel or nitinol , but desirably stainless steel encased in a polymer such as a polyimide , hdpe , teflon or urethane , but desirably polyimide or teflon . other suitable materials which may be used are well known in the art . portions of the sleeves may be radio opaque for the user to track the positioning within the body . methods of making the sleeve material radio opaque are well known . suitable examples include doping the raw material with radio opaque materials . the above sleeves also provide strain relief on joint of the catheter by diffusing the strain placed upon the catheter during storage and use . portions of the sleeves may be removed while other portions are maintained as part of the final catheter when desired . the sleeve may also take the form of a film / coating , paste or gel . typically , this embodiment may be used in parts of catheters which are not subject to a significant degree of contraction or pressure , such as a distal tip . a spray producing a dried film can be used , providing adequate axial resistance for welding purposes . suitable materials include urethanes , polystyrenes and polyesters . for pastes or gels , suitable ground up micro particles are dissolved and applied to the medical device where needed . axial resistance is provided with time drying or via a catalyst . the medical device delivery systems may be subjected to additional processing steps prior to and / or subsequent to disposing the retaining sleeve about the stent and balloon . for example , bumpers and / or marker bands may be disposed about the inner tube or other portions of the medical device delivery system . a retractable sheath may be provided over the balloon and stent . a manifold may also be provided at the proximal end of the medical device delivery system . other additional steps include providing to the inventive medical device delivery devices any of the features disclosed in u . s . pat . no . 6 , 096 , 056 , u . s . pat . no . 6 , 007 , 543 , u . s . pat . no . 5 , 968 , 069 , u . s . pat . no . 5 , 957 , 930 , u . s . pat . no . 5 , 944 , 726 and u . s . pat . no . 5 , 653 , 691 . in addition to being directed to the embodiments described above and claimed below , the present invention is further directed to embodiments having different combinations of the dependent features described above and / or claimed below . every patent , application or publication mentioned above is herein incorporated by reference . the above examples and disclosure are intended to be illustrative and not exhaustive . these examples and description will suggest many variations and alternatives to one of ordinary skill in this art . all these alternatives and variations are intended to be included within the scope of the claims , where the term “ comprising ” means “ including , but not limited to ”. those familiar with the art may recognize other equivalents to the specific embodiments described herein which equivalents are also intended to be encompassed by the claims . further , the particular features presented in the dependent claims can be combined with each other in other manners within the scope of the invention such that the invention should be recognized as also specifically directed to other embodiments having any other possible combination of the features of the dependent claims . for instance , for purposes of claim publication , any dependent claim which follows should be taken as alternatively written in a multiple dependent form from all prior claims which possess all antecedents referenced in such dependent claim if such multiple dependent format is an accepted format within the jurisdiction ( e . g . each claim depending directly from claim 1 should be alternatively taken as depending from all previous claims ). in jurisdictions where multiple dependent claim formats are restricted , the following dependent claims should each be also taken as alternatively written in each single dependent claim format which creates a dependency from a prior antecedent - possessing claim other than the specific claim listed in such dependent claim below ( e . g . claim 6 may be taken as alternatively dependent from any of claims 2 - 5 , claim 4 may be taken as alternatively dependent from claim 3 ; etc . ).

a medical device delivery system comprises an inner tube , a medical device disposed about a portion of the distal region of the inner tube , a medical device sheath disposed about the medical device , a medical device sheath retraction device extending proximally from the medical device sheath and an outer sheath disposed about a portion of the medical device sheath retraction device . the distal end of the outer sheath terminates at least one medical device length proximal of the medical device . the medical device sheath is movable relative to the outer sheath and relative to the inner tube .

the detailed embodiments of the present invention are disclosed herein . it should be understood , however , that the disclosed embodiments are merely exemplary of the invention , which may be embodied in various forms . therefore , the details disclosed herein are not to be interpreted as limited , but merely as the basis for the claims and as a basis for teaching one skilled in the art how to make and / or use the invention . fig1 to 3 illustrate a standard golf putter 10 including a ball striking face 12 , a heel 14 , a toe 16 , bottom surface 18 , top edge 20 , and hosel 22 for connection to a shaft , not shown . the ball striking face 12 is formed with a series of vertically oriented , free standing , raised rectangular projections 24 . the projections 24 are staggered row to row and form a brick type configuration , whereby the centers of one row of projections 24 are directly opposite the ends of projections 24 of an adjacent row . each projection has vertical parallel sides 26 and parallel horizontal ends 28 . the void area 30 between the projections 24 creates columns of spaces 32 between columns of projections 24 and spaces 34 between horizontal ends of the projections . the depth of the spaces 32 formed by the void area 30 is approximately 0 . 015 inches and does not exceed 0 . 017 inches . the dimensions of each projection 24 is preferably 0 . 125 inches in length , 0 . 063 inches in width and does not exceed 0 . 017 inches in height . the spaces 32 , 34 are the same width as the width of the projections 24 , that is 0 . 063 inches . preferably , in accordance with the present invention , the width of the projections 24 is the same as the width of the spaces 32 , 34 . however , the length , width , and spacing between the projections may be varied . fig4 and 5 show a second embodiment of a golf putter 100 having a series of horizontal rows of free standing , rectangular projections 102 on the ball striking face 104 . the projections 102 are staggered row to row and form a brick type configuration , whereby the centers of one row of projections 102 are opposite ends of projections 102 of an adjacent row . fig6 shows a third embodiment of a golf putter 200 having a series of elongated , vertical projections 202 at the center of the club face 204 and a series of free standing , raised rectangular projections 206 which are staggered in a vertical brick configuration at the heel 208 and toe 210 sections of the putter face 204 . fig7 shows a forth embodiment of a golf putter 300 using a series of spaced , hyphenated vertical raised projections 302 at the center of the club face 304 and a series of raised , free standing , rectangular projections 306 which are staggered in a vertical brick configuration at the heel 308 and toe 310 sections of the putter face 304 . fig8 and 12 show a fifth embodiment of a golf putter 400 using an array of three sided equilateral triangular shaped , free standing , raised projections 402 on the ball striking face 404 . fig9 shows a sixth embodiment of a golf putter 500 using a vertical , hyphenated groove configuration 502 on the ball striking face 504 . the hyphenated groove configuration 502 includes a series of individual lengths of grooves 506 vertically oriented across the ball striking face 504 . the grooves 506 have vertical sides 510 and horizontal ends 512 which form gripping edges on the putter striking face 504 . the individual lengths of grooves 506 are vertically spaced , in an end to end relationship , forming a gap 508 , between the vertically adjacent individual lengths of grooves 506 . fig1 shows a seventh embodiment of a golf putter 600 using a series of full length vertical grooves 602 centrally located on the club face 604 and an array of punch marks 606 at the heel 608 and toe 610 . fig1 shows an eighth embodiment of a golf putter 700 using an array of punch marks 702 centrally located on the club face 704 and a series of full length vertical grooves 706 at the heel 708 and toe 710 . while various preferred embodiments have been shown and described , it will be understood that there is no intent to limit the invention by such disclosure , but rather , is intended to cover all modifications and alternate constructions falling within the spirit and scope of the invention as defined in the appended claims .

a putter type golf club head having a variety of ball striking face configurations including free standing , raised projections , punch marks , vertical and horizontal grooves and combinations thereof .

in fig9 and 10 , the preferred embodiment of the hyperbaric resuscitation system of the present invention is designated by the numeral 10 . the system is preferably composed of a hyperbaric chamber 20 with minimum dimensions of 96 ″ ( 2 . 44 m ) in diameter with a 14 ′( 4 . 27 m ) usable length , capable of being pressurized to four atm abs , and built to pressure vessel human occupancy ( pvho ) standards . access to the chamber 20 can be through doors 81 and 82 large enough to roll equipment and patient 1 in and out ( e . g ., 34 ″× 54 ″— 86 cm × 137 cm ). access is preferably also provided by a quick - opening closure 22 with an opening diameter equal to the diameter of the chamber 20 . the entire resuscitation cart 21 will roll in and out of the chamber . the resuscitation cart comprises the patient gurney 27 , floor space around the gurney 27 for two to five emergency personnel 60 , a capnometer ( monitor of co2 in exhaled gas — not shown ), a defibrillator / cardiac monitor 31 with intravascular pressure monitoring capability , suction equipment 32 , volume cycled patient regulator / ventilator 33 , american heart association approved code cart 34 , a blood gas monitor 35 , an arterial line blood pressure manometer 36 , continuous ekg cardiac monitor with recorder 37 , rectal core thermistor 38 , x - ray equipment ( not shown ) for anterior / posterior neck , chest , and abdomen conventional views by portable x - ray equipment , a pulse oximeter ( not shown ) and a niroscope 51 capable of rapidly and continuously measuring cytochrome oxidase redox ratio in the cerebral cortex of the patient 1 . if one is willing to forego the quick - opening closure 22 , one could use a standard hospital hyperbaric chamber commercially available from perry oceonographics company . all niroscope - related equipment on the resuscitation cart 21 must be checked for suitability for operation in an hyperbaric atmosphere and , if necessary , the requisite modifications must be made . all above equipment is installed on a cart capable of being moved in and out of the entrance doors 81 / 82 of hyperbaric chamber 20 . the method of the present invention comprises placing a patient 1 with endotracheal tube 42 in place into hyperbaric chamber 20 having a volume sufficient to enclose a human patient 1 and at least two operating personnel 60 , pressurizing the hyperbaric chamber 20 to greater than existing barometric pressure ( preferably to at least 1 . 5 atmospheres ), providing oxygen - rich gas to be breathed by the patient 1 through endotracheal tube 42 , pressurizing the oxygen - rich gas to a pressure similar to that of the hyperbaric chamber 20 , and monitoring oxygen in cerebral tissue of the patient 1 with a non - invasive monitoring means ( such as niroscope 51 , 52 ). the method preferably also includes the step of automatically regulating the concentration of oxygen in the oxygen - rich gas in response to readings of the non - invasive monitoring means . at the option of the emergency center / attending emergency physician , a monoplace chamber 520 can house the patient 1 and all acls procedures conducted from the outside of the chamber 520 by robotic design ( see fig1 ). chamber 520 is provided with a connecting tunnel 43 to chamber 620 in case patient access is needed by medical personnel 560 . in such a case , medical personnel 560 would enter chamber 620 , chamber 620 would be pressurized to the same pressure as chamber 520 , then the personnel 560 would enter chamber 520 to work with patient 1 . description of present niroscope algorithm technology — multi - component analysis ( mca ) niroscopy is the application of absorption spectroscopy in the near infrared range for measuring the change in concentration of specific chromophores . the primary chromophores that are designated for measurement are oxidized and reduced cytochrome oxidase and oxygenated and deoxygenated hemoglobin . currently , measuring the change of the concentration of these chromophores by niroscopy is based on the following considerations and procedures . given an absorption curve over a range of wave lengths in the near infrared region ( 700 - 950 nm ) and assuming beer &# 39 ; s law is applicable , a set of simultaneous equations can be generated which , when solved , will result in concrete values for the relative concentrations of each of the chromophores . the number of equations is equal to the number of chromophores whose concentrations are to be determined . for example , in the brain , for the near infrared spectral region , there are the four aforementioned chromophores . if any four different near infrared wave lengths are selected for making total absorption measurements , four total absorption values will be obtained . using beer &# 39 ; s law , it is possible to solve for the concentration of each of the chromophores . the equations that are generated will contain the following variables : total absorption , chromophore extinction coefficients , concentration of each chromophore , and path length . total absorption is obtained by direct measurement . chromophore extinction coefficients are determined experimentally . total path length involves a complex series of events which may be considered constant for the system and therefore can be assumed to be unity . by solving these simultaneous equations by matrix operations it is possible to calculate the relative concentrations of each of the chromophores . the ratio of oxidized and reduced cytochrome is then calculated from the values obtained from the solution of the equations . the present method has certain errors inherent in its application . these are : 1 . the method assumes beer &# 39 ; s law is linear . however , beer &# 39 ; s law is not linear in a scattered media or in the presence of large absorbance changes of other chromophores . 2 . the extinction coefficients of cytochrome have been measured in bloodless rats where cytochrome oxidase was assumed to exist either entirely in the oxidized or completely reduced state . experimental evidence has shown that a condition of total oxidation or reduction of cytochrome oxidase does not exist . also a slight hemoglobin contamination was present during these measurements for which no correction was made . therefore , the relative concentrations of the cytochromes that were calculated were not accurate . 3 . the effects of water absorption overtones cannot be taken into account by modeling with beer &# 39 ; s law . 4 . because of the limitations associated with items 1 and 2 , current niroscopic techniques do not permit consistent measurements in adult humans . the signal obtained in adult humans is extremely faint since it is being masked by the high hemoglobin concentration . the present inventors perceived a need to develop niroscopic techniques that would obviate these limitations . the following is the theoretical description of the bases of the innovation of the present invention . it is the contention of the present inventors that the aforementioned limitations of the niroscopic techniques can be overcome by the use of a specific range of near infrared waves ( 600 - 1100 nm ) from which the change of a single absorption curve is obtained and used directly or corrected and from which the relevant data can be extracted via model - free mathematical operations , i . e . fourier transform / deconvolution analyses ( fta / fda ). fourier transforms are commonly used for infrared analysis and in digital signal filtering techniques , but are not so used in analyses of near infrared data . there is no obvious theoretical reason why such analyses could not be performed on data obtained from near infrared analyses . therefore , the present inventors decided to incorporate such analyses in theoretical models . the data used to demonstrate our proposed fourier transform operations are derived from a theoretical construct . a family of spectra is generated using beer &# 39 ; s law , and a set of measured extinction coefficients for each of the chromophores ( nioka 1991 ), and assuming a certain published physiological concentration of each chromophore obtained from cope ( 1988 ) and miyake ( 1991 ). after assuming hemoglobin is 100 % oxygenated , each calculated spectrum for a specific cytochrome oxidase ( cyt - aa 3 ) redox ratio ( i . e . varying from reduced to oxidized in steps of 10 % is plotted as optical density versus the wave length range of 700 to 950 mn ( fig1 )). the cyt - aa 3 absorbance extraction is as follows . each spectrum in the resultant family of spectra ( fig1 ) is subjected to removal of the dc component by subtraction of the average ( i . e . total area under each curve divided by the wave length interval ), resulting in the curves shown in fig3 . the curves in fig3 are then subjected to fourier transform procedures . form the results of fourier transforms , it is observed that the only value that changes as a function of the cytochrome redox ratio is the real component in the fundamental frequency . fig2 shows the amplitude of this real component of the fundamental frequency is linearly proportional to the percent oxidized cytochrome oxidase ( i . e . redox ratio ) to the fifth significant figure ( i . e . 0 . 04212 div ./ redox ratio of cyt - aa 3 ). the theory of fourier transforms ( brighan 1988 ) explains the reason for linearity . fig2 displays the absorbance for each chromophore in the 700 - 1100 nm wave length range . notice that the oxidized cyt - aa 3 spectrum 454 completes one cycle ( i . e . the fundamental frequency in the 700 - 950 nm wave length interval ). none of the other chromophores have this feature . fourier transform operator separates out the contribution of each component harmonic . the only spectrum completing one cycle in the chosen wave length interval is oxidized cyt - aa 3 . the effect is to extract the cyt - aa 3 while filtering out all other absorbance bands . signal extraction is improved by another fourier transform feature . when a fourier transform is performed on a function ( i . e . absorbance spectra ), one real value and one imaginary value will be determined for each component frequency . the real value represents the symmetrical portion of the component frequency , and the imaginary represents the asymmetrical portion of the component frequency . for a wave length interval of 700 - 950 nm , cyt - aa 3 is symmetrical ( i . e . only the real component is representative ) which once again extracts the cyt - aa 3 absorbance peak and filters out all others . this is the reason why the real component of the fundamental frequency is significantly linearly proportional to cyt - aa 3 redox ratio . the extraction technique is also quite robust with respect to signal to noise ratios ( s / n ). calculations have shown , when reducing the s / n ratios from 45 to 1 . 39 , the fundamental real component 468 does not change appreciably (± 2 %). even when considering inexpensive , noisy spectrophotometers which have a low s / n ratio , the s / n , although low , usually remains relatively constant . it will be removed with the dc portion of absorbance spectra . this implies that as long as the signal can be extracted ( i . e . not completely buried ) noise will have little effect . removing the dc component and the fourier transform also reduces the effect of noise due to scattering . the effects of large variations in hb and water were studied by generating another theoretical construct of spectra ( i . e ., high and low concentrations for hb and water ). these spectra were processed , and the resultant real component of fourier transfer change approximately 2 %. because our goal is to have hb or water affect the signal by 1 % or less , a second fourier transfer tool may be required . this second tool , fourier deconvolution analysis ( fda ) has been explained in detail by blass ( 1981 ). the expected nir total absorbance spectra is a combination of the major absorbance curves shown in fig2 . both de - oxygenated hb 452 and reduced cytochrome oxidase 456 have spectra resembling exponential decay , except de - oxygenated hb has a narrow peak 469 with a half width of 30 nm , centered at approximately 760 nm . the oxygenated form of hemoglobin 450 and the oxidized state of cytochrome oxidase 454 have broad peaks , with cytochrome oxidase having a half width of 175 nm ( 725 - 900 nm ) centered at 830 nm and deoxygenated hemoglobin having a halfwidth of 400 nm centered at 812 nm . because both water and de - oxygenated hb have distinct peaks , fourier self - deconvolution can be applied ( blass 1981 ). it is a method for resolving intrinsically overlapping absorbency bands ( an nir total absorbance spectrum ) into each component absorption curve of interest ( de - oxygenated hemoglobin and water ). it is , however , noise sensitive ( i . e ., will resolve noise if s / n ratios are large enough ) and therefor requires an expensive ( noise free ) ccd spectrophotometer . if a noise free ( i . e ., s / n greater than 1000 ) spectrophotometer is used , fda allows monitoring deoxygenated hemoglobin , and water separately . if there is a change in cyt - aa 3 absorbance inflicted by hb or water overtones , a corresponding correction can be made to the cyt - aa 3 result . the ability to monitor cerebral edema or de - hydration ( changing water content ) will also be useful information and could be easily displayed separately . a third tool called differential absorption spectroscopy may also be utilized to enhance the extraction of the cyt - aa 3 absorbance contribution . rather than use an arbitrary reference ( water for transparent spectroscopy or water plus microspheres for diffuse spectroscopy ) a reference spectra is taken in vivo either at a certain time ( admission of the patient ) or tissue location ( lower distance from light source than sample — see fig1 , 14 , or 15 , probe 203 ). using these spectra as reference will allow sensitivity to be increased by measuring change in absorbance rather than the actual value of absorbance . in summary , increasing the sensitivity of measurement with differential absorption spectroscopy and by combining the accurate measurement of fta with the possible correction to the cyt - aa 3 measurement made by fda , we can non - invasively measure the change in the cyt - aa 3 redox ratio with a model - free analysis using standard digital signal conditioning techniques . this should result in improved accuracy in adolescent swine and ultimately in the adult human head . the preferred equipment ( see fig5 ) comprises a near infra - red light source 100 , an optical pickup unit 211 , and dual wave interval spectrophotometer 300 , and computational equipment 316 . near infra - red light source 100 ( see fig1 ) is preferably a 100 watt power light source 101 in a steady or pulsating mode ( frequency range 0 . 5 - 2 hz ). an example of a suitable unit would be oriel 100 watt quartz halogen light source with dc stabilized radiometric power supply , including photofeedback system , water filter , multiple filter holder / fiber optic adaptor ( oriel model numbers 66195 , 68850 , 61940 , 62020 and 77797 ). optical pickup unit 200 / 211 ( see fig1 , 14 , 15 , 17 , 18 , 19 ) consists of fiber optics light conduit 23 connected to a single or ring of collimating beam probes 202 which inputs the light . the background light receivers are recessed single or ring collimated beam probes 203 adjusted at the proper angle to received background light . the sample light is again a recessed single collimated beam probe 202 either at the center of the rings ( fig1 and 16 ) or in single operation adjusted at the proper angle to receive light input ( fig1 ) ( oriel model 77545 and 77645 ). it should be noted that if the signal separation is satisfactorily accurate , subtraction of the background signal will not be necessary thereby eliminating the need for 16 each background pickup optodes 203 , optical chopper 301 , and bifurcated fiber optics bundle 302 . the preferred alternate equipment schematic is shown in fig8 . dual wave interval spectrophotometer 300 consists of an optical chopper 301 , bifurcated bundle 302 , and ccd spectrophotometer with sensitivity adequate to measure 0 . 005 o . d . absorbance and a dynamic range capable of measuring 4 o . d . in a wave length range of 600 - 1150 nm . an example of a suitable unit would be oriel insta iv ccd system 1024 × 128 with instaspec wedge flange , multispec spectrograph and grating assembly ( oriel model numbers 77118 , 77439 , 77400 , 77415 ). computational equipment preferably comprises a computer 311 with at least the speed and storage capability of an ibm personal computer , pentium with math co - processor , 10 gigabyte hard disk with tape back up drive , a national instruments a / d converter card , labview software for control , and galatic grams 32 / igor software for analysis . all data storage will preferably be done on a 105 megabyte removable cartridge type hard disk 312 ( i . e . sydos ). the present inventors have access to a pre - existing swine model for acute resuscitation under hyperbaric oxygen conditions using external cardiac massage . measured parameters include ekg ; eeg ; arterial , mixed venous , and sagittal sinus blood gases ; arterial , pulmonary arterial , pulmonary arterial wedge , mixed venous , and sagittal sinus pressures ; mixed venous and sagittal sinus hemoglobin saturation by direct oximetry ; cardiac output ; core temperature ; and expired gas . presently , the animal is maintained for two hours after resuscitation during which time normal pressures and blood gases are maintained . the model will require modification to include validation by niroscope measurements against cerebral po 2 measurements taken by inserting an oxygen sensing electrode through a burr hole drilled in the skull . the model should also be extended to include a 72 hour chronic model . 4 . serial improvement in single photon emission computerized tomography ( spect ) brain scan by ceretec ® ( technetium hexamethylpropyleneamine oxime ( hmpao )). case work on injured and resuscitated divers indicates that ceretec spect brain scanning elucidates perfusion / metabolism defects in the brain . ( 19 ). to test the system and method of the present inventions , the following human studies will be conducted with proper informed consent from immediate family or custodial person with power of attorney . two groups of 20 human patients arriving in cardiopulmonary arrest at emergency departments with ongoing cardiopulmonary resuscitation and acls will be stabilized by an emergency department hyperbaric acls team . the patients will be randomized into two groups . both groups will have the advantage of having hyperbaric environment modified michigan instrument automatic thumper ® and conventional acls pharmacology and acls algorithmic american heart association protocol . the subjects will be connected to a hyperbarically adapted volume cycled ventilator ( 10 mg / kg for tidal volume ) by endotracheal tube . partial arterial pressure of carbon dioxide ( paco 2 ) will be maintained at 40 mm hg by the rate of ventilation . the control group will be brought to pressure of 4 fsw ( 1 . 22 msw — meters of sea water ) and administered 100 % o 2 by the endotracheal tube . the niroscope will record the cerebral cortex redox ratio of cytochrome aa 3 . the treatment group will be initially administered 100 % o 2 , pressurized to minimum depths 60 fsw ( 18 . 3 msw ). once at 60 fsw ( 18 . 3 msw ), both breathing gas mixture and chamber pressure will be controlled by the attending emergency physician using the output of the niroscope as a guide . both groups will have cardiac monitoring by ekg and arterial continuous manometry by chart recorder . the patients post resuscitation , if successful , would have spect brain scan by ceretec ® hmpao utilizing a dedicated siemens triple head high resolution radionuclide camera with three - dimensional computer reconstructed brain images to determine the extent of ischemia - induced brain damage and the presence of potentially recoverable brain tissue . post - resuscitation treatment will include hbot at 1 . 5 ata ( atmospheres absolute ) twice a day for three days and once a day for four days . outcome indicators will include numbers 1 through 4 used in the animal experiment above , as well as percentage of improvement in hbot resuscitated patients . in addition , neurological function will be evaluated by a to - be - determined method . the development of superior mathematical separation techniques was necessary because although the technology for small animals and neonates has been available , it has not successfully been applied to adults . the niroscope is considered necessary for hbot resuscitation . it would also be considered an invaluable tool for routine acls resuscitations at one atmosphere . niroscopy will help to optimize treatments thereby limiting the exposure of patients and attending medical personnel to pressure environments greater than that which is necessary . thus , it helps prevent patients from being exposed unnecessarily to too high pressures of oxygen while simultaneously helping to reduce the possibility of dysbaric incidents in the attending personnel . any technology that informs physicians as to the efficacy of their resuscitation efforts would be extremely helpful . three different authors are proposing to use tissue or blood oxygen content for helping to evaluate success of resuscitative efforts by physicians . the niroscope 51 and 52 is shown in fig1 through 21 with the total niroscopic system shown in fig2 and 22 . the system is composed of a stabilized near infrared ( nir ) light source 100 ( fig1 ) which includes a stabilized power supply 110 , quartz tungsten halogen light element 102 , a parabolic light collector 111 , a hot mirror 105 which eliminates visible and far infrared , and fiber optics light conduit 107 . a band pass ( 600 - 1100 nm ) optical ( special order from oriel ) filter can also be used . nir light is transported via a fiber optics light conduit 216 and introduced into the patient &# 39 ; s cranium by the pickup unit 200 , 211 . the pickup unit 200 , 211 can be arranged in a single point mode ( fig1 ) or for maximum nir light delivery , a ring arrangement ( fig1 , 15 , and 16 ) or without background correction ( fig1 , 18 , or 19 ). referring back again to fig2 , nir light is delivered to the pickup unit 211 / 230 / 250 by fiber optics light conduit 216 through the wall 24 of the chamber 20 to the light input optode 202 , traverses through the scalp 205 ( see fig1 ), skull 206 , dura matter 207 , pia 208 , arachnoid 209 and cerebral cortex 210 , and back out again in reverse order via the nir diffuse light path 212 , 213 . it has been theoretically predicted by bonner and experimentally validated by mccormick that the depth of light penetration into the cranium is a function of optode spacing . an optode spacing of 5 cm has been found to be necessary to reach the cerebral cortex . background pickup optode / ring 203 is located at a distance of approximately 3 cm . this distance is adequate to receive photons that have traversed the scalp and skull but not deep enough to reach the cerebral cortex . the sample pickup optode 204 is positioned to receive photons that have traversed the scalp , skull dura matter , and pia . subtraction of the background signal from the sample signal results in only the signal representing the cerebral cortex . absorption spectroscopy requires that the initial light source spectrum be subtracted from the measured light spectrum after traversing through the tissue . the source absorbance spectrum emanating from the cerebral cortex can be highlighted by subtracting any absorbance due to the overlying tissues ( i . e ., scalp , skull , etc . ), from the spectrum measured at pickup optode 204 . the spectrum from the signal pickup optode 204 and the background pickup optode 203 are routed to the dual wave interval spectrophotometer 300 by fiber optic conduits 218 , 220 ( fig2 ). both signals are received by a optical chopper 301 where they are presented to the charge - coupled device 307 in sequence via an aperture 304 and optical grading 306 . it should be noted that electronic shutters ( made by newport model 845 hp ) could replace the optical chopper of low light level applications where needed . the optical grading 306 spreads the spectrum out over the ccd in such a manner that the photon spectra is converted into an electronic spectra which is amplified by amplifier 308 and converted into a digital signal by a / d converter 309 and digitally stored by digital data storage unit 312 . proper sequencing and timing is performed by clock driver 315 . in memory digital data storage unit 312 , two data streams are stored ( i . e . sample and background spectra ) ( see fig2 ). data storage unit 312 has available real time alternating background spectra 402 and real time alternating sample spectra 403 . all noise pixels are corrected in all spectra 412 and smoothed by sav - golay smoothing function ( 2 nd degree polynomial with 51 points ) 405 . a difference absorption spectrum is then calculated 413 using each pair of background 402 and sample 403 spectrum . an example of calculated difference absorption spectrum 3 is shown in fig1 . next , the dc component of the difference spectrum 3 is removed by integrating the spectrum 3 over the wave length span 400 to 1100 nm , calculating the average wavelength adjustment by dividing the result of the integral by the wave length span interval , and then subtracting the resultant from each wave length absorbance value in the wave length span . an example of absorbance spectrum with dc component removed 5 is in fig2 . at this point the fourier window 406 will be established . the fourier window is the wave length interval about which the fourier transform will be taken . it can be a general window which will separate each chromophore ( i . e . oxidized and reduced cytochrome oxidase , oxyhemoglobin , deoxyhemoglobin , and water ) into specific harmonic components , or a window for each chromophore can be established . at this point a fourier transform 408 of the spectrum is computed resulting in values for each chromophore . as an alternate , fourier deconvolution analysis 409 may be used if a more accurate indices of chromophore change is resulted . the resulting indices ( for change in oxidized and reduced cytochrome oxidase , oxyhemoglobin and deoxyhemoglobin , and water ) are stored 410 in data storage unit 312 . these values may be displayed directly on monitor 313 as a function of time start of data acquisition or summed 411 and applied 460 to correct the cytochrome oxidase indices if the absorbance peaks are found to be interdependent . an alternate simplified method shown in fig2 is as follows . rather than taking background spectra alternately with sample spectra , a single background spectrum is established before any sample spectrum is taken . immediately after setup , a series of twenty spectra 418 are taken ( for example with 6 second exposure and 4 second interval ) and stored in data storage unit 312 . individual noise pixels are corrected 412 . these twenty spectra are averaged 404 resulting in one average spectrum . the average spectrum is used as a constant background spectrum for the absorbance calculation of all subsequent sample spectra . all other steps remain the same as in fig2 . this technique allow a less complicated arrangement as shown in fig8 verses the more complex arrangement shown in fig7 . all processing is preferably done in pentium computer 311 , with galatic - gram 32 software . all of this equipment is commercially available in the form of a personal computer and a ccd spectrophotometer made by oriel inc . all optical equipment used with the present invention is preferably from oriel inc . all control software is preferably from national instrument and analytical software is preferably grams 32 from galatic and igor . the computer is preferably a standard pentium . all measurements disclosed herein are at standard temperature and pressure , at sea level on earth , unless indicated otherwise . all materials used or intended to be used in a human being are biocompatible , unless indicated otherwise . 1 . virtis , m . cost / benefit analysis of cardiopulmonary resuscitation : a comprehensive study - part ii . nursing management 23 ( 4 ): 50 - 54 , 1992 . 2 . ebell , m . & amp ; kruse , j . a proposed model for the cost of cardiopulmonary resuscitation . medical care 32 ( 6 ): 640 - 649 , 1994 . 3 . safar , p . cerebral resuscitation after cardiac arrest : research initiatives and future directions . ann of emerg med 22 ( 2 ): 2324 - 2349 . 4 . holbach , l ., et al . differentiation between reversible and irreversible post - stroke changes in brain tissue : its relevance for cerebrovascular surgery . surg neurol , 7 : 325 - 331 , 1977 . 5 . iwatsuki , n ., et al . hyperbaric oxygen combined with nicardipine administration accelerates neurologic recovery after cerebral ischemia in a canine model . critical care medicine , 22 ( 5 ): 858 - 863 , 1994 . 6 . van meter , k ., gottlieb , s ., & amp ; whidden , s . hyperbaric oxygen as an adjunct in acls on guinea pigs after 15 minutes of cardiopulmonary arrest . undersea biomedical research , 15 ( suppl ): 55 - 56 , 1988 . 7 . neubauer , r ., gottlieb , s . enhancing “ idling neurons .” lancet 335 : 542 , 1990 . 8 . neubauer , r ., gottlieb , s ., & amp ; miale , a . identification of hypometabolic areas in the brain using brain imaging and hyperbaric oxygen . clinical nuclear medicine 17 : 477 - 481 , 1992 . 9 . neubauer , r . gottlieb , s ., pevsner , h . hyperbaric oxygen for treatment of closed head injury . southern medical journal 84 ( 9 ): 933 - 936 , 1994 . 10 . waxman , k ., annas , c ., daughters , k ., et al . a method to determine the adequacy of resuscitation using tissue oxygen monitoring . journal of trauma 36 ( 6 ): 852 - 857 . 11 . rivers , e ., martin , g ., et al . the clinical implications of continuous central venous oxygen saturation during human cpr . annals of emergency medicine 21 : 1094 - 1101 , 1992 . 12 . mccormick , p ., stewart , g ., et al . measurement of human hypothermic cerebral oxygen metabolism by transmission spectroscopy . advances in experimental medicine and biology 333 : 33 - 41 , 1993 . 13 . jobsis , f ., piantadosi , g . et al . near infrared monitoring of cerebral oxygen sufficiency . neuro resea 10 : 7 - 17 , 1988 . 14 . brazy , j . & amp ; lewis , d . changes in cerebral blood volume and cytochrome aa3 during hypertensive peaks in pre - term infarcts 108 : 983 - 987 , 1986 . 15 . glaister , d ., jobsis , f . a near infrared spectrophotometric method for studying brain o 2 sufficiency in man during + g z acceleration . aviation , space and environmental medicine 59 ( 3 ): 199 - 207 , 1988 . 16 . cope , m . et al . system for long term measurement of cerebral blood and tissue oxygenation on newborn infants by near infrared translumination . med and biol eng comp 26 : 289 - 294 , 1988 . 17 . hoshi , y . et al . oxygen dependence of redox state of copper in cytochrome oxidase in vitro . j app phys 74 ( 9 ): 1622 - 1627 , 1993 . 18 . wray , s ., et al . characterization of near infrared absorption spectra of cytochrome aa3 and hemoglobin for the non - invasive monitoring of cerebral oxygenation , bioch and biophy acta 933 : 918 - 929 , 1987 . 19 . adkisson g h , hodgson m , smith f , torok z , macleon m a , sykes j j w , strack c , pearson r r , cerebral perfusion deficits in dysbaric illness , the lancet , 2 , 119 - 121 , 1989 . 20 . matcher s , elwell c , cooper e , cope m , delpy d . performance comparison of several published tissue near - infrared spectroscopy algorithms . analytical biochemistry 1995 ; 227 : 54 - 68 . 21 . miyake h ., nioda s ., zaman a ., smith d ., chance b . the detection of cytochrome oxidase , heme iron , and copper absorption in blood perfused and blood free brain in normoxia and hypoxia . analytical biochemistry 1991 ; 192 : 149 - 155 . incorporated herein by reference is the paper entitled “ cytochrome oxidase reduction / oxidation charge coupled monitor with large area pickup optode ”, which describes results of the invention of the present inventors applied to a swine model . the foregoing embodiments are presented by way of example only ; the scope of the present invention is to be limited only by the following claims .

a hyperbaric resuscitation system includes a hyperbaric chamber having a volume sufficient to enclose a human patient and at least two operating personnel . the system also includes a device for pressurizing the hyperbaric chamber to at least 1 . 5 atmospheres with air . the concentration of oxygen in high pressure , oxygen - rich gas to be breathed by the patient provided by an independent system at chamber pressure is automatically regulated by a regulating system which receives information about the amount of oxygen in cerebral tissue of the patient from a spectrophotometer . although devices for measuring the exact amount of oxygen in cerebral tissue do not yet exist , the presently available devices can show trends in the amount of oxygen in the tissue . since the physician working on a patient in a hyperbaric resuscitation system is more concerned about trending than exact values , the present system can still be of great benefit in resuscitating patients .

fig1 shows schematically an endoscopic system 1 with eyepiece 2 and insertion part 3 . the insertion part 3 can be configured as a rigid tube or flexibly . ahead of or instead of the eyepiece with optic transmission of the observed image , a video camera can be provided with the observed image depicted on a monitor . mounted in a supply unit 10 is an excitation beam source 5 , which contains a laser diode 14 and a coupling lens 7 for feeding the excitation light into a light conductor 13 , which is configured as a glass fiber . the coupling of the excitation light can also occur directly without insertion of a coupling lens by quasi - contacting the surface of the chip of the laser diode with the proximal end of the glass fiber 13 , where if necessary a minimum distance to the output mirror of the laser chip must be guaranteed for sufficient recoupling into the laser medium . it is also possible of course to provide additional laser diodes with emission of additional wavelengths , whose radiance can likewise be fed into the light conductor 13 or into additional glass fibers . thus , for instance , spectral weaknesses of the white light can be compensated . the laser diodes can be battery - operated or provided with energy by a network part . the glass fiber 13 is passed through a coupling element 19 configured as a metallic eyelet . the metallic eyelet 19 is soldered onto the housing 6 of the actuator 11 , which is configured as vibration motor . the vibration motor 11 is positioned on a holder element 21 , which is secured on the housing 12 of the supply unit 10 . the holder element 21 is at least partly made of materials that possess high elasticity and / or a high damping effect . through a corresponding appropriate selection of material components of the holder element 21 , it is possible to reduce any transmission of mechanic motions , caused by the vibration motor 11 , onto the housing 12 of the supply unit 10 . the holder element 21 exerts an effect that is comparable to a shock absorber in automotive technology . the eyelet 19 is struck against the glass fiber 13 by means of the motions of the vibration motor 11 . the reserve length of the glass fiber 13 can be formed into a spiral . this allows a great part of the glass fiber 13 to be excited to mechanical motions , without at the same time necessarily raising the amplitudes of the vibration motions of the vibration motor 11 . in fig1 the double arrow indicates the direction of motions caused by the actuator 11 in the illustrated embodiment . to connect the supply unit 10 with the endoscopic system 1 , a light - conducting cable 24 is provided , which can be connected to the supply unit 10 by special or commercially produced plug - in connection on the endoscope or for instance with a light - conducting plug 15 . other types of connection are also possible , such as demonstrated in the detail in fig2 . the plug - in connections can , in particular , be produced as autoclavable and laser - protected . the glass fiber 8 is usually fed through the insertion part 3 to the distal end , either loose or in a separate illumination channel or in a protective casing . at the distal end a fluorescence converter 4 is positioned , in which the conversion occurs in white light . the fluorescence converter 4 can be functionally replaceable or integrated into a replaceable exchange head on the distal end of the insertion part . the imaging lens is not further illustrated here . the supply unit 10 of the endoscopic system 1 is shown in fig2 . the supply unit 10 comprises a housing 12 in which a light source 14 , a light conductor 13 , an actuator 11 , coupling element 19 , and a cooling device 18 are positioned . the light source 14 is thermally conducting in connection with the cooling device 18 ; that is , with a heat conductible cooling body 20 , where a thermally conducting connection is understood as a direct or indirect thermal coupling of both components . the cooling body 20 is positioned on a side of the light source 14 turned away from the optic light conductor 13 , where the light source 14 is mounted preferably directly on the cooling body 20 , so that heat produced by the light source 14 can be given off directly to the cooling body 20 and removed by it . the cooling body 20 , in addition , is thermally conducting in connection with the housing 12 , so that heat absorbed by the cooling body can be diverted to the housing 12 . the cooling body 20 in terms of its dimensions is configured to be large in comparison to the light source 14 , so that the cooling body 20 can efficiently absorb and remove heat produced by the light source 14 . the actuator 11 sits on an elastic carrier element 23 that is secured onto a holder element 21 . the holder element is directly connected with the housing 12 . a motor 27 with an imbalance element 29 is positioned in the housing 25 of the actuator 11 . when the motor 27 is in operation , the imbalance element , configured in the form of an eccentric disc , rotates around the motor shaft 31 . the housing 25 of the actuator 21 is deflected by the rotary motion of the imbalance element . these deflections are transmitted directly onto the coupling elements 19 , which are in material connection with the housing 25 . the elastic carrier element 23 prevents transmission of the deflections onto the holder element 21 , whereby the deflections could spread themselves to the housing 12 and thus in the entire supply unit and would lead to unintended disturbances of the endoscopic system 1 . the light - conducting element 11 is configured as light - conducting fiber . it is in a light - conducting connection by a light - conducting connector 15 with the light source 14 , which is configured in the form of a diode laser . the light - conducting element 13 is conducted through by the larger openings of the coupling elements 19 , which are configured in the form of metal rings . the coupling elements 19 , when the motor 27 is in operation , strike from time to time unforeseeably against the light - conducting element 13 because the eccentric disc 29 , which rotates around the motor axis 31 , deflects the housing 25 of the actuator 11 and the coupling elements mounted on it . as a result , the course of the beam path is modified in the light - conducting fiber , so that the coherence of the light of the laser diode 14 on the distal transition of the light fiber 13 to the optic light - conducting coupling element 17 is destroyed . the light - conducting coupling element 17 produces a light - conducting connection between the light - conducting fiber 13 and the optic light - conducting element 16 . a proximal end 22 of a light - conducting cable 24 , which is connected with an insertion part ( compare fig1 ), can be inserted into the housing 12 through a cylinder 28 mounted in an aperture 26 of the housing 12 , or the proximal end 22 of the light - conducting cable 24 can be mounted , once inserted , firmly in the supply unit 10 . the proximal end 22 of the light - conducting cable 24 comes to rest in the housing 12 in such a way that a front surface 30 of the proximal end 22 of the light - conducting cable 24 points in the direction of the light source 14 and is positioned at a close distance from it . mounted between the front surface 30 of the proximal end 22 of the light - conducting cable 24 and the light source 24 is the electrically insulating optic light - conducting element 16 , which is held by an electrically insulating holder element 32 in the housing 12 . according to fig3 , the cylinder 28 is positioned in the opening 26 in order to insert the proximal end 22 of the light - conducting cable 25 into the housing 12 of the supply unit 10 . the cylinder 28 is configured as a short , cylindrical hollow tube with a ring - shaped widening 34 that serves to secure the cylinder 28 on the housing 12 . mounted in material connection in the cylinder 28 is a frame 36 , which likewise is configured as a cylindrical hollow tube . a first end area 38 of the frame 36 , which is positioned outside the cylinder 28 , that is , outside the housing 12 and is inserted through the proximal end 22 of the light - conducting cable 24 into the housing 12 , is widened in a ring shape . a second end area 40 of the frame 36 comprises a fully surrounding recess 42 , whose diameter is greater than an interior diameter of the frame 36 . a first segment 44 of a disc 46 is enclosed , in material connection , in the recess 42 . a second ring - shaped segment 48 of the disc 46 comprises a greater outer diameter than the first segment 44 of the disc 46 and than the frame 36 , so that it extends beyond the frame 36 . the disc 46 also comprises a cylindrical passage 50 whose inner diameter corresponds approximately to an inner diameter of the frame 36 . the optic light - conducting element 16 is mounted in the passage 50 of the disc 46 . the holder element 32 shown in fig2 is configured here as the frame 36 and the disc 46 , where both components are produced from an electrically insulating material such as plastic . the light source 14 is positioned at a distance from the a front side 52 of the second segment of the disc 46 and connected backwards with the cooling body 20 by at least one screw 54 , where the at least one screw 54 can be configured , for instance , as an m3 thread . a light - conducting fiber 13 is in a light - conducting connection with the light source 14 by way of a light - conducting plug connector 15 . the distal end of the light - conducting fiber 13 is in light - conducting connection with the optic light - conducting element 16 , which is positioned in the cylindrical passage 50 , by means of a light - conducting coupling element 17 . the light - conducting fiber 13 is surrounded by the coupling element 19 , which is configured for instance as a metallic ring . in the embodiment of fig2 , no material or form - locking connection exists between the coupling element 19 and the light - conducting fiber 13 . the coupling element 19 is in material connection with the actuator 11 , which takes the form of a vibration motor in the embodiment illustrated in fig2 , as it is used for tactile signaling in mobile telephones . the actuator 11 is connected , by non - illustrated connecting connections , with a control can be operated by a switch and regulator on the front side ( not illustrated ) of the supply unit 10 . the actuator 11 in particular can be switched on and off , so that more complex switchings of the powering of the actuator 11 can also be arranged . the actuator 11 is positioned on an elastic carrier element 23 , which is mounted on a holder element 21 that is secured on the inside of the housing 12 of the illumination system 10 . the elastic carrier element is configured in such a way that as few vibrations as possible of the actuator 11 are transmitted to the housing 12 . the cooling device 18 is configured as a passive cooling in this preferred embodiment and functions by heat conduction between the light source 14 and the cooling body 20 . it comprises the heat conducting cooler body 20 that serves for conducting heat produced by the light source 14 and is positioned on the side of the light source 14 turned away from the optic light - conducting element 13 . the cooling body 20 also comprises raised ribs 58 to increase heat deflection , which taper toward their free ends . the ribs are spaced apart in such a way that screws 62 are positioned in the intervening surfaces 60 and serve to secure the cooling body 20 to the housing 12 . heat produced by the light source 14 is transferred to the cooling body 20 by the direct contact between the light source 14 and the cooling body 20 as well as by the at least one screw 54 . heat conducted to the cooling body 20 is distributed along the cooling body 20 and is conducted by it onto the housing 12 . the cooling device 18 can likewise be configured as a heat pipe , where the cooling body 20 is configured for this purpose , for instance as a closed - off hollow body of a heat - conducting material such as aluminum . a capillary - acting , wick - like material is positioned on an inside surface of the hollow body . the hollow body is also filled with a liquid under its own pressure or possibly under a reduced pressure . if heat is conveyed from the light source 14 to a surface of the heat pipe , then the liquid in the interior of the heat pipe starts to boil and converts to steam by absorbing heat energy . this steam is distributed in the hollow body and condensed while emitting heat to a cooler place on the inner wall of the heat pipe . the capillary acting , wick - type material again absorbs the condensed liquid and transports it back to a place on the heat pipe on which heat is conveyed . the heat pipe therefore forms a closed cooling circuit by which the illuminating system 10 can be cooled efficiently . the proximal end 22 of the light - conducting cable 24 can be held in the frame 36 by a fixing mechanism . for this purpose a locking lever 64 is positioned on the frame 36 , by means of which the proximal end 22 of the light - conducting cable , for instance , can be clamped shut . fig4 shows a proximal supply unit 10 in which a fluorescence converter 4 is already positioned . the fluorescence converter 4 closes off the three - legged housing 9 of the excitation ray source 5 . the light source 14 is configured as a laser chip whose active surface is turned toward the fluorescence converter 4 and illuminates said converter . the laser chip 14 is positioned on a cooling body or heat conducting body 20 . the heat conducting body 20 is mounted on the housing 9 . the heat is emitted from the laser chip 12 onto the heat conducting body 20 and then to the housing 9 and from there is conveyed onward to the supply unit 12 by cooling sheet metal that is not shown and by fixing elements . the laser chip 14 , which in this example supplies excitation light in the blue spectral range , excites the fluorescence converter 4 . the fluorescent radiance of the fluorescence converter 4 and the transmitted excitation light of the laser chip 14 form a white light . this white illuminating light is radiated in a wide angle of the space ( not shown ) in the direction of the light - conducting element 16 , which in this example takes the form of conical glass conical stump . between the cover surface of the glass conical stump 16 and the fluorescence converter 4 , compensating media , not illustrated , can be provided for flexible compensation of the index of refraction . the glass conical stump 16 is secured on a socket - shaped elastic carrier element 23 made of rubber . the carrier element 23 is positioned on a holder element 21 , which is installed in the housing 12 of the supply unit 10 in the form of a metal plate or circuit board . situated beside it is an actuator 11 . the motor 27 of the actuator 11 is mounted on an additional elastic carrier element 23 ′. the rotary motor 27 comprises an imbalance 29 , which is secured on its motor axis . the coupling element 19 , which is formed from an open , three - member chain of ring - shaped links , is secured on the housing 25 of the motor 27 and on the glass conical stump 16 . a connection for power transmission between the motor 27 and the glass conical stump 16 is thereby produced . the rotary motions of the motor 27 , because of the imbalance 29 , set the motor housing 25 in vibrations , which are transmitted by the individual chain members of the coupling element 19 onto the glass conical stump 16 , so that the loose configuration of the transmission chain modifies the time sequence of the vibrations . the resulting disturbances cause tension modifications in the glass conical stump 16 , which lead to corresponding time changes in the index of refraction of the glass conical stump . the oscillations of the index of refraction modulate the phase of the electromagnetic light , which is conducted by the glass conical stump 16 . the temporal coherence of the excitation radiance is conveyed with the oscillations of the phase induced by the temporal variations of the index of refraction , so the index coherence is reduced and in the best case is realigned . the front side 30 of a class fiber bundle 8 is positioned at a close distance essentially parallel to the ground surface of the glass conical stump 16 . the intermediate space formed thereby can in turn comprise compensating media ( not illustrated ) for flexible compensation of the index of refraction in order to keep the light losses at this coupling site of the light conduction as low as possible . the glass fiber bundle 8 runs inside a light - conducting cable 25 whose distal end , not illustrated , is connected to the light - conducting connection of an endoscope . the light - conducting cable 24 includes on its proximal end 22 a plug - in connection 15 , which is inserted form - locked into the connection cylinder 28 of the housing 12 of the supply unit 10 . the actuator 11 can , as shown for example in fig5 , also take the form of a commercially available speaker 310 . the speaker housing 312 is secured on the housing 12 of the illuminating system 10 ( not shown ). the coupling element 19 is cemented onto the speaker membrane 320 and is configured as a plastic ring . the light fiber 13 is conducted through the plastic ring 19 and is in light - conducting connection with the light source 14 , which takes the form of a diode laser ( not shown ). the connecting lines 335 and 336 connect the speaker 310 with the frequency generator 340 by means of the connector cylinders 336 and 338 . the frequency generator has available a regulator 342 and a frequency monitor 344 . the speaker membrane can be impacted with signals of the frequency generator that can no longer be perceived by the human ear . these signals deflect the speaker membrane 320 , which in turn deflects the cemented - on plastic ring 19 , which pushes against the light - conducting fiber 13 and thus causes disturbances of the ray path in the light - conducting fiber 13 . in the preferred embodiment shown in fig6 , a metallic flywheel 400 serves as coupling element between the actuator 11 and the light - conducting element 13 . the flywheel is mounted rotatably on the axle 404 that is secured to the fixing rod 470 . the fixing rod 470 is positioned on the elastic carrier element 23 . the flywheel 400 comprises , in addition to the central borehole 402 for the rotary axle 404 an outer axial borehole 430 through which the light conductor 13 is passed in form - locking connection . the light conductor 13 here can in addition be in a material connection with the flywheel , for instance by an appropriate cement or a molding mass that is inserted into the bore - hole 430 between the flywheel 400 and the light conductor 13 . the inner end of a spiral spring 440 is connected on the rotary axle 402 with the flywheel 400 . the outer end of the spiral spring 440 engages in a borehole 442 of a lever 450 , in which borehole the outer end of the spiral spring 440 is secured . the lever 440 is rotatably connected on the rotary axle 402 and rotatably connected with the drive rod 420 by a pin 444 , which is surrounded by a borehole of the lever in form - locking connection . the actuator 11 comprises an eccentric disc 410 , which rotates around the rotary axle 412 of the motor 27 . the drive rod 420 is form - locked through a borehole with the pin 446 , which is secured on the eccentric disc 410 . the rotary motion of the eccentric disc , which is set off by the motor 27 , is transformed into a rotary motion of the flywheel 400 by means of the transmission chain , which is made up of the drive rod 420 , the lever 450 , and the spiral spring 440 . a permanent magnet 460 is positioned on the elastic carrier element 23 . upon the rotation of the metallic flywheel 400 , induction currents are set off by the permanent magnet 460 and their magnetic field works against the magnetic field of the permanent magnet , so that the motion of the flywheel 400 is braked . an imbalance 29 can , in addition , be positioned on the flywheel 400 . the motion of the flywheel 400 can be described by the angle that is formed by the axles 480 and 490 . the motion of the flywheel be described by a differential equation of the type where the high - placed vertical line signifies the derivation over time . the horizontal rule ω designates the motor &# 39 ; s rotation frequency . the constants a1 , a2 , a3 , and a4 are linked with the moment of inertia of the flywheel 400 , the mass of the imbalance 29 , the gravity acceleration , the spring constant of the spiral spring 440 , and the damping constant , which is a result of the braking effect of the permanent magnet 460 on the metallic flywheel 400 . the values of these magnitudes can be attuned in such a way that a chaotic course is derived for the angle θ as a function of time , as can be seen in the book nonlinear dynamics and chaos , by j . m . t . thomson and h . b . steward ( new york : john wiley and sons , 1986 ). in a chaotic deflection of the flywheel 400 , the course of the ray path inside the light - conducting fiber 13 is perturbed in corresponding manner , so that the coherence of light is perturbed and this works against the occurrence of speckles at the distal end of the endoscopic system 1 . fig7 shows an especially simple embodiment of the coupling of an actuator 11 with a light conductor 13 . the actuator 11 , which is configured as an electromotor , is positioned on a holder element 21 , which is configured as a socket . the light conductor 13 in the form of a glass fiber is cemented directly on the housing 6 of the electromotor 11 by a drop of cement . the electromotor 11 sets an imbalance element 29 in motion by a drive shaft 500 , as shown by the bent arrow in fig6 . the housing 6 of the electromotor 11 is set in motion through the rotation of the imbalance element 29 , so that the directions of rotation are shown by the double arrow . the rotations are transmitted directly onto the glass fiber 13 by the material - locked connection , which is produced by the drop of cement . an especially favorable suspension of the actuator 11 is shown in fig8 . the holder element 21 of the actuator 11 is configured as a circuit board , which comprises a right - angle recess 600 . the circuit board 21 is built into the housing 12 ( not illustrated ) of the supply unit 10 . the recess 600 has on its longer sides slit - shaped fixers 612 , 614 , 616 , and 618 , which are placed opposite one another in pairs . the motor 27 of the actuator 11 is held in shaking motion in the right - angle recess 600 of the circuit board 21 by o rings 622 , 624 , 626 , and 628 . the o rings surround the housing 25 of the motor 27 and are secured in the fixers 612 , 624 , 616 , 618 . the surface of the motor housing 25 includes grooves for better control of the o rings . the imbalance 29 is secured on the rotary axle of the motor 27 . a coupling element 19 is soldered onto the motor housing 25 in the form of a metal ring 19 . the metal ring 19 surrounds a light - conducting element 13 , which is configured as a laser fiber . as a result of the shifting suspension of the motor 27 , the transmission of motor vibrations onto the housing 12 or other components of the proximal supply unit 10 is kept small , so that unintended disturbances of the endoscopic system are to the greatest possible extent avoided .

an endoscopic system with at least one light source for generating at least partially coherent light , for exciting fluorescent light , with at least one light - conducting element , where the at least one light source and the at least one light - conducting element are positioned in a proximal supply unit . it is further provided with an optical radiance transmission link in an insertion part and with at least one fluorescence converter for conversion into white light . according to the invention , at least one actuator is present , which is coupled with at least one light - conducting element and / or with the at least one light source and / or with the at least one fluorescence converter . with the help of the actuator , perturbations or fluctuations concerning the at least one light - conducting element and / or the at least one light source and / or the at least one fluorescence converter are generated and thereby reduce the speckles in the endoscopic image .

referring now to fig1 an apparatus 100 constructed for the purpose of sanitizing boneless meat is shown . the apparatus 100 includes a horizontally disposed conduit 9 with end caps 7 and 25 sealed thereto . end caps 7 and 25 are securely attached to conduit 9 and are removable to allow cleaning of the internal components of the apparatus 100 . port 2 is located centrally on the upstream side of the apparatus 100 in the end cap 7 and arranged to allow injection under pressure of boneless meat in a continuous stream therethrough , and into the pressure vessel 9 . at the downstream end of the conduit 9 , a driveshaft 28 is centrally located in end cap 25 . a connection to pressure vessel 9 is located on the downstream underside of pressure vessel 9 to connect to a receptacle 31 . a driveshaft 32 is mounted to receptacle 31 . gas injection ports 4 , 20 , and 24 , for example , are provided and an exhaust port 14 , is located centrally and on the upper side of pressure vessel 9 . referring now to fig2 a cross section illustration through the apparatus 100 shown in fig1 is provided . port 2 allows the pressurized transfer of boneless meat in the direction shown by arrow 1 , and into the pressure vessel 9 . boneless meat is transferred therein , under pressure , by pumping means such as with a meat pump manufactured by marlen . meat is transferred in the direction shown by arrow 1 continuously and at an adjustable mass flow rate . endplate 7 is attached to pressure vessel 9 , by suitable means such as bolts , and gas ports shown as 5 and 4 provide for the injection of selected gases , such as ozone or carbon dioxide , both of which may be in atomized solution form , wherein the quantity of ozone and water is injected at a variable and precise rate , and generally according to the mass flow of boneless meat transferred the pressure vessel also . at the downstream end of pressure vessel 9 , endplate 25 is securely attached and sealed , and is arranged with driveshaft 28 centrally disposed on endplate 25 ; driveshaft 28 is attached to archimedes screw 8 , which is located inside pressure vessel 9 in such a way that , when shaft 28 is rotated , the flights of archimedes screw 8 rotate in close proximity to the internal surface of conduit 9 but do not touch the internal surface . as the screw 8 is rotated , boneless meat is transferred through pressure vessel 9 . as the meat is transferred along a substantially horizontal path , boneless meat is rotated thereby exposing all surfaces of the meat to gas also injected into pressure vessel 9 , thereby allowing for the killing of bacteria that may be present at the surfaces of meat by contact with the ozone solution and ozone gas . ozone gas is injected at a suitable pressure that may be at 25 psi , or as high as 200 psi or more , and in volumes adequate to substantially ensure killing of surface bacteria on the meat . ports 20 and 19 are also provided and ozone gas can be injected therethrough in the direction of arrows 10 and 11 . additionally , a precisely measured quantity of water may be injected via an atomizing injection device ( not shown ) directly into the pressure vessel 9 . the water can be any amount . in some instances , the amount is any amount that exceeds the regulated allowable quantity of water in meat , for example . however , the water content in beef can be reduced with a gas as will be described below . the amount of water introduced can be metered and regulated . the water injection devices can be located adjacent the ozone injection ports 19 and 20 , for example , such that ozone gas can dissolve into the atomized water . in this way , the dissolved ozone gas will provide a solution of ozonated water that can then contact the boneless meat &# 39 ; s surfaces . therefore , both ozone gas and ozonated water in an atomized condition will be present in the free spaces in the chamber of vessel 9 such that the gas can dissolve in the moisture on the meat &# 39 ; s surfaces . additionally , ozonated water will also be available to increase the quantity of ozone that contacts the meat &# 39 ; s surface . in order to satisfy hazard analysis and critical control point ( haccp ) requirements for meat decontamination processes , ozone measuring ( monitoring ) devices can be located at the point of ozone entry into the chamber 9 and even inside the ports such as 4 and 5 , for example , so as to provide a reliable means of measuring the concentration of ozone gas at the entrance to vessel 9 . an additional ozone measuring ( monitoring ) device ( s ) can be located at the point of gas exhaust from the chamber 9 and inside the exhaust port 14 so as to provide a reliable means of measuring the concentration of ozone gas at the point of exhaust and after it has been transferred the chamber 9 . in this way , when all relevant conditions such as temperature of the meat and the mass flow of the meat transferred through the chamber 9 are known and maintained within acceptable ranges , a reproducible process of decontaminating meat can be specified by controlling the quantity of ozone that is transferred into the chamber 9 . a large proportion of the ozone gas that is provided into chamber 9 through ports , such as ports 4 and 5 , will decompose into oxygen gas but a quantity may survive and therefore be exhausted via port 14 . the bactericidal effectiveness of the ozone gas during its passage through the chamber 9 can be determined by the quantity of ozone gas that remains in the exhausted gases through port 14 . in this way , a reproducible process of decontaminating meat that meets the haccp standards , for example , can be developed and maintained . ports 18 , 38 , and 40 are located immediately downstream from exhaust port 14 , and a suitable gas that has , for example , been pretreated , such as by compressing , filtering and chilling , is injected therethrough in the direction of arrows 17 and 39 ( arrow for port 40 not shown ). gas injected through ports 18 , 38 , and 40 can be chilled and dried thoroughly ; and such gas may be filtered air , and injected at a pressure equal to other gases that are injected into pressure vessel 9 , through other gas injection ports , such as ports 4 and 5 . the purpose of injecting a dry gas , such as air , through ports 18 , 38 , and 40 is to dry and to reduce to a desired level the quantity of water that has been injected with ozone gas , through ports 5 , 4 , 20 , and 19 , for example . in some instances , the dry gas will reduce the amount of water in the vessel to produce a water content in the meat that is acceptable . the amount of dry gas can be metered and regulated in a specific amount . the dry gas injected through ports , 40 , 38 , and 18 will become saturated with water vapor , which will then be carried out of pressure vessel 9 , through exhaust port 14 , and in the direction of arrows 15 and 16 . ports 21 , 24 , 26 , 41 , 42 , and 44 are provided to allow the injection of other selected gases , such as carbon dioxide , at a pressure equal to the injected pressure of other gases that are injected into pressure vessel 9 . carbon dioxide injected into these ports may be in atomized and chilled and be in solution form , where the carbon dioxide has been dissolved in water , under pressure , thereby producing carbonic acid that is then atomized prior to injection into pressure vessel 9 . such carbonic acid , which may have a ph of approximately 3 . 7 , will provide additional sanitizing capability by killing bacteria that may have been injured by ozone injected upstream , or alternatively any bacteria that have escaped contact with ozone at the upstream end of pressure vessel 9 . exhaust port 14 is centrally located on the upper side conduit 9 , and has a pressure regulator 13 fitted thereto . unused ozone gas , oxygen , moisture - laden air , and carbon dioxide or other gases will escape through exhaust port 14 , at a preset pressure , such as 200 psi . however , the pressure within vessel 9 may be at more or less than 200 psi , and is most preferably at an optimum pressure that will maximize death of bacteria that may be present at the surface of the boneless meat being processed in the apparatus . exhaust gas escapes in the direction shown by arrow 12 , and may be vented to atmosphere or bubbled through water , and cleaned prior to exhausting to atmosphere . when used in the manner hereinabove described , the apparatus shown in fig2 will not only process boneless meat at a controlled mass flow rate , and in doing so kill bacteria contained therein , it also provides a means of adjusting , with precise accuracy , the amount of water added to the boneless meat . for example , a mass flow of boneless meat equal to “ x ” pounds per hour , can be injected into pressure vessel 9 , through port 2 , and a quantity of water equal to 10 % of “ x ,” for example , can be injected through gas injection ports , with the ozone gas and / or alternatively , with carbon dioxide gas . however , dry chilled air ( or nitrogen gas ), or any other suitable gas that is chilled and dried prior to injection , can be injected at such a rate that will vaporize the equivalent of half of the water transferred therein , and carry this vaporized water out of pressure vessel 9 through exhaust port 14 . therefore , in this way , a quantity of water equal to 5 % of the volume of meat transferred therethrough , will be retained with the meat as it is transferred out of pressure vessel 9 , and into receptacle 31 in the direction of arrows 36 . to this end , injection ports for meat , ozone , dry gas or any other injection port can be fitted with a measuring instrument . a driveshaft 32 , with archimedes screw 33 , is arranged to rotate and compress boneless meat into a single stream and directly into a coarse grinding plate , and in the direction of arrows 34 and 35 . the rate of mass flow of coarse ground meat is equal to the rate of boneless meat transferred into pressure vessel 9 through conduit 2 . referring now to fig3 a plan view of a plant layout is illustrated . the equipment detailed in fig3 is arranged to automatically sanitize or wash , grind , and proportion boneless meat with a selected lean to fat ratio . combination dumpers 201 and 202 transfer boneless meat , in the direction shown by arrows 203 and 204 , into conduits 205 and 206 via meat pumps 255 and 256 . a supply of low fat content boneless meat is loaded at combination dumper 201 , and a supply of relatively high fat content boneless meat is transferred in the direction of arrow 204 , by dumper 202 . meat in the direction shown by arrow 203 , is pumped by pump 255 , through conduit 205 , and through x - ray fat measuring device 207 , toward valve 209 , and boneless meat is transferred in the direction of arrow 204 , by pumping into conduit 206 , by meat pump 256 , through x - ray fat measuring device 208 and toward valve 209 . valve 209 is arranged to combine the two streams , or alternatively divert only meat from either stream 203 or stream 204 , according to the measured fat content of each stream . therefore , a single stream of meat is transferred directly into conduit 215 , and transferred into meat processing apparatus 214 , which is the apparatus described in connection with fig1 and 2 hereinabove . gas injection ports 210 , 211 , 212 , 213 , and 220 allow selected gas injection in the direction of dotted arrows associated with each port . processed boneless meat is then transferred through receptacle 219 , into coarse meat grinder 218 , and through x - ray fat measuring device 217 , and into conduit 222 . conduit 222 is arranged to hold a predetermined quantity of boneless meat and is connected directly to diverter valve 223 . diverter valve 223 is arranged to directly transfer coarse ground meat from conduit 222 , into any one of three conduits shown as 224 , 225 , or 226 . the selection of any of the conduits 224 , 225 , and 226 , is made according to the measured fat content continuously transferred through conduit 222 , and according to the fat content measured by x - ray fat measuring device 217 . in this way , a stream of boneless meat can be transferred along conduit 224 , wherein the stream of meat has a relatively high level of fat . alternatively , a stream of meat with a relatively low fat content can be transferred into conduit 225 . in the event that any quantity of boneless meat has a level of fat content that is greater or lower than is acceptable , it can be transferred through conduit 226 into silo 227 . most preferably , the boneless meat stream directed through conduit 225 will be of relatively high fat content . the stream of meat transferred through conduit 224 , is delivered into preblender 240 , where it is blended and treated with liquid carbon dioxide . similarly , boneless meat transferred along conduit 225 is delivered into preblender 229 , where it is also blended and chilled with liquid carbon dioxide . carbon dioxide gas is collected at locations 231 and 230 , and tested for its purity . if testing shows that the carbon dioxide gas is substantially free of any other gases , such as atmospheric oxygen , it can be diverted to compressor 239 and stored in pressure vessels 243 until required for further use . such further use may be in processing pressure vessel 214 . in which case , the pressurized co 2 gas can be transferred along conduits 244 and 245 . blended , coarse ground meat is transferred into blender 234 , from preblender 240 , through x - ray fat measuring device 232 , at a rate that is determined by the fat content as measured in x - ray device 232 . preblended boneless meat is transferred into continuous blender 234 , from preblender 229 , through x - ray fat measuring device 233 , at a flow rate that is determined by fat content measured by device 233 . a continuous single stream of blended boneless , coarse - ground meat is transferred from continuous blender 234 , along conduit 236 , through x - ray measuring device 235 , and into diverter valve 237 . coarse - ground meat produced to specification is then diverted into either conduit 248 , 247 , 246 , or 257 , according to its measured fat content . any such coarse - ground meat that does not meet specification , to the extent that its fat content is too high or too low , will be transferred into silo 238 . coarse - ground meat that has been produced according to requirements will be transferred into silos 249 , 250 , or 251 , and retained therein , until required for further processing when the stored coarse - ground meat will be transferred from each silo , through respective conduits 254 , 253 , and 252 . any ground meat that does not meet specification and therefore has been transferred into silo 238 is then gradually transferred along conduit 228 , into blender 227 . boneless meat that is stored in 227 is gradually transferred at a slow rate , into preblender 229 . it should be noted that the entire apparatus shown in fig3 has an atmosphere maintained within it that substantially eliminates the presence of oxygen gas , and is maintained at substantially 100 % carbon dioxide . it should be noted that x - ray measuring devices 207 , 208 , 217 , 232 , 233 , and 235 , can be arranged to provide a sanitizing effect on the boneless meat that is transferred therethrough by elevating the intensity of x rays to the extent that bacteria is injured or killed as it passes therethrough . in this way , a systematic and gradual reduction in bacteria can be achieved , without the need for exposing the meat to a single source of x rays , sufficient to kill bacteria in a single step . x - ray measuring devices may also be configured to measure flow rate as well as any other meat attribute , including fat content .

the invention is directed to a method and apparatus for sanitizing perishable goods by mixing the goods with sanitizing liquor for a suitable period of time followed by separating the liquor and substantially neutralizing any residual sanitizing agent left in the goods . in one instance , the sanitizing agent includes ozone and water ; therefore , separation of the ozonated water advantageously proceeds with a squeezing effect to more adequately remove the ozonated water from the goods .

in fig1 the article of footwear ch shown is a snowboard boot . the invention applies to any type of boot whose flexible upper is reinforced either to increase the stiffness in bending of the upper , or to protect the foot and ankle from impacts and external attacks . this type of boot is found in sports such as snowboarding , in - line roller skating , and ice skating , for example . the invention also applies to boots provided with an external rigid shell made of plastic , for example , and used , in particular , for alpine skiing , snowboarding , in - line roller skating , ice skating , mountain skiing , or telemark skiing , for example . the article of footwear ch includes an upper o comprising two portions 12 a and 12 b adapted to be brought closer together by a lace - up device . this lace - up device generally includes a tightening zone 16 , which here is divided into two zones 16 e and 16 f , zone 16 e being a lower tightening zone and zone 16 f being an upper tightening zone . in a conventional and known manner , the tightening zone 16 comprises return elements 50 a - 54 a and 50 b - 54 b positioned on each of the two portions 12 a and 12 b , respectively . a linkage 15 , such as a lace or cable , connects at least two return elements 50 a and 50 b along a predetermined length of travel . the linkage 15 can advantageously connect all of the return elements to complete the tightening . in addition , the linkage 15 forms a loop 2 located outside the tightening zone 16 . to maintain the tension in the linkage 15 , the lace - up device also includes a mechanism 20 for locking , or blocking , the linkage 15 . fig1 more specifically illustrates a first tightening phase of the device , which is adapted to tighten a boot with a high upper . this phase ensures the tightening of the lower tightening zone 16 e , which extends approximately from the metatarsophalangeal articulation up to the ankle , by making it possible to hold the instep firmly in the article of footwear ch . the lower tightening zone 16 e includes a series of return elements 53 a and 53 b which advantageously specially adapted to make it possible to reduce the friction of the linkage 15 in the return elements . despite the use of specially adapted return elements as described in french application publication no . 2 706 743 , tests have shown that it is preferable to limit to four , for example , the number of return elements 53 a and 53 b arranged on each of the portions 12 a and 12 b for each tightening zone 16 e and 16 f in order to optimize the tightening . the upper end of the lower tightening zone 16 e is demarcated by two return elements 52 a and 52 b , arranged on each of the portions 12 a and 12 b of the upper , which possibly have specific functions which will be detailed subsequently , and which separate the two tightening zones 16 e and 16 f . the linkage 15 , which extends from the return elements 52 a and 52 b , forms a loop 2 that includes a gripping device 1 arranged on the linkage 15 . this gripping device 1 enables the user of the article of footwear ch to grab the loop 2 easily and , likewise , to exert a generally upward force f 1 on the loop 2 easily . this force f 1 generates a tension in each strand of the linkage 15 that contributes to the tightening power of the lace - up device by bringing the two portions 12 a and 12 b of the upper of the article of footwear closer together . however , since the tension in each strand of the linkage 15 corresponds substantially to one half of such force f 1 , it is important that the gripping device 1 ensure the user &# 39 ; s comfort during the tightening . to achieve this object , the gripping device 1 comprises a rigid frame 3 . this rigidity makes it possible to distribute the tension of the linkage 15 over the user &# 39 ; s hand by limiting the shearing effect of the linkage on the skin . thus , the more the pain on the hand is reduced , the more firmly the user can pull on the gripping device 1 . the rigid frame 3 can be advantageously made out of a material having a certain bending strength , in particular thermoplastic materials such as polyamide , polypropylene , and according to an adapted geometry that promotes greater inertia along the direction of force f 1 . once the tension is exerted in the linkage 15 , it is necessary to maintain this tightening tension in order to be able to release the gripping device 1 . this function is ensured by a locking mechanism 22 that is integrated into the return elements 52 a and 52 b . these elements 52 a and 52 b simultaneously ensure a sliding function in one direction , and a locking , or blocking , function in another direction . the return elements 52 a , 52 b , can be constructed as described in french application publication no . 2 757 026 . to combine these two functions , the return elements 52 a and 52 b can be suitably oriented on the upper o , such that the force f 1 on the linkage 15 makes it possible to slide the linkage in the return elements 52 a and 52 b , and also to exert a reverse - locking action . but the return elements 52 a and 52 b can also be oriented so as to promote the sliding along the direction of the force f 1 . then , once the force f 1 has been applied , the user exerts a force f 2 oriented substantially forward . this force f 2 changes the orientation of the linkage 15 in the return elements 52 a and 52 b and makes it possible to use the return elements 52 a and 52 b in their locking function . to facilitate the sequence of the actions of tightening and loosening the lower tightening zone 16 e , the return elements 52 a , 52 b , 53 a , and 53 b , which are located in the lower tightening zone 16 e , include guiding means adapted to prevent the linkage 15 from escaping during the loosening . one way to implement these guiding means consists of using return elements which include a channel from which the linkage 15 cannot escape unexpectedly . fig2 shows the second and last tightening phase of the footwear ch , which is still a boot adapted to snowboarding . this tightening phase makes it possible to tighten the upper tightening zone 16 f by bringing the portions 12 a and 12 b of the upper o closer together . the lace - up device of the invention , therefore , makes it possible to separate the tightenings and their intensities for the lower tightening zone 16 e and the upper tightening zone 16 f . indeed , the tightening of the upper tightening zone 16 f does not have any effect on , that is , is independent of , the tightening of the lower tightening zone 16 e due to the locking function of the linkage 15 which is integrated into the return elements 52 a and 52 b . to undertake the second tightening phase , the user first positions the linkage 15 manually in the return elements 51 a and 50 a and their counterparts , located on the opposite portion 12 b . the user criss - crosses the linkage 15 in a known fashion by going upward from the return element 52 a to the return element 50 a . to be able to perform this manual operation , the return elements 50 a , 50 b , 51 a , and 51 b , located in the upper tightening zone 16 f , are of the hook type . in other words , they are open so as to retain the linkage 15 in the direction that brings the two portions 12 a and 12 b of the upper o closer together . once the linkage 15 is positioned , the user pulls , along a substantially upward force f 3 , on the gripping device 1 which is positioned on the linkage 15 in the area of loop 2 . this action tensions the linkage 15 which brings the two portions 12 a and 12 b of the upper o closer together , in the area of the upper tightening zone 16 f . the tightening tension is maintained in this zone 16 f due to a means for locking the linkage 15 . this locking can be obtained in two different ways . first , the return elements 50 a and 50 b , which are positioned at the end of the tightening zone 16 , and at the junction of the upper tightening zone 16 f and the loop 2 , integrate a locking means 23 . this locking means is substantially similar to the locking means 22 arranged on the return elements 52 a and 52 b and described previously . similarly , the user can lock the linkage 15 by pulling along the direction of the force f 3 if the return elements 50 a and 50 b are arranged on the upper o along a specific orientation . conversely , the user pulls on the gripping device 1 with the force f 3 , then displaces the device 1 forwardly along a direction f 4 to ensure the locking of the linkage 15 according to a previously described mechanism . second , the locking means 20 can be integrated into an independent locking element 21 that is slidably mounted on the loop 2 . to perform the locking , the user pulls on the gripping device 1 along the direction f 3 , then displaces the locking element 21 along a direction δ that brings the locking element 21 closer to the return elements 50 a and 50 b . preferably , the locking element 21 is slidably mounted concurrently on the two strands of the loop 2 . the locking means 20 can be embodied as two locking elements sliding on each of the strands of the loop 2 , respectively . in this case , the user must displace the two locking elements to lock the linkage 15 . moreover , the two aforementioned locking devices can be combined for increased safety against an ill - timed loosening , which may occur on this type of boot , which can be subject to substantial forces during the sporting activity . fig2 shows this combination with locking means 23 integrated into the return elements 50 a and 50 b and the locking element 21 mounted on the loop 2 of the linkage 15 . the tests conducted have shown the interest of using a flexible and substantially non - stretching linkage 15 . the flexibility is necessary in the travel imposed by the position of the return elements , and the non - stretching ability makes it possible to limit the elongation of the linkage 15 , in particular in the area of the loop 2 , during the tightening . indeed , the tension obtained by the rigid frame 3 of the gripping device 1 is so substantial that , in the case of a conventional lace , or even a string , the user would spend his energy in untying the lace instead of bringing the two portions 12 a and 12 b closer together . the best results were obtained with a linkage 15 obtained with a linkage made of kevlar or aramid , and whose outer diameter is between 2 and 4 mm . fig3 shows a detail of the lace - up device in the area of the gripping device 1 and its rigid frame 3 . this frame 3 comprises a contact surface 4 which is complementary of at least three fingers 25 x , 25 y , and 25 z of the hand m . this contact surface 4 comprises three cavities 4 x , 4 y , and 4 z which assume the morphology of the fingers 25 x , 25 y , and 25 z , respectively , when folded around the frame 3 . tests have shown that to obtain a more powerful tightening , the fingers used preferably are the forefinger , second finger , and third finger . in addition , in the preferred embodiment shown , the frame 3 also serves to close the loop 2 constituted by the linkage 15 . the gripping device 1 includes hooking zones , or connection arrangements , 5 c and 5 d that are adapted to cooperate with the two ends , or end portions , 15 c and 15 d , respectively , of the linkage 15 . the connection arrangements 5 c , 5 d can be constituted by a wall 100 , perpendicular to the linkage 15 , which is integral with the rigid frame 3 . a hole 101 in which the end 15 c of the linkage 15 passes is provided in this wall 100 . this end 15 c is equipped with a locking means , such as a knot 102 whose diameter is greater than the diameter of the hole 101 . as shown in fig4 the linkage 15 can also extend right through the frame 3 . however , like the gripping device shown in fig3 the frame 3 serves to separate , i . e ., to space apart , the linkage portions that are connected to , or pass through , the frame to allow the fingers of the hand to extend within the loop 2 . the ends 15 c and 15 d , or end portions , of the linkage 15 are connected to return elements 54 a and 54 b located substantially at the ends of the tightening zone 16 . however , in this embodiment , the loop 2 which includes the frame 3 is not located at one of the ends of the tightening zone 16 . the loop 2 is located outside the tightening zone 16 , but extends substantially perpendicular to the plane defined by the tightening zone 16 so as to divide the zone 16 into two tightening sub - zones 105 and 106 . furthermore , the gripping device can be provided with an improvement not shown . in this improvement , the gripping device includes a fastening means complementary of the article of footwear which makes it possible to store the gripping device on the article of footwear . this fastening means can advantageously be of the self - gripping type , or in the form of a snap - fastener . the footwear can also be provided with a pocket or a strap forming a loop in which the gripping device could be housed when it is out of the tightening and loosening phases . in addition , the gripping device can advantageously include comfort elements constituted of a softer material than that of the frame , and positioned in the area of the contact surface adapted to be in contact with the fingers of the hand . the invention is not limited to the embodiments described hereinabove , which are provided for guidance only , but encompasses all similar or equivalent embodiments .

a lace - up device for tightening an article of footwear , providing for the tieing of the lacing without causing discomfort to the user &# 39 ; s hands , as well as to the article of footwear equipped with such device . the lace - up device includes a gripping mechanism arranged on the linkage in the area of a loop formed by the lacing outside the tightening zone . the gripping device includes a rigid frame , making it possible to distribute the tension of the lacing over the hand of the user .

referring down to the drawings wherein like numerals indicate like parts , the numeral 10 indicates an anchor plate having apertures 12 , 14 , 16 and 18 disposed near its perimeter . the apertures are adapted to receive a plurality of stakes 20 having pointed ends 22 and headed ends 24 . the heads are of a greater circumference than the apertures 12 , 14 , 16 and 18 . the plate is secured to the ground by driving the stakes through the above - mentioned apertures . it should be noted that the taper on ends 24 mate with the complementary tapers of the apertures so as to receive the downwardly and inwardly inclined lower surfaces of the heads so as to reduce the possibility of entanglement by a tether chain with the hook . a standard 28 extends upwardly from the plate and has its lower end secured to the plate by weld 30 . at its upper end the standard 28 is provided with a boss 32 of less diameter than the standard 28 and thereby forms a horizontal annular ledge 34 . a hollow rotator member 38 is received over the standard 28 with its lower end near the plate 10 . disposed slightly below the upper end of rotator 38 is an outwardly extending flange 40 having a plurality of apertures 42 . an annular bearing member 44 has an inner circumference 46 received about the boss 32 and an outer circumference 48 engaged by the upper , inner surface 50 of rotator 38 . the length of the standard 28 , including the boss 32 , is the same as standard 28 . the height of bearing 44 is approximately the height of boss 32 . therefore , when rotator 38 is slipped over boss 32 , the top surface of the bearing is flush with the top surface of the rotator . a cover 52 is disposed over the bearing member and has the same circumference and diameter as flange 40 . the cover 52 is formed with apertures 54 of the same diameter and relative location as apertures 42 . the apertures 54 and 42 are aligned so as to receive the bolts 56 which are used to secure the cover to the flange by way of nuts 58 . the upper surface of cover 52 has a u - shaped hook 60 welded thereto . hook 62 is adapted for connection to the swivel chain 64 by way of a clasp 66 . at the other end of chain 64 , there is another clasp 65 that is connected to a dog collar , or other animal restrainer , 68 . intermediate the length of swivel chain 64 are three universal swivel joints 70 , 72 , and 74 . swivel joints 70 and 74 are disposed at the ends of the chain 64 and swivel joint 72 is disposed approximately midway of its length . as above described , there has been provided a fixed standard number 28 about which a rotator 38 and its top cover 52 are rotatable with friction reduced by the bearing 44 . connected to this freely rotatable member is the chain 64 having three swivel joints throughout its length . the stakes 20 can be pounded into the ground so as to secure anchor plate 10 . thus , no pounding force is transmitted to the rotating elements . fig3 is a diagrammatic sketch of a desired stake location . the chain in this diagram can be approximately twenty feet in length and has swivels at either end and a third swivel intermediate of its length . the dog or other animal , cannot become entangled if the stake is placed a distance from the dog house 76 , ( or other obstruction such as a tree ) to prevent the dog from wrapping about such an obstruction . the device should be connected to the ground so that the chain will not extend more than half way around an object such as a dog house . in describing the invention , reference has been made to a preferred embodiment and illustrative advantages of the invention . those skilled in the art , however , and familiar with the instant disclosure of the subject invention , may recognize additions , deletions , modifications , subsitutions and / or other changes which may fall within the purview of the subject invention and claims .

a tangle free animal stake wherein means are provided to secure a plate to the earth &# 39 ; s surface . a rotating member is provided of said plate to which a chain is attached having a plurality of universal swivels disposed intermediate the length of the chain .

in this application , the terms “ distal part ” and “ proximal part ” are used relative to the medical professional , i . e . the “ distal part ” is used to describe the part of the device that is inserted first into the patient . the terms “ anterior ” and “ posterior ” are used relative to the patient to designate his front and his back , respectively . the laryngoscope ( 1 ) of fig1 comprises a handle ( 2 ) for holding and maneuvering the laryngoscope and a rigid blade ( 3 ) that is pivotally attached to the handle ( 2 ). the laryngoscope ( 1 ) further comprises means of visualisation including a display screen ( 4 ) to visualise the area captured , for example , by a camera ( not shown ). a guiding device ( 5 ) is shown that comprises a guiding means ( 6 ) for guiding an endotracheal tube through the patient &# 39 ; s mouth and upper airways and an attachment means embodied as a sleeve ( 7 ). the blade ( 3 ) of the laryngoscope ( 1 ) is inserted into the sleeve ( 7 ). the sleeve ( 7 ) should preferably fit the blade ( 3 ) so that it is sufficiently secured during use and so that it can be removed after use . the guiding means ( 6 ) deflects the tube towards the surface of the sleeve ( 7 ) and deflects the distal tip of the tube towards the distal end of the blade and into the laryngeal inlet . preferably , the guiding means ( 6 ) has mechanical and geometric properties or external maneuverability such that it deflects the distal endotracheal tube tip towards the blade and thereafter along a pathway through the glottic opening . the flexibility or maneuverability of the guiding means ( 6 ) permits the endotracheal tube to disengage from the blade when intubation has been achieved and the laryngoscope needs removing . the guiding means ( 6 ) may be externally movable relative to the attachment means so that the distal end of the endotracheal tube is pushed along the surface of laryngoscope blade ( 3 ). the guiding means ( 6 ) may be hinged or be made of a flexible material . to substantially deflect the distal end of the endotracheal tube along the blade surface there needs to be sufficient force from the guiding means ( 6 ). however once tracheal intubation is achieved it is desirable that there is very little force holding the endotracheal tube between the blade ( 3 ) and the guiding means ( 6 ) because it is desirable to remove the laryngoscope from the patient &# 39 ; s upper airway whilst applying minimal forces so as to avoid disrupting the endotracheal tube position or damaging the airway structures . the guiding means ( 6 ) may be hinged , be externally movable or of stiffness sufficient to guide a range of external diameters of endotracheal tubes along the line of the surface of the rigid blade and anteriorly ( i . e . at the distal end ) into the laryngeal inlet under indirect vision . the guiding means ( 6 ) may be flexible enough such that the endotracheal tube can slip out laterally easily when the laryngoscope needs to be removed following intubation . the blade ( 3 ) may be straight , e . g . a miller laryngoscope blade . alternatively , a curved blade may be used , e . g . a macintosh blade . another suitable type of blade is one that comprises a moveable and / or hinged blade tip , e . g . mccoy laryngoscope . fig1 shows a straight blade ( 3 ) and a guiding device ( 5 ) that extends longitudinally from the distal end of the blade ( 3 ) to form an extended tip or tongue ( 8 ). this guiding device ( 5 ) is particularly suitable for indirect videolaryngoscopy and the tip ( 8 ) facilitates a good laryngoscopic view for the user , for example , on a display screen ( 4 ). an important advantage of the guiding device ( 5 ), and in particular of the use of an attachment means , is that it may be used in combination with any type of laryngoscope , including those with straight , curved , angled or hinged blades as described above , and can therefore be used as a universal guiding means ( 6 ). furthermore , the guiding means ( 6 ) may include a tip ( 8 ) that may be straight , curved or angled to modify an existing laryngoscope blade . for example , a guiding means with a straight tip may be used with a miller laryngoscope to extend the length of the existing blade ; a guiding means with a curved tip may be used with a straight blade to transform it into a macintosh - type blade . the guiding device ( 5 ) may be reusable , disposable , partly reusable or partly disposable . prior art reusable laryngoscopes must be cleaned and sterilized after use and the process is time consuming and incurs costs . clinicians may use a disposable sheath to cover the blade of a laryngoscope to minimize the need for cleaning and sterilization . alternatively , a reusable laryngoscope or a reusable blade may be used but are more costly to produce than a disposable or partly disposable guiding device ( 5 ). the laryngoscope ( 1 ) may comprise visualisation means such as a light source , fibreoptics , camera or other technology that enable external indirect visualisation of the laryngeal inlet . indirect visualisation of the laryngeal inlet through fibreoptics , camera or other means , is particularly useful to assist the user to juxtapose the tip of the blade with the laryngeal inlet . in a preferred embodiment , the laryngoscope ( 1 ) may consist of a disposable sleeve ( 7 ) and separate reusable camera and light source components ( not shown ). the disposable sleeve ( 7 ) may comprise a channel for the camera or light source component to be inserted prior to use and removed from after use . for example in the laryngoscope of fig1 , a camera and a light source are located at the distal end of the blade ( 3 ) and are protected from bodily fluids by the disposable sleeve ( 7 ). it may be desirable that the guiding means ( 6 ) is partly or wholly transparent so as not to impede the line of view from the camera or similar to the laryngeal inlet . for example , the distal section of the channel where the camera is positioned may be transparent to permit visualisation . similarly , where the guiding device ( 5 ) comprises a distal extension ( 8 ), the extension may be transparent for improved visualisation of the patient &# 39 ; s airways . in a preferred embodiment , the whole guiding device ( 5 ) may be made out of a transparent material . in use , the guiding device ( 5 ) may be attached to the laryngoscope ( 1 ) by inserting the blade ( 3 ) into the sleeve ( 7 ). the endotracheal tube may be attached to the guiding means ( 6 ) that positions the tube along the surface of the blade ( 3 ) or along the surface of the sleeve ( 7 ). the distal end of the tube may be positioned so that its distal tip aligns with the distal end of the blade ( 3 ). the laryngoscope ( 1 ) is inserted into the mouth of the patient . the blade ( 3 ) will push the tongue of the patient to the side of the oropharynx to create space through which the larynx and the epiglottis can be viewed . the blade is manipulated to lift the epiglottis thereby exposing the laryngeal inlet . the endotracheal tube can then be advanced past the vocal cords into the trachea . the user can visualise the distal end of the blade for example on the display screen ( 4 ) and manipulate the laryngoscope accordingly . once the tube is correctly positioned , it is released from the guiding device ( 5 ) without displacing the tube and without damage to the surrounding tissues . the size and shape of guiding devices ( 5 ) according to the present invention can vary . in particular , the size and shape of the guiding devices ( 5 ) may vary to suit a patient &# 39 ; s anatomy . in the embodiment depicted in fig1 , the laryngoscope ( 1 ) and blade ( 3 ) are reusable whilst the guiding device ( 5 ) is disposable . this enables the laryngoscope ( 1 ) and its blade ( 3 ) to be used with a number of patients , whilst a different guiding device ( 5 ) is used with each patient . therefore , the clinician is free to choose the size and shape of guiding device ( 5 ) best suited to use with an individual patient . fig2 to 6 depict a guiding device ( 5 ) with a guiding means ( 6 ) in the form of a single guiding paddle extending outwards substantially level to the lower surface of the laryngoscope blade ( 3 ). the embodiment of fig2 to 6 includes attachment means in the form of a sleeve ( 7 ) that may be reversibly attached to the laryngoscope blade ( 3 ). fig7 to 11 depict an alternative embodiment of a guiding device ( 5 ) with a guiding means ( 6 ) in the form of two guiding paddles , each extending outwards substantially level to the lower surface of the laryngoscope blade ( 3 ) but on different sides of the guiding device ( 5 ). one of the guiding paddles extends under the upper surface of the guiding device ( 5 ) to partially enclose an endotracheal tube located between the two surfaces . fig1 to 16 depict another alternative embodiment of a guiding device ( 5 ), in which the extended tip ( 8 ) is anteriorly deflected to enable an endotracheal tube inserted using the device ( 5 ) to be deflected anteriorly .

a guiding device for use with a laryngoscope for assisting in the insertion of an endotracheal tube into a patient , the device comprising a guiding means for guiding an endotracheal tube through the patient &# 39 ; s upper airways , and an attachment means to attach the guiding means to the blade of the laryngoscope . a laryngoscope comprising the guiding device is also disclosed .

the dispersion of the coloring agents in the coloring products composition , as well as its distribution , diffusion , interaction and maintenance in the keratin fibers , resulting in greater color vitality and retarding of discoloration , can be particularly improved when these agents are formulated with a oil - in - glycol lamellar gel system according to the present invention . furthermore , the employment of the lamellar gel helps simultaneously improve the general characteristics of the hair , like conditioning , combing and texture . firstly , the present invention is about an oil - in - glycol lamellar gel that comprises ( a ) at least one glycol , ( b ) at least on fatty alcohol , ( c ) at least one cationic surfactant , ( d ) at least one non - ionic surfactant and ( e ) at least one amino acid . the glycols used in the lamellar gel of the present invention are those which have at least two hydroxyls , like the butylene glycol or propylene glycol , particularly those which have three hydroxyls , like the 1 , 2 , 3 - propanotriol . the amount of glycol in the lamellar gel can vary between about 40 to about 90 %, preferably between about 50 % and about 80 %, more particularly between about 65 % and about 75 % in weight , based on the total weight of the lamellar gel . the fatty alcohols that are used in the lamellar gel described herein comprise rch 2 oh compounds , wherein r denotes saturated or unsaturated hydrocarbon radical having from 5 to 27 in average , preferably from 10 to 22 atoms of carbon , in a linear or branched chain . appropriate fatty alcohols according to the present invention can be selected from cetyl , isocetyl , stearyl , isostearyl , behenic , oleic , linoleic and / or cetearyl alcohols . fatty alcohols can be used individually or in the form of mixtures . an appropriate amount of fatty alcohol in the lamellar gel of the present invention ranges from about 0 . 1 to about 40 %, preferably between about 3 to about 35 % and more preferably between about 5 to about 10 % in weight , based on the lamellar gel total weight . cationic surfactants that are useful to the present invention can be all those that can form a lamellar gel structure , particularly quaternized surfactants . the preferable quaternized surfactants according to the present invention are the quaternary compounds of ammonium with general formula ( r , r ′, r ″, r ′″ n ) + x − , where r , r ′, r ″ and r ′″ are similar or different and where x − represents an anion , for example , chloride . the r group can be aliphatic or carry additional substitutionals and n can be part of a heterocyclic or aromatic ring . in the most preferable quaternized surfactants , r and r ′ are ch 3 , and r ″ and r ′″ are aliphatic or aromatic chains , for example cetearyl - amido - propyl - dimonium hydroxyethyl chloride , dimethylpabamidopropyl laurdimonium tosylate , quaternium 70 , or mixtures thereof . an appropriate amount of cationic surfactant in the lamellar gel of the present invention ranges from about 0 . 001 to about 30 %, preferably between about 0 . 01 to about 25 % and most preferably between about 0 . 2 to about 20 % in weight , based on the lamellar gel total weight . the non - ionic surfactant , according to the present invention , is an alkyl pyrrolidone , particularly a lauryl pyrrolidone , and its amount can range from about 0 . 1 to about 20 %, particularly between about 5 to about 15 %, more particularly between about 9 to about 11 % in weight in relation to the lamellar gel total weight . the amino acid can be selected from among glycine , lauroyl lysine , arginine hcl , n - acetyl cysteine or their mixtures and their quantities in the lamellar gel composition in accordance with the present invention can range from about 0 . 1 to about 5 %, particularly between about 0 . 5 to about 1 . 5 % in weight in relation to the total weight of the composition . the lamellar gel of the present invention is , preferably , substantially water free , i . e ., it can comprise a small amount of water provided that its profile is not substantially altered . other object of the present invention is a process of preparation of a oil - in - glycol lamellar gel , which consists of ( 1 ) heating separately at least one glycol , at least one cationic surface - active agent and at least one fatty alcohol up to a temperature of from about 65 ° c . to about 85 ° c ., particularly between about 70 ° c . to about 75 ° c . ; ( 2 ) mixing the heated components in the previous step under agitation ; ( 3 ) keeping the agitation until homogenization is reached ; ( 4 ) cooling down the homogenized mixture from about 30 ° c . to about 50 ° c ., particularly up to 40 ° c . ; ( 5 ) adding at least one non - ionic surfactant and ( 6 ) adding at least one amino acid . other object of the present invention is the use of the oil - in - glycol lamellar gel to prepare a composition for tinting keratin fibers and a process for preparation of the said composition . the process consists of pre - dispensing all or part of the coloring agents that will be employed in the oil - in - glycol lamellar gel coloring composition according to the present invention , particularly in 1 : 1 proportion . the amount of coloring agents in a fiber coloring composition can range from about 0 . 5 to about 5 % in weight , therefore , the amount of lamellar gel employed in the pre - dispersion of these agents can also range from about 0 . 5 to about 5 % in weight , being that the limiting factor , is the complete dissolution of the coloring agents in the lamellar gel . one can understand by coloring agents in the present invention , all the compounds that direct or indirectly give color to the keratin fibers , whether they are pigments or direct or indirect hair coloring products or their intermediaries . in other aspect , the present invention is about a composition for tinting keratin fibers that comprises the oil - in - glycol lamellar gel according to the present invention and cosmetically acceptable excipients . without any limitations , the excipients can include those mentioned in the “ handbook of food drug and cosmetic excipients ”, florida : crc press , 2000 . the fiber coloring compositions according to the present invention include , without restriction , solution , liquid , emulsion , pseudo - emulsion , gel - convertible oil , gel , shampoo or powder , with particular preference for emulsions . the technical advantages mentioned herein , without limiting the present invention to the any technical explanation , are due to the fact that the lamellar gel according to the present invention to regulate the reaction of oxidation through the presence of its non - ionic surface - active agent , which resonates and balances the byproducts elaborated in the oxidative processes , consequently the color of the coloring agent . furthermore , the oil - in - glycol lamellar gel according to the present invention provides greater affinity of the coloring agents to the keratin fibers , through the formation of anionic - cationic complexes of the lamellar gel and keratin fiber system itself , especially when they are damaged . furthermore , the lamellar gel medium has weaker polarity than the water medium , which , in contact with the coloring agents , cause them to spread out more evenly , interact easier with the fibers and wear less after wash . the lamellar gel according to the present invention also causes the fusion point of all the system components to drop , or , in consequence , causes the glass transition point to drop of about 10 ° c ., combining the advantages of a gel and a cream at the same time , although there is only one additive for pre - dispersion of the coloring agents . another object of the present invention is a cosmetic process for coloring the keratin fiber , prepared in any kind of shop that involves any esthetics and / or cosmetics activity , which consists of applying onto them an efficacious amount of a fiber coloring product that comprises the oil - in - glycol lamellar gel according to the present invention . the following examples serve to illustrate aspects of the present invention without any restricting character . application to the hair is mentioned only for simplicity of presentation , without being limited to this use . 69 g of 1 , 2 , 3 - propanotriol were heated in a first recipient until 75 ° c . in a second recipient 20 g of a mixture of behenic alcohol , cetearyl alcohol , isostearyl alcohol and hydroxyethyl chloride cetearyl - amide - propyl - dimonium were heated until 70 ° c ., which was added to the first recipient while being agitated . the agitation was kept and the new solution was cooled down until 40 ° c . next 10 g of lauryl pyrrolidone and 1 g of glycine were added under agitation , terminating the process . study of the functional properties of the lamellar gel in example 1 effect of the oil - in - gel lamellar gel in color intensity and homogeneity and its resistence to sles washes hair coloring products containing many families of coloring agents with ( bsr001 ) and without ( control ) oil - in - gel lamellar gel of the example 1 in their compositions were applied in caucasian standard - type hair tufts , discolored 1 or 2 times according to the lab market methodology . next , the tufts were washed 10 to 15 times with sodium lauryl ether sulfate ( sles ). the procedure was applied to check the interference of the lamellar gel in the characteristics concerning the initial quality and post - wash for comparison , revealing that in the three different families of pigments utilized , the lamellar gel served to intensify the tonality of the color , improve the distribution of the pigments and the maintenance of the color after the wash with sles in all the pigment families . in all these tests , the lamellar gel was used in 1 : 1 proportion . we can observe through the comparative images of the fig1 to 3 , which , for all the evaluated groups , there was an improvement in coloring power for all the samples that contained the lamellar gel according to the present invention . being this improvement relative to the initial coloring power , causing color to be more vibrant as well as maintaining the color after 10 to 15 washes in relation to the benchmark samples without the lamellar gel . even with the inclusion of greater percentage of damage to the fiber , due to 2 previous processes of discoloration at high temperature , we can observe through the comparative images of the fig4 to 5 , that for all the evaluated groups , a better coloring power improvement was achieved for all the samples that had the oil - in - glycol lamellar gel ( bsr005 ). being this improvement relative to the initial coloring power , causing color to be more vibrant color as well as maintaining the color after 15 washes in relation to the benchmark samples without the lamellar gel .

the present application is directed to an oil - in - glycol lamellar gel , which comprises at least one glycol , at least one fatty alcohol , at least one cationic surfactant , at least one non - ionic surfactant and at least one amino acid , for application as an addictive for permanent or semi - permanent keratin fiber color products , being the said lamellar gel able to improve dispersion of colorant agents in the color composition and the distribution , diffusion , interaction and maintenance of the colorant agents in the keratin fibers , which results in greater color vitality and retardation of the discoloring process .

with full consents from three donors , each of an age between 19 and 25 years old , according to approved study guidelines from the department of health in taiwan , impacted molar teeth are collected from the three donors and rinsed with normal saline . the rinsed molar teeth sample is put into in a 50 ml conical test tube containing 30 ml of normal saline , and vigorously shaken or vortexed for 30 minutes to produce a suspension of cells . the cell suspension is subjected to centrifugation at 2000 rpm for 10 minutes . after decanting supernatant , the pellet cells are suspended in medium 199 ( gibco , a tissue culture medium ) containing 5 to 10 % fbs ( fetal bovine serum ) to have a concentration of cells of 1 × 10 6 to 3 × 10 6 / ml , and the cell suspension is transferred to a 25 cm 2 tissue culture flask having 4 to 5 ml of medium 199 containing 5 to 10 % fbs . the cells are cultured at a 37 ° c . incubator supplied with 5 % co 2 atmosphere for 4 to 10 days and began to appear with morphology of neuron stem cells . as shown in fig1 to 3 , the isolated cells have the morphology of neuron stem cells . fresh medium 199 containing 5 to 10 % fbs is replaced at day 5 or 6 and every 3 to 4 days thereafter , which may or may not contain penicillin and streptomycin ( biowest ). according to this method , the primary neuron stem cells being isolated from human molar teeth can be cultured for over 10 passages . the neuron stem cells are cultured to be 85 % confluence in a tissue culture flask and stripped from the tissue culture flask by means of an optimal volume of trypsin - edta ( ethylenediaminetetraacetate ). to facilitate the removal of the adherent cells , cells treated with trypsin may be incubated in a 37 ° c . incubator for 10 to 15 minutes . after incubation , 2 ml of the cell suspension with a concentration of 1 × 10 5 to 5 × 10 5 / ml is collected into a 15 ml conical test tube and added with 12 ml of normal saline . then , the cell suspension is subjected to centrifugation at 1800 rpm for 10 minutes . after centrifugation , supernatant is decanted , and the above steps of adding normal saline and centrifugation are repeated . after decanting the supernatant , 0 . 5 ml of medium 199 containing 5 to 10 % fbs is added to the pellet cells obtained by centrifugation and mixed with the cells thoroughly to form a cell suspension . 0 . 5 ml of a solution of 55 % w / v dimethyl sulfoxide ( dmso ) with 5 % dextran 40 is added to the cell suspension , wherein this solution acts as a cryoprotectant . a mixture of the cells and the cryoprotectant is then distributed in 0 . 5 ml aliquot into freezing vials that are stored immediately at − 80 ° c . freezer until use . to thaw the frozen - stored cells , a vial of the cells is removed from the freezer and placed in a 37 ° c . water bath to quickly thaw the cells . the thawed cell suspension is then transferred to a 25 cm 2 tissue culture flask having 4 to 5 ml of medium 199 containing 5 to 10 % fbs and is incubated at a 37 ° c . incubator supplied with 5 % co 2 . for identification of cell type specific antigens , an immune fluorescence cytostaining process is performed . the neuron stem cells isolated in the present invention are seeded overnight in 24 - well culture plate with 1 × 10 4 cells per well and fixed with a pre - chilled solution of acetone : methanol ( 1 : 1 ) for 15 min at − 20 ° c . nonspecific binding is blocked with normal serum from the species in which the secondary antibodies were produced ( 10 % secondary antibodies in pbs containing 0 . 25 % triton x - 100 ). the fixed neuron stem cells are incubated with primary antibodies diluted in pbs containing 0 . 25 % triton x - 100 for 2 hours at 25 ° c . after being rinsed with pbs , the neuron stem cells are incubated with fitc - or rhodamine - conjugated secondary antibodies for 1 hour at the room temperature in dark and then observed with axiovert 200 m ( zeiss ) fluorescence - inverted microscope . the observed images are taken and processed by metamorph ( universal imaging co . ver 6 . 0 rev 5 ) equipped with coolsnap hq ccd camera . in the control wells , all the above procedures are performed except the use of the primary antibodies . the primary antibodies used in this study include : anti - cd34 ( 1 : 200 ; pharmingen ), anti - cd45 ( 1 : 200 ; pharmingen ), anti - cd90 ( 1 : 200 ; pharmingen ), anti - gfap ( 1 : 200 ; sigma ), anti - nestin ( 1 : 400 ; chemicon ), anti - β 3 - tublin , and anti - human o 2 microglobulin ( 1 : 400 ; santa cruz ). cell types for the above primary antibodies are listed in table 1 . the results are shown in fig4 and 5 that the neuron stem cells isolated in the present invention do have cell markers ( nestin and β 3 - tublin ) of neuron stem cells but no cell marker ( gfap ) of non - neuron stem cells . rna ( ribonucleic acid ) is extracted using rneasy kit ( qiagen , gmbh ) from the neuron stem cells isolated in this invention that are grown to 80 % confluence in a 75t tissue culture flask . messenger rna ( mrna ) is reverse - transcribed using omniscript rt ( qiagen gmbh ) to complementary dna ( cdna ), and one tenth of the cdna is subjected to 30 cycles of pcr amplification ( abi prism 9700 , applied biosystems ) with the following conditions / parameters for pcr . 1 . initial denaturation at 95 ° c . for 10 minutes 2 . denaturation at 95 ° c . for 30 seconds 3 . annealing at 55 ° c . for 30 seconds 4 . elongation at 72 ° c . for 60 seconds 5 . repeat steps 2 to 4 for 30 cycles controls are performed with the amplification reaction without addition of cdna template and without reverse transcription . the authenticity and sizes of pcr products are confirmed by electrophoresis analysis . the sizes of expected pcr products corresponding to primers used are shown in table 2 . before amplification , the mrna levels of the samples are normalized by gapdh as housekeeping gene . fig6 and 7 show the results of electrophoresis analysis that the neuron stem cells isolated in the present invention do have cell markers ( nurr1 , nfm and nestin ) of neuron stem cells but not a cell marker ( gfap ) of non - neuron stem cells . from the above results , the isolation method according to the present invention , the cells isolated from different donors &# 39 ; molar teeth are proved as neuron stem cells , which can be nurr1 - positive cells . the present invention not only provides a simple and fast isolation method of neuron stem cells but also allows nurr1 - positive neuron stem cells to be isolated . it is known that nurr1 neuron stem cells primarily reside in the brain . however , for the drug development , etiology study , treatment and cell - based therapy for nurr1 - related neurodegenerative diseases , a simple and fast method to obtain nurr1 - positive cell lines is deemed necessary . therefore , according to the method in the present invention , primary nurr1 - positive neuron stem cells can be easily obtained without using complicated surgical operations , and the obtained primary nurr1 - positive neuron stem cells can be cultured for subsequent passages and preserved by simple methods . male sprague - dawley rats ( lasco , taiwan ) weighing 250 - 320 g were used in the present study . the animals were housed under conditions of 12 h light : 12 h darkness cycle , 18 ± 2 ° c ., 70 ± 5 % humidity . they had allowed free access to water and food throughout the experiment . the animals were divided into two group as follow : control group ( ischemia animal treated with pbs ) & amp ; treated group ( ischemia animal treated with 1 × 10 5 cells intracerebral injection ). as showing fig9 , mcao does cause an ischemia area in rat brain ( white area ). the operation of middle cerebral artery occulusion ( mcao ) was described previously . briefly , rats were anesthetized with isofluorate 2 . 5 %. a midline incision was made in the neck , exposing the right carotid artery bifurcation . the branches of the external carotid artery were dissected . the external carotid artery was incised , and a nylon suture ( 4 - o monofilament nylon suture ) was inserted via this incision 19 - 21 mm into the internal carotid artery . then 90 minutes after mcao , rats were reanesthetized with isofluorate , and reperfusion occurred through withdraw of the nylon suture . the body temperature was monitored by a rectal probe and maintained at 37 . 5 ± 0 . 5 ° c . during the operation with a heating blanket regulated by an animal blanket system . behavioral tests ( swing test ) were performed on 1 , 7 , 15 , 21 , 27 days after the surgery . day 0 means one day prior to results of mcao surgeries were assessed by triphenyl terazolium chloride ( ttc ) staining method and by swing test . for swing test , surgeries inflicted sd rats were suspended in the air by the tails and twisting directions of the rats were scored . as showing in fig1 , the percentage is calculated by the following formula : the percentage is a positive value when the twisting direction is recorded to right side in the swing test , and the percentage is a negative value when the twisting direction is recorded to opposite side of the right side in the swing test . the detailed results were shown in table 3 ( treated group ) and table 4 ( control group ). according to the results , it is apparently that animals have been subjected stem cells injection in treated group , the percentage value is more close to zero ( zero means a normal value ) than control group in the swing test . the method for quantification of infarct size was performed exactly as previously reported . briefly , after 24 h after transient middle cerebral artery occlusion , the animal was sacrificed under deep anesthesia and brains were removed , frozen and coronally sectioned into six 2 - mm - thick slices ( from rostral to caudal , first to sixth ). the brain slices were incubated 25 min in a 2 % solution of 2 , 3 , 5 - triphenyltetrazolium chloride ( ttc ) ( sigma ) at 37 ° c . and fixed by immersion in a 10 % saline - buffered neutral formalin solution . cells or vehicle are transplanted into the subvertrical zone of rats by using a stereotaxic apparatus 24 hours after mcao at the following coordinates : 0 . 0 mm rostral to the bregma , 1 . 0 mm lateral to the midline , and 3 . 0 mm ventral to the dura . the burr hole was sealed by bone wax after the injection to prevent the shedding of these materials . the invention has been described using exemplary preferred embodiments . however , it is to be understood that the scope of the invention is not limited to the disclosed embodiments . on the contrary , it is intended to cover various modifications and similar arrangements . the scope of the claims , therefore , should be accorded the broadest interpretation so as to encompass all such modifications and similar arrangements .

the present invention relates to a population of nurr1 - positive neuron stem cells , a pharmaceutical composition including the population of nurr1 - positive neuron stem cells , and methods for isolation , culture and preservation of the nurr1 - positive neuron stem cells . more specifically , the present invention provides a method of isolation of nurr1 - positive neuron stem cells from human teeth . the present invention further provides methods of culturing and preserving of the nurr1 - positive neuron stem cells .

referring now to the figures , a discussion of the above features with respect to preferred embodiments is provided below . it should be understood that such embodiments are for illustrative purposes , and should not be construed as limiting the scope of the invention . fig1 shows a golf club 10 that comprises a tubular multi - layer shaft 12 of the present invention . the shaft 12 substantially tapers downward through its entire length from an upper ( larger diameter ) butt portion 14 to a lower ( smaller diameter ) tip portion 16 . a club head 18 is attached to the end of the tip portion 16 , and an optional grip 19 is attached to the butt portion 14 . the tip portion 16 ( typically less than about ⅓ the entire length of the shaft 12 ) and / or the butt portion 14 ( typically less than about ⅓ the entire length of the shaft 12 ) can be tapered or parallel . an alternative multi - layer shaft 20 , as depicted in fig2 has a stepped - down shaft 20 with the club head 18 attached to its tip portion 16 and the optional grip 19 attached to its butt portion 14 . the shaft 22 is assembled from a plurality of tubular portions 24 having decreasing diameters . each of the tubular portions 24 can independently be either substantially tapered or substantially parallel . of course , the present invention is also applicable to shafts that are substantially parallel throughout their entire lengths . that is , butt portion 14 and tip portion 16 and any portion therebetween have about the same outer diameter . the butt portion 14 has an outer diameter of between about 0 . 5 inches and about 0 . 9 inches , while the tip portion 16 has an outer diameter of between about 0 . 2 inches and about 0 . 6 inches . the shafts 12 and 22 typically have a length of about 30 inches to about 65 inches . fig3 and 4 illustrate the longitudinal sectional views of shafts 12 and 22 in fig1 and 2 , respectively . shaft 12 has a tubular cover layer 30 and a tubular core layer 32 , both coextensive substantially the entire length of the shaft 12 . similarly , shaft 22 also includes cover layer 30 and core layer 32 . for simplicity reasons , the following descriptions use shaft 12 as the example . a person of ordinary skill in the art can readily apply the same compositions , dimensions , and configurations for shaft 12 in the production of shaft 22 . referring to fig3 cover layer 30 may be a continuous layer formed from at least one isotropic material having a young &# 39 ; s modulus of preferably greater than about 5 mpsi , and more preferably greater than about 10 mpsi . the isotropic material may be a metallic material such as metal matrix composites , metals , or alloys thereof including one or more combinations of metallic constituents . among the numerous metals that are suitable for cover layer 30 , ferrous metals such as titanium , steel , stainless steel , aluminum and tungsten are particularly useful . additionally , certain non - ferrous metals including nickel , copper , zinc , brass , bronze , magnesium , tin , gold and silver may be employed generally as alloying agents . metal matrix composites that are quasi - isotropic may also be desirable for use in cover layer 30 . preferably , cover layer 30 is a single solid , continuous and non - porous metallic sheath of steel , titanium , or an alloy thereof . core layer 32 is formed from a non - isotropic ( i . e . either anisotropic or quasi - isotropic ) material , preferably having a reinforcement material . the reinforcement material may be in the forms of particles , flakes , whiskers , continuous or discontinuous fibers , filaments , ribbons , sheets , and the like or mixtures thereof . suitable reinforcement material includes carbon fibers , graphite fibers , glass fibers , quartz fibers , boron fibers , ceramic fibers or whiskers such as alumina and silica , metal - coated fibers , ceramic - coated fibers , diamond - coated fibers , carbon nanotubes , aramid fibers such as kevlar ® from dupont , extended - chain polyethylenes such as spectra ® from honeywell , poly - p - phenylenebenzobisoxazole (“ pbo ”) fibers such as zylon ® from toyobo , metal fibers , polythenes , polyarylates , polyacetals , liquid crystalline polymers , aromatic polyesters such as vectran ® from celanese , polyallylates , other high performance fibers , and combinations thereof . metal - coated fibers may be any of the above fibers coated with a metal such as titanium , nickel , copper , cobalt , gold , silver , lead , etc . the reinforcement material is impregnated with thermosetting or thermoplastic resins , serving as the matrix binder and providing vibration damping effect to shaft 12 . suitable resins include epoxy ; polyester ; polystyrene ; polyurethane ; polyurea ; polycarbonate ; polyamide ; polyimide ; polyethylene ; polypropylene ; polyether ; polyvinyl halide ; polyvinylidene halide ; nylon , nylon 6 , polyphenylene sulfide (“ pps ”), polyether ether ketone , polyether ketone ketone , polyamide imide , polyether imide , polyaryl sulfone , polyether sulfone , liquid crystal polymer , and the like or mixtures thereof . as is well known in the art , these resins may further include modifying agents such as hardeners , catalysts , fillers , crosslinkers , and the like . preferably , the reinforcement materials is present in core layer 32 at a volume percentage of from about 10 % to about 80 %, and at a weight percentage of from about 5 % to about 90 %. more preferably , the volume percentage is from about 30 % to about 70 %, and the weight percentage is from about 20 % to about 75 %. in the preferred embodiment , core layer 32 is formed from epoxy - impregnated carbon or graphite fibers . commercial sources of resin pre - impregnated carbon or graphite fibers are well known in the industry . thickness of shaft 12 depend on specific characteristics desirable from the shaft , as well as the particular club head 18 used , and may vary from one portion of the shaft to another , but should be in a range of between about 0 . 01 inches and about 0 . 5 inches . in one embodiment , cover layer 30 preferably has a thickness of less than about 0 . 2 inches , more preferably from about 0 . 001 inches to about 0 . 15 inches , and most preferably from about 0 . 01 inches to about 0 . 12 inches . core layer 32 should have a thickness of less than about 0 . 3 inches , preferably less than about 0 . 25 inches , more preferably from about 0 . 001 inches to about 0 . 2 inches , and most preferably from about 0 . 01 inches to about 0 . 18 inches . in another embodiment , a volume ratio of core layer 32 to cover layer 30 is preferably less than about 20 : 1 , more preferably less than about 15 : 1 , and most preferably less than about 10 : 1 . furthermore , the thickness of each layer may be non - uniformed and vary depending upon the location along the shaft . for example , cover layer 30 and / or core layer 32 may be thicker at the butt portion 14 and / or thinner at the tip portion 16 . in general , at any point along the shaft , a ratio of wall thickness between cover layer 30 and core layer 32 ranges from about 5 : 95 to about 90 : 10 , more preferably from about 10 : 90 to about 70 : 30 , and most preferably from about 20 : 80 to about 50 : 50 . weight of cover layer 30 is preferably less than about 80 grams , more preferably from about 1 gram to about 60 grams , and most preferably from about 10 grams to about 50 grams . weight of core layer 32 is preferably less than about 100 grams , more preferably from about 1 gram to about 80 grams , and most preferably from about 10 grams to about 70 grams . overall weight of shaft 12 is preferably less than about 130 grams , more preferably less than about 110 grams , and most preferably less than about 95 grams . advantageously , the isotropic material of cover layer 30 increases the shaft torque resistance ( i . e . torsional stiffness ). cover layer 30 reinforces shaft 12 , particularly the tip portion 16 , to prevent club head 18 from twisting around the shaft &# 39 ; s longitudinal axis during impact , thereby keeping the ball flight straight . cover layer 30 also improves shaft 12 in its resistances to breakage at the tip portion 16 and to abrasion and weathering , as well as improves esthetic appearance of the shaft 12 , and facilitates the coupling between shaft 12 and club head 18 . the non - isotropic composite material of core layer 32 reduces the overall weight of the shaft 12 , and enhances its bending and flexion characteristics . in the preferred embodiment , substantially all of the reinforcement materials such as carbon or graphite fibers within core layer 32 are aligned at about 0 ° with respect to the shaft axis ( i . e ., longitudinally along the shaft , or parallel to the length of the shaft ), so that the longitudinal stiffness of core layer 32 is greater than its transverse stiffness . with this configuration , core layer 32 controls majority of the flexural stiffness ( i . e . bending resistance ) of the shaft 12 . bending stiffness ranging from l to x can be achieved simply by incrementally incorporating 0 ° fibers in the core layer 32 . preferably , cover layer 30 and / or core layer 32 extend the entire tip portion 16 and middle portion of the shaft 12 , and more preferably extend substantially the entire length of the shaft 12 . in an alternative embodiment , between about 5 weight percent and about 90 weight percent of the reinforcement material may be aligned preferably at an angle of from about 10 ° to about 170 ° with respect to the shaft axis . more preferably , the alignment angle is from about 30 ° to about 150 °, and most preferably , from about 45 ° to about 135 °. in another embodiment , alternating layers of fiber - reinforced composite material having fiber alignment angles of about 45 °, 0 ° and 135 ° are stacked together to form core layer 32 . preferably the amount of 45 ° fibers and the amount of 135 ° fibers are substantially the same . optionally certain portions of the shaft 12 may be further strengthened by fiber - reinforced composite material having a fiber alignment angle of about 90 °. by virtue of its material composition , core layer 32 can reduce vibration transmission along the shaft 12 , diminish acoustic noise generation upon impact between the club head 18 and the ball , and improve the feel of the club 10 . the thermosetting or thermoplastic resins of core layer 32 as described above provide a certain level of vibration damping to the shaft 12 . preferably , the thermosetting or thermoplastic resin of core layer 32 has a loss factor of from about 0 . 2 to about 1 . 2 at 100 hz and 68 ° f ., a shear storage modulus of at least about 1 , 000 psi , and a young &# 39 ; s modulus of at least about 0 . 01 mpsi . the young &# 39 ; s modulus of the isotropic material of cover layer 30 should be at least about one order of magnitude greater than that of resin in core layer 32 . core layer 32 may be formed by any conventional methods used to manufacture composite ( graphite ) shafts , including sheet or ply rolling , filament winding , multiaxial braiding , ply stacking and rolling , etc . these and other methods appropriate for the fabrication of core layer 32 are well known to one of ordinary skill in the art . fig5 - 8 illustrate the cross - sections of different embodiments of the golf club shaft 12 of the present invention . fig5 depicts the basic dual - layer design having cover layer 30 encircling core layer 32 . shown in fig6 an optional vibration damping layer 34 comprising a viscoelastic material is disposed between cover layer 30 and core layer 32 . the viscoelastic material is capable of dissipating vibration energy by converting it into heat . preferably , the viscoelastic material has a shear storage modulus of at least about 10 psi and a loss factor of at least about 0 . 01 at a temperature range of − 40 ° c . to 100 ° c . and a frequency range of 1 hz to 10 , 000 hz . the viscoelastic material preferably has a young &# 39 ; s modulus of at least about 15 psi , and is less than that of the isotropic material of cover layer 30 by at least about one order of magnitude , preferably by at least about three orders of magnitude . also preferred , the viscoelastic material has a strain energy ratio of at least about 2 %. vibration damping layer 34 may be a continuous layer , a discontinuous layer , a layer of uniformed or non - uniformed thickness , a lattice network layer , a wound layer , a woven or braided layer , or a laminar layer . the viscoelastic material of vibration damping layer 34 may optionally have adhesive properties , be crosslinked , and further comprise additives such as fibrous and / or particulate materials , curing agents , crosslinking agents , fillers , colorants , processing aids , antioxidants , foaming agents , and mixtures thereof . specific viscoelastic materials for the present invention include , but are not limited to , vinyl copolymers ; polyvinyl acetate and copolymers thereof ; acrylics ; polyesters ; polyurethanes ; polyethers ; polyamides ; polybutadienes ; polystyrenes ; polyisoprenes ; polyethylenes ; polyolefins ; polyvinyl butyral ; styrene / isoprene block copolymers ; metallized polyesters ; metallized acrylics ; epoxies ; epoxy and graphite composites ; epoxy - acrylate interpenetrating networks ; natural and synthetic rubbers ; silicon rubbers ; nitrile rubbers ; butyl rubbers ; styrene - butadiene copolymers ; piezoelectric ceramics ; thermosetting and thermoplastic rubbers ; foamed polymers ; ionomers ; low - density fiber glass ; bitumen ; air bladders ; liquid bladders ; and mixtures thereof . the metallized polyesters and acrylics preferably comprise aluminum as the metal . piezoelectric ceramics particularly allow for specific vibration frequencies to be targeted and selectively damped electronically . examples of additives and alternative configurations of vibration damping layer 34 are described in u . s . pat . no . 5 , 902 , 656 , the disclosure of which is incorporated herein by reference in its entirety . commercially available viscoelastic materials applicable in the present invention include resilient polymeric materials such as scotchdamp ™ from 3m , sorbothane ® d from sorbothane , inc ., dyad ® and gp ® from soundcoat company inc ., dynamat ® from dynamat control of north america , inc ., noviflex ™ sylomer ® ( from pole star maritime group , llc , and legetolex ™ from piqua technologies , inc . another group of suitable viscoelastic materials is low - density granular materials that when coupled to structures for the purpose of reducing structural vibrations , provide a concomitant attenuation in airborne acoustic noises radiated from the structure . such low - density granular materials include without limitation perlite ; vermiculite ; polyethylene beads ; glass microspheres ; expanded polystyrene ; nylon flock ; ceramics ; polymeric elastomers ; rubbers ; dendritic particles ; and mixtures thereof . preferably , low - density granular materials with dendritic structures and low bulk sound speeds are used for vibration damping layer 34 to maximize damping of low - frequency vibrations and attenuating acoustic noises in golf shafts . technology associated with the use of these low - density granular materials for damping structural vibrations is described by the trademark name lodengraf ™. other choices of materials for vibration damping layer 34 are within the knowledge of one skilled in the art of vibration damping . vibration damping layer 34 preferably has a thickness of less than about 0 . 1 inches , more preferably from about 0 . 0005 inches to about 0 . 05 inches , and is typically no thicker than cover layer 30 or core layer 32 . the thickness of vibration damping layer 34 may be constant or it may vary along the shaft 12 . for example , vibration damping layer 34 may be thicker in the butt portion 14 and thinner in the tip portion 16 . vibration damping layer 34 may be placed only in specific regions along the shaft 12 , preferably only in the butt portion 14 , or cover the entire length of the shaft 12 to prevent propagation of vibrations and shocks . in a preferred embodiment , vibration damping layer 34 comprises a thermosetting or thermoplastic resin identical to the resin in core layer 32 . vibration damping layer 34 preferably covers at least about 5 % of the entire length of the shaft , more preferably from about 25 % to about 100 %, and most preferably from about 50 % to about 100 %. in an alternative embodiment of the present invention , as illustrated in fig7 an intermediate member 36 and an outer layer 38 in combination may replace cover layer 30 of fig5 . intermediate member 36 juxtaposes both core layer 32 and outer layer 38 , and preferably is a porous grid , web , mesh , cloth , woven member , braided member , wound member , coil member , continuous member , discontinuous member , or lattice network member formed of an isotropic material , preferably metallic fibers , filaments , wires , strips , or ribbons . intermediate member 36 may further comprise any of the reinforcement material described above . any of these filaments and / or fibers may be arranged at different angles with respect to the longitudinal axis of shaft 12 . preferably , isotropic ( metallic ) fibers and non - isotropic reinforcement fibers are meshed or inter - woven together . to provide shaft 12 with sufficient stiffness , intermediate layer 36 comprises at least about 50 weight percent of an isotropic or non - isotropic material having a yong &# 39 ; s modulus of greater than about 10 mpsi . intermediate layer 36 is preferably embedded within core layer 32 , so that the outer surfaces of the two are flush with each other . in one embodiment , intermediate member 36 has a thickness of preferably less than about 0 . 2 inches , more preferably between about 0 . 001 inches and about 0 . 15 inches . thickness of intermediate member 36 is also preferred to be less than that of core layer 32 , so that it is partially or fully embedded in the outer surface of core layer 32 . alternatively , thickness of intermediate member 36 may be greater than or equal to that of core layer 32 , and no less than about 0 . 2 inches . by integrating , or “ fusing ,” intermediate member 36 with core layer 32 , torsional rigidity of the shaft 12 is significantly enhanced , yet bending stiffness of shaft 12 is only marginally affected . bending stiffness , as mentioned before , can be modified by incorporating appropriate amounts of 0 ° reinforcement fibers into core layer 32 . suitable isotropic materials for intermediate member 36 include metals such as titanium , steel , stainless steel , aluminum , tungsten , nickel , copper , zinc , chromium , brass , bronze , magnesium , tin , gold , silver , and the like or alloys thereof . other useful materials for intermediate member 36 include quasi - isotropic metallic matrix composites . intermediate member 36 may be applied in any portions of the shaft as a continuous or discontinuous layer having uniformed or non - uniformed thickness . preferably , intermediate member 36 covers at least the tip portion 16 of the shaft 12 where torsional rigidity is most demanded and desired . the tip portion 16 typically is about 2 inches to about 10 inches in length , measured from the lower tip end upward along the shaft 12 . overall , intermediate member 36 covers at least about 5 % of the length of the shaft 12 , more preferably at least about 75 %, and most preferably about 100 %. in one embodiment , intermediate member 36 and vibration damping layer 34 may be used together in a multi - layer hybrid shaft , as shown in fig8 . vibration damping layer 34 may juxtapose both core layer 32 and outer layer 38 . intermediate member 36 is preferably integrated with , or embedded within , vibration damping layer 34 , having a thickness of no greater than vibration damping layer 34 . intermediate member 36 and vibration damping layer 34 may be substantially coextensive and have substantially the same thickness , in which case they are combined to form a single hybrid layer that provide both structural strength and vibration damping to the shaft 12 . in the presence of intermediate member 36 , as in fig7 and 8 , it is preferred to cover the entire shaft 12 with an outer layer 38 of an isotropic material for added durability and aesthetic appeal . suitable isotropic materials for outer layer 38 are metals , preferably the same metal used to form intermediate member 36 , and comprises titanium , steel , stainless steel , aluminum , tungsten , nickel , copper , zinc , chromium , brass , bronze , magnesium , tin , gold , silver , and the like or alloys thereof . preferably , outer layer 38 has a thickness of less than about 0 . 05 inches , more preferably between about 0 . 0004 inches and about 0 . 03 inches , and most preferably between about 0 . 001 inches and about 0 . 02 inches . conventional methods for metal polishing may be used in fabricating outer layer 38 , as detailed below . furthermore , a reinforcing layer 40 formed from an isotropic or quasi - isotropic material may be disposed on the inner surface of core layer 32 , as illustrated in fig9 and 10 . such configurations sandwich core layer 32 between reinforcing layer 40 on the inside and cover layer 30 ( fig9 ) or the combination of intermediate member 36 and outer layer 38 ( fig1 ), forming a classic strained layer vibration damping system that effectively dissipate mechanical energy in the shaft 12 resulted from striking . reinforcing layer 40 may be continuous or discontinuous , porous or nonporous , similar in construction and / or material composition to cover layer 30 or intermediate member 36 , with a thickness of preferably less than about 0 . 1 inches , more preferably from about 0 . 001 inches to about 0 . 05 inches . alternatively , reinforcing layer 40 may be one or more discrete elements placed at predetermined locations on the shaft 12 to achieve certain objectives , such as weight adjustment , structural reinforcement , stiffness modification , or kick point adjustment , among others . reinforcing layer 40 preferably covers a length of at least about 5 % of shaft 12 , more preferably it is coextensive to core layer 32 and / or cover layer 30 . materials suitable for reinforcing layer 40 include those described above for cover layer 30 and intermediate member 36 . shaft 12 of the present invention is typically produced in a two - stage process . first , cover layer 30 is pre - formed using conventional methods known to one of ordinary skill in the art , including sheet welding , cold drawing and extrusion . preferably , cover layer 30 is produced and then air hardened for extra strength using methods described in u . s . pat . no . 6 , 293 , 313 . cover layer 30 may further be coated with one or more metallic elements using any of the metal polishing and deposition methods disclosed below , or coated with one or more non - metallic materials as finishing layers . certain dimensions of the shaft 12 , including overall length and outer diameters of the butt portion 14 and the tip portion 16 , as well as its general shape ( tapered or stepped ) are determined by cover layer 30 . in the second stage , core layer 32 is typically bladder - molded directly onto the inner surface of cover layer 30 . specifically , as depicted in fig1 , a metal mandrel 50 is provided , which has a length slightly greater than that of the shaft 12 , and a profile substantially tapered uniformly . a channel network 52 is fabricated within the mandrel 50 to connect multiple openings on the surface of mandrel 50 to an external fluid or gas source ( not shown ). the mandrel 50 is covered with a bladder 54 made out of a stretchable and impervious material , such as rubber or latex . the thin bladder 54 in the shape of the mandrel 50 may be formed by dipping a counter - form of the mandrel 50 in a liquid bath of latex or similar material . this produces a bladder 54 which fits the mandrel 50 perfectly , and avoids folds and other surface defects . alternatively , as described in u . s . pat . no . 6 , 361 , 840 , the bladder 54 may be formed by injection molding , which allows the bladder wall to have variable thickness , thereby enabling core layer 32 to have variable wall thickness and complex interior profile , or allowing core layer 32 to conform to inner contours of cover layer 30 . plus , the injection - molded bladder 54 has added advantages of withstanding high compaction pressures , being durable and reusable and therefore cost - effective , and being easy to remove . bladder 54 is preferably comprised of an elastomeric , heat - resistant material . bladder 54 is required to expand but very little when the bladder is pressurized to compress core layer 32 against cover layer 30 , and it must also be stretched and removed from the interior of the finished cured part . resilient and flexible materials that are suitable to form bladder 54 include , without limitation , silicon rubber , neoprene , polyvinyl chloride , polyurethane esters , polyurethane ethers , olefins , polyesters , polyethylterephthalate , elastomers , polyethylene , polypropylene , latex , thermoplastics , and mixtures thereof . bladder 54 may be provided using conventional molding techniques such as blow molding , injection molding , rotational molding , thermoforming , vacuum - forming , thermal shrink - wrapping , or the like . it is understood by the skilled artisan that other materials and techniques known or yet unknown may be employed to produce desirable bladder 54 . bladder 54 may have a single cell or compartment , or a plurality of segregated cells or compartments that can be independently inflated or pressurized , or the multiple cells or compartments are interconnected with each other . bladder 54 may further have surface features and / or contours such as bumps , ribs , grooves , protrusions , recesses , dimples , and the like that are in linear , helical , interleaving , spiral , scattered , lattice , wavy , or any other patterns . varying angles and orientation of the features may result in different stiffness and stress resistance for the shaft . during the bladder molding process , these features and / or contours on bladder 54 can create complementary features and / or contours on the inner surface of core layer 32 . in one embodiment , the grooves , recesses and / or dimples are filled with one or more reinforcing materials or reinforcing layer 40 disclosed herein , so that the reinforcing materials or reinforcing layer 40 can be co - molded onto or into core layer 32 in an integrated fashion . examples of bladder 54 having groove patterns capable of molding integrated ribs on the inner surface of a tubular structure are described in international publication no . wo 01 / 97990 , the disclosure of which is incorporated herein by reference in its entirety . the bladder - covered mandrel 50 is then wrapped with resin - impregnated reinforcement fibers to form core layer 32 . typically , the pre - impregnated fiber sheets (“ prepregs ”) are draped or “ laid up ” over the bladder - covered mandrel 50 , so that the uni - directional fibers are aligned at 0 ° to the longitudinal axis of the shaft 12 . plies of prepregs having fiber alignment angles of from about 30 ° to about 150 ° relative to the shaft axis are preferably used to provide additional torsional stiffness , particularly to critical areas such as the tip portion 16 . core layer 32 preferably adopts a laminar structure , having 0 ° prepreg plies interleaving 45 ° ( i . e . + 45 °) plies and 135 ° ( i . e . − 45 °) plies , as described in u . s . pat . no . 5 , 569 , 099 . methods for forming core layer 32 in alternative to the sheet - rolling process described above include filament - winding process and braiding process . a filament - rolled shaft 12 is formed by winding fiber bundles of reinforcing fibers ( yarns ) over the mandrel 50 while reciprocating them along the longitudinal axis of the mandrel 50 . a braided shaft 12 is formed by braiding a plurality of fiber bundles of reinforcing fibers ( yarns ) or tow prepregs ( or yarn prepregs ) over the mandrel 50 to cover substantially the entire length of the shaft 12 . in manufacturing any of the shafts , the reinforcing fibers may be impregnated with thermosetting or thermoplastic resins before or after wrapping the fibers around mandrel 50 . the resin of core layer 32 and / or vibration damping layer 34 may be spin - sprayed onto the inner surface of cover layer 30 , or coated onto the outer surface of bladder 54 by dipping . in the case of thermosetting resins , it is critical that the resins remain uncured until the start of the bladder - molding process described below . otherwise the cured thermosetting resin will be un - moldable . as for thermoplastic resins , they can be uncured , partially cured or fully cured prior to bladder - molding . partially or fully cure thermoplastic resins may be softened by heat , therefore enabling the molding process . the pre - formed cover layer 30 is placed securely in a pre - determined position in a mold 56 . cover layer 30 is secured in its position by the entire interior wall mold 56 of portion of it snuggly pressing around it , or by various clamps , holders , and the like . a pre - assembled core insert is prepared by covering mandrel 50 sequentially with bladder 54 and core layer 32 , the later of which may be constructed from any combinations of prepreg plies known to one of ordinary skill in the art . the pre - assembled core insert is placed into cover layer 30 . mold 56 is then closed to hold the mandrel 50 firmly in place at one end or both ends , so that the pre - assembled core insert is substantially concentric to cover layer 30 , leaving a space 58 between cover layer 30 and core layer 32 . typically the space 58 is limited to a minimum in order to lower the expansion of core layer 32 during bladder inflation and resin curing . to produce a shaft of fig6 or 10 , a vibration damping layer 34 is further wrapped around core layer 32 on mandrel 50 as part of the pre - assembled core insert prior to placing into cover layer 30 . deposition methods for vibration damping layer 34 include sheet - rolling , filament - winding , braiding , dip coating , spin spraying , or any others known to the skilled artisan . referring to fig1 , core layer 32 may be molded onto the inner surface of cover layer 30 through , among other methods , bladder - molding . specifically , heated and pressurized fluid or gas , or heat - expandable foam , bead or paste is forced into bladder 54 via channel network 52 to inflate bladder 54 . mold 56 , cover layer 30 and optionally mandrel 50 are pre - heated just prior to expansion of bladder 54 and then maintained at a regulated constant temperature during the molding cycle . bladder 54 expands progressively , pushing core layer 32 outward toward the inner surface of cover layer 30 . air in space 58 prior to molding is displaced by the outwardly moving core layer 32 and vented out through small openings on mold 56 . the pressurized fluid or gas fills gap 60 left by the expanding bladder 54 . when the outer surface of core layer 32 is in firm contact with the inner surface of cover layer 30 , expansion of bladder 54 ceases , and the internal pressure of bladder 54 reaches a certain stable level , preferably between about 50 psi and about 300 psi . bladder 54 is maintained at this pressure for a few minutes , allowing the heated thermosetting or thermoplastic resins in core layer 32 to cure , and then depressurized and deflated , while core layer 32 continues to be exposed to heat until at least about 90 % cure is achieved . in this embodiment , cover layer 30 is preferably a solid tubular piece with or without any gaps or spaces on its inner surface . the outward movement of core layer 32 , together with optional chemical treatment and / or physical roughening described below , ensures the formation of a tight bond between core layer 32 and cover layer 30 . when core layer 32 is sufficiently cured , the heat is removed and hybrid shaft 12 can then be extracted out of mold 56 . variables such as duration , temperature , and pressure in each steps above depend upon , among other factors , the nature and reactivity of the resins in core layer 32 , as well as the nature of the material used to form bladder 54 . the conjoining between the inner surface of cover layer 30 and the outer surface of core layer 32 during the bladder molding process above may involve structural adhesives , contact adhesion , physical bonding , chemical bonding , and the like or a combination thereof . in order to facilitate the bonding between the two layers , it may be desirable to physically and / or chemically roughen the inner surface of cover layer 30 to increase area of contact , or chemically functionalize the inner surface , through processes such as chromate treatment , phosphonation , or silanation , among others . suitable structural adhesives for bonding between isotropic materials and non - isotropic materials of the present invention include epoxies , acrylics , acrylic / epoxy hybrids , and the like or mixtures thereof . examples of these structural adhesives are commercially available from 3m of st . paul , minn . two - part reaction - cured epoxies , one - part heat - cured epoxies , and two - part urethane adhesives are sold under the trademark of scotchweld ™. moisture - curing polyurethane adhesives are sold under the trademark of jet - weld ™, double - coated pressure - sensitive all - acrylic foam tapes are sold under the trademark of vhb ™, and heat - cured acrylic / epoxy hybrid structural bonding tapes are sold under the trademark of sbt ™. both vhb ™ and sbt ™ tapes are preferred adhesives , because their materials provide added seals against moisture and corrosion , and they can serve as a replacement for vibration damping layer 34 to diminish vibration generation and propagation in the shaft 12 . other suitable structural adhesives for the present invention are known to one of ordinary skill in the art , and include hot melts and polyvinyl acetate . depending on the nature of the adhesives , they can be coated or wrapped around core layer 32 during the assembly process and then co - molded onto the inner surface of cover layer 30 , or they can be spin - sprayed onto the inner surface of the cover layer 30 . in another embodiment , prepreg plies forming core layer 32 are directly assembled onto mandrel 50 without bladder 54 , seal - wrapped with a scrim - type material , and heat - cured to form core layer 32 . then a layer of structural adhesives such as the vhb ™ or sbt ™ tapes is applied over core layer 32 through dip coating , spray coating , tape winding , or sheet wrapping . a volatile material such as mineral spirit can be used to coat the adhesive - covered core layer 32 for lubrication , so that core layer 32 can be easily slid into cover layer 30 . finally , the jointed cover layer 30 and core layer 32 are co - heated to evaporate off the volatile lubricant , allowing the adhesive to firmly bond cover layer 30 and core layer 32 together to form hybrid shaft 12 of the present invention . fabrication of shafts of the present invention using a combination of intermediate member 36 and outer layer 38 as the cover layer are shown in fig1 and 14 . porous intermediate member 36 is first placed with its outer surface firmly pressed against the inner surface of mold 56 in a pre - determined position . pre - assembled mandrel 50 covered around with bladder 54 , core layer 32 , optional vibration damping layer 34 , and optional adhesive layer is inserted into intermediate member 36 . mold 56 closes to secure and center the mandrel pre - assembly within intermediate member 36 . bladder molding ensue , the detail of which is described above . under the pressure of the expanding bladder 54 , the material of the outer surface of the pre - assembly , may it be core layer 32 , vibration damping layer 34 , or optional adhesive layer , completely fills the gaps and spaces within the porous intermediate member 36 . when the outer surface of the pre - assembly reaches the outer surface of intermediate member 36 , it is stopped by the inner surface of mold 56 . internal pressure of bladder 54 build up to a steady level in a range of from about 100 psi to about 500 psi . as a result , intermediate member 36 is effectively embedded tightly into the resin matrix of core layer 32 , with its outer surface substantially flush with that of core layer 32 to jointly form a continuous outer surface . after core layer 32 is allowed to cure , the resulting pre - finished shaft 12 of intermediate member 36 and core layer 32 is removed from mold 56 , and outer layer 38 is applied thereon . metal coating methods for this step include , but are not limited to , thermal spraying , hot - dip galvanizing , painting , flow coating , electroless deposition , electroplating , chemical vapor deposition , physical vapor deposition , kinetic energy metallization , sputtering , ion implantation , or the like . thickness of outer layer 38 preferably ranges from about a few layers of molecules to about 0 . 05 inches , more preferably from about 0 . 0004 inches to about 0 . 05 inches , and most preferably from about 0 . 001 inches to about 0 . 02 inches . optionally , selective regions of the shaft 12 , such as the tip portion 16 , may be coated with a thicker outer layer 38 than other regions , thereby imparting desired properties such as extra torsional stiffness and resistance to breakage to the selected regions . reinforcing layer 40 may be incorporated into hybrid shaft 12 by embedding it in or depositing it on an inner surface of core layer 32 either during the construction of the pre - assembled core insert , or after core layer 32 is fully cured . in one embodiment , reinforcing layer 40 is a pre - formed , porous and expandable grid , cloth , filament wound layer , or coil layer , in which case it may be wrapped immediately around bladder 54 before lay - up of core layer 32 , and co - molded into shaft 12 with core layer 32 . this way reinforcing layer 40 is partially or fully embedded into the inner surface of core layer 40 . in another embodiment , core layer 32 is first bladder - molded onto cover layer 30 or intermediate member 36 . reinforcing layer 40 is then formed by depositing one or more metal element on the inner surface of core layer 32 using any of the methods mentioned above for fabrication outer layer 38 . in an alternative embodiment , reinforcing layer 40 is a solid sheath , a discontinuous layer , or a lattice network layer wrapped directly on mandrel 50 . core layer 32 and optional vibration damping layer 34 are laid up on reinforcing layer 40 to form a pre - assembled core insert . the core insert is wrapped with a scrim - type layer and fully cured in an oven as a typical composite shaft . then the cured core insert is coated with a layer of structural adhesive , lubricated with mineral spirit , and placed snuggly into cover layer 30 . heat is applied to evaporate off the mineral spirit so that the adhesive bonds the cured insert to cover layer 30 to yield hybrid shaft 12 . after shaft 12 is molded and optionally coated with outer layer 38 , certain cosmetic steps such as finishing , painting and varnishing are performed . desirably , any burrs of resin located along the mold joint are removed by grinding or other methods . painting can be followed by a post - curing operation , which entails heating shaft 12 at a temperature of between about 80 ° c . and about 180 ° c . for approximately 25 minutes to 2 hours . this step completes the curing of shaft 12 and releases the volatile organic compounds and hazardous air pollutants from within core layer 32 . any of the layers disclosed herein for hybrid shaft 12 may further include one or more layers to achieve certain functions or properties . for example , cover layer 30 may be coated with one or more metallic or non - metallic layers for enhanced appearance or weather - proofing . core layer 32 may include multiple plies of prepreg having reinforcement fibers aligned at different angles to the shaft axis for added strength and / or stiffness . shaft 12 may further incorporate one or more decorative layers to enhance aesthetics , such as those disclosed in u . s . pat . no . 5 , 773 , 154 . all patents and patent applications cited in the foregoing text are expressly incorporated herein by reference in their entirety . the invention described and claimed herein is not to be limited in scope by the specific embodiments herein disclosed , since these embodiments are intended as illustrations of several aspects of the invention . any equivalent embodiments are intended to be within the scope of this invention . indeed , various modifications of the invention in addition to those shown and described herein will become 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 .

a hollow golf club shaft of circular cross - section comprises a tubular cover layer formed from an isotropic material and a tubular core layer formed from a non - isotropic material , wherein the cover layer and the core layer coextend substantially the entire length of the shaft .

references are made herein to the attached drawings . like reference numerals are used throughout the drawings to depict like or similar elements of the interchangeable hair dryer styling attachments . for the purposes of presenting a brief and clear description of the present invention , the preferred embodiment will be discussed as used to style hair with a hair dryer . the figures are intended for representative purposes only and should not be considered to be limiting in any respect . referring now to fig1 , there is shown a view of the interchangeable hair dryer styling attachment 21 of the present invention . the present invention comprises a flexible , heat - insulated hose 22 having a first end 43 and a second end 44 . in the illustrated embodiment , the hose 22 is an accordion style hose that can be flexed and bent in any direction . the first end 43 of the hose 22 comprises a hair dryer connector 23 having a funnel - shape with a proximal end 45 and a distal end 46 , wherein both of the proximal end 45 and the distal end 46 are open . the proximal end 45 is connected to the first end 43 of the hose 22 via a joint 47 , which may be a component of the hair dryer connector 23 or the hose 22 , depending upon embodiment . the distal end 46 comprises an opening 31 , which provides access to the hollow interior 27 of the hose 22 . the hair dryer connector 23 is tapered so that the distal end 46 comprises a larger diameter than the proximal end 45 . it is contemplated that the tapering increases the velocity of the air flow to ensure that the air flow speed is not lowered due to the distance that the air must travel through the hose 22 . the hair dryer connector 23 is composed of flexible and resilient material , such as rubber , silicone , or the like . in this way , the hair dryer connector 23 can conform to the shape of the barrel of a hair dryer . in use , the hair dryer connector 23 can be press - fitted to the barrel of a hair dryer and remain removably secured thereto . the opening 31 comprises a lip 48 therearound , which helps to increase the grip the barrel of a hair dryer . additionally , the user can grab the lip 48 with his or her fingertips to detach the hair dryer connector 23 from the hair dryer . the second end of the hose 22 comprises a hair styling tool connector 24 having a proximal end 49 that is connected to the second end 44 of the hose 22 , and a grooved distal end 30 . similar to the hair dryer connector 23 , both of the ends 30 , 49 of the hair styling tool connector 24 are opened . the distal end 30 is adapted to removably secure to a hair styling tool 25 at the opened connecting end 26 thereof . the opened connecting end 26 comprises a greater diameter than the diameter of the distal end 30 so that the distal end 30 and the connecting end 26 can removably attach via a press fit or a friction fit . in the illustrated embodiment , the hair styling tool 25 comprises a round brush . the round brush comprises a cylindrical body 50 with a plurality of bristles 51 around the exterior thereof and a hollow interior 29 . the cylindrical body 50 of the brush comprises a plurality of vents 28 thereon . the vents 28 provide access to the hollow interior 29 of the brush . in this way , air can flow from the hair dryer , travel through the hose 22 , and flow out of the air vents 28 of the hair styling tool 25 . referring now to fig2 , there is shown a view of the present invention as connected to a barrel 52 of a hair dryer 32 . the hair dryer connector 23 is connected to the barrel 52 of the hair dryer 32 so that the opening 31 on the distal end of the hair dryer connector 23 is aligned with the barrel of the hair dryer 32 and the hair dryer connector 23 is pressed towards the back of the barrel until it is resisted . the hair dryer connector 23 may comprise a diameter that is slightly greater than the diameter of the barrel 52 to form a mating friction fit with the barrel 52 of the hair dryer 32 . the hair dryer connector 23 is adapted to snugly fit the barrel of the hair dryer 32 via a friction fit so that air can flow directly from the hair dryer 32 into the first end 43 of the hose 22 . the hair dryer connector 23 further comprises a biased lip 48 which resiliently retains the dryer barrel 52 . in other embodiments , however , the hair dryer connector 23 may further comprise a clip or a similar fastening means that can attach onto the end of the barrel 52 of a hair dryer 32 . the second end 44 of the hose 22 is connected to a hair styling tool 33 via a hair styling tool connector 24 . in the illustrated embodiment , the hair styling tool 33 comprises a comb having a handle 53 , a base 54 , and a plurality of teeth 55 thereon . the handle 53 is insulated so that it is not excessively hot to the touch during usage thereof . the base 54 of the comb comprises a plurality of apertures through which air can escape . the teeth 55 may be spaced far apart or close together , depending upon embodiment . additionally , the teeth 55 may be slideably attached to the base 54 so that different types of comb or brush may be utilized . preferably , the apertures are positioned between the teeth 55 of the comb so that the air flow is distributed evenly along the comb . the hose 22 is elongated and is dimensioned so that the hair dryer 32 can rest on a surface while the hair styling tool 33 is held by the user during use . in this way , the user is not required to hold the hair dryer 32 in one hand and a hair styling tool 33 in the other , allowing the user to utilize his or her free hand to style his or her hair . furthermore , the hair styling tool 33 may be rotatably attached to the hair styling tool connector 24 so that it can rotate 360 degrees . this eliminates the need for the user to adjust his or her grip when turning the hair styling tool 33 or when using the hair styling tool 33 on different parts of the user &# 39 ; s head . referring now to fig3 , there is shown a view of an embodiment of an interchangeable styling attachment of the present invention . the illustrated hair styling tool 34 comprises a paddle brush having a handle 56 , a base 57 , and a plurality of bristles 58 extending therefrom . the bristles 58 may be composed of natural or synthetic material , and in some embodiments , may comprise a brush - comb hybrid . the base 57 of the brush comprises a plurality of apertures 59 thereon . the apertures 59 provide access to a hollow interior of the brush , which is in air communication with the hose 22 and a hair dryer on which it is attached . the apertures 59 are spaced evenly throughout the base so that the air flow is evenly distributed . in the illustrated embodiment , the handle 56 of the brush is connected to the hose 22 by means of a second embodiment of the hair styling tool connector 35 . the hair styling tool connector 35 is affixed to the second end of the hose 22 , and may comprise a curved end that connect to the handle 56 of the brush . preferably , the exterior surface 62 of the hair styling tool connector 35 is substantially contiguous with the exterior surface 63 of the handle 56 so that it comprises a unitary appearance and is comfortable to hold . in the illustrated embodiment , the hair styling tool connector 35 further comprises a plurality of ridges 61 thereon . the ridges 61 allow the user to grip the connector 35 easily when installing and removing the hair styling tool 34 . fig4 shows a view of another embodiment of an interchangeable styling attachment of the present invention . the illustrated styling tool comprises a hood 38 that is attached to a cylindrical handle 36 by means of a hood connector 37 . each of the handle 36 and the hood connector 37 comprises an open upper end and an open lower end . the upper end 65 of the connector 37 is affixed to an opening 64 on the underside of the hood 38 . the opening 64 is sealed around the perimeter thereof so that air does not escape therefrom . the lower end 66 of the connector 37 is attached to the upper end 67 of the handle 36 . the lower end 68 of the handle 36 is attached to the hair styling tool connector 35 at the second end of the hose 22 . the hood 38 is composed of nylon , or other lightweight , durable material . the hood 38 is adapted to cover the user &# 39 ; s hair and can secure to the user &# 39 ; s head by means of drawstrings 40 disposed around the opening 39 thereof . the drawstring 40 can be tightened or loosened as desired by the user . additionally , the hood 38 may comprise elastic 41 along the top portion 69 of the opening 39 so that the top portion 69 of the hood 38 can be fitted to the contours of a user &# 39 ; s face . the elastic 41 may be sewn along the top portion 69 of the hood 38 so that it corresponds with the user &# 39 ; s forehead when worn . the hood 38 is constructed so that it can over the user &# 39 ; s head while the user is wearing hair rollers thereunder . the hood 38 comprises a plurality of apertures 42 that provide ventilation so that air can escape out of the hood 38 . the apertures 42 are sparsely disposed on the hood 38 so that it does not allow excessive amount of air to escape therethrough , allowing the hood 38 to retain sufficient amount of heat therein . thus , the hood 38 is ideal for use when the user is receiving heat - activated hair treatments , or applying conditioners , hot oils , and the like . it is therefore submitted that the instant invention has been shown and described in what is considered to be the most practical and preferred embodiments . it is recognized , however , that departures may be made within the scope of the invention and that obvious modifications will occur to a person skilled in the art . with respect to the above descriptions then , it is to be realized that the optimum dimensional relationships for the parts of the invention , to include variations in size , materials , shape , form , function , and manner of operation , assembly and use , are deemed readily apparent and obvious to one skilled in the art , and all equivalent relationships to those illustrated in the drawings and described in the specifications are intended to be encompassed by the present invention . therefore , the foregoing is considered as illustrative only of the principles of the invention . further , since numerous modifications and changes will readily occur to those skilled in the art , it is not desired to limit the invention to the exact construction and operation shown and described , and accordingly , all suitable modifications and equivalents may be resorted to , falling within the scope of the invention .

disclosed is an interchangeable hair dryer styling attachment . the device includes an elongated hose having a first end and a second end . the first end includes a hair dryer connector and the second end includes a hair styling tool connector . the hose is flexible and heat - insulated so that it can be manipulated easily while withstanding hot air from a hair dryer . the hair dryer connector is funnel - like in shape and is configured to snugly fit to a barrel of the hair dryer . the hair styling tool connector includes a grooved end that removably connects to various hair styling tools such as brushes and hoods or bonnets . the hose provides air communication between the hair dryer and the hair styling tools , and is of sufficient length that the hair dryer can rest on a surface while the hair styling tools are used .

the principles and operation of the present invention may be better understood with reference to the drawings and the accompanying description . the following figure reference labels are used throughout the description to refer to similarly functioning components are used throughout the specification hereinbelow . 5 drug delivery infusion set with low cost pump ; 6 treatment element ; 8 drug or medicament reservoir ; 10 reusable unit ; 12 drug delivery pump ; 15 coupler ; 20 disposable unit ; 22 infusion cannula ; 24 adhesive surface ; 30 electronic module ; 32 controller ; 34 communication module ; 36 power supply module ; 50 auxiliary device ; 100 infusion set ; 110 cannula ; 110 i entry port ; 120 adhesive layer and laminate ; 130 catheter housing ; 140 rotating circular disc ; 150 functional unit member ; 160 drug reservoir ; 170 drug reservoir cavity ; 180 connection exit port ; 190 plunger ; 200 manual pump member ; 210 treatment element ; 220 electronics module ; fig1 a shows a block diagram of an optional embodiment of the present invention showing infusion set and mechanical pump apparatus 5 comprising a reusable unit 10 and a disposable unit 20 , a treatment element 6 and drug and / or medicament reservoir 8 . most preferably reusable unit and disposable unit may be coupled in a one to one relationship with coupler 15 so as to render the apparatus 5 operational and / or functional only when reusable unit 10 and disposable unit 20 are coupled in the correct manner . optional embodiments of the present invention provide for the treatment element 6 and drug reservoir 8 to be disposed about and / or configured to be a part of and / or integrated with , either one or both of reusable unit 10 and disposable unit 20 , or in any combination thereof . for example both treatment element 6 and reservoir 8 may be disposed within disposable unit 20 , as shown in fig1 d . for example both treatment element 6 and reservoir 8 may be disposed within reusable unit 10 , as shown in fig1 e . for example treatment element 6 may be disposed within disposable unit 20 while reservoir 8 disposed within reusable unit 10 , as shown in fig1 b . for example treatment element 6 may be disposed within reusable unit 10 while reservoir 8 disposed within disposable unit 20 , as shown in fig1 c . optionally drug reservoir 8 may be provided in a plurality of optional forms as a drug source for example including but not limited to vial , cartridge , iv bag , drug storage bag , or the like . most preferably reusable unit 10 comprises a drug delivery pump 12 that is most preferably a low cost manual pump that may for example take the form of a syringe like pump providing for pumping and / or delivering a drug and / or medicament from reservoir 8 to a drug delivery site ( not shown ). optionally and most preferably pump 12 is provided in the form of a manual pump and / or mechanical pump . optionally pump 12 may be provided in the form of a low cost electrical pump . optionally pump 12 may be provided in the form of an automatic injection pen . most preferably disposable unit 20 comprises a single use and / or single use period and / or disposable infusion catheter and / or infusion cannula 22 provided for delivering the drug from its reservoir 8 to the tissue site . most preferably cannula 22 is coupled to a user for the duration of a single use period with an adhesive layer 24 covered with a laminate that may be to couple cannula 22 to the user &# 39 ; s skin . most preferably coupler 15 provides for coupling and aligning cannula 22 with corresponding opening in pump 12 so as to allow and ensure drug delivery flow from reservoir 8 to the drug delivery site ( not shown ). optionally and preferably coupler 15 may further provide a drug delivery safety element provided to avoid accidental infusion . optionally coupler 15 may further comprise an approval button and / or safety catch or the like member provided to ensure and / or approve drug delivery prior to infusion and / or manual pumping as a further safety and / or failsafe measure . optionally reusable unit 10 may further comprise an electronics module 30 provided for controlling and operating treatment element 6 , for example provided in the form of a heating element . electronics module 30 and / or circuitry may comprise a controller 32 for example a microprocessor , a power supply module 36 for example comprising rechargeable power source , and a communication module 34 . optionally communication module 34 may provide for wireless and / or wired and / or contactless communication with at least one or more optional auxiliary device 50 for example including but not limited to blood glucose monitor , computer , server , mobile communication device or the like , for example as shown in fig1 b optionally electronics module 30 may be provided to operate and control treatment element 6 when disposed on either of disposable unit 20 or reusable unit 10 . optionally module 30 may be coupled or otherwise functionally associated with treatment element 6 . optionally treatment element 6 may be rendered operational with manual means for example including but not limited to user manual manipulation such as rubbing , pinching , twisting or the like manual or mechanical means for increasing local blood perfusion the drug infusion area . fig1 b shows an optional infusion set system 7 according to an optional embodiment of the present invention comprising the drug delivery infusion set 5 and an optional auxiliary device 50 . most preferably auxiliary device 50 and infusion set 5 may be in contactless and / or wireless and / or wired communication via an optional communication module 34 . most preferably auxiliary device 50 comprises processing and display capabilities for interfacing with a user and / or device . optionally , auxiliary device 50 may provide for controlling the amount of infused drug to be delivered . fig1 c shows an optional configuration of infusion set 5 wherein treatment element 6 is disposed with the reusable unit 10 . optionally and preferably treatment element 6 may be powered with a electronics module 30 . fig1 d shows an optional configuration of infusion set 5 wherein both drug reservoir 8 and treatment element 6 are disposed within disposable unit 20 . most preferably coupler 15 provides for coupling and aligning pump 12 with reservoir 8 and cannula 22 . optionally coupler 15 may further provide for coupling electronic module 30 to treatment element 6 . fig1 e shows an optional configuration of infusion set 5 wherein both drug reservoir 8 and treatment element 6 are disposed within reusable unit 20 . most preferably coupler 15 provides for coupling and aligning pump 12 with reservoir 8 and cannula 22 . fig2 a - e show a schematic illustration of an optional embodiment of the present invention , similar to that described in fig1 a above , comprising an infusion set disposable member 100 comprising a catheter and / or cannula 110 for subcutaneous delivery of a medicament , that may be coupled to the body with an adhesive layer 120 provided for coupling to the injection site for a single use period , for example of up to about 3 days . most preferably infusion set member 100 comprises a housing 130 , provided for coupling a reusable pump member 200 . optionally and most preferably housing 130 comprises external threading , or the like coupling means , provided for coupling infusion set member 100 and pump member 200 in a one to one manner such that when coupled cannula 120 is aligned and rendered functional and can receive a flowing drug from pump member 200 . fig2 b and 2c provide a top view and side view of functional unit 150 comprising treatment element 210 and drug reservoir 160 . most preferably functional unit 150 may be provided in a reusable , multiuse configuration or in a single use and / or disposable configuration . functional unit 150 may be coupled to infusion set member 100 over corresponding external threading disposed about housing 130 . most preferably drug reservoir 160 and drug reservoir cavity 170 may be provide with an exit port 180 that is aligned with a corresponding entry port disposed about cannula 110 i , in a one to one manner such that infusion set 100 is rendered functional only when exit port 180 and entry port 110 i are successfully coupled and aligned . optionally and preferably reservoir 160 may be placed in reservoir cavity 170 . optionally a third coupling member or drug safety element , for example in the form of a push button and / or safety catch and / or pin , that may be provided as a further failsafe prior to drug delivery and verification prior to drug infusion . for example coupler 15 ( fig1 a - e ) may be realized by way of coupling three members comprising , exit port 180 , entry port 110 i and a safety catch all of which must be aligned and functional to allow infusion . most preferably treatment element 210 , for example provided in the form of a heating element , is provided such that it may provide treatment in the form of heat over the infusion site to modify pharmacodynamic and pharmacokinetic properties of the delivered drug . preferably treatment element 210 may be controlled and rendered functional with optional electronic module 220 comprising power supply . optionally electronic module 220 may comprise a controller , communication module and power supply module , for example as described in fig1 b - e . fig2 d depicts a schematic illustration of a pump member 200 according to an optional embodiment of the present invention , for example as described in fig1 a . manual pump member 200 comprises a plunger 190 that provides for manually pumping a flowing drug from drug reservoir 160 to cannula 110 at the infusion site . optionally , plunger 190 may be a friction free plunger comprises a freely rotating ball to allow ease of manipulation of pump 200 with plunger 190 about housing 130 for example by the rotation of the circular disk 140 along the threads of the catheter housing , 130 . optionally functional unit 150 may be integrated with infusion set housing 130 , therein provided for single use . optionally functional unit 150 may be integrated with pump housing 200 , therein provided for multiuse . optionally plunger 190 or electronics module 220 may provide for setting the dosage to be dispensed and / or delivered through reservoir 160 . optionally dosage setting with plunger 190 may be provided by way of communication with an auxiliary device 50 ( not shown ). although particular embodiments have been disclosed herein in detail , this has been done by way of example and for purposes of illustration only , and is not intended to be limiting . in particular , it is contemplated by the inventors that various substitutions , alterations , and modifications may be made without departing from the spirit and scope of the disclosed embodiments . other aspects , advantages , and modifications are considered to be within the scope of the disclosed and claimed embodiments , as well as other embodiments disclosed herein . the claims presented hereafter are merely representative of some of the embodiments disclosed herein . other , presently unclaimed embodiments are also contemplated . the inventors reserve the right to pursue such embodiments in later claims and / or later applications claiming common priority . there are many inventions described and illustrated herein . the present inventions are neither limited to any single aspect nor embodiment thereof , nor to any combinations and / or permutations of such aspects and / or embodiments . moreover , each of the aspects of the present inventions , and / or embodiments thereof , may be employed alone or in combination with one or more of the other aspects of the present inventions and / or embodiments thereof . for the sake of brevity , many of those permutations and combinations will not be discussed separately herein . importantly , the summary may not be reflective of or correlate to the inventions protected by the claims in this or continuation / divisional applications hereof even where this summary is reflective of or correlates to the inventions protected by the claims hereof , this summary may not be exhaustive of the scope of the present inventions . while the invention has been described with respect to a limited number of embodiment , it is to be realized that the optimum dimensional relationships for the parts of the invention , to include variations in size , materials , shape , form , function and manner of operation , assembly and use , are deemed readily apparent and obvious to one skilled in the art , and all equivalent relationships to those illustrated in the drawings and described in the specification are intended to be encompassed by the present invention . therefore , the foregoing is considered as illustrative only of the principles of the invention . further , since numerous modifications and changes will readily occur to those skilled in the art , it is not described to limit the invention to the exact construction and operation shown and described and accordingly , all suitable modifications and equivalents may be resorted to , falling within the scope of the invention . having described a specific preferred embodiment of the invention with reference to the accompanying drawings , it will be appreciated that the present invention is not limited to that precise embodiment and that various changes and modifications can be effected therein by one of ordinary skill in the art without departing from the scope or spirit of the invention defined by the appended claims . further modifications of the invention will also occur to persons skilled in the art and all such are deemed to fall within the spirit and scope of the invention as defined by the appended claims . while the invention has been described with respect to a limited number of embodiments , it will be appreciated that many variations , modifications and other applications of the invention may be made .

the subject matter described herein relates generally to systems and methods for delivering one or more drugs to a user while applying treatment to the infused drug site . in particular , the subject matter described herein relates to device , systems and methods for drug delivery using manual pump with an infusion set that includes one or more treatment sources to improve effectiveness of the injected medicament

the foregoing and other aspects of the present invention will now be described in more detail with respect to other embodiments described herein . it should be appreciated that the invention can be embodied in different forms and should not be construed as limited to the embodiments set forth herein . rather , these embodiments are provided so that this disclosure will be thorough and complete , and will fully convey the scope of the invention to those skilled in the art . the terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention . as used in the description of the invention and the appended claims , the singular forms “ a ”, “ an ” and “ the ” are intended to include the plural forms as well , unless the context clearly indicates otherwise . unless otherwise defined , all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs . all publications , u . s . patent applications , u . s . patents and other references cited herein are incorporated by reference in their entireties . with reference to fig1 a and 1b there is shown a cross section of a heart valve leaflet treated with concentrations of 0 . 03 % sds . total leaflet decellularisation was observed at this concentration . however , at concentrations below 0 . 05 % ( fig2 a and 2b ), whole cells or cell fragments were found to have been retained by the matrix . cross section of a heart valve leaflet treated with 0 . 02 % sds is therefore a concentration below which decellularisation does not occur . it can be seen that cell fragments and whole cells have been retained within the matrix ( blue / black pigment ). following the method of the present invention , patella tendons may also be successfully decellularised ( fig3 b ). porcine hearts were procured from a local abattoir within 2 hours of slaughter and transported on ice to the laboratory . on arrival at the laboratory , aortic valve roots were dissected from the heart and washed in transport solution [ hanks &# 39 ; balanced salt solution ( hbss ), 10 kiu / ml aprotinin , 10 u / ml penicillin , 100 μg / ml streptomycin , 100 u / ml nystatin , 10 mm hepes ph7 . 6 ). the aortic valves were incubated overnight ( 14 hours ) in hypotonic tris buffer ( 10 mm tris ph8 , 0 . 1 % ( w / v ) ethylene diamine tetraacetic acid ( tdta ), 10 kiu aprotinin in distilled water dw ). subsequently , the aortic valves were incubated for 24 hours with shaking at ambient temperature in ( 0 . 05 %- 0 . 1 %) ( w / v ) sodium dodecyl sulphate ( sds ) or 0 . 5 % sodium deoxycholate in hypotonic tris buffer . they were then washed (× 3 ) with tris buffered saline ( 0 . 15m nacl , 0 . 05m tris ph 7 . 6 in dw ) containing protease inhibitors ( 0 . 1 % w / v edta and 10 kiu / ml aprotinin ). they were then subjected to a further wash (× 3 ) with tris buffered saline ( tbs ) without protease inhibitors . the aortic valves were then incubated for 4 - 6 hours at 37 ° c . with dnase i ( 20 μg / ml ) and rnase a ( 1 μg / ml ). after this they were washed (× 3 ) in tbs containing protease inhibitors . finally , in preparation for storage they were placed in cryoprotectant [ dulbecco modified eagles medium ( dmem ) containing 10 % ( v / v ) foetal bovine serum ( fbs ) and 10 % ( v / v ) dimethyl sulphoxide ( dmso ) and cryopreserved in liquid nitrogen until they were required for implantation . porcine patella tendons were dissected and then washed in pbs . the tendons were incubated overnight ( 24 hours ) in hypotonic tris buffer ( 10 mm tris ph 8 , 0 . 1 % ethylene diamine tetraacetate ( edta ), 10 kiu aprotinin in distilled water ( dw )]. tendons were subsequently incubated for a further 24 hours with shaking at ambient temperature in 0 . 03 - 0 . 1 % w / v sodium dodecyl sulphate ( sds ) or 0 . 5 % sodium deoxycholate in hypotonic tris buffer . they were then washed (× 3 ) with pbs containing protease inhibitors ( 0 . 1 % edta and 10 kiu / ml aprotinin ). with reference to fig3 a there is shown a photomicrograph of fresh porcine patella tendon , stained with heamatoxylin and eosin (× 400 ). fig3 b shows a photomicrograph of porcine patellar tendon following de - cellularisation treatment as described above and also stained with heamatoxylin and eosin (× 400 ). it is apparent from comparing the figures that decellularisation has been achieved whilst maintaining the histoarchitecture of the material .

a method of preparing matrices or tissue engineered biomaterials for implantation , and in particular to a method of improving decellularisation of matrices or tissue engineered biomaterials prior to implantation . the method employs a single anionic detergent in combination with protease inhibitors .

referring now to the figures of the drawings in detail and first , particularly , to fig1 thereof , there is seen a torque - transmitting , variably - flexible , corrugated insertion device 1 according to the invention . the insertion device 1 has a hollow body with a proximal end 2 for manipulation by an operator and for receiving an instrument such as an endoscope or a colonoscopy . the insertion device 1 also has a distal end 3 for insertion into a patient and for protrusion of the instrument . a handle 4 of the hollow body for control by the operator is disposed at the proximal end 2 . an outer jacket 5 of the hollow body extends to a tip 7 , which may be formed of rubber , at the distal end 3 , but only a portion of the outer jacket has been shown in order to illustrate other details of the device disposed within the outer jacket 5 . a flexible strain relief retainer 6 is disposed between the handle 4 and the outer jacket 5 . the outer jacket 5 and the flexible strain relief retainer 6 provide a flexible section with a given length extending beyond the handle 4 . the handle 4 has a sliding valve 28 and a septum valve assembly 29 , which will be explained in greater detail below with regard to fig2 . the handle 4 also has a vacuum connection or nipple 35 for controlling stiffness of the device , as will be explained below as well . a corrugated tube 30 , which is only illustrated in the region of the distal tip 7 , actually extends to the flexible strain relief retainer 6 . the insertion device 1 may be steerable or non - steerable . if the device is steerable , a steering assembly 10 is provided which includes six vertebrae 13 - 18 shown as being disposed along the hollow body . however , more or fewer vertebrae can be provided in dependence on the length , diameter and use of the hollow body . eight tendons 11 , 11 ′ are equally spaced apart about the circumference of the hollow body between the vertebra 17 and the handle 4 , although only five can be seen in fig1 . four of the tendons which extend from a tendon termination bushing 31 at the tip 7 to the handle 4 are so - called steering tendons 11 ′. other tendons which only extend between the vertebra 17 and the handle 4 are so - called non - steering tendons 11 . each of the four steering tendons 11 ′ is attached at its proximal end to a respective knob 36 which slides within a respective slot 38 in the handle 4 . a stop 39 is also disposed on each tendon 11 ′. when a knob 36 is slid proximally , it pushes a stop 39 and pulls a tendon 11 ′ to steer the hollow body . in the condition shown in fig1 , the knob 36 at the bottom has been slid proximally so that the tip 7 of the hollow body has been steered downward . if different knobs 36 are moved , the hollow body will be steered in different directions . when the knobs 36 are forced distally , the knobs can freely slide independently of the tendons 11 ′ to prevent buckling of the tendons 11 ′. it will be readily understood that if two of the knobs are slid proximally , the tip 7 will move in a direction between the two directions that each one of the knobs would have moved the tip if moved individually . in fig2 , an outer covering of the handle 4 has been removed to show details of the sliding valve 28 and the septum valve assembly 29 . the handle 4 has an inner handle 19 disposed within an outer handle 18 , defining an annular vacuum plenum volume 24 therebetween which extends in longitudinal direction of the handle 4 . a vacuum inlet / outlet hole or port 25 is formed in the body of the outer handle 18 and communicates with the volume 24 . a sliding so - called tire valve thumb grip 20 encircles the outer handle 18 and is sealed thereto by o - ring seals having o - rings 21 in recesses 22 in the grip 20 . an o - ring seal is also disposed at the proximal end of the handle 4 . the grip 20 also has a vacuum inlet / outlet 23 for the connection or nipple 35 . when the grip 20 is slid toward an annular stop 26 , the vacuum inlet / outlet 23 is not in alignment with the vacuum inlet / outlet hole 25 . however , when the grip 20 is slid toward an annular stop 27 , the vacuum inlet / outlet 23 and the vacuum inlet / outlet hole 25 are aligned , providing communication between the connection or nipple 35 and the volume 24 . therefore , during operation , the grip 20 is slid toward the stop 27 to apply vacuum to stiffen the hollow body or to vent the vacuum to the atmosphere or supply air at atmospheric pressure to make the hollow body flexible again . the grip 20 is slid toward the stop 26 to maintain the stiffened or flexible condition of the hollow body attained by vacuum or venting or air supply through the connection or nipple 35 . the septum valve assembly 29 is in the form of an end cap which is inserted into the proximal end of the outer handle 18 and provides a so - called septum seal for insertion of an instrument 44 , such as an endoscopy or a colonoscopy , represented by a dot - dash line . end caps with various sized openings may be used in dependence on the instrument being used . the instrument passes through the hollow body and emerges at the distal tip 7 . a diaphragm seal is provided between the septum valve assembly 29 and the inner handle 19 . if the insertion device 1 is non - steerable , the number of tendons 11 may also be varied as shown in fig3 to provide stiffness zones . for example , a stiffness zone a closest to the distal tip 7 has four tendons , a stiffness zone b has eight tendons and a stiffness zone c closest to the handle 4 has sixteen tendons . a zone with more tendons will be stiffer than a zone with fewer tendons . the number of tendons and their location within the zones as well as the number of zones can be increased or decreased , depending on the application of the device . vertebrae 12 - 18 , which in this case are seven in number , are also shown . the four tendons in the zone a all end at the termination bushing 31 but are free to slide elsewhere . four of the eight tendons in zone b , which do not extend to zone a , are fixed at the vertebra 14 between zones a and b , which is therefore referred to as a termination vertebra , but are free to slide elsewhere . similarly , eight of the sixteen tendons in zone c , which do not extend into zones a and b , are fixed at the termination vertebra 16 between zones b and c but are free to slide elsewhere . fig4 shows the device 1 with the handle 4 removed , from which it can be seen that the four steering tendons 11 ′ of the steering assembly 10 continue toward the handle from the tip 7 , whereas the non - steering tendons 11 only run from the termination vertebra 15 to the handle . it is also seen that as the insertion device is steered , the steering tendons 11 ′ on the outside of the bend become shorter and the steering tendons 11 ′ on the inside of the bend become longer . fig5 shows a similar view to fig4 , in which it can be seen how a greater number of vertebrae react to bending . in the case of fig5 , eight steering tendons 11 ′ extend to the termination bushing 31 , whereas six non - steering tendons 11 extend from the termination vertebra 18 to the handle . in the enlarged view of fig6 , a portion of the corrugated tube 30 in the region of the tip 7 and the termination bushing 31 are shown . the tendons 11 , 11 ′, which have been omitted in fig6 for the sake of clarity , are shown in fig7 as extending through the vertebrae 13 , 14 to the termination bushing 31 . a tip restrictor 32 can also be seen at the tip 7 . it may also be seen that an inner liner 33 extends within the corrugated tube 30 . one purpose of the inner liner is to provide a surface on which the instrument will pass smoothly within the corrugated tube . the corrugated tube 30 may be formed of nylon or another suitable material . the inner liner 33 is made from a sheet of white plastic material which has an adhesive coating on one side . the inner liner 33 is rolled around an inflatable mandrel and heated in an oven , to form a bonded seam 42 ( shown in fig1 - 13 ) and is sealed to an inner surface of the corrugated tube 30 . the corrugations of the corrugated tube 30 have peaks and valleys . as viewed from within the corrugated tube 30 , the inner liner 33 adheres to the peaks and extends somewhat into the valleys of the corrugations as dimples . therefore , as the insertion device bends , the inner liner 33 stays tight along the corrugations on the outside of the bend and crinkles at the inside of the bend . the peaks and valleys of the corrugations also need not be of equal length along the length of the corrugated tube 30 . for example , 70 % of the length may be peaks and 30 % valleys or 80 % of the length may be peaks and 20 % valleys . these variations will add to the adhesion of the inner liner to the corrugated tube and reduce the formation of dimples . however , a 50 / 50 corrugation ratio is shown in the figures . the outer jacket 5 may be formed of polyurethane or another suitable material which is similarly a flat sheet that is rolled and seamed . the outer jacket 5 and the inner liner 33 both extend to the termination bushing 31 , which may be formed of polycarbonate . the corrugated tube is cuffed in order to prevent leakage paths for the vacuum applied within the hollow body and to protect the material of the inner liner . fig8 illustrates two types of molded corrugation cuffs 34 , namely a straight cuff on the left and a stepped cuff on the right , of the figure , both with a 50 / 50 corrugation ratio . fig9 shows the inner handle 19 which is attached to a corrugation cuff 34 , as well as the inner liner 33 that is sealed to the corrugated tube 30 and to the inner handle 19 to prevent a vacuum leakage path . the perspective view of fig1 illustrates the insertion device 1 in the region of the tip 7 , including the outer jacket 5 extending to the tip , which is not shown in the other figures . the fragmentary , perspective view of fig1 illustrates the insertion device 1 in the region of the tip 7 , with the outer jacket removed to reveal the termination bushing 31 at the tip 7 , the corrugated tube 30 , the vertebrae 13 , 14 , the tendons 11 or 11 ′ and the inner liner 33 . it is seen that the tendons slide through channels 37 in the vertebrae . in fig1 , not only the outer jacket 5 but also the tip 7 have been removed to show how the tendons 11 , 11 ′ are anchored in the termination bushing 31 . as can been seen , each tendon 11 , 11 ′ passes through a respective hole 40 in the termination bushing 31 . each two tendons together have a u - shape in the form of a large staple having a crosspiece 41 extending between two of the holes 40 . this avoids the necessity of welding ends of tendons to a terminating vertebra or ring . the u - shaped tendons and crosspiece are best seen in fig1 a . in fig1 , not only the outer jacket 5 and the tip 7 but also the termination bushing 31 have been removed to show a portion of the inner liner 33 which is sealed on the inner surface of the termination bushing 31 for vacuum sealing and smooth movement of the instrument or scope 44 . the crosspieces 41 of the tendons 11 , 11 ′ as well as the seam 42 of the inner liner are also clearly shown . fig1 is a cross - sectional view of the insertion device 1 which is taken through the flexible tip restrictor 32 , as seen in the direction of the vertebra 13 . therefore , the outer jacket 5 , the vertebra 13 with the tendons 11 . 11 ′, the corrugated tube 30 with the peaks and valleys and the tip restrictor 32 , can be seen . representative vertebrae 12 - 18 are shown in fig1 and 16 . the vertebra of fig1 is a so - called latch ring constructed for snap installation . the vertebra is formed of elastic material which permits it to be expanded at a parting line and opened at a gap 43 , so that it can be snapped over the corrugated tube 30 between two peaks thereof . therefore , the vertebra can be installed at any location desired along the corrugated tube for support of the tendons . the vertebra shown in fig1 is intended to be placed at an end of the corrugated tube 30 , where no expansion and snapping into place are required . the operation of the variably flexible insertion device 1 will now be described below by making reference to the above - described figures . if the steerable embodiment is used , the device 1 is flexed against the stiffness of the corrugated tube 30 , for example upon traversing the rectosigmoid junction , by sliding one or more of the knobs 6 . in either the steerable or non - steerable embodiment , if it is desired to maintain that flexed condition for guiding an endoscope , such as a colonoscopy , vacuum is applied at the connection or nipple 35 . when suction is applied to create the vacuum , it causes the inner sleeve 33 and the outer jacket 5 to approach each other with the corrugated tube 30 and the tendons 11 , 11 ′ sandwiched and frictionally locked therebetween . therefore , the vacuum connection or nipple 35 acts as a device for transitioning the hollow body 4 , 7 , 19 , 5 , 33 , 30 between a relatively flexible condition and a relatively stiff condition through the application of a vacuum . as long as the vacuum is applied , the device 1 maintains its flexed condition . the positions of the knobs 6 in fig1 , 2 , 4 and 5 show that in the flexed condition , the tendons 11 ′ at the outer periphery of the bend become shorter and the tendons 11 ′ at the inner periphery of the bend become longer , since they are all fixed in place at the termination bushing 31 . the tendons or wires are passive elements which are not in tension at any time . the tendons float within the hollow body when it is in the flexible condition , except where they are fixed to termination vertebrae or the termination bushing 31 at the distal end . the tendons are frictionally locked by the inner sleeve 33 and the outer jacket 5 when the hollow body is in the stiff condition . however , in both the relatively flexible condition and the relatively stiff condition , the tendons have no active control imposed on them and are not pulled or constrained . when it is desired to resume flexibility of the device 1 , the vacuum is vented or replaced by air at ambient or positive pressure . this causes the inner sleeve 33 and the outer jacket 5 to release the tendons and allows the stiffness of the corrugated tube 30 to place the device 1 into its normally flexible condition . the device is intended to be used in a manner similar to prior art devices . therefore , the device will be placed over the endoscope . the endoscope will then be inserted into the rectum . the device will then be pushed in its flexible condition , to follow the curvature of the scope . the device will then be stiffened , allowing the scope to be pushed forward with less pressure exerted on the colon of the patient . this procedure can be repeated until the scope reaches the cecum . an alternative use of the device is to aid in small bowel endoscopy . the device is placed over the endoscope . the endoscope is inserted into the patient transorally , through the stomach and then partially into the small bowel . the device is then pushed in its flexible condition , to follow the curvature of the scope . the device is then stiffened , allowing the scope to be pushed forward without the scope looping in the stomach . another use of the device is for aiding in access to internal body parts , such as the gallbladder , through an opening of an internal body cavity , such as the stomach . the device is placed over the endoscope . the endoscope is inserted into the patient transorally , through the stomach and then up against the internal surface of the stomach . the device is then pushed in its flexible condition , to follow the curvature of the scope . the device is then stiffened , allowing the surgeon to create an opening in the stomach wall without the scope looping in the stomach . once the opening is created , the device and the scope can be advanced outside the stomach . the device can then be stiffened to create a stable platform to perform surgical procedures outside of the stomach . the device could contain one or more features ( i . e . balloons ) for sealing the outer periphery of the device to the stomach wall to prevent gastric fluids from exiting the stomach . in each of these procedures described above , the knobs and tendons are used to steer the insertion device within the body as needed , while the corrugated tube allows the device to be twisted as needed .

a method for variably flexing and steering an insertion device that receives an instrument , which comprises providing a hollow body having tendons disposed therewithin and a distal end , changing a condition of the hollow body by selectively applying suction to create a vacuum in the hollow body to place the hollow body in a relatively stiff condition and relieving the vacuum to place the hollow body in a relatively flexible condition , maintaining the hollow body in the relatively flexible and relatively stiff conditions with the tendons , the vacuum created by the applied suction frictionally locking the tendons in place in the relatively stiff condition , and individually adjusting at least one of the tendons in length to steer the distal end of the hollow body .

in the present invention , it is preferable that a plurality of channels and analysis portions are provided with respect to one lancing portion . with this configuration , a plurality of items can be measured by performing lancing only once . in the present invention , it is preferable that a plurality of lancing portions are provided in one sensor , and at least one channel and analysis portion are provided with respect to each lancing portion . with this configuration , one sensor can be used in a plurality of measurements . in the present invention , it is preferable that at least the lancing portion of the cover is hydrophilic . blood normally is hydrophilic . thus , when the lancing portion of the cover is hydrophilic , blood can adhere well to the burr formed . accordingly , with this configuration , blood can be supplied to the analysis portion more reliably . in the present invention , it is preferable that an air vent hole is provided in a portion of the cover that corresponds to the channel . by providing the air vent hole , it is possible to cause a capillary phenomenon . the sensor of the present invention may be , for example , a sensor utilizing a redox reaction . in this case , a reagent containing an oxidoreductase that reacts with an analyte is disposed on the analysis portion , and the amount of the analyte is measured by causing a redox reaction between the oxidoreductase and the analyte contained in the blood and then measuring the degree to which the redox reaction has occurred . the degree to which the redox reaction has occurred can be measured by optical means or electrochemical means , for example . the measurement using the optical means can be achieved by forming the reagent layer so as to contain a substrate that develops color by the redox reaction in addition to the oxidoreductase and measuring the degree of the color developed by this substrate with an optical measuring device such as a spectrophotometer . on the other hand , the measurement using the electrochemical means can be achieved by disposing the electrodes in the analysis portion and measuring a current generated by the redox reaction with these electrodes . in this case , the reagent preferably contains a mediator . an analyte to which the sensor of the present invention is applicable is not particularly limited , and examples thereof include glucose , lactic acid , and cholesterol in blood . the oxidoreductase to be contained in the reagent may be selected depending on the analyte . for example , when the analyte is glucose in blood , the oxidoreductase may be glucose oxidase or glucose dehydrogenase . hereinafter , an example of a sensor according to the present invention will be described with reference to the drawings . fig1 and fig2 shows an example of a sensor according to the present invention . note here that the sensor shown in fig1 and fig2 is a sensor with a basic structure . fig1 is an exploded view of the sensor , and fig2 is a cross - sectional view of the same . as shown in the drawings , in this sensor 100 , a cover 109 is disposed on an insulating substrate 101 with a spacer 106 intervening therebetween . on the insulating substrate 101 , a working electrode 102 and a counter electrode 103 are formed , which are connected to a lead 122 and a lead 123 , respectively . furthermore , the insulating substrate 101 has a through hole 105 through which a needle or an edge of a lancet can pass . the spacer 106 has a space 107 that serves as a through hole through which a needle or an edge of a lancet can pass and also as a channel . the cover 109 has an air vent hole 110 at a portion corresponding to the rear side of the channel . the through hole 105 of the insulating substrate 101 and a part of the space 107 of the spacer 106 together form a through hole through which a needle or an edge of a lancet can pass . the top of this through hole is covered with the cover , thereby forming a lancing portion . the remaining portion of the space 107 of the spacer 106 serves as a channel 112 . furthermore , as shown in fig2 , a reagent layer 104 is disposed on the working electrode 102 and the counter electrode 103 , thereby forming an analysis portion . in the present invention , the material for the insulating substrate is not particularly limited , and may be , for example , polyethylene terephthalate ( pet ), polycarbonate ( pc ), polyimide ( pi ), polyethylene ( pe ), polypropylene ( pp ), polystyrene ( ps ), polyvinyl chloride ( pvc ), polyoxymethylene ( pom ), monomer - cast nylon ( mc ), polybutylene terephthalate ( pbt ), polymethyl methacrylate ( pmma ), an abs resin ( abs ), or glass . among them , polyethylene terephthalate ( pet ), polycarbonate ( pc ), and polyimide ( pi ) are preferable , and polyethylene terephthalate ( pet ) is more preferable . the size of the insulating substrate is not particularly limited . for example , the insulating substrate may have an overall length of 5 mm to 100 mm , a width of 3 mm to 50 mm , and a thickness of 0 . 1 mm to 2 mm ; preferably an overall length of 10 mm to 50 mm , a width of 3 mm to 20 mm , and a thickness of 0 . 2 mm to 1 mm ; and more preferably an overall length of 15 mm to 30 mm , a width of 5 mm to 10 mm , and a thickness of 0 . 3 mm to 0 . 6 mm . in the insulating substrate , the through hole may be formed , for instance , by perforating the insulating substrate with a laser , a drill , or the like , or by forming the insulating substrate using a die that can form the insulating substrate provided with the through hole . the shape of the through hole is not particularly limited , and may be circular , oval , semicircular , semioval , polygonal , or the like . the maximum diameter of the through hole is not particularly limited , and may be , for example , 0 . 5 mm to 20 mm , preferably 0 . 5 mm to 5 mm , and more preferably 1 mm to 3 mm . the electrodes and leads on the insulating substrate may be formed , for example , by forming a conductive layer with gold , platinum , palladium , or the like by sputtering or vapor deposition and then processing the conductive layer into a particular electrode pattern with a laser . examples of the laser include yag lasers , co 2 lasers , and excimer lasers . the reagent layer contains an oxidoreductase , a mediator , and the like , for example . when an analyte is glucose in blood , the oxidoreductase may be glucose oxidase , glucose dehydrogenase , or the like . examples of the mediator include potassium ferricyanide . in addition to the oxidoreductase and the mediator , the reagent layer further may contain a hydrophilic polymer , an enzyme stabilizer , a crystal homogenizing agent , and the like , for example . the hydrophilic polymer serves to keep the reagent layer in a predetermined shape ( i . e ., the hydrophilic polymer serves as an excipient ), and examples thereof include carboxymethyl cellulose ( cmc ). the enzyme stabilizer prevents an enzyme from being deteriorated during storage , and examples thereof include maltitol . the crystal homogenizing agent serves to homogenize the reagent layer , which allows the reagent layer to dissolve quickly and uniformly when blood touches it . examples of the crystal homogenizing agent include taurine . the reagent layer can be formed , for example , by dissolving a predetermined reagent in water or a buffer solution and then drying it . as one example , the reagent layer can be formed in the following manner . first , in a 0 . 01 wt % to 2 . 0 wt % cmc aqueous solution , 0 . 1 u / sensor to 5 . 5 u / sensor of pqq - gdh , 10 mm to 200 mm of potassium ferricyanide , 0 . 05 mm to 30 mm of maltitol , and 10 mm to 300 mm of taurine are added and dissolved . the reagent layer can be formed by dropping the thus - obtained solution on the analysis portion of the substrate and then drying it . the drying may be either air drying or forced drying using warm air . however , if the temperature of the warm air is too high , there is a possibility that the enzyme contained in the solution might be deactivated . thus , the temperature of the warm air preferably is around 50 ° c . in the present invention , the material for the spacer is not particularly limited . for example , the same material as that for the insulating substrate can be used . the size of the spacer also is not particularly limited . for example , the spacer may have an overall length of 5 mm to 100 mm , a width of 3 mm to 50 mm , and a thickness of 0 . 01 mm to 1 mm ; preferably an overall length of 10 mm to 50 mm , a width of 3 mm to 20 mm , and a thickness 0 . 05 mm to 0 . 5 mm ; and more preferably an overall length of 15 mm to 30 mm , a width of 5 mm to 10 mm , and a thickness of 0 . 05 mm to 0 . 25 mm . the spacer has the space that serves as the through hole and as the channel this space may have , for example , an overall length of 1 mm to 30 mm and a width of 0 . 05 mm to 10 mm , preferably an overall length of 2 mm to 10 mm and a width of 0 . 3 mm to 5 mm , and more preferably an overall length of 2 mm to 10 mm and a width of 0 . 5 mm to 2 mm . this space can be formed in the same manner as the through hole of the insulating substrate . in the present invention , the material for the cover is not particularly limited . for example , the same material as that for the insulating substrate can be used . it is more preferable that not only a portion of the cover corresponding to the lancing portion but also a portion of the cover corresponding to the ceiling of the sample supply channel is subject to a treatment for imparting hydrophilicity . the treatment for imparting hydrophilicity may be carried out by , for example , applying a detergent or introducing a hydrophillic functional group such as a hydroxyl group , a carbonyl group , or a carboxyl group to the cover surface by plasma processing or the like . the size of the cover is not particularly limited . for example , the cover may have an overall length of 5 mm to 100 mm , a width of 3 mm to 50 mm , and a thickness of 0 . 01 mm to 0 . 5 mm ; preferably an overall length of 10 mm to 50 mm , a width of 3 mm to 20 mm , and a thickness of 0 . 05 mm to 0 . 25 mm ; and more preferably an overall length of 15 mm to 30 mm , a width of 5 mm to 10 mm , and a thickness of 0 . 05 mm to 0 . 1 mm . the cover preferably has an air vent hole , which may have , for example , a maximum diameter of 0 . 01 mm to 10 mm , preferably 0 . 05 mm to 5 mm , and more preferably 0 . 1 mm to 2 mm . the air vent hole can be formed in the same manner as the through hole of the insulating substrate . the sensor of the present invention can be produced by laminating the insulating substrate , the spacer , and the cover in this order and integrating them . the integration can be achieved by adhering these three components with an adhesive or through heat - sealing . as the adhesive , an epoxy adhesive , an acrylic adhesive , a polyurethane adhesive , a thermosetting adhesive ( a hot melt adhesive or the like ), a uv curable adhesive , or the like can be used , for example . next , the method of using the sensor shown in fig1 and fig2 will be described . first , the sensor is set in a predetermined dedicated measuring device . in this state , the sensor 100 is placed on a pulp of a finger 115 , as shown in fig3 . then , the pulp of the finger 115 is punctured with a needle 114 of a lancet . by so doing , as shown in fig4 , the needle breaks through a lancing portion of the cover 109 , passes through a through hole , and then injures the pulp of the finger 115 to cause bleeding . at this time , a burr protruding downward is formed in the lancing portion of the cover 109 . blood 116 coming out from the finger 115 is guided by the burr so that , as indicated by the arrow , it flows through the channel 112 to be led to an analysis portion , where the blood 116 comes into contact with the reagent layer 104 to cause a component in the blood 116 to react with an oxidoreductase or the like contained in the reagent layer 104 . when a voltage is applied between the electrodes after a lapse of a certain period , a redox current flows due to the redox reaction caused by the oxidoreductase . the redox current is detected by the working electrode and the counter electrode , which then is measured by the dedicated measuring device . the measuring device converts the measured value into an amount of the blood component and displays the value obtained by the conversion . note here that in fig4 the same reference numerals are assigned to the same elements as in fig1 and fig2 . in the above - described example of a method of using the sensor , lancing is performed with the sensor being set in the measuring device . however , the present invention is not limited thereto . for example , lancing may be performed without setting the sensor in the measuring device and the sensor may be set in the measuring device after the lancing . next , another example of the sensor of the present invention is shown in fig5 . in this sensor 500 , the positional relationship between an analysis portion and a lancing portion is inverse to that in the above - described sensor ( see fig1 and fig2 ). more specifically , in this sensor , a lancing portion 511 is located closer to one end with respect to the center of the sensor ( on the left in fig5 ), and an analysis portion is located still closer to the end . except for the above , the sensor 500 is configured in the same manner as the above sensor , and the size , materials , production method , method of use , etc . also are the same as those of the above sensor . in fig5 , reference numeral 501 denotes an insulating substrate , 502 denotes a working electrode , 503 denotes a counter electrode , 522 and 523 denote a lead , 504 denotes a reagent layer , and 513 denotes an air vent hole of a cover . next , fig6 shows an example of a sensor in which two analysis portions are provided in series . in this sensor 600 , a lancing portion 611 is provided in one end portion of the sensor 600 , and two analysis portions are provided in series toward the center of the sensor 600 . these two analysis portions communicate with each other via a channel 612 , and the channel 612 communicates with a through hole of the lancing portion 611 . thus , at the time of lancing , blood is guided by a burr formed when a needle or the like of a lancet breaks through a cover so that it is led to the channel 612 and then to the two analysis portions sequentially . except for the above , the sensor 600 is configured in the same manner as the above sensor ( see fig1 and fig2 ), and the size , materials , production method , method of use , etc . also are the same as those of the above sensor . in fig6 , reference numeral 601 denotes an insulating substrate , 602 denotes a working electrode , 603 denotes a counter electrode , 604 denotes a reagent layer , 613 denotes an air vent hole of the cover , and 622 and 623 denote a lead . next , fig7 shows an example of a sensor in which two analysis portions are provided in parallel . in this sensor 700 , a lancing portion 711 is provided in one end portion of the sensor 700 , and a channel 712 extends from the lancing portion 711 toward the center of the sensor 700 and then branches so that the channel 712 as a whole forms a t - shape . the analysis portions are provided on the ends of the branched portions , respectively . the channel 712 communicates with a through hole of the lancing portion 711 . thus , at the time of lancing , blood is guided by a burr formed when a needle or the like of a lancet breaks through a cover so that it is led to the channel 712 and then to the two analysis portions substantially simultaneously . except for the above , the sensor 700 is configured in the same manner as the above sensor ( see fig1 and fig2 ), and the size , materials , production method , method of use , etc . also are the same as those of the above sensor . in fig7 , reference numeral 701 denotes an insulating substrate , 702 denotes a working electrode , 703 denotes a counter electrode , 704 denotes a reagent layer , 713 denotes an air vent hole of the cover , and 722 and 723 denote a lead . note here that in this example , instead of providing the air vent hole 713 in the cover , the t - shaped channel 712 may be formed so that the branched portions extend to side faces of the sensor and the tips thereof are open to the outside , thereby allowing these openings serve as air vent holes . next , fig8 shows an example of a sensor in which four analysis portions are provided radially with respect to one lancing portion . as shown in fig8 , in this sensor 800 , a cover 814 is disposed on a circular insulating substrate 801 with a spacer ( not shown ) intervening therebetween . the sensor 800 is divided in the circumferential direction so as to give four equal portions , namely , a first region 830 , a second region 831 , a third region 832 , and a fourth region 833 . at the center of the sensor 800 , one lancing portion 811 is provided . for example , in the first region 830 , a channel 812 extends from a through hole of the lancing portion 811 toward an analysis portion . in the analysis portion , a reagent layer 804 , a working electrode 802 , and a counter electrode 803 are disposed . the same applies to the other regions . in the respective regions , the electrodes and leads as a whole have a shape of a sector . in the first region 830 , the working electrode 802 and its lead 822 as a whole form a l - shape , and the counter electrode 803 and its lead 823 constitute the remaining portion . the same applies to the other regions . the cover 814 is in a circular shape that is smaller than the insulating substrate 801 so that the analysis portions are covered with the cover 814 but the leads are allowed to be exposed . the cover 814 has air vent holes provided so as to correspond to the four channels ( an air vent hole 813 in the first region 830 ). note here that the number of the analysis portions is not particularly limited in the present invention . instead of providing four analysis portions as described above , two , three , or five or more analysis portions may be provided , for example . moreover , the shape of the working electrode and its lead is not particularly limited , and thus is not limited to the above - described l - shape . the size of the sensor 800 is not particularly limited . for example , the sensor 800 may have a diameter of 10 mm to 200 mm and a thickness of 0 . 1 mm to 5 mm , preferably a diameter of 20 mm to 150 mm and a thickness of 0 . 2 mm to 3 mm , and more preferably a diameter of 30 mm to 120 mm and a thickness of 0 . 2 mm to 1 mm . this sensor can be produced by laminating an insulating substrate , a spacer , and a cover that are formed in a predetermined shape and integrating them . in this sensor , other conditions such as materials are the same as those of the above sensor ( see fig1 and fig2 ). when the sensor 800 is placed on a pulp of a finger and a needle or the like of a lancet breaks through the lancing portion of the cover to injure the finger to cause bleeding , the blood is guided by a burr formed at this time so that , as indicated by the arrow , it is led to the respective channels and flows through the channels to be led to the respective analysis portions . next , fig9 shows an example of a cartridge - type sensor in which a plurality of sensor portions are formed on one substrate . as shown in fig9 , in this sensor 900 , on a circular insulating substrate 901 , a circular cover 914 that is smaller than the insulating substrate is disposed with a spacer ( not shown ) intervening therebetween . a sensor 900 is divided in the circumferential direction so as to give four equal portions , namely , a first sensor portion 930 , a second sensor portion 931 , a third sensor portion 932 , and a fourth sensor portion 933 . each of the sensor portions has a shape of a sector . the sensor 900 has four lancing portions provided in one - to - one correspondence with the sensor portions at its center . for example , in the first sensor portion 930 , a channel 912 extends from a through hole of a lancing portion 911 to an analysis portion , and a reagent layer 904 , a working electrode 902 , and a counter electrode 903 are disposed in the analysis portion . the same applies to the other sensor portions . in each of the sensor portions , the electrodes and leads as a whole have a shape of a sector . in the first sensor portion 930 , the working electrode 902 and its lead 922 as a whole form a l - shape , and the counter electrode 903 and its lead 923 constitute the remaining portion . the same applies to the other sensor portions . the cover 914 is in a circular shape that is smaller than the insulating substrate 901 so that the analysis portions of the respective sensor portions are covered with the cover 914 but the leads are allowed to be exposed . the cover 914 has air vent holes provided so as to correspond to the four channels ( an air vent hole 913 in the sensor portion 930 ). note here that the number of the analysis portions is not particularly limited in the present invention . instead of providing four analysis portions as described above , two , three , or five or more analysis portions may be provided , for example . moreover , the shape of the working electrode and its lead is not particularly limited , and thus is not limited to the above - described l - shape . also , the positions of the lancing portions are not particularly limited , and thus are not limited to the center of the circle as in the above . for example , the lancing portions may be provided closer to the circumference than the analysis portions so that blood flows from the circumferential side to the center of the circle . the size of the sensor 900 is not particularly limited . for example , the sensor 900 may have a diameter of 10 mm to 200 mm and a thickness of 0 . 1 mm to 5 mm ; preferably a diameter of 20 mm to 150 mm and a thickness of 0 . 2 mm to 3 mm ; and more preferably a diameter of 30 mm to 120 mm and a thickness of 0 . 2 mm to 1 mm . this sensor can be produced by laminating an insulating substrate , a spacer , and a cover that are formed in a predetermined shape and integrating them . in this sensor , other conditions such as materials are the same as those of the above sensor ( see fig1 and fig2 ). this sensor 900 can be used as a cartridge type sensor . for example , the sensor 900 is set in a dedicated measuring device , and at first , the first sensor portion 930 is used . more specifically , the first sensor portion 930 is placed on a pulp of a finger , and a needle or the like of a lancet breaks through the lancing portion of the cover to injure the finger to cause bleeding . by so doing , the blood is guided by a burr formed at this time so that , as indicated by the arrow , it is led to the channel 912 and flows through the channel to be led to the analysis portion . after the completion of the measurement using the first sensor portion 930 , subsequent measurement can be carried out by switching the selected sensor portion from the first sensor portion 930 to the second sensor portion 931 by rotation or the like , and performing lancing and blood supply to the analysis portion in the same manner as in the above . measurement to be performed subsequent to this measurement also can be carried out by switching the selected sensor portion and performing the same operations . as specifically described above , the present invention provides a sensor for blood component analysis , which allows even a trace amount of blood to be led to an analysis portion reliably . thus , there is no particular limitation on the use of the sensor of the present invention as long as it is used for blood component analysis . for example , the sensor of the present invention is applicable to a clinical test , self - measurement of blood glucose level by diabetics , etc . moreover , an analyte is not limited to glucose . for example , lactic acid , cholesterol , etc . can be an analyte of this sensor . specific embodiments and examples described in the detailed description of the present invention are intended merely to clarify the technical details of the present invention . the present invention should not be limited to such specific examples to be understood narrowly . the present invention can be changed variously to be carried out within the spirit of the present invention and the range of the following claims .

a sensor for blood component analysis , which allows even a trace amount of blood to be led to an analysis portion reliably . the sensor for blood component analysis includes a substrate , a spacer , and a cover . the cover is disposed on the substrate with the spacer intervening between the cover and the substrate , whereby a space that serves as an analysis portion and a channel for leading blood to the analysis portion is formed inside the sensor . through holes are formed in the substrate and the spacer , respectively , so that a common through hole through which a needle of a lancet can pass is formed when the spacer is disposed on the substrate . the through hole of the spacer communicates with the channel and a top of the through hole of the spacer is covered with the cover , whereby a lancing portion is formed by the common through hole and a portion of the cover covering the top of the through hole of the spacer . in use , the sensor is placed at a position where blood collection is to be performed , the portion of the cover covering the lancing portion is broken through with the needle of the lancet so that the needle is allowed to pass through the common through hole to puncture the position , and blood that has come out is guided by a downwardly protruding burr formed when the cover is broken through so that the blood is led to the channel and flows through the channel to be led to the analysis portion .

fig1 is a schematic , perspective overall representation of an exemplary embodiment of a ligament - tensioning device 1 configured according to the invention for a knee joint , in which displaceability of the claws relative to one another in the anteroposterior direction is achieved . the ligament - tensioning device 1 comprises a base member 2 , which , for reliable introduction of the spreading force into the tibia , has a first claw 3 with a distal bearing surface 4 relative to the knee joint gap , which bearing surface 4 rests on the tibia in the case of the knee joint . opposite the first claw 3 , a handle 5 is accordingly attached to the base member 2 , which handle 5 allows the ligament - tensioning device 1 to be held and tensioned with one hand . likewise in accordance with the arrangement of the first claw 3 and located thereabove , the ligament - tensioning device 1 comprises a tensioning lever 6 , on which a second claw 7 is arranged . according to the invention , the second claw 7 is of two - part construction . a first part 8 is connected to the tensioning lever 6 , a second part 9 is arranged proximally , and displaceably , relative to the first part 8 with regard to the knee joint gap . the second part 9 comprises a proximal bearing surface 10 , which bears on the opposite portion of the joint to be treated , i . e . the femur in the case of the knee joint . the spreading action is produced by actuating the handle 5 together with an operating lever 11 . with regard to the bearing surfaces 4 and 10 , a parallel displacement device 12 allows parallel displacement of the second claw 7 with the bearing surface 10 relative to the first claw 3 with the bearing surface 4 . during such displacement , the second claw 7 is in active connection with the tensioning lever 6 . in the exemplary embodiment , the parallel displacement device 12 is constructed as a four - bar linkage in the form of intersecting rods and comprises four levers 13 , 14 , 15 , 16 , wherein a lever 13 on the tensioning lever side and a lever 16 on the base member side are arranged in parallel , while the levers 14 and 15 cross . the four levers 13 , 14 , 15 , 16 are connected together by means of five axes 17 , 18 , 19 , 20 , 21 . two of the axes 17 , 18 are mounted in the parallel levers 13 , 16 displaceably in grooves 22 , 23 extending parallel to the bearing surfaces 4 , 10 . this configuration of the parallel displacement device 12 allows the lever 13 on the tensioning lever side and the lever 16 on the base member side to move in parallel towards one another or away from one another . the lengths of the levers 13 , 14 , 15 , 16 are so selected that , in the case of any desired tensioning width x between the bearing surface 4 on the first claw 3 and the bearing surface 10 on the second claw 7 , which may be for example between 5 mm and 40 mm , a given conversion ratio prevails between the tensioning force applied manually to the handle 5 and the operating lever 11 and the distraction force exerted on the bones adjoining the joint . the degree of spreading force may be read off from the force display 24 comprising a scale 25 and a movable display lever 26 . the display lever 26 is moved by the longitudinal bending of the operating lever part 27 bendable by manually applied tensioning force relative to the other , display lever 26 arranged in the manner of a fork and not acted upon by this tensioning force . if the display lever 26 and the operating lever part 27 are moved relative to one another by means of the tensioning force , the display lever 26 turns around a pivot 29 , whereby the manually applied tensioning force is displayed on the scale 25 by the display lever 26 . in addition , a locking device , not illustrated in any more detail in fig1 , may be provided between the handle 5 and the operating lever 11 , which locking device allows the ligament - tensioning device 1 to be locked in a given position . as already mentioned above , the second , proximal claw 7 is of two - part construction . the first , distal part 8 is connected to the tensioning lever 6 or is of one - piece construction therewith . the second , proximal part 9 is arranged on the first part 8 and may be shaped like a horseshoe , for example , in order to take account of the shape of the femur condyles , which bear thereon . the proximal part 9 comprises a projection 30 which extends in the anteroposterior direction in a guide 31 formed in the lever 13 . the projection comprises catches 32 , into which a locking device 33 , which in the exemplary embodiment is configured in the manner of a tilting arm or rocker , engages with an appropriately shaped extension 34 . the locking device 33 pivots about an axis 35 , which is disposed on the lever 13 . a free end 36 of the locking device 33 serves in actuation of the locking device 33 . fig2 is a schematic plan view of the exemplary embodiment illustrated in fig1 of a ligament - tensioning device 1 according to the invention . identical components are provided with matching reference numerals . as already explained with regard to fig1 , the ligament - tensioning device 1 configured according to the invention comprises a proximal claw 7 which is at least partially displaceable relative to the distal claw 3 and on whose bearing surface 10 the femur condyles bear in the case of an operation on a knee joint . in fig2 , the proximal part 9 of the second , proximal claw 7 is shown with the bearing surface 10 in the unlatched state . the catches 32 visible on the projection 30 are no longer in engagement with the extension 34 of the locking device 33 . the mode of operation of the ligament - tensioning device configured according to the invention is as follows : if , during preparation for a knee joint implant , a device for tensioning the ligaments is introduced into the knee joint gap and spread apart by an amount x , forces acting obliquely , i . e . not in a craniocaudal or anteroposterior direction , may arise between the tensioning device and the bones bearing thereon due to superimposition of the stresses in ligaments and other soft tissue . these stresses , which may in principle act in any direction , may lead on the one hand , due to resultant frictional forces , to distortion of the quantifiable craniocaudal force and on the other hand to disturbances in the course of the operation , if for example the bones slip off the surface of the pretensioning device or stresses thereby dissipate jerkily or in an uncontrolled manner . to prevent this , the ligament - tensioning device 1 configured according to the invention has a claw 7 arranged so as to be displaceable in the anteroposterior direction and movable relative to the other claw 3 . the displaceable claw 7 is locked during introduction and spreading apart of the ligament - tensioning device 1 by means of the locking device 33 already described . once the desired spreading force has been reached , the operator may release the locking device 33 by pressing on the end 36 thereof preferably with the thumb , such that the extension 34 is no longer engaged with the catches 32 of the projection 30 . in this way , the proximal part 9 of the claw 7 slides in the posterior direction , pulled by the femur condyles bearing on the bearing surface 10 of the claw 7 , until the knee joint is stress - free in this direction . in this way , no jerky stress dissipation can occur during the operation . in addition , the frictional force on the periosteum is reduced and the latter is thereby protected . a scale 37 applied to the guide 31 allows quantification of anteroposterior displacement . this is useful , for example , for detecting the craniocaudal tensioning reaction and thus the influence of the rear cruciate ligament and other soft tissue systems on the relative displacement of the femur relative to the tibia and in addition for monitoring individual steps in soft tissue release . in addition , this quantification serves in objectifying experience gained from operations performed , whereby the knowledge collected therefrom may have an influence for the purpose of increased reproducibility in future operations . it is advantageous to provide a corresponding apparatus also for the other translational and rotational degrees of freedom . for example , it is possible without difficulty to allow mediolateral movement by means of further guidance of the second part 9 of the proximal claw 7 . rotational degrees of freedom , which allow rotation about various axes , are also feasible . spheroid joint connections between the claws 3 and 7 and the ligament - tensioning device 1 would , for example , allow tilting of the claws 3 and 7 relative to one another and could be freely inserted into the exemplary embodiment described . the advantages of such extensions are , in particular , problem - free adaptation to individual anatomical parameters of any particular ( knee ) joint and easy spreading apart of the device for quantifying the actual craniocaudal reaction forces .

a ligament tensing device for activating a ligament and / or capsule system during implantation of a joint implant , comprising a base body having a first lug with a distal bearing surface resting upon a first bone , and a second lug resting upon a second bone with a proximal bearing surface thereof . the second lug is displaceable in an anterior - posterior and / or medial - lateral direction parallel to the first lug .

throughout this document , the term “ attendees ” means individuals attending a meeting . in an embodiment of the present invention , a meal plan designed to balance nutritional value and quantity of food , and type and quantity of fluids is provided . such meal plan is configured to enhance energy levels thereby promoting post - prandial alertness , concentration , and optimal health . the meal plan is designed for multi - day meetings which include three meals ( i . e . breakfast , lunch , and dinner ) and two break periods ( i . e . morning and afternoon break periods ) each day . the meal plan may be provided for any number of days with the option of including or excluding dinner on the last day . the meal plan typically serves between 20 - 60 attendees . the plan uses food groups as defined by canada &# 39 ; s food guide to healthy eating ( published by health canada , 1997 , and incorporated herein by reference ). the meal plan includes foods from the following food groups ( provided with their portions ): ( 1 ) grain products , preferably whole grains ( e . g . whole wheat , oats , barley and rye ) and enriched products ( e . g . enriched pasta , ready - to - eat bran cereals or oatmeal , and multi - grain breads ): between 5 - 12 servings a day . sample grain servings are one slice of bread or ½ cup rice or pasta ; ( 2 ) vegetables and fruits , preferably dark green and orange vegetables ( e . g . spinach , broccoli , yams , and carrots ) and orange fruit ( e . g . oranges and cantaloupes ): between 5 - 10 servings a day . sample fruit and vegetable servings are one medium piece of fruit or ½ cup of cut fruit ; milk products , preferably lower fat milk products ( e . g . skim milk and low fat yoghurt ): between 2 - 4 servings a day . sample milk servings are 1 cup milk , 50 grams cheese or ¾ cup yoghurt ; and meats and alternatives , preferably , leaner meats , fish , poultry , as well as beans and lentils : between 2 - 3 servings a day . sample meat servings are 50 grams ( cooked ) meat , 1 egg or ⅓ cup tofu . in an embodiment of the invention , whole grain foods are provided throughout the day whenever possible , including products such as multi - grain breads at breakfast and enriched pasta at lunch and / or dinner . typically , fruits and vegetables are provided throughout the day and preferably , a fruit basket is available in the meeting space at all times . milk products , which typically include fruit yoghurt and low - fat cream cheese , are provided at breakfast . meats and other protein alternatives , typically including turkey , beef , and fish , are provided at lunch and / or dinner . the average daily intake of 2500 - 2700 total calories a day is adequate for most people to maintain their body weight . the quantity of food for the meal plan which provides food for two meals ( e . g . breakfast and lunch ) and two break periods ( e . g . a morning and an afternoon break period ) per day is designed to provide a total caloric value of 1700 - 2000 calories per attendee . alternatively , the quantity of food for the meal plan which provides a full day of food ( i . e . three meals and two break periods ) is designed to provide a total caloric value of 2500 - 2700 calories per attendee . typically , the total calories of each meal and each break period is as follows : [ 0034 ] fig1 sets out a sample of foods from the meal plan for two meals and two break periods and fig2 sets out a sample of foods from the meal plan for dinner . the main sources of calories from the meal plan include carbohydrates , fats , and proteins . in an embodiment of the invention , carbohydrates are between 45 %- 55 % of total calories , fats are between 25 %- 30 % of total calories , and proteins are between 15 %- 20 % of total calories . total carbohydrate content of the meal plan usually includes breads , rice , pasta , and potatoes . total fat content of the meal plan is limited to healthy levels , especially with respect to saturated fats . typically , fat is limited to approximately 30 % of total calories wherein saturated fats constitute less than 10 % of total calories . vegetable oils , such as olive and canola , are used in food preparation . the use of animal fats is limited . total protein content of the meal plan is mainly derived from leaner cuts of meat products ( e . g . chicken breast ) and fish and seafood . foods that are higher in sugar and fat including desserts and salad dressings are a part of the meal plan but are provided in moderation . in an embodiment of the present invention , the recommended quantity of food per attendee is based on the total caloric needs an average adult requires as set out above , as seen in fig7 to 10 . typically , food from the meal plan is served buffet style with small signs indicating the type of food ( e . g . oven - grilled chicken breast or penne with oyster mushrooms and seasonal vegetables ) and the recommended quantity of food ( e . g . one piece or two serving spoons ) based on the desired total caloric value per day set out above . the signs are preferably printed on standard shipping labels which are 1 ″ by 2⅝ ″ and placed on tent cards , but any display means may be used as long as the printed matter is clearly visible . in an alternative embodiment , a chart of the major allergens and items suitable for common restricted diets is provided . for example , foods suitable for vegans and vegetarians are listed , and foods containing peanuts are identified for attendees who have a peanut allergy . in another alternative embodiment , any higher fat and sugar foods are removed from the in - room snack baskets if attendees stay overnight at a hotel . suitable foods to be placed in the snack basket for attendees include pretzels , trail mix , nuts , dried fruit , and granola bars ( not chocolate covered ). hydrating fluids are provided to assist the central nervous system ( i . e . brain function ). hydrating fluids , including water , herbal tea , and 100 % fruit juices , are provided instead of dehydrating fluids such as alcohol , caffeine - containing drinks , and high sugar drinks . alternatively , lightly caffeinated and decaffeinated coffee are provided with a sign recommending decaffeinated coffee to the attendees . preferably , alcohol is not provided as a part of the meal plan . however , if attendees do consume alcohol , it is recommended that no more than one to two glasses of wine or beer are consumed and that the alcohol is consumed only with dinner . in an alternative embodiment , all alcoholic beverages , pop , and other dehydrating fluids are removed from the mini bar if attendees stay overnight at a hotel . suitable fluids to be placed in the mini bar for attendees include water , juice , and natural juice spritzers . in an embodiment of the invention , a breakfast period , a lunch period and a dinner period is provided during which meals from the meal plan are served . preferably , two break periods are provided throughout a day ( e . g . morning break period and afternoon break period ) and foods and fluids from the meal plan are provided during such break periods . the typical duration of a break period is 10 minutes . preferably , a break period is provided every 50 minutes , but is typically provided between 1 hour and 50 minutes to 2 hours , as , for most attendees , attention starts to wane after 1 hour and 50 minutes . in an embodiment of the invention , breakfast is served at 7 : 00 a . m . and the meeting commences at 8 : 00 a . m . the morning break period is at 10 : 00 a . m . and lunch is provided at 12 : 00 p . m . the meeting recommences at 1 : 00 p . m ., the afternoon break is at 2 : 30 p . m . and dinner is served at 5 : 00 p . m . in an embodiment of the invention , atmospheric conditions of the environment of the meeting space , including arrangement of furniture , temperature , air quality , and lighting are manipulated to promote concentration . the temperature is maintained between 18 ° c . and 23 ° c . ( and ideally between 19 ° c . and 21 ° c .). preferably , ventilation , air filtration , and humidity - management systems are provided . typically , two high efficiency particulate arrestance (“ hepa ”) filters and two humidifiers are placed in the meeting space . the meeting room should be illuminated to at least between 20 - 50 foot candles of light . other modifications to the environment could include aromatherapy or sounds ( such as classical music or nature sounds ). the combination of the above elements presented to attendees of the meeting , including the quality and amount of food served , the environment of the meeting , and the timing of breaks , have a desirable effect of making the attendees considerably more alert and productive than has been the case for meetings . while the principles of the invention have now been made clear in the illustrated embodiments , it will be immediately obvious to those skilled in the art that many modifications may be made of structure , arrangements , and algorithms used in the practice of the invention , and otherwise , which are particularly adapted for specific environments and operational requirements , without departing from those principles . the claims are therefore intended to cover and embrace such modifications within the limits only of the true spirit and scope of the invention .

a method of sustaining alertness of attendees during a meeting is provided , comprising the steps of providing at least a meal from a meal plan to said attendees , each of said meals comprising at least a food and at least a fluid , said meal plan configured to enhance energy levels by selection of a quantity of each of said foods for said meal based on a nutritional value of said food ; and a quantity of each of said fluids for said meal plan based on a nutritional value of said fluid ; providing a time schedule configured to promote attentiveness by providing break periods wherein foods and fluids from said meal plan are served to said attendees ; and providing an environment configured to promote concentration by manipulating atmospheric conditions of a meeting space wherein said meeting takes place .

referring to fig1 , a plan view of one embodiment of a cylinder mandrel 21 illustrates a smooth cylindrical surface 23 interrupted just before each end by a pair of grooves 25 . the grooves 25 are utilized by other structures to help engage and move the cylinder mandrel 21 when its hot . other structures can be used , including projections , loops , and other structures . an internal bore 27 is seen in dashed line format in fig1 . referring to fig2 , a view looking into the end of the cylinder mandrel 21 of fig1 illustrating its hollow through bore 27 . as can be seen the bore 27 is large to leave the cylinder mandrel 21 with a relatively thin wall , but not so thin that the grooves 25 cannot be effectively made with enough depth to provide a catch to an edge of another structure so as to enable the other structure to engage the grooves . in one embodiment , where the exterior diameter of the smooth cylindrical surface 23 of the cylinder mandrel 21 is to have a diameter of 0 . 50 inches , the internal diameter of the bore 27 is preferably about 0 . 44 inches . this leaves 0 . 06 inches to be distributed to both sides to yield a wall thickness of about 0 . 03 inches . the grooves 25 may then be about 0 . 20 inches deep , and possibly as much as 0 . 06 inches wide . overall , the cylinder mandrel 21 may be about 6 . 5 inches long . the use of a large bore 27 permits a relatively thin walled cylinder mandrel 21 which will hold up well under rolling pressure , less metal material for faster heating , quicker cooking and quicker cooling after cooking , and a bore through which hot liquid oil may freely circulate . holes or apertures which extend circumferentially about the cylinder mandrel 21 can be added for increased oil circulation and quick draining , but in such a case , the draining cannot be controlled and directed as it can with a solid cylinder mandrel 21 . further , the surface 23 need not be smooth , but may also be longitudinally grooved to give more hot oil the ability to circulate around the flauta being cooked , so long as the grooves are thin enough ( perhaps along with a layer of flauta which is not very pasty ) to cause the flauta material to sink into the longitudinal grooves within the cylinder mandrel 21 . referring to fig3 , a rolling support 31 is shown combined ( although they need not be ) with a the cylinder mandrel ( cylinder mandrel 21 ) unloading and cooked flauta drainage support 33 , hereafter referred to as unloading and drainage support 33 . although shown as having a common board 35 , the rolling support 31 and unloading and drainage support 33 may have separate boards . on the unloading and drainage support 33 , a vertical stop 37 is used as a low friction guide along which a cylinder mandrel 21 can slide as the cylinder mandrel 21 is rolled over a circular area 39 used for circular shaped flauta or a rectangular area 41 used for rectangular shaped flauta . the vertical stop 37 also sets the position of the flauta material from the end of the cylinder mandrel 21 . a lowered surface 43 may be provided to give some additional clearance for grasping the flauta material and cylinder mandrel 21 after the flauta material is rolled on it . typically the cylinder mandrel 21 will be placed about an inch toward the inside of the material on the side farthest from the unloading and drainage support 33 , the end edge is placed over the cylinder mandrel 21 in the direction of the unloading and drainage support 33 , and then the cylinder mandrel 21 is rolled in a tight manner to form wrapped configuration . once the flauta material is rolled onto the cylinder mandrel 21 , the flauta material should be held manually tightly as the wrapped flauta and cylinder mandrel 21 are transferred . since the rolling support 31 and unloading and drainage support 33 are shown as an integrated unit , the unloading and unloading and drainage support 33 ( hereafter drainage support ) will be discussed . on the same side of the board 35 as the vertical stop 37 , a channel 45 having an overall “ u ” shape is seen . the far side has a straight edge , but the near side has a series of notches 47 , each having a “ v ” upper portion and a curved lower portion ( as will be seen in greater detail ). this structure facilitates the engagement of the near side of the channel 45 with the grooves 25 on the cylinder mandrel 21 . this enables the cylinder mandrels 21 to be removed from a structure supporting them in a configuration approximating their spacing seen in fig3 . also seen on one of the cylinder mandrels 21 is a cooked shell 49 . because the near side of the channel 45 is raised an inch or two above the level of the board 35 , and because the other ends of the cylinder mandrels 21 are supported at board 35 level , the cylinder mandrels 21 are tilted . this enables any excess cooking oil , either within the cylinder mandrels 21 , or on the outside to drain into a separate area or container or absorbent material which may optionally be provided . in the alternative , other structures may be provided to support the cylinder mandrels 21 without touching the board 35 and possibly at a lesser angle of tilt . a catch basin may be provided to collect the excess oil . referring to fig4 , a frying support 51 is seen . frying support 51 includes a handle portion 53 , a support structure 55 , and a multi support tray 57 . the handle portion 53 may be angled for maximum ease and utilization for a given orientation immersion fryer ( not shown ). the handle portion 53 may be removable from or permanently affixed to the support structure 55 . the support structure 55 has a structure which provides force matching between the handle portion 53 and the multi support tray 57 . the multi support tray 57 is seen as a sharply angled undulation series of slots and ridges . it is understood that the purpose of the multi support tray 57 is to provide adequate support for a wrapped flauta and cylinder mandrel 21 before cooking which will stably support it in its wrapped condition before and throughout the cooking process . the wrapped flauta and cylinder mandrel 21 may be formed from a single sheet of material and may have a series of guard tabs 59 to enable the multi support tray 57 to be tilted in the direction longitudinal with respect to the ridges without loss of the wrapped flauta and cylinder mandrel 21 . the guard tabs 59 in essence create a drainage side preference where turning and drainage can occur without touching the wrapped flauta and cylinder mandrel 21 . it is understood that the triangular folds of the multi support tray 57 are generally good for supporting a round wrapped flauta and cylinder mandrel 21 and also for supporting a wide variety of other shapes of wrapped flauta and cylinder mandrel 21 . the shape of the multi support tray 57 can vary to become more complementary to the shape of the wrapped flauta and cylinder mandrel 21 . the dimensions which have been found to work well for multi support tray 57 include a length of material from peak to peak of about 1 . 25 inches , where each section is angled at about ninety degrees . each of the guard tabs by have a square dimension of about 0 . 4 inches . after folding , the multi support tray 57 is about 5 . 0 inches by about 5 . 5 inches with the longer unfolded dimension extending away from the support structure 55 . before folding , each of the folds is approximately 1 inch , which causes the unfolded multi support tray 57 to have a dimension of about 5 . 5 inches by about 8 . 0 inches . the mounting of the support structure 55 in fig4 is along an edge of the multi support tray 57 . an alternative location is along the serpentine edge of the multi support tray 57 , especially adjacent the location in which the guard tabs 59 are shown in fig4 . also seen in fig4 are some details of the handle portion 53 including a pair of outwardly directed members 61 which fits through a slot 63 on the support structure 55 and into engagement with a pair of apertures 65 . a sliding hold off member 67 can be moved downward to lock the handle portion 53 into place . referring to fig5 , a top view of an unfolded multi support tray 57 indicates a location of an alternative support structure with dashed lines indicating a support area 71 . a series of openings 73 are shown which , given the dimensions set forth above , may be formed as 0 . 5 inch diameter holes prior to folding . referring to fig6 , a folded box bracket is seen as a support structure 75 which may be advantageously located in the support area 71 seen in fig5 . support structure 75 has a lower plate 77 which will be tack welded to the multi support tray 57 . a pair of laterally extending wings 79 will extend the interference of an upper plate 71 of the support structure 75 which naturally guards or interferes with the middle two “ v ” shaped channels of the multi support tray 57 . the presence and location of the support structure 75 , along with the presence of the laterally extending wings 79 , provides a stop for all four “ v ” shaped channels seen . the upper plate 81 has a pair of side plates 83 and 85 , each of which have opposing upper tab folds 87 . the upper tab folds 87 help guide the ends of the handle portion 53 in the same manner as was explained for fig4 , and prevents a hinge action between the portions of the handle portion 53 adjacent ends 61 . the structure needed to prevent forward motion should be slight as the loaded weight upon the multi support tray 57 should urge the weight of the handle portion 53 adjacent a vertical plate 81 . stuffing of the cooked shell 49 can be accomplished with a variety of structures and techniques . where a cream is stuffed , a smaller pipe can be introduced to extrude material as the pipe is withdrawn back through the shell 49 . stuffing with solid foodstuffs presents a completely different set of problems . stuffing with shredded meat , for example , can be difficult . shredding the stuffing material to too small a size can change the taste and consistency of the final foodstuff structure . another problem is support , both during stuffing and during eating . where the stuffing material has no structural support contribution , the shell 49 can collapse when bitten . where a material having significant structural characteristics are stuffed , it can catch and block further insertion . where it is further forced , it can break the shell 49 either upon the occurrence of a blockage , as well as upon over - stuffing . the alternative of using thicker and more structurally hardened shells 49 detracts from the aesthetic and quality of the finished food product . the design and construction of a completely automated mechanical stuffer will either result in significant breakage of the shells 49 , or will be prohibitively expensive . a mechanical stuffing system is described which will permit rapid manual stuffing along with minimal chance for breakage of the shell 49 . a simple stuffing support 85 is seen which is formed from a single sheet of material and which has four , upwardly folded flaps . a base 87 supports an end flap 89 and a pair of side flaps 91 and a front flap 93 . end flap 89 is designed as a food stop . the front flap 93 has a pair of slots occupied by bushings 95 , which may be preferably made of nylon or plastic . referring to fig8 , a side view of the bushing 95 is seen as having an “ h ” shape , including a main cylindrical body having a pair of enlarged flanges . this enables the bushing 95 to be supported between a semi - circular support and yet allow easy removal for cleaning and the like . referring to fig9 , a front view of the simple stuffing support 85 without the bushings 93 reveals a pair of front slots 97 each having a central circular portion 99 and a pair of flanking angled openings 101 . the slots 97 have approximately the same shape as the slots 47 which were partially seen in fig3 . the bushings 93 are used to provide a low friction transition surface and create minimum wear on a push rod , and depending upon the design of the push rod can be used to help retain the push rods in operational use by preventing their slipping past the bushings 93 . the spacing of the slots 97 represent a wider spacing than is absolutely necessary to accommodate two shells 49 , and “ u ” shaped spacers can be located on the base 87 to provide support and separation for the two shells 49 located within the simple stuffing support 85 . referring to fig1 , a plan view of a stuffer rod 111 which can be cylindrical , oval , or square . stuffer rod 111 , if cylindrical , will have a first diameter cylindrical portion 113 and a second diameter cylindrical portion 115 , and if square will have a first width cylindrical portion 113 and a second width cylindrical portion 115 . the discussion will be continued based upon a cylindrical stuffer rod 111 , but in the case of a square or other shaped stuffer rod 111 , the openings in the bushings 95 will be appropriately matched . in one instance , a portion 113 having a diameter of about three eighths of an inch and a rod portion 115 having a diameter of about five - sixteenths of an inch may work well . a reduced diameter rod portion is used in conjunction with the bushings 95 to help prevent the stuffer rod 111 from becoming inadvertently dis - engaged from a stuffer box ( to be shown ) when the simple stuffing support 85 is used to support both cooked shells 49 and the stuffer box ( to be shown ). a series of etched lines 117 and 119 may be formed to indicated to the user the maximum run and minimum engagement positions for the stuffer rod 111 . this will help self train the user not to over - extend the stuffer rod 111 when stuffing begins , such as line 119 , and not to continue stuffing once the stuffer rod shows resistance at a given level , such as line 117 . referring to fig1 , a plan view of a stuffer rod 121 having a constant cross sectional dimension is seen . as before , the stuffer rod 121 can have any cross sectional shape , including cylindrical , oval , square , rectangular , pentagonal , hexagonal , and the like . in this instance , a single structure a diameter of about three eighths of an inch is seen . this dimension will work with the stuffer box to be seen in subsequent figures , as well as through bushings 95 having a larger internal diameter , as there is no larger diameter portion to be captured . the constant diameter rod 121 may used for a less bulky material which may not be subject to shearing , for a given sized stuffer box dimension . a series of etched lines 123 and 125 may be formed to indicated to the user the maximum run and minimum engagement positions for the stuffer rod 121 . a stuffer apparatus will pass food to be stuffed through the bushings 95 of the simple stuffing support 85 . as before , especially for a commercial production operation a pump operated stuffer may be used . for smaller operations , the main requirement of a stuffer unit is that it be simple and easy to clean thoroughly . referring to fig1 , a perspective of a stuffer box 131 is seen . a base 133 interfits with a four sided box 135 . two of the sides of the box 135 , including sides 137 and 139 are lower than two other opposite sides 141 and 143 . in one embodiment of the invention , the lower edge of sides 137 and 139 may simply overlap the outside of the base 133 , where the lower edges of sides 141 and 143 fit into grooves ( not completely seen in fig1 ) and form a stable engagement . the base 133 has lowered grooves to interfit with the lower edges of sides 137 and 139 to insure that the box 135 is properly oriented with respect to the base 133 . from a wall 145 of the base 133 a pair of canula shaped conduits 147 and 149 are seen . the longer extent of the cannulated shapes of the canula shaped conduits 147 and 149 at the bottom extent of the canula shaped conduits 147 and 149 . this enables the canula shaped conduits 147 and 149 to become more easily inserted into the ends of the cooked shells 49 . having the ends of the canula shaped conduits 147 and 149 oriented to the bottom will insure that less food spillage will occur upon docking and un - docking of the stuffer box 131 with respect to the simple stuffing support 85 . also partially seen in fig1 is a hopper feed area 151 surrounding a hopper opening 153 . both the hopper feed area 151 and hopper opening 153 may be machined into an upper surface 155 of the base 133 . the removable four sided box 135 gives the cleaner wide open access to the hopper feed area 151 , hopper opening 153 , and upper surface 155 . the canula shaped conduit 147 is in fluid communication with its respective hopper opening 153 , while the canula shaped conduit 149 is in fluid communication with its respective hopper opening ( not seen in fig1 ). both the canula shaped conduits 147 and 149 and their respective hopper openings are in communication with their respective through bores which extend horizontally through the base 133 . the back openings cannot be seen in fig1 but are located just under the side 143 . the stuffer rods 111 and 121 operate from the back openings . referring to fig1 , a top plan view of the base 133 with the four sided box 135 removed illustrates further details . back openings are seen as back opening 161 which is in fluid communication with a through bore 163 , the hopper opening 153 and canula shaped conduit 147 . similarly , a back opening 165 is in fluid communication with a through bore 167 , a hopper opening 169 and canula shaped conduit 147 . the through bores 163 and 167 will have a shape matching the stuffer rods 111 and 121 . hopper opening 169 is surrounded by a hopper feed area 171 . a front groove 173 for supporting a lower edge of the side 141 is seen , as is a rear groove 175 for supporting a lower edge of the side 143 . referring to fig1 , a side view of the base 133 is seen along with a clearer view of the grooves 173 and 175 . as can be seen from fig1 and 14 , the bores 163 and 167 are generally linear . note also that the hopper feed areas 151 and 171 could be closer together , but that separation enables additional control of the material fed through those hopper feed areas 151 and 171 . referring to fig1 , a top down view illustrates the mating parts of the simple stuffing support 85 which supports a pair of cooked shells 49 and the stuffer box 131 . also seen for the first time is one or more shell separator structures 181 which may be a simple “ u ” shaped channel tack welded to the base 87 of the simple stuffing support 85 . note that the canula shaped conduits 147 and 149 are seen as extending into the cooked shells , and that one of the shell separator structures 181 is positioned somewhat as a stop for stabilizing the stuffer box 131 in the direction of the cooked shells 49 . any material within the four sided box 135 will fall into the hopper openings 153 and 169 where it may be gently pushed forward by the stuffer rod 121 ( or stuffer rod 111 ). the spacing shown between the front flap 93 and the stuffer box 131 may exist or there may be a close fit . where the structures 181 are moveable , such as by engagement in a series of slots in the base 87 of the simple stuffing support 85 , the structures 181 can be moved about to accommodate different lengths of cooked shells 49 , and different sized stuffer boxes 131 . where stuffer rod 111 is used , note that its withdrawal will be limited by the bushings 95 to prevent the end of the stuffer rod 111 from becoming disengaged from the stuffer box 131 and thus saving the time necessary to re - insert it . this enables a much more mechanically affirmative mode of action . movement of stuffer rod 111 may be set to either partially or completely clear the hopper opening 153 to enable material present over hopper feed area 151 and hopper opening 153 will fall into the hopper feed area 151 . each time the stuffer rod 111 is advanced , the material within the feed area 151 will be advanced through the canula shaped conduit 147 and into the shell 49 . it is understood that the hopper feed area 151 and hopper opening 153 could be made longer to load more material per forward stroke of the stuffer rod 121 , but increasing the length of the hopper opening 153 could also compact the food stuffing present and subject the shell to a greater chance of damage or breakage . the smaller the amount loaded with each stroke of the stuffer rod 121 , the more gentle the loading steps will become . referring to fig1 - 19 , one embodiment of a handling tool 191 is seen . the handling tool 191 is described which can be used to engage , carry and disengage the hollow open ends of the cylinder mandrel 21 . the handling tool 191 has a main cylindrical body 193 which should be long enough to manually grasp with enough distance between main cylindrical body 193 and a conical section 195 which will be inserted into the through bore 27 of cylinder mandrel 21 to form an interference fit . the interference fit will depend upon the force with which the handling tool 191 is inserted , as well as the taper of the conical section 195 . a blunt end 197 is provided to make the handling tool 191 less of an injury and destruction threat during use . a sharp tip might encourage user to more rapidly approach the cylinder mandrel 21 and a missed engagement would cause either damage to the cooked shell 49 or hand contact with the cylinder mandrel 21 . at the end of the handling tool 191 opposite the conical section 195 an end plate 199 is located . the end plate carries a curved notch 201 which should closely match the outer diameter of the cylindrical surface 23 of the cylinder mandrel 21 . the axial edges of the curved notch 201 may be sharply angled . at the end of the main cylindrical body 193 is an end plate 197 which functions as a combination end member , shell removal fitting and cleaning fitting . as an end member , it acts as an end grasp register for the main cylindrical body 193 so that users can “ feel ” the end of the handling tool 191 and preferentially keep the hand nearest the end . as a shell removal fitting , the end plate 199 curved notch 201 is made to fit over the exterior surface of the cylinder mandrel 21 and urged along the surface to help remove the cooked shell 49 . this use enables the user to avoid touching the hot cylinder mandrel 21 just after cooking , as well as the hot cooked shell 49 . as a cleaning fitting , the end plate 199 curved notch 201 can be closely conforming to the exterior of the smooth cylindrical surface 23 of the cylinder mandrel 21 so that movement of the end plate 199 along its length removes all debris including bits of the cooked shell 49 which either remained or was inadvertently stuck to the cylinder mandrel 21 , as well as any debris the cylinder mandrel 21 may have picked up from the last cooking operation . referring to fig1 , an alternative embodiment of a cylinder mandrel is seen as a cylinder mandrel 211 . cylinder mandrel 211 may have the same dimensions for a smooth cylindrical surface 213 as were seen for smooth cylindrical surface 23 . a pivot fitting 215 may be spring loaded to urge a keeper 217 against the smooth cylindrical surface 213 . the nature of the spring fitting ( not shown in fig1 ) may be simply to urge the keeper 217 in one direction , or it may act with a cam action to enable the keeper 217 to assume a right angle with respect to the smooth cylindrical surface 213 to facilitate wrapping of the flauta material . in this position , the pivot fitting 215 may be freely rotatable about the axis of the smooth cylindrical surface 213 to enable the main extent of the cylinder mandrel 211 to rotate with respect to the pivot fitting 215 . in the alternative , a tool such as a spring loaded pliers with radius gripping tips can be utilized with cylinder mandrels 21 . a handle 219 can be used to manipulate the keeper 217 . note that the fitting pivot point is raised slightly in the view of fig1 with no flauta material present , so that a more even contact of the keeper 217 against the flauta material can occur when the flauta material is present . the keeper 217 can have a curvature about the smooth cylindrical surface 213 to match it , or more preferably of a lesser curvature to provide a better match with the exterior of the rolled flauta material which the keeper 217 is to hold in place . at the end of the cylinder mandrel 211 , a fitting 221 may include a flange 223 which is engaged by a fitting cylinder 225 which can attach to another structure . it is contemplated that a number of cylinder mandrels 211 may be supported by a common support to enable complete immersion in cooking oil so that more of the flauta material and the shell 49 produced may have a more direct contact with the cooking oil . the cylinder mandrel 211 and the combination of the cylinder mandrel 21 along with the multi support tray 57 are just two example of a structures which facilitate securing of the flauta material in place during cooking . the system of the present invention can be used to prepare shells 49 and stuff any cook hardened material with meats , vegetables , desserts , and more . cooking of the flauta material may be accomplished in a preheated deep fryer to a range of 300 360 degrees , but other cooking media and environment may be used . when utilizing some layers of material with which the shell 49 is formed , it may be necessary to pre - heat or pre - moisturize to obtain better self - adherence . once rapid production begins the cylinder mandrel 21 may remain hot , and handling with the handling tool 191 permits a better result in which the cylinder mandrel 21 remains hot and covered with oil . in terms of operation of the invention , place a tapered end of the conical section 195 of the handling tool 191 engages a cylinder mandrel 21 and is used to transfer it to the circular area 39 or rectangular area 41 of the rolling support 31 . the cylinder mandrel 21 is placed about an one inch from the leading edge of a sheet of flauta material with the cylinder mandrel 21 pushed against the vertical stop 37 . the leading edge of the flauta material is rolled over the cylinder mandrel 21 until it tucks in enough to begin rolling until it is completely wrapped around the cylinder mandrel 21 . keeping the roll tight , the cylinder mandrel 21 covered with the flauta material is transferred to one of the “ v ” shaped slots of the multi support tray 57 and placed in a position to make sure the outer , free edge of the rolled flauta material is facing down to keep it from unraveling . the weight of the cylinder mandrel 21 will keep it in place and shape . the frying support 51 is loaded with other wrapped cylinder mandrels 21 , and are immersed , supported by the multi support tray 57 , in a deep fryer . after cooking for 1 - 2 minutes ( depending upon the temperature of the oil and the type of flauta material used , lift the frying support 51 and allow some drainage over the cooking oil . any tilting of the multi support tray 57 should be done with the guard tabs 59 or laterally extending wings 79 downward . the frying support 51 is positioned so that each protruding end of the cylinder mandrel 21 is over a corresponding notch 47 of the channel 45 . as the frying support 51 is lowered , each of the grooves 25 of the exposed cylinder mandrel 21 engages its associated notch 47 . once lowered , the frying support 51 the grooves 25 on the cylinder mandrels will hook themselves on the notches 47 . as the frying support 51 is then moved laterally away from the channel 45 , the cylinder mandrels 21 bearing the cooked shell 49 are dragged from the multi support tray 57 and supported at an angle over the board 35 . next , the handling tool 191 can be used to begin to slide the shell 49 away from the channel 45 along its cylinder mandrel 21 . the handling tool 191 can be used to lift the cylinder mandrel 21 to enable the shell 49 to clear the board 35 . the shells 49 are then transferred to the simple stuffing support 85 between a side flap 91 and a shell separator structure 181 . the assembled stuffer box 131 is mated with the simple stuffing support 85 , and food to be stuffed is added to the assembled stuffer box 131 . depending on the foodstuff selected , stuffer rod 111 or 121 is used to perform the stuffing operation . each stuffing stroke should terminate when the user feels resistance on the stuffer rod 111 or 113 . once the shell 49 is full , the stuffer rod 111 or 113 is removed from the stuffer box 131 and the filled shell is removed from the simple stuffing support 85 . all of the components of the inventive system can be made in a variety of materials — plated metal , wire mesh metal , wire mesh rod , or approved plastics , hardwood , or any other moldable materials in a variety of colors . metals used can be aluminum , iron , steel , stainless steel , titanium and more . although the stuffer box 131 has been shown as having a two piece construction for ease of cleaning and a dual stuffing capacity , a stuffer can be used with unitary or multiple parts and may have multiple stuffing capacity . two stuffer box 131 can be used with a two sided stuffing support 85 to stuff shells 49 from the middle outwardly . the stuffing combination shown in fig1 or other stuffer can be made to work in a vertical or angled position . the operation of the stuffing rods 111 and 121 within the stuffer box can be made to operate by motor . all sizes for all components of fig1 - 19 can be varied as needed . through bores 167 , 27 , and stuffer rods 111 and 121 can be of any shape , square , triangular , hexagonal , octagonal , and the like . while the present invention has been described in terms of a food preparation system , and particularly to a multi - component user friendly system for semi - automated production of cooked shells , the present invention may be applied in any situation where formation and stuffing of structures is desired to yield a complete and integrated cooked shell production system of a scale from manual to batch - continuous operation . although the invention has been derived with reference to particular illustrative embodiments thereof , many changes and modifications of the invention may become apparent to those skilled in the art without departing from the spirit and scope of the invention . therefore , included within the patent warranted hereon are all such changes and modifications as may reasonably and properly be included within the scope of this contribution to the art .

a rolled shell and stuffer apparatus , particularly useful for deep frying , utilizes a number of structures which together provide the ability to quickly produce a large number of stuffed taquito type shells having high quality . the basic components of the system include a shell mold having an outer diameter of about 0 . 5 inches for example , formation mandrel , a rolling support , a frying support , a removal support , a stuffing system , and an optional handling tool . as will be seen , the degree of interrelatedness of these components can vary , but the result is a uniformity of high quality product which enables a wider range of food stuffing .

a detailed description of the hereinafter described embodiments of the disclosed apparatus and method are presented herein by way of exemplification and not limitation with reference to the figures . although certain embodiments are shown and described in detail , it should be understood that various changes and modifications may be made without departing from the scope of the appended claims . the scope of the present invention will in no way be limited to the number of constituting components , the materials thereof , the shapes thereof , the relative arrangement thereof , etc ., and are disclosed simply as an example of embodiments of the present invention . please refer to fig1 . fig1 shows a flow diagram of the method for producing an α - calcium sulfate hemihydrate bone graft in an embodiment of the present invention . in an embodiment of the present invention , the method comprises the following steps : s 1 : mixing calcium sulfate dihydrate and pure water to produce a calcium sulfate dihydrate paste , wherein the pure water mentioned above can either be sterile water or deionized water ; s 2 : stirring and heating the calcium sulfate dihydrate paste to at least 160 ° c . for producing a conversion calcium sulfate hemihydrate ; s 3 : filtering the conversion calcium sulfate hemihydrate with a high temperature to produce a filtered calcium sulfate hemihydrate ; and s 4 : washing the filtered calcium sulfate hemihydrate by an absolute alcohol to generate the α - calcium sulfate hemihydrate bone graft . in step s 2 , the calcium sulfate dihydrate paste is stirred by a magnetic stir bar . besides , the step s 2 is for heating the calcium sulfate dihydrate paste to 160 ° c . and then maintaining at the temperature for 10 minutes to produce the conversion calcium sulfate hemihydrates . therefore , the conversion calcium sulfate hemihydrates are comprised with the α - calcium sulfate hemihydrate bone graft and other by - products that we need . furthermore , the step s 2 is for heating the calcium sulfate dihydrate paste to 160 ° c . in 20 minutes and then maintaining at the temperature for 10 minutes to produce the conversion calcium sulfate hemihydrates . besides , the step s 2 is executed in a teflon tube and the tube pressure in the teflon tube is set between 100 psi and 350 psi . in an embodiment , the method may include heating 1 . 5 g of calcium sulfate dihydrate and 10 ml of deionized water in a teflon tube with a magnetic stir bar inside . the output power of the microwave device may be set to 800 watts ( w ), the pressure in the teflon tube is set between 100 psi and 350 psi . the calcium sulfate dihydrate paste may be heated to 160 ° c . by microwave in 20 minutes and then kept at the temperature for 10 minutes to produce the conversion calcium sulfate hemihydrates . the specifications of the magnetic stir bar mentioned above may be the diameter of 6 mm and the length of 15 mm , wherein the stirring process may be assisted by rotating the magnetic stir bar or adding other mechanical swing or other stirring methods . in an embodiment , the high temperature to produce a filtered calcium sulfate hemihydrate at step s 3 is above 100 ° c . in an embodiment , the conversion calcium sulfate hemihydrate is subjected to a cooling filtration action at 100 ° c . or higher by means of an evacuating filtration method to obtain the filtered calcium sulfate hemihydrate . in addition , the method for producing an alpha - calcium sulfate hemihydrate bone graft , further comprising the following step of : s 5 : drying the alpha - calcium sulfate hemihydrate bone graft . the drying temperature of drying the alpha - calcium sulfate hemihydrate bone graft may be 60 ° c . to 80 ° c . for 6 hours to 8 hours . in an embodiment , the α - calcium sulfate hemihydrate bone graft may be dried through an oven , wherein the drying temperature may be 60 ° c . to 80 ° c . for 6 hours to 8 hours . then , through procedures with grinding , filtering , and packaging , the dried α - calcium sulfate hemihydrate bone graft can be applied to biomedical use . please refer to fig2 . fig2 shows a surface diagram of calcium sulfate dihydrate and different kinds of calcium sulfate hemihydrate , wherein the diagram is taken on a scanning electron microscope ( sem ) with a scale of 10 μm . according to the scanning results of sem , the calcium sulfate dihydrate raw material as shown in ( a ) in fig2 , is in the form of crystalline aggregates having the appearance of flaky cracks ; ( b ) in fig2 is the present invention α - calcium sulfate hemihydrate bone graft with the structure of columnar crystal , having an average size of 10 μm ; ( c ) in fig2 is the commercially available α - calcium sulfate hemihydrate bone graft with the structure of granular crystal , having an average size of 20 μm . compared with the commercially available α - calcium sulfate hemihydrate bone graft , the structure of the present invention is more conducive to reduce the size of the micro - channel after curing , that is , to improve the structural strength of curing . please refer to fig3 . fig3 shows an x - ray diffraction ( xrd ) diagram of calcium sulfate dihydrate and different kinds of calcium sulfate hemihydrate , wherein the abscissa is 2θ degrees , and the ordinate is the intensity ( arb . unit ). ( i ) in fig3 is the xrd of calcium sulfate dihydrate raw material . ( ii ) in fig3 is the xrd of the present invention α - calcium sulfate hemihydrate bone graft . ( iii ) in fig3 is the xrd of the commercially available α - calcium sulfate hemihydrate bone graft . compared with ( i ) and ( iii ) in fig3 , the present invention ( ii ) in fig3 is similar to the commercially available α - calcium sulfate hemihydrate bone graft and has no characteristic peak ( 202 ) signal of calcium sulfate dihydrate raw material . it is presumed that the present invention has been completely converted into α - calcium sulfate hemihydrate bone graft . please refer to fig4 . fig4 shows a differential scanning calorimeter ( dsc ) schematic diagram of the calcium sulfate dihydrate and the present invention α - calcium sulfate hemihydrate bone graft , wherein the abscissa is the temperature (° c . ), and the ordinate is the intensity ( arb . unit ). ( i ) in fig4 is the dsc signal of calcium sulfate dihydrate raw material . ( ii ) in fig4 is the dsc signal of the present invention α - calcium sulfate hemihydrate bone graft . according to fig4 , there is no obvious reaction peak at about 150 ° c . and about 195 ° c ., whereby it is presumed that the product of the α - calcium sulfate hemihydrate (( ii ) in fig4 ) has no residual calcium sulfate dihydrate raw material (( i ) in fig4 ). please refer to fig5 . fig5 shows a ph comparison diagram of calcium sulfate dihydrate and different kinds of calcium sulfate hemihydrate , wherein the abscissa shows different components , and the ordinate is the ph value . ( i ) in fig5 is the ph value of the calcium sulfate dihydrate raw material . ( ii ) in fig5 is the ph value of the present invention α - calcium sulfate hemihydrate bone graft . ( iii ) in fig5 is the ph value of the commercially available α - calcium sulfate hemihydrate bone graft . each bar is measured five times . the present invention α - calcium sulfate hemihydrate ( ii ) in fig5 and the commercially available α - calcium sulfate hemihydrate ( iii ) in fig5 have the same ph value as the neutral to weak base , while the calcium sulfate dihydrate raw material shows acid . it is presumed that the product of the α - calcium sulfate hemihydrate (( ii ) in fig5 ) has no residual calcium sulfate dihydrate raw material (( i ) in fig5 ). please refer to fig6 . fig6 shows a test result diagram on cytotoxicity ( according to iso 10993 - 5 standard test ) of the present invention α - calcium sulfate hemihydrate bone graft . fig6 shows the test result of the bone cell and epithelial cells cultured in vitro in the α - calcium sulfate hemihydrate extract , wherein the ordinate shows cell activity , the abscissa shows different groups , including the control group , positive control group ( hdpe , high density polyethylene ), negative control group ( zdbc , zinc dibutyldithiocarbamate ), commercially available group ( commercially available α - calcium sulfate hemihydrate ), and an experimental group ( prepared by the present invention of α - calcium sulfate hemihydrate bone graft ). according to the test result of fig6 , it is presumed that the product of the α - calcium sulfate hemihydrate ( the experimental group shows cell viability above 70 %) has no cytotoxicity . please refer to fig7 . fig7 shows a concentration comparison diagram on different impurities of the present invention α - calcium sulfate hemihydrate bone graft . according to the measurement results of the sgs taiwan ltd ., the purity of the present invention α - calcium sulfate hemihydrate bone graft converted from calcium sulfate dihydrate yields above 97 weight percent ( 97 wt %). impure ingredients including arsenic , lead , mercury , and cadmium are less than 2 ppm , in line with the usp 38 calcium sulfate specification ( usp 38 calcium sulfate specifications of arsenic , lead , mercury , and cadmium are required to be less than 10 ppm ). the iron content is about 15 . 5 ppm , which is also in line with the usp 38 calcium sulfate specification ( iron is required to be less than 100 ppm in accordance with the usp 38 calcium sulfate specification ). the minimum detection limit for each element is 2 . 0 ppm . besides , in physical properties detections , the present invention α - calcium sulfate hemihydrate bone graft has a curing time of about 6 . 5 to 7 . 5 minutes ( in comparison with about 15 to 20 minutes of commercially available α - calcium sulfate hemihydrate ). in the curing time of 25 minutes , its temperature rises by about 8 ° c . and a maximum temperature of about 31 ° c . the compressive strength of the present invention bone craft is 6 . 62 ± 1 . 01 mpa by controlling the concentration of curing water powder with 0 . 6 ml / g . please refer to fig8 . fig8 shows a flow diagram of the animal experiments by using different kinds of α - calcium sulfate hemihydrate bone grafts , more particularly , by compared with using the present invention α - calcium sulfate hemihydrate bone graft . the animal experiment is conducted by using chorioallantoic membrane ( cam ) of the chicken embryo , wherein the bone regeneration and angiogenesis are about to be confirmed . the animal experiment further comprises the following step of e 01 : taking the hatched eighteen days of chicken embryo eggs ; e 02 : getting chicken embryo ; e 03 : sacrificing the embryo ; e 04 : intercepting the embryo femur ; e 05 : recording the length of the femur before the experiment ; e 06 : making the femur defect and fill in α - calcium sulfate hemihydrate bone powder ; e 07 : taking a hatched seven days of chicken embryo eggs , making a notch ; e 08 : stripping eggs intima ; e 09 : implanting the experimental femur to embryonic development area ; e 10 : repairing the notch ; and e 11 : observing the result after ten days . please refer to fig9 , fig1 , and fig1 . fig9 shows a comparison diagram of the femur length after ten days of incubation in animal experiments using different kinds of α - calcium sulfate hemihydrate bone grafts . fig1 shows a schematic diagram of bone growth and angiogenesis after ten days of incubation in animal experiments using the present invention αcalcium sulfate hemihydrate bone graft . fig1 shows an x - ray diagram of the femur after ten days of incubation in animal experiments using different kinds of α - calcium sulfate hemihydrate bone graft . in the observation results after ten days of incubation , the length of the femur shows no change of 18 mm to 18 mm without using α - calcium sulfate hemihydrate bone powder ( chart ( a )). besides , the bone defect has obvious reactions on periosteal regeneration , angiogenesis and osteogenesis when using the present invention α - calcium sulfate hemihydrate bone graft as bone powder ( chart ( c )) on bone defect of the chicken femur ( arrow mark ), wherein the femur length grows from 19 mm to 21 mm . the increase of 2 mm is more effective than that commercially available bone powder ( chart ( b )) of 1 mm ( from original 23 mm to 24 mm ). in conclusion , the present invention α - calcium sulfate hemihydrate bone graft can be applied to the implementation on biomedical bone powder , including dental implant surgery , bone transplantation and osteosynthesis surgery . furthermore , the implementation mentioned above can effectively shorten the operation time for doctors , wherein the temperature of the use is lower than the average body temperature of 37 ° c ., so that the patient will not suffer physical damage caused by severe changes in temperature . compared with the conventional technique , the method for producing α - calcium sulfate hemihydrate bone graft from the calcium sulfate dihydrate paste , including promoting the reaction evenly by stirring in high pressure , filtering the conversion calcium sulfate hemihydrate under high temperature , and washing the filtered calcium sulfate hemihydrate by an absolute alcohol . the present invention uses pure water and biomedical - used absolute alcohol rather than catalyst and other heterogeneous substances , hence the impurities in the preparation process can be effectively reduced . therefore , the method for producing biomedical - used α - calcium sulfate hemihydrate bone graft can be more secure . with the examples and explanations mentioned above , the features and spirits of the invention are hopefully well described . more importantly , the present invention is not limited to the embodiment described herein . those skilled in the art will readily observe that numerous modifications and alterations of the device may be made while retaining the teachings of the invention . accordingly , the above disclosure should be construed as limited only by the metes and bounds of the appended claims .

the present invention discloses a method for producing the alpha - calcium sulfate hemihydrate bone graft , which comprises the following steps : mixing calcium sulfate dihydrate and deionized water to produce calcium sulfate dihydrate paste ; stirring and heating the calcium sulfate dihydrate paste at least 160 ° c . within 100 - 350 psi to produce the conversion calcium sulfate hemihydrate , filtering the conversion calcium sulfate hemihydrate with high temperature to produce the filtered calcium sulfate hemihydrate , and washing the filtered calcium sulfate hemihydrate by absolute alcohol to get the alpha - calcium sulfate hemihydrate bone graft . the present invention does not use any catalyst , possesses a high purity , high mechanical strength , and good biocompatibility , facilitates bone growth and angiogenesis , requires only 31 ° c ., the highest temperature , during the curing process . it makes the present invention more secure in the biomedical applications .

in fig1 the outside appearance of the presently preferred embodiment of the toy 20 is shown . the toy 20 has a base 22 having a top 24 which fits thereon and centered in the top 24 is an activating button 26 . a movable extension has a head 28 attached on its end . the head 28 is shown in fig1 in a retracted position . a right front foot 30 and a left front foot 32 project out of the front of the toy 20 and analogously a right rear foot 34 and a left rear foot 36 project out of the rear of the toy 20 . additionally , a tail 38 is also attached to the body . the right front and rear feet 32 and 34 are shown in a retracted position in solid line and the right and left front feet 30 and 32 and the right rear foot 34 as well as the tail 38 and head 28 are shown in their extended position in phantom in fig1 . all of the movable appendages , that is the head 28 , the feet 30 , 32 , 34 and 36 and the tail 38 , are capable of being manually pushed from their extended position into their retracted position and are held in the retracted position by internal components as hereinafter described . after pushing the above noted appendages into the retracted position the child playing with the toy pushes on the button 26 , and as will be hereinafter described one of a plurality of , or all of , the appendages are freed from their retracted position and assume their extended position . additionally when the child pushes the button 26 the toy may or may not be propelled along the surface on which it is supported . the action of releasing the appendages or propelling the toy is governed in what , to the child would seem like a random fashion . however , the particular sequence of releasing the appendages and / or propulsion of the toy is in fact governed by certain internal components as hereinafter described . referring now to fig4 the lowermost internal working components of the toy 20 are shown . projecting out of the base 22 are the feet 30 , 32 , 34 and 36 as hereintofore described . all of these feet 30 , 32 , 34 and 36 are integrally formed with a bracketed member 40 , 42 , 44 and 46 respectively . each of these bracketed members have a similar function , except that depending on the placement , i . e ., left , right , front or rear , their symmetery is slightly different . each of the bracketed membrs 40 , 42 , 44 and 46 contains an integrally formed projections 48 , 50 , 52 and 54 , respectively , which have detent teeth 56 , 58 , 60 and 62 respectively integrally formed thereon . since the bracketed members 40 , 42 , 44 and 46 , and also the projections 48 , 50 , 52 , and 54 , are preferredly formed of a plastic material , the projections 48 , 50 , 52 and 54 serve as springs allowing the detent teeth 56 , 58 , 60 and 62 to rise and fall with respect to the bracketed members 40 , 42 , 44 and 46 . two identically shaped support members , front support member 64 and rear support member 66 , fit over two upstanding axles 68 and 70 which project from the surface of the base 22 . the bracketed members 40 , 42 , 44 and 46 slide over the support members 64 and 66 and are each retained thereon by a small detent tooth 67 ( illustrated only for one foot 36 in fig6 , but found also on feet 30 , 32 and 34 ) on the bottom of the support members 64 and 66 . two identical springs , front spring 72 and rear spring 74 , fit within support members 64 and 66 , respectively , and bias the bracketed members 40 , 42 , 44 and 46 and their associated feet , 30 , 32 , 34 and 36 , away from the center of the base 22 . a front wheel 76 appropriately suspended by an axle 77 is rotatably mounted in the base 22 . two rear wheels 78 and 80 are fixeldy mounted about axle 82 which fits into appropriate bearing surfaces ( not numbered ) in base 22 . the front and rear wheels 78 and 80 both have a rubber tread 84 on their surface which provides gripping power for these wheels with the support surface on which the toy is placed . the toy is suspended from a support surface by the triangular wheel arrangement provided by wheels 76 , 80 and 84 . mounted on axle 82 near wheel 78 is a pinion 86 which is free - wheeling about axle 82 . fixedly mounted on axle 82 slightly off center toward wheel 80 is a cam 88 . as shown in fig5 this cam is off center from the center of the axle 82 and as axle 82 spins , the cam spins eccentrically . slidably mounted on the surface of base 22 is a sliding member 90 . sliding member 90 has two vertical projections collectively identified by the numeral 92 which project from the surface of sliding member 90 . cam 88 fits within these two vertical projections 92 and as axle 82 spins the rotation of cam 88 within the vertical projections 92 causes sliding member 90 to oscillate back and forth on the surface of base 22 . also projecting in a vertical direction from sliding member 90 is a front peg 94 and a rear peg 96 . these pegs are caused to move by the movement of sliding member 90 . attached to front support member 64 is an arm 98 having an elongated groove 100 in its surface . groove 100 fits over peg 94 and as sliding member 90 slides back and forth , this motion is transferred to arm 98 by the interaction of peg 94 in groove 100 . this causes front support member 64 to pivot about axle 68 ultimately causing feet 30 and 32 to move in a forward and backward motion . likewise , rear support 66 has an arm 101 having a groove 103 which fits on peg 96 which transfers the motion of sliding members 90 to back and forth motion of rear feet 34 and 36 . a housing 102 mounts over the base 22 in essentially the center of the toy . attached to this housing 102 is a compartment 104 . mounted within the compartment 104 is a gear 106 having a set of pinion teeth 108 and a set of spur teeth 110 . an axle 112 is integrally formed as part of the gear 106 . in the opposite walls of compartment 104 are two identical grooves 114 which lie at an oblique angle to both the horizontal and vertical axis . the gear 106 is mounted by its axle 112 within the grooves 114 and as such the gear 106 has a degree of play within compartment 104 . fixedly mounted within compartment 104 is a second gear 116 which has a set of pinion teeth 118 and a set of spur teeth 120 . the spur teeth 120 of gear 116 mate with and are in continuous contact with the pinion teeth 108 throughout the limited travel of gear 106 within groove 114 . the spur teeth 110 of gear 106 mate with the pinion 86 when gear 106 is in its lowermost limited travel within grooves 114 . when gear 106 slides in an upward direction in grooves 114 the spur teeth 110 disengage the pinion 86 and any motion of either gear 106 or pinion 86 is not transferred from one to the other . integrally formed with pinion 86 is a slip clutch member 122 having a series of obliquely formed detent teeth collectively identified by the numeral 124 integrally formed thereon . within the interior of wheel 78 is a matching slip clutch member 126 having matching detent teeth 128 formed thereon . pinion 86 and slip clutch member 122 are free - wheeling about axle 82 and are biased toward slip clutch member 126 by spring 130 which fits around axle 82 between slip clutch member 126 and cam 88 . the function of this clutch mechanism will be described below . a sliding member 132 has a rack of gear teeth 134 on a portion thereof . the sliding member 132 fits within housing 102 such that the rack of gear teeth 134 mates with and interacts with pinion teeth 118 on gear 116 . a compression spring 136 fits within sliding member 132 and abuts against the rear of housing 102 . this biases sliding member 132 in a forward direction in respect to housing 102 . a major extension member 138 , having head 28 on its end fits over one end of sliding member 132 . interposed between the end of sliding member 132 and an interior wall 142 of major extension member 138 is a compression spring 144 . compression spring 144 is of slightly less compression strength than compression spring 136 . if the major extension member 138 and head 28 attached to it are pushed from an extended position into the interior of the toy 20 to a retracted position , first compression spring 144 is compressed until the end 146 of major extension member 138 contacts a shoulder 148 on sliding member 132 . further movement of major extension member 138 is transferred via end 146 abutting against shoulder 148 to sliding member 132 . as sliding member 132 slides within compartment 104 compression spring 136 is compressed . as sliding member 132 moves in a rearward direction within housing member 102 gear rack 134 interacts with and spins gear 116 . as shown in fig3 this causes gear 116 to move in a clockwise direction . the clockwise spin of gear 116 is transferred to gear 106 causing it to spin counterclockwise ; however , this clockwise spin of gear 116 also lifts gear 106 within grooves 114 causing gear 106 to lift free of pinion 86 . conversely , when the force of the compression spring 136 is allowed to push sliding member 132 in a forward direction in housing 102 as hereinafter described , gear rack 134 causes gear 116 to spin counterclockwise which in turn causes gear 106 to spin clockwise . this forces gear 106 downward within grooves 114 causing gear 106 to mate with pinion 86 transferring motion to axle 82 via the interaction of the slip clutch components 122 and 126 . this motion causes the wheels 78 and 80 to spin in a counterclockwise direction propelling the toy forward . if the child should push the toy backwards , the interaction of gear rack 134 with gear 116 and gear 116 with gear 106 , and finally gear 106 with pinion 86 , will freeze the movement of pinion 86 . however , when this happens the two slip clutch parts 122 and 126 will slip on each other allowing wheels 78 and 80 to spin without damaging any of the gears or their associated parts . housing 102 has a rearmost section 150 in which fits tail 38 . tail 38 has a central shaft 152 integrally formed with it around which fits a compression spring 154 . compression spring 154 abuts against the back of housing 102 and biases tail 38 in an outward direction . a housing cover 156 fits over the top of housing 102 and is maintained thereon by screws ( not numbered or shown ) which fit into appropriate drillings within both housing cover 156 and housing 102 . the drillings are also not numbered in order to simplify the drawing . cover 156 is best seen in fig8 . projecting from near the center of cover 156 is a shaft 158 having a shoulder 160 near its bottom extremity . a spring member 162 formed out of a material having spring properties fits on the top of the surface of cover 156 . integrally formed with cover 156 are two brackets collectively identified by the numeral 164 . a lever 166 having an axle 168 integrally formed with it is held on to the top of cover 156 by brackets 164 . a projection 170 of spring member 162 fits underneath the end 172 of lever 166 which biases the opposite end 174 of lever 166 through a cutout 176 in cover 156 . a slot 178 formed in the top of sliding member 132 receives end 174 of lever 166 when sliding member 132 is in its rearmost position , a position wherein compression spring 136 is fully compressed . the sliding member 132 is held in this position by the interaction of end 174 of lever 166 with slot 178 . a small pin 180 integrally formed with the top of compartment cover 156 extends in an upward direction . fitting on this pin is tail holding member 182 . tail holding member 182 has a small wedge shaped member 184 on its bottom surface . additionally it has a second wedge shaped member 186 on its top surface . the placement of these two wedge shaped members are best seen in fig7 and 8 . extending out of the side of tail holding member 182 is a spring member 188 which is appropriately held in two projections 190 integrally formed on the surface of cover 156 . spring member 188 biases tail member 182 toward the position shown in fig7 and 8 . a small projection 190 on tail 38 is capable of being retained by wedge member 184 . when the tail 38 is pushed from an extended position to a retracted position projection 190 pushes against wedge member 184 causing tail member 182 to be displaced against the biasing spring 188 . when the projection 190 clears the wedge member 184 tail member 182 returns to its central position as shown in fig7 and 8 which locks the tail 38 in a retracted position because projection 190 is now held against the backside of wedge member 184 . a front release member 192 has two identical pins collectively identified by the numeral 194 extending from both its sides . these pins fit into two bearing surfaces collectively identified by the numeral 196 in upright projections collectively identified by the numeral 198 which project in a vertical direction and are integrally formed with compartment cover 156 . front release member 192 has two legs , right leg 200 and left leg 202 which project in a downward direction . additionally , front release member 192 has a retaining finger 204 which projects from its foremost surface toward the front of the toy . when the toy is assembled and the major extension member 138 is slid from its extended position to its retracted position , retaining finger 204 fits within a hole 206 in head 28 attached to major extension member 138 . a projection 208 of spring member 162 biases front release member 192 about pins 192 such that a detent tooth 210 on the end of retaining finger 204 locks major extension member 138 in a retracted position . a rear release member 212 is similar to front release member 192 in that it is suspended by two pins collectively identified by the numeral 214 which rests in two bearing surfaces collectively identified by the numeral 216 formed in upright projections 198 . two projections collectively identified by the numeral 218 of spring member 162 biases rear release member 212 about the pins 214 . two legs 220 and 222 project in a downward direction on the opposite end of rear release member 212 . projecting out of the rear of rear release member 212 is tail release pin 223 , which is so placed as to be capable of interacting with wedge shaped member 186 . integrally formed as part of housing 102 are four holding members , right front holding member 224 , left front holding member 226 , right rear holding member 228 , and left rear holding member 230 . these holding members project near the path of travel of the detent teeth 56 , 58 , 60 and 62 on the bracketed members 40 , 42 , 44 and 46 of the feet 30 , 32 , 34 and 36 respectively . when the feet 30 , 32 , 34 and 36 are pushed against the bias of springs 72 and 74 the respective feet are held in a retracted position by interaction of detent teeth 56 , 58 , 60 and 62 with the holding members 224 , 226 , 228 and 230 respectively . the feet 30 , 32 , 34 and 36 are released from the retracted position to their extended position in pairs , that is , a front pair and a rear pair , whenever either front release member 192 pivots about pins 194 against the bias of spring projection 208 such that leg 200 depresses detent tooth 56 and leg 202 depresses detent tooth 58 freeing these detent teeth from their respective holding members 224 and 226 . likewise , the rear feet 34 and 36 are released when the rear legs 220 and 226 interact with detent teeth 60 and 62 . the depression of rear release member 212 also causes tail release pin 223 to fit against wedge shaped member 186 which causes displacement of tail holding member 182 which allows the tail 38 to travel from its retracted position to its extended position . projecting from the upper surface of front release member 192 is front release pin 232 and projecting from the upper surface of rear release member 212 is rear release pin 234 . when front release member 192 and rear release member 212 are mounted on housing cover 156 front release pin 232 is slightly closer to the center axis of shaft 158 than is rear release pin 234 . a mode disk 236 fits over shaft 158 and its bottom - most limit of travel on shaft 158 is governed by mode disk 236 coming to rest against shoulder 160 . interspaced between the top of cover 156 and mode disk 236 about shaft 158 is a compression spring 238 . this biases mode disk 236 in an upward direction on shaft 158 . as is best seen in fig7 integrally formed on the bottom surface of mode disk 236 are a series of pins . these pins are arranged in what could be envisioned as three concentric circles on the bottom of mode disk 236 . the innermost circle of pins , two pins collectively identified by the numeral 240 , are capable of interacting with the end 172 of lever 166 . the next concentric circle of pins , collectively identified by the numeral 242 , are capable of interacting with the front release pin 232 and the outermost concentric circle of pins , collectively identified by the numeral 244 , are capable of interacting with the rear release pin 234 . if mode disk 236 is depressed against the bias of compression spring 238 as hereinafter described depending upon the rotational displacement of mode disk 236 about shaft 158 , pins 240 may or may not be in position to interact with lever 166 , pins 242 may or may not be in position to interact with front release pin 232 , and pins 244 may or may not be in position to interact with rear release pin 234 . the mode disk 236 is caused to rotate in an arc about shaft 158 each time button 26 is depressed as hereinafter described . this degree of rotation is such that each time the mode disk rotates through this arc a new set of pins ( that is , a set of pins falling on a line colinear with a diameter line of mode disk 236 , e . g ., lines a and b in fig7 ) are in position to interact with the combination of lever 166 and front and rear release pins 232 and 234 . as can be seen in fig7 when a set of pins such as the set lying on line a are in this position interaction will be had with all three of the above noted components 166 , 232 and 234 . however , when the set of pins such as those falling on the line identified as line b in fig7 are in position , interaction will only be with front release pin 232 . attached to the top of cover 156 is placement collar 246 . placement collar 246 is fixedly attached to cover 156 by several screws not shown in the drawing . placement collar 246 includes a large ring section 248 and a small ring section 250 integrally attached to the top of the large ring and extending a short distance within the interior of the large ring 248 . incorporated within the walls of small ring 250 are two guide grooves collectively identified by the numeral 252 . extending vertically along the sides of button 26 are two guide ridges collectively identified by the numeral 254 . button 26 fits within the small ring 250 and the guide ridges 254 on button 26 slide in the guide grooves 252 . this allows button 26 to freely go up and down within the small ring 250 but prevents button 26 from any rotational movement within small ring 250 . along the bottom edge of button 26 is a continuous series of teeth collectively identified by the numeral 256 . these teeth 256 are triangular in shape and are symmetrical about their central axis . on the inside of large ring 248 are four mode placement plates collectively identified by the numeral 258 . these four plates 258 are located in two groups of two each on opposite sides of the interior of large ring 248 . on the top surface of mode disk 236 is a ring of mode teeth 260 . the mode teeth 260 are mirror images of the button teeth 256 and are sized and placed on the mode disk 236 such that they are capable of interacting and fitting with the button teeth 256 as is best illustrated in fig1 . along the circumference of the mode disk 236 are a series of mode placement teeth collectively identified by the numeral 262 . the mode disk 236 fits within the large ring 248 as is seen in fig3 in side view and in fig9 in bottom view . the mode placement teeth 262 are so shaped and the mode disk 236 is so dimensioned that when the mode disk 236 is in its uppermost placement within large ring 248 the mode placement plates 258 on the inside surface of large ring 248 fit within the spaces between two adjacent mode placement teeth 262 . this locks the mode disk 236 from rotating when the mode disk 236 is located within the upper portion of large ring 248 . when in this upper placement the mode teeth 260 fit within the small ring 250 and are theoretically capable of perfectly meshing with the button teeth 256 ; however , in this placement the mode teeth 260 are radially displaced a few degrees from a perfect alignment with button teeth 256 . because button 26 is locked with respect to its radial displacement by the interaction of guide ridges 254 in guide grooves 252 and the mode disk 236 is similarly locked as to its radial displacement by the mode placement teeth 260 with the mode placement projections 258 neither can radially shift its position which results in the interaction of the button teeth 256 with the mode teeth 260 as is shown in fig3 . when the button 26 is depressed the downward motion similarly depresses the mode disk 236 against the bias of compression spring 238 . when the button 26 is depressed it and the mode disk 236 start their descent locked in their initial position with respect to their button teeth 256 and the mode teeth 260 . the button 26 throughout its whole limit of travel is maintained fixed radially wihin the small ring 250 by the guide groove 252 and guide ridges 254 . the mode disk 236 , however , is maintained in a fixed radial position for only a portion of its descent . as soon as the mode placement teeth 262 clear the bottom of the mode placement plates 258 the mode disk 236 is free to rotate . because the button teeth 256 and the mode teeth 260 are not in perfect alignment and because of the shape of the button teeth 256 and mode teeth 260 as soon as the mode disk 236 is free of the mode placement plates 258 , the mode disk 236 will rotate a few degrees until the button teeth 256 and the mode teeth 260 become aligned as shown in fig1 . at this time the mode placement teeth 262 have assumed an alignment with the mode placement plates 258 as is shown in fig1 as viewed from the bottom and fig1 as viewed from the side . when the button 26 is released compression spring 238 forces the mode disk 236 in an upward direction . however , before the mode disk 236 can travel upward within large ring 248 it must further turn in order that the mode placement teeth 262 be aligned within the spaces between the mode placement plates 258 . because both the mode placement teeth 262 and the mode placement plates 258 have inclined surfaces which mate , these inclined surfaces slip on one another causing the mode disk 236 to rotate until the mode placement teeth 262 can once again slide within the spaces between the mode placement plates 258 . if the button 26 is once again depressed the cycle is repeated causing the mode disk 236 to again rotate through an arc which is equal to the radial distance between the centers of any two mode placement teeth 262 . the pins 240 , 242 and 244 are so placed on the bottom of mode disk 236 that when button 26 is depressed and mode disk 236 is in its most downward displacement , the interaction of mode teeth 260 with button teeth 256 correctly places the mode disk 236 such that pins 240 , 242 and 244 are positioned over the respective parts which they interact with -- that is , front release pin 232 , rear release pin 234 and lever 166 , respectively .

a mechanical toy which has a seemingly random movement of both its extendable parts and its motion is described . the toy has a base to which is attached several extendable members which can be pushed into the toy by the child to a retractable position . the extendable members are held in the retractable position by a series of independently acting holding members . the toy includes a button which is positioned so that a child may easily push it . on depression of the button one , several or all of the extendable members may be released from the retracted position allowing them to extend out of the toy into an extended position . concurrently the propulsion mechanism of the toy may or may not also be activated causing the toy to move along the surface on which it is set . the propulsion mechanism is energized by the child mechanically depressing one of the extensions into its retracted position .

referring to fig1 - 3 , an embodiment of a lancet actuator assembly in accordance with the present invention is generally designated by reference character 10 . the illustrated embodiment of actuator 10 is designed for single - use disposibility and employs a pre - loaded , sterile needle 12 which is automatically thrusted into and immediately retracted through an operating opening 14 in a molded housing 16 . in the illustrated embodiment , the metal needle 12 is encapsulated within an integrally molded , plastic lancet needle structure generally designated by reference character 18 . in the assembled configuration of the actuator assembly 10 , the lancet needle structure 18 includes a frangibly removable needle shield 20 which encapsulates the end 12a of the needle 12 but can be manually twisted for frangible removal from the preferred rectilinear , needle - holding body 22 of the molded structure 18 to expose the sharp , skin - penetrating end 12a of the needle 12 immediately prior to the penetration operation of the assembly 10 for blood sampling . as a result , the insert molded lancet needle 12 is fully encapsulated in thermoplastic of sufficiently high melting point so that the conventional molding temperatures sterilize the needle ; the encapsulation maintains the sterility to eliminate the need for individual sterile packaging of the needle structure 18 prior to assembly in the actuator assembly 10 . referring again to fig2 and 3 , the integral needle lancet structure 18 includes both the needle holding body portion 22 and an ( operating drive motion ) transmission linkage portion generally designated 24 which is joined to the needle - holding portion 22 through an integral , attenuated hinge portion 26 serving as a &# 34 ; live hinge &# 34 ; for articulated operation as more fully described hereinafter . the linkage portion 24 has a generally planar , elongate main body 28 which has a transversely projecting cylindrical spring bearing 30 formed generally on the opposite end of the body 28 in relation to the integral hinge 26 . the movable end 32 of a torsion drive spring 34 is inserted and secured in the spring bearing 32 . the stationery end 36 of the torsion drive spring 34 is anchored by insertion into an anchoring bore 38 formed in the housing portion 16a of the split housing 16 . the housing half 16a has an integrally formed , guiding cam track wall 40 which guides travel of a cam follower pin 44 integrally formed on the main body 28 of the needle linkage portion 24 as best shown in fig3 . the cam follower pin 44 laterally projects from the opposite face of the main body 28 in axial alignment with the cylindrical spring bearing 30 so that the movable spring end 32 extends through the spring bearing 30 into the bored cam pin 44 for particularly balanced stability of the bearing force by the drive spring end 32 internally imposed also on the cam follower pin 44 , which promotes stabilized guidance of the transmission linkage motion as hereinafter described . as best shown in comparing fig2 and 5 , the cam track wall 40 and slot 42 have a configuration including three general portions 46 , 48 and 50 . in the assembled actuator 10 , prior to use as illustrated in fig5 the cam following pin 44 is lodged against the wall of the short , initial cam slot portion 46 which is arranged at approximately right angle relative to the adjoining slot portion 48 so that the slot portion 46 serves as a pre - cocking notch leading to the slot portion 48 ; the cam following pin 44 is retained in the slot or notch portion 46 by the bearing force of the movable spring end 32 from the pre - wound condition of the torsion spring 34 imposing transverse , seating force of the pin 44 relative to the direction of travel necessary to release the pin 44 from the notch 46 to enter the slot portion 48 . the &# 34 ; pre - cocked &# 34 ; position of the cam following pin 44 cannot be accidentally dislodged from the slot notch 46 by pulling on the exposed twist - off needle shield 20 and is positively locked in the cocked position of fig5 until the actuator 10 is deliberately triggered for blood sampling operation . the manual trigger structure 52 is integrally molded with the housing half 16a and is pivotally joined by the attenuated hinge portion 51 . the trigger structure 52 also includes a ramped barb formation 53 which will catch under the trigger edge 17 of the housing after the first inward deflection of the trigger structure 52 for blood sampling operation to retain the inwardly deflected position of the trigger structure 52 as a visual indicator of use , as shown in fig6 - 8 , so that the user will not attempt any second blood sampling operation of the actuator 10 which will thereafter be discarded . to operate the lancet assembly 10 for skin penetration with reference to fig6 - 8 , the frangible , protective shield 20 is removed by twisting from the needle end 12a , and then the housing opening 14 is gently aligned against the target skin . thereafter , the trigger structure 52 is manually deflected inwardly as indicated by arrow a so that a trigger cam projection 54 presses the end of the linkage body 28 and dislodges the cam pin 44 inwardly , against the transverse force of the spring end 32 so that the cam pin 44 is released to enter the adjoining cam slot portion 48 along which the expansion force of the spring is directed to drive the cam pin through the slot portion 48 . with the downward entry of cam pin 44 into the guide slot portion 48 , the same downward deflection of the linkage body 28 is transmitted through the integral hinge 26 to the needle - holding body portion 22 to initially begin downward displacement guided along a highly linear path . upper , spaced guide ribs 56 and lower , spaced guide ribs 58 integrally formed with the housing half 16a form a linear guide track for the downward and upward displacement of the needle holding body portion 22 and needle end 12a . as the cam pin 44 is driven by the spring 34 through the medial guide slot portion 48 pulling the linkage body 28 therewith , the integral hinge 26 converts the relative pivotal motion to the needle holding body 22 inducing further linear travel thereof through the track ribs 56 and 58 thrusting the needle end 12a through the housing opening 14 with maximum extension therefrom and resulting skin penetration depth as the cam pin 44 reaches the end of the medial slot portion 48 at the entry to the succeeding slot portion 50 as shown in fig7 . from the position shown in fig7 continued unwinding force of the spring 34 drives the cam pin 44 through the upwardly inclined cam slot portion 50 which automatically induces , through the integral hinge 26 , sequentially continuous reversal in the motion of the needle holding body 22 pulled upwardly along the same linear path through the track ribs 56 and 58 , so that the needle end 12a is withdrawn from the skin penetration position of fig7 . in the position of fig8 the cam following pin 44 reaches the end of the guide slot 50 , and in the corresponding terminal position , the needle end 12a is retracted from the housing opening 14 for protection against any further danger of subsequent inadvertent skin penetration . in the illustrated embodiment , the needle end 12a can only project from the housing opening 14 during a single , deliberately triggered blood sampling operation of the lancet assembly 10 , because the entirely enclosed drive mechanism prevents any re - winding of the drive spring 34 so that after a single blood sampling operation , the lancet assembly 10 cannot be re - cocked or reused and will be discarded , effectively preventing any cross - contamination of sampled blood . the blood sampling operation is powered by the torsion spring 34 which assures preset drive and fast penetration and retraction of the lancet needle end 12a for minimized user discomfort and precise actuation without dependence upon variable manual power . as best shown in fig2 - 4 , the transmission linkage portion 24 has a laterally projecting spacer 31 which provides for narrow clearance with the internal wall surface of the housing portion 16b to prevent any potential twisting of the lancet needle structure 18 by the operating unwinding of the torsion spring 34 . additional stability is provided by the comparatively wide and flat linkage body portion 28 to promote smooth relatively sliding engagement of the spring coil portion 35 thereagainst during the actuator operation . referring again to fig2 and 3 , in order to ensure the highly accurate linear path of both thrusting and retracting of the needle holding portion 22 , the guide track formed by the spaced guide ribs 56 and 58 is further enclosed by an extended medial guide rib 57 in housing half 16a and the opposing guide rib 59 in housing 16b . additionally , in order to minimize tracking friction against the guide ribs , the rectilinear needle holding portion 22 has upper and lower sets of facially projecting nibs 60 and 62 . referring now to fig9 a modified embodiment of an actuator assembly in accordance with the invention is shown in which one of the housing halves 116a or 116b can be provided with an internally projecting ledge adjacent the needle projection opening 114 and the frangibly removable needle shield 120 , which encapsulates the needle end 112a within the integrally molded needle portion 122 can be provided with a small stop member 121 which abuts the ledge in the assembled and pre - cocked actuator assembly so that the shield 120 cannot be merely pulled through the opening 114 , thereby encouraging only a manual twisting on the shield 120 for frangible removal thus discouraging any premature advancing motion of the needle end 112a prior to actual needle sampling operation of the actuator 10 . while a preferred embodiment of the present invention is shown and described , it is envisioned that those skilled in the art may devise various modifications and equivalents without departing from the spirit and scope of the appended claims .

an actuator mechanism and assembly for sequentially advancing and retracting a lancet needle includes a housing having an opening for operating projection of the needle . two guide tracks are provided within the housing for guiding separate motions of a two - part needle holder structure propelled by a drive spring , and the needle itself is smoothly guided along one of the tracks to advance and thrust the needle into a tissue penetration position immediately followed by automatic retraction along the same highly accurate linear path .

in one aspect , the current invention in part stems from recognition of the fact that the effect of electroporation on tissue can be modulated by selecting a specific direction relatively to a cell for application of a pulsed electric field . for elongated cells similar to muscle fibers the length - to - width ratio can be as high as 20 to 30 . for the nerve cells this ratio can be even higher . the vulnerability of cells to electroporation is different for different directions of the applied field . it depends on the size of a cell in the direction of the applied field . in other words , elongated cells can be killed with significantly lower electric field if the field is applied along the cells . if the field is applied across the cell , the cell is capable of surviving much higher amplitudes of the electric field . in the current invention relief of symptoms is achieved by electroporation treatment , which is used to create a necrotic zone in the bph tissue around the urethra . necessary control of the volume of the necrotic area , its shape and location relatively to the healthy tissues of the prostate and urethra can be provided by a system of electrodes generating electric field in the area of the benign enlargement of the prostate . application of multiple electrical pulses with appropriate voltage and duration leads to necrosis of prostatic tissues around the urethra . anatomically , predominant direction of fibers in the fibro - muscular glandular tissue of bph is radial to the urethra . in the present invention the preferred direction of applied electric field is also radial to the urethra , coinciding with the direction of fibers . application of the electroporating pulses along the muscular fibers and nerves that anatomically follow them selectively kills both types of fibers . thus two intermediate goals of the present therapy become achieved : first , a significant volume of necrotic bph tissue around the urethra is created ; second , the nerves causing elevation in tension of the muscle fibers are destroyed . removal of the necrotic tissue by macrophages decreases the total volume of bph and reduces pressure on the urethra . destruction of the nerves results in relaxation of the prostate . subsequently , both effects contribute to the improvement of the urethra and bladder functions after treatment . to apply a pulsed electric field to the bph region in the transition zone of the prostate , a set of electrodes is placed into the urethra ( and the bladder ) on the urethral catheter . in other embodiments of the invention , external electrodes are utilized or needle - type electrodes may be introduced into the volume of bph tissue . the electrodes are electrically connected to a generator producing high voltage pulses , the amplitude and duration of which are selected to provide electric field in the prostatic tissue exceeding the upper electroporation limit for the fibro - muscular cells . duration of pulses may be selected from the range of 10 microseconds to 500 milliseconds . the amplitude and number of pulses are preselected to cause necrosis of the bph cells , mainly muscle cells and nerves . sphincters , located on the urethra anterior and posterior to the prostate gland , consist of smooth muscle cells wrapped circumferentially around the urethra . they control shutting down the flow of urine from the bladder and should be preserved during the treatment . radial electric field applied to the prostate is transversal to the sphincter muscle fibers to which they are relatively resistant . however , to ensure that electroporation injury to the sphincters is avoided , the electrode in the urethra between the sphincters should not be positioned too close to them . for the same reason the amplitude of the electric field during treatment should be selected not to exceed the upper electroporation limit of the sphincter muscles in the transversal direction . in another aspect , the present invention provides an apparatus and method for treatment of the prostate . the invention is generally described in the context of an apparatus and method for the treatment of bph as a specific example for illustrative purposes only . upon review of the following description and figures , those skilled in the art will understand that an apparatus in accordance with the present invention may be used for a wide variety of indications . an apparatus for treatment of the prostate in accordance with the present invention is shown in fig1 . a foley type urethral catheter 101 includes balloon 102 at its distal end . urethral catheter 101 is introduced into the urethra 111 ( 411 in fig4 ) and balloon 102 positioned within the bladder 115 . as illustrated , transition zone 120 of the prostate is being treated for bph . anatomically , central zone 121 , peripheral zone 125 seminal vesicle 123 , and ejaculatory duct 122 , are illustrated . ejaculatory duct 122 delivers the sperm into the prostatic urethra during sexual climax . the catheter can include an electrode 103 adjacent to the prostate in the transition zone 120 , and an electrode 104 , placed into the bladder distally to the urethra or outside of the urethra on the skin ( not shown ) of the patient . an implementation of the present invention having three electrodes is shown in fig1 : electrode 104 is in the bladder , electrode 103 is adjacent to the transition zone , electrode 105 can be placed proximally to the electrode 103 in the urethra . placing more than two electrodes allows achieving better concentration of electric field on affected region of the prostate in the transition zone . a port 106 may be provided in the proximal end of the urethral catheter serving as an inlet for the coolant intended to cool the urethra as the prostate is heated . in one aspect , the prostate may be heated using rf . therefore , an radio frequency ( rf ) generator 110 is illustrated for exemplary purposes . in this embodiment , a port 107 can also be provided to serve as an outlet for the coolant carrying the heat from the electrodes 103 and 105 via a flexible tube 117 to the coolant system 118 . wires 108 ( 408 in fig4 ) can be provided to connect electrodes 103 , 104 , 105 with a generator 109 , sending electroporation pulses to bph . for purposes of electroporation , generator 109 is typically configured to provide high voltage . during treatment , the urethra may be cooled by a cooling system 118 . outlet 130 is a channel , fluidly connected to the balloon 102 and serving for its inflation in the bladder 115 . in fig2 a cross - section of an embodiment of the urethral catheter 101 inserted through a prostate is illustrated . number 100 corresponds to the transition zone of the prostate 120 effected by bph . electrode 103 is positioned in the prostatic urethra 111 . fig3 and fig4 show a longitudinal - section and a cross - section of an embodiment of the urethral catheter 101 . number 103 corresponds to the urethral electrode , 406 is the channel in the catheter , fluidly connected to the inlet 106 at the proximal end of the catheter and accepting the coolant liquid from the pump , not shown in the figure . number 407 is designated for two channels in the catheter in which the coolant moves back to the proximal end , where through the outlet 107 it is returned to the cooling system . another apparatus for implementing the method in accordance with the present invention employing a perineal needle template for placement of electrodes into bph is depicted in the fig5 . here 520 is a needle perineal template with holes 521 for directing needles having proximal end 522 , distal ends 523 and elongated part 525 . the proximal ends are electrically connected to multi electrode connector 526 , leading to a switch board circuit 527 , which , in turn , is connected to the output of the high voltage pulse generator 109 . an apparatus for treatment of bph by electroporation employing a urethral probe — an applicator for placement of electrodes into the prostate via urethra , is shown in fig6 . the apparatus comprises a urethral probe 600 having a proximal end 601 , elongated member 603 and a distal end 602 . the elongated member 603 has a passageway 606 extending from the proximal end of the probe 601 to its distal end 602 and ending at a side port 604 of the probe 601 . in the passageway at the proximal end of the probe , an endoscope 611 is introduced . the endoscope has a wide - angle view and allows one to visualize the urethra at the distal end of the probe and thus provides visual control during manipulation of the probe . the endoscope has a fiber optic port 630 secured to a cable 640 connected to a light source 650 . the light source 650 provides necessary illumination of the urethra beyond the distal end of the probe . probe 600 is attached to a control handle piece 612 . a flexible needle 605 inside passageway 606 extends throughout its length from the proximal end where it is engaged with a finger 607 via a mechanism adapted for advancement or retraction of the needle along the probe . being advanced forward , the needle 605 bends at the distal end 602 of the probe 601 and comes out from the side port 604 under an angle close to 90 degrees to the urethra . control handle piece 612 is used for manipulation of angular and longitudinal positions of the probe in the urethra and placement of the distal end 602 of the probe 601 into several locations along the transition zone of the prostate . the needle has a sharp tip 608 which easily penetrates through the urethra wall 619 . electrodes 610 on the distal part 609 of the needle thus placed into the volume of the bph . the electrodes are spatially and electrically separated and , being pulsed by a high voltage , are capable of creating a substantial radial electric field along the muscle fibers of the bph . two wires leading from the electrodes 610 are extended through the needle 605 to its proximal end and further inside the handle 612 to the connector 613 , where they are connected to the cable 614 . the cable 614 is connected to the generator 109 . under endoscopic guidance the probe is introduced by a physician into the patient &# 39 ; s urethra with the distal end of the probe positioned inside the prostate . the needle of the probe is advanced into the bph tissue surrounding the urethra and multiple hv pulses are applied . the end point of the electroporation therapy is a significant and stable drop in the electrical resistance of the treated volume . the resistance drop indicates profound electroporation damage to the fibro muscular cells , which later on leads to their necrosis . overall treatment of one site takes about 10 pulses and several seconds to several tens of seconds in time depending on the repetition rate of the pulse generator . another implementation of the current invention is shown in the fig7 . in this version of the apparatus , the needle electrodes are delivered to the prostate by a urethra - perineal apparatus . this apparatus is a combination of a urethral probe carrying a central electrode in the prostatic segment of the urethra and a cartridge of needle electrodes placed into the body of the prostate via a perineal approach . the urethral probe 701 is made of a rigid material , preferably metal , and has a proximal end 702 , a distal end 703 and an elongated member 704 . the distal end of the probe 703 is terminated with a balloon 705 adapted for inflation in the patient bladder 115 . during treatment , the probe is introduced into urethra 706 of penis 707 and balloon 705 is inflated . inflated balloon 705 anchors the probe longitudinally relatively to the bladder and prostate . the length of the urethral electrode and the distance between the electrode and the balloon are selected in such a way that the electrode is placed precisely adjacent to the bph in the transition zone of the prostate 709 . balloon 705 via a channel inside the probe 701 fluidly communicates with inflation port 710 connected to a syringe 711 actually inflating the balloon . the urethral electrode 708 electrically connected to a wire 712 coming out of the distal end of the probe 702 to switching board circuit 713 whose function is the distribution of the high voltage pulses received from the generator 109 between electrodes placed into prostate during electroporation treatment . the urethral probe 701 is attached to a handle piece 714 used for longitudinal and angular manipulation of the probe . a cartridge 720 used for placement of needle electrodes into prostate via perineal approach is secured at the opposite side of the handle piece 714 . the cartridge 720 has a proximal cap 721 , a distal cap 722 and a cylinder 723 between them . a piston 724 secured at the end of a plunger 725 slides inside the cylinder 723 between two extreme positions , a proximal and a distal one . in the proximal position the needles are hidden in the cylinder . being pushed by a knob 730 the piston 724 moves the needles forward through holes 731 in the distal cap 722 forcing the needles to prick perineum 700 situated between scrotum 715 and anus 716 and penetrate prostate 709 . an exemplary needle 727 ( for simplicity only two needles are shown ) has proximal end 726 , distal end 728 and electrode 729 . the proximal ends of all needles are mounted on the distal surface of the piston 724 , electrically insulated from the needles . through holes on the proximal surface of the piston the needles are electrically connected to wires 731 , leading to switchboard circuit 713 , used for commutating the high voltage pulsed between separate electrodes or groups of electrodes . the switchboard circuit 713 is coupled to a high voltage pulse generator 109 . the needles may be mounted on the piston 724 in two or three rows along concentric circumferences . the electrodes 729 , preferentially electrically insulated from the needles , are connected to wires 731 , leading to the switchboard circuit 713 , with insulated wires disposed inside the hollow needles . the needles in each row may be electrically connected to each other and kept at the same potential during high voltage pulsing . these connections decrease the number of wires that should be placed between the needles and the switchboard circuit 713 and generate an electric field in a predominantly radial direction , the direction that is especially efficient in killing fibro muscular cells positioned radially . the shape of urethral probe 701 , its spatial position relatively to the needle cartridge 720 and spacing between the needles are selected to insure that the needles move parallel to the distal part of the urethra and can be placed in the urethra at predetermined radial and longitudinal positions from each other and from the urethra electrode 708 . stated otherwise , the probe member 704 may be configured to include a substantially linear distal end segment that serves to straighten the prostatic urethra when the probe is placed in an operative position in the urethra as shown in the figure . this distal end segment carries the balloon 705 and the urethral electrode 708 . the distal end segment and the needle electrodes 727 each define linear axes that are substantially parallel to each other . with this configuration , then , the needle electrodes 727 may be advanced such that they move substantially parallel to the distal end segment and thus the distal or prostatic urethra . with this configuration of rigid probe , handle , and needle cartridge , the electrodes 729 may be precisely positioned relative to the urethral electrode 708 for application of the electroporation therapy , as will be explained in greater detail with respect to fig8 , below . the relative positioning of the urethral electrode and the needle electrodes in the prostate during treatment is illustrated by fig8 . fig8 shows a cross - section of the prostate with all electrodes in place . numbers 813 and 815 stand for peripheral and central zones of the prostate respectively . number 812 corresponds to anterior fibro muscular area and 814 — for ejaculatory ducts . as can be seen from the fig8 , the urethral electrode 808 is placed in the center of the prostate with the needle electrodes 829 positioned around it . a channel 809 connects the distal balloon of the urethral probe and the inflating port located at the proximal end of the probe . two circumferential rows of needle electrodes are placed concentrically around the urethra . high voltage pulsing applied to the central electrode and any of the rows of electrodes creates a predominantly radially directed electric field . also , the radial electric field can be created by pulsing the rows of the needle electrodes only , without applying voltage to the central urethral electrode , or it can be created by consecutive pulsing pairs of electrodes positioned at different distances from the urethra along the same radius . the treatment procedure with a urethra - perineal applicator starts by placing the probe 701 into the urethra 706 . balloon 705 at the distal end of the probe 703 is inflated . inflated balloon 705 anchors the probe relatively to the urethra and the bladder . due to selection of the location of electrode 708 on the probe 701 , it can be positioned in the urethra at the exact location of the transition zone in the middle of the bph overgrowth . as the probe 701 is being placed in the urethra , the needles 727 in cartridge 720 stay inactive , hidden in the back position . after the probe 701 is placed and anchored , the scrotum 715 is pulled aside and gently secured at a side and up position to avoid injury by the needles 727 to be advanced . then the needles 727 are advanced into the forward position . they pierce the perineum 700 and the prostate 729 and deliver the needle electrodes 729 into the treatment positions around the central urethral electrode 708 . after placement of all electrodes , the electroporation treatment is performed . multiple high voltage pulses are delivered to the electrodes to create a radial to the urethra electric field to cause cell death and necrosis of a significant volume of neoplastic tissue , resulting in a relief of bph symptoms . as the hv pulses are delivered the electrical resistance of the tissue is monitored . the end of the therapy is marked by a significant and stable drop in the resistance of the treated volume of tissue . placement of electrodes in the vicinity of prostate using a urethra - perineal applicator does not require ultrasound or other imaging guidance . precise placement of the needles is provided by high mechanical tolerances of the applicator and high rigidity of the urethral probe . using the urethra - perineal applicator allows for a short treatment time because it provides treatment in only one position of the electrodes , and does not require repositioning electrodes and multiple manipulation of the applicator . the urethra - perineal applicator can be used for delivery of electrical energy to the prostate not only in the form of high voltage pulses causing electroporation necrosis , but also in the form of rf energy causing thermal necrosis of bph . different needle electrodes used in the electroporation treatment are shown in fig9 a , b , c . fig9 a shows a one electrode needle adapted for creating electric field normal to the axis of the needle . the needle has a proximal end 901 , distal end 902 and a metal hollow body 906 . at the distal end 902 the needle is terminated by a sharp metal tip 910 ( 911 ), brazed into the hollow body of the needle . a cylindrical electrode 903 is secured on an insulator layer 905 deposited on the needle surface . the electrode 903 ( 904 ) is electrically connected to high voltage generator via a wire 907 ( 908 ). a version of a similar needle with two electrodes adapted for creating electric field directed along the axis of the needle is shown in the fig9 b . in versions 9 a and 9 b the sharp tips are electrically separated from the hv electrodes . in version 9 c the tip is made of an insulating material , like glass , dielectric crystal or ceramics . this feature of the design prevents electric breakdowns and sparking from the tip through the tissue during hv pulsing . although preferred embodiments of the invention have been described in some detail , it is understood that obvious variations can be made without departing from the spirit and the scope of the invention as defined by the appended claims .

an apparatus and method for treatment of a tubular anatomical structure is disclosed . the method includes using an electrical signal to destroy elongated cells on the tubular anatomical structure . the apparatus may include one or more electrodes for creating an electric field , and a cooling system for carrying heat away from the electrode . the elongated cells can include nerve cells on the tubular anatomical structure .

this invention allows interconnectability of flat , flexible objects through a series of slits along the perimeter of the objects . the width of slits along the perimeter is approximately the same as the width of the paper or other medium which is being used . the objects connect together by fitting one or more of the slits of one object into one or more of the slits of another object . multiple objects can be connected together to allow for vertical , horizontal or 3 - demential connecting . in one embodiment a rectangle card 2 . 5 inches wide ( fig1 - x ) by 3 . 5 inches long ( fig1 - y ), could have two slits ( fig1 - a , b ), perpendicular to the edge , on each of the four sides of the card which are centered with respect to the corresponding edge ( fig1 - g , h ) and approximately 1 . 5 inches apart . keeping the distance between the slits equal allows for the cards to be connected both horizontally and vertically . the perpendicular slits on the 3 . 5 inch sides of the card ( fig1 - y ) would be 0 . 5 inches in length ( fig1 - f ) and the perpendicular slits on the 2 . 5 inch sides of the card would be 0 . 25 inches in length ( fig1 - e ). the length of the slits is such that after connecting two cards along each &# 39 ; s 3 . 5 inch side and with the 0 . 5 inch slits , allows the 0 . 25 inch slits ( fig1 - a ) to line up ( fig2 - a ). by connecting two cards along each &# 39 ; s 2 . 5 inch side and with the 0 . 25 inch slits , allows the 0 . 5 inch slits ( fig1 - b ) to maintain an even spacing of 1 . 5 inches between the two connected cards ( fig3 - a ). having the slits line up and maintain an even spacing allows for additional connections to be made which will both strengthen and broaden the user &# 39 ; s design ( fig5 ). additional connections can be made indefinitely . the slits in the cards are also used to connect the cards 3 - dimensionally . one method to create a simple 3 - dimensional object is shown in ( fig7 ).

a series of slits along the perimeter of flat , flexible objects in that the objects can be connected together in a variety of ways for entertainment and / or functional benefit .

fig1 a is a schematic diagram showing a first box spring pre - assembly attached to wooden frame 17 and to wooden slats 18 . the box spring pre - assembly includes a substantially rectangular border wire 11 , longitudinal wires 12 and lateral wires 13 . the lateral wires are welded to the longitudinal wires at each point that these wires intersect . the box spring pre - assembly also includes a plurality of formed wire structural support wire 14 ( shown also in fig2 a and 2b ), which may be attached to the lateral wires 13 by clips 19 . the formed wire structural support wires are attached to wooden slats 18 at the vertices 15 of the vs in the structural support wire . it is also attached to wooden frame 17 at both ends of the structural support wire , at ends 16 . fig1 b is a detailed view of the encircled area in fig1 a , showing how the structural support wire is bent at 90 ° for a short lateral segment . the lateral segments of the structural support wire are attached to lateral wires 13 using clips 19 , as shown in fig4 c . however , as shown in fig4 b , the ends of the structural support wire are attached to a longitudinal wire , not to a lateral wire . fig2 a and 2b are schematic diagrams of structural support wires 14 for a three - slat foundation and for a four - slat foundation , respectively . fig2 a and 2b show the ends 16 of the structural support wires , and the vertices 15 of the structural support wires . the structural support wire is attached to the wooden frame and to the slats of the foundation at ends 16 and vertices 15 , respectively . in the preferred embodiment of the present invention , curved segments or notches 20 of the structural support wires are formed such that they rise slightly above the longitudinal and lateral support wires ( as shown in fig1 b and 4a - 4c ). this restricts lateral movement of the structural support wire by trapping the fixed longitudinal wire between clip 19 and notch 20 . fig3 a and 3b are perspective views of a portion of a structural support wire 14 , showing the ends 16 , the vertices 15 , the short lateral segments 30 and the notches 20 . fig3 a provides a good view of the inverted pyramid structure formed by the v portions of the structural support wire . fig3 b shows how the two adjacent structural support wires are angled towards each other , such that the plane of the structural support wires form oppositely - directed angles that are substantially less than 90 °, preferably about 45 ° to about 75 °, even more preferably about 60 ° to about 70 °, with respect to the top support surfaces . fig4 a is a top view of the box spring pre - assembly showing the rectangular border wire 11 , longitudinal wires 12 , lateral wires 13 , structural support wires 14 , the vertices 15 of the structural support wires and the ends 16 of the structural support wires . fig4 a shows that the vertices 15 of two adjacent structural support wires 14 do not actually come in contact with each other . the distance between two adjacent vertices is typically about three - quarters of an inch . however , it can be varied according to the particular requirements of the foundation . fig4 b is an enlarged view of the circular area marked &# 34 ; a &# 34 ; in fig4 a . it shows how the end of the structural support wire is attached to a longitudinal support wire 12 by clip 19 . each end 41 of a lateral support wire , or end 42 of a longitudinal support wire , is bent over rectangular border wire 11 from below , firmly attaching the support wires to the rectangular border wire . fig4 c is an enlarged view of the circular area marked &# 34 ; b &# 34 ; in fig4 a . it shows how , except at the ends of the structural support wire , short lateral segments of the structural support wire are attached to the lateral support wires 13 by clips 19 . fig4 c also shows a notch 20 , which rises above longitudinal wire 12 , ensuring that the structural support wire cannot slide along the lateral support wire . as shown in fig4 a , notches 20 on adjacent structural support wires are located on alternate sides of the longitudinal wires ( i . e ., as shown in fig4 a , if notch 20l is to the left of its longitudinal wire , notch 20r is to the right of its longitudinal wire ). this configuration of alternate left and right notches , and clips securing the structural support wire to the lateral support wires , ensures the rigidity and stability of the formed wire foundation . in an alternate embodiment of the present invention as shown in phantom in fig5 a , the structural support wires do not include lateral segments . in that embodiment , the structural support wires are clipped to the longitudinal support wires . the notches along each structural support wire rise up on alternate sides of the longitudinal support wire , to fix the angular position of the structural support wire relative to the support surface , by physically contacting the underside of the lateral support wire . fig5 a is a perspective view of two adjacent structural support wires 14 , showing how the structural support wires are secured to a wooden slat 18 at short flat segments 36 using , e . g , staples , and to lateral support wires 13 using clips 19 . clips 19 allow a limited rotation of the lateral segments 30 of the structural support wire . the limited rotation within the clips , and the use of spring wire for the structural support wire results in a top support surface that is not completely rigid , i . e ., a support surface that is flexible enough to form limited contours and to flex in response to applied loads . the length and positioning of lateral segments 30 , and the angle the v sections form with the top support surface , determine the position of flat segments 36 on slats 18 . the distance between two adjacent segments 36 is preferably 0 . 5 to 1 . 0 inches . for the second preferred embodiment of the present invention , discussed below with reference to fig7 the space between adjacent segments 36 must be sufficient to allow the structural support wires to slide readily on either side of additional longitudinal support wires 71 ( shown in fig7 ). in fig5 a , notches 20l and 20r are shown rising slightly above longitudinal wires 12 , on alternating sides of the longitudinal wires 12 , i . e ., notch 20l is on the left of the longitudinal wire immediately next to it , and notch 20r is on the right of the longitudinal wire immediately next to it . fig5 b is a perspective view of two adjacent structural support wires 14 , at one end of the pre - assembly , showing how the structural support wires are secured to wooden frame 17 using , e . g ., staples , to secure short , flat segments 32 of the end sections 16 to the wooden frame , and clips 19 to secure the structural support wire to longitudinal support wires 12 . end sections 16 also include a second short segment 33 , and a closing segment 34 . segments 32 , 33 and 34 form a substantially closed , roughly oblong loop . as shown by fig5 b , segment 32 can be stapled to the wooden frame using a stapling machine that accesses segment 32 from directly above . the loop formed by segments 32 , 33 and 34 must be substantially closed , i . e ., the size of the opening left between the end of closing segment 34 and the downward leg 35 of v - support wire 14 must be less than one - half the diameter of the structural support wire , so that succeeding pre - assemblies cannot get entangled by end sections 16 . fig5 b also shows how the longitudinal wires are attached to rectangular border wire 11 , by bending longitudinal wire 12 over and around border wire 11 . lateral support wires 13 are similarly attached to rectangular border wire 11 . fig6 is an end view of five stacked pre - assemblies , showing a sixth pre - assembly being added to the stack . fig6 shows the &# 34 ; v &# 34 ; portions of structural support wires 14 extending down towards the support frame ( not shown in fig6 ). fig6 also shows that the vertex of each &# 34 ; v &# 34 ; is open . fig7 is a schematic diagram of a second preferred embodiment of the present invention . the second preferred embodiment differs from the first preferred embodiment by having an additional set of longitudinal support wires 71 . longitudinal support wires 71 are co - planar with longitudinal wires 12 , but are positioned directly above the apex of the four - sided pyramid structures formed by the &# 34 ; v &# 34 ; portion of the structural support wire . because the vertices of the vs are open ( as shown in fig3 a , 3b , 5a , 5b and 6 ), additional longitudinal support wires 71 , if used , do not affect the stackability of the box spring pre - assemblies . the foregoing disclosure of embodiments of the present 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 forms disclosed . many variations and modifications of the embodiments described herein will be obvious to one of ordinary skill in the art in light of the above disclosure . the scope of the invention is to be defined only by the claims appended hereto , and by their equivalents .

a nestably stackable pre - assembly for a box spring foundation having a top support surface formed by a substantially rectangular border wire , lateral surface support wires and longitudinal surface support wires . the top support surface is supported by a series of longitudinal formed wire structural support members having v - shaped sections extending down from the top support surface . the structural support members are attached to the surface support wires by clips . the v - sections of adjacent structural support members are angled towards each other in pairs such that they form a series of four - sided open - apex pyramids . the pre - assemblies can be stored and shipped by attaching a first pre - assembly to a bottom wooden frame , and stacking additional pre - assemblies on top of the first .

in the subject invention , a chemodenervative agent is given in a therapeutically effective dose to reduce inflammation , and may be used in any application in which inflammation is present or to augment other inflammatory agents . the administration may be by injection , topical application , or other means to assure a therapeutically effective dose delivered to the site . not only is the subject treatment efficacious in disease treatment normally associated with the occurrence of inflammation , it is also efficacious in the treatment of other diseases . note that mechanical or adjuvant chemical activity may be necessary to increase penetration by topical application . the efficacy of botulinum toxin to treat inflammation is demonstrated in the following examples : a 53 - year - old woman had a history of bell &# 39 ; s palsy five years prior to being evaluated for asymmetric facial movements from synkinesis . the facial movements were causing involuntary eyelid closure . additionally , she noted abnormality in forehead creases and desired achieving facial forehead crease wrinkle symmetry by injection of botulinum into the frontalis muscle . after exercising , she noted that she would traditionally break out in hives , eg . urticaria , throughout her body , with the facial region being most severely involved . this urticarial reaction was closely associated with itching . two weeks after botulinum toxin injection at a dose of 2 . 5 units per injection site , an unusual phenomenon was noted on her forehead after exercising . an area measuring three to four centimeters around each injection area was protected from hive , itching or erythema . other areas of the face were involved in the usual hive , erythema and flushing reaction experienced with exercising . the protective area phenomena could be seen to be concentrated around each injection site , and could be observed after each period of exercise for about 10 to 14 weeks after which the protected area could no longer be demonstrated . as can be seen by the photograph of fig1 , the effect detected by the use of red sensitive kodachrome film -™ is demonstrated . here , the arrow heads denote where botulinum toxin was injected , with the lines denoting the area where reactive vasodilation , erythema and edema were blocked . note that the photo was taken six weeks after injection . this phenomenon could be consistently reproduced after each injection cycle , and has been observed in additional patients . after the effect dissipated in 20 weeks , another injection was given in similar locations . the same protected geometric area was again in evidence within 48 hours after botulinum toxin administration . a 44 - year old woman with interest in having glabellar lines reduced with botulinum toxin experienced generally facial flushing and swelling sometimes associated with headache following extreme exertion . after regional botulinum toxin was administered at a dose of 5 units , an area with diameter measuring 25 mm around the injection sites was protected from the flushing and abnormal sensory effect associated with such exertion . she noted this protective effect lasted 10 - 14 weeks . fig2 is a photograph of this woman within three days after injection , showing the blocking effect on heat release , vasodilation , erythema and edema , which effect expands to its maximum in 12 days , and persists for at least four months . urticaria refers to the formation of hives occurring usually in response to allergic reactions to pollens , foods , dander or other forms of antigens . the process often involves binding of allergens to the ige receptor of the mast cell membrane bound ige , causing release of preformed mediators such as histamine and serotonin as well as newly formed mediators from arachadonic acid such as prostaglandins and leukotrienes , platelet activating factor , kinoginase and tryptase , as well as cytokines . a late response can be seen after an allergic urticarial reaction which may be painful . urticaria may be provoked by non - allergens , including codeine , morphine , compound 48 / 80 , synthetic acth , and anaphylatoxins c3a , c5a . important , relative to the case observation , is the reactivity of mast cells to acetycholine as described by fantozzi , r ., masini , e ., blandina , p ., mannaioni , p . f ., bani - sacchi , t ., release of histamine from rat mast cells by acetylcholine , nature ( 1978 jun . 8 ) 273 ( 5662 ): 473 - 4 . mast cells are known to be abundant around blood vessels in the scalp , orbit and lids , and are thought to be important in allergic conjunctivitis as described by allensmith , m . r ., baird , r . s ., percentage of degranulated mast cells in vernal and giant papillary conjunctivitis , am j . opthalmol , 9 , 71 - 75 , 1981 , and henriquez , a . s ., kenyon , k . r ., allansmith , m . r . mast cell ultrastructure , comparison in contact lens - associates giant papillary conjunctivitis and vernal conjunctivitis , arch opthalmol 99 : 1266 - 1272 , 1981 . mast cells reactivity has been associated with hayfever bepharoconjunctivitis , asthma , allergic rhinnitis , and allergic forms of eczema . mast cells are also seen abundantly in inflammatory responses in rheumatoid arthritis and inflammatory bowel disease . mast cells are closely associated with type 1 hypersensitivity reactions . in such reactions , the typical response involves sensitization with an antigen , formation of immunoglobulin , ige class , binding of immunoglobulin to the external cell membrane by its fce receptor , and setting the stage for hypersensitivity to the second exposure to the antigen . upon second exposure , ige reacts with the antigen effect in a degranulation response of the mast cell , in which there is a release of preformed mediators such as histamine and serotonin , platelet activating factor , and newly formed mediators such as leukotrienes , prostaglandins , tryptase , kininogenase which effect vasodilatation , vascular permeability , microthrombi , edema , mucous secretion . the response persists manifesting a late response after 8 hours . the late response is associated with pain as described by roit , i ., brostoff , j ., male , d ., immunology 5 th edition mosby , 1998 . experiments were conducted on the effects of chemodenervation on the biologic reactivity of mast cells on the guinea pig conjuctiva . in order to test the viability of using chemodenervating agents as a method of reducing the inflammatory response associated with hypersensitivity , an animal model consisting of sensitization of hartley guinea pig conjunctiva to short ragweed pollen , eg ambrosia artemisiaefolia , was used . this animal model of ocular allergy involves exposing the nasal and conjunctival mucosae to topical ragweed pollen , followed by subsequent challenge . after challenge , these animals develop an acute hypersensitivity reaction within 2 - 3 minutes which strongly resembles clinical hayfever conjunctivitis and represents a rapid inflammatory response . histology evaluation of this animals model from exenterated orbis indicated marked infiltration of eosinophiles , as well as strong evidence of mast cell degranulation as described by merayo - lloves , j ., calonge , m ., foster , c . s ., experiential model of allergic conjunctivitis to ragweed in guinea pig , current eye research 14 : 487 - 494 , 1995 . each animal was sensitized by spraying spores of ragweed pollen into the conjunctiva and nasal cavities for two weeks at a quantity of 2 . 5 mg per exposure . after two weeks , the animals demonstrated the conventional signs of acute hypersensitivity within several minutes after , exposure , including edema , erythema , microvascular thrombi , mucous exudation , and irritation as demonstrated by animals scratching behavior . after hypersensitivity was established using this animal model , the left eye of each test animal was injected with 0 . 675 mouse units of botulinum toxin type a , the preferred chemodenervating unit within the peribulbar area . appropriate anti - inflammatory effect was monitored by two observations within the animal model : 1 . edema . 2 . erythema . 3 . behavior changes in animals measured by scratch limb rubbing time 15 minutes after exposure to the ragweed . the protective effect of the eye injection with the chemodenervating agent could be demonstrated within one week with respect to animals behavior , as well as observed edema and erythema comparing the test eye to the contra lateral eye not injected . this effect appeared most prominent within the first 10 minutes of the inflammatory exposure with allergen to the sensitized ocular surface and lasts up to six months . specifically , and as shown in fig3 , the animal was exposed to an aerosol containing ragweed pollen which initially had no inflammatory effects on the ocular surface . after 10 days of exposure to the antigen , the guinea pigs ocular response converted to a rapid onset of edema , conjunctival vascular dilation , microhemmorphages , and scratching behavior . as can be seen in fig4 , the eye which received the epibulbar injection after being sensitized shows reduced edema and erythema , with the duration of the effect being 4 - 5 months . as shown in the bar graph of fig5 a , animals injected with botulinum toxin scratch significantly less often , with fig5 b being a graph showing protection up to six months . four patients experiencing severe conjunctival and lid margin erythema , itching and ocular mucous discharge associated with ocular irritation were tested . each patient had been treated with conventional therapy , including anti - histamine eyedrops , steroid drops , and sympathomimetic ocular preparations without relief in symptoms . because of unrelenting symptoms , the subject anti - inflammatory agent was offered as an “ off label ” use in an attempt to alleviate their distressing affliction . as botox -™ from allergan is the only denervating pharmaceutical currently available for use in ocular movement disorders , botox -™ was injected into the periocular region close to the lid margin in each patient , using dose injection doses less than 5 ld 50 units per injection site to limit undesirable diffusion . subsequently , each patient was followed up after 4 - 7 days . each patient noticed improvement in irritation , itching , erythema and general discomfort associated with their condition . as shown in fig6 , a patient demonstrating severe atopic conjunctivitis for four months had his left eye treated 48 hours prior to the photograph . after periocular injection in a low dose of 5ld 50 units , injected eye lids showed vasodilation , redgress and irritation . a visual analogue evaluation of 20 patients with essential blepharospasm were compared with a 10 patient control population . the essential blepharospasm patient clearly had statistically significant differences with respect to light sensitivity compared to controls in which p & lt ; 0 . 05 using the visual analogue scale . 15 units of botulinum toxin were administered to each periorbital area . the effect of botulinum toxin on photophobia was evaluated using the visual analogue scale pre - injection and 2 - 3 weeks after injection in an open label study . in a series of 14 patients , the effects on photophobia were reported to be significantly mitigated ( p & lt ; 0 . 05 ). here , the anti - inflammatory mechanism of the subject agent is clearly active . in the past , it was thought that the tissue mechanisms associated with using chemodenervating agents have solely involved the use of botulinum toxin as a means of causing muscle relaxation or to produce certain autonomic effects blocking decreased sweating . although there have been conditions treated by chemodenervating agents which have had associated inflammatory reaction as a part of the clinical syndrome , the concept of muscle relaxation induced by such agents has been thought to be the mechanism by which such agents induce the beneficial effects . it has now been found that the subject agent has useful anti - inflammatory properties capable of blocking ocular surface allergic inflammation in man and animal models , as well as generalized inflammation within the denervation field created . for treatment , the practitioner defines a fixed anatomic area in which symptomatic and / or destructive inflammatory processes are occurring . knowledgeable of dose related diffusion properties and potency of the preparation being used , the practitioner defines the anatomic area to be treated . avoiding critical structures , e . g . blood vessels , nerves and anatomic cavities , the practitioner injects a fixed dosage of the chemodenervating agent so as to create a denervation field , reducing the intensity of tissue destruction occurring within the area of treatment . such a field can be defined internally , e . g . stomach mucosae - gastrits , joint - arthritis and muscle myositis . follow - up involves monitoring for the cardinal sign of inflammation - pain redness , edema and discharge . adjuvant therapy with other anti - inflammatory agents would be contemplated . spasmodic torticollis , eg . cervical dystonia , regional and segmental dystonia of neck , was first treated with botulinum toxin in 1984 . the condition involves involuntary movements , postures and tremors of the head and neck region often associated with pain . muscle hypertrophy and neck rigidity are often associated components of the syndrome . the condition often occurs in mid - life , and generally is chronic with occasional remissions . heredity and genetic etiology has been implicated , as patients often have other family members afflicted with similar conditions as described by borodic , g . e ., joseph , m ., fay , l ., cozzolino , d ., ferrante , r ., botulinum a toxin for the treatment of spasmodic torticollis , dysphagia and regional toxin spread . head & amp ; neck 12 : 392 - 398 , 1990 , borodic , g . e ., mills , l ., joseph , m . botulinum a toxin for adult onset spasmodic torticollis , plastic and reconstructive surgery 87 : 2 , 285 - 289 , 1991 . the cause of this condition has been attributed in the past to direct derangement within the central nervous system , as patients have been noted to have abnormal eye movement patterns and auditory and other sensory brainstem - evoked measurements , as reported by drake , m . e ., jr ., brian - stem auditory - evoked potentials in spasmodic torticollis arch , neural 1988 february ; 45 ( 2 ): 174 - 5 . however , convincing evidence has been lacking , as discussed by horner , j ., riski , j . e ., weber , b . a ., nashold , b . s ., jr . swallowing , speech , and brainstem auditory - evoked potentials in spasmodic torticollis , dysphagia 1993 ; 8 ( 1 ): 29 - 34 . regional and segmental dystonias have been associated with atypical patterns of brain metabolism when measured with pet scanning , as described by becker , g ., et al , comparison of transcranial sonography , magnetic resonance imaging , and single photon emission computed tomography findings in idiopathic spasmodic torticollis , mov disord 1997 january ; 12 ( 1 ): 79 - 88 . as illustrated in fig7 a - d , it has been discovered and is a part of the subject invention that an important clinical sign , not previously described in the medical literature , is associated with the syndrome . this sign involves the formation of red patches noted on the skin , often associated with painful areas , best demonstrated with red wavelength sensitive photography . here , four patients with cervical dystonia were diagnosed with red patches . this sign involves the formation of red patches noted on the skin often associated with painful areas . these areas are generally warmer to touch , and not associated with any intrinsic skin changes such as scaling , crusting or any signs of cutaneous inflammation or cell proliferation . it has been found that these changes are more prominent in patients with cervical dystonia who are having more difficulty with pain . these patches typically occur posterior to the scalene muscle and inferior to the ear , although they have been seen over the trapezius and sternomastoid muscle . the red patch has been found to represent an area of maximal tenderness , and provides evidence that inflammation is an integral component of the spasmodic torticollis syndrome . moreover , the red patch indicates that spasms inherent in the torticollis syndrome are driven at least in part by the inflammatory process , and that pain occurring in torticollis is , in part , inflammatory in nature . additionally , the red patch indicates that inflammation in torticollis in peripheral tissues may be neurogenically mediated , and that proprioceptive information to the brain leaving muscles is to some degree mediated by elements of neurogenically provoked inflammation or inflammation associated autocoids . botulinum toxin injected into red areas noted to be painful and thermally active in accordance with the subject invention has been demonstrated to block the erythema , pain , increased tenderness , and heat loss within the area consistent with the denervation diffusion potential for the given dose , as can be seen in fig8 a and 8b , in which fig8 a shows the red patch and fig8 b shows a blanched area of blocked inflammation at the injection site . minimum doses range between 0 . 6 units to 15 units and are far lower than that required to produce regional weakness . this finding points to and further demonstrates the anti - inflammatory effect of botulinum toxin on deeper muscular tissues which are demonstrating cardinal signs of inflammation at the body &# 39 ; s surface , namely , pain , erythema , tenderness , increased heat loss , and spasm . one of the most devastating chronic internal inflammatory diseases is rheumatoid arthritis , characterized by joint and periocular involvement and chronic inflammation causing destruction of cartilage and ligamentous structures involving joints throughout the body . imnunologic causes have been cited as the underlying pathologic mechanism of the chronic destructive process , and mast cells have been noted in large quantities within the tissue pannus surrounding joints afflicted . edema , joint effusions , stiffness , spasms , pain , and erythema , are all components of the arthritis involved regions . multiple anti - inflammatory agents have been tried , with variable results to suppress the destructive effects of this systemic disease on bone and joints . the invention described herein offers a means of localized application of an anti - inflammatory agent which is injected directly into joints or perarticular muscular tissues which creates an effect on the rapid inflammatory response and peripheral neural elements governing the inflammatory response . the dose is quantified using the ld 50 to limit diffusion away from the injected area . the application may be repeated at 3 - month intervals and at titrated doses by clinical methods so as to limit any weakness within the injected region . the animals model and clinical examples described herein were used to test the various botulinum toxins for this anti - inflammatory bioeffect . in patients tested having exertion urticaria , spasmodic torticollis , type i hypersensitivity , pollen induced conjunctivitis , allergic blepharoconjunctivitis , there has been : 2 . improvement in sensation , pain and or itching within the denervation field the rational for the treatment for dystonia with botulinum toxin is that regional dose dependent weakening of the abnormally hyperactive muscles with botulinum toxin should lead to clinical improvement . botulinum toxin is known to cause a form of reversible denervation atrophy , which is reversible in 3 - 4 months . the process of pre - axonal terminal sprouting with spread of acetylcholine receptors and cholinesterase has been well characterized by duchenne and subsequently many others . in most if not all applications , weakness of injected muscles is easily assessed , and such as limb dystonia , improvement is not generally seen without detectable weakness . notwithstanding the well - known effects at the neuromuscular junction and muscular weakness which ensues , many clinicians who treat regional movement disease with botulinum toxin have questioned whether there may be a clinical effect of the toxin beyond mere weakening of the muscles . the reasons for this view are as follows : the beneficial effects may not occur in parallel with the weakness ; often there is a latency period of up to 2 weeks before a benefit is observed , whereas the weakness developed within a few days . the opposite is also a common experience , where patients report a response within a few hours or even shorter . a placebo effect is often suspected here . the duration of response may outlast the weakness so that the benefit continues after strength has recovered . the degree of benefit may seem much greater than expected from the degree of weakness . there may be clinical benefit from muscles quite remote from the original denervation field and sites of injection . for example , injections into orbicularis oculi for blepharospasm may reduce dystonic movements of the lower face and jaw , not due to spread of the toxin . in writer &# 39 ; s cramp , dystonic posturing of proximal muscles or “ overflow phenomenon ” frequently improves after injection of distal muscles . photophobia is an important component of essential blepharospasm syndrome , and is often improved after botulinum toxin injections . instead , improvement occurs often at doses less than necessary to produce substantial weakness such as 15 units per lid . because of weakness created by botulinum toxin and possible dry eye syndrome and keratitis that can result , photophobia should be worse after botulinum toxin injections . the suppression of photophobia is counterintuitive , but may be explained by the subject bioeffect . these observations may be explained by a direct or indirect central effect of the toxin . it is well - known that radioactivity after injection of labeled botulinum toxin into a muscle can be tracked back into the spinal cord , suggesting retrograde axonal transport as described by weignad , h ., erdmann , g ., weillhoner , h . i ., labeled botulinum a neurotoxin : pharmacokinetics in cats after intramuscular injection , naunyn schmeidbergs arch pharmacol 1976 : 292 : 161 - 165 . it is not known whether this activity represents the label itself or the presence of the toxin in whole or part within the cord . the influence of this phenomenon on the mechanism of botulinum toxin however , is at best conjectural . although direct central effects of the toxin could explain some of these findings , it is also possible that they are secondary to a peripheral action , such as an effect on muscle spindle afferents or efferents . to date there is no conclusive evidence of direct central activity in the toxin . pet studies of patients with writer &# 39 ; s cramp have shown some motor cortex re - organization after treatment , possibly as a result of denervation , but did not affect the abnormal pattern of cortical dysfunction . additionally , pain relief , often the most sensitive component to the beneficial effects of botulinum toxin , is often out - of - proportion to weakness created by the injections . the above observations lend credence to second receptors within injected tissue remote from the neuromuscular junction . the subject invention has been found to rest on a new bioeffect on release of mediators within the denervation field created by a point injection of botulinum toxin which have an onset of effect much shorter than the neuromuscular weakening effect . the above offers an explanation as to why beneficial effects are out of proportion to weaknesses created , and explains different dose response relationships among the various immunotypes of botulinum toxin . application for the treatment of blepharospasm , photophobia and its mitigation are previously unrecognized bioeffects of botulinum toxin . having now described a few embodiments of the invention , and some modifications and variations thereto , it should be apparent to those skilled in the art that the foregoing is merely illustrative and not limiting , having been presented by the way of example only . numerous modifications and other embodiments are within the scope of one of ordinary skill in the art and are contemplated as falling within the scope of the invention as limited only by the appended claims and equivalents thereto .

pharmaceutical application of a chemodenervating agent , particularly botulinum toxin , reduces inflammatory response and serves as an anti - inflammatory agent without systemic side effects and with long duration action , on the order of 12 - 24 weeks . in one embodiment , the effective dosage for allergy provoked inflammation reduction is an order of magnitude less than dosages associated with treatment of regional movement diseases , since the agent works to reduce inflammation by reducing histamine and other preformed mediator releases associated with mast cell degranulation .

advances in molecular biology now attack the viruses directly in their transcriptional machinery and activate the macrophages widely distributed throughout tissues by pirydine carboxylates to destroy numerous existing viruses and to change the configuration of the viral nucleoproteins and other proteins which effectively become antigens for auto vaccination . inclusive of the four types of dengue viruses and numerous other tested viruses , the present invention offers a “ quantum jump ” for prevention and control of viral diseases with non - toxic antiviral agents that also are capable of conferring immunity against critical proteins against replication of dengue viruses and numerous other rna or dna animal viruses . the immune system employs a variety of strategies to combat virus infection . these can be divided into innate or “ non - specific ” defenses , which include interferons , natural killer cells ( nk ) cells , blood monocytes and macrophages [ derived from blood monocytes ] and adaptive or specific immunity that involves t cell lymphocytes and antibodies . immunological defenses , “ non - specific ” or “ specific ,” concentrate at strategic areas in the body where entry of a virus occurs following millions of years of evolution . for example , iga at all mucosal surfaces of the body functions by blocking virus adsorption and penetration . macrophages are located through the body in various tissues and interferons are produced by most in response to viral infection . once the primary line of defenses is breached , viruses and viral antigens ( many processed by macrophages to generate antibodies ) become directed into the lymphoid system where they encounter t and b lymphocytes . from such interactions , antiviral t cells are generated that target and rapidly destroy infected cells , and antiviral antibodies are produced that protect the host from viremia . in the following section , the protection by the immune system will be contrasted with the evasion strategies employed by the viruses , particularly the dengue viruses . because the first line of defense mobilizes instantaneously , in a matter of minutes or hours , the innate defenses may determine the balance between the host resistant responses to the virus or wide - speed systemic infection . restricting the early infection is the task of interferons alpha and beta , natural killer cells , and macrophages . the inflammatory response , that follows this initial encounter with viruses , signals other immune cells to indicate the location of the virus to the specific immune system , which is rapidly activated , and becomes effective after a few days to a week . at the end of this period , t cells will converge on the site of infection attracted by cytokines and the antibodies are active in limiting the virus spread . interferons , the first line of defense against viruses , have two families ( ifn ): type i , which includes ifn - alpha ( leukocyte produce ) encoded by about 20 genes located on chromosome 9 , ifn - beta ( fibroblast - type ) encoded by a single gene on chromosome 9 , ifn - omega and ifn - tau ( trophoblastic ); and , type ii , which includes ifn - gamma ( immune ), encoded by a single human gene on human chromosome 12 . ifn - gamma can exert direct antiviral activity , a pivotal role in the activation of the immune cell system : activation of macrophages and the induction of other anti - viral cytokines and defense molecules . it is also associated with the terminal differentiation of b and t lymphocytes . ifn - gamma is strongly stimulated by alpha - picolinic acid and derivatives thereof ( picolinic acids produced by macrophages ) to produce more ifn - gamma . nk cells are large granular lymphocytes distinct from t and b lymphocytes and can be activated directly by interleukin 2 ( il - 2 ). picolinic acid and derivatives thereof also strongly stimulate nk cells which become active and destroy viruses , cancer cells and also virally - transformed cells . when activated , nk cells produce numerous cytokines involved in antiviral immunity and tumor destruction , including ifn - gamma , tumor necrosis factor ( tnf ), transforming growth factor - beta ( tgf - beta - 1 ), which inhibits and destroys tumors , and numerous other cytokines including gm - csf ( granulocyte - macrophage colony stimulating factor ). a subtype of nk cells stimulated by picolinic acids , denoted nk1 . 1 , cd8 - positive cells , have been shown to have important regulatory functions in the immunological response . functionally , nk cells are characterized by their ability to kill tumor cell lines in vitro and in mice . varesio et al . has further shown that the killing ability and production of cytokines can be greatly increased by picolinic acid . nk cells can also recognize igg antibody - bound to cell surfaces of virus - infected cells via the cd16 receptor and kill target cells . this important process is known as antibody - dependent cell cytotoxicity : a highly efficient mechanisms for activating nk cells that rapidly destroy virus - infected cells . cell killing is mediated by a performing - dependent system . nk cells are rapidly mobilized following viral infection , stimulated by picolinic acid and derivatives thereof . they are detected at the site of infection within 2 days of virus entry . viruses with pronounced susceptibility to nk cells in vivo include herpes viruses of all types . herpes viruses have been extensively studied for more than 20 years with greater than 98 % effective in aborting the disease and destroying the viruses in humans , animals and tissue culture . in humans , nk cells play an important role in immunity to herpes virus infection , including cytomegalovirus , and varicella - zoster . when patients having outbreaks of these viruses undergo treatment with preparations of picolinic acid and derivatives thereof , both the herpes labialis and the herpes - zoster viruses are destroyed in less than 2 hours and the pain disappears within less than three hours , if the patients are treated early , during the onset of the disease . the key role of macrophages in immunity to viruses and picolinic acid macrophages are strategically placed through the body as first line of defense against infectious agents . the inventors have developed experimental antiviral pharmaceutical agents , based on picolinic acids and derivatives thereof , that greatly and directly increase the potent antiviral activity of macrophages by two main mechanisms : 1 ) activating macrophages and 2 ) destroying the zinc finger proteins and other metalloproteins of the viruses . fernandez - pol , 1995 . these two mechanisms render the virus unable to replicate . then the viruses disintegrate by proteolysis enzymes and depending upon the degree of damage of the virus to the macrophage , this cell either recovers or enters into apoptosis . this process eliminates both the virus infected macrophage and the intracellular viruses thus effectively stopping the viral infection . the picolinic acids are also very potent antiviral agents in the extracellular spaces by attacking intra - viral zinc finger proteins such as the nucleoprotein np - 7 of the aids virus and disintegrating the virus . macrophage antiviral activity includes intracellular and extracellular defense mechanisms that can be pharmacologically enhanced greatly by agents such as picolinic acids and derivatives thereof . macrophages are the major producers of ifn - alpha found in the blood stream following viral infection . other antiviral molecules produced by macrophages include : 1 . tumor necrosis factor - alpha , which functions by inducing gene coding for 2 ′ 5 ′- a synthetase and mx , and lysing virus - infected cells , by apoptosis ; 2 . the enzyme arginase , which is induced following ifn - gamma activation of macrophages and effectively aborts hsv infection ; 3 . the enzyme nitric acid synthase , which is induced following ifn - gamma activation of macrophages and leads to generation of nitric oxide which inhibits the replication of vaccinia virus and hsv ; 4 . the cessation of the production of picolinic acid by viruses in macrophages , effectively neutralizes the capacity of macrophages to destroy viruses and activate the immunological defense systems . the inhibition of picolinic acid production in macrophages is most likely due to the inhibition of the substrate ( beta - muconic acid ) of picolinic acid , and / or picolinic acid carboxylase , which leads to the formation of picolinic acid resulting in the destruction of zinc finger proteins of the invading viruses , and activates the antiviral activities of macrophages to produces ifn - gamma and other antiviral cytokines . tryptophan metabolism inhibition by viral infection is another viral strategy to shut off antiviral picolinic acid production . the pathogenic virus has taken control of viral replication inside the cell by disabling the powerful macrophage defense systems . however , combining ifn - gamma and picolinic acid yields a potent inhibitor of replication of the j2 recombinant retrovirus that has v - raf and v - myc oncogenes present in macrophages . blasi , et al . 1988 . while picolinic acid operates in synergism with ifn - gamma , thus activating macrophages to express tumoricidal actions . varesio , et al . 1990 . and further , interleukin - 4 also inhibits the costimulation of interleukin - 2 and the picolinic acid and ifn - gamma activated macrophages . cox et al . 1991 . as a catabolite of tryptophan , picolinic acid also inhibits the in vitro and in vivo growth of cell lines and transformed those line to have heightened sensitivity to picolinic acid and thus interference with transition metal ion uptake . fernandez - pol , 1977 . picolinic acid also improves hormonal stimulation and the amp response to pge1 , or isoproterenol , by several fold . picolinic acid further increases the gtp dependent activities of the adenylate cyclase system . johnson and fernandez - pol 1977 . 5 . for many viruses , the hostile intracellular environment of a phagolysosome ( producing superoxide radicals and other deleterious chemical radicals ), leads to a loss of infectivity and viral destruction . these processes are of two types : 1 ) oxygen - dependent and 2 ) oxygen independent mechanisms that contribute to the inactivation of numerous viruses which shows that viruses can be targeted for intracellular destruction by phagocytosis of infected cells . 6 . picolinic acid and fenton reactions . the applicants have demonstrated in vitro and in vivo that chelate picolinic acid - fe 2 + can produce fenton reactions which produce superoxide ions and other oxygen free radicals that are deleterious for the virus and the infected cells . thus , this compound can destroy virally infected cells without any significant effect in normal cells , which do not allow the penetration of the picolinic acid - fe 2 + . 7 . when activated by picolinic acid , macrophages can also kill virus infected - cells by direct contact . despite the hostile nature of macrophages , some viruses , such as dengue virus , may exploit these cells for growth and survival . these phenomena occur because of the capacity of certain viruses to shut off critical defense mechanism of macrophages , such as picolinic acids . thus , the pharmacological use of picolinic acid and derivatives thereof as anti - dengue virus pharmacological agents to replenish endogenous picolinic acid shut off by the virus appears effective and has already defeated other viral diseases , such as herpes , herpes - zoster varicella and others , in tissue culture . picolinic derivatives include radicals about the pyridine ring from the butyl group , carboxyl group , ethyl group , hydrogen , isobutyl group , isopentyl group , isopropyl group , methyl group , neopentyl group , pentyl group , propyl group , secondary butyl group , and the tertiary butyl group . cytokines induced during viral infections have numerous functions such as modulation of the immune response . this section summarizes , in table 1 , the human interferons , their genes , proteins produced , their producer cells and their effects which could act in concert with picolinic acid . the effector functions of a macrophage lead to tumoricidal , microbicidal and antivirial activities of mononuclear phagocytes . the tryptophan catabolite picolinic acid ( pa ) has the ability to modulate the expression of chemokines in macrophages . pa is a potent activator of the inflammatory chemokines macrophage inflammatory protein ( mip )- 1 - alpha and mip - 1 - beta mrna expression macrophages through a novo protein synthesis - dependent process ( bosco et al ., j . immunology , 2000 , 164 : 3283 - 3291 ). iron chelation may be involved in mip induction by pa because iron sulfate inhibited the process and the iron chelating desferroxmine , induced mip expression . thus , bosco et al . discovered the existence of a new pathway leading to inflammation initiated tryptophan metabolism that communicates with the immune system by the production of pa . the increase of intracellular pa concentration in macrophages then leads to secretion of chemokines by macrophages . these findings establish the importance of pa as an activator of macrophage pro - inflammatory functions , providing evidence that pa can be biologically active without one or more co - stimulatory agents . ( bosco et al , j . immunology , 2000 , 164 : 3283 - 3291 ). the attraction of inflammatory cell populations to sites of injury or infection is controlled by the local secretion of chemotactic signals , often released by macrophages . the chemokine super - family of small chemotactic proteins contains numerous members which have been characterized chemically and biologically . chemokines are produced by both immune and non - immune cells in response to inflammatory stimuli or tissue damage produce by microbes such as numerous positive strand viruses , including dengue , hepatitis c , sinbis and others . the chemokines are involved in a large array of immuno - regulatory , inflammatory and anti - viral activities , including leukocyte migration and activation . the primary synthetic source for chemokines is activated mononuclear phagocytes , which are critical mediators of cellular immunity against infections and tumors . the mononuclear phagocytes release the effector molecules , or recruit t lymphocytes and nk cells , to target tissues though the release of chemokines . for instance , the metabolism of two essential amino acids , l - typtophan ( l - trp ) and l - arginine , have been implicated in antimicrobial activity , t cell tolerance , and in biological effects of ifn - gamma . the inducible enzyme controlling l - trp catabolic pathway [ indoleamine 2 , 3 - dioxygenase ( ido )] is present in an active form in inflammatory tissues . l - trp catabolism , initiated by ido , leads to the production of biologically active molecules . among the most important antiviral agent , pa is the end - product of l - trp degradation . pa is endowed with important immuno - modulatory properties including activation of mononuclear phagocyte effector functions . pa is a potent co - stimulus for the induction of macrophage mediated cytotoxicity . pa also contributes to the microbicidal and antiviral activity of macrophages in vitro and in vivo . pa , in combination with ifn - gamma , inhibits retrovirus expression in macrophages both in vitro and in vivo , and activates the transcriptional activity of the inducible no synthase gene , leading to production of no , a potent effector molecule identify in the expression of macrophage microbicidal activities . macrophages are cells derived from monocytes produced in the bone marrow , as in fig2 . monocyte - derived macrophages ( mdm ) migrate and reside in numerous tissues . the developmental differentiation of macrophages from progenitor cells in the bone marrow to tissue of residence is controlled by numerous hormones denoted cytokines ( hashimoto et al , 1999 ). gene expression during this complex process has involved about 35 , 000 different transcripts expressed in human blood monocytes and macrophages after induction by the cytokines gm - csf or m - csf . blood monocytes migrate to various tissue targets in response to the release of various chemotactic factors due to infection or cell damage . in such tissues , a complex differentiation of the monocytes takes place which results in a macrophage population denoted “ resident macrophages .” these macrophages can be characterized in subsets , and in ifn - gamma - stimulated macrophages by using monoclonal antibodies , ( leenen et al ; 1994 ). resident macrophages ( also denoted normal macrophages as in fig1 a ) are found in numerous tissues , as in fig1 b , such as liver , lung , lymph nodes , spleen , bone marrow , synovial fluids , skin , brain , lipophages ( which are lipid - laden macrophages , siderophages ( which accumulate insoluble precipitates of fe 3 + , including connective tissue contains resident macrophages and are denoted histiocytes . other resident macrophages are identified in fig1 b . one important type of resident skin macrophage is known as langherans cells . langherans cells are the preferred target for mosquitoes carrying all four types of dengue virus . in these cells , the production of intracellular virus after infection paralleled that for secreted dengue virus ( pryor et al ; am j trop med hyg , 65 , 2001 , 427 - 343 ). the local populations of macrophages are replenished by proliferation of resident progenitor macrophages and the continuous influx of monocytes from the blood while the cell damage or infection lasts . inflammatory macrophages are derived from monocytes , have analogous properties and are present in various exudates such as pericarditis , peritonitis , synovial fluids among others . activated macrophages , including m1 macrophages , are resident macrophages that have been activated in response to lps , cytokines or ifn - gamma . these cells participate in immune reactions to antiviral agents or other microbes . the gene expression patterns of activated macrophages confers them the capacity to secrete mediators of immune reactions . thus , the different types of macrophages above and the m1 macrophages are a heterogeneous population of cells differing in 1 ) origins and differentiation stage , and 2 ) response to viral infection and to micro - environmental influences by chemokines and cytokines . the versatility of these cells displays a spectrum of responses to microbial invaders in a myriad of damaging circumstances . activated resident macrophages have proliferative capacity , show potent phagocytic activity , and respond to various biological and chemical stimuli , but in the absence of noxious forces the m1 macrophages remain relatively quiescent with respect to immunological and secretor functions utilized to maintain tissue integrity . macrophages are critical in all phases of the immune response , and since the populations of macrophages are functionally distinct , they provide for an impressive , powerful and flexible response . they play a key role in host defenses against intracellular parasitic micro - organisms such as bacteria and viruses and also in the control of tumor cell growth . macrophages can kill extracellular targets by the use of antibody - dependent cellular cytotoxicity macrophages activated by pathogenic prokaryotic or eukaryotic cells are a critical link in the following defense processes : 1 ) presentation of antigens to t - cells and , 2 ) production of chemokines and cytokines . these macrophage properties interact with other cells in synergism and the cells become bioactive . activated macrophages secrete a large array of cytokines , growth factors , and other small molecule chemicals which participate in autocrine and paracrine activities that affect many other cell types . because activated macrophages are also a primary cell target in vivo for dengue virus ( dv ) infection , replication , and propagation , these macrophage responses and functions must have an antiviral role to control the dv invasion . pa , in combination with interferon - gamma ( ifn - gamma ), inhibits retrovirus expression in macrophages , both in vivo and in vitro and triggers the transcriptional activation of inducible isoform of the nitric oxide ( no ) synthase gene , stimulating production of no as in table 2 , a major effector molecule implicated in the expression of macrophage tumoricidal and microbicidal activities ( varesio et al ., 2000 ). varesio et al . also investigated the gg2ee transformed by the recombinant j2 retrovirus carrying the v - raf and v - myc oncogenes to study the effects of biological response modifiers ( brm ), picolinic acid ( pa ) and / or ifn - gamma , varesio et al . et al ( j . immunology , 141 , 2153 - 2157 , 1988 ). j2 retrovirus expression was not affected by picolinic acid or ifn - gamma alone but it was dramatically decreased by the picolinic acid plus ifn - gamma . these results indicate that transformed gg2ee macrophages can be inhibited by the combination of pa plus ifn - gamma . in addition , the combination resulted in a potent inhibition of j2 retrovirus mrna expression in the cells , inhibition of cell growth and activated the tumoricidal capacity of macrophages ( varesio et al ., 1991 ). picolinic acid is a potent co - stimulator for the induction of tumoricidal activity and the production of l - arginine - dependent reactive nitrogen intermediates ( rni ) in macrophages . the results indicate that ifn - gamma and picolinic acid can regulate nitric - oxide synthase , or transcription and mrna expression and nitric oxide transcription . ( mellilo et al , j . biol . chem ., 269 , 8128 - 8133 , 1994 ). further results demonstrate that picolinic acid is a potent biologic macrophage secondary signal , in the activation of ifn - gamma - prime macrophages and indicate the existence of an autocrine effect mediated by picolinic acid . ( varesio et al ., 1990 ). picolinic acid , a naturally occurring product of tryptophan catabolism is a biological response modifier , endowed with a variety of effects on transition metal ion traffic , cell cycle , bacterial , viral and fungal growth and host immune responses mediated by macrophages . picolinic acid is an immune - response modifier inducing a variety of chemokines and cytokines , including interferons , tumor necrosis factor , and interleukins . in animal model systems and in vitro , picolinic acid has demonstrated antiviral activity , for example in herpes viruses , and immune modulatory activities . in addition , inactive macrophages respond to picolinic acid with macrophage activation , a mechanism of elimination of viruses . ( fernandez - pol , 2001 ). it is conceivable that in addition to the effects of picolinic acid described above , picolinic acid and structurally related derivatives inactivate zinc finger proteins ( zfp ). picolinic acid renders the viral zfps inactive by ejecting zn 2 + from the zinc finger domain . picolinic acid inhibits viral replication in transformed cells and normal cells treated with picolinic acid enter into a temporarily dormant state with no toxicity observed . the action of picolinic acid on zfps matches the results showing activation of macrophages by picolinic acid . ( fernandez - pol , 2001 ). studies on the antiviral activity of picolinic acid and derivatives thereof on virulence of arboviruses face many problems because of the availability of human monocyte - derived macrophages infected with dengue in which the virus can replicate and the lack of a suitable animal model for dengue infection . the evaluation of antiviral efficacies , mode of action , toxicity and toxicity profiles of picolinic acid using cultured cells — those at sites of virus replication in humans infected with togaviridae or flaviviridae — may provide important models of the antiviral effects of picolinic acid on dengue viruses . some of the viruses , described in this section , were used to evaluate the broad spectrum of antiviral efficacies of picolinic acid and fusaric acid against human cytomegalovirus ( cmv ), human varicella - zoster virus ( vzv ), human hepatitis b virus ( hbv ), and bovine viral diarrhea virus ( bvdv ). before presenting the examples a few basic concepts on togaviridae and flaviviridae will be described to facilitate the interpretation of the antiviral effects of picolinic acid and derivatives thereof . the group of arboviruses is a heterogeneous group of viruses in seven taxonomic families , including togaviridae and flaviviridae . arboviruses have a global distribution but are mostly found in tropical regions . because important limiting factors are temperature , rainfall patterns , and urbanization , they are rapidly emerging diseases . togaviridae is a family of enveloped , positive (+) stranded rna viruses containing many agents responsible for important diseases in animals and humans . togaviridae was initially established with two genera , alphavirus and flavivirus ( wildy , 1971 ). the family flaviviridae contains three genera : flavivirus , pestivirus and hepatitis c viruses . the virion structure contains a nucleocapside protein complexed with single - stranded positive (+) sense rna . target cells are usually of the mononuclear phagocyte lineage . treatment is supportive and restricted to non specific measures , including maintenance of fluids and electrolyte balances and replacement of significant amounts of blood lost through hemorrhage . in the case of dengue , no lasting cross - protective immunity exists , the immunity lasts at the most for 3 months ( sabin , 1952 ). no good animal model for dengue hemorrhagic fever ( dhf ) exists at present . currently , prevention depends on mosquito control without vaccines . despite the evidence demonstrating the importance of pa for the activation of macrophages alone or in combination with cytokines and the capacity of pa to destroy viral zinc finger proteins - essential for viral replication and mutation of the zinc finger domain , no information exists on pa and derivatives thereof on dengue viruses , or other togaviridae and flaviviridae ( fernandez - pol , 2001 ). evaluation of antiviral activities of picolinic acid and fusaric acid against human hepatitis c virus the sequence of the hcv genome shares several features with other positive (+) strand rna viruses . hcv is most like members of the flaviviridae in that the genomes of flaviviridae , dengue fever virus , and yellow fever virus , have similar organization and have common features with hcv . they have a similar genome size to hcv ( yellow fever virus : 10862 bases ( ruce et al ., 1985 ) and compared with 9379 of g + hcv ( coho et al , 1991 )). certain features of hcv are shared with pestiviruses . structurally , hcv is more like the pestiviruses than the flaviviruses . the difference is related to extensive glycosylated proteins in the virus envelope , in contrast to flaviviruses envelope glycoproteins that contains a few sites for n - linked glycosylation . the genome of hcv is single - stranded rna of positive ( protein coding ) polarity . the genomic rna of positive - strand rna viruses is infectious . many aspects of the pathology of hcv infection result from the host immune response . hcv is capable of cytophathic replication in cell types outside the liver , including monocytes and macrophages . replication can also occur in certain lymphoid cells . using a highly strand specific polymerase chain reaction ( pcr ) method , initiation of transcription is understood for some positive - strand rna viruses . picornaviridae , togaviruses and flaviviruses contain a single strand of positive - strand rna that has mrna activity . detection of hcv genome is indispensable for the accurate diagnosis , the complete characterization of hcv infection in a patient and for evaluation of antiviral drugs . the pcr test is the method of choice for these studies . here we determine the effects of picolinic acid and fusaric acid on hcv replicon cell lines . the hcv replicons ( qrtcpcr / icycler ) were contained in the ava . 5 cell line tested . normalization by od and serial dilutions were done in the untreated cell line . the experimental design was as follows : cells were grown in 12 well cell culture plates ; the compounds interaction was done for 24 hours ; at extraction , cell confluence was 75 %; and rna was extracted using qiagen rneasy extraction kit . table 3 shows the hcv replicon data for both picolinic acid and fusaric acid at various concentrations . the results show that picolinic acid at 250 ug / ml shows approximately 60 % inhibition of hcv replicon . by od , no overt cytotoxicity was observed . at a concentration of 100 ug / ml , fusaric acid show about 60 % inhibition of hcv replicon and by od , no overt cytotoxicity was observed . antiviral effects of picolinic acid and fusaric acid on sindbis virus replicons sindbis virus has been designated as the prototype alphavirus and belongs to the togaviridae family . sindbis is a positive - single stranded dna virus related to hcv . here we determine the effects of picolinic acid and fusaric acid on sindbis replicon in huh7b / sindbis cells . the sindbis replicons were studied by qrtcpcr / icycler . normalization by od and serial dilutions were done in the untreated cell line . the experimental design was as follows : cells were grown in 12 well cell culture plates ; the compounds interaction was done for 24 hours ; at extraction , cell confluence was 75 %; and rna was extracted using qiagen rneasy extraction kit . table 3 shows the sinbis replicon data for both picolinic acid and fusaric acid at various concentrations . the results show greater than 90 % inhibition of sindbis replicon at all concentrations of picolinic acid . by od , no overt cytotoxicity was observed . fusaric acid show & gt ; 85 % inhibition of sindbis replicon at all concentrations tested . no overt cytotoxicity was observed by od . the endogenous template of hbv virus is a circular partial double stranded dna . it was found that the dna strand of negative polarity was transcribed inside the core particle from an encapsidated rna - template , indicating a similarity to retroviruses ( summers and mason 1982 ). although the genome organization , biology and replication of hepadnaviruses ( hbv ) and reverse transcription define hbv as virus order “ retroviral ,” hepadnavirire are quite different from those of the retroviridae , the common strategy has also been denoted para retroviruses . because hbv dna in infected hepatocytes is not integrated , it remains as an episomal mini - chromosome ( newbold et al . 1995 ). the hbv polymerase is , in contrast to retroviral polymerase , devoid of an integrated domain . integration of the hvb dna into the host genome is not part of the hepadnaviral life cycle , in contrast to the retroviruses . here we evaluate the antiviral efficacy of picolinic acid and fusaric acid against human hepatitis b virus ( hbv ). hepg2 . 2 . 15 cells , a cell line that was stably transfected with hbv genome was used to study the antiviral effects of pa and fa against hbv . hepg2 . 2 . 15 cells were cultured under standard conditions . hepg2 . 2 . 15 cells were seeded in a 96 - well plate at 2 × 10 4 cells / well and grown for 24 hours . the medium was replaced with 100 ul of medium containing pa at increasing concentrations ( 0 , 10 , 100 , 250 , and 500 ug / ml ). the concentrations of fu used were 0 , 1 , 10 , 30 , 60 , and 100 ug / ml . the cells were incubated at 37 ° c . for 9 days . the control medium and the medium containing the antivirals were changed every 24 hours . at day 9 , the culture medium containing the released hbv virions was collected , the cells washed with pbs , and lysed with lysis buffer . all samples were stored at − 70 ° c . until analyzed . hbv dna from drug - treated hepg2 . 2 . 2 . 15 cell culture medium and cell lysates was extracted using qiaamp dna mini kit , according to manufacturer &# 39 ; s specifications . pcr reaction was performed in 20 ul , comprising the following compounds : dh 2 o ; 25 mm mgcl 2 ; 10 um sense primer ; 10 um antisense primer ; lightcycler probe 1 ( fluorescent - labeled , 5 um ); lightcycler probe 2 ( lc red 640 - labeled , 10 um ); lc faststart dna master hyb probes ; and uracil dna glycosylase ( 1 ul ). pcr mix was aliquoted and 5 ul dna template was then added to the pcr mix . a range of hbv plasmid dna ( 1 × 10 8 , 1 × 10 7 , 1 × 10 6 , [ . . . ], 1 × 10 2 , 25 copies ) were used as standards for quantitative analysis . the cycling conditions are shown in table 4 . hepg2 . 2 . 2 . 15 cell line was created by transfection of full - length hbv genome into hepg2 cells , and continuously secreted hbv virions into the medium . this cell line is the prototype cell line used in studying the efficacy of antiviral compounds against hbv infection . to study the antiviral activities of pa and fa against hbv , hepg2 . 2 . 15 cells were incubated with increasing concentrations of test compounds for 9 days with medium change daily . at day 9 , the medium containing secreted hbv virions was collected and used for extraction of extracellular virus dna . the cells were lysed by 0 . 5 % sds and used for extraction of intracellular virus dna . dna was extracted using qiagen column and then quantitatively detected by real - time pcr assay . the results showed that pa at concentrations of 250 ug / ml inhibited released hbv dna by 72 . 3 % and intracellular hbv dna by 79 . 4 % with overall ec 50 of approximately 139 ug / ml , see table 5 . fa at concentration of 60 ug / ml inhibited the released of hbv dna by 76 . 5 % and intracellular hbv dna by 28 % with overall ec 50 greater than 60 ug / ml , see table 6 . then table 7 shows the antiviral effects of pa ( a ) and fa ( b ) on hbv after 9 - days of treatment on the cell line hepg2 . 2 . 15 cells . vzv ellen cell line , from atcc , and was used as the reference strain in the susceptibility tests . human fibroblast cell line hel - 299 ( atcc ) was used in the virus yield reduction assay . hel - 299 cells ( 90 % confluent ) in a 24 - well plate were washed and subsequently infected with vzv ellen strain at a moi of 0 . 5 pfu / cell for 2 h at 37 ° c . following removal of viral inoculums , the infected cells were washed and covered with culture medium final concentrations of pa ( final concentrations were : 0 , 1 , 10 , 100 , 250 , and 500 ug / ml ) or fa ( final concentrations : 0 , 0 . 1 , 1 , 10 , and 60 ug / ml ) for 3 days , see tables 8 , 9 . at the end of the drug treatment , the culture medium was collected for extraction of released virus dna . the infected cells were washed with pbs and lyzed with 400 ul of sds lysis buffer ( 0 . 5 % sds , 10 mm tris . hcl ph 8 . 0 , 1 mm edta ). the cells were used for extraction of intracellular vzv virus dna . for extraction of the released virus dna , 200 ul of drug - treated culture medium was digested with 500 ug / ml of proteinase k at 37 ° c . overnight in a buffer containing 0 . 01 m tris . hcl ( ph 7 . 8 ), 0 . 001 m edta and 0 . 5 % sds . the vzv dna was purified by extractions with phenol / chloroform and chloroform . the vzv dna was precipitated by addition of 1 : 10 vol of 3 m sodium acetate ( ph 5 . 2 ) and 2 . 5 volumes of absolute ethanol . following washing with 70 % ethanol , the dna was air - dried and dissolved in 20 ul sterile water . for purification of the intracellular vzv dna , the cell lysates were directly digested with 500 ug / ml of proteinase k at 37 ° c . overnight . the dna was then extracted by phenol / chloroform and precipitated with ethanol as described above . after washing with 75 % ethanol , the dna was dissolved in 20 ul of sterile water . pcr reaction was performed in 20 ul , comprising the following compounds : dh 2 o ; 25 mm mgcl 2 ; 10 um sense primer ; 10 um antisense primer ; lightcycler probe 1 ( fluorescent - labeled , 5 um ); lightcycler probe 2 ( lc red 640 - labeled , 10 um ); lc faststart dna master hyb probes ; and uracil dna glycosylase ( 1 ul ). pcr mix was aliquoted and 5 ul dna template was then added to the pcr mix . a vzv dna standard was serially diluted ( 1 × 10 7 , 1 × 10 6 , 1 × 10 5 , [ . . . ], 1 × 10 2 , 10 copies ) and were used as standards for quantitative analysis . the cycling conditions are shown in table 9 . the data was generated from triplicate experiments . the effect of a test compound at various concentrations is expressed as % of control ( the mean dna copies in drug - treated wells / the mean dna copies in control wells without test compound ). the 50 % effective concentrations ( ec 50 : effective concentration giving 50 % reduction of dna copies ) were calculated with a computer program . the primers and probes for the lightcycler assay were previously published ( espy et al ., diagnosis of varicella - zoster virus infection in the clinical laboratory by lightcycler pcr . j . clin microbiol 38 , 3187 - 3189 , 2000 ). previous experiments show no significant toxicity to hel cells when pa was used at concentration of 500 ug / ml and for fa at concentration of 60 ug / ml . the culture medium was collected for the detection of released virion dna and the cells were lysed for the detection of intracellular virus dna . the antiviral efficacies were determined by quantitative detection of total vzv dna copy numbers using lightcycler assay . the results showed that pa was active against vzv replication with ec 50 and ec 90 approximately 89 ug / ml and 505 ug / ml , respectively . anti - vzv activity was also seen for fa with ec 50 approximately 14 ug / ml and ec 90 approximately 41 ug / ml , see infra tables 8 , 9 . evaluation of antiviral efficacies of picolinic acid and fusaric acid against bovine viral diarrhea virus ( bvdv ) bvdv trangie strain , a well characterized non - cytopathic australian isolate , was used in this study . the virus was cultured in mdbk cells ( atcc ), and titred by immunoperoxidase staining . 80 % confluent mdbk cells were infected with bvdv at a moi of 0 . 01 at 37 ° c . for 1 h . after viral inoculums was removed , infected cells were washed with pbs and then incubated with culture medium containing pa at concentrations of 0 , 10 , 100 , 250 , 500 , and 1000 ug / ml or fa at concentrations of 0 , 1 , 10 , 30 , 60 , and 100 ug / ml at 37 ° c . for 3 days . the culture medium was then collected and stored at − 70 ° c . the cells were harvested by one frozen / thawed cycle and centrifugation to pellet debris . the supernatant was collected and stored at − 70 ° c . pa of fa - treated cultures were 10 - fold serially diluted , 50 ul of each dilution was added to 80 % confluent mdbk cells in a 96 - well plate , and incubated at 37 ° c . for 1 h . the innoculum was removed by washing with pbs once . the infected cells were covered with 200 ul of 0 . 5 % methylcellulose in culture medium and incubated at 37 ° c . for 2 days . after washing with pbs , the cells were fixed with 200 ul of 5 % formalin in pbs for 10 min at room temperature . subsequently , they were washed with 0 . 05 % tween − 20 / dh 2 o three times . then , the cells were incubated with 50 ul mixture of three monoclonal antibodies against bvdv ns3 for 80 min at 37 ° c . in a humidified box . the cells were then washed as above and incubated with 50 ul of rabbit anti - mouse igg peroxidase - conjugate ( dako ) diluted 1 : 200 in 1 % gelatin / pbs for 90 min at 37 ° c . in a humidified box . after final washes as described above , 200 ul of 3 - amino - 9 - ethyl - carbazole was added to each well and incubated at room temperature for 30 min until the cells were stained . the studies of antiviral agents against hcv have been hampered by their inability to propagate the virus efficiently in cell culture . comparative studies indicate that hcv is closely related to flaviviruses ( i . e . dengue virus and more closely to pestiviruses ( i . e . bovine viral diarrhea virus ( bvdv ). in fact , pestiviruses have been used as a model and surrogate for hcv . information obtain by the bvdv virus is also useful to understand flavivirus replication such as dengue viruses . the bvdv closely resembles hcv persistent infection . after infection with bvdv cultured mbdk were treated with different concentrations of pa or fa for 3 days . the antiviral effect was determined by virus yield reduction assays ( i . e . staining using monoclonal antibodies against ns3 , or titration of intracellular and extracellular virus by immunoperoxidase staining . the results , see tables 10 , 11 , showed that after treatment of infected cells for 3 days pa at a concentration of 250 ug / ml reduced bvdv virus yield by 76 % ( ec 50 = 60 ug / ml . this indicates that both pa and fa are active against bvdv . 90 % confluent hel - 299 cells were washed and then infected with cmv ad169 at 0 . 5 moi for 2 h at 37 ° c . following removal of viral inoculums , the infected cells were washed and exposed to different concentrations of pa ( final concentrations : 0 , 10 , 100 , 250 , 500 , and 1000 ug / ml ) or fa ( final concentrations : 0 , 1 , 10 , 30 , 60 , and 100 ug / ml for 3 days . the culture medium was collected for titration of released virions and the cells were harvested for titration of intracellular virions . 90 % confluent hel - 299 cells in 24 well plates were infected with 200 ul of cmv dilutions at 37 ° c . for 2 h . following removal of virus inoculums , the infected cells were washed with pbs and overlaid with 0 . 5 % methylcellulose in culture medium . we then treated cmv infected cells for 3 days at 37 ° c . with different concentrations of pa and fa . the culture medium was collected for titration of released virus and the cells were harvested for titration of intracellular virus . the results showed that both pa and fa can inhibit cmv replication with ec 50 of approximately 230 ug / ml for pa and approximately 60 ug / ml for fa . a systemic preparation of picolinic acid , its derivatives or analogs , containing approximately 1 % to 100 % active ingredient , may be administered orally , intravenously , intramuscularly or by any acceptable route for the treatment of viral systemic infections such as dengue . for example , picolinic acid prepared in 00 gelatin capsules at 500 mg per capsule has been shown to be effective in the control in humans of certain lymphomas , and viral diseases such as herpes simplex labialis , herpes zoster and papilloma viruses . likewise , an injectable form may be prepared . as set out above , the safe and effective daily systemic dose may range from 250 mg to 6 grams a day , and the most preferred dose being 500 mg to 2000 mg per day . because of the intimate association between rna or dna viruses with the dna and rna molecules of their host cell &# 39 ; s synthesizing machines , the development of antiviral agents followed the chemical path of synthesizing compounds against apparently specific targets provided by these molecules . the results of “ nucleic acid approach ”, although successful in some instances showed that they due to the complexity of the host response of viruses that include much more that nucleic acid was rather simplistic and empirical for the most part . thus , these agents were either marginally effective or toxic with little benefits for the patients . the discovery by isaacs and lindenmann ( 1957 ) of interferon ( ifn ), a low molecular weight protein produced by cells in response to cells infected with pathogenic viruses , changed the dogma of interfering with nucleic acids that essentially are common for both viruses and host cells in its chemical properties . there are three classes of interferons ( alpha , beta and gamma ) with different functions and properties and they inhibit a wide range of viruses and are effective on some of them event to curing a few viral diseases . however , they are clearly not a universal panacea because the resistant of host cells to viruses comprises a myriad of molecular mechanism that act in concert . a growing body of evidence suggests that the most effective targets to disintegrate viruses reside in proteins that are essential for replication of viruses in host cells . these proteins contain essential domains for viral survival denoted zinc finger domains , that when disrupted by disrupting agents such as picolinic acids and the derivatives thereof , have their zpf deactivated . the zn 2 + is necessary to provide the zfps a stable configuration to function as transcription factors . even a single mutation in the zinc finger biding domain , and in particular the cysteines or histidines residue of the zf domain , to which zn 2 + coordinately binds , results in a protein incapable of functioning . under these conditions the zn 2 + cannot bind the c and h amino acids and maintain the active zfp configuration . up to the present time all mutations in the zfd have been found to be lethal for the virus . during this process of zfp mutation , the protein is denature , linearized , exposed to host cells proteolytic enzymes and the host cell enters in apoptosis , eliminating both the virus and the virally infected cell . ( for details , please see fernandez - pol et al , anti - cancer research 2001 ). because picolinic acid acts in potent concert with ifns , cytokines , chemokines and hundreds of growth factors which act to protect infected host cells , it is highly likely that the use of biological response modifier , such as picolinic acid and derivatives thereof , will be able to prevent , control or attenuate replication of dengue viruses in human hosts ( and numerous other viruses ) in combination with ifns , chemokines , and cytokines . these results have been amply documented in previous sections of the instant invention . dengue , widespread through tropical and subtropical regions of the world , puts an estimated 2 . 5 billion people at risk for dengue vascular permeability , dengue hemorrhage fever , dengue shock syndrome ( dss ), and involvement of the liver accompanies dhf and / or dss . culture monocytes or macrophages support replication of dengue viruses . these australian investigations have established a well defined cell culture of macrophages and infection system for den - 2 that produces high titers of viral growth , and permanent infection with den - 2 in relevant human primary cells in the absence of enhancing antibody . in this model , the production of intracellular virus paralleled that for secreted virus ( pryor et al 2001 ). macrophages are ubiquitous cells critical for host defense ( varesio et al ., 1985 ). metchnikoff &# 39 ; s original report in the last portion of the 19 th century first indicated that phagocytes are the body &# 39 ; s primary detectors of foreign invaders . initially , the functions of macrophages have been studied at the cellular level . presently , macrophage study includes powerful genetic engineering techniques ( vareisio et al .) and isolation of recombinant growth factors which has found a list of macrophage secretor products and the interaction with metabolites of l - tryptophan , such as picolinic acid , that is impressive . this modern study has lead to a new approach of antiviral therapy ; often the prevention , therapy and attenuation of dengue viruses . anti - plasma leaking of nicotinamide and antithrombotic effects of nicotinic acid : potentially useful pharmacological actions of these agents to treat dengue hemorrhagic fever ( dhf ) and dengue shock syndrome ( dss ) nicotinic acid , also known as niacin , functions in the body after conversion to either nicotinamide adenine dinucleotide ( nad ) or nicotinamide adenine dinucleotide phosphate ( nadp ). nicotinic acid functions in both nad and nadp in the form of amide , nicotinamide . the chemical structures of nad and nadp are as follows in table 13 : nicotinic acid and nicotinamide are identical in their physiological functions . however , nicotinic acid is unable to be converted directly to nicotinamide , which is originated from the metabolism of nad . niacin has multifarious lipoprotein and anti - atherothrombosis effects that improve endothelial cell function , reduces inflammation , and decreases thrombosis . it is the most effective agent for increasing high - density lipoprotein cholesterol . niacin reduces blood viscosity through a variety of mechanisms , thus improving blood flow and perfusion through stenotic or thrombotic segments of the veins and arteries . niacin preserves glycolysis during periods of ischemia , and thus may accelerate the recovery functions of affected organs ( rosenson , rs , 2003 ). fernandez - pol et al ., in 1977 ( proc . natl . acad . of sci . usa ) showed that nicotinamide in tissue culture added to sv40 - virally transformed cells have a pronounced effect on cell shape : the sv40 - c become very flat and increase the adhesiveness between them in petri dishes , to the point of forming a mosaic of tightly adherent cells . this indicates that nicotinamide has the capacity to increase the adhesive cell surface proteins , indicating that the monolayer , even at high cell densities , prevents the free passage of culture media to the bottom of the cells which are strongly attached to the plastic petri dish . these observations suggested to the inventors that nicotinamide could be useful to prevent leakage of culture media , or if in an intact animal , plasma which will prevent edema and extravasation of fluids . the inventors believe that those are the bases for the use of nicotinamide in dss in which extravasation of blood fluids causes the disequilibrium in the blood - extracellular compartment due to increased permeability . thus , nicotinamide may be a useful pharmacological agent to treat dengue dss . it has been recently shown that niacin ( tavintharan , s . et al ., 1977 ) decreases atherothrobotic events in vein and arteries by lowering prothrombotic factors such as pai - 1 . it also reduces cell adhesion molecules ( cam ) ( as does nicotinamide ). the results showed that treatment with niacin suppressed pai - 1 and icam - 1 levels in the cells tested ( hepg2 ). thus , niacin at pharmacological concentrations can be used for the prevention and / or treatment against thrombotic disease in patients with dss . in addition to the antithrombotic effects , niacin inhibits vascular oxidative stress , and monocyte adhesion to human aortic endothelial cells ( ganji , sh et al ., 2008 ). in pharmacological doses , niacin reduces stroke and artherosclerosis . these effects are mediated by the actions of niacin on lipoproteins . niacin increases nicotinamide adenine dinucleotide phosphate ( nad ( p ) h ) levels by 54 % and reactive oxygen species ( ros ) by & gt ; 50 %, vascular adhesion molecules ( vcam - i ) by 80 %, and very significantly monocyte chemotactic protein - i ( mcp - i ) secretion by 34 to 124 %. tnf - alpha is also reduced and adhesion decreases . these studies indicate that niacin inhibits : endothelial vascular inflammation , ros production and inflammatory cytokine production . these are key events in the production of damage to the endothelium of arteries , atherogenesis , and subsequent thrombosis in the damage areas by ldl . these results demonstrate that in addition to the anti - atherogenic properties , niacin has potent anti - inflammatory vascular properties that could prevent the development of lethal thrombosis . thrombocytopenia is frequently associated with dengue virus infection in humans . basu , a et al . have demonstrated that dengue 2 virus inhibits in vitro megakaryocytic ( mk ) colony formation and induces apoptosis in thrombopoieting - inducible megakaryocytic differentiation in blood cd34 + cells . in summary , dengue 2 viruses can inhibit in vitro megakaryopoiesis ( production of mk cells ), and infect the mk , to such an extent that induce apoptosis of mk cells , depriving the human body from platelets that would prevent uncontrollable bleeding . the inventors believe that these pathological events of the virus play a key role in the etiology of the thrombocytopenia in dengue thrombosis and plasma fluid leakage syndromes ( dhf and dss ). the inventors consider that prevention of megakaryocytic destruction by use of picolinic acid in combination with prevention of dhf and dss with niacin or nicotinamide can be effective in controlling these deathly syndromes . 1 - methylnicotinamide ( mna ), a metabolite of nicotinamide , also exerts anti - thrombotic activity which is mediated by cyclooxygenase - 2 / prostacyclin pathway ( chlopicki , s , et al . br . j . pharmacol , 2007 ). n - methylnicotinamide inhibits arterial thrombosis in experimental animals . mna is effective in animals with thrombolysis , intra - aterial thrombus formation and in venous thrombosis . when compared with compounds used in standard clinical practice , mna was more effective in inhibiting platelet - dependent thrombosis . it is conceivable that nicotinic acid or mna can be effective in preventing the plasma and blood leakage to tissues and the subsequent thrombosis that may result by the stagnant blood and sera that accumulates extravascularly . in animal experiments , nicotinamide ( na ) can function as a cytoprotectant for acute and chronic neurodegenerative disorders and viral encephalopathies . na prevents neuronal and vascular cell injury , apoptosis , and maintains phosphatidyl serine membrane asymmetry , which prevents inflammation , cellular phagocytosis and vascular thrombosis , maiese , k & amp ; chong , z z , in 2003 ( trends pharmacol . sci .). furthermore , noa maintains high mitochondrial membrane potentials , increasing cellular energy which remains independent of cytoplasmic intracellular ph and growth factor activated protein kinases . cysteine protease activity , during cerebral vascular endothelial cell injury induced by viruses undergoes modulation by na . considering the association of dengue fever with clinical manifestations of encephalopathy , neurologic disorders , peripheral neuropathy , polyneuritis , and bell &# 39 ; s palsy , the inventors propose that the neurological manifestations of dengue hemorrhagic fever can be treated , or attenuated , with appropriate doses of na ranging from about 500 mg to about 6 grams for a 70 kg weight patient . in conclusion , the demonstration of the co - stimulatory effects of picolinic acid , ifn - gamma and other critical cytokines and chemokines has made it possible for picolinic acid to act as an autocrine mediator in the induction of antiviral activity against numerous viruses including dengue . the production of picolinic acid by macrophages in conjunction with ifn - gamma clearly shows that pa and ifn - gamma can induce apoptosis in virally infected cells . furthermore , the actions of pa on zfp render them unable to replicate dna or rna viruses ( fernandez - pol , 2001 ). from the aforementioned description , a method to control dengue viruses in humans by picolinic acid and derivatives thereof has been described . the method is uniquely capable of stimulating development and introduction of macrophages in the vicinity of the site of virus introduction . the method reduces the release of intercellular fluids and byproducts into the intra - cellular environment within the body of an animal or a person . the method and its various steps and components may be manufactured from many materials , including but not limited to , polymers , amino acids , minerals , vitamins , compounds thereof , and substitutions . as such , those skilled in the art will appreciate that the conception , upon which this disclosure is based , may readily be utilized as a basis for the designing of other structures , methods and systems for carrying out the several purposes of the present invention . therefore , the claims include such equivalent constructions insofar as they do not depart from the spirit and the scope of the present invention .

a method treats and then prevents a virus for afflicting an animal or a human as a metalloprotein mediates the virus . the method administers systemically a therapeutic pharmacological agent of picolinic acid either singly or with interferons , chemokines or cytokines to fight dengue fever virus . the picolinic acid inactivates the metalloprotein that allows replication of the virus . the picolinic acid has the structure of : where r1 , r2 , r3 , and r4 are mutually exclusive . the viral proteins disintegrate by macrophage proteolytic enzymes stimulated by the picolinic acid .

various embodiments will be described in detail with reference to the drawings , wherein like reference numerals represent like parts and assemblies throughout the several views . reference to various embodiments does not limit the scope of the claims attached hereto . additionally , any examples set forth in this specification are not intended to be limiting and merely set forth some of the many possible embodiments for the appended claims . fig1 - 6 illustrate an example of fishing lure 100 according to the present disclosure . fig1 is a perspective view , fig2 - 4 are left side views , fig5 is a front view , and fig6 is a top view . in the example shown in fig1 , fishing lure 100 includes head section 10 and tail section 20 coupled together with a joint 28 . head section 10 includes rear surface 12 , front surface 13 , and line connection device 16 . tail section 20 includes front surface 21 , rear end 22 , upper edge 32 , lower edge 33 , and hook connection devices 23 and 25 . tail section 20 further includes a forward region 27 that includes and is adjacent to the front surface 21 . tail section 20 also includes lip 50 that extends from the forward region 27 of the tail section 20 . in the example embodiment shown in fig1 - 3 , joint 28 includes eyelet members 30 and 31 . some embodiments further include additional joint components , such as one or more split rings , a swivel , or another fastener . some embodiments further include hooks 40 and 41 connected to the hook connection devices 23 and 25 . the fishing lure 100 can include one or more hook connection devices 23 and 25 . in one example , the hook connection device 23 extends from the lower edge 33 of the tail section 20 , and the hook connection device 25 extends from the rear end 22 of the tail section 20 . examples of hook connection members are eyelets . the connection between hook connection devices 23 and 25 and hooks may include additional coupling devices , such as split rings 24 and 26 . in some embodiments , head section 10 , joint 28 , and tail section 20 extend along a longitudinal axis 14 . head section 10 is forward of the tail section 20 . head section 10 is coupled to tail section 20 by joint 28 to permit head section 10 and tail section 20 to pivot with respect to each other about joint 28 . head and tail sections 10 and 20 are typically made of a buoyant material , such as wood or plastic . an example of a suitable wood is balsa wood . an example of a plastic is a moldable polymer . it is preferred that the material have some buoyancy so that lure 100 floats when at rest on a water surface . head section 10 includes a concave front surface 13 , a rear surface 12 , an upper edge 18 , and a lower edge 19 . concave front surface 13 is configured to catch the water when the lure is given a sharp jerk to provide a “ popping ” action . accordingly , the front surface 13 forms a front popper surface . the front surface 13 includes a recessed region 8 , wherein the apex 9 of the concave surface is the most recessed point of the front surface 13 . a fishing line connection device 16 , such as an eyelet , is secured to concave front surface 13 in some embodiments to provide a location for securing a fishing line to lure 100 . head section 10 is typically free of hook connection devices , and instead , hook connection devices are provided on tail section 20 . in some embodiments , head section 10 further includes an eye portion 11 . the eye portion 11 is slightly recessed ( or , alternatively , slightly protrudes ) from the adjacent surfaces of head section 10 in some embodiments . the eye portion 11 can be painted or an adhesive material can be applied to the eye region to increase visibility of the eye , which can help to draw attention to lure 100 . in some embodiments the eye region is painted onto a surface of head section 10 . in some embodiments , rear surface 12 extends between upper and lower edges 18 and 19 of the head section 10 , and slopes rearward from the lower edge 19 to the upper edge 18 . in some embodiments , at least a portion of the recessed rear surface forms a channel 17 that directs water toward the lip when the lure is being retrieved . in some embodiments , the rear surface 12 is recessed and defines a fluid channel 17 . in some embodiments , the fluid channel is longitudinally aligned with the lip 50 , such that when the lure is retrieved through the water , some of the water is directed through the channel and toward the lip . in this way , the channel improves the action of the tail , by increasing the amount of water interacting with lip 50 . in addition , the channel permits the lower edge 19 of the head to be lower , which provides at least a partial barrier to deflect objects in the water ( such as weeds , sticks , or other debris ) from the path of the lip 50 . this reduces the chance that objects will get caught on the lip . the lip 50 includes a proximal end 52 and a distal end 53 . in some embodiments the distal end 53 of lip 50 extends lower than the lower edge 19 of the head section 10 . in other embodiments , the lower edge 19 is substantially aligned with the distal end 53 of the lip . with at least some retrieves , lure 100 can be retrieved such that the head remains generally stationary without significant side - to - side motion . joint 28 , however , permits tail section 20 to pivot relative to head section 10 , such as to have a side - to - side wobble independent of head section 10 . this side - to - side wobble can help to attract attention to lure 100 . joint 28 is provided between head section 10 and tail section 20 to permit the sections to pivot with respect to each other . in this example , joint 28 includes eyelet members 30 and 31 . eyelet member 30 is anchored to head section at rear end 22 . eyelet member 31 is anchored to tail section 20 through front surface 21 . various alternative joint configurations are used in other embodiments . several examples are shown in fig3 and 4 . fig3 depicts an example ball joint 28 ′ configuration . the ball joint 28 ′ configuration is an example of an offset joint , where the point where the joint 28 ′ connects to front surface 21 of tail portion is offset from ( e . g ., lower than ) the point where the joint 28 ′ connects to rear surface 12 . fig4 depicts an example universal joint 28 ″ configuration . the universal joint 28 ″ configuration is an example of a linear joint , which permits pivoting movement of the tail section 20 in all directions relative to the head section 10 , including side to side , and up and down . fig4 also illustrates an example of an inserted lip 28 ″ that is formed as a separate piece from the tail section 20 . tail section 20 includes lip 50 extending downward and forward of a lower portion of front surface 21 . in some embodiments lip 50 includes a generally planar forward - facing surface 51 extending between proximal end 52 and distal end 53 of lip 50 . the surface 51 is arranged at a diving angle a 1 ( fig2 ) relative to a longitudinal axis 14 of the tail section 20 . in some embodiments , the diving angle a 1 is in a range from about 35 degrees to about 55 degrees from the longitudinal axis 14 . in another embodiment , the diving angle a 1 is about 45 degrees . during a steady retrieve , for example , lip 50 interacts with the water — causing lure 100 to be pulled downward , and causing tail section 20 to wobble back and forth . as shown in fig2 , some embodiments of lure 100 includes tail section 20 having an integrally molded lip 50 extending therefrom . in some embodiments , the lip 50 and tail section 20 are formed as a single piece . in another possible embodiment , however , lip 50 is formed separate from tail section 20 . for example , as shown in fig4 , some embodiments of tail section 20 include a groove 54 formed therein . a matching protrusion is formed in lip 50 that can be inserted into groove 54 and secured in position , such as with adhesive or other fastener . some embodiments have a tail section 20 with a body shape in which at least a portion of the tail section tapers in size toward the rear end , as shown in fig2 . for example , the section of tail section 20 rearward of the hook connection device 23 has a lateral cross - sectional area that decreases toward the rear end , such that the lateral cross - sectional area of the tail section 20 is greater than the lateral cross - sectional area of the tail section 20 adjacent rear end 22 . in some embodiments , lure 100 includes a joint that is near to the front end of lure 100 . in some embodiments , the distance between the most forward point of lure 100 and the center of the joint is in a range from about ⅕ to about ⅙ the total length of lure 100 . however , other embodiments include other configurations . in another example embodiment , a ratio of a length of the tail section to a length of the head section is in a range from about 1 : 1 to about 5 : 1 . for example , some embodiments include shortened tail sections , such as to form a bait having a shorter overall length . fig7 - 11 illustrate the operation of lure 100 using various types of retrieves . fig7 illustrates lure 100 when at rest on a surface of water 61 . when in this position , lure 100 is preferably buoyant , such that lure 100 floats partially above the surface of water 61 and partially below the surface of water 61 . in some embodiments , tail section 20 rests at an angle , such that rear end 22 of lure 100 is angled downward relative to the surface of water 61 . fig8 illustrates a surface popping action of lure 100 . the surface popping action is imparted on lure 100 by pulling lure 100 with fishing line 15 with a short and quick snapping action . the force pulls lure 100 forward suddenly , causing front surface 13 of head section 10 to scoop and throw some of water 61 . a “ popping ” sound is also generated in some embodiments that can further help to attract fish to lure 100 . in some embodiments , during a surface popping action of lure 100 , tail section 20 will move with a side - to - side swimming action in which the lure rolls back and forth in the direction of arrow 80 . fig9 illustrates the operation of lure 100 during another exemplary retrieve , in which the lure moves in a zigzag type motion . this is alternatively referred to as a “ walking ” action . the walking action is imparted on lure 100 by applying short snapping forces to lure 100 with fishing line 15 in the direction of arrow 72 . a short pause between tugs allows lure 100 to briefly glide through the water , after which another snapping force is applied to lure 100 . tail section 20 can then be caused to move side - to - side as illustrated in fig9 . for example , after a first force , tail section 20 will glide in a first angled position . the second force then causes tail section 20 to move to the second position ( in the direction of arrows 81 ) and glide in the second direction . continued snapping results in a zigzag type motion . when pulled , lip 50 causes lure 100 to dive . if the subsequent pulls on lure 100 are provided before lure 100 floats back up to the surface , a sub - surface retrieve can be obtained . alternatively , lure 100 can be allowed to return to the surface after each pull . fig1 illustrates the operation of lure 100 during a steady retrieve . in this example , a steady force is applied to lure 100 by line 15 in the direction of arrow 70 . lip 50 interacts with water 61 to pull lure 100 downward , while also generating a side - to - side motion in the direction of arrow 80 . the motion of lip 50 is transferred through tail section , causing the entire tail - section to wiggle in the side - to - side direction of arrow 80 . the joint of lure 100 allows head section 10 to remain substantially stationary and forward - facing relative to tail section 20 during a steady retrieve . a medium to high retrieve speed will maintain lure 100 under the surface of the water . this motion mimics a live baitfish . fig1 illustrates the operation of lure 100 during a slow and steady retrieve . in this example , a steady force is applied to lure 100 by line 15 in the direction of arrow 70 , but the speed of the retrieve is relatively slow . as a result , the interaction between the water and lip 50 does not generate a downward force that is sufficient to pull lure 100 completely significantly under the water . instead , lure 100 remains at or just below the surface 60 of water 61 . lip 50 creates a side - to - side motion as shown by arrow 80 . the side - to - side motion causes tail section 20 to move back and forth in the direction of arrow 82 . the movement of tail section 20 causes a disturbance to the surface of the water that ripples out from lure 100 . this surface disturbance is noticeable by fish and can help to bring attention to lure 100 . the various embodiments described above are provided by way of illustration only and should not be construed to limit the claims attached hereto . those skilled in the art will readily recognize various modifications and changes that may be made without following the example embodiments and applications illustrated and described herein , and without departing from the true spirit and scope of the following claims .

a multi - action fishing lure includes a buoyant head section , a tail section , a joint , and a lip . the head section includes a front surface and an opposing rear surface . the tail section includes a lip that protrudes from a forward region of the tail section . the front surface includes a recessed region , and also includes a line connection device extending from the recessed region . a joint flexibly couples the head section to the tail section . the fishing lure can be retrieved to generate multiple different actions .

in accordance with the present invention , a method is provided for the prophylaxix or treatment of chronic lymphocytic leukemia ( cll ) in a patient , comprising administering to said patient a therapeutically effective amount of an indole derivative of the formula : in which r 1 is selected from the group consisting of hydrogen , lower alkyl , lower alkenyl , lower alkynyl , alkoxyloweralkyl , lower cycloalkyl , phenyl , benzyl and 2 - thienyl ; r 2 and r 3 are the same or different and are each selected from the group consisting of hydrogen and lower alkyl ; r 4 and r 5 are the same or different and are each selected from the group consisting of hydrogen , lower alkyl , — nh 2 , — nhcho , — nhconh 2 , ═ nw , oxo , — oh and — och 3 , wherein w is hydroxy , alkoxy , aryloxy , carboxyalkyloxy , arylamino or alkylsulfonylamino ; r 6 is selected from the group consisting of hydrogen , lower alkyl lower alkenyl , lower alkynyl , trifluoromethyl , hydroxy , lower alkoxy , trifluoroloweralkoxy , benzyloxy , araloxy , lower alkanoyloxy , acyl , amino , nitro , cyano , alkylimido , halo , mercapto , loweralkylthio , alkylsulfinyl , alkylsulfonyl , alkylsulfonamido and sulfamoyl ; r 7 is selected from the group consisting of hydrogen , lower alkyl and lower alkenyl ; x is selected from the group consisting of carbon , oxy and thio ; y is selected from the group consisting of carbonyl , in which each of r 8 , r 9 , r 10 , r 11 , r 12 and r 13 is hydrogen or lower alkyl ; and z is selected from the group consisting of hydroxy , lower alkoxy , amino , lower alkylamino , di ( lower ) alkylamino and phenylamino , or a pharmaceutically acceptable salt thereof . also included within the scope of this invention are pyrano [ 3 , 4 - b ] indole and thiopyrano [ 3 , 4 - b ] indole derivatives of formula i in which r 6 represents from one to four substituents , which may be present simultaneously , at positions 5 , 6 , 7 and 8 thereof . the exact nature of such substituents does not have to be limited necessarily by the above definitions of r 6 , and r 6 may also include additional substituents , for example , mercapto , lower alkylthio , trifluoromethyl and other halo ( lower ) alkyls , amino and sulfamoyl , provided that any two such substituents do not interfere with each others presence . accordingly the indole derivatives of this invention are represented also by general formula ia : in which r 1 , r 2 , r 3 , r 4 , r 5 , r 7 , x , y and z are as defined above and r 6a , r 6b , r 6c and r 6d are the same or different and each is selected from the group consisting of hydrogen , lower alkyl , lower alkenyl , lower alkynyl , trifluoromethyl , hydroxy , lower alkoxy , trifluoroloweralkoxy , benzyloxy , araloxy , lower alkanoyloxy , acyl , amino , nitro , cyano , alkylimido , halo , mercapto , loweralkylthio , alkylsulfinyl , alkylsulfonyl , alkylsulfonamido and sulfamoyl , or a pharmaceutically acceptable salt thereof . the preparation of compounds of formulas 1 and 1a is disclosed in u . s . pat . nos . 3 , 843 , 681 , 3 , 939 , 178 , 3 , 974 , 179 , 4 , 686 , 213 , 4 , 748 , 252 , 5 , 776 , 967 , 5 , 824 , 699 and 5 , 830 , 911 the disclosures of which are incorporated herein by reference . in a presently preferred embodiment of the invention , the indole compound of formula i is etodolac , having the formula or a pharmaceutically acceptable salt thereof . methods for the synthesis of etodolac are disclosed in u . s . pat . nos . 4 , 585 , 877 and 5 , 599 , 946 , which are incorporated herein by reference . etodolac is commercially available under the tradename lodine ®, wyeth - ayerst laboratories division of american home products corporation , philadelphia , pa ., u . s . a . also included within the scope of this invention are the isomers of the compounds of formula i resulting from the asymmetric centers contained therein . the commercially available etodolac product is a racemic mixture . u . s . pat . no . 5 , 561 , 151 discloses the resolution of a mixture of the enantiomers of etodolac using conventional means , and the use of the separated r (−) isomer as an analgesic . thus , it is further contemplated that the ( r )- and ( s ) isomers of etodolac may be separated , and used separately in the practice of the invention . as used herein in connection with the indole derivatives of the invention , the term “ lower alkyl ” contemplates both straight and branched chain alkyl radicals containing from one to six carbon atoms and includes methyl , ethyl , propyl , isopropyl , butyl , isobutyl 2 - methylpentyl and the like . as used herein , the term “ lower alkenyl ” contemplates both straight and branched chain alkenyl radicals containing from two to six carbon atoms and includes vinyl , allyl , 1 - propenyl methallyl , 2 - ethyl - 3 - butenyl and the like . as used herein the term “ lower alkynyl ” contemplates both straight and branched chain alkynyl radicals containing from two to six carbon atoms and includes ethynyl , propargyl , 1 , 1 - dimethylpropargyl and the like . as used herein , the term “ lower cycloalkyl ” contemplates saturated cyclic hydrocarbon radicals containing from three to six carbon atoms and includes cyclopropyl , cyclobutyl , cyclopentyl and the like . as used herein , the term “ lower alkoxy ” contemplates both straight and branched chain alkoxy radicals containing from one to four carbon atoms and includes methoxy , ethoxy , isopropoxy and the like . as used herein , the term “ lower alkanoyloxy ” contemplates both straight and branched chain alkanoyloxy radicals containing from two to six carbon atoms and includes acetoxy , propionyloxy , hexanoyloxy and the like . as used herein , the term “ acyl ” refers to the divalent group — c ( o )—. the term “ aryl ” as used herein refers to cyclic aromatic hydrocarbon chains having twenty or fewer carbon atoms , e . g ., phenyl , naphthyl , biphenyl and anthracenyl . one or more carbon atoms of the aryl group may also be substituted with , e . g . : alkyl ; aryl ; heterocycle ; halogen ; nitro ; cyano ; hydroxyl , alkoxyl or aryloxyl ; thio or mercapto , alkyl -, or arylthio ; ammo , alkylamino , arylamino , dialkyl -, diaryl -, or arylalkylamino ; aminocarbonyl , alkylaminocarbonyl , arylaminocarbonyl , diaalylaminocarbonyl , diarylaminocarbonyl or arylalkylaminocarbonyl ; carboxyl , or alkyl - or aryloxycarbonyl ; carboxaldehyde , or aryl - or alkylcarbonyl ; iminyl , or aryl - or alkyliminyl ; sulfo ; alkyl - or arylsulfonyl ; hydroximinyl , or aryl - or alkoximinyl ; carbamido ; or thiocarbamido . in addition , two or more alkyl or heteroalkyl substituents of an aryl group may be combined to form fused aryl - alkyl or aryl - heteroalkyl ring systems ( e . g ., tetrahydronaphthyl ). substituents including heterocyclic groups ( e . g ., heterocycleoxy , heteroaryloxy , and heteroamalkylthio ) are defined by analogy to the above - described terms . the terms “ aralkyl ” or “ aralkoxy ” as used herein refers to an aryl group that is joined to a parent structure by an alkyl or alkoxy group as described above , e . g ., benzyl , α - methylbenzyl , phenethyl , and the like . as used herein , the term “ halo ” contemplates halogens and includes fluorine , chlorine , bromine and iodine . where the term “ lower ” is used herein as part of the description of alkylamino and dialkylamino , it contemplates one to six carbon atoms of each alkyl group of such a radical and includes a methylamino , n - hexylamino , dimethylamino , diethylamino and the like . when the present indole derivatives of this invention are employed in accordance with the invention in warm - blooded animals , e . g ., mice , rats , or humans , they may be administered orally , alone or in dosage forms , i . e ., capsules or tablets , combined with pharmacologically acceptable carriers or excipients , such as starch , milk sugar and so forth . they may also be administered orally in the form of solutions in suitable vehicles such as vegetable oils , or they may be injected parenterally . for parenteral administration they may be used in the form of a sterile solution containing other solutes , for example , enough saline or glucose to make the solution isotonic . the dosage of the indole derivatives of this invention will vary with the particular compound chosen and form of administration . furthermore , it will vary with the particular host under treatment . the proportion of the compound is determined by the solubility and chemical nature of the compound , chosen route of administration and standard biological practice . generally , the compounds of this invention are administered at a concentration level that affords the benefits of the invention without any deleterious side effects . effective concentration levels are usually obtained within a therapeutic range of 1 . 0 mg to 500 mg of an indole compound of the invention per kg of body weight of the patient per day , with a preferred range of 10 to 100 mg / kg per day . the compounds of the present invention can be used in the form of salts derived from inorganic or organic acids . these salts include but are not limited to the following : acetate , adipate , alginate , citrate , aspartate , benzoate , benzenesulfonate , bisulfate , butyrate , camphorate , camphorsulfonate , digluconate , cyclopentanepropionate , dodecylsulfate , ethanesulfonate , glucoheptanoate , glycerophosphate , hemisulfate , heptanoate , hexanoate , fumarate , hydrochloride , hydrobromide , hydroiodide , 2 - hydroxyethanesulfonate , lactate , maleate , methanesulfonate , nicotinate , 2 - napthalenesulfonate , oxalate , pamoate , pectinate , sulfate , 3 - phenylpropionate , picrate , pivalate , propionate , succinate , tartrate , thiocyanate , p - toluenesulfonate and undecanoate . also , the basic nitrogen - containing groups can be quaternized with such agents as loweralkyl halides , such as methyl , ethyl , propyl , and butyl chloride , bromides , and iodides ; dialkyl sulfates like dimethyl , diethyl , dibutyl , and diamyl sulfates , long chain halides such as decyl , lauryl , myristyl and stearyl chlorides , bromides and iodides , aralkyl halides like benzyl and phenethyl bromides , and others . water or oil - soluble or dispersible products are thereby obtained . examples of acids which may be employed to form pharmaceutically acceptable - acid addition salts include such inorganic acids as hydrochloric acid , sulphuric acid and phosphoric acid and such organic acids as oxalic acid , maleic acid , succinic acid and citric acid . basic addition salts can be prepared in situ during the final isolation and purification of the compounds of formula ( i ), or separately by reacting carboxylic acid moieties with a suitable base such as the hydroxide , carbonate or bicarbonate of a pharmaceutically acceptable metal cation or with ammonia , or an organic primary , secondary or tertiary amine . pharmaceutically acceptable salts include , but are not limited to , cations based on the alkali and alkaline earth metals , such as sodium , lithium , potassium , calcium , magnesium , aluminum salts and the like , as well as nontoxic ammonium , quaternary ammonium , and amine cations , including , but not limited to ammonium , tetramethylammonium , tetraethylammonium , methylamine , dimethylamine , trimethylamine , triethylamine , ethylamine , and the like . other representative organic amines useful for the formation of base addition salts include diethylamine , ethylenediamine , ethanolamine , diethanolamine , piperazine and the like . pharmaceutical compositions comprising at least one indole or carbazole compound of formula i or formula ia , may also include suitable solutions for administration intravenously , subcutaneously , dermally , orally , mucosally or rectally and may be administered by injection or orally , and contain from about 0 . 01 to 99 percent , preferably from about 20 to 75 percent of active component together with the excipient . pharmaceutical compositions for oral administration include tablets and capsules . compositions which can be administered rectally include suppositories . pharmaceutical compositions according to the invention may be administered via the conventional ways of administration . preferred ways of administration are oral , intravenous , intramuscular or subcutaneous . the pharmaceutical compositions may also be administered continuously , i . e ., by way of infusion . the formulation and dose will depend on the condition to be treated , the route of administration and the condition and the body weight of the patient to be treated . the exact dose will be determined by the attending physician . the pharmaceutical compositions according to the invention are prepared in the usual manner , for example by mixing the active ingredient with pharmaceutically and physiologically acceptable carriers and / or stabilizers and / or excipients , as the case may be , and are prepared in dosage form , e . g ., by lyophilization in dosage vials . as used herein , the term “ pharmaceutically acceptable ” refers to a carrier medium which does not interfere with the effectiveness of the biological activity of the active ingredients and which is not toxic to the hosts to which it is administered . the composition used in these therapies can be in a variety of forms . these include , for example , solid , semi - solid , and liquid dosage forms , such as tablets , pills , powders , liquid solutions or suspensions , liposomes , and injectable and infusible solutions . the preferred form depends on the intended mode of administration and therapeutic application . the compositions also preferably include conventional pharmaceutically acceptable carriers and adjuvants , as is well known to those of skill in the art . see , e . g ., remington &# 39 ; s pharmaceutical sciences , mack publishing co . : easton , pa ., 17th ed . ( 1985 ). preferably , administration will be by oral or parenteral ( including subcutaneous , intramuscular , intravenous , and intradermal ) routes . more preferably , the route of administration will be oral . the therapeutic methods and agents of this invention can of course be used concomitantly or in combination with other methods and agents for treating cll . while it is possible to administer the active ingredient of this invention alone , it is preferable to present a therapeutic agent as part of a pharmaceutical formulation or composition . the formulations of the present invention comprise at least one compound of this invention in a therapeutically or pharmaceutically effective dose together with one or more pharmaceutically or therapeutically acceptable carriers and optionally other therapeutic ingredients . various considerations for preparing such formulations are described , e . g ., in gilman et al . ( eds .) goodman and gilman &# 39 ; s : the pharmacological bases of therapeutic , 8th ed ., pergamon press ( 1990 ); and remington &# 39 ; s supra , each of which is incorporated herein by reference for all purposes . methods for administration are discussed therein , e . g ., for oral , intravenous , intraperitoneal , intramuscular , and other forms of administration . typically , methods for administering pharmaceutical compositions will be either topical , parenteral , or oral administration methods for prophylactic and / or therapeutic treatment . oral administration is preferred . the pharmaceutical compositions can be administered in a variety of unit dosage forms depending upon the method of administration . as noted above , unit dosage forms suitable for oral administration include powders , tablets , pills , and capsules . one can use topical administration to deliver a compound of the invention by percutaneous passage of the drug into the systemic circulation of the patient . the skin sites include anatomic regions for transdermally administering the drug , such as the forearm , abdomen , chest , back , buttock , and mastoidal area . the compound is administered to the skin by placing on the skin either a topical formulation comprising the compound or a transdermal drug delivery device that administers the compound . in either embodiment , the delivery vehicle is designed , shaped , sized , and adapted for easy placement and comfortable retention on the skin . a variety of transdermal drug delivery devices can be employed with the compounds of this invention . for example , a simple adhesive patch comprising a backing material and an acrylate adhesive can be prepared . the drug and any penetration enhancer can be formulated into the adhesive casting solution . the adhesive casting solution can be cast directly onto the backing material or can be applied to the skin to form an adherent coating . see , e . g ., u . s . pat . nos . 4 , 310 , 509 ; 4 , 560 , 555 ; and 4 , 542 , 012 . in other embodiments , the compound of the invention will be delivered using a liquid reservoir system drug delivery device . these systems typically comprise a backing material , a membrane , an acrylate based adhesive , and a release liner . the membrane is sealed to the backing to form a reservoir . the drug or compound and any vehicles , enhancers , stabilizers , gelling agents , and the like are then incorporated into the reservoir . see , e . g ., u . s . pat . nos . 4 , 597 , 961 ; 4 , 485 , 097 ; 4 , 608 , 249 ; 4 , 505 , 891 ; 3 , 843 , 480 ; 3 , 948 , 254 ; 3 , 948 , 262 ; 3 , 053 , 255 ; and 3 , 993 , 073 . matrix patches comprising a backing , a drug / penetration enhancer max , a membrane , and an adhesive can also be employed to deliver a compound of the invention transdermally . the matrix material typically will comprise a polyurethane foam . the drug , any enhancers , vehicles , stabilizers , and the like are combined with the foam precursors . the foam is allowed to cure to produce a tacky , elastomeric matrix which can be directly affixed to the backing material . see , e . g ., u . s . pat . nos . 4 , 542 , 013 ; 4 , 460 , 562 ; 4 , 466 , 953 ; 4 , 482 , 534 ; and 4 , 533 , 540 . also included within the invention are preparations for topical application to the skin comprising a compound of the invention , typically in concentrations in the range from about 0 . 001 % to 10 %, together with a non - toxic , pharmaceutically acceptable topical carrier . these topical preparations can be prepared by combining an active ingredient according to this invention with conventional pharmaceutical diluents and carriers commonly used in topical dry , liquid , and cream formulations . ointment and creams may , for example , be formulated with an aqueous or oily base with the addition of suitable thickening and / or gelling agents . such bases may include water and / or an oil , such as liquid paraffin or a vegetable oil , such as peanut oil or castor oil . thickening agents that may be used according to the nature of the base include soft paraffin , aluminum stearate , cetostearyl alcohol , propylene glycol , polyethylene glycols , woolfat , hydrogenated lanolin , beeswax , and the like . lotions may be formulated with an aqueous or oily base and will , in general , also include one or more of the following : stabilizing agents , emulsifying agents , dispersing agents , suspending agents , thickening agents , coloring agents , perfumes , and the like . powders may be formed with the aid of any suitable powder base , e . g ., talc , lactose , starch , and the like . drops may be formulated with an aqueous base or non - aqueous base also comprising one or more dispersing agents , suspending agents , solubilizing agents , and the like . topical administration of compounds of the invention may also be preferred for treating diseases such as skin cancer and fungal infections of the skin ( pathogenic fungi typically express telomerase activity ). the topical pharmaceutical compositions according to this invention may also include one or more preservatives or bacteriostatic agents , e . g ., methyl hydroxybenzoate , propyl hydroxybenzoate , chlorocreosol , benzalkonium chlorides , and the like . the topical pharmaceutical compositions also can contain other active ingredients such as antimicrobial agents , particularly antibiotics , anesthetics , analgesics , and antipruritic agents . the compounds of the present invention can also be delivered through mucosal membranes . transmucosal ( i . e ., sublingual , buccal , and vaginal ) drug delivery provides for an efficient entry of active substances to systemic circulation and reduces immediate metabolism by the liver and intestinal wall flora transmucosal drug dosage forms ( e . g ., tablet , suppository , ointment , pessary , membrane , and powder ) are typically held in contact with the mucosal membrane and disintegrate and / or dissolve rapidly to allow immediate systemic absorption . note that certain such routes may be used even where the patient is unable to ingest a treatment composition orally . note also that where delivery of a telomerase inhibitor of the invention would be enhanced , one can select a composition for delivery to a mucosal membrane , e . g ., in cases of colon cancer one can use a suppository to deliver the telomerase inhibitor . for delivery to the buccal or sublingual membranes , typically an oral formulation , such as a lozenge , tablet , or capsule , will be used . the method of manufacture of these formulations is known in the art , including , but not limited to , the addition of the pharmacological agent to a pre - manufactured tablet ; cold compression of an inert filler , a binder , and either a pharmacological agent or a substance containing the agent ( as described in u . s . pat . no . 4 , 806 , 356 ); and encapsulation . another oral formulation is one that can be applied with an adhesive , such as the cellulose derivative hydroxypropyl cellulose , to the oral mucosa , for example as described in u . s . pat . no . 4 , 940 , 587 . this buccal adhesive formulation , when applied to the buccal mucosa , allows for controlled release of the pharmacological agent into the mouth and through the buccal mucosa . parenteral administration is generally characterized by injection , either subcutaneously , intramuscularly , or intravenously . thus , this invention provides compositions for intravenous administration that comprise a solution of a compound of the invention dissolved or suspended in an acceptable carrier . injectables can be prepared in conventional forms , either as liquid solutions or suspensions , solid forms suitable for solution or suspension in liquid prior to injection , or as emulsions . suitable excipients are , for example , water , buffered water , saline , dextrose , glycerol , ethanol , or the like . these compositions will be sterilized by conventional , well known sterilization techniques , such as sterile filtration . the resulting solutions can be packaged for use as is or lyophilized , the lyophilized preparation being combined with a sterile solution prior to administration . in addition , if desired , the pharmaceutical compositions to be administered may also contain minor amounts of non - toxic auxiliary substances , such as wetting or emulsifying agents , ph buffering agents and the like , such as for example , sodium acetate , sorbitan monolaurate , triethanolamine oleate , etc . such formulations will be useful in treating ovarian cancers . another method of parenteral administration employs the implantation of a slow - release or sustained - release system , such that a constant level of dosage is maintained . see , e . g ., u . s . pat . no . 3 , 710 , 795 , incorporated herein by reference . liquid pharmaceutically administrable compositions can , for example , be prepared by dissolving , dispersing , etc ., an active compound as defined above and optional pharmaceutical adjuvants in an excipient , such as , for example , water , saline , aqueous dextrose , glycerol , ethanol , olive oil , and other lipophilic solvents , and the like , to form a solution or suspension . if desired , the pharmaceutical composition to be administed may also contain minor amounts of nontoxic auxiliary substances , such as wetting or emulsifying agents , ph buffering agents , and the like , for example , sodium acetate , sorbitan monolaurate , triethanolamine sodium acetate , triethanolamine oleate , etc . actual methods of preparing such dosage forms are known and will be apparent to those skilled in this art ; for example , see remington &# 39 ; s pharmaceutical sciences , supra . the composition or formulation to be administered will contain an effective amount of an active compound of the invention . for solid compositions , conventional nontoxic solid carriers can be used and include , for example , pharmaceutical grades of mannitol , lactose , starch , magnesium stearate , sodium saccharin , talcum , cellulose , glucose , sucrose , magnesium carbonate , and the like . for oral administration , a pharmaceutically acceptable nontoxic composition is formed by incorporating any of the normally employed excipients , such as those carriers previously listed , and generally 0 . 1 - 95 % of active ingredient , preferably about 20 %. the compositions containing the compounds of the invention can be administered for prophylactic and / or therapeutic treatments . in therapeutic applications , compositions are administered to a patient already suffering from cll , as described above , in an amount sufficient to cure or at least partially arrest the symptoms of the disease and its complications . an amount adequate to accomplish this is defined as a “ therapeutically effective amount or dose .” amounts effective for this use will depend on the severity of the disease and the weight and general state of the patient . in addition to internal ( in vivo ) administration , the compounds and compositions of the invention may be applied ex vivo to achieve therapeutic effects . in such an application , cells to be treated , e . g ., blood or bone marrow cells , are removed from a patient and treated with a pharmaceutically effective amount of a compound of the invention . the cells are returned to the patient following treatment . such a procedure can allow for exposure of cells to concentrations of therapeutic agent for longer periods or at higher concentrations than otherwise available . once improvement of the patient &# 39 ; s conditions has occurred , a maintenance dose is administered if necessary . subsequently , the dosage or the frequency of administration , or both , can be reduced , as a function of the systems , to a level at which the improved condition is retained . when the symptoms have been alleviated to the desired level treatment can cease . patients can , however , require additional treatment upon any recurrence of the disease symptoms . in prophylactic applications ( e . g . chemoprevention ), compositions containing the compounds of the invention are administered to a patient susceptible to or otherwise at risk of a cll . such an amount is defined to be a “ prophylactically effective amount or dose .” in this use , the precise amounts again depend on the patient &# 39 ; s state of health and weight a patient was confirmed to have b - cell cll by lymphocyte typing and bone marrow studies . the patient was staged at 0 by the rai classification system . the patents lymphcyte phenotype , cd5 +, cd19 +, cd20 +, cd25 + and fmc7 +. on oct . 23 , 1997 , the patient &# 39 ; s white blood cell count was 34 . 3 × e3 and the lymphocyte count was 27 . 44 × e3 . on oct . 25 , 1997 through oct . 27 , 1997 , the patient was administered 300 mg of etodolac bid for neck pain . on oct . 28 , 1997 , the patient developed petechiae ( bleeding from the capillaries ) on the shins . a complete blood count revealed that the patient &# 39 ; s platelet count was normal , but that both the white blood cell count ( 13 . 40 × e3 ) and the lymphocyte count ( 6 . 70 × e3 ) were significantly reduced , as shown in fig1 . subsequently , etodolac was administered to the patient at a dose of 300 mg bid for the periods nov . 5 , 1997 - nov . 9 , 1997 , jan . 21 , 1998 - jan . 25 , 1998 , feb . 26 , 1998 - mar . 2 , 1998 and apr . 8 , 1998 - apr . 13 , 1998 . the results are shown in fig1 and 2 , with the effect on platelet count also being shown in fig2 , and are compared with the results of administration to the same patient during intervening periods of the nsaids naproxen ( n ), diclofenac ( d ), sulindac ( s ), nabumetone ( r ), oxaprozin ( o ), piroxicam ( p ), indomethacin ( i ), tolmetin ( t ) and ibuprofen ( m ). the results from the etodolac administration are averaged and compared with the data for naproxin , diclofenac , sulindac , nabumetone , oxaprozin piroxicam , indomethacin , tolmetin and ibuprofen in the following table 1 . as is readily apparent from the foregoing , etodolac treatment resulted in substantial reductions of the white blood cell count and lymphocyte count of the patient , while treatment with the nsaids naproxen , diclfenac , sulindac , nabumetone , oxaprozin , piroxicam , indomethacin , tolmetin and ibuprofen exhibited relatively little impact on these factors . the platelet count also increased significantly with etodolac . to examine the possibility that a metabolite of etodolac or a serum factor may be necessary to achieve the clinical effect , the in vivo percentages of viable , apoptotic and late apoptotic or necrotic cells of isolated mononuclear cells were measured by flow cytometry using fitc annexin and propridium iodide assay . during early apoptosis and preceding dna fragmentation , phosphatydylserine becomes exposed and bond by annexin v . later in apoptosis and in cell necrosis , cells also become permeable to propidium iodide . fitc labeled annexin b and propidium iodide are easily detected by flow cytometry . mononuclear cells were isolated from the peripheral blood of the patient by differential centrifugation on ficoll - hypaque at baseline and then daily for three additional days after administration of etodolac . as the lymphocyte count dropped after administration of etodolac , the percentage of apoptotic cells remained the same . however , the percentage of viable cells increased and the percentage of late apoptotic or necrotic cells decreased . this result suggests that etodolac does not achieve the reduction of lymphocytes by direct killing , but likely increases the clearance of leukemic cells either into the phagocytic system or diverts them to various tissue compartments . to examine the possibility that etodolac might enhance the clearance of leukemic lymphocytes by enhancing phagocytosis by macrophages , tamra stained isolated mononuclear cells from the patient were incubated with normal human adherent mononuclear cells in the presence of naproxen or etodolac in vitro . after an overnight incubation , the adherent cells were isolated and analyzed by flow cytometry for uptake of tamra stained cells from the patient . no increase in the uptake of the stained leukemic mononuclear cells by the normal adherent cells could be detected for etodolac compared to naproxen . to test the possibility that a metabolite of etodolac could be responsible for the effect , serum from the patient was collected free of drug , after receiving naproxen 375 mg bid for two days and after receiving etodolac 400 mg bid for two days , and tested in the above manner . no enhancement of phagocytosis of lymphocytes with etodolac serum was apparent . although not wishing to be bound by any particular theory , these data suggest that etodolac achieves its effect most likely by a novel mechanism of changing the compartmentalization of b cell cll leukemic lymphocytes . while the preferred embodiment of the invention has been illustrated and described , it will be appreciated that various changes can be made therein without departing from the spirit and scope of the invention .

the level of the leukemic lymphocytes in patients suffering from chronic lymphocytic leukemia is reduced by the administration of certain indole or carbazole compounds , such as the nonsteroidal anti - inflammatory drug etodolac or related indole or carbazol compounds .

the present invention is a remotely controllable model vehicle , including various audio and visual features providing entertainment and other functions as well . the present remotely controlled vehicle preferably makes use of conventional radio control model control systems for controlling at least the direction and speed of the vehicle , with various other systems installed in the vehicle as well . however , it will be seen that other types of control systems ( e . g ., electrical or mechanical cable , etc .) may be used if desired , at the expense of the longer range provided by radio control systems . the present vehicle includes an audio output system , with the apparatus being installable in various types of model vehicles , including boats . however , the present remotely controlled model vehicle is preferably in the form of a wheeled vehicle , particularly a model automobile , such as the automobile model 10 illustrated particularly in fig1 of the drawings . the automobile model 10 includes a series of additional electrical and electronic components , in addition to the control system noted above . the present vehicle 10 is intended for entertainment and display purposes , and includes at least one ( and preferably several different ) audio output systems , allowing the model 10 to be operated in an area at some distance from the operator , while playing music , an advertising message , etc . from the model 10 as it travels through the area and is seen and heard by persons in the vicinity . [ 0038 ] fig1 of the drawings illustrates the provision for a compact disc ( cd ) player in the model . such a cd deck 12 may be installed beneath the openable hood 14 of the model 10 , as shown . the volume beneath the hood of the model 10 provides sufficient volume for the installation of a relatively compact cd player 12 therein , essentially as shown . the model 10 may be provided in any practicable scale , but a scale of 1 : 12 results in a model having a length of approximately fifteen inches and a width of approximately six inches for an exemplary model 10 such as the late &# 39 ; 60s pontiac gto illustrated in the accompanying drawings . such a size provides more than sufficient interior volume for receivers , tuners , amplifiers , and speakers associated with various compact audio output systems . however , it will be seen that if further miniaturization of componentry is achieved , and / or fewer components are installed in the model , that the model may be constructed to a smaller scale , if so desired . alternatively , the present model vehicle may be scaled up to a larger scale , if so desired . preferably , the vehicle model 10 is representative of a somewhat “ customized ” car , and includes visual features such as larger rear tires 16 , “ wheelie ” bars 18 , etc . as desired . fig2 shows further functional and decorative features of the present model vehicle 10 , wherein a lighting system is provided . as all full size automobiles are equipped with headlights , the present model vehicle 10 may also be equipped with lighting means 20 as well . these lights 20 may be actuated by opening the miniature headlight doors 22 , as shown in fig2 of the drawings and as provided on the full scale vehicle upon which the model 10 is based . other headlight actuation means may be provided as desired ( e . g ., a switch / switches disposed on , within , or beneath the body , etc . ), but the actuation of the headlights 20 by means of the openable and closable headlight covers or doors 22 , adds a realistic touch to the model 10 . the lighting means 20 are preferably sufficiently bright and sufficiently narrowly focussed , as to serve as a flashlight or other supplemental lighting means as required . another “ customizing ” detail which may be provided with the vehicle 10 , is the installation of a pair of model longhorn steer horns 24 on the hood 14 . such a flamboyant detail adds considerably to the customized appearance of the model vehicle 10 , serving to draw further attention to the model , just as full scale customized vehicles attract attention . however , the model steer horns 24 may serve an additional purpose , due to their configuration . the horns 24 may be made to be removable from the hood 14 of the model 10 , if so desired , by means of a conventional plug and socket or other arrangement . the length of the horns 24 , when constructed to a size approximately as indicated in fig2 for a 1 : 12 scale automobile model , corresponds quite well to the length of a conventional portable telephone receiver . one end of the horns 24 may include a miniaturized microphone to serve as a mouthpiece , with the opposite end having a miniature speaker therein to serve as the earpiece for the phone . the central juncture of the two horns acts as the hand grip for the horn / phone 24 . the relatively small volume of the horns 24 need not contain all of the telephone componentry ( e . g ., keypad , amplifier , transmitter , etc . ), but may contain only a speaker and receiver , with the phone 24 being wired back to the keypad and other componentry contained within the larger volume of the model 10 . access may be gained to such componentry by removing the body shell from the underlying chassis , as is explained further below in describing various internal components . [ 0041 ] fig2 also illustrates another feature which may be provided with the present model 10 . the display area of the front license plate ( and rear plate , as well ) may be used as a clock or timer display 26 . the display 26 may indicate real time , or may serve as the readout for a radio broadcast frequency tuned on the onboard receiver ( described further below ), numerical readout for a telephone number selected , etc ., as desired and depending upon the electronics provided on board . as noted further above , the interior volume of a 1 : 12 scale model automobile provides a considerable amount of interior volume for the containment of various electronic systems . fig3 further illustrates provision for a tape cassette player ( designated with the cd player as component 12 , in fig5 of the drawings ), with access being gained by means of an openable grille 28 between the two headlight covers or doors 22 . a tape cassette 30 may be installed or removed conventionally in the cassette slot of a tape player installed immediately behind the grille 28 , with the grille 28 serving as the tape access door for the player , as is known in the art . [ 0043 ] fig4 provides a rear perspective view of the present model vehicle 10 , illustrating further details thereof . in fig4 the tail lights 32 of the model 10 are shown being activated , as by conventional pushbutton on / off switches therebehind . the tail lights 32 may include a conventional flasher circuit to allow them to pulsate or flash at regular intervals , and / or may be configured to provide a steady light when activated , as desired . the location of the rear license plate may also provide for a clock or timer display 26 , just as in the case of the front plate location shown in fig2 of the drawings . the two timers or clocks 26 may be connected together to provide identical displays , or may be independent units to show different information , as desired . [ 0044 ] fig5 provides a top plan view of the chassis 34 and various operational componentry of the present model vehicle 10 , with the body 36 removed therefrom . the front portion of the chassis 34 contains the cd and / or tape player unit or units 14 , as previously discussed further above . ( it should be noted that fig5 is schematic in nature , and that the componentry is not necessarily drawn to scale .) an am / fm radio receiver 38 may also be provided on board the vehicle 10 , if so desired . the heart of the system is a radio control receiver 40 , which receives appropriate signals from a conventional transmitter ( shown in fig7 ) and provides appropriate control signals to the drive motor 42 to control the speed of the model 10 and to a steering servo 44 for directional control of the model via an appropriate linkage 46 and the steerable wheel ( s ) 48 . the drive motor 42 drives the rear wheels 16 ( or wheel , in the case of a model having a single drive wheel ) by means of a gear train 50 and drive axle 52 . the gear ratio may be selected as desired to provide the desired acceleration and top speed characteristics , depending upon tire 16 diameter and motor 42 speed . various means may be used to control the rotational speed of the motor 42 , e . g ., variable frequency , voltage control , etc ., as is known in the art . typically , the motor 42 provides considerable counter electromotive force when power is reduced , thus providing sufficient braking action for a relatively lightweight model vehicle 10 . however , additional conventional braking means , e . g ., a disc brake ( not shown ) on the drive axle 52 , etc ., may be provided as required . the above described electronic componentry shown in fig1 through 5 is powered by a conventional battery pack 54 ( dry cells , rechargeable nicads , etc .) which may be placed on the chassis 34 in any convenient volume contained by the body 36 when installed . [ 0046 ] fig6 provides a bottom plan view of the chassis , illustrating the audio output for the present model vehicle 10 . in fig6 one or more audio speakers 56 ( preferably a plurality thereof ) is provided beneath the chassis 34 . these speakers 56 are preferably relatively small but powerful , with the weight of their magnets and coils being placed low in the chassis 34 for good weight distribution . a convenient location providing the required volume for such speakers 56 is in the area where the mufflers and fuel tank are located on a full scale automobile , as shown in fig6 . these areas contain only the speakers 56 in the present model vehicle 10 , and are preferably covered with a conventional protective speaker cloth or screen , as indicated by the crosshatched areas over the speakers 56 in fig6 . while the audio output of the speakers 56 is projected downwardly beneath the model 10 , the reflection of the sound output provides quite satisfactory audio output from the model 10 , particularly when the model is operated on a relatively hard surface ( tile , hardwood , vinyl flooring , etc .). [ 0047 ] fig7 provides a schematic view of the basic electronic componentry of the present model 10 and its operating systems . the componentry contained aboard the model 10 is shown generally to the right side of the drawing figure , and is interconnected by a series of lines representing appropriate electrical wiring between the components . it will be understood that this figure is not an electrical schematic , and that the interconnections are shown only generally ; considerably more wiring is required for operability . the receiver 40 receives radio frequency control signals from a transmitter 58 , shown to the left side of the drawing figure , via an antenna 60 . the antenna 60 is not illustrated in other drawing figures , as the preferred plastic body shell 36 is essentially transparent to radio frequencies , and accordingly , the receiver antenna 60 and other antennae required for telephone operation , etc . may be enclosed beneath the body shell 36 during operation of the model vehicle 10 . the receiver 40 controls the other componentry according to input from the transmitter 58 as desired by the operator of the transmitter 58 , as is conventionally known in the art of radio controlled model vehicles . for example , when the operator desires to turn the model 10 to the left or right , he / she may do so by means of the steering control 62 on the transmitter 58 . a digital proportional signal is sent from the transmitter 58 to the receiver 40 aboard the model 10 , which converts and relays the signal as required to the steering servo 44 , to drive the servo 44 in the selected direction , amplitude , and / or rate to accomplish the maneuver . in much the same manner , speed control of the drive motor 42 is accomplished by means of an appropriate speed control 64 on the transmitter 58 , e . g ., a signal selectively increasing or decreasing electrical frequency or voltage to the motor 42 , etc ., as is conventional in the art . in much the same manner , the transmitter 58 may be used to control at least the volume of the audio output , comprising the cd and tape players 12 and / or am / fm receiver 38 and speakers 56 . preferably , the audio media ( cd , tape , or am / fm radio output ) is selected by hand by the operator , e . g ., inserting a disc in the cd player or tape in the tape player , or tuning the radio as desired . however , the volume of the audio output is easily controlled by remote control means , as is known in the art , and may be accomplished using a volume control 66 on the transmitter 58 , as desired . in much the same manner , the model automobile 10 may be equipped with a horn ( shown schematically in fig7 as component 68 , with the lights 20 and 32 ) which may be selectively activated by means of a horn button control 70 on the transmitter 58 . while the lights 20 and 32 were described further above as being activated by hand , it will be seen that additional remotely actuated controls ( not shown ) are easily provided , for remote control of such accessories in addition to the horn 68 , if so desired . such remotely actuated on / off controls are well known , e . g ., by sending a pulse to a switching transistor for alternately actuating an on / off accessory ( e . g ., lights 20 and / or 32 ), or sending a continuous signal to maintain actuation of a device ( e . g ., horn 68 ). the horn 68 may represent a conventional automobile horn sound , or may be made to have virtually any sound desired ( e . g ., music , animal sound , such as a cow or steer ), etc ., by means of solid state audio chips commonly available or easily programmable with the sound desired . in conclusion , the present remotely controlled vehicle model provides a popular attraction for various gatherings , such as remote on site radio broadcasts at various venues , store openings , parties , etc . the use of radio control for the model provides significantly greater range over hard wire or cable control , for use in parking lots and other relatively large areas . yet , the audio systems incorporated with the present model require no additional bandwidth or licensing requirements than conventional radio control model equipment , as the audio signal is not transmitted between the transmitter and the model . rather , all audio equipment remains on board the model , with the only remote control required being for control of the volume of the preselected audio output . accordingly , the equipment and licensing requirements for the present model are relatively economical , being essentially identical to such requirements for other radio control model cars , boats , and aircraft . the inventive concept of providing all audio systems in the model itself , rather than transmitting the audio signal to the model , opens the availability of the present model to a much greater number of potential purchasers and users than would be the case with other configurations , and the present model with its audio system will enjoy widespread popularity not achievable with other mobile audio systems . it is to be understood that the present invention is not limited to the embodiments described above , but encompasses any and all embodiments within the scope of the following claims .

a remotely controllable model vehicle includes one or more audio output or playback devices onboard . the model vehicle may have a cassette player , cd player , and / or am / fm radio contained therein , for selectively providing audio output according to the desire of the operator of the model . conventional speed and directional control systems are also provided . the operator of the model selects the audio system to be used and installs the appropriate media or tunes the radio as desired , and operates the vehicle to provide a mobile audio program according to the travel of the model . additional functions may also be included . the present model vehicle is particularly valuable for advertising and entertainment wherever crowds may gather , such as remote live radio broadcast shows , store openings , parties , dances , etc .

referring to fig1 and 2 , an exemplary computed tomography ( ct ) imaging system 10 is shown as including a gantry 12 representative of a “ third generation ” ct scanner . one skilled in the art will appreciate that the present invention is applicable with other configured ct scanners , such as those generally referred to as first generation , second generation , fourth generation , fifth generation , sixth generation , etc . scanners . further , the present invention will be described to a ct detector cell geometry that is applicable with energy integrating cells as well as photon counting and / or energy discriminating cells . gantry 12 has an x - ray source 14 that projects a beam of x - rays 16 toward a detector array 18 on the opposite side of the gantry 12 . detector array 18 is formed by a plurality of detectors 20 which together sense the projected x - rays that pass through a medical patient 22 . each detector 20 produces an electrical signal that represents the intensity of an impinging x - ray beam and hence the attenuated beam as it passes through the patient 22 . during a scan to acquire x - ray projection data , gantry 12 and the components mounted thereon rotate about a center or plane of rotation 24 . rotation of gantry 12 and the operation of x - ray source 14 are governed by a control mechanism 26 of ct system 10 . control mechanism 26 includes an x - ray controller 28 that provides power and timing signals to an x - ray source 14 and a gantry motor controller 30 that controls the rotational speed and position of gantry 12 . a data acquisition system ( das ) 32 in control mechanism 26 samples analog data from detectors 20 and converts the data to digital signals for subsequent processing . an image reconstructor 34 receives sampled and digitized x - ray data from das 32 and performs high speed reconstruction . the reconstructed image is applied as an input to a computer 36 which stores the image in a mass storage device 38 . computer 36 also receives commands and scanning parameters from an operator via console 40 that has a keyboard . an associated cathode ray tube display 42 allows the operator to observe the reconstructed image and other data from computer 36 . the operator supplied commands and parameters are used by computer 36 to provide control signals and information to das 32 , x - ray controller 28 and gantry motor controller 30 . in addition , computer 36 operates a table motor controller 44 which controls a motorized table 46 to position patient 22 and gantry 12 . particularly , table 46 moves portions of patient 22 through a gantry opening 48 . as alluded to above , the present invention is directed to a ct detector comprised of individual detector cells or pixels . these cells are defined by an active surface or area and convert x - rays into a form that may be processed for image reconstruction . in this regard , the cells may , through a scintillator - photodiode combination , convert x - rays to light , detect the light , and provide an electrical signal to a data acquisition system for image reconstruction . the present invention , however , is not limited to scintillator - photodiode constructions . that is , as will be illustrated below , the present invention is also applicable with direct conversion detector cells that directly convert x - rays to electrical signal . additionally , the invention is applicable with conventional energy integrating cells as well as photon counting / energy discriminating cells . in a conventional integrating cell , the output of the scintillator or other x - ray conversion component is the product of the energy of the x - rays received and the number of x - rays received . thus , there is no separation of the number of x - rays received from the energy level of the individual x - rays . thus , it is possible , with energy integrating detector cells , for one cell to provide an output equal to that of another cell despite the one cell receiving more x - rays than the another cell . this equality in outputs is a result of the energy level of the x - rays received by the “ another ” cell being greater than the x - rays received by the “ one ” cell . to provide photon count and / or energy discriminating information , ct detectors are increasingly being formed of energy discriminating and / or photon counting cells . these ed / pc detectors are capable of providing photon count and energy level information . despite the differences between conventional energy integrating detectors and ed / pc detectors , there remains a need to improve spatial coverage / sampling density in both cases . therefore , the present invention is applicable with both general types of detectors and , in fact , is not limited to a particular type of detector . additionally , this invention is not limited to detectors for ct systems . to achieve a ct detector with improved spatial coverage , detector cells with diagonal edges or perimeter walls is proposed . an exemplary construction is illustrated in fig5 . as shown , a ct detector 20 is defined by an array or matrix 50 of detector cells 52 . as shown , each detector cell 52 has a non - rectangular shape . this non - rectangularity increases the spatial coverage of the detector in the z direction . despite the non - rectangularity in the geometry of each detector cell , as illustrated , the detector cells in each column ( channel ) are uniformly aligned with one another . this eases the fabrication process relative to the staggered - channel approach illustrated in fig2 . as shown in fig5 , most of the detector cells are similarly shaped . however , because of the non - rectangularity of the detector cells , irregular shaped sections of the matrix must be accounted for . this is achieved by specially - shaped cells 53 that are constructed to “ fill ” the matrix . a skilled artisan will appreciate that each “ specially - shaped ” cell 53 may include multiple cells to fill the matrix . referring now to fig6 , a single exemplary detector cell 52 according to one aspect of the invention is shown . the detector cell 52 has an active area 54 that is generally parallel to the plane of x - ray projection ( not shown ) during data acquisition . in the exemplary illustration , the active area 54 is defined by four perimeter walls or edges 56 . as shown , the exemplary cell has the shape of a rhombus . in this regard , the angle , α 1 , formed by the intersection of edges 56 ( a ) and 56 ( b ) is acute . likewise , the angle , α 2 , between edges 56 ( c ) and 56 ( d ), is acute . conversely , the angle , β 1 , at the intersection of edges 56 ( a ) and 56 ( c ) and the angle , β 2 , formed at the intersection of 56 ( b ) and 56 ( d ) are each obtuse . in short , edges 56 ( b ) and 56 ( c ) are not perpendicular to the plane of gantry rotation as in conventional rectangular shaped cells ; however , channel edges 56 ( a ) and 56 ( d ) are perpendicular to the plane of gantry rotation . in this regard , the diagonal edges 56 ( b ) and 56 ( c ) extend in the x - z plane whereas edges 56 ( a ) and 56 ( d ) extend only in the z direction . the geometry of the detector cell can be more generally described as follows . as shown , the z boundaries of the detector cell are formed by straight diagonal edges . thus , with the cell pitch in the z direction referenced “ a ” and the cell pitch in the x direction referenced “ b ”, the diagonal boundary makes an angle α with the x axis such that : for a = b , alpha is approximately 26 . 5 degrees . however , one skilled in the art will appreciate that the present invention is not limited to the case where a = b . for example , in one preferred embodiment , b = a √{ square root over ( 3 )}/ 2 . in this case , which was found to be particularly optimal for sampling density , alpha is 30 degrees . with an alpha of 30 degrees , a hexagonal lattice detector matrix or array would result . other values for alpha are of course contemplated . as a result of edges 56 ( b ) and 56 ( c ) being in the x - z plane , the sampling density of the overall detector is improved , as illustrated in fig7 . specifically , as illustrated , the z axis profile of a conventional rectangular detector cell is enveloped by the collective profiles of the diagonally edged cells illustrated in fig5 - 6 . not only does the present invention provide a detector cell geometry with improved spatial coverage , it does so without requiring significant variants to conventional detector fabrication techniques . specifically , the detector cell illustrated in fig6 can be fabricated using two cuts in a cutting process . that is , after making a straight cut , i . e ., edges 56 ( a ) and 56 ( d ), the wafer or bulk of x - ray converting material need only be rotated acutely a fixed degree of rotation followed by a second cut . thus , instead of making four ninety degree cuts , a detector according to one embodiment of the present invention can be formed with two ninety degree cuts and two acute ( less than ninety degree ) diagonal cuts . this can be done without requiring a significant change to a typical cutting setup . referring now to fig8 , a ct detector 20 having an array 50 of detector cells 52 shaped according to another embodiment of the present invention is shown . in this embodiment , each of the detector cells 52 is diamond - shaped . thus , four diagonal edges rather than two , as in the cell shown in fig6 , define each cell . one advantage of the cell geometry illustrated in fig8 is that there is substantial sample overlap in the x and z directions . moreover , the z axis profile is narrower than that of conventional rectangular detector cells . one skilled in the art will appreciate that fabrication of the diamond - shaped detector cell can be carried out with a conventional wire - saw process . referring to fig9 , the axial profile of a diamond - shaped cell relative to a rectangular - shaped cell is illustrated . as shown , notwithstanding the more narrow profile , the sampling coverage of the diamond - shaped cell is equal to that of a conventional rectangular - shaped cell . the present invention may be incorporated in medical scanners , such as that shown in fig3 - 4 , or non - medical scanners . referring now to fig1 , package / baggage inspection system 100 incorporating the present invention includes a rotatable gantry 102 having an opening 104 therein through which packages or pieces of baggage may pass . the rotatable gantry 102 houses a high frequency electromagnetic energy source 106 as well as a detector assembly 108 having detector cells similar to those described herein . a conveyor system 110 is also provided and includes a conveyor belt 112 supported by structure 114 to automatically and continuously pass packages or baggage pieces 116 through opening 104 to be scanned . objects 116 are fed through opening 104 by conveyor belt 112 , imaging data is then acquired , and the conveyor belt 112 removes the packages 116 from opening 104 in a controlled and continuous manner . as a result , postal inspectors , baggage handlers , and other security personnel may non - invasively inspect the contents of packages 116 for explosives , knives , guns , contraband , etc . as noted above , the present invention is not limited to a particular type of detector cell . in this regard , it is contemplated that the invention can be applied to energy integrating , photon counting , or energy discriminating constructions . thus , the invention is applicable with scintillators or direct conversion x - ray conversion material , charge collectors , such as photodiodes , charge - storage devices , charge collection anodes or cathodes , as well as , anti - scatter , collimator , and reflector grids . as described herein and appreciable by one skilled in the art , the present invention provides a detector cell geometry that enables overlapping samples in the z and / or x directions without requiring additional data acquisition system channels . moreover , the active area of each cell is equivalent to those of conventional detector cells . the detector cells can be fabricated with slight modification of a conventional wire - saw process ; thus , fabrication costs are comparable to conventional detector cells . moreover , since the diagonal and diamond - shaped cells described herein can be fabricated using wire - saw cuts of the same pitch , only a single wire - saw setup is required . additionally , the detector cell is applicable with x direction flying - focal - spot deflection techniques , e . g ., x - direction wobble , for improved sampling in the x direction . further , for the embodiment illustrated in fig6 , the channel edges of each cell are aligned with the channel edges of each other detector cell in the channel . thus , a conventional 1d scatter grid may be used . also , one skilled in the art will appreciate that the present invention is applicable with czt photon counting detectors . in such a case , the scintillator is not diced in a manner described above . the charge collection electrodes are formed with overlapping rows . therefore , the invention includes a detector cell having a generally planar active surface and a set of perimeter walls defining the generally planar active surface . the cell is constructed such that an angle of intersection formed between a pair of perimeter walls is acute . a detector assembly is also disclosed . the assembly comprises a detector array having a plurality of detectors and is arranged along an x direction and a z direction perpendicular to the x direction . at least one detector of the plurality of detectors has one edge in an x - z plane . the invention is also embodied in a ct system . the ct system includes a gantry that rotates about a plane of rotation , and an x - ray source disposed in the gantry and designed to project an x - ray beam . the system further has an x - ray detector situated parallel to the plane of gantry rotation and disposed in the gantry . the x - ray detector is configured to convert radiation projected by the x - ray source and attenuated by a subject to be imaged into a form that may be processed to reconstruct an image of the subject . the x - ray detector includes an array of detector cells , wherein each detector cell has a rhombus - shaped active area . the present invention has been described in terms of the preferred embodiment , and it is recognized that equivalents , alternatives , and modifications , aside from those expressly stated , are possible and within the scope of the appending claims .

a ct detector cell is constructed to have diagonally oriented perimeter walls . with such a construction , the resulting ct detector comprised of such detector cells has improved spatial coverage . the number of detector channels is also not increased despite the increase in spatial coverage . moreover , the detector cells can be constructed without much variance from conventional fabrication techniques .

reference is made to fig1 a - 1e which schematically illustrate various stages of a cell division process . fig1 a illustrates a cell 10 at its normal geometry , which can be generally spherical ( as illustrated in the drawings ), ellipsoidal , cylindrical , “ pancake - like ” or any other cell geometry , as is known in the art . fig1 b - 1d illustrate cell 10 during different stages of its division process , which results in the formation of two new cells 18 and 20 , shown in fig1 e . as shown in fig1 b - 1d , the division process of cell 10 is characterized by a slowly growing cleft 12 which gradually separates cell 10 into two units , namely sub - cells 14 and 16 , which eventually evolve into new cells 18 and 20 ( fig1 e ). a shown specifically in fig1 d , the division process is characterized by a transient period during which the structure of cell 10 is basically that of the two sub - cells 14 and 16 interconnected by a narrow “ bridge ” 22 containing cell material ( cytoplasm surrounded by cell membrane ). reference is now made to fig2 a and 2b , which schematically illustrate non - dividing cell 10 being subjected to an electric field produced by applying an alternating electric potential , at a relatively low frequency and at a relatively high frequency , respectively . cell 10 includes intracellular organelles , e . g ., a nucleus 30 . alternating electric potential is applied across electrodes 28 and 32 that can be attached externally to a patient at a predetermined region , e . g ., in the vicinity of the tumor being treated . when cell 10 is under natural conditions , i . e ., part of a living tissue , it is disposed in a conductive environment ( hereinafter referred to as a “ volume conductor ”) consisting mostly of electrolytic inter - cellular liquid . when an electric potential is applied across electrodes 28 and 32 , some of the field lines of the resultant electric field ( or the current induced in the tissue in response to the electric field ) penetrate the cell 10 , while the rest of the field lines ( or induced current ) flow in the surrounding medium . the specific distribution of the electric field lines , which is substantially consistent with the direction of current flow in this instance , depends on the geometry and the electric properties of the system components , e . g ., the relative conductivities and dielectric constants of the system components , that can be frequency dependent . for low frequencies , e . g ., frequencies lower than 10 khz , the conductance properties of the components completely dominate the current flow and the field distribution , and the field distribution is generally as depicted in fig2 a . at higher frequencies , e . g ., at frequencies of between 10 khz and 1 mhz , the dielectric properties of the components becomes more significant and eventually dominate the field distribution , resulting in field distribution lines as depicted generally in fig2 b . for constant ( i . e ., dc ) electric fields or relatively low frequency alternating electric fields , for example , frequencies under 10 khz , the dielectric properties of the various components are not significant in determining and computing the field distribution . therefore , as a first approximation , with regard to the electric field distribution , the system can be reasonably represented by the relative impedances of its various components . using this approximation , the intercellular ( i . e ., extracellular ) fluid and the intracellular fluid each has a relatively low impedance , while the cell membrane 11 has a relatively high impedance . thus , under low frequency conditions , only a fraction of the electric field lines ( or currents induced by the electric field ) penetrate membrane 11 of the cell 10 . at relatively high frequencies ( e . g ., 10 khz - 1 mhz ), in contrast , the impedance of membrane 11 relative to the intercellular and intracellular fluids decreases , and thus , the fraction of currents penetrating the cells increases significantly . it should be noted that at very high frequencies , i . e ., above 1 mhz , the membrane capacitance can short the membrane resistance and , therefore , the total membrane resistance can become negligible . in any of the embodiments described above , the electric field lines ( or induced currents ) penetrate cell 10 from a portion of the membrane 11 closest to one of the electrodes generating the current , e . g ., closest to positive electrode 28 ( also referred to herein as “ source ”). the current flow pattern across cell 10 is generally uniform because , under the above approximation , the field induced inside the cell is substantially homogeneous . the currents exit cell 10 through a portion of membrane 11 closest to the opposite electrode , e . g ., negative electrode 32 ( also referred to herein as “ sink ”). the distinction between field lines and current flow can depend on a number of factors , for example , on the frequency of the applied electric potential and on whether electrodes 28 and 32 are electrically insulated . for insulated electrodes applying a dc or low frequency alternating voltage , there is practically no current flow along the lines of the electric field . at higher frequencies , the displacement currents are induced in the tissue due to charging and discharging of the electrode insulation and the cell membranes ( which act as capacitors to a certain extent ), and such currents follow the lines of the electric field . fields generated by non - insulated electrodes , in contrast , always generate some form of current flow , specifically , dc or low frequency alternating fields generate conductive current flow along the field lines , and high frequency alternating fields generate both conduction and displacement currents along the field lines . it should be appreciated , however , that movement of polarizable intracellular organelles according to the present invention ( as described below ) is not dependent on actual flow of current and , therefore , both insulated and non - insulated electrodes can be used efficiently . advantages of insulated electrodes include lower power consumption , less heating of the treated regions , and improved patient safety . according to one exemplary embodiment of the present invention , the electric fields that are used are alternating fields having frequencies that are in the range from about 50 khz to about 500 khz , and preferably from about 100 khz to about 300 khz . for ease of discussion , these type of electric fields are also referred to below as “ tc fields ”, which is an abbreviation of “ tumor curing electric fields ”, since these electric fields fall into an intermediate category ( between high and low frequency ranges ) that have bio - effective field properties while having no meaningful stimulatory and thermal effects . these frequencies are sufficiently low so that the system behavior is determined by the system &# 39 ; s ohmic ( conductive ) properties but sufficiently high enough not to have any stimulation effect on excitable tissues . such a system consists of two types of elements , namely , the intercellular , or extracellular fluid , or medium and the individual cells . the intercellular fluid is mostly an electrolyte with a specific resistance of about 40 - 100 ohm * cm . as mentioned above , the cells are characterized by three elements , namely ( 1 ) a thin , highly electric resistive membrane that coats the cell ; ( 2 ) internal cytoplasm that is mostly an electrolyte that contains numerous macromolecules and micro - organelles , including the nucleus ; and ( 3 ) membranes , similar in their electric properties to the cell membrane , cover the micro - organelles . when this type of system is subjected to the present tc fields ( e . g ., alternating electric fields in the frequency range of 100 khz - 300 khz ) most of the lines of the electric field and currents tend away from the cells because of the high resistive cell membrane and therefore the lines remain in the extracellular conductive medium . in the above recited frequency range , the actual fraction of electric field or currents that penetrates the cells is a strong function of the frequency . fig2 schematically depicts the resulting field distribution in the system . as illustrated , the lines of force , which also depict the lines of potential current flow across the cell volume mostly in parallel with the undistorted lines of force ( the main direction of the electric field ). in other words , the field inside the cells is mostly homogeneous . in practice , the fraction of the field or current that penetrates the cells is determined by the cell membrane impedance value relative to that of the extracellular fluid . since the equivalent electric circuit of the cell membrane is that of a resistor and capacitor in parallel , the impedance is a function of the frequency . the higher the frequency , the lower the impedance , the larger the fraction of penetrating current and the smaller the field distortion ( rotshenker s . & amp ; y . palti , changes in fraction of current penetrating an axon as a function of duration of stimulating pulse , j . theor . biol . 41 ; 401 - 407 ( 1973 ). as previously mentioned , when cells are subjected to relatively weak electric fields and currents that alternate at high frequencies , such as the present tc fields having a frequency in the range of 50 khz - 500 khz , they have no effect on the non - dividing cells . while the present tc fields have no detectable effect on such systems , the situation becomes different in the presence of dividing cells . reference is now made to fig3 a - 3c which schematically illustrate the electric current flow pattern in cell 10 during its division process , under the influence of alternating fields ( tc fields ) in the frequency range from about 100 khz to about 300 khz in accordance with one exemplary embodiment . the field lines or induced currents penetrate cell 10 through a part of the membrane of sub - cell 16 closer to electrode 28 . however , they do not exit through the cytoplasm bridge 22 that connects sub - cell 16 with the newly formed yet still attached sub - cell 14 , or through a part of the membrane in the vicinity of the bridge 22 . instead , the electric field or current flow lines — that are relatively widely separated in sub - cell 16 — converge as they approach bridge 22 ( also referred to as “ neck ” 22 ) and , thus , the current / field line density within neck 22 is increased dramatically . a “ mirror image ” process takes place in sub - cell 14 , whereby the converging field lines in bridge 22 diverge as they approach the exit region of sub - cell 14 . it should be appreciated by persons skilled in the art that homogeneous electric fields do not exert a force on electrically neutral objects , i . e ., objects having substantially zero net charge , although such objects can become polarized . however , under a non - uniform , converging electric field , as shown in fig3 a - 3c , electric forces are exerted on polarized objects , moving them in the direction of the higher density electric field lines . it will be appreciated that the concentrated electric field that is present in the neck or bridge area in itself exerts strong forces on charges and natural dipoles and can disrupt structures that are associated therewith . one will understand that similar net forces act on charges in an alternating field , again in the direction of the field of higher intensity . in the configuration of fig3 a and 3b , the direction of movement of polarized and charged objects is towards the higher density electric field lines , i . e ., towards the cytoplasm bridge 22 between sub - cells 14 and 16 . it is known in the art that all intracellular organelles , for example , nuclei 24 and 26 of sub - cells 14 and 16 , respectively , are polarizable and , thus , such intracellular organelles are electrically forced in the direction of the bridge 22 . since the movement is always from lower density currents to the higher density currents , regardless of the field polarity , the forces applied by the alternating electric field to organelles , such as nuclei 24 and 26 , are always in the direction of bridge 22 . a comprehensive description of such forces and the resulting movement of macromolecules of intracellular organelles , a phenomenon referred to as “ dielectrophoresis ” is described extensively in literature , e . g ., in c . l . asbury & amp ; g . van den engh , biophys . j . 74 , 1024 - 1030 , 1998 , the disclosure of which is hereby incorporated by reference in its entirety . the movement of the organelles 24 and 26 towards the bridge 22 disrupts the structure of the dividing cell , change the concentration of the various cell constituents and , eventually , the pressure of the converging organelles on bridge membrane 22 results in the breakage of cell membrane 11 at the vicinity of the bridge 22 , as shown schematically in fig3 c . the ability to break membrane 11 at bridge 22 and to otherwise disrupt the cell structure and organization can be enhanced by applying a pulsating ac electric field , rather than a steady ac field . when a pulsating field is applied , the forces acting on organelles 24 and 26 have a “ hammering ” effect , whereby pulsed forces beat on the intracellular organelles towards the neck 22 from both sub - cells 14 and 16 , thereby increasing the probability of breaking cell membrane 11 in the vicinity of neck 22 . a very important element , which is very susceptible to the special fields that develop within the dividing cells is the microtubule spindle that plays a major role in the division process . in fig4 , a dividing cell 10 is illustrated , at an earlier stage as compared to fig3 a and 3b , under the influence of external tc fields ( e . g ., alternating fields in the frequency range of about 100 khz to about 300 khz ), generally indicated as lines 100 , with a corresponding spindle mechanism generally indicated at 120 . the lines 120 are microtubules that are known to have a very strong dipole moment . this strong polarization makes the tubules , as well as other polar macromolecules and especially those that have a specific orientation within the cells or its surrounding , susceptible to electric fields . their positive charges are located at the two centrioles while two sets of negative poles are at the center of the dividing cell and the other pair is at the points of attachment of the microtubules to the cell membrane , generally indicated at 130 . this structure forms sets of double dipoles and therefore they are susceptible to fields of different directions . it will be understood that the effect of the tc fields on the dipoles does not depend on the formation of the bridge ( neck ) and thus , the dipoles are influenced by the tc fields prior to the formation of the bridge ( neck ). since the present apparatus ( as will be described in greater detail below ) utilizes insulated electrodes , the above - mentioned negative effects obtained when conductive electrodes are used , i . e ., ion concentration changes in the cells and the formation of harmful agents by electrolysis , do not occur when the present apparatus is used . this is because , in general , no actual transfer of charges takes place between the electrodes and the medium and there is no charge flow in the medium where the currents are capacitive , i . e ., are expressed only as rotation of charges , etc . turning now to fig5 , the tc fields described above that have been found to advantageously destroy tumor cells are generated by an electronic apparatus 200 . fig5 is a simple schematic diagram of the electronic apparatus 200 illustrating the major components thereof . the electronic apparatus 200 generates the desired electric signals ( tc signals ) in the shape of waveforms or trains of pulses . the apparatus 200 includes a generator 210 and a pair of conductive leads 220 that are attached at one end thereof to the generator 210 . the opposite ends of the leads 220 are connected to insulated conductors 230 that are activated by the electric signals ( e . g ., waveforms ). the insulated conductors 230 are also referred to hereinafter as isolects 230 . optionally and according to another exemplary embodiment , the apparatus 200 includes a temperature sensor 240 and a control box 250 which are both added to control the amplitude of the electric field generated so as not to generate excessive heating in the area that is treated . the generator 210 generates an alternating voltage waveform at frequencies in the range from about 50 khz to about 500 khz ( preferably from about 100 khz to about 300 khz ) ( i . e ., the tc fields ). the required voltages are such that the electric field intensity in the tissue to be treated is in the range of about 0 . 1 v / cm to about 10 v / cm . to achieve this field , the actual potential difference between the two conductors in the isolects 230 is determined by the relative impedances of the system components , as described below . when the control box 250 is included , it controls the output of the generator 210 so that it will remain constant at the value preset by the user or the control box 250 sets the output at the maximal value that does not cause excessive heating , or the control box 250 issues a warning or the like when the temperature ( sensed by temperature sensor 240 ) exceeds a preset limit . the leads 220 are standard isolated conductors with a flexible metal shield , preferably grounded so that it prevents the spread of the electric field generated by the leads 220 . the isolects 230 have specific shapes and positioning so as to generate an electric field of the desired configuration , direction , and intensity at the target volume and only there so as to focus the treatment . the specifications of the apparatus 200 as a whole and its individual components are largely influenced by the fact that at the frequency of the present tc fields ( 50 khz - 500 khz ), living systems behave according to their “ ohmic ”, rather than their dielectric properties . the only elements in the apparatus 200 that behave differently are the insulators of the isolects 230 ( see fig7 - 9 ). the isolects 200 consist of a conductor in contact with a dielectric that is in contact with the conductive tissue thus forming a capacitor . the details of the construction of the isolects 230 is based on their electric behavior that can be understood from their simplified electric circuit when in contact with tissue as generally illustrated in fig6 . in the illustrated arrangement , the potential drop or the electric field distribution between the different components is determined by their relative electric impedance , i . e ., the fraction of the field on each component is given by the value of its impedance divided by the total circuit impedance . for example , the potential drop on element δ v a = a /( a + b + c + d + e ). thus , for dc or low frequency ac , practically all the potential drop is on the capacitor ( that acts as an insulator ). for relatively very high frequencies , the capacitor practically is a short and therefore , practically all the field is distributed in the tissues . at the frequencies of the present tc fields ( e . g ., 50 khz to 500 khz ), which are intermediate frequencies , the impedance of the capacitance of the capacitors is dominant and determines the field distribution . therefore , in order to increase the effective voltage drop across the tissues ( field intensity ), the impedance of the capacitors is to be decreased ( i . e ., increase their capacitance ). this can be achieved by increasing the effective area of the “ plates ” of the capacitor , decrease the thickness of the dielectric or use a dielectric with high dielectric constant . in order to optimize the field distribution , the isolects 230 are configured differently depending upon the application in which the isolects 230 are to be used . there are two principle modes for applying the present electric fields ( tc fields ). first , the tc fields can be applied by external isolects and second , the tc fields can be applied by internal isolects . electric fields ( tc fields ) that are applied by external isolects can be of a local type or widely distributed type . the first type includes , for example , the treatment of skin tumors and treatment of lesions close to the skin surface . fig7 illustrates an exemplary embodiment where the isolects 230 are incorporated in a skin patch 300 . the skin patch 300 can be a self - adhesive flexible patch with one or more pairs of isolects 230 . the patch 300 includes internal insulation 310 ( formed of a dielectric material ) and the external insulation 260 and is applied to skin surface 301 that contains a tumor 303 either on the skin surface 301 or slightly below the skin surface 301 . tissue is generally indicated at 305 . to prevent the potential drop across the internal insulation 310 to dominate the system , the internal insulation 310 must have a relatively high capacity . this can be achieved by a large surface area ; however , this may not be desired as it will result in the spread of the field over a large area ( e . g ., an area larger than required to treat the tumor ). alternatively , the internal insulation 310 can be made very thin and / or the internal insulation 310 can be of a high dielectric constant . as the skin resistance between the electrodes ( labeled as a and e in fig6 ) is normally significantly higher than that of the tissue ( labeled as c in fig6 ) underneath it ( 1 - 10 kω vs . 0 . 1 - 1 kω ), most of the potential drop beyond the isolects occurs there . to accommodate for these impedances ( z ), the characteristics of the internal insulation 310 ( labeled as b and d in fig6 ) should be such that they have impedance preferably under 100 kω at the frequencies of the present tc fields ( e . g ., 50 khz to 500 khz ). for example , if it is desired for the impedance to be about 10 k ohms or less , such that over 1 % of the applied voltage falls on the tissues , for isolects with a surface area of 10 mm 2 , at frequencies of 200 khz , the capacity should be on the order of 10 − 10 f ., which means that using standard insulations with a dielectric constant of 2 - 3 , the thickness of the insulating layer 310 should be about 50 - 100 microns . an internal field 10 times stronger would be obtained with insulators with a dielectric constant of about 20 - 50 . using an insulating material with a high dielectric constant increases the capacitance of the electrodes , which results in a reduction of the electrodes &# 39 ; impedance to the ac signal that is applied by the generator 1 ( shown in fig5 ). because the electrodes a , e are wired in series with the target tissue c , as shown in fig6 , this reduction in impedance reduces the voltage drop in the electrodes , so that a larger portion of the applied ac voltage appears across the tissue c . since a larger portion of the voltage appears across the tissue , the voltage that is being applied by the generator 1 can be advantageously lowered for a given field strength in the tissue . the desired field strength in the tissue being treated is preferably between about 0 . 1 v / cm and about 10 v / cm , and more preferably between about 2 v / cm and 3 v / cm or between about 1 v / cm and about 5 v / cm . if the dielectric constant used in the electrode is sufficiently high , the impedance of the electrodes a , e drops down to the same order of magnitude as the series combination of the skin and tissue b , c , d . one example of a suitable material with an extremely high dielectric constant is cacu 3 ti 4 o 12 , which has a dielectric constant of about 11 , 000 ( measured at 100 khz ). when the dielectric constant is this high , useful fields can be obtained using a generator voltage that is on the order of a few tens of volts . since the thin insulating layer can be very vulnerable , etc ., the insulation can be replaced by very high dielectric constant insulating materials , such as titanium dioxide ( e . g ., rutile ), the dielectric constant can reach values of about 200 . there a number of different materials that are suitable for use in the intended application and have high dielectric constants . for example , some materials include : lithium niobate ( linbo 3 ), which is a ferroelectric crystal and has a number of applications in optical , pyroelectric and piezoelectric devices ; yttrium iron garnet ( yig ) is a ferromagnetic crystal and magneto - optical devices , e . g ., optical isolator can be realized from this material ; barium titanate ( batio 3 ) is a ferromagnetic crystal with a large electro - optic effect ; potassium tantalate ( ktao 3 ) which is a dielectric crystal ( ferroelectric at low temperature ) and has very low microwave loss and tunability of dielectric constant at low temperature ; and lithium tantalate ( litao 3 ) which is a ferroelectric crystal with similar properties as lithium niobate and has utility in electro - optical , pyroelectric and piezoelectric devices . insulator ceramics with high dielectric constants may also be used , such as a ceramic made of a combination of lead magnesium niobate and lead titanate . it will be understood that the aforementioned exemplary materials can be used in combination with the present device where it is desired to use a material having a high dielectric constant . one must also consider another factor that affects the effective capacity of the isolects 230 , namely the presence of air between the isolects 230 and the skin . such presence , which is not easy to prevent , introduces a layer of an insulator with a dielectric constant of 1 . 0 , a factor that significantly lowers the effective capacity of the isolects 230 and neutralizes the advantages of the titanium dioxide ( rutile ), etc . to overcome this problem , the isolects 230 can be shaped so as to conform with the body structure and / or ( 2 ) an intervening filler 270 ( as illustrated in fig1 c ), such as a gel , that has high conductance and a high effective dielectric constant , can be added to the structure . the shaping can be pre - structured ( see fig1 a ) or the system can be made sufficiently flexible so that shaping of the isolects 230 is readily achievable . the gel can be contained in place by having an elevated rim as depicted in fig1 c and 10 c ′. the gel can be made of hydrogels , gelatins , agar , etc ., and can have salts dissolved in it to increase its conductivity . fig1 a - 10 c ′ illustrate various exemplary configurations for the isolects 230 . the exact thickness of the gel is not important so long as it is of sufficient thickness that the gel layer does not dry out during the treatment . in one exemplary embodiment , the thickness of the gel is about 0 . 5 mm to about 2 mm . preferably , the gel has high conductivity , is tacky , and is biocompatible for extended periods of time . one suitable gel is ag603 hydrogel , which is available from amgel technologies , 1667 s . mission road , fallbrook , calif . 92028 - 4115 , usa . in order to achieve the desirable features of the isolects 230 , the dielectric coating of each should be very thin , for example from between 1 - 50 microns . since the coating is so thin , the isolects 230 can easily be damaged mechanically or undergo dielectric breakdown . this problem can be overcome by adding a protective feature to the isolect &# 39 ; s structure so as to provide desired protection from such damage . for example , the isolect 230 can be coated , for example , with a relatively loose net 340 that prevents access to the surface but has only a minor effect on the effective surface area of the isolect 230 ( i . e ., the capacity of the isolects 230 ( cross section presented in fig1 b ). the loose net 340 does not affect the capacity and ensures good contact with the skin , etc . the loose net 340 can be formed of a number of different materials ; however , in one exemplary embodiment , the net 340 is formed of nylon , polyester , cotton , etc . alternatively , a very thin conductive coating 350 can be applied to the dielectric portion ( insulating layer ) of the isolect 230 . one exemplary conductive coating is formed of a metal and more particularly of gold . the thickness of the coating 350 depends upon the particular application and also on the type of material used to form the coating 350 ; however , when gold is used , the coating has a thickness from about 0 . 1 micron to about 0 . 1 mm . furthermore , the rim illustrated in fig1 can also provide some mechanical protection . however , the capacity is not the only factor to be considered . the following two factors also influence how the isolects 230 are constructed . the dielectric strength of the internal insulating layer 310 and the dielectric losses that occur when it is subjected to the tc field , i . e ., the amount of heat generated . the dielectric strength of the internal insulation 310 determines at what field intensity the insulation will be “ shorted ” and cease to act as an intact insulation . typically , insulators , such as plastics , have dielectric strength values of about 100v per micron or more . as a high dielectric constant reduces the field within the internal insulator 310 , a combination of a high dielectric constant and a high dielectric strength gives a significant advantage . this can be achieved by using a single material that has the desired properties or it can be achieved by a double layer with the correct parameters and thickness . in addition , to further decreasing the possibility that the insulating layer 310 will fail , all sharp edges of the insulating layer 310 should be eliminated as by rounding the corners , etc ., as illustrated in fig1 d using conventional techniques . fig8 and 9 illustrate a second type of treatment using the isolects 230 , namely electric field generation by internal isolects 230 . a body to which the isolects 230 are implanted is generally indicated at 311 and includes a skin surface 313 and a tumor 315 . in this embodiment , the isolects 230 can have the shape of plates , wires or other shapes that can be inserted subcutaneously or a deeper location within the body 311 so as to generate an appropriate field at the target area ( tumor 315 ). it will also be appreciated that the mode of isolects application is not restricted to the above descriptions . in the case of tumors in internal organs , for example , liver , lung , etc ., the distance between each member of the pair of isolects 230 can be large . the pairs can even by positioned opposite sides of a torso 410 , as illustrated in fig1 . the arrangement of the isolects 230 in fig1 is particularly useful for treating a tumor 415 associated with lung cancer or gastro - intestinal tumors . in this embodiment , the electric fields ( tc fields ) spread in a wide fraction of the body . in order to avoid overheating of the treated tissues , a selection of materials and field parameters is needed . the isolects insulating material should have minimal dielectric losses at the frequency ranges to be used during the treatment process . this factor can be taken into consideration when choosing the particular frequencies for the treatment . the direct heating of the tissues will most likely be dominated by the heating due to current flow ( given by the i * r product ). in addition , the isolect ( insulated electrode ) 230 and its surroundings should be made of materials that facilitate heat losses and its general structure should also facilitate head losses , i . e ., minimal structures that block heat dissipation to the surroundings ( air ) as well as high heat conductivity . using larger electrodes also minimizes the local sensation of heating , since it spreads the energy that is being transferred into the patient over a larger surface area . preferably , the heating is minimized to the point where the patient &# 39 ; s skin temperature never exceeds about 39 ° c . another way to reduce heating is to apply the field to the tissue being treated intermittently , by applying a field with a duty cycle between about 20 % and about 50 % instead of using a continuous field . for example , to achieve a duty cycle of 33 %, the field would be repetitively switched on for one second , then switched off for two seconds . preliminary experiments have shown that the efficacy of treatment using a field with a 33 % duty cycle is roughly the same as for a field with a duty cycle of 100 %. in alternative embodiments , the field could be switched on for one hour then switched off for one hour to achieve a duty cycle of 50 %. of course , switching at a rate of once per hour would not help minimize short - term heating . on the other hand , it could provide the patient with a welcome break from treatment . the effectiveness of the treatment can be enhanced by an arrangement of isolects 230 that focuses the field at the desired target while leaving other sensitive areas in low field density ( i . e ., protected areas ). the proper placement of the isolects 230 over the body can be maintained using any number of different techniques , including using a suitable piece of clothing that keeps the isolects at the appropriate positions . fig1 illustrates such an arrangement in which an area labeled as “ p ” represents a protected area . the lines of field force do not penetrate this protected area and the field there is much smaller than near the isolects 230 where target areas can be located and treated well . in contrast , the field intensity near the four poles is very high . the following example serves to illustrate an exemplary application of the present apparatus and application of tc fields ; however , this example is not limiting and does not limit the scope of the present invention in any way . to demonstrate the effectiveness of electric fields having the above described properties ( e . g ., frequencies between 50 khz and 500 khz ) in destroying tumor cells , the electric fields were applied to treat mice with malignant melanoma tumors . two pairs of isolects 230 were positioned over a corresponding pair of malignant melanomas . only one pair was connected to the generator 210 and 200 khz alternating electric fields ( tc fields ) were applied to the tumor for a period of 6 days . one melanoma tumor was not treated so as to permit a comparison between the treated tumor and the non - treated tumor . after treatment for 6 days , the pigmented melanoma tumor remained clearly visible in the non - treated side of the mouse , while , in contrast , no tumor is seen on the treated side of the mouse . the only areas that were visible discernable on the skin were the marks that represented the points of insertion of the isolects 230 . the fact that the tumor was eliminated at the treated side was further demonstrated by cutting and inversing the skin so that its inside face was exposed . such a procedure indicated that the tumor has been substantially , if not completely , eliminated on the treated side of the mouse . the success of the treatment was also further verified by histopathological examination . the present inventor has thus uncovered that electric fields having particular properties can be used to destroy dividing cells or tumors when the electric fields are applied to using an electronic device . more specifically , these electric fields fall into a special intermediate category , namely bio - effective fields that have no meaningful stimulatory and no thermal effects , and therefore overcome the disadvantages that were associated with the application of conventional electric fields to a body . it will also be appreciated that the present apparatus can further include a device for rotating the tc field relative to the living tissue . for example and according to one embodiment , the alternating electric potential applies to the tissue being treated is rotated relative to the tissue using conventional devices , such as a mechanical device that upon activation , rotates various components of the present system . moreover and according to yet another embodiment , the tc fields are applied to different pairs of the insulated electrodes 230 in a consecutive manner . in other words , the generator 210 and the control system thereof can be arranged so that signals are sent at periodic intervals to select pairs of insulated electrodes 230 , thereby causing the generation of the tc fields of different directions by these insulated electrodes 230 . because the signals are sent at select times from the generator to the insulated electrodes 230 , the tc fields of changing directions are generated consecutively by different insulated electrodes 230 . this arrangement has a number of advantages and is provided in view of the fact that the tc fields have maximal effect when they are parallel to the axis of cell division . since the orientation of cell division is in most cases random , only a fraction of the dividing cells are affected by any given field . thus , using fields of two or more orientations increases the effectiveness since it increases the chances that more dividing cells are affected by a given tc field . in vitro experiments have shown that the electric field has the maximum killing effect when the lines of force of the field are oriented generally parallel to the long axis of the hourglass - shaped cell during mitosis ( as shown in fig3 a - 3c ). in one experiment , a much higher proportion of the damaged cells had their axis of division oriented along the field : 56 % of the cells oriented at or near 0 ° with respect to the field were damaged , versus an average of 15 % of cells damaged for cells with their long axis oriented at more than 22 ° with respect to the field . the inventor has recognized that applying the field in different directions sequentially will increase the overall killing power , because the field orientation that is most effectively in killing dividing cells will be applied to a larger population of the dividing cells . a number of examples for applying the field in different directions are discussed below . fig2 a , 27 b , and 27 c show a set of 6 electrodes e 1 - e 6 , and how the direction of the field through the target tissue 1510 can be changed by applying the ac signal from the generator 1 ( shown in fig1 ) across different pairs of electrodes . for example , if the ac signal is applied across electrodes e 1 and e 4 , the field lines f would be vertical ( as shown in fig2 a ), and if the signal is applied across electrodes e 2 and e 5 , or across electrodes e 3 and e 6 , the field lines f would be diagonal ( as shown in fig2 b and 27c , respectively ). additional field directions can be obtained by applying the ac signal across other pairs of electrodes . for example , a roughly horizontal field could be obtained by applying the signal across electrodes e 2 and e 6 . in one embodiment , the ac signal is applied between the various pairs of electrodes sequentially . an example of this arrangement is to apply the ac signal across electrodes e 1 and e 4 for one second , then apply the ac signal across electrodes e 2 and e 5 for one second , and then apply the ac signal across electrodes e 3 and e 6 for one second . this three - part sequence is then repeated for the desired period of treatment . because the efficacy in cell - destruction is strongly dependant on the cell &# 39 ; s orientation , cycling the field between the different directions increases the chance that the field will be oriented in a direction that favors cell destruction at least part of the time . of course , the 6 electrode configuration shown in fig2 a - c is just one of many possible arrangements of multiple electrodes , and many other configurations of three or more electrodes could be used based on the same principles . application of the field in different directions sequentially is not limited to two dimensional embodiments , and fig2 shows how the sequential application of signals across different sets of electrodes can be extended to three dimensions . a first array of electrodes a 1 - a 9 is arranged around body part 1500 , and a last array of electrodes n 1 - n 9 is arranged around the body part 1500 a distance w away from the first array . additional arrays of electrodes may optionally be added between the first array and the last array , but these additional arrays are not illustrated for clarity ( so as not to obscure the electrodes a 5 - a 9 and b 5 - b 8 on the back of the body part 1500 ). as in the fig2 embodiment , the direction of the field through the target tissue can be changed by applying the ac signal from the generator 1 ( shown in fig1 ) across different pairs of electrodes . for example , applying the ac signal between electrodes a 2 and a 7 would result in a field in a front - to - back direction between those two electrodes , and applying the ac signal between electrodes a 5 and a 9 would result in a roughly vertical field between those two electrodes . similarly , applying the ac signal across electrodes a 2 and n 7 would generate diagonal field lines in one direction through the body part 1500 , and applying the ac signal across electrodes a 2 and b 7 would generate diagonal field lines in another direction through the body part . using a three - dimensional array of electrodes also makes it possible to energize multiple pairs of electrodes simultaneously to induce fields in the desired directions . for example , if suitable switching is provided so that electrodes a 2 through n 2 are all connected to one terminal of the generator , and so that electrodes a 7 through n 7 are all connected to the other terminal of the generator , the resulting field would be a sheet that extends in a front - to - back direction for the entire width w . after the front - to - back field is maintained for a suitable duration ( e . g ., one second ), the switching system ( not shown ) is reconfigured to connect electrodes a 3 through n 3 to one terminal of the generator , and electrodes a 8 through n 8 to the other terminal of the generator . this results in a sheet - shaped field that is rotated about the z axis by about 40 ° with respect to the initial field direction . after the field is maintained in this direction for a suitable duration ( e . g ., one second ), the next set of electrodes is activated to rotate the field an additional 40 ° to its next position . this continues until the field returns to its initial position , at which point the whole process is repeated . optionally , the rotating sheet - shaped field may be added ( sequentially in time ) to the diagonal fields described above , to better target cells that are oriented along those diagonal axes . because the electric field is a vector , the signals may optionally be applied to combinations of electrodes simultaneously in order to form a desired resultant vector . for example , a field that is rotated about the x axis by 20 ° with respect to the initial position can be obtained by switching electrodes a 2 through n 2 and a 3 through n 3 all to one terminal of the generator , and switching electrodes a 7 through n 7 and a 8 through n 8 all to the other terminal of the generator . applying the signals to other combinations of electrodes will result in fields in other directions , as will be appreciated by persons skilled in the relevant arts . if appropriate computer control of the voltages is implemented , the field &# 39 ; s direction can even be swept through space in a continuous ( i . e ., smooth ) manner , as opposed to the stepwise manner described above . fig2 a and 29b depict the results of in vitro experiments that show how the killing power of the applied field against dividing cells is a function of the field strength . in the fig2 a experiment , b16f1 melanoma cells were subjected to a 100 khz ac field at different field strengths , for a period of 24 hours at each strength . in the fig2 b experiment , f - 98 glioma cells were subjected to a 200 khz ac field at different field strengths , for a period of 24 hours at each strength . in both of these figures , the strength of the field ( ef ) is measured in volts per cm . the magnitude of the killing effect is expressed in terms of ter , which is which is the ratio of the decrease in the growth rate of treated cells ( gr t ) compared with the growth rate of control cells ( gr c ). the experimental results show that the inhibitory effect of the applied field on proliferation increases with intensity in both the melanoma and the glioma cells . complete proliferation arrest ( ter = 1 ) is seen at 1 . 35 and 2 . 25 v / cm in melanoma and glioma cells , respectively . fig3 a and 30b depict the results of in vitro experiments that show how the killing power of the applied field is a function of the frequency of the field . in the experiments , b16f1 melanoma cells ( fig3 a ) and f - 98 glioma cells ( fig3 b ) were subjected to fields with different frequencies , for a period of 24 hours at each frequency . fig3 a and 30b show the change in the growth rate , normalized to the field intensity ( ter / ef ). data are shown as mean ± se . in fig3 a , a window effect is seen with maximal inhibition at 120 khz in melanoma cells . in fig3 b , two peaks are seen at 170 and 250 khz . thus , if only one frequency is available during an entire course of treatment , a field with a frequency of about 120 khz would be appropriate for destroying melanoma cells , and a field with a frequency on the order of 200 khz would be appropriate for destroying glioma cells . not all the cells of any given type will have the exact same size . instead , the cells will have a distribution of sizes , with some cells being smaller and some cells being larger . it is believed that the best frequency for damaging a particular cell is related to the physical characteristics ( e . g ., the size ) of that particular cell . thus , to best damage a population of cells with a distribution of sizes , it can be advantageous to apply a distribution of different frequencies to the population , where the selection of frequencies is optimized based on the expected size distribution of the target cells . for example , the data on fig3 b indicates that using two frequencies of 170 khz and 250 khz to destroy a population of glioma cells would be more effective than using a single frequency of 200 khz . note that the optimal field strengths and frequencies discussed herein were obtained based on in vitro experiments , and that the corresponding parameters for in vivo applications may be obtained by performing similar experiments in vivo . it is possible that relevant characteristics of the cell itself ( such as size and / or shape ) or interactions with the cell &# 39 ; s surroundings may result in a different set of optimal frequencies and / or field strengths for in vivo applications . when more than one frequency is used , the various frequencies may be applied sequentially in time . for example , in the case of glioma , field frequencies of 100 , 150 , 170 , 200 , 250 , and 300 khz may be applied during the first , second , third , fourth , fifth , and sixth minutes of treatment , respectively . that cycle of frequencies would then repeat during each successive six minutes of treatment . alternatively , the frequency of the field may be swept in a stepless manner from 100 to 300 khz . optionally , this frequency cycling may be combined with the directional cycling described above . fig3 a is an example of such a combination using three directions ( d 1 , d 2 , and d 3 ) and three frequencies ( f 1 , f 2 , and f 3 ). of course , the same scheme can be extended to any other number of directions and / or frequencies . fig3 b is an example of such a combination using three directions ( d 1 , d 2 , and d 3 ), sweeping the frequency from 100 khz to 300 khz . note that the break in the time axis between t 1 and t 2 provides the needed time for the sweeping frequency to rise to just under 300 khz . the frequency sweeping ( or stepping ) may be synchronized with directional changes , as shown in fig3 a . alternatively , the frequency sweeping ( or stepping ) may be asynchronous with respect to the directional changes , as shown in fig3 b . in an alternative embodiment , a signal that contains two or more frequencies components simultaneously ( e . g ., 170 khz and 250 khz ) is applied to the electrodes to treat a populations of cells that have a distribution of sizes . the various signals will add by superposition to create a field that includes all of the applied frequency components . turning now to fig1 in which an article of clothing 500 according to one exemplary embodiment is illustrated . more specifically , the article of clothing 500 is in the form of a hat or cap or other type of clothing designed for placement on a head of a person . for purposes of illustration , a head 502 is shown with the hat 500 being placed thereon and against a skin surface 504 of the head 502 . an intra - cranial tumor or the like 510 is shown as being formed within the head 502 underneath the skin surface 504 thereof . the hat 500 is therefore intended for placement on the head 502 of a person who has a tumor 510 or the like . unlike the various embodiments illustrated in fig1 - 13 where the insulated electrodes 230 are arranged in a more or less planar arrangement since they are placed either on a skin surface or embedded within the body underneath it , the insulated electrodes 230 in this embodiment are specifically contoured and arranged for a specific application . the treatment of intra - cranial tumors or other lesions or the like typically requires a treatment that is of a relatively long duration , e . g ., days to weeks , and therefore , it is desirable to provide as much comfort as possible to the patient . the hat 500 is specifically designed to provide comfort during the lengthy treatment process while not jeopardizing the effectiveness of the treatment . according to one exemplary embodiment , the hat 500 includes a predetermined number of insulated electrodes 230 that are preferably positioned so as to produce the optimal tc fields at the location of the tumor 510 . the lines of force of the tc field are generally indicated at 520 . as can be seen in fig1 , the tumor 510 is positioned within these lines of force 520 . as will be described in greater detail hereinafter , the insulated electrodes 230 are positioned within the hat 500 such that a portion or surface thereof is free to contact the skin surface 504 of the head 502 . in other words , when the patient wears the hat 500 , the insulated electrodes 230 are placed in contact with the skin surface 504 of the head 502 in positions that are selected so that the tc fields generated thereby are focused at the tumor 510 while leaving surrounding areas in low density . typically , hair on the head 502 is shaved in selected areas to permit better contact between the insulated electrodes 230 and the skin surface 504 ; however , this is not critical . the hat 500 preferably includes a mechanism 530 that applies a force to the insulated electrodes 230 so that they are pressed against the skin surface 502 . for example , the mechanism 530 can be of a biasing type that applies a biasing force to the insulated electrodes 230 to cause the insulated electrodes 230 to be directed outwardly away from the hat 500 . thus , when the patient places the hat 500 on his / her head 502 , the insulated electrodes 230 are pressed against the skin surface 504 by the mechanism 530 . the mechanism 530 can slightly recoil to provide a comfortable fit between the insulated electrodes 230 and the head 502 . in one exemplary embodiment , the mechanism 530 is a spring based device that is disposed within the hat 500 and has one section that is coupled to and applies a force against the insulated electrodes 230 . as with the prior embodiments , the insulated electrodes 230 are coupled to the generator 210 by means of conductors 220 . the generator 210 can be either disposed within the hat 500 itself so as to provide a compact , self - sufficient , independent system or the generator 210 can be disposed external to the hat 500 with the conductors 220 exiting the hat 500 through openings or the like and then running to the generator 210 . when the generator 210 is disposed external to the hat 500 , it will be appreciated that the generator 210 can be located in any number of different locations , some of which are in close proximity to the hat 500 itself , while others can be further away from the hat 500 . for example , the generator 210 can be disposed within a carrying bag or the like ( e . g ., a bag that extends around the patient &# 39 ; s waist ) which is worn by the patient or it can be strapped to an extremity or around the torso of the patient . the generator 210 can also be disposed in a protective case that is secured to or carried by another article of clothing that is worn by the patient . for example , the protective case can be inserted into a pocket of a sweater , etc . fig1 illustrates an embodiment where the generator 210 is incorporated directly into the hat 500 . turning now to fig1 and 16 , in one exemplary embodiment , a number of insulated electrodes 230 along with the mechanism 530 are preferably formed as an independent unit , generally indicated at 540 , that can be inserted into the hat 500 and electrically connected to the generator ( not shown ) via the conductors ( not shown ). by providing these members in the form of an independent unit , the patient can easily insert and / or remove the units 540 from the hat 500 when they may need cleaning , servicing and / or replacement . in this embodiment , the hat 500 is constructed to include select areas 550 that are formed in the hat 500 to receive and hold the units 540 . for example and as illustrated in fig1 , each area 550 is in the form of an opening ( pore ) that is formed within the hat 500 . the unit 540 has a body 542 and includes the mechanism 530 and one or more insulated electrodes 230 . the mechanism 530 is arranged within the unit 540 so that a portion thereof ( e . g ., one end thereof ) is in contact with a face of each insulated electrode 230 such that the mechanism 530 applies a biasing force against the face of the insulated electrode 230 . once the unit 540 is received within the opening 550 , it can be securely retained therein using any number of conventional techniques , including the use of an adhesive material or by using mechanical means . for example , the hat 500 can include pivotable clip members that pivot between an open position in which the opening 550 is free and a closed position in which the pivotable clip members engage portions ( e . g ., peripheral edges ) of the insulated electrodes to retain and hold the insulated electrodes 230 in place . to remove the insulated electrodes 230 , the pivotable clip members are moved to the open position . in the embodiment illustrated in fig1 , the insulated electrodes 230 are retained within the openings 550 by an adhesive element 560 which in one embodiment is a two sided self - adhesive rim member that extends around the periphery of the insulated electrode 230 . in other words , a protective cover of one side of the adhesive rim 560 is removed and it is applied around the periphery of the exposed face of the insulated electrode 230 , thereby securely attaching the adhesive rim 560 to the hat 500 and then the other side of the adhesive rim 560 is removed for application to the skin surface 504 in desired locations for positioning and securing the insulated electrode 230 to the head 502 with the tumor being positioned relative thereto for optimization of the tc fields . since one side of the adhesive rim 560 is in contact with and secured to the skin surface 540 , this is why it is desirable for the head 502 to be shaved so that the adhesive rim 560 can be placed flushly against the skin surface 540 . the adhesive rim 560 is designed to securely attach the unit 540 within the opening 550 in a manner that permits the unit 540 to be easily removed from the hat 500 when necessary and then replaced with another unit 540 or with the same unit 540 . as previously mentioned , the unit 540 includes the biasing mechanism 530 for pressing the insulated electrode 230 against the skin surface 504 when the hat 500 is worn . the unit 540 can be constructed so that side opposite the insulated electrode 230 is a support surface formed of a rigid material , such as plastic , so that the biasing mechanism 530 ( e . g ., a spring ) can be compressed therewith under the application of force and when the spring 530 is in a relaxed state , the spring 530 remains in contact with the support surface and the applies a biasing force at its other end against the insulated electrode 230 . the biasing mechanism 530 ( e . g ., spring ) preferably has a contour corresponding to the skin surface 504 so that the insulated electrode 230 has a force applied thereto to permit the insulated electrode 230 to have a contour complementary to the skin surface 504 , thereby permitting the two to seat flushly against one another . while the mechanism 530 can be a spring , there are a number of other embodiments that can be used instead of a spring . for example , the mechanism 530 can be in the form of an elastic material , such as a foam rubber , a foam plastic , or a layer containing air bubbles , etc . the unit 540 has an electric connector 570 that can be hooked up to a corresponding electric connector , such as a conductor 220 , that is disposed within the hat 500 . the conductor 220 connects at one end to the unit 540 and at the other end is connected to the generator 210 . the generator 210 can be incorporated directly into the hat 500 or the generator 210 can be positioned separately ( remotely ) on the patient or on a bedside support , etc . as previously discussed , a coupling agent , such as a conductive gel , is preferably used to ensure that an effective conductive environment is provided between the insulated electrode 230 and the skin surface 504 . suitable gel materials have been disclosed hereinbefore in the discussion of earlier embodiments . the coupling agent is disposed on the insulated electrode 230 and preferably , a uniform layer of the agent is provided along the surface of the electrode 230 . one of the reasons that the units 540 need replacement at periodic times is that the coupling agent needs to be replaced and / or replenished . in other words , after a predetermined time period or after a number of uses , the patient removes the units 540 so that the coupling agent can be applied again to the electrode 230 . fig1 and 18 illustrate another article of clothing which has the insulated electrodes 230 incorporated as part thereof . more specifically , a bra or the like 700 is illustrated and includes a body that is formed of a traditional bra material , generally indicated at 705 , to provide shape , support , and comfort to the wearer . the bra 700 also includes a fabric support layer 710 on one side thereof . the support layer 710 is preferably formed of a suitable fabric material that is constructed to provide necessary and desired support to the bra 700 . similar to the other embodiments , the bra 700 includes one or more insulated electrodes 230 disposed within the bra material 705 . the one or more insulated electrodes are disposed along an inner surface of the bra 700 opposite the support 710 and are intended to be placed proximate to a tumor or the like that is located within one breast or in the immediately surrounding area . as with the previous embodiment , the insulated electrodes 230 in this embodiment are specifically constructed and configured for application to a breast or the immediate area . thus , the insulated electrodes 230 used in this application do not have a planar surface construction but rather have an arcuate shape that is complementary to the general curvature found in a typical breast . a lining 720 is disposed across the insulated electrodes 230 so as to assist in retaining the insulated electrodes in their desired locations along the inner surface for placement against the breast itself . the lining 720 can be formed of any number of thin materials that are comfortable to wear against one &# 39 ; s skin and in one exemplary embodiment , the lining 720 is formed of a fabric material . the bra 700 also preferably includes a biasing mechanism 800 as in some of the earlier embodiments . the biasing mechanism 800 is disposed within the bra material 705 and extends from the support 710 to the insulated electrode 230 and applies a biasing force to the insulated electrode 230 so that the electrode 230 is pressed against the breast . this ensures that the insulated electrode 230 remains in contact with the skin surface as opposed to lifting away from the skin surface , thereby creating a gap that results in a less effective treatment since the gap diminishes the efficiency of the tc fields . the biasing mechanism 800 can be in the form of a spring arrangement or it can be an elastic material that applies the desired biasing force to the insulated electrodes 230 so as to press the insulated electrodes 230 into the breast . in the relaxed position , the biasing mechanism 800 applies a force against the insulated electrodes 230 and when the patient places the bra 700 on their body , the insulated electrodes 230 are placed against the breast which itself applies a force that counters the biasing force , thereby resulting in the insulated electrodes 230 being pressed against the patient &# 39 ; s breast . in the exemplary embodiment that is illustrated , the biasing mechanism 800 is in the form of springs that are disposed within the bra material 705 . a conductive gel 810 can be provided on the insulated electrode 230 between the electrode and the lining 720 . the conductive gel layer 810 is formed of materials that have been previously described herein for performing the functions described above . an electric connector 820 is provided as part of the insulated electrode 230 and electrically connects to the conductor 220 at one end thereof , with the other end of the conductor 220 being electrically connected to the generator 210 . in this embodiment , the conductor 220 runs within the bra material 705 to a location where an opening is formed in the bra 700 . the conductor 220 extends through this opening and is routed to the generator 210 , which in this embodiment is disposed in a location remote from the bra 700 . it will also be appreciated that the generator 210 can be disposed within the bra 700 itself in another embodiment . for example , the bra 700 can have a compartment formed therein which is configured to receive and hold the generator 210 in place as the patient wears the bra 700 . in this arrangement , the compartment can be covered with a releasable strap that can open and close to permit the generator 210 to be inserted therein or removed therefrom . the strap can be formed of the same material that is used to construct the bra 700 or it can be formed of some other type of material . the strap can be releasably attached to the surrounding bra body by fastening means , such as a hook and loop material , thereby permitting the patient to easily open the compartment by separating the hook and loop elements to gain access to the compartment for either inserting or removing the generator 210 . the generator 210 also has a connector 211 for electrical connection to the conductor 220 and this permits the generator 210 to be electrically connected to the insulated electrodes 230 . as with the other embodiments , the insulated electrodes 230 are arranged in the bra 700 to focus the electric field ( tc fields ) on the desired target ( e . g ., a tumor ). it will be appreciated that the location of the insulated electrodes 230 within the bra 700 will vary depending upon the location of the tumor . in other words , after the tumor has been located , the physician will then devise an arrangement of insulated electrodes 230 and the bra 700 is constructed in view of this arrangement so as to optimize the effects of the tc fields on the target area ( tumor ). the number and position of the insulated electrodes 230 will therefore depend upon the precise location of the tumor or other target area that is being treated . because the location of the insulated electrodes 230 on the bra 700 can vary depending upon the precise application , the exact size and shape of the insulated electrodes 230 can likewise vary . for example , if the insulated electrodes 230 are placed on the bottom section of the bra 700 as opposed to a more central location , the insulated electrodes 230 will have different shapes since the shape of the breast ( as well as the bra ) differs in these areas . fig1 illustrates yet another embodiment in which the insulated electrodes 230 are in the form of internal electrodes that are incorporated into in the form of a probe or catheter 600 that is configured to enter the body through a natural pathway , such as the urethra , vagina , etc . in this embodiment , the insulated electrodes 230 are disposed on an outer surface of the probe 600 and along a length thereof . the conductors 220 are electrically connected to the electrodes 230 and run within the body of the probe 600 to the generator 210 which can be disposed within the probe body or the generator 210 can be disposed independent of the probe 600 in a remote location , such as on the patient or at some other location close to the patient . alternatively , the probe 600 can be configured to penetrate the skin surface or other tissues to reach an internal target that lies within the body . for example , the probe 600 can penetrate the skin surface and then be positioned adjacent to or proximate to a tumor that is located within the body . in these embodiments , the probe 600 is inserted through the natural pathway and then is positioned in a desired location so that the insulated electrodes 230 are disposed near the target area ( i . e ., the tumor ). the generator 210 is then activated to cause the insulated electrodes 230 to generate the tc fields which are applied to the tumor for a predetermined length of time . it will be appreciated that the illustrated probe 600 is merely exemplary in nature and that the probe 600 can have other shapes and configurations so long as they can perform the intended function . preferably , the conductors ( e . g ., wires ) leading from the insulated electrodes 230 to the generator 210 are twisted or shielded so as not to generate a field along the shaft . it will further be appreciated that the probes can contain only one insulated electrode while the other can be positioned on the body surface . this external electrode should be larger or consist of numerous electrodes so as to result in low lines of force - current density so as not to affect the untreated areas . in fact , the placing of electrodes should be designed to minimize the field at potentially sensitive areas . optionally , the external electrodes may be held against the skin surface by a vacuum force ( e . g ., suction ). fig2 illustrates yet another embodiment in which a high standing collar member 900 ( or necklace type structure ) can be used to treat thyroid , parathyroid , laryngeal lesions , etc . fig2 illustrates the collar member 900 in an unwrapped , substantially flat condition . in this embodiment , the insulated electrodes 230 are incorporated into a body 910 of the collar member 900 and are configured for placement against a neck area of the wearer . the insulated electrodes 230 are coupled to the generator 210 according to any of the manner described hereinbefore and it will be appreciated that the generator 210 can be disposed within the body 910 or it can be disposed in a location external to the body 910 . the collar body 910 can be formed of any number of materials that are traditionally used to form collars 900 that are disposed around a person &# 39 ; s neck . as such , the collar 900 preferably includes a means 920 for adjusting the collar 900 relative to the neck . for example , complementary fasteners ( hook and loop fasteners , buttons , etc .) can be disposed on ends of the collar 900 to permit adjustment of the collar diameter . thus , the construction of the present devices are particularly well suited for applications where the devices are incorporated into articles of clothing to permit the patient to easily wear a traditional article of clothing while at the same time the patient undergoes treatment . in other words , an extra level of comfort can be provided to the patient and the effectiveness of the treatment can be increased by incorporating some or all of the device components into the article of clothing . the precise article of clothing that the components are incorporated into will obviously vary depending upon the target area of the living tissue where tumor , lesion or the like exists . for example , if the target area is in the testicle area of a male patient , then an article of clothing in the form of a sock - like structure or wrap can be provided and is configured to be worn around the testicle area of the patient in such a manner that the insulated electrodes thereof are positioned relative to the tumor such that the tc fields are directed at the target tissue . the precise nature or form of the article of clothing can vary greatly since the device components can be incorporated into most types of articles of clothing and therefore , can be used to treat any number of different areas of the patient &# 39 ; s body where a condition may be present . now turning to fig2 - 22 in which another aspect of the present device is shown . in fig2 , a body 1000 , such as any number of parts of a human or animal body , is illustrated . as in the previous embodiments , two or more insulated electrodes 230 are disposed in proximity to the body 1000 for treatment of a tumor or the like ( not shown ) using tc fields , as has been previously described in great detail in the above discussion of other embodiments . the insulated electrode 230 has a conductive component and has external insulation 260 that surrounds the conductive component thereof . each insulated electrode 230 is preferably connected to a generator ( not shown ) by the lead 220 . between each insulated electrode 220 and the body 1000 , a conductive filler material ( e . g ., conductive gel member 270 ) is disposed . the insulated electrodes 230 are spaced apart from one another and when the generator is actuated , the insulated electrodes 230 generate the tc fields that have been previously described in great detail . the lines of the electric field ( tc field ) are generally illustrated at 1010 . as shown , the electric field lines 1010 extend between the insulated electrodes 230 and through the conductive gel member 270 . over time or as a result of some type of event , the external insulation 260 of the insulated electrode 230 can begin to breakdown at any given location thereof . for purpose of illustration only , fig2 illustrates that the external insulation 260 of one of the insulated electrodes 230 has experienced a breakdown 1020 at a face thereof which is adjacent the conductive gel member 270 . it will be appreciated that the breakdown 1020 of the external insulation 260 results in the formation of a strong current flow - current density at this point ( i . e ., at the breakdown 1020 ). the increased current density is depicted by the increased number of electric field lines 1010 and the relative positioning and distance between adjacent electric field lines 1010 . one of the side effects of the occurrence of breakdown 1020 is that current exists at this point which will generate heat and may burn the tissues / skin which have a resistance . in fig2 , an overheated area 1030 is illustrated and is a region or area of the tissues / skin where an increased current density exits due to the breakdown 1020 in the external insulation 260 . a patient can experience discomfort and pain in this area 1030 due to the strong current that exists in the area and the increased heat and possible burning sensation that exist in area 1030 . fig2 illustrates yet another embodiment in which a further application of the insulated electrodes 230 is shown . in this embodiment , the conductive gel member 270 that is disposed between the insulated electrode 230 and the body 1000 includes a conductor 1100 that is floating in that the gel material forming the member 270 completely surrounds the conductor 1100 . in one exemplary embodiment , the conductor 1100 is a thin metal sheet plate that is disposed within the conductor 1100 . as will be appreciated , if a conductor , such as the plate 1100 , is placed in a homogeneous electric field , normal to the lines of the electric field , the conductor 1100 practically has no effect on the field ( except that the two opposing faces of the conductor 1100 are equipotential and the corresponding equipotentials are slightly shifted ). conversely , if the conductor 1100 is disposed parallel to the electric field , there is a significant distortion of the electric field . the area in the immediate proximity of the conductor 1100 is not equipotential , in contrast to the situation where there is no conductor 1100 present . when the conductor 1100 is disposed within the gel member 270 , the conductor 1100 will typically not effect the electric field ( tc field ) for the reasons discussed above , namely that the conductor 1100 is normal to the lines of the electric field . if there is a breakdown of the external insulation 260 of the insulated electrode 230 , there is a strong current flow - current density at the point of breakdown as previously discussed ; however , the presence of the conductor 1100 causes the current to spread throughout the conductor 1100 and then exit from the whole surface of the conductor 1100 so that the current reaches the body 1000 with a current density that is neither high nor low . thus , the current that reaches the skin will not cause discomfort to the patient even when there has been a breakdown in the insulation 260 of the insulated electrode 230 . it is important that the conductor 1100 is not grounded as this would cause it to abolish the electric field beyond it . thus , the conductor 1100 is “ floating ” within the gel member 270 . if the conductor 1100 is introduced into the body tissues 1000 and is not disposed parallel to the electric field , the conductor 1100 will cause distortion of the electric field . the distortion can cause spreading of the lines of force ( low field density - intensity ) or concentration of the lines of field ( higher density ) of the electric field , according to the particular geometries of the insert and its surroundings , and thus , the conductor 1100 can exhibit , for example , a screening effect . thus , for example , if the conductor 1100 completely encircles an organ 1101 , the electric field in the organ itself will be zero since this type of arrangement is a faraday cage . however , because it is impractical for a conductor to be disposed completely around an organ , a conductive net or similar structure can be used to cover , completely or partially , the organ , thereby resulting in the electric field in the organ itself being zero or about zero . for example , a net can be made of a number of conductive wires that are arranged relative to one another to form the net or a set of wires can be arranged to substantially encircle or otherwise cover the organ 1101 . conversely , an organ 1103 to be treated ( the target organ ) is not covered with a member having a faraday cage effect but rather is disposed in the electric field 1010 ( tc fields ). fig2 illustrates an embodiment where the conductor 1100 is disposed within the body ( i . e ., under the skin ) and it is located near a target ( e . g ., a target organ ). by placing the conductor 1100 near the target , high field density ( of the tc fields ) is realized at the target . at the same time , another nearby organ can be protected by disposing the above described protective conductive net or the like around this nearby organ so as to protect this organ from the fields . by positioning the conductor 1100 in close proximity to the target , a high field density condition can be provided near or at the target . in other words , the conductor 1100 permits the tc fields to be focused at a particular area ( i . e ., a target ). it will also be appreciated that in the embodiment of fig2 , the gel members 260 can each include a conductor as described with reference to fig2 . in such an arrangement , the conductor in the gel member 260 protects the skin surface ( tissues ) from any side effects that may be realized if a breakdown in the insulation of the insulated electrode 230 occurs . at the same time , the conductor 1100 creates a high field density near the target . there are a number of different ways to tailor the field density of the electric field by constructing the electrodes differently and / or by strategically placing the electrodes relative to one another . for example , in fig2 , a first insulated electrode 1200 and a second insulated electrode 1210 are provided and are disposed about a body 1300 . each insulated electrode includes a conductor that is preferably surrounded by an insulating material , thus the term “ insulated electrode ”. between each of the first and second electrodes 1200 , 1210 and the body 1300 , the conductive gel member 270 is provided . electric field lines are generally indicated at 1220 for this type of arrangement . in this embodiment , the first insulated electrode 1200 has dimensions that are significantly greater than the dimensions of the second insulated electrode 1210 ( the conductive gel member for the second insulated electrode 1210 will likewise be smaller ). by varying the dimensions of the insulated electrodes , the pattern of the electric field lines 1220 is varied . more specifically , the electric field tapers inwardly toward the second insulated electrode 1210 due to the smaller dimensions of the second insulated electrode 1210 . an area of high field density , generally indicated at 1230 , forms near the interface between the gel member 270 associated with the second insulated electrode 1210 and the skin surface . the various components of the system are manipulated so that the tumor within the skin or on the skin is within this high field density so that the area to be treated ( the target ) is exposed to electric field lines of a higher field density . fig2 also illustrates a tapering tc field when a conductor 1400 ( e . g ., a conductive plate ) is disposed in each of the conductive gel members 270 . in this embodiment , the size of the gel members 270 and the size of the conductors 1400 are the same or about the same despite the differences in the sizes of the insulated electrodes 1200 , 1210 . the conductors 1400 again can be characterized as “ floating plates ” since each conductor 1400 is surrounded by the material that forms the gel member 270 . as shown in fig2 , the placement of one conductor 1400 near the insulated electrode 1210 that is smaller than the other insulated electrode 1200 and is also smaller than the conductor 1400 itself and the other insulated electrode 1200 is disposed at a distance therefrom , the one conductor 1400 causes a decrease in the field density in the tissues disposed between the one conductor 1400 and the other insulated electrode 1200 . the decrease in the field density is generally indicated at 1410 . at the same time , a very inhomogeneous tapering field , generally indicated at 1420 , changing from very low density to very high density is formed between the one conductor 1400 and the insulated electrode 1210 . one benefit of this exemplary configuration is that it permits the size of the insulated electrode to be reduced without causing an increase in the nearby field density . this can be important since electrodes that having very high dielectric constant insulation can be very expensive . some insulated electrodes , for example , can cost $ 500 . 00 or more ; and further , the price is sensitive to the particular area of treatment . thus , a reduction in the size of the insulated electrodes directly leads to a reduction in cost . as used herein , the term “ tumor ” refers to a malignant tissue comprising transformed cells that grow uncontrollably . tumors include leukemias , lymphomas , myelomas , plasmacytomas , and the like ; and solid tumors . examples of solid tumors that can be treated according to the invention include sarcomas and carcinomas such as , but not limited to : fibrosarcoma , myxosarcoma , liposarcoma , chondrosarcoma , osteogenic sarcoma , chordoma , angiosarcoma , endotheliosarcoma , lymphangiosarcoma , lymphangioendotheliosarcoma , synovioma , mesothelioma , ewing &# 39 ; s tumor , leiomyosarcoma , rhabdomyosarcoma , colon carcinoma , pancreatic cancer , breast cancer , ovarian cancer , prostate cancer , squamous cell carcinoma , basal cell carcinoma , adenocarcinoma , sweat gland carcinoma , sebaceous gland carcinoma , papillary carcinoma , papillary adenocarcinomas , cystadenocarcinoma , medullary carcinoma , bronchogenic carcinoma , renal cell carcinoma , hepatoma , bile duct carcinoma , choriocarcinoma , seminoma , embryonal carcinoma , wilms &# 39 ; tumor , cervical cancer , testicular tumor , lung carcinoma , small cell lung carcinoma , bladder carcinoma , epithelial carcinoma , glioma , astrocytoma , medulloblastoma , craniopharyngioma , ependymoma , pinealoma , hemangioblastoma , acoustic neuroma , oligodendroglioma , meningioma , melanoma , neuroblastoma , and retinoblastoma . because each of these tumors undergoes rapid growth , any one can be treated in accordance with the invention . the invention is particularly advantageous for treating brain tumors , which are difficult to treat with surgery and radiation , and often inaccessible to chemotherapy or gene therapies . in addition , the present invention is suitable for use in treating skin and breast tumors because of the ease of localized treatment provided by the present invention . in addition , the present invention can control uncontrolled growth associated with non - malignant or pre - malignant conditions , and other disorders involving inappropriate cell or tissue growth by application of an electric field in accordance with the invention to the tissue undergoing inappropriate growth . for example , it is contemplated that the invention is useful for the treatment of arteriovenous ( av ) malformations , particularly in intracranial sites . the invention may also be used to treat psoriasis , a dermatologic condition that is characterized by inflammation and vascular proliferation ; and benign prostatic hypertrophy , a condition associated with inflammation and possibly vascular proliferation . treatment of other hyperproliferative disorders is also contemplated . furthermore , undesirable fibroblast and endothelial cell proliferation associated with wound healing , leading to scar and keloid formation after surgery or injury , and restenosis after angioplasty or placement of coronary stents can be inhibited by application of an electric field in accordance with the present invention . the non - invasive nature of this invention makes it particularly desirable for these types of conditions , particularly to prevent development of internal scars and adhesions , or to inhibit restenosis of coronary , carotid , and other important arteries . in addition to treating tumors that have already been detected , the above - described embodiments may also be used prophylactically to prevent tumors from ever reaching a detectable size in the first place . for example , the bra embodiment described above in connection with fig1 and 18 may be worn by a woman for an 8 hour session every day for a week , with the week - long course of treatment being repeated every few months to kill any cells that have become cancerous and started to proliferate . this mode of usage is particularly appropriate for people who are at high risk for a particular type of cancer ( e . g ., women with a strong history of breast cancer in their families , or people who have survived a bout of cancer and are at risk of a relapse ). the course of prophylactic treatment may be tailored based on the type of cancer being targeted and / or to suit the convenience of the patient . for example , undergoing a four 16 hour sessions during the week of treatment may be more convenient for some patients than seven 8 hour session , and may be equally effective . experiments were also performed on two different types of bacteria — pseudomonas aeruginosa strain pao1 and staphylococcus aureus strain sh1000 . all strains were grown in lb media ( 1 . 0 % bacto tryptone , 0 . 5 % yeast extract , 1 % nacl ). broth cultures of freshly plated bacteria strains were grown in 3 ml of liquid medium at 37 ° c . for 15 hours in an orbital shaker ( 220 rpm ) and diluted in fresh lb broth to a predetermined absorbance at 595 nm which yielded the desired cfu per ml . fig3 a depicts the construction of the electrodes 1610 used in the experiment . each electrode is 15 mm long and 5 mm high . it include an electrical conductor 1611 with its outer face coated with a thin layer of lead magnesium niobate - lead titanate ( pmn - pt ) ceramic insulation 1612 , which has a high dielectric constant (∈& gt ; 5000 ) such that their capacitance was about 10 nf each . the rear of the conductor 1611 was insulated using a 5 mm layer 1614 of 353nd medical grade epoxy ( epoxy technology , billerica , mass ., usa ) and a wire 1613 is connected to the conductor 1611 . of course , it may be appropriate to vary the dimensions of the electrodes depending on the intended application . fig3 b depicts a test chamber that includes four electrodes 1610 , arranged in pairs and positioned in a 50 mm petri dish 1626 . the electrodes were held in place by a polycarbonate holder 1624 . electric fields were generated in the test chamber by applying an ac voltage across one pair of opposing electrodes , then applying an ac voltage across the other pair of opposing electrodes , in an alternating sequence to produce electric fields in the medium that are oriented at 90 ° with respect to each other . the electrodes were placed 23 mm apart . the electrodes were completely insulated from the medium in the petri dish by the ceramic insulation 1614 on the face of the electrode 1610 , so the field is capacitively coupled through the layer 1614 into the target region . fig3 c depicts a setup that was used to induce fields in the test chamber 1620 . the output of a sinewave generator 1632 ( model 662 , or - x , israel ) is routed to an rf amplifier 1634 ( 75a250 , ar worldwide , souderton , pa ., usa ), and the output of the rf amplifier 1634 is routed to a field direction switching relay 1636 that either imposes the amplified sine wave between the upper and lower electrodes or between the right and left electrodes . the switching relay is configured to switch back and forth between those two states periodically , thereby switching the direction of the field at the desired interval . the entire field generating system was placed inside a faraday cage 1644 in order to meet the guidelines for limiting exposure to time - varying electric , magnetic , and electromagnetic fields of the international non - ionizing radiation committee ( inirc ). temperature was measured continuously using insulated t type thermocouple ( omega , stamford , conn .) with its tip positioned at the center of the chamber 1620 . the thermocouples were connected to a tc - 08 thermocouple data logger ( pico technologies , uk ) the output of which was connected to computer 1630 . when high field frequencies ( 30 - 50 mhz ) were used , the fields interfered with the temperatures measurements . so to measure the temperature , the field was temporarily turned off for two seconds during each temperature measurement . as electric fields are associated with heat production , the chamber temperature was held at the desired value by computer feedback control of the amplitude of the waveform at the input of the power amplifier . the electric field intensities in the culture medium were measured using a shielded coaxial probe having two exposed tips fixed at a distance of 1 cm . the probe was connected , through a coaxial cable , to a 190b floating scope meter ( fluke , the netherlands ). field intensities were measured at the end of each treatment by dipping the probe in the culture media , such that the two measuring points were in parallel with the lines of the electric field . field intensities are expressed as peak - to - peak voltage per centimeter distance ( v / cm ). overnight bacterial cultures were diluted in fresh lb broth to an od that corresponds to bacterial counts of 1 × 10 7 colony forming units ( cfu )/ ml . petri plates containing the electric fields chamber 1620 were filled with 7 ml of the diluted cultures , and placed inside a pre - cooled incubator ( foc 2251 , velp scientifica ). fields were applied for 2 hours for s . aureus and 2 . 5 hours for p . aeruginosa with the field direction alternating every 300 ms ( i . e ., 300 ms in one direction followed by 300 ms in the other direction ). preliminary experiments indicated that these durations were sufficient to allow for approximately one order of magnitude growth of the control ( unexposed to electric fields ) group . temperature within the chamber 1620 was controlled by modifying the field strength within a predetermined range since the field causes heating . the electric fields chamber temperature reached 37 ± 0 . 2 ° c . within the first 5 minutes of the experiment in both the treated group and in the control group . ( the control bacteria groups were not exposed to the electric fields , but were temperature - controlled to match the temperature in the test groups .) at the end of treatment , the cultures were stirred several times by up and down pipetting . four aliquots of 250 μl were dispensed into a 96 microwells plate ( nunclon ™ δ , nunc , denmark ) and the od was determined spectrophotometrically with a microplate reader ( infinite 200 , tecan , austria ) at 750 nm . the optical densities ( ods ) of the blanks , which consisted of uninoculated lb , were subtracted from the ods of the inoculated plates . the percentage of growth for each well was calculated by dividing the od of the wells by that of the control : ( od 750nm of treated wells / od750nm of the control well )× 100 . the effect of the electric fields &# 39 ; frequency was tested by applying fields between 100 khz and 50 mhz . the results , depicted in fig3 a and 33b , show that 2 - 4v / cm electric fields inhibit the growth of the s . aureus ( after 2 hours treatment ) and p . aeruginosa ( after 2 . 5 hours treatment ), respectively . the calculated effect , expressed in % ( using the scale on the left side of the graphs ), is based on od measurements . averages of at least two independent experiments ± standard errors are presented . the corresponding average field intensities ± standard errors are indicated by the solid line ( using the scale on the right side of the graphs ). the results show that the growth inhibition is frequency dependent , having a maximum growth inhibition at 10 mhz fields for both s . aureus and p . aeruginosa . note that as the electric fields generating system was designed to maintain a constant temperature in the chamber by adjustment of the field intensity , and therefore the fields &# 39 ; intensities vary between the different frequency tests . the field intensity variations in the tests was limited to a range of ± 1 v / cm . the results presented are means ± standard errors ( se ) of at least 2 independent experiments , each consisting of 6 - 8 plates . higher field frequencies were not tested due to equipment limitations . the effect of the electric fields &# 39 ; intensity was tested by applying 10 mhz fields to s . aureus at different intensities for 6 hours . the relative growth , based on cfu counts , is expressed as a percentage of the heat control ± standard errors . the initial s . aureus concentration in this set of experiments was 0 . 5 - 1 × 10 5 cfu / ml . as seen in fig3 , the growth inhibition is field intensity dependent reaches a plateau of just above an 80 % inhibition , at field intensities of about 2 - 2 . 5 v / cm . note that although this intensity worked best for treating s . aureus at 10 mhz , field strengths between 0 . 5 and 10 v / cm may be used . the effect of the switching rate of the electric fields between the two perpendicular directions was tested by applying 10 mhz , 3 . 5 v / cm fields and varying the switching rate ( i . e ., the time the field was applied in each direction ). the dependency of the fields &# 39 ; inhibitory effect is illustrated in fig3 a and 35b for s . aureus and p . aeruginosa , respectively ( after treatment for 2 hours for s . aureus or 2 . 5 hours for p . aeruginosa ). the results indicate that for s . aureus , durations of 100 msec , 1 sec , and 30 sec resulted in a significantly higher inhibition than the other durations tested . in the case of p . aeruginosa the maximal inhibition was observed when the duration of each field direction was 30 sec . the combined effect of the electric fields and antibiotics was also tested . chloramphenicol was obtained as powder and dissolved in etoh ( 99 %, frutarom ). all the stock solutions were filter sterilized and held at − 20 ° c . until use . serial twofold dilutions of each antibiotic agent were prepared following nccls guidelines . the mic of an antibiotic was defined as the lowest concentration that completely inhibited growth of the organism , as determined by the unaided eye . these results were in agreement with over 95 % inhibition compared with that of drug - free wells , as determined using the microplate reader at 750 nm . the mic of electric fields was defined as the lowest intensity that inhibits growth by 80 % or more compared with control , as determined using the microplate reader . drug interactions with the electric fields were assessed according to the checkerboard method , with the following modifications : s . aureus inocula were diluted in lb medium containing the antibiotic to final concentration of 0 . 5 to 1 . 0 × 10 5 cfu / ml . the final concentrations of the chloramphenicol ranged from 0 . 125 to 16 ng / ml . petri dishes containing the electric fields chamber were filled with 7 ml of the diluted cultures , and placed inside a pre cooled incubator . fields were applied for 6 hours with the field direction alternating every 300 ms and the field intensities were varied by changing the incubator ambient temperature . thus , lower ambient temperatures allowed for higher field intensities while maintaining the proper culture temperature of 37 ° c . control plates containing the same electric fields chambers were placed in a pre - warmed incubator set at 37 ° c . at the end of the treatment , the cultures were stirred by pipetting the plate content up and down . quadruplicates of 250 μl each were transferred to a 96 microwells plate ( nunc ) and the od was determined using tecan microplate reader . cultures were subjected to serial 10 - fold dilution ( up to 1 / 10 , 000 ) by adding 20 n 1 of sample to 180 μl of saline solution ( 0 . 85 % nacl ), from which 80 μl aliquots were plated on lb agar plates ( 1 . 5 % agar , 1 . 0 % bacto tryptone , 1 % nacl , 0 . 5 % yeast extract ). cfu counts were performed after overnight incubation at 37 ° c . the results were grouped and the effect was calculated by dividing the od or cfu of the experiments plates with those of the control plates . to evaluate the effect of the combinations , the fractional inhibitory concentration ( fic ) was calculated for the electric fields and for each antibiotic . the following formulas were used to calculate the fic index : synergy was defined as an fic index of ≦ 0 . 5 . indifference was defined as an fic index of & gt ; 0 . 5 but of ≦ 4 . antagonism was defined as an fic index of & gt ; 4 . the mic of chloramphenicol against s . aureus was found to be 4 μg / ml , similar to the concentrations reported in the literature . the combined effect of electric fields and chloramphenicol on the growth of s . aureus is given in table 1 . the results demonstrate that there is an additive effect between electric fields and chloramphenicol . as seen , in the presence of 4 v / cm 10 mhz electric fields applied for 6 hours , with the field direction alternating every 300 ms , much lower concentrations of chloramphenicol ( 1 μg / ml ) are sufficient to produce complete inhibition of the growth of s . aureus . the fic index was found to be 0 . 625 , indicating that there is an additive effect for the combined exposure to electric fields and chloramphenicol . note that these calculations are based on od measurements . tests were also performed to determine whether repeated exposure of p . aeruginosa to electric fields could select for bacteria that are resistant to the fields . for this test , overnight bacterial cultures were diluted in fresh lb broth to an od that corresponds to bacterial counts of 1 × 10 6 cfu / ml . bacteria were exposed to 10 mhz electric fields of approximately 5 v / cm for 6 hours as described above , with the field direction alternating every 300 ms . control bacteria groups , placed in inactivated electric fields chambers , were positioned in a pre - warmed incubator . the electric fields &# 39 ; effect was determined based on the od measurements . after the initial electric fields inhibition experiment , the fields &# 39 ; effect was determined anew daily , for four passages as follows : samples from the plates treated with electric fields were pooled and used again for electric fields effect determination in the subsequent generation . in parallel , the fields &# 39 ; effect evolution during these subcultures was compared concomitantly with each new generation , using bacteria harvested from control wells ( wells cultured in the pre - warmed incubator ). the relative effect was calculated for each experiment from the ratio of inhibition obtained for a given subculture to that obtained for first - time exposure . the results of this repeated exposure test of p . aeruginosa to electric fields are presented in fig3 . as demonstrated , four passages of exposure to electric fields did not result in development of resistance , and the inhibition percentage remained around 70 % in each iteration . numerical calculations , based on finite element mesh , were used in order to calculate the electric field distribution inside dividing p . aeruginosa and s . aureus , and the following geometries and parameters were used for the calculations : p . aeruginosa was assumed to be an ellipse with a large radius of 2 . 0 μm and a small radius of 0 . 6 μm having two membranes ( external and internal ) of 8 nm thickness . the two membranes were assumed to be separated by a periplasmic space of 50 nm . the dividing bacterium furrow diameter was assumed to be 0 . 2 μm and the applied external field was 20 v / cm . since no published data on the electric properties of p . aeruginosa was found , the following data for e . coli was substituted in the calculations : inner membrane conductivity — 1 μs / m , outer membrane conductivity — 3 ms / m , medium conductivity — 0 . 5 s / m , cytoplasm conductivity — 0 . 5 s / m and the conductivity of the periplasmic space — 50 ms / m . s . aureus was assumed to be a sphere with a radius of 0 . 6 μm and a membrane thickness of 8 nm . the bacterial cell wall thickness was assumed to be 20 nm , and the dividing bacterium furrow diameter was assumed to be 0 . 2 μm . the applied external field was 20 v / cm . in the simulation the membrane conductivity was assumed to be 1 μs / m , and the cell wall conductivity 10 ms / m . the conductivity of the medium was 0 . 5 s / m and the conductivity of the cytoplasm was assumed to be 0 . 8 s / m . the electric field distribution in and around p . aeruginosa and s . aureus was calculated using finite element mesh method , and the results are depicted in fig3 and 38 . in the simulation ( fig3 ) it is seen that the inside dividing rod - like bacteria , close to the furrow , the electric field is strongest and is non uniform . this non uniformity generates dielectrophoresis forces . when the field intensity is 20 v / cm , the magnitude of the force acting on a dipole of 3000 debyes inside dividing bacteria as a function of field frequency is depicted in fig3 a for p . aeruginosa , which peaks at about 2 mhz , and depicted in fig3 b for s . aureus , which peaks at about 7 mhz . in vivo tests were also performed to test the ability of electric fields to inhibit the growth of bacterial pathogen in vivo . 2 × 10 8 s . aureus bacteria were injected s . c . into the dorsum of 8 weeks old female icr mice . mice in which abscess was developed in the site of injection within 24 hours were anesthetized and 4 electrodes were placed on their back . the electrodes were similar to those described above but also contained a thermistor positioned inside the electrodes near the electrode surface . the electrodes were arranged in two electrode pairs positioned perpendicular to each other so as to generate electric fields in two different directions , spaced 90 ° apart , and the distance between each electrode within any given pair was 2 cm . note , however , that alternative electrode configurations may be used , e . g ., as discussed above in connection with fig2 and 28 . mice in the control group were identical to those in the electric fields group , but carrying heating electrodes . mice were held in an ivc system ( techniplast , italy ) whose cages were modified in order to allow for electric fields application inside the cage . 10 mhz electric fields were applied for 48 hours at a nominal field strength of about 5 v / cm , with the field direction alternating every 300 ms , and the temperature at the electrode surface was monitored continuously . the electrodes temperature was held at the desired value by computer feedback control of the amplitude of the waveform at the input of the power amplifier . sham control electrodes were heated to the same temperature as the electric fields electrodes . no adverse side effects were observed . after 48 hours the mice were anesthetized , sacrificed , and the electrodes were removed . a 2 × 2 cm square of the skin surrounding the abscess was harvested , weighed and homogenized . the homogenate was serially diluted and plated in triplicates for cfu determination . the initial s . aureus concentration in these experiments was 2 × 10 7 cfu / ml . the results of this experiment are depicted in fig3 , which indicate that the electric fields can inhibit bacterial growth in mature abscesses . depending on the location of the target region within the body , the electrodes may be either placed on the patient &# 39 ; s body or implanted in the patient &# 39 ; s body . for example , in a patient with an infected cyst , the electrodes could be implanted near the cyst . note that the megahertz - range frequencies that were found to be effective against bacteria have virtually no impact on eukaryotic cells , so specificity is excellent , and adverse side effects are not a major concern . optionally , different frequencies may be applied to the target region , either simultaneously or sequentially , to target one or more types of bacteria that may be present , as discussed above in connection with the other embodiments . the method may also be used in vitro , e . g ., to combat bacteria in food , on media , cell cultures , etc . in vivo experiments were also performed on pseudomonas aeruginosa strain pao1 in lungs of infected mice . for this example , bacteria were grown in lb media ( 1 . 0 % bacto tryptone , 0 . 5 % yeast extract , 1 . 0 % nacl ( frutarom , haifa , israel ). broth cultures of freshly plated bacteria were grown in 250 ml of liquid medium at 37 ° c . in an orbital shaker at 220 rpm ( new brunswick scientific , n . j ., usa ) up to logarithmic phase , centrifuged and resuspended in saline containing 15 % glycerol . stocks were divided into aliquots of 50 μl each containing 2 . 17 × 10 7 colony forming units ( cfu )/ ml and kept at − 70 ° c . until use . experiments were conducted on 7 - to 8 - week - old ( body weight 26 - 35 g ) icr female mice obtained from harlan laboratories ( israel ). mice were housed under standard conditions of light and temperature , and were fed standard laboratory chow and water ad libitum . electric fields were generated by 2 pairs of parallel metal electrodes , 15 mm - long ; 3 mm - high . the front of the electrodes was completely insulated from the medium by a ceramic [( lead magnesium niobate - lead titanate ( pmn - pt ) ( edo , new york , n . y .)] having a very high dielectric constant (∈& gt ; 5000 ) such that their capacitance was about 10 nf each . the back of the electrodes was insulated by a 2 . 5 mm thick layer of 353nd medical grade epoxy ( epoxy technology , billerica , mass ., usa ). each electrode contained a thermistor placed within the epoxy directly on top of the ceramic in order to allow for constant monitoring of the electrodes &# 39 ; temperature . the four insulated electrodes were attached to the skin using hydrogel after mouse depilation . the electrodes were wrapped with leucoplast and electrodes wires were connected to the electric fields generating system or to the sham control system . the four electrodes were functionally divided into two pairs , identified by the red or blue wires . the electrode pairs were placed so as to create two perpendicular field directions at the center of the animal body . in order to allow for electric fields generation in mice , while maintaining the strict isolation required when working with animal infected with pathogens , the mice were held in an individually ventilated cage system ( ivc ) ( touchslim ™, techniplast , italy ) that was modified as follows : each cage ( gr900 , techniplast , italy ) was split by a polycarbonate partition into two units , each housing one mouse . each mouse was treated with a separate field generator consisting of an rf amplifier ( 75a250 , ar worldwide , souderton , pa ., usa ) activated by a sine - wave generator ( model 662 , or - x , israel ). six hermetically sealed , shielded electric connection sockets ( sm3416 bnc , s . m . electronics , tx , usa ) were positioned at the front panel of the cage . each socket allowed for the connection ( by means of coax cables ) of a connection box placed inside the cage to an exterior device ; an rf amplifier or a temperature measuring system . the connection box served for transferring the electric currents to the mice electrodes , and the mice temperature readout to the computer . the entire ivc system , together with the electric fields generating system , were placed inside a faraday cage in order to meet the guidelines for limiting personnel exposure to time - varying electric , magnetic , and electromagnetic ( international non - ionizing radiation committee — inirc ). to avoid field interference with temperature measurements , temperatures were measured periodically while the field was briefly turned off . as electric fields are associated with heat production , the electrodes surface temperature was kept constant at the desired level by computer feedback control of the field amplitude . the current source output was switched , every 300 ms , between the two electrodes pairs . this interval was found previously to be effective against p . aeruginosa while preventing the formation of temperature gradients that could affect bacterial growth rate ( giladi et al ., 2008 ). the lung temperature was measured periodically by inserting a thermocouple connected to a temperature data logger ( tc08 usb ) ( pico technology , cambridgeshire , uk ) into the mouse trachea . two control groups were set in each experiment : sham heat control , and non treated control ( referred to as “ control ”). control electrodes of identical size and shape to the electric fields electrodes , were placed on mice of the two control groups . the sham heat electrodes produced equal temperature changes to those produced by the field electrodes by means of a heating resistor incorporated within them , and the sham heat electrodes were placed in the same positions as the real electrodes . except for the differences in the electrodes , the control mice and the sham heat treated mice were held in conditions identical to those of the electric fields treated mice . the electric field intensity was measured using a shielded coaxial cable and probe having two exposed tips positioned at a distance of 1 cm from each other . the probe was connected to a floating input oscilloscope ( 190b fluke , the netherlands ). field intensities within lungs were measured by performing a 5 mm long incision in the thoracic skin of an anesthetized mouse and inserting the measurement probe at an intercostal space to a depth of 5 mm into the thorax . the probe was oriented such that the line connecting the two measuring points was parallel to the lines of the electric field . field intensities are expressed as peak - to - peak volts per centimeter distance ( v / cm ). mice were rendered neutropenic ( neutrophil counts , & lt ; 100 / mm 3 ), as described in andes and craig ( 1998 ), by two intraperitoneal injections of cyclophosphamide ; four days before infection ( 150 mg / kg of body weight ) and an additional injection one day before infection ( 100 mg / kg of body weight ). the pulmonary infection model of takeda et al ., ( 2006 ) was used with minor modifications : anesthetized icr mice were challenged intra - nasally with 20 μl of saline containing various concentrations ( 10 4 - 10 7 cfu / ml ) of p . aeruginosa strain pao1 . on the day of infection , immediately before use , frozen bacterial cultures were thawed and diluted in saline to the desired concentration . anesthetized mice were challenged intra - nasally with the bacterial suspension . mice were sacrificed at 0 , 3 , 6 , 9 , 24 , and 48 hours after infection in order to determine cfu counts in their lungs . after skin disinfection with 70 % alcohol , lungs from sacrificed mice were removed aseptically , photographed , weighted and their cfu content was determined . application of electric fields to the mouse torso was carried out as follows : 4 days before infection , the torso of anesthetized mice was shaved with electrical clippers and depilated using cold wax . electric fields treatment was applied through four insulated electrodes placed around the mouse torso so as to generate fields of two perpendicular directions . mice were placed inside the ivc cages and the electrodes were connected to the connection box . application of electric fields began 3 hours after infection and was maintained for 48 h with two brief stops daily for monitoring the physical condition of the mice . after 48 h of treatment , the mice were sacrificed and bacterial numbers in lung were determined . the combined effect of electric fields and antibiotics was tested using ceftazidime , an agent recommended by the infectious disease society of america for the treatment of hospital acquired pneumonia . experiments were conducted as described above for electric fields treatment of p . aeruginosa pulmonary infection with the following modifications : mice were challenged intra - nasally with a predetermined bacterial titer . ceftazidime ( 5 mg / kg body weight ) was administered intra - peritoneally twice daily for 48 hours starting 3 h after infection . antibiotic administration was stopped at least 12 h before experiment termination . cold sterile saline was added to each lung sample tube , saline : tissue weight ratio being 10 : 1 . tubes were placed in an ice bath and the suspensions were homogenized using omni tissue homogenizer ( omni , ga ., usa ) with omni disaggregation tips . appropriate suspension dilutions were plated on lb agar plates and kept at 37 ° c . for 24 h . bacterial counts were expressed as number of p . aeruginosa cfu per lung . bacterial growth in the lungs of each mouse was expressed using the following formula : log ( cfu t48 / cfu t0 ), where cfu t48 is the cfu counts in the mouse lungs at the end of treatment and cfu t0 is the initial number of bacteria used for inoculation in the specific experiment . the results of all mice that received the same treatment were pooled and the average bacterial growth was calculated for each group . t test with two tailed distribution and equal variance was used to compare the mean values . lungs were first inflated with formaldehyde to their normal volume and then underwent fixation . the specimens were processed and embedded in paraffin wax . histological sections of 5 μm were cut , stained with haematoxylin - eosin ( he ) and examined using light microscopy by an independent expert who was blinded to the source of the sections . a semi - quantitative grading scheme was used to evaluate the extent of the lesions in the sections as follows : minimal ( grade 1 ) lesions involving less than 10 % of the lung section ; mild ( grade 2 ), 11 %- 40 %; moderate ( grade 3 ), 41 %- 80 %; marked ( grade 4 ), 81 %- 100 %. the results of the experiments are described below . field intensities and temperature measurements were done during electric fields treatment and sham heat application . the average electric fields intensities in the lungs were 12 ± 4 v / cm . under these conditions lung temperature was identical to , or up to 1 ° c . lower than the electrode surface temperatures which were set to 37 ° c . for both the electric fields and the sham heat control . pulmonary infection was induced by intranasal administration of different amounts of p . aeruginosa strain pao1 to neutropenic icr mice . bacteria concentrations that were found to induce a severe pulmonary infection which persisted for at least 48 h were around 5 × 10 4 cfu / mouse . higher concentrations ( 5 × 10 5 cfu / mouse ) resulted in a high mortality rate ( 100 % within the first 24 h ) while lower concentrations ( 5 × 10 3 cfu / mouse ) resulted in a complete recovery . table 2 shows the electric fields &# 39 ; effect on mice with p . aeruginosa lung infection , used alone and combined with ceftazidime . the log cfu at both the start of treatment ( t 0 ) and 48 hours later ( t 48 ) is listed in table 2 . table 3 shows the electric fields &# 39 ; effect on mice with p . aeruginosa lung infection , used alone and combined with ceftazidime . the growth listed in table 3 is relative to the inoculums after 48 hours of treatment . table 4 shows the electric fields &# 39 ; effect on mice with p . aeruginosa lung infection , used alone and combined with ceftazidime . the lung weights listed in table 4 are the weights at the end of the 48 hour treatment . 48 hours electric fields treatment of mice suffering from pulmonary infection resulted in 3 . 4 log reduction in the cfu content of the treated mice as compared to the untreated control mice ( see table 2 ). the sham heated control treatment resulted in 2 . 5 log reduction as compared to the control mice ( see table 2 ). the average bacterial growth [ log ( cfu t48 / cfu t0 )] of both electric fields treated mice and the sham heat treated mice was significantly lower than in the control mice ( see table 3 ). a significant reduction was also observed in the weight of lungs of electric fields treated mice as compared to both the sham heated control mice ( p = 0 . 02 ) and to the untreated control mice ( p & lt ; 0 . 001 ) ( see table 4 ). finally , histopathology examination of the lung samples of the mice that were treated with electric fields were rated as normal to grade 1 with focal acute inflammation . in contrast , lungs of control mice or the sham heat group were rated as grade 2 to 3 associated with acute necrotizing pneumonia and the presence of numerous bacterial colonies . experiments were also performed to test the effects of combined treatment of pulmonary infection caused by p . aeruginosa by electric fields combined with ceftazidime . the inoculums that were found to induce a persistent pulmonary infection in the presence of ceftazidime ( 10 mg / kg bw / day ) alone were around 5 × 10 5 cfu per mouse . the results presented in table 2 demonstrate that 48 h combined treatments of electric fields and ceftazidime resulted in a 1 . 5 log reduction in the lung cfu content compared to the antibiotic - only treated control . the combined treatment of sham heat and ceftazidime did not result in a significant count reduction compared to the control ( see table 2 ). bacterial growth [ log ( cfu t48 / cfu t0 )] in the lungs of mice treated with electric fields and ceftazidime was significantly lower than in the control mice ( p = 0 . 004 ) ( see table 3 ). the average lung weight was significantly lower in both the ceftazidime / electric fields combination treatment group ( p & lt ; 0 . 001 ) and in the ceftazidime / sham heat combination treatment group ( p = 0 . 047 ) as compared to the control group ( see table 4 ). the results obtained demonstrate that electric fields , previously shown to be an effective in - vitro tool for combating bacterial pathogens ( giladi et al ., 2008 ), are also effective in the in - vivo arena . specifically , it was demonstrated that electric fields , applied by means of external insulated electrodes , have a significant inhibitory effect on the growth of a bacterial pathogen in - vivo . the inhibitory effect was observed when electric fields were applied either as a sole treatment or as an adjuvant to antibiotic therapy . one striking outcome of the electric fields application was the fact that the number of bacteria in the lungs of electric fields treated mice was increased only by a fraction of an order of magnitude compared to the number in the inoculums used for infection , while at the same time the number of bacteria in the control group grew by 3 . 8 orders of magnitude . this observation could be the consequence of either an electric fields inhibitory effect or a bactericidal effect . histopathology analysis demonstrated that in the electric fields treated mice , the lung morphology was normal with no evidence of a former massive infection . thus it is reasonable to assume that the electric fields treatment led to cell proliferation arrest , rather than to the elimination of the bacteria after thriving in the lungs . supportive evidence for this conclusion can be found in the results of the experiment in which combined electric fields / ceftazidime treatment was tested . ceftazidime is a third - generation cephalosporin antibiotic with a broad bactericidal activity against gram positive and gram negative bacteria . like other beta - lactam antibiotics , ceftazidime is most effective against dividing bacteria . indeed , ceftazidime treatment of 10 mg / kg bw / day , alone , resulted in a growth reduction of close to 2 logs , compared to the non treated lungs ( 1 . 9 vs . 3 . 8 respectively , see table 3 ). yet , the combined treatment of electric fields and ceftazidime did not lead to a reduction in the bacterial growth compared to the electric fields treatment alone ( 0 . 4 vs . 0 . 5 , respectively , see table 3 ), nor did it reduce cfu counts in the lungs compared to the inoculums suggesting that bacterial growth was arrested . previously we demonstrated that application of electric fields in vitro led only to a 20 % reduction in the number of treated bacteria compared to the control , which is considerably less than the inhibition that occurred in the in vivo study discussed herein . one possible explanation for the enhanced efficacy in the in vivo experiments could be derived from the fact that the electric fields inhibitory effect is positively correlated with field intensity ( giladi et al ., 2008 ). while the electric fields intensity in the in vitro experiments was limited to 4 v / cm , in order to avoid over heating of the culture , the electric fields intensity in the in vivo experiments was significantly higher ( i . e ., about 12 v / cm ). the application of such electric fields with higher intensities was made possible in view of the active heat removal that occurs in the mouse &# 39 ; s body . experimental data obtained for both microorganisms and proliferating living cells , such as cancer cells , indicates that higher field intensities result in higher efficacy . however , there is a practical limit on field intensity due to the heat generated under the electrodes and within the treated animal , and the relevant anatomy &# 39 ; s ability to carry that heat away . for example , in the case of a human brain , the blood can carry away the heat that is generated in the tissue , and the total blood flow is about 2000 cc / min . assuming that we want to keep the temperature of the brain below 39 ° c ., which is 2 ° above the normal body temperature , this blood flow should be able to carry away 4000 calories / min , which corresponds to about 280 w . we should therefore be able to apply 278 w safely to the brain . since the side to side electric resistance of the human brain is about 100 ohms , and power equals voltage squared divided by resistance , we should be able to use a voltage of 167 v safely . this voltage drops over a distance of about 10 cm , in which case the field strength will be about 17 v / cm . thus , for the brain , it would be reasonable to operate at field strengths between 5 and 20 v / cm , and more preferably at field strengths between 10 and 17 v / cm . in the case of resting skin , the blood flow is sufficient to handle fields of 5v / cm , and in the case of hyperemic heated skin the blood flow is sufficient to handle fields of 50 v / cm or even 80 v / cm . it is therefore expected that practical useful fields will range from 2 v / cm to 100v / cm , depending on the treated organ and its state . note that the above calculations are for rms voltage , and not peak to peak voltage . another possible factor for the enhanced efficacy of the electric fields treatment in the in vivo arena could be related to the fact that the sham heat treatment also led to an inhibitory effect on bacterial growth . though the sham heat control effect was smaller than the electric fields effect , it was nevertheless significant . bacterial growth inhibition due to elevated temperatures may result from either a direct effect of the heat on bacterial growth or from local and systemic “ host ” reactions and responses to the heating . the former hypothesis was tested in vitro by comparing the growth rate of p . aeruginosa at various temperatures within the range of normal to febrile temperatures . similar to the reports in the literature ( magnusson et al ., 1995 ), we found that the growth rate of p . aeruginosa is positively correlated with increase in the temperature in the range of 34 - 38 ° c . thus we can rule out the possibility of a direct effect of heat on bacterial growth . the alternative notion , i . e . that local and systemic host reactions to elevated temperatures negatively affect bacterial growth is not new . in fact , heat and fever were used as a tool against microbial pathogens for over a century ( reviewed by atkins , 1982 and hasday et al ., 2000 ). there are numerous reports regarding the effect of elevated host temperatures on the growth of bacterial pathogens demonstrating for example that : fever induced after malaria inoculation can serve as a treatment against treponema pallidum ( wagner - jauregg , 1919 ), febrile core temperature is essential for optimal host defense against klebsialla pneumonia peritonitis in mice ( jiang et al ., 2000 ), fever in elderly patients with community - acquired pneumonia is positively correlated with high survival rates ( ahkee et . al , 1997 ) and maintaining a normal core body temperature ( 36 . 6 ± 0 . 5 ° c .) after anesthesia decreases the incidence of infectious complications in patients undergoing colorectal resection ( kurz et al ., 1996 ). amongst the mechanisms suggested to play a role in the antibacterial effect of heat , augmentation of the innate immune function is probably the most intensively studied one ( hanson , 1993 ; hasday et al ., 2001 ; mackowiak et al ., 1983 ; lederman et al ., 1987 ; rosenpire et al ., 2002 ). though our results demonstrate that electric fields and sham heat application did not cause an increase in the lung temperatures , they did raise the temperature of the peripheral organs of the treated mice , by at least 2 degrees ( the normal skin temperature of mice is 34 - 35 ° c . while in the present study the electrodes temperature was set to 37 ° c .). hanson ( 1993 ) demonstrated that mature primary t - cells response is strongly regulated by temperature changes in the range of 29 ° to 37 ° c ., which corresponds to the peripheral tissue temperature elevation during febrile episodes . this finding provides a possible explanation for the sham heat inhibitory effect reported in the present study . since application of electric fields is always associated with heat production it is reasonable to assume that the enhanced efficacy of the fields reported in the present study compared to our previous report ( giladi et al ., 2008 ) is in part due to elevated temperatures of the peripheral tissue . thus , electric fields can be an effective and safe antibacterial treatment modality which could be applied in cases of both superficial and deep infections , either as a sole treatment or in combination with antibiotics , for both p . aeruginosa pathogens and other types of bacteria . such treatments will involve placement of insulated electrodes on the skin surrounding the infected organs , and generating electric fields by applying the appropriate ac voltages to those electrodes . while the invention has been particularly shown and described with reference to preferred embodiments thereof , it will be understood by those skilled in the art that various changes in form and details can be made without departing from the spirit and scope of the invention .

cells that are in the process division are vulnerable to damage by ac electric fields that have specific frequency and field strength characteristics . the selective destruction of rapidly dividing cells can therefore be accomplished by imposing an ac electric field in a target region for extended periods of time at particular frequencies with particular filed strengths . some of the cells that divide while the field is applied will be damaged , but the cells that do not divide will not be harmed . this selectively damages rapidly dividing cells like bacteria , but does not harm normal cells that are not dividing . since the vulnerability of the dividing cells is strongly related to the alignment between the long axis of the dividing cells and the lines of force of the electric field , improved results can be obtained when the field is sequentially imposed in different directions .

referring to fig1 there is shown an elevation view of the device 1 of the preferred embodiment . the device 1 is comprised of only three parts : the rod holder 2 that is an elongated hollow tube with a first end , a second end , and an inside and an outside is the first part ; the base member 3 is the second part , and the imbed h bar 4 is the third part . the device 1 is shown set on a dock 8 that is comprised of planks 9 or boards . the planks 9 have a gap 14 between said planks for rain water and wave water to flow through . the planks 9 with gaps 14 between each plank 9 is common for docks 8 , decks or piers . the dock 8 is further shown with at least one plank support beam 10 and at least one dock support stanchion 11 which is also common for docks , decks and / or piers . the dock 8 is further shown in the water 12 . the device 1 is set on the dock by placing the second end of the imbed h bar 4 into the gap 14 wherein the second end of the imbed h bar 4 or lower inverted t 21 is parallel to the gap 14 and wherein when the inverted t 21 is below the underside of at least two planks 9 wherein the imbed h bar 4 is rotated at least fifteen degrees ( 15 °), but it could also be rotated more than ninety degrees ( 90 °) until the inverted t 21 is underneath at least two planks 9 . with the inverted t 21 underneath the two planks 9 the base member 3 is rotated in the direction necessary to cause the second end of the base member 3 to move in the direction of the top of the planks 9 until the base member 3 pulls up on the rod holder 2 and the imbed h bar 4 thus pulling up on the lower inverted t 21 until the upper surface of the lower inverted t 21 comes in contact with the underside of the planks 9 thus locking the planks 9 between the lower end of the base member 3 and the upper end of the inverted t 21 thereby locking the device to the planks 9 of the dock 8 and further allowing a fishing rod 19 to be placed in the device in the first position 5 , the second position 6 , the third position 7 , all at the same time or in any one position at different times . referring to fig2 there is shown a plan view of the device 1 on a dock 8 . planks 9 are shown with gaps 14 between each plank 9 . two planks support beams 10 are shown below the planks 9 . the device 1 is shown with a fishing rod 19 shown in a first direction 13 and a second fishing rod 19 in a second direction 20 . the fishing rod 19 could also be placed in a third direction 22 or a fourth direction 23 . it is possible to hold at least two fishing rods 19 pointing in two or more directions at the same time , with only one rod holder 2 . although the rod holder 2 is shown a square , it could be round , triangular , rectangular or other shape by design choice . referring to fig3 there is a plan view of the first end of the square rod holder 2 of the device 1 . the square rod holder 2 is shown with a first side 15 , a second side 16 , a third side 17 , and a fourth side 18 . the second side 16 and the third side 17 are similar to each other in hole and slot configuration . the first side and the fourth side are also similar to each other in hole configuration . the similarities of hole and slot configuration of the second side and third side and the hole configuration of the first side 15 and the fourth side 18 allow the rod holder 2 to be rotated one hundred eighty degrees ( 180 °) and be used in the same way in the opposite direction if one is fishing on the other side of the dock . referring to fig4 there is shown a section elevation view of the device 1 as taken through fig3 . the rod holder 2 is shown with a first end and a second end . the second end is shown with the imbed h bar 4 imbedded in the plastic rod holder 2 . plastic is used by design choice , but it could be steel , aluminum or other suitable material by design choice . the second end of the rod holder 2 is also shown with outside threads 33 formed on the outer periphery . the outside threads 33 suitably mesh with the inside threads 34 formed on the inside of the base member 3 . the imbed h bar 4 has been inserted through the gap 14 between the planks 9 , rotated to where the lower inverted t 21 is below the planks 9 and the base member 3 is turned in a suitable direction while the rod holder 2 is held and prevented from turning . as the base member 3 is turned , the outside threads 33 of the rod holder 2 react with the inside threads 34 of the base member 3 , causing the rod holder 2 to move in an upward direction 35 further pulling up on the imbed h bar 4 until the lower inverted t 21 of the imbed h bar 4 is compressed against the underside of the planks 9 and the second end of the base member 3 is compressed against the top side of the planks 9 thereby locking the device to the planks 9 ; to remove the device 1 from the planks 9 the base member 3 is rotated in the opposite direction until the lower inverted t 21 no longer is in contact with the underside of the planks 9 after which the rod holder 2 is rotated until the lower inverted t 21 is parallel to the gap 14 and the inverted t 21 is pulled out of the gap 14 . at the first end of the rod holder 2 there are shown the various holes and slots and their relationship to each other . it should be noted that no holes on one side are at the same elevation as holes on the opposite side ; therefore , holes on the first side are at a different elevation then holes on the fourth side 17 and holes on the second side are at a different elevation than holes on the third side . the different elevations will allow the fishing rod or fishing rods to be placed in the holes of the rod holder at an angle off of horizontal and therefore prevent the fishing rod from being pulled out by a fish . in fig4 the fishing rods 19 are represented by a centerline for clarity . one fishing rod 19 is shown in the first position 6 wherein the fishing rod is inserted into the first hole 27 on the second side 16 and the fourth hole 30 on the fourth side 18 . a fishing rod 19 is shown in the first position 5 wherein it is placed into the first slot 25 on the second side 16 and the fifth hole 31 on the fourth side 18 . a third fishing rod 19 is placed in the third position 7 through the inside of the hollow or open center of the rod holder 2 of the device 1 . a fourth fishing rod 19 is placed in a fourth position 24 through the fifth hole 31 on the fourth side 18 and the first hole 27 on the second side 16 . as shown , there is a possible combination of four possible positions in which to inset a fishing rod in one setting ; however , the same number of possible combinations exists if fishing rods were to be placed in the rod holder 2 from the holes in the first side and the third side which would be eight possible fishing rod placements . if the rod holder were rotated one hundred eighty degrees ( 180 °), another eight possible combinations would be possible and if the rod holder were lengthened and more holes were added , the combination of angles and directions that the fishing rod or rods could be placed would increase . all of these possible combinations are possible with a device 1 that is comprised of only three parts . referring to fig5 there is shown an elevation view of the outside of the fourth side 18 of the rod holder 2 . the fourth hole 30 and the fifth hole 31 are shown on the fourth side 18 . the outside threads 33 are shown at the second end of the rod holder 2 . the imbed h bar 4 is shown at the second end of the rod holder 2 . referring to fig6 there is shown an elevation view of the outside of the first side 15 of the rod holder . the second hole 28 and the third hole 29 are shown formed in the first side of the rod holder 2 . the imbed h bar 4 with lower inverted t 21 are shown at the second end of the rod holder 2 . referring to fig7 there is shown an elevation view of the outside of the second side 16 of the rod holder 2 . the first slot 25 is shown at the first end of the rod holder 2 and the first hole 27 is shown near the center of the rod holder 2 . referring to fig8 there is shown an elevation view of the outside of the third side 17 of the rod holder 2 . the second slot 26 is shown at the first end of the rod holder 2 and the sixth hole 32 is shown near the center of the rod holder 2 . although the system described in detail supra has been found to be most satisfactory and preferred , many variations are possible . for example , the rod holder could be round or triangular , the rod holder could be longer with three or four holes in line on each side and the holes could be square or triangular or round . the holes could also be on the corners of the box rod holder . the configuration of the rod holder could be a pentagon , a hexagon or an octagon . although the invention has been described with reference to the preferred embodiment , it will be understood by those skilled in the art , that additions , modifications , substitutions , deletions , and other changes not specifically described may be made in the embodiments herein , it should be understood that the details herein are to be interpreted as illustrative and are not in a limiting sense .

a device that can be fixed to a sun deck , dock and pier by means of an inverted t fixed to the second end of said device wherein said inverted t bar is placed into the gap between the planks or boards that comprise the deck , dock or pier wherein said inverted t is rotated to wherein the inverted t extends below the underside of said planks or boards and wherein a threaded base member is turned on the second end of said device further fastening said device to the topside of said boards or planks thereby locking said device to said boards or planks for the placement of and support for fishing rods , tools , umbrellas or other devices wherein multiple fishing rods or tools may be placed at different horizontal and vertical angles relative to one another .

the following description is presented to enable any person skilled in the art to make and use the invention . various modifications to the embodiments described will be readily apparent to those skilled in the art , and the generic principles defined herein can be applied to other embodiments and applications without departing from the spirit and scope of the present invention as defined by the appended claims . thus , the present invention is not intended to be limited to the embodiments shown , but is to be accorded the widest scope consistent with the principles and features disclosed herein . to the extent necessary to achieve a complete understanding of the invention disclosed , the specification and drawings of all issued patents , patent publications , and patent applications cited in this application are incorporated herein by reference . as will be appreciated by those of skill in the art , methods recited herein may be carried out in any order of the recited events which is logically possible , as well as the recited order of events . furthermore , where a range of values is provided , it is understood that every intervening value , between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the invention . also , it is contemplated that any optional feature of the inventive variations described may be set forth and claimed independently , or in combination with any one or more of the features described herein . the practice of the present invention can employ , unless otherwise indicated , conventional and digital methods of x - ray imaging and processing , x - ray tomosynthesis , ultrasound including a - scan , b - scan and c - scan , computed tomography ( ct scan ), magnetic resonance imaging ( mri ), optical coherence tomography , single photon emission tomography ( spect ) and positron emission tomography ( pet ) within the skill of the art . such techniques are explained fully in the literature and need not be described herein . see , e . g ., x - ray structure determination : a practical guide , 2nd edition , editors stout and jensen , 1989 , john wiley & amp ; sons , publisher ; body ct : a practical approach , editor slone , 1999 , mcgraw - hill publisher ; x - ray diagnosis : a physician &# 39 ; s approach , editor lam , 1998 springer - verlag , publisher ; and dental radiology : understanding the x - ray image , editor laetitia brocklebank 1997 , oxford university press publisher . see also , the essential physics of medical imaging ( 2 nd ed . ), jerrold t . bushberg , et al . the present invention provides methods and compositions for repairing joints , particularly for repairing articular cartilage and for facilitating the integration of a wide variety of cartilage repair materials into a subject . among other things , the techniques described herein allow for the customization of cartilage repair material to suit a particular subject , for example in terms of size , cartilage thickness and / or curvature . when the shape ( e . g ., size , thickness and / or curvature ) of the articular cartilage surface is an exact or near anatomic fit with the non - damaged cartilage or with the subject &# 39 ; s original cartilage , the success of repair is enhanced . the repair material can be shaped prior to implantation and such shaping can be based , for example , on electronic images that provide information regarding curvature or thickness of any “ normal ” cartilage surrounding the defect and / or on curvature of the bone underlying the defect . thus , the current invention provides , among other things , for minimally invasive methods for partial joint replacement . the methods will require only minimal or , in some instances , no loss in bone stock . additionally , unlike with current techniques , the methods described herein will help to restore the integrity of the articular surface by achieving an exact or near anatomic match between the implant and the surrounding or adjacent cartilage and / or subchondral bone . advantages of the present invention can include , but are not limited to , ( i ) customization of joint repair , thereby enhancing the efficacy and comfort level for the patient following the repair procedure ; ( ii ) eliminating the need for a surgeon to measure the defect to be repaired intraoperatively in some embodiments ; ( iii ) eliminating the need for a surgeon to shape the material during the implantation procedure ; ( iv ) providing methods of evaluating curvature of the repair material based on bone or tissue images or based on intraoperative probing techniques ; ( v ) providing methods of repairing joints with only minimal or , in some instances , no loss in bone stock ; ( vi ) improving postoperative joint congruity ; ( vii ) improving the postoperative patient recovery in some embodiments and ( viii ) improving postoperative function , such as range of motion . thus , the methods described herein allow for the design and use of joint repair material that more precisely fits the defect ( e . g ., site of implantation ) or the articular surface ( s ) and , accordingly , provides improved repair of the joint . the methods and compositions described herein can be used to treat defects resulting from disease of the cartilage ( e . g ., osteoarthritis ), bone damage , cartilage damage , trauma , and / or degeneration due to overuse or age . the invention allows , among other things , a health practitioner to evaluate and treat such defects . the size , volume and shape of the area of interest can include only the region of cartilage that has the defect , but preferably will also include contiguous parts of the cartilage surrounding the cartilage defect . as will be appreciated by those of skill in the art , size , curvature and / or thickness measurements can be obtained using any suitable technique . for example , one - dimensional , two - dimensional , and / or three - dimensional measurements can be obtained using suitable mechanical means , laser devices , electromagnetic or optical tracking systems , molds , materials applied to the articular surface that harden and “ memorize the surface contour ,” and / or one or more imaging techniques known in the art . measurements can be obtained non - invasively and / or intraoperatively ( e . g ., using a probe or other surgical device ). as will be appreciated by those of skill in the art , the thickness of the repair device can vary at any given point depending upon patient &# 39 ; s anatomy and / or the depth of the damage to the cartilage and / or bone to be corrected at any particular location on an articular surface . fig1 a is a flow chart showing steps taken by a practitioner in assessing a joint . first , a practitioner obtains a measurement of a target joint 10 . the step of obtaining a measurement can be accomplished by taking an image of the joint . this step can be repeated , as necessary , 11 to obtain a plurality of images in order to further refine the joint assessment process . once the practitioner has obtained the necessary measurements , the information is used to generate a model representation of the target joint being assessed 30 . this model representation can be in the form of a topographical map or image . the model representation of the joint can be in one , two , or three dimensions . it can include a physical model . more than one model can be created 31 , if desired . either the original model , or a subsequently created model , or both can be used . after the model representation of the joint is generated 30 , the practitioner can optionally generate a projected model representation of the target joint in a corrected condition 40 , e . g ., from the existing cartilage on the joint surface , by providing a mirror of the opposing joint surface , or a combination thereof . again , this step can be repeated 41 , as necessary or desired . using the difference between the topographical condition of the joint and the projected image of the joint , the practitioner can then select a joint implant 50 that is suitable to achieve the corrected joint anatomy . as will be appreciated by those of skill in the art , the selection process 50 can be repeated 51 as often as desired to achieve the desired result . additionally , it is contemplated that a practitioner can obtain a measurement of a target joint 10 by obtaining , for example , an x - ray , and then select a suitable joint replacement implant 50 . as will be appreciated by those of skill in the art , the practitioner can proceed directly from the step of generating a model representation of the target joint 30 to the step of selecting a suitable joint replacement implant 50 as shown by the arrow 32 . additionally , following selection of suitable joint replacement implant 50 , the steps of obtaining measurement of target joint 10 , generating model representation of target joint 30 and generating projected model 40 , can be repeated in series or parallel as shown by the flow 24 , 25 , 26 . fig1 b is an alternate flow chart showing steps taken by a practitioner in assessing a joint . first , a practitioner obtains a measurement of a target joint 10 . the step of obtaining a measurement can be accomplished by taking an image of the joint . this step can be repeated , as necessary , 11 to obtain a plurality of images in order to further refine the joint assessment process . once the practitioner has obtained the necessary measurements , the information is used to generate a model representation of the target joint being assessed 30 . this model representation can be in the form of a topographical map or image . the model representation of the joint can be in one , two , or three dimensions . the process can be repeated 31 as necessary or desired . it can include a physical model . after the model representation of the joint is assessed 30 , the practitioner can optionally generate a projected model representation of the target joint in a corrected condition 40 . this step can be repeated 41 as necessary or desired . using the difference between the topographical condition of the joint and the projected image of the joint , the practitioner can then design a joint implant 52 that is suitable to achieve the corrected joint anatomy , repeating the design process 53 as often as necessary to achieve the desired implant design . the practitioner can also assess whether providing additional features , such as rails , keels , lips , pegs , cruciate stems , or anchors , cross - bars , etc . will enhance the implants &# 39 ; performance in the target joint . as will be appreciated by those of skill in the art , the practitioner can proceed directly from the step of generating a model representation of the target joint 30 to the step of designing a suitable joint replacement implant 52 as shown by the arrow 38 . similar to the flow shown above , following the design of a suitable joint replacement implant 52 , the steps of obtaining measurement of target joint 10 , generating model representation of target joint 30 and generating projected model 40 , can be repeated in series or parallel as shown by the flow 42 , 43 , 44 . fig1 c is a flow chart illustrating the process of selecting an implant for a patient . first , using the techniques described above or those suitable and known in the art at the time the invention is practiced , the size of area of diseased cartilage or cartilage loss is measured 100 . this step can be repeated multiple times 101 , as desired . once the size of the cartilage defect is measured , the thickness of adjacent cartilage can optionally be measured 110 . this process can also be repeated as desired 111 . either after measuring the cartilage loss or measuring the thickness of adjacent cartilage , the curvature of the articular surface is then measured 120 . alternatively , the subchondral bone can be measured . as will be appreciated measurements can be taken of the surface of the joint being repaired , or of the mating surface in order to facilitate development of the best design for the implant surface . once the surfaces have been measured , the user either selects the best fitting implant contained in a library of implants 130 or generates a patient - specific implant 132 . these steps can be repeated as desired or necessary to achieve the best fitting implant for a patient , 131 , 133 . as will be appreciated by those of skill in the art , the process of selecting or designing an implant can be tested against the information contained in the mri or x - ray of the patient to ensure that the surfaces of the device achieves a good fit relative to the patient &# 39 ; s joint surface . testing can be accomplished by , for example , superimposing the implant image over the image for the patient &# 39 ; s joint . once it has been determined that a suitable implant has been selected or designed , the implant site can be prepared 140 , for example by removing cartilage or bone from the joint surface , or the implant can be placed into the joint 150 . the joint implant selected or designed achieves anatomic or near anatomic fit with the existing surface of the joint while presenting a mating surface for the opposing joint surface that replicates the natural joint anatomy . in this instance , both the existing surface of the joint can be assessed as well as the desired resulting surface of the joint . this technique is particularly useful for implants that are not anchored into the bone . as will be appreciated by those of skill in the art , the physician , or other person practicing the invention , can obtain a measurement of a target joint 10 and then either design 52 or select 50 a suitable joint replacement implant . a wide variety of materials find use in the practice of the present invention , including , but not limited to , plastics , metals , crystal free metals , ceramics , biological materials ( e . g ., collagen or other extracellular matrix materials ), hydroxyapatite , cells ( e . g ., stem cells , chondrocyte cells or the like ), or combinations thereof . based on the information ( e . g ., measurements ) obtained regarding the defect and the articular surface and / or the subchondral bone , a repair material can be formed or selected . further , using one or more of these techniques described herein , a cartilage replacement or regenerating material having a curvature that will fit into a particular cartilage defect , will follow the contour and shape of the articular surface , and will match the thickness of the surrounding cartilage . the repair material can include any combination of materials , and typically includes at least one non - pliable material , for example materials that are not easily bent or changed . currently , joint repair systems often employ metal and / or polymeric materials including , for example , prostheses which are anchored into the underlying bone ( e . g ., a femur in the case of a knee prosthesis ). see , e . g ., u . s . pat . no . 6 , 203 , 576 to afriat , et al . issued mar . 20 , 2001 and u . s . pat . no . 6 , 322 , 588 to ogle , et al . issued nov . 27 , 2001 , and references cited therein . a wide - variety of metals are useful in the practice of the present invention , and can be selected based on any criteria . for example , material selection can be based on resiliency to impart a desired degree of rigidity . non - limiting examples of suitable metals include silver , gold , platinum , palladium , iridium , copper , tin , lead , antimony , bismuth , zinc , titanium , cobalt , stainless steel , nickel , iron alloys , cobalt alloys , such as elgiloy ®, a cobalt - chromium - nickel alloy , and mp35n , a nickel - cobalt - chromium - molybdenum alloy , and nitinol ™, a nickel - titanium alloy , aluminum , manganese , iron , tantalum , crystal free metals , such as liquidmetal ® alloys ( available from liquidmetal technologies , www . liquidmetal . com ), other metals that can slowly form polyvalent metal ions , for example to inhibit calcification of implanted substrates in contact with a patient &# 39 ; s bodily fluids or tissues , and combinations thereof . suitable synthetic polymers include , without limitation , polyamides ( e . g ., nylon ), polyesters , polystyrenes , polyacrylates , vinyl polymers ( e . g ., polyethylene , polytetrafluoroethylene , polypropylene and polyvinyl chloride ), polycarbonates , polyurethanes , poly dimethyl siloxanes , cellulose acetates , polymethyl methacrylates , polyether ether ketones , ethylene vinyl acetates , polysulfones , nitrocelluloses , similar copolymers and mixtures thereof . bioresorbable synthetic polymers can also be used such as dextran , hydroxyethyl starch , derivatives of gelatin , polyvinylpyrrolidone , polyvinyl alcohol , poly [ n -( 2 - hydroxypropyl ) methacrylamide ], poly ( hydroxy acids ), poly ( epsilon - caprolactone ), polylactic acid , polyglycolic acid , poly ( dimethyl glycolic acid ), poly ( hydroxy butyrate ), and similar copolymers can also be used . other materials would also be appropriate , for example , the polyketone known as polyetheretherketone ( peek ™). this includes the material peek 450g , which is an unfilled peek approved for medical implantation available from victrex of lancashire , great britain . ( victrex is located at www . matweb . com or see boedeker www . boedeker . com ). other sources of this material include gharda located in panoli , india ( www . ghardapolymers . com ). it should be noted that the material selected can also be filled . for example , other grades of peek are also available and contemplated , such as 30 % glass - filled or 30 % carbon filled , provided such materials are cleared for use in implantable devices by the fda , or other regulatory body . glass filled peek reduces the expansion rate and increases the flexural modulus of peek relative to that portion which is unfilled . the resulting product is known to be ideal for improved strength , stiffness , or stability . carbon filled peek is known to enhance the compressive strength and stiffness of peek and lower its expansion rate . carbon filled peek offers wear resistance and load carrying capability . as will be appreciated , other suitable similarly biocompatible thermoplastic or thermoplastic polycondensate materials that resist fatigue , have good memory , are flexible , and / or deflectable have very low moisture absorption , and good wear and / or abrasion resistance , can be used without departing from the scope of the invention . the implant can also be comprised of polyetherketoneketone ( pekk ). other materials that can be used include polyetherketone ( pek ), polyetherketoneetherketoneketone ( pekekk ), and polyetheretherketoneketone ( peekk ), and generally a polyaryletheretherketone . further other polyketones can be used as well as other thermoplastics . reference to appropriate polymers that can be used for the implant can be made to the following documents , all of which are incorporated herein by reference . these documents include : pct publication wo 02 / 02158 a1 , dated jan . 10 , 2002 and entitled bio - compatible polymeric materials ; pct publication wo 02 / 00275 a1 , dated jan . 3 , 2002 and entitled bio - compatible polymeric materials ; and pct publication wo 02 / 00270 a1 , dated jan . 3 , 2002 and entitled bio - compatible polymeric materials . the polymers can be prepared by any of a variety of approaches including conventional polymer processing methods . preferred approaches include , for example , injection molding , which is suitable for the production of polymer components with significant structural features , and rapid prototyping approaches , such as reaction injection molding and stereo - lithography . the substrate can be textured or made porous by either physical abrasion or chemical alteration to facilitate incorporation of the metal coating . other processes are also appropriate , such as extrusion , injection , compression molding and / or machining techniques . typically , the polymer is chosen for its physical and mechanical properties and is suitable for carrying and spreading the physical load between the joint surfaces . more than one metal and / or polymer can be used in combination with each other . for example , one or more metal - containing substrates can be coated with polymers in one or more regions or , alternatively , one or more polymer - containing substrate can be coated in one or more regions with one or more metals . the system or prosthesis can be porous or porous coated . the porous surface components can be made of various materials including metals , ceramics , and polymers . these surface components can , in turn , be secured by various means to a multitude of structural cores formed of various metals . suitable porous coatings include , but are not limited to , metal , ceramic , polymeric ( e . g ., biologically neutral elastomers such as silicone rubber , polyethylene terephthalate and / or combinations thereof ) or combinations thereof . see , e . g ., u . s . pat . no . 3 , 605 , 123 to hahn , issued sep . 20 , 1971 . u . s . pat . no . 3 , 808 , 606 to tronzo issued may 7 , 1974 and u . s . pat . no . 3 , 843 , 975 to tronzo issued oct . 29 , 1974 ; u . s . pat . no . 3 , 314 , 420 to smith issued apr . 18 , 1967 ; u . s . pat . no . 3 , 987 , 499 to scharbach issued oct . 26 , 1976 ; and german offenlegungsschrift 2 , 306 , 552 . there can be more than one coating layer and the layers can have the same or different porosities . see , e . g ., u . s . pat . no . 3 , 938 , 198 to kahn , et al ., issued feb . 17 , 1976 . the coating can be applied by surrounding a core with powdered polymer and heating until cured to form a coating with an internal network of interconnected pores . the tortuosity of the pores ( e . g ., a measure of length to diameter of the paths through the pores ) can be important in evaluating the probable success of such a coating in use on a prosthetic device . see , also , u . s . pat . no . 4 , 213 , 816 to morris issued jul . 22 , 1980 . the porous coating can be applied in the form of a powder and the article as a whole subjected to an elevated temperature that bonds the powder to the substrate . selection of suitable polymers and / or powder coatings can be determined in view of the teachings and references cited herein , for example based on the melt index of each . repair materials can also include one or more biological material either alone or in combination with non - biological materials . for example , any base material can be designed or shaped and suitable cartilage replacement or regenerating material ( s ) such as fetal cartilage cells can be applied to be the base . the cells can be then be grown in conjunction with the base until the thickness ( and / or curvature ) of the cartilage surrounding the cartilage defect has been reached . conditions for growing cells ( e . g ., chondrocytes ) on various substrates in culture , ex vivo and in vivo are described , for example , in u . s . pat . nos . 5 , 478 , 739 to slivka et al . issued dec . 26 , 1995 ; 5 , 842 , 477 to naughton et al . issued dec . 1 , 1998 ; 6 , 283 , 980 to vibe - hansen et al ., issued sep . 4 , 2001 , and 6 , 365 , 405 to salzmann et al . issued apr . 2 , 2002 . non - limiting examples of suitable substrates include plastic , tissue scaffold , a bone replacement material ( e . g ., a hydroxyapatite , a bioresorbable material ), or any other material suitable for growing a cartilage replacement or regenerating material on it . biological polymers can be naturally occurring or produced in vitro by fermentation and the like . suitable biological polymers include , without limitation , collagen , elastin , silk , keratin , gelatin , polyamino acids , cat gut sutures , polysaccharides ( e . g ., cellulose and starch ) and mixtures thereof . biological polymers can be bioresorbable . biological materials used in the methods described herein can be autografts ( from the same subject ); allografts ( from another individual of the same species ) and / or xenografts ( from another species ). see , also , international patent publications wo 02 / 22014 to alexander et al . published mar . 21 , 2002 and wo 97 / 27885 to lee published aug . 7 , 1997 . in certain embodiments autologous materials are preferred , as they can carry a reduced risk of immunological complications to the host , including re - absorption of the materials , inflammation and / or scarring of the tissues surrounding the implant site . in one embodiment of the invention , a probe is used to harvest tissue from a donor site and to prepare a recipient site . the donor site can be located in a xenograft , an allograft or an autograft . the probe is used to achieve a good anatomic match between the donor tissue sample and the recipient site . the probe is specifically designed to achieve a seamless or near seamless match between the donor tissue sample and the recipient site . the probe can , for example , be cylindrical . the distal end of the probe is typically sharp in order to facilitate tissue penetration . additionally , the distal end of the probe is typically hollow in order to accept the tissue . the probe can have an edge at a defined distance from its distal end , e . g . at 1 cm distance from the distal end and the edge can be used to achieve a defined depth of tissue penetration for harvesting . the edge can be external or can be inside the hollow portion of the probe . for example , an orthopedic surgeon can take the probe and advance it with physical pressure into the cartilage , the subchondral bone and the underlying marrow in the case of a joint such as a knee joint . the surgeon can advance the probe until the external or internal edge reaches the cartilage surface . at that point , the edge will prevent further tissue penetration thereby achieving a constant and reproducible tissue penetration . the distal end of the probe can include one or more blades , saw - like structures , or tissue cutting mechanism . for example , the distal end of the probe can include an iris - like mechanism consisting of several small blades . the blade or blades can be moved using a manual , motorized or electrical mechanism thereby cutting through the tissue and separating the tissue sample from the underlying tissue . typically , this will be repeated in the donor and the recipient . in the case of an iris - shaped blade mechanism , the individual blades can be moved so as to close the iris thereby separating the tissue sample from the donor site . in another embodiment of the invention , a laser device or a radiofrequency device can be integrated inside the distal end of the probe . the laser device or the radiofrequency device can be used to cut through the tissue and to separate the tissue sample from the underlying tissue . in one embodiment of the invention , the same probe can be used in the donor and in the recipient . in another embodiment , similarly shaped probes of slightly different physical dimensions can be used . for example , the probe used in the recipient can be slightly smaller than that used in the donor thereby achieving a tight fit between the tissue sample or tissue transplant and the recipient site . the probe used in the recipient can also be slightly shorter than that used in the donor thereby correcting for any tissue lost during the separation or cutting of the tissue sample from the underlying tissue in the donor material . any biological repair material can be sterilized to inactivate biological contaminants such as bacteria , viruses , yeasts , molds , mycoplasmas and parasites . sterilization can be performed using any suitable technique , for example radiation , such as gamma radiation . any of the biological materials described herein can be harvested with use of a robotic device . the robotic device can use information from an electronic image for tissue harvesting . in certain embodiments , the cartilage replacement material has a particular biochemical composition . for instance , the biochemical composition of the cartilage surrounding a defect can be assessed by taking tissue samples and chemical analysis or by imaging techniques . for example , wo 02 / 22014 to alexander describes the use of gadolinium for imaging of articular cartilage to monitor glycosaminoglycan content within the cartilage . the cartilage replacement or regenerating material can then be made or cultured in a manner , to achieve a biochemical composition similar to that of the cartilage surrounding the implantation site . the culture conditions used to achieve the desired biochemical compositions can include , for example , varying concentrations . biochemical composition of the cartilage replacement or regenerating material can , for example , be influenced by controlling concentrations and exposure times of certain nutrients and growth factors . using information on thickness and curvature of the cartilage , a physical model of the surfaces of the articular cartilage and of the underlying bone can be created . this physical model can be representative of a limited area within the joint or it can encompass the entire joint . this model can also take into consideration the presence or absence of a meniscus as well as the presence or absence of some or all of the cartilage . for example , in the knee joint , the physical model can encompass only the medial or lateral femoral condyle , both femoral condyles and the notch region , the medial tibial plateau , the lateral tibial plateau , the entire tibial plateau , the medial patella , the lateral patella , the entire patella or the entire joint . the location of a diseased area of cartilage can be determined , for example using a 3d coordinate system or a 3d euclidian distance as described in wo 02 / 22014 . in this way , the size of the defect to be repaired can be determined . this process takes into account that , for example , roughly 80 % of patients have a healthy lateral component . as will be apparent , some , but not all , defects will include less than the entire cartilage . thus , in one embodiment of the invention , the thickness of the normal or only mildly diseased cartilage surrounding one or more cartilage defects is measured . this thickness measurement can be obtained at a single point or , preferably , at multiple points , for example 2 point , 4 - 6 points , 7 - 10 points , more than 10 points or over the length of the entire remaining cartilage . furthermore , once the size of the defect is determined , an appropriate therapy ( e . g ., articular repair system ) can be selected such that as much as possible of the healthy , surrounding tissue is preserved . in other embodiments , the curvature of the articular surface can be measured to design and / or shape the repair material . further , both the thickness of the remaining cartilage and the curvature of the articular surface can be measured to design and / or shape the repair material . alternatively , the curvature of the subchondral bone can be measured and the resultant measurement ( s ) can be used to either select or shape a cartilage replacement material . for example , the contour of the subchondral bone can be used to re - create a virtual cartilage surface : the margins of an area of diseased cartilage can be identified . the subchondral bone shape in the diseased areas can be measured . a virtual contour can then be created by copying the subchondral bone surface into the cartilage surface , whereby the copy of the subchondral bone surface connects the margins of the area of diseased cartilage . in shaping the device , the contours can be configured to mate with existing cartilage or to account for the removal of some or all of the cartilage . fig2 a shows a slightly perspective top view of a joint implant 200 of the invention suitable for implantation at the tibial plateau of the knee joint . as shown in fig2 a , the implant can be generated using , for example , a dual surface assessment , as described above with respect to fig1 a and b . the implant 200 has an upper surface 202 , a lower surface 204 and a peripheral edge 206 . the upper surface 202 is formed so that it forms a mating surface for receiving the opposing joint surface ; in this instance partially concave to receive the femur . the concave surface can be variably concave such that it presents a surface to the opposing joint surface , e . g . a negative surface of the mating surface of the femur it communicates with . as will be appreciated by those of skill in the art , the negative impression , need not be a perfect one . the upper surface 202 of the implant 200 can be shaped by any of a variety of means . for example , the upper surface 202 can be shaped by projecting the surface from the existing cartilage and / or bone surfaces on the tibial plateau , or it can be shaped to mirror the femoral condyle in order to optimize the complimentary surface of the implant when it engages the femoral condyle . alternatively , the superior surface 202 can be configured to mate with an inferior surface of an implant configured for the opposing femoral condyle . the lower surface 204 has a convex surface that matches , or nearly matches , the tibial plateau of the joint such that it creates an anatomic or near anatomic fit with the tibial plateau . depending on the shape of the tibial plateau , the lower surface can be partially convex as well . thus , the lower surface 204 presents a surface to the tibial plateau that fits within the existing surface . it can be formed to match the existing surface or to match the surface after articular resurfacing . as will be appreciated by those of skill in the art , the convex surface of the lower surface 204 need not be perfectly convex . rather , the lower surface 204 is more likely consist of convex and concave portions that fit within the existing surface of the tibial plateau or the re - surfaced plateau . thus , the surface is essentially variably convex and concave . fig2 b shows a top view of the joint implant of fig2 a . as shown in fig2 b the exterior shape 208 of the implant can be elongated . the elongated form can take a variety of shapes including elliptical , quasi - elliptical , race - track , etc . however , as will be appreciated the exterior dimension is typically irregular thus not forming a true geometric shape , e . g . ellipse . as will be appreciated by those of skill in the art , the actual exterior shape of an implant can vary depending on the nature of the joint defect to be corrected . thus the ratio of the length l to the width w can vary from , for example , between 0 . 25 to 2 . 0 , and more specifically from 0 . 5 to 1 . 5 . as further shown in fig2 b , the length across an axis of the implant 200 varies when taken at points along the width of the implant . for example , as shown in fig2 b , l 1 ≠ l 2 ≠ l 3 . turning now to fig2 c - e , cross - sections of the implant shown in fig2 b are depicted along the lines of c - c , d - d , and e - e . the implant has a thickness t 1 , t 2 and t 3 respectively . as illustrated by the cross - sections , the thickness of the implant varies along both its length l and width w . the actual thickness at a particular location of the implant 200 is a function of the thickness of the cartilage and / or bone to be replaced and the joint mating surface to be replicated . further , the profile of the implant 200 at any location along its length l or width w is a function of the cartilage and / or bone to be replaced . fig2 f is a lateral view of the implant 200 of fig2 a . in this instance , the height of the implant 200 at a first end h 1 is different than the height of the implant at a second end h 2 . further the upper edge 208 can have an overall slope in a downward direction . however , as illustrated the actual slope of the upper edge 208 varies along its length and can , in some instances , be a positive slope . further the lower edge 210 can have an overall slope in a downward direction . as illustrated the actual slope of the lower edge 210 varies along its length and can , in some instances , be a positive slope . as will be appreciated by those of skill in the art , depending on the anatomy of an individual patient , an implant can be created wherein h 1 and h 2 are equivalent , or substantially equivalent without departing from the scope of the invention . fig2 g is a cross - section taken along a sagittal plane in a body showing the implant 200 implanted within a knee joint 1020 such that the lower surface 204 of the implant 200 lies on the tibial plateau 1022 and the femur 1024 rests on the upper surface 202 of the implant 200 . fig2 h is a cross - section taken along a coronal plane in a body showing the implant 200 implanted within a knee joint 1020 . as is apparent from this view , the implant 200 is positioned so that it fits within a superior articular surface 224 . as will be appreciated by those of skill in the art , the articular surface could be the medial or lateral facet , as needed . fig2 i is a view along an axial plane of the body showing the implant 200 implanted within a knee joint 1020 showing the view taken from an aerial , or upper , view . fig2 j is a view of an alternate embodiment where the implant is a bit larger such that it extends closer to the bone medially , i . e . towards the edge 1023 of the tibial plateau , as well as extending anteriorly and posteriorly . fig2 k is a cross - section of an implant 200 of the invention according to an alternate embodiment . in this embodiment , the lower surface 204 further includes a joint anchor 212 . as illustrated in this embodiment , the joint anchor 212 forms a protrusion , keel or vertical member that extends from the lower surface 204 of the implant 200 and projects into , for example , the bone of the joint . as will be appreciated by those of skill in the art , the keel can be perpendicular or lie within a plane of the body . additionally , as shown in fig2 l the joint anchor 212 can have a cross - member 214 so that from a bottom perspective , the joint anchor 212 has the appearance of a cross or an “ x .” as will be appreciated by those of skill in the art , the joint anchor 212 could take on a variety of other forms while still accomplishing the same objective of providing increased stability of the implant 200 in the joint . these forms include , but are not limited to , pins , bulbs , balls , teeth , etc . additionally , one or more joint anchors 212 can be provided as desired . fig2 m and n illustrate cross - sections of alternate embodiments of a dual component implant from a side view and a front view . in an alternate embodiment shown in fig2 m it may be desirable to provide a one or more cross - members 220 on the lower surface 204 in order to provide a bit of translation movement of the implant relative to the surface of the femur , or femur implant . in that event , the cross - member can be formed integral to the surface of the implant or can be one or more separate pieces that fit within a groove 222 on the lower surface 204 of the implant 200 . the groove can form a single channel as shown in fig2 n 1 , or can have more than one channel as shown in fig2 n 2 . in either event , the cross - bar then fits within the channel as shown in fig2 n 1 - n 2 . the cross - bar members 220 can form a solid or hollow tube or pipe structure as shown in fig2 p . where two , or more , tubes 220 communicate to provide translation , a groove 221 can be provided along the surface of one or both cross - members to interlock the tubes into a cross - bar member further stabilizing the motion of the cross - bar relative to the implant 200 . as will be appreciated by those of skill in the art , the cross - bar member 220 can be formed integrally with the implant without departing from the scope of the invention . as shown in fig2 q - r , it is anticipated that the surface of the tibial plateau will be prepared by forming channels thereon to receive the cross - bar members . thus facilitating the ability of the implant to seat securely within the joint while still providing movement about an axis when the knee joint is in motion . fig2 s ( 1 - 9 ) illustrate an alternate embodiment of implant 200 . as illustrated in fig2 s the edges are beveled to relax a sharp corner . fig2 s ( 1 ) illustrates an implant having a single fillet or bevel 230 . the fillet is placed on the implant anterior to the posterior portion of the tibial spine . as shown in fig2 s ( 2 ) two fillets 230 , 231 are provided and used for the posterior chamfer . in fig2 s ( 3 ) a third fillet 234 is provided to create two cut surfaces for the posterior chamfer . turning now to fig2 s ( 4 ) a tangent of the implant is deselected , leaving three posterior curves . fig2 s ( 5 ) shows the result of tangent propagation . fig2 s ( 6 ) illustrates the effect on the design when the bottom curve is selected without tangent propagation . the result of tangent propagation and selection is shown in fig2 s ( 7 ). as can be seen in fig2 s ( 8 - 9 ) the resulting corner has a softer edge but sacrifices less than 0 . 5 mm of joint space . as will be appreciated by those of skill in the art , additional cutting planes can be added without departing from the scope of the invention . fig2 t illustrates an alternate embodiment of an implant 200 wherein the surface of the tibial plateau 250 is altered to accommodate the implant . as illustrated in fig2 t ( 1 - 2 ) the tibial plateau can be altered for only half of the joint surface 251 or for the full surface 252 . as illustrate in fig2 t ( 3 - 4 ) the posterior - anterior surface can be flat 260 or graded 262 . grading can be either positive or negative relative to the anterior surface . grading can also be used with respect to the implants of fig2 t where the grading either lies within a plane or a body or is angled relative to a plane of the body . additionally , attachment mechanisms can be provided to anchor the implant to the altered surface . as shown in fig2 t ( 5 - 7 ) keels 264 can be provided . the keels 264 can either sit within a plane , e . g . sagittal or coronal plane , or not sit within a plane ( as shown in fig2 t ( 7 )). fig2 t ( 8 ) illustrates an implant which covers the entire tibial plateau . the upper surface of these implants are designed to conform to the projected shape of the joint as determined under the steps described with respect to fig1 , while the lower surface is designed to be flat , or substantially flat to correspond to the modified surface of the joint . turning now to fig3 a - i an implant suitable for providing an opposing joint surface to the implant of fig2 a is shown . this implant corrects a defect on an inferior surface of the femur 1024 ( e . g ., the condyle of the femur that mates with the tibial plateau ) and can be used alone , i . e ., on the femur 1024 , or in combination with another joint repair device . formation of the surfaces of the devices can be achieved using the techniques described above with respect to the implant of fig2 . fig3 a shows a perspective view of an implant 300 having a curved mating surface 302 and convex joint abutting surface 304 . the joint abutting surface 304 need not form an anatomic or near anatomic fit with the femur in view of the anchors 306 provided to facilitate connection of the implant to the bone . in this instance , the anchors 306 are shown as pegs having notched heads . the notches facilitate the anchoring process within the bone . however , pegs without notches can be used as well as pegs with other configurations that facilitate the anchoring process or cruciate stems . pegs and other portions of the implant can be porous coated . the implant can be inserted without bone cement or with use of bone cement . the implant can be designed to abut the subchondral bone , i . e . it can substantially follow the contour of the subchondral bone . this has the advantage that no bone needs to be removed other than for the placement of the peg holes thereby significantly preserving bone stock . the anchors 306 could take on a variety of other forms without departing from the scope of the invention while still accomplishing the same objective of providing increased stability of the implant 300 in the joint . these forms include , but are not limited to , pins , bulbs , balls , teeth , etc . additionally , one or more joint anchors 306 can be provided as desired . as illustrated in fig3 , three pins are used to anchor the implant 300 . however , more or fewer joint anchors , cruciate stems , or pins , can be used without departing from the scope of the invention . fig3 b shows a slightly perspective superior view of the bone mating surface 304 further illustrating the use of three anchors 306 to anchor the implant to the bone . each anchor 306 has a stem 310 with a head 312 on top . as shown in fig3 c , the stem 310 has parallel walls such that it forms a tube or cylinder that extends from the bone mating surface 304 . a section of the stem forms a narrowed neck 314 proximal to the head 312 . as will be appreciated by those of skill in the art , the walls need not be parallel , but rather can be sloped to be shaped like a cone . additionally , the neck 314 need not be present , nor the head 312 . as discussed above , other configurations suitable for anchoring can be used without departing from the scope of the invention . turning now to fig3 d , a view of the tibial plateau mating surface 302 of the implant 300 is illustrated . as is apparent from this view , the surface is curved such that it is convex or substantially convex in order to mate with the concave surface of the plateau . fig3 e illustrates the upper surface 304 of the implant 300 further illustrating the use of three pegs 306 for anchoring the implant 300 to the bone . as illustrated , the three pegs 306 are positioned to form a triangle . however , as will be appreciated by those of skill in the art , one or more pegs can be used , and the orientation of the pegs 306 to one another can be as shown , or any other suitable orientation that enables the desired anchoring . fig3 f illustrated a cross section of the implant 300 taken along the lines f - f shown in fig3 e . typically the pegs are oriented on the surface of the implant so that the peg is perpendicular to the femoral condyle , which may not result in the peg being perpendicular to the surface of the implant . fig3 g illustrates the axial view of the femur 1000 having a lateral condyle 1002 and a medial condyle 1004 . the intercondylar fossa is also shown 1006 along with the lateral epicondyle 1008 and medial epicondyle 1010 . also shown is the patellar surface of the femur 1012 . the implant 300 illustrated in fig3 a , is illustrated covering a portion of the lateral condyle . the pegs 306 are also shown that facilitate anchoring the implant 300 to the condyle . fig3 h illustrates a knee joint 1020 from an anterior perspective . the implant 300 is implanted over a condyle . as shown in fig3 i the implant 300 is positioned such that it communicates with an implant 200 designed to correct a defect in the tibial plateau , such as those shown in fig2 . fig3 j - k illustrate an implant 300 for placement on a condyle . in this embodiment , at least one flat surface or chamfer cut 360 is provided to mate with a cut made on the surface of the condyle in preparing the joint . the flat surface 360 typically does not encompass the entire proximal surface 304 of the implant 300 . fig4 a illustrates the design of a typical total knee arthroplasty (“ tka ”) primary knee 499 . posterior cuts 498 , anterior cuts 497 and distal cuts 496 are provided as well as chamfer cuts 495 . fig4 b and 4c illustrate another implant 400 . as shown in fig4 b , the implant 400 is configured such that it covers both the lateral and medial femoral condyle along with the patellar surface of the femur 1012 . the implant 400 has a lateral condyle component 410 and a medial condyle component 420 and a bridge 430 that connects the lateral condyle component 410 to the medial condyle component 420 while covering at least a portion of the patellar surface of the femur 1012 . the implant 400 can optionally oppose one or more implants , such as those shown in fig2 , if desired . fig4 c is a side view of the implant of fig4 b . as shown in fig4 c , the superior surface 402 of the implant 400 is curved to correspond to the curvature of the femoral condyles . the curvature can be configured such that it corresponds to the actual curvature of one or both of the existing femoral condyles , or to the curvature of one or both of the femoral condyles after resurfacing of the joint . one or more pegs 430 can be provided to assist in anchoring the implant to the bone . as will be appreciated by those of skill in the art , the implant can be configured such that the superior surface contacting a first condyle is configured to male with the existing condule while a surface contacting a second condyle has one or more flat surfaces to mate with a condyle surface that has been modified . fig4 d illustrates a top view of the implant 400 shown in fig4 b . as is should be appreciated from this view , the inferior surface 404 of the implant 400 is configured to conform to the shape of the femoral condyles , e . g . the shape healthy femoral condyles would present to the tibial surface in a non - damaged joint . fig4 e and f illustrate perspective views of the implant from the inferior surface ( i . e ., tibial plateau mating surface ). fig4 g illustrates the axial view of the femur 1000 having a lateral condyle 1002 and a medial condyle 1004 . the intercondylar fossa is also shown 1006 along with the lateral epicondyle 1008 . the implant 400 illustrated in fig4 b , is illustrated covering both condyles and the patellar surface of the femur 1012 . the pegs 430 are also shown that facilitate anchoring the implant 400 to the condyle . fig4 h illustrates a knee joint 1050 from an anterior perspective . the implant 400 is implanted over both condyles . as shown in fig4 i the implant 400 is positioned such that it communicates with an implant 200 designed to correct a defect in the tibial plateau , such as those shown in fig2 . as will be appreciated by those of skill in the art , the implant 400 can be manufactured from a material that has memory such that the implant can be configured to snap - fit over the condyle . alternatively , it can be shaped such that it conforms to the surface without the need of a snap - fit . fig5 a and 5b illustrate yet another implant 500 suitable for repairing a damaged condyle . as shown in fig5 a , the implant 500 is configured such that it covers only one of the lateral or medial femoral condyles 510 . the implant differs from the implant of fig3 in that the implant 500 also covers at least a portion of the patellar surface of the femur 512 . similar to the implant of fig4 , the implant can optionally oppose one or more implants or opposing joint surfaces , such as those shown in fig2 , and can be combined with other implants , such as the implants of fig3 . fig5 c is a perspective side view of the implant of fig5 a . as shown in fig5 c , the superior surface 502 of the implant 500 is curved to correspond to the curvature of the femoral condyle that it mates with and the portion of the patellar surface of the femur that it covers . one or more pegs 530 can be provided to assist in anchoring the implant to the bone . additionally , an angled surface 503 can be provided on an interior surface 502 of the condyle component that conforms to an optionally provided cut made on the surface of the joint surface with which the implant mates . fig5 d illustrates a perspective top view of the implant 500 shown in fig5 a . as is should be appreciated from this view , the inferior surface 504 of the implant 500 is configured to conform to the projected shape of the femoral condyles , e . g . the shape healthy femoral condyles would present to the tibial surface in a non - damaged joint . fig5 e is a view of the implant 500 showing a hatched three point loading support area which extends from a top portion 513 to a line ( plane 17 ) and from a line ( plane 18 ) to a bottom portion 515 . also illustrated are the pegs 530 extending from the superior surface . fig5 f illustrates the superior surface of the implant 500 with the pegs 530 extending from the superior surface . fig5 f also illustrates the hatched cantilever loading support area , which extends from the line ( plane 18 ) to the top portion 513 of the implant . the loading forces and directions for each support condition are based on physiological load encounters . table 1 shows the physiological loadings taken from a study by seth greenwald . 1 “ tibial plateau surface stress in tka : a factor influencing polymer failure series iii - posterior stabilized designs ;” paul d . postak , b . sc ., christine s . heim , b . sc ., a . seth greenwald , d . phil . ; orthopaedic research laboratories , the mt . sinai medical center , cleveland , ohio . presented at the 62 nd annual aaos meeting , 1995 . using the implant 500 described in this application , the three point loading will occur from set - up 1 ( 2900 n ). to replicate a worst case loading scenario , a 75 / 25 load distribution ( 75 % of 2900 n = 2175 n ) will be used . the loading will be concentrated on a 6 mm diameter circular area located directly below and normal to the ped on the bearing surface . turning to the cantilever loading shown in fig5 f , the loading will occur from set - up 3 , or 90 °, at a 75 / 25 load distribution ( 75 % of 3625 n = 2719 n ). as with the above example , the loading will be concentrated on a 6 mm diameter circular area located at the center of the posterior - most portion of the medial condyle normal to the flat cut surface of the posterior condyle . fig5 g and h illustrate alternate embodiments of the implant 500 having a rail design that provides one or more rails 521 along medial and / or lateral sides of the implant 500 . the rail 521 can be positioned so that it extends along a portion of the medial 517 and / or lateral 519 sides before communicating with the angled surface 503 . as will be appreciate , a single side rail 521 can be provided without departing from the scope of the invention . fig5 i illustrates another embodiment of an implant 500 having a keel design . a keel 523 ( or centrally formed rail ) is provided on the superior surface of the implant . in this embodiment , the keel 523 is located on the surface of the implant , but not at the sides . as will be appreciated , the keel can be centered , as shown , substantially centered , or located off - center . an angled surface 503 can be provided to communicate with a modified joint surface . alternatively , where the joint surface is worn or modified , the cut 503 could be configured to mate with the worn or modified surface . fig5 j illustrates the axial view of the femur 1000 having a lateral condyle 1002 and a medial condyle 1004 . the intercondylar fossa is also shown 1006 along with the lateral epicondyle 1008 and the medial epicondyle 1010 . the patellar surface of the femur 1012 is also illustrated . the implant 500 , illustrated in fig5 a , is shown covering the lateral condyle and a portion of the patellar surface of the femur 1012 . the pegs 530 are also shown that facilitate anchoring the implant 500 to the condyle and patellar surface . fig5 k illustrates a knee joint 1020 from an anterior perspective . the implant 500 is implanted over the lateral condyle . fig5 l illustrates a knee joint 1020 with the implant 500 covering the medial condyle 1004 . as illustrated in fig5 k and l the shape of the implant 500 corresponding to the patella surface can take on a variety of curvatures without departing from the scope of the invention . turning now to fig5 m and n the implant 500 is positioned such that it communicates with an implant 200 designed to correct a defect in the tibial plateau , such as those shown in fig2 . in another embodiment of the invention , the implant 500 can have a superior surface 502 which substantially conforms to the surface of the condyle but which has at one flat portion corresponding to an oblique cut on the bone as shown in fig5 o . turning now to fig5 p - q an implant 500 is shown from a side view with a 7 ° difference between the anterior and posterior cuts . fig5 r - s illustrate an implant 500 having a contoured surface 560 for mating with the joint surface and an anterior cut 561 and a posterior cut 562 . fig5 shows the same implant 500 from a slightly different angle . fig5 t illustrates another implant 500 having a contoured surface 560 for mating with the joint surface and posterior cut 562 , a distal cut 563 , and a chamfer cut 564 . in this embodiment no anterior cut is provided . fig5 u illustrates the implant 500 of fig5 t from a side perspective . the cuts are typically less than the cut required for a tka , i . e ., typically less than 10 mm . the design of the cuts for this implant allow for a revision surgery to the knee , if required , at a later date . fig6 a - g illustrate the implant 500 of fig5 with a graphical representation of the cross - sections 610 , 620 from which a surface shape of the implant is derived . fig6 a illustrates a top view of the implant 500 sitting on top of the extracted surface shape 600 . this view of the implant 500 illustrates a notch 514 associated with the bridge section of the implant 512 which covers the patellar surface of the femur ( or the trochlea region ) to provide a mating surface that approximates the cartilage surface . as will be appreciated by those of skill in the art , the shape of an implant designed for the medial condyle would not necessarily be a mirror image of the implant designed for the lateral condyle because of differences in anatomy . thus , for example , the notch 514 would not be present in an implant designed for the medial condyle and the patellar surface of the femur . therefore , the implant can be designed to include all or part of the troclea region or to exclude it entirely . fig6 b illustrates a bottom view of the implant 500 layered over another derived surface shape 601 . fig6 c is a bottom view showing the implant 500 extending through the extracted surface shape 600 shown in fig6 a . fig6 d is a close - up view of the fig6 c showing the condylar wing of the implant covering the extracted surface 600 . fig6 e illustrates a top posterior view of the implant 500 positioned over the graphical representation of the surface shape 600 . fig6 f is an anterior view and fig6 g is a bottom - posterior view . fig7 a - c illustrate an implant 700 for correcting a joint similar to the implant 500 above . however , implant 700 consists of two components . the first component 710 engages a condyle of the femur , either medial or lateral depending on the design . the second component 720 engages the patellar surface of the femur . as discussed with the previous embodiments , the surfaces of the implant 700 can be configured such that the distal surface 722 ( e . g ., the surface that faces the tibial plateau ) is shaped based on a projection of the natural shape of the femur compensating the design for valgus or varus deformities and / or flattening of the surface of the femur . alternatively , the distal surface can be shaped based on the shape of the tibial plateau to provide a surface designed to optimally mate with the tibial plateau . the proximal surface 724 ( e . g ., the surface that engages the femoral condyle ) can be configured such that it mirrors the surface of the femur in either its damaged condition or its modified condition . likewise , the proximal surface can have one or more flattened sections 726 that form , e . g ., chamfer cuts . additionally the surface can include mechanisms facilitating attachment 728 to the femur , such as keels , teeth , cruciate stems , and the like . the medial facing portion of the condyle implant has a tapered surface 730 while the lateral facing portion of the patellar component also has a tapered surface such that each component presents tapered surfaces 730 to the other component . by dividing the surfaces of the medial and lateral compartments into independent articulating surfaces , as shown in fig7 , the implant provides improved fit of the conformal surfaces to the subchondral bone . additionally , the lateral - anterior portion of the femur is shielded from stress which could cause bone loss . also , the smaller size of each component of the implant , enables the implant to be placed within the joint using a smaller incision . finally , the wear of the patellar component is improved . fig8 a - f illustrate a patella 00 with an implants 810 . the implant 810 can have one or more pegs , cruciate stems , or other anchoring mechanisms , if desired . as will be appreciated by those of skill in the art , other designs can be arrived at using the teachings of this disclosure without departing from the scope of the invention . fig8 a illustrates a perspective view of an intact patella 800 . fig8 b illustrates the patella 800 wherein one surface of the patella 800 has been cut for form a smooth surface 802 to mate with an implant . fig8 c illustrates the patella 800 with an implant 810 positioned on the smooth surface 802 . the implant 810 has a plate structure 812 that abuts the smooth surface of the patella 802 and a dome 814 positioned on the plate 812 so that the dome is positioned in situ such that it will match the location of the patellar ridge . the implant 810 can be configured such that the edge of the plate is offset 1 mm from the actual edge of the patella , as illustrated . as will be appreciated by those of skill in the art , the plate 812 and dome 814 can be formed as a single unit or formed from multiple components . fig8 d is a side view of the implant 810 positioned on the patella 800 . as shown , the dome is positioned on the implant such that it is off - center . optimal positioning of the dome will be determined by the position of the patellar ridge . turning now to fig8 e - f , the implant 810 is shown superimposed on the unaltered patella 800 in order to illustrate that the position of the dome 814 of the implant corresponds to the location of the patellar ridge . fig8 g - j illustrate an alternative design for the patellar implant . fig8 g illustrates the implant 850 in its beginning stages as a blank with a flat inferior surface 852 having pegs 854 extending therefrom for anchoring to the patella . the articular or superior surface 860 has a rounded dome 856 , and a round plate section 858 that can be machined to match the bone cut . the articular surface 860 takes on the appearance of a “ hat ” or somberero , having a dome with a rim . the center of the dome 856 is also the center of the bearing surface . the rim 858 is cut to conform to the needs of the particular patient . fig8 j illustrates an implant which has been formed from the blank shown in fig8 g - i . fig8 i shows a plurality of possible cut lines 862 , 862 ′ for purposes of illustration . fig9 a - c illustrate a lateral view of a knee 1020 having a combination of the implants of implanted thereof . in fig9 a , an implant covering the condyle 900 , is illustrated . suitable implants can be , for example , those shown in fig3 - 8 , as will be appreciated the portion of the condyle covered anterior to posterior can include the entire weight bearing surface , a portion thereof , or a surface greater than the weight bearing surface . thus , for example , the implant can be configured to terminate prior to the sulcus terminalis or after the sulcus terminalis ( e . g ., the groove on the femur that coincides with the area where load bearing on the joint surface stops ). as shown in fig9 a - b , a patellar implant 900 can also be provided . fig9 c illustrates a knee having a condyle implant 900 , a patellar implant 800 and an implant for the tibial plateau 200 . fig1 a - d provide an alternate view of the coronal plane of a knee joint with one or more implants described above implanted therein . fig1 a illustrates a knee having a tibial implant 200 placed therein . fig1 b illustrates a knee with a condyle implant 300 placed therein . as described above , a plurality of the implants taught herein can be provided within a joint in order to restore joint movement . fig1 c illustrates a knee joint having two implants therein . first , a tibial implant 200 is provided on the tibial plateau and a second implant 300 is provided on the facing condyle . as will be appreciated by those of skill in the art . the implants can be installed such that the implants present each other mating surfaces ( as illustrated ), or not . for example , where the tibial implant 200 is placed in the medial compartment of the knee and the condyle implant 300 is placed in the lateral compartment . other combinations will be appreciated by those of skill in the art . turning now to fig1 d , a tibial implant 200 is provided along with a bicompartmental condyle implant 500 . as discussed above , these implants can be associated with the same compartment of the knee joint , but need not be . the arthroplasty system can be designed to reflect aspects of the tibial shape , femoral shape and / or patellar shape . tibial shape and femoral shape can include cartilage , bone or both . moreover , the shape of the implant can also include portions or all components of other articular structures such as the menisci . the menisci are compressible , in particular during gait or loading . for this reason , the implant can be designed to incorporate aspects of the meniscal shape accounting for compression of the menisci during loading or physical activities . for example , the undersurface 204 of the implant 200 can be designed to match the shape of the tibial plateau including cartilage or bone or both . the superior surface 202 of the implant 200 can be a composite of the articular surface of the tibia ( in particular in areas that are not covered by menisci ) and the meniscus . thus , the outer aspects of the device can be a reflection of meniscal height . accounting for compression , this can be , for example , 20 %, 40 %, 60 % or 80 % of uncompressed meniscal height . similarly the superior surface 304 of the implant 300 can be designed to match the shape of the femoral condyle including cartilage or bone or both . the inferior surface 302 of the implant 300 can be a composite of the surface of the tibial plateau ( in particular in areas that are not covered by menisci ) and the meniscus . thus , at least a portion of the outer aspects of the device can be a reflection of meniscal height . accounting for compression , this can be , for example , 20 %, 40 %, 60 % or 80 % of uncompressed meniscal height . these same properties can be applied to the implants shown in fig4 - 8 , as well . in some embodiments , the outer aspect of the device reflecting the meniscal shape can be made of another , preferably compressible material . if a compressible material is selected it is preferably designed to substantially match the compressibility and biomechanical behavior of the meniscus . the entire device can be made of such a material or non - metallic materials in general . the height and shape of the menisci for any joint surface to be repaired can be measured directly on an imaging test . if portions , or all , of the meniscus are torn , the meniscal height and shape can be derived from measurements of a contralateral joint or using measurements of other articular structures that can provide an estimate on meniscal dimensions . in another embodiment , the superior face of the implants 300 , 400 or 500 can be shaped according to the femur . the shape can preferably be derived from the movement patterns of the femur relative to the tibial plateau thereby accounting for variations in femoral shape and tibiofemoral contact area as the femoral condyle flexes , extends , rotates , translates and glides on the tibia and menisci . the movement patterns can be measured using any current or future test know in the art such as fluoroscopy , mri , gait analysis and combinations thereof . the arthroplasty can have two or more components , one essentially mating with the tibial surface and the other substantially articulating with the femoral component . the two components can have a flat opposing surface . alternatively , the opposing surface can be curved . the curvature can be a reflection of the tibial shape , the femoral shape including during joint motion , and the meniscal shape and combinations thereof . examples of single - component systems include , but are not limited to , a plastic , a polymer , a metal , a metal alloy , crystal free metals , a biologic material or combinations thereof . in certain embodiments , the surface of the repair system facing the underlying bone can be smooth . in other embodiments , the surface of the repair system facing the underlying bone can be porous or porous - coated . in another aspect , the surface of the repair system facing the underlying bone is designed with one or more grooves , for example to facilitate the in - growth of the surrounding tissue . the external surface of the device can have a step - like design , which can be advantageous for altering biomechanical stresses . optionally , flanges can also be added at one or more positions on the device ( e . g ., to prevent the repair system from rotating , to control toggle and / or prevent settling into the marrow cavity ). the flanges can be part of a conical or a cylindrical design . a portion or all of the repair system facing the underlying bone can also be flat which can help to control depth of the implant and to prevent toggle . non - limiting examples of multiple - component systems include combinations of metal , plastic , metal alloys , crystal free metals , and one or more biological materials . one or more components of the articular surface repair system can be composed of a biologic material ( e . g . a tissue scaffold with cells such as cartilage cells or stem cells alone or seeded within a substrate such as a bioresorable material or a tissue scaffold , allograft , autograft or combinations thereof ) and / or a non - biological material ( e . g ., polyethylene or a chromium alloy such as chromium cobalt ). thus , the repair system can include one or more areas of a single material or a combination of materials , for example , the articular surface repair system can have a first and a second component . the first component is typically designed to have size , thickness and curvature similar to that of the cartilage tissue lost while the second component is typically designed to have a curvature similar to the subchondral bone . in addition , the first component can have biomechanical properties similar to articular cartilage , including but not limited to similar elasticity and resistance to axial loading or shear forces . the first and the second component can consist of two different metals or metal alloys . one or more components of the system ( e . g ., the second portion ) can be composed of a biologic material including , but not limited to bone , or a non - biologic material including , but not limited to hydroxyapatite , tantalum , a chromium alloy , chromium cobalt or other metal alloys . one or more regions of the articular surface repair system ( e . g ., the outer margin of the first portion and / or the second portion ) can be bioresorbable , for example to allow the interface between the articular surface repair system and the patient &# 39 ; s normal cartilage , over time , to be filled in with hyaline or fibrocartilage . similarly , one or more regions ( e . g ., the outer margin of the first portion of the articular surface repair system and / or the second portion ) can be porous . the degree of porosity can change throughout the porous region , linearly or non - linearly , for where the degree of porosity will typically decrease towards the center of the articular surface repair system . the pores can be designed for in - growth of cartilage cells , cartilage matrix , and connective tissue thereby achieving a smooth interface between the articular surface repair system and the surrounding cartilage . the repair system ( e . g ., the second component in multiple component systems ) can be attached to the patient &# 39 ; s bone with use of a cement - like material such as methylmethacrylate , injectable hydroxy - or calcium - apatite materials and the like . in certain embodiments , one or more portions of the articular surface repair system can be pliable or liquid or deformable at the time of implantation and can harden later . hardening can occur , for example , within 1 second to 2 hours ( or any time period therebetween ), preferably with in 1 second to 30 minutes ( or any time period therebetween ), more preferably between 1 second and 10 minutes ( or any time period therebetween ). one or more components of the articular surface repair system can be adapted to receive injections . for example , the external surface of the articular surface repair system can have one or more openings therein . the openings can be sized to receive screws , tubing , needles or other devices which can be inserted and advanced to the desired depth , for example , through the articular surface repair system into the marrow space . injectables such as methylmethacrylate and injectable hydroxy - or calcium - apatite materials can then be introduced through the opening ( or tubing inserted therethrough ) into the marrow space thereby bonding the articular surface repair system with the marrow space . similarly , screws or pins , or other anchoring mechanisms . can be inserted into the openings and advanced to the underlying subchondral bone and the bone marrow or epiphysis to achieve fixation of the articular surface repair system to the bone . portions or all components of the screw or pin can be bioresorbable , for example , the distal portion of a screw that protrudes into the marrow space can be bioresorbable . during the initial period after the surgery , the screw can provide the primary fixation of the articular surface repair system . subsequently , ingrowth of bone into a porous coated area along the undersurface of the articular cartilage repair system can take over as the primary stabilizer of the articular surface repair system against the bone . the articular surface repair system can be anchored to the patient &# 39 ; s bone with use of a pin or screw or other attachment mechanism . the attachment mechanism can be bioresorbable . the screw or pin or attachment mechanism can be inserted and advanced towards the articular surface repair system from a non - cartilage covered portion of the bone or from a non - weight - bearing surface of the joint . the interface between the articular surface repair system and the surrounding normal cartilage can be at an angle , for example oriented at an angle of 90 degrees relative to the underlying subchondral bone . suitable angles can be determined in view of the teachings herein , and in certain cases , non - 90 degree angles can have advantages with regard to load distribution along the interface between the articular surface repair system and the surrounding normal cartilage . the interface between the articular surface repair system and the surrounding normal cartilage and / or bone can be covered with a pharmaceutical or bioactive agent , for example a material that stimulates the biological integration of the repair system into the normal cartilage and / or bone . the surface area of the interface can be irregular , for example , to increase exposure of the interface to pharmaceutical or bioactive agents . as described herein , repair systems of various sizes , curvatures and thicknesses can be obtained . these repair systems can be catalogued and stored to create a library of systems from which an appropriate system for an individual patient can then be selected . in other words , a defect , or an articular surface , is assessed in a particular subject and a pre - existing repair system having a suitable shape and size is selected from the library for further manipulation ( e . g ., shaping ) and implantation . as noted above , the methods and compositions described herein can be used to replace only a portion of the articular surface , for example , an area of diseased cartilage or lost cartilage on the articular surface . in these systems , the articular surface repair system can be designed to replace only the area of diseased or lost cartilage or it can extend beyond the area of diseased or lost cartilage , e . g ., 3 or 5 mm into normal adjacent cartilage . in certain embodiments , the prosthesis replaces less than about 70 % to 80 % ( or any value therebetween ) of the articular surface ( e . g ., any given articular surface such as a single femoral condyle , etc . ), preferably , less than about 50 % to 70 % ( or any value therebetween ), more preferably , less than about 30 % to 50 % ( or any value therebetween ), more preferably less than about 20 % to 30 % ( or any value therebetween ), even more preferably less than about 20 % of the articular surface . the prosthesis can include multiple components , for example a component that is implanted into the bone ( e . g ., a metallic device ) attached to a component that is shaped to cover the defect of the cartilage overlaying the bone . additional components , for example intermediate plates , meniscal repair systems and the like can also be included . it is contemplated that each component replaces less than all of the corresponding articular surface . however , each component need not replace the same portion of the articular surface . in other words , the prosthesis can have a bone - implanted component that replaces less than 30 % of the bone and a cartilage component that replaces 60 % of the cartilage . the prosthesis can include any combination , provided each component replaces less than the entire articular surface . the articular surface repair system can be formed or selected so that it will achieve a near anatomic fit or match with the surrounding or adjacent cartilage or bone . typically , the articular surface repair system is formed and / or selected so that its outer margin located at the external surface will be aligned with the surrounding or adjacent cartilage . thus , the articular repair system can be designed to replace the weight - bearing portion ( or more or less than the weight bearing portion ) of an articular surface , for example in a femoral condyle . the weight - bearing surface refers to the contact area between two opposing articular surfaces during activities of normal daily living ( e . g ., normal gait ). at least one or more weight - bearing portions can be replaced in this manner , e . g ., on a femoral condyle and on a tibia . in other embodiments , an area of diseased cartilage or cartilage loss can be identified in a weight - bearing area and only a portion of the weight - bearing area , specifically the portion containing the diseased cartilage or area of cartilage loss , can be replaced with an articular surface repair system . in another embodiment , the articular repair system can be designed or selected to replace substantially all of the articular surface , e . g . a condyle . in another embodiment , for example , in patients with diffuse cartilage loss , the articular repair system can be designed to replace an area slightly larger than the weight - bearing surface . in certain aspects , the defect to be repaired is located only on one articular surface , typically the most diseased surface . for example , in a patient with severe cartilage loss in the medial femoral condyle but less severe disease in the tibia , the articular surface repair system can only be applied to the medial femoral condyle . preferably , in any methods described herein , the articular surface repair system is designed to achieve an exact or a near anatomic fit with the adjacent normal cartilage . in other embodiments , more than one articular surface can be repaired . the area ( s ) of repair will be typically limited to areas of diseased cartilage or cartilage loss or areas slightly greater than the area of diseased cartilage or cartilage loss within the weight - bearing surface ( s ). in another embodiment , one or more components of the articular surface repair ( e . g ., the surface of the system that is pointing towards the underlying bone or bone marrow ) can be porous or porous coated . a variety of different porous metal coatings have been proposed for enhancing fixation of a metallic prosthesis by bone tissue in - growth . thus , for example , u . s . pat . no . 3 , 855 , 638 to pilliar issued dec . 24 , 1974 , discloses a surgical prosthetic device , which can be used as a bone prosthesis , comprising a composite structure consisting of a solid metallic material substrate and a porous coating of the same solid metallic material adhered to and extending over at least a portion of the surface of the substrate . the porous coating consists of a plurality of small discrete particles of metallic material bonded together at their points of contact with each other to define a plurality of connected interstitial pores in the coating . the size and spacing of the particles , which can be distributed in a plurality of monolayers , can be such that the average interstitial pore size is not more than about 200 microns . additionally , the pore size distribution can be substantially uniform from the substrate - coating interface to the surface of the coating . in another embodiment , the articular surface repair system can contain one or more polymeric materials that can be loaded with and release therapeutic agents including drugs or other pharmacological treatments that can be used for drug delivery . the polymeric materials can , for example , be placed inside areas of porous coating . the polymeric materials can be used to release therapeutic drugs , e . g . bone or cartilage growth stimulating drugs . this embodiment can be combined with other embodiments , wherein portions of the articular surface repair system can be bioresorbable . for example , the first layer of an articular surface repair system or portions of its first layer can be bioresorbable . as the first layer gets increasingly resorbed , local release of a cartilage growth - stimulating drug can facilitate in - growth of cartilage cells and matrix formation . in any of the methods or compositions described herein , the articular surface repair system can be pre - manufactured with a range of sizes , curvatures and thicknesses . alternatively , the articular surface repair system can be custom - made for an individual patient . in certain instances shaping of the repair material will be required before or after formation ( e . g ., growth to desired thickness ), for example where the thickness of the required cartilage material is not uniform ( e . g ., where different sections of the cartilage replacement or regenerating material require different thicknesses ). the replacement material can be shaped by any suitable technique including , but not limited to , casting techniques , mechanical abrasion , laser abrasion or ablation , radiofrequency treatment , cryoablation , variations in exposure time and concentration of nutrients , enzymes or growth factors and any other means suitable for influencing or changing cartilage thickness . see , e . g ., wo 00 / 15153 to mansmann published mar . 23 , 2000 ; if enzymatic digestion is used , certain sections of the cartilage replacement or regenerating material can be exposed to higher doses of the enzyme or can be exposed longer as a means of achieving different thicknesses and curvatures of the cartilage replacement or regenerating material in different sections of said material . the material can be shaped manually and / or automatically , for example using a device into which a pre - selected thickness and / or curvature has been input and then programming the device using the input information to achieve the desired shape . in addition to , or instead of , shaping the cartilage repair material , the site of implantation ( e . g ., bone surface , any cartilage material remaining , etc .) can also be shaped by any suitable technique in order to enhance integration of the repair material . the articular repair system can be formed or selected so that it will achieve a near anatomic fit or match with the surrounding or adjacent cartilage , subchondral bone , menisci and / or other tissue . the shape of the repair system can be based on the analysis of an electronic image ( e . g . mri , ct , digital tomosynthesis , optical coherence tomography or the like ). if the articular repair system is intended to replace an area of diseased cartilage or lost cartilage , the near anatomic fit can be achieved using a method that provides a virtual reconstruction of the shape of healthy cartilage in an electronic image . in one embodiment of the invention , a near normal cartilage surface at the position of the cartilage defect can be reconstructed by interpolating the healthy cartilage surface across the cartilage defect or area of diseased cartilage . this can , for example , be achieved by describing the healthy cartilage by means of a parametric surface ( e . g . a b - spline surface ), for which the control points are placed such that the parametric surface follows the contour of the healthy cartilage and bridges the cartilage defect or area of diseased cartilage . the continuity properties of the parametric surface will provide a smooth integration of the part that bridges the cartilage defect or area of diseased cartilage with the contour of the surrounding healthy cartilage . the part of the parametric surface over the area of the cartilage defect or area of diseased cartilage can be used to determine the shape or part of the shape of the articular repair system to match with the surrounding cartilage . in another embodiment , a near normal cartilage surface at the position of the cartilage defect or area of diseased cartilage can be reconstructed using morphological image processing . in a first step , the cartilage can be extracted from the electronic image using manual , semi - automated and / or automated segmentation techniques ( e . g ., manual tracing , region growing , live wire , model - based segmentation ), resulting in a binary image . defects in the cartilage appear as indentations that can be filled with a morphological closing operation performed in 2 - d or 3 - d with an appropriately selected structuring element . the closing operation is typically defined as a dilation followed by an erosion . a dilation operator sets the current pixel in the output image to 1 if at least one pixel of the structuring element lies inside a region in the source image . an erosion operator sets the current pixel in the output image to 1 if the whole structuring element lies inside a region in the source image . the filling of the cartilage defect or area of diseased cartilage creates a new surface over the area of the cartilage defect or area of diseased cartilage that can be used to determine the shape or part of the shape of the articular repair system to match with the surrounding cartilage or subchondral bone . as described above , the articular repair system can be formed or selected from a library or database of systems of various sizes , curvatures and thicknesses so that it will achieve a near anatomic fit or match with the surrounding or adjacent cartilage and / or subchondral bone . these systems can be pre - made or made to order for an individual patient . in order to control the fit or match of the articular repair system with the surrounding or adjacent cartilage or subchondral bone or menisci and other tissues preoperatively , a software program can be used that projects the articular repair system over the anatomic position where it will be implanted . suitable software is commercially available and / or readily modified or designed by a skilled programmer . in yet another embodiment , the articular surface repair system can be projected over the implantation site using one or more 3 - d images . the cartilage and / or subchondral bone and other anatomic structures are extracted from a 3 - d electronic image such as an mri or a ct using manual , semi - automated and / or automated segmentation techniques . a 3 - d representation of the cartilage and / or subchondral bone and other anatomic structures as well as the articular repair system is generated , for example using a polygon or nurbs surface or other parametric surface representation . for a description of various parametric surface representations see , for example foley , j . d . et al ., computer graphics : principles and practice in c ; addison - wesley , 2 nd edition , 1995 ). the 3 - d representations of the cartilage and / or subchondral bone and other anatomic structures and the articular repair system can be merged into a common coordinate system . the articular repair system can then be placed at the desired implantation site . the representations of the cartilage , subchondral bone , menisci and other anatomic structures and the articular repair system are rendered into a 3 - d image , for example application programming interfaces ( apis ) opengl ® ( standard library of advanced 3 - d graphics functions developed by sgi , inc . ; available as part of the drivers for pc - based video cards , for example from www . nvidia . com for nvidia video cards or www . 3dlabs . com for 3dlabs products , or as part of the system software for unix workstations ) or directx ® ( multimedia api for microsoft windows ® based pc systems ; available from www . microsoft . com ). the 3 - d image can be rendered showing the cartilage , subchondral bone , menisci or other anatomic objects , and the articular repair system from varying angles , e . g . by rotating or moving them interactively or non - interactively , in real - time or non - real - time . the software can be designed so that the articular repair system , including surgical tools and instruments with the best fit relative to the cartilage and / or subchondral bone is automatically selected , for example using some of the techniques described above . alternatively , the operator can select an articular repair system , including surgical tools and instruments and project it or drag it onto the implantation site using suitable tools and techniques . the operator can move and rotate the articular repair systems in three dimensions relative to the implantation site and can perform a visual inspection of the fit between the articular repair system and the implantation site . the visual inspection can be computer assisted . the procedure can be repeated until a satisfactory fit has been achieved . the procedure can be performed manually by the operator ; or it can be computer - assisted in whole or part . for example , the software can select a first trial implant that the operator can test . the operator can evaluate the fit . the software can be designed and used to highlight areas of poor alignment between the implant and the surrounding cartilage or subchondral bone or menisci or other tissues . based on this information , the software or the operator can then select another implant and test its alignment . one of skill in the art will readily be able to select , modify and / or create suitable computer programs for the purposes described herein . in another embodiment , the implantation site can be visualized using one or more cross - sectional 2 - d images . typically , a series of 2 - d cross - sectional images will be used . the 2 - d images can be generated with imaging tests such as ct , mri , digital tomosynthesis , ultrasound , or optical coherence tomography using methods and tools known to those of skill in the art . the articular repair system can then be superimposed onto one or more of these 2 - d images . the 2 - d cross - sectional images can be reconstructed in other planes , e . g . from sagittal to coronal , etc . isotropic data sets ( e . g ., data sets where the slice thickness is the same or nearly the same as the in - plane resolution ) or near isotropic data sets can also be used . multiple planes can be displayed simultaneously , for example using a split screen display . the operator can also scroll through the 2 - d images in any desired orientation in real time or near real time ; the operator can rotate the imaged tissue volume while doing this . the articular repair system can be displayed in cross - section utilizing different display planes , e . g . sagittal , coronal or axial , typically matching those of the 2 - d images demonstrating the cartilage , subchondral bone , menisci or other tissue . alternatively , a three - dimensional display can be used for the articular repair system . the 2 - d electronic image and the 2 - d or 3 - d representation of the articular repair system can be merged into a common coordinate system . the articular repair system can then be placed at the desired implantation site . the series of 2 - d cross - sections of the anatomic structures , the implantation site and the articular repair system can be displayed interactively ( e . g . the operator can scroll through a series of slices ) or non - interactively ( e . g . as an animation that moves through the series of slices ), in real - time or non - real - time . rapid protyping is a technique for fabricating a three - dimensional object from a computer model of the object . a special printer is used to fabricate the prototype from a plurality of two - dimensional layers . computer software sections the representations of the object into a plurality of distinct two - dimensional layers and then a three - dimensional printer fabricates a layer of material for each layer sectioned by the software . together the various fabricated layers form the desired prototype . more information about rapid prototyping techniques is available in us patent publication no 2002 / 0079601a1 to russell et al ., published jun . 27 , 2002 . an advantage to using rapid prototyping is that it enables the use of free form fabrication techniques that use toxic or potent compounds safely . these compounds can be safely incorporated in an excipient envelope , which reduces worker exposure a powder piston and build bed are provided . powder includes any material ( metal , plastic , etc .) that can be made into a powder or bonded with a liquid . the power is rolled from a feeder source with a spreader onto a surface of a bed . the thickness of the layer is controlled by the computer . the print head then deposits a binder fluid onto the powder layer at a location where it is desired that the powder bind . powder is again rolled into the build bed and the process is repeated , with the binding fluid deposition being controlled at each layer to correspond to the three - dimensional location of the device formation . for a further discussion of this process see , for example , us patent publication no 2003 / 017365a1 to monkhouse et al . published sep . 18 , 2003 . the rapid prototyping can use the two dimensional images obtained , as described above in section i , to determine each of the two - dimensional shapes for each of the layers of the prototyping machine . in this scenario , each two dimensional image slice would correspond to a two dimensional prototype slide . alternatively , the three - dimensional shape of the defect can be determined , as described above , and then broken down into two dimensional slices for the rapid prototyping process . the advantage of using the three - dimensional model is that the two - dimensional slices used for the rapid prototyping machine can be along the same plane as the two - dimensional images taken or along a different plane altogether . rapid prototyping can be combined or used in conjunction with casting techniques . for example , a shell or container with inner dimensions corresponding to an articular repair system can be made using rapid prototyping . plastic or wax - like materials are typically used for this purpose . the inside of the container can subsequently be coated , for example with a ceramic , for subsequent casting . using this process , personalized casts can be generated . rapid prototyping can be used for producing articular repair systems . rapid prototyping can be performed at a manufacturing facility . alternatively , it may be performed in the operating room after an intraoperative measurement has been performed . prior to performing surgery on a patient , the surgeon can preoperatively make a determination of the alignment of the knee using , for example , an erect ap x - ray . in performing preoperative assessment any lateral and patella spurs that are present can be identified . using standard surgical techniques , the patient is anesthetized and an incision is made in order to provide access to the portion or portions of the knee joint to be repaired . a medial portal can be used initially to enable arthroscopy of the joint . thereafter , the medial portal can be incorporated into the operative incision and / or standard lateral portals can be used . once an appropriate incision has been made , the exposed compartment is inspected for integrity , including the integrity of the ligament structures . if necessary , portions of the meniscus can be removed as well as any spurs or osteophytes that were identified in the ap x - ray or that may be present within the joint . in order to facilitate removal of osteophytes , the surgeon may flex the knee to gain exposure to additional medial and medial - posterior osteophytes . additionally , osteophytes can be removed from the patella during this process . if necessary , the medial and / or lateral meniscus can also be removed at this point , if desired , along with the rim of the meniscus . as would be appreciated by those of skill in the art , evaluation of the medial cruciate ligament may be required to facilitate tibial osteophyte removal . once the joint surfaces have been prepared , the desired implants can be inserted into the joint . to insert the device 200 of fig2 into the medial compartment , perform a mini - incision arthrotomy medial to the patella tendon . once the incision is made , expose the medial condyle and prepare a medial sleeve to about 1 cm below the joint line using a suitable knife and curved osteotome . after preparing the medial sleeve , place a z - retractor around the medial tibial plateau and remove anterior portions of the meniscus and the osteophytes along the tibia and femur . at this point , the knee should be flexed to about 60 ° or more . remove the z - retractor and place the implant against the most distal aspect of the femur and over the tibial plateau edge . push the implant straight back . in some instances , application of valgus stress may ease insertion of the implant . to insert the device of fig2 into the lateral compartment , perform a mini - incision arthrotomy lateral to the patella tendon . once the incision is made , expose the lateral condyle and prepare a lateral sleeve to about 1 cm below the joint line using a suitable knife and curved osteotome . after preparing the lateral sleeve , place a z - retractor around the lateral tibial plateau and remove anterior portions of the meniscus and the osteophytes along the tibia and femur . remove the z - retractor and place the implant against the distal aspect of the femur and over the tibial plateau edge . hold the implant at a 45 ° angle and rotate the implant against the lateral condyle using a lateral to medial push toward the lateral spine . in some instances , application of varus stress may ease insertion of the implant . once any implant shown in fig2 is implanted , the device should be positioned within 0 to 2 mm of the ap boundaries of the tibial plateau and superimposed over the boundary . verification of the range of motion should then be performed to confirm that there is minimal translation of the implant . once positioning is confirmed , closure of the wound is performed using techniques known in the art . as will be appreciated by those of skill in the art , additional treatment of the surface of the tibial plateau may be desirable depending on the configuration of the implant 200 . for example , one or more channels or grooves may be formed on the surface of the tibial plateau to accommodate anchoring mechanisms such as the keel 212 shown in fig2 k or the translational movement cross - members 222 , 221 shown in fig2 m - n . to insert the device 300 shown in fig3 , depending on the condyle to be repaired either an antero - medial or antero - lateral skin incisions is made which begins approximately 1 cm proximal to the superior border of the patella . the incision typically can range from , for example , 6 - 10 cm along the edge of the patella . as will be appreciated by those of skill in the art , a longer incision may be required under some circumstances . it may be required to excise excess deep synovium to improve access to the joint . additionally , all or part of the fat pad may also be excused and to enable inspection of the opposite joint compartment . typically , osteophytes are removed from the entire medial and / or lateral edge of the femur and the tibia as well as any osteophytes on the edge of the patella that might be significant . although it is possible , typically the devices 300 do not require resection of the distal femur prior to implanting the device . however , if desired , bone cuts can be performed to provide a surface for the implant . at this juncture , the patient &# 39 ; s leg is placed in 90 ° flexion position . i guide can then be placed on the condyle which covers the distal femoral cartilage . the guide enables the surgeon to determine placement of apertures that enable the implant 300 to be accurately placed on the condyle . with the guide in place , holes are drilled into the condyle to create apertures from 1 - 3 mm in depth . once the apertures have been created , the guide is removed and the implant 300 is installed on the surface of the condyle . cement can be used to facilitate adherence of the implant 300 to the condyle . where more than one condyle is to be repaired , e . g ., using two implants 300 of fig3 , or the implant 400 of fig4 , or where a condyle and a portion of the patellar surface is to be repaired , e . g ., using the implant 500 of fig5 , the surgical technique described herein would be modified to , for example , provide a greater incision for accessing the joint , provide additional apertures for receiving the pegs of the implant , etc . to insert the device shown in fig7 , it may be appropriate to use the incisions made laterally or medially to the patella tendon and described above with respect to fig2 . first the patella is everted laterally and the fat pad and synovium are bent back from around the periphery of the patella . if desired , osteophytes can be removed . prior to resurfacing the natural patella 620 , the knee should be manually taken through several range of motion maneuvers to determine whether subluxation is present . if subluxation is present , then it may be necessary to medialize the implant 600 . the natural patella can then be cut in a planar , or flat , manner such that a flat surface is presented to the implant . the geometric center of the patella 620 is then typically aligned with the geometric center of the implant 600 . in order to anchor the implant 600 to the patella 620 , one or more holes or apertures 612 can be created in the patellar surface to accept the pegs 610 of the implant 600 . one or more of the implants described above can be combined together in a kit such that the surgeon can select one or more implants to be used during surgery . the foregoing description of embodiments of the present invention has been provided for the purposes of illustration and description . it is not intended to be exhaustive or to limit the invention to the precise forms disclosed . many modifications and variations will be apparent to the practitioner skilled in the art . the embodiments were chosen and described in order to best explain the principles of the invention and its practical application , thereby enabling others skilled in the art to understand the invention and the various embodiments and with various modifications that are suited to the particular use contemplated . it is intended that the scope of the invention be defined by the following claims equivalents thereof .

disclosed herein are methods and devices for repairing articular surfaces in a knee joint . the articular surface repairs are customizable or highly selectable for each patient and geared toward providing optimal fit and function . kits are also provided to enable customized repairs to be performed .

for the purposes of promoting an understanding of the principles in accordance with the embodiments of the present invention , reference will now be made to the embodiments illustrated in the drawings and specific language will be used to describe the same . it will nevertheless be understood that no limitation of the scope of the invention is thereby intended . any alterations and further modifications of the inventive feature illustrated herein , and any additional applications of the principles of the invention as illustrated herein , which would normally occur to one skilled in the relevant art and having possession of this disclosure , are to be considered within the scope of the invention claimed . fig1 shows a perspective view of a nail polish container including a nail polish applicator 18 and bottle 10 in a closed position . the nail polish applicator 18 includes a cap 24 which may be a separate piece or integral with the nail polish applicator 18 . removal of the cap 24 allows access to housed electrical components . while the nail polish applicator 18 is shown having an elongated tapered configuration and the bottle 10 is shown having a bulbous configuration , those skilled in the art will recognize that the nail polish applicator 18 and bottle 10 may take on any shape , form and size suitable to apply and hold nail polish . fig2 and 3 show cross - sectional and exploded views , respectively , of the nail polish applicator 18 and bottle 10 . fig4 shows a perspective view of the nail polish applicator 18 and bottle 10 separated . the nail polish applicator 18 has a main body having a conventional brush holder 12 extending therefrom wherein the brush holder 12 retains nail polish brush 11 . the active electronic components which facilitate the embodiments of the present invention reside within internal cavities housed within the main body of the nail polish applicator 18 and enclosed with cap 24 . in one embodiment , three light emitting devices 14 a , 14 b and 14 c are spaced evenly ( i . e ., 120 degrees apart ) about and connected to a printed circuit board ( pcb ) 15 . a pcb cover 13 protects the pcb 15 and includes openings through which leds 14 a , 14 b and 14 c insert . in one embodiment , the leds are white and conventional in nature . in another embodiment , the leds may be focused slightly inward towards the brush 11 to enhance the effects of the light . in other embodiments , more or less than three leds may be used . in other embodiments , different light devices , including mini cfls , oleds and mini halogen lamps , may be used in place of the leds . activation of the leds 14 a , 14 b and 14 c is controlled by the configuration of switch 16 , switch spring 17 and pcb 15 . switch spring 17 is compressed by the switch 16 when the nail polish applicator 18 is screwed in place on the bottle 10 and the upper disc of the switch 16 is not in contact with the pcb 15 such that the leds 14 a , 14 b and 14 c are not illuminated . in other words , the light circuit is open . the upper surface of the bottle 10 adjacent to the threaded protrusion maintains the switch 16 fully contained within the nail polish applicator 18 when the nail polish applicator 18 is screwed closed . when the nail polish applicator 18 is unscrewed from the bottle 10 , the switch spring 17 expands and pushes the switch 16 downward causing the upper disc of the switch 16 to make contact with the pcb 15 thereby closing the light circuit . in this position , a lower portion of the switch 16 extends below and out of the bottom surface of the nail polish applicator 18 . with the light circuit closed , power from the batteries 21 a , 21 b , 21 c and 21 d is transmitted to the leds 14 a , 14 b and 14 c via wires ( not shown ) connected to a bottom contact plate 20 and top contact plate 23 though wire passages 19 . the bottom contact plate 20 and top contact plate 23 sandwich batteries 21 a - 21 d and the leds 14 a , 14 b and 14 c . in another embodiment , a manually operated switch or button on the nail polish applicator 18 allows a user to activate the leds 14 a , 14 b and 14 c when desired . the switch or button operate to close and open the circuit in the same or similar manner as the automated configuration described above . the batteries 21 a - 21 d , as shown , are button cell , silver button cell , coin cell or similar types stacked on top of one another . the batteries 21 a - 21 d are sandwiched between a bottom contact plate 20 and top contact plate 23 . a battery spring 22 is positioned above the top contact plate 23 to maintain the batteries 21 a - 21 d in firm contact with one another . those skilled in the art will recognize that other battery types may be used . it is conceivable that the nail polish container may be powered by one or more rechargeable batteries such that the a power cord is insertable at a first end into the nail polish container and a second end into an electrical outlet thereby charging the rechargeable batteries . now referring to fig5 , in one embodiment , the leds 14 a , 14 b and 14 c are spaced evenly 120 degrees around the pcb 15 and through the pcb cover 13 . this configuration provides an even light pattern at the area of the brush 11 thereby lighting the fingernail and brush 11 contact point . focused leds can further focus the light on the contact point . those skilled in the art will understand that additional leds may be used and spaced evenly ( e . g ., 4 leds spaced 90 degrees ). less than three leds may be used as well ( e . g ., 2 leds spaced 180 degrees ). fig5 also shows the switch 16 extending from the nail polish applicator 18 . fig6 and 7 show an alternative configuration wherein the batteries 21 a - 21 d are directly wired to the leds 14 a , 14 b and 14 c . in this embodiment , the bottom contact plate 20 , top contact plate 22 and battery spring 23 are not necessary . a first positive wire 25 a and second negative wire 25 b lead to each of the leds 14 a , 14 b and 14 c through wire passage 19 thus transmitting the necessary power . the main body , including the electrical component cavities , of the nail polish applicator 18 may be formed using injection molding , machining or other fabrication methods . the elements described herein may be made of any suitable materials including plastics , composites , alloys and the like . although the invention has been described in detail with reference to several embodiments , additional variations and modifications exist within the scope and spirit of the invention as described and defined in the following claims .

a nail polish applicator having illumination means . a main body of the nail polish applicator supports a brush holder and brush . the main body houses a power source , one or more light devices arranged on a printed circuit board housed by said main body to direct light to the brush and activation means configured to illuminate the light devices . the light devices may be conventional or focused light emitting diodes . three light emitting diodes may be evenly spaced about the printed circuit board housed in the main body and activated by an automatic or manual switch .

when chemical structures are depicted or described , unless explicitly stated otherwise , all carbons are assumed to have hydrogen substitution to conform to a valence of four . for example , in the structure on the left - hand side of the schematic below there are nine hydrogens implied . the nine hydrogens are depicted in the right - hand structure . sometimes a particular atom in a structure is described in textual formula as having a hydrogen or hydrogens as substitution ( expressly defined hydrogen ), for example , — ch 2 ch 2 —. it is understood by one of ordinary skill in the art that the aforementioned descriptive techniques are common in the chemical arts to provide brevity and simplicity to description of otherwise complex structures . if a group “ r ” is depicted as “ floating ” on a ring system , as for example in the formula : then , unless otherwise defined , a substituent “ r ” may reside on any atom of the ring system , assuming replacement of a depicted , implied , or expressly defined hydrogen from one of the ring atoms , so long as a stable structure is formed . if a group “ r ” is depicted as floating on a fused ring system , as for example in the formulae : then , unless otherwise defined , a substituent “ r ” may reside on any atom of the fused ring system , assuming replacement of a depicted hydrogen ( for example the — nh — in the formula above ), implied hydrogen ( for example as in the formula above , where the hydrogens are not shown but understood to be present ), or expressly defined hydrogen ( for example where in the formula above , “ z ” equals ═ ch —) from one of the ring atoms , so long as a stable structure is formed . in the example depicted , the “ r ” group may reside on either the 5 - membered or the 6 - membered ring of the fused ring system . when a group “ r ” is depicted as existing on a ring system containing saturated carbons , as for example in the formula : where , in this example , “ y ” can be more than one , assuming each replaces a currently depicted , implied , or expressly defined hydrogen on the ring ; then , unless otherwise defined , where the resulting structure is stable , two “ r &# 39 ; s ” may reside on the same carbon . a simple example is when r is a methyl group ; there can exist a geminal dimethyl on a carbon of the depicted ring ( an “ annular ” carbon ). in another example , two r &# 39 ; s on the same carbon , including that carbon , may form a ring , thus creating a spirocyclic ring ( a “ spirocyclyl ” group ) structure with the depicted ring as for example in the formula : “( c 1 - c 6 ) alkyl ” or “ alkyl ” means a linear or branched hydrocarbon group having one to six carbon atoms . examples of lower alkyl groups include methyl , ethyl , propyl , isopropyl , butyl , s - butyl , t - butyl , isobutyl , pentyl , hexyl , and the like . “ c 6 alkyl ” refers to , for example , n - hexyl , iso - hexyl , and the like . “ yield ” for each of the reactions described herein is expressed as a percentage of the theoretical yield . “ patient ” for the purposes of the present invention includes humans and other animals , particularly mammals , and other organisms . thus the methods are applicable to both human therapy and veterinary applications . in another embodiment the patient is a mammal , and in another embodiment the patient is human . a “ pharmaceutically acceptable salt ” of a compound means a salt that is pharmaceutically acceptable and that possesses the desired pharmacological activity of the parent compound . it is understood that the pharmaceutically acceptable salts are non - toxic . additional information on suitable pharmaceutically acceptable salts can be found in remington &# 39 ; s pharmaceutical sciences , 17 th ed ., mack publishing company , easton , pa ., 1985 , which is incorporated herein by reference or s . m . berge , et al ., “ pharmaceutical salts ,” j . pharm . sci ., 1977 ; 66 : 1 - 19 both of which are incorporated herein by reference . examples of pharmaceutically acceptable acid addition salts include those formed with inorganic acids such as hydrochloric acid , hydrobromic acid , sulfuric acid , nitric acid , phosphoric acid , and the like ; as well as organic acids such as acetic acid , trifluoroacetic acid , propionic acid , hexanoic acid , cyclopentanepropionic acid , glycolic acid , pyruvic acid , lactic acid , oxalic acid , maleic acid , malonic acid , succinic acid , fumaric acid , tartaric acid , malic acid , citric acid , benzoic acid , cinnamic acid , 3 -( 4 - hydroxybenzoyl ) benzoic acid , mandelic acid , methanesulfonic acid , ethanesulfonic acid , 1 , 2 - ethanedisulfonic acid , 2 - hydroxyethanesulfonic acid , benzenesulfonic acid , 4 - chlorobenzenesulfonic acid , 2 - naphthalenesulfonic acid , 4 - toluenesulfonic acid , camphorsulfonic acid , glucoheptonic acid , 4 , 4 ′- methylenebis -( 3 - hydroxy - 2 - ene - 1 - carboxylic acid ), 3 - phenylpropionic acid , trimethylacetic acid , tertiary butylacetic acid , lauryl sulfuric acid , gluconic acid , glutamic acid , hydroxynaphthoic acid , salicylic acid , stearic acid , muconic acid , p - toluenesulfonic acid , and salicylic acid and the like . “ prodrug ” refers to compounds that are transformed ( typically rapidly ) in vivo to yield the parent compound of the above formulae , for example , by hydrolysis in blood . common examples include , but are not limited to , ester and amide forms of a compound having an active form bearing a carboxylic acid moiety . examples of pharmaceutically acceptable esters of the compounds of this invention include , but are not limited to , alkyl esters ( for example with between about one and about six carbons ) the alkyl group is a straight or branched chain . acceptable esters also include cycloalkyl esters and arylalkyl esters such as , but not limited to benzyl . examples of pharmaceutically acceptable amides of the compounds of this invention include , but are not limited to , primary amides , and secondary and tertiary alkyl amides ( for example with between about one and about six carbons ). amides and esters of the compounds of the present invention may be prepared according to conventional methods . a thorough discussion of prodrugs is provided in t . higuchi and v . stella , “ pro - drugs as novel delivery systems ,” vol 14 of the a . c . s . symposium series , and in bioreversible carriers in drug design , ed . edward b . roche , american pharmaceutical association and pergamon press , 1987 , both of which are incorporated herein by reference for all purposes . “ therapeutically effective amount ” is an amount of a compound of the invention , that when administered to a patient , ameliorates a symptom of the disease . a therapeutically effective amount is intended to include an amount of a compound alone or in combination with other active ingredients effective to modulate c - met , and / or vegfr2 , or effective to treat or prevent cancer . the amount of a compound of the invention which constitutes a “ therapeutically effective amount ” will vary depending on the compound , the disease state and its severity , the age of the patient to be treated , and the like . the therapeutically effective amount can be determined by one of ordinary skill in the art having regard to their knowledge and to this disclosure . “ treating ” or “ treatment ” of a disease , disorder , or syndrome , as used herein , includes ( i ) preventing the disease , disorder , or syndrome from occurring in a human , i . e . causing the clinical symptoms of the disease , disorder , or syndrome not to develop in an animal that may be exposed to or predisposed to the disease , disorder , or syndrome but does not yet experience or display symptoms of the disease , disorder , or syndrome ; ( ii ) inhibiting the disease , disorder , or syndrome , i . e ., arresting its development ; and ( iii ) relieving the disease , disorder , or syndrome , i . e ., causing regression of the disease , disorder , or syndrome . as is known in the art , adjustments for systemic versus localized delivery , age , body weight , general health , sex , diet , time of administration , drug interaction and the severity of the condition may be necessary , and will be ascertainable with routine experience . or a pharmaceutically acceptable salt thereof . as indicated previously , compound 1 is referred to herein as n -( 4 -{[ 6 , 7 - bis ( methyloxy ) quinolin - 4 - yl ] oxy } phenyl )- n ′-( 4 - fluorophenyl ) cyclopropane - 1 , 1 - dicarboxamide . wo 2005 / 030140 discloses compound 1 and describes how it is made ( example 12 , 37 , 38 , and 48 ) and also discloses the therapeutic activity of this compound to inhibit , regulate and / or modulate the signal transduction of kinases , ( assays , table 4 , entry 289 ). example 48 is on paragraph [ 0353 ] in wo 2005 / 030140 . in other embodiments , the compound of formula i , formula ia , or compound 1 , or a pharmaceutically acceptable salt thereof , is administered as a pharmaceutical composition , wherein the pharmaceutical composition additionally comprises a pharmaceutically acceptable carrier , excipient , or diluent . in a specific embodiment , the compound of formula i is compound 1 . the compound of formula i , formula ia , and compound 1 , as described herein , includes both the recited compounds as well as individual isomers and mixtures of isomers . in each instance , the compound of formula i includes the pharmaceutically acceptable salts , hydrates , and / or solvates of the recited compounds and any individual isomers or mixture of isomers thereof . in other embodiments , the compound of formula i , formula ia , or compound 1 can be the ( l )- malate salt . the malate salt of the compound of formula i and of compound 1 is disclosed in pct / us2010 / 021194 and u . s . patent application ser . no . 61 / 325 , 095 . in other embodiments , the compound of formula ia can be malate salt . in other embodiments , the compound of formula i can be the ( d )- malate salt . in other embodiments , the compound of formula ia can be the ( l )- malate salt . in another embodiment , the malate salt is in the crystalline n - 1 form of the ( l ) malate salt and / or the ( d ) malate salt of the compound 1 as disclosed in u . s . patent application ser . no . 61 / 325 , 095 . also see wo 2008 / 083319 for the properties of crystalline enantiomers , including the n - 1 and / or the n - 2 crystalline forms of the malate salt of compound 1 . methods of making and characterizing such forms are fully described in pct / us10 / 21194 , which is incorporated herein by reference in its entirety . in another embodiment , the invention is directed to a method for ameliorating the symptoms of osteoblastic bone metastases , comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of formula i in any of the embodiments disclosed herein . in a specific embodiment , the compound of formula i is compound 1 . in another embodiment , the compound of formula i is administered post - taxotere treatment . in a specific embodiment , the compound of formula i is compound 1 . in another embodiment , the compound of formula i is as effective or more effective than mitoxantrone plus prednisone . in a specific embodiment , the compound of formula i is compound 1 . in another embodiment , the compound of formula i , formula ia , or compound 1 or a pharmaceutically acceptable salt thereof is administered orally once daily as a tablet or capsule . in another embodiment , compound 1 is administered orally as its free base or malate salt as a capsule or tablet . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing up to 100 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 100 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 95 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 90 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 85 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 80 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 75 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 70 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 65 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 60 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 55 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 50 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 45 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 40 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 35 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 30 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 25 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 20 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 15 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 10 mg of compound 1 . in another embodiment , compound 1 is administered orally once daily as its free base or as the malate salt as a capsule or tablet containing 5 mg of compound 1 . in another embodiment , compound 1 is administered as its free base or malate salt orally once daily as a tablet as provided in the following table . in another embodiment , compound 1 is administered orally as its free base or malate salt once daily as a tablet as provided in the following table . in another embodiment , compound 1 is administered orally as its free base or malate salt once daily as a tablet as provided in the following table . any of the tablet formulations provided above can be adjusted according to the dose of compound 1 desired . thus , the amount of each of the formulation ingredients can be proportionally adjusted to provide a table formulation containing various amounts of compound 1 as provided in the previous paragraphs . in another embodiment , the formulations can contain 20 , 40 , 60 , or 80 mg of compound 1 . administration of the compound of formula i , formula ia , or compound 1 , or a pharmaceutically acceptable salt thereof , in pure form or in an appropriate pharmaceutical composition , can be carried out via any of the accepted modes of administration or agents for serving similar utilities . thus , administration can be , for example , orally , nasally , parenterally ( intravenous , intramuscular , or subcutaneous ), topically , transdermally , intravaginally , intravesically , intracistemally , or rectally , in the form of solid , semi - solid , lyophilized powder , or liquid dosage forms , such as for example , tablets , suppositories , pills , soft elastic and hard gelatin dosages ( which can be in capsules or tablets ), powders , solutions , suspensions , or aerosols , or the like , specifically in unit dosage forms suitable for simple administration of precise dosages . the compositions will include a conventional pharmaceutical carrier or excipient and a compound of formula i as the / an active agent , and , in addition , may include carriers and adjuvants , etc . adjuvants include preserving , wetting , suspending , sweetening , flavoring , perfuming , emulsifying , and dispensing agents . prevention of the action of microorganisms can be ensured by various antibacterial and antifungal agents , for example , parabens , chlorobutanol , phenol , sorbic acid , and the like . it may also be desirable to include isotonic agents , for example sugars , sodium chloride , and the like . prolonged absorption of the injectable pharmaceutical form can be brought about by the use of agents delaying absorption , for example , aluminum monostearate and gelatin . if desired , a pharmaceutical composition of the compound of formula i may also contain minor amounts of auxiliary substances such as wetting or emulsifying agents , ph buffering agents , antioxidants , and the like , such as , for example , citric acid , sorbitan monolaurate , triethanolamine oleate , butylalted hydroxytoluene , etc . the choice of composition depends on various factors such as the mode of drug administration ( e . g ., for oral administration , compositions in the form of tablets , pills or capsules ) and the bioavailability of the drug substance . recently , pharmaceutical compositions have been developed especially for drugs that show poor bioavailability based upon the principle that bioavailability can be increased by increasing the surface area i . e ., decreasing particle size . for example , u . s . pat . no . 4 , 107 , 288 describes a pharmaceutical composition having particles in the size range from 10 to 1 , 000 nm in which the active material is supported on a crosslinked matrix of macromolecules . u . s . pat . no . 5 , 145 , 684 describes the production of a pharmaceutical composition in which the drug substance is pulverized to nanoparticles ( average particle size of 400 nm ) in the presence of a surface modifier and then dispersed in a liquid medium to give a pharmaceutical composition that exhibits remarkably high bioavailability . compositions suitable for parenteral injection may comprise physiologically acceptable sterile aqueous or nonaqueous solutions , dispersions , suspensions or emulsions , and sterile powders for reconstitution into sterile injectable solutions or dispersions . examples of suitable aqueous and nonaqueous carriers , diluents , solvents or vehicles include water , ethanol , polyols ( propyleneglycol , polyethyleneglycol , glycerol , and the like ), suitable mixtures thereof , vegetable oils ( such as olive oil ) and injectable organic esters such as ethyl oleate . proper fluidity can be maintained , for example , by the use of a coating such as lecithin , by the maintenance of the required particle size in the case of dispersions and by the use of surfactants . one specific route of administration is oral , using a convenient daily dosage regimen that can be adjusted according to the degree of severity of the disease - state to be treated . solid dosage forms for oral administration include capsules , tablets , pills , powders , and granules . in such solid dosage forms , the active compound is admixed with at least one inert customary excipient ( or carrier ) such as sodium citrate or dicalcium phosphate or ( a ) fillers or extenders , as for example , starches , lactose , sucrose , glucose , mannitol , and silicic acid , ( b ) binders , as for example , cellulose derivatives , starch , alignates , gelatin , polyvinylpyrrolidone , sucrose , and gum acacia , ( c ) humectants , as for example , glycerol , ( d ) disintegrating agents , as for example , agar - agar , calcium carbonate , potato or tapioca starch , alginic acid , croscarmellose sodium , complex silicates , and sodium carbonate , ( e ) solution retarders , as for example paraffin , ( f ) absorption accelerators , as for example , quaternary ammonium compounds , ( g ) wetting agents , as for example , cetyl alcohol , and glycerol monostearate , magnesium stearate and the like ( h ) adsorbents , as for example , kaolin and bentonite , and ( i ) lubricants , as for example , talc , calcium stearate , magnesium stearate , solid polyethylene glycols , sodium lauryl sulfate , or mixtures thereof . in the case of capsules , tablets , and pills , the dosage forms may also comprise buffering agents . solid dosage forms as described above can be prepared with coatings and shells , such as enteric coatings and others well known in the art . they may contain pacifying agents , and can also be of such composition that they release the active compound or compounds in a certain part of the intestinal tract in a delayed manner . examples of embedded compositions that can be used are polymeric substances and waxes . the active compounds can also be in microencapsulated form , if appropriate , with one or more of the above - mentioned excipients . liquid dosage forms for oral administration include pharmaceutically acceptable emulsions , solutions , suspensions , syrups , and elixirs . such dosage forms are prepared , for example , by dissolving , dispersing , etc ., the compound of formula i , or a pharmaceutically acceptable salt thereof , and optional pharmaceutical adjuvants in a carrier , such as , for example , water , saline , aqueous dextrose , glycerol , ethanol and the like ; solubilizing agents and emulsifiers , as for example , ethyl alcohol , isopropyl alcohol , ethyl carbonate , ethyl acetate , benzyl alcohol , benzyl benzoate , propyleneglycol , 1 , 3 - butyleneglycol , dimethylformamide ; oils , in particular , cottonseed oil , groundnut oil , corn germ oil , olive oil , castor oil and sesame oil , glycerol , tetrahydrofurfuryl alcohol , polyethyleneglycols and fatty acid esters of sorbitan ; or mixtures of these substances , and the like , to thereby form a solution or suspension . suspensions , in addition to the active compounds , may contain suspending agents , as for example , ethoxylated isostearyl alcohols , polyoxyethylene sorbitol and sorbitan esters , microcrystalline cellulose , aluminum metahydroxide , bentonite , agar - agar and tragacanth , or mixtures of these substances , and the like . compositions for rectal administration are , for example , suppositories that can be prepared by mixing the compound of formula i with , for example , suitable non - irritating excipients or carriers such as cocoa butter , polyethyleneglycol or a suppository wax , which are solid at ordinary temperatures but liquid at body temperature and therefore , melt while in a suitable body cavity and release the active component therein . dosage forms for topical administration of the compound of formula i include ointments , powders , sprays , and inhalants . the active component is admixed under sterile conditions with a physiologically acceptable carrier and any preservatives , buffers , or propellants as may be required . ophthalmic compositions , eye ointments , powders , and solutions are also contemplated as being within the scope of this disclosure . compressed gases may be used to disperse the compound of formula i in aerosol form . inert gases suitable for this purpose are nitrogen , carbon dioxide , etc . generally , depending on the intended mode of administration , the pharmaceutically acceptable compositions will contain about 1 % to about 99 % by weight of a compound ( s ) of formula i , or a pharmaceutically acceptable salt thereof , and 99 % to 1 % by weight of a suitable pharmaceutical excipient . in one example , the composition will be between about 5 % and about 75 % by weight of a compound ( s ) of formula i , formula ia , or compound 1 , or a pharmaceutically acceptable salt thereof , with the rest being suitable pharmaceutical excipients . actual methods of preparing such dosage forms are known , or will be apparent , to those skilled in this art ; for example , see remington &# 39 ; s pharmaceutical sciences , 18th ed ., ( mack publishing company , easton , pa ., 1990 ). the composition to be administered will , in any event , contain a therapeutically effective amount of a compound of formula i , or a pharmaceutically acceptable salt thereof , for treatment of a disease - state in accordance with the teachings of this disclosure . the compounds of this disclosure , or their pharmaceutically acceptable salts or solvates , are administered in a therapeutically effective amount which will vary depending upon a variety of factors including the activity of the specific compound employed , the metabolic stability and length of action of the compound , the age , body weight , general health , sex , diet , mode and time of administration , rate of excretion , drug combination , the severity of the particular disease - states , and the host undergoing therapy . the compound of formula i , formula ia , or compound 1 , can be administered to a patient at dosage levels in the range of about 0 . 1 to about 1 , 000 mg per day . for a normal human adult having a body weight of about 70 kilograms , a dosage in the range of about 0 . 01 to about 100 mg per kilogram of body weight per day is an example . the specific dosage used , however , can vary . for example , the dosage can depend on a number of factors including the requirements of the patient , the severity of the condition being treated , and the pharmacological activity of the compound being used . the determination of optimum dosages for a particular patient is well known to one of ordinary skill in the art . in other embodiments , the compound of formula i , formula ia , or compound 1 , can be administered to the patient concurrently with other cancer treatments . such treatments include other cancer chemotherapeutics , hormone replacement therapy , radiation therapy , or immunotherapy , among others . the choice of other therapy will depend on a number of factors including the metabolic stability and length of action of the compound , the age , body weight , general health , sex , diet , mode and time of administration , rate of excretion , drug combination , the severity of the particular disease - states , and the host undergoing therapy . the starting 1 , 1 - cyclopropanedicarboxylic acid was treated with thionyl chloride ( 1 . 05 equivalents ) in approximately 8 volumes of isopropyl acetate at 25 ° c . for 5 hours . the resulting mixture was then treated with a solution of 4 - fluoroaniline ( 1 . 1 equivalents ) and triethylamine ( 1 . 1 equivalents ) in isopropyl acetate ( 2 volumes ) over 1 hour . the product slurry was quenched with 5n naoh solution ( 5 volumes ) and the aqueous phase is discarded . the organic phase was extracted with 0 . 5n naoh solution ( 10 volumes ) and the basic extract was washed with heptane ( 5 volumes ) and subsequently acidified with 30 % hcl solution to give a slurry . compound a - 1 was isolated by filtration . compound a - 1 was prepared on a 1 . 00 kg scale using 1 , 1 - cyclopropanedicarboxylic acid as the limiting reagent to furnish 1 . 32 kg of compound a - 1 ( 77 % isolated yield ; 84 % mass balance ) with 99 . 92 % purity ( hplc ) and 100 . 3 % assay . a synthetic route that can be used for the preparation of n -( 4 -{[ 6 , 7 - bis ( methyloxy ) quinolin - 4 - yl ] oxy } phenyl )- n ′-( 4 - fluorophenyl ) cyclopropane - 1 , 1 - dicarboxamide and the ( l )- malate salt thereof is depicted in scheme 1 . another synthetic route that can be used for the preparation of n -( 4 -{[ 6 , 7 - bis ( methyloxy ) quinolin - 4 - yl ] oxy } phenyl )- n ′-( 4 - fluorophenyl ) cyclopropane - 1 , 1 - dicarboxamide and the ( l )- malate salt thereof is depicted in scheme 2 . a reactor was charged sequentially with 6 , 7 - dimethoxy - quinoline - 4 - ol ( 47 . 0 kg ) and acetonitrile ( 318 . 8 kg ). the resulting mixture was heated to approximately 60 ° c . and phosphorus oxychloride ( pocl 3 , 130 . 6 kg ) was added . after the addition of pocl 3 , the temperature of the reaction mixture was raised to approximately 77 ° c . the reaction was deemed complete ( approximately 13 hours ) when less than 3 % of the starting material remained ( in - process high - performance liquid chromatography [ hplc ] analysis ). the reaction mixture was cooled to approximately 2 to 7 ° c . and then quenched into a chilled solution of dichloromethane ( dcm , 482 . 8 kg ), 26 % nh 4 oh ( 251 . 3 kg ), and water ( 900 l ). the resulting mixture was warmed to approximately 20 to 25 ° c ., and phases were separated . the organic phase was filtered through a bed of aw hyflo super - cel nf ( celite ; 5 . 4 kg ), and the filter bed was washed with dcm ( 118 . 9 kg ). the combined organic phase was washed with brine ( 282 . 9 kg ) and mixed with water ( 120 l ). the phases were separated and the organic phase was concentrated by vacuum distillation with the removal of solvent ( approximately 95 l residual volume ). dcm ( 686 . 5 kg ) was charged to the reactor containing organic phase and concentrated by vacuum distillation with the removal of solvent ( approximately 90 l residual volume ). methyl t - butyl ether ( mtbe , 226 . 0 kg ) was then charged and the temperature of the mixture was adjusted to − 20 to − 25 ° c . and held for 2 . 5 hours resulting in solid precipitate , which was then filtered and washed with n - heptane ( 92 . 0 kg ), and dried on a filter at approximately 25 ° c . under nitrogen to afford the title compound ( 35 . 6 kg ). 4 - aminophenol ( 24 . 4 kg ) dissolved in n , n - dimethylacetamide ( dma , 184 . 3 kg ) was charged to a reactor containing 4 - chloro - 6 , 7 - dimethoxyquinoline ( 35 . 3 kg ), sodium t - butoxide ( 21 . 4 kg ), and dma ( 167 . 2 kg ) at 20 - 25 ° c . this mixture was then heated to 100 - 105 ° c . for approximately 13 hours . after the reaction was deemed complete as determined using in - process hplc analysis ( less than 2 % starting material remaining ), the reactor contents were cooled at 15 to 20 ° c . and water ( pre - cooled , 2 to 7 ° c ., 587 l ) charged at a rate to maintain 15 to 30 ° c . temperature . the resulting solid precipitate was filtered , washed with a mixture of water ( 47 l ) and dma ( 89 . 1 kg ) and finally with water ( 214 l ). the filter cake was then dried at approximately 25 ° c . on filter to yield crude 4 -( 6 , 7 - dimethoxy - quinoline - 4 - yloxy )- phenylamine ( 59 . 4 kg wet , 41 . 6 kg dry calculated based on lod ). crude 4 -( 6 , 7 - dimethoxy - quinoline - 4 - yloxy )- phenylamine was refluxed ( approximately 75 ° c .) in a mixture of tetrahydrofuran ( thf , 211 . 4 kg ) and dma ( 108 . 8 kg ) for approximately 1 hour and then cooled to 0 to 5 ° c . and aged for approximately 1 hour after which time the solid was filtered , washed with thf ( 147 . 6 kg ) and dried on a filter under vacuum at approximately 25 ° c . to yield 4 -( 6 , 7 - dimethoxy - quinoline - 4 - yloxy )- phenylamine ( 34 . 0 kg ). 4 - chloro - 6 , 7 - dimethoxyquinoline ( 34 . 8 kg ) and 4 - aminophenol ( 30 . 8 kg ) and sodium tert pentoxide ( 1 . 8 equivalents ) 88 . 7 kg , 35 weight percent in thf ) were charged to a reactor , followed by n , n - dimethylacetamide ( dma , 293 . 3 kg ). this mixture was then heated to 105 to 115 ° c . for approximately 9 hours . after the reaction was deemed complete as determined using in - process hplc analysis ( less than 2 % starting material remaining ), the reactor contents were cooled at 15 to 25 ° c . and water ( 315 kg ) was added over a two hour period while maintaining the temperature between 20 and 30 ° c . the reaction mixture was then agitated for an additional hour at 20 to 25 ° c . the crude product was collected by filtration and washed with a mixture of 88 kg water and 82 . 1 kg dma , followed by 175 kg water . the product was dried on a filter drier for 53 hours . the lod showed less than 1 % w / w . in an alternative procedure , 1 . 6 equivalents of sodium tert - pentoxide were used and the reaction temperature was increased from 110 to 120 ° c . in addition , the cool down temperature was increased to 35 to 40 ° c . and the starting temperature of the water addition was adjusted to 35 to 40 ° c ., with an allowed exotherm to 45 ° c . oxalyl chloride ( 12 . 6 kg ) was added to a solution of 1 -( 4 - fluoro - phenylcarbamoyl )- cyclopropanecarboxylic acid ( 22 . 8 kg ) in a mixture of thf ( 96 . 1 kg ) and n , n - dimethylformamide ( dmf ; 0 . 23 kg ) at a rate such that the batch temperature did not exceed 25 ° c . this solution was used in the next step without further processing . a reactor was charged with 1 -( 4 - fluoro - phenylcarbamoyl )- cyclopropanecarboxylic acid ( 35 kg ), 344 g dmf , and 175 kg thf . the reaction mixture was adjusted to 12 to 17 ° c . and then to the reaction mixture was charged 19 . 9 kg of oxalyl chloride over a period of 1 hour . the reaction mixture was left stirring at 12 to 17 ° c . for 3 to 8 hours . this solution was used in the next step without further processing . the solution from the previous step containing 1 -( 4 - fluoro - phenylcarbamoyl )- cyclopropanecarbonyl chloride was added to a mixture of compound 4 -( 6 , 7 - dimethoxy - quinoline - 4 - yloxy )- phenylamine ( 23 . 5 kg ) and potassium carbonate ( 31 . 9 kg ) in thf ( 245 . 7 kg ) and water ( 116 l ) at a rate such that the batch temperature did not exceed 30 ° c . when the reaction was complete ( in approximately 20 minutes ), water ( 653 l ) was added . the mixture was stirred at 20 to 25 ° c . for approximately 10 hours , which resulted in the precipitation of the product . the product was recovered by filtration , washed with a pre - made solution of thf ( 68 . 6 kg ) and water ( 256 l ), and dried first on a filter under nitrogen at approximately 25 ° c . and then at approximately 45 ° c . under vacuum to afford the title compound ( 41 . 0 kg , 38 . 1 kg , calculated based on lod ). a reactor was charged with 4 -( 6 , 7 - dimethoxy - quinoline - 4 - yloxy )- phenylamine ( 35 . 7 kg , 1 equivalent ), followed by 412 . 9 kg thf . to the reaction mixture was charged a solution of 48 . 3 kg k 2 co 3 in 169 kg water . the acid chloride solution of described in the alternative preparation of 1 -( 4 - fluoro - phenylcarbamoyl )- cyclopropanecarbonyl chloride above was transferred to the reactor containing 4 -( 6 , 7 - dimethoxy - quinoline - 4 - yloxy )- phenylamine while maintaining the temperature between 20 to 30 ° c . over a minimum of two hours . the reaction mixture was stirred at 20 to 25 ° c . for a minimum of three hours . the reaction temperature was then adjusted to 30 to 25 ° c ., and the mixture was agitated . the agitation was stopped and the phases of the mixture were allowed to separate . the lower aqueous phase was removed and discarded . to the remaining upper organic phase was added 804 kg water . the reaction was left stirring at 15 to 25 ° c . for a minimum of 16 hours . the product precipitated . the product was filtered and washed with a mixture of 179 kg water and 157 . 9 kg thf in two portions . the crude product was dried under a vacuum for at least two hours . the dried product was then taken up in 285 . 1 kg thf . the resulting suspension was transferred to reaction vessel and agitated until the suspension became a clear ( dissolved ) solution , which required heating to 30 to 35 ° c . for approximately 30 minutes . 456 kg water was then added to the solution , as well as 20 kg sdag - 1 ethanol ( ethanol denatured with methanol over two hours ). the mixture was agitated at 15 to 25 ° c . for at least 16 hours . the product was filtered and washed with a mixture of 143 kg water and 126 . 7 kg thf in two portions . the product was dried at a maximum temperature set point of 40 ° c . in an alternative procedure , the reaction temperature during acid chloride formation was adjusted to 10 to 15 ° c . the recrystallization temperature was changed from 15 to 25 ° c . to 45 to 50 ° c . for 1 hour and then cooled to 15 to 25 ° c . over 2 hours . cyclopropane - 1 , 1 - dicarboxylic acid [ 4 -( 6 , 7 - dimethoxy - quinoline - 4 - yloxy )- phenyl ]- amide ( 4 - fluoro - phenyl )- amide ( 13 . 3 kg ), l - malic acid ( 4 . 96 kg ), methyl ethyl ketone ( mek ; 188 . 6 kg ) and water ( 37 . 3 kg ) were charged to a reactor and the mixture was heated to reflux ( approximately 74 ° c .) for approximately 2 hours . the reactor temperature was reduced to 50 to 55 ° c ., and the reactor contents were filtered . these sequential steps described above were repeated two more times starting with similar amounts of cyclopropane - 1 , 1 - dicarboxylic acid [ 4 -( 6 , 7 - dimethoxy - quinoline - 4 - yloxy )- phenyl ]- amide ( 4 - fluoro - phenyl )- amide ( 13 . 3 kg ), l - malic acid ( 4 . 96 kg ), mek ( 198 . 6 kg ), and water ( 37 . 2 kg ). the combined filtrate was azeotropically dried at atmospheric pressure using mek ( 1133 . 2 kg ) ( approximate residual volume 711 l ; kf & lt ; 0 . 5 % w / w ) at approximately 74 ° c . the temperature of the reactor contents was reduced to 20 to 25 ° c . and held for approximately 4 hours , resulting in solid precipitate which was filtered , washed with mek ( 448 kg ) and dried under vacuum at 50 ° c . to afford the title compound ( 45 . 5 kg ). cyclopropane - 1 , 1 - dicarboxylic acid [ 4 -( 6 , 7 - dimethoxy - quinoline - 4 - yloxy )- phenyl ]- amide ( 4 - fluoro - phenyl )- amide ( 47 . 9 kg ), l - malic acid ( 17 . 2 kg ), 658 . 2 kg methyl ethyl ketone , and 129 . 1 kg water ( 37 . 3 kg ) were charged to a reactor and the mixture was heated 50 to 55 ° c . for approximately 1 to 3 hours , and then at 55 to 60 ° c . for an additional 4 to 5 hours . the mixture was clarified by filtration through a 1 μm cartridge . the reactor temperature was adjusted to 20 to 25 ° c . and vacuum distilled with a vacuum at 150 to 200 mm hg with a maximum jacket temperature of 55 ° c . to the volume range of 558 to 731 l . the vacuum distillation was performed two more times with the charge of 380 kg and 380 . 2 kg methyl ethyl ketone , respectively . after the third distillation , the volume of the batch was adjusted to 18 v / w of cyclopropane - 1 , 1 - dicarboxylic acid [ 4 -( 6 , 7 - dimethoxy - quinoline - 4 - yloxy )- phenyl ]- amide ( 4 - fluoro - phenyl )- amide by charging 159 . 9 kg methyl ethyl ketone to give a total volume of 880 l . an additional vacuum distillation was carried out by adjusting 245 . 7 kg methyl ethyl ketone . the reaction mixture was left with moderate agitation at 20 to 25 ° c . for at least 24 hours . the product was filtered and washed with 415 . 1 kg methyl ethyl ketone in three portions . the product was dried under a vacuum with the jacket temperature set point at 45 ° c . in an alternative procedure , the order of addition was changes so that a solution of 17 . 7 kg l - malic acid dissolved in 129 . 9 kg water was added to cyclopropane - 1 , 1 - dicarboxylic acid [ 4 -( 6 , 7 - dimethoxy - quinoline - 4 - yloxy )- phenyl ]- amide ( 4 - fluoro - phenyl )- amide ( 48 . 7 kg ) in methyl ethyl ketone ( 673 . 3 kg ). the met and vegf signaling pathways appear to play important roles in osteoblast and osteoclast function . strong immunohistochemical staining of met has been observed in both cell types in developing bone . hgf and met are expressed by osteoblasts and osteoclasts in vitro and mediate cellular responses such as proliferation , migration , and expression of alp . secretion of hgf by osteoblasts has been proposed as a key factor in osteoblast / osteoclast coupling , and in the development of bone metastases by tumor cells that express met . osteoblasts and osteoclasts also express vegf and its receptors , and vegf signaling in these cells is involved in potential autocrine and / or paracrine feedback mechanisms regulating cell migration , differentiation , and survival . bone metastases are present in 90 percent of patients with castration - resistant prostate cancer ( crpc ), causing significant morbidity and mortality . activation of the met and vegfr signaling pathways is implicated in the development of bone metastases in crpc . three metastatic crpc patients treated with compound 1 , an inhibitor of met and vegfr , had dramatic responses with near complete resolution of bone lesions , marked reduction in bone pain and total serum alkaline phosphatase ( talp ) levels , and reduction in measurable disease . these results indicate that dual modulation of the met and vegfr signaling pathways is a useful therapeutic approach for treating crpc . compound 1 is an orally bioavailable multitargeted tyrosine kinase inhibitor with potent activity against met and vegfr2 . compound 1 suppresses met and vegfr2 signaling , rapidly induces apoptosis of endothelial cells and tumor cells , and causes tumor regression in xenograft tumor models . compound 1 also significantly reduces tumor invasiveness and metastasis and substantially improves overall survival in a murine pancreatic neuroendocrine tumor model . in a phase 1 clinical study , compound 1 was generally well - tolerated , with fatigue , diarrhea , anorexia , rash , and palmar - plantar erythrodysesthesia being the most commonly observed adverse events . based on target rationale and observed antitumor activity in clinical studies , an adaptive phase 2 trial was undertaken in multiple indications including crpc ( http :// clinicaltrials . gov / ct2 / results ? term = nct00940225 for study nct00940225 last visited sep . 20 , 2011 )), in which compound 1 was administered as a 100 mg dose to patients . the findings in the first three crpc patients with evidence of bone metastases on bone scan enrolled to this study are described in the following case studies . all patients provided informed consent before study screening . baseline characteristics for patients 1 - 3 are summarized in table 1 . the results for patients 1 - 3 are also depicted in fig1 - 13 . patient 1 was diagnosed with localized prostate cancer in 1993 and treated with radical prostatectomy ( gleason score unavailable ; psa , 0 . 99 ng / ml ). in 2000 , local disease recurrence was treated with radiation therapy . in 2001 , combined androgen blockade ( cab ) with leuprolide and bicalutamide was initiated for rising psa ( 3 . 5 ng / ml ). in 2006 , diethystillbestrol ( des ) was administered briefly . in 2007 , 6 cycles of docetaxel were given for new lung metastases . rising psa was unresponsive to antiandrogen withdrawal . androgen ablation therapy was continued until clinical progression . in october 2009 , bone metastasis to the spine associated with impingement on the spinal cord and back pain , was treated with radiation therapy ( 37 . 5 gy ). in february 2010 , a bone scan was performed due to increasing bone pain and showed diffuse uptake of radiotracer in the axial and appendicular skeleton . a ct scan revealed new pulmonary and mediastinal lymph node metastases . psa was 430 . 4 ng / ml . patient 2 was diagnosed in april of 2009 after presenting with a pathologic fracture ( gleason score , 4 + 5 = 9 ; psa , 45 . 34 ng / ml ). bone scan showed uptake of radiotracer in the left iliac wing , left sacroiliac joint , femoral head , and the pubic symphysis . biopsy of the left pubic ramus confirmed metastatic adenocarcinoma with mixed lytic and blastic lesions . cab with leuprolide and bicalutamide and radiation therapy ( 8 gy ) to the left pubic ramus and acetabulum resulted in bone pain relief and psa normalization . rising psa in november 2009 ( 16 ng / ml ) was unresponsive to antiandrogen withdrawal . in february 2010 , bone scan showed multiple foci throughout the axial and appendicular skeleton . a ct scan revealed retroperitoneal lymph node enlargement and liver metastases ( psa , 28 . 1 ng / ml ). further progression of disease was marked by recurrent bone pain , new lung and hepatic metastases . patient 3 was diagnosed in april 2009 after presenting with right hip pain ( gleason score , 4 + 5 = 9 ; psa , 2 . 6 ng / ml ). bone scan showed uptake of radiotracer at multiple sites throughout the axial and appendicular skeleton . a ct scan revealed retroperitoneal , common iliac , and supraclavicular adenopathy . cab with leuprolide and bicalutamide was initiated . the patient received 6 cycles of docetaxel through december 2009 . following treatment , a bone scan showed no changes . a ct scan revealed near resolution of the retroperitoneal and common iliac adenopathy . in march 2010 , psa began to rise , and bone pain worsened . a repeat bone scan showed new foci , and a ct scan showed an increase in the retroperitoneal , para - aortic , and bilateral common iliac adenopathy . rising psa in april 2010 ( 2 . 8 ng / ml ) and increasing bone pain were unresponsive to antiandrogen withdrawal . fig1 depicts a flowchart of ibis bone scan image analysis . fig3 shows a lesion detection receiver operator characteristic ( roc ) curve for selection of region - specific intensity thresholds . fig5 shows bone scan response criterion determination based on prior development study cohort . fig6 is an example of bone scan assessment demonstrating the advantage of bone scan lesion area over lesion count in assessing partial response . fig8 depicts the best time point response of bone scan lesion area in patients treated at 40 mg ( n = 11 ). fig9 depicts ibis - calculated metrics at baseline and time point of best response in patients ( n = 11 ). fig1 shows the ibis - calculated metrics at baseline and time point of best response in patients treated at 40 mg ( n = 11 ). patient 1 started compound 1 on feb . 12 , 2010 . four weeks later , significant reduction in bone pain was reported . at week 6 , bone scan showed a dramatic decrease in radiotracer uptake by bone metastases ( fig1 a ). a ct scan showed a partial response ( pr ) with a 33 % decrease in measurable target lesions ( fig1 c ). at week 12 , near complete resolution of bone lesions and a 44 % decrease in target lesions was observed and was stable through week 18 . corresponding with the bone scan response , after an initial rise , serum talp levels decreased from 689 u / l at baseline to 159 u / l at week 18 ( fig1 b and table 1 ). in addition , there was an increase in hemoglobin of 1 . 4 g / dl at week 2 compared with baseline ( table 1 ). psa decreased from 430 ng / ml at baseline to 93 . 5 ng / ml at week 18 ( fig1 b and table 1 ). the patient was on open - label treatment through week 18 when he withdrew after developing grade 3 diarrhea . patient 2 started compound 1 on mar . 31 , 2010 . at week 4 , reduction in bone pain was reported . at week 6 , bone scan showed a slight flair in radiotracer uptake by bone lesions ( fig1 a ), and a ct scan showed a 13 % decrease in target lesions ( fig1 c ). at week 12 , a substantial reduction of radiotracer uptake ( fig1 a ) and a 20 % decrease in measurable disease were observed ( table 1 ). after randomization to placebo at week 12 the patient developed severe bone pain and sacral nerve root impingement . radiation to the spine was administered , and the patient crossed over to open - label compound 1 treatment at week 15 . serum talp levels were within the normal range ( 101 - 144 u / l ) ( fig1 b ). hemoglobin increased by 1 . 8 g / dl at week 12 compared with baseline ( table 1 ). psa peaked at close to 6 - fold of baseline by week 16 , but then decreased to 2 - fold of baseline by week 18 subsequent to crossing over to compound 1 from placebo ( fig1 b and table 1 ). the patient continues on compound 1 treatment as of september 2010 . patient 3 started compound 1 on apr . 26 , 2010 . after three weeks a complete resolution of pain was reported . at week 6 , bone scan showed a dramatic reduction in radiotracer uptake ( fig1 a ), and a ct scan showed a pr with a 43 % decrease in measurable target lesions . at week 12 a complete resolution of bone lesions on bone scan ( fig1 a ) and a 51 % decrease in measurable disease were observed ( table 1 and fig1 b )). after an initial rise , serum talp levels steadily decreased , with talp at 869 u / l at baseline and 197 u / l at week 18 ( fig1 b and table 1 ). hemoglobin increased 2 . 2 g / dl at week 2 compared with baseline ( table 1 ). psa decreased from 2 . 4 ng / ml at screening to 1 . 2 ng / ml at week 18 ( fig1 b and table 1 ). the patient continues on compound 1 treatment as of september 2010 . all three patients experienced a striking decrease in uptake of radiotracer on bone scan upon treatment with compound 1 . these findings were accompanied by substantial reductions in bone pain and evidence of response or stabilization in soft tissue lesions during therapy with compound 1 . the onset of the effect was very rapid in two of the patients , with substantial improvement or near resolution of bone scan and improvement in pain occurring in the first 6 weeks . in the third patient , an apparent flare in the bone scan was observed at 6 weeks , followed by improvement by 12 weeks . to our knowledge , such a comprehensive and rapid impact on both osseous and soft tissue disease has not been observed in this patient population . uptake of radiotracer in bone depends on both local blood flow and osteoblastic activity , both of which may be pathologically modulated by the tumor cells associated with the bone lesion . resolving uptake may therefore be attributable to either interruption of local blood flow , direct modulation of osteoblastic activity , a direct effect on the tumor cells in bone , or a combination of these processes . however , decreased uptake on bone scan in men with crpc has only been rarely noted with vegf / vegfr targeted therapy , despite numerous trials with such agents . similarly , observations of decreased uptake on bone scan in crpc patients have only been reported rarely for abiraterone , which targets the cancer cells directly , and for dasatinib , which targets both cancer cells and osteoclasts . thus , targeting angiogenesis alone , or selectively targeting the tumor cells and / or osteoclasts , has not resulted in effects similar to those observed in the patients treated with compound 1 . these results indicate a potential critical role for the met and vegf signaling pathways in the progression of crpc and point to the promise that simultaneously targeting these pathways may hold in reducing morbidity and mortality in this patient population . the foregoing disclosure has been described in some detail by way of illustration and example , for purposes of clarity and understanding . the invention has been described with reference to various specific and preferred embodiments and techniques . however , it should be understood that many variations and modifications can be made while remaining within the spirit and scope of the invention . it will be obvious to one of skill in the art that changes and modifications can be practiced within the scope of the appended claims . therefore , it is to be understood that the above description is intended to be illustrative and not restrictive . the scope of the invention should , therefore , be determined not with reference to the above description , but should instead be determined with reference to the following appended claims , along with the full scope of equivalents to which such claims are entitled .

this invention is directed to a method for quantifying cancer treatment response in patients with bone metastases using computer aided bone scan assessment , comprising : obtaining a bone scan image ; normalizing the obtained bone scan image to identify normalized bone scan lesions ; and quantitatively assessing the normalized bone scan lesions using bone scan lesion area , bone scan intensity , or bone scan lesion count .

reference will now be made in detail to embodiments of the present invention , examples of which are illustrated in the accompanying drawings . in regard to fig1 a a perspective view of the device is provided . in this embodiment of the invention the device 100 is generally configured in a cylinder tube configuration with a twist opening feature . the device 100 generally has a device first end 110 and a device second end 120 . further , the device includes a tube 200 , a neck 300 , and a cap 400 . the tube section 200 includes a tube first end 210 , a tube second end 220 , a tube upper end 230 , and tube lower end ( not shown ). in addition , the tube 200 includes a tube exterior surface 250 , tube interior surface ( not shown ), and tube thickness . the neck portion of the device 100 includes a neck 300 . the neck 300 includes a neck first end 310 , a neck second end 320 , a neck upper end 330 , neck lower end ( not shown ), neck exterior surface 350 . the cap section 400 of the device 100 includes a cap first end 410 , a cap second end 420 , a cap exterior surface 430 , and a cap second exterior surface 440 . furthermore , the cap 400 includes a cap fluid discharge opening 490 . fig1 a depicts the device 100 in the closed configuration that is unable to discharge its contents . referring now to fig1 b , a perspective view of the device 100 is presented . fig1 b is similar to fig1 a except the cap 400 section of the device 100 has been rotated into its open position , allowing fluid or the contents of the device 100 to be discharged . the device 100 generally has a device first end 110 and a device second end 120 . further , the device includes a tube 200 , a neck 300 , and a cap 400 . the tube section 200 includes a tube first end 210 , a tube second end 220 , a tube upper end 230 , and a tube lower end ( not shown ). in addition , the tube 200 includes a tube exterior surface 250 , tube interior surface ( not shown ), and tube thickness . the neck portion of the device 100 includes a neck 300 , including a neck first end 310 , a neck second end 320 , a neck upper end 330 , and a neck lower end ( not shown ). the cap section 400 of the device 100 comprises a cap first end 410 , a cap second end 420 , a cap exterior surface 430 , and a cap second exterior surface 440 . furthermore , the cap 400 includes a cap fluid discharge opening 490 . fig1 b depicts the device 100 in the open configuration that is able to discharge its contents . referring now to fig2 a - 2c , an end view of the device 100 is presented showing the rotation of the cap 400 from its closed position shown in fig2 a through an intermediary position shown in fig2 b to an open position shown as fig2 c . specifically , fig2 a presents an end view of the cap 400 of the device 100 , showing the cap 400 features of a cap first end 410 , a cap second end 420 , a cap first exterior surface 430 , a cap second exterior surface 440 , and a cap fluid discharge opening 490 . in fig2 c , the device 100 is shown in the open configuration . the cap 400 includes cap first end 410 , cap first exterior surface 430 , cap second exterior surface 440 , and cap fluid discharge opening 490 . fig2 a - c illustrates the cap opening in a counter clockwise manner shown in its interim rotation state as fig3 b . referring now in detail fig3 a - f , various ends and cross - sectional side views of the device in the cylinder tube configuration with twist opening feature are presented . fig3 a presents the device 100 featuring a tube 200 , device first end 110 , and device second end 120 . further , fig3 a illustrates the neck portion 300 , a neck thickness 370 , and a cap fluid discharge opening 490 . a broken seal 530 is also shown in this open configuration . fig3 b illustrates an end view of fig3 a and fig3 c presents a close up cross sectional end view of fig3 a . in fig3 b the cap 400 is shown with a cap first end 410 , cap first exterior surface 430 , a cap second exterior surface 440 , cap thickness 470 , and cap fluid discharge opening 490 . fig3 c presents a close up cross - sectional view of fig3 a depicting the neck 300 and features of the cap 400 . referring to fig3 c , the neck 300 is shown with a neck thickness 370 , and the cap 400 is shown with cap first exterior surface 430 , and cap fluid discharge opening 490 illustrated . fig3 a - c presents the device 100 in the open configuration allowing fluid or substance to be emitted along path 600 ( the fluid discharge channel ) out from the device 100 through cap fluid discharge opening 490 . further , fig3 c illustrates a seal component 500 and seal second thickness 520 in the configuration of the fig3 a - c . the device has been rotated according to fig2 a - c to move to the open discharge configuration . fig3 d - e presents the device 100 in the closed configuration , which does not allow fluid contents 620 to be discharged from the device 100 . fig3 d presents an end view of the device 100 focusing on the cap 400 elements , shown in fig3 are the cap 400 , the cap first end 410 , the cap first exterior surface 430 , the cap second exterior surface 440 , the cap thickness 470 , and cap fluid discharge opening 490 . fig3 e presents a cross - sectional view of fig3 d of the device 100 as figured in its closed configuration and includes the tube 200 , neck 300 and cap 400 . fig3 e depicts cap fluid discharge opening 490 , cap first exterior opening 430 , neck thickness 370 , seal 500 , and seal second thickness 520 . fig3 f presents the device 100 in its closed configuration similar to fig3 e except with the cap structure 400 disassembled from the tube portion 200 and neck section 300 . fig3 f presents features of neck thickness 370 , cap first exterior surface 430 , and cap fluid discharge opening 490 . also depicted in fig3 f are seal first thickness 510 and seal second thickness 520 . upon engagement between the cap 400 and neck 300 , the seal initially with seal first thickness 510 , typically reduces to seal second thickness 520 . fig4 a - b presents additional close up cross - sectional views of the device first end 110 . fig4 a presents the device 100 in the closed configuration , while fig4 b presents the device 100 in the open configuration . turning now to fig4 a , the device 100 includes the tube 200 , neck thickness 370 , neck cap inner connection structure 380 , cap - neck interconnect structure 480 , cap 400 , cap first exterior surface 430 , cap second exterior surface 440 , and cap fluid discharge opening 490 . fig4 a also presents seal 500 and seal second thickness 520 . fig4 a presents the device 100 in the open configuration in which fluid contents 620 may be emitted through the device cap 400 at the cap fluid discharge opening 490 . the fluid contents 620 are emitted along path fluid discharge channel 600 . turning now to fig4 b , the device first end 110 is shown with elements tube 200 , neck thickness 370 , neck cap inner connection structure 380 , cap 400 , cap first exterior surface 430 , cap second exterior surface 440 , and cap fluid discharge opening 490 are shown . the device 100 is in the open configuration in which fluid contents 620 may be emitted through the device cap 400 at the cap fluid discharge opening 490 . the fluid contents 620 are emitted along path fluid discharge channel 600 . fig5 a - b presents a disassembled view of the device 100 with particular focus on the seal 500 element . fig5 b is a reverse view of fig5 a . both fig5 a and 5b depict the device in the open configuration in which fluid content 620 may be emitted through cap fluid discharge opening 490 . in fig5 a the device 100 is shown with a tube 200 , neck 300 , cap 400 , and seal 500 . in addition , neck alignment ridge 382 in identified . fig5 b , is a reverse view of fig5 a , and presents the device 100 with tube 200 , neck 300 , cap 400 , and seal 500 . fig5 b also identifies the cap alignment grove 484 . both fig5 a and 5b present an additional view of the seal 500 for additional detail . only one seal 500 is present in the device in this embodiment of the device 100 . neck alignment ridge 382 engages cap alignment grove 484 to secure a connection between the cap 400 component and the neck component 300 . fig6 a - d provides additional views of the embodiment of the device 100 in a cylinder tube configuration with a twist opening feature . fig6 a - 6b illustrate side views of the device 100 in an open configuration and a closed configuration , respectably . fig6 a presents the device 100 with tube 200 , neck 300 , cap first exterior surface 430 , cap second exterior surface 440 , and fluid containment area 610 . fig6 b presents the device 100 in its closed configuration with tube 200 , neck 300 , cap first exterior surface 430 , cap second exterior surface 440 as well as fluid containment area 610 . the dashed lines in fig6 a and 6b depict extensions of the device 100 to allow additional fluid containment area 610 . in each of the dashed line configurations of fig6 a and 6b specific volumes of fluid contents 620 would be featured , e . g ., 5 ml , 10 ml , and 15 ml . the size of the device and its ability to contain varying degrees of fluid content 620 are enabled by extension of the tube portion 200 . fig6 c and 6d depicts the device 100 in a top view showing the tube portion 200 , a tube second end 220 , cap first end 410 , cap second end 420 , and cap second exterior surface 420 . similar to fig6 a and 6b , fig6 c and 6d depict the device with varying degrees of elongation of the tube section 200 to allow for varying levels of fluid containment area 610 and therefore varying amounts of fluid content 620 volume . fig6 d includes a tube second end location 220 that enables fluid content 620 filling of fluid containment area 610 . more specifically , the second end location 220 is used to fill the tube 200 to the desired volume and then sealed in a thermal compression manner as known in the art . fig7 - 15 depicts the device in the cylinder tube configuration with a hinged fracture tab opening feature . fig7 a presents device 100 with tube 200 , cap first exterior surface 430 , cap second exterior surface 440 , and fracture tab 700 with fracture tab pressing point 710 and fracture tab position one 712 . fig7 b is a front view of fig7 a presenting the cap fluid discharge opening 490 , cap second exterior surface 440 , cap first exterior surface 430 , and cap thickness 470 . fig7 c presents a close up cross - sectional view of the device 100 as depicted in fig7 c . fig7 c presents the tube 200 , cap first exterior surface 430 , cap second exterior surface 440 , fracture tab 700 with fracture tab position one 712 and fracture tab position two 714 . when a user depresses by applying a downward vertical force at fracture tab pressing point 720 fracture tab 700 depresses thereby allowing fluid to discharge from device 100 . fig7 d - 7e presents additional views of the device 100 . fig7 d is a cross - sectional front end view of the device at section a - a of fig7 e . fig7 e depicts the fracture tab 700 in both its fracture tab positions one 712 position and its fracture tab position two 714 configuration . when the fracture tab 700 is in its fracture tab position one 712 position , fluid is unable to discharge from device 100 through cap fluid discharge opening 490 . however , when a user engages device 100 by pressing hinge 700 at fracture tab pressing point 710 , the hinge 700 rotates downward as shown in fig7 e to the position of fracture tab position two 714 thereby allowing fluid to emit through cap fluid discharge opening 490 . fig7 d depicts cap fluid discharge opening 490 , cap second exterior surface 440 , and cap first exterior surface 430 . in this embodiment , the fracture tab 700 has a radius of curvature to permit easier fracturing and allow the fracture tab 700 to be a location closer to an inner surface of the tube . fig8 a - l depicts the device 100 in various configurations ; in particular , various configurations of the tube shape and length . fig8 a - c depicts three different views of a configuration of device 100 , detailing the tube 200 , the tube first end 210 , tube second end 220 , cap first exterior surface 430 , cap second exterior surface 440 , and cap fluid discharge opening 490 . fig8 a - l are representative of cylinder tube configurations which could feature a twist opening feature and / or a hinge fracture tab opening feature or other embodiments of the opening feature . fig8 d - f depict another three different views of a configuration of the device 100 . the embodiment of fig8 d - f are similar to fig8 a - c , yet would allow a greater amount of fluid content 620 to be stored in fluid containment area 610 . fig8 g - i presents three different views of the device 100 . the embodiments shown in fig8 g - i would contain an additional fluid content 620 through those of fig8 d - f and figure fig8 a - c . fig8 g - i depict the device 100 with elements tube 200 , tube first end 210 , cap second exterior surface 440 , cap first exterior surface 430 , and cap fluid discharge opening 490 . fig8 j - l illustrates another embodiment of the invention shown with a particularly large fluid containment area 610 . the intended fluid containment area 610 would store at least 50 ml of fluid content 620 . fig8 j - l depicts the device 100 with tube 200 , tube first end 210 , cap first exterior surface 430 , cap second exterior surface 440 , and cap fluid discharge opening 490 . fig9 a - c depicts the device 100 in a cylinder tube configuration with hinged fracture tab opening feature . fig9 a is a front view of the device with cap fluid discharge opening 490 , cap first exterior surface 430 , and cap second exterior surface 440 . fig9 b is a cross - sectional view of the device 100 depicting the cap fluid discharge opening 490 , the fracture tab 400 and details of the fracture tab 700 in both fracture tab position one 712 and fracture tab position two 714 . further , fig9 b identifies the front fracture line 730 . a user , in pressing the fracture tab 700 downward , would impart a force to the fracture tab position 700 such that the fracture tab 700 rotates between fracture tab position one 712 and fracture tab position two 714 . in fracture tab position one 712 no fluid is emitted from cap fluid discharge opening 490 . however , in fracture tab position two 714 , fluid may be emitted through fluid discharge opening 490 . fig9 c presents a cross - sectional a - a of fig9 b showing the cap fluid discharge opening 490 and the fracture tab 700 in both its fracture tab position one 712 and fracture tab position two 714 configurations . fig1 a - c presents another configuration of the device 100 in a cylinder tube configuration with hinged fracture tab opening feature . fig1 a is a front view of the device depicting the cap fluid discharge opening 490 , cap second exterior surface 440 , and cap first exterior surface 430 . fig1 b depicts a cross - sectional side view of the device with fracture tab 700 with both the fracture tab position one 712 and fracture tab position two 714 positions . fig1 c presents section a - a of 10 b showing cap fluid discharge opening 490 , and fracture tab 700 with both the fracture tab position one 712 and fracture tab position two 714 configurations . fig1 a - c presents another embodiment of the device 100 in an oblong cylinder tube configuration with hinged fracture tab opening feature . fig7 a depicts the front view of the device 100 cap fluid discharge opening 490 , cap first exterior surface 430 , and cap second exterior surface 440 . fig7 b presents a cross - sectional side view of the device featuring a fracture tab 700 with both the fracture tab position one 712 and fracture tab position two 714 configurations . fig1 c presents a cross - sectional a - a of fig1 b showing the cap fluid discharge opening 490 and the fracture tab 700 in both its fracture tab position one 712 and fracture tab position two 714 configurations . fig1 a - d presents the device 100 in yet another embodiment of the cylinder tube configuration . the embodiment of fig1 a and 12d are contemplated for use with both the twist opening feature and hinged fracture tab opening feature and could also be useful in other opening feature configurations . fig1 a - c presents a three view of the device 100 while fig1 d presents a perspective view . shown in fig1 a - d are the device 100 , tube 200 , tube first end 210 , tube second end 220 , cap first exterior surface 430 , cap second exterior surface 440 , and cap fluid discharge opening 490 . in this embodiment , the second end 220 is used to file the tube 200 and subsequently sealed via thermal compression or other technique as known in the art . fig1 a - d present yet another embodiment of the invention configured as a generally cylinder or round tube 200 . fig1 a - c presents a three view perspective of this embodiment , while fig1 d presents a perspective view . elements shown in fig1 a - d are the device 100 , tube 200 , cap first exterior surface 430 , cap second exterior surface 440 , and cap fluid discharge opening 490 . fig1 a - d present yet another embodiment of the invention configured as a generally cylinder or round tube 200 . fig1 a - c presents a three view perspective of this embodiment , while fig1 d presents a perspective view . elements shown in fig1 a - d are the device 100 , tube 200 , cap first exterior surface 430 , cap second exterior surface 440 , and cap fluid discharge opening 490 . this embodiment is dubbed the “ racetrack ” embodiment . fig1 a - d present yet another embodiment of the invention configured as a generally cylinder or round tube 200 . fig1 a - c presents a three view perspective of this embodiment , while fig1 presents a perspective view . elements shown in fig1 a - d are the device 100 , tube 200 , cap first exterior surface 430 , cap second exterior surface 440 , and cap fluid discharge opening 490 . turning to fig1 , a cross - sectional side view of the device 100 is depicted with tube upper end 230 , tube lower end 240 , cap fluid discharge opening 490 , and fracture tab 700 in both its fracture tab position one ( or closed position ) 712 , and fracture tab position two ( or open position ) 714 . when a user presses on the tube upper end 230 , so as to engage fracture tab 700 , with sufficient pressure to push fracture tab 700 downward , tab 700 rotates in the direction as depicted by the arrow in fig1 . the fracture tab 700 rotates to its fracture tab position two 714 so as to allow fluid contents 620 contained in the fluid containment area 610 to be discharged through cap fluid discharge opening 490 . in this embodiment , the tube end 230 is a flexible material while the tube lower end 240 has less flexible material . fig1 a is a partial cut - away view of the device with hinged / slot opening feature . fig1 b is a partial cut - away view of the device with hinged / slot opening feature . fig1 c is a cross - sectional side view of the hinged opening feature of fig1 a . fig1 d is a cross - sectional side view of the hinged opening feature of fig1 b . turning to fig1 a , the device 100 is depicted with tube 200 , and fracture tab 700 in both its fracture tab position one 712 ( or open position ) and fracture tab position two 714 . fig1 a depicts a configuration for the device 100 where the tube 200 is generally configured parallel with the fracture tab 700 . fig1 b presents a configuration of the device 100 particularly suited for tube configurations in which tube 200 could be dome or clam - shelled shaped , thus requiring the open position of the fracture tab 700 to be projected at an angular orientation upwards as shown in fig1 b . fig1 b presents the device 100 with tube 200 and fracture tab 700 , and both its fracture tab position one 712 and fracture tab position two 714 . a close up of the fracture tab of fig1 a is shown in fig1 c . fig1 c presents a side cut - away view of the fracture tab 700 assembly in the configuration particularly suited in configurations of the device 100 in which the tube 200 is generally parallel with a fracture tab 700 . fig1 c presents the device with a tube upper end 230 , cap fluid discharge opening 490 , fracture tab 700 , and features of fracture tab 700 of fractured line 730 and fractured plane 732 . when a user presses downward on the tube upper end 230 , to engage the fracture tab 700 , the fracture tab would rotate from its fig1 closed position downward to allow fluid to escape from cap fluid discharge opening 490 . fig1 d presents a close - up cross - sectional view of the tube upper end 230 of the embodiment of fig1 b . in fig1 d , the fracture tab 700 is shown with features of fracture line 730 and fracture plane 732 . when a user engages tube upper end 230 in a downward manner the fracture tab 700 would rotate downward so as to open cap 490 to allow fluid to discharge . fig1 e - h depicts various views of the clam shell configuration . in fig1 e - i the hinge 700 configuration depicted in 17 b would be particularly useful in clam - shelled or some configurations of tube 200 . fig1 a - d depicts various top views of the device 100 in the clam shell or dome configuration with hinged fracture tab opening feature . fig1 a depicts the tube first end 210 with tube upper end 230 and internal fracture tab 700 . the dome shape of tube upper end 230 is slightly offset from the overall external structure of the device . in contrast in fig1 b the external structure of the device 100 in generally centered with the dome shape of the tube upper end 230 . in fig1 c the device 100 is shown with tube first end 210 , tube upper end 230 , and fracture tab 700 with a slight elongation at the forward end tube first end 210 . lastly , fig1 d depicts another embodiment of the invention with tube first end 210 substantially elongated and with tube upper end 230 and fracture tab 700 identified . in regard to fig1 a a perspective view of the device is provided . in this embodiment of the invention the device 100 is generally configured in an oval cylinder tube configuration with a slider opening feature . the device 100 generally includes a tube 200 , a neck 300 , and a cap 400 . the tube section 200 includes a tube first end 210 and a tube second end 220 . the neck 300 includes a neck first end 310 . the cap section 400 of the device 100 includes a cap first end 410 and a cap second end 420 . furthermore , the cap 400 includes a cap fluid discharge opening 490 . fig1 a depicts the device 100 in the closed configuration , that is , unable to discharge its contents . in regard to fig1 b a perspective view of the device is provided . in this embodiment of the invention the device 100 is generally configured in an oval cylinder tube configuration with a slider opening feature . the device 100 generally includes a tube 200 , a neck 300 , and a cap 400 . the tube section 200 includes a tube first end 210 and a tube second end 220 . the neck 300 includes a neck first end 310 and neck extended channel 316 . the cap section 400 of the device 100 includes a cap first end 410 and a cap second end 420 . furthermore , the cap 400 includes a cap fluid discharge opening 490 . fig1 b depicts the device 100 in the open configuration , that is , able to discharge its contents . in fig1 c the cap 400 is shown with a cap first end 410 , cap first exterior surface 430 , a cap second exterior surface 440 , cap fluid discharge opening 490 . fig1 d and 19e illustrate side views of the device 100 in closed configuration and open configuration , respectfully . fig1 c presents the device 100 with tube 200 , neck 300 and cap 400 . also shown are cap first end 210 , cap second end 220 , neck first end 310 , and cap fluid discharge opening 490 . fig1 d presents the device 100 with tube 200 , neck 300 and cap 400 . also shown are cap first end 210 , cap second end 220 , neck first end 310 , and cap fluid discharge opening 490 . in addition , neck extended channel 316 , neck indent upper 312 , neck indent lower 314 , cap indent upper 422 , and cap indent lower 424 are shown . cap first end 410 and cap second end 420 are also provided . fig1 f and 19g illustrate top views of the device 100 in closed configuration and open configuration , respectfully . fig1 f presents the device 100 with tube 200 , neck 300 , cap 400 , neck first end 310 , and cap first exterior surface 430 . fig1 g presents the device 100 with tube 200 , neck 300 , cap 400 , neck first end 310 , and cap first exterior surface 430 . also shown is neck extended channel 316 . while various embodiment of the present disclosure have been described in detail , it is apparent that modifications and alterations of those embodiments will occur to those skilled in the art . however , it is to be expressly understood that such modifications and alterations are within the scope and spirit of the present disclosure , as set forth in the following claims . the foregoing discussion of the disclosure has been presented for purposes of illustration and description . the foregoing is not intended to limit the disclosure to the form or forms disclosed herein . in the foregoing detailed description for example , various features of the disclosure are grouped together in one or more embodiments for the purpose of streamlining the disclosure . this method of disclosure is not to be interpreted as reflecting an intention that the claimed disclosure requires more features than are expressly recited in each claim . rather , as the following claims reflect , inventive aspects lie in less than all features of a single foregoing disclosed embodiment . thus , the following claims are hereby incorporated into this detailed description , with each claim standing on its own as a separate preferred embodiment of the disclosure . moreover , though the present disclosure has included description of one or more embodiments and certain variations and modifications , other variations and modifications are within the scope of the disclosure , e . g ., as may be within the skill and knowledge of those in the art , after understanding the present disclosure . it is intended to obtain rights which include alternative embodiments to the extent permitted , including alternate , interchangeable and / or equivalent structures , functions , ranges or steps to those claimed , whether or not such alternate , interchangeable and / or equivalent structures , functions , ranges or steps are disclosed herein , and without intending to publicly dedicate any patentable subject matter .

an oral disposable apparatus to deliver a fluid , e . g ., pharmacological agent to a patient in a one handed easy to use and sanitary manner . the apparatus includes a container capable of holding the fluid . the container is hermetically sealed with a specified quantity of fluid . a nozzle is coupled to the container . the nozzle is configured to permit comfortable insertion into a patient &# 39 ; s mouth . an integral valve is coupled to the container and the nozzle . the valve is configured to be activated via rotation of the nozzle , thereby releasing the fluid .