Abstract: The present invention relates to compounds which may be useful as inhibitors of PTPN11 for the treatment or prevention of cancer and other PTP-mediated diseases. Disclosed herein are new compounds and compounds based on pyrazolopyrazines and their application as pharmaceuticals for the treatment of disease.

Abstract: The invention relates to the atomistic functional understanding of the M2 protein from the influenza A virus. This acid-activated selective proton channel has been the subject of numerous conductance, structural, and computational studies. Previously, little was known at the atomic level about the heart of the functional mechanism of this tetrameric protein, a tetrad of HxxxW residues. The structure of the M2 conductance domain in a lipid bilayer is disclosed and displays the defining features of the native protein that have not been attainable from structures solubilized by detergents. A detailed mechanism for acid activation and proton conductance, involving a strong hydrogen bond between two adjacent histidines and specific interactions with the tryptophan gate, is provided and elucidates many observations on the M2 proton conductance.

Abstract: The invention relates to the atomistic functional understanding of the M2 protein from the influenza A virus. This acid-activated selective proton channel has been the subject of numerous conductance, structural, and computational studies. Previously, little was known at the atomic level about the heart of the functional mechanism of this tetrameric protein, a tetrad of HxxxW residues. The structure of the M2 conductance domain in a lipid bilayer is disclosed and displays the defining features of the native protein that have not been attainable from structures solubilized by detergents. A detailed mechanism for acid activation and proton conductance, involving a strong hydrogen bond between two adjacent histidines and specific interactions with the tryptophan gate, is provided and elucidates many observations on the M2 proton conductance.

Abstract: Disclosed is a method for detection of ligand-cell membrane protein binding by solid state NMR spectroscopy. The method starts by forming a lipid bilayer inside nanopores of an anodic aluminum oxide (AAO) substrate, the lipid bilayer containing a membrane protein sample. The AAO substrate is treated with multiple candidate ligands having potential binding affinity for the membrane protein. Solid-state NMR analysis is performed on the treated AAO/lipid preparation so as to generate an NMR spectrum for the treated membrane protein. The solid-state NMR spectrum of the treated membrane protein is compared with the spectrum of the same preparation of membrane protein in the absence of the ligands. It is then determined whether the solid-state NMR spectrum of the treated membrane protein has shifted from the NMR spectrum of the untreated membrane protein, a shift being indicative of protein binding by the candidate ligand.

Abstract: Disclosed is a method for detection of ligand-cell membrane protein binding by solid state NMR spectroscopy. The method starts by forming a lipid bilayer inside nanopores of an anodic aluminum oxide (AAO) substrate, the lipid bilayer containing a membrane protein sample. The AAO substrate is treated with multiple candidate ligands having potential binding affinity for the membrane protein. Solid-state NMR analysis is performed on the treated AAO/lipid preparation so as to generate an NMR spectrum for the treated membrane protein. The solid-state NMR spectrum of the treated membrane protein is compared with the spectrum of the same preparation of membrane protein in the absence of the ligands. It is then determined whether the solid-state NMR spectrum of the treated membrane protein has shifted from the NMR spectrum of the untreated membrane protein, a shift being indicative of protein binding by the candidate ligand.

Abstract: Disclosed is a method for detection of ligand-cell membrane protein binding by solid state NMR spectroscopy. The method starts by forming a lipid bilayer inside nanopores of an anodic aluminum oxide (AAO) substrate, the lipid bilayer containing a membrane protein sample. The AAO substrate is treated with multiple candidate ligands having potential binding affinity for the membrane protein. Solid-state NMR analysis is performed on the treated AAO/lipid preparation so as to generate an NMR spectrum for the treated membrane protein. The solid-state NMR spectrum of the treated membrane protein is compared with the spectrum of the same preparation of membrane protein in the absence of the ligands. It is then determined whether the solid-state NMR spectrum of the treated membrane protein has shifted from the NMR spectrum of the untreated membrane protein, a shift being indicative of protein binding by the candidate ligand.

Abstract: There is provided a hybrid human/computing arrangement which advantageously involves humans in the process of scrutinizing video image frames and processing said video image frames to detect and characterize objects of interest while ignoring other features of said image frame. The invention overcomes the problems of missed and false detections by humans. Said features of interest may comprise equipment and installations found on or in the vicinity of roads including road signs of the type commonly used for traffic control, warning, and informational display.

Abstract: There is provided an efficient, fast image processing apparatus with low error probability for rapidly scrutinizing a digitized video image frame and processing said image frame to detect and characterize features of interest while ignoring other features of said image frame. There is further provided an efficient fast image processing method with low error probability for rapidly scrutinizing a digitized video image frame and processing said image frame to detect and characterize features of interest while ignoring other features of said image frame. In a first embodiment of the invention an image processing apparatus comprises an imaging device coupled to a digital electronic image processor. Video data from the imaging device is linked to a location data source. Objects of interest in a scene are identified by comparing computed Maximally Stable Extremal Regions (MSERs) of captured images with MSERs of images of objects contained in a object template database.

Abstract: The present invention includes a method and apparatus of managing time for a processing system located on a machine. The processing system includes a plurality of controllers and a communication network connecting each of the controllers. Each of the controllers has a local clock. The method includes the steps of establishing an operating characteristic of the machine, determining whether to update a local time in response to said operating characteristic, and updating said local time based upon the local clock in response to said update determination.

Abstract: The invention relates generally to the field of quantitative sedimentologic and stratigraphic prediction. Specifically, geological data observed or inferred from core samples, cuttings, geophysical well logs and seismic data from locations within a sedimentary basin, in conjunction with a stratigraphic forward model and an inverse optimization technique, are used to predict sedimentologic and stratigraphic attributes at locations within the basin other than those at which data were collected. The model's output consists of a three-dimensional model of the sedimentologic and stratigraphic attributes for the specified basin volume.

Abstract: The invention relates generally to the field of quantitative sedimentologic and stratigraphic prediction. Specifically, geological data observed or inferred from core samples, cuttings, geophysical well logs and seismic data from locations within a sedimentary basin, in conjunction with a stratigraphic forward model and an inverse optimization technique, are used to predict sedimentologic and stratigraphic attributes at locations within the basin other than those at which data were collected. The model's output consists of a three-dimensional model of the sedimentologic and stratigraphic attributes for the specified basin volume.

Abstract: The present invention includes a method and apparatus of managing time for a processing system located on a machine. The processing system includes a plurality of controllers and a communication network connecting each of the controllers. Each of the controllers has a local clock. The method includes the steps of establishing an operating characteristic of the machine, determining whether to update a local time in response to said operating characteristic, and updating said local time based upon the local clock in response to said update determination.

Abstract: The present relates generally to the field of quantitative sedimentologic and stratigraphic prediction in which errors, uncertainties, risk and accuracy are calculated. Specifically, geologic data observed or inferred from core, outcrop, well log and/or seismic data from particular locations, in conjunction with a stratigraphic forward model and an optimization technique (mathematical inverse algorithm), are used to predict stratigraphic and sedimentologic attributes at locations other than those at which data were collected. This is accomplished by inverting a stratigraphic/sedimentologic forward model with simultaneous multi-parameter inversion or other mathematical optimization technique, such that forward model predictions are forced to obtain a best match with observations. The geologic data used to constrain the inversion are a small sample set of the larger, complete, rock volume simulated by the model.

Abstract: The present invention provides a control which automatically elevates engine speed to a preselected value when the vehicle coasting in neutral above a preselected speed. In order to accomplish this objective, the engine controller is adapted to receive an actual gear ratio signal and a vehicle speed signal, If the vehicle is in neutral and engine speed is above a preselected threshold, the controller sets the desired engine speed to a preselected value which has been empirically determined to ensure sufficient transmission cooling and lubrication, Controlling to this speed also reduces transmission wear when the transmission is reengaged at high ground speeds.