The present invention relates to a water-based binder composition containing. A) an aqueous solution or dispersion of a water-dilutable organic polyol component containing a mixture of at least 5% by weight each of at least two hydroxy-functional polymers selected from PA0 B) a polyisocyanate component which is emulsified in the aqueous solution or dispersion A), has a viscosity at 23.degree. C. of 50 to 10,000 mPa.s and contains at least one organic polyisocyanate,. A1) polyester resins containing hydroxyl, urethane and carboxylate groups, PA1 A2) polyester resins containing hydroxyl and carboxylate groups, but no urethane or sulfonate groups, PA1 A3) polyester resins containing hydroxyl and sulfonate groups and, optionally, carboxylate groups and/or urethane groups, PA1 A4) polyacrylate resins containing hydroxyl, carboxylate and/or sulfonate groups, PA1 A5) acrylate-grafted polyester resins containing hydroxyl, carboxylate and/or sulfonate groups, and. wherein the NCO:OH equivalent ratio, based on the isocyanate groups of component B) and the hydroxyl groups of the polyol component present in A), is 0.2:1 to 5:1.. The present invention also relates to a process for the production of a coating or sealing composition containing this aqueous binder composition.

1. Field of the Invention
This invention relates to a water-containing binder composition based on polyisocyanates and mixtures of at least two different water-dispersible or water-soluble polyol components polymers, to a process for the production of these binder compositions and to their use as binders for coating and sealing compositions.
2. Description of the Prior Art
Ecological factors play an important part in coatings technology. A particularly important problem is to reduce the quantities of organic solvents used in coating compositions.
In the case of chemically crosslinking polyurethane lacquers, which are particularly important in the coating field by virtue of their outstanding properties, it has not been possible until very recently to eliminate the use of organic solvents. The use of water instead of organic solvents in two-component polyurethane coating compositions based on polyisocyanates containing free isocyanate groups did not appear possible for some considerable time because isocyanate groups are known to react not only with alcoholic hydroxyl groups, but also with water. In addition, the concentration of active hydrogen atoms from water in these systems is far higher than the concentration of hydroxyl groups from the organic NCO-reactive component. Accordingly, it must be assumed that the isocyanate/water reaction with formation of urea and carbon dioxide takes place in the ternary polyisocyanate/organic polyhydroxyl compound/water system. This isocyanate/water reaction is detrimental because it does not result in crosslinking of the organic polyhydroxyl compounds and also causes foaming of the mixture through the formation of carbon dioxide.
It was only recently recognized (DE-OS 3,829,587) that selected polyhydroxy polyacrylates could be combined with polyisocyanates containing free isocyanate groups to form water-based two-component systems. These coating compositions have a pot life of several hours and cure to form high-quality crosslinked films which are comparable in their properties to coatings previously obtained from solvent-containing two-component polyurethane coating compositions.
It has now been found that certain mixtures of water-containing polymer polyols based on at least two different polyester- and/or polymer-based polymers and polyisocyanates containing free isocyanate groups can also be used as binders. These binders have long pot lives, excellent flow during film formation and good pigment wettability.

Water-based binder composition and its use for the production of coating or sealing compositions


A plurality of signal processing functions are achieved with the same arithmetic processing circuit by controlling wiring arrangements or signal modulation in accordance with a predetermined arrangement control signal that is output based on circuit arrangement information read from a circuit arrangement information storage unit. Hierarchical parallel processing is realized with small-scale circuit configuration. Further, detection of a predetermined feature and integration of the detection results can be efficiently performed.

Conventionally, as image sensors having an image processing function by integrating an analog processing circuit with an image sensor serving as a solid-state image sensing element, for example, semiconductor chip structures (Japanese Patent Laid-Open Nos. 2000-13694 and 11-266002) and the like are known, in which a solid-state image sensing element and a spatial filter processing function and the like are integrated.
Examples of attempts to add the early visual function of a living body to an image sensor are a study of silicon retina by Mead et al. (C. Mead, "Analog VLSI and Neural Systems", Addison Wesley Pub., 1989, U.S. Pat. No. 4,786,81) and an artificial retina LSI which integrates a pixel array, pixel access control circuit, multiplexer, and weight control circuit on one chip to realize a predetermined filtering function (Journal of the Institute of Image Information and Television Engineers Vol. 53, No. 2, pp. 178–183, 1999).
The operation of a CMOS sensor circuit will be described below as a prior art. FIG. 8 is a schematic circuit diagram of a sensor circuit (a drive circuit diagram of a CMOS sensor) disclosed in Japanese Patent Laid-Open No. 11-196332. This sensor circuit outputs a video signal to, e.g., the spatial filter circuit of the above-described image sensing signal processing circuit.
Referring to FIG. 8, photoelectric conversion elements are formed by photodiodes PD11 to PD22 . . . with p-n junctions and transfer MOS transistors ST11 to ST22 . . . connected to the cathodes of the photodiodes. A vertical selection circuit VSR sequentially sets outputs V1 to V8 to "H" to sequentially activate vertical selection lines HL1, HL2, . . . . In addition, outputs H1 to H8 from a horizontal selection circuit HSR are sequentially set to "H" to turn on horizontal transfer switch MOS transistors HT1 to HT8. Image charges accumulated in the respective pixels are time-serially read out from vertical output lines HV1 to HV8 to an output line HOL and output through an amplifier AMP.
A reset MOS transistor RES is turned on every time pixel charges are output, thereby resetting the output line HOL every time pixel charges are output. Of the photodiodes PD11 to PD22 . . . , the photodiodes PD11, PD12, PD21, PD22, PD31, . . . which are connected to the vertical output lines HV1 and HV2 are shielded from light on their cathode sides to extract dark charges.
FIG. 9 is a timing chart of the interlaced read of the solid-state image sensing apparatus. The pixels are read out every other pixel in the horizontal and vertical directions of photoelectric conversion elements in the effective signal range.
First, the vertical selection circuit VSR sets the output V1 to "H" to set the vertical selection line HL1 to "H". Subsequently, the outputs H1, H2, H3, H5, H7, . . . from the horizontal selection circuit HSR are sequentially set to "H". With this operation, the horizontal transfer switch MOS transistors HT1, HT2, HT3, HT5, HT7, . . . are sequentially turned on. Image charges accumulated in the respective pixels are time-serially read out from vertical output lines HV1, HV2, HV3, HV5, HV7, . . . to the output line HOL and output through the amplifier AMP.
After the outputs H1, H2, H3, H5, H7, . . . from the horizontal selection circuit HSR are sequentially set to "H", the reset MOS transistor RES is turned on to reset the output line HOL every time the pixel charges are read out, thereby eliminating the influence of adjacent pixels.
Referring to FIG. 9, an output OUT from the amplifier AMP changes to "H" first because the reference signal output photoelectric conversion elements of the photodiodes PD11 and PD12 of the pixels are shielded from light. After that, a low-potential-side level is output in accordance with the charges of the first effective signal output photoelectric conversion elements of the photodiodes PD13, PD15, and PD17. In addition to such an interlaced read, a block read for reading an arbitrary range from an entire image is also done.
The interval of the interfaced read can be arbitrarily changed. A prior art which applies a spatial filter after the above-described read is disclosed in Japanese Patent Laid-Open No. 2000-13694.
However, in the above prior art, a plurality of predetermined different geometrical features cannot be efficiently sequentially extracted from time-serially input image data by the single circuit.
In addition, to extract a plurality of predetermined different geometrical features using an array circuit in which feature extraction circuits are spatially parallelly arrayed, time-serial image signals from a sensor must be spatially separated and individually input to corresponding feature extraction circuits. Furthermore, a sensor output must have one-to-one correspondence with the address of a feature extraction circuit on the array circuit.
Image recognition or voice recognition schemes are roughly classified into a type for sequentially calculating and executing a recognition processing algorithm as computer software that is specialized to a specific recognition object and a type for executing recognition processing by a dedicated parallel image processor (e.g., an SIMD or MIMD machine).
Typical examples of image recognition algorithms for calculating a feature vector associated with the similarity to a model to be recognized are a method using similarity calculation or higher-order correlation coefficient calculation, which is done by representing the model data of an object to be recognized as a template model and executing template matching with an input image (or its feature vector), and a method using hierarchical parallel processing (Japanese Patent No. 2741793).
Especially, to fully detect even a partially occluded object to be detected, a scheme of determining the similarity to a local portion of a model to be detected is proposed in Japanese Patent Laid-Open No. 11-15945. In this proposal, matching processing between a local model and a local portion of an object is executed, and the degree of support for supporting the presence of the object at each local portion is obtained by integration processing based on the Dempster-Shafer theory or Fuzzy theory, thereby doing highly accurate detection.
In Japanese Patent Laid-Open No. 6-176158, a plurality of types of feature vectors for an input pattern are individually recognized by obtaining a single category similarity. Then, the results are normalized by the maximum similarity value to obtain the integrated similarity, thereby executing final recognition.
In Japanese Patent Laid-Open No. 9-153021, in a parallel processing apparatus which sequentially receives digital signals and integrates one or more processing results obtained by divisionally processing the digital signals by one or more processors, the digital signals are divided using a means for converting an input signal into unit signals, thereby obtaining an optimum arrangement in terms of capability or economics in accordance with the input signal.
However, of the above prior arts, the arrangement disclosed in Japanese Patent Laid-Open No. 11-15945 does not explain how to integrate matching results when object models have a plurality of categories, and which local model yields matching results to be integrated. In this prior art, confidence degrees for the presence of features by a non-additive measure are integrated on the basis of, e.g., the Dempster-Shafer theory, though it does not guarantee optimum estimation.
In addition, if the size of an object in an image is different from that of an object model, or if a plurality of objects with different sizes simultaneously exist, the method is hard to apply. Even if object models corresponding to a plurality of sizes are prepared in advance, and similarity to each model is determined sequentially for the difference sizes, it is not preferable from the viewpoint of processing efficiency or circuit scale (memory size) In the parallel processing apparatus disclosed in Japanese Patent Laid-Open No. 9-153021, appropriate data division processing can hardly be executed when a plurality of objects having different sizes are present in image data or the like. Hence, when the type or size of object is unknown, appropriate pattern recognition can hardly be executed by parallel processing only by simply uniquely dividing data in synchronism with an input signal.
The arrangement of the pattern recognition apparatus disclosed in Japanese Patent Laid-Open No. 6-176158 cannot improve the memory efficiency or reduce the circuit scale. Generally, in an arrangement for executing pattern recognition processing using hierarchical parallel processing circuits (e.g., the arrangement disclosed in Japanese Patent No. 2741793), a plurality of features are simultaneously parallelly detected at sampling points on input data. In any of the above prior arts, hence, the number of elements in the lower layer increases depending on the size of an input image, resulting in an increase in circuit scale.
Conventionally, as a logic IC that allows a user to construct an arbitrary logic, an FPGA (Field Programmable Gate Array) is provided.
An FPGA is formed by periodically arraying a plurality of relatively large circuit blocks and interconnection blocks on a chip. A number of "devices capable of programming" electrical connection or disconnection of the circuits are arranged in the circuit blocks and interconnection blocks. A user can design connections in and between the blocks in a field (site of use) by programming (defining) these devices. Cell library blocks having various kinds of logic circuits are arrayed in a matrix in a chip. Signal interconnections are formed horizontally and vertically between the cell library blocks. Switch elements are arranged at the interunits of the interconnections and between the interconnections.
Three schemes below are employed as switch elements.
(1) Amorphous Si is inserted between metal interconnections to insulate them in the initial state. A current is supplied between desired metal interconnections to break the insulating film, thereby short-circuiting the interconnections (anti-fuse scheme). Conversely, metal interconnections are short-circuited in advance using polysilicon or the like and then disconnected by a laser or the like (fuse scheme).
(2) A normal MOS transistor is used as a switching element, and the potential state of its gate is stored in a memory. As the memory, a volatile DRAM or SRAM, or a nonvolatile EEPROM is used. Use of a ferroelectric memory (FRAM) is also proposed. A volatile memory must receive the information of logic connection and wiring connection into the FPGA every time it is used. However, this memory can be a Reconfigurable Logic capable of changing information a number of times. To the contrary, a nonvolatile memory can maintain the information of logic connection and wiring connection even when the power supply is turned on/off.
(3) A switching element itself is formed from an EEPROM or the like to store the ON/OFF information of a transistor.
In designing a logic system using an FPGA, a desired logic function is described by an HDL (Hardware Description Language) using a support tool provided by an EDA vendor, and logic circuit data (the type of logic gate to be used and inter-terminal connection information) is obtained using a logic synthesizing tool. To implement the resultant logic circuit, the logic operation data of a basic logic cell CLB and connection data between the basic logic cells CLB are obtained. In addition, interconnections to be used and the ON/OFF control data of a cross-point switch CSW are determined from the connection data, thereby building a whole logic circuit system. Such logic design can easily be done by the user, and its convenience is widely recognized.
Arrangements disclosed in Japanese Patent Laid-Open Nos. 11-168185 and 2000-331113 are known as methods of reconfigurably connecting an analog processing element using an FPGA. In the former arrangement, an FPGA is formed on one surface of a stacked substrate, an analog processing circuit is formed on the other surface, and input and output terminals and an interface circuit, which connect the FPGA and analog processing circuit, are prepared. In the latter arrangement, first and second analog signals are converted into PWM (Pulse Width Modulation) signals and input to an FPGA circuit, and logical operation of the two PWM signals is executed by the FPGA circuit, thereby allowing reconfiguration.
A hierarchical neural network disclosed in Japanese Patent No. 2679730 is related to the architecture of a hierarchical neural network that allows time-divisionally multiplexed use of single-layered hardware, and has as its object to allow equivalently making a multi-layered structure by time-divisionally using single-layered hardware. This prior art discloses a hierarchical neural network formed by connecting a plurality of neuron models to each other, comprising a single-layered unit assembling means for forming a single-layered unit assembly by installing a plurality of units of neuron models which allow to time-divisionally output a voltage through a nonlinear output function by generating a product of a time-divisionally multiplexed analog signal and external digital weight data and by time-divisionally adding the product through a capacitor to integrate the product, a feedback means for feeding back the output from the single-layered unit assembling means to the input unit of the same single-unit assembly, and a control means for executing control to time-divisionally multiplex analog signals from units, which are output from the single-layered unit assembling means, and to time-divisionally use the single-layered unit assembling means through the feedback means, wherein the single-layered unit assembling means is time-divisionally used to equivalently form a neural network having a hierarchical structure.
In an FPAA (Field Programmable Analog Array) circuit according to U.S. Pat. No. 5,959,871, programmable analog processing cells including a multiplexer, demultiplexer, control circuit, and analog processing element are parallelly arrayed through signal lines, thereby executing programmable analog processing.
In all the above prior arts, a so-called FPGA is based on a logic circuit. That is, only the connection state between logic blocks can be changed. Hence, only with the FPGA, analog parallel arithmetic processing of a neural circuit network or like cannot be implemented.
In applying the arrangement of Japanese Patent Laid-Open No. 11-168185 to a neural circuit network, when the number of neural elements increases, the number of input/output terminals exponentially increases, resulting in difficulty in handling. For this reason, in principle, it is difficult to set an arbitrary interconnection structure, and a special process for mounting the elements on a stacked substrate is required. In the arrangement disclosed in Japanese Patent Laid-Open No. 2000-331113, it is basically possible to form a pseudo addition circuit or pseudo integration circuit for two analog signals. However, it is difficult to implement a large-scale parallel hierarchical processing circuit.
In the hierarchical neural network disclosed in Japanese Patent No. 2679730, since no means for variably arbitrarily controlling the inter-layer connection is prepared, the number of types of processing that can be substantially realized is considerably limited.
In the arrangement according to U.S. Pat. No. 5,959,871, each of the analog processing units (cells) has a control circuit, analog processing circuit element, signal branch circuit, and the like. For this reason, the scale of the circuit component (analog processing cell) becomes very large, and therefore, the total circuit area inevitably increases. Additionally, in a structure in which analog processing units each incorporating a multiplexer and demultiplexer are arrayed on a two-dimensional plane, it is difficult to realize an arbitrary connection structure and, more particularly, hierarchical connection.

Dynamically reconfigurable signal processing circuit, pattern recognition apparatus, and image processing apparatus


Systems and methods relating to a clutch system for use in controllably transmitting torque from an input shaft to an output shaft. The clutch system has a torque transmission fluid that has a viscosity that changes based on the strength of an electromagnetic field passing through the fluid. A number of sensors are placed at different radial locations on the torque transmission disks to detect the strength of the electromagnetic field. Based on the strength of the electromagnetic field, the amount of torque being transmitted from the input shaft to the output shaft can be adjusted. Also disclosed is a distributed actuation architecture that uses this clutch system. The distributed actuation architecture allows for the use of a single drive motor in conjunction with multiple instances of the clutch system to actuate a mechanical linkage, such as a robotic arm.

Increasingly, we are witnessing a growing number of developments in the field of robotics characterized by their intent to integrate man and machine in a safe and functional manner. The suitability of a manipulator to work in close proximity with humans is determined first by the level of safety it can guarantee towards its human counterparts. Guaranteeing safety is a difficult if not impossible exercise as we can rarely guarantee the dependability of the numerous components required to complete a modern manipulator. Add in the human factor, and our task becomes insurmountable.
Thus, much focus has been centered on interactive robots which are expected to perform in a safe and dependable manner in unknown and unpredictable environments. Arguably, the chief safety concern is the manipulator's response to collisions with humans. Such collisions are responsible for numerous injuries each year, despite the existence of barriers, and other fail-safe mechanisms. As we move closer and closer towards a shared environment between robots and humans, new approaches to manipulator design are becoming increasingly important.
Devices utilizing the unique properties of Magneto-Rheological (MR) and Electro-Rheological (ER) fluids have been developed for robotic applications, however almost entirely for use in haptic systems. While it has been suggested in the literature how such devices might be used in a manipulator to improve both safety and performance, there appears to be a general reluctance towards adopting such technology as a viable alternative to the current solutions.
There are several sources of danger when working closely with robotic devices. However, collisions involving robots and humans pose arguably the largest degree of danger. It is expected that collisions will become unavoidable, if not routine as we continue to integrate man and machine into a single working environment.
In the prior art, friction and other nonlinearities present in the transmission of industrial manipulators led to the development of joint torque controlled systems. Characterized by torque sensors located at the joints, such manipulators are capable of achieving precise force control. Moreover, this class of manipulators can be controlled to exhibit very low impedance when operating within the controllable bandwidth. Barring the potential for high velocity collisions, i.e., collisions having their dynamics above the controllable frequency, this implementation can successfully attenuate the impact loads associated with collisions.
However, collisions occurring above the controllable bandwidth are subject to the open loop characteristics of the manipulator. As the demands for performance are increased, such systems require faster and more powerful actuators in order to successfully control and minimize impact forces during a collision. Any degree of safety introduced by a joint torque controlled system relies on the proper operation of system electronics. Thus guaranteeing collision safety becomes difficult as electronic components are susceptible to failure.
In attempts to guarantee the safety of humans within a shared workspace, much research has been focused on the development of manipulators which are intrinsically safe. That is, manipulators which by means of their mechanical properties can guarantee some level of collision safety in the absence of a controller.
To understand the degree of safety one might associate with a manipulator, one can examine the results of an uncontrolled collision through the use of the Head Injury Criterion (HIC). The HIC along with its variations have long been used by the automotive industry to gauge the severity of collisions. In the field of robotics, it can also be used to gain similar insight. The HIC is defined as:
                    HIC        =                              max                                          t                1                            ,                              t                2                                                                    {                                                            (                                                            t                      2                                        -                                          t                      1                                                        )                                                                  [                                                            1                                                                        t                          2                                                -                                                  t                          1                                                                                ∫                                                  t                          1                                                                          t                          2                                                                                a                                                                                (                            t                            )                                                                                ⅆ                          t                                                                                ]                                            2.5                        }                                              (        1        )            where a is the acceleration of the head (in g's), and t1 and t2 are times within the collision selected to maximize the HIC, such that t1 <t2.
An HIC of 100 is the maximum value considered to be non-life threatening. To gauge how the effective inertia of a link is related to a manipulator's inherent ability to collide safely, a single axis robot colliding with a human head is simulated. With reference to FIG. 1, the results of the HIC show that a manipulator's safety can be improved by reducing its effective inertia. This find inspired the generation of light weight robots.
One of the first manipulators to be designed under the lightweight paradigm was the Whole Arm Manipulator (WAM). The WAM uses steel cable transmission allowing actuators to be located at the manipulator's base. Removing the actuators from the links reduces the associated link mass, and hence the associated link inertia. This works to improve the inherent safety of the manipulator.
According to the prior art, one manipulator uses light weight carbon composites to form its links. Furthermore, an advanced actuator design integrated with low weight harmonic reduction gears allows this manipulator to attain a fully integrated light weight design.
Locating actuators at the base of the manipulator, or the use of advanced light weight material and actuator design successfully reduce a link's mass, and thus its associated inertia.
However, this approach in the prior art addresses only half of the problem. Robotic manipulators make use of high performance servo motors to drive their links. The output of these servomotors have inverse characteristics to what is desired when actuating the manipulator. More specifically, servo motors produce low output torque, and at high velocity with respect to what is suitable for most robots. To remedy this, gear reduction systems are most commonly employed. The resulting torque at the link is the actuator torque multiplied by the gear ratio Gr, while the reflected actuator inertia associated with the rotor of the motor is multiplied by Gr2. Thus, the effective inertia experienced by a robotic link can be expressed asJr=J1+Gr2Jr,  (2)
where Jl is the inertia of the link, and Jr is the rotor inertia of the motor. The reflected actuator inertia of a manipulators can in fact be much larger than that of the link inertia, thereby contributing a larger share of the inertial load during collisions.
In response to this, several prior art actuation systems have been proposed which work to decouple the reflected actuator inertia from the link. However, none of these actuation systems provide enough of a safety margin while providing the desired performance.
Therefore, there is a need for an actuation system which would provide a useful safety margin while providing the required mass and performance.

Magneto- and electro-rheological based actuators for human friendly manipulators


In a method of constructing a eukaryotic host microorganism for production of a heterologous protein encoded by a trangenically introduced gene, production efficiency of the heterologous protein by the transformant obtained by introducing the gene encoding the heterologous protein into the host is improved.

Recombinant DNA technology is used for production of heterologous proteins in various host microorganisms and animals including Escherichia coli (hereinafter referred to as E. coli). The target products are various biogenous proteins (herein, inclusive of polypeptides), and many of them have already been produced industrially for medical and other uses so far.
Among various hosts developed for production of heterologous proteins, yeasts seem favorable for expression of animal and plant proteins because of their eukaryotic similarity in the transcription and translation systems to animals and plants, and the baker's yeast (Saccharomyces cerevisiae) is a widely used host. Among yeasts, S. pombe is known to be close to animal cells in nature as is evident from the fact that it grows by fission not by budding as a result of the different evolution process it has followed since it diverged from other yeasts at early stages. Therefore, the use of S. pombe as the host for expression of heterologous proteins is expected to provide a gene product closer to its natural form in animal cells.
Though studies of gene expression in S. pombe is delayed, the recent discovery of potent promoters functional in S. pombe has accelerated the development of expression systems using S. pombe as the host, and various improvements have been added to expression vectors to develop more stable and efficient expression systems (Japanese Patent No. 2776085, JP-A-07-163373, JP-A-10-215867, JP-A-10-234375, JP-A-11-192094, JP-A-2000-136199, JP-A-2000-262284). As a result, expression systems using S. pombe as the host show high production efficiency now.
Production systems for heterologous proteins using eukaryotic microorganisms such as yeasts can be realized easily by conventional microbiological techniques and recombinant DNA technology with high productivity. Large cultures are already available and are acceleratingly used for actual production. Even after the scale is enlarged for actual production, cells retain the high production efficiency per cell obtained in the laboratory.
However, considering that cost reduction is often demanded in actual production, it is necessary to improve the production efficiency of heterologous proteins through improvement in cell growth efficiency, suppression of degradation of the heterologous protein of interest, more efficient eukaryotic modifications in the microorganisms or more efficient utilization of the nutrition sources. For example, increase in the conversion of the carbon sources added to the medium for culture growth into the heterologous protein of interest is expected to drastically improve cell growth efficiency and therefore production efficiency of the heterologous protein, because efficient utilization of the carbon sources in the medium for production of the heterologous protein of interest seems to be sacrificed for their consumption by metabolic systems unnecessary for cell growth or production of the heterologous protein of interest (such as the ethanol fermentation system for production of ethanol).

Method of constructing host and method of producing heterologous protein

Abstract: Part or all of the genome unnecessary or detrimental to production of the heterologous protein by the transformant in culture is deleted or inactivated.

Abstract: The eukaryotic host microorganism is preferably Schizosaccharomyces pombe. The part of the genome of the eukaryotic host microorganism to be deleted or inactivated is preferably a gene selected from the genes associated with energy metabolism and the genes associated with proteases, such as a pyruvate decarboxylase gene, a serine protease gene, an aminopeptidase gene and a carboxypeptidase gene.


A method for modeling a system configuration, including isotonizing an unconstrained additive model of a cache architecture to obtain an isotonic additive model for the cache architecture, wherein the isotonic additive model is of the same functional form as the unconstrained additive model, smoothing the isotonic additive model using a flat spot technique to obtain a characterization of the cache architecture, and modeling a system configuration using the characterization of the cache architecture.

Generally, a microprocessor operates much faster than main memory can supply data to the microprocessor. Therefore, many computer systems temporarily store recently and frequently used data in smaller, but much faster cache memory. There are many levels of cache, e.g., level one (L1), level two (L2), level three (L3), etc. L1 cache typically is closest to the processor, smaller in size, and faster in access time. Typically, as the level of the cache increases (e.g., from L1 to L2 to L3), the level of cache is further from the microprocessor, larger in size, slower in access time, and supports more microprocessors.
Referring to FIG. 1 and FIG. 2, a typical parallel processing computer system includes boards (20A–20N) connected to a L3 cache (22), i.e., an external cache memory. Each board (20A–20N) has, among other things, chips (14A–14N) and a L2 cache (18), i.e., an on-board cache L3 cache (22) is connected to a main memory (24). Main memory (24) holds data and program instructions to be executed by the microprocessor (8). Microchips (14A–14N) include microprocessors (8A–8N) that are associated with L1 cache (12A–12N), i.e., an on-chip cache memory. In addition to the microprocessors (8A–8N), virtual microprocessors (not depicted) may also use the L1 cache (12A–12N). Virtual microprocessors are considered threads or placeholders for current processes associated with microprocessors (8A–8N). One skilled in the art can appreciate that L1 cache may be associated with multiple microprocessors rather than accessed by a single microprocessor as depicted in FIG. 2.
Program instructions that are usually stored in main memory are physical operations given by a program to the microprocessor (8A–8N), e.g., specifying a register or referencing the location of data in cache memory (either L1 cache (12), L2 cache (18), or L3 cache (22)). A sequence of program instructions linked together is known as a trace. The program instructions are executed by the microprocessor (8A–8N). Each program instruction is fetched by a memory controller (not shown). Upon command from one of the microprocessors (14A–14N), the memory controller searches for data, such as the program instruction, first in the L1 cache (12A–12N). If the data is not found in the L1 cache (12A–12N), the memory controller next searches the L2 cache (18). If the data is not found in the L2 cache (18), the memory controller then searches the L3 cache (22). If the data is not found in the L3 cache (22), the memory controller finally searches the main memory (24). Once the data is found, the memory controller returns the data to the microprocessor that issued the command. If the data is not found, an error message is returned to the microprocessor that issued the command.
One skilled in the art can appreciate that the architecture of the cache may be structured in a variety of ways, e.g., the architectural components may include cache hierarchy, cache size, cache line size, cache associativity, cache sharing, and cache write type may be designed in a number of ways.
Cache hierarchy refers to the different levels of memory, i.e., L1 cache, L2 cache, etc., that take advantage of the "principle of locality". The "principle of locality" asserts that most programs do not access data uniformly. Thus, the cache hierarchy may be designed using different types of cache memories (i.e., faster more expensive cache memory or slower less expensive cache memory) in conjunction with the "principle of locality" to improve computer system performance. As mentioned above, L1 cache is typically located on the same chip as the microprocessor while, in contrast, L2 cache is typically located on the same board as the microprocessor. Further, L2 cache is typically larger in size and has a slower access time than L1 cache.
Cache size refers to the total size of the cache memory. The cache memory is configured to store data in discrete blocks in the cache memory. A block is the minimum unit of information within each level of cache. The size of the block is referred to as the cache line size. The manner in which data is stored in the blocks is referred to as cache associativity. Cache memories typically use one of the following types of cache associativity: direct mapped (one-to-one), fully associative (one to all), or set associative (one to set).
Cache sharing of cache refers to the manner in which data in the blocks are shared. Specifically, cache sharing is the number of processors (physical or virtual) sharing one L1 cache, the number of L1 caches sharing one L2 cache, and the number of L2 caches sharing one L3 cache, etc. Most program instructions involve accessing (reading) data stored in the cache memory; therefore, the cache associativity, cache sharing, cache size, and cache line size are particularly significant to the cache architecture.
Likewise, writing to the cache memory (cache write type) is also critical to the cache architecture, because the process of writing is generally a very expensive process in terms of process time. Cache memory generally uses one of the following methods when writing data to the cache memory: "write through, no-write allocate" or "write back, write allocate".
In a parallel processing computer system, the issue of cache coherency is raised when writing to the cache memory that is shared by many processors. Cache coherency resolves conflicts in multiple processors accessing and writing (or changing) the value of variables stored in the same cache memory. The following protocols are typically used to resolve cache coherency issues: Modified Shared Invalid (MSI), Modified Exclusive Shared Invalid (MESI), Modified Owner Shared Invalid (MOSI), Modified Owner Exclusive Shared Invalid (MOESI), etc. One skilled in the art can appreciate the particular aspects of these protocols and that other protocols can be used to resolve cache coherency issues.
The performance of the cache architecture is evaluated using a variety of parameters, including a miss rate, a hit rate, an instruction count, an average memory access time, etc. The miss rate is the fraction of all memory accesses that are not satisfied by the cache memory. In contrast, the hit rate is the fraction of all memory accesses that are satisfied by the cache memory. The instruction count is the number of instructions processed in a particular amount of time. The average memory access time is the amount of time on average that is required to access data in a block of the cache memory.

Isotonic additive models in workload characterization


The invention provides a device for detecting non-cavitated caries lesions, including a measuring electrode having an electrically conductive tip. The tip is dimensionally configured to fit within a fissure and provide electrical contact with a patient's tooth. A reference electrode is also included, the reference electrode being configured for electrical contact with the patient's body. A measuring means is also provided for determining electrical conductance between the measuring electrode and the reference electrode, wherein the device is further configured to receive a current source for providing electrical current between the measuring electrode and the reference electrode.

Dental caries is a disease that frequently occurs soon after teeth erupt into the oral cavity, an environment that is generally hostile to the teeth of most individuals. Sites particularly prone to caries development are the occlusal surfaces of the posterior teeth. This is largely because these surfaces possess a morphology (i.e. pits, fissures and fossae) that favors retention of both fermentable carbohydrate and bacterial biofilms. These two entities are primary elements in dental caries causation. Combined, they result in the production of the acid that leads to tooth demineralization and the initiation and development of dental caries lesions. More tooth decay occurs in occlusal locations and to lesser degree in interproximal dentition sites (where teeth are in contact with one another) than elsewhere in the human dentition. This is because bacteria and fermentable carbohydrate collect more easily there, and are protected from the caries inhibiting effects of saliva, than occurs in other more salivary accessible dentition locations.
Dental caries begins as a demineralization process which leads to the development of pores and tunnels through the protective, non-electrically conductive enamel (Longbottom, C. and Huysmans, M.C.D.N.J.M. Electric measurements for use in caries clinical trials. Caries Res. 29, 94-99, 1995. Longbottom C and Huysmans M.C.D.N.J.M. Electrical measurements for use in caries clinical trials. J. Dent. Res. 83 (Spec. Issue C) C76-C79, 2004). Continued demineralization eventually results in enamel breaching. Once the enamel is breached, caries advances and spreads rapidly through the underlying dentine, a tissue much less mineralized than enamel. Such spreading is made easy because dentine is traversed by numerous tubules. Many, if not most of these dentinal tubules, especially in younger teeth, reach all the way to the dental pulp (Pashley D. H. Theory of dentin sensitivity. J. Clin. Dent. 5:65-67, 1994).
Non-cavitated caries lesions, particularly in the pits, fissures and fossae of the posterior teeth are difficult to detect and assess in humans. Teeth mainly involved include the first and second primary molars and the premolars and molars of the permanent dentition. These teeth and interproximal dentition sites are where the majority of dental cavities occur.
Presently, detection of caries development is mostly done by a dentist or other dental care provider with a simple, pick-like device, generally referred to as a dental explorer. Such detection is performed by visual examination for indications of mineral loss, and is done with or without x-rays. None of these tools is suitable for detection of a high percentage of non-cavitated occlusal caries lesions even when there is caries penetration into the dentine. Many of these early developing caries lesions are not cavitated, but do involve extensive tunneling through the enamel and such tunneling may not be detectable. Such caries development is frequently hard to discover until destruction of tooth substance becomes more substantial and the dentine becomes progressively more and more involved. As a consequence of the difficulty of their discovery, these lesions are commonly referred to as hidden dental caries (Weerheijm K L, van Amerongen W E, and Eggink C O. The clinical diagnosis of occlusal caries: A problem. J. Dent. Child. 56, 196-200, 1989). Their early discovery is often missed or involves much uncertainty. Not surprisingly, there is opportunity for pulpal damage to occur and for teeth to be lost unnecessarily (Verdonschot E. H., Wenzel A., Truin G. J. and Konig K. G. Performance of electrical resistance measurements adjunct to visual inspection in the early diagnosis of occlusal caries. J. Dent. 21: 332-337, 1993). Ironically, the anti-caries agent, fluoride, can be detrimental to early detection, because it favors less cavitation (Hudson P. and Kutsch V. K. Microdentistry: Current pit and fissure caries management. Compendium 22: 469-483, 2001). This is because fluoride reduces the solubility of the enamel covering the dentine, thereby enabling the enamel to remain largely intact while underlying dentine continues to be demineralized (Lussi A., Firestone A., Schoenberg V., Hotz P., and Stich H. In vivo diagnosis of fissure caries using a new electrical resistance monitor. Caries Res. 29: 81-87, 1995). For these reasons, it has become very important that caries lesions be detected as early and as easily as possible.
Because the enamel of freshly erupted teeth commonly exhibit a certain degree of porosity, such teeth are more prone to dental caries development than if they had been exposed in the mouth for an extended period under non-cavity producing and mineralizing conditions. Such improvement is called maturation and occurs because many of these exposed teeth acquire calcium and phosphate ions from saliva along with various proteinaceous accretions. These changes involve increased enamel mineralization, reduced enamel permeability and greater caries resistance. This is helped by fluoride if applied or taken up naturally during the tooth maturation process (Ie Y. L., Verdonschot E. H., Schaeken, M. J. M. and vant H of M. A. Electrical conductance of fissure enamel in recently erupted molar teeth as related to caries status. Caries Res. 29: 94-99, 1995). In contrast, in a caries-prone mouth where a demineralization environment is present, an opposite result occurs more readily, i.e. development of increased porosity and cavitation.
Several approaches have been unsuccessfully used to detect dental caries in its early stages. One of these involves testing for a tooth's ability to conduct electrical current even when there is no visible tooth mineral loss from the enamel and no cavitation can be seen. Electrical resistance is associated with the presence of intact, non-demineralized enamel; but, as a caries lesion develops and enamel mineral is progressively lost, fluid can seep therein and electrical resistance of the enamel correspondingly and progressively decreases (Williams, D. L., Tsamtsouris A., and White, G. E. Electrical resistance correlation with tactile examination on occlusal surfaces. J. Dent. Res. 57: 31-35, 1978, Longbottom C and Huysmans M.C.D.N.J.M. Electrical measurements for use in caries clinical trials. J. Dent. Res. 83 (Spec. Issue C) C76-C79, 2004).
Breaching of enamel occurs more easily in occlusal pit and fissure sites. As noted above, these dentition locations are where continual presence of acidogenic bacteria and fermentable carbohydrate can undergo significant and continual interaction. This favors prolonged generation of acid and in turn, prolonged and extensive tooth demineralization. As this happens, a point is reached where the enamel is sufficiently demineralized and porous that saliva penetrates therethrough and because of the ions that saliva contains, flow of electrical current can take place as a result. The more extensive the demineralization, the more readily these events occur and the easier it is to detect caries lesion development.
Earlier investigators measured electrical resistance or conductivity with direct current devices to determine if a tooth had lost mineral and had become carious (Pincus, P. A new method of examination of molar tooth grooves for the presence of dental caries. J. Physiol 113: 13-14, 1951. Mumford, J. M. Relationship between the electrical resistance of human teeth and the presence and extent of dental caries. Brit. Dent. J. 100, 239-244, 1956. Mayuzumi, Y, Suzuki, K and Sunada, J. A method of diagnosing incipient caries in pits and fissures by measuring electrical resistance. J. Dent. Res. 43, 431, 1964. Takeuchi, M., Kizu, T., Shimizu, T., Eto, M. and Amano, F. Sealing of the pit and fissure with resin adhesive. II. Results of nine months' field work, an investigation of electrical conductivity of teeth. Bull Tokyo Dent Coll 7, 60-71, 1966. Williams, D. L., Tsamtsouris A., and White, G. E. Electrical resistance correlation with tactile examination on occlusal surfaces. J. Dent. Res. 57: 31-35, 1978). Others subsequently used alternating current and measured impedance to do essentially the same thing White G. E., Tsamtsouris A., and Williams D. L. A longitudinal study of electronic detection of occlusal caries. J. Pedod. 5, 191-201, 1981. Pitts N. B. Clinical diagnosis of dental caries: a European perspective J. Dent. Educ. 65: 972-978, 2001). In each case, a cavity detecting device was provided, including a measuring probe made of a conducting metal, a direct or alternating current source, a resistance source, an impedance or conductance detector, and a reference electrode suitable for application, generally by attachment to a non-oral soft tissue part of the body. The human body is sufficiently conductive electrically to enable complete electrical continuity via the body between the measuring probe (i.e. the indicator electrode) and a reference electrode usually attached by adhesive means to a body surface such as the ventral surface of the forearm or the back of the neck or by means of a metal hook, the end of which is immersed in the mouth saliva usually by curling around the lower lip.
Tooth enamel is electrically non-conductive unless it is breached by demineralization or fracture. When this occurs, fluid at or entering the breached enamel site enables completion of an electrical circuit that allows current to flow. The electrical current used may be as low as a few micro-amperes (μA) in magnitude. Hence, it is safe even for use in medically compromised patients. In addition, the procedure is painless.
It has previously been found that special precautions have to be taken while making measurements to ensure electrical continuity without causing any peripheral electrical conductance to saliva or other moisture on the tooth or to saliva or other conductance means elsewhere in the mouth. Such isolation of the measuring electrode from surrounding saliva is an absolute requirement for success. Complete isolation can be achieved by using a rubber dam (Williams, D. L., Tsamtsouris A., and White, G. E. Electrical resistance correlation with tactile examination on occlusal surfaces. J. Dent. Res. 57: 31-35, 1978). However, such use of a dam is cumbersome and is not practical when an extensive mouth examination is required. Instead, most investigators have used a stream of air from an air syringe in an attempt to dry the tooth around but not at the measuring site. To do this simply, consistently and rapidly has been a major problem.
Ricketts et al. used a stream of air surrounding the measuring electrode to isolate the measuring site from surrounding surface electrical conduction (Ricketts, D. N. J. Kidd, E. A. M., and Wilson, R. F. A re-evaluation of electrical resistance measurements for the diagnosis of occlusal caries. Brit. Dent. J. 178: 11-17, 1995). However, the large size of the measuring tips used by these investigators prevented accurate measurements. Further, such large tips, with their drying feature, were not suitably shaped or sized for many of the sites that required more effective probing.
Current methods often yield false and/or variable readings. Current methods also lack the ability to rapidly and consistently detect non-cavitated caries lesions early and accurately. Basically, detection of non-cavitated caries lesions requires electrical linkage between the measuring electrode at the enamel surface measuring site and fluid within the caries lesion. Detection also requires the absence of any electrical conductance immediately around the lesion site. Furthermore, a method of instantly knowing that detection is operating properly is necessary.

Device for the detection of non-cavitated early dental caries lesions

The Research Foundation for the State University of New York


A direct memory access system consists of a direct memory access controller establishing a direct memory access data channel and including a first interface for coupling to a memory. A second interface is for coupling to a plurality of nodes. And a processor is coupled to the direct memory access controller and coupled to the second interface, wherein the processor configures the direct memory access data channel to transfer data between a programmably selectable respective one or more of the plurality of nodes and the memory. In some embodiments, the plurality of nodes are a digital signal processor memory and a host processor memory of a multi-media processor platform to be implemented in a wireless multi-media handheld telephone.

The present invention relates to wireless handheld multi-media devices, such as digital telephones, and more specifically to processor platforms in wireless handheld multi-media devices. Even more specifically, the present invention relates to such processor platforms having minimal size and power consumption and that enable efficient data transfers between multiple processors of the processor platform and multiple peripherals.
New standards for digital cellular systems incorporate high speed packet data network capability in addition to traditional circuit switched voice and data channels. At the same time, among the general public, there is wide spread use of the Internet which offers a host of personal communication, information, electronic commerce and entertainment services. The next generation cellular systems offers the opportunity to market wireless products which have voice, data, and personal information management capabilities, i.e. multi-media devices. These products are destined to become portable information appliances with the potential for significant market share.
In such multi-media devices, in particular digital cellular telephones, processor platforms include two main processor cores: a digital signal processor (DSP) core coupled to the radio interface and a host processor core for running the device and coordinating data movements from several peripherals. Such a device may include as peripherals, a Universal Serial Bus (USB), a Universal Asynchronous Receiver/Transmitter (UART) with an optional mode to support the IrDA standard, a Synchronous Serial Interface (SSI), a Multi-Media Card (MMC), and a Bluetooth interface supporting the Bluetooth standard.
It is desirable to be able to move data to and from the various peripherals and the memory of the host processor, and also to and from the various peripherals and the memory of the DSP, and furthermore, to and from the memory of the DSP and the memory of the host processor. Using a technique known in the art as Direct Memory Access (DMA), such transfers advantageously take place without involving either the host processor or the DSP. Thus, for example, instead of the host processor initiating a data transfer from a particular peripheral to the host processor memory, a DMA controller performs the data transfer, allowing the host processor to focus on more important functions. Advantageously, the DMA technique relieves the host processor and the DSP from the cumbersome tasks of simple data transfers, enabling faster and more efficient use of the processors within the device.
However, a DMA controller forms a hardwired unidirectional data channel between two nodes. The DMA controller is coupled between a particular peripheral and the system bus which accesses both the processor to be relieved of the task of performing the data transfer and it's memory. The DMA controller provides the hardware to implement the direct memory access. Because each data channel is unidirectional, two separate DMA data channels are required for bidirectional data transfers between the two nodes. Furthermore, since each data channel is implemented in hardware, once established, the data channel may not be reconfigured to allow a data transfer to and from different nodes or in a different direction.
Thus, separate unidirectional data channels must be hardwired to allow direct memory access for multiple processors and multiple peripherals. Disadvantageously, in handheld multi-media devices, there may be a large number of peripherals; thus, requiring many DMA controllers to hardwire all of the possible DMA connections. For example, to adequately relieve the host processor and the DSP from having to perform data transfers between the peripherals and the respective memories, DMA controllers must be implemented in hardware between each peripheral and the host processor memory and the DSP memory, such that each DMA controller establishes the desired unidirectional data channels.
Disadvantageously, in small handheld applications, implementing a large number of DMA controllers expends valuable real estate on the processor platform. In other words, the more hardware DMA controllers needed, the more transistors are required on the processor platform and the more space is consumed on the platform by the DMA hardware. What is needed is a processor platform that implements DMA functionality to allow efficient operation of multiple processors without using traditional DMA hardware for all of the various data transfer paths.
Another concern in processor platforms for small handheld multi-media processors is minimizing power consumption. Employing a processor platform without concern for saving power unnecessarily reduces the battery life, which is important in handheld applications because this decreases the time in between battery charges that are required. Furthermore, in multi-media applications which require a large random access memory (RAM), it is desirable to employ dynamic RAM (DRAM) as opposed to static RAM (SRAM), since DRAM is much less costly than SRAM in terms of die size versus array density.
Additionally, embedded DRAM (eDRAM), which is DRAM embedded on the processor platform, may be used to reduce the overall space required by the processor platform. However, in comparison to SRAM, both DRAM and eDRAM must be periodically refreshed in order to ensure that the data contained therein is saved. The refreshing process, typically performed by a refresh controller, consumes valuable power to make sure that data remains stored. What is needed is a method to refresh the DRAM in such a way as to conserve as much power as possible.
Furthermore, in such handheld multi-media devices, such as telephones, liquid crystal displays (LCDs), such as those found in personal digital assistants (PDAs), are implemented to allow the user to readily view web pages, for example. A typical LCD requires data to be moved from the video buffer to the display driver circuit. This presents problems in that the large LCD bus must transmit and receive data from 8, 16, or 32 bit busses from a memory (e.g. eDRAM) that is only 8, 16 or 32 bits wide. Disadvantageously, the LCD controller and image processor of the LCD spend much time using the system memory, as a video buffer, relative to other peripherals and devices that are required to access the system memory for DMA techniques, which makes the system memory less accessible to these other peripherals and devices. Thus, when video images are displayed on the LCD, the system memory (e.g. eDRAM) acts primarily as the video buffer and also as the system RAM. A separate RAM (e.g. another eDRAM) may be implemented to act as the video buffer; however, such additional memory disadvantageously adds to the transistor count and thus size of the processor platform. What is needed is an efficient memory that can adequately support an LCD controller and at the same time be used as a system RAM and for DMA data transfers.
The present invention advantageously addresses the above and other needs.
Corresponding reference characters indicate corresponding components throughout the several views of the drawings.

Integrated processor platform supporting wireless handheld multi-media devices


The invention provides inhibitors of matrix metalloproteinases that are useful for encouraging the development of healthy skin and for treating wounds. The inhibitors are peptides having sequences related to cleavage regions of the proenzyme forms of matrix metalloproteinases. The peptide inhibitors of the invention can be formulated into therapeutic compositions, lotions, creams, skin covering and wound dressings that facilitate healing and healthy skin development, discourage scarring and wrinkling and ameliorate the effects of healing.

The condition of the skin is always affected by factors such as humidity, ultraviolet rays, cosmetic compositions, aging, diseases, stress and eating habits. As the result, various skin troubles can arise. The skin also becomes less resilient with age as illustrated by the formation of wrinkles. Aging is generally associated with the thinning and general degradation of skin. As the skin naturally ages, there is a reduction in the number of cells and blood vessels that supply the skin. There is also a flattening of the dermal-epidermal junction that results in weaker mechanical resistance of this junction. As a consequence, older persons are more susceptive to blister formation in cases of mechanical trauma or disease processes. (See Oikarinen, (1990) "The Aging of Skin: Chronoaging Versus Photoaging", Photodermatal. Photoimmunol. Photomed., Vol. 7, pp 3–4).
Skin contains an elaborate network of elastin fibers that is responsible for maintaining its elastic properties. With excessive exposure to sunlight the elastic fiber system becomes hyperplastic, disorganized and ultimately disrupted. This process is known as actinic elastosis and it is a principal cause of wrinkling, discoloration and laxity of the skin in the exposed areas of the body. As new fibroblasts, endothelial cells and keratinocytes form, the skin can repair itself. However, the skin becomes less able to do so as it ages. Therefore, agents that can accelerate the growth and repair of prematurely aged skin are needed.
Wound healing is also accelerated by increased cellular proliferation and migration of certain cell types. The mechanisms involved in wound healing are often divided into four phases: hemostasis, inflammation, proliferation and maturation. During inflammation, leucocytes accumulate to combat bacteria and the permeability blood vessel walls increases, leading to swelling. If an infection does not develop the number of leucocytes diminishes. Monocytes replace the leukocytes. Macrophages and lymphocytes release growth factors (cytokines) as well as a number of chemical substances, such as histamine, serotonin, and prostaglandins. These substances help regulate the wound healing process. In the proliferation phase, new fibroblasts, endothelial cells and keratinocytes arise, connective tissue is formed, new blood vessels grow and injured tissue is regenerated. Fibroblasts become dominant after about a week, and the inflammation decreases and the strength of the tissues around the wound site is rapidly increased. During the maturation phase collagen is laid down and scar tissue is formed. This maturation phase might go on for a long time during which tissues of various types are regenerated. In order to obtain an optimal healing of skin and associated tissues, the supply of different vitamins and trace elements as well as nutrients should be sufficient as well as the oxygen supply.
Chronic wounds or indolent, nonhealing wounds may arise from different causes including infection, the presence of foreign bodies or toxic irritants, bums, prolonged cutaneously applied pressure and poor blood supply owing to impaired circulation. In a chronic wound the tissue homeostasis and the wound environment are compromised so that either healing fails to occur or healing begins but is subsequently halted. Factors contributing to the failure of healing in chronic wounds are tissue necrosis, dehydration, chronic wound edema, fibrotic induration and small blood vessel disease.
One of the major reasons that chronic wounds do not heal is that a class of proteinases, called matrix metalloproteinases (MMPs), destroys the newly formed wound bed (Vaalamo et al., 1997; Weckroth et al., 1996; DiColandrea et al., 1998; Moses et al., 1996). These matrix metalloproteinases are normally prevented from destroying the wound bed by the action of four Tissue Inhibitors of MetalloProteinase (TIMPs1–4) that form very specific inhibitory complexes with the matrix metalloproteinases (Olson et al., 1997; Taylor et al., 1996; Howard et al., 1991). That is, each TIMP only inhibits a specific subset of matrix metalloproteinases. In chronic wounds the ratio of matrix metalloproteinase to TIMP is high, such that most of the matrix metalloproteinases are uninhibited (Vaalamo et al., 1996; Saarialho-Kere, 1998). In fact, with elevated proteinase levels, the TIMP molecules themselves can be hydrolyzed. There is no naturally occurring TIMP molecule that singly inhibits all types of matrix metalloproteinases.
Many approaches have been suggested to control matrix metalloproteinase activity, including both small molecule (Levy et al., 1998; Wojtowicz-Praga et al., 1997; Duivenvoorden, et al., 1997) and peptide based inhibitors (Odake et al., 1994) and anti-MMP antibodies (Su et al., 1995). However, an ideal composition for wound healing and reversing the effects of aging would not only provide optimal inhibition of metalloproteinase but would stimulate the growth and regeneration of injured tissues.


A high current (0.2 to at least 2 milliamperes), low-energy (2.2 to 4 MV) ion beam is generated and is utilized to produce clinically significant quantities of medical isotopes useful in applications such as positron emission tomography. For a preferred embodiment, a tandem accelerator is utilized. Negative ions generated by a high current negative-ion source are accelerated by an electrostatic accelerator in which the necessary high voltage is produced by a solid state power supply. The accelerated ions then enter a stripping cell which removes electrons from the ions, converting them into positive ions. The positive ions are then accelerated to a target which is preferably at ground potential. For a preferred embodiment, the solid state power supply utilized to develop the required voltages is a cascade rectifier power supply which is coaxial with the accelerator between the ion source and the stripper, and is designed to have a voltage gradient which substantially matches the maximum voltage gradient of the accelerator.

A number of non-invasive methods of examining internal bodily organs, or sections of such organs, have become popular for diagnosing a variety of illnesses. One of these techniques is called Positron Emission Tomography (PET) or Positron Emission Transaxial Tomography (PET). In this method of developing internal bodily images, an array of sensors detects gamma rays emitted from tissues after the subject has been administered a natural biochemical substance (for example, gases, glucose or fatty acids) into which position-emitting radio-isotopes have been incorporated. A computer calculates the paths of the gamma rays (which result from collisions of positrons and electrons) and interprets the data to generate a tomographic image. The resultant tomogram represents local concentrations of the isotope-containing substance in the tissues. By proper choice of isotope-containing substance, various processes such as brain function, local blood flow, blood volume and other metabolic processes can be studied.
The short-lived radio-isotopes are administered by intravenous injection or by having the subject inhale a gas containing small quantities of the radio-isotope. Isotopes which are often incorporated into such gases or injections are carbon-11, nitrogen-13, oxygen-15 and fluorine-18. In present PET facilities, these radio-isotopes are derived from boron, carbon, nitrogen and neon targets, respectively, by bombarding the targets with high-energy (approximately 6-15 MV) protons or deuterons obtained from a particular accelerator.
Conventionally, the acelerator which is used to produce the isotope-generating particles is a cyclotron accelerator. However, cyclotron accelerators have significant drawbacks. Due to the short half-lives of the isotopes (ranging from approximately 2 minutes for oxygen-15 to 110 minutes for fluorine-18), the accelerator must be physically located in the medical center within a short distance from the PET scanning apparatus. At present, cyclotron accelerators suitable for use in a medical environment are expensive (on the order of 1-2 million dollars); large and heavy (15 to 20 tons) and require a trained staff to operate and maintain the apparatus.
In addition, the high-energy ions produced by the cyclotron accelerator are generally used to bombard gas targets to obtain the isotopes. Gas targets must be separated from the high vacuum of the accelerator by a metallic-foil window. Because the ion beam has high energy, the window is rapidly destroyed, thus increasing the costs of maintenance and requiring highly trained operators who must disassemble the device to replace the window.
These drawbacks have restricted the use of position emission tomography to large research hospitals that have sufficient space, staff and funding to support a conventional cyclotron accelerator facility.
While smaller, lower cost, low energy ion accelerators, such as tandem Van de Graff accelerators, have existed, it has not heretofore been considered possible to use such low energy accelerators to generate clinically significant quantities of medical isotopes and such accelerators have not been capable of generating anion beam with sufficient ion current to produce such isotopes.
Accordingly, it is an object of the present invention to provide an ion accelerator which can generate sufficient ion current in a low energy range for the production of clinically significant quantities of medical isotopes such as PET isotopes.
Another object of this invention is to provide an ion accelerator which can deliver higher currents than conventional low energy accelerators.
It is another object of the present invention to provide an ion accelerator which is smaller and lighter than existing cyclotron accelerators.
It is a further object of the present invention to provide an ion accelerator which costs less than conventional cyclotron accelerators.
It is yet another object of the present invention to provide an ion accelerator which can be easily operated by a single moderately-trained technician.
It is still a further object of the present invention to provide an ion accelerator which can operate with a solid target and thus does not require a metallic-foil window.
It is a further object of the present invention to provide an ion accelerator which has lower maintenance costs than conventional cyclotron accelerators.


Phthalic anhydride can be photochlorinated in the vapor phase to give good yields of 4-chlorophthalic anhydride at temperatures of 250.degree. to 400.degree. C. Optionally, the process can be run to produce di, tri, and tetrachlorophthalic anhydrides.

The present invention relates to a method for chlorinating phthalic anhydride. More specifically, it relates to a method of photochlorinating phthalic anhydride vapor.
Several methods have been employed for direct chlorination of phthalic anhydride using chlorine. U.S. Pat. No. 4,297,283 reports that both phthalic anhydride and orthophthalonitrile may be chlorinated in the vapor phase using chlorine gas at temperatures above 350.degree. C., and usually below 600.degree. C. The optimum temperature is said to be between 350.degree. and 475.degree. C. The 4-chloro isomer is a favored product and the molar ratio of the 4-chloro to the 3-chloro compound ranges between 5 and 11. It is preferred to use an inert gas carrier such as nitrogen or helium, etc. in the reaction chamber. It is also preferred to use a molar excess of chlorine over the aromatic compound of between 0.5 to 20 moles of chlorine per mole of aromatic compound.
German patent DE 3,911,951, discloses a process for preparing chlorophthalates by chlorinating the parent compounds, in the gas phase, at a temperature range in from 300.degree. to 700.degree. C. The chlorine to substrate ratio is between 0.7:1 to 5:1 and the process employs activated carbon catalyst prepared by doping activated charcoal, zeolite, alumina, or silica with a metal salt or oxide from the first, second or eighth sub groups. In the chlorination of phthalic anhydride, the best example presented reaction product consisting of 70% 4-chlorophthalic anhydride, 1% 3-chlorophthalic anhydride, 3% dichlorophthalic anhydride, and 23% unreacted phthalic anhydride.
Japanese patent 62185082, as abstracted in CA 108:95092s, discloses the gas phase chlorination of phthalic anhydride in the presence of a catalyst consisting of iron compounds and activated carbon to produce tetrachlorophthalic anhydride. The process is conducted at a temperature of approximately 320.degree. C.
Japanese patent 60161974, as abstracted in CA 104:89172u, discloses the gas phase reaction of phthalic anhydride with chlorine at a temperature range of 200.degree.-400.degree. C. to form tetrachlorophthalic anhydride in the presence of a catalyst composed of CoCl.sub.2 and a component selected from CaCl.sub.2, BaCl.sub.2, and LaCl.sub.3, all deposited on active carbon.
The photochlorination of aromatic compounds is not always predictable. For example, U.S. Pat. No. 2,499,120 discloses that a mixture of benzene and chlorine may be photochlorinated to produce predominately the gamma isomer of hexachlorocyclohexane.
U.S. Pat. No. 4,268,457 discloses that photochlorination of paraphenoxytoluene produces chlorination on the side chain rather than on the ring. Accordingly, the product of the chlorination is paraphenoxybenzotrichloride.
U.S. Pat. No. 4,046,656 discloses that bromine acts as a catalyst in the photochlorination of methyl-substituted aromatic compounds. In this photochlorination process, all chlorines substitute on the methyl group, while the ring hydrogens are considered inert substituents, that is, they are not readily displaced by chlorine.
U.S. Pat. No. 4,643,811 discloses a photochemical process for the preparation of 1,1-dichloro-2,2,2-trifluoroethoxybenzene derivatives. The process involves photochlorination of 2,2,2-trifluoroethoxybenzene derivatives. The chlorination occurs at the .alpha.-carbon of the ethoxy side chain, rather than on the ring.
Zweig and Epstein (J. Org. Chem. vol. 43, p. 3690, 1978 (at page 3691)) report that as part of another research effort, they attempted to induce the liquid phase chlorination of phthalic anhydride using ultraviolet radiation. They report that the reaction could not be induced by ultraviolet irradiation at temperatures up to 235.degree. C.


In network access controlled networks, it is desirable to prevent access to the network by any non-authenticated entities. Access control may be established through a trusted agent that, in some embodiments, may be implemented with a management co-processor. In some cases, active management technology may establish a connection while a host is inactive. Then, after the host becomes active, the host can attempt to use the management co-processor connection without obtaining the necessary authentications. This may be prevented, in some embodiments, by scanning for an active host and, if such an active host is found, blocking the host from using a layer 2 authentication channel unless the host is properly authenticated and has a proper Internet Protocol address.

This relates generally to the fields of data processing and data communication. Various embodiments relate to access controlled networks.
The proliferation of computer viruses and/or worm attacks in combination with the tendency for many of these malware mechanisms (e.g., worms, viruses, Trojan horses, rootkits) to propagate into corporate networks reinforces the movement for industry-wide development of network security measures to ensure that unauthorized and incompliant devices are not allowed access to various network assets. One manifestation of these efforts can be seen in the various proprietary and/or standards-based solutions for operating systems to measure various pertinent attributes of a host device. To eliminate, isolate, and reduce the impact and/or effects of malware, these measured attributes of a host device are now often evaluated, with the assistance of operating systems, before allowing that host device to connect to a protected network.

Synchronizing between host and management co-processor for network access control


A concealable mirror comprises motor housing 110, motor 111, motor shaft 112, pivot arm 131, link arm 140, frame 210, hinge 212, cover deck 220, mirror frame 301, mirror 310, remote control device 400, and clevis assembly 502.

The present invention relates to mirror apparatus, and in particular to mirror apparatus that are mounted in ceilings that can be positioned for viewing reflections of specific areas in a room that are at some arbitrary angle from vertical in addition to directly below the mirror. E.g. Birthing room mirrors.
Floor stand mirrors have been used to assist in the birthing process. They take up valuable floor space, are difficult to position for optimum viewing and create a distraction to the procedure when setting up. Accordingly, it would be advantageous to provide a mirror that eliminates these shortcomings.
Ceiling mounted mirrors have been used but have several disadvantages.
The present invention overcomes these disadvantages by incorporating various improvements.
The invention allows the mirror to be easily adjusted to optimize the field of view. When not in use, it is stored flush with the ceiling.
It is designed to be mounted in a suspended ceiling plenum area and directly replaces an existing ceiling tile. The mirror position can be variably adjusted by the observer to optimize the view.
The mirror is stored flush with the ceiling in the closed position. This is advantageous because its presence is minimized when not in use. Viewing space is maximized since the mirror is essentially the same size as the ceiling tile it replaces.
The limit switch arrangement for the stored position of the mirror assures that the mirror is always flush with the ceiling, irrespective of any wear in the raising-lowering mechanism.
The invention is nearly totally enclosed thus prohibiting plenum debris from entering the patient area of the room.
The motor and some linkage are separated from the patient area. Other units are not sealed and therefore debris from the plenum area can infiltrate into the patient area.
An improved actuating mechanism provides a lower profile that essentially eliminates mechanical interference with existing equipment and other appurtenances in the plenum area.
Other units have a higher profile and therefore restrict installation to ceiling locations where there is sufficient vertical clearance in the plenum above the ceiling grid. The device therefore provides greater flexibility in mounting locations.
The mirror is not manipulated by a linear actuator as other units are. They are comprised of a greased jack screw that is exposed to the patient area. This is further disadvantageous because such an embodiment necessitates a higher, less compact profile by virtue of the need for a robust motor frame.
The actuating mechanism (discussed below) of the present invention does not require such a motor housing to be welded and is therefore less expensive to construct.
The present invention is lighter because it is made from aluminum and does not need the aforementioned motor frame. The lighter weight of the preferred embodiment facilitates installation.
A novel actuating mechanism comprises fewer moving parts with no exposed greased elements. Actuation of the mirror is accomplished by means of a simple reversible gear motor.
The present invention is self locking in the stored (closed) position. A force equivalent to the weight of the mirror must be constantly applied to keep the mirror in the stored position. Other devices are not self locking. Therefore, a braking mechanism must be employed to hold the mirror in the closed position. The novel actuator arrangement of this invention substantially eliminates the reaction torque on the motor when the mirror is stored.


A reusable linker arm for solid support oligonucleotide synthesis, the linker arm comprising formula (a) wherein Z is a linker moiety and T is an organic radical. A method for adding one or more nucleosides on the linker arm is also described

The art of organic chemistry on solid supports is generally known. A useful review article on this topic may be found in "Organic Chemistry on Solid Supports" by Früchtel et al., Angew. Chem. Int. Ed. Engl., 1996, 35, pgs. 17–42, the contents of which are hereby incorporated by reference.
As discussed in Früchtel et al., the art has developed automated solid-phase synthesis of polypeptides, oligonucleotides and oligosaccharaides. Of particular interest here is solid-phase synthesis of oligonucleotides. The following are useful review articles/textbooks on this topic:    Beaucage et al., Tetrahedron, 1992, 48, 2223;    Davis et al., Innovation and Perspectives in Solid Phase Synthesis (Ed.; R. Epton), Intercept, Andover, 1992, pg. 63;    Montserra et al., Tetrahedron, 1994, 50, 2617; and    S. L. Beaucage et al., Tetrahedron, 1993, 49, 6123–6194;the contents of each of which are hereby incorporated by reference.
In the solid-phase synthesis of oligonucleotides, it is known to synthesize the oligonucleotide on an inorganic solid support bearing a succinyl linker arm—see, for example, any of the following references:    Caruthers et al., Genetic Engineering, Plenum Press, New York (1982), Vol. 4, pgs. 1–17;    Letsinger et al., Genetic Engineering, Plenum Press, New York (1985), Vol. 5, pg. 191;    Froehler et al., Nucleic Acids Research, 14:5399–5407 (1986); and    Matteucci et al., Journal of American Chemical Society, 103:3185–3186 (1981);the contents of each of which are hereby incorporated by reference.
Typically, the succinyl linker arm has the following general formula:
Thus, the succinyl group links the growing oligonucleotide from its terminal 3′ hydroxyl group by an ester bond to a primary amine on the support, which may be, for example, conventional controlled pore glass (CPG) or silica, by an amide bond. Once the desired oligonucleotide has been synthesized, it is freed or cleaved from the succinyl linker arm hydrolyzing the ester carbonyl group. The hydrolysis agent is usually concentrated ammonium hydroxide. Typically, this reaction can take from 1–4 hours to complete. With improvements to current solid-phase oligonucleotide synthesizers, this cleavage step can represent 50% or more of the total time require to synthesize the desired oligonucleotide.
Another type of linker arm is disclosed in U.S. Pat. No. 5,112,962 [Letsinger et al. (Letsinger)], the contents of which are hereby incorporated by reference. Letsinger teaches a linker arm for solid support synthesis of oligonucleotides and oligonucleotide derivatives have the following formula:
Thus, Letsinger teaches an oxalyl linker arm which purportedly release the synthesized oligonucleotide or oligonucleotide derivate in a period of 1–30 minutes in a manner that leaves the oligonucleotide fully protected. The oxalyl linker arm purportedly can be rapidly cleaved by 5% ammonium hydroxide in methanol, ammonium hydroxide, wet tertiary amine, triethylamine/alcohol, triethylamine/methanol, triethylamine/ethanol, aqueous trimethylamine and other bases. Unfortunately, the oxalyl linker arm of Letsinger suffers from its purported advantage. Specifically, the present inventors have discovered that the oxalyl linker arm of Letsinger is susceptible to significant spontaneous hydrolysis (e.g. spontaneous hydrolysis of ˜10–40% per month) which renders it difficult to use in commercial operations. The oxalyl arm is also difficult to prepare because it requires using oxalyl chloride, which is highly reactive, toxic and therefore dangerous.
Regardless of the specific nature of the linker arm, it is generally accepted in the art that the linker arm is not reusable after production and cleavage of the desired oligonucleotide. Thus, conventional linker arms may be regarded as non-recyclable. This is illustrated in FIG. 1 which illustrates the conventional use of a succinyl linker arm for the production of an oligonucleotide. Thus, as illustrated, after cleavage of the desired oligonucleotide, the support is irreversibly linked to the linker compound (i.e., the succinyl moiety) and cannot be reused.
The art is in need of a linker arm for solid support oligonucleotide synthesis, which linker arm is recyclable. More specifically, the art is in need of a linker arm capable of repeated oligonucleotide synthesis/cleavage.
In published International patent application WO 97/23496 [Pon et al.], the contents of which are hereby incorporated by reference, there is reported the first recyclable linker arm. This linker arm is based on a derivatized solid support having the following formula:
wherein: R8 is selected from the group consisting of a substituted or unsubstituted C1–C20 alkyl group, a substituted or unsubstituted C5–C30 aryl group and a substituted or unsubstituted C5–C40 alkylaryl group; X3 and X4 are the same or different and are selected from the group consisting of —O—, —S—, —S(O)2— and —N(R12)—; R12 is selected from the group consisting of a substituted or unsubstituted C1–C20 alkyl group a substituted or unsubstituted C5–C30 aryl group and a substituted or unsubstituted C5–C40 alkylaryl group; and Y is selected from the group consisting of:                —CH2—CH2—; —CH2—;        —CH2—O—CH2—; —CH2—CH2—CH2—;        —CH═CH—; —CH═C(CH3)—;        —C(CH3)═C(CH3)—; —CH2—C(═CH2)—; and        —CH2—S—CH2—.
While a linker arm based on the solid support described by Pon et al. is a significant advance in the art, there is still room for improvement. Specifically, the solid support described by Pon et al. has the following disadvantages.
First, prior to attachment of the linker moiety, the solid support must be derivatized by a process comprising the step of reacting together the compounds of Formulae I, II and III:
wherein R8, X3, X4 and Y are as defined above. Practically, this involves two steps—i.e., reaction of the compound of Formula III with one of the compounds of Formulae I and II and subsequent reaction with the other of compounds of Formulae I and II. Thus, the disadvantage is additional labour required to effect a two-step derivatization of the solid support.
Second, each step of the derivatization described in the previous paragraph has the potential of incompletely derivatizing each HX4-moiety on the support thereby increasing the likelihood of a heterogeneous surface. Practically, it becomes necessary to block or cap underivatized HX4-moieties so that the linker moiety does interact with them. Thus, the disadvantage is additional labour and cost required to effect derivatization of the solid support.
Third, a linker arm based on the derivatized support described by Pon et al. is not as resistant to partial cleavage during regeneration as a derivatized support having a more fully saturated moiety.
In light of these disadvantages, it would be desirable to have an improved recyclable solid state support material useful in the oligonucleotide synthesis. It would be especially desirable if the the linker moiety could be attached to the support material with little or no derivatization required of the latter.

This patent is subject to a terminal disclaimer.

Reusable solid support for oligonucleotide synthesis

University Technologies International Inc.


Embodiments include methods, apparatus, and systems for determining bandwidth in storage systems. One embodiment includes a method receiving a recovery point objective (RPO) for a disaster recovery (DR) system that uses asynchronous replication. The method then computes a queue depth for queued data waiting to be transmitted to a secondary storage location and uses the RPO and the queue depth to calculate a bandwidth for transmitting data from a first storage location to the secondary storage location.

Enterprises commonly maintain multiple copies of important data and expend large amounts of time and money to protect this data against losses due to disasters or catastrophes. One class of techniques for maintaining redundant data copies is known as mirroring, in which copies of data are located at both a primary storage location and a secondary or remote storage location. If the data is mirrored to an offsite location, then the data is protected against disasters and catastrophes, such as fire, power outages, theft, earthquakes, tornados, hurricanes, floods, etc. Many data processing systems employ multiple levels of redundancy to protect data and locate these systems at separate geographical locations.
Data processing systems often utilize disk mirroring to replicate data onto separate logical disk volumes using one of various techniques, such as synchronous mirroring or asynchronous mirroring. Synchronous mirroring can achieve a Recovery Point Objective (RPO) with zero data loss, while asynchronous mirroring can achieve an RPO from a few minutes to several hours or more. Synchronous mirroring is generally used when response distances between copy storage are short and data cannot be lost. By contrast, asynchronous mirroring is used when the smallest possible performance impact is to be imposed on the primary site and mirrored data is to travel long distances. Asynchronous mirroring is often used for very large geographical scale operations.
Leasing or purchasing communication links connecting the primary and recovery sites is a large cost for maintaining disaster recovery systems. Companies spend thousands or even millions of dollars to maintain communication bandwidth over fiber optic networks and telecommunication lines in order to mirror data.
One challenge is to determine an optimal amount of bandwidth to lease or purchase for performing data mirroring operations. If a company leases too much bandwidth, then unnecessary money is spent for capacity that is not needed. On the other hand, if insufficient bandwidth is acquired, then valuable data can be lost in the event of a failure.

Bandwidth sizing in replicated storage systems

Hewlett-Packard Development Company, L.P.


A communication device includes: an antenna unit through which electric waves are transmitted and received; a scatterer which reflects the electric waves; a communication unit configured to wirelessly communicate with a first communication partner device via the antenna unit; and a scatterer control unit configured to change a state of the scatterer when communication fails between the communication unit and the first communication partner device.

In recent years, a system has been developed for exchanging information among devices, such as home electric appliances in a home, by connecting these devices via a wireless network. In such a system, for example, a control device and a plurality of electric apparatuses which are communication devices are installed in a home. A wireless network is configured through which these communication devices are connected according to a star topology having the control apparatus at the center. Examples of these communication devices include, for example, a TV, an air conditioner, a refrigerator, a washing machine, and a mobile phone.
In such a configuration, depending on an installation status of a communication device, reception intensity of electric waves from other communication devices (communication partner devices) decreases significantly to the point of being null due to multipath propagation in some cases.
Even when the reception intensity of the electric waves decreases to the point of being null, if the communication device is a portable apparatus (movable object) such as a mobile phone, propagation of the electric waves changes as the communication device moves. Thus, the communication device can recover from null of the reception intensity of electric waves, whereby communication succeeds with a communication partner device.
Furthermore, a technique is disclosed which allows two communication devices to communicate with each other even when the communication devices are being moved, by controlling the direction of directional antennas in accordance with a position relationship between the two communication devices (see Patent Literature (PTL) 1, for example).

Communication device and communication method

Panasonic Intellectual Property Management Co., Ltd.


To accommodate high power densities associated with high performance integrated circuits, an integrated circuit package includes a heat-dissipating structure in which heat is dissipated from a surface of one or more dice to an integrated heat spreader (IHS) through a high capacity thermal interface formed of diamond, a diamond composite, or graphite. In an embodiment, a diamond layer is grown on the IHS. In another embodiment, a diamond layer is separately formed and affixed to the IHS. Methods of fabrication, as well as application of the package to an electronic assembly and to an electronic system, are also described.

Integrated circuits (IC's) are typically assembled into packages by physically and electrically coupling them to a substrate made of organic or ceramic material. One or more IC packages can be physically and electrically coupled to a printed circuit board (PCB) to form an "electronic assembly". The "electronic assembly" can be part of an "electronic system". An "electronic system" is broadly defined herein as any product comprising an "electronic assembly". Examples of electronic systems include computers (e.g., desktop, laptop, hand-held, server, etc.), wireless communications devices (e.g., cellular phones, cordless phones, pagers, etc.), computer-related peripherals (e.g., printers, scanners, monitors, etc.), entertainment devices (e.g., televisions, radios, stereos, tape and compact disc players, video cassette recorders, MP3 (Motion Picture Experts Group, Audio Layer 3) players, etc.), and the like.
In the field of electronic systems there is an incessant competitive pressure among manufacturers to drive the performance of their equipment up while driving down production costs. This is particularly true regarding the packaging of IC's on substrates, where each new generation of packaging must provide increased performance, particularly in terms of an increased number of components and higher clock frequencies, while generally being smaller or more compact in size. As the density and clock frequency of IC's increase, they accordingly generate a greater amount of heat. However, the performance and reliability of IC's are known to diminish as the temperature to which they are subjected increases, so it becomes increasingly important to adequately dissipate heat from IC environments, including IC packages.
An IC substrate may comprise a number of metal layers selectively patterned to provide metal interconnect lines (referred to herein as "traces"), and one or more electronic components mounted on one or more surfaces of the substrate. The electronic component or components are functionally connected to other elements of an electronic system through a hierarchy of electrically conductive paths that include the substrate traces. The substrate traces typically carry signals that are transmitted between the electronic components, such as IC's, of the system. Some IC's have a relatively large number of input/output (I/O) terminals (also called "lands"), as well as a large number of power and ground terminals or lands.
As the internal circuitry of IC's, such as processors, operates at higher and higher clock frequencies, and as IC's operate at higher and higher power levels, the amount of heat generated by such IC's can increase their operating temperature to unacceptable levels.
For the reasons stated above, and for other reasons stated below which will become apparent to those skilled in the art upon reading and understanding the present specification, there is a significant need in the art for apparatus and methods for packaging an IC on a substrate that minimize heat dissipation problems associated with high clock frequencies and high power densities.

Electronic assembly with high capacity thermal interface and methods of manufacture