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Biocompatible material

Monomers of formula (I) which include a vinyl group, polymers and articles, such as contact lenses, made therefrom, all of which are biocompatible, are described.




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Dental materials on the basis of highly acidic polymerizable bisphosphonic acids

The invention relates to a dental material which comprises a polymerizable bisphosphonic acid of Formula I: The invention also relates to the use of a polymerizable bisphosphonic acid of Formula I for the preparation of a dental material and in particular for the preparation of an adhesive, cement or composite.




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Method for optimizing spin time in a centrifuge apparatus for biologic fluid

A method for controlling a centrifuge blood component separation system for separating components of a blood product, the separation system comprising a centrifuge and a separation bag and at least one transfer bag. The method comprises selecting a nominal hematocrit value such that an actual hematocrit value is expected to be less than said nominal hematocrit; centrifuging a separation bag containing a volume of composite liquid so as to cause the sedimentation of at least a first component and a second component; transferring some of the first component to a first transfer bag; detecting time of passage of a red blood cell interface at a pre-selected location in the separation bag; and adjusting a predicted processing time based on the time of passage of the red blood cell interface.




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Apparatus for processing biological material

A gripper unit for handling a vessel for receiving biological material is proposed, inter alia. The vessel has a lid which can assume an open position and a closed position. The gripper unit comprises a gripper for gripping and releasing the vessel, and a lid holder, for holding a lid in a defined position in relation to the vessel. The defined position is an open position of the lid.




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Pharmaceutical combination for the treatment and/or chemosensibilization of refractory tumors to anticancer drugs

This invention is related to a pharmaceutical combination that contains a Casein kinase 2 (CK2) peptide inhibitor (termed P15) along with the standard chemotherapeutic drugs used in cancer treatment and which are administered together, separated or sequentially. The chemotherapeutic drugs include cisplatin, taxol, alkaloids from Vinca, 5-fluorouracil, doxorubicin, cyclophosphamide, etoposide, mitomicin C, imatinib, iressa and velcade (vortezomib). The synergism between the P15 peptide and the anticancer drugs achieves an efficient concentration of each cytostatic drug in the combination which is from 10- to 100-fold lower than that for each cytostatic drug alone. The pharmaceutical combination described in this invention exhibits lower toxicity compared to that reported by the anticancer therapeutics and therefore, it represents a crucial advantage for its use in cancer therapy. Furthermore, the sequential administration of this pharmaceutical combination through the pretreatment with the P15 peptide leads to the chemo sensibilization of refractory tumors to the anticancer therapeutics.




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Integrated biorefinery for production of liquid fuels

A system for the production of conversion products from synthesis gas, the system including a mixing apparatus configured for mixing steam with at least one carbonaceous material to produce a reformer feedstock; a reformer configured to produce, from the reformer feedstock, a reformer product comprising synthesis gas comprising hydrogen and carbon monoxide from the reformer feedstock; a synthesis gas conversion apparatus configured to catalytically convert at least a portion of the synthesis gas in the reformer product into synthesis gas conversion product and to separate from the synthesis gas conversion product a tailgas comprising at least one gas selected from the group consisting of carbon monoxide, carbon dioxide, hydrogen and methane; and one or more recycle lines fluidly connecting the synthesis gas conversion apparatus with the mixing apparatus, the reformer, or both.




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Biomass gasification gas purification system and method and methanol production system and method

A biomass gasification gas purification system includes a dust collector for removing dust in biomass gasification gas (containing tar components) acquired by gasifying biomass by a biomass gasification furnace, a desulfurizer for removing sulfur oxide components in the dust-removed biomass gasification gas, a pre-reforming reactor for reforming tar components in the desulfurized biomass gasification gas, a steam feed unit for feeding steam to an upstream side of the pre-reforming reactor, and a natural-gas feed unit for feeding natural gas on an upstream side of the desulfurizer.




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Integrated bioprocessing for fuel production

Systems and methods are provided for enhancing the integration of processes for recovering products from algae-derived biomass. The enhanced process integration allows for increased use of input streams and other reagents that are derived from renewable sources. This increases the overall renewable character of the products extracted from the algae-derived biomass. The process integration can include exchange of input streams or energy between an algae processing system and a system for processing non-algal biomass. One example of improving process integration is using oxygenates that are generated in a renewable manner as a reagent for enhancing the algae processing system.




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Conversion of carbon dioxide to methanol using bi-reforming of methane or natural gas

The invention provides for a method of forming methanol by combining a mixture of methane, water and carbon dioxide under reaction conditions sufficient to form a mixture of hydrogen and carbon monoxide. Hydrogen and carbon monoxide are reacted under conditions sufficient to form methanol. The molar ratio of hydrogen to carbon monoxide is at least two moles of hydrogen to one mole of carbon monoxide and the overall molar ratio between methane, water and carbon dioxide is about 3:2:1. Methane, carbon dioxide and water are bi-reformed over a catalyst. The catalyst includes a single metal, a metal oxide, a mixed catalyst of a metal and a metal oxide or a mixed catalyst of at least two metal oxides.




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Device for the collection and processing of information relating to the exposure of one or more persons to one or more products of chemical or biological origin and method for the use of such a device

A device for the collection and processing of information relating to the exposure of one or more persons to one or more products of chemical or biological origin has: at least one coded sensor for automatic or semi-automatic identification of a person likely to be exposed to at least one product,at least one coded sensor for the collection of information relating to the handling of at least one product by the person likely to be exposed to the product,at least one sensor for validating the information collected by the identification and collection sensors,at least one module for reading at least one coded sensor, anda module for processing information collected by the sensors.




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Computer-implemented systems and methods for testing large scale automatic forecast combinations

Systems and methods are provided for evaluating performance of forecasting models. A plurality of forecasting models may be generated using a set of in-sample data. Two or more forecasting models from the plurality of forecasting models may be selected for use in generating a combined forecast. An ex-ante combined forecast may be generated for an out-of-sample period using the selected two or more forecasting models. The ex-ante combined forecast may then be compared with a set of actual out-of-sample data to evaluate performance of the combined forecast.




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Method for perfusing a biocompatible material graft with a liquid and perfusion kit

A method for perfusing a biocompatible material graft with a perfusion liquid includes the steps of: introducing the graft (100) in a perfusion chamber (2), arranging a transfer chamber (3) partly filled with the perfusion liquid (101), coupling in a tight manner the perfusion chamber (2) and the transfer chamber (3) for establishing a fluid communication between them, lowering the pressure in the transfer chamber (3) for transferring therein part of the air existing in the perfusion chamber (2), increasing the pressure within the transfer chamber (3) for injecting in the perfusion chamber (2) the perfusion liquid (101) existing in the transfer chamber (3). A perfusion kit includes a perfusion chamber (2) apt to contain a graft (100) to be perfused with a liquid (101) and a transfer chamber (3) apt to contain a liquid (101) to be perfused, the perfusion chamber (2) being connectable in a tight manner with the transfer chamber (3) for allowing a fluid exchange between the two chambers (2, 3) and inhibiting a fluid exchange between the two chambers (2, 3) and the external environment.




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Dual cure method for ink for increased durability and adhesion to golf balls

A method is disclosed for curing ink printed images on golf balls by printing an image onto a golf ball and exposing the printed image to infrared radiation, then exposing the printed image to ultraviolet radiation.




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Low temperature silicon carbide deposition process

Methods for formation of silicon carbide on substrate are provided. Atomic layer deposition methods of forming silicon carbide are described in which a first reactant gas of the formula SinHaXb wherein n=1-5, a+b=2n+2, a>0, and X=F, Cl, Br, I; and a second reactant gas of the formula MR3-bYb, wherein R is a hydrocarbon containing substituent, Y is a halide, hydride or other ligand and b=1-3 are sequentially deposited on a substrate and then exposed to a plasma. The process can be repeated multiple times to deposit a plurality of silicon carbide layers.




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Superhydrophobic aerogel that does not require per-fluoro compounds or contain any fluorine

Provided are superhydrophobic coatings, devices and articles including superhydrophobic coatings, and methods for preparing the superhydrophobic coatings. The exemplary superhydrophobic device can include a substrate component and one or more superhydrophobic coatings disposed over the substrate component, wherein at least one of the one or more superhydrophobic coatings has a water contact angle of at least about 150° and a contact angle hysteresis of less than about 1°. The one or more superhydrophobic coatings can include an ultra high water content acid catalyzed polysilicate gel, the polysilicate gel including a three dimensional network of silica particles having surface functional groups derivatized with a silylating agent and a plurality of pores.




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Method and apparatus for the formation of hydrophobic surfaces

The invention relates to the application of a coating to a substrate in which the coating includes a polymer material and the coating is selectively fluorinated and/or cured to improve the liquid repellance of the same. The invention also provides for the selective fluorination and/or curing of selected areas of the coating thus, when completed, providing a coating which has regions of improved liquid repellance with respect to the remaining regions and which remaining regions may be utilized as liquid collection areas.




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Combination heart assist systems, methods, and devices

The various embodiments disclosed herein relate to combination heart assist systems, methods, and devices that include both an electrical therapy device and a mechanical heart assist device. Various operational modes can be implemented using these embodiments, including a synchronized pacing mode, an internal CPR mode, and an internal workout mode.




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Transducer mounting assembly for plumbing fixture

A mounting assembly for mounting a transducer to a plumbing fixture is provided. The mounting assembly includes a bracket configured to be affixed to an exterior wall of the plumbing fixture. The mounting assembly further includes a shield defining an internal cavity and configured to be removably coupled to the bracket. The shield is configured to be coupled to the transducer and to enclose at least a portion of the transducer within the internal cavity.




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Method and system for combined energy therapy profile

A method and system for treating tissue with a combined therapy profile is disclosed. In one exemplary embodiment, ultrasound energy is used to treat numerous depths of tissue within a region of interest and the spatial and temporal properties of the ultrasound energy are varied for more effective treatment. The method and system of the present invention are configured to treat all of the tissue from the surface on down and not spare intervening tissue.




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Systems and methods for monitoring and controlling ultrasound power output and stability

Some embodiments provide a method of providing ultrasound energy having a stable power output. The method can comprise providing ultrasound energy from a ultrasound transducer; determining a power level threshold of the ultrasound energy; monitoring a power level of the ultrasound energy over time of the ultrasound energy; communicating a power level to a controller; adjusting the frequency of the ultrasound energy upon a change in the power level; and maintaining the power level threshold of the ultrasound energy.




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Unitary elastic mold and cutter combination

A unitary elastic mold and cutter combination configured to mold and cut moldable material is disclosed herein. The mold and cutter combination comprises an elastic mold cavity having an elastic bottom wall with an embossed inner surface and an elastic sidewall extending from and unitary with a perimeter of the bottom wall. An elastic cutting blade extends from and is unitary with the sidewall of the mold cavity and is configured to cut moldable material and maintain a substantially consistent perimeter upon cutting. The cutting blade comprises a cutting edge disposed between an inner cutting blade surface and an outer cutting blade surface. The mold and cutter combination may have an elasticity sufficient to release molded material therefrom by hand stretching, wherein the cutting edge, inner cutting blade surface, and the inner surface of the sidewall of the mold cavity are stretched by an amount sufficient to release the molded material.




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Combustion device for a gas turbine configured to suppress thermo-acoustical pulsations

A combustion device (1) for a gas turbine includes portions (12) having an inner and an outer wall (13, 14) with an interposed noise absorption plate (15) having a plurality of holes (16). The combustion device (1) further has first passages (17) connecting zones between the inner wall (13) and the plate (15) to the inside of the combustion device (1) and second passages (21) for cooling the inner wall (13). The portions (12) also have an inner layer (22) between the inner wall (13) and the plate (15) defining inner chambers (23), each connected to at least a first passage (17), and an outer layer (24) between the outer wall (14) and the plate (15) defining outer chambers (25) connected to the inner chambers (23) via the holes (16) of the plate (15).




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Utilizing a diluent to lower combustion instabilities in a gas turbine engine

A method of influencing combustion dynamics, including measuring a combustion dynamics parameter, and controlling a diluent flow (26) delivered to a fuel flow (32) upstream of a pilot burner fuel outlet (40) in response to the measured combustion dynamics parameter.




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Systems and methods for detecting combustor casing flame holding in a gas turbine engine

In a gas turbine engine that includes a compressor and a combustor, wherein the combustor includes a primary fuel injector within a fuel nozzle and a secondary fuel injector that is upstream of the fuel nozzle and configured to inject fuel into a flow annulus of the combustor, a method for detecting a flame holding condition about a fuel injector. The method may include the steps of: detecting an upstream pressure upstream of the secondary fuel injector; detecting a downstream pressure downstream of the secondary fuel injector; determining a measured pressure difference between the upstream pressure and the downstream pressure; and comparing the measured pressure difference to an expected pressure difference.




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Technique for executing communication of object data with mobile device

In a case where a communication device belongs to a first wireless network for the communication device to execute a wireless communication, the communication device may execute using a wireless communication with a mobile device via the first wireless network after sending to the mobile device a first wireless setting. The first wireless setting may be for the mobile device to belong to the first wireless network and include a password. In a case where the communication device belongs to a second wireless network for the communication device to execute a wireless communication, the communication device may execute a wireless communication with the mobile device via the second wireless network after sending to the mobile device a second wireless setting. The second wireless setting may be for the mobile device to belong to the second wireless network and not including the password.




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System for streaming using mobile devices and servers

A method and apparatus in which multiple Internet Protocol (IP) based wireless data transmissions are simultaneously provided between a wireless device and a server, including providing multiple antennas, multiple T/R units, multiple processors and multiple I/O ports on the wireless device. The method includes receiving multiple IP data packets on the I/O ports at substantially the same time, and sending multiple data packets from the wireless device to the server, whereby the transmission rate between the wireless device and the server is increased.




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Mobile user terminal, mobile communication system, base station, and communication method

A mobile user terminal, which communicates with a base station in an intermittent fashion, the mobile user terminal includes a radio transmitter which transmits downlink channel quality information indicating downlink channel quality and an uplink pilot signal to a base station in an intermittent fashion; and a transmit time controller which synchronizes transmit time of the downlink quality information and transmit time of the uplink pilot signal relative to each other, such that the downlink quality information and the uplink pilot signal are sent in adjacent different timings in a period corresponding to a state of intermittent communicate.




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Apparatus for adjusting a position of a bicycle derailleur

A bicycle transmission control apparatus comprises a control unit that provides a first signal to operate a first derailleur a gear shift distance from a first origin sprocket to a first destination sprocket. The control unit receives a condition signal that indicates a condition resulting from at least one of the first derailleur and a second derailleur; and an adjustment controller moves the first derailleur an adjustment distance less than the gear shift distance in response to the condition signal.




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Bicycle derailleur adjusting apparatus

A bicycle derailleur adjusting apparatus for adjusting a bicycle derailleur includes a controller. The bicycle derailleur includes a base member adapted to be mounted to a bicycle, a movable member, a linkage coupled between the base member and the movable member, and an actuator configured to move the movable member of the bicycle derailleur among a plurality of derailleur positions. The controller is configured to control the actuator based on a travel value indicative of a travel distance of the movable member between adjacent derailleur positions to update the derailleur positions of the movable member.




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Bicycle gear shift control system capable of avoiding frequent gear shifting

A bicycle gear shift control system capable of avoiding frequent gear shifting includes: a power module; a microcomputer electrically connected to the power module for allowing a cyclist to switch between the automatic gear shifting mode and a manual gear shifting mode; a gear shifting driver electrically connected to the microcomputer, substantially connected to a derailleur, and instructed by the microcomputer to drive the derailleur to perform gear shift control; and a manual shifting controller electrically connected to the microcomputer. The microcomputer has an automatic gear shifting logic whereby the microcomputer determines the timing of automatic gear shifting and performs gear shifting. The microcomputer further has a gear shifting delay logic that involves delaying for a delay time interval from commencement of gear shifting according to a gear shifting criterion and ruling out all other gear shifting commands during the delay time interval.




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Bicycle sprocket for use with a multi-gear rear cassette

A rear bicycle sprocket for use with a multi-gear rear cassette is provided. The sprocket includes a chain engaging portion and a mounting portion having generally annular shape about a central axis and a plurality of support arms, integrally formed with the chain engaging portion and with the mounting portion. The sprocket further includes a plurality of space maintaining protrusions, each space maintaining protrusion extending axially forwardly from an axially forward surface of a corresponding support arm and integrally formed therewith. A multi-gear rear cassette having a plurality of sprockets coaxially mounted together wherein the plurality of sprockets includes the rear bicycle sprocket mounted axially rearmost and a bicycle including the multi-gear rear cassette are further provided.




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Method for electronically controlling a bicycle gearshift and electronically servo-assisted bicycle gearshift

A method for electronically controlling a bicycle gearshift comprising at least one derailleur is disclosed, comprising the sequential steps of: a) imparting a movement on the derailleur of the gearshift until the derailleur is in an intended position;b) waiting for a predetermined time period,c) performing a check whether the derailleur is in the intended position, within a possible predetermined tolerance,d) in case said check has a negative outcome, imparting a movement on the derailleur of the gearshift until the derailleur is in the intended position. A derailleur and an electronically servo-assisted bicycle gearshift comprising control electronics comprising modules adapted to carry out the method outlined above are also disclosed.




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Rear derailleur device for a bicycle shifting system

A derailleur device, particularly a rear derailleur, includes at least one locking device for locking a chain guide at least in one locking position that is different from the starting position in relation to a movable element, and it is provided therein that the locking device includes a locking element displaceable between a passive position, in which the chain guide is released in relation to the movable element, and at least one active position, in which the chain guide is held in the at least one locking position.




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Method for modifying plant architecture and enhancing plant biomass and/or sucrose yield

The present invention relates to methodology and constructs for modifying plant architecture and enhancing plant biomass and/or sucrose yield.




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Herbicide tolerant soybean plants and methods for identifying same

The invention provides specific transgenic soybean plants, plant material and seeds, characterized in that these products harbor a stack of specific transformation events at specific locations in the soybean genome (elite event EE-GM3 and elite event EE-GM2, or elite event EE-GM3 and elite event EE-GM1). The invention also provides for methods of producing soybean plants and seeds having elite event EE-GM3 and elite event EE-GM2, or elite event EE-GM3 and elite event EE-GM1.




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Method and an apparatus/universal combine for agitation of liquids

A method of mixing together liquids or liquid/solid combinations, and mixing apparatus/universal combine utilizing a vertical spinning container or vessel having a rib, or a cross rib in its bottom wall. The container is spun about a vertical axis with no wobbling component to the motion. Meshed elements are used for high shear mixing. Start/stop routines, and variable acceleration/speed values are used, to facilitate complete mixing. Use of ‘impeller’ blade stirrers is completely eliminated.




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Mixer for biphasic compounds

Mixer for biphasic compounds, including a chamber for containing a solid phase and a cartridge containing a phial of a liquid phase, said chamber and said cartridge being able to communicate through respective channels, wherein said cartridge includes an external casing made in a deformable material and said phial is of the breakable type.




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Dinitroxide-type biradical compounds optimized for dynamic nuclear polarization (DNP)

The present invention relates to the field of organic chemistry and in particular to organic free radicals used as polarizing agents in the technique of Dynamic Nuclear Polarization (DNP), which involves transferring the polarization of electron spins to the nuclei of a compound whose Nuclear Magnetic Resonance (NMR) is being observed. It concerns Dinitroxide-type Biradical polarizing agents characterized by a rigid linkage between the aminoxyl groups of said nitroxide units. This particular structure enables, at low temperatures and high fields, optimal transfer of polarization and optimal enhancement of NMR/MAS signals of the polarized nuclei of the compound studied.




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Process for preparing a biphenyl-2-ylcarbamic acid

The invention provides a process of preparing an intermediate useful in the synthesis of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester, and a process of preparing a crystalline freebase of the ester.




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Process for preparing a compound useful for producing an optically active diazabicyclooctane compound

A process for preparing the compound of the following formula (E): wherein Bn represents a benzyl group, and tBu represents a tert-butyl group, the process including: (a) subjecting the following compound (B) to trifluoroacetylation, wherein tBu represents a tert-butyl group to produce the following compound (C): wherein tBu represents a tert-butyl group, and TFA represents a trifluoroacetyl group; (b) reacting the compound (C) with benzyloxyamine in the presence of a hydroxyl group activating agent to produce the following compound (D): wherein Bn represents a benzyl group, tBu represents a tert-butyl group, and TFA represents a trifluoroacetyl group; and (c) subjecting the compound (D) to detrifluoroacetylation.




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Compounds as rearranged during transfection (RET) inhibitors

This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.




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N-(1,2,5-oxadiazol-3-yl)pyridinecarboxamides and use thereof as herbicides

A description is given of N-(1,2,5-oxadiazol-3-yl)pyridinecarboxamides of the general formula (I) as herbicides. R in this formula (I) stands for radicals such as hydrogen, organic radicals, and other radicals such as halogen. W stands for a substituted pyridyl radical.




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CCR9 inhibitors and methods of use thereof

The invention relates to compounds represented by Structural Formula I, which can bind to CCR9 receptors and block the binding of a ligand (e.g., TECK) to the receptors. The invention also relates to a method of inhibiting a function of CCR9, and to the use compounds represented by Structural Formula I in research, therapeutic, prophylactic and diagnostic methods.




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Compositions of protein receptor tyrosine kinase inhibitors

The present invention relates to novel synthetic substituted heterocyclic compounds and pharmaceutical compositions containing the same that are capable of inhibiting or antagonizing a family of receptor tyrosine kinases, Tropomysosin Related Kinases (Trk), in particular the nerve growth factor (NGF) receptor, TrkA. The invention further concerns the use of such compounds in the treatment and/or prevention of pain, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, or a disease, disorder or injury relating to dysmyelination or demyelination or the disease or disorder associated with abnormal activities of NGF receptor TrkA.




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Chlorobis copper (I) complex compositions and methods of manufacture and use

A method of manufacturing an anhydrous copper complex of formula C12H10CICuN2O4 and methods of treating neuromuscular and other diseases, including but not limited to fibromyalgia, multiple sclerosis, muscular dystrophy, rheumatoid arthritis, pain, fatigue, sleeplessness, loss of fine motor control, speech loss, inflexibility, Alzheimer's, dementia, amyotrophic lateral sclerosis, depression, lyme disease, lyme disease co-infection, gastroparesis (GP), myopathy, chronic inflammation and/or incontinence. The anhydrous copper complex preferably is administered in a pharmaceutical and/or dietary supplement composition of the invention.




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Small molecule inhibitors of polynucleotide kinase/phosphatase, poly(ADP-ribose) polymerase and uses thereof

The present invention generally relates to use of compounds and compositions as a chemosensitizers and/or radiosensitizers and/or inhibitors of PNKP phosphatase activity. The present invention provides pharmaceutical combinations and/or a pharmaceutically acceptable salt thereof, kits containing such compounds and/composition and methods of using such compounds and/or compositions.




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Substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors

The invention is directed to novel substituted benzylamino quinolines, compounds comprising substituted benzylamino quinolines, methods of making substituted benzylamino quinolines, the use of substituted benzylamino quinolines for treating or preventing a variety of conditions or diseases associated with lipoprotein metabolism, and the use of substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors.




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Dual inhibitors of farnesyltransferase and geranylgeranyltransferase I

Many GTPases such as Ras, Ral and Rho require post-translational farnestylation or geranylgeranylation for mediating malignant transformation. Dual farnesyltransferase (FT) (FTI) and geranylgeranyltransferase-I (GGT-1) inhibitors (GGTI) were developed as anticancer agents from based on an ethylenediamine scaffold. On the basis of a 4-fold substituted ethylenediamine scaffold, the inhibitors are structurally simple and readily derivatized, facilitating extensive structure-activity relationship studies. The most potent inhibitor is compound exhibited an in vitro hFTase IC50 value of 25 nM and a whole cell H-Ras processing IC50 value of 90 nM. Several of the inhibitors proved highly selective for hFTase over the related prenyltransferase enzyme geranylgeranyltransferase-I (GGTase-I). A crystal structure of an inhibitor cocrystallized with farnesyl pyrophosphate in the active site of rat FTase illustrates that the para-benzonitrile moiety is stabilized by a π-π stacking interaction with the Y361β residue, suggesting an importance of this component of the inhibitors.




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Substituted pyridine and pyrazine compounds as PDE4 inhibitors

The invention provides a chemical entity of Formula (I) wherein R1, R2, R3, R4, Y and Z have any of the values described herein, and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies, detection and imaging techniques, and radioactive treatments; and therapies, including inhibiting PDE4, enhancing neuronal plasticity, treating neurological disorders, providing neuroprotection, treating a cognitive impairment associated with a CNS disorder, enhancing the efficiency of cognitive and motor training, providing neurorecovery and neurorehabilitation, enhancing the efficiency of non-human animal training protocols, and treating peripheral disorders, including inflammatory and renal disorders.




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Luminescent platinum(II) complexes with biazolate chelates

A platinum complex of a formula (I): whereR1 and R2 are each fluoroalkyl,X is C—H or nitrogen, andL1 is a bidentate, nitrogen-containing heteroaromatic ligand.