Abstract: The invention provides inhibitors of ghrelin O-acyltransferase, and methods of making and using them. In some embodiments, the invention provides bisubstrate analog inhibitors of ghrelin O-acyltransferase, which can be effective in treating, for example, obesity and diabetes mellitus.

Abstract: A machine data acquisition system is disclosed. The data acquisition system may include a sensor disposed on a machine and configured to produce a signal indicative of an operational parameter of the machine. The system may also include a data processor and controller configured to convert the signal into a plurality of parameter data points. The system may further include a primary data circular buffer disposed on the machine and configured to store the plurality of parameter data points. Additionally, a variable resolution circular buffer may be disposed on the machine and configured to store a compressed parameter data point calculated from the plurality of parameter data points.

Abstract: The present invention relates to a method for identifying compounds that modulate the activity of p300/CBP. Compounds of the invention are identified by designing or screening for a compound which binds to at least one amino acid residue of the newly identified lysine-CoA inhibitor binding site, L1 loop, electronegative pocket, or electronegative groove of the HAT domain of p300/CBP and testing the compound for its ability to modulate the activity of p300/CBP. Compositions and methods for preventing or treating diseases or disorders associated with p300/CBP are also provided as is a method for producing a semi-synthetic HAT domain.

Abstract: The invention provides methods and compositions for the modulation of EGFR activity, in particular, inhibition of EGFR activation through an allosteric mechanism is discloses, as is a method for targeted drug discovery and design based on models of the three dimensional structure of the kinase domains of the protein dimers.

Abstract: A method for data transfer between a client system and a server comprises receiving one or more user-defined file transfer specifications and establishing a communication channel between a client system and a server system based on the file transfer specifications. The method also includes initializing transfer of operation data between the client system and the server system via the communication channel. The method further includes providing an exception notification to one or more user-designated recipients if the transfer of the operation data between the client system and the server system is inconsistent with the file transfer specifications.

Abstract: A machine data acquisition system is disclosed. The data acquisition system may include a sensor disposed on a machine and configured to produce a signal indicative of an operational parameter of the machine. The system may also include a data processor and controller configured to convert the signal into a plurality of parameter data points. The system may further include a primary data circular buffer disposed on the machine and configured to store the plurality of parameter data points. Additionally, a variable resolution circular buffer may be disposed on the machine and configured to store a compressed parameter data point calculated from the plurality of parameter data points.

Abstract: A method for data transfer between a client system and a server comprises receiving one or more user-defined file transfer specifications and establishing a communication channel between a client system and a server system based on the file transfer specifications. The method also includes initializing transfer of operation data between the client system and the server system via the communication channel. The method further includes providing an exception notification to one or more user-designated recipients if the transfer of the operation data between the client system and the server system is inconsistent with the file transfer specifications.

Abstract: Protein kinase inhibitors have applications as anti-cancer therapeutic agents and biological tools in cell signalling. Potent and selective bisubstrate inhibitors for the insulin receptor tyrosine kinase are based on a phosphoryl transfer mechanism involving a dissociative transition state. One such inhibitor is synthesized by linking ATP?S to a peptide substrate analog via a two-carbon spacer. The compound is a high-affinity competitive inhibitor against both nucleotide and peptide substrate and shows a slow off-rate. A crystal structure of this inhibitor bound to the tyrosine kinase domain of the insulin receptor confirms the key design features inspired by a dissociative transition state, and reveal that the linker takes part in the octahedral coordination of an active site Mg2+ ion.

Abstract: By providing a single house (21) which incorporates an elongated probe (22) receiving zone interconnected to a pump member (55), a plurality of automated valves (51-54), a disinfectant dispensing chamber (20), a water supply (41), and a control system for automatically cycling each of the components to achieve the desired result, a fully automated disinfection system (20) for transesophageal ultrasonic probes is achieved. In accordance with the present invention, a simple, easily employed, convenient, fully integrated system (20) is attained for quickly and easily receiving the transesophageal ultrasonic probe in its entirety, supporting the electronic bearing head portion independently from the disinfection portion, and automatically performing various disinfection and rinse cycles for providing a completely disinfected ultrasonic probe member ready for use.

Abstract: The present invention provides a method of cleaving a recombinantly expressed protein from an intein and ligating the protein to a peptide containing an N-terminal cysteine having an unoxidized sulfhydryl side chain which comprises contacting the protein with the peptide in a reaction solution comprising a conjugated thiophenol, thereby forming a C-terminal thioester of the recombinant protein which spontaneously rearranges intramolecularly to form an amide bond linking the protein to the peptide.

Abstract: A method and apparatus in a data processing system for managing distribution of data structures. A first data structure is received including a first version identifier. The version identifier is stored for the first data structure. A second structure is received including a second version identifier. Responsive to receiving a second data structure, a determination is made as to whether the second data structure is a replacement for the first data structure. Responsive to the second data structure being a replacement for the first data structure, a determination is made as to whether the first version identifier is different from the second version identifier. Responsive to a determination that the first version identifier is different from the second version identifier, the first data structure is replaced with the second data structure.

Abstract: The present invention provides a method of cleaving a recombinantly expressed protein from an intein and ligating the protein to a peptide containing an N-terminal cysteine having an unoxidized sulfhydryl side chain which comprises contacting the protein with the peptide in a reaction solution comprising a conjugated thiophenol, thereby forming a C-terminal thioester of the recombinant protein which spontaneously rearranges intramolecularly to form an amide bond linking the protein to the peptide.

Abstract: Histone acetyltransferase inhibitors, especially those that are differentiate between p300 and PCAF histone acetyltransferase; also therapeutic processes comprising their administration to humans.

Abstract: Protein kinase inhibitors have applications as anti-cancer therapeutic agents and biological tools in cell signalling. Potent and selective bisubstrate inhibitors for the insulin receptor tyrosine kinase are based on a phosphoryl transfer mechanism involving a dissociative transition state. One such inhibitor is synthesized by linking ATP&ggr;S to a peptide substrate analog via a two-carbon spacer. The compound is a high-affinity competitive inhibitor against both nucleotide and peptide substrate and shows a slow off-rate. A crystal structure of this inhibitor bound to the tyrosine kinase domain of the insulin receptor confirms the key design features inspired by a dissociative transition state, and reveal that the linker takes part in the octahedral coordination of an active site Mg2+ ion.

Abstract: A detailed three-dimensional structure for the complex formed between Ras and the Son of sevenless (Sos) protein is provided. Crystals of this complex are also included in the invention. The present invention farther provides procedures for identifying agents that can inhibit tumor proliferation through the use of rational drug design predicated on the crystals and crystallographic data disclosed.

Abstract: A detailed three-dimensional structure for the complex formed between Ras and the Son of sevenless (Sos) protein is provided. Crystals of this complex are also included in the invention. The present invention further provides procedures for identifying agents that can inhibit tumor proliferation through the use of rational drug design predicated on the crystals and crystallographic data disclosed.

Abstract: This invention is directed to a compound having the formula I. ##STR1## This invention is directed to a pharmaceutical composition comprising a compound which inhibits serotonin N-acetyltransferase having the formula I and a pharmaceutical acceptable carrier. The present invention relates to novel compounds and analogs which inhibit the serotonin N-acetyltransferase enzyme, and to processes for their preparation.