One or a plurality of valve-operated branch pieces can be attached to any point of any pipe. To this end, two opposite openings (16, 18) are made in the pipe (10), and a branch valve body is clamped about the pipe in bracket-like manner at the prepared site.

The present invention relates to a process for producing one or a plurality of valve-operated branch pieces for a pipe conducting a medium. The invention further proposes embodiments of the parts required for this purpose. In many technological fields one is confronted with the task of forming branch pieces for a main pipe conducting a medium, said branch pieces each diverting a certain amount of said medium from the main pipe, with a valve provided at the branching site controlling the amount to be diverted.
Examples of such may be the so-called heating circuit distributors in central heating systems, although the medium to be distributed thereby may also be oil or lubricant, one may consider pipe branches which become necessary in chemical process engineering. The range of applications is unlimited. The medium to be circulated may also be gaseous.
Just like the media to be diverted from a main pipe may be of very different nature, the present invention also comprises all kinds of materials from which the pipes and the branch pieces are made. These may be metallic pipes, iron pipes or pipes made of non-ferrous metals or they may also be reinforced or non-reinforced plastic pipes. Even the use of glass pipes may be considered.
Moreover, it is irrelevant for the purposes of the present invention whether the branch pieces are installed at a later stage in an already existing system, whether they are produced upon completion of a system in an assembling state or whether they are prefabricated branch pieces.
Various means are known for tap-boring pipes which will remain in operation during this process. German patent DE 42 39 573 A1 for example discloses a tap-boring device for pipes under pressure. This device will first serve as a hole gauge for a drilling tool which gauge may be clamped onto said pipe. This drilling tool is connected with a valve disk which will assume the function of the valve.
German utility model DE-GM 74 10 858 discloses a tap-boring pipe clip for pressurized air and water. Also in this case the drilling tool is provided with a sealing element. This prior art aims at providing a pipe in operation with a branch piece, with the drilling aid remaining on the pipe as a valve organ.
In contrast thereto, it is the object of the present invention to provide any number of valve-operated branch pieces at any point on a pipe which is not in operation.

Process and prefabricated parts for producing branch pieces for pipes


An apparatus for measuring a depth and a gradient of a trench in a semiconductor device including: a light emitting element for making a light incident on a wafer while varying an incident angle, the wafer having a trench structure carried by a test sample carrying unit; a detect unit for detecting a light reflected from the wafer at a position symmetrical to the light emitting element on the basis of a virtual vertical line perpendicular to the wafer; a photoelectric conversion unit for converting an intensity of a light detected by the detect unit to an electric signal; an operating unit for receiving an output signal from the photoelectric conversion unit, catching a time point where the size of the received signal is increased or maintained, computing a depth of the trench by using a critical angle, that is, an incident angle where the incident light is reflected from the central portion of a lower surface of the trench, and judging the time point when the increasing output signal of the photoelectric conversion unit is maintained when the incident angle is below a critical angle as a sloping angle of the trench; and a display unit for displaying an operating result of the operating unit. By having such a construction, the gradient of the trench as well as the depth can be easily obtained by using the wafer where the semiconductor device is to be formed, without additionally making a test sample for measurement, so that a production cost can be much reduced and a reliability of the semiconductor device is much improved.

1. Field of the Invention
The present invention relates to an apparatus for measuring a depth and a gradient of a trench in a semiconductor device, and more particularly, to an apparatus for measuring a depth and a gradient of a trench in a semiconductor device which is capable of accurately measuring a depth and a gradient of a trench actually on a wafer without damaging it, and to its method.
2. Description of the Background Art
Generally, as an isolating method of a highly integrated semiconductor device, a structure is taken that a trench is formed, in which an oxide film is filled. Therefore, forming the trench and measuring its depth and gradient is a requisite step to obtain a reliability for the process of the semiconductor device.
An apparatus for measuring characteristics of a semiconductor pattern uses an optical path difference between a light reflected from the surface of a test sample and a light having passed a medium. This is effective in measuring a thickness of a stacked film, which, however, is not suitably applied in case that the substrate is partially etched to form a step in an arbitrary depth, such as the trench.
For this reason, in order to measure the depth of the trench, the wafer is cut to observe its section, a method using a measuring instrument of xcex1-step is employed, or a method using an equipment xe2x80x98AFMxe2x80x99 for measuring a roughness of a surface is employed.
An apparatus and a method for measuring a depth and a gradient of a trench in a semiconductor device in accordance with a conventional art will now be described with reference to the accompanying drawings.
FIG. 1 is a flow chart of a process of a method for measuring a depth and a gradient of a trench in a semiconductor device in accordance with a conventional art, which employes the method that the wafer test sample where a trench is formed is cut and its section is observed, including the steps of: preparing a section-observing test sample wafer for observing a section besides an actual wafer for forming a semiconductor device; forming a trench on the section-observing test sample wafer by a photolithographic process; and cutting the section-observing test sample wafer in a manner that the position where the trench is formed is shown in the cross section, and observing a depth and a gradient of the trench.
In this respect, as to the depth-measuring test sample wafer, the trench is to be formed the same as the actual product, and after it is cut, its section is observed by using an electron microscope SEM.
However, such an testing method is a kind of destructive test that needs to cut the wafer, which is not able to measure a depth and the gradient of the trench formed on the actual wafer where the semiconductor device is formed, degrading a reliability and causing an increase of expense due to the additional fabrication of he test sample wafer.
FIG. 2 is a schematic view of a method for measuring a depth of a trench by using an xcex1-step equipment.
As shown in this drawing, a probe needle 1 is moved on a wafer 2 where a trench is formed, so as to measure a depth of the trench by a piezoelectric transducer by using a pressure difference between the upper portion of the wafer 2 where the trench is not formed and the lower portion of the trench.
In case of using the probe needle 1, since a pressure is high at the upper surface of the wafer 2 where a trench is not formed, while it is relatively low at the lower surface of the trench where the step is low, the depth of the trench can be calculated by using the pressure difference. But, since the wafer is damaged while the probe needle is being moved, this method can not be adopted to the actual wafer to fabricate a semiconductor device, and thus, a specific test sample needs to be separately made like in the above method for observing the section.
FIG. 3 is a schematic view showing a method for measuring a depth of a trench by using an AFM equipment in accordance with a conventional art.
As shown in this drawing, the AFM equipment measures a roughness of the wafer 2 by using the probe needle 1 at a position separated by 100 xc3x85 at maximum from the upper surface of the wafer.
Unlike the above described two conventional embodiments, this measuring method uses a Van der Waals"" force that works on the mutually separated probe needle 1 and the water 2 so as to numerically express a variation in the force working on a separated distance, thereby measuring the roughness of a specific thin film. This is a non-destructive testing which advantageously does not do a direct damage to the wafer.
However, the ATM equipment is applied to measure a roughness with deviation of tens of nm, which is not suitable to measure a depth of a trench formed in deviation of hundreds of nm in the process for fabricating semiconductor device.
Noticing from a graph of FIG. 4 showing a variation of Van der Waals"" force depending on a distance, as the distance between the probe needle 1 and the wafer 2 becomes close, a repulsive force works on therebetween, while the distance between the two becomes more distant, an attractive force works on therebetween. In this respect, in case of more than a predetermined distance, the attractive force is maintained at the same value in spite of the variation in the distance. Then, measurement of a depth would be impossible for a structure having a depth longer than a predetermined depth.
In addition, except the method for observing the section by cutting the wafer, other methods are not suitably applied to characteristic test for a trench in terms of accuracy because the gradient of the trench can be hardly measured.
Thus, currently in order to test the characteristics of the trench formed on the wafer, a method is yet largely taken in that a trench is formed on the test sample, which is then cut to observe a section thereof.
Accordingly, as to the apparatus and method for measuring the depth and the gradient of the trench in the semiconductor device, since the depth and the gradient of the trench formed on the actual wafer for forming the semiconductor device can not be measured, a test sample is to be additionally fabricated, causing an increase in expense and degrading a reliability.
Especially, methods for attempting to measure the gradient of the trench is very limited, causing a problem in that characteristics of the trench can not be accurately measured, resulting in degradation of the semiconductor device.
Therefore, an object of the present invention is to provide an apparatus for measuring a depth and a gradient of a trench in a semiconductor device which is capable of accurately measuring a depth and a gradient of a trench on an actual wafer without damaging it, and to its method.
To achieve these and other advantages and in accordance with the purposed of the present invention, as embodied and broadly described herein, there is provided an apparatus for measuring a depth and a gradient of a trench in a semiconductor device including: a light emitting element for making a light incident on a wafer while varying an incident angle, the wafer having a trench structure carried by a test sample carrying unit; a detect unit for detecting a light reflected from the wafer at a position symmetrical to the light emitting element on the basis of a virtual vertical line perpendicular to the wafer; a photoelectric conversion unit for converting an intensity of a light detected by the detect unit to an electric signal; an operating unit for receiving an output signal from the photoelectric conversion unit, catching a time point where the size of the received signal is increased or maintained, computing a depth of the trench by using a critical angle, that is, an incident angle where the incident light is reflected from the central portion of a lower surface of the trench, and judging the time point when the increasing output signal of the photoelectric conversion unit is maintained when the incident angle is below a critical angle as a sloping angle of the trench; and a display unit for displaying an operating result of the operating unit.
In order to obtain the above object, there is also provide a method for measuring a depth and a gradient of a trench in a semiconductor device including: a test-sample preparing step for preparing a test sample trench on a wafer, where a semiconductor device is to be formed; critical angle and sloping angle detecting step for making a light, of which incident angle is sequentially varied, incident on the wafer where the trench was formed, detecting a light reflected from the wafer, and detecting both a critical angle in which the incident light is first reflected from the bottom of the trench and an incident angle at the time point when the intensity of the incident light is maximized; and a trench depth computing step for computing a depth of the trench by using the critical angle and the width of the trench.

Apparatus for measuring depth and gradient of trench in semiconductor device and method thereof

Hyundai Electronics Industries Co., Ltd.


The present invention relates to a built-in sun-shading device of hollow glass. The built-in sun-shading device comprises a cord-winding mechanism, a transmission mechanism controlling the rotation of the cord-winding mechanism and a sun-shading mechanism connected onto the cord-winding mechanism. The cord-winding mechanism comprises a cord-winding shaft, a group of cord-winding propellers are arranged on the cord-winding shaft, the transmission mechanism is connected with the cord-winding mechanism, and the sun-shading mechanism is connected onto the cord-winding propellers. The built-in sun-shading device of the hollow glass, which uses a single cord-winding shaft, can wind a plurality of cords and enable the sun-shading mechanism to be folded and unfolded in a balanced mode. The single cord-winding shaft does not need to move back and forth, is simple in terms of structure and has high assembling efficiency. In addition, the built-in sun-shading device of the hollow glass uses the cords to limit slats from moving to and fro, which thus enables the slats to stack up orderly, reduces contact between the slats and hollow glass, protects the coating film on the surface of the hollow glass and reduces friction. Furthermore, the built-in sun-shading device of the hollow glass uses a handle with frictional damping in one direction and overcomes a phenomenon that the large sun-shading mechanism may easily decline itself due to the large self-weight after being lifted.

Owing to excellent insulating and sun-shading effects, the pleated blinds of hollow glass become increasingly important in the modern construction in terms of energy efficiency; the blinds or pleated blinds of hollow glass have gradually been put into various applications, since blinds or pleated blinds of hollow glass are easy to clean, durable, fire-resistance and have special decorative effects. However, the blinds or pleated blinds of hollow glass currently in the market are all reduced to some drawbacks. Take the insulated glass blind assembly disclosed in U.S. Pat. No. 6,601,633B2 as an example. There, the blind cord is pulled downward under the magnetic force to raise the slats; once the cord is let go upward, the slats go downward under the gravity effect. In such a design, the several strands of cords can easily become tangled, making the blinds completely inoperable or making the lower frame of the blinds slid. In the U.S. Pat. No. 5,908,062, the lifting track of curtain makes use of two or more cord-winding shafts having a tapered cylindrical body; when the cord-winding shafts are operated to turn, two or more cords are wound orderly from the larger diametrical end to the smaller diametrical end, the curtain is lifted; when the cord-winding shafts are operated to turn in opposite direction, the curtain is lowered. However, in reality, such a device may face the problem that the curtain becomes slid as a result of cords being stuck between the cord-winding shaft and the end cap of the cord-winding shaft, or cords going up at varied speeds arising from difference between the exterior diameters of the cord-winding shafts. In the U.S. Pat. No. 6,817,401B2, the window blind assembly comprises a rotatable rod capable of simultaneously winding a plurality of cords; for the purpose of orderly winding, the rotatable rod needs to move back and forth, which nevertheless increases mechanical complexity and results lower efficacy in manufacturing and assembling.
Additionally, the width of the slats of the blinds is smaller than the spacing distance inside the hollow glass, such that the blinds can go up and down freely. However, when lifted up, the stack of slats of the blinds may be out of synch so as to result in collision with glass on two sides. In this case, friction would increase when the slats moves upward and downward, then the blind cannot be operated easily; meanwhile, the friction between the slats and the glass may cause scratches on the coating on the surface of the glass. In case of a large blind, the magnetic attract would be inadequate to raise or lower the blinds smoothly, or even the blinds can be raised up to the header position, the blind would be unable to retain at a desired position, because it may probably automatically drop down for a certain height under its weight.

Hollow glass built-in sun-shading apparatus


A system, method, computer program and article of manufacture for sharing metadata among cursors is provided. A metadata object marked as a versioned object can have multiple versions. Program units can share these versions of object metadata as opposed to copying the non-versioned object metadata into their memory. These program units may contain a pointer to an object's metadata but are otherwise void of the metadata information for the object. A locking protocol for the metadata ensures concurrency control and triggers dependency tracking. A locking protocol for the cursors controls cursor dependency status.

This invention related to computer systems, and more particularly to sharing metadata between program units.
A system global cache can serve as a global repository of cached metadata for objects. As requests from clients are received, each request is converted through compilation into a program unit, or cursor. The program unit stores the information needed to execute, including the metadata for the object being acted upon. If the object being accessed is partitioned, the metadata contains information about each partition. The memory needs of the metadata for a partitioned object is proportional in size to the number of object partitions. Therefore, as the number of partitions increases, the metadata storage requirements for the cursor program unit increases. Program unit memory usage can become significant in a system with partitioned objects having a large number of partitions or is a system that receives a large number of requests which access partitioned objects. Significant program unit memory usage can impact scalability.
A system, method, computer program, and article of manufacture for sharing metadata among program units is provided. A metadata object marked as a versioned object can have multiple versions. Program units can share these versions of object metadata as opposed to copying the non-versioned object metadata into their memory. These program units may contain a pointer to an object's metadata but are otherwise void of the metadata information for the object. A locking protocol for the metadata ensures concurrency control and triggers dependency tracking. A locking protocol for the program unit controls cursor dependency status.
A method of sharing metadata can include: receiving a plurality of requests to access a resource, creating a program unit for each of the plurality of requests, creating an execution representation of the metadata object of the resource, and sharing the execution representation of the metadata among the plurality of program units.

System for allowing object metadata to be shared between cursors for concurrent read write access


An object region data describing method of describing information about the object region in an image over a plurality of frames determines the region of a target object in an image using an approximate function that approximates the trajectory obtained by arranging, in the direction of frame advance, one representative point of an approximate figure for the object region and the difference values for determining the other representative points and describes information about the object region using a parameter for the function.

The present invention relates to an object region data describing method of describing information about the object region in a video and an object region data creating apparatus.
Hyper media are configured such that related information called a hyper link is given in between mediums, such as videos, sounds or texts, to permit mutual reference. When videos are mainly used, related information has been provided for each object which appears in the video. When the object is specified, related information (text information or the like) is displayed. The foregoing structure is a representative example of the hyper media. The object in the video is expressed by a frame number or a time stamp of the video, and information for identifying a region in the video which are recorded in video data or recorded as individual data.
Mask images have frequently been used as means for identifying a region in a video. The mask image is a bit map image constituted by giving different pixel values between the inside portion of an identified region and the outside portion of the same. A simplest method has an arrangement that a pixel value of "1" is given to the inside portion of the region and "0" is given to the outside portion of the same. Alternatively, α values which are employed in computer graphics are sometimes employed. Since the α value is usually able to express 256 levels of gray, a portion of the levels is used. The inside portion of the specified region is expressed as 255, while the outside portion of the same is expressed as 0. The latter image is called an α map. When the regions in the image are expressed by the mask images, determination whether or not a pixel in a frame is included in the specified region can easily be made by reading the value of the pixel of the mask image and by determining whether the value is 0 or 255. The mask image has freedom with which a region can be expressed regardless of the shape of the region and even a discontinuous region can be expressed. The mask image must have pixels, the size of which is the same as the size of the original image. Thus, there arises a problem in that the quantity of data cannot be reduced.
To reduce the quantity of data of the mask image, the mask image is frequently compressed. When the mask image is a binary mask image constituted by 0 and 1, a process of a binary image can be performed. Therefore, the compression method employed in facsimile machines or the like is frequently employed. In the case of MPEG-4 in which ISO/IEC MPEG (Moving Picture Experts Group) has been standardized, an arbitrary shape coding method is employed in which the mask image constituted by 0 and 1 and the mask image using the α value are compressed. The foregoing compression method is a method using motion compensation and capable of improving compression efficiency. On the other hand, complex compression and decoding processes are required.
To express a region in a video, the mask image or the compressed mask image has usually been employed. However, data for identifying a region is required to permit easy and quick extraction, to be reduced in quantity and to permit easy handling. Stated another way, the mask image is not suitable for identifying the object region in the video since it has a large quantity of data. The compressed mask image has a drawback in that coding/decodig is complicated and directly accessing to the pixel of a predetermined frame cannot be performed causing handling to become difficult.
Furthermore, only the positional information about the object region is represented and information about depth is not given. It is impossible to represent a state where the object disappears temporarily behind a thing. When shooting is done while the camera is following the moving object, the actual motion of the object is not represented. Thus, it is difficult to make a search, taking into account information about depth, disappearance behind another thing occlusion, and the movement of the camera. Therefore, in searching, all the things including unrelated ones must be processed.

Object region data describing method and object region data creating apparatus


A method for producing a three-dimensional preform from reinforcing fibers for producing a component from a fiber-reinforced plastic comprises the steps of introducing at least one layer of fibers having a binder into a draping mold, forming the at least one layer of fibers by at least one forming element which is displaceable along the draping mold, applying an airtight film to the at least one layer of fibers during or directly after the forming, creating a negative pressure in the intermediate space between the airtight film and the draping mold, activating the binder and removing the negative pressure after curing of the binder.

In airliners and other vehicles, components of fiber-reinforced plastics are often used to reduce weight. These could, for instance, consist of carbon fibers that are embedded in a matrix material and cured. There are known methods in which preformed semifinished fiber products are impregnated with a matrix material, the impregnation being performed, for example, by a vacuum infusion process. For this purpose, it is required that the fiber-based preforms are already in the desired product form and have a certain intrinsic stability.
While a vacuum infusion process has certain advantages for the industrial production of components from fiber-reinforced plastics, the industrial-scale fabrication of more complexly shaped, three-dimensional preforms using in particular nonwoven fibrous sheets can be difficult. There are no methods at present for producing preforms for stiffening components or similar elements that have a T-shaped profile cross section in a continuous forming process.
DE 10 2008 028 865 A1 shows for instance a method for producing a preform which can be curved or twisted in a way corresponding to a desired curvature and/or torsion of the profile component to be produced, the method comprising the introduction of mold core parts and the fibers that are used being embedded in prepregs.

Method for producing a three-dimensional preform from reinforcing fibers


A dishwasher includes a casing arranged within the dishwasher, an odor eliminating material installed within the casing, a shutter which selectively opens a part of the casing to expose the odor eliminating material, and a shutter driving device which operates the shutter. A control unit of the dish washer counts an actual drying time in a drying operation of the dishwasher, and opens the shutter by operating the shutter driving device in response to the counted drying time being equal to or greater than a preset drying time. The odor eliminating material eliminates odors in the dishwasher.

1. Field of the Invention
The present invention relates to dishwashers, and more particularly, to a dishwasher which removes unpleasant odors within the dishwasher and a method thereof.
2. Description of the Related Art
Generally, dishwashers are devices which wash dishes by supplying wash water in a washing tub of the dishwasher, and injecting the wash water through injection nozzles while circulating the wash water in the washing tub to coincide with washing, rinsing and drying operations.
In such a dishwasher, after a washing is completed, food dregs remain in a drain filter within the washing tub. In such a case, odors generated from the food dregs filtered by the drain filter permeate throughout a dish washing space, and cause unpleasantness to a user.
Therefore, various methods of removing the unpleasant odors within the dish washing space have been proposed.
FIG. 1 shows a vertical sectional view of a conventional dishwasher which prevents unpleasant odors within a dish washing space.
The conventional dishwasher comprises a casing 1 having a washing tub 2 formed therein, and a door 3 to selectively open and close a front opening of the dishwasher in a vertically rotating manner.
Upper and lower dish baskets 4 and 5, which accommodate dishes to be washed, are removably arranged in upper and lower portions within the washing tub 2, respectively. Upper and lower injection nozzles 6 and 7 are supplied with wash water, and inject the wash water into the upper and lower dish baskets 4 and 5, respectively. The upper and lower injection nozzles 6 and 7 are positioned under the corresponding upper and lower dish baskets 4 and 5.
A feed motor 8 is arranged under the washing tub 2 and supplies the wash water to the washing tub 2. Feed pipes 9 are respectively connected to upper and lower portions of the washing tub 2 and enable the wash water to be supplied to the washing tub 2 by the feed motor 8. A drain filter 10 is formed in the lower portion of the washing tub 2 and filters food dregs.
An air-flow hole (not shown), which controls the inflow/outflow of air into/from the washing tub 2, and a communicating vessel 11, which allows the washing tub 2 and the outside of the casing 1 to mutually communicate with each other, are connected to a portion of the washing tub 2. A net-shaped dreg removing member 12 is installed in an inlet of the communicating vessel 11.
The communicating vessel 11 includes an adsorption member 13 which adsorbs and eliminates odors of air passing through the adsorption member 13 from a dish washing space, a heater 14 which is installed to surround the adsorption member 13, and an insulating material 15 which is formed to surround the heater 14 and insulates the communicating vessel 11 from overheating.
The communicating vessel 11 further includes an exhaust fan 16 which discharges the air flowing from the dish washing space to the outside of the dishwasher. A filter 17 is disposed between the adsorption member 13 and the exhaust fan 16, and eliminates food odors remaining in the air passing through the adsorption member 13.
With the dishwater having the above construction, where a washing procedure of dishes is completed, food dregs remain in the dish washing space and are filtered by the drain filter 10 arranged in the lower portion of the washing tub 2. In such a case, odors generated from the food dregs are sucked into the communicating vessel 11 by the exhaust fan 16. The odors sucked into the communicating vessel 11 pass through the communicating vessel 11, while being adsorbed by the adsorption member 13, which is an activated carbon, installed within the communicating vessel 11.
On the other hand, the heater 14 heats the adsorption member 13 to a high temperature for a predetermined period of time, activating the movement of odor molecules. Accordingly, adsorptive power is improved, further eliminating the odors sucked into the communicating vessel 11. In addition, the odor air filtered by the adsorption member 13 passes through the filter 17 arranged in the downstream of the adsorption member 13. Therefore, the remaining odors, which were not adsorbed by the absorption member 13, can be eliminated. Furthermore, the possibility of food dregs flowing into the communicating vessel 11 along with the air sucked into the communicating vessel 11 is prevented by the net-shaped dreg removing member 12 installed in the inlet of the communicating vessel 11.
As described above, the communicating vessel 11 is connected to the washing tub 2 so as to enable the dish washing space and the outside of the casing 1 to mutually communicate with each other. Additionally, the adsorption member 13 is installed in the communicating vessel 11 to adsorb odors in the air passing through the communication vessel 11 from the dish washing space.
However, the conventional dishwasher having the above construction requires an additional communicating vessel, in which an adsorption member, a heater, an insulating material, an exhaust fan and a filter must be arranged. This complicates the construction and assembly of the dishwasher, and increases the manufacturing costs of the dishwasher.
In addition, the conventional dishwasher is problematic in its efficiency of eliminating the odors because the adsorption member is arranged in the communication vessel located outside of the dish washing space. Thus, it is difficult for the adsorption member to communicate with the air inside the dish washing space. Moreover, the conventional dishwasher is problematic in that, the exhaust fan must be driven excessively at all times to allow the air in the dish washing space to easily communicate, and be sucked through the adsorption member.

Dishwasher and method of controlling the same


A System Management Mode is transparent to normal system operations and dynamic RAM (DRAM) is available in the Upper Memory Block address range that is normally not accessible in many configurations. Therefore, the DRAM is advantageously used to attain System Management Mode read/write storage requirements. The System Management Mode time-multiplexes the Upper Memory Block memory-mapped address space with other non-DRAM resources in a timely manner by switching the SMM memory into the DRAM Upper Memory Block space in a "just in time" (JIT) basis. The JIT operation is achieved by latching the first memory address emitted from the CPU after SMM entry. The first memory address is designated as the top address of a memory block that extends downward into memory address space, defining an SMM memory range. All subsequent memory accesses that are addressed within the SMM memory range are directed to DRAM Upper Memory Block regardless of any other memory-mapped resources that normally reside within the same range of addresses as the SMM memory range. Upon the occurrence of an SMM resume instruction, the memory device mapping is automatically restored to the configuration existing prior to SMM activation. Using this technique, memory-mapped address space that is normally used for non-SMM purposes is employed for SMM operations in a method that is transparent to the system and application programs. Advantageously, DRAM that may not be normally available for usage due to the presence of other memory-mapped devices residing in the same address space is made available for SMM operations.

1. Field of the Invention
The present invention relates to computer systems. More particularly, the present invention relates to a software/hardware interface of a computer system for automatically initiating a predetermined operating mode in response to a signal.
2. Description of the Related Art
A processor operating in a PC/AT computer architecture may operate in various functional modes. One mode of operation is an 80.times.86 real mode in which memory is addressed using a segment value that is multiplied by 16 and added to an offset value to generate a physical memory address. In the real mode no access checks are made to verify that the processor is addressing a correct code, data segment and I/O address space, thereby improving performance but limiting system robustness and security since illegal codes and addresses are not detected by hardware. FIG. 1 illustrates a memory map of a processor address space 100 including a conventional disk operating system (DOS) 104 with a first 640 kbytes that are reserved for the operating system and application programs. Above the first 640 kbytes are stored a video RAM and various optional Basic Input/Output System (BIOS) extensions 108. Extended memory 110 begins above 1 Mbyte and may extend to 4 gigabytes. Memory addresses in the range of A0000h and FFFFFh are commonly referred to as "Upper Memory Blocks" (UMB) 106. The UMB is a highly overused resource when the computer executes in the 80.times.86 real mode since system memory addressability is limited to 1 MB. For example, various resources that typically reside in the UMB include:
ROM modules which are located on ISA adapter cards PA1 Ethernet transmit/receive buffers PA1 System BIOS in E0000 and F0000 segments PA1 VGA BIOS from C0000-C8000 PA1 Flash or ROM Disks in embedded applications, and PA1 DOS extenders which use V8086 mode to page DRAM from above 1 MB into the UMB for use by DOS and applications.
The DOS memory configuration is a relic of the limited memory address space of early generation microprocessors. Subsequent computer systems and architectures have conformed to the memory configuration limitations in varying degrees. Resource conflicts have been common and still frequently occur in attempting to conform architectures with multiple peripheral devices to antiquated memory configurations. Some computer system architectures, for example an ElanSC400 architecture, increase the demand for memory address space in the Upper Memory Blocks by allowing new memory-mapped resources, such as a PCMCIA (Personal Computer Memory Card International Association) and MMS (Memory Management System) windowing hardware, to be mapped into the Upper Memory Blocks.
System Management Mode (SMM) is a feature of computer systems such as the Enhanced AM486 CPU Core, manufactured by Advanced Micro Devices, Santa Clara, Calif. SMM is often used to support system-level power management. Under certain circumstances, the system's power management driver may shut power off to selected system peripherals. When operating system or application software subsequently performs an I/O access to the powered down device, an SMI may be generated which places the system into SMM. Inside of SMM, the SMI handler can turn the power back on to the required peripheral(s), and reconfigure the peripherals to a pre-powered down state. When SMM is exited, the I/O instruction may be restarted automatically by the CPU and the I/O access will occur transparently as if the power had never been shut off to the peripheral device in the first place. The System Management Mode is typically activated by an external signal to a dedicated terminal that generates an interrupt, specifically a System Management Interrupt (SMI), and redirects execution by directing addressing of executable program code to an SMI handler which resides in SMM RAM. The System Management Mode supports a technique that is application software transparent for taking control of the processor to handle selected system-related events. To achieve a control shift that is transparent to application software, the System Management Mode must save the state of the CPU, handle the SMM event, then restore the CPU state to the condition prior to the SMI. Optimally, the SMM handler should reside in memory (SMRAM) that is not normally accessible to either the operating system (O/S) or any application program. A failure to allocate the SMM handler to restricted memory raises the constraint that the SMRAM address must be known to the O/S or application and usage at the address avoided so that the memory region is not inadvertently allocate to O/S or application usage. The processes of saving and restoring the state of the CPU are performed automatically by the SMM hardware in the CPU upon detection of the SMI event. Both the state save process and the SMM handler code are possible only through a grant of read/write access to the SMRAM region.
Memory regions in the High Memory Area (HMA) above the 1 Mbyte boundary (1 MB+(64K-16)) are discounted for use by devices that compete for UMB space since the DOS kernel is located in the UMB when "dos-high" is specified in config.sys. Accordingly, the upper memory block (UMB) space is valuable and advantageously conserved. Operations utilizing memory regions below 640 kbytes are also prohibited since the memory region from 0 to 640 kbytes is reserved for DOS execution. Accordingly, if real mode execution is sought for a particular function, memory addressing is to be constrained to the memory region between 640 kbyte and the 1 Mbyte boundary. Unfortunately, in a typical computer system many resources are mapped into the Upper Memory Blocks from 640 kbyte to 1 Mbyte region.
What is needed is a circuit and operating method that support shared access for multiple resources in the Upper Memory Blocks region of memory in a range of memory addresses from 640 kbyte to 1 Mbyte.

Apparatus and method for automatically accessing a dynamic RAM for system management interrupt handling


An improved bucky drive utilizes a reversible rotary motor which drives a screw received in a nut fixed to a bucky grid. A integrated control circuit board for the motor insures that the motor is quickly operated. In other features, the motor is a DC motor with a position sensor. A transistor speed control is utilized. The bucky system may be operated in either a semi-automatic or an automatic mode. The speed of the grid may be controlled. Further, other operational parameters of the system may also be controlled.

This invention relates to improvements in the motor drive for an x-ray bucky system.
In the prior art, a bucky with a moving grid is utilized to prevent exposure of x-ray film to secondary radiations that might otherwise create shadows that could blur or obscure the image to be produced on the x-ray film. The grid is moved during the exposure of the x-ray film to prevent such shadows on the film.
In the prior art, a grid is often driven to reciprocate during the exposure of the x-ray. The drive systems must be controlled in combination with the x-ray system.
It would be desirable to improve the drive systems for such a bucky, including mechanical features of the drive, and the electronic controls for such drives.


A Fifth Generation Core (5GC) Long Term Evolution (LTE) network authenticates a wireless User Equipment (UE) for LTE data service using a 5GC Subscriber Concealed Identifier (SUCI). A Mobility Management Entity (MME) receives the 5GC SUCI and transfers the 5GC SUCI to a 5GC authentication system. The 5GC authentication system determines a 5GC Subscriber Permanent Identifier (SUPI) and authentication vector based on the 5GC SUCI. The 5GC authentication system transfers the 5GC SUPI and the 5GC authentication vector to the MME. The MME exchanges 5GC authentication data with the UE. The MME authenticates the UE based on the 5GC authentication vector and the 5GC authentication data. In response to the 5GC authentication, the MME initiates the LTE data service for the UE based on the 5GC SUPI.

Wireless communication networks provide wireless data services to wireless user devices. Exemplary wireless data services include machine-control, Internet-access, media-streaming, and social-networking. Exemplary wireless user devices comprise phones, computers, vehicles, robots, and sensors. The wireless communication networks have wireless access nodes that exchange wireless signals with the wireless user devices using wireless network protocols. Exemplary wireless network protocols include Institute of Electrical and Electronic Engineers (IEEE) 802.11 (WIFI), Long Term Evolution (LTE), Fifth Generation New Radio (5GNR), and Low-Power Wide Area Network (LP-WAN). In some examples, both LTE and 5GNR networks serve the same wireless user device at the same time with an integrated data service called dual-connectivity.
The wireless communication networks authenticate the wireless user devices before delivering non-emergency data services to the user devices. A given wireless user device and its wireless communication network share a secret key that identifies the user device. To authenticate the wireless user device, the wireless communication network hashes the secret key with a random number to generate an expected result. The wireless communication network transfers the random number to the wireless user device. The wireless user device hashes its secret key with the random number and returns the hash to the wireless communication network. The wireless communication network matches the hash from the wireless user device to the expected result to authenticate the wireless user device. After successful authentication, the wireless communication network delivers various data services to the wireless user device.
In 5GNR networks, the 5GNR user devices and encrypt their device identifiers for transfer over-the-air. The encrypted device identifiers are referred to as Subscriber Concealed Identifiers (SUCIs). The decrypted version of the SUCIs are referred to as Subscriber Permanent Identifiers (SUPIs). The SUPIs may be International Mobile Subscriber Identifiers (IMSIs). 5GNR networks use the 5GNR SUCIs to authenticate 5GNR user devices for 5GNR data services.
Unfortunately, LTE networks do not effectively use these 5GNR SUCIs to authenticate LTE user devices for LTE data services. Moreover, the LTE networks do not efficiently use the 5GNR SUCIs to control the Quality-of-Service (QoS) for the LTE data services that are delivered to the LTE user devices.

Fifth generation core (5GC) authentication for long term evolution (LTE) data service


A device for preventing electrical shock from a device with electrical interfaces. A shutter or other barrier associated with the device that physically prevents access or contact to one of the electrical interfaces while another electrical interface is in use.

1. The Field of the Invention
Embodiments of the invention generally relate to preventing users from receiving electrical shocks from operating medical devices. More specifically, embodiments of the invention relate to systems and methods for preventing electrical shock or reducing a risk of electrical shock from devices that analyze analytes.
2. The Relevant Technology
Diabetes is a disease that afflicts many people. Fortunately, much has been learned about the disease and today, diabetes can often be managed quite successfully. Managing diabetes often includes attention to both diet and exercise. It is also advisable to monitor blood glucose levels. Blood glucose levels can provide valuable information that contributes to the effective management of diabetes.
Monitoring blood glucose levels can be performed several times a day. Each time, a user typically draws a small sample of blood that is placed on a test strip. A measuring device analyzes the blood sample and provides a measurement of the person's blood glucose level from the blood sample.
In order to monitor or measure the glucose level of the blood sample, the measurement device may provide an electrical interface (e.g. port) that is constructed to receive a test strip and electrically connect with the test strip. This electrical interface is often exposed to the environment, including to the user of the measurement device. Similarly, the measurement device may have other electrical interfaces that may be used to connect the measurement device to a computer or to recharge an internal battery.
Measurement devices that allow access to electrical circuits can, in some situations, give a user an electrical shock if the user closes the circuit. More specifically, the electrical circuits of various measurement devices that are accessible via the port used to receive a test strip may be electrically connected to the port used to link or connect the measurement device to a computer or to recharge an internal battery.
For safety reasons, it is sometimes necessary to prevent the measurement device from being electrically connected to external equipment such as a computer or power supply when the measurement device is in contact with the user's body. The proximity of these electrical interfaces and their use can result in harm to the device and/or to the user. For example, the user of a measurement device may receive an electrical shock from the device if a circuit is inadvertently closed by the user. This could potentially occur, for example, when a user performs a finger stick test while the device is recharging or uploading data to a computer. In other words, current can flow to or from the external device through the person when they are "connected" to the measurement device.

Apparatus for preventing electrical shock in devices


A process is disclosed for preparing an alkylene glycol by reacting an alkylene oxide with water in the presence of a catalyst comprising a polymeric organosiloxane ammonium salt having a silica-like skeleton and comprising units of the general formula (I) ##STR1## wherein R.sup.1 to R.sup.4, Y and x are as specified in claim 1. Preferred are the catalysts wherein the anion Y is selected from the group of carboxylates having from 1-20 carbon atoms, hydrogen carbonate, hydrogen sulphite, hydrogen phosphate and metalate. These catalysts exhibit an enhanced selectivity stability.

Alkylene glycols, in particular monoalkylene glycols, are of established commercial interest. For example, monoalkylene glycols are being used in anti-freeze compositions, as solvents and as base materials in the production of polyethylene terephthalates e.g. for fibres or bottles.
The production of alkylene glycols by hydrolysis of alkylene oxides is known. It is performed either by liquid phase hydration with an excess amount of water, e.g. of 20 to 25 moles of water per mole of alkylene oxide, or by hydration in a heterogeneous system. The reaction is deemed to be a nucleophilic substitution reaction, whereby opening of the alkylene oxide ring occurs, water acting as the nucleophile. Because the primarily formed monoalkylene glycol likewise acts as nucleophile, as a rule a mixture of monoalkylene glycol, dialkylene glycol and higher alkylene glycols is formed. In order to increase the selectivity to monoalkylene glycols, it is necessary to suppress the secondary reaction between the primary product and alkylene oxide, which competes with the hydrolysis of alkylene oxide.
One effective means for suppressing the secondary reaction is to increase the relative amount of water present in the reaction mixture. Although the selectivity with respect to the monoalkylene glycol is thus improved, a problem is created in that for the recovery of the monoalkylene glycol from the reaction mixture large amounts of water have to be removed, which in turn involves large energy expenditure and is economically unattractive.
Considerable efforts have been made to find alternatives for increasing the selectivity of the process with respect to the monoalkylene glycols, without having to use a large excess of water. Usually, these efforts have focused on the selection of more active hydration catalysts and there are many publications, in which results obtained with various types of catalysts are disclosed.
Both acid and alkaline hydration catalysts have been investigated, whereby it would appear that the use of acid catalysts enhances the reaction rate without significantly affecting the selectivity, whereas by using alkaline catalysts generally lower selectivities with respect to the monoalkylene glycol are obtained.
High conversions, good selectivity and a low water/alkylene oxide ratio can be obtained with the process, disclosed in EP-A-156.449. According to this document, the hydrolysis of alkylene oxides is carried out in the presence of a selectivity-enhancing metalate anion-containing material, preferably a solid having electropositive complexing sites having affinity for the metalate anions. The said solid is preferably an anion exchange resin, the metalate anions are specified as molybdate, tungstate, metavanadate, hydrogenpyrovanadate and pyrovanadate anions. A complication of this process is that the alkylene glycol-containing product stream also comprises a substantial amount of metalate anions, displaced from the electropositive complexing sites of the solid metalate anion containing material. In order to reduce the amount of metalate anions in the alkylene glycol product stream, this stream is contacted with a solid having electropositive complexing sites associated with anions which are replaceable by the said metalate anions.
It has been proposed to simplify the product recovery procedure by using water-insoluble vanadate and molybdate salts. However, with these metalate anion salts the obtained selectivities are significantly lower than with the water-soluble metalates.
In JP-A-57-139026 there is disclosed a method for reacting alkylene oxide with water in the presence of a halogen type anion exchange resin and in the co-presence of carbon dioxide.
In RU-C-2001901 it is pointed out that the former disclosure has the disadvantage of the formation of carbonates in the reaction mixture which are difficult to separate from the glycols on account of the closeness of their boiling points. This patent publication discloses as its invention the performance of the alkylene oxide hydrating reaction in one or a sequence of `extrusion reactor(s)` (continuous reaction), in the presence of `anionite` (anion exchange resin of the quaternary ammonium type) in bicarbonate form and carbon dioxide. The essential difference with the former, Japanese, patent publication appears to be the use of the bicarbonate form of the anion exchanger instead of the halogen form thereof. And yet, the Russian patent does not dispense with the addition of carbon dioxide to the feed.
According to WO 95/20559, the presence of carbon dioxide in the feed is detrimental to the catalytic effect of bicarbonate-exchanged resins of the quaternary ammonium type. In this document there is disclosed a process for the preparation of alkylene glycols wherein an alkylene oxide is reacted with water in the presence of a catalyst composition comprising a solid material having one or more electropositive sites, which are coordinated with one or more anions other than metalate or halogen anions, with the proviso that when the solid material is an anionic exchange resin of the quaternary ammonium type and the anion is bicarbonate the process is performed in the substantial absence of carbon dioxide.
A drawback shared by the conventional anionic exchange resins which are based on purely organic polymers is their limited tolerance to heat. In practicing the process of alkylene oxide hydrolysis according to WO 95/20559 with catalyst compositions based on conventional purely organic quaternary ammonium ion exchangers it has been unexpectedly found, that under severe reaction conditions (high temperature and/or long service) the selectivity of the conventional resin-based catalysts tends to deteriorate strongly while their activity is even enhanced.
Anion exchanging polymeric organosiloxane ammonium salts have been known for some time, but their use as carriers in the instant process has never been contemplated before.
In EP-B 0 065 643 (corresponding to U.S. Pat. No. 4,410,669) polymeric ammonium compounds with a silica type backbone are disclosed, comprising units of the general formula (III) ##STR2## in which R.sup.1 and R.sup.2 represent a group of the general formula (II) ##STR3## in which R.sup.5 is linear or branched alkylene having 1 to 10 C atoms, cycloalkylene having 5 to 8 C atoms, ##STR4## in which n is a number from 1 to 6 and indicates the number of nitrogen-terminated methylene groups, and R.sup.1 and R.sup.2 can be the same or different, and the free valencies of the oxygen atoms are saturated either by silicon atoms of further groups of the formula (II) and/or by crosslinking bridge members of the formula: ##STR5## in which R' is methyl or ethyl and the ratio of the silicon atoms in (II) to the bridge atoms silicon, titanium and aluminum is 1:0 to 1:10,
R.sup.3 and R.sup.4 can have the same scope of meaning as R.sup.1 and R.sup.2 or represent hydrogen, a linear or branched alkyl containing 1 to 20 C atoms, cycloalkyl containing 5 to 8 C atoms or the benzyl group and PA1 R.sup.3 and R.sup.4 can be identical or different and be identical or different to R.sup.1 and/or R.sup.2 PA1 X represents an inorganic or organic, 1- to 3-valent anion of an inorganic or organic protonic acid which forms stable salts with amine bases and x is a number from 1 to 3.
In EP-B 0 065 643 it is also indicated in general terms, that the polymeric organosiloxane ammonium salts are useful as ion exchangers, catalytic carriers or active substance carriers.
In EP-B 0 327 796 (corresponding to U.S. Pat. No. 5,130,396) a method is disclosed for preparing the above organosiloxane amine compounds in spherical form.
In EP-A 0 491 144 (corresponding to U.S. Pat. No. 5,286,885) there are disclosed polymeric organosiloxane amine compounds, having units as in the formula (III) above with the proviso that X is an anion of a monooxo acid, an isopolyoxo acid or a heteropolyoxo acid of the elements vanadium, niobium, tantalum, molybdenum to tungsten. The use of these compounds as catalysts in oxidation reactions whereby peroxo compounds are involved is also disclosed.

Process for the preparation of alkylene glycols

Van Kruchten; Eugene Marie Godfried Andre


A modular manifold system is provided for interconnecting fluid components of a fluid system in a reduced area. The system is comprised of a one or more bridge fittings having an internal fluid passageway which has an inlet end in fluid communication with an outlet port of a first fluid component, and an outlet end in fluid communication with an inlet port of a second fluid component. The bridge fittings may additionally comprise two or more ports, which one of said ports may be in fluid communication with a manifold on another substrate level. The bridge fittings may be mounted within a channel of a backing plate for structural support or in channel blocks of varying sizes. An optional locator plate may be utilized which is mounted over the ends of the bridge fittings in order to align the inlet and outlet ports of the fluid components with the inlet and outlet ends of the bridge fittings. The bridge fittings may also be mounted to the locator plate in multiple directions forming multiple flow paths. Additionally, the bridge fittings may be stacked to form multiple layers where bridge fittings of one layer may be in fluid communication with bridge fittings of another layer. The invention may further comprise seals provided in a recess between the fluid ports and the mating bridge fittings ends.

This application is a continuation of copending International patent application No. PCT/US99/10980 filed on May 18, 1999 and which designated the U.S. This application claims the benefit of International patent application No. PCT/US99/04973 filed on Mar. 5, 1999, U.S. provisional application No. 60/085,817 filed on May 18, 1998 and U.S. provisional application No. 60/102,277 filed on Sep. 29, 1998.
To manufacture semiconductors, the industry uses various high purity gases. These gases are controlled by systems made up of high purity valves, regulators, pressure transducers, mass flow controllers and other components connected together by welding and high purity metal seal fittings. These connections may be undesirable in some applications because they add additional time and cost for welding operations, unnecessary space between components and make it difficult to replace a component located between other components. Further, these systems are typically custom designed and manufactured which make the manufacturing costs and procurement of replacement parts quite expensive.
New modular manifold systems have been recently introduced into the industry in order to overcome these problems. Typical components of these systems such as valves, pressure regulators and other typical fluid components have been reconfigured so that their inlet and outlet ports and attachment mechanisms are compatible with surface mount manifolds. These manifolds are typically comprised of modular blocks which are machined of high purity metal and have machined internal flow passageways. These prior art modular systems typically utilize a metallic seal between the component and a modular block face, as well as face seals machined on the exterior sides of the modular block faces for sealing engagement with mating modular blocks. One objective of such systems is to use surface mount standard configurations based upon industry standards to permit interchangeability of surface mount components.
One disadvantage to these type of prior art modular systems is that the entire modular block is made of high purity metal. Further, these block components also have higher manufacturing costs due to the complexity of machining multiple passageways of a single block as well as a higher risk of expensive scrap being formed due to the manufacturing complexity. In addition, the mating blocks require the use of mating seals therebetween, which require additional manufacturing time, and further require proper installation and makeup torque of the fastener members in order to ensure a leak-tight seal.

Modular surface mount manifold assemblies


In an embodiment of this invention, a memory includes an array of memory cells, an address decoder configured to generate a decoded signal for selecting a plurality of memory cells in a memory access, an input/output block configured to transfer data corresponding to the selected memory cells into and out of the memory, a first timing circuit configured to generate a first timing signal, and a second timing circuit configured to receive the first timing signal and in response generate a strobe signal coupled to the input/output block. An interconnect line carrying the first timing signal is routed through the array so that in the memory access a time delay from when the decoded signal is generated to when the data arrives at an input terminal of the I/O block is substantially the same as a time delay from when the first timing signal is generated to when the strobe signal is generated. A memory access time is thus improved by providing tracking between time-critical signals.

The present invention relates to semiconductor memories, and more particularly to a memory architecture and busing scheme which improve memory access time and reduce die size.
FIG. 1 shows a block diagram of a conventional semiconductor memory 200, such as a dynamic random access memory (DRAM). Memory 200 has two banks B0, B1 of two memory arrays each (Arrays 1, 2 and 3, 4). Each bank has a dedicated I/O block 240-1, 240-2 for data transfer into and out of memory 200. Each of arrays 1-4 has a dedicated global column decoder 250-1 to 250-4 for column selection.
Memory 200 operates as follows. An externally provided column address COL ADD is delivered via address bus 260 to each of the four global column decoders for selection of a predetermined number of columns from each bank. Simultaneously, an externally provided row address (not shown) is provided to row decoders (not shown) for selection of a row from each bank. Each of the four arrays is divided into a number of sub-arrays (not shown) with local bitline sense amplifiers (not shown) and column selection circuitry (not shown) between the sub-arrays. In selecting columns, each global column decoder provides decoded column address signals on global column decoder (GCD) lines which extend across each array. The GCD lines are coupled to the column select circuitry located between the sub-arrays. An output of the column select circuitry is coupled to global data bus (GDB) lines for transferring data between the array and the I/O block.
Memory 200 further includes first and second timing circuits 220, 230 which control the selection and transfer of data in memory 200. The first timing circuit 220 receives a set of control signals CTRL, such as the DRAM clock signal {overscore (CAS)}, and generates a first timing signal which is coupled to the four global column decoders and the second timing circuit 230 via interconnect line 210. A column access operation is initiated when the first timing circuit issues the first timing signal to selectively enable the global column decoders. At the same time, the first timing signal is delivered to the second timing circuit 230. As data selection and transfer through the memory banks takes place, second timing circuit 230 issues a second timing signal coupled to the two I/O blocks via interconnect lines 270-1, 270-2. The second timing signal is used to strobe the I/O blocks for sampling and transferring data through the I/O blocks.
Second timing circuit 230 is ideally designed to issue the second timing signal at substantially the same time that array data becomes available at the input of the I/O blocks in a read operation. Issuing the second timing signal earlier than the arrival of array data at the input of I/O blocks will result in sampling the wrong data. Issuing the second timing signal later than the arrival of array data will result in slow column access time. Accordingly, the second timing circuit needs to be carefully designed to issue the second timing signal at just the right time. Further, to avoid sampling and transfer of incorrect data, the second timing signal must be synchronized with the slowest column path. This requires very careful study of the layout of memory 200 to identify the slowest column path, and accurate extraction of all interconnect parasitic resistance and capacitance. With the second timing circuit designed for the worst case column speed path, normally fast column paths will externally appear slow, and thus advantage can not be taken of the faster speed paths.
Another drawback of the conventional memory 200 is that the interconnect lines 270-1, 270-2 coupling the second timing circuit 230 to the I/O blocks extend across a full length of an array. Because of the RC delay in these interconnect lines, a skew is created between the times that the left-most and the right-most I/O circuits in each I/O block are strobed. This timing skew results in slower column access time.
Therefore, a memory configuration and busing scheme which eliminate the above-mentioned timing problems causing speed degradation, and provide other improvements, is desired.
In accordance with the present invention a memory architecture and busing scheme improve speed by providing tracking between time-critical signals and reducing timing skews in data transfers through the I/O blocks, and reduce die size.
In one embodiment, a memory includes an array of memory cells, an address decoder configured to generate a decoded signal for selecting a plurality of memory cells in a memory access, an input/output block configured to transfer data corresponding to the selected memory cells into and out of the memory, a first timing circuit configured to generate a first timing signal, and a second timing circuit configured to receive the first timing signal and in response generate a strobe signal coupled to the input/output block. An interconnect line carrying the first timing signal is routed through the array so that in the memory access a time delay from when the decoded signal is generated to when the data arrives at an input terminal of the I/O block is substantially the same as a time delay from when the first timing signal is generated to when the strobe signal is generated.
In another embodiment, the address decoder and the first timing circuit are located along one end of the memory, and the I/O block and the second timing circuit are located along an end of the memory opposite the first end.
In yet another embodiment, the I/O block has at least a first and a second I/O circuits each being configured to transfer one bit of the data. The second timing circuit is located between the first and second I/O circuits so that a time delay through an interconnect line coupling the strobe signal to the first I/O circuit is the same as a time delay through another interconnect line coupling the strobe signal to the second I/O circuit.
The following detailed description and the accompanying drawings provide a better understanding of the nature and advantages of the present invention.

High speed memory architecture and busing


An endoscopic surgical clip applier is provided, wherein a distal end of the surgical clip applier is introduced to a target surgical site through a cannula having a fixed diameter lumen. The surgical clip applier comprises an endoscopic portion supported by and extending from a handle assembly, and a pair of jaws supported at a distal end of an outer tube, wherein the pair of jaws are movable between a fully open condition and approximated conditions. When the pair of jaws are in the fully open condition the pair of jaws extend radially beyond an outer diameter of the outer tube to a dimension greater than the fixed diameter of the lumen of the cannula; and when the pair of jaws are in at least one approximated condition the pair of jaws have a transverse dimension permitting passage through the lumen of the cannula.

1. Technical Description
The present disclosure relates to surgical clip appliers and, more particularly, to surgical clip appliers including a constant engagement wedge plate and independent manual release.
2. Background of Related Art
Laparoscopic procedures are performed in the interior of the abdomen. These procedures are through a small incision and through a narrow endoscopic tube or cannula inserted through a small entrance incision in the skin. Meanwhile, minimally invasive procedures performed elsewhere in the body are often generally referred to as "endoscopic" procedures. A surgeon will typically insert and extend a tube or cannula device into the body through the entrance incision to provide an access port. This port allows insertion of various surgical instruments therethrough, including endoscopic surgical clip applier.
These instruments are used for performing surgical procedures on organs, blood vessels, ducts, or body tissue far removed from the incision. Often during these procedures, it is necessary to apply hemostatic clips to blood vessels or various ducts to prevent the flow of body fluids therethrough during the procedure. Many different hemostatic clips having different geometries may be used and all are within the scope of the present disclosure.
One advantage of minimally invasive surgical procedures is the reduction of trauma to the patient as a result of accessing internal organs through smaller incisions. Known endoscopic clip appliers have greatly facilitated the advent of more advanced minimally invasive procedures by permitting a number of clip applications during a single entry into the body cavity. Commercially available endoscopic clip appliers are generally of 10 mm outer diameter and are adapted to be introduced through a 10 mm cannula. Other commercially available endoscopic clip appliers may also be generally have a 5 mm outer diameter and are adapted to be introduced through a 5 mm cannula.
In order for a 5 mm clip applier to be able to pass through a 5 mm cannula, it may be necessary for the jaws of the clip applier to deflect closed or be held in a closed state during insertion. However, following insertion, it is desirable for the jaws of the 5 mm clip applier to return to a fully opened condition and, preferably be held in the fully open condition, during manipulation in the anatomical cavity, so that the jaws may retain their alignment with one another and so that the jaws may proper receive a surgical clip therein for formation, as needed.
Accordingly, a need exists for a surgical clip applier including a mechanism for supporting the pair of jaws at substantially all times except during an insertion/retraction of the surgical clip applier to the anatomical cavity, and during a firing of the surgical clip applier.
Accordingly, a need also exists for a surgical clip applier including a pair of jaws that may be held in a fully open condition, during manipulation in the anatomical cavity, and which may be selectively approximated for insertion through a 5 mm cannula.


A hairbrush is provided which includes a brush head that is detachable from the handle whereby numerous brush heads may be rolled into the hair and the handle removed such that the detached brush heads may act as curlers. The hairbrush includes a handle with a polygonal socket tool extending therefrom. A detent, preferably a spring loaded ball detent, protrudes from one of the side walls of the socket tool. The hairbrush also includes a brush head having a central core. An end wall of the central core defines a socket which is sized and shaped to receive the socket tool. A ridge defined by the socket engages the detent when the socket tool is inserted in the socket. Preferably, the hairbrush also includes a retraction mechanism for retracting the detent so that when the retraction mechanism is actuated the detent no longer engages the ridge of the socket. Most preferably, the retraction mechanism comprises a button protruding through an outer longitudinal surface of the handle so that the detent is retracted when the button is depressed.

Hairbrushes and other hair care implements having detachable handles are well known. Such products have long been used where it is desirable to have several interchangeable heads with varying properties and purposes. Such products have also been used as an effective and efficient means for inserting rollers or curlers into the hair. When used for this purpose, the handle and roller are attached and the roller is tightly curled into the hair. Once inserted, the handle is removed from the roller, inserted into another roller, and the process is repeated. However, although devices of this type are known, certain deficiencies in the prior art designs exist.
U.S. Pat. No. 3,871,391 to Boudal discloses a hair roller having a central cylindrical support on which are mounted tufts of bristles. The patent envisions a handle which may be removably attached to the roller, but no disclosure is made as to how such attachment can be accomplished.
U.S. Pat. No. 5,603,339 to Brazeal et al. discloses a motorized rotating comb device. The comb includes a polygonal bit which engages a corresponding chuck in the rotating means. A spring-loaded ball detent projects from a side of the polygonal bit and engages a detent recess within the chuck. The patent does not disclose, however, a bristle hairbrush or curler.
U.S. Pat. No. 2,463,390 to Jacobowitz et al. discloses a hairbrush which includes interchangeable recurling implements attached to a handle by a mating male and female thread arrangement. U.S. Pat. No. 5,479,951 to Denebeim discloses a bendable, extendable hairbrush with a removable brush head. The brush head is attached to the handle either by a bayonet connection or by a conical friction connection. A disadvantage of Jacobowitz and of the bayonet connection embodiment of Denebeim is that the handle cannot be easily separated from the brush head. When one is attempting to roll multiple curlers into the hair, quick and easy separation of the handle is desirable. Most desirable is the ability to separate the handle from the brush head with one hand so that another brush head can be held ready in the other hand. This cannot be accomplished with Jacobowitz or with the bayonet connection embodiment of Denebeim. A disadvantage of the conical friction connection embodiment of Denebeim is that the brush head may be rotable and/or become detached from the handle before detachment is desired. To properly act as curlers, the brush heads must be wound tightly into the hair. A conical friction connection may allow for rotation of the roller due to the tangential forces exerted by the hair upon the roller. These same tangential forces may lead to the premature and unintentional separation of the brush head from the handle.
U.S. Pat. No. 3,967,630 to Zuhlsdorff et al. discloses a bristle hairbrush and curler combination with a removable handle. In one embodiment the handle includes a central mandrel which engages a corresponding central cavity of the curler element. The mandrel extends substantially to the end of the curler element, and attachment is accomplished by frictional engagement. A disadvantage of Zuhlsdorff is that the handle may not be easily separable from the curler element with one hand. One hand would be required to grasp the curler element, while the other hand would be used to pull free the handle. Moreover, a substantial amount of force may be necessary to overcome the frictional engagement between the mandrel and the central cavity. In addition to hindering separation, this may lead to discomfort or even injury to the user's scalp as the handle is pulled free, since pulling of the user's hair which is wound around the curler element is possible.
What is desired, therefore, is a hairbrush which includes a brush head that is detachable from the handle whereby numerous brush heads may be rolled into the hair and the handle removed such that the detached brush heads may act as curlers, which allows for quick and easy separation of the handle and the brush head, which inhibits the brush head from rotating about the handle, which inhibits separation of the brush head from the handle before detachment is desired, which allows for separation of the brush head and handle without requiring a substantial force, and which allows for separation of the handle from the brush head with one hand so that another brush head can be held ready in the other hand.


The invention provides a method for preventing or treating male erectile dysfunction or female sexual arousal disorder by administering an effective amount of one or more factors from a group of factors including vascular endothelial growth factor, brain-derived neurotrophic factor, basic fibroblast growth factor, neurotrophin-3, neurotrophin-4, or angiopoietin-1, wherein the factor is a full length protein or a nucleic acid encoding the factor, or a functional derivative or fragment thereof, or an agent that enhances production and/or male erection or female sexual arousal stimulating function of the factor(s). Combinations, kits, and combinatorial methods are also provided.

VEGF is a family of proteins that were discovered on the basis of their ability to stimulate VEC (vascular endothelial cell) growth (angiogenesis). It now comprises five members, namely, VEGF-A, VEGF-B, VEGF-C, VEGF-D, and PLGF (placenta growth factor) that are encoded from distinct genes. Achen, et al., Proc. Nat'l. Acad. Sci. USA, 95: 548 (1998), Joukov, et al., EMBO J., 15: 1571 (1996), Maglione, et al., Oncogene, 8: 925 (1993), Olofsson, et al., Proc. Nat'l. Acad. Sci. USA, 93: 2576 (1996), Yamada, et al., Genomics, 42: 483 (1997). Each of the five members in turn comprises two or more isoforms that arise by the splicing of their respective pre-mRNAs. For example, the VEGF-A family includes VEGF206, VEGF189, VEGF83, VEGF165, VEGF145, VEGF121, and VEGF111. Anthony, et al., Placenta, 15: 557 (1994), Neufeld, et al., FASEB J., 13: 9 (1999), Lei, et al., Biochim. Biophys. Acta, 1443: 400 (1998), Jingjing, et al., Ophthamol. Vis. Sci., 40: 752 (1999), Cheung, et al., Am. J. Obstet. Gynecol., 173: 753 (1995), Burchardt, et al., Biol. Reprod., 60: 398 (1999). Among all VEGF proteins and isoforms, VEGF165 is by far the most frequently used form of VEGF both in basic and clinical studies.
It has been shown that, among different vascular cell types (endothelial, smooth muscle cells (SMC), and fibroblasts), SMC is the principal source for the secreted VEGF. Pueyo, et al., Exp. Cell Res., 238: 354 (1998). Expression of VEGF in SMC is upregulated by multiple factors including phorbol esters (Tischer, et al., J. Biol. Chem., 266: 11947 (1991)), cAMP (Claffey, et al., J. Biol. Chem., 267: 16317 (1992)), and hypoxia (Goldberg, et al., J. Biol. Chem., 269: 4355 (1994), Shweiki, et al., Proc. Nat'l Acad. Sci. USA, 92: 768 (1995)). The secreted VEGF acts on VEC principally through two different cell surface receptors, VEGFR-1 and VEGFR-2. Activation of VEGFR-1 results in VEC migration, while activation of VEGFR-2 VEC migration and proliferation. Waltenberger, et al., J. Biol. Chem., 269: 26988 (1994), Neufeld, et al., FASEB J., 13: 9 (1999), Ortega, et al., Front. Biosci., 4: D141 (1999). Although VEGFR-1 and VEGFR-2 have long been considered endothelium-specific, they have both been detected in human uterine and bovine aorta SMC. Grosskreutz, et al., Microvasc. Res., 58: 128 (1999), Brown, et al., Lab. Invest., 76: 254 (1997). Cultured uterine SMC responded to VEGF in the form of cell proliferation and cultured aorta SMC cell migration. Cultured human colon SMC, however, did not express VEGF receptors, nor did they respond to VEGF treatment. Brown, et al., Lab. Invest., 76: 254 (1997).
Angiogenesis is a complex process that includes activation, migration and proliferation of endothelial cells and formation of new blood vessels. D'Amore, et al., Ann. Rev. Physiol., 49(9––10): 453–64 (1987). VEGF has been shown to be intimately involved in the entire sequence of events leading to growth of new blood vessels. Gross, et al., Proc. Nat'l Acad. Sci., 80(9): 2623–27 (1983), Folkman, et al., Proc. Nat'l. Acad. Sci., 76(10): 5217–21 (1979). Five hum VEGF isoforms of 121, 145, 165, 189 and 206 amino acids have been isolated. Gross, et al., Proc. Nat'l. Acad. Sci., 80(9): 2623–27 (1983), Leung, et al., Science, 246: 1306–09 (1989), Poltorak, et al., J. Biol. Chem., 272(11): 7151–78 (1997). Among the isoforms, VEGF 165 seems to be the most effective and most commonly used. The effect of VEGF 165 in augmenting perfusion and in stimulating formation of collateral vessels has been shown in animal models Hopkins, et al., J. Vascular Surgery, 27(5): 886–94 (1998), Asahara, et al., Circulation, 91(11): 2793–801 (1995), Hariawala, et al., J. Surg. Res., 63(1): 77–82 (1996), Bauters, et al., Circulation, 91(11): 2802–9 (1995), Bauters, C., et al., Am. J. Physiol., 267(4 Pt 2): H (1994), Takeshita, et al., J. Clin. Invest., 93(2): 662–70 (1994), Takeshita, et al., Circulation, 90(5 Pt 2): II228–34 (1994), Takeshita, et al., Am. J. Path., 147(6): 1649–60 (1995) Banai, et al., Circulation, 89(5): 2183–9 (1994). In clinical trials, successful induction of collateral blood vessels in ischemic heart disease and critical limb ischemia by VEGF have also been reported. Baumgartner, et al., Circulation, 97(12): 1114–23 (1998), Losordo, et al., Am. Heart J., 138(2Pt 2): 132–41 (1999).
Platelet-derived growth factor (PDGF) is a potent mitogen for cells of mesenchymal origin, stimulating both connective tissues and neuroglial cells. PDGF also acts as a potent chemoattractant for mesenchymal cells, mononuclear cells, and neutrophils. PDGF is stored in platelet granules and released with platelet activation. Other cell types also produce PDGF, including endothelial cells, monocytes/macrophages, vascular smooth muscle cells, fibroblasts, and cytotrophoblasts. PDGF consists of disulfide-linked dimers of αα, αβ, or ββ configuration. PDGF has a short half-life and usually produces only local effects. Two distinct PDGF receptors have been identified that are structurally related and have an intracellular protein kinase domain.
Neurotrophins are a class of structurally related growth factors that promote neural survival and differentiation. They stimulate neurite outgrowth, suggesting that they can promote regeneration of injured neurons, and act as target-derived neurotrophic factors to stimulate collateral sprouting in target tissues that produce the neurotrophin. Korsching, J. Neurosci., 13: 2739 (1993). Recently, local synthesis and autocrine mechanisms of action have been reported. Lewin and Barde, Ann. Rev. Neurosci., 19: 289 (1996). In vivo overexpression of a neurotrophic factor, through gene transfer, would ensure local and continuous neurotrophin production in a manner resembling the physiologic, as these proteins are usually produced and secreted by target and glial cells surrounding neurons.
Neurotrophin-3 (NT-3) is a member of the neurotrophin class of structurally related growth factors. NT-3 is a 27 kDa homodimer that supports the growth and survival of sympathetic neurons as well as sensory neurons. NT-3 is highly conserved across species and is primarily expressed in kidney, spleen, and heart with lower expression levels found in the skin, skeletal muscle, lung, thymus, and ovaries. NT-3 binds the low affinity NGF receptor, p75NTR, and may initiate apoptosis through this receptor. NT-3 also binds and induces signaling through the TrkC receptor.
Neurotrophin-4 (NT-4) is yet another member of this class of neurotrophins. NT-4 is a homodimer that supports the growth and survival of sympathetic neurons, dorsal root ganglion neurons, nodose ganglion neurons, basal forebrain cholinergic neurons and neurons of the locus coeruleus. NT-4 is less highly conserved between species, unlike other neurotrophins. NT-4 expression is widespread in brain and peripheral tissues. NT-4 induces cellular signaling through the p75NTR receptor as well as the TrkB receptor.
Brain-derived neurotrophic factor (BDNF), another member of the neurotrophins, was initially characterized as a basic protein present in brain extracts and capable of increasing the survival of dorsal root ganglia. Leibrock, et al., Nature, 341: 149 (1989). When axonal communication with the cell body is interrupted by injury, Schwann cells produce neurotrophic factors such as nerve growth factor (NGF) and BDNF. Neurotrophins are released from the Schwann cells and dispersed diffusely in gradient fashion around regenerating axons, which then extend distally along the neurotrophins' density gradient. Ide, Neurosci. Res., 25: 101 (1996). Local application of BDNF to transected nerves in neonatal rats has been shown to prevent the massive death of motor neurons that follows axotomy. DiStefano, et al., Neuron, 8:983 (1992), Oppenheim, et al., Nature, 360: 755 (1992), Yan, et al., Nature, 360: 753 (1992). The mRNA titer of BDNF increases to several times the normal level 4 days after axotomy and reaches its maximum at 4 weeks. Meyer, et al., J. Cell Biol., 119: 45 (1992). Moreover, BDNF has been reported to enhance the survival of cholinergic neurons in culture. Nonomura, et al., Brain Res., 683: 129 (1995).
Angiopoietin-1 (Ang-1) is a member of a family of endothelium growth factors. Ang-1 is a ligand for the Tie-2 receptor, a receptor tyrosine kinase with immunoglobulin and epidermal growth factor homology domains expressed primarily on endothelial cells and very early hematopoietic cells. Ang-1 promotes chemotaxis, cell survival, cell sprouting, vessel growth and stabilization of Tie-2-expressing endothelial cells. Ang-1 is thought to have a distinct angiogenic role from that of VEGF involving the recruitment of peri-endothelial cells that will become pericytes and smooth muscle tissue of the blood vessel, thereby maintaining the stability of the blood vessels. See, e.g., Hanahan, D., Science, 277: 48–50.
Basic fibroblast growth factor (bFGF) is a member of the fibroblast growth factor family. bFGF stimulates the proliferation of all cells of mesodermal origin including smooth muscle cells, neuroblasts, and endothelial cells. bFGF stimulates neuron differentiation, survival, and regeneration. In vitro functions suggest that bFGF modulates angiogenesis, wound healing and tissue repair, and neuronal function in vivo. bFGF, a heparin-binding growth factor, is capable of inducing functionally significant angiogenesis in models of myocardial and limb ischemia. Zbeng, et al., Am. J. Physiol. Heart Circ. Physiol., 280: H909–17 (2001), Laham, et al., J. Am. Coll. Cardiol., 36: 2132–39 (2000), Laham, et al., Curr. Interv. Cardiol. Rep., 1: 228 (1999), Unger, et al., Am. J. Cardiol., 85: 1414–19 (2000), Kawasuji, et al., Ann. Thorac. Surg., 69: 1155 (2000), Rajanayagam, et al., J. Am. Coll. Cardiol., 35: 519 (2000), Kornowski, et al., Circulation, 101: 545–48 (2000), Ohara, et al., Gene Ther., 8: 837 (2001), Lazarous, et al., J. Am. Coll. Cardiol., 36: 1239 (2000), Rakue, et al., Japan Circ. J., 62: 933–39 (1998), Baffour, et al., J. Vasc. Surg., 16: 181 (1992).
Erectile function is a hemodynamic process of blood in-flow and pressure maintenance in the cavernosal spaces. Christ, Urol. Clin. North Am., 22: 727 (1995). Following sexual arousal and the release of nitric oxide to the erectile tissue, three processes occur to achieve an erection. These are relaxation of the trabecular smooth muscle, arterial dilation and venous compression. Id. During this final stage, arterial flow fills sinusoidal spaces, compressing subtunical venules thereby reducing venous outflow. Blood flows into the cavernous spaces of the penis, thus expanding and stretching the penis into a rigid organ. The flow of blood in and out of the cavernous spaces is controlled by cavernous smooth muscle cells (CSMC) embedded in the trabeculae of the cavernous spaces. With normal erectile function, a high intracavemous pressure (ICP) is maintained with a low inflow rate. Karadeniz, et al., Urol. Int., 57: 85 (1996).
As such, the penis is a predominantly vascular organ, and vascular or penile arterial insufficiency is the most common etiology of erectile dysfunction (ED). Sinusoidal smooth muscle atrophy and collagen deposition is a common finding in men with long standing ED of various etiologies, whether due to hormonal, neurological or vascular causes. Karadeniz, et al., Urol. Int., 57: 58 (1996). Such degradation in smooth muscle quantity and quality leads to veno-occlusive dysfunction. This represents an end-stage muscular degeneration akin to myocardial changes with congestive heart failure or dilated cardiomyopathy for which no treatment currently exists with hope of reversing the underlying pathologic process.
Veno-occlusive disease is a common finding among patients with erectile dysfunction (ED). Following radical prostatectomy, for example, approximately 30% of patients may have vasculogenic ED in addition to neurogenic ED and at least half of these men may have venous leak. Regardless of the etiology of organic ED (neurogenic, traumatic, hormonal, and vascular, etc.), venous leakage is a common final condition resulting from smooth muscle atrophy. Mersdorf, et al., J. Urol., 154: 749 (1991). Veno-occlusive dysfunction is the most common etiology of ED among non-responders to medical management of ED. None of the medical therapy currently exists is curative for this condition. Patients with veno-occlusive dysfunction exhibit a poor response to intracavernous injection with vasoactive agents (papavarine, prostaglandin El, phentolamine, or combinations, for example), despite good arterial flow demonstrated by duplex ultrasound. The diagnosis of veno-occlusive disease may be confirmed with specific findings on cavernosometry and cavernosography. Nehra, et al., J. Urol., 156: 1320 (1996).
Atherosclerotic or traumatic arterial occlusive disease of the pudendal-cavernous-helicine arterial tree can decrease the perfusion pressure and arterial flow to the sinusoidal spaces, thus decreasing the rigidity of the erect penis. Common risk factors associated with generalized arterial insufficiency include hypertension, hyperlipidemia, cigarette smoking, diabetes mellitus, and pelvic irradiation. Goldstein, et al., JAMA, 251: 903–910 (1984), Rosen, M. P., et al., Radiology, 174(3 Pt 2): 1043–48 (1990), Levine, F. J., et al., J. Urology, 144(5): 1147–53(1990). Epidemiological studies have shown a high incidence of ED in patients with coronary arterial disease. Heaton, J. P., et al., Int'l J. Impotence Res., 8(1): 35–39 (1996). Focal lesion of the common penile or cavernous artery is most often seen in young patients who have sustained blunt pelvic or perineal trauma such as in cases of biking accidents. Levine, F. J., et al., J. Urology, 144(5): 1147–53 (1990).
Because of the close proximity of the cavernous nerves to the capsule of the prostate, ED is a frequent complication after radical prostatectomy or cystectomy and prostatic cryosurgery. Although the nerve-sparing prostatectomy technique developed by Walsh, et al., Br. J. Urol., 56: 694 (1984) has significantly reduced the postoperative impotence rate, a large number of patients still suffer from inadequate penile rigidity. Peripheral nerve regeneration is a slow process, and the fact that most patients do not recover potency for 6 months to 2 years indicates substantial axonal damage, even with preservation of the neural sheath. An anatomic study of the cavernous nerves by Paick et al., Urology, 42: 145 (1993) revealed both a medial and a lateral bundle of cavernous nerves at the level of the prostate, suggesting that in some cases the lateral bundle can be saved, even in non-nerve-sparing prostatectomy.
The sprouting of the remaining nerves in penile tissue appears to be more important in regeneration than re-growth of nerves through the damaged and fibrotic tissues. The importance of sprouting in the remaining nerves was confirmed in an animal study that revealed regeneration of the cavernous nerves after unilateral resection. Carrier, et al., J. Urol., 153: 1722 (1995). In addition, a previous study in our laboratory showed that systemic growth hormone injection significantly enhanced cavernous nerve regeneration after unilateral injury. Jung, et al., J. Urol., 160: 1899 (1998).
Methods for treating erectile dysfunction have included from the administration of prostaglandin E (U.S. Pat. No. 5,942,545), local administration of vascular muscle relaxants and vasoactive pharmaceutical agents. See, for example, U.S. Pat. Nos. 5,942,545, 6,056,966; and 5,646,181.
Advancement in molecular biology has brought improved understanding of pathophysiology on the gene and molecular level, and offers promise of treatment possibilities aimed at a specific pathologic molecular mechanism. As in other vasculopathies such as limb claudication (Baumgartner, et al., Circulation, 97: 1114 (1998) and coronary artery disease (Symes, et al., Ann. Thorac. Surg., 68: 830 (1999), treatment with VEGF in either protein or gene form has increased neovascularity in animal models and improved symptomatic angina and wound healing in humans with inoperable heart disease and critical limb ischemia, respectively. The penis represents a convenient tissue target for gene or growth factor therapy due to the penis' external location on the body, ubiquity of endothelial-lined spaces and low-level blood flow in the flaccid state. In addition, the penis is filled with billions of endothelial and smooth muscle cells both are rich in VEGF receptors. Liu, et al., J. Urol., 166: 354–360 (2001).
Recently, we have established an animal model in which CSMC was seen decreased following internal iliac artery ligation that restricted blood supply to the penis. However, rats treated with intracavernous injection of vascular endothelial growth factor (VEGF) shortly after internal iliac artery ligation had nearly normal CSMC. The protective effects of VEGF on CSMC could be due to partial restoration of blood supply as VEGF is expected to stimulate vascular endothelial cell (VEC) proliferation. Lin, et al., Proc. Nat'l Acad. Sci. USA, 97: 10242–47 (2000). Alternatively, VEGF might act directly on CSMC, as we will present evidence that CSMC express one of the two principal VEGF receptors. Sondell, et al., Eur. J. Neurosci., 12: 4243–54 (2000); Liu, et al., J. Urol., 166: 354–360 (2001).
Females can also have sexual dysfunction, and this dysfunction can increase with age. It is usually associated with the presence of vascular risk factors, genital smooth muscle atrophy, and onset of menopause. Some of the vascular and muscular mechanisms that contribute to penile erection in the male are believed to be similar vasculogenic factors in the female genital response. It is known that in women sexual arousal is accompanied by arterial inflow which engorges the vagina and increases vaginal lubrication, and that the muscles in the clitoris and the perineum assist in achieving clitoral erection.
In the female patient, sexual arousal disorder can arise from organic and pyschogenic causes, or from a combination of the foregoing. Female sexual arousal disorder is classified into five categories: 1) hypoactive sexual desire disorder, 2) sexual aversion disorder, 3) sexual arousal disorder, 4) orgasmic disorder, and 5) sexual pain disorder. The present invention applies to sexual arousal disorder. Sexual arousal disorder is the persistent or recurring inability to attain or maintain adequate sexual excitement, causing personal distress. It may be experienced as the lack of subjective excitement or the lack of genital lubrication or swelling or other somatic responses. Organic female sexual arousal disorder is known to be related in part to vasculogenic impairment resulting in inadequate blood flow, vaginal engorgement insufficiency and clitorial erection insufficiency. Animal studies have demonstrated the dependence of vaginal vascular engorgement and clitoral erection on blood flow. See, for example, Park et al., "Vasculogenic female sexual dysfunction: the hemodynamic basis for vaginal engorgement insufficiency and clitoral erectile insufficiency," Int'l J. Impotence Res., 9(1), 27–37 (March 1997).
Female sexual dysfunction has been treated with pharmacological intervention to stimulate blood flow as well as with prostaglandins. See, for example, U.S. Pat. Nos. 6,193,992 B1; 5,945,117; 6,031,002; and 5,891,915.

Methods and compositions for preventing and treating male erectile dysfunction and female sexual arousal disorder

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