A child-resistant dispensing closure includes a base having a deck with a dispensing opening and a peripheral skirt. A lid is integrally molded with the base and coupled by a hinge to a periphery of the base so as to be pivotable between closed and open positions. One of the base and the lid has a latch arm resiliently extending from its periphery diametrically opposite the hinge. The latch arm has a pair of oppositely extending tabs adjacent to a free end of the arm. The other of the base and the lid has an axial passage for receiving the latch arm, and a pair of laterally spaced ledges in the passage for engagement by the tabs to lock the lid in the closed position. The latch arm is directly manually engageable by a user from a radial direction external to the closure to pivot the latch arm radially inwardly within the passage and release the tabs from the ledges so that the lid can be pivoted to the open position.

U.S. Pat. Nos. 4,638,916 and 5,489,035 disclose dispensing closures of one-piece integrally molded plastic construction. These closures include a base with a dispensing opening and an internally threaded skirt for securement to a container finish. A lid is integrally connected by a hinge to the periphery of the base. It is a general object of the present invention to provide a dispensing closure of this type having a feature that resists opening by a child.
A child-resistant dispensing closure in accordance with a first aspect of the present invention includes a base having a deck with a dispensing opening and a peripheral skirt. A lid is integrally molded with the base and coupled by a hinge to the base so as to be pivotable between closed and open positions. One of the base and the lid has a latch arm resiliently extending from its periphery diametrically opposite the hinge. The latch arm has a pair of oppositely extending tabs adjacent to a free end of the arm. The other of the base and the lid has an axial passage for receiving the latch arm, and a pair of laterally spaced ledges in the passage for engagement by the tabs to lock the lid in the closed position. The latch arm is directly manually engageable by a user from a radial direction external to the closure to pivot the latch arm radially inwardly within the passage and release the tabs from the ledges so that the lid can be pivoted to the open position.

Child-resistant flip-top dispensing closure and package


Method and apparatus for implementing communication between a software side and a hardware side of a test bench in a transaction-based acceleration verification system are described. In one example, transactors and communication channels are identified in a hierarchy of the test bench. Software side endpoints of the communication channels are automatically bound to hardware side endpoints of the communication channels during verification based on naming attributes of the transactors and communication channels with respect to the software side and the hardware side of the test bench.

1. Field of the Invention
Embodiments of the invention generally relate to simulation of logic designs and, more specifically, to a method and apparatus for implementing communication between a software side and a hardware side of a test bench in a transaction-based acceleration verification system.
2. Description of the Related Art
In electronic design automation (EDA), functional verification is the task of verifying that a logic design conforms to its specification. Logic simulation is the process of simulating a logic design before the logic design manufactured as integrated circuits (ICs). In software simulation, a description of the logic design is simulated on computers or workstations. Logic designs may be described using various languages, such as hardware description languages (HDLs) or other more abstract languages (e.g., synthesizable SystemC). In software simulation, engineers write a test-bench program to functionally verify the logic design by providing meaningful scenarios to check that, given certain input stimuli, the design performs to specification. A test-bench may be written using various languages, including lower-level languages, such as very high speed integrated circuit HDL (VHDL), Verilog, and the like, as well as more abstract languages, such as C/C++, SystemC, SystemVerilog, and the like. Higher-level languages, such as SystemC, enable engineers to write more abstract test-bench models for simulation, such as transaction-level models (TLMs), as opposed to lower-level register transfer level (RTL) models. Pure software simulation, however, decreases in performance as the logic design becomes larger and more complex.
Simulation acceleration addresses the performance shortcomings of pure software simulation. In simulation acceleration, the logic design is mapped into a hardware accelerator to provide a design under verification (DUV), which allows the design to run much faster than on a general-purpose computer or workstation. The test-bench continues to run using a software simulator on a computer or workstation. A communication channel connects the software simulator and the hardware accelerator to exchange data between the test-bench and design. In signal-based acceleration, actual signal data is exchanged between the test-bench and design. Signal-based acceleration is also referred to as lock-step acceleration, as the software simulator and the hardware accelerator are normally locked together cycle-by-cycle. In simulation acceleration, verification of the logic design can only run as fast as the slowest element in the chain, which is typically the software simulator. With a very efficient test-bench, such as a TLM-based test-bench, the communication channel between the software simulator and the hardware accelerator may become the bottleneck.
Transaction-based acceleration (TBA) is a methodology that overcomes some of the performance limitations of signal-based acceleration and, in some instances, can achieve performance close to in-circuit emulation. In the TBA methodology, a TLM-based test-bench runs on a software simulator at an un-timed level of abstraction and communicates with a DUV on a hardware accelerator through an abstraction bridge. By "un-timed" it is meant that the test-bench has no notion of a clock, but rather exchanges data with the DUV in the form of messages (transactions). The abstraction bridge provides an interface between the un-timed test-bench model and the RTL-based DUV in the hardware accelerator. The abstraction bridge facilitates the exchange of messages between the software model (test bench running on the simulator) and the hardware model (DUV running on the hardware accelerator) using transactors. A transactor may decompose an un-timed message from the software model to a series of cycle-accurate clocked events for the hardware model. Conversely, a transactor may compose a series of clocked events from the hardware model into a single message for the software model.
In particular, a transactor includes three partitions: a software side, a hardware side, and one or more communication channels. The software side is the un-accelerated partition that runs on the software simulator with the test-bench. The hardware side is the accelerated partition that runs on the hardware accelerator with the DUV. It is necessary that a transactor operate as one logical unit, which requires the software and hardware partitions to communicate with each other. This communication is performed using available communication channels.
In a test-bench environment, a logical transactor is represented as an instance of the software side partition and an instance of the hardware side partition. The required endpoints of the communication channel(s) are embedded into the physical partitions and are connected via a binding process. The location of each physical partition of a transactor is dependent upon the needs of the test-bench. Therefore, the actual location of the software side partition, within the test-bench hierarchy, differs from the location of the hardware side partition. To allow the two physical partitions to operate as a single logical unit, the software side partition must have knowledge of the location of the hardware side so that the endpoints of the communication channel(s) can be bound during verification. Once the endpoints are bound, the communication channel(s) are formed. The current approach to provide the software side partition with the location of the hardware side partition requires that the user manually provide the location of the hardware side partition. This computed location takes the form of a hierarchical path from a designated reference point. The hierarchical path is then annotated to the software side partition by the user.
There are several disadvantages to manually annotate the software side partition with the location of the hardware side partition. First, the hierarchical path can be derived or entered incorrectly by the user, resulting in errors during verification. Different tests that require changes to the test-bench architecture result in revised hierarchical paths, requiring the user to re-annotate the software side partition. In some cases, test-benches are not portable between simulation acceleration platforms due to differing reference points for the hierarchical path. Finally, the need to manually annotate the software side partition increases the workload of the user. Therefore, there exists a need in the art for automatic binding of transactor communication channel endpoints in transaction-based acceleration platforms for functional verification.


The addition of a chelating agent or a chelating agent and an antioxidant in combination to a rare-earth bonded magnet composition and a rare-earth bonded magnet comprising a rare-earth magnetic powder and a resin component can provide improved moldability and magnets having high performance and high corrosion resistance. Further, the regulation of property values of the magnet composition enables the occurrence of troubles to be avoided during molding, resulting in improved productivity. Furthermore, the use of at least two resins as a resin component in an extruding composition contributes to improvement in moldability and consequently increase in throughput. Furthermore, the use of extrusion, involving setting by cooling, and not compression molding in the production of magnets can provide high-density, high-performance magnets.

Rare-earth bonded magnets hitherto been produced by the following methods.
1. Compression molding
2. Injection molding
3. Extrusion molding
Compression molding is generally a method wherein a magnet composition comprising a magnetic powder and a thermosetting resin is filled into a mold in a press at room temperature, compressed the composition and heated to cure the resin, thereby molding a magnet. In the case of the compression molding method, since the resin content of the magnet composition is lower than that for the other molding methods, the freedom of shape in molding a magnet is smaller although the magnetic properties of the resultant magnet are superior.
Injection molding is a method wherein a magnet composition comprising a magnet power and a resin component is heat-melted to prepare a melt having sufficient fluidity which is then injected into a mold where the melt is molded into a desired shape. In the case of the injection molding, in order to impart sufficient fluidity to the magnet composition, the resin content of the magnet composition is higher than that for the compression molding, resulting in lowered magnetic properties. The freedom in molding, however, is higher than that for the compression molding.
Extrusion molding is a method wherein a magnet composition comprising a magnet powder and a resin component is heat-melted to prepare a melt having sufficient fluidity which is then formed into a shape in a die and set by cooling, thereby providing a product having a desired shape. In the extrusion, like the injection molding, the resin content needs to be high enough to impart the magnet composition to fluidity. This method has an advantage that a thin-walled and long magnet can be easily produced.
Among the above methods, injection molding and extrusion generally use a thermoplastic resin as the resin. These are disclosed in Japanese Patent Laid-Open Nos. 123702/1987, 152107/1987, 194503/1985 and 211908/1985.
However, the conventional rare-earth bonded magnet composition comprising a-rare-earth magnet powder and a thermoplastic resin, used in the prior art methods, particularly in injection molding and extrusion, has the following problems. Specifically, since the rare-earth magnet powder comprises a transition metal element, such as Fe or Co, when it is mixed and kneaded with a thermoplastic resin to prepare a composition which is then molded, the transition metal element catalytically acts on the resin component and causes an increase in molecular weight of the resin component, which results in a change in properties of the composition, such as an increase in melt viscosity. This suggests a lowering in heat stability of the rare-earth bonded magnet composition. The above phenomenon is partly described in "Journal of The Magnetics Society of Japan, vol. 16, No. 2, 135-138 (1992)," indicating that a composition comprising an Nd-Fe-B-based magnet powder and a polyamide resin, due to the influence of temperature and shearstress, undergoes changes in properties, particularly viscosity. The higher the content of the rare-earth magnet powder in the composition and the larger the specific surface area of the rare-earth magnetic powder, the higher the above tendency. The above phenomenon raises problems including that the phenomenon makes it impossible to produce a rare-earth bonded magnet composition; even though a rare-earth bonded magnet composition could be successfully produced, it cannot be stably molded due to the deterioration during molding; and it is difficult to improve the magnetic properties of the molded magnet.
For the rare-earth bonded magnet composition, the relationship between the properties of the composition and the moldability has not been fully-clarified particularly in the case of extrusion. Japanese Patent Laid-Open No. 162301/1989 discloses a method wherein the viscosity of a molding composition is specified. In this method, however, the viscosity is specified in relation to the magnetic field for alignment. Further, the resin used is a thermosetting resin, and there is no clear description on the properties, involved in the moldability, of a magnet composition using a thermoplastic resin. Furthermore, no particular attention is paid to a change in properties of the composition during moldings In actual molding, a change in properties derived from the phenomenon, as described above, occurs in the course of feed of the composition into a mold of the molding machine, which makes it impossible to conduct molding. In the case of injection molding, a sprue and a runner are generated due to the nature of the molding method and should be recycled. The change in properties of the composition renders the recycling difficult, unfavorably increasing the loss of material. This incurs an increase in cost of the rare-earth bonded magnet. In the case of the extrusion, unlike the injection molding, there is little or no need of recycling. Since, however, the operation is carried out in a continuous manner, staying of the composition in an extruder or a die often renders the molding impossible. Further, the deterioration of the composition causes a load to be applied to the machine, which often results in failure of the machine and damage to a screw and a die and a nozzle and the like of the injection molding machine.
For the magnet composition used in the extrusion, Japanese Patent Laid-Open No. 264601/1987 discloses the addition of a lubricant, Japanese Patent Laid-Open Nos. 289807/1988 and 162301/1989 disclose a magnet composition using a thermoplastic resin, and Japanese Patent Application No. 270884/1991 discloses a magnet composition having a specified viscosity. As described above, in the case of the conventional magnet composition for extrusion, the properties in a molten state and additives, such as a lubricant, are taken into consideration. However, no satisfactory consideration is given to a resin component particularly when a thermoplastic resin is used as the resin component. In the production of a rare-earth-resin bonded magnet by extrusion, in order to enhance the magnetic properties of the molded magnet, a very large amount of a magnetic powder is incorporated into the magnet composition, resulting in lowered strength, i.e., melt strength, of the magnet composition in a molten state. Therefore, in the case of the extrusion of the above composition, unlike the extrusion of a general resin, it is impossible to adopt a method wherein a resin is formed into a shape in a die which is then taken off to the outside of the die by means of a take-off device, cooled and sized outside the die to provide a final shape. For this reason, in the extrusion of a magnet composition, it is necessary to adopt a method wherein the composition is formed into a final shape in a die which, as such, is set by cooling at the forward end of the die and extruded to the outside of the die. In this method, the magnet composition, which has been set by cooling at the forward end of the die (hereinafter referred to as "cooling section"), should be extruded. This raises a problem that, when only one resin, particularly a crystalline resin, is used in the magnetic composition, the change from a molten state to a solid state is so rapid that the extrusion cannot be carried out, or the extrusion rate (molding rate) is limited by properties of the resin at a temperature around the melting point thereof.
Further, as described above, the rare-earth magnetic powder is highly active enough to deteriorate the resin component during molding, causing the resultant magnet molding to rust by oxidation when it is allowed to stand.
Among the above three methods for producing a rare-earth bonded magnet, the compression molding can produce magnets having the highest performance. Since, however, a thermosetting resin is employed as the resin, the step of heat-curing the resin must be additionally provided in the molding, so that the properties of the resin at the time of heat setting should be taken into consideration. For this reason, the resin cannot be selected based on the moldability alone, and consequently the kind and amount of the resin and the molding conditions cannot be determined from the viewpoint of the moldability alone. Furthermore, since the resin used is a thermosetting resin, defective molded body cannot be recycled.
Accordingly, the present invention provides a solution to the above problems, and an object of the present invention is to provide a high-performance rare-earth bonded magnet with high productivity. Another object of the present invention is to provide rare-earth bonded magnets having various shapes according to the applications thereof.

Rare-earth bonded magnet composition, rare-earth bonded magnet and process for producing said rare-earth bonded magnet


This invention relates a cellulose solution comprising cellulose and at least one tetraalkylammonium alkylphosphate and processes to produce the cellulose solution. Another aspect of this invention relates to shaped articles prepared from a cellulose solution comprising cellulose and at least one tetraalkylammonium alkylphosphate. Another embodiment of this invention relates to compositions comprising derivatives of cellulose prepared from a cellulose solution comprising at least one tetraalkylammonium alkylphosphate. Another embodiment of this invention relates to compositions comprising regioselectively substituted cellulose esters prepared from a cellulose solution comprising cellulose and at least one tetraalkylammonium alkylphosphate. In another embodiment of the invention, the cellulose esters of the present invention are used as protective and compensation films for liquid crystalline displays.

Cellulose is a β-1,4-linked polymer of anhydroglucose. Cellulose is typically a high molecular weight, polydisperse polymer that is insoluble in water and virtually all common organic solvents. The use of unmodified cellulose in wood or cotton products such as housing or fabric is well known. Unmodified cellulose is also utilized in a variety of other applications usually as a film, such as cellophane, as a fiber, such as viscose rayon, or as a powder, such as microcrystalline cellulose used in pharmaceutical applications. Modified cellulose such as cellulose esters are also widely utilized in a wide variety of commercial applications [Prog. Polym. Sci. 2001, 26, 1605-1688]. Cellulose esters are generally prepared by first converting cellulose to a cellulose triester before hydrolyzing the cellulose triester in an acidic aqueous media to the desired degree of substitution (DS, the number of substituents per anhydroglucose monomer). Hydrolysis of cellulose triacetate under these conditions yields a random copolymer that can consist of 8 different monomers depending upon the final DS [Macromolecules 1991, 24, 3050].
The dissolution of cellulose in ionic liquids is known. Those skilled in the art will recognize that the maximum amount of cellulose dissolved at any given temperature in a particular ionic liquid will depend upon the degree of polymerization (DP) of the initial cellulose and the extent of degradation of the cellulose during the dissolution process.
In the broadest sense, an ionic liquid (IL) is simply any liquid containing only ions. Hence, molten salts such as NaCl which melts at temperatures greater than 800° C. could be classified as ionic liquids. From a practical point of view, the term ionic liquid is now used for organic salts that melt below approximately 100° C.
Although the cations of ionic liquids are structurally diverse, they generally contain nitrogen or phosphorus that can be converted to a quaternary ammonium or phosphonium. In general, the most useful ionic liquids contain nitrogen that is part of a ring structure. Examples of these cations include pyridinum, pyridazinium, pyrimidinium, pyrazinium, imidazolium, pyrazolium, oxazolium, triazolium, thiazolium, piperidinium, pyrrolidinium, quinolinium, and isoquinolinium.

The anions of ionic liquids can also be structurally diverse. The anion can be either inorganic or organic and they can have a significant impact on the solubility of the ionic liquids in different media. For example, ionic liquids containing hydrophobic anions such as hexafluorophosphates or triflimides have very low solubilities in water while ionic liquids containing hydrophilic anions such chloride or acetate are completely miscible in water.
The names of ionic liquids are generally abbreviated. Alkyl cations are often named by the letters of the alkyl substituents and the cation which are given within a set of brackets followed by the abbreviation for the anion. Although not expressively written, it is understood that the cation has a positive charge and the anion has a negative charge. For example, [BMIm]OAc means 1-butyl-3-methylimidazolium acetate and [AMIm]Cl means 1-allyl-3-methylimidazolium chloride.
In the case in which nitrogen is part of a cyclic cation (e.g. imidazolium), these ionic liquids typically have lower melting points, are less hydroscopic, and are more stable that the corresponding ammonium or phosphonium containing ionic liquids. In terms of cellulose dissolution and esterification, ionic liquids containing imidazolium as the cation are generally preferred. With these ionic liquids, it is possible to achieve concentrated cellulose solutions (ca. 20 wt % in [EMIm]OAc) from which a variety of cellulose esters can be prepared (U.S. Pat. No. 6,824,599, US application 20080194807, US application 20080194808, and US application 20080194834).
The most commonly utilized non-cyclic ammonium based ionic liquids are tetraalkylammonium halides. This class of ionic liquids has limited utility in cellulose dissolution and esterification. Only two tetraalkylammonium halides, tetraethylammonium chloride (U.S. Pat. No. 4,597,798) and tetrabutylammonium fluoride hydrate (Macromol. Biosci. 2007, 7, 307-314), have been shown to solubilize cellulose at a significant level (ca. 6 wt % cellulose). In both cases, significant concentrations of cosolvents (30-90 wt %) such as DMSO or DMF were required for cellulose solubilization. Due to low concentrations of cellulose in the ionic liquids, the difficulty of removing water from theses ionic liquids, the instability of these ionic liquids, as well as the corrosive and toxic nature of these ionic liquids, these tetraalkylammonium halides are not practical media for making cellulose derivatives.

Cellulose solutions comprising tetraalkylammonium alkylphosphate and products produced therefrom


A setting device used in an illumination control system to realize a separate control, a group control, and a pattern control is disclosed. The object of the present invention is to enable a setting operation to be performed easily, and to prevent missing. In connection with the switch arranged on a wall side, the setting device sets a separate address of the separate control, a group number of the group control, and a pattern number of the pattern control by using an infrared ray communication. On the other hand, the corresponding relationships between each switch and the relay controlling the load actually is established by mounting the setting device on the operation terminal, and connecting it to the transmission unit via the communication line. Accordingly, it is possible to perform a setting operation easily by performing two kinds of setting as one pair. Further, missing can be prevented by mounting the movable setting device on the operation terminal arranged on the wall side.

1. Field of the Invention
The present invention relates to a setting device which is suitably used in a system for controlling many load devices, for example, in an illumination control system.
2. Description of the Related Art
As a system for controlling many load devices such as the illumination control system, a control system is commercially used wherein a load control terminal including a relay for actually controlling a load device, and a plurality of the operation terminals such as a wall side switch are connected to a control unit via a communication line, and said control unit drives the load device through a corresponding load control terminal, or the plurality of load control terminals in response to the operations of each of the operation terminals, thereby various controls of the load device may be performed. For example, in the illumination control system, a separate control which enables each wall side switch to control turning on and off of one corresponding illumination device or a plurality of illumination devices, a group control which controls turning on and off of one corresponding illumination device or a plurality of illumination devices that are divided into a group per a group, and a pattern control which changes the lighting pattern according to the outside brightness can be performed by setting arbitrarily the corresponding relationships between each of the operation terminals and the load control terminals.
But, it is necessary to set a load device for a target of control such as a separate address of the separate control, a group number of the group control, and a pattern number of the pattern control into each of the operation terminals in order to realize various controls. On the other hand, it is necessary to set the corresponding relationships between each of the operation terminals and the load control terminals such as the load device corresponding to a group 1, and the load device corresponding to a pattern 1 into the control unit.
Therefore, conventionally, the setting device which is required for the setting operation is disclosed, In the Patent Reference 1, an integral setting device of a load control data which allows a load address setting, and a pattern/group setting to be performed easily and simultaneously is disclosed. Further, In the Patent Reference 2, a wireless switch is disclosed in which an addressable remote controller is formed as a shape which is same to the standardized plated so that it may be used as a general wall side switch.
(Patent Reference 1) Japanese Patent Laid-Open NO. 2000-115865
(Patent Reference 2) Japanese Patent Laid-Open NO. H04-233895
In all the previous technology, an infrared ray remote controller is used for setting the load devices into each of the operation terminals which are arranged on an arbitrary wall side. The Patent Reference 1 includes a function to set a pattern/a group as well as a function of an infrared ray remote controller by connecting to a control unit. But, the wire connection to the control unit is not described in detail, but it is judged that a terminal connection to a communication line drawn from the neighborhood of the operation terminal is established. Therefore, in the pattern/the group setting, there is a troublesome problem that a plate of the wall side must be removed and a communication line has to be drawn out. Further, if the setting is performed, there is a shortcoming that it is not possible to manage a remote controller which is not used in the outside places because of the change of the room or the change of the seasons, and thereby it is vulnerable to the missing.
In the Patent Reference 2, a remote controller is accommodated into a wall side, and is used as a wall side switch by mounting it on the wall side. But, in the Patent Reference 2, only the fact that a remote controller is accommodated into the wall side is described. On the other hand, in case of this setting device, in connection with the operation terminal which is arranged on an arbitrary wall side of the indoor room, since the control unit is arranged at a remote place such as a management room or an electricity-division room, there was a troublesome problem that the person had to go to the place in order to set the parameters with a remote controller.


The disclosure relates to methods and apparatus for determining the velocity of an ultrasound pulse in drilling fluids in downhole environments. A method for determining a velocity of ultrasound propagation in a drilling fluid in a downhole environment includes emitting an ultrasound pulse into the drilling fluid in a borehole using a first ultrasound transducer (37); detecting the ultrasound pulse after the ultrasound pulse has traveled a distance (d); determining a travel time (t) required for the ultrasound pulse to travel the distance (d); and determining the velocity of ultrasound propagation from the known distance (d) and the travel time (t). An apparatus for determining a velocity of ultrasound propagation in a drilling fluid in a downhole environment includes a first ultrasound transducer (37) disposed on a tool; and a circuitry (82) for controlling a timing of an ultrasound pulse transmitted by the first ultrasound transducer (37) and for measuring a time lapse between ultrasound transmission and detection after the ultrasound pulse has traveled a distance (d).

Accurate borehole dimension data are important for well logging and well completion. Measurements performed by many logging tools, whether wireline, logging-while-drilling (LWD), or measurement-while-drilling (MWD) tools, are sensitive to borehole sizes or tool standoffs. Therefore, accurate borehole dimension information may be required to correct measurements obtained with these tools. Furthermore, information regarding a borehole dimension is used to determine well completion requirements, such as the amount of cement required to fill the annulus of the well. In addition, borehole dimension data may be used to monitor possible borehole washout or impending borehole instability such that a driller may take remedial actions to prevent damage or loss of the borehole or drilling equipment.
Borehole dimensions, such as diameter, may be determined with various methods known in the art, including ultrasound pulse echo techniques disclosed by U.S. Pat. Nos. 4,661,933 and 4,665,511. Such ultrasound measurements rely on knowledge of the velocity of the ultrasound pulse in the particular medium, e.g., drilling fluids.
However, the velocity of an ultrasound pulse, typically, is not easily measured in a wellbore. Instead, the velocity of an ultrasound pulse in the well is typically extrapolated from an ultrasound velocity measurement made at the surface based on certain assumptions concerning the mud properties under downhole conditions. Such assumptions may not be accurate. Furthermore, mud properties in a drilling operation may change due to changes in the mud weight used by the driller, pump pressure, and mud flow rate. In addition, the drilling mud may become contaminated with formation fluids and/or earth cuttings. All these factors may render inaccurate the velocity of an ultrasound pulse estimated from a surface determination.
Therefore, there is a need for improved methods and apparatus for the measurement of ultrasound velocity in downhole environments.

Method and apparatus for ultrasound velocity measurements in drilling fluids


This invention relates to a novel polypeptide involving in the modulation of central nervous system function, circulatory function, immune function, gastrointestinal function, metabolic function, reproductive function, etc., it can be used as a drug for treating or preventing a variety of diseases, e.g. HIV infection or AIDS (acquired immune deficiency syndrome) or the like.

The present invention relates to a novel ligand polypeptide for the G protein-coupled receptor protein, APJ and a DNA comprising a DNA encoding the ligand polypeptide.
Many hormones and neurotransmitters mediate biological functions through specific receptors present on the cell membrane. Many of these receptors engage themselves in the intracellular transduction of signals through activation of the coupled guanine nucleotide-binding protein (hereinafter sometimes referred to briefly as G protein) and have the common structure comprising 7 transmembrane domains. Therefore, these receptors are collectively referred to as G protein-coupled receptor or 7-transmembrane receptor.
Through the interaction of such hormones or neurotransmitters with G protein-coupled receptors, a variety of regulatory functions of vital importance, for example maintenance of homeostasis, reproduction, development, metabolism and growth, and regulation of the nervous system, circulatory system, immune system, gastrointestinal system and metabolic system are all discharged. While it is known, as mentioned above, that receptor proteins exist for various hormones or neurotransmitters and are playing important roles in the control of vital functions, it is still unknown in many respects whether unknown active substances (hormones or neurotransmitters) and their receptors ever exist or not.
In recent years, by taking advantage of the similarity of such G protein-coupled receptor proteins in partial amino acid sequence, searches for DNAs coding for novel receptor proteins have been undertaken by the polymerase chain reaction technique (abbreviated as PCR) and actually a large number of orphan G protein-coupled receptors, so called because their ligands are unknown, have been cloned to this day (Libert, F., et al., Science, 244, 569-572, 1989; Welch, S. K., et al., Biochem. Biophys. Res. Commun., 209, 606-613, 1995; Marchese, A., et al., Genomics, 23, 609-618, 1994; Marchese, A., Genomics, 29, 335-344, 1995). Furthermore, as the result of random sequencing of genomic DNAs and cDNAs, novel G protein-coupled receptor proteins have been discovered one after another (Nomura, N., et al., DNA Research, vol. 1, 27-35, 1994). The only general means so far available for determining the ligands to such orphan G protein-coupled receptor proteins is a mere estimation based on the similarity in primary structure among G protein-coupled receptor proteins. However, many orphan G protein-coupled receptor proteins have low homology with known receptors and it is, therefore, difficult to estimate their ligands based on the similarity in primary structure alone except in those cases where they are actually subtypes of receptors for known ligands. On the other hand, since many orphan G protein-coupled receptors have been discovered as the result of gene analysis, it is supposed that there still exist many unknown corresponding ligands. However, only in a few cases, ligands have actually been identified for such orphan G protein-coupled receptors.
Recently, investigation for novel opioid peptides by introducing a cDNA coding for a receptor protein which a ligand is unknown, i.e. an orphan G protein-coupled receptor protein, into animal cells have been reported (Reinsheid, R. K. et al., Science, 270, 792-794, 1995, Menular, J. -C., et al., Nature 377, 532-535, 1995). However, in view of similarities to known G protein-coupled receptor proteins and tissue distributions, it could be easily anticipated in these cases that the ligand would be belonging to the family of opioid peptides. The history of research and development in the realm of substances acting on the living body through the opioid receptor dates back to many years ago and various antagonists and agonists have been developed. Therefore, among the compounds artificially synthesized, an agonist of the receptor was picked out and, using it as a probe, expression of the receptor in the receptor cDNA-transfected cells was verified. Then, a search was made for an activator of the intracellular signal transduction which was similar to the agonist, the activator so found was purified, and the structure of the ligand was determined. However, when the homology of an orphan receptor to known G protein-coupled receptor proteins is low, it was very difficult to predict its ligand.
APJ is one of the orphan G protein-coupled receptors so far reported (O""Dowd, B. F., et al., Gene, 436, 355-359, 1993). APJ has low homology with an angiotensin receptor (AT1) but its ligand has remained unknown since no reaction was detected at all with angiotensin II despite the expression of APJ in CHO cells.
Ligands for APJ, which is an orphan G protein-coupled receptor expressed in the central nervous system, circulatory system, reproductive system, immune system, digestive organs and so forth, are expected to be useful as drugs but their structure and functions have not been elucidated as yet.
Employing a cell in which a cDNA coding for orphan G protein-coupled receptor protein (APJ) has been expressed by a suitable means and using measurement of a specific cell stimulation activity exemplified by a signal transduction activity as an indicator, the inventors of the present invention succeeded in screening for a polypeptide which said receptor protein recognizes as a ligand.
Furthermore, the inventors found that a compound can be screened which is capable of changing the binding activity of this ligand which is an activating factor to said receptor protein.
The present invention, therefore, relates to
(1) a polypeptide capable of binding to a receptor protein which comprises an amino acid sequence represented by SEQ ID NO:3 or a substantial equivalent thereto, a precursor polypeptide thereof, its amide or ester, or a salt thereof,
(2) a polypeptide as mentioned in the above (1), which comprises an amino acid sequence represented by SEQ ID NO:1 or a substantial equivalent thereto,
(3) a polypeptide as mentioned in the above (1), which comprises a partial sequence of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42,
(4) a polypeptide as mentioned in the above item (1), which comprises
(a) a peptide comprising the 6th to 77th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42,
(b) a peptide comprising the 40th to 77th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42,
(c) a peptide comprising the 42nd to 77th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42,
(d) a peptide comprising the 47th to 77th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42,
(e) a peptide comprising the 61st to 77th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42,
(f) a peptide comprising the 65th to 77th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42, or a derivative thereof resulting from conversion of the N-terminal amino acid (Gln) to a pyroglutamic acid residue,
(g) a peptide comprising the 1st to 25th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42,
(h) a peptide comprising the 6th to 25th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42,
(i) a peptide comprising the 42nd to 64th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42,
(j) a peptide comprising the 61st to 64th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42,
(k) a peptide comprising the 43rd to 77th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42,
(l) a peptide comprising the 41st to 77th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42,
(m) a peptide comprising the 66th to 77th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42,
(n) a peptide comprising the 67th to 77th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42,
(o) a peptide comprising the 64th to 77th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42,
(p) a peptide comprising the 63rd to 77th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42,
(q) a peptide comprising the 65th to 76th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42,
(r) a peptide comprising the 65th to 75th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42, or
(s) a peptide comprising the 65th to 75th amino acid residues of the amino acid sequence represented by SEQ ID NO:15, 38, 40 or 42,
(5) a polypeptide as mentioned in the above (1) which comprises an amino acid sequence of from the 65th amino acid residue to the 77th amino acid residue of the amino acid sequence represented by SEQ ID NO:15, SEQ ID NO:38, SEQ ID NO:40 or SEQ ID NO:42,
(6) a polypeptide as mentioned in the above (1) which has the amino acid sequence: pGlu Arg Pro Arg Leu Ser His Lys Gly Pro Met Pro Phe,
(7) a polypeptide as mentioned in the above (1) which comprises an amino acid sequence of from the 42nd amino acid residue to the 77th amino acid residue of the amino acid sequence represented by SEQ ID NO:15, SEQ ID NO:38, SEQ ID NO:40 or SEQ ID NO:42,
(8) a polypeptide as mentioned in the above (1) which is a precursor polypeptide having an amino acid sequence represented by SEQ ID NO:15 or a substantial equivalent thereto,
(9) a polypeptide as mentioned in the above (1) which is a precursor polypeptide having an amino acid sequence represented by SEQ ID NO:38 or a substantial equivalent thereto,
(10) a polypeptide as mentioned in the above (1) which is a precursor polypeptide having an amino acid sequence represented by SEQ ID NO:40 or a substantial equivalent thereto,
(11) a polypeptide as mentioned in the above (1) which is a precursor polypeptide having an amino acid sequence represented by SEQ ID NO:42 or a substantial equivalent thereto,
(12) a DNA which comprises a DNA having a nucleotide sequence coding for a polypeptide capable of binding to a receptor protein which comprises an amino acid sequence represented by SEQ ID NO:3 or a substantial equivalent thereto, or a precursor polypeptide thereof,
(13) a DNA as mentioned in the above (12) wherein the polypeptide encoded thereby comprises an amino acid sequence represented by SEQ ID NO:1 or a substantial equivalent thereto,
(14) a DNA as mentioned in the above (12) wherein the polypeptide encoded thereby comprises an amino acid sequence of from the 65th amino acid residue to the 77th amino acid residue of the amino acid sequence represented by SEQ ID NO:15, SEQ ID NO:38, SEQ ID NO:40 or SEQ ID NO:42,
(15) a DNA as mentioned in the above (12) wherein the polypeptide encoded thereby comprises an amino acid sequence of from the 42nd amino acid residue to the 77th amino acid residue of the amino acid sequence represented by SEQ ID NO:l5, SEQ ID NO:38, SEQ ID NO:40 or SEQ ID NO:42,
(16) a DNA as mentioned in the above (12) wherein the precursor polypeptide encoded thereby comprises an amino acid sequence represented by SEQ ID NO:15 or a substantial equivalent thereto,
(17) a DNA as mentioned in the above (12) wherein the precursor polypeptide encoded thereby comprises an amino acid sequence represented by SEQ ID NO:38 or a substantial equivalent thereto,
(18) a DNA as mentioned in the above (12) wherein the precursor polypeptide encoded thereby comprises an amino acid sequence represented by SEQ ID NO:40 or a substantial equivalent thereto,
(19) a DNA as mentioned in the above (12) wherein the precursor polypeptide encoded thereby comprises an amino acid sequence represented by SEQ ID NO:42 or a substantial equivalent thereto,
(20) a recombinant vector which comprises the DNA as mentioned in the above (12),
(21) a transformant carrying the DNA as mentioned in the above (12) or the recombinant vector as mentioned in the above (20),
(22) a method for producing a polypeptide, a precursor polypeptide thereof or a salt thereof which comprises cultivating the transformant as mentioned in the above (21),
(23) a pharmaceutical composition which comprises the polypeptide, the precursor polypeptide thereof, its amide or ester, or a salt thereof as mentioned in the above (1),
(24) a pharmaceutical composition which comprises the DNA as mentioned in the above (12),
(25) a pharmaceutical composition as mentioned in the above (23) or (24) which is a central nervous system function modulator, a circulatory function modulator, an immune function modulator, a gastrointestinal function modulator, a metabolic function modulator or a reproductive function modulator,
(26) an antibody against the polypeptide or the precursor polypeptide thereof as mentioned in the above (1),
(27) a diagonostic composition which comprises the antibody as mentioned in the above (26), and
(28) a method for screening for a compound changing binding activity of the polypeptide as mentioned in the above (1) to a receptor protein which comprises an amino acid sequence represented by SEQ ID NO:3, which comprises using the polypeptide as mentioned in the above (1) and said receptor protein,
The present invention further provides:
(29) a polypeptide as mentioned in the above (1) which is of mammalian origin, and
(30) a pharmaceutical composition as mentioned in the above (23) or (24) which is an agent for the treatment and/or prevention of dementia, depression, hyperactive child syndrome (microencephalopathy), disturbance of consciousness, anxiety disorder, schizophrenia, phobia, growth hormone secretory disorder, hyperphagia, polyphagia, hypercholesterolemia, hyperglyceridemia, hyperlipemia, hyperprolactinemia, diabetes mellitus, cancer, pancreatitis, diseases of kidney, Turner""s syndrome, neurosis, rheumatoid arthritis, spinal injury, transient brain ischemia, amyotrophic lateral sclerosis, acute myocardial infarction, spinocerebellar degeneration, bone fracture, wounds, atopic dermatitis, osteoporosis, asthma, epilepsy, sterility, arteriosclerosis, pulmonary emphysema, pulmonary edema, galactorrhea, AIDS, or the like.
In the practice of the present invention, the G protein-coupled receptor protein for the ligand polypeptide is specifically:
(31) a G protein-coupled receptor protein characterized by containing an amino acid sequence represented by SEQ ID NO:3, or a substantial equivalent thereto, or a salt thereof, or
(32) a G protein-coupled receptor protein as mentioned in the above (31) which comprises an amino acid sequence derived from the amino acid sequence represented by SEQ ID NO:3 by deletion of 1 to 30, preferably 1 to 10 amino acid residues therefrom, by addition (or insertion) of 1 to 30, preferably 1 to 10 amino acid residues thereto (or thereinto), or by substitution of 1 to 30, preferably 1 to 10 amino acid residues with a different amino acid residue or residues, or a salt thereof, for instance.
In the present specification, the term xe2x80x9csubstantial equivalent(s)xe2x80x9d means that the activity of the protein, e.g., nature of the binding activity of the ligand and the receptor and physical characteristics are substantially the same. Substitutions, deletions or insertions of amino acids often do not produce radical changes in the physical and chemical characteristics of a polypeptide, in which case polypeptides containing the substitution, deletion, or insertion would be considered to be substantially equivalent to polypeptides lacking the substitution, deletion, or insertion. Substantially equivalent substitutes for an amino acid within the sequence may be selected from other members of the class to which the amino acid belongs. The non-polar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan and methionine. The polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine, and glutamine. The positively charged (basic) amino acids include arginine, lysine and histidine. The negatively charged (acidic) amino acids include aspartic acid and glutamic acid.


A layered architecture for communication of reporting system reports to users connecting via a web server. Users communicate via HTTP with web servers without download of plugins or executable files to the user system. The web servers are clustered to balance requests and transmit the requests. The web servers pass report requests via XML to the business intelligence servers to perform the work with the databases. The business intelligence servers convert reports into XML and provide the XML-based version to the web server. The web server then transmits an HTML or DHTML report back to the client over the web.

Decision support systems (DSS) have been developed to efficiently retrieve selected information from data warehouses, thereby providing business intelligence information to the organization. One type of decision support system is known as an on-line analytical processing system ("OLAP"). In general, OLAP systems analyze the data from a number of different perspectives and support complex analyses against large input data sets.
In conventional web-based OLAP access systems, the exchange of business intelligence information between World Wide Web client computer systems and business intelligence server computer systems requires substantial processing capabilities and resources on the individual client computer systems. Often, the interface between the client and the server systems require the client systems to download, install and run a plurality of web browser plugin utilities in order to view or effectively interact with the exchanged information. By requiring the client-side systems to perform a substantial portion of the information processing, server-side applications were able to effectively manipulate the large quantities of data typically in business intelligence or OLAP environments. However, the ever changing landscape of browser and plugin software (e.g., java) makes it difficult for client-side systems to remain current with every element of technology necessary to interact with the server-side applications providing the business intelligent information. Further, for individuals who routinely use more than one client-side machine to access information, ensuring that each machine includes all required elements is difficult and sometimes impossible
Accordingly, existing business intelligence systems fail to provide a method and system for exchanging business intelligence information over a computer network wherein client-side processing and software requirements are reduced to a level compatible with virtually all client-side systems.

Method and system for providing business intelligence web content with reduced client-side processing


A technique includes receiving, by a user device, a plurality of semi-persistent scheduling (SPS) configurations, each SPS configuration including an SPS identifier and an interval for each of the plurality of SPS configurations; receiving, by the user device, an SPS activation corresponding to each of the plurality of SPS configurations, each SPS activation indicating a set of resources and a modulation and coding scheme (MCS) to be used for transmission of data for the corresponding SPS configuration; determining, by the user device, that a collision will occur for the plurality of SPS configurations during a transmission time interval (TTI); selecting a MCS corresponding to one of the plurality of SPS configurations that have been determined to collide during the TTI; and transmitting, by the user device during the TTI, data using the selected MCS via an aggregated set of SPS resources that includes at least a portion of each of the sets of resources for the plurality of SPS configurations that have been determined to collide during the TTI.

A communication system may be a facility that enables communication between two or more nodes or devices, such as fixed or mobile communication devices. Signals can be carried on wired or wireless carriers.
An example of a cellular communication system is an architecture that is being standardized by the 3rd Generation Partnership Project (3GPP). A recent development in this field is often referred to as the Long Term Evolution (LTE) of the Universal Mobile Telecommunications System (UMTS) radio-access technology. E-UTRA (evolved UMTS Terrestrial Radio Access) is the air interface of 3GPP's Long Term Evolution (LTE) upgrade path for mobile networks. In LTE, base stations or access points (APs), which are referred to as enhanced Node AP (eNBs), provide wireless access within a coverage area or cell. In LTE, mobile devices, or mobile stations are referred to as user equipments (UE). LTE has included a number of improvements or developments.
5G New Radio (NR) development is part of a continued mobile broadband evolution process to meet the requirements of 5G, similar to earlier evolution of 3G & 4G wireless networks. A goal of 5G is to provide significant improvement in wireless performance, which may include new levels of data rate, latency, reliability, and security. 5G NR may also scale to efficiently connect the massive Internet of Things (IoT), and may offer new types of mission-critical services.
Some types of applications, such as voice (e.g., voice over LTE), may use periodic resources to transmit data (e.g., the application may transmit data via uplink resources every so often, such as every 20 ms or other period. For example, for such applications that may need regularly scheduled resources, rather than requiring a user device/UE to request uplink resources for each transmission/instance, the eNB/BS may use semi-persistent scheduling (SPS) to allocate resources at a specific interval, e.g., to allocate uplink resources every 20 ms (every 20 TTIs), as an example. In this manner, a eNB/BS may use semi-persistent scheduling to schedule resources to a user device/UE at a particular interval or period, while decreasing signaling overhead.

Techniques for handling semi-persistent scheduling collisions for wireless networks


A method of combination therapy for prevention and/or treatment of c-Met- and/or EGFR-induced diseases including co-administering a pharmaceutically effective amount of an EGFR antagonist and a pharmaceutically effective amount of an anti-c-Met antibody to a subject in need thereof is provided.

1. Field
Provided is a method of combination therapy for prevention and/or treatment of c-Met- and/or EGFR-induced diseases including co-administering a pharmaceutically effective amount of an EGFR antagonist and a pharmaceutically effective amount of an anti-c-Met antibody to a patient in need thereof.
2. Description of the Related Art
c-Met, a typical receptor tyrosine kinase (RTK) present at the surface of cells, binds to its ligand, hepatocyte growth factor (HGF) to promote intracellular signal transduction, thereby not only promoting the growth of cells but also being over-expressed in cancer cells so that it is widely implicated in cancer incidence, cancer metastasis, cancer cell migration, cancer cell penetration, angiogenesis, etc.
In general, common cancer therapies include surgery, chemotherapy, radiotherapy, or a combination thereof. These therapies have significant limits. For example, surgery may not completely remove newly-generated tissues, and may not be used for treatment of several disseminated neoplastic conditions such as acute lymphoblastic leukemia. Radiotherapy may be effective only when neoplastic tissues exhibit higher sensitivity to radiation than normal tissues, and may cause serious side effects.
Although various anticancer drugs may be used in chemotherapy, almost all anticancer drugs are toxic and frequently cause dangerous side effects. In addition, many tumor cells exhibit resistance to various anticancer drugs used in chemotherapy, which becomes a serious obstacle in anticancer therapy.
To counteract the side effects and decrease resistance, studies relating to combined use of two or more anticancer drugs are being actively progressed. Since a combination therapy may achieve synergistic effects of two or more anticancer drugs, combination therapies are becoming a main trend in recent anticancer therapies.
Accordingly, there is a demand for development of a combination therapy for achieving increased synergistic effects and decreased resistance.

Method of combination therapy using an EGFR antagonist and anti-c-Met antibody


A phased array coil for a Magnetic Resonance Imaging (MRI) system is provided that includes a first coil and a second coil adjacent the first coil. The first and second coils are configured in a shifted arrangement from a center of examination of the MRI system.

This invention relates generally to medical imaging systems, and more particularly, to a phased array coil for a Magnetic Resonance Imaging (MRI) system.
MRI or Nuclear Magnetic Resonance (NMR) imaging generally provides for the spatial discrimination of resonant interactions between Radio Frequency (RF) waves and nuclei in a magnetic field. NMR signals are typically detected using a receive RF coil, which is placed in the vicinity of a volume excited by the magnet system of the MRI or NMR scanner.
It is known to use a phased array configuration for RF coils in MRI to receive NMR signals. For example, a phased array surface coil for horizontal field MRI systems may include a surface phased array having multiple loop element coils. Any two adjacent loop elements typically have physical overlap in order to provide isolation. The multiple loop elements can be arranged, for example, in one row or in a triangle shape array.
Typically, a set of surface coil loops are critically decoupled relative to each other and simultaneously receive the NMR signal that is generated in the imaging region that is excited by a dedicated volume coil. The signal from these surface coils is then reconstructed to generate an image that is multiple times larger than the size of each individual loop in the array. Because the size of each element in the phased array is relatively small compared with the final reconstructed image, the noise figure is reduced and the signal obtained from each element of the phased array is increased. Thus, the final result is a significant increase in SNR for the final reconstructed image. The first application of such a phased array design was intended for the spine region because the required coverage of the spine area for the human body is extremely large and a single receive coil structure could not adequately provide the image necessary for clinical evaluation.
The use of these phased array coil structures, for example, a row of square loop coils for spine scanning when the coils are lined up in the head-foot (HF) direction, results in a shading problem with axial and coronal imaging. When a loop coil is used to scan the human body in a 3 T or higher field strength system, the sensitivity map of the coil in the transverse plane that is perpendicular to the main field direction of the system is not symmetrical. If the main field directs from the back of magnet to the front (patient end), the sensitivity map of the loop coil, which is put under the human body, tilts to left side (on the transverse plane, not the left side of the human body). If the main field direction reverses, the sensitivity map tilts to right side. Thus, if the left-right center of this phased array is positioned to the center of the spine, the coil does not provide the best SNR in the spine region because the coil sensitivity tilts to one side. The signals received from the right and left side of the spine are not symmetrically equal. The intensity difference between the signals from two symmetrical point on the left and right side of the spine can be more than twenty percent. This causes the transverse and coronal images of the coil to have obvious left-right shading.
Other variations use a two-dimension phased array surface coil structure having circular-shaped loop coils positioned adjacent loop coils at three apexes of an equilateral triangle. This structure is not suitable for spine imaging. When a phased array coil is used for spine imaging it should be able to scan any section of the spine. The coil should be made of several coil stations that are lined up in the HF direction. This triangle shape array is not suitable to make a spine coil with several coil sections in the HF direction.
Various modifications and deviations to the phased array coil were developed. For example, a phased array coil with figure "8" shaped element coils was developed and are which are commonly known as "butterflies." Instead of using a loop coil array, a quadrature coil array for spine imaging has also been provided. This coil is made of four quadrature pairs lined up in the HF direction with each quadrature pair having a loop and a butterfly element coil. This coil has several sections in the HF direction. Each section is made of one loop coil and a butterfly coil and they are quadrature analogically combined inside the coil or inside the MRI system. When a spine coil with this structure is used in 3 T system, the images generated by the coil also have left-right (LR) shading problems. This is because not only the loop coil, but also that butterfly coil has a tilted asymmetrical sensitivity map when used in a MRI system with 3 T or higher main field. The sensitivity map of the butterfly coil is shifted to the same direction as the loop coil because the field inside the human body generated by the two wings of the butterfly coil are not symmetrical. The sensitivity map looks like two mountain peaks and the peak on the side to which the field tilts is higher than the other side. Thus, the signals received by the loop and butterfly coil quadrature analogically combined field still show an asymmetrical pattern. The best SNR area of this coil is not in the center where the spine lies, but shifts to one side. For example, one of the images on one side of the kidney is brighter than the other side.
Other coil arrays are also known that include six quadrature pairs. The six pairs are aligned in the HF direction to cover the whole Cervical-Thoracic-Lumbar (CTL) spine area. The first pair may be positioned on a former that is conformal to the human neck. The quadrature pairs can be used separately or jointly to image any desirable section of the spine. Two elements in each pair are either quadrature analogically combined or digitally combined depending on how many receive channels are in the MRI system.
In order to enhance the ability to image the CTL spine area, a phased array design was proposed that covered the intended area. The proposed design included six quadrature pairs (six loop and six saddle coils in a quadrature configuration) separated in a multiple list of modes in which the coil can operate and further can image any desirable section of the spine. These coils have six quadrature pairs lined up in HF direction. The first pair that covers the neck is put on the former with a conformal shape to the neck. The butterfly coil of this quadrature pair looks more like a saddle coil. All the quadrature pairs in coils are either analogically combined inside the coil or digitally combined in the system. The sensitivity map of a saddle coil also has an asymmetrical pattern. Because both two element coils of a quadrature pair have asymmetrical sensitivity, the digitally combined images still have the LR shading problem. Thus, when a coil with this structure is used in a system with 3 T or higher main field, it still has the left and right shading problem no matter whether it is analogically combined or digitally combined. An alternative embodiment is to use twelve elements independently or in any receiver configuration based on the MRI system. This system still has the LR shading problem.
Thus, in operation, when a surface coil (e.g., a loop coil) is used in high field MRI systems whose main magnetic field strength is 1.5 Tesla (T) or higher, an asymmetrical signal sensitivity of the coil is observed. Even though the loop coil has a symmetrical structure, the sensitivity map of the coil tilts to one side. The tilting direction is related to the direction of the main magnetic field. This phenomenon is more obvious in a system that has the main magnetic field strength equal or higher than 3 T. This phenomenon is caused by the dielectric and conductive effect of the human body on the high RF frequency electromagnetic field. The RF electromagnetic field generated by nuclei resonant spins inside the body is a circular polarized field and propagates inside the body because the electromagnetic wavelength inside the body is not much larger than the dimension of the body at high RF frequency. The MR signals received by the coil from the left and the right side are no longer equal because of propagation of the circular polarized field generated by nuclei resonant spins.
When a traditional spine coil (e.g., CTL coil) with the quadrature structure described above is used in a 3 T system, the coil sensitivity map is tilted to one side. For example, on transverse and coronal spine images, the signals of tissues on the left and right sides of the spine are not equal. The difference of the signal intensity on the two sides can cause LR shading on the transverse and coronal spine images. This is known as LR shading problem for spine imaging with the traditional CTL coil. This problem may result in an improper or failed diagnosis.
Further developments in MRI include Simultaneous Acquisition of Spatial Harmonics (SMASH) that use a parallel processing algorithm to exploit spatial information inherent in a surface coil array. The result is an increase in MR image acquisition speed, resolution and/or field of view. In a similar fashion, another parallel processing algorithm is known where the acceleration of image acquisition is performed on the time domain space instead of the frequency domain space. This parallel acquisition technique is referred to as Sensitivity Encoding (SENSE). In SENSE, images are obtained by means of magnetic resonance (MR) of an object placed in a static magnetic field and includes simultaneous measurement of a number of sets of MR signals by application gradients and an array of receiver coils. Reconstruction may bee provided from a number of receiver coil images from the sets of MR signals measured and/or reconstruction of a final image may be from a distant dependent sensitivity of the receiver coils and a first plurality of receiver coil images.
The characteristics of all of these parallel imaging techniques is that the acceleration speed is directly proportional to the number of independent receivers along the direction that the image acceleration needs to be applied. Thus, the higher the number of receiver coils, the faster the acceleration speed for acquiring an image with better SNR and improved image quality.
However, if the phased array surface coil has one row of square loop coils, it only has parallel imaging capability in the HF direction. Further, the quadrature phased arrays described above also only have parallel imaging capability in the HF direction. The two element coils of a quadrature pair in these coils have a large common coverage in the LR direction. The g-factor values for such a quadrature coil are severely elevated because the B1 field profile for these two element coils is nearly indistinguishable around the spine region. Thus, they have no parallel imaging capability in the LF direction.

Cervical-thoracic-lumbar spine phased array coil for horizontal field MRI systems


Compositions of matter for treating cancer patients are used to prevent or limit cardiotoxicity during or after treatment with anthracycline drugs, and to prevent or lower resistance to anthracycline drugs, both of which are believed to be caused by the human enzyme carbonyl reductase. Preferred embodiments comprise a pharmaceutical composition comprising compounds having halogenated (or pseudo-halogenated) aryl groups, preferably halogenated (or pseudo-halogenated) arylcyanooximes or phenylcyanooximes and derivatives or analogs thereof, including those comprising —CL or —F, or other substituents on an aryl/phenyl ring. The preferred composition of arylcyanooxime(s) may be administered in a pharmaceutical composition also comprising at least one anthracycline compound, or may be administered separately from the at least one anthracycline compound.

1. Field of the Invention
This invention relates to compositions of matter, and methods of using said compositions for inhibiting human reductase enzyme(s) that destroy the cell-killing efficacy of anthracycline cancer drugs and that catalyze the formation of dangerous or damaging metabolites during or after cancer treatment. More specifically, embodiments of the invented compositions and methods inhibit human carbonyl reductase, thus inhibiting conversion of anthracycline to metabolites that are less effective cell-killing agents and that also lead to cardiotoxicity during or after treatment of cancer patients. Thus, the invented compositions and methods are believed to lower the amount needed, and the cardiotoxic side-effects, of anthracyclines in cancer treatment.
2. Related Art
Anthracyclines are a family of drugs that are effective anti-neoplastic agents, and are commonly used to treat cancer, including leukemia, soft tissue sarcomas, and breast and lung cancer. Anthracyclines intercalate into DNA and are described as topoisomerase Type II poisons. The anthracycline family comprises adriamycin, daunomycin, daunorubicin, doxorubicin, epirubicin, and idarubicin. See, for example, representations of doxorubicin and daunorubicin in FIG. 1.
While the anthracyclines are known to be potent anti-tumor drugs, their use has been limited due to potentially life-threatening cardiotoxicity associated therewith. This problem may be described as cumulative dose-dependent cardiotoxicity, which can ultimately result in congestive heart failure. There is significant evidence that the toxic effects on the heart alcohol metabolite(s) that can form and accumulate in cardiac cells. These metabolites are known to disrupt several key processes in heart muscle and thus impair heart function. See, for example, Minotti, et al., "Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardioitoxicity," Pharmacological Reviews, 56: 185-229, 2004.
Enzymes belonging to the aldo-keto reductase and short chain dehydrogenase/reductase protein superfamilies catalyze the formation of the anthracycline metabolites. Of these enzymes, carbonyl reductase ("CR") has been specifically linked to the development of anthracycline-induced cardiotoxicity. See, for example, Olson, et al., "Protection from Doxorubicin-Induced Cardiac Toxicity in Mice with a Null Allele of Carbonyl Reductase 1," Cancer Research, 63, 6602-6606, Oct. 15, 2003. Findings that support the hypothesis that CR is a key factor in anthracycline-induced cardiotoxicity include studies wherein heart-specific over-expression of human carbonyl reductase in transgenic mice substantially increased the development of cardiotoxicity after anthracycline treatment. See, for example, Forrest, et al., "Human Carbonyl Reductase Overexpression in the Heart Advances the Development of Doxorubicin-induced Cardiotoxicity in Transgenic Mice," Cancer Research, 60, 5158-5164, Sep. 15, 2000.
Further, several studies have implicated the reduction of anthracyclines by carbonyl reductase in drug resistance. This is largely because the alcohol metabolites of anthracyclines have been shown to exhibit significantly lowered anticancer properties. Relevant to this are studies performed by Tanaka, et al., (reported in Tanaka, et al., "An Unbiased Cell Morphology-Based Screen for New, Biologically Active Small Molecules," PLoS Biology, Vol. 3, Iss. 5, 0764-0776, May 2005). Tanaka, et al. report that a potent inhibitor of human carbonyl reductase (3-(7-isopropyl-4-(methylamino)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenol, when coadministered with daunorubicin to A549 adenocarcinoma cells, was found to enhance the cytotoxicity of daunorubicin. It was concluded that inhibition of carbonyl reductase led to enhanced cytotoxicity of daunorubicin.
See, for example, the FIG. 2 representation of carbonyl reductase catalysis (reduction via NADPH+H+ mechanism) of the anthracycline daunorubicin to daunorubicinol. While daunorubicin is an effective anti-cancer agent by means of its effective disruption of DNA replication, daunorubicinol exhibits reduced anti-cancer properties and is a potent cardiotoxin. Therefore, conversion to the alcohol metabolite not only creates a potent cardiotoxin, but also lowers the efficacy of the treatment for a given amount of anthracycline.
Therefore, the inventor believes that there is a need for pharmaceutical interventions that block the action of human carbonyl reductase. The inventor believes that such pharmaceutical interventions will increase the efficacy of anthracycline therapy in cancer/tumor treatment by preventing or lowering conversion of anthracyclines to less potent cell-killing species and by reducing the risk of cardiotoxicity.

Cyanooxime inhibitors of carbonyl reductase and methods of using said inhibitors in treatments involving anthracyclines


A system and method that allows an administrator to provide application extensions in a platform-neutral shell environment is provided. The administrator defines a graphical interface, such as an icon, used to launch the platform dependent software application. The administrator centrally manages the application extensions by defining the extension and including the extension definition in self-contained desktops. The administrator defines the executables and directories used to launch the corresponding application. The administrator selects desktop components, including application extensions, needed for a particular job role and packages the components into the self-contained desktop package file. The desktop packages and included application extensions are received and loaded on a platform-neutral desktop shell application. The shell application exists in a platform-neutral environment such as a Java virtual machine. The application extensions are launched from the shell application in order to invoke or utilize platform-dependent software applications.

1. Technical Field
The present invention relates to a system and method for extending Application types in a centrally managed desktop computing environment. In particular, the present invention relates to a system and method for including application extensions to launch platform-dependent applications from a platform-neutral shell operating environment.
2. Description of the Related Art
Today's modern computer software systems are often enterprise systems organized in a distributed fashion throughout the organization. The various people in the organization perform different roles using the computer system depending upon the user's job description. In a banking example, one user may be a teller and therefore need teller applications in order to serve banking customers. Another user may be a loan officer, and need to access loan officer applications to serve customers that are applying for loans. A third user may be the branch manager, and need to access computer functions used to manage the bank branch.
Traditional computer systems are typically designed to either provide all necessary functions through each computer, for example by using a computer network to access the needed functions, or the system is designed so that individual workstations perform particular roles and are therefore used by a particular user or set of users. This presents challenges in organizations where multiple users use the same client computer system. In the banking example, there may be several tellers that use the same client computer system, depending on the shift, day of the week, or which teller happens to be assigned to a particular workstation.
If all organizational functions are provided from the same workstation, users that are not authorized to perform a particular function may accidentally or deliberately perform functions for which they are not authorized. For example, a teller may accidentally perform a loan officer or branch manager function if the function is available from the teller's workstation. One way traditional systems handle authorizations is by installing software components to handle each job role at each workstation, but limiting access based upon the user login. A challenge of this approach, however, is that each workstation needs to receive any new or modified software components in order to be available for any user that may need such functionality from any given workstation.
Some of the functions performed by users may be client-server functions, while other functions may involve using software systems that have been installed on the user's workstation. Software systems installed on the user's workstation may include legacy software applications and other software that has been written for a particular operating system environment.
A challenge in using a platform-neutral shell environment to launch applications (such as from a Java™ application) is that the shell environment does not have information needed to launch software applications that have previously been installed on the user's workstation. In addition, the platform-neutral shell may operate in a variety of operating system environments, such as any system that has a Java virtual machine (JVM™). Thus, the challenge is exacerbated by needing to interface with software applications that have been installed on a variety of operating system platforms.
What is needed, therefore, is a system and method that provides application extension information to a platform neutral shell environment. Furthermore, what is needed is a graphical user interface, such as an icon, that can be used from the platform-neutral shell environment to launch the platform dependent software application. Finally, what is needed is a system and method to centrally manage the creation and dissemination of application extensions throughout an organization.

System and method of extending application types in a centrally managed desktop environment

International Business Machines Corporation


A process for the preparation of fluorinated compounds having at least one —OSF5 group, said method comprising the step of reacting SOF4 with a fluorinated 3- or 4-membered cyclic ether in the presence of a fluoride catalyst.

It is known to modify the bulk and surface properties of polymers with the use of monomers having side groups and/or functional groups. For instance, the use of fluorinated vinyl ethers as monomers in the preparation of fluorinated polymers has been extensively described; e.g. CARLSON, Peter, et al. Organic Fluoropolymers; Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH Verlag, 2000. p. 495-533.
The bulkiness of the —OSF5 moiety in the side chain of monomeric units may provide advantages in the modification of the crystallinity and of the surface properties of fluorinated polymers or of fluorinated compounds in general. Compounds comprising the —OSF5 moiety might also find use in the preparation of surface active agents, such as surfactants.
So far, however, the preparation of only one fluorinated unsaturated compound comprising the —OSF5 moiety, namely CF2═CFCF2OSF5, has been achieved, see WO 2013/000735 A (SOLVAY SPECIALTY POLYMERS ITALY SPA) Jan. 3, 2013.
The synthesis of other fluorinated unsaturated compounds comprising the —OSF5 moiety via the direct addition of SOF4 to a fluorinated unsaturated compound has so far been unsuccessful in standard conditions, see DU, L., et al. Synthesis of pentafluorosulfanyl trifluorovinyl ether and its facile rearrangement to difluoro(pentafluorosulfanyl)acetyl fluoride. Angew. Chem., Int. Ed. Engl. 2007, vol. 46, p. 6626-6628.
MARCELLIS, Alphonso W., et al. Synthesis of pentafluorosulfuroxydifluoroacetly fluoride. Journal of Fluorine Chemistry. 1975, vol. 5, p. 71-75. teaches to prepare SF5OCF2C(O)F by the action of both ozone and oxygen on the olefin SF5CF═CF2.
SCHACK, Carl J., et al. Introduction of functional Groups into Some Chlorofluorocarbon Ethers. Journal of Fluorine Chemistry. 1979, vol. 14, p. 519-522. discloses SF5OCF2C(O)F, which is prepared by addition of SF5OCl to a perfluoroolefin.
EP 1889832 A (AIR PROD) Feb. 20, 2008 discloses compositions that may comprise a molecular compound of the formula ZOSF5, wherein Z is a member selected from C1-20 alkyl, aryl, cycloalkyl, combinations thereof, and analogues containing at least one halogen and/or heteroatom (page 2, par. [0004]). The compound ZOSF5 can be obtained by addition of the OSF5 function to a compound ZL, wherein L is a leaving group and Z is as defined above, by way of a nucleophilic displacement reaction (page 2, par. [0009] and page 3, par. [0013]).
DE 102011114650 (MERCK PATENT GMBH) May 3, 2012 relates to compounds comprising —OSF5 end groups, including certain compounds complying with formula (III) reported on page 14. The compounds of formula (III) are prepared by addition of SF5OCl to an olefin or by nucleophile substitution of triflates with, for instance, TAS+F5SO−.
CASE, J. R., et al. Pentafluorosulpuroxy-derivatives of Hexafluoropropene. Journal of the Chemical Society. 1964, no. 946, p. 948. discloses the reaction of bispentafluorosulphur peroxide and pentafluorosulphur hypofluorite with hexafluoropropene to give a series of compounds SF5O[C3F6]nOSF5 where n=2, 3, or 4.
A new method for the preparation of fluorinated compounds comprising the pentafluorosulfanyl moiety —OSF5, as starting materials for the preparation of a wide range of novel fluorinated compounds comprising —OSF5 groups, has now been found.

This patent is subject to a terminal disclaimer.


An improvement is provided in a screw gun used in the drywall installation industry. The improved screw gun has a conventional screw driving head at the forward end of the gun. A rear drive shaft extends from the motor of the gun, and an access member is provided at the back of the screw gun to provide access to the distal end of the drive shaft. An adapter member is adapted to be received in and withdrawn from the access member. The adapter member has a rotatable cutting tool associated therewith. Rotational motion is transmitted from the drive shaft to the rotatable cutting tool by the adapter member when the adapter member is received in the access member and the rear drive shaft is driven by the motor.

1. Field of the Invention
The present invention relates to an adapter device which can be inserted into an access opening in the rearward, handle portion of a screw gun which has been provided with means for accepting the adapter device. The screw gun is otherwise conventional having a spring biased clutch at its forward drive end that must be engaged before the screw gun will transmit rotational motion from its motor to its forward, output drive member. The present invention allows an adapter to engage the drive shaft of the motor from the rearward handle end of the screw gun to provide a rotatable cutting or drilling tool at the rearward handle end of the screw gun in a quick and easy manner thereby eliminating the need for a separate drill or cutting tool.
2. State of the Art
Conventional power tools as used in the drywall industry typically perform only one function. For example, a screw gun is used for inserting screw type fasteners or attachments through the sheets of drywall, and a separate, distinct router is used to cut openings in the drywall panels after they have been attached to their stud supports. Typical screw gun devices are shown in U.S. Pat. Nos. 2,857,997, 2,950,626, 4,159,050 and 4,804,048. Such tools allow the drive member to slip when a desired tightening torque has been attained in the screw type fasteners or attachments being driven through the drywall panels. However, such screw gun tools do not eliminate the need for the operator to carry a router tool in addition to the screw gun.
Generally, heretofore an installer of drywall typically employed a screw gun for securing the drywall to the framework along with a drywall cutout tool or router which is specifically designed for making cutouts in the drywall for electrical boxes, window openings, splices, etc. In U.S. Pat. No. 5,090,545 a modification of a conventional screw gun is disclosed in which a nose cone adapter is fit on the nose cone of the screw gun so that the screw gun can function both as a drive tool and as a drywall cutout device. Unfortunately, to fit on the nose cone of a conventional screw gun, the adapter must be of a size that is awkward in actual use. In addition complex mechanisms are required for activating and transmitting proper speed of rotation to the drive tool. The adapter tool of U.S. Pat. No. 5,090,545 is relatively expensive and cumbersome to use.
3. Objectives
A principal objective of the present invention is to provide a simplified, relatively small, inexpensive adapter for a screw gun which is attachable to the back side of the handle of the screw gun for readily converting the screw gun into a router or cutting member and back to a screw gun by merely attaching and removing the adapter in an access provided at the back side of the handle of the screw gun.
A further object of the present invention is to provide an adapter for the back side of a screw gun which is relatively simple to manufacture, install and operate.

Screw gun router for drywall installation


A method and system for dynamically providing a composite source information report whenever source information of a composite object is updated. The system includes a subscription handler for receiving a subscription request and generating a subscription query, a means for determining whether source information of an element in a composite object has been edited (added, deleted and/or modified), a source information determining handler for automatically determining source information of an element in a composite object and a composite source information report generation handler for generating a composite source information report and providing the report to users. The system further comprises an authentication handler, an editing handler, an editing monitor, a source information recording handler, subscription source information retrieving handler and a server database.

The present invention relates to generating a composite source information report (i.e., a report including elements of a composite object (i.e., an object composed of one or more elements) and source information (e.g., creators, owners, importers, origins, access rights) of the elements). More particularly, the present invention is related to tracking source information of a composite object while developing the composite object.
One of major costs in a creation of a composite object (i.e., an object composed of one or more elements which are software, hardware or a combination of them) like software applications, automobiles, television shows or movies products is a tracking of source information (e.g., creators, importers, owners, etc.) of the elements in the composite object. With current existing technology, it takes a long time to determine, find out and trace source information of every element in a composite object.
A commonly owned and copending U.S. patent application Ser. No. 11/780,583) (hereinafter "Ariadne"), which is incorporated by reference, discusses a system and method for monitoring source information of each and every element in a composite object. In addition, Ariadne can provide the source information of all the elements in a composite object upon requesting (e.g., SQL query).
However, Ariadne and existing solutions do not provide any mechanism allowing a user to subscribe to receive an update in source information of an element in a composite object. Thus, when using Ariadne or existing solutions, a user has to make requests (or SQL queries) periodically in order to check whether there is an update in an element in a composite object or whether there is an update on source information of an element in a composite object.
Therefore, it would be highly desirable to provide a system and method for dynamically providing a composite source information report whenever source information of an element in a composite object is updated.

Method of dynamically providing a compound object's source information during its development


Users define virtual views to generate and execute queries across one or more existing application databases in order to implement new applications, including applications that require viewing images linked to existing database records. Mainframe, minicomputer or client-server computer system-based users link electronic documents stored in distributed or centralized image storage volumes on a PC-based system to existing database records, and retrieve those electronic documents when the linked database record is retrieved.

A. Field of the Invention
This invention relates generally to database systems and document imaging systems. The present invention facilitates the use of existing databases with document images by linking the images to database records.
B. Description of the Related Art
Medium to large size computer user groups have spent large sums of money in developing multiple, independent application databases on mainframe, minicomputer, and client-server computer systems. When seeking to add the functionality of an image processing application, however, these users encounter a significant obstacle. Specifically, image processing application developers have focused most development efforts on a different platform, i.e., the personal computer (PC). This difference in platforms, and the corresponding incompatibility between the PC and the other platforms, makes it difficult for users to integrate their older databases on mainframe, minicomputer and client-server computer systems with an image processing application.
Users needing access to both database and image processing applications must therefore select from the following unattractive and expensive alternatives to accommodate their need for both technologies. They can install a new database application on a PC platform with image processing functions. This option requires a major re-recording, re-educating and re-design effort to adapt the databases to the PC platform. Alternatively, users can employ the expensive and typically underdeveloped image processing products designed for mainframe, minicomputer and client-server computer systems.
Neither option, however, really allows the user to make full use of its existing investment in the database application. For example, database applications for the PC are not as sophisticated as those on mainframes. Moving the database from the mainframe to the PC is thus likely to result in a significant loss of functionality that may, in turn, affect the user's ability to use the database effectively in day-to-day operations.
There is, therefore, a need for a system that bridges the gap between existing mainframe, minicomputer or client-server databases and PC platform image processing applications. Such a system would preferably allow users to leave database applications intact and, at the same time, allow them to develop new applications using those databases tightly interfaced with image processing capabilities. Further, the system would allow users to maintain the integrity of information in existing databases, and not require re-keying any information from the databases into a new PC-based image processing application.

Document image and query management system for application databases