A system for determining the position of an airplane in a hangar and for limiting the motion of a plurality of gantry cranes around the airplane, the system including a plurality of movable scanners which ascertain locations of a plurality of collinear points along the leading edges of the wings of the airplane, including a processor system for determining a point of intersection of lines through the collinear points, the point of intersection and lines having a known positional relationship with the other portions of the airplane from which the processor system also determines the locations of other portions of the airplane, the processor system determining limits on the cranes' motion relative to the airplane.

This invention relates generally to control systems and more particularly to position detection and collision avoidance systems.
In the aircraft industry, it is necessary to provide access of persons to the outer surfaces of large aircraft to paint and maintain the aircraft. To provide such access to the outer surfaces of large aircraft, a plurality of large gantry cranes, known as stackers or stacker cranes hanging from rails mounted within and near the ceiling of an aircraft hangar, have been employed. Each of these gantry cranes has been operated by an operator riding on a platform on the lower end of a vertically extendible and retractable crane mast.
Employing a plurality of such cranes has presented particular problems with respect to collisions between the cranes themselves, between the cranes and other objects in the hangar and most importantly between the cranes and the aircraft. The problem of collisions between the cranes and the aircraft has been exacerbated by the fact that, in order for the painters/crane operators to effectively prepare and paint the aircraft, the crane platforms need to be positioned within an approximate range of four inches to ten feet from the aircraft, depending on the task.
A single collision between a crane and one of today's modern aircraft can be very costly, not to mention the danger of human injury. Thus, it is extremely important that the gantry cranes not hit the aircraft.
Because of the magnitude of the task of painting a large commercial aircraft, because of the potential for economic loss associated with collisions, and because of the inadequacy of previous crane control systems, the painting state has become a "bottle neck" in aircraft manufacturing.
One reason for the difficulty experienced in developing control systems for avoiding collisions between cranes and aircraft has been due to the fact that each aircraft is not parked in the exact same location and with the exact same positioning and orientation relative to the cranes and the hangar. In other words, it has been difficult to determine the position of the surfaces of the aircraft relative to the hangar and the cranes, and this in turn has made difficult the development of adequate control systems.
Control systems for cranes operable around large aircraft have evolved from the earliest stages where crane operators themselves were alone responsible for manually and visually keeping the crane and the movable platform on the crane away from the aircraft and other objects in the hangar by appropriately operating the crane's controls to avoid collisions. Of course, with such a system, human error and accidental depressions of crane controls have resulted in both minor and major collisions.
A first attempt at solving some of the problems has been termed a collision detection system. With such a system, a number of strategically placed wands, contact tapes and bumpers have been placed around the perimeter of the crane's platform and on the crane structure itself at locations where the platform or the crane could collide with the aircraft or other objects in the hangar. Upon touching or bumping the aircraft or other objects, these systems have, through a system of relays, interrupted control power to the cranes to avoid further and more damaging movement.
Though such collision detection systems often have avoided major collisions, they have had several disadvantages, including the fact that activation of the collision detection wand, contact tape or bumper has cut control power to all stacker crane functions and has required service calls to restart the stackers. This has required as many as 20-30 service calls per week to enable further crane operation. Also, these prior detection systems have damaged wet paint on the aircraft or the aircraft as they have had to touch the aircraft before interrupting power to the crane. Moreover, these prior control and collision detection systems have not been found infallible. There have continued to be both minor and major collisions in the paint hangar.
A second generation of control systems termed anti-collision systems have been developed in an attempt to solve the problems associated with the aforementioned first generation collision detection systems. These anti-collision systems have employed commercially available non-contact sensors, such as ultrasonic and diffused reflective infrared sensors wherein either an ultrasonic or reflective infrared wave has been propagated toward the object or aircraft to be avoided. Upon detection of a reflected ultrasonic or light wave from an object, the non-contact sensors have interrupted motion of the crane. With such systems, the operator has usually been able to manually operate the crane away from the danger, i.e., by pulling the crane upwardly, and if necessary, the operator has been able to manually override the anti-collision system to move the crane away from danger.
While the second generation control system virtually eliminated the need for service calls to repower the cranes after detection of an impending collision, such systems still have had several disadvantages. For example, compound curved surfaces on the aircraft have scattered ultrasonic signals so as not to provide sufficient feedback. Also, differing surface reflectiveness of objects have caused the stacker cranes to stop at varying distances, between 6 and 18 inches from the aircraft, depending on the brightness of the surface. Moreover, certain objects within the hangar have not provided an upper surface effective to stop motion of the crane before a collision has occurred. Still further, in the painting environment, the use of the diffused reflective infrared sensors has become limited, since overspray can cover the light emitting portion of the sensors causing the sensors to become less effective.

Variable parameter collision avoidance system for aircraft work platforms


A store operation architecture in which store operation latency and read-for-ownership (RFO) throughput are improved. Embodiments of the invention relate to a method and apparatus to improve store performance in a microprocessor by allowing out-of-order issuance of RFO operations and more efficiently using the store buffer latency periods.

A microprocessor typically communicates with a computer system via a shared computer system bus known as a "front-side bus" (FSB). However, as microprocessor performance is improved and as computer systems use multiple processors interconnected along the same FSB, the FSB has become a performance bottleneck.
One approach to this problem is the use of point-to-point (PtP) links between the various processors in a multiple processor system. PtP links are typically implemented as dedicated bus traces for each processor within the multi-processor network. Although typical PtP links provide more throughput than FSB, the latency of PtP links can be worse than the latency of FSB.
Latency of PtP can particularly impact the performance of store operations performed by microprocessor, especially in microprocessor architectures requiring strong ordering among the store operations. Because of the strong ordering requirements, for example, previously issued store operations must typically be accessible, or at least detectable, to other bus agents within the system before later store operations may be issued by the processor. The detectability of an operation, such as a store, load, or other operation, to other bus agents within a computer system is often referred to as "global observation" of the operation. Typically, microprocessor operations or instructions only become globally observable after they have been stored to a cache or other memory in which other agents in the system may detect the presence of the operation or instruction.
In the case of store operations within a strong ordering microprocessor architecture, typical microprocessors will not issue a store operation from a store buffer, or other store queuing structure, or, in some cases, from the processor execution unit, until the previous store operation has been globally observed. The issuance of a store operation in typical microprocessor architectures is preceded by an operation, such as read-for-ownership (RFO) operation, to gain exclusive control of a line of the cache or other storage area in which the store operation is to be stored so that it may be globally observed. However, in typical microprocessor architectures, RFO operations are not issued until preceding store operations are globally observed.
FIG. 1 illustrates a prior art cache architecture for handling issued store operations within a strongly ordered microprocessor architecture. The store buffer contains data X1 and Y1 that are to be stored in addresses X and Y, respectively of the level-1 (L1) cache via the cache line fill buffer (LFB). However, in typical prior art architectures, neither the store data, X1 and Y1, nor their corresponding RFO operations may be issued until the data X0 and address X in the L1 cache has been globally observed.
Due to latency in the issuance, and ultimately the retiring, of store operations within prior art architectures, the overall performance of a microprocessor and the system in which it exists may be compromised. Furthermore, as PtP multiple processor systems become more pervasive, the problem may be exacerbated as each processor in the system may dependent upon data being stored by other processors within the system.

Store performance in strongly-ordered microprocessor architecture


A vacuum seal valve is applied to a lid for the air-tight closing of a container for the packaging of products, particularly food products, including a closing body arranged for sealing a hole for evacuating air from the container, from which at least one punching member stems that is adapted to pierce the lid closing the container so as to form such evacuating hole. A reciprocating mechanical vacuum pump, with manual actuation, evacuates air from a container arranged for the vacuum packaging of products, for example food products, via application of the vacuum sealing valve. The pump has, at its base, a recess adapted to form a housing for retaining the valve, whereby the lowering movement of the plunger allows driving the valve in a lid of the container.

Containers for the vacuum packaging of food products, or in any case items which are perishable if placed in prolonged contact with the atmosphere, have been known for a number of decades. Among these, the most widespread containers in the domestic field for preserving freshly-prepared foods are the rigid containers of generally cylindrical shape, such as jars or pots made of glass, aluminium or plastic, equipped with a sealing lid for closing the mouth. The containers intended for use for vacuum packaging are industrially produced and comprise a lid provided with a valve or similar vacuum sealing device, adapted to reclose an air evacuation hole previously made during the industrial production of such lids. Attachable to such containers is a common pumping device for sucking air and creating reduced pressure ("the vacuum") therein, e.g. a vacuum packaging machine.
A vacuum sealing device is for example described in the U.S. Pat. No. 2,416,900, and is formed by a valve body housed in a dedicated seat made in a lid arranged for the air-tight and vacuum closure of a jar.
Similar solutions, in which the air evacuation hole is previously made during the industrial production of the container and before the assembly of the valve, are typically used in providing flexible, collapsible containers. Among these, the patent application WO 2005/093303 A1 describes a vacuum sealing device applied to a bag for vacuum packaging foods, which includes a flexible closing body coupled with a valve seat welded by heat-sealing on the border of an evacuation hole made on one face of the bag. The closing body has a sealing diaphragm, adapted to cooperate with a surface of the valve seat surrounding a plurality of radial evacuation openings, in order to ensure the air-tight closure of the container. From the closing body head, there emerges an axial stem whose end, spike-shaped, interferes with a coaxial, annular abutment surface of the sealing device in a manner so as to stably retain the closing body, preventing any translation movement thereof along the stem axis. The diaphragm is flexible and capable of being removed from the surface of the valve seat in an operating suction condition, thus to allow the air evacuation.
A reciprocating mechanical pump, manually actuatable, for sucking air from a receptacle and a multipurpose lid in disc form for closing a mouth of the receptacle and maintaining the reduced pressure created at its interior over time are for example described in the U.S. Pat. No. 5,364,241.
As an alternative to the industrial manufacture of containers equipped with suitable lid for vacuum packaging of the same, artisanal solutions are known for transforming a common air-tight closure jar into a container suitable for vacuum packaging. Such solutions are based on the provision of set of devices, generally comprising a pin or similar tool for punching a jar lid and a plurality of portions of an adhesive film, adapted to be arranged on the surface of the lid at the obtained hole and to allow the air evacuation and subsequent sealing closure of the hole due to the reduced pressure inside the container.
Such solution is at the base of the device known by the commercial name "Pump 'n' Seal" of Pioneering Concepts, Inc.

Vacuum packaging in containers provided with an air-tight closing lid


A data protection system that integrates a database with Windows Explorer in the Microsoft Windows 9X and NT Environments that mimics the Windows Explorer user interface, enabling the user to apply already known use paradigms. The data protection system appears as an extension to Windows Explorer and visibly appears as a folder item called the data vault. The data vault is a virtual disk that represents the underlying database. The database creates records and stores information about files backed up to removable secondary storage medium. Files may be backed up manually or automatically. A schedule can be set up for automatic protection of selected files and file types. The database can be searched to find files for restoration purposes without having to load secondary storage medium. Once a file or files are selected, the data protection system indicates which labeled removable secondary storage medium must be loaded for retrieval.

Most computer users in the desktop environment employ some sort of data protection procedures and devices to protect computer system files and data files in the event of an accidental delete or overwrite of these files from the primary storage medium, which is usually the computer's hard drive. Computer data protection systems usually involve the backup of system and data files onto some sort of secondary storage device utilizing removable storage media, such as floppy disk drives, other hard disk drives, tape drives, etc. More sophisticated users may utilize automatic data protection devices and procedures that backup the entire system on a regular basis, allowing for a full system recovery if needed.
In many cases, however, computer users employ only manual backup procedures for data files and some system files on an inconsistent basis. This is because many users find the cost of automatic backup systems to be prohibitive. Others find the performance of automatic backup systems to be lacking, especially when trying to restore one file or a particular version of a file. Many users complain that finding and retrieving a backup file is very time consuming and difficult to do. Some also find that an automatic backup system does not lend itself very well to an unscheduled manual backup of a particular file or group of files. Many users are only interested in backups of their current data files rather than backups for system files or for a full system recovery. Other users do not want to take the time to learn a backup system's methods and procedures. Still others do not want to spend the time it takes to manually backup their data and system files, and fail to backup at all.
Recent research indicates that 70-80% of those who have purchased a compact disk device, such as a CD-R drive, are today using the device for performing simple data backup manually, even if they originally purchased the drive for another purpose. Simple data backup refers to backup of the user's data, and sometimes executable programs, as opposed to backup for the purposes of full system recovery. This use is obvious in light of the storage capability of the CD medium and the speed at which data can be transferred to and from it.
However, even with the increased storage capacity and speed of such disks, restoring a backup file to the hard drive involves shuffling disks in and out of the CD drive until the right disk is located that contains the desired file or files. This can be quite time consuming, especially if the user has a number of disks and does not have a listing of what files are on each disk. In addition, if a file is backed up in a number of different versions, which may also be on different disks, the user has to check for the date, time, or size of the file in addition to the file name to find the right version.
Thus, there is a need in the art in the desktop environment today for a simple and efficient automatic data protection system directed toward protecting current data or executable files that utilizes CD-R (Recordable) drives and CD-RW (Re-Writeable) drives. There is a further need in the art for a data protection system that has a simple, intuitive user interface that does not require the user to learn a whole new method and procedure. There is also a need in the art for a data protection system that allows for both manual and automatic data backup. There is a further need in the art for a method of off-line browsing of data stored on removable storage media that does not require the shuffling of the media in and out of the storage device. There is also a need in the art for a method that will indicate which removable storage medium to insert in the storage device in order to restore a particular file. The present invention meets these and other needs in the art.

Integration of a database into file management software for protecting, tracking and retrieving data


Systems and methods may be provided for a prescription safety network program. The systems and methods may include receiving an eligibility verification request for a prescribed drug or product, where the eligibility verification request may include a pharmacy identifier, a patient identifier, and physician identifier; determining, based upon the received pharmacy identifier, that a pharmacy associated with the pharmacy identifier has enrolled in the prescription safety network program for filling the prescribed drug or product; determining, based upon the received patient identifier, that a patient associated with the patient identifier has enrolled in the prescription safety network program for utilizing the prescribed drug or product; and determining, based upon the received physician identifier, that a physician associated with the physician identifier has enrolled in the prescription safety network program for prescribing the prescribed drug or product; and generating an approval authorization by the validation engine in response to the eligibility verification request.

The U.S. Food & Drug Administration (FDA) has provided industry guidance on Risk Management, including the development and use of Risk Minimization Action Plans (RiskMAPS) and Risk Evaluation and Mitigation Strategy (REMS). Specifically, risk management is an iterative process of (1) assessing a product's benefit-risk balance, (2) developing and implementing tools to minimize its risks while preserving its benefits, (3) evaluating tool effectiveness and reassessing the benefit-risk balance, and (4) making adjustments, as appropriate, to the risk minimization tools to further improve the benefit-risk balance. Accordingly, there is a need in the industry for systems and methods for supporting Risk Management of prescribed drugs or other products.

Systems and methods for a prescription safety network utilizing eligibility verification transactions


When a piece 6a has stopped at an empty element 3, a castle 10 can be built at the element, and ownership can be set to the element. When another piece 6b has stopped at the element to which the ownership has been set, a sub-game is executed so that a player who owns the castle 10 (element 3), another player who uses a piece 6b, and a third player who uses a piece 6c that is positioned within a given range from the castle 10 participate in the sub-game. When the player who owns the castle 10 has won the sub-game, the player can collect the cost of staying from the player who uses the piece 6b. When the player who uses the piece 6b has won the sub-game, the player who uses the piece 6b can acquire the ownership of the castle 10.

A board game has been known as a video game. A board game is normally configured so that a course in which a plurality of elements are arranged is provided on a game field, a piece (e.g., character or card) used by each player (human player or computer-controlled player) being disposed in each element. The piece is moved based on the number determined by roulette or a dice, and each player aims to reach a given goal earlier than other players (competitive game).
A board game is mainly differentiated by changing the design of the character (piece) or the game field, setting a specific view of the world, setting an event that occurs when the piece has stopped at a specific element on the course, or setting a disturbance rule between the players.
When executing a battle sub-game as an event that occurs during the game, a situation in which a player other than a player who participates in the sub-game must wait for the sub-game to end, and may lose interest in the game may occur. The following technology focuses on this problem. Specifically, a first mode in which a plurality of players sequentially play the game, and a second mode in which at least one player plays the game are executed in parallel, and a player skips the game play in the second mode if his turn came in the first mode, and the next player plays the game in the second mode (see JP-A-2004-105534, for example).

Game execution control method, storage medium, and electronic instrument


An image forming apparatus includes: a body frame having an opening, a cartridge being configured to be removably mounted to the body frame through the opening; and a cover configured to open and close the opening, wherein the cover includes a metallic reinforcement plate that is configured to face the cartridge mounted to the body frame when the cover is closed, and wherein the reinforcement plate includes a first recess part configured to receive therein a part of the cartridge mounted to the body frame when the cover is closed.

There have been proposed an image forming apparatus which has a body frame having an opening, through which a cartridge can be replaced, and a cover for opening and closing the opening. The related-art image forming apparatus is provided with a metallic shield plate (reinforcement plate) in the cover so as to improve strength of the cover.


A custom-fitting prosthetics liner is made without mixing silicone and without making a mold. A thermoformable liner is made by preparing a negative cast from a patient""s residual limb, preparing a positive cast from the negative cast, and placing a thermoformable tubular liner over the positive cast. The positive cast and liner are heated in an oven for a predetermined time and temperature. Having acquired a new geometry, the cast and liner are removed from the oven and allowed to cool to room temperature. The liner is then removed from the cast. Alternatively the liner is heated, placed over the positive cast, cooled and removed. The interior surface of the liner conforms to the shape of the cast. The liner is elastic so that it returns to its new geometry when stretched and released. It therefore holds on to a residual limb even when the residual limb shrinks.

1. Field of the Invention
This invention relates, generally, to the art of prosthetics. More particularly, it relates to a method for making a hard socket or a liner by thermoforming.
2. Description of the Prior Art
Some amputees wear socks on their residual limb to provide cushioning between the residual limb and the surface of a hard socket. However, socks cannot provide an airtight seal between the residual limb and the socket. As a result, various means are employed to prevent relative motion between the residual limb and the socket, but such means are largely inadequate.
Accordingly, inventors in the prosthetics industry have developed various rubber-like cushioning means that are adapted to be worn like socks over the residual limb.
Such cushioning means provide an airtight seal around the residual limb. This enables creation of a vacuum in the unoccupied part of the hard socket, i.e., in the lowermost end of the socket below the residual limb. The vacuum substantially prevents relative movement between the residual limb and the socket.
Most rubber-like liners are unacceptable, however, because they are skin-unfriendly and have other unwanted side effects. Urethane, for example, provides the desired cushioning effect but can irritate the skin and create odors.
Silicone RTV has become the material of choice for custom liners. A mold is made that duplicates the geometry of the patient""s stump and liquid RTV silicone is poured into the mold. The mold is opened after twenty four hours and the custom silicone liner is retrieved.
There are several drawbacks to this process. First, it requires the mixing of silicone. Second, it requires the making of a mold. Moreover, the process takes more than a day to complete.
However, in view of the prior art considered as a whole at the time the present invention was made, it was not obvious to those of ordinary skill in the art how a custom liner could be made in the absence of silicone mixing, mold-making, and the like.
The longstanding but heretofore unfulfilled need for an improved method for making custom liners is now met by a new, useful, and nonobvious invention. The heart of the invention is its provision of a thermoformable prosthetic liner. The novel method of making a thermoformable tubular liner for use in a prosthetic appliance includes the steps of preparing a negative cast from a patient""s residual limb, preparing a positive cast from the negative cast, and placing a thermoformable tubular liner over the positive cast.
The positive cast and the thermoformable tubular liner are then heated in an oven for a predetermined amount of time, such as thirty minutes, at a predetermined temperature such as about ninety to one hundred degrees Celsius. The cast and thermoformable tubular liner are removed from the oven and allowed to cool to room temperature. The thermoformable tubular liner is then removed from the cast. An interior surface of the thermoformable tubular liner will now be observed to conform to the shape of the positive cast.
A procedure that produces the most consistent results includes the steps of preheating the positive cast, placing the thermoformable liner over the heated cast, placing both the positive cast and the thermoformable liner in the oven, and removing both items from the oven and letting them cool to room temperature.
A faster procedure includes the steps of preheating the thermoformable liner, placing the thermoformable liner over the positive cast, and letting both items cool to room temperature.
The thermoformable tubular liner exhibits elasticity when cooled to room temperature. Accordingly, it returns to its pre-stretched size and shape when stretched and released at room temperature.
The thermoformable tubular liner is adapted to be stretched and fitted over a residual limb. Due to its elasticity, it remains on the residual limb even as the residual limb shrinks during the day.
The positive cast may also be preheated in the oven for a predetermined amount of time such as two to three hours at a predetermined temperature such as about ninety to one hundred degrees Celsius prior to said step of placing the thermoformable tubular liner over the positive cast.
The thermoformable tubular is formulated by mixing triblock copolymers of the styrene, ethylene styrene type with mineral oils at a predetermined concentration. The predetermined concentration is about 200 to 400 parts of mineral oil per 100 parts of polymer.
A fabric may also be applied in overlying relation to an exterior surface of the liner. When a fabric is applied, the step of applying the fabric is performed after the step of placing the thermoformable tubular liner over the positive cast and prior to the step of heating the positive cast and thermoformable tubular liner in the oven.
A general object of the invention is to provide a method for making a custom prosthetic liner by a thermoforming process.
A more specific object is to provide a method for making a custom prosthetic liner where the method requires no silicone mixing and no mold-making.
Another very important object is to provide a thermoformable liner that acquires a new geometry upon being heating in an oven and cooled to room temperature, and which returns to that new geometry upon being stretched and released at room temperature so that it may be worn on a residual limb all day without becoming loose if the residual limb shrinks during the day.
It is also an object of this invention to provide a method for making a thermoformable liner that is easy and economical to follow and that results in high quality liners.
Another object is to provide a thermoformable liner having elasticity so that it may be turned inside out to facilitate putting it on and taking it off.
Yet another object is to provide a thermoformable liner exhibiting elasticity so that it can be used with residual limbs having irregular geometries.
These and other important objects, advantages, and features of the invention will become clear as this description proceeds.
The invention accordingly comprises the features of construction, combination of elements, and arrangement of parts that will be exemplified in the description set forth hereinafter and the scope of the invention will be indicated in the claims.

Method for making a thermoformable liner


An isolated polypeptide comprising an amino acid sequence selected from amino acids 506-582 of SV2A, wherein position 573 is N and is glycosylated, or amino acids 449-525 of SV2B, wherein position 516 is N and is glycosylated. The present invention also provides an antibody that binds specifically to the polypeptide, an isolated nucleic acid comprising a polynucleotide that encodes the polypeptide; a method for reducing BoNT/E toxicity in an animal; a method for identifying an agent that blocks or inhibits binding between BoNT/E and an SV2A or SV2B protein; a method for monitoring synaptic vesicle endo- or exocytosis, a method for specifically delivering a chemical entity to a cell which has a specific receptor to a BoNT toxin. Also provided are a chimeric toxin for targeting a proteolytic domain of a toxin to a cell, the chimeric toxin comprising a catalytic or proteolytic domain of the BoNT toxin, and a ligand or a fragment thereof for a non-BoNT receptor on the cell; a method for targeting a proteolytic domain of a BoNT toxin to a cell, an isolated non-neuronal cell comprising a BoNT toxin receptor; and a method for screening for an inhibitor of a BoNT toxin.

Botulinum neurotoxins (BoNTs), produced by the anaerobic bacterium Clostridium botulinum, are the most potent toxins known1. These toxins cause botulism, a severe disease in humans and animals. Botulism usually results from ingestion of contaminated food. The toxins are first absorbed in the digestive system, possibly through a form of transcytosis across epithelial cells that line the gastrointestinal tract. Once in the bloodstream, the toxins target and enter motor nerve terminals and block the release of acetylcholine at neuromuscular junctions (NMJs), causing flaccid paralysis and may lead to death due to respiratory failure1, 2. Botulism is a rare disease in humans and thus the general population has not been immunized against these toxins; this is one of the reasons that BoNTs are among the most dangerous potential bioterrorism threats3.
There are seven serotypes of BoNTs (BoNT/A to G)1, 2. Each toxin is composed of a light chain (˜50 kDa) and a heavy chain (˜100 kDa), connected through a disulfide bond1. The heavy chain mediates cell-entry, via receptor-mediated endocytosis, and translocation of the light chain across the endosomal membrane into the cytosol1. The light chain is a protease that cleaves target proteins in cells1. BoNT/A and E cleave the peripheral membrane protein SNAP-25 (synaptosomal-associated protein of 25 kDa); BoNT/B,D,F and G cleave the vesicle membrane protein synaptobrevin (Syb); BoNT/C cleaves both SNAP-25 and the plasma membrane protein syntaxin4-9. SNAP-25, syntaxin and Syb are collectively referred to as SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor) proteins. These three SNAREs assemble into a complex that mediates the fusion of synaptic vesicles with the plasma membrane10-12; cleavage of these proteins thus inhibits synaptic vesicle exocytosis and blocks the release of neurotransmitters. Because of their ability to inhibit synaptic transmission, BoNTs are used to treat a wide spectrum of medical conditions ranging from overactive muscle disorders to chronic pain13-17.
The extremely high efficacy of these toxins is not only due to their enzymatic activity, but also involves their ability to recognize and enter presynaptic nerve terminals with high affinity and specificity. Thus, a major focus of research has been to identify the neuronal receptors for BoNTs. A "double-receptor" hypothesis has been proposed, in which BoNTs recognize nerve terminals by binding to two components: a group of membrane glycosphingolipids called gangliosides, and specific protein receptors18.
Complex forms of gangliosides, called polysialiogangliosides (PSG), have been shown to bind BoNT/A, B and E with low affinity19-22. Cells lacking gangliosides are resistant to the binding and entry of BoNT/A, B and G; entry can be rescued by loading cell membranes with exogenous gangliosides23-25. Furthermore, mice lacking PSG showed decreased sensitivities to BoNT/A, B, C and G25-29. Interestingly, it was recently reported that BoNT/D does not interact with gangliosides and loss of PSG does not diminish the entry of BoNT/D into neurons27. Furthermore, mice lacking PSG exhibit the same sensitivity to BoNT/D as wild type (WT) mice, indicating that not all BoNTs utilize gangliosides as co-receptors27. It has not been reported whether gangliosides are essential for the entry of BoNT/E or BoNT/F into neurons.
Among the seven BoNTs, the protein receptors for BoNT/A, B and G have been identified (see e.g. U.S. patent application Ser. No. 10/695,577). Two homologous synaptic vesicle membrane proteins, synaptotagmins I and II (Syts I/II), were first found to bind BoNT/B30, 31 and were subsequently shown to function as the protein receptors that mediate entry of BoNT/B into cells25, 32. The toxin binding site lies in a short intravesicular region that is conserved between Syt I and II32. In addition, BoNT/G was also found to utilize Syt I/II as its receptor by recognizing the same toxin binding site on Syt I/II as BoNT/B25, 29, 33.
The co-crystal structure of BoNT/B bound to the toxin binding domain of Syt II was recently reported. This structure revealed that the toxin binds Syt II through a hydrophobic groove within the C-terminal region of BoNT/B24, 34. This hydrophobic groove is conserved in all subtypes of BoNT/B, as well as in BoNT/G24, 29, 34.
The receptor for BoNT/A was recently identified as another synaptic vesicle membrane protein, SV235, 36. All three isoforms of SV2 in mammals (SV2A, B and C) bind BoNT/A and mediate its entry into cells35. SV2 contains twelve transmembrane domains with one large luminal domain (the fourth luminal domain, L4) between the seventh and eighth transmembrane domains37-40. SV2 is a proteoglycan on synaptic vesicles and is heavily glycosylated, possibly through three putative N-glycosylation sites within the L4 luminal domain37, 38, 40-42. Interestingly, the BoNT/A binding site was mapped to a region within the SV2-L4 domain that contains two putative glycosylation sites35. It is not clear whether glycosylation of SV2 affects the binding of BoNT/A.
BoNT/E is one of four BoNTs (BoNT/A, B, E and rarely F) that are associated with human botulism43. It is also one of the leading causes of botulism outbreaks among wild fish and birds44. The protein receptor for BoNT/E, however, has not been identified.
Previous studies revealed that neuronal activity facilitated paralysis in diaphragm muscle preparations exposed to BoNT/E, and increased the cleavage of the substrate protein—SNAP-25—in cultured hippocampal neurons45, 46, providing indirect evidence that synaptic vesicle recycling may enhance the entry of BoNT/E. However, it was reported that BoNT/E does not bind to the recombinant luminal domains of Syt I/II or SV2 purified from E. coli32 33 35, 36.
Previously, BoNT/A and E was reported to bind Syt I in a ganglioside independent manner (Li and Singh, 1998, Isolation of synaptotagmin as a receptor for types A and E botulinum neurotoxin and analysis of their comparative binding using a new microtiter plate assay. J. Nat. Toxins. 7:215-26). This reported binding, however, turned out to be at best non-specific, as subsequent work could not confirm any significant binding between BoNT/E and Syt I (see Dong et al., 2003, Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells, J. Cell. Bio. 162:1293-1303, at FIG. 1A). The lack of binding between BoNT/E and Syt I has also been further confirmed by others (see Rummel et al., 2004, Synaptotagmins I and II Act as Nerve Cell Receptors for Botulinum Neurotoxin G, J. Biol. Chem. 279:30865-30870, at FIG. 1B).
There is thus a need to identify the protein receptor for BoNT/E and to determine whether gangliosides serve as co-receptors for this toxin. Identification of the receptor for BoNT/E will be extremely useful for designing molecules that can reduce or completely inhibit its toxicity. Similarly, knowledge of the BoNT/E binding domain of the receptor will allow the use of polypeptides containing the domain and peptidomimetics thereof as competitors for BoNT binding, thereby reducing or completely inhibiting BoNT toxicity.
There is also a need to target the enzymatic domain of BoNTs, i.e. the light chain that can cleave SNARE proteins, into non-neuronal cells. Many types of cells use SNARE proteins to mediate vesicle release of hormones, cytokines, etc. It is well-known that vesicle-mediated release of transmitters and hormones constitutes a fundamental means of intercellular communication and malfunction of this process leads to many diseases. BoNTs have proven to be a powerful tool to treat diseases caused by over-active neurons. Currently, however, one cannot use BoNTs to treat non-neuronal cells for excessive secretion, mainly because BoNTs cannot enter these cells which do not express BoNT receptors. Even if non-neuronal cells did express BoNT receptors, it was not known if BoNT would be effective in these cells, as non-neuronal cells are known to lack synaptic vesicle recycling pathway, but no entry pathway other than synaptic vesicle recycling was known to result in functional entry of BoNT.
There is a further need for non-neuronal cells who express a BoNT receptor. Such cells would be more stable and more easily to culture, and can be used to replace using primary culture neurons for studying toxin actions and screening toxin inhibitors.

Botulinum neurotoxin E receptors and uses thereof


The present invention is based, in part, on the discovery that galectin-1 (Gal1) plays a role in immune disorders, including Hodgkin lymphoma, anaplastic large cell lymphoma, or MLL+ pre B-cell ALL. Accordingly, the invention relates to compositions, kits, and methods for diagnosing, prognosing, and monitoring immune disorders, e.g., Hodgkin lymphoma, anaplastic large cell lymphoma, or MLL+ pre B-cell ALL.

Classical Hodgkin lymphoma (cHL) is a B-cell malignancy diagnosed in approximately 20,000 new patients in North America and Europe each year; over 90% of these patients are young adults. Classical HLs include small numbers of malignant Reed-Sternberg (RS) cells within an extensive inflammatory infiltrate (Re et al. (2005) J Clin Oncol 23:6379-6386) which includes abundant T helper (Th)-2 and T regulatory (Treg) cells. The tumor cells derive from pre-apoptotic germinal center B cells that have undergone crippling mutations of their rearranged immunoglobulin genes (Re et al. (2005) J Clin Oncol 23:6379-6386; Kanzler et al. (1996) J Exp Med 184:1495-1505). Classical HL RS cells lack B-cell receptor-mediated signals and rely on alternative survival and proliferation pathways activated by transcription factors such as NF-κB and AP1 (Mathas et al. (2002) EMBO J. 21: 4104-4113; Kuppers et al. (2002) Ann Oncol 13:11-18; Schwering et al. (2003) Blood 101:1505-1512). In cHL, the tumor cells exhibit constitutive AP1 activation, express high levels of the AP1 components, cJUN and JUNB, and depend upon AP1-mediated proliferation signals (Mathas et al. (2002) EMBO J. 21: 4104-4113).
Although primary cHLs have a brisk inflammatory infiltrate, there is little evidence of an effective host anti-tumor immune response. The reactive T-cell population includes predominantly Th2-type and CD4+ CD25high FOXP3+ Treg cells that directly suppress immune responses and protect cHL RS cells from immune attack (Re et al. (2005) J Clin Oncol 23:6379-6386; Marshall et al. (2004) Blood 103:1755-1762; Gandhi et al. (2006) Blood 108:2280-2289, Ishida et al. (2006) Cancer Res 66:5716-5722); Th1, NK and cytotoxic T cells are markedly under-represented. In addition, primary cHLs are characterized by a unique cytokine and chemokine profile, including IL-4, IL-5, IL-10 and IL-13 (Re et al. (2005) J Clin Oncol 23:6379-6386; Skinnider et al. (2002) Leuk Lymphoma 43:1203-1210). In fact, IL-13 is a critical growth factor for cHL RS cells (Re et al. (2005) J Clin Oncol 23:6379-6386; Skinnider et al. (2002) Leuk Lymphoma 43:1203-1210). However, the molecular signals and endogenous factors responsible for creating and maintaining the Th2-skewed immunosuppressive microenvironment in cHL remain to be defined.
Galectins have recently emerged as novel regulators of immune cell homeostasis, and tumor immune escape (Rabinovich et al. (2002) Trends Immunol 23:313-320; Liu and Rabinovich (2005) Nature Reviews Cancer 5:29-41; Rubinstein et al. (2004) Cancer Cell 5:241-251; Le et al. (2005) J Clin Oncol 23:8932-8941). Galectin-1 (Gal1), an evolutionarily conserved member of this family (Vasta et al. (2004) Curr Opin Struct Biol 14:617-630), preferentially recognizes multiple Gal β1,4 GlcNAc (LacNAc) units which may be presented on the branches of N- or O-linked glycans on cell surface glycoproteins such as CD45, CD43 and CD7 (Stillman et al. (2006) J Immunol 176:778-789). Through binding and crosslinking of specific glycoconjugates, Gal1 has the potential to inhibit T-cell effector functions and regulate the inflammatory response (Perillo et al. (1995) Nature 378:736-739; Rabinovich et al. (1999) J Exp Med 190:385-397; Toscano et al. (2006) J Immunol 176:6323-6332; Santucci et al. (2003) Gastroenterol 124: 1381-1394; Baum et al. (2003) Clin Immunol 109:295-307). In several murine models of chronic inflammatory diseases, recombinant Gal1 suppressed Th1-dependent responses and increased T-cell susceptibility to activation-induced cell death (Rabinovich et al. (1999) J Exp Med 190:385-397; Toscano et al. (2006) J Immunol 176:6323-6332; Santucci et al. (2003) Gastroenterol 124: 1381-1394; Baum et al. (2003) Clin Immunol 109:295-307).
In a recently described solid tumor (murine melanoma) model, Gal1 was also found to play a pivotal role in promoting escape from T-cell-dependent immunity and conferring immune privilege to tumor cells (Rubinstein et al. (2004) Cancer Cell 5:241-251). In this model, Gal1 blockade markedly enhanced syngeneic tumor rejection and tumor-specific T-cell-mediated immune responses (Rubinstein et al. (2004) Cancer Cell 5:241-251). In another recently described solid tumor (head and neck squamous cell carcinomas), Gal1 overexpression was inversely correlated with the number of infiltrating T cells and was an independent prognostic factor for shorter overall survival (Le et al. (2005) J Clin Oncol 23:8932-8941).
In view of the above, it is clear that there remains a need in the art for compositions and methods to combat immune disorders, including Hodgkin lymphoma, anaplastic large cell lymphoma, and MLL+ pre B-cell ALL. The present invention relates in general to a role of Gal1 in immune disorders, including Hodgkin lymphoma, anaplastic large cell lymphoma, and MLL+ pre B-cell ALL.

Compositions, kits, and methods for the diagnosis, prognosis, and monitoring of immune disorders using galectin-1

Consejo Nactional De Investigaciones Cientificias Y Tecnicas


Small, fast, and inexpensive in-line spectrophotometers can produce in-line spectrums of a substrate before or after printing on the substrate. In-line spectrums are generally far less complete than a reference spectrum produced with a large, slow, and expensive reference spectrophotometer. An in-line spectrum can be mapped to a reference spectrum using a variety of known algorithms. However, the mapping is erroneous when the media substrate type changes. Reference transform matrices and in-line transform matrices can correct the erroneous mapping.

Printers, copiers, and xerographic machines are machines that produce a pattern on a substrate. Typically they consist of a means of obtaining the desired pattern and a marking engine that fixes the pattern to a substrate. Paper, cloth, and plastic are examples of substrates. A pattern can be fixed to a substrate using ink, pigment, or a similar material. Precise control is required to ensure that the pattern produced by the marking engine is acceptably similar to the desired pattern. Over time, the marking engine can experience unintentional change because its mechanical components can change, the ink can change, and the substrate can change. To compensate for unintentional change, a controller can make intentional changes to the marking process such that the marking engine produces a consistent product.
In performing its function, a controller runs control algorithms and needs control inputs and outputs. An ideal control input for a marking engine controller is the reflectance spectrum of printed materials. A spectrophotometer can be used to produce a reflectance spectrum. An in-line spectrophotometer is a device that can be used for monitoring and control of production processes such as printing and copying. A spectrophotometer that can be used as an in-line spectrophotometer is disclosed in U.S. Pat. No. 6,384,918, which is incorporated herein by reference. Utilized as an in-line sensor, an aspect of the disclosed spectrophotometer produces a measurement, called an in-line spectrum that consists of the reflectance measured at eight different wavelengths. Other types of in-line spectrophotometers can also produce in-line spectrums and those in-line spectrums can have a different number of reflectance measurements made at different wavelengths.
In many applications, a spectrum that includes at least 30 different wavelengths is desired. A well-calibrated and precise spectrophotometer or a similar device, hereinafter called a reference spectrophotometer, can make the desired measurement, hereinafter called a reference spectrum. Reference spectrophotometers typically cannot be used in-line because they tend to be large expensive and slow. A close approximation of a reference spectrum, called a reconstructed spectrum, can be calculated from an in-line spectrum using methods disclosed in U.S. patent application publications numbers 20030050768, 20030055611, and 20030055575. The disclosed methods produce a reconstruction matrix that maps an in-line spectrum to a reconstructed spectrum. The referenced methods use an in-line spectrum and a reference spectrum to produce a reconstruction matrix, but thereafter use in-line spectrums and the reconstruction matrix to produce corrected spectrums.
Current art teaches systems and methods by which a reconstructed spectrum having the quality of a reference spectrum can be produced from an in-line spectrum and a reconstruction matrix when the substrate does not change. In the real world, substrates do change. For example, a specific type of paper used as a printing substrate can change between manufacturing batches. Another example is that two versions of a publication can be printed, one on a high quality paper and the other on a low quality paper. Substrate changes cause the reconstruction matrix to become inaccurate. The reason is because the reflectance spectrum of printed material depends on the reflectance spectrums of both the substrate and the printed pattern and because different types of substrates can have significantly different reflectance spectrums. Prior methods and systems produce excellent results as long as the substrate does not change.
Linear algebra, which includes vector and matrix manipulations, is well known. The prior art and the present embodiment are presented via linear algebraic notation. A few of these notations are of particular interest. One is the diag() function that transforms an M element vector into an M by M matrix with the vector elements on the main diagonal of the matrix. Another is the matrix inverse. A matrix multiplied by its own matrix inverse results in an identity matrix. Another concept is the distance between two vectors. One common measure is the Euclidean distance. Given two vectors with two elements, (a, b) and (c, d), the Euclidean distance is sqrt((a−c)*(a−c)+(b−d)*(b−d)), where sqrt( ) is the square root function. Other distance measures such as the Mahalinobis distance, or absolute difference are also common.
The embodiments described herein therefore overcome the aforementioned limitations and flaws of the prior art.

Method for corrected spectrophotometer output for measurements on multiple substrates


A multi-needle sewing machine includes a plurality of needle bars to each bottom end of which a needle can be attached, a needle bar case in which the plurality of needle bars are disposed in a line and that supports the plurality of the needle bars movably in an up-and-down direction, a needle bar case moving device that, by moving the needle bar case, moves one of the plurality of the needle bars to an image capture position, the image capture position being a position that is located directly above a needle drop position that is a sewing position, and an image capture device that is provided in a position that is lined up with the plurality of the needle bars, that is positioned in the image capture position by the needle bar case moving device's moving of the needle bar case, and that captures an image.

The present disclosure relates to a multi-needle sewing machine that has a plurality of needle bars. More specifically, the present disclosure relates to a multi-needle sewing machine that is provided with an image capture device that captures an image.
A sewing machine is known that is provided with an image capture device that captures an image. For example, a sewing machine is known that uses an image capture device to capture an image of and detect a pattern on a work cloth, then moves the work cloth based on the detection result. A sewing machine is also known that uses an image capture device to capture an image of an area that includes a needle drop position of a needle and displays the image on a display device. By looking at the displayed image on the display device a user may easily check the needle position and the state of the sewing without putting his/her face close to the needle drop position. Various effects may thus be obtained by mounting the image capture device on a sewing machine.


An apparatus which outputs an image using a plurality of chroma-key colors is provided. The apparatus includes a chroma-key-color-storage unit that stores multiple chroma-key colors; a microprocessor unit (MPU) that sets a block where the chroma-key color is applied using a pixel address of a foreground image; and a video controller that composes a background image and the foreground image using the block set by the MPU, and displays the composed image in the display unit.

1. Field of the Invention
Methods and apparatuses consistent with the present invention relate to reducing errors that may occur in an on-screen display (OSD) image output device while outputting an image using a chroma-key as a color. More particularly, the present invention relates to an apparatus and method for outputting an image using a plurality of chroma-key colors that sets a block in a foreground image where the chroma-key is applied, applies N chroma-keys (at least two or more) in a predetermined area of the set block, and combines the foreground image with a background image by including p pixels that excludes n pixels and a parity bit in a horizontal line at the (N+1)th pixel.
2. Description of the Related Art
A chroma-key-color-application method, which is one of the methods for composing two images in an OSD image output device, applies a chroma key color to one of two images, which can be a background or a foreground.
The chroma-key color is an effect used when substituting an image by another image or color using a certain color of the image as a key (alpha channel). Keying refers to a process of superimposing a certain part of another image on a certain part of a random image, and refers to a process where an image or a caption to be composed is shown superimposed on the background image. Three types of keys: a chroma key, a luminance key and an external key are currently used in broadcasting and other fields.
A frame buffer is a memory device that temporarily stores image information to be shown on a screen using the raster scan method. A graphics processor receives a display list that expresses a figure from the CPU, converts the list, and records the converted list in the frame buffer. Each memory unit of the frame buffer is reflected on the screen as it is.
FIG. 1 illustrates the structure of an OSD image output device in the related art.
This device includes a system memory 100, a video controller 130, a display unit 160, and a microprocessor unit (MPU) 190.
The system memory 100 includes a background-frame buffer 110 that stores a background image 170, and a foreground-frame buffer 120 that stores a foreground image 180.
The video controller composes the foreground image 180 with the background image 180 where a chroma-key color can be applied in the MPU 190, and displays the composed image in the display unit 160 as if outputting one image.
The control logic 140 of the video controller 130 includes a chroma-key-color-storage unit 150 that stores one chroma-key color.
The MPU 190 applies the chroma-key color to the foreground image 180 using a chroma-key color stored in the chroma-key-color-storage unit 150, and applies the chroma-key color for all pixels of a part where the chroma-key color is applied in the foreground image 180.
FIG. 2 illustrates a method of outputting an OSD image according to the related art.
This method composes a background image 170 and a foreground image 180 where a chroma-key color is applied through the video controller 130, and displays the composed image as one image.
There is a window A 200, which is capable of reproducing video, and a window B 210 which may be used for some other purpose, and there is also a portion where window A 200 and window B are overlapped in a window system.
In other words, when composing the foreground image 180 width the background image 170, a predetermined area 220 of the foreground image, overlapped width window B 210, is handled to be transparent so that the window B 210 is not covered.
In order to make the area 220 transparent by applying one chroma-key color stored in the chroma-key-color-storage unit 150 to all pixels of the area 220 of the foreground image, the area 220 of the composed image 230 is handled to be transparent so that the window B 210 is not covered.
Likewise, according to the related art, the chroma-key color is applied to all pixels of the predetermined area 220, where the window A 200 and the window B 210 are overlapped, using one chroma-key color stored in the chroma-key-color-storage unit 150.
In the case where the foreground image 180, where the chroma-key color is applied, is not a still image, but a video, applying the chroma-key color to all pixels can lower the performance of the MPU 190 that applies the chroma-key color, and can lower the system performance by the overhead generated in the video controller 130 that composes the background image 170 and the foreground image 180 and displays the combined image.
Further, in the case where there is a color that is the same as the chroma-key color stored in the chroma-key-color-storage unit in the area where the window A 200 and the window B 210 are overlapped, the area can be erroneously shown as a transparent image when combined.

Apparatus and method for outputting image using a plurality of chroma-key colors


Various embodiments are generally directed to an apparatus, method and other techniques for receiving image information for a current frame, determining an amount of change between the current frame and a previous based on the image information for the current frame and image information for a previous frame and determining an adjustment of a frame time based on the amount of change between the current frame and the previous frame.

Many existing applications generate visual graphics and update the visual graphics on a screen or display in a constant or high-as-possible rate regardless of the contribution of the actual frame rate to the delivered visual quality. More specifically, a constant frame rate or time frame may be used even when the visual graphics on the display have a relative low amount of change from one frame to the next frame where a lower frame rate would not degrade a user's experience. Thus, a large amount of power is wasted while processing these visual graphics on the display at these constant frame rates or time frames. In today's world, with more and more devices running on battery power, this wasted power shortens the battery life without any added advantage to the user of the device.

Techniques for determining an adjustment for a visual output


Wood products, specifically wood commonly used in construction including dimension lumber, pressure treated pine, composite wood materials such as plywood, particle board, and wafer board, and samples of paper and fabric were variously treated with concentrations of sodium silicate (Na2OSiO2) also known as water glass. Cellulosic materials including dimension lumber, plywood, particle board, wafer board, paper, and fabric were treated with sodium silicate (Na2O.SiO2) in concentrations ranging from 400-0.04 g Na2O.SiO2/kg water. To overcome the disadvantages of sodium silicate, sodium silicate treated samples were further treated to convert the water soluble sodium silicate to a water insoluble form, thereby overcoming the disadvantages of water solubility. and rendering the material effective for internal and external uses. Although treated sodium silicate samples are composed of the same elements in similar proportions, as the untreated sodium silicate samples, the water solubility of the treated and untreated substances is very different.

1. Field of the Invention
The purpose of this invention is to provide 1) sodium silicate (water glass) impregnated wood materials introducing a fire retardant property to wood products, 2) water glass impregnation of other materials, such as paper and cloth, in such a way as to allow their intended functions while reducing the risk of flammability, and 3) wood products treated with sodium silicate can be used simultaneously to impart flame resistant properties to wood and to cause the wood to become termite resistant, providing an environmentally friendly method for long term termite control. Liquid sodium silicate (water glass), applied to the surface of various products, can impart fire retardant properties. In the presence of fire, the sodium silicate will form foam-like crystals that help to provide an insulating barrier between the product and the flame, and will thus slow down the spread of fire. Wood and other products will become less flammable when treated with sodium silicate. The foam-like product appears to be more than a mere change in form of the sodium silicate. It is believed that the foam-like material is the product of a chemical reaction, and also imparts fire retardant properties to the material treated with sodium substrate.
It is a further purpose of the invention to provide a polymerized form of sodium silicate that is water insoluble: As a result of the application of heat, the sodium silicate undergoes dehydration (loss of water) and a process of polymerization that forms increasingly larger moieties of (SiO4)n−1 while still maintaining an overall charge of −1 that forms an association with the free sodium. As the material polymerizes the resultant material increases in size to the point that it is no longer able to dissolve in water, thus becoming insoluble.
Cellulosic materials including dimension lumber, plywood, particle board, wafer board, paper, and fabric were treated with sodium silicate (Na2O.SiO2) in concentrations ranging from 400-0.04 g Na2O.SiO2/kg water and the surfaces of selected samples were further treated with silicon monoxide (SiO), applied in a molecular layer by vapor deposition. Tests were conducted to determine the effectiveness of these materials in terms of fire resistance, durability, duration of effectiveness, and moisture resistance.
Sodium silicate treated samples were further treated by the deposition of a molecular coating of silicon monoxide by vapor deposition. Samples treated by this technique were found to be completely moisture resistant. The combined application of sodium silicate and silicon monoxide was found to provide a fire retardant product that is moisture resistant and decomposition resistant, and therefore effective for internal and external uses. Sodium silicate coated with a thin layer of silicon monoxide does appear to provide an effective fire retardant material.
The purpose of this invention is also to provide 1) sodium silicate (water glass) impregnated wood materials will introduce a fire retardant property to wood, paper and cloth products, 2) the chemical and physical alternations of wood and other samples impregnated with sodium silicate, 3) the effects of moisture, air, temperature fluctuations, and weathering on sodium silicate treated samples, and 4) silicon oxide applied as a micro-layer to the surface of sodium silicate treated materials as an effective moisture barrier and guard against long term deterioration.
Liquid sodium silicate (water glass), applied to various products, can impart fire retardant properties. In the presence of fire, the sodium silicate will form foam-like crystals that help to provide an insulating barrier between the product and the flame, and will thus slow down the spread of fire.
Wood products, specifically wood commonly used in construction including 1″×4″×12″ pine and composite wood materials, such as plywood, were treated with different concentrations of sodium silicate—40% (Na,OSiO,) also known as water glass to test the hypothesis that water glass would make these products flame retardant. Water glass is readily available, is relatively cheap and virtually non-toxic. It can be applied to wood at industrial wood-preserving operations and can be easily applied to the homeowner. The sodium silicate will enter the voids in the wood, and harden into glass. The sodium silicate will separate the wood fibers from one another, and not allow burning.
In addition the sodium silicate penetrates the interiors of porous materials altering cellular structures and forming many microscopically thin glassy layers. A micro-layer of silicon oxide applied to the surface of a sodium silicate-treated material will make the material waterproof as well as prevent long term deterioration.
This invention provides impressive fire retardant properties for sodium silicate treated samples that would make this material all that would be desired in a fire retardant—highly effective, water insoluble, providing strengthening properties, and economical.
A further purpose of this study is to apply sodium silicate solutions to various samples for the purpose of evaluating the fire retardant properties of the resultant products. In the presence of fire, it is anticipated that the presence of non-combustible sodium silicate will render the cellulosic material less available to the flame and will retard vaporization of the cellulosic material; also sodium silicate is expected to form foam-like crystals that help to provide an insulating barrier between the product and the flame which will further separate the sample and the fire source, helping to reduce the temperature of the sample thus slowing down the spread of fire.
Sodium silicate is defined as water soluble (Condensed Chemical Dictionary, 1971). However, during pilot studies, it was noticed that as sodium silicate is exposed to large amounts of heat, parts of sodium silicate buildup would foam up, and this foam was water insoluble. This raised questions about the effect that excessive heating was having on sodium silicate. It was also noticed that when sodium silicate treated wood was subjected to heat from a flame torch, the flame was an orange/yellow color, as opposed to the light yellow traditional color of untreated wood burning. Two kinds of experiments were devised to examine the changes in sodium silicate that occur during exposure to intense flame and heat in the presence of wood. The first test was to examine water solubility versus temperature. The solubility of sodium silicate was measured after being exposed to different temperatures. The second test utilized an x-ray photoelectron spectrometer to examine the chemical composition of foamed sodium silicate byproducts.
Sodium silicate was expected to penetrate the interior of porous materials, altering cellular structures and forming many microscopically thin glassy layers. It is anticipated that the presence of sodium silicate was evident microscopically, and that the distribution patterns and interaction with cellular structures were discernible.
Products treated with sodium silicate were tested for durability, strength, and ability to withstand the effects of prolonged exposure to air, moisture, and weathering.
2. Description of the Related Art
Throughout history, house fires have been a major threat to the well-being of many families. According to the National fire Protection Association, in the United States in 1995 there were 600,000 structural fires in homes and businesses, causing approximately $7,620,000,000 in damages to property. The average loss per fire was $12,700. Over 30,000 people were injured in fires; there were 4585 deaths (12-13 per day) due to fire.
The possibility of awakening to the spectre of threatening flames strikes fear in the hearts of many, including this author, who was awakened to the acrid smell of smoke early on the morning of Jan. 26, 1995. An electrical fire in the garage had spread to nearby materials and had become a raging inferno before being discovered by a family member. The damage in this fire approached $150,000, but fortunately the effects on health were limited to a minor case of smoke inhalation. Unmeasured is the lingering fear, the memories of billowing smoke and fire, and the uneasy knowledge that it could and just might happen again, and that next time the damages might not be limited to property.
In spite of years of research, the United States remains the leader among developed nations in the number of fires occurring per year, the number of injuries and lives lost to fire, and total dollar value of property losses due to fire. The injuries and losses of life due to fire are highest among the elderly (more than double the average population), the infirm and among children. In spite of efforts to the contrary, the monetary damages, numbers of injuries and loss of life are likely to increase substantially in the future.
Fires occur in homes and business largely because of the flammability of the materials of construction and the large quantities of flammable materials placed in homes, offices and other buildings. Fires frequently start with a small flame or a spark that may last only a few seconds. The flames grow because this quick release of energy ignites nearby materials that are readily flammable especially when there is an ample supply of air. The flames then spread to other materials and grow in size and heat intensity. As the temperature increases the kindling temperature of other less flammable materials is reached and they can ignite suddenly causing the fire to spread quickly.
In recent years due to increasing costs for wood, there have been majors changes in the type of wood used in home construction. Historically, solid wood products were used as primary building materials in homes, for example 2×4's and 1×4's were used for framing, and rough wood planks were used for sub flooring and roofing support structures. The trend over the past several years has been to convert more and more from solid materials to composite materials. This is due to decreased costs for composite materials, and to the fact that many composite materials have advantages of lighter weight, less warping and increased strength. In the rush to convert to composite materials, properties related to flammability may not have received due consideration.
FIG. 1 compares weight loss profiles of 2×4 dimension lumber, 1×4 dimension lumber, 1×4 pressure treated pine, roofing shingles, plywood, pressed wood and wafer board samples. All samples were 30 cm in length, and were tested in a chamber in which two propane torches were applied to the bottom surface of each sample according to the procedures described elsewhere in this paper.
The data show that 2×4 samples exhibited the slowest rates of burn and the lowest weight loss of all samples tested. Although 2×4 lumber definitely will burn, the combined effects of two torches applied indefinitely was insufficient to cause a 30 cm sample to ignite and burn spontaneously. All other samples [11-16] ignited and burned readily; however, 1×4 pressure treated pine [11] and 1×4 untreated dimension lumber [12] generally showed slower times for ignition and lower combustion rates that the remaining samples [13-16] as follows: [13] particle board, [14] plywood, [15] shingle, and [16] wafer board.
Data listing ignition times and combustion rates is presented in Table 1 and in FIG. 2. The data for wafer board, shingles and plywood was particularly important because the steep slope of the weight loss profiles for these samples indicated that between 20 and 70 percent of these samples were burned per minute. Plywood (70%/min) is the material of choice in most homes for subflooring, subroofing and occasionally in walls of homes. Wafer board is becoming increasingly popular as a structural material, replacing 2×4's and 4×4's. Each of these three materials was completely consumed in 2-6 minutes in the standard fire tests conducted. In FIG. 2 [17] represents the results of combustion duration (min) for 2×4 lumber; the test was stopped at 60 minutes. in the sample only, combustion was incomplete. In FIG. 2 [18] indicates that spontaneous burning did not occur in the 2×4 lumber sample.
TABLE 1Burn Characteristics of Common Building MaterialsIgnitionCombustion% ofCombustionTimerate (%SampleCompletedBuilding Material(min)sample/min)Consumed(min)2 × 4 dimension>601.63320lumber(test ended)1 × 4 pressure treated56.78918pine1 × 4 dimension16.58715.5lumberparticle board1.27.17910.5wafer board323.3886shingle0.1721.1804plywood0.270.7852.5
Currently, new homes are frequently constructed with sub floors, sub roofs, and all structural components incorporating plywood and wafer board, highly flammable materials that burn at a rate 13 to 45 times greater than that of 2×4 dimension lumber.
There is therefore a need to identify building materials that provide the desired construction-properties and yet decrease the flammability of the materials to below that of 2×4 dimension lumber. There is also a need to increase the fire retardant properties of furniture, fabrics, paper and other combustible materials that are stored inside structures.
Materials to be made resistant to fire in the present study—wood, wood composites, paper and fabric—are primarily natural polymers. As has been demonstrated above, these substances vary in flammability due to the nature of the polymers, and the density and particle size of the substance, eg 2×4 very dense with large particle sizes, and loosely woven fabric—low density with small particle sizes.
The major problems preventing widespread use of fire retardants are the costs of use, effects on physical properties of the treated materials, the water solubility of most fire retardant chemicals, making the treated samples vulnerable to leaching, and the lack of regulations requiring the use of these materials.
Based on the fact that the burn characteristics described above (FIG. 1) were obtained from samples purchased randomly in retail outlets, this investigator concluded that the fire retardants described in the literature have not yet developed attributes that are sufficiently attractive to be implemented in large scale in commercial applications in wood products. Therefore this investigator decided to search for another substance to use in fire retardant applications.
This investigator observed that sodium silicate exhibited strong adhesive properties in addition to being a noncombustible material, and theorized that the adhesive properties might be used to provide fire retardant properties in certain products. This investigator was intrigued by the fact that the possible incorporation of glass-like materials into wood and other products potentially would possibly strengthen the products as well as impart fire retardant properties.
This investigator coated small samples of wood and noticed that when the sodium silicate treated samples were applied to a flame, sodium silicate residues formed bubbles that provided a physical barrier against the flame in addition to reducing available access to flammable materials by oxygen, as heating continued the sample became incandescent. It appeared that as sodium silicate formed bubbles and droplets, the wood remained unaffected by the flame.
The idea for this invention came to me easily. My sister was using water glass to glue glass planes together to make test chambers for her science fair project. I wondered if it was possible to coat wood with water glass and help make the wood fire retardant. As I watched her work with the water glass, I played around with it and coated small pieces of wood and noticed that when the pieces were applied to a very hot flame, the water glass bubbled over forming a natural barrier against the flame. Thus, it appeared to me that as the sodium silicate formed bubbles, the wood remained unaffected by the flame.
A fire retardant material is one having properties that provide comparatively low flammability or flame spread properties (ASTM 1992). There are a number of materials that have been used to treat wood for fire retardancy including ammonium phosphate, ammonium sulfate, zinc chloride, dicyandiamide-phosphoric acid and sodium borate. Solutions of these fire-retardant formulations are effective when injected into the wood under pressure (Condensed Chemical Dictionary 1971). The sodium salts of silicon, or water glass, however, have not been identified as a fire retardant. If my hypothesis is correct, that water glass is an effective fire retardant when applied as a coating, then it could be an important finding since it is virtually non-toxic, safe to use, relatively cheap, readily available and can be easily used by the homeowner.
Sodium silicate (water glass) is a member of the family of soluble sodium silicates and is considered the simplest form of glass. The formula varies from Na2O3 SiO2 to 2 Na2OSiO2 depending on the proportions of water. The composition used in this study was a 40 percent concentration. Water glass is derived by fusing sand and soda ash; it is noncombustible with low toxicity. It is used as catalysts and silica gels; soaps and detergents; adhesives; water treatment; bleaching and sizing of textiles and paper pulp; ore treatment; soil solidification; glass foam; pigments; drilling muds; binder for foundry cores and molds; waterproofing mortars and cements; and impregnating wood. The latter use, however, has not been linked with fire retardancy (Condensed Chemical Dictionary 1971).
The terms used with flame-resistant materials are sometimes confusing. Fire resistance and flame resistance are often used in the same context as the terms fireproof or flameproof. A material that is flame resistant or fire resistant does not continue to burn or glow once the source of fire has been removed, although there is some change in the physical and chemical characteristics of the material. Fireproof or flameproof refer to material that is totally resistant to fire or flame, such as asbestos. Most organic material like wood undergo a glowing action after the flame has been eliminated. This "afterglow" may cause as much damage as the flaming itself.
The mechanisms of fire-retardancy are complicated. The coating theory reveals that fire resistance is due to the formation of a layer of fusible material which melts and forms a coating, thereby excluding the air necessary for the flame to propagate. This theory, first reported by Gay-Lussac in 1821, was the basis for the development of fusible salts such as carbonates, borates, and ammonium salts. The gas theory theorizes that the flame retardant produces noncombustible gases which dilutes the flammable gases. The thermal theory suggests that the flame is dissipated by an endothermic change in the retardant and the heat supplied from the source is conducted away from the wood so fast that combustion temperatures are never reached. Chemical theory says that the strong acids and bases (water glass is a strong base) impart some degree of fire retardancy (Concise Encyclopedia of Chemical Technology 1985).
My theory, and the basis for my hypothesis, is that sodium silicate can make wood and other products fire retardant. The sodium silicate will enter the voids in the wood, and harden into glass. The sodium silicate will separate the wood fibers from one another, and not allow burning. Any flame applied to the samples will not burn or spread, because it comes in direct contact with the sodium silicate. The preliminary observations I made on my own with sodium silicate and small pieces of wood showed that when in contact with a very hot flame, the sodium silicate bubbles over, forming a natural barrier against the flame and the wood remains unaffected by the flame.
To test my theory, I decided to treat (by dipping and soaking) dimension lumber with different concentrations of water glass and to burn the treated products with a propane torch to determine the potential for fire retardancy.

This patent is subject to a terminal disclaimer.

Process of using sodium silicate to create fire retardant products


An anti-shake apparatus of a photographing apparatus comprises a movable unit and a fixed unit. The movable unit has an imaging device and is movable in first and second directions. The fixed unit slidably supports the movable unit in both the first and second directions. The movable unit has a hall-element unit. The magnetic-field change-detecting unit has a horizontal hall-element which is used for detecting a position of the movable unit in the first direction as a first location, and a vertical hall-element which is used for detecting a position of the movable unit in the second direction as a second location. Application of voltage to input terminals of the horizontal hall-element and the vertical hall-element is performed during a position detecting operation of the movable unit, and is stopped at a time other than that for the position detecting operation.

1. Field of the Invention
The present invention relates to an anti-shake apparatus for a photographing device (apparatus), and in particular to a position-detecting apparatus for a movable unit that includes the imaging device etc., and that can be moved for correcting the hand-shake effect.
2. Description of the Related Art
An anti-shake apparatus for a photographing apparatus is proposed. The anti-shake apparatus corrects for the hand-shake effect by moving a hand-shake correcting lens or an imaging device on a plane that is perpendicular to the optical axis, corresponding to the amount of hand-shake which occurs during imaging.
Japanese unexamined patent publication (KOKAI) No. 2002-229090 discloses an anti-shake apparatus for a photographing apparatus. The anti-shake apparatus performs a moving operation of a movable unit, which includes a hand-shake correcting lens, by using a permanent magnet and a coil, and a position-detecting operation of the movable unit, by using a hall element and a permanent magnet.
However, an application of voltage to input terminals of the hall element is performed during the position detecting operation of the movable unit and at a time other than that for the position detecting operation. This application of voltage to the input terminals of the hall element at a time other than that for the position detecting operation, is an unnecessary consumption of electric power.


An apparatus and method for curling hair using sheets of paper is shown and described in detail. Two sheets of paper are used to fold a locket of hair and attach the hair adjacent the user""s scalp for curling. The curlers are disposable after use. Each sheet is folded in a unique pattern to hold the hair during curling and to connect the sheets together. The method permits the user access to curlers during travel.

The present invention relates to a method and device for curling hair using conventional disposable sheets of paper such as toilet or tissue paper. A roll of toilet paper is commonly provided to guests of hotels. The present invention provides a method and device for using the paper to form curlers which may be used by the guest. The availability of the sheets makes the invention a desirable product for those travelers who would rather not bring plastic or conventional curlers on a trip.
Conventional curlers used to curl hair are commonly sold in a container and are often accompanied by a curling iron and other hair supply products. The container is usually the size of a small suitcase which must be packed inside a larger suitcase or carried separately by hand. The additional suitcase or storage space taken up by the curlers is an extra burden for the traveler.
There are many patents on curlers. Most curlers include surfaces for catching the hair or clips for supporting a locket of hair on a curler roller. These curlers are reusable and may be cleaned in a dishwasher or by hand. For example, the patent to Grooms U.S. Pat. No. 5,694,955 discloses a device for curling hair having a soft deformable core with two ends and a rolling surface. Bonneau U.S. Pat. No. 2,601,428 discloses a hair curler made of an envelope of tin foil, wire tie and paper sheets. Brams U.S. Pat. No. 5,813,419 discloses a hair curler made of sheet semi-rigid material. All of these curlers are factory made curlers designed for sale and reuse.
Although there have been many attempts to invent the perfect curler, all the curlers mentioned above fail to provide the user with a simple inexpensive answer. There is a need for a disposable curler in the industry. Moreover, there is a need in the industry for a hair curling solution which is readily available at most hotel rooms or in most households.
An object of the present invention is to provide a method of curling hair on a live human or animal using a roll of perforated sheet material which has been perforated into removable sections of sheet material.
Another object of the present invention is to provide a method of curling hair using sheet materials in the form of polygon shaped blanks.
Yet another object of the present invention is to provide a curler formed from two sheets of paper material.
A sheet of paper approximately four inches by four inches is removed from a perforated roll of paper, such as toilet paper. The sheet of material is folded to form two ends including a first pocket and a second pocket. A second sheet of material is removed from the roll and twisted to form an elongated twisted sheet of material having two ends.
The second sheet of material is folded and each end is inserted into a corresponding pocket of the first sheet of material to form an opening for receiving a section of hair. The paper sheets may dipped in permanent solution or water prior to use. After inserting a section of hair, the paper and the hair are rolled into a curl adjacent the user""s scalp. Finally, the curler and hair may be heated to curl the hair.


A disposable, absorbent diaper comprising a topsheet, a liquid impervious backsheet associated with the topsheet, and an absorbent core disposed between the topsheet and the backsheet, wherein the absorbent core has a dusting layer of mechanical pulp fibers, a continuous primary layer of mechanical pulp fibers containing from about 8% to about 60%, on a total primary layer dry weight basis, of discrete particles of polymeric gelling material, and a water-permeable core reinforcing layer disposed between the dusting layer and the primary layer. The mechanical pulp fibers, preferably chemithermomechanical pulp fibers, have an average fiber length of at least about 1.9 mm and are in a highly disintegrated condition.

Absorbent articles, such as disposable diapers, are generally provided with absorbent cores to receive and retain body fluids. In order for such absorbent articles to function efficiently, the absorbent cores must quickly acquire body liquids into the structure from the point of application and subsequently distribute the body liquids within and throughout the absorbent core to provide maximum absorbency and containment. In order to efficiently perform these functions, the absorbent core should substantially maintain its shape during manufacture, shipping and packing, and fitting and usage by the user, including usage subsequent to initial wetting by the user.
Various material have been employed as the absorbent media in disposable absorbent articles. The most commonly utilized absorbent media in recent years is chemically pulped wood fibers provided in a highly individualized, i.e., disintegrated, state referred to in the art as "fluff". Fluff is typically air-laid in the form of webs, which are then utilized as the absorbent core of absorbent disposable articles.
Performance of disposable diapers has, in recent years, been improved through the incorporation into the absorbent cores of polymeric gelling materials, which have the capability of absorbing fluids to form gels which lock-away the fluids and which do not release such fluids upon application of pressure to the absorbent core (e.g., by the user rolling about after discharging fluids into the absorbent article). Due, at least in part, to the performance capabilities of disposable absorbent articles having absorbent cores of chemical pulp fibers and polymeric gelling materials, the trend has been to manufacture disposable articles having absorbent cores which are thinner, and of higher density, than conventionally practiced prior to the widespread usage of polymeric gelling materials.
Although the chemically pulped fibers commonly used in disposable absorbent articles provide good overall performance, especially in terms of web integrity, it is desirable to utilize fibers in disposable absorbent articles which are more efficient from the standpoint of utilization of natural resources. Typically, the chemically pulped fibers that are utilized as fluff in absorbent articles constitute only about 40% of the wood source from which the fibers are processed. Additionally, it is desirable to provide absorbent cores of fibers made by processes which require reduced levels of pulping chemicals (e.g., sulfate in the "Kraft" chemical pulping process) relative to processes conventionally used to make chemical pulp fibers. One type of absorbent fibrous media which fits these objectives is known generally as mechanical pulp, which term includes such variants as thermomechanical pulp and chemithermomechanical pulp. The processes used to make these mechanical pulps, which are known to those skilled in the art, provide substantially higher yields (typically in excess of 85%) than chemical pulp processes. In addition, mechanical pulp processes involve reduced usage of processing chemicals.
In spite of the above advantages, mechanically pulped fibers have not been commonly utilized in commercially marketed disposable absorbent articles, except in countries where environmental concerns are especially prevalent. One of the drawbacks conventionally associated with mechanically pulped fibers is that they provide relatively low strength when formed into air-laid webs. The use of such low strength webs as absorbent cores in disposable absorbent articles has conventionally required the use of a strength-imparting envelope. Webs of low strength mechanical fibers including an interior reinforcing layer in addition to the required tissue envelope layers are also known. See, for example, U.S. Pat. No. 4,327,729, L. W. King, issued May 4, 1982. Unfortunately, the presence of an additional structural element between the absorbent core and the topsheet of an absorbent article can impede the rapid absorption of fluids discharged during use. Other drawbacks traditionally associated with low strength mechanical pulp webs are that mechanical pulp fibers are less hydrophilic than chemical pulp fibers and have reduced ability to retain fluids in the void spaces between fibers. Both of these factors contribute to reduced performance in the context of absorbent article performance relative to chemical pulp fibers.
In view of these drawbacks, it is desirable to provide a disposable absorbent diaper which incorporates, as its primary absorbent fibrous media, high yield, mechanical pulp fibers. It is an object of the invention to provide such a disposable absorbent article which has absorbency and containment performance, as well as absorbent core structural integrity, comparable to disposable absorbent diapers having chemically pulped fibers as the principal absorbent fibrous media. It is particularly an object of this invention to provide disposable absorbent diapers having thin absorbent cores made from mechanical pulp fibers which provide absorbency and containment performance, as well as absorbent core structural integrity, comparable to disposable absorbent articles chemical pulp fibers and polymeric gelling materials incorporated therein.
These objectives, and other benefits as may become apparent to those skilled in the art, are believed to be achieved by the invention which is described hereinafter.

Absorbent articles containing mechanical pulp and polymeric gelling material


An electrically erasable programmable nonvolatile memory cell includes a semiconductor substrate having a first substrate region and a second substrate region apart from the first substrate region in a lateral direction, a channel region between the first substrate region and the second substrate region, an electrically conductive control gate insulated from and disposed over a first channel portion of the channel region, an electrically conductive floating gate insulated from and disposed over a second channel portion of the channel region, an electrically conductive source line electrically connected to the second substrate region, and an electrically conductive erase gate insulated from and disposed over a tip of the floating gate.

There is a constant need to shrink the size of electrically programmable and erasable nonvolatile memory cells. However, as memory cell sizes scale down, dimension size changes result in changes in capacitive coupling between memory cell elements, and in the widths of various critical regions, all of which have the potential to negatively affect the operation margin of the memory cells, unless significant design changes are made to the structure of the memory cell. Further, as floating gate sizes scale down, an erased floating gate has decreased capacity for storing positive charges, which leads to lower signal-to-noise (SNR) ratios and higher error rates unless design changes are made to compensate.

NOR memory cell with L-shaped floating gate


Receptor protein kinases (RPTKs) transmit extracellular signals across the plasma membrane to cytosolic proteins, stimulating formation of complexes that regulate key cellular functions. Over half of the known tyrosine kinases are implicated in human cancers and are therefore highly promising drug targets. A large-scale loss-of-function analysis of tyrosine kinases using RNA interference in the clinically relevant Erb-B2 positive, BT474 breast cancer cell line showed that Bruton's tyrosine kinase (BTK), a cytosolic, non-receptor tyrosine kinase that has been extensively studied for its role in B cell development, is required, in altered form, for BT474 breast cancer survival. This alternative form contains an amino-terminal extension that is also present in tumorigenic breast cells at significantly higher levels than in normal breast cells.

Protein tyrosine kinases (PTKs) mediate the reversible process of tyrosine phosphorylation, providing the signals that activate or block signal transduction pathways that govern cell survival decisions and as such are tightly regulated. Genes that regulate extracellular growth, differentiation and developmental signals are commonly mutated in cancers. Perhaps it is not surprising therefore that PTKs comprise the largest group of dominant oncogenes. Thirty of the 58 receptor protein tyrosine kinases (RPTKs) have been implicated in human cancer (Blume-Jensen and Hunter, 2001). Less than half of the cytoplasmic protein tyrosine kinases have been associated with tumorigenesis, due not to a less critical role in signal transduction regulation, however, but from an experimental bias that has focused on viral counterparts to gain insight into potential transforming mechanisms (Blume-Jensen and Hunter, 2001).
In recent years there has been a surge in efforts to discover genes critical to cancer signaling pathways that when inhibited would provide specific anti-cancer therapies (Lu and Chu, 2008) (Sabbah et al., 2008). Trastuzumab, (Herceptin), a humanized monoclonal antibody that specifically inhibits the HER2/neu/ErbB-2 (hereafter referred to as ErbB-2) receptor tyrosine kinase, which is amplified and/or over-expressed in 25-30% of metastatic breast cancers, was the first targeted therapy to be approved by the FDA. As a single-agent monotherapy, however, the primary response rate to trastuzumab is low, (12% to 34%) and the rate of primary resistance high, between 66% to 88% (Nahta and Esteva, 2006). Notably, however, the time to disease progression, response rate and overall survival increase when trastuzumab is used in combination with paclitaxel or docetaxel (Nahta and Esteva, 2006). Indeed, recent successes in targeting molecules integral to survival pathways in combination with traditional chemotherapeutics has led to significant efforts to identify new drug targets that sensitize the breast cancer cell towards cell death (MacKeigan et al., 2005); (Call et al., 2008). Such additional drug targets, specific to or over-expressed in breast cancer cells compared to normal tissues, and known to be functionally relevant, are still needed, as are cancer-specific markers for use in detecting or diagnosing cancer.

Bruton's tyrosine kinase as anti-cancer drug target

THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK