Embodiments described herein relate to systems, devices, and methods for use in the implementation of a human-computer interface using high-speed, and efficient tracking of user interactions with a User Interface/User Experience that is strategically presented to the user. Embodiments described herein also relate to the implementation of a hardware agnostic human-computer interface that uses neural, oculomotor, and/or electromyography signals to mediate user manipulation of machines and devices.

Embodiments described herein relate to systems, devices, and methods for use in the implementation of a brain-computer interface that integrates real-time eye-movement and/or head-movement tracking with brain activity tracking to present and update a user interface (UI) or a user experience (UX) that is strategically designed for high speed and accuracy of human—machine interaction. Embodiments described herein also relate to the implementation of a hardware agnostic brain-computer interface that uses real-time eye tracking and online analysis of neural activity to mediate user manipulation of machines.
A human-computer interface (HCI) is a hardware and software communications system that permits brain activity to control computers or external devices with direct communication pathways between a wired brain and the external device. HCIs have been mainly designed as an assistive technology to provide access to operating machines and applications directly from interpreting brain signals. One of the main goals of HCI development is to provide communication capabilities to severely disabled people who are totally paralyzed or 'locked in' by neurological neuromuscular disorders, such as amyotrophic lateral sclerosis, brainstem stroke, or spinal cord injury, for whom effective communication with others may be extremely difficult.
Some known implementations of brain computer interfaces include spellers like the one designed by Farwell and Donchin. In this speller, the 26 letters of the alphabet, together with several other symbols and commands, are displayed on-screen in a 6×6 matrix with randomly flashing rows and columns. The user focuses attention on the screen and concentrates successively on the characters to be written, while the neural response of the brain is monitored for signature neural brain signals. Once detected the signature brain signals allow the system to identify the desired symbol. The Farwell-Donchin speller allows people to spell at the rate of about two characters per minute.

Human-computer interface using high-speed and accurate tracking of user interactions


Disclosed are water based, viscoelastic compositions comprising a mixture of high molecular weights hyaluronic salts and water soluble poly(ethylene oxides). Also disclosed are cosmetic formulations including said compositions.

1. Field of the Invention
The present invention relates to hyaluronate based compositions, and more particularly, to such compositions, including in addition to hyaluronate, a high molecular weight poly(ethylene oxide). The invention also relates to cosmetic formulations comprising such compositions.
2. The Prior Art
Hyaluronic acid (hereinafter referred to as "HA") as well as its salts, such as sodium hyaluronate and other alkali metal and alkaline earth metal salts (hereinafter referred to as "NaHA") is a known, naturally occurring high viscosity glycosaminoglycan having alternating .beta. 1-3 glucuronidic and .beta. 1-4 glucosaminidic bonds. The molecular weight of this material is generally within the range of 50,000 to 8,000,000 (although there are reports of HA having molecular weights as high as 13,000,000) depending on the source, method of isolation and method of determination. It is found in animal tissue, e.g., in umbilical cord, vitreous humor, synovial fluid, rooster combs, group A and C hemolytic streptococci and in skin.
The isolation and characterization of HA is described in Meyer et al, J. Biol. Chem. 107, 629 (1934); J. Biol. Chem. 114, 689 (1936); Balazs Fed. Proc. 17, 1086 (1958); Laurent et al; Biochim. Biophys. Acta 42, 476 (1960). The structure of HA was elucidated by Weissman et al, J. Am. Chem. Soc. 76, 1753 (1954) and Meyer, Fed. Proc. 17, 1075 (1958).
For certain uses, extremely pure HA preparations are required; see, for example Balazs U.S. Pat. No. 4,141,973, which describes the preparation and use of such an HA.
Poly(ethylene oxides) are known water soluble non-ionic homopolymers of ethylene oxide having molecular weights up to 5,000,000. Aqueous solutions of these polymers are highly viscoelastic and are known to be used in many areas including adhesives, lubricating agents, coatings, cosmetics, etc.
Poly(ethylene oxide) is also known to form strong association complexes with a large number of other materials, such as urea, phenolics, poly(acrylic acid), etc. The reaction products formed between poly(ethylene oxide) and polymeric polycarboxylic acids are insoluble in hot and cold water. (U.S. Pat. No. 3,387,061).
Poly(ethylene oxide) is known to be used in cosmetics. See, e.g., U.S. Pat. Nos. 2,991,229; 3,783,872; 3,811,349 and 4,192,862.

Hyaluronate-poly (ethylene oxide) compositions and cosmetic formulations thereof


In a communication system where a primary cell is controlled by a first base station and a secondary cell is controlled by a second, different base station, flow control is performed between the primary cell and the secondary cell for data for a radio link control layer. According to the flow control, the data for the radio link control layer is communicated between the first and second base stations using a link between the first and second base stations. Flow control may be performed between the primary cell and the secondary cell by dynamically controlling a depth of queued radio link control data in the secondary cell for one or more UEs based on one or more factors, e.g., current/future loading of secondary cell, peak theoretical throughput for a UE in the secondary cell, and/or a UE's current channel quality information. Apparatus, methods, and computer program products are disclosed.

This section is intended to provide a background or context to the invention disclosed below. The description herein may include concepts that could be pursued, but are not necessarily ones that have been previously conceived, implemented or described. Therefore, unless otherwise explicitly indicated herein, what is described in this section is not prior art to the description in this application and is not admitted to be prior art by inclusion in this section. Acronyms used in this application or the drawings are defined below.
In 3GPP Rel-10 Carrier Aggregation (CA), two or more Component Carriers (CCs) are aggregated in order to support wider transmission bandwidths up to 100 MHz. A UE may simultaneously receive or transmit on one or multiple CCs, depending on its capabilities.
CA operation uses a number of serving cells, one for each CC. The Primary Serving Cell (PCell) is served by the Primary Component Carrier (PCC) and handles the Radio Resource Control (RRC) Connection with the UE. One or more Secondary Serving Cells (SCells) are served by the Secondary Component Carriers (SCCs) and provide the additional transmission bandwidth.
CA operation may be thought of as one aspect of dual connectivity. According to 3GPP TR 36.842 V12.0.0 (2013-12), Section 7.1, the term "dual connectivity" is used to refer to operation where a given UE consumes radio resources provided by at least two different network points connected with non-ideal backhaul. Furthermore, each eNB involved in dual connectivity for a UE may assume different roles. Those roles do not necessarily depend on the eNB's power class and can vary among UEs. See Section 7 of 3GPP TR 36.842 for additional description regarding dual connectivity.
The Rel-10 3GPP specification supports CA operation only in a scenario where the PCell and SCell(s) are co-located in the same eNB. It would be beneficial to improve on this scenario.

This patent is subject to a terminal disclaimer.


The invention relates to an intake arrangement (1) for the combustion air (2) of an internal combustion engine (3) in a handheld work apparatus (4) such as a cutoff machine, a motor-driven chain saw or the like. An air filter (5) is provided for the cleaning of the combustion air (2) drawn in via an opening (6) of a filter housing (7). To discharge dust (11) accumulated in the air filter (5) a carrier airflow (10) is provided in a flow channel (16) and the filter housing (7) is fluidly connected with the aid of a discharge tube (13) to the flow channel (16). For a dosed metering of dust (11) from the filter housing (7), a shutoff member (14) is provided and the shutoff member (14) clears or closes the fluid connection between the flow channel (16) and the filter housing (7).

U.S. Pat. No. 5,526,777 discloses an intake arrangement for an internal combustion engine in a portable handheld work apparatus. An air filter is provided in a filter housing for purifying the combustion air. Unfiltered air is conveyed through an opening into the filter housing by the cooling blower of the engine and is moved along the air filter. The carburetor of the engine is connected to the clean air side of the filter housing and the engine draws dust-free combustion air into a combustion chamber of the engine via the air filter. When an intensely dirty ambient is present as is often the case for cutoff machines, the dust, which is contained in the air, deposits on the air filter and quickly clogs the same. For this reason, the power developed by the engine is affected. The large dust load of the air filter requires frequent cleaning so that a maintenance intensive operation of the engine results.


A method is provided for regenerating deactivated sulfonated aromatic organic ion-exchange resin beds, such as a polystyrene ion-exchange resin bed, having chemically combined amino organo mercaptan groups with anhydrous phenol at an elevated temperature.

The present invention relates to an anhydrous phenol treatment method for restoring deactivated sulfonated aromatic organic polymeric ion-exchange resin having chemically combined aminoorganomercaptan groups. More particularly, a method is provided for treating a deactivated ion exchange resin with anhydrous phenol at elevated temperatures to effect the reaction of phenol with deactivated aminoorganomercaptan groups and the simultaneous elution of phenolic reaction products from the ion-exchange resin.
As shown in copending application Ser. No. 08/236,816 a sulfonated aromatic organic polymeric ion-exchange resin bed having chemically combined aminoorganomercaptan groups can be used to catalyze the condensation of phenol and ketone, such as acetone. However, excessive exposure of such "thiol containing" ion-exchange resin to phenol contaminated with at least 1 ppm of hydroxyacetone can substantially reduce the effectiveness or "deactivate" the ion-exchange resin. It has been found that contact between the hydroxyacetone contaminant and aminoorganomercaptan groups can result in the formation of a chemically combined species. The species can substantially interfere with the ability of the ion-exchange resin to perform effectively as a condensation catalyst for making bisphenol.
Another application of the thiol containing ion exchange resin taught in copending application Ser. No. 08/236,816 is as a sacrificial ion-exchange resin guard bed having chemically combined aminoorganomercaptan groups. The ion-exchange resin guard bed can be used to provide a purified phenol effluent substantially free of hydroxyacetone which can extend the life of the ion-exchange resin condensation reactor bed.

Method for regenerating a sulfonated aromatic organic polymeric ion-exchange resin bed having deactivated aminoorganomercaptan groups with phenol


A friction material composition containing an alkali metal salt as a friction adjusting material. The alkali metal salt is spherical and porous. The alkali metal salt has an average particle diameter of 20 μm to 240 μm. A friction material is produced by using the friction material composition.

Technical Field
An aspect of the present invention relates to a friction material composition, a friction material using the friction material composition, and a production method thereof.
Background Art
A friction material to be used for a disc brake, a drum brake, etc. is composed of a fiber base material for imparting a reinforcing action, a friction adjusting material for imparting a friction action and adjusting its friction performance, and a binder for binding these components. These constituents are appropriately adjusted according to the intended use, the required performance, etc.
For example, JP-A-10-139894 discloses that, in a non-asbestos friction material for brakes, which uses a thermosetting resin as a binder component and contains a fiber base material, a filler and an additive, a porous spherical particle formed by binding of crystal grains of titanic acid compounds as a friction adjusting material is added. According to this technique, the fade resistance can be improved without impairing the strength or wear resistance of the friction material. In JP-A-10-139894, the titanium acid compound to be added as a friction adjusting material is produced by preparing a granulated powder through wet mixing and spray drying of raw materials and firing it.
In a friction material for brakes, the porosity of the friction material is generally adjusted to a range of approximately from 10 to 30% for enhancing the fade resistance or high speed effectiveness. Therefore, in the case of passing a puddle in rain, washing a car or parking a vehicle outdoors during the night, the friction material comes into a moisture-absorbed state. In such a moisture-absorbed state, when the vehicle speed is reduced to generally 5 km/h or less, i.e. just before stop by braking, or when a brake is completely released after loosening the brake at the time of starting an automatic car, a low-frequency abnormal noise attributable to a creep torque is generated. This low-frequency abnormal noise is also called creep noise and accompanied by discomfort and therefore, reduction thereof is demanded.
In order to solve such a problem, JP-A-2000-191800 discloses that a fluorine-based polymer having water repellency is blended with a friction material including a fiber base material, a friction adjusting material, a lubricant, and a binder. In such a friction material, the fluorine-based polymer having water repellency is scattered in a conventional matrix having hydrophilicity and therefore, even when the friction material is caused to absorb a large amount of water by car washing, etc., the creep noise can be reduced.
However, it has been reported that even by the technique described in this document, when the friction material is in a moisture-absorbed state after braking under a light load, creep noise is generated. Therefore, development of a friction material further improved in the properties preventing creep noise generation (noise characteristics) is demanded.
Patent Document 1: JP-A-10-139894
Patent Document 2: JP-A-2000-191800

Friction material composition, friction material and production method thereof


Provided are water-dispersible sulfopolyester compositions having relatively large proportions of pigments and/or fillers. Such compositions are useful as packaging materials and are substantially non-blocking when processed using packaging rolls and are comprised of at least one sulfopolyester as described herein, about 10 to about 75 weight percent of a pigment and/or filler, and a wax.

Water soluble or water-dispersible films are known, but there are few commercially viable examples. Polyvinyl alcohol (PVOH) film constitutes nearly all of the volume and is used for disposable bags and packaging. A solution process is typically employed for PVOH since it lacks thermal stability. This is cumbersome and adds to the cost of the manufactured film.
Sulfopolyesters are another class of materials where cast films may subsequently be re-dispersed into water. Typical sulfopolyesters, such as those disclosed in U.S. Pat. No. 3,734,874, result in brittle films or films having low strength.
More recently, a family of branched sulfopolyesters has been developed for water-dispersible adhesive formulations as disclosed in U.S. Pat. Nos. 5,543,488; 5,552,495; 5,552,511; 5,571,876; and 5,605,764. These polymers are easily dispersible into water, but have glass transition (Tg) values not greater than 20.degree. C. and result in films that undergo blocking during storage.

Water-dispersible films and fibers based on sulfopolyesters


Apparatus for connecting a cable television system utilizing a multi-channel converter having a preselector switch and a preselected converter very high frequency output signal to a video cassette recorder and/or a television receiver. The apparatus includes an input for receiving the signals transmitted by the cable system; first and second conduits defining first and second flow paths, with the converter being disposed in the first flow path; a trap disposed in the second flow path for eliminating the preselected converter output signal from the signals transmitted by the cable system and passing through the second flow path; and a device for combining the preselected converter output signal in the first flow path and the signals transmitted through the second flow path and for transmitting the combined signal to the video cassette recorder and/or television receiver.

This invention relates to broadening the utility of video cassette recorders and in particular to apparatus for enabling a user of a video cassette recorder connected to a cable television system employing a multi-channel converter box to achieve full programmer utility for the recorder.
The number of television receivers nationwide connected to cable television systems has grown dramatically in the last several years. Market surveys indicate approximately 13,000,000 homes are connected to a cable system, accounting for approximately a 20% market penetration. Forecasts indicate the market penetration will increase to at least 30% by 1982. Many of these cable television systems utilize a multi-channel converter for descrambling the very high frequency signals transmitted through the cable system. The converter has a preselected very high frequency output signal to which the television receiver is continuously set, e.g. channel 4. The converter also includes a preselector switch unit for permitting the user to select a single very high frequency signal from the entire range of signals transmitted by the cable system. The converter alters the selected very high frequency signal to the predetermined or preselected output signal for transmission to the television receiver. As used herein the term "very high frequency signals" includes the low and high band channels 2 through 13. Channels 2-13 are broadcast by the commercial television systems, whereas cable systems transmit both standard channels 2-13 and generally one or more of the special channels such as subchannels A, C, or E, mid band channels A through I, or super band channels J through S.
In addition to the widespread use of cable television systems, the introduction of consumer video cassette recorders in the past few years has further increased the utility and overall user enjoyment of television. Video cassette recorders enable a person to video tape a television show for his own personal viewing pleasure. Essentially, the video cassette recorder is a convenience device for enabling a viewer to tape a television program that he may be unable to view when actually broadcast, either because the broadcast time is inconvenient or the viewer wishes to watch another program broadcast simultaneously with the program he wishes to record. A recent improvement in video cassette recroders enables a user to program the video cassette recorder to operate at preselected times during any consecutive seven days to record preselected programs appearing on any of the channels whether very high frequency or ultra high frequency, broadcast within the viewing area and received through the standard television antenna. However, video cassette recorders used in conjunction with cable television systems employing a multi-channel converter have not afforded the user full recorder utility.
For example, heretofore it has often been necessary for a user to obtain from a cable company a second converter box if the user wishes to record a first channel while viewing a second channel. In addition, the user must manually manipulate an external co-axial switch or switches to achieve the desired recording and viewing capabilities. The cable company's monthly charge to the user is increased by the foregoing arrangement since the cable company generally charges a monthly fee which increases with the number of converter boxes rented to the user.
Further, although programmable video cassette recorders are designed to automatically turn on and off and change channels at a predetermined time, on a given day within a seven day time span, the programmable video cassette recorder cannot override the preselector switch used in conjunction with the multi-channel converter box. Thus, programmable video cassette recorders are not fully functional with cable systems employing multi-channel converter boxes. For example, the programmable video cassette recorder may be connected to the cable system through a manual switch whereby the recorder may select any regular or standard very high frequency channel, i.e. channels 2-13, transmitted through the cable system. However, if it is desired to record a special channel, i.e., a channel transmitted through the cable system that is not a standard very high frequency channel, such as the sub band, mid band or super band channels, it is necessary to connect the multi-channel converter to the video recorder. Once the input of the recorder is connected to the output of the converter, the channel changing feature of the programmable video cassette recorder is eliminated.
Although the present invention achieves particular utility with television receivers in association with video cassette recorders and cable systems of the type described, the invention may also be employed with television receivers connected to the described cable systems and utilizing remote control channel changers. In cable systems using the multi-channel converter, the television receiver tuner is set at one channel, which is the preselected converter output channel, e.g. channel 4. Thus, the remote channel changer presently cannot be employed to change channels transmitted through the multi-channel converter device.

Method and apparatus for video recording


An online object reservation system includes a database and an object reservation server. The database stores multiple objects associated with individual selection status. The object reservation server establishes a continuous connection with a client to provide a reservation page and receive reservation requirements from the client. The object reservation server automatically selects connection objects according to the reservation requirements. The object reservation server also establishes other connections with other clients. Whenever the selection status of any of the objects is altered, the object reservation server sends a refresh notification to the client to update contents rendered on the reservation page.

Field of Invention
The present disclosure relates to an online object reservation system and an online object reservation method. More particularly, the present disclosure relates to the online object reservation system and the method providing real-time information of a reservation status.
Description of Related Art
Conventionally, when reserving limited objects such as tickets of a performance, hotel rooms, or appointments to see a doctor, it needs people to manage reservation data to avoid a duplication of a reservation. However, the labor resource does not meet the requirement as a scale of business is getting larger. The technology of database drives an electronization of an object reservation system, improves the efficiency of the labor management, and decreases a probability of causing an error.
The daily widespread of the Internet changes the business model again. An online reservation system can continuously take reservations on 24 hours a day. It saves the labor cost for a reservation process and becomes the first choice of the industry to promote the business.
However, when using the online reservation system, it usually has a situation that multiple available objects are shown when a connection is succeed, but a user knows that a selected object has been reserved by someone else after he delivers a confirmation. It causes that the user has to start over the reservation process, and it is not convenient. In addition, such short time gap can usually let all the objects be reserved for popular performances and popular places to stay. It causes an unfair situation that the user logging in the online reservation system first cannot successfully reserve the objects.

Online object reservation system and online object reservation method


A method for dividing a heterogeneous collection of ore particles prior to concentration thereof into groups differing in size and density of the particles by passing the particles in dispersion in a liquid through a space having obstacles therein which are arranged such that the sizes of the openings between the obstacles are always larger in size than the major number of particles arriving at the openings while simultaneously agitating the medium. This results in a variation of the path of the particles depending on their size and density and allows only the smaller and/or heavier particles to be brought to the concentration.

1. Field of the Invention
This invention pertains to the field of classification of ore particles for a subsequent concentration process.
2. Description of the Prior Art
An ore is a mixture of valuable ore minerals and less valuable gangue minerals. These minerals appear as crystals or grains in the solid ore body. Utilization of the ore is almost always combined with a concentration process or an ore dressing process which aims at recovering the valuable ore minerals from the ore.
In the concentration of an ore or a similar mixture of different substances, the first step usually is to crush or grind the mixture to particles. Grinding results in a collection of different types of particles, e.g., pure monogranular particles consisting of a single substance, and polygranular particles, which can consist of up to as many different substances as there are different mineral grains included in the particles.
The more the ore is ground, the finer are the particles, also in relation to the size of the crystals, and the higher is the degree of liberation or of difference in composition between polygranular mixed particles. Both these properties regulate the grade of the concentrate and the feasibility of the concentration process.
Grinding or crushing is an expensive process, and particularly expensive is the production of small particle sizes.
Additionally, very fine particles, e.g., slime, are also to be avoided because they disturb the concentration process. To diminish the production of slime, grinding is carried out in steps so that the ore is brought to a mill and ground, commonly in water, to a coarse size such that only a modest liberation is achieved. The ground material then goes to a dividing device that produces a fine product which has the desired liberation for the concentration process and a coarse product which is recirculated back to the mill, reground and then again brought to the dividing device. The fine product from this device has less slime than the ore would have had if ground directly to the desired liberation and the product has also been cheaper to make.
In most cases, classifiers are used as such a dividing device and operate on the principle that particles that are setting slowly, i.e. smaller and/or higher particles, are brought to the concentration process while particles falling more rapidly, i.e. larger and/or heavier particles, are returned to repeated grinding. Small, pure, heavy particles fall with the same velocity as larger, light mixed particles. The concentration process, therefore must operate with a particle mixture where the heavier material is in a more ground state than the lighter material. Pure, heavy particles are returned to the grinding device and come back often as a too finely ground slurry while light mixed particles, which would have needed to be additionally ground, are discharged to be concentrated.
If, instead, this dividing device were a conventional screen, the separation would take place according to particle size only, regardless of particle density. However, conventional screens are not sufficiently reliable at the fine size ranges in question; they are commonly used for relatively coarse separations, e.g., at 5 mm or more and are, therefore, rare in this context.

Method of pre-concentrating heterogeneous mineral mixtures


A multi-chamber dispensing container for storing at least two substances in an impervious and sterile environment. The container has a tubular body, with a bottom end and an end having an opening. At least one means of occlusion having a continuous outer edge is disposed in an oblique position inside the body between the ends prior to activation of the container. The means of occlusion seals the body imperviously and divides it into two chambers, each containing a substance. The container further has a means for dispensing the substances contained in the body, these means being disposed near the end presenting the opening and sealing this end imperviously. The means of occlusion has two different areas, one of which is partially tearable under the effect of activating pressure from the fingers, the other being designed so as to not tear under the effect of the pressure. This second area maintains the means of occlusion in place within the body after activation.

The present invention relates to a multi-chamber dispensing container for storing at least two substances which must be stored separately, the extemporaneous mixture thereof, and the dispensing of the mixture of these substances. The present invention will be more particularly described with respect to a dropper flask with two chambers, containing, sterile during storage, for example, a lyophilized powder in a first chamber, and a liquid in a second chamber, these two substances then being mixed extemporaneously in the container, and the mixture then being dispensed.
A multi-chamber dispensing container of the type mentioned hereinabove is known, described by International Patent Application published under No. WO-A-91/00094. This Application generally describes the use of a multi-chamber dispensing container for storing and, extemporaneously, dispensing a mixture of two liquids, in the present case a solution of papaverine sulfate and a basic solution such as bicarbonate of soda. It is necessary to separate the two solutions in order to prevent the precipitation of papaverine H during storage thereof. The two solutions are stored in a container body in the form of a rubber tube, presenting an end having an opening and a bottom end, in two chambers separated by a disc of plastics material. This disc is disposed perpendicularly to the container body and is of larger diameter than the inner diameter of the container body. In this way, the disc is maintained in place by the elastic hold of the container body on the peripheral edge thereof. Dispensing means are also provided in the vicinity of the end having an opening of the container body, hermetically closing said opening, and take the form of an injection needle. Before activation, i.e. during storage, the two liquids are therefore hermetically separated by the disc. Activation of the dispensing container is effected by a displacement of the disc caused by the pressure of the hand and thumb in a reciprocating movement on the body of the container. The disc is thus caused to drop into the bottom of the tube, and the two solutions can mix. The mixture is then dispensed by injection into the body through the needle.
However, such a container presents the following drawbacks:
the pressure necessary for displacing the disc in order to be able to mix the two substances is high, as the diameter of said disc is larger than the inner diameter of the container body, the disc being, moreover, positively retained in the body via an annular groove provided on the inner wall of said container body; PA1 once disengaged, the disc may move freely in the tubular body, and, during dispensing of the mixture by injection, the body is inverted, which causes the disc to block at least partially the exit of the mixture via the needle.

Multi-chamber dispensing container for storing at least two substances, the extemporaneous mixture of these substances, and distribution of the mixture


A scan converter processes an input video signal having a fixed number of an lines per frame, a horizontal synchronization rate and a vertical synchronization rate on an input video line to produce an output video signal having a predetermined number of scan lines per frame and a selected number of pixels per line on a video output line. The scan converter locks to the vertical synchronization rate of the input video signal to make the output video signal have a vertical synchronization rate equal to the vertical synchronization rate of the input video signal. The output horizontal rate is determined by multiplying the vertical synchronization rate by the predetermined number of scan lines per frame in the output video signal. The input horizontal synchronization rate is multiplied by the selected number of pixels per line to produce a WRITE pointer signal for writing input picture lines into a memory. The output horizontal rate is multiplied by the selected number of pixels per line to produce a READ pointer signal for reading picture lines of the output video signal out of the memory.

1. Field of the Invention
This invention relates generally to video signal processing and particularly to video signal processing systems and methods for converting an incoming video signal to an output having a standard NTSC 525-line interlaced or non-interlaced picture.
2. Description of the Prior Art
Video signals having 525, 675 and 875 horizontal scan lines are used in various commercial, industrial and military applications. Previous video signal processing circuitry is designed to operate with a single input horizontal scan line rate. Therefore, a video system designed for a 525 line rate is unusable with a 675 line signal.
Previous video scanners have the disadvantage of requiring storage of an entire picture sweep or more and require a relatively large amount of memory. A typical system must store at least as many lines as the lesser of the number of lines in the vertical sweep of the input or the output. For standard NTSC signals typical systems store at least 240 picture lines. The necessity of storing an entire picture sweep causes a delay of 6 to 24 msec between input and output signals. The delay between input and output signals is important in systems where the content of the picture is used to direct some action. The problem with the delay between input and output is analogous to driving an automobile while watching out the window what happened a second or so earlier.

The United States of America as represented by the Secretary of the Navy


A membrane-based tangential flow filtration system is disclosed which includes optimized performance capabilities by taking into account the variety of flux and component passage behavior occurring during filtration processing. The system maximizes the recovery of a desired component in the permeate from a sample solution containing two or more components, in minimum time and with minimum filtration area, by optimizing the mass flux of the desired component by continuously controlling the rate of addition of a diafiltrate solution to the system to maintain the optimum balance of component concentrations.

The present invention relates to membrane-based filtration systems and more particularly to techniques for optimizing the operation of such systems to maximize recovery of a desired component in minimum time.
Filtration systems commonly used in industrial applications today include tangential flow filtration (TFF) systems which use membranes to separate components in a liquid sample solution on the basis of their effective size differences. The sample solution housed in a tank or other suitable reservoir flows across the face of the membrane at an elevated pressure which drives permeable components smaller than the pore size of the membrane through the membrane as permeate while retaining larger components in a retentate stream. The retentate stream is recirculated to the tank and ultimately pumped across the membrane in a continuous fashion. Notwithstanding the sweeping flow action of TFF systems, certain component species within the sample solution typically remain trapped on the surface of the membrane and form a concentration polarization gradient which affects the permeability of those components passing through the membrane.
Depending on the mode of operation of the TFF system, the volume of the sample solution can be significantly reduced as permeate is withdrawn from the system as the sample solution becomes concentrated (i.e. concentration mode). On the other hand, many applications involving the separation of two or more components add a diafiltrate solution at the same rate as permeate is withdrawn to maintain the overall system volume constant while removing the permeable component from the sample solution (i.e. constant volume diafiltration mode). Control strategies also can involve combinations of concentration and diafiltration modes of operation. These strategies involve control of both the diafiltrate flow (q.sub.d) and the permeate flow (q.sub.p). There have been numerous attempts published in the literature to try to optimize processing conditions by controlling certain parameters of the TFF system.
As described by Blatt et al., Anal. Biochem., 26 (1968) 151, discontinuous batch diafiltration involves varying the diafiltrate flow rate from a pure concentration mode (q.sub.d =0) to a pure dilution mode (q.sub.p =0) in a step wise manner. This process is repeated as a series of n sequential concentrations (from volume V.sub.O to volume V) and dilutions where system concentrations decline from an initial value c.sub.O to a value c=c.sub.0 (V.sub.0 /V).sup.-.sigma.n for component passage .sigma.. However, as subsequently recognized (see Ch. 3 in Mears, "Membrane Separation Processes", 1976) the discontinuous diafiltration method produces lower average fluxes due to the higher average system concentrations of the polarizing species over the diafiltration process. This will require long processing times or large system membrane areas to reach the target purity. Additionally, discontinuous diafiltration is cumbersome to implement in a production scale system.
As described in the same publication as above, Blatt et al. also refer to constant volume batch diafiltration which involves keeping the diafiltrate flow rate equal to the permeate flow rate over the entire process. This maintains a constant system fluid volume V.sub.O during the process while component concentrations in the system decline from an initial value of c.sub.0 to a value c=c.sub.0 e.sup.-.sigma.V.sbsp.d.sup./V.sbsp.o for component passage .sigma. and diafiltrate volume V.sub.d. While high fluxes can be maintained using this technique, the large amount of diafiltrate required can result in long process times or large membrane areas, both of which lead to uneconomical results.
A modification of constant volume batch diafiltration was described by Ng et al., Sep. Sci., 11, (1976) 499. In this scheme, initial experimental data is generated to produce a plot of flux versus concentration of the polarizing species. The optimum diafiltration point (c.sub.g /e) is determined by first extrapolating the generated data points to find the zero flux intercept or gel point (c.sub.g) and then dividing by 2.718 (the value of e). After c.sub.g /e is determined, implementation of the control strategy occurs in two steps, first by conducting either a pure concentration mode (q.sub.d =0) step or pure dilution mode (q.sub.p =0) step to bring the concentration of the polarizing species from its initial value c.sub.o to c.sub.g /e. The next step is to run the system under constant volume diafiltration conditions at this empirically obtained optimized polarizing species concentration point until the desired retentate concentration of the passing species is obtained.
The existence of an optimum diafiltration concentration according to the teachings of Ng et al. arises from a tradeoff between the decreasing volume of permeate produced as one concentrates the initial batch, and the decreasing flux produced as the concentration of retained components are increased. The N get al. strategy is economically optimal when the diafiltration step process time dominates the total process time, the polarizing species is completely retained, the passage of the permeating species is constant, and the flux (J) variation with the concentration of the polarizing species (c) is described by the film model as J=k ln (c.sub.g /c). In this model, c.sub.g is the gel point and k represents the mass transfer coefficient. The foregoing conditions are not always met over the wide range of variables typical of most TFF applications.
Beaton and Klinkowski, J. Sep. Proc. Techn., 4 (1983) 1, use the same strategy as Ng et al. but account for deviations in flux (J) from the film model. They identify the optimum batch concentration of the polarizing species (c) at which to diafilter as that value of (c) which produces a minimum in the plot of 1/Jc vs c. While this publication recognizes in some cases that flux varies with both the retained species concentration and the permeating species concentration, the authors suggest using the Ng et al. diafiltration strategy with a flux versus polarizing species relationship, J(c), which is determined at low permeating species concentrations. Hence this technique ignores the flux dependence on the permeating species and thus will not produce optimum results when the flux varies over the course of the diafiltration.
Jaffrin et al., Recents Progres Genie Procedes, 6 (1992) 299, considered the effect of both retained species concentration and permeating species concentration on flux by adding another step to the Ng et al. strategy for an application involving the removal of ethanol from albumin. The feed is first diluted with water to reduce ethanol concentration, then concentrated to increase the albumin concentration. After these steps, a constant volume diafiltration was run to reduce ethanol concentration to a final specification. The Jaffrin et al. step-wise process is a discontinuous approximation of actual conditions and thus does not accurately reflect optimal system operations. This publication also hints at a possible different strategy involving diafiltration under diminishing volume. However, no analysis or data is shown as to how one might implement this approach. More recently, Jaffrin et al., J. Mem. Sci. 97 (1994) 71, elaborate on the above strategy by describing operation at a constant diafiltrate to permeate flow ratio over the entire process. The "trial and error" optimization strategy used to identify the best value for this ratio provides little guidance as to when this approach has utility. In addition by requiring a fixed ratio over the entire process, this strategy does not account for the effect of changing concentrations of the species.
DiLeo et al., U.S. Pat. No. 4,728,430, described the first significant departure from the Ng et al. strategy by proposing a new diafiltration processing technique based on maintaining a constant system concentration of a particular polarizing species instead of maintaining a constant volume. This strategy allows for the case where the polarizing species is only partially retained by specifying a diafiltrate addition flow where the system volume decreases over the course of processing. While this strategy is described in the context of blood plasma separation, it is generally applicable to all separations using TFF where only one particular component controls the flux and passage over the course of processing.
All of the foregoing attempts have failed to adequately take into account when more than one species in the sample to be filtered controls the flux and passage of the permeating species during diafiltration and thus are deficient in the processing goal of maximizing recovery of the desired component in the minimum amount of time.

Membrane filtration with optimized addition of second liquid to maximize flux


A nontoxic cellulose solvent and process for forming and utilizing the same. The solvent includes a metal chelating agent, a metal compound, an oxygen scavenging stabilizing agent and a caustic swelling agent with the disclosed solvent being prepared in either aqueous or solid form. The solvent is caused to contact cellulosic materials in order to dissolve cellulose therefrom. The dissolved cellulose may be reprecipitated and may then be hydrolyzed by cellulose enzyme or acid to yield glucose with lignin being removed either before or after hydrolysis has occurred.

The utilization of cellulosic waste materials, such as cornstalks, sawdusts, straws, bagasse, and the like, hereinafter referred to as cellulosic material or cellulosic residue, has been the subject of strong interest recently, particularly with respect to utilization of such waste materials for developing alternate sources of fuels, feedstuffs, chemicals and other useful products.
It is known that cellulosic materials include three principal components--cellulose, hemicellulose and lignin. Methods for extraction or hemicellulose heretofore have been suggested and/or utilized and such extracted hemicellulose can be utilized by many existing methods including hydrolysis, fermentation, pyrolysis, and the like.
Lignin has also been isolated from cellulosic materials and since it is higher in hydrogen and carbon and lower in oxygen content than cellulose and hemicellulose it has the highest fuel utility of the three. Isolated lignin can be burned to generate steam and electricity and also can be used to produce a number of useful products including vanillin, dimethylsulfoxide, dimethyl sulfide, and methyl mercaptan and catechol.
Recovery of cellulose and/or utilization of the same, as by hydrolysis to provide glucose, has presented a problem heretofore primarily due to the crystalline structure of the cellulose molecules and the presence therein of a lignin seal.
While attempts have been made to hydrolyze cellulosic materials by means of acids or enzymes, such attempts have not been completely successful, at least not in providing an economically attractive method that is capable of providing a satisfactorily high yield of glucose from the cellulose in such cellulosic materials.
Also, while solvents have been suggested and/or utilized in conjunction with cellulosic materials, improvements in such solvents can still be utilized in recovering cellulose. In this regard, dissolution of pure cellulose using a ferric sodium tartrate based solvent heretofore has been suggested. See, for example, Valtassari, Papper och Tra 4 (1957) 243.

Nontoxic cellulose solvent and process for forming and utilizing the same


An optical information recording medium includes a first dielectric protective layer, a recording layer provided on the first dielectric protective layer, including a material represented by a chemical formula of Ag.alpha.In.beta.Sb.gamma.Te.delta., wherein .alpha., .beta., .gamma. and .delta. respectively represent an atomic percent of Ag, an atomic percent of In, an atomic percent of Sb, and an atomic percent of Te, and satisfy the conditions of:. 1.ltoreq..alpha.<10, PA1 1<.beta..ltoreq.20, PA1 35.ltoreq..gamma..ltoreq.70, PA1 20.ltoreq..delta..ltoreq.35, PA1 .alpha.+.beta.+.gamma.+.delta.=100, PA1 4.beta.-.delta..ltoreq.0, PA1 .gamma.-2.delta..gtoreq.0, and PA1 .gamma.-8.alpha..gtoreq.0, PA1 a second dielectric protective layer provided on the recording layer, and a light reflection and heat dissipation layer provided on the second dielectric protective layer.

1. Field of the Invention
The present invention relates to a rewritable phase-change optical information recording medium having a large recording capacity and capable of rewriting information recorded therein.
2. Discussion of Background
As optical information recording media which are capable of recording information therein, and from which recorded information can be reproduced or erased by the application of semi-conductor laser beams thereto, there are conventionally known (1) a magneto-optical recording medium in which information can be recorded, and recorded information can be erased by reversing a magnetization direction of a recording layer thereof, utilizing heat, and (2) a phase-change optical information recording medium in which information can be recorded, and recorded information can be erased, utilizing phase changes between a crystalline phase and an amorphous phase of a recording layer thereof.
The latter phase-change optical information recording medium is capable of performing single beam overwriting, and is advantageous over other optical recording media in the compatibility with CD-ROM and CD-R media, so that the standardization of the phase-change optical information recording media as rewritable media, namely as CD-RW, has now been established, and the phase-change optical information media have now been commercialized.
In the meantime, large capacity storage by the phase-change optical information recording media has been studied, and DVD-ROM media have been placed on the market. In accordance with the apparatus of the DVD-ROM on the market, media called DVD-RAM are now being developed as rewritable DVD media. A DVD-RAM with a capacity of 2.6 GB will be shortly commercialized, but there is now a demand for a DVD-RAM with a capacity larger than that of ROM media.
As the materials for use in the recording layer of the phase-change optical information recording medium, chalcogen-based alloys, such as Ge--Sb--Te, In--Sb--Te, Ge--Se--Te, Ge--Te--Bi, Sb--Se--Te, and In--Te--Au have been investigated. Of these chalcogen-based alloys, Ge--Sb--Te has now reached a level for use in practice. However, even with this Ge--Sb--Te, further improvements are desired on the recording sensitivity, erasing sensitivity, and erasing ratio at overwriting.
Japanese Laid-Open Patent Applications 4-78031 and 9-263055 disclose phase-change information recording media using as recording materials in the recording layers thereof Ag--In--Sb--Te based alloys by use of which the erasing ratio of the phase-change information recording media at the overwriting is improved.
However, the repeated use overwriting characteristics of a phase-change optical information recording medium using the above-mentioned Ag--In--Sb--Te based recording material cannot be improved by using the Ag--In--Sb--Te based recording materials only, but by using upper and lower protective layers, and a heat dissipation layer which are overlaid.
As the materials for such protective layers, ZnS.SiO.sub.2 as disclosed in Japanese Patent Publication 7-114031, metallic oxides, metallic sulfides and metallic nitrides, and mixtures thereof are conventionally proposed. However, the improvement of the repeated use overwriting characteristics of the phase-change optical information recording medium is still insufficient for use in practice.
As mentioned above, the phase-change optical information recording media have now been commercialized as CD-RW. The CD-RW is used as an external memory device for use with personal computers. Recently DVD-ROM players are placed on the market, so that there is a great demand for large capacity, rewritable DVD media.
The DVD-RAM which has now been commercialized as rewritable DVD medium has a capacity of 2.6 GB, and recording and reproduction is conducted at a linear speed of about 6 m/sec, while in DVD-ROM, the linear speed for recording and reproduction is about 3.5 m/sec, and the capacity of DVD-ROM is 4.7 GB. It is required that rewritable DVD media have a capacity greater than that of ROM, be capable of peforming recording and reproduction at a speed of two times greater than that of ROM, and be compatible with ROM. In order to meet such requirements, it is strictly required that the DVD media have a high line density, a low jitter, and a large overwriting repetition number. In particular, the improvement of the overwriting repetition number is one of most significant targets to be cleared in the phase-change optical information recording media in order to enhance the performance reliability of the media. The Ag--In--Sb--Te based phase-change recording materials are suitable for high density recording, so that how to improve the overwriting repetition characteristics thereof is still a significant target to be cleared.


A resource distribution method capable of lending surplus resources among a plurality of services and reducing the maintenance cost of the surplus resources is provided. Computer resources in the standby system have a dead standby state in which at least an application is not installed. A plurality of services or a plurality of users share the computer resources in the standby system. As a result, improvement of the utilization factor of idle computer resources and server integration are implemented, and the cost required to maintain the computer resources is reduced. Furthermore, load prediction is conducted as regards individual services by using past operation history. Idle computer resources secured from services having surplus and maintained are thrown in according to a result of the prediction.

The present invention provides a method for automatically shifting computer resources from a standby system to an active system by using a prediction technique.
In recent years, outsourcing with the object of reducing the necessary expense is proceeding in purchase, supply and maintenance of service, software and infrastructures. Computer use of "on demand" type has been proposed. In the computer use of "on demand" type, necessary computer resources are used when needed, and a charge is paid according to the amount used. Outsourcing to computer centers having a large quantity of computer resources represented by conventional computer centers such as data centers and utility centers is proceeding. It is considered that this movement will be further accelerated by application of the grid computing technique to the business field. Here, the maintenance of idle computer resources and a resultant cost pose a problem. In the conventional computer operation, computer resources are introduced in expectation of specifications at the time of maximum operation needed instantaneously. Usually, therefore, a large number of idle computer resources are present. Maintaining the computer resources constitutes a barrier to the cost reduction. In a method disclosed in JP-A-9-81409, a computer has an active system and a standby system. A standby system processing function that can be automatically associated when a fault has occurred is selected and associated. A hot standby relation is constructed, and the standby system becomes an active system for another computer. Since the standby system can become an active system for another computer in this method, it becomes possible to implement reduction of standby system resources and reduction of idle computer resources. In a method disclosed in JP-11-328129, only resources shared by all jobs are connected and it is made possible to cope with any execution system job. As a result, the number of standby system jobs in the system is reduced, and it is attempted to use resources efficiently as regards computers and memories and reduce the system operation load and cost.
In the conventional techniques, other services are not operated on the same server. Therefore, the total number of servers cannot be decreased in the form of, for example, server integration. The same holds true for computer resources other than servers. In the case where the load varies depending upon the time zone, it is necessary to prepare enough computer resources to withstand a high load and it is difficult to reduce computer resources. In addition, since the standby system becomes a computer resource group always having the same setting as that of the active system in the conventional technique, it is necessary to maintain a standby system every service and it is difficult to reduce the computer resources. Furthermore, since overload in computer resources of the active system is predicted in the conventional technique on the basis of the current load value, precision of resource scheduling is low. In that respect as well, it is difficult to form a configuration in which surplus resources are mutually lent among a plurality of services.

Computer resource distribution method based on prediction


An illumination apparatus is provided that includes a yellow phosphor converter to receive a blue laser light beam and to convert a portion of the blue laser light beam to yellow light, a dichroic mirror optically coupled to the yellow phosphor converter to receive the phosphor-emitted light beam and to filter the phosphor-emitted light beam to provide a dichroic-filtered light beam, the dichroic mirror configured to pass yellow light and to reflect at least some blue light, and a blue light source optically coupled to the dichroic mirror to provide a blue light beam, the dichroic mirror configured to reflect the blue light beam in a same direction as the dichroic-filtered light beam.

Field of the Disclosure
Embodiments of the present disclosure generally relate to illumination for headlamps, and more specifically relate to hybrid illumination for headlamps.
Description of the Related Art
Laser based headlamp systems are currently being used in or are planned for some high end automobiles, e.g., automobiles made by Audi and BMW, and are likely to appear in more models in the future. The high beam setting for such systems may have twice the light range and three times the luminosity of light emitting diode (LED) headlamp systems. The safety of using such headlamps is of concern due to the use of the laser technology. Accordingly, improvements in the safety of such headlamp systems are desirable.

Hybrid illumination system having a blue laser diode, dichroic mirror and yellow transmissive phosphor converter for generating white light


A method and apparatus for endpointing a planarization process of a microelectronic substrate. The apparatus can include a source of electrical power having first and second electrical contacts coupled to the microelectronic substrate to form a conductive path through the substrate. An impedance of the conductive path changes as conductive material is removed from the substrate during planarization. In one embodiment, one contact can be attached to an upper surface of the substrate and the other contact can be attached to an intermediate surface between the upper surface and a lower surface of the substrate. In another embodiment, both contacts are connected to the intermediate surface and in still another embodiment, one contact can be connected to a retainer adjacent the substrate. In yet another embodiment, the power source induces a current in the conductive material, and the endpoint is detected by detecting a change in the induced current as the conductive material is removed.

Mechanical and chemical-mechanical planarizing processes (collectively "CMP") are used in the manufacturing of microelectronic devices for forming a flat surface on semiconductor wafers, field emission displays, and many other microelectronic substrates. FIG. 1 schematically illustrates a planarizing machine 10 with a platen or table 20, a carrier assembly 30, a polishing pad 21 positioned on the table 20, and a planarizing fluid 23 on the polishing pad 21. The planarizing machine 10 may also have an under-pad 25 attached to an upper surface 22 of the platen 20 for supporting the polishing pad 21. In many planarizing machines, a platen drive assembly 26 rotates (arrow A) and/or reciprocates (arrow B) the platen 20 to move the polishing pad 21 during planarization.
The carrier assembly 30 controls and protects a substrate 80 during planarization. The carrier assembly 30 typically has a substrate holder 32 with a pad 34 that holds the substrate 80 via suction. A carrier drive assembly 36 typically rotates (arrow C) and/or translates (arrow D) the substrate holder 32. The substrate holder 32, however, may be a weighted, free-floating disk (not shown) that slides over the polishing pad 21.
The combination of the polishing pad 21 and the planarizing fluid 23 generally defines a planarizing medium 28 that mechanically and/or chemically-mechanically removes material from the surface of the substrate 80. The polishing pad 21 may be a conventional polishing pad composed of a polymeric material (e.g., polyurethane) without abrasive particles, or it may be an abrasive polishing pad with abrasive particles fixedly bonded to a suspension material. In a typical application, the planarizing fluid 23 may be a CMP slurry with abrasive particles and chemicals for use with a conventional non-abrasive polishing pad. In other applications, the planarizing fluid 23 may be a chemical solution without abrasive particles for use with an abrasive polishing pad.
To planarize the substrate 80 with the planarizing machine 10, the carrier assembly 30 presses the substrate 80 against a planarizing surface 24 of the polishing pad 21 in the presence of the planarizing fluid 23. The platen 20 and/or the substrate holder 32 then move relative to one another to translate the substrate 80 across the planarizing surface 24. As a result, the abrasive particles and/or the chemicals in the planarizing medium 28 remove material from the surface of the substrate 80.
CMP processes must consistently and accurately produce a uniformly planar surface on the substrate to enable precise fabrication of circuits and photo-patterns. Prior to being planarized, many substrates have large "step heights" that create a highly topographic surface across the substrate. Yet, as the density of integrated circuits increases, it is necessary to have a planar substrate surface at several stages of substrate processing because non-uniform substrate surfaces significantly increase the difficulty of forming sub-micron features or photo-patterns to within a tolerance of approximately 0.1 .mu.m. Thus, CMP processes must typically transform a highly topographical substrate surface into a highly uniform, planar substrate surface (e.g., a "blanket surface").
In the competitive semiconductor industry, it is desirable to maximize the throughput of CMP processing by producing a blanket surface on a substrate as quickly as possible. The throughput of CMP processing is a function of several factors, one of which is the ability to accurately stop CMP processing at a desired endpoint. In a typical CMP process, the desired endpoint is reached when the surface of the substrate is a blanket surface and/or when enough material has been removed from the substrate to form discrete components on the substrate (e.g., shallow trench isolation areas, contacts, damascene lines, etc.). Accurately stopping CMP processing at a desired endpoint is important for maintaining a high throughput because the substrate may need to be re-polished if the substrate is "under-planarized." Accurately stopping CMP processing at the desired endpoint is also important because too much material can be removed from the substrate, and thus the substrate may be "over-polished." For example, over-polishing can cause "dishing" in shallow-trench isolation structures, or over-polishing can completely destroy a section of the substrate. Thus, it is highly desirable to stop CMP processing at the desired endpoint.
In one conventional method for determining the endpoint of CMP processing, the planarizing period of one substrate in the run is estimated using the polishing rate of previous substrates in the run. The estimated planarizing period for a particular substrate, however, may not be accurate because the polishing rate may change from one substrate to another. Thus, this method may not accurately planarize all of the substrates in a run to the desired endpoint.
In another method for determining the endpoint of CMP processing, the substrate is removed from the pad and the substrate carrier, and then a measuring device measures a change in thickness of the substrate. Removing the substrate from the pad and substrate carrier, however, is time consuming and may delay further processing until the measurement is completed. Thus, this method generally reduces the throughput of CMP processing.
In still another method for determining the endpoint of CMP processing, a portion of the substrate is moved beyond the edge of the pad, and an interferometer directs a beam of light directly onto the exposed portion of the substrate and through a layer of the substrate to detect a thickness of the layer. The substrate, however, may not be in the same reference position each time it overhangs the pad. For example, because the edge of the pad is compressible, the substrate may not be at the same elevation for each measurement. Thus, this method may inaccurately measure the change in thickness of the layer of the wafer.
In yet another method for determining the endpoint of CMP processing, U.S. Pat. No. 5,036,015 discloses detecting the planar endpoint by sensing a change in friction between a wafer and the polishing medium. Such a change in friction may be produced by a different coefficient of friction at the wafer surface as one material (e.g., an oxide) is removed from the wafer to expose another material (e.g., a nitride). In addition to the different coefficients of friction caused by a change of material at the substrate surface, the friction between the wafer and the planarizing medium generally increases during CMP processing because more surface area of the substrate contacts the polishing pad as the substrate becomes more planar. U.S. Pat. No. 5,036,015 discloses detecting the change in friction by measuring the change in current through the platen drive motor and/or the drive motor for the substrate holder.
In still a further method for determining the endpoint of CMP processing, such as is disclosed in U.S. Pat. No. 5,559,428, the chemical composition of the CMP slurry is analyzed to determine when a layer of a first material has been removed to expose a layer of a second, different material. For example, planarization may continue through the first material until the second material is exposed, at which point some of the second material is removed and enters the slurry. The second material and the slurry is identified using instrumentation such as inductively coupled plasma for atomic emission spectroscopy, and the planarization process is halted.
In yet another method for determining the endpoint of CMP processing, such as is disclosed in U.S. Pat. No. 5,321,304, the substrate includes parasitic conductive contacts or terminals buried beneath an insulative layer. When the insulative layer over the contacts has been removed by planarization, the terminals come into electrical contact with probes in the polishing pad or the planarizing liquid, completing an electrical circuit and indicating the endpoint. A drawback with this method is that it is not suitable for determining the endpoint of a conductive layer.
In still a further method for determining the endpoint of CMP processing, such as is disclosed in U.S. Pat. No. 4,793,895, the substrate includes contacts or terminals positioned beneath an insulative layer and coupled to each other through circuitry internal to the substrate. The insulative layer is placed face down against a polishing pad that has two corresponding terminals coupled to a power source. When the insulative layer has been removed by planarization, the terminals in the polishing pad make electrical contact with the terminals of the substrate, completing an electrical circuit and indicating that the endpoint has been reached. The method can also be used to monitor the resistivity of a conductive layer. One drawback with this method is that at least one terminal is positioned in the polishing pad where it can become contaminated with slurry and other particulates. Another drawback with this method is that a conductive path must be maintained between the substrate and the polishing pad, which may be difficult during planarization because the substrate and the polishing pad move relative to one another.

Method and apparatus for electrically endpointing a chemical-mechanical planarization process


An infusion pump includes a piezoelectric actuator located in a housing and operable to deflect a flexible wall of a detachable pump body. The pump body defines a chamber of variable volume with non-return inlet and outlet valves. The pump body is disposable and connected to the housing by a releasable connector which biases the wall into operative engagement with the transducer. The transducer is provided with sense electrodes to measure the amplitude of deflection which is used to trigger alarms indicating the presence of bubbles in the chamber or of occlusion.

This invention relates to pump apparatus for biomedical use and in particular but not exclusively for use in intravenous infusion of liquids to the human body or animal body.
Many medical procedures require the controlled introduction of liquids over a prolonged period into the human or animal body for example where a patient is to receive a drug, blood products, saline or nutrients etc at a controlled dose rate. Existing pump apparatus for such applications includes syringe pumps, drip monitors and peristaltic pumps each of which suffer the disadvantages of being expensive, complex to set up and operate and are generally inhibiting of patient movement. It is also known to introduce liquids into plants in a controlled manner in situations where it is inconvenient to have complex pump apparatus relying on external power supplies.
It has also been proposed in DE-2920975 for example to have a peristaltic pump within a housing which also contains means for controlling and actuating the pump so that the apparatus is self-contained and portable and may for example be attached to the body receiving an infusion.
A disadvantage of such peristaltic pumps is that the rate of flow at which liquid is delivered by the pump cannot be accurately controlled. Typically flow rate is measured by counting revolutions of the peristaltic roller mechanism and errors of up to 15% are typical in measured flow rate. A further difficulty is that, in the event of occlusion of the infusion flow path, known pumps and particularly syringe pumps are generally capable of building-up liquid pressure to a dangerous level. It is also difficult to effectively detect the presence of air bubbles within known pumps and typically a bubble detector relies on the use of sensors responsive to the difference in refractive index between air and the liquid being pumped. The presence of air bubbles is extremely dangerous during infusion and a disadvantage of known pumps is that any air bubble will easily pass through the pump.
It is also known from U.S. Pat. No. 4,596,575 to provide an implantable pump apparatus in which a pump chamber has a flexible wall movable by actuation of a piezoelectric transducer, the chamber having inlet and outlet valves which are electromagnetically actuated poppet valves. The pump is used to pump a buffer fluid which in turn pressurises a bag containing infusate. The infusate therefore does not pass through the pump chamber and the problems associated with bubble formation within the chamber are dealt with by ensuring that the buffer fluid is de-aerated before filling.


An electric brake system comprising: a master cylinder configured to a reservoir storing oil therein and configured to generate hydraulic pressure according to a pedal effort of a brake pedal; a cut valve installed at a backup flow path connecting the master cylinder to a wheel cylinder; a simulation device including a simulation chamber connected to the master cylinder at a front end of the cut valve to provide a reaction force according to the pedal effort of the brake pedal, a simulation valve provided at a flow path connecting the master cylinder to the simulation chamber; a hydraulic pressure supply device configured to operate in response to an electrical signal of a pedal displacement sensor sensing a displacement of the brake pedal, and a damping member provided at a flow path connecting the hydraulic pressure chamber to the front end of the cut valve, wherein the damping member delivers a pressure pulsation generated in the hydraulic pressure chamber to the brake pedal in an anti-lock brake system (ABS) mode.

1. Field
Embodiments of the present disclosure relate to an electric brake system, and more particularly, to an electric brake system capable of sensing a pressure pulsation according to a request of a driver while an anti-lock brake system (ABS) operates.
2. Description of the Related Art
A brake system for braking is necessarily mounted on a vehicle, and a variety of systems for providing stronger and more stable braking have been proposed recently.
For example, there are brake systems including an anti-lock brake system (ABS) for preventing a wheel from sliding while braking, a brake traction control system (BTCS) for preventing a driving wheel from slipping when a vehicle is unintentionally or intentionally accelerated, an electronic stability control (ESC) system for stably maintaining a driving state of a vehicle by combining an ABS with a traction control to control hydraulic pressure of a brake, and the like.
Generally, an electric brake system includes a hydraulic pressure supply device which receives a braking intent of a driver in the form of an electrical signal from a pedal displacement sensor which senses a displacement of a brake pedal when the driver steps on the brake pedal and then supplies hydraulic pressure to a wheel cylinder.
An electric brake system configured with such a hydraulic pressure supply device is disclosed in European Registered Patent No. EP 2 520 473. According to the disclosure in that document, the hydraulic pressure supply device is configured such that a motor is operated according to a pedal effort of a brake pedal to generate braking pressure. At this point, the braking pressure is generated by converting a rotational force of the motor into a rectilinear movement to pressurize a piston.
Also, the electric brake system includes a simulation device capable of providing a driver with a reaction force according to the pedal effort of the brake pedal. At this point, the simulation device is connected to an oil reservoir, and a simulation valve is installed at an oil flow path which connects the simulation device to the oil reservoir. The simulation valve is provided to be blocked when the electric brake system operates abnormally and to deliver hydraulic pressure discharged from a master cylinder to the wheel cylinder such that stable braking may be performed.
Such an electric brake system has a structure in which a reaction force according to the pedal effort of the brake pedal is provided through the simulation device and the hydraulic pressure is delivered to a wheel cylinder through the hydraulic pressure supply device so that a pressure pulsation, which is generated during an ABS control, is not delivered to a driver. Therefore, although the driver requests to deliver the pressure pulsation thereto during the ABS control, a cut valve provided at a flow path, which connects a master cylinder to the wheel cylinder, should be maintained in a blocked state for stable braking so that there is a problem in that the pressure pulsation is not delivered to the driver.


The present invention relates to an improved transfer molding method for encapsulating semiconductor, electrical and optical devices with epoxy or other thermoset resins wherein liner film is provided over the surfaces of the package cavities, runners, and pot prior to inserting the preform tablet in the pot and the devices in the package cavities.

1. Field of the Invention
This invention relates to transfer molding methods used to encapsulate semiconductor, electrical and optical devices ("device") with epoxy or other thermoset resin formulations ("formulation").
2. Description of the Prior Art
Transfer molding involves inserting a preform tablet of formulation in a pot, heating the preform, either prior to or after inserting the tablet in the pot, to soften the formulation, using a plunger to transfer the softened formulation from the pot into device cavities in metal molds. The plunger is used to force the soft encapsulating composition along runners into a package cavity in which the device has previously been inserted. The molten formulation surrounds the device in each cavity and encapsulates it.
The formulation which constitutes the preform tablets comprises abrasive fillers and mold release agents which cause problems insofar as the metal molds are subjected to wear and to "staining."
A method is described in Semiconductor Packaging Update, 1994, Vol. 9, No. 6 (ISSN: 0889-9193) in which a special pencil-shaped, film wrapped preform, prepared according to Pas, U.S. Pat. No. 5,098,626, is employed, along with specialized molds which eliminate the conventional pots and runners. Film is drawn into the cavities by vacuum molding. That method has disadvantages in that it requires special preforms, and extensive, complex, and expensive retooling of the molding equipment.

Transfer molding process for encapsulating semiconductor devices


A printed circuit board to be tested on a test fixture mounts sealingly on a movable top plate having through holes located directly beneath test points on the board. A base plate below the top plate is provided with a plurality of upstanding, spring-loaded test probes arranged to pass through the holes in the top plate when the two plates are drawn together by a vacuum established in the space between the plates. A resilient gasket seals the perimeter of the plates defining the vacuum chamber between the plates. The plates are held resiliently apart by compression springs. A vacuum source is connected to the vacuum chamber by a vacuum control. The test probes are of two different heights. When a full vacuum is applied to the vacuum chamber, the plates are pulled close together and all test probes contact test points on the circuit board in a first test mode of operation. The vacuum control includes a sensor of the distance between plates and admits enough vacuum to maintain a preset interplate distance for a second test mode, wherein the plates are spaced apart sufficiently to enable a first population of test probes to contact test points on the circuit board while a second, shorter population of test probes remain spaced apart from the circuit board. An atmospheric venting valve with feedback control facilitates moving from one test mode to another. In another embodiment additional levels or test modes are provided.

The present invention relates to a test fixture for use in automatic test equipment for electronically checking a printed circuit board (PCB) and more particularly for such a fixture which is provided with means for contacting a first set of contact points on the board with a first set of test probes and for contacting additional points with additional probes in at least one additional operating mode using a vacuum actuated feedback mechanism.
Automatic electronic test equipment for checking printed circuit boards are well known. Hundreds of test points on the circuit board must be selectively tested. This is generally accomplished with a vacuum actuated test fixture employing a first plate with an array of upstanding, spring-mounted test probes. The probes are positioned to engage the test points on the board. The board is mounted on a second plate parallel to the first plate with holes arranged to pass the probes therethrough. Springs hold the plates apart until a vacuum between the plates pulls them together, whereupon the probes contact the test points.
For certain testing applications, it is desirable to have two or more testing modes in which only selected ones of the probes are in contact with their test points while other probes are spaced away from their test points. Prior art test fixtures have employed spring-mounted test probes having two different lengths. These have regulated the spacing apart of the plates by means of a pressure regulator for maintaining a preset partial vacuum great enough to force the plates close enough for only the long probes to make contact in a first level test mode and applying full vacuum to force the plates so close together that all the probes make contact in a second level test mode.
Fixtures using the vacuum regulator to control board position relative to the test probes rely upon the principle that a given vacuum will result in a given atmospheric pressure forcing the plates together against the springs in the vacuum chamber. This system controls only the vacuum, not the distance between plates directly. It has been found in practice that any change in atmospheric pressure, spring tension, and leaks at the various gaskets or through the circuit board results in fluctuations in the partial travel position at a preset pressure on the regulator, resulting in inconsistent performance and requiring individual adjustment of the regulator for each board in some cases.

Vacuum actuated multiple level printed circuit board test fixture


Process of making compounds having the formula ##STR1## wherein --OR.sup.1 comprises alkanoyl or the C-13 side-chain of taxol; R.sup.2, R.sup.3, and R.sup.6 can be oxygenated or hydrogen in various combinations; and R.sup.4 and R.sup.5 are acyl groups.

The present invention relates to plant-derived chemotherapeutic compounds. More particularly, the invention is directed to deoxygenated taxol compounds prepared from a natural product which is isolated from Taxus canadensis, as well as novel analogs of taxol prepared therefrom.
Taxol, a member of the taxane family of terpenes, is of interest as a chemotherapeutic agent against a broad range of cancers. Derived primarily from the Pacific yew Taxus brevifolia, taxol has been shown to be active against advanced breast and ovarian cancers in clinical trials, and has exhibited promising activity against a number of other tumor types in preliminary investigations. A summary of the current state of taxol research, development and clinical testing may be found in Rotherberg, Curr. Opin. Invest. Drugs, 1(12):1269-1277 (1993); a review of synthetic efforts in the taxol field is provided by D. G. I. Kingston in Prog. Chem. Org. Nat. Prod., 61:1-206 (1993).
Although taxol, which possesses the structural formula ##STR2## has shown considerable therapeutic potential, its scarcity in nature and the need for more potent cytostatic agents have led researchers to pursue alternative sources as well as analogs of the compound. Some efforts have been made to produce taxol in tissue and cell culture. Total chemical synthesis of the compound and its related analogs has been attempted but has not yet been achieved. The chemical conversion of naturally occurring taxol precursors such as baccatin III and cephalomannine to taxol itself or its analogs has been reported; however, additional routes for the production of potentially active taxanes are still needed.
One line of inquiry has focused on a more abundant taxane precuror, 13-acetyl-9-dihydrobaccatin III, which can be obtained from the widely distributed Canadian yew Taxus canadensis as described in published international application No. PCT/US93/03532, published on Oct. 28, 1993 as publication No. WO 93/21173 and incorporated herein by reference. This 9-dihydro modication makes possible the preparation of a new series of taxol analogs.
Modifications of the C-7 and C-10 positions of the baccatin moiety, including 7-deoxy, 10-desacetoxy and 7,10-dideoxytaxol derivatives, have also been described. 7-Deoxybaccatin or 7-deoxytaxol derivatives have been described in the international (PCT) application publication No. WO 93/02064, published Feb. 4, 1993 and J. Org. Chem. 58:3798-3799 (1993). 10-Desacetoxytaxol derivatives have been described in the international (PCT) application publication No. WO 93/06093, published Apr. 1, 1993; U.S. Pat. No. 5,248,796, published Sep. 28, 1993; European Patent Application EP 558959, published Sep. 8, 1993; J. Org. Chem. 58:2927-2928 (1993); and Tetrahedron Lett. 34(31):4921-24 (1993). 7,10-Dideoxytaxol derivatives have been described in J. Org. Chem. 58:5028-5029 (1993) and Tetrahedron Lett. 34(43):6845-6848 (1993).
Certain patents and patent applications also purport to generically disclose 9-deoxotaxanes, namely, U.S. Pat. Nos. 4,876,399, 5,015,744 and 5,175,315 and international (PCT) application publication No. WO 93/20036. While these disclosures refer generically to 9-deoxo compounds, they contain no teaching as to how to prepare these compounds and contain no specific examples, prophetic or actual, of 9-deoxo taxanes. Consequently, these disclosures provide no more than a motivation to attempt the preparation of such compounds.
In fact, the ability to synthesize 9-deoxygenated compounds having potentially superior biological or pharmacologic properties may offer significant advantages to the chemist and pharmacologist. It is therefore an object of the present invention to provide such compounds and the means for their preparation.

Process for making 9-deoxotaxane compounds


A shield termination means comprising an annular member having a plurality of axially extending fingers for terminating individual wire shields and/or a bulk cable shield against the inside wall of a back shell accessory body or around the cable leading into the accessory body.

1. Field of the Invention
This invention relates to shield termination means for shields of individual wire leads and/or for a bulk cable shield.
2. Description of the Prior Art
Heretofore shields from electrical leads or cables have been terminated at a connector by time consuming or ineffective means. For example, inside of a connector body, a wire is connected to the shields which is brought out and attached to the connector by way of a clamp. This procedure can be very time consuming. In another example, shields have been clamped between two solid rings surrounding the cable which are electrically coupled to the connector. This shield termination arrangement has disadvantages since irregularities in the size of the shields may result in ineffective electrical connection between the shields and the solid rings.

Shield termination means for electrical connector


An insulating, tinted glass window assembly of components that can be efficiently assembled and disassembled for repair or cleaning provides a three-layer glass window assembly having a tinted-glass layer sandwiched between two clear, transparent glass panes. The tinted-glass layer is formed by a lattice inner frame holding a plurality of preformed tinted glass sized to fit in the lattice frame. The inner frame also holds the clear, transparent glass panes resting on the inner frame in a spaced-apart relation to the internal tinted glass layer. Thus, two insulating layers of air is presented within each of which air movement is restricted by the lattice of the inner frame, thereby further improving insulation properties of the assembly. The perimeter frame 20 and the inner frame each comprise two matching members in face-to-face contact with the inner frame perimeter fitting into a channel in the perimeter frame, and the clear, transparent glass panes secured to the outer frame thereby holding the assembly together without permanent adhesives.

This invention relates to decorative window panes, and more particularly to a laminar assembly of glass panes with a plurality of inner panes of tinted glass held within an lattice network of inner frames between clear outer panes.
Stained glass windows are common. Traditionally, such windows are constructed with lead cames, adhesives, or solder holding together an assembly of tinted glass pieces. Often, a curing process is required to permanently secure the assembly. When a piece of glass of the window is broken, it must be removed and the window rebuilt with a new lead came. The window assembly characteristically is handmade and therefore is expensive as is its repair.
Insulating windows are also common, typically comprising two glass panes secured in a window frame, although windows with more than two panes are also known. A frequent problem with insulating windows is that moisture and dirt accumulate within the window where it is impossible to clean without taking the window apart. However, the such windows are not designed to be taken apart.
It is also well-known that insulation properties are largely due to the low thermal conductivity of air and are improved when air movement is restricted within a volume such as a window.
This invention provides an improved 3-pane insulating window with restricted air movement that simulates a stained-glass window with leaded cames which simultaneously is comparatively inexpensive to assemble and may be disassembled for repair or cleaning without destroying the window assembly.


Compounds of Formula I:

The present invention relates to novel compounds, to pharmaceutical compositions comprising the compounds, to processes for making the compounds and to the use of the compounds in therapy. More particularly, it relates to pyrrolidinyl urea and pyrrolidinyl thiourea compounds which exhibit TrkA kinase inhibition, and which are useful in the treatment of pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.
The current treatment regimens for pain conditions utilize several classes of compounds. The opioids (such as morphine) have several drawbacks including emetic, constipatory and negative respiratory effects, as well as the potential for addictions. Non-steroidal anti-inflammatory analgesics (NSAIDs, such as COX-1 or COX-2 types) also have drawbacks including insufficient efficacy in treating severe pain. In addition, COX-1 inhibitors can cause ulcers of the mucosa. Accordingly, there is a continuing need for new and more effective treatments for the relief of pain, especially chronic pain.
Trk's are the high affinity receptor tyrosine kinases activated by a group of soluble growth factors called neurotrophins (NT). The Trk receptor family has three members: TrkA, TrkB and TrkC. Among the neurotrophins are (i) nerve growth factor (NGF) which activates TrkA, (ii) brain-derived neurotrophic factor (BDNF) and NT-4/5 which activate TrkB and (iii) NT3 which activates TrkC. Trk's are widely expressed in neuronal tissue and are implicated in the maintenance, signaling and survival of neuronal cells (Patapoutian, A. et al., Current Opinion in Neurobiology, 2001, 11, 272-280).
Inhibitors of the Trk/neurotrophin pathway have been demonstrated to be effective in numerous pre-clinical animal models of pain. For example, antagonistic NGF and TrkA antibodies such as RN-624 have been shown to be efficacious in inflammatory and neuropathic pain animal models (Woolf, C. J. et al. (1994) Neuroscience 62, 327-331; Zahn, P. K. et al. (2004)J. Pain 5, 157-163; McMahon, S. B. et al., (1995) Nat. Med. 1, 774-780; Ma, Q. P. and Woolf, C. J. (1997) NeuroReport 8, 807-810; Shelton, D. L. et al. (2005) Pain 116, 8-16; Delafoy, L. et al. (2003) Pain 105, 489-497; Lamb, K. et al. (2003) Neurogastroenterol. Motil. 15, 355-361; Jaggar, S. I. et al. (1999) Br. J. Anaesth. 83, 442-448) and neuropathic pain animal models (Ramer, M. S. and Bisby, M. A. (1999) Eur. J. Neurosci. 11, 837-846; Ro, L. S. et al. (1999); Herzberg, U. et al., Pain 79, 265-274 (1997) Neuroreport 8, 1613-1618; Theodosiou, M. et al. (1999) Pain 81, 245-255; Li, L. et al. (2003) Mol. Cell. Neurosci. 23, 232-250; Gwak, Y. S. et al. (2003) Neurosci. Lett. 336, 117-120).
It has also been shown that NGF secreted by tumor cells and tumor invading macrophages directly stimulates TrkA located on peripheral pain fibers. Using various tumor models in both mice and rats, it was demonstrated that neutralizing NGF with a monoclonal antibody inhibits cancer related pain to a degree similar or superior to the highest tolerated dose of morphine. Because TrkA kinase may serve as a mediator of NGF driven biological responses, inhibitors of TrkA and/or other Trk kinases may provide an effective treatment for chronic pain states.
Recent literature has also shown that overexpression, activation, amplification and/or mutation of Trk kinases are associated with many cancers including neuroblastoma (Brodeur, G. M., Nat. Rev. Cancer 2003, 3, 203-216), ovarian (Davidson. B., et al., Clin. Cancer Res. 2003, 9, 2248-2259), colorectal cancer (Bardelli, A., Science 2003, 300, 949), melanoma (Truzzi, F., et al., Dermato-Endocrinology 2008, 3 (1), pp. 32-36), head and neck cancer (Yilmaz, T., et al., Cancer Biology and Therapy 2010, 10 (6), pp. 644-653), gastric carcinoma (Du, J. et al., World Journal of Gastroenterology 2003, 9 (7), pp. 1431-1434), lung carcinoma (Ricci A., et al., American Journal of Respiratory Cell and Molecular Biology 25 (4), pp. 439-446), breast cancer (Jin, W., et al., Carcinogenesis 2010, 31 (11), pp. 1939-1947), Glioblastoma (Wadhwa, S., et al., Journal of Biosciences 2003, 28 (2), pp. 181-188), medulloblastoma (Gruber-Olipitz, M., et al., Journal of Proteome Research 2008, 7 (5), pp. 1932-1944), secratory breast cancer (Euthus, D. M., et al., Cancer Cell 2002, 2 (5), pp. 347-348), salivary gland cancer (Li, Y.-G., et al., Chinese Journal of Cancer Prevention and Treatment 2009, 16 (6), pp. 428-430), papillary thyroid carcinoma (Greco, A., et al., Molecular and Cellular Endocrinology 2010, 321 (1), pp. 44-49) and adult myeloid leukemia (Eguchi, M., et al., Blood 1999, 93 (4), pp. 1355-1363). In preclinical models of cancer, non-selective small molecule inhibitors of Trk A, B and C were efficacious in both inhibiting tumor growth and stopping tumor metastasis (Nakagawara, A. (2001) Cancer Letters 169:107-114; Meyer, J. et al. (2007) Leukemia, 1-10; Pierottia, M. A. and Greco A., (2006) Cancer Letters 232:90-98; Eric Adriaenssens, E., et al. Cancer Res (2008) 68:(2) 346-351).
In addition, inhibition of the neurotrophin/Trk pathway has been shown to be effective in treatment of pre-clinical models of inflammatory diseases with NGF antibodies or non-selective small molecule inhibitors of Trk A. For example, inhibition of the neurotrophin/Trk pathway has been implicated in preclinical models of inflammatory lung diseases including asthma (Freund-Michel, V; Frossard, N., Pharmacology & Therapeutics (2008) 117(1), 52-76), interstitial cystitis (Hu Vivian Y; et. al. The Journal of Urology (2005), 173(3), 1016-21), inflammatory bowel diseases including ulcerative colitis and Crohn's disease (Di Mola, F. F, et. al., Gut (2000) 46(5), 670-678) and inflammatory skin diseases such as atopic dermatitis (Dou, Y.-C., et. al. Archives of Dermatological Research (2006) 298(1), 31-37), eczema and psoriasis (Raychaudhuri, S. P., et al., J. Investigative Dermatology (2004) 122(3), 812-819).
The TrkA receptor is also thought to be critical to the disease process in the infection of the parasitic infection of Trypanosoma cruzi (Chagas disease) in human hosts (de Melo-Jorge, M. et al., Cell Host & Microbe (2007) 1(4), 251-261).
Trk inhibitors may also find use in treating disease related to an imbalance of the regulation of bone remodeling, such as osteoporosis, rheumatoid arthritis, and bone metastases. Bone metastases are a frequent complication of cancer, occurring in up to 70 percent of patients with advanced breast or prostate cancer and in approximately 15 to 30 percent of patients with carcinoma of the lung, colon, stomach, bladder, uterus, rectum, thyroid, or kidney. Osteolytic metastases can cause severe pain, pathologic fractures, life-threatening hypercalcemia, spinal cord compression, and other nerve-compression syndromes. For these reasons, bone metastasis is a serious and costly complication of cancer. Therefore, agents that can induce apoptosis of proliferating osteoblasts would be highly advantageous. Expression of TrkA receptors has been observed in the bone forming area in mouse models of bone fracture (K. Asaumi, et al., Bone (2000) 26(6) 625-633). In addition, localization of NGF was observed in almost all bone forming cells (K. Asaumi, et al.). Recently, it was demonstrated that a Trk inhibitor inhibits the tyrosine signaling activated by neurotrophins binding to all three of the Trk receptors in human hFOB osteoblasts (J. Pinski, et al., (2002) 62, 986-989). These data support the rationale for the use of Trk inhibitors for the treatment of bone remodeling diseases, such as bone metastases in cancer patients.
Several classes of small molecule inhibitors of Trk kinases said to be useful for treating pain or cancer are known (Expert Opin. Ther. Patents (2009) 19(3), 305-319).

Pyrrolidinyl urea, pyrrolidinyl thiourea and pyrrolidinyl guanidine compounds as TrkA kinase inhibitors

Abstract: Compounds of Formula I:

Abstract: or stereoisomers, tautomers, or pharmaceutically acceptable salts, or solvates or prodrugs thereof, where R1, R2, Ra, Rb, Rc, Rd, X, Y, B, and Ring C are as defined herein, and wherein the Y—B moiety and the NH—C(═X)—NH moiety are in the trans configuration, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.