A debridement sponge made from a nonwoven fabric comprising, in a preferred form, yarn-like strands of bleached cotton fibers. In the preferred form, the strands are interconnected at multiple junctures to form fewer than 31 generally rectangular apertures per cm.sup.2. Moreover, each aperture has an area of 1.3 mm.sup.2. Furthermore, the fabric has a Calculated Strand Density of 0.17l g/cc, a Clarity Index of at least 0.75, and an Absorbent Capacity of at least 7 grams of a colored, aqueous, saline solution per gram of the fabric when compressed under a pressure of 3.3 g/cm.sup.2. Plug Harshness and Compression Recovery of the fabric are excellent.

Packing and debridement are extensively practiced for the management of acute and chronic wounds. Presenting a clean wound free from necrotic tissue, slough, and eschar that would interfere with repair is a most important preparatory step for effective wound healing. The removal of nonviable material reduces the incidence of infection and facilitates healing through the formation of healthy granulation tissue and through re-epithelization.
Packing refers to the filling of a wound or cavity with a sponge or other material. Packing is used to absorb excess wound exudate, along with any bacteria present therein, and to facilitate the formation of granulation tissue. Debridement refers to the removal of necrotic tissue from the wound site until healthy tissue is exposed.
The primary objectives of debridement are to encourage granulation and to prevent infection. A freshly debrided wound will express considerable amounts of serous fluid from the denuded cells. Granulation can be encouraged by preventing such fluid from accumulating and reclotting in the wound.
Various methods of debridement are known. These methods include surgical debridement, liquefaction through autolysis or with the aid of added enzymes, and mechanical debridement wherein the endogenous material is scrubbed or pulled away from the wound by means of a sponge or dressing. The procedure selected by the physician depends on numerous factors including the nature of the wound, the condition of the patient, and the situation in which the wound is presented for management.
The use of gauze sponges woven from bleached cotton yarn for packing and debriding wounds is widely practiced. When applied, such sponges are wetted with saline or other prescribed solutions. Such sponges are believed to be effective for mechanical debridement because their densely packed, twisted fiber, yarn elements in the wet state conform freely to the wound topography and upon partially drying embed themselves in or otherwise attach themselves to the necrotic tissue. When the partially dry sponge is removed, the necrotic tissue adhering thereto is also removed. Under some conditions, woven cotton gauze can be too aggressive so that trauma can result if such gauze is allowed to dry completely before it is removed. Often, to prevent excessive disruption of newly formed granulation tissue, woven cotton gauze is not allowed to dry completely or is redampened prior to its removal.
Typically, a sponge made from woven cotton gauze has multiple plies, e.g. twelve plies, with 20.times.8 yarns per square inch in each ply, so as to provide void volume for holding viscous, purulent exudate. Including the spaces between the plies and the large apertures, such a sponge has a rather limited void volume in which to store wound exudate. However, its highly twisted yarns are effective in wicking and lateral transport of liquids and suspended solids.
Altogether, for the management of acute and chronic wounds, woven cotton gauze has significant limitations. As noted above, such gauze can be too aggressive and is not selective in its adherence to material at the surface of the wound. Moreover, such gauze can shed yarn fragments and particles when opened and unfolded, and especially when cut. Such fragments and particles can contaminate the wound and can be very difficult to remove. Furthermore, being woven from twisted yarns, such gauze has relatively low absorptive capacity. Under some conditions, woven cotton gauze can become wadded in a deep, cavernous, undermined wound.
Nonwoven fabrics, made from entangled fibers, have become widely accepted for use as wound dressings and bandages because of their qualities of absorbent capacity, softness, bulk, low linting, and ease of removal from wounds. Nonwoven fabrics of a type known as spunlace fabrics have been widely accepted for general use sponges, wound dressings, and bandages. Typically, spunlace fabric sponges are made from rayon fibers or blends of rayon and polyester fibers. Spunlace fabrics are exemplified in Buyofsky et al. U.S. Pat. No. 4,693,922 and U.S. Pat. No. 4,735,842.
In contrast with woven gauze sponges, spunlace fabric sponges known heretofore are typically comprised of low density strands and have "cloudy", i.e. indistinct, apertures. When wet, the strands of spunlace fabric sponges known heretofore do not conform readily to the wound surface. Upon drying, such strands do not become as deeply embedded in or as firmly attached to necrotic tissue. Thus, when removed, spunlace fabric sponges known heretofore are less aggressive and may be not entirely effective in removing eschar and necrotic debris. Including their inter-ply spaces, cloudy apertures, and low density strands, spunlace fabric sponges have substantially greater void volumes, as compared to the rather limited void volumes of woven gauze sponges. However, spunlace fabric sponges known heretofore have rather low ability to mechanically debride necrotic tissue.
Despite its limitations, and particularly as compared to spunlace fabrics known heretofore, woven cotton gauze has remained a preferred material for sponges used to pack and debride wounds.
There has been a need, to which this invention is addressed, for a debridement sponge combining the best features of woven gauze sponges and spunlace fabric sponges known heretofore without the significant limitations of either.


A piston/damper tube assembly may include a damper tube with damping fluid, a movable piston rod, a working piston, a controllable 4-way bottom valve with a control member, and a compensation space. Two flow passage ways of the bottom valve connect the working space remote from the piston rod via the control member to the compensation space. Two control ways of the bottom valve load the control member on a first side with a pressure of the piston rod-side working space and on a second side with a pressure of the compensation space. The control member may control the flow passage ways in a manner dependent on the pressure of the piston-rod-side working space that prevails on the control member on the first side via a fluidic connection, and on the pressure of the compensation space that prevails on the control member on the second side via an opening.

Many piston/damper tube assemblies and vibration dampers are known in the prior art. For example, German Patent Publication No. DE 10 2007 009 012 B3 has disclosed a piston/cylinder assembly with an adjustable damping force in a vibration damper. A bottom valve is provided in the piston/cylinder assembly, which bottom valve is loaded hydraulically with the pressure of the piston rod-side working space and mechanically with the prestressing force of a spring.
It is a problem in the case of the embodiments which are known in the prior art, during the determination of bottom valve characteristics, to achieve a compromise between driving comfort (damping force lower limit) and driving safety (damping force upper limit) with an overall design which is at the same time as simple and inexpensive as possible, in particular with a small number of element components.
Thus a need exists for an improved, compact piston/damper tube assembly and a vibration damper comprising the improved, compact piston/damper tube assembly. In particular, a need exists for a piston/damper tube assembly that is set to pressure changes in the compensation space and, at different gas pressures in the compensation space, provides a maximum possible adjusting range between a damping force lower limit and a damping force upper limit, especially in the compression stage.

Piston/damper tube assembly, vibration damper and method for operating a compression stage of a vibration damper


A duplexing circularly polarized composite antenna comprises at least one pair of radiator elements supportings orthogonal (vertical and horizontal) linear polarization. One radiator element is fed with a signal with a phase difference of 90.degree. relative to the signal fed to the other radiator element. Each radiator element transmits and/or receives signals at two different frequencies having orthogonal polarization. One radiator element operates at a first frequency with vertical polarization and a second frequency with horizontal polarization. The other radiator element operates at the first frequency with horizontal polarization and at the second frequency with vertical polarization.

1. Field of the Invention
The present invention concerns composite antennas transmitting and receiving simultaneously on two frequencies. A duplexer is generally used to separate the receive channel from the transmit channel, the power in which is much higher. It is necessary to provide a duplexer for each active element of the antenna with the result that the number of duplexers is equal to the number of active elements.
2. Description of the Prior Art
The duplexers are generally larger and heavier than the radiator elements; because of this the use of duplexers leads to a considerable increase in weight and overall dimensions, which is particularly troublesome in space applications. For this reason it is desirable to reduce the weight and the overall dimensions of the duplexer or even to eliminate it altogether.
One solution is to use opposite polarization for transmission and reception, the polarizer carrying out the necessary separation; however, this solution is generally not acceptable in complex systems.
Another solution described in the article by T SHIOKAWA et al in the journal IECE of Japan, technical report, AP 86-60, proposes the use of duplexing radiator elements to achieve operation with circular polarization. The radiator elements proposed in this document provide between 20 and 30 dB of isolation between transmission and reception and it is currently necessary to provide bandpass filters to achieve the necessary separation.
In both cases described the radiator elements are made up of two elementary radiator elements, one operating in transmission and the other in reception. These are ingeniously mounted to occupy the same area. In an implementation the first radiator element is a duplexing dual patch in the form of two plates of dielectric material coated with metal. This solution uses frequency selectivity between the top and bottom patches; it is of interest but it complicates the structure of the radiator element and consequently increases the weight and overall dimensions.
The impedance, the cross polarization performance and the configuration are affected by the disymmetry of the feed system. Also, major redesign is necessary to make the single patch dual and duplexing.
Another solution is described in French patent No. 2 570 546; this is a multifilar helix antenna comprising distinct helical radiators wound on a common core, offset in the angular direction and in a regular way relative to each other, at least two radiators of said antenna being connected continuously to a separate transmitter or receiver device.
This latter solution is not frequency selective and entails a loss of gain.
An object of the present invention is an antenna of the aforementioned type which makes it possible to avoid the problems that have just been described and to eliminate the duplexers. Also, the invention proposes to deal with the problem of passive intermodulation products, which can be a decisive factor in avoiding the use of two separate arrays for Tx-Rx operation (transmission and reception).
The invention has also the capability to cancel on-axis cross polarization and to yield symmetrical radiation patterns.

Duplexing circularly polarized composite


An electrical connector crimping tool head comprising a frame; and a ram movably connected to the frame. The ram comprises a first member and a second member longitudinally movable along the first member. The first member comprises a shaft section removably insertable into a rotatable drive for a fixed connection to the rotatable drive.

1. Field of the Invention
The present invention relates to electrical connector crimping tools and, more particularly, to a tool head for connection to a rotatable drive.
2. Prior Art
U.S. Pat. Nos. 4,942,757 and 5,062,290 disclose hydraulic crimping presses for electrical connectors. The tool heads include a general C-shaped frame, a ram movably connected to the frame, and dies for compressing or crimping an electrical connector.


Compositions and methods for relaxing smooth muscle in a warm-blooded animal are provided, comprising the step of administering to the animal a transition-metal nitrosyl complex. In one aspect, the transition-metal nitrosyl complex is represented by the formula L.sub.3 M(NO).sub.y X.sub.3-y where L is a two-electron Lewis base or L.sub.3 is a six-electron Lewis base, M is a Group 6 or 8 transition-metal, and when y is 1, X is carbon monoxide, and when y is 2, X is a halide or pseudohalide. In another aspect, the transition-metal nitrosyl complex is represented by the formula [M(NO).sub.2 X.sub.y ].sub.2 where X is a halide or pseudohalide, and when M is a Group 6 transition-metal, y is 2, and when M is a Group 8 transition-metal, y is 1. Methods are also described for treating hypertension, angina pectoris, congestive heart disease, and impotence utilizing pharmaceutical compositions comprising the above-described transition-metal nitrosyl complexes.

Muscle is divided into three types: skeletal, cardiac, and smooth. Briefly, smooth muscle is found in all muscles where contraction is involuntary, except for heart muscle. Generally, smooth muscle is composed of elongated, spindle-shaped, nucleated cells arranged parallel to one another and to the long axis of the muscle.
Smooth muscle is classified both functionally, and anatomically. When classified functionally, it is broken into two groups: multi-unit, and single-unit smooth muscle. Briefly, multi-unit smooth muscle is activated by nerves which cause contraction of independent muscle units, and thus is not spontaneously active. Examples of multi-unit muscle may be found in large arteries and veins, the urinary bladder, and the iris and ciliary muscles of the eye. In contrast to multi-unit smooth muscle, single-unit smooth muscle is usually spontaneously active, and contains tight junctions which facilitate the contraction of the muscle as a single unit. Examples of single-unit smooth muscle may be found in the vasculature (small veins, small arteries, and arterioles), the bile duct, and the walls of the gastrointestinal and urinogenital systems (gut, ureter, and uterus).
When smooth muscle is anatomically classified, it is generally divided into two groups: vascular and non-vascular. Briefly, vascular smooth muscle consists only of blood vessels (arteries, arterioles, and veins), whereas non-vascular muscle includes all other types of smooth muscle (e.g., gastrointestinal (stomach, duodenum, ileum, jejunum, caecum, and colon), spleen, trachea/bronchus, seminal vesicle, ductus deferens, corpus cavernosum, biliary tract, ureter, and uterus).
Many diseases are characterized by the inability of smooth muscle to relax. For example, hypertension is a disease found in 15%-20% of all adults in the United States. This condition is characterized by persistently high arterial blood pressure which, if left untreated, may lead to other serious cardiovascular diseases such as heart failure, ischemia, renal failure, and stroke. Hypertension is one of the most important public health problems facing developed countries.
Because of the health risk associated with untreated hypertension, the importance of treating those who suffer from elevated blood pressure has been recognized. Clinical trials have shown that appropriate pharmacological treatment of patients with moderate or severe hypertension reduces the risk of stroke, renal failure, and congestive heart failure. Based upon these studies, patients are now commonly treated with antihypertensive drags in order to lower diastolic blood pressure ("DBP") to levels below 90 mmHg. Common drugs which are used for this purpose include diuretics (hydrochlorothiazide, chlorthalidone), sympatholytics (clonidine, atenolol, prazosin), vasodilators (minoxidil, sodium nitroprusside), angiotensin converting enzyme inhibitors (captopril, enalapril), and calcium entry blockers (nifedipine, nitrendipine). The selection of a specific drug depends upon the severity of the disease, the patient's age and lifestyle, side effects, cost, and concomitant diseases and therapies.
One approach to the treatment of hypertension is to effect the reduction of elevated blood pressure through blood vessel dilation, which results in an increase of blood vessel diameter and concomitant blood pressure reduction. One class of compounds which are commonly utilized to dilate blood vessels are nitrovasodilators, which have been utilized for the relief of anginal attacks and the treatment of hypertension. Clinically useful nitrovasodilators include organic nitrites and nitrates such as amyl nitrite, glyceryl trinitrate (nitroglycerin), isosorbide dinitrate, erythrityl tetranitrate, and pentaerythritol as well as an inorganic nitric oxide donor, sodium nitroprusside.
Nitroglycerin and sodium nitroprusside are the most commonly used nitrovasodilators. Nitroglycerin is therapeutically useful for the treatment of angina pectoris and gastrointestinal spasm, while sodium nitroprusside is primarily utilized for the treatment of hypertensive emergencies. Nitroglycerin may either be administered at the time of anginal attack or prophylactically in anticipation of exercise or stress. Although nitroglycerin is effective in relief of acute attack, continual exposure to nitroglycerin and other organic nitrates results in a reduction in the ability of these compounds to vasodilate blood vessels. Because of the tolerance that develops from their chronic use, these nitrovasodilators have limited applicability.
Sodium nitroprusside is likewise effective in lowering blood pressure, although its use is primarily limited to hypertensive emergencies due to its efficacy and toxicity. In particular, the infusion of sodium nitroprusside at high doses or for long periods of time (over 24 hours) is associated with the toxicities resulting from the accumulation of cyanide and or thiocyanate.
Accordingly, there is a need in the art for physiologically acceptable smooth muscle relaxants which do not result in the development of tolerance and do not have toxic side effects. The present invention fulfills these needs, and further, provides other, related advantages.

Compositions and methods for relaxing smooth muscles


Techniques are disclosed for forming Schottky diodes on semipolar planes of group III-nitride (III-N) material structures. A lateral epitaxial overgrowth (LEO) scheme may be used to form the group III-N material structures upon which Schottky diodes can then be formed. The LEO scheme for forming III-N structures may include forming shallow trench isolation (STI) material on a semiconductor substrate, patterning openings in the STI, and growing the III-N material on the semiconductor substrate to form structures that extend through and above the STI openings, for example. A III-N structure may be formed using only a single STI opening, where such a III-N structure may have a triangular prism-like shape above the top plane of the STI layer. Further processing can include forming the gate (e.g., Schottky gate) and tied together source/drain regions on semipolar planes (or sidewalls) of the III-N structure to form a two terminal Schottky diode.

In the fields of wireless communication and power management, various components can be implemented using solid-state devices. For example, in radio frequency (RF) communication, the RF front-end is a generic term for the circuitry between an antenna and a digital baseband system. The RF front-end may include multiple components, such as power amplifiers, low-noise amplifiers, and voltage regulators. Such RF front-end components may include one or more semiconductor devices, such as diodes and transistors. Diodes are two-terminal devices, typically allowing the flow of current in only one direction. Semiconductor diodes come in multiple types, such as point-contact diodes, tunnel diodes, PIN diodes, and junction diodes. Junction diodes include p-n diodes and Schottky diodes. A p-n diode is formed by the junction of a p-type semiconductor (having a larger hole concentration than electron concentration) with an n-type semiconductor (having a larger electron concentration than hole concentration), thus the name p-n diode. A Schottky diode (also known as a hot carrier diode) is formed by the junction of a semiconductor with a metal or metal alloy.
There also exists multiple different semiconductor transistor devices, such as field-effect transistors (FETs). A FET is a semiconductor device that includes three terminals: a gate, a source, and a drain. A FET uses an electric field applied by the gate to control the electrical conductivity of a channel through which charge carriers (e.g., electrons or holes) flow from the source to the drain. In instances where the charge carriers are electrons, the FET is referred to as an n-channel device, and in instances where the charge carriers are holes, the FET is referred to as a p-channel device. Some FETs have a fourth terminal called the body or substrate, which can be used to bias the transistor. A metal-oxide-semiconductor FET (MOSFET) is configured with an insulator between the gate and the body of the transistor, and MOSFETs are commonly used for amplifying or switching electronic signals. In some cases, MOSFETs include sidewall spacers (or so-called gate spacers) on either side of the gate that can help determine the channel length and can help with replacement gate processes, for example. Complementary MOS (CMOS) structures use a combination of p-channel MOSFET (PMOS) and n-channel MOSFET (NMOS) to implement logic gates and other digital circuits.
These and other features of the present embodiments will be understood better by reading the following detailed description, taken together with the figures herein described. In the drawings, each identical or nearly identical component that is illustrated in various figures may be represented by a like numeral. For purposes of clarity, not every component may be labeled in every drawing. Furthermore, as will be appreciated, the figures are not necessarily drawn to scale or intended to limit the described embodiments to the specific configurations shown. For instance, while some figures generally indicate straight lines, right angles, and smooth surfaces, an actual implementation of the disclosed techniques may have less than perfect straight lines and right angles, and some features may have surface topography or otherwise be non-smooth, given real-world limitations of fabrication processes. Further still, some of the features in the drawings may include a patterned and/or shaded fill, which is primarily provided to assist in visually differentiating the different features. In short, the figures are provided merely to show example structures.

Schottky diodes on semipolar planes of group III-N material structures


An electrically conductive carriageway marking includes a carrier strip, electrically conductive wires extending along the carrier strip, an electrically insulating covering layer covering the wires, a power feed formed by an interface connecting the wires to a supply line, and interfaces arranged spaced apart from each other along the carriageway marking and having electrical contact areas. The contact areas include contact elements protruding laterally from the carriageway marking, and the supply line is connectable to a first contact area of the wires and a second contact area of the wires by electrical contacts that can be tapped off. In the region of the contact areas the covering layer is formed by a detachable adhesive protective strip, and the protective strip is connected via predetermined break points or perforations to adjoining sections of the covering layer, and the wires are exposed by detaching the protective strip.

Electrically conductive carriageway markings are known from WO 201 301 741 0 A1. This carriageway marking has a layer structure which is applied to the carriageway. For this purpose, a channel is milled into the carriageway, which receives the carriageway marking. The layer structure used here consists of a carrier layer, under which a protective layer and an adhesive layer are arranged. On the carrier layer two electrically conductive layers are arranged on top of each other, one as a return electrode and the other as a front electrode. Underneath the front electrode a light-limiting layer is provided, wherein the light imitated thereby can shine through the transparent front electrode and a multi-layered, transparent covering layer. The front electrode and the return electrode supply the light-limiting layer with the necessary voltage and are connected to an AC power source.
The known carriageway marking has the disadvantage that it can only be used for illuminating the covering layer and other electrical consumers cannot be connected to it. Another disadvantage is that, due to the complex layered structure the channel must be let into the carriageway, which not only involves additional effort but also damages the carriageway. Thus, for example, whenever the carriageway marking needs to be changed and a marking must be removed, the channel needs to be refilled.
U.S. Pat. No. 3,836,275 A1 discloses a system for carriageway marking, in which to provide improved visibility at night or in the rain, light-emitting elements, in particular light-emitting diodes, are used. To achieve this, a channel is laid in the carriageway, into which a prefabricated strip is inserted, which has pocket-shaped recesses spaced apart from each other, into which the light emitting elements are inserted. Electrical conductors running through the strip are exposed at the opposite edges of the recesses, so that they come into contact with corresponding contacts of the light-emitting elements when inserted into the recess. However, this system has the same disadvantages as those previously described in WO 201 301 741 0 A1.


Signal (SIF) field capacity can be significantly increased by encoding SIG field data using two streams in accordance with a space-time block code (STBC) encoding scheme. Dual-stream SIG field encoding allows for the utilization of higher order modulation schemes, such as quadrature phase-shift keying (QPSK), which increases SIG field capacity. Dual-stream encoded SIG fields are transmitted using an omnidirectional beam to allow mobile stations to accurately decode the SIG field irrespective of their spatial location.

Institute of Electrical and Electronics Engineers (IEEE) standards publications 802.11 outline protocols for implementing wireless local area networks (WLAN), and sets forth a physical (PHY) layer frame format that includes a preamble portion carrying control data and a payload portion carrying data. The preamble portion may include an omnidirectional portion that is transmitted using one stream, as well as a beamformed portion that is transmitted using multiple streams. The omnidirectional portion of the preamble carries a variety of preamble fields, including a legacy short training field (L-STF), a legacy long training field (L-LTF), a legacy signal (L-SIG) field, and a very high throughput (VHT) SIG field. The beamformed portion of the preamble also includes a variety of fields, including VHT long training fields (VHT LTFs) and VHT short training fields (VHT STFs).

Dual-stream signal (SIG) field encoding with higher order modulation


A collapsible container holder that can be used to hold a variety of containers, and can be used during physical activities such as walking, jogging or hiking. The container holder includes a vertical member which is folded along its width to form two legs of a J-shape and has a plurality of loops along the length of the vertical member which are positioned so as to align one loop to another with one loop positioned on the main leg and the other loop positioned on the reentrant leg of the J-shaped vertical member; a plurality of horizontal members which are inserted into the loops in the vertical member with the ends of the horizontal members juxtaposed by adjustable hook and loop fastening means to form a round shaped pouch for holding the container; and a separate loop at the top of the vertical member to allow for external support.

I. Field of the Invention
The present invention relates generally to the field of container holders, and more particularly to container holders that are collapsible and suitable for multiple uses.
II. Description of the Prior Art
It is well known in the prior art to support a container with some type of a pouch-shaped holder. However, none of the prior art container holders provide the combination of ease of use, ease of construction, collapsibility, and adjustability which is represented by the present invention.


A method of processing a wafer includes: a grinding step of grinding a back surface of the wafer to form, on the back side of the wafer, a recess corresponding to a device region and an annular projecting portion corresponding to a peripheral marginal region; and a splitting groove forming step of forming, after the grinding step is conducted, a splitting groove for splitting the device region and the peripheral marginal region from each other at the boundary between the recess and the annular projecting portion, the splitting groove extending from the front surface of the wafer to reach the back surface of the wafer. The splitting groove is formed by dry etching.

Field of the Invention
The present invention relates to a method for processing a wafer into a thinner form.
Description of the Related Art
In recent years, in order to realize smaller and lighter devices, there has been a demand for processing wafers formed of silicon or the like into a thinner form. A wafer is, for example, thinned by grinding the back side thereof after devices such as ICs are formed in regions sectioned by predetermined division lines (streets) on the front surface thereof.
Meanwhile, when a wafer is thinned by grinding, the wafer is greatly lowered in rigidity and becomes difficult to handle in the subsequent steps. In consideration of this problem, a processing method for permitting a wafer to retain a predetermined rigidity after grinding thereof has been proposed in which the back side of a wafer is ground in correspondence to a central device region while maintaining the thickness of a peripheral portion of the wafer (see, for example, Japanese Patent Laid-open No. 2007-19461). In this processing method, the back side of a wafer is ground, for example, by use of a grinding wheel smaller than the wafer in diameter to form a recess corresponding to the device region. The rigidity of the wafer is retained by an annular reinforcement portion (annular projecting portion) remaining on the back side of the peripheral marginal region surrounding the device region. Incidentally, the annular projecting portion is removed later by such a method as cutting (see, for example, Japanese Patent Laid-open No. 2011-61137).


A semiconductor device includes: a voltage regulator generating, based on a power supply voltage, an internal power supply voltage having a voltage value lower than that of the power supply voltage and to apply the internal power supply voltage to a power supply line; an internal circuit receiving the internal power supply voltage via the power supply line and a grounding line; and a protection circuit in which first to n-th transistors of PNP type which are Darlington-connected. A collector terminal of each of the first to the n-th transistors is connected to the grounding line. An emitter terminal of the first transistor within the first to the n-th transistors is connected to the power supply line while a base terminal of the n-th transistor within the first to the n-th transistors is connected to the grounding line.

1. Field of the Invention
The present invention relates to a semiconductor device and in particular to a semiconductor device having a voltage regulator and a protection circuit formed therein.
2. Description of the Related Art
There is known a semiconductor device having an internal circuit and a voltage regulator, in which the voltage regulator generates an internal power supply voltage lower than a power supply voltage supplied via a power supply terminal and then, the internal circuit operates under the internal power supply voltage. Further, there is also known another semiconductor device having such a voltage regulator and an electrostatic discharge protection circuit (referred to as an ESD protection circuit hereinafter). The ESD protection circuit is operative so as to prevent that the internal circuit is applied with a high voltage via the power supply terminal, wherein the high voltage is caused by an electrostatic discharge (referred to as an ESD hereinafter) occurring outside of the semiconductor device (See Japanese Patent Application Kokai No. 2010-3982, for example).
The particular ESD protection circuit protects the internal circuit against the high voltage value caused by the ESD by such an arrangement that a power supply line used for the internal power supply voltage and a grounding line are forced to be connected to each other when the power supply line becomes in a state that the high voltage value is equal to or more than a predetermined voltage value in a relatively short steep rising time (protecting function).
There is however a possibility that the protecting function does not work in case that the voltage regulator operates incorrectly due to the influence of external noise and then outputs an internal power supply voltage higher than the withstanding voltage of the internal circuit. When, for example, the voltage regulator including an output transistor of P-channel MOS (metal-oxide-semiconductor) type transistor is subjected to the influence of external noise resulting in decreasing the gate voltage of the output transistor, then the internal power supply voltage increases. The increase of the internal power supply voltage due to such decrease of the gate voltage of the output transistor is gradual less than the voltage increment due to an ESD. Therefore the protecting function may not occur.


An adjustable rotary positioning mechanism comprising a clevis having a central axis, a first arm, a second arm, and a plurality of bores arcuately spaced around the central axis through the first arm of the clevis. A rod end having a central axis and a plurality of sockets is rotatably connected to the clevis through the central axis. The plurality of sockets are arcuately spaced around the central axis and positioned colinearly with the plurality of bores. A plurality of locking pins are carried in the sockets and configured to project into the plurality of bores to lock the clevis and the rod end together and to retract from the plurality of bores to permit relative movement of the clevis and the rod end. Another embodiment of the invention is a wheelchair comprising a frame, drive wheels and steerable wheels supporting the frame, and paired foot supports each adjustably connected to the frame using the adjustable rotary positioning mechanism described above.

This invention relates in general to wheelchairs and to a rotary adjustment mechanism for wheelchair components. More particularly, the invention relates to a mechanism for releasably locking two relatively rotatable members for adjusting the positioning of a wheelchair footrest or other components.
Wheelchairs generally include a frame that supports a pair of drive wheels and a pair of front casters. The drive wheels make contact with the ground and are driven to propel the wheelchair. The drive wheels may be driven manually or powered by an electrical motor. The wheelchair frame also supports a seat assembly comprising a seat and a backrest. The seat assembly is oriented above and between the drive wheels and the front casters to provide stability. Generally, a pair of rigid frame extensions extend off the frame relatively forward from the front casters. Paired foot supports, is consisting of a foot support arm and a foot support plate, are connected to the rigid frame extensions.
Typically, each foot support is joined to its corresponding frame extension using an adjustable mechanism to permit the angle of each foot support to be easily adjusted to meet the specific needs of the user. For example, if the wheelchair user has a leg or foot fracture or other injury in one leg, the foot support can be adjusted to position the affected limb parallel to the ground.
An adjustable locking mechanism is described in U.S. Pat. No. 5,689,999, titled Adjustable Rotary Locking and Unlocking Apparatus. This locking mechanism consists of two members rotatably connected by a bolt through a central bore. A first member has a plurality of arcuately spaced locking pins that are movable between a projected and a retracted position. A second member has a plurality of arcuately spaced sockets configured so that each socket can accommodate any of the locking pins. To reposition the foot support, the user pushes an actuator to retract all the locking pins into the second member thereby permitting the first member and the second member to rotate freely relative to each other.
Any mechanism for adjusting the angle of the foot support must be solidly constructed because the foot support arm acts as a lever arm to concentrate pressure placed on the foot support plate. In the rotary locking apparatus described in the '999 patent, pressure on the footplate is focused on the bolt. The '999 patent describes careful fabrication to provide a snug fit between the locking pins and the sockets and the supporting bolt and the central bore. Unfortunately, this increases cost without a proportional increase in the overall strength of the mechanism.
Thus, it would be desirable to have an improved adjustable rotary positioning mechanism of increased strength that can be inexpensively fabricated.

Robust adjustable rotary positioning mechanism


A system is provided for the integration of freight transportation from the producers work site to the freight carrier, including any intermediate carriers using carriers adapted for carrying motor vehicles. The system of the invention allows a producer to load a module at the work site, move the module directly from the work site to a vehicle carrier for a return trip, which it would normally make empty, carrying general freight. The present system adapts vehicle carriers for carrying general freight by utilizing a portable module that is carried by the vehicle carrier in substantially the same way as a vehicle to carry general freight. The system of the invention is applicable both to rail vehicle carriers and ships especially adapted for carrying vehicles as well as to over-the-road vehicle carriers. The base of the module is substantially the same length and width as the motor vehicles normally transported by the vehicle carrier and it is provided with at least one set of wheels for portability and for allowing of the module to be loaded onto a vehicle carrier by moving the module onto the carrier with a suitable tractor.

This invention relates to a freight distribution system and more particularly to an intermodal transport system utilizing a single module for the intermodal transport of freight, including ship, rail and over-the-road transport.
In the shipment of freight it is common for the freight to be carried by different transport means from the shipping point to the destination. Thus, freight will often travel by ship for a part of its journey, be transferred to a rail car for part of the journey and finally transferred to a truck for delivery to the destination. Each change of its transportation mode presents certain problems, not the least of which is the time required to shift the freight to a different mode of transportation such as a rail car and/or truck or truck to a rail car or ship. As a partial solution to this problem the development of container shipping allows individual shippers to load a container at the origination point, normally the factory, that can then be loaded on a truck trailer, rail car or transferred to a ship. The popularity of container shipping has grown to the point where there are now are in operation ships designed solely to carry containers. In a similar fashion vehicles, such as passenger automobiles, pickup trucks, vans and alike are transported from assembly plants to distribution points where they are again shipped to dealers. The vehicles are normally shipped on carriers that are especially adapted for carrying vehicles. Thus for example, wherever possible, vehicles are most economically transported over water, normally using ships that are specially adapted for carrying the vehicles. The vehicles are offloaded from the ship, normally onto rail cars or vehicle trailers for shipment to various distribution points and may be reloaded again for shipment to dealers.
Although these modes of transportation are somewhat efficient, both containers and vehicle carriers must often return empty to their point of origin. On occasion empty containers collect at a port which may create a shortage of containers at points of origin while creating a storage problem at the destination port""s. Also, shipping empty containers back to the point of origin adds to the cost of shipping products. Likewise, vehicle carriers, be they ship, rail or truck, normally return empty to their origin points. It has been estimated that vehicle carriers are empty 48% of the time. The cost of returning empty containers and empty vehicle carriers is born by the shipping customer and ultimately by the consumer adding to the cost of goods.
Vehicle carriers are not adapted for carrying general freight, such as, for example, auto parts back to the assembly plant or a mixed load of vehicles and general freight. During periods of slow business cycles in the vehicle industry, the vehicle carriers are under utilized or not utilized at all resulting in substantial costs to the carrier companies and loss of jobs. These factors all produce a cost to the shipper which translates to higher prices for the consumer at the dealer when purchasing a vehicle. Likewise, containers, which are relatively large, are not suited for being transported by vehicle carriers. Vehicle carriers are relatively easy to load and unload while containers present more difficulties in loading and unloading. For example, a containerized ship may require five to six days to unload while a ship that is adapted to carry vehicles can be unloaded in a much shorter period of time.
Several systems have been suggested for inter-modal transportation systems have been suggested in the prior art, for example, U.S. Pat. No. 5,017,064 discloses an intermodal transport system designed for use in the hauling of semi-trailers by means of railway bogies. However, this system requires a turntable and spring loaded chock design to enable efficient loading and unloading of semi-trailers on the bogies.
In yet another inter-modal transport system, U.S. Pat. No. 6,123,029 also relates to a transport system combining trucking and railway technology for the transport of passengers and freight. Essentially this system integrates a highway truck drive system in powered vehicles suited for pulling passenger coaches and highway type trailer containers on rails.
Another system is disclosed in U.S. Pat. No. 5,107,772 that uses a railway bogie incorporating a platform and pivot arm adapted to connect directly to a truck-trailers. The platform is raised by a pneumatic system integrated into the bogie to couple it to the underside of the trailer.
The foregoing systems require the use of additional equipment in order to adapt the truck-trailer for use in a railroad environment. These systems do not address the more efficient use of vehicle carriers nor do these systems address a system for more efficient loading of products on a carrier.
Accordingly, is an object of the present invention to provide a system for fully utilizing vehicle carriers for transporting general freight as well as vehicles.
Another object of the invention is to provide a system for reducing xe2x80x9cdead headxe2x80x9d trips by the vehicle carrier.
Yet another object of the invention is to provide a system for integrating the shipment of vehicles and general freight on the same carrier.
Yet still another object of the invention is to provide a system that reduces shipping costs.
The foregoing objects and other objects and advantages of the present invention are achieved by the intermodal system of the present invention.
In accordance with the invention a system is provided for the integration of freight transportation from the producers work site to the freight carrier, including any intermediate carriers. Thus, the system of the invention allows a producer to load a module at the work site, move the module directly from the work site to a suitable carrier, such as a vehicle carrier, for example, that can transport the module to a rail head or dockside for loading on a rail road freight car and/or a ship It is within the scope of the invention to apply the system disclosed herein to aircraft as well.
Although the system of the present invention can be utilized with general freight carriers, such as for example, with conventional truck-trailers, conventional railway freight cars and conventional cargo ships, the system is particularly advantageous and most efficient when used in conjunction with vehicle carriers.
The present system adapts vehicle carriers for carrying general freight by utilizing a portable module that is adapted to be carried by the vehicle carrier in substantially the same way as a vehicle to carry general freight. As mentioned, the system of the invention is applicable both to rail vehicle carriers and ships especially adapted for carrying vehicles as well as to over-the-road vehicle carriers. The base of the module is substantially the same length and width as the motor vehicles normally transported by the vehicle carrier and it is provided with at least one set of wheels for portability and for allowing of the module to be loaded onto a vehicle carrier by moving the container module onto the carrier with a suitable tractor. The vehicle carrier can carry as many container modules as it can carry vehicles. For example, the combined cargo space of an over-the-road vehicle carrier fully loaded with container modules is equivalent to a semi-trailer.
In accordance with one aspect of the invention a vehicle carrier delivers vehicles to a distribution point or to a dealer and then can be re-loaded with modules containing general freight for the return trip to the assembly plant. Such general freight may comprise parts used in the assembly of the vehicles or freight to be delivered to a point in the vicinity of the assembly plant. In this manner the vehicle carrier is utilized to transport a payload on its return trip.
In another aspect of the invention the system can be utilized to deliver parts from a parts distribution point to an assembly plant and make a return trip carrying vehicles assembled at the factory.
In yet another aspect of the invention, the vehicle carrier transports a mixed load of vehicles and modules containing general freight. Thus, both vehicles and parts can be transported from the factory in a single vehicle carrier.
In yet another aspect of the invention the module utilized in the system serves as a shipping palette and, as such, can be positioned in the manufacturing facility for loading directly at the point of manufacture. As thus loaded, the module can then be integrated into the system for shipping the products.
Even under the best of circumstances it may still be necessary to ship empty modules to a loading point. The modules utilized in the present system are collapsible so that when empty and collapsed four modules can be stacked in the space taken by one uncollapsed module.
The system of the invention will be more fully understood from the following detailed description of the invention taken in conjunction with the drawings.


A portable hand-held remote control unit device is disclosed which may be utilized for selecting designated functions in a plurality of remotely controllable multimedia processing units. Multiple user selectable screen objects may be created from a general purpose computer and transferred to the remote control unit. The screen objects include screen layout and descriptions of soft keys to be displayed on a graphic display of the remote control unit, as well as commands associated with the screen object, the soft keys and programmable keys on the remote control unit. The user may select any of the loaded screen objects for controlling various multimedia processing units, for performing complex functions of commands to various multimedia processing units.

1. Field of the Invention
The present invention relates generally to remote control devices for electronics products.
2. Description of Related Art
The modern home may have a wide array of consumer electronics devices. These may include nearly any type of audio or video entertainment product, such as televisions, video cassette recorders, audio cassette recorders, audio/video receivers and preamps, cable boxes, laser disc players and camcorders.
Consumer electronics devices typically utilize hand-held remote control units to permit a user to rapidly and efficiently control selected functions from a distance. Early mechanical/ultrasonic remote control units were fairly limited and generally permitted only one or two functions to be controlled. For example, television remote control units utilizing mechanical/ultrasonic technology generally permitted a user to turn the power on to the television and to cycle through each channel in a preselected rotation. For some time, remote control units have been available which transmit control signals by way of infrared or radio frequency transmitters. These wireless remote control units have freed the user to move about a room or even about their home and to control the device from wherever it is most convenient to the user.
Consumer electronics devices and systems have become very complex and loaded with functionality. Particularly, with the expanding use of microprocessor-based devices and the ability to interconnect audio systems, video systems, security system, home automation systems and personal computers, the possible ways to interconnect and operate device has grown significantly. Remote control units have correspondingly become highly complex. A number of manufacturers sell remote control units which include as many as one hundred small buttons or keys, resulting in a severe decrease in the usability of these devices. This is remarkable, considering the huge number of consumers who cannot set the time on their VCR. Furthermore, the number and complexity of remote control units typically found in a home have reached a level where the convenience provided by the remote control units is often overcome by the difficulty in locating and operating them.
Thus, several problems have arisen. First, there is the problem of how to allow the user to control a huge number of features from a remote control unit. Second, there is the problem of how to avoid overwhelming the user with controls on a remote control unit which the user will never use. Third, there is the problem of users having to deal with multiple remote control units with overlapping operability. Fourth, there is the problem of the considerable amount of space which an aggregation of remote control units often occupy.
One solution which has found some acceptance in the market is the universal remote control unit. A universal remote control unit consolidates multiple remote control units and, it is hoped, improves their usability. Typical universal remote control units can learn the commands of other Remote control units, either through pre-programmed lists of consumer electronics devices or by teaching the universal remote control unit each command which the user might wish to have available on the universal Remote control unit. One of the problems with universal remote control units has been that their generic keypads are often cumbersome and not particularly intuitive in layout or labeling. Furthermore, the designers of these devices must compromise between having separate buttons for each possible command and small button sizes.
With the advent of home theater systems, the complexity of controls has advanced to an even greater plateau. Now, the remote must not only control the TV, the VCR, the cable box and the stereo, it must be able to control the surround sound quality, turn on multiple devices at the same time, and issue a series of commands to multiple devices to accomplish a single task. Naturally, the consumer electronics industry has developed products to serve this new need in the marketplace. These more advanced universal remote control units are exemplified by the Home Producer 8 from Universal Electronics, Inc. (Tustin, Calif.), the RC 2000 from Marantz (Roselle, Ill.), the RR990 from Rotel (North Reading, Mass.), and the RC-R0905 from Kenwood.
There has also been an increasing desire to integrate consumer electronics with security systems and to provide some control from a remote control unit of the home environment. For example, it is desirable that, when a user wishes to watch a cable program, not only is the TV set powered on and set to receive the video input, the A/V receiver is powered on and set to play the cable program at a reasonable loudness, the cable decoder is powered on and set to a favorite channel, but also the room's lighting is dimmed, the air conditioner is set to a comfortable level and the home security system is armed against perimeter violations. Some products (not necessarily Remote control units) are available which can be programmed to do these kinds of things. These products include the HAS-1350 HomeVision Intelligent Home Controller available from Home Automation Systems, Inc. (Irvine, Calif.), the ISR TronArch Intelligent Home Automation System, the BrightTouch from Crestron, the TheaterLink from Vantage, and the Landmark System from PHAST, the IntelliControl from Niles, and the 700T from Lexicon.
One of the common problems with universal remote control units, and a problem which is especially severe with the most flexible and programmable remote control units, is programming. A universal remote control unit simply cannot be factory-programmed with every possible configuration. The user is left with poor choices--do without some functions, spend many hours programming and reprogramming their programmable remote control unit, suffer through a remote control unit which is not programmed in a memorable manner, or paying a professional to program the remote control unit. Despite the availability of programmable remote control units, the best remote control unit for a multimedia processing unit is usually the one which is provided with a multimedia processing unit. It is very difficult to overcome this one-to-one correspondence of remote control units and multimedia processing units. These problems have resulted in the marketplace largely rejecting the more advanced universal remote control units.


A jewelry chain clasp is provided which is comprised of two unitary pieces which may be attached directly to the terminated ends of a jewelry chain. The two pieces include a spring catch arranged to be received within a receptacle which may be provided with a movable safety means for preventing inadvertent disconnection of the catch from the receptacle.

This invention relates generally to fasteners for articles of jewelry, and, more particularly, to a clasp for connecting the terminated ends of a jewelry chain.
The principal objective of this invention is to present the jewelry art a novel and improved means of connecting the ends of a jewelry chain which is convenient, reliable, secure and economical to produce. In pursuit of this objective, specific characteristics and qualities of jewelry fasteners have been studied resulting in the emergence of a set of design criteria that jewelry designers and manufacturers look for in a chain clasp. These criteria are: (1) ease of manipulation by the user; (2) secure and positive closure; (3) compactness of size; (4) aesthetic appearance; (5) strength and reliability; (6) simplicity of construction; (7) economy of manufacture; (8) ease of assembly to chain ends; (9) absence of sharp or snagging edges; and (10) application to a wide spectrum of utility.
In considering the present invention it will be helpful to view the current state of the art relating to jewlery fasteners. Many types of spring operated chain clasps are in use today, but the well known spring ring is by far the most widely used clasp throughout the jewelry industry.
The spring ring assembly consists of five pieces assembled in two parts. One part consists of a C-shaped tubular housing having a split jump ring attached to its outer surface for securing the device to one terminated end of a chain. A very small spring, usually of the helical type, is inserted into the tubular housing, and an arcuate post is arranged for reciprocal movement within the housing for spanning the open portion of the C-shaped housing and closing the ring. The housing is usually stacked or crimped in order to provide a backing against which the spring bears to urge the post into the closed position spanning the open portion of the housing, and a small tab is provided on the post to facilitate manual opening of the ring by retracting the post within the housing against the force of the spring. Since the post is generally too large to be secured directly to the last link at the opposite end of the chain, it is necessary to provide a relatively large jump ring on that link to which the spring ring fastener can be attached.
In addition to being comprised of a plurality of parts as described above, the conventional spring ring is also characterized by the disadvantage that the spring is formed of either a heat treated or cold drawn wire. If a jeweler were to attempt to secure the spring ring to the end link of a chain by employing conventional soldering techniques, he runs a substantial risk that the heat required to perform the soldering will deleteriously effect the spring. Therefore, either the split jump ring attached to the housing must be closed mechanically without use of heat, or the housing can be provided with a closed ring, and an additional jump ring can be used to safely attach the spring ring to the chain by soldering.
Accordingly, there has existed a need for a convenient and effective device for releasably connecting the terminated ends of a jewelry chain, which device is comprised of a relatively small number of parts and can be secured directly to the ends of the chain, and which conforms generally with the above criteria. As will become apparent from the following, the present invention satisfies that need.


The present invention provides methods for improving blood supply through a grafted blood vessel. In some embodiments, the methods comprise the step of locally administering a botulinum toxin to the grafted blood vessel, thereby improving blood supply through the grafted blood vessel.

The present invention relates to methods for treating vascular disorders. In particular the present invention relates to methods for treating vascular disorders with a botulinum toxin.
A vascular disorder can include a vasomotor instability condition, which is a condition associated with, or caused by, abnormal tone or abnormal constriction or dilation of a blood vessel. Thus, a vasomotor instability condition can include an excessive dilatation, an excessive contraction, or abnormality in the contraction-relaxation process of a blood vessel, including in a region or complex of blood vessels. A vasomotor instability condition is normally regulated by elements in the blood vessel wall and/or by attendant innervation. A blood vessel includes an artery, vein, and capillary and any similar structure which carries blood in the body of a mammal.
An indicated a vasomotor instability condition can be characterized by an excessive blood vessel contraction. The afflicted blood vessel can be located in the periphery, within an organ, on top of an organ, feeding an organ, including the brain and in any other tissue of the body.
Vasomotor instability can include conditions such as Raynaud's syndrome, an arterial-venous malformation, atherosclerosis, pulmonary hypertension, or can result from a blood vessel graft or from a kidney transplant. Raynaud's syndrome is characterized by a pale-blue-red sequence of color changes of the digits, most commonly after exposure to cold. Raynaud's syndrome occurs associated with spasm of a blood vessel. An arterial-venous malformation can involve just the arterial or the venous circulation or both. Atherosclerosis is a disease of the large arteries and the primary cause of heart disease and stroke. Apparently, atherosclerosis is not simply an inevitable degenerative consequence of ageing, but is rather a chronic inflammatory condition that can be converted into an acute clinical event by plaque rupture and thrombosis.
In pulmonary hypertension the vascular lumen is reduced because of proliferation of endothelial cells forming plexiform or concentric lesions, myofibroblasts embedded in a mucopolysaccharide matrix, and media vascular thickening. Excessive vasoconstriction has been the prevailing hypothesis of the pathobiology of pulmonary hypertension and several studies have investigated whether a deficiency of vasodilators such as prostacyclin is present in patients.
Kidney Transplantation is the therapy of choice for nearly all patients with end-stage renal disease and is the most common type of transplant in the United States. Common post-transplant complications are toxicity due to vasoconstriction of renal arterioles and the vasoconstrictive properties may be responsible for severe bone pain and hypertension.
Botulinum Toxin
The genus Clostridium has more than one hundred and twenty seven species, grouped according to their morphology and functions. The anaerobic, gram positive bacterium Clostridium botulinum produces a potent polypeptide neurotoxin, botulinum toxin, which causes a neuroparalytic illness in humans and animals referred to as botulism. The spores of Clostridium botulinum are found in soil and can grow in improperly sterilized and sealed food containers of home based canneries, which are the cause of many of the cases of botulism. The effects of botulism typically appear 18 to 36 hours after eating the foodstuffs infected with a Clostridium botulinum culture or spores. The botulinum toxin can apparently pass unattenuated through the lining of the gut and attack peripheral motor neurons. Symptoms of botulinum toxin intoxication can progress from difficulty walking, swallowing, and speaking to paralysis of the respiratory muscles and death.
Botulinum toxin type A is the most lethal natural biological agent known to man. About 50 picograms of a commercially available botulinum toxin type A (purified neurotoxin complex)1 is a LD50 in mice (i.e. 1 unit). One unit of BOTOX® (a botulinum toxin type A purified neurotoxin complex, which is also referred to as a botulinum toxin type A complex) contains about 50 picograms (about 56 attomoles) of botulinum toxin type A complex. Interestingly, on a molar basis, botulinum toxin type A is about 1.8 billion times more lethal than diphtheria, about 600 million times more lethal than sodium cyanide, about 30 million times more lethal than cobra toxin and about 12 million times more lethal than cholera. Singh, Critical Aspects of Bacterial Protein Toxins, pages 63–84 (chapter 4) of Natural Toxins II, edited by B. R. Singh et al., Plenum Press, New York (1976) (where the stated LD50 of botulinum toxin type A of 0.3 ng equals 1 U is corrected for the fact that about 0.05 ng of BOTOX® (a botulinum toxin type A complex) equals 1 unit). One unit (U) of botulinum toxin is defined as the LD50 upon intraperitoneal injection into female Swiss Webster mice weighing 18 to 20 grams each. 1Available from Allergan, Inc., of Irvine, Calif. under the tradename BOTOX® in 100 unit vials)
Seven generally immunologically distinct botulinum neurotoxins have been characterized, these being respectively botulinum neurotoxin serotypes A, B, C1, D, E, F and G each of which is distinguished by neutralization with type-specific antibodies. The different serotypes of botulinum toxin vary in the animal species that they affect and in the severity and duration of the paralysis they evoke. For example, it has been determined that botulinum toxin type A is 500 times more potent, as measured by the rate of paralysis produced in the rat, than is botulinum toxin type B. Additionally, botulinum toxin type B has been determined to be non-toxic in primates at a dose of 480 U/kg which is about 12 times the primate LD50 for botulinum toxin type A. Moyer E et al., Botulinum Toxin Type B: Experimental and Clinical Experience, being chapter 6, pages 71–85 of "Therapy With Botulinum Toxin", edited by Jankovic, J. et al. (1994), Marcel Dekker, Inc. Botulinum toxin apparently binds with high affinity to cholinergic motor neurons, is translocated into the neuron and blocks the release of acetylcholine as well as other substances and neurotransmitters. Additional uptake can take place through low affinity receptors, as well as by phagocytosis and pinocytosis.
Regardless of serotype, the molecular mechanism of toxin intoxication appears to be similar and to involve at least three steps or stages. In the first step of the process, the toxin binds to the presynaptic membrane of the target neuron through a specific interaction between the heavy chain, H chain, and a cell surface receptor; the receptor is thought to be different for each type of botulinum toxin and for tetanus toxin. The carboxyl end segment of the H chain, HC, appears to be important for targeting of the toxin to the cell surface.
In the second step, the toxin crosses the plasma membrane of the cell. The toxin is first engulfed by the cell through receptor-mediated endocytosis, and an endosome containing the toxin is formed. The toxin then escapes the endosome into the cytoplasm of the cell. This step is thought to be mediated by the amino end segment of the H chain, HN, which triggers a conformational change of the toxin in response to a pH of about 5.5 or lower. Endosomes are known to possess a proton pump which decreases intra-endosomal pH. The conformational shift exposes hydrophobic residues in the toxin, which permits the toxin to embed itself in the endosomal membrane. The toxin (or at a minimum the light chain) then translocates through the endosomal membrane into the cytoplasm.
The last step of the mechanism of botulinum toxin activity appears to involve reduction of the disulfide bond joining the heavy chain, H chain, and the light chain, L chain. The entire toxic activity of botulinum and tetanus toxins is contained in the L chain of the holotoxin; the L chain is a zinc (Zn++) endopeptidase which selectively cleaves proteins essential for recognition and docking of neurotransmitter-containing vesicles with the cytoplasmic surface of the plasma membrane, and fusion of the vesicles with the plasma membrane. Tetanus neurotoxin, botulinum toxin types B, D, F, and G cause degradation of synaptobrevin (also called vesicle-associated membrane protein (VAMP)), a synaptosomal membrane protein. Most of the VAMP present at the cytoplasmic surface of the synaptic vesicle is removed as a result of any one of these cleavage events. Botulinum toxin serotype A and E cleave SNAP-25. Botulinum toxin serotype C1 was originally thought to cleave syntaxin, but was found to cleave both syntaxin and SNAP-25. Each of the botulinum toxins specifically cleaves a different amino acid sequence, except botulinum toxin type B (and tetanus toxin) which cleave the same amino acid sequence of the relevant docking protein. Each of these cleavages block the process of vesicle-membrane docking, thereby preventing exocytosis of vesicle content.
Botulinum toxins have been used in clinical settings for the treatment of neuromuscular disorders characterized by hyperactive skeletal muscles (i.e. motor disorders). In 1989 a botulinum toxin type A complex has been approved by the U.S. Food and Drug Administration for the treatment of blepharospasm, strabismus and hemifacial spasm. Subsequently, a botulinum toxin type A was also approved by the FDA for the treatment of cervical dystonia and for the treatment of glabellar lines, and a botulinum toxin type B was approved for the treatment of cervical dystonia. Non-type A botulinum toxin serotypes apparently have a lower potency and/or a shorter duration of activity as compared to botulinum toxin type A. Clinical effects of peripheral intramuscular botulinum toxin type A are usually seen within one week of injection. The typical duration of symptomatic relief from a single intramuscular injection of botulinum toxin type A averages about three months, although significantly longer periods of therapeutic activity have been reported.
Although all the botulinum toxins serotypes apparently inhibit release of the neurotransmitter acetylcholine at the neuromuscular junction, they do so by affecting different neurosecretory proteins and/or cleaving these proteins at different sites. For example, botulinum types A and E both cleave the 25 kiloDalton (kD) synaptosomal associated protein (SNAP-25), but they target different amino acid sequences within this protein. Botulinum toxin types B, D, F and G act on vesicle-associated protein (VAMP, also called synaptobrevin), with each serotype cleaving the protein at a different site. Finally, botulinum toxin type C1 has been shown to cleave both syntaxin and SNAP-25. These differences in mechanism of action may affect the relative potency and/or duration of action of the various botulinum toxin serotypes. Apparently, a substrate for a botulinum toxin can be found in a variety of different cell types. See e.g. Biochem J 1;339 (pt 1):159–65:1999, and Mov Disord, 10(3):376:1995 (pancreatic islet B cells contains at least SNAP-25 and synaptobrevin).
The molecular weight of the botulinum toxin protein molecule, for all seven of the known botulinum toxin serotypes, is about 150 kD. Interestingly, the botulinum toxins are released by Clostridial bacterium as complexes comprising the 150 kD botulinum toxin protein molecule along with associated non-toxin proteins. Thus, the botulinum toxin type A complex can be produced by Clostridial bacterium as 900 kD, 500 kD and 300 kD forms. Botulinum toxin types B and C1 is apparently produced as only a 700 kD or 500 kD complex. Botulinum toxin type D is produced as both 300 kD and 500 kD complexes. Finally, botulinum toxin types E and F are produced as only approximately 300 kD complexes. The complexes (i.e. molecular weight greater than about 150 kD) are believed to contain a non-toxin hemaglutinin protein and a non-toxin and non-toxic nonhemaglutinin protein. These two non-toxin proteins (which along with the botulinum toxin molecule comprise the relevant neurotoxin complex) may act to provide stability against denaturation to the botulinum toxin molecule and protection against digestive acids when toxin is ingested. Additionally, it is possible that the larger (greater than about 150 kD molecular weight) botulinum toxin complexes may result in a slower rate of diffusion of the botulinum toxin away from a site of injection of a botulinum toxin complex.
In vitro studies have indicated that botulinum toxin inhibits potassium cation induced release of both acetylcholine and norepinephrine from primary cell cultures of brainstem tissue. Additionally, it has been reported that botulinum toxin inhibits the evoked release of both glycine and glutamate in primary cultures of spinal cord neurons and that in brain synaptosome preparations botulinum toxin inhibits the release of each of the neurotransmitters acetylcholine, dopamine, norepinephrine (Habermann E., et al., Tetanus Toxin and Botulinum A and C Neurotoxins Inhibit Noradrenaline Release From Cultured Mouse Brain, J Neurochem 51(2);522–527:1988) CGRP, substance P and glutamate (Sanchez-Prieto, J., et al., Botulinum Toxin A Blocks Glutamate Exocytosis From Guinea Pig Cerebral Cortical Synaptosomes, Eur J. Biochem 165;675–681:1897. Thus, when adequate concentrations are used, stimulus-evoked release of most neurotransmitters is blocked by botulinum toxin. See e.g. Pearce, L. B., Pharmacologic Characterization of Botulinum Toxin For Basic Science and Medicine, Toxicon 35(9);1373–1412 at 1393; Bigalke H., et al., Botulinum A Neurotoxin Inhibits Non-Cholinergic Synaptic Transmission in Mouse Spinal Cord Neurons in Culture, Brain Research 360;318–324:1985; Habermann E., Inhibition by Tetanus and Botulinum A Toxin of the release of [3H]Noradrenaline and [3H]GABA From Rat Brain Homogenate, Experientia 44;224–226:1988, Bigalke H., et al., Tetanus Toxin and Botulinum A Toxin Inhibit Release and Uptake of Various Transmitters, as Studied with Particulate Preparations From Rat Brain and Spinal Cord, Naunyn-Schmiedeberg's Arch Pharmacol 316;244–251:1981, and; Jankovic J. et al., Therapy With Botulinum Toxin, Marcel Dekker, Inc., (1994), page 5.
Botulinum toxin type A can be obtained by establishing and growing cultures of Clostridium botulinum in a fermenter and then harvesting and purifying the fermented mixture in accordance with known procedures. All the botulinum toxin serotypes are initially synthesized as inactive single chain proteins which must be cleaved or nicked by proteases to become neuroactive. The bacterial strains that make botulinum toxin serotypes A and G possess endogenous proteases and serotypes A and G can therefore be recovered from bacterial cultures in predominantly their active form. In contrast, botulinum toxin serotypes C1, D and E are synthesized by nonproteolytic strains and are therefore typically unactivated when recovered from culture. Serotypes B and F are produced by both proteolytic and nonproteolytic strains and therefore can be recovered in either the active or inactive form. However, even the proteolytic strains that produce, for example, the botulinum toxin type B serotype only cleave a portion of the toxin produced. The exact proportion of nicked to unnicked molecules depends on the length of incubation and the temperature of the culture. Therefore, a certain percentage of any preparation of, for example, the botulinum toxin type B toxin is likely to be inactive, possibly accounting for the known significantly lower potency of botulinum toxin type B as compared to botulinum toxin type A. The presence of inactive botulinum toxin molecules in a clinical preparation will contribute to the overall protein load of the preparation, which has been linked to increased antigenicity, without contributing to its clinical efficacy. Additionally, it is known that botulinum toxin type B has, upon intramuscular injection, a shorter duration of activity and is also less potent than botulinum toxin type A at the same dose level.
High quality crystalline botulinum toxin type A can be produced from the Hall A strain of Clostridium botulinum with characteristics of ≧3×107 U/mg, an A260/A278 of less than 0.60 and a distinct pattern of banding on gel electrophoresis. The known Shantz process can be used to obtain crystalline botulinum toxin type A, as set forth in Shantz, E. J., et al, Properties and use of Botulinum toxin and Other Microbial Neurotoxins in Medicine, Microbiol Rev. 56;80–99:1992. Generally, the botulinum toxin type A complex can be isolated and purified from an anaerobic fermentation by cultivating Clostridium botulinum type A in a suitable medium. The known process can also be used, upon separation out of the non-toxin proteins, to obtain pure botulinum toxins, such as for example: purified botulinum toxin type A with an approximately 150 kD molecular weight with a specific potency of 1–2×108 LD50 U/mg or greater; purified botulinum toxin type B with an approximately 156 kD molecular weight with a specific potency of 1–2×108 LD50 U/mg or greater, and; purified botulinum toxin type F with an approximately 155 kD molecular weight with a specific potency of 1–2×107 LD50 U/mg or greater.
Botulinum toxins and/or botulinum toxin complexes can be obtained from List Biological Laboratories, Inc., Campbell, Calif.; the Centre for Applied Microbiology and Research, Porton Down, U.K.; Wako (Osaka, Japan), Metabiologics (Madison, Wis.) as well as from Sigma Chemicals of St Louis, Mo. Pure botulinum toxin can also be used to prepare a pharmaceutical composition.
As with enzymes generally, the biological activities of the botulinum toxins (which are intracellular peptidases) is dependant, at least in part, upon their three dimensional conformation. Thus, botulinum toxin type A is detoxified by heat, various chemicals surface stretching and surface drying. Additionally, it is known that dilution of the toxin complex obtained by the known culturing, fermentation and purification to the much, much lower toxin concentrations used for pharmaceutical composition formulation results in rapid detoxification of the toxin unless a suitable stabilizing agent is present. Dilution of the toxin from milligram quantities to a solution containing nanograms per milliliter presents significant difficulties because of the rapid loss of specific toxicity upon such great dilution. Since the toxin may be used months or years after the toxin containing pharmaceutical composition is formulated, the toxin can stabilized with a stabilizing agent such as albumin and gelatin.
A commercially available botulinum toxin containing pharmaceutical composition is sold under the trademark BOTOX® (available from Allergan, Inc., of Irvine, Calif.). BOTOX® (a botulinum toxin type A complex) consists of a purified botulinum toxin type A complex, albumin and sodium chloride packaged in sterile, vacuum-dried form. The botulinum toxin type A is made from a culture of the Hall strain of Clostridium botulinum grown in a medium containing N-Z amine and yeast extract. The botulinum toxin type A complex is purified from the culture solution by a series of acid precipitations to a crystalline complex consisting of the active high molecular weight toxin protein and an associated hemagglutinin protein. The crystalline complex is re-dissolved in a solution containing saline and albumin and sterile filtered (0.2 microns) prior to vacuum-drying. The vacuum-dried product is stored in a freezer at or below −5° C. BOTOX® (a botulinum toxin type A complex) can be reconstituted with sterile, non-preserved saline prior to intramuscular injection. Each vial of BOTOX® (a botulinum toxin type A complex) contains about 100 units (U) of Clostridium botulinum toxin type A purified neurotoxin complex, 0.5 milligrams of human serum albumin and 0.9 milligrams of sodium chloride in a sterile, vacuum-dried form without a preservative.
To reconstitute vacuum-dried BOTOX® (a botulinum toxin type A complex), sterile normal saline without a preservative; (0.9% Sodium Chloride Injection) is used by drawing up the proper amount of diluent in the appropriate size syringe. Since BOTOX® (a botulinum toxin type A complex) may be dispersed or denatured by bubbling or similar violent agitation, the diluent is gently injected into the vial. For sterility reasons BOTOX® (a botulinum toxin type A complex) is preferably administered within four hours after the vial is removed from the freezer and reconstituted. During these four hours, reconstituted BOTOX® (a botulinum toxin type A comniex) can be stored in a refrigerator at about 2° C. to about 8° C. Reconstituted, refrigerated BOTOX® (a botulinum toxin type A complex) has been reported to retain its potency for at least about two weeks. Neurology, 48:249–53:1997.
It has been reported that botulinum toxin type A has been used in clinical settings as follows:    (1) about 75–125 units of BOTOX® (a botulinum toxin type A complex) per intramuscular injection (multiple muscles) to treat cervical dystonia;    (2) 5–10 units of BOTOX® (a botulinum toxin type A comniex) per intramuscular injection to treat glabellar lines (brow furrows) (5 units injected intramuscularly into the procerus muscle and 10 units injected intramuscularly into each corrugator supercilii muscle);    (3) about 30–80 units of BOTOX® (a botulinum toxin woe A complex) to treat constipation by intrasphincter injection of the puborectalis muscle;    (4) about 1–5 units per muscle of intramuscularly injected BOTOX® (a botulinum toxin type A complex) to treat blepharospasm by injecting the lateral pre-tarsal orbicularis oculi muscle of the upper lid and the lateral pre-tarsal orbicularis oculi of the lower lid.    (5) to treat strabismus, extraocular muscles have been injected intramuscularly with between about 1–5 units of BOTOX® (a botulinum toxin type A complex), the amount injected varying based upon both the size of the muscle to be injected and the extent of muscle paralysis desired (i.e. amount of diopter correction desired).    (6) to treat upper limb spasticity following stroke by intramuscular injections of BOTOX® (a botulinum toxin type A complex) into five different upper limb flexor muscles, as follows:    (a) flexor digitorum profundus: 7.5 U to 30 U    (b) flexor digitorum sublimus: 7.5 U to 30 U    (c) flexor carpi ulnaris: 10 U to 40 U    (d) flexor carpi radialis: 15 U to 60 U    (e) biceps brachii: 50 U to 200 U. Each of the five indicated muscles has been injected at the same treatment session, so thai the patient receives from 90 U to 360 U of upper limb flexor muscle BOTOX® (a botulinum toxin type A complex) by intramuscular injection at each treatment session.    (7) to treat migraine, pericranial injected (injected symmetrically into glabellar, frontalis and temporalis muscles) injection of 25 U of BOTOX® (a botulinum toxin type A complex) has showed significant benefit as a prophylactic treatment of migraine compared to vehicle as measured by decreased measures of migraine frequency, maximal severity, associated vomiting and acute medication use over the three month period following the 25 U injection.
It is known that botulinum toxin type A can have an efficacy for up to 12 months (European J. Neurology 6 (Supp 4): S111–S1150:1999), and in some circumstances for as long as 27 months, when used to treat glands, such as in the treatment of hyperhydrosis. See e.g. Bushara K., Botulinum toxin and rhinorrhea, Otolaryngol Head Neck Surg 1996;114(3):507, and The Laryngoscope 109:1344–1346:1999. However, the usual duration of an intramuscular injection of BOTOX® (a botulinum toxin type A complex) is typically about 3 to 4 months.
The success of botulinum toxin type A to treat a variety of clinical conditions has led to interest in other botulinum toxin serotypes. Two commercially available botulinum type A preparations for use in humans are BOTOX® (a botulinum toxin type A complex) available from Allergan, Inc., of Irvine, Calif., and DYSPORT® (a botulinum toxin A complex) available from Beaufour Ipsen, Porton Down, England. A Botulinum toxin type B preparation (MYOBLOC®) is available from Elan Pharmaceuticals of San Francisco, Calif.
U.S. Pat. No. 5,989,545 discloses that a modified Clostridial neurotoxin or fragment thereof, preferably a botulinum toxin, chemically conjugated or recombinantly fused to a particular targeting moiety can be used to treat pain by administration of the agent to the spinal cord.
A botulinum toxin has also been proposed for or has been used to treat a number of ailments, including for example otitis media of the ear (U.S. Pat. No. 5,766,605), inner ear disorders (U.S. Pat. Nos. 6,265,379; 6,358,926), tension headache, (U.S. Pat. No. 6,458,365), migraine headache pain (U.S. Pat. No. 5,714,468), post-operative pain and visceral pain (U.S. Pat. No. 6,464,986), hair growth and hair retention (U.S. Pat. No. 6,299,893), psoriasis and dermatitis (U.S. Pat. No. 5,670,484), injured muscles (U.S. Pat. No. 6,423,319), various cancers (U.S. Pat. No. 6,139,845), smooth muscle disorders (U.S. Pat. No. 5,437,291 including vasospastic disorders and injecting a botulinum toxin into the smooth muscle of a blood vessel)), and neurogenic inflammation (U.S. Pat. No. 6,063,768). Controlled release toxin implants are known (see e.g. U.S. Pat. Nos. 6,306,423 and 6,312,708) as is transdermal botulinum toxin administration (U.S. patent application Ser. No. 10/194,805).
International patent application WO 03/084567 discusses use of a botulinum toxin to treat a cardiovascular disorder, and WO 01/10458 discusses use of a botulinum toxin to treat a cardiac muscle disorder. Resolution of fainting spells after hyperhydrosis treatment is discussed in Moro E., et al, Suppression of syncopes after botulinum toxin treatment, Mov Disord 2002;17(Suppl 5):S242 ABS P780, and a reduction of facial flushing is discussed in Tugnoli V., et al., The role of gustatory flushing in Frey's syndrome and its treatment with botulinum toxin type A, Clin Auton Res 2002;12(3):174–178.
Tetanus toxin, as well as derivatives (i.e. with a non-native targeting moiety), fragments, hybrids and chimeras thereof can also have therapeutic utility. The tetanus toxin bears many similarities to the botulinum toxins. Thus, both the tetanus toxin and the botulinum toxins are polypeptides made by closely related species of Clostridium (Clostridium tetani and Clostridium botulinum, respectively). Additionally, both the tetanus toxin and the botulinum toxins are dichain proteins composed of a light chain (molecular weight about 50 kD) covalently bound by a single disulfide bond to a heavy chain (molecular weight about 100 kD). Hence, the molecular weight of tetanus toxin and of each of the seven botulinum toxins (non-complexed) is about 150 kD.
Furthermore, for both the tetanus toxin and the botulinum toxins, the light chain bears the domain which exhibits intracellular biological (protease) activity, while the heavy chain comprises the receptor binding (immunogenic) and cell membrane translocational domains.
Further, both the tetanus toxin and the botulinum toxins exhibit a high, specific affinity for gangliocide receptors on the surface of presynaptic cholinergic neurons. Receptor mediated endocytosis of tetanus toxin by peripheral cholinergic neurons results in retrograde axonal transport, blocking of the release of inhibitory neurotransmitters from central synapses and a spastic paralysis. Contrarily, receptor mediated endocytosis of botulinum toxin by peripheral cholinergic neurons results has not been demonstrated to exhibit retrograde transport, but has the property of inhibition of acetylcholine exocytosis from the intoxicated peripheral motor neurons and a flaccid paralysis.
Finally, the tetanus toxin and the botulinum toxins resemble each other in both biosynthesis and molecular architecture. Thus, there is an overall 34% identity between the protein sequences of tetanus toxin and botulinum toxin type A, and a sequence identity as high as 62% for some functional domains. Binz T. et al., The Complete Sequence of Botulinum Neurotoxin Type A and Comparison with Other Clostridial Neurotoxins, J Biological Chemistry 265(16);9153–9158:1990.
Acetylcholine
Typically only a single type of small molecule neurotransmitter is released by each type of neuron in the mammalian nervous system, although there is evidence which suggests that several neuromodulators can be released by the same neuron. The neurotransmitter acetylcholine is secreted by neurons in many areas of the brain, but specifically by the large pyramidal cells of the motor cortex, by several different neurons in the basal ganglia, by the motor neurons that innervate the skeletal muscles, by the preganglionic neurons of the autonomic nervous system (both sympathetic and parasympathetic), by the bag 1 fibers of the muscle spindle fiber, by the postganglionic neurons of the parasympathetic nervous system, and by some of the postganglionic neurons of the sympathetic nervous system. Essentially, only the postganglionic sympathetic nerve fibers to the sweat glands, the piloerector muscles and a few blood vessels are cholinergic as most of the postganglionic neurons of the sympathetic nervous system secrete the neurotransmitter norepinephine. In most instances acetylcholine has an excitatory effect. However, acetylcholine is known to have inhibitory effects at some of the peripheral parasympathetic nerve endings, such as inhibition of heart rate by the vagal nerve.
The efferent signals of the autonomic nervous system are transmitted to the body through either the sympathetic nervous system or the parasympathetic nervous system. The preganglionic neurons of the sympathetic nervous system extend from preganglionic sympathetic neuron cell bodies located in the intermediolateral horn of the spinal cord. The preganglionic sympathetic nerve fibers, extending from the cell body, synapse with postganglionic neurons located in either a paravertebral sympathetic ganglion or in a prevertebral ganglion. Since, the preganglionic neurons of both the sympathetic and parasympathetic nervous system are cholinergic, application of acetylcholine to the ganglia will excite both sympathetic and parasympathetic postganglionic neurons.
Acetylcholine activates two types of receptors, muscarinic and nicotinic receptors. The muscarinic receptors are found in all effector cells stimulated by the postganglionic, neurons of the parasympathetic nervous system as well as in those stimulated by the postganglionic cholinergic neurons of the sympathetic nervous system. The nicotinic receptors are found in the adrenal medulla, as well as within the autonomic ganglia, that is on the cell surface of the postganglionic neuron at the synapse between the preganglionic and postganglionic neurons of both the sympathetic and parasympathetic systems. Nicotinic receptors are also found in many nonautonomic nerve endings, for example in the membranes of skeletal muscle fibers at the neuromuscular junction.
Acetylcholine is released from cholinergic neurons when small, clear, intracellular vesicles fuse with the presynaptic neuronal cell membrane. A wide variety of non-neuronal secretory cells, such as, adrenal medulla (as well as the PC12 cell line) and pancreatic islet cells release catecholamines and parathyroid hormone, respectively, from large dense-core vesicles. The PC12 cell line is a clone of rat pheochromocytoma cells extensively used as a tissue culture model for studies of sympathoadrenal development. Botulinum toxin inhibits the release of both types of compounds from both types of cells in vitro, permeabilized (as by electroporation) or by direct injection of the toxin into the denervated cell. Botulinum toxin is also known to block release of the neurotransmitter glutamate from cortical synaptosomes cell cultures.
A neuromuscular junction is formed in skeletal muscle by the proximity of axons to muscle cells. A signal transmitted through the nervous system results in an action potential at the terminal axon, with activation of ion channels and resulting release of the neurotransmitter acetylcholine from intraneuronal synaptic vesicles, for example at the motor endplate of the neuromuscular junction. The acetylcholine crosses the extracellular space to bind with acetylcholine receptor proteins on the surface of the muscle end plate. Once sufficient binding has occurred, an action potential of the muscle cell causes specific membrane ion channel changes, resulting in muscle cell contraction. The acetylcholine is then released from the muscle cells and metabolized by cholinesterases in the extracellular space. The metabolites are recycled back into the terminal axon for reprocessing into further acetylcholine.
What is needed therefore is a therapeutically effective method for treating a vascular disorder.


A radioactive ray detecting apparatus provides for reduction of the dead area or region where radioactive rays cannot be detected, even if disposing the radioactive ray detectors to be dense or crowded. The radioactive ray detecting apparatus satisfies the following relationships, when assuming that distance between semiconductor elements is “XG1”, while the distance from the semiconductor element of one of the radioactive ray detectors up to the semiconductor element of other radioactive ray detectors is “XG2”, and distance between the semiconductor elements alighted in a Y-direction is “YG1”, and a horizontal pitch of a predetermined pixel pitch to be used as the radioactive ray detector is “a” and a vertical pitch thereof is “b”, width of a surface of each of plural numbers of semiconductor elements is “c” and length thereof is “d”, respectively:c=a−(XG1+XG2)/2d=b−YG1=2e+(n−2)f.

As a conventional radioactive ray detector is already known a radioactive ray detector, being constructed with providing layers therein, wherein plural numbers of common electrodes, plural number of semiconductor cells and plural numbers of electrodes are laminated with, such as, a common electrode, a semiconductor cell, an electrode, a semiconductor cell, a common electrode . . . , between two (2) pieces of frames, while one of the frames is fixed with the other frame by a pin (for example, see the Patent Document 1).
With the radioactive ray detector described in the Patent Document 1, since a pair of semiconductor cells neighboring with each other in the horizontal direction share the common electrode, it is possible to reduce areas or regions where the radioactive rays cannot be detected, comparing to that of the conventional art, and thereby to increase an efficiency of detecting the radioactive rays.