A method of making an intraluminal device having an implanted configuration and a modified configuration following the implanted configuration. The method includes preparing the implanted configuration of the intraluminal device by forming a support scaffold, creating a patch, and coupling the patch to the support scaffold. The support scaffold can include a lumen defined by a luminal surface. The patch can be coupled to the support scaffold along a length of the luminal surface such that the patch covers less than a full circumference of the luminal surface along the length. The patch is designed to be removed from the support scaffold following implantation of the intraluminal device to transition the intraluminal device from the implanted configuration to the modified configuration.

Chronic venous insufficiency (CVI) is a long-term condition caused by malfunctioning (incompetent) valves in the veins. It may also occur as the result of a past blood clot in the legs. CVI is a medical condition where the valves of the vein do not fully close and permit blood to travel upstream. The condition causes blood to pool in the legs. FIGS. 1A-1B illustrate an exemplary vein having a properly functioning valve in which blood may pass through the vein in a single direction back to the heart. FIGS. 1C-1D illustrate an exemplary vein suffering from chronic venous insufficiency in which the vein valve does not fully close and thereby permits blood to flow away from the heart. Typical symptoms include swelling of the legs, varicose veins and ulcers.
Currently, the only effective way to replace a damaged valve is surgery to either modify an existing valve or create a new valve by separating venous wall layers. However, these methods are extremely invasive and require the external access to the vein through dissection. FIGS. 2A-2C illustrate an exemplary deep venous reconstruction surgery in which the vein is opened in FIG. 2A, the venous layers are dissected in FIG. 2B, and a valve is created from the dissected layers in FIG. 2C. As illustrated, the surgery is very invasive requiring external vein dissection, reconstruction, and closure.

Device and associated percutaneous minimally invasive method for creating a venous valve


A phenylacetamide derivative of formula (I) have potent analgesic and anti-inflammatory activities and exhibit less irritability and toxicity: ##STR1## wherein, X, Y, W, n, m and Ar are as defined in the specification.

Capsaicin, N-vanillyl-trans-8-methyl-6-nonenamide, is a hot substance found in the fruit juice of a plant belonging to the genus Capsicum. U.S. Pat. No. 4,313,958 issued to LaHann, and European Patent No. 0 282 127 granted to Garnder, disclose as having analgesic activities such natural capsaicin and synthetic capsaicin derivatives, e.g., N-{4-(2-aminoethoxy)- 3-methoxybenzyl}amide derivatives.
Also reported in LaHann et al., U.S. Pat. No. 4,424,205; Gardner et al., U.S. Pat. No. 5,045,565; and Park et al., U.S. Pat. No. 5,242,944 are various homovanillic amides, i.e., phenylacetamide derivatives, as having pharmacologically and physiologically activities superior to the conventional capsaicin derivatives. However, each of thoese disclosed in the prior art still exhibits some of the skin irritability and toxicity unique to a capsaicin.

Korea Research Institute of Chemical Technology


Systems and methods for locating the shooter of supersonic projectiles are described. The system uses at least five, preferably seven, spaced acoustic sensors. Sensor signals are detected for shockwaves and muzzle blast, wherein muzzle blast detection can be either incomplete coming from less than 4 sensor channels, or inconclusive due to lack of signal strength. Shooter range can be determined by an iterative computation and/or a genetic algorithm by minimizing a cost function that includes timing information from both shockwave and muzzle signal channels. Disambiguation is significantly improved over shockwave-only measurements.

The present invention relates to law enforcement technologies and security, and more particularly to methods and systems for determining the origin and direction of travel of supersonic projectiles based on shockwave and muzzle sound information. The methods and systems are capable of determining and disambiguating shooter locations even for large distances between shooter and sensor and when the signal from the muzzle sound is weak.
Systems and methods are known that can determine the general direction and trajectory of supersonic projectiles, such as bullets and artillery shells by measuring parameters associated with the shockwave generated by a projectile. One such system, described in U.S. Pat. No. 5,241,518 includes at least three spaced-apart sensors, with each sensor incorporating three acoustic transducers arranged in a plane. The sensors generate signals in response to the shockwave which are related to the azimuth and elevation angle to the origin of the shockwave. However, shock-wave-only measurements are unable to determine the distance between the sensor(s) and the origin of the shockwave. With additional information from the muzzle blast, an accurate location of the origin of the projectile and a line of bearing to the origin of the projectile can be determined. However, when the muzzle blast is masked, shadowed or otherwise distorted, the signal from the muzzle blast may be difficult to discern from spurious signals and noise, so that the derived distance information may become inaccurate. Moreover, even if a clearly discernable muzzle blast signal were received from distant shooter locations, determining the range (distance) of the shooter can still remain a problem.
Conventional systems employ acoustic sensors, e.g., microphones, which can be relatively closely spaced (e.g., 1 meter apart) or widely dispersed (e.g., mounted on a vehicle or carried by soldiers on a battlefield), and measure shockwave pressure omni-directionally at their respective locations.
The azimuth angle, elevation angle, and range of a shooter with reference to the sensor location can be determined by measuring Time-of-Arrival (TOA) information of the muzzle signal and shockwave signal at each sensor. Each of the sensors encounters these signals at a different time and generates an electric signal in response to the shockwave pressure. The signals from the various sensors are processed, and a direction (azimuth and elevation) from the sensor(s) to the origin of the shockwave as well as the range, and hence the trajectory of the projectile can be determined.
Conventional algorithms require at least 4 shockwave and muzzle detections so that a 4×4 matrix can be inverted to map a plane wave on the shockwave TOA. Small errors in shock and muzzle TOA determination can produce substantial errors in the range estimations. Moreover, the conventional algorithms assume a constant bullet speed along the bullet trajectory, which gives inaccurate range estimates for long-range shots being fired from a distance of more than approximately 300 m.
Accordingly, there is a need for rapidly converging algorithms capable of accurately estimating a distant shooter range.
In addition, there is a need to disambiguate shock-wave only solutions for the shooter direction. This is typically accomplished by using the muzzle signal. Disadvantageously, however, less than 4 muzzle sounds may be detected in many situations, for example, due to extraneous noise, reflections, etc., that can mask the muzzle signal. It would therefore be desirable to provide a method for reliably disambiguating shock-wave only solutions even if muzzle blast signals are detected on less than 4, for example 2 or 3, acoustic sensors.
In some situations, an initially detected muzzle signal may be discarded as being unreliable, for example, because the detection level is too low to indicate a muzzle blast signal; or because the muzzle energy is not readily evident in the raw signal; or because echoes from the shockwave are stronger than the muzzle blast and arrive earlier than the actual muzzle blast, causing the detection system to falsely identify shock as muzzle. These uncertain muzzle blast signals, if properly identified and extracted, may still be useful for refining detection of the shooter position, in particular in conjunction with the detection of shock-wave signals.
It would therefore also be desirable to provide a method for extracting muzzle signals that may be obscured by acoustic signatures unrelated to the muzzle blast.

Systems and methods for determining shooter locations with weak muzzle detection


A segmented, belt-driven conveyor system for use in clean environments is described. High speed, high density, collision free throughput of work piece carriers is enabled through belt-driven conveyor segments each having co-rotating drive wheels. The drive wheels have a cylindrical profile. Predefined acceleration/deceleration profiles may be employed by a motor controller to affect optimal changes in work piece carrier speed across the respective drive segment.

Many manufacturing factory environments consist of spatially distributed processing tools, as opposed to sequential tools located along a linearly arranged assembly line. This is especially true for manufacturing environments where work in process, or a "work entity," re-enters a tool after being processed by another tool or tools. Re-entry into the same tool avoids tool duplication, which is particularly important in environments where the capital cost of the tools is high.
A semiconductor manufacturing environment is an example of an environment where, due to high tool cost, a work entity enters a given tool, or type of tool, multiple times. Processing tools in a semiconductor manufacturing environment are typically spatially distributed in the factory according to function. Thus, the work flow resembles a chaotic movement of the work entity. With multiple work entities being operated upon and moving between multiple tools at the same time, the respective work flows intersect.
In modern factories, the progress of multiple work entities through the high number of manufacturing steps and associated tools is enabled by transport networks. Simultaneous processing of plural work entities, necessary to maximize usage of the factory tools and to maximize product output, results in highly complicated logistics. High efficiency and coordination in work entity movement is thus required. Without an efficient transportation network capable of rapid, real time response, bottlenecks in the work flow into or out of some process tools can develop (flow density), while other process tools are starved of work. Such an efficient transportation network thus must have high delivery capacity, high speed, and asynchronous capability by which work carriers can move independently of each other. The transport infrastructure is the enabling technology for such efficient logistics.
In a recursive process flow environment, such as within a semiconductor manufacturing environment, the simultaneous utilization of up to hundreds of individual process tools requires a logistics network that is capable of delivering the right work entity at the right time to each one of the tools. The higher the utilization of each processing tool, the higher the factory output, which simultaneously translates to the increased efficiency of business capital.
Conveyor systems are one particular type of transportation system used in contemporary factory environments. A conveyor network may be shared by several hundred moving work carriers concurrently dispatched to various tools. Delivery capacity will depend on flow density and conveyor speed. However, flow density and speed are limited by the additional requirements of zero tolerance for collisions between work entities within the conveyor system, and of a particulation free environment. Thus, a conflict arises between the above requirements.
A conveyor network typically has intersections, nodes, and branches to multiple locations in a factory. The open conveyor ends, at work processing locations, are the input and output ports for the conveyor transport domain. At these ports, work entities enter and leave the conveyor domain. When a work entity needs to travel from one of these ports to another in the prior art, a path needed to be cleared for the transit to satisfy the requirement of collision avoidance. Normally, external or centralized dispatch software arranges for such a transit by simultaneously controlling the movement of all other work entities that would otherwise interfere with the work entity in question. This dispatch software is complex, due to the aforementioned throughput requirements. The work entities need be moved concurrently with each other and at maximum rate without collisions.
In addition to the challenge of highly complex control in dense manufacturing environments, particulate generation by conveyor systems is of great concern in clean room environments. Thus, the efficiency of transport systems in such environments must be weighed against the opportunities for contamination.
Traditional roller conveyors have achieved extremely low particulate generation. However, such arrangements have not been able to achieve high acceleration of items or carriers transported thereon (generically referred to simply as "carriers" herein) from a stopped condition. This is not due to a lack of torque available for the drive rollers but instead due to the fact that when high starting torque is applied the roller wheels may slip and squeal. This is akin to auto tires squealing when accelerating too rapidly from a stop.
In certain embodiments, a hysteresis clutch has been utilized in conjunction with synchronous or stepper motor driven rollers or wheels, depending upon the embodiment, to eliminate such slippage between the carriers and drives. Hysteresis clutches enable asynchronous soft buffering, a process for moving carriers independent of each other and starting and stopping the carriers in a smooth fashion. However, while successful at preventing slippage, hysteresis clutches may make it difficult to achieve high rates of acceleration, including in the multiple g range. Very fast acceleration and deceleration are required in order to increase throughput and thus the density of carriers traveling on the soft buffered conveyor where carriers must never collide. Since the carriers move asynchronously, they need to stop fast and short of a collision with a downstream carrier to achieve increased density in a conveyor environment, as well as start fast so as to minimize interference with upstream carriers. Preferably, start and stop should occur within a line segment that is a little larger than the carrier.
Principles of physics dictate that the frictional force required to move an object on a surface is dependent on the normal force and the coefficient of friction for the materials. In other words, it is independent of the area in contact. However, with compressive materials, higher friction forces can be achieved by selectively increasing the surface contact. A result of this realization was the increased utilization of belts for carrier transport, instead of wheels with a rubber drive surface in contact with carriers. This increase in surface area contact in effect increased the friction force between driving and driven surfaces.
Unfortunately, simply disposing a driving belt on a respective set of wheels is not clean in terms of particulate generation, particularly with respect to that resulting from the use of driven and idler wheels alone. The particulation of the belts results primarily from interaction of the belt with the wheels below the belt, i.e. those supporting the weight of a carrier. Previous investigations into the source of particulate generation determined that in many cases the belt was not in continuous, full contact with the wheels below it due to machining tolerances in the wheels, the respective axles, and/or the rails that support the wheels. For example, some supporting idler wheels were found to be in constant contact with the overlying belt and thus were turning in concert with the belt while others started and stopped depending on when the belt touched them. The latter contact was haphazard, resulting in frictionally-induced spin up and stops of the supporting idler wheels. This effect was sometimes dependent upon whether a carrier was above the respective portion of belted conveyor.
In order to impart continuous contact between the belt and all of the wheels in a respective conveyor section, including the idler wheels, it was proposed that the belt be woven in a serpentine path between wheels, such as over two idler wheels and then down under the next. While successful in maintaining contact between the belt and all of the respective wheels, this resulted in an increased motor torque requirement, which also required increased electrical current and thus operational cost.
There remains the need for an optimized transport solution that results in high density, rapid, flexible, and asynchronous work entity transport, high delivery capacity, avoidance of work entity collisions, and low particulation, for use in clean room environments.

High volume conveyor transport for clean environments


It is provided an insulating substrate including through holes for conductors arranged in the insulating substrate. A thickness of the insulating substrate is 25 to 100 μm, and a diameter of the through hole is 20 to 100 μm. The insulating substrate includes a main body part and exposed regions exposed to the through holes and is composed an alumina sintered body. A relative density of the alumina sintered body is 99.5 percent or higher. The alumina sintered body has a purity of 99.9 percent or higher, and has an average grain size of 3 to 6 μm in said main body part. Alumina grains are plate-shaped in the exposed region and the plate-shaped alumina grains have an average length of 8 to 25 μm.

As a substrate for mounting an electronic device such as a SAW filter or the like, a via substrate is used. The via substrate has the structure of providing through holes in an insulating substrate such as ceramics and of filling the through holes with a conductor to form through electrodes. Recently, as communication devices, such as mobile phones, are miniaturized, it is demanded to miniaturize, and reduce a height of, an electronic device used therefor. The via substrate forming a part of the device is also required to be thinned.
Further, as to a diameter of the through hole of such substrate, it is demanded reduction of a size of the hole to 100 μm or smaller, for example, and it is further demanded to form many holes at a high density. Further, as a material of the supporting substrate, a high resistance is required for suppressing leak current between wirings.
Therefore, it is demanded that the via substrate has a strength for enduring handling of it during production process in the case it is thinned. On the other hand, since the via substrate is finally divided into individual pieces by dicing, its processability is required to be good.
Since through electrodes of the via substrate are produced by a thin film-formation process such as vapor deposition, sputtering or the like, it is required that the upper face, bottom face and inside of the through hole are smooth, for avoiding disconnections or the like due to unevenness. The through holes are formed by pressing using a metal mold and laser processing before the sintering, or by laser processing or blast processing after the sintering (Patent documents 1 to 3).
As a material of the via substrate, alumina ceramics has been used, because of excellent mechanical strength, heat resistance, insulating property or the like. Further, an alumina ceramic material of a high purity is superior in transparency and resistances to alkali and plasma, it has been widely used for a luminous vessel for a high-luminance discharge lamp, a member for a semiconductor production system and a dummy wafer (patent documents 4 to 7).

Insulating substrates including through holes


A contrast agent composition and a method of diagnostic imaging are provided. The composition comprises a pharmaceutically acceptable carrier and a metal-complex comprising a ligand having structure (XXX):

Non-invasive magnetic resonance imaging (MRI) provides anatomical details for diagnosis and offers a highly resolved contrast between the specific tissues or organs of interest. The MR contrast enhancement agents improves both the quality of images obtained in an MR imaging procedure and the efficiency with which such images can be gathered. The use of MR contrast enhancement agents in MR imaging protocols has proven to be a valuable addition to the MRI technique.
Various metal chelates may serve as MR contrast enhancement agents, however the toxicity of free metal ions, stability of metal-chelate complex, and rapid rate of clearance of the chelates from the body during the imaging procedure are a few of the disadvantages associated with metal chelates. For example, while gadolinium (Gd) chelates are non-toxic, the Gd metal in free ionic form is toxic. For manganese (Mn)-chelate, dissociation of the chelating ligand from the metal center happens, which is also not desirable. As such, considerable efforts have been made to increase the efficiency and reduce the latent toxicity of the existing contrast enhancement agents. In comparing metal chelates, the contrast enhancement agents comprising iron (Fe) is an attractive alternative as compared to contrast agents with other metals, and one of the reasons is biocompatibility of Fe. This has led to increased interest in the use of iron-based materials as contrast agents for MRI.
The image quality of an agent may be increased by incorporating a moiety within the agent, wherein the moiety increases the agent size or targets a disease related biomarker. Either of these approaches improves selective localization of the agent at a diseased tissue lesion. This incorporation may be accomplished by the use of a bifunctional chelate, which binds to the metal as well as to a second moiety. The examples of iron-based bifunctional chelates are EDTA and deferoxamine, however, these chelates either pose a safety concern as they are redox active or have an insufficient MR signal. Furthermore, the known chelates employ isocyanate and isothiocyanate conjugation chemistries to attach a second moiety, which are hydrolytically sensitive functionalities that provide unstable conjugates in-vivo.
The alternative forms of bifunctional chelates and alternative methods of attaching a second moiety to an agent to enable bifunctionality is a long felt need. Therefore, a contrast enhancement agent comprising a bifunctional chelate having high in vitro and/or in vivo stability, prompt clearance from the body, ability to generate improved image quality at lower patient dosages, greater patient tolerance and safety for higher doses is highly desirable.

This patent is subject to a terminal disclaimer.

Contrast enhancement agents and method of use thereof

Abstract: wherein R1, R2, R3, R7, R8, R′1, R′2, R′3, R7′ and R8′ are selected form hydrogen, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group; R4, R′4 are selected from a hydrogen, a hydroxyl, a protected hydroxyl group, a protected C1-C3 hydroxyalkyl group, a C1-C3 alkyl group; n is an integer between 0 and 4; R5, R′5 are selected from a hydrogen, a protecting group comprising C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, C2-C30 aromatic radicals, m is an integer between 1 and 10; at least one of R7 and R′7 is acidic groups or protected acidic groups; Y comprises a protein or peptide moiety, a particle, a micelle, a liposome, an organic molecule, oligomer, polymer or a hydrophilic moiety.


Provided is a synthesis system of a time-of-flight (ToF) camera and a stereo camera for reliable wide range depth acquisition and a method therefor. The synthesis system may estimate an error per pixel of a depth image, may calculate a value of a maximum distance multiple per pixel of the depth image using the error per pixel of the depth image, a left color image, and a right color image, and may generate a reconstructed depth image by conducting phase unwrapping on the depth image using the value of the maximum distance multiple per pixel of the depth image.

1. Field
Example embodiments relate to three-dimensional (3D) scene modeling, and more particularly, to a system and method for reliable wide range depth acquisition for a depth image.
2. Description of the Related Art
A Time-of-Flight (ToF) camera, a type of depth camera, has an advantage of providing depth information of a scene in real time, and thus is being used widely for various purposes, for example, human motion tracking, object modeling, and the like.
The ToF camera includes a light emitting device to emit an infrared ray light, for example, a light emitting diode (LED), and a sensor to detect the light. The ToF camera allows distance calculation by measuring a travel time taken by light to return to the sensor after bouncing off an object, as represented by Equation 1.
                    r        =                              ct                          time                                            -                                          of                                            -                                          flight                                2                                    [                  Equation                                                              1                ]
where r denotes a distance from an object, c denotes a speed of light, and ttime-of-flight denotes a travel time taken by light to return to a sensor after bouncing off the object.
Measuring a ttime-of-flight is difficult because the speed of light is exceptionally fast. To resolve this issue, ttime-of-flight is calculated in an indirect manner of measuring the intensity of light based on at least two different phases after frequency-modulated light is emitted. A further detailed description is provided with reference to FIG. 1.

Synthesis system of time-of-flight camera and stereo camera for reliable wide range depth acquisition and method therefor


The present invention provides a method of separating unreacted monomer from a polymerization process effluent stream. The polymerization process effluent stream has at least the following components: unreacted monomer, polymer, and solid fines. The method comprises passing the effluent stream through one or more filters disposed within a vessel at a pressure of from about 150 psig to about 400 psig and thereby obtaining a stream of vapor containing less than about 0.5 weight percent solid fines.

In a typical slurry polymerization system, monomer (and possibly co-monomer, liquid diluents, and catalyst) are fed into a continuously stirred reactor. The monomer (and possibly co-monomer) reacts to produce a product effluent containing solid polymer particles of various sizes, liquid diluents (if used), unreacted monomer, and catalyst. The effluent, is removed from the reactor, and typically contains between about 40 to 60 wt % unreacted monomer and/or diluents. For economical operation of this process the unreacted monomer and/or diluents are separated from the polymer solids and then returned to the reactor(s).
U.S. Publication No. 2005/0095176 is hereby incorporated by reference in full. U.S. Publication No. 2005/0095176 describes a conventional method of separating polymer solids from unreacted monomer by first vaporizing at least a portion of the reactor effluent. The withdrawn slurry is passed into a high-pressure flash chamber. After leaving the high-pressure flash chamber, the monomer stream is condensed using a simple heat exchange condenser and recycled into the reactor. However, in this conventional method the monomer stream contains a relatively large amount of residual solid particles. These residual solid particles may contain catalyst that will cause further polymerization and could foul the system.
EP 0100550 is hereby incorporated by reference in full. EP 0100550 describes an alternative conventional method of separating olefin solids from unreacted monomer by first vaporizing at least a portion of the reactor effluent. The solids are removed from the unreacted monomer by passing the reactor effluent through a series of bag filters. The unreacted monomer stream is relatively free of residual particles, however, because of the relatively low operating pressure of the filters the unreacted monomer stream must undergo compression before it can be recycled. Compressors are undesirable in this process as they have relatively high capital expense and operating costs.
Accordingly, there is a need for a process that can separate unreacted monomer from an effluent stream into a relatively pure stream, and does not require compression.

High pressure filter method of separating polymer solids and unreacted monomer


An improved technique of utilizing a centralized control protocol for lighting devices such as DALI. A technique is disclosed for utilizing such protocols in a wireless environment. The first step involves associating particular slave devices with a specified master control device, and a second step involves associating specific functions within the master device with specific slave devices.

Home and office centrally controlled lighting systems are known in the art. One such system is known as DALI (Digital Addressable Lighting Interface). DALI is a widely accepted standard for lighting controls. In a DALI system, a plurality of lighting devices are dispersed throughout a site, such as a home or office, and are controlled by an intelligent control unit or central computer. The plurality of lighting devices may be termed "slaves" and the central control computer is denoted a "master".
In most prior art systems such a DALI, the connections between the master and the slave is in the form of hardwiring. In the present art, a DALI type system is usually used for the lighting in one room, i.e. master and slave are in the same room. By adding a gateway to each DALI control unit, a building-wide control system can be built. Introducing wireless lighting control is to eliminate the wires that have to be installed inside the walls or ceilings, which creates obstacles for retrofit in most old buildings.
Wireless control of a lighting system in a commercial or office building can bring a number of advantages to the building owners, users and lighting system manufacturers. Wireless control can be achieved by communicating between the master and slave utilizing radio frequency (RF) technology. RF technology however, poses obstacles of its own that are not present in a hardwired system. More specifically, in order to take the advantage of RF technology, the wireless lighting control system must employ a technique to combine the operation of standards such as DALI with RF communication protocol standards.
The current state of the art however, only includes solutions for hardwired lighting networks implementing DALI standard. There is no technique to extend DALI standard to manage plural wireless slaves. Most current available wireless lighting control systems use proprietary protocols instead of DALI. Additionally, the DALI protocol, and similar protocols, operate by assuming reliable communication between master and slave. These protocols assume for example, that every transmitted bit from every slave device will be reliably and timely received by the master without interference from other slave devices in the system. The DALI protocol also assumes that all information from the master will be correctly received by the proper slave device. The protocol does not provide for the errors, delays, and interference that may corrupt data in a wireless environment. The protocol also does not provide for a way to initialize slaves and bind the commands on the remote control master to the slaves. Binding is the process used to assign certain slaves to certain commands on the remote control master dynamically.

Wireless addressable lighting method and apparatus


The present invention is to provide an epoxy resin composition for encapsulating a semiconductor having a high flame resistance without using a flame retarder and having an excellent solder reflow resistance, and a semiconductor device using the same for encapsulating a semiconductor element. An epoxy resin composition for encapsulating a semiconductor of each of the first, second and third aspects essentially comprises (A) a phenol aralkyl type epoxy resin having a phenylene structure, (B) a phenol aralkyl type phenolic resin having a biphenylene structure and (D) an inorganic filler as common components, wherein (D) the inorganic filler is contained at the rate of 84 wt % or more and 92 wt % or less of the total amount of the epoxy resin composition.

1. Field of the Invention
The present invention relates to an epoxy resin composition for encapsulating a semiconductor and a semiconductor device using the same.
2. Description of the Related Art
In an electronic device such as a diode, a transistor or an IC (Integrated Circuit), an epoxy resin composition is conventionally used for encapsulating. Particularly, an epoxy resin composition comprising an epoxy resin, a phenolic resin and an inorganic filler such as fused silica or crystalline silica and excellent in heat resistance and moisture resistance is used for the IC. Recently, however, a market trend is inclined to downsizing, weight saving and high-end product of electronics, and thereby a highly integrated semiconductor device is continuously under development. Additionally, a surface mount type semiconductor device is becoming popular more and more. In the circumstances, a demand for the epoxy resin composition for encapsulating a semiconductor element is increasing severe. Particularly, in the circumstance that a surface mount type semiconductor device is becoming general, the semiconductor device which absorbed moisture is subjected to a high temperature environment during a solder reflow treatment. Furthermore, as a part of a zero-emission movement, replacement to a lead-free solder is proceeded. Such a lead-free solder has a higher melting point than that of the conventional solder, and thereby requires a reflow temperature of 260° C., which is 20° C. higher than that of the conventional solder, when mounting on a surface. Thereby, the semiconductor device is subjected to a higher temperature environment than ever, which is apt to cause a defect greatly detracting the reliability of the semiconductor device such as delamination at an interface between a semiconductor element or a lead frame and a cured product of the epoxy resin composition, or a crack in the semiconductor device.
Also, with regard to the lead frame, from the viewpoint of excluding any lead, the number of a semiconductor device in which a preplating frame plated with Ni, Ni—Pd, Ni—Pd—Au or the like in advance is used instead of solder plating on outer lead is increasing. However, such plating has a problem of notably poor adhesion with a cured product of the epoxy resin composition, which may cause delamination at the interface when mounting on a surface. Therefore, there is a demand for preventing such a defect, that is, a demand for an improvement in solder reflow resistance.
On the other hand, from the environmental concerns, there is a movement for restricting a use of a halogen based flame retardant such as a bromine-contained organic compound or the like, and an antimony compound such as diantimony trioxide, diantimony tetraoxide or the like, which are conventionally used as a flame retardant in a encapsulant for the semiconductor. Therefore, there is a demand for a new flame retardant technology for replacing the conventional one. As such a replacing flame retardant technology in a encapsulant for semiconductor, there is proposed a method using a metal hydroxide such as aluminum hydroxide, magnesium hydroxide or the like, which is less harmful to the environment. However, this method has a problem that a large amount of the metal hydroxide is required to obtain an expected flame retardant effect. Additionally, if the compound ratio of the metal hydroxide is increased to obtain a sufficient flame resistance, the flowability and curability of the epoxy resin composition during molding are decreased, and the mechanical strength of the cured product is deteriorated. As a result, the solder reflow resistance is deteriorated in the temperature range of mounting the lead-free solder.
In order to prevent the deterioration of the solder reflow resistance associated with the increase of the mounting temperature, an epoxy resin or a curing agent having a low water absorption rate respectively is used (e.g. Japanese Patent Application Laid-open Nos. Hei 1-275618 (pp. 1 to 5) and Hei 5-097965 (pp. 2 to 6) and Hei 5-097967 (pp. 2 to 7)). However, such an epoxy resin composition does not have a sufficient flame resistance and thereby requires addition of a flame retardant. Additionally, such an epoxy resin composition exhibits a low adhesion to the preplating frame. Thereby, the reliability is low, particularly in a package using such a preplating frame.
Furthermore, such an epoxy resin composition has a low crosslinking density and thereby a molded article immediately after curing is so soft that a problem may arise in a continuous molding process such as an insufficient release of the resin from the mold, which may reduce productivity.
In order to improve productivity, there is proposed a method adding oxidized polyethylene (e.g. Japanese Patent Application Laid-open Nos. Hei 8-258077 (pp. 2 to 9) and Hei 11-152393 (pp. 2 to 5)). However, it is required to increase a compounding amount of oxidized polyethylene in order to obtain sufficient releasing property owing to oxidized polyethylene only. In this case, the adhesion is deteriorated. Furthermore, in order to improve the dispersibility of oxidized polyethylene, there is proposed a method using epoxy polyether silicone having dimethyl siloxane structure as a main chain together (e.g. Japanese Patent Application Laid-open No. Hei 5-315472 (pp. 2 to 7)). Although a silicone oil having a polyether chain greatly contributes to improvement of productivity, the solder reflow resistance is deteriorated because of increased moisture absorption due to the polyether chain.
In order to improve the solder reflow resistance, there is also proposed a method using a resin having flexibility and flame resistance in addition to a low water absorption property (e.g. Japanese Patent Application Laid-open Nos. Hei 1-275618 (pp. 1 to 5), Hei 5-097965 (pp. 2 to 6) and Hei 5-097967 (pp. 2 to 7)). However, if a compounding ratio of an inorganic filler is increased in order to apply for a case of using a lead-free solder, a sufficient flowability cannot be obtained, which prevents the realization of this method.
In circumstances as described above, there is a demand for developing a resin composition for encapsulating a semiconductor device having a high flame resistance without addition of any flame retardant, and having a high solder reflow resistance which is applicable to a lead-free solder without declining flowability.

Epoxy resin composition and semiconductor device


The present invention relates to a method of quickly preparing a large amount of octacalcium phosphate and octacalcium phosphate prepared thereby. A method of preparing octacalcium phosphate according to an embodiment of the present invention includes preparing a calcium phosphate solution, controlling an initial pH by controlling a pH of the calcium phosphate solution to a range from 5 to 6 using an acidic solution at a time point at which the pH of the calcium phosphate solution increases, heating the calcium phosphate solution to a temperature ranging from 60° C. to 90° C., and controlling a terminal pH by controlling the pH of the calcium phosphate solution to a range from 5 to 6 using a basic solution at a time point at which the pH of the heated calcium phosphate solution decreases.

Hydroxyapatite (HA) is mainly found in the teeth and bones in the body. Therefore, HA is mainly used to improve the proliferation of bone cells or as a coating agent to promote the ingrowth of bones in the field of fillers or artificial implants to replace broken bones. However, HA is problematic because reabsorption into the body does not occur well, even after bone regeneration in the broken region.
Hence, research is ongoing into increasing the reabsorption rate in the body and biocompatibility for bone cells using octacalcium phosphate (OCP), which is a precursor of HA.
However, conventional methods of synthesizing OCP have problems such as difficulties in obtaining highly pure OCP, high production costs and low yield. Therefore, there remains the need for research on an optimal OCP synthesis (preparation) method in order to solve the above problems.

Method for preparing octacalcium phosphate and octacalcium phosphate prepared thereby


A transmission unit of a signal transmission device includes: a transmission-side detection unit that detects image information from an inputted electrical signal; a receiving unit that receives, from a reception unit, a status signal representing an arrival status of an outputted optical signal; and a control unit that controls an electrical-optical conversion unit on the basis of the detection result of the transmission-side detection unit and the status signal of the receiving unit so that the output of the optical signal is shut down in at least one of a case where image information is not included in an electrical signal and a case where an optical signal has not arrived.

1. Field of the Invention
The present invention relates to a signal transmission device, and in particular to a signal transmission device that uses optical signals.
2. Description of the Related Art
In accompaniment with the increase in the resolution of liquid crystal panels and plasma displays, there is a demand to transmit, as digital signals, large-capacity image signals from a host. For example, in the Digital Visual Interface standard (DVI: a digital image transmission standard), which was established by the Digital Display Working Group (DDWG) that is an industry group, high-speed signals of 1.65 Gbps per 1 bit are transmitted using a differential signaling specification called transition minimized differential signaling (TMDS). A shield-attached metal cable widely used as a display cable is used as the transmission medium.
FIG. 11 shows an example where a host computer 86 and a monitor 88 are connected by a DVI cable 71 and image signals from the host computer 86 are displayed on the monitor 88. FIG. 12 shows a configural diagram of the DVI cable 71. TMDS signals in the DVI cable 71 are 4-bit differential signal pairs, and R, G and B of image signals and pixel clocks are allocated. The DVI cable 71 has a maximum transmission speed of 1.65 Gbps depending on the resolution of the image. Display data channel (DDC: display information) signals comprise (DDC Clock) and (DDC Data), and the display information (DDC) is exchanged between the host computer 86 and the monitor 88. A 5V Power signal and a hot plug detect signal (HPD: corresponding signal of the monitor) are level signals that give notification of the connection status of the host computer 86 and the monitor 88. When the host computer 86 starts up, the 5V Power signal becomes a high level, and when the 5V Power signal is inputted to the monitor 88 in a state where the host computer 86 and the monitor 88 are connected, the HPD signal becomes a high level. In addition to these, shield (GND) lines are plurally disposed in the metal DVI cable 71.
However, the length of the DVI cable 71 cannot be stretched more than 10 m because the signals that the DVI cable 71 handles are high speed. For this reason, cables (fiber cables, etc.) that convert high-speed signals to optical signals to realize long-distance transmission have also been proposed, but problems that must be resolved remain in terms of power consumption and safety in handling a laser light source for the optical signals.
For example, laser light is used in these optical transmission devices for emission light from the light source, but when there is unintentional cutting of the fiber cable or removal of the optical connector during operation, there is the potential for the laser light to leak to the outside and cause damage to human eyes. For this reason, technology that incorporates a safety circuit to stop laser light emission when the optical cable is unplugged has been proposed (e.g., see Japanese Patent Application Laid-pen Publication (JP-A) No. 2001-185783).
However, with respect to cables in which optical fiber and electrical wiring are mixed together, problems remain in that, when cutting of the light is determined only by the connection status of the electrical wiring, the cutting cannot be grasped when only the fiber cable has been cut, and the light emission cannot be appropriately stopped. Thus, it is actually preferable to monitor the reception status of the optical signal and stop light emission when normal optical signal is not being received. As a method of determining the status of transmission from the optical reception unit, technology has been proposed in the field of bi-directional optical communication that monitors the reception status of the optical signal and detects abnormalities (e.g., see Japanese Patent No. 2838454). By reflecting this technology in the aforementioned safety circuit that stops the laser light emission, it is possible to determine the connection status of the electrical wiring and the fiber cable and stop the laser light emission.
Also, as technology that achieves power saving in relation to optical extension cables, technology has been proposed that turns the power ON in accordance with the startup of the host in a state where the host and the monitor are normally connected (e.g., see JP-A No. 2003-209920). This technology proposes shutting down the power supply when the host computer and the monitor are not connected, to thereby reduce unnecessary power consumption. Thus, as long as the host computer and the monitor are normally connected, the optical transmission unit also starts up together with the startup of the host computer resulting from the power being turned ON, and the power supply of the optical transmission unit is also cut off due to the power of the host computer being cut off.
However, with respect to optical transmission devices, the function of detecting abnormalities in the optical signals and rapidly handling them and the function of achieving power saving are conflicting functions. Namely, the function of achieving power saving is technology that contradicts the safety circuit monitoring the actual optical signals. For example, sometimes the optical signal does not reach the reception circuit and, as a result, sometimes it is perceived that trouble has arisen during the time of the system startup from when the host computer is turned ON until the image signal is outputted when the initial setting of the system is being conducted (the so-called time lag), or in cases where the image signal stops when the resolution of the image is switched, or even in cases where the host computer temporarily stops the image signal within the range of normal operation.


It is an object of this invention to reduce image sensing errors due to wrong white balance control using wrong color temperature information in an image sensing device capable of performing white balance control using a color image signal from an image sensing device. In order to attain the above object, when the color in the vicinity of the locus of a blackbody cannot be extracted in detection of a color temperature in a color image signal, color temperature information is corrected on the basis of a piece of color temperature information output from a calorimetric sensor, thereby controlling the white balance of a color image signal output from an image sensing element. The number of achromatic data extracted from the color image signal is counted. The color temperature is calculated by weighting a color temperature obtained from the color image signal and that obtained from the colorimetric sensor in accordance with the count, thereby performing white balance control.

Conventionally, an electronic still camera which captures an object image by a solid-state image sensing element such as a CCD and records it on a storage medium as a still image signal is known as an image sensing apparatus having a function of controlling the white balance of a color image signal. An electronic still camera of this type will be described below as an example.
In an electronic still camera of this type, to control the white balance of a sensed color image signal, three methods are available: a method of framing a sheet of white paper or the like within the entire field of the finder under the light source in a photographing place, photographing the sheet by manual operation in this state, detecting color temperature information using the sensed color image signal, and performing white balance control on the basis of the obtained color temperature information; a method of extracting achromatic image data from a photographed color image signal and determining the color temperature information of the light source from the information of the extracted image data; and a method of detecting color temperature information by a calorimetric sensor which detects the color temperature of ambient light.
If color temperature information is detected using a sheet of white paper or the like, the obtained color temperature information is almost accurate. However, the color temperature cannot predict in principle by a method of detecting color temperature information using a photographed color image signal, if achromatic data is not present in the image.
Also, if very little achromatic data is obtained from a color image signal, the detected color temperature information has a low reliability, i.e., accurate color temperature information cannot be obtained.


A pop-up sprinkler unit includes an outer cylindrical fixed housing for subsurface mounting, with a riser reciprocally mounted in a central bore of the housing for extending up through a portion of the soil. A radially retractable and expandable resilient plastic containment ring is mounted at an outlet end of the housing and engages an annular inner shoulder of the housing for retaining a coil spring and the riser in the bore. The containment ring is split to enable expansion and retraction. It has a first height throughout a first portion of its circumference and a second lower height throughout a second portion of its circumference to enable overlap during insertion of the ring into the upper end of the fixed housing. This configuration eliminates a gap at the split when the ring is in its retaining position, thereby preventing debris from entering the bore of the housing and preventing complete extension and/or retraction of the riser.

The present invention relates to sprinkler units, and pertains particularly to an improved containment ring for pop-up sprinkler units.
Pop-up sprinkler units are widely used in both residential and commercial applications to irrigate lawns and shrubs. They typically include a riser that is axially retracted into a fixed outer cylindrical housing buried in the ground when not in use, and which extends from the outer housing to a position above the surface of the ground when water pressure is applied. The top of the riser is level with the ground when retracted. Seals inside the housing wipe the surface of the riser as it extends from, and retracts into, the housing.
In many applications of retractable sprinkler units, such as playing fields, golf courses and the like, it is important that the tops of the risers of the sprinkler units reliably retract to a position level with the surface of the playing field, so that they not become obstacles. However, the typical riser of a conventional retractable sprinkler unit frequently jams or sticks in a partially retracted position. This usually occurs when dirt and debris get between the seals and the surface of the retractable riser. This often results in the riser being stuck, i.e. it will not retract.
In a conventional pop-up sprinkler unit the riser and its retraction spring and seals are assembled into the fixed outer housing from the top. These components are typically retained in place by a plastic containment spring which snaps into an annular groove at the top of the fixed outer housing. The containment ring is split so that it can be compressed inward in diameter and inserted into the upper end of the bore of the fixed outer housing. The resilient ring is then allowed to expand to engage in the annular groove in the housing bore to retain the riser in the housing. The containment ring has a sufficient gap at its split to enable the ring to be compressed in diameter sufficiently to be inserted in the bore of the outer housing. When the containment ring expands into the annular groove, the vertical opposing faces or ends of the ring spread apart, leaving a gap which allows dirt and debris to enter the outer housing. The dirt and debris can work its way between the seals and riser. This can damage the seals and/or cause the riser to jam.
It is, therefore, desirable that an improved simple and effective containment ring be available to hold a riser inside the fixed outer housing of a pop-up sprinkler unit.

Pop-up sprinkler unit with split containment ring


To increase inspection throughput, the field of view (FOV) of an IR camera can be moved over the sample at a constant velocity. Throughout this moving, a modulation (e.g. optical or electrical) can be provided to the sample and IR images can be captured using the IR camera. Moving the FOV, providing the modulation, and capturing the IR images can be synchronized. The IR images can be filtered to generate the time delay LIT, thereby providing defect identification. In one embodiment, this filtering accounts for the number of pixels of the IR camera in a scanning direction. For the case of optical modulation, a dark field region can be provided for the FOV throughout the moving, thereby providing an improved signal-to-noise ratio (SNR) during filtering.

1. Field of the Invention
The present invention relates to defect detection on a sample using time delay lock-in thermography (LIT) to ensure high throughput and improve defect detection sensitivity in production environments. Dark field illumination can be used to minimize background noise in certain LIT embodiments.
2. Related Art
During the manufacturing process samples may develop localized electrical defects that cause current leakage. Exemplary samples could include photovoltaic materials (e.g. 156 mm×156 mm wafers or 2160 mm×2460 mm panels), semiconductor wafers, or printed circuit boards (PCBs). Electrical defects, such as shunts and localized weak diodes, leak current and therefore can reduce the efficiency of the sample or even jeopardize the functioning of the devices on the sample. Therefore, it is highly desirable to accurately detect the positions of such electrical defects.
Defects have high current density passing through them and therefore heat up to a higher temperature than that of the sample. These temperature changes can be detected in the image from a focal plane array (FPA) IR camera. However, the change in temperature at a defect may be 5 orders of magnitude smaller than the background in the image. Thus, separating the defects from background noise may be challenging.
Lock-in thermography (LIT) is one known method for locating such defects. In LIT, the sample is modulated, e.g. by direct current injection into the sample or by photocurrent generated from illumination of the sample. When the modulation is by illumination, the method is sometimes called illuminated lock-in thermography (ILIT). Temperature changes caused by heating of the sample from the injected current or photocurrent are modulated at the same frequency. With either form of modulation, multiple frames of IR images are captured while the sample remains stationary.
Due to the shot noise of background IR radiation from the sample at room temperature as well as the very small temperature difference between the defects and the rest of the sample, and the limited dynamic range of the IR imaging sensor, a large number of images of the same field of view (FOV) are needed to average out the background noise, thereby improving the signal to noise ratio (SNR). Although the captured images are taken from the identical spatial location, they are a function of time as the temperature of the sample oscillates at the frequency of modulation. In a typical embodiment, the images are filtered by multiplying each image by a weighting factor that varies sinusoidally in time at the same frequency as the modulation or "lock-in" frequency. In general, the improvement of SNR is proportional to the square root of N, wherein N is the total number of frames.
Conventional LIT requires that the sample remains stationary while the IR camera acquires the necessary number of images for lock-in averaging. If the size of the sample is greater than the field of view (FOV) of the camera, the sample (or the IR camera) needs to move to a completely different location to capture a new set of IR images after one set of images is captured for one location on the sample. Unfortunately, this stop-go time as well as the settling time (which includes repositioning with its attendant velocity ramp up and ramp down) takes a large portion of the total inspection time, especially for very large samples that can be greater than 2 m×2 m in size, thereby undesirably reducing throughput. This overhead in conventional lock-in thermography becomes a significant limiting factor of inspection throughput.
Therefore, a need arises for a technique of detecting defects on a sample that increases inspection throughput compared to conventional LIT while maintaining its accuracy.

Defect detection using time delay lock-in thermography (LIT) and dark field LIT


An equalizer is used with complex modulation modems to reduce intersymbol interference. The equalizer includes an equalizer filter that receives an input data signal and adapts to compensate for the noisy communications channels to reduce intersymbol interference to the input signal. A branch metric computer demodulates the equalizer filter adapted input data signal. A decision device delivers an alpha value, starting phase information and confidence values from the demodulated input data signal. A gain determination function receives the confidence values and determines adaptation gain for the equalizer filter. A remodulator receives the alpha value and starting phase information and remodulates the alpha value and starting phase information into a remodulated data signal. A summing function compares the remodulated data signal to a delayed version of the input signal to generate an error signal for the equalizer filter to adjust the equalizer filter.

This invention relates to communications systems, data transmission, modulation, coding, a bandwidth efficient advanced modulation waveform, and more specifically a channel equalization algorithm for use in these systems.
In digital communications systems such as cellular and PCS (personal communications systems), computer communications systems, and SATCOM (satellite communications) systems digital data is modulated by a modem onto a signal to be transmitted over a communications channel. The communications channel may add noise, interference, multipath, fading, and other corrupting influences that may result in loss of the data when demodulated at a receiver in the communications link. Channel coding has been used in communications systems for many years to detect and/or correct data bit errors by introducing redundant bits. The use of channel coding results in a reduction of data rate or an increase in required bandwidth due to the additional redundant bits.
Block codes and convolutional codes are two types of channel codes commonly used in the art of channel coding. A block code is an error detection and/or correction code in which an encoded block of data consists of n coded bits, containing k information bits (k<n) and n-k redundant check bits to detect and/or correct most errors. Types of block codes known in the art include Hamming codes, Golay code, BCH codes, and Reed Solomon codes.
Convolutional codes are widely used in the communications art to provide real time error correction. Convolutional codes continuously convert an entire data stream to encode the k information bits. The encoded bit stream depends on the current information bits and also on the previous input information bits. With a convolutional code, k information bits are coded into n coded bits in an encoder with m memory stages that store the state information of the encoder. A constraint length K of a convolutional code is defined as m+1 and a code rate r as k/n. The well-known Viterbi algorithm is commonly used in convolutional coding.
Recent advances in the art of coding to further improve error detection and correction while reducing bandwidth requirements include turbo codes and trellis coded modulation. Trellis coded modulation combines coding and modulation into one operation. By combing coding and modulation, redundancy can be obtained with no reduction in data rate or increase in bandwidth.
Continuous phase modulation (CPM) is being applied in communications due to its bandwidth efficiency and constant envelope characteristics. With CPM, the modulated signal phase transitions are smoothed. With BPSK (binary phase shift keying) a logic one is transmitted as one phase of a modulated signal and a logic zero is transmitted as a 180-degree shifted phase with a sharp transition in phase. This sharp phase transition results in broadening of the transmitted spectrum. With CPM the phase of the transmitted signal makes smooth phase changes over the bits of the modulating digital signal. An example of CPM currently in use is MSK (minimum shift keying).
Turbo codes allow reliable transmission of data across a communications channel near the theoretical limit predicted by Claude Shannon. A turbo code is generated by a parallel concatenation of two component convolutional codes separated by an interleaver. Turbo decoding uses a soft decoder at the input followed by an inverse interleaver and a second soft decoder. The output of the second soft decoder feeds back to the input of the first soft decoder through an interleaver. The data is passed through the turbo decoder in several iterations with each pass improving the quality of error correction.
A new data communications waveform has been developed by Rockwell-Collins called BEAM (bandwidth efficient advanced modulation). A goal of the BEAM waveform development is to increase the throughput of a typical 25-kHz UHF SATCOM channel by a factor of five over the MIL-STD-188-181A FSK waveform, while maintaining a reasonable Eb/No. The throughput will thus increase from the current 16 kbps to 80 kbps. The BEAM waveform must operate with current UHF satellites and have a constant envelope. The constant envelope requirement is important for this application because all current UHF satellites use saturating amplifiers. In addition, most, if not all, of the UHF user terminals utilize saturating amplifiers for power efficiency. The BEAM waveform jointly combines coded CPM modulation with turbo decoding. Although the BEAM waveform has been invented for UHF SATCOM applications, the BEAM waveform concept can be extended to any type of AWGN (additive white Gaussian noise) communications channel. Because of the underlying CPM modulation, it is particularly useful to those communications systems that rely on saturated amplifiers.
Channel equalization is widely used in communications systems to compensate for communications channel degradation of the transmitted signal in phase and amplitude. Equalizers compensate for the effects of frequency dependent phase and amplitude distortion caused by multipath and transmit and receive filters. In digital communications systems, the digital data can be subject to intersymbol interference (ISI) that may be caused by the transmitter filter, distortion, communications channel conditions, and the receiver filter. The communications channel acts like an analog low pass filter with a frequency response that smears a digital signal such that received pulses that correspond to different symbols are not separable. An equalizer can be used to compensate for the effects of the communications channel by performing as a filter with a frequency response that approximates the inverse of the communications channel frequency and filter responses.
Several methods of determining the filter characteristics of an equalizer filter are known in the art. One method is automatic synthesis where the equalizer compares a received signal to a stored copy of an undistorted training signal. Comparing the two signals results in an error signal that can then be used to determine coefficients of the inverse filter. The automatic synthesis method is used in zero-force equalization (ZFE) and minimum mean-square error (MMSE) equalization. A shortcoming of the automatic synthesis method is the need to transmit the training signal.
Another method of calculating the filter coefficients for an equalizer filter is known as adaptive equalization. With the adaptive method, the equalizer attempts to minimize an error signal. In the case of decision-directed adaptive equalization, the error signal is based on the comparison of the equalizer output and an estimate of the transmitted signal generated in a decision device. Examples of decision-directed adaptive equalizers include the least mean square (LMS) algorithm, also called the stochastic gradient algorithm, and the recursive least squares (RLS) algorithm. The decision device makes an estimate of the transmitted signal from the output of the equalizer, and determines which, of a constellation of possible signals, was most likely to have been transmitted.
Many communication systems employ memory either implicitly in the modulation, such as continuous-phase modulation (CPM), or explicitly in a code, such as a convolutional code. In these systems, the receiver typically detects the transmitted sequence by a Viterbi or APP (a posterior probability) decoder that, in turn, operate on a trellis description of the memory in the system. These trellis-based algorithms typically require considerable time to make reliable decisions. Many subsystems within the demodulator require decisions from the demodulator and/or decoder in a timely manner. Decision-directed adaptive equalizers and decision-feedback equalizers represent two such classes of subsystems. In addition, recent coding advances, in particular iterative decoding of concatenated systems like turbo codes, allow the receiver to operate at unprecedentedly low signal-to-noise ratios (SNRs). At very low SNRs, the decoded decisions are initially very unreliable, which adversely affects the operation of the subsystems requiring these decisions. Typically, the subsystem, e.g., equalizer, has no indication of the confidence of the decisions.
What is needed is an algorithm for supplying timely decisions with confidence values ("soft decisions") to an adaptive decision-directed equalizer in a trellis-based communication system. The channel equalizer may use a simplified version of a demodulator that supplies soft decisions in parallel with the complete demodulator. A method for using the soft decisions from the decoder within the equalizer is required.

Equalizer for complex modulations in very noisy environments


For controlling a traffic on a network including a plurality of links, the apparatus includes a collecting unit that collects information on the traffic for each of the links periodically; an acquiring unit that acquires basic data collected from a link for a predetermined period; and a predicting unit that predicts a future traffic on the link based on the basic data. The start time of the predetermined period is the time when the latest control of the traffic was performed on the link or other link adjacent to the link.

1) Field of the Invention
The present invention relates to a technology for controlling a network traffic by improving an accuracy in predicting the network traffic and by optimizing a timing of a traffic control.
2) Description of the Related Art
In a conventional communication network, a prediction technology for future traffic based on past traffic (actual measurement value), such as a method of a linear-time-series analysis based on an autoregressive integrated moving average (ARIMA) model, has been suggested.
The linear-time-series analysis is used for analyzing a value (data) measured over time to perform a prediction or a verification of an assumption.
In the linear-time-series analysis, a measurement value at a certain point in time is represented by a linear polynomial of past measurement value and past noise components. Therefore, a value predicted by the linear-time-series analysis largely depends on the past measurement value.
In the ARIMA model, a time series zt is represented by a linear polynomial of autoregressive components zt-1, zt-2, . . . , and zt-p, and moving average components at, at-1, . . . , and at-g of white noise. The model is generally expressed asφ(B)Φ(BS)ΔSDΔdzt=θ(B)Θ(Bs)at where
zt: Deviation from the time series average,
at: White noise (error),
B: Lug operator (Bzt=zt-1),
Δ: Difference operator (Δzt=zt−zt-1),
ΔS: Seasonal difference operator (Δszt=zt−zt-s),
φ(B)=1−φ1B−φ2B2− . . . −-φpBp (Autoregressive components),
Φ(BS)=1−Φ1Bs−Φ2B2s− . . . −ΦPBPs (Periodic autoregressive components),
θ(B)=1−θ1B−θ2B2− . . . −θqBq (Moving average components of white noise), and
Θ(Bs)=1−Θ1Bs−Θ2B2s− . . . −ΘQBQs (Periodic moving average components of white noise).
FIG. 25 is a diagram for explaining conventional traffic prediction using the ARIMA model. In FIG. 25, at step SZ1, information on traffic measured in the target network (that is, data amount passing through the network) is input.
At step SZ2, ARIMA model identification processing is executed. That is, after an autocorrelation function (ACF) and a partial autocorrelation function (PACF) in the input information are calculated, the ARIMA model (p, d, q, P, D, Q, s) is identified by the shapes thereof.
At step SZ3, parameter presumption processing is executed. That is, the parameters of the ARIMA model (φ1 . . . φp, θ1 . . . θq, Φ1 . . . Φp, Θ1 . . . ΘQ) are presumed by the method of maximum likelihood or the method of least squares.
At step SZ4, the accuracy of the ARIMA model identified at step SZ2 and the parameters presumed at step SZ3 are determined. At step SZ5, future date and time are applied to the ARIMA model to predict the future traffic.
By the way, in the conventional network, traffic control for decreasing the traffic is performed before the traffic reaches the maximum capacity.
A preparation time is required since the traffic control is started until the effect of the control is seen. Conventionally, therefore, a threshold is set to a predetermined percentage (for example, 80%) of the maximum capacity to start the traffic control when the traffic reaches the threshold.
Conventionally, as shown in FIG. 26, when the traffic control such as a discard control (control of discarding a low-preference traffic) and a path route switching control is executed, the traffic in the affected link largely fluctuates before and after the traffic control (in the example shown in FIG. 26, the traffic decreases suddenly, as shown by solid line, due to the execution of the traffic control).
Therefore, when the traffic is predicted by the conventional ARIMA model, a sudden change appears in the predicted traffic in the prediction period (as shown in FIG. 26 by a broken-line) since the traffic in the data collection period for prediction is fluctuated due to the traffic control.
Thus, the traffic control adversely affects the predicted traffic, thereby decreasing the accuracy in predicting the traffic.
On the other hand, in the conventional traffic control in which a threshold to a certain percentage of the maximum capacity is set, it is difficult to ascertain to which percentage the threshold is to be set. Further, in the conventional traffic control in which the traffic control is executed when the traffic exceeds the threshold, control may be too early, too late to cause an excess of the maximum capacity, or unnecessary control may be executed.

Method and apparatus for controlling network traffic, and computer product


The present invention is directed to compounds of formula I-V and tautomers thereof or pharmaceutically acceptable salts, esters, and prodrugs thereof which are inhibitors of syk kinase. The present invention is also directed to intermediates used in making such compounds, the preparation of such a compound, pharmaceutical compositions containing such a compound, methods of inhibition syk kinase activity, methods of inhibition the platelet aggregation, and methods to prevent or treat a number of conditions mediated at least in part by syk kinase activity, such as undesired thrombosis and Non Hodgkin's Lymphoma.

This invention is directed to pyrimidine-5-carboxamide compounds which act as inhibitors of Spleen tyrosine kinase (syk) and/or 'JAK kinases. This invention is also directed to pharmaceutical compositions containing the pyrimidine-5-carboxamide compounds and methods of using the compounds or compositions to treat a condition characterized by other indications. The invention is also directed to methods of making the compounds described herein.
State Of The Art
Protein kinases constitute a large family of structurally related enzymes that are responsible for the control of a variety of signal transduction processes within cells (see, e.g., Hardie and Hanks, The Protein Kinase Facts Book, I and II, Academic Press, San Diego, Calif., 1995). Protein kinases are thought to have evolved from a common ancestral gene due to the conservation of their structure and catalytic function. Almost all kinases contain a similar 250-300 amino acid catalytic domain. The kinases can be categorized into families by the substrates they phosphorylate (e.g., protein-tyrosine, protein-serine/threonine, lipids, etc.). Sequence motifs have been identified that generally correspond to each of these families (see, e.g., Hanks & Hunter, (1995), FASEB J. 9:576-596; Knighton et al., (1991), Science 253:407-414; Hiles et al., (1992), Cell 70:419-429; Kunz et al., (1993), Cell 73:585-596; Garcia-Bustos et al., (1994), EMBO J. 13:2352-2361).
Many diseases are associated with abnormal cellular responses triggered by protein kinase-mediated events. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease and hormone-related diseases. As a consequence, there has been substantial efforts in medicinal chemistry to find inhibitors of protein kinases for use as therapeutic agents.
Immunoreceptor tyrosine activation motif (ITAM)-mediated signaling has emerged as a primary event in signaling pathways responsible for human pathologies. ITAM-mediated signaling is responsible for relaying activation signals initiated at classical immune receptors such as T-cell receptors, B-cell receptors, Fc receptors in immune cells and at GPVI and FcγRIIa in platelets to downstream intracellular molecules such as syk and ZAP-70 (Underhill, D. M and Goodridge, H. S., Trends Immunol., 28:66-73, 2007).
The binding of a ligand to an ITAM-containing receptor triggers signaling events which allows for the recruitment of proteins from a family of nonreceptor tyrosine kinases called the Src family. These kinases phosphorylate tyrosine residues within the ITAM sequence, a region with which the tandem SH2 domains on either syk or ZAP-70 interact.
Syk, along with Zap-70, is a member of the syk family of protein tyrosine kinases. The interaction of syk or ZAP-70 with diphosphorylated ITAM sequences induces a conformation change in the kinases that allows for tyrosine phosphorylation of the kinase itself. Phosphorylated Syk family members activate a multitude of downstream signaling pathway proteins which include Src homology 2 (SH2) domain containing leukocyte-specific phosphoprotein of 76 kDa (SLP-76), Linker of Activation of T-cells (LAT) and PLC (phospholipase C) γ2.
Human pathologies attributed to dysfunctional ITAM-mediated signaling include autoimmune diseases such as rheumatoid arthritis, systemic lupus, multiple sclerosis, hemolytic anemia, immune-thrombocytopenia purpura, and heparin-induced thrombocytopenia and arteriosclerosis. Interestingly, many of the above mentioned diseases are thought to occur through crosslinking of Fc receptors by antibodies which, via syk, activate a signaling cascade in mast, basophil and other immune cells that result in the release of cell mediators responsible for inflammatory reactions. The release of mediators and the production of cytokines in IgE stimulation-dependent allergic and inflammatory reactions from mast cells and basophiles can be controlled by inhibiting the tyrosine kinase activity of syk (Rossi, A. B. et al., J Allergy Clin Immunol., 118:749-755, 2006). In immune-thrombocytopenia, antibody bound platelets are cleared by the spleen by an Fc receptor/ITAM/syk-mediated process (Crow, A. R. et al., Blood, 106:abstract 2165, 2005). Drug-induced thrombocytopenia, caused by heparin-platelet factor 4 immune complexes that activate platelet FcγRIIa, also involve syk signaling downstream of receptor engagement (Reilly, M. P., Blood, 98:2442-2447, 2001).
Platelet agonists induce inside-out integrin signaling resulting in fibrinogen binding and platelet aggregation. This initiates outside-in signaling which produces further stimulation of platelets. syk is activated during both phases of integrin signaling, and inhibition of syk is shown to inhibit platelet adhesion to immobilized proteins (Law, D. A. et al., Blood, 93:2645-2652, 1999). Release of arachidonic acid and serotonin and platelet aggregation induced by collagen are markedly inhibited in platelets derived from syk deficient mouse (Poole, A. et al., EMBO J., 16:2333-2341, 1997). Thus syk inhibitors may also possess anticoagulation action.
Because of the role syk plays in Ig-induced platelet activations, it is likely to be important in arteriosclerosis and restenosis. Arteriosclerosis is a class of diseases characterized by the thickening and hardening of the arterial walls of blood vessels. Although all blood vessels are susceptible to this serious degenerative condition, the aorta and the coronary arteries serving the heart are most often affected. Arteriosclerosis is of profound clinical importance since it can increase the risk of heart attacks, myocardial infarctions, strokes, and aneurysms.
The traditional treatment for arteriosclerosis includes vascular recanalization procedures for less-serious blockages and coronary bypass surgery for major blockages. A serious shortcoming of intravascular procedures is that, in a significant number of treated individuals, some or all of the treated vessels restenose (i.e., re-narrow). For example, restenosis of an atherosclerotic coronary artery after PTCA occurs in 10-50% of patients undergoing this procedure and subsequently requires either further angioplasty or a coronary artery bypass graft. Furthermore, restenosis of an atherosclerotic coronary artery after stenting occurs in 10-20% of patients undergoing this procedure and subsequently requires repeat treatments to maintain adequate blood flow through the affected artery. Restenosis generally occurs in a relatively brief time period, e.g., roughly less than six months, after treatment.
While the exact hormonal and cellular processes promoting restenosis have not been determined, restenosis is thought to be due in part to mechanical injury to the walls of the blood vessels caused by the balloon catheter or other intravascular device. For example, the process of PTCA, in addition to opening the obstructed artery, also injures resident coronary arterial smooth muscle cells (SMCs). In response to this injury, adhering platelets, infiltrating macrophages, leukocytes, or the smooth muscle cells themselves release cell-derived growth factors such as platelet-derived growth factor (PDGF), with subsequent proliferation and migration of medial SMCs through the internal elastic lamina to the area of the vessel intima. Further proliferation and hyperplasia of intimal SMCs and, most significantly, production of large amounts of extracellular matrix over a period of three to six months results in the filling in and narrowing of the vascular space sufficient to significantly obstruct blood flow.
In addition to the role syk plays in Ig-induced platelet activations, syk plays a very important role in collagen-mediated signaling. The primary adhesive protein responsible for platelet adhesion and activation is collagen. Collagen is a filamentous protein contained within the fibrotic caps of atheromas which becomes exposed to blood during plaque rupture. Collagen functions initially by binding von Willebrand factor which tethers platelets through binding platelet membrane GPIb. Collagen functions secondarily by engaging the two collagen receptors on platelets, GPVI and integrin α2β1.
GPVI exists in platelet membranes as a complex with FcRγ, an interaction required for the expression of GPVI. Activation of FcγRIIa on platelets results in platelet shape change, secretion and thrombosis. Signaling by the GPVI/FcRγ complex is initiated by tyrosine phosphorylation of the ITAM domain of FCRγ followed by the recruitment of syk. Activation of GPVI leads to induction of multiple platelet functions including: activation of integrins α2β1 to achieve firm platelet adhesion, and GP IIb-IIIa which mediates platelet aggregation and thrombosis growth; platelet secretion, allowing for the delivery of inflammatory proteins such as CD40L, RANTES and TGFβ to the vessel wall; and the expression of P-selectin which allows for the recruitment of leukocytes. Therefore, it is believed that syk inhibitors can inhibit thrombotic events mediated by platelet adhesion, activation and aggregation.
It has been reported that the tyrosine phosphorylation of intracellular protein (activation) induced by stimulation of a receptor for IgG antibody, FcγR, and the phagocytosis mediated by FcγR are considerably inhibited in macrophages derived from syk deficient mouse (Crowley, M. T. et al., J. Exp. Med., 186:1027-1039, 1997). This suggests that syk has a markedly important role in the FcγR-mediated phagocytosis of macrophages.
It has also been reported that an antisense oligonucleotide of syk suppresses the apoptosis inhibition of eosinophils induced by GM-CSF (Yousefi, S. et al., J. E. Med., 183:1407-1414, 1996), showing that syk is essential for the life extending signal of eosinophils caused by GM-CSF and the like. Since life extension of eosinophils is closely related to the transition of diseases into a chronic state in allergic disorders, such as asthma, syk inhibitors can also serve as therapeutic agents for chronic eosinophilic inflammation.
Syk is important for the activation of B-cells via a B-cell antigen receptor and is involved in the phosphatidylinositol metabolism and increase in the intracellular calcium concentration caused by the antigen receptor stimulation (Hutchcroft, J E. et al., J. Biol. Chem., 267:8613-8619, 1992; and Takata, M. et al., EMBO J., 13:1341-1349, 1994). Thus, syk inhibitors may be used to control the function of B-cells and are, therefore, expected to serve as therapeutic agents for antibody-related diseases.
Syk binds to a T-cell antigen receptor, quickly undergoes tyrosine phosphorylation through crosslinking of the receptor and synergistically acts upon intracellular signals mediated by Src tyrosine kinases such as Lck (Couture, C. et al., Proc. Natl. Acad. Sci. USA, 91:5301-5305, 1994; and Couture, C. et al., Mol. Cell. Biol., 14:5249-5258, 1994). syk is present in mature T-cell populations, such as intraepithelial γδ T-cells and naïve αβ T-cells, and has been reported to be capable of phosphorylation of multiple components of the TCR signaling cascade (Latour, S. et. al., Mol Cell Biol., 17:4434-4441, 1997). As a consequence, syk inhibitors may serve as agents for inhibiting cellular immunity mediated by T-cell antigen receptor.
Recent comparative genomic hybridization studies have identified syk as another gene important in the pathogenesis of Mantle Cell Lymphoma (MCL) (Chen, R. et al. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 25, No 18S (June 20 Supplement), 2007: 8056). MCL represents 5-10% of all non-Hodgkins lymphomas and it is a difficult form of lymphoma to treat. It has the worst prognosis among the B cell lymphomas with median survival of three years. It has been reported that Syk is overexpressed in MCL (Rinaldi, A, et. al, Br. J Haematol., 2006; 132:303-316) and that Syk mediates mTOR (mammalian target of Rapamycin) survival signals in follicular, mantel cell, Burkitt's, and diffuse large B-cell non-Hodgkin's lymphomas (Leseux, L., et. al, Blood, 2006; 108:4156-4162).
Several lines of evidence suggest that many B-cell lymphomas depend upon B-cell receptor (BCR)-mediated survival signals. BCR signaling induces receptor oligomerization and phosphorylation of Igα and β immunoreceptor tyrosine-based activated motifs by SRC family kinases. ITAM phosphorylation results in the recruitment and activation of syk that initiates downstream events and amplifies the original BCR signal. Given the role of tonic BCR signaling in normal B cell and syk-dependent survival of non-Hodgkins lymphoma cell lines in vitro (Chen, L., et. al, Blood, 2006; 108:3428-3433), syk inhibition is a promising rational treatment target for certain B-cell lymphomas and chronic lymphocytic leukemia (CLL) (Stefania Gobessi, Luca Laurenti, Pablo Longo, Laura Carsetti, Giuseppe Leone, Dimitar G. Efremov, Constitutive activation of the protein tyrosine kinase Syk in Chronic Lymphocytic Leukemia B-cells, Blood, 2007, 110, Abstract 1123). Recent data shows that administration of a multikinase inhibitor which inhibits syk, may have significant clinical activity in CLL patients (Friedberg J W et al, Blood 2008; 112(11), Abstract 3).
The oncogenic potential of the spleen tyrosine kinase (Syk) has been described in a number of different settings. Clinically, Syk over-expression is reported in Mantle Cell Lymphoma (Rinaldi, A, et. al, Br. J. Haematol., 2006; 132:303-316) and the TEL-Syk fusion protein (Translocated ETS Leukemia) generated by a chromosomal translocation (t(9;12)(q22;p12)) leads to increased Syk activity and is associated with myelodysplastic syndrome (Kuno, Y., et. al, Blood, 2001; 97:1050-1055). Leukemia is induced in mice by adoptively transferring bone marrow cells that express human TEL-Syk (Wossning, T., JEM, 2006; 203:2829-2840). Further, in mouse primary bone marrow cells, over-expression of Syk results in IL-7 independent growth in culture (Wossning, T., et. al, JEM, 2006; 203:2829-2840).
Interestingly, Syk signaling appears to be required for B-cell development and survival in humans and mouse. Inducible loss of the B-cell receptor (Lam, K., et. al, Cell, 1997; 90:1073-1083) or Igα (Kraus, M., et. al, Cell, 2004; 117:787-800) results in loss of peripheral B-cells in mice. Over-expression of the protein tyrosine phosphatase PTP-RO, which is known to negatively regulate Syk activity, inhibits proliferation and induces apoptosis in cell lines derived from non-Hodgkin's lymphomas (Chen, L., et. al, Blood, 2006; 108:3428-3433). Finally, B-cell lymphomas rarely exhibit loss of BCR expression, and anti-idiotype therapy rarely leads to resistance (Kuppers, R. Nat Rev Cancer, 2005; 5:251-262).
Engagement of the antigen-specific B cell receptor (BCR) activates multiple signaling pathways that ultimately regulate the cells activation status, promoting survival and clonal expansion. Signaling through the BCR is made possible by its association with two other members of the immunoglobulin super-family; Igα and Igβ, each bearing an immuno-tyrosine based activation motif (ITAM) (Jumaa, Hendriks et al. Annu Rev Immunol 23: 415-45 (2005). The ITAM domain is directly phosphorylated by Src family kinases in response to BCR engagement. The spleen tyrosine kinase (Syk) docks with and phosphorylates the ITAM, a process that enhances its kinase activity, resulting in Syk autophosphorylation and tyrosine phosphorylation of multiple downstream substrates (Rolli, Gallwitz et al. Mol Cell 10(5): 1057-69 (2002). This signaling pathway is active in B cells beginning at the transition from pro- to pre-B cell stage of development, when the newly formed pre-BCR is expressed. In fact, B cell development arrests at the pro-B cell stage in Syk knockout mice (Cheng, Rowley et al. 1995; Turner, Mee et al. Nature 378(6554): 303-6 (1995). Inducible loss of the B cell receptor (Lam, Kuhn et al. Cell 90(6): 1073-83 (1997) or Igα (Kraus, Alimzhanov et al. Cell 117(6): 787-800 (2004) results in loss of peripheral B cells in mice. Human B cells also appear to require Syk for proliferation and survival. Over-expression of the protein tyrosine phosphatase PTP-RO, a negative regulator of Syk activity, inhibits proliferation and induces apoptosis in cell lines derived from non-Hodgkin's lymphomas (NHL) (Chen, Juszczynski et al. Blood 108(10): 3428-33 (2006). Knock down of Syk by siRNA in the NHL line SUDHL-4 led to a block in the G1/S transition of the cell cycle (Gururajan, Dasu et al. J Immunol 178(1): 111-21 (2007). Together, these data suggest that Syk signaling is required for the development, proliferation, and even survival of human and mouse B cells.
Conversely, the oncogenic potential of Syk has been described in a number of different settings. Clinically, Syk over-expression is reported in Mantle Cell Lymphoma (Rinaldi, Kwee et al. Br J Haematol 132(3): 303-16 (2006) and the TEL-Syk fusion protein (Translocated ETS Leukemia) generated by a chromosomal translocation (t(9;12)(q22;p12)) leads to increased Syk activity and is associated with myelodysplastic syndrome (Kuno, Abe et al. Blood 97(4): 1050-5 (2001). Leukemia is induced in mice by the adoptive transfer of bone marrow cells that express human TEL-Syk (Wossning, Herzog et al. J Exp Med 203(13): 2829-40 (2006). Further, in mouse primary bone marrow cells, over-expression of Syk results in IL-7 independent growth in culture (Wossning, Herzog et al. 2006). Consistently, Syk was reported to mediate mTOR (mammalian target of Rapamycin) survival signals in follicular, mantle cell, Burkitt's, and diffuse large B-cell NHL (Leseux, Hamdi et al. Blood 108(13): 4156-62 (2006). Additional recent studies also suggest that Syk-dependant survival signals may play a role in B-cell malignancies, including DLBCL, mantle cell lymphoma and follicular lymphoma (Gururajan, Jennings et al. 2006; Irish, Czerwinski et al. J Immunol 176(10): 5715-9 (2006). Given the role of tonic BCR signaling in normal B cells and Syk-dependent survival of NHL cell lines in vitro, the specific inhibition of Syk may prove promising for the treatment of certain B-cell lymphomas.
Recently, R406 (Rigel Pharmaceuticals) was reported to inhibit ITAM signaling in response to various stimuli, including FcεR1 and BCR induced Syk activation (Braselmann, Taylor et al. J Pharmacol Exp Ther 319(3): 998-1008(2006). Interestingly, this ATP-competitive inhibitor of Syk was also active against Flt3, cKit, and JAK kinases, but not against Src kinsase (Braselmann, Taylor et al. 2006). Activating mutations to Flt3 are associated with AML and inhibition of this kinase is currently under clinical development (Burnett and Knapper Hematology Am Soc Hematol Educ Program 2007: 429-34 (2007). Over-activation of the tyrosine kinase cKit is also associated with hematologic malignancies, and a target for cancer therapy (Heinrich, Griffith et al. Blood 96(3): 925-32 (2000). Similarly, JAK3 signaling is implicated in leukemias and lymphomas, and is currently exploited as a potential therapeutic target (Heinrich, Griffith et al. 2000). Importantly, the multi-kinase inhibitory activity of R406 attenuates BCR signaling in lymphoma cell lines and primary human lymphoma samples, resulting in apoptosis of the former (Chen, Monti et al. Blood 111(4): 2230-7 (2008). Further, a phase II clinical trial reported favorable results by this compound in refractory NHL and chronic lymphocytic leukemia (Friedberg J W et al, Blood 2008; 112(11), Abstract 3). Although the precise mechanism of action is unclear for R406, the data suggest that inhibition of kinases that mediate survival signaling in lymphocytes is clinically beneficial.
Additional recent studies also suggest that syk-dependant survival signals may play a role in B-cell malignancies, including DLBCL, mantle cell lymphoma and follicular lymphoma (see e.g., S. Linfengshen et al. Blood, February 2008; 111: 2230-2237; J. M. Irish et al. Blood, 2006; 108: 3135-3142; A. Renaldi et al. Brit J. Haematology, 2006; 132: 303-316; M. Guruoajan et al. J. Immunol, 2006; 176: 5715-5719; L. Laseux et al. Blood, 2006; 108: 4156-4162.
Patents and patent applications describing substituted pyrimidinediamine compounds include: U.S. application Ser. No. 10/355,543 filed Jan. 31, 2003 (US2004/0029902A1), international application Serial No. PCT/US03/03022 filed Jan. 31, 2003 (WO 03/063794), U.S. application Ser. No. 10/631,029 filed Jul. 29, 2003, international application Serial No. PCT/US03/24087 (WO 04/014382), U.S. application Ser. No. 10/903,263 filed Jul. 30, 2004, and international application Serial No. PCT/US2004/24716 (WO 05/016893), the disclosures of which are incorporated herein by reference. Substituted pyrimidinediamine compounds are also described in international patent application publication numbers: WO 02/059110, WO 03/074515, WO 03/106416, WO 03/066601, WO 03/063794, WO 04/046118, WO 05/016894, WO 05/122294, WO 05/066156, WO 03/002542, WO 03/030909, WO 00/39101, WO 05/037800 and U.S. Pat. Pub. No. 2003/0149064.
While progress has been made in this field, there remains a need in the art for compounds that inhibit syk kinase, as well as for methods for treating conditions in a patient, such as restenosis, thrombosis, and/or inflammation that can benefit from such inhibition. Moreover, the availability of compounds that selectively inhibit one of these kinases as compared to other kinases would also be desirable. The present invention satisfies this and other needs.

Inhibitors of syk and JAK protein kinases