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排序方式: 共有947条查询结果,搜索用时 15 毫秒
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Dr. Hui Qiu Richard Caldwell Dr. Lesley Liu-Bujalski Dr. Andreas Goutopoulos Reinaldo Jones Justin Potnick Dr. Brian Sherer Dr. Andrew Bender Dr. Roland Grenningloh Dr. Daigen Xu Dr. Anna Gardberg Dr. Igor Mochalkin Dr. Theresa Johnson Dr. Ariele Viacava Follis Jared Head Dr. Federica Morandi 《ChemMedChem》2019,14(2):217-223
Bruton's tyrosine kinase (Btk) is an attractive target for the treatment of a wide array of B-cell malignancies and autoimmune diseases. Small-molecule covalent irreversible Btk inhibitors targeting Cys481 have been developed for the treatment of such diseases. In clinical trials, probe molecules are required in occupancy studies to measure the level of engagement of the protein by these covalent irreversible inhibitors. The result of this pharmacodynamic (PD) activity provides guidance for appropriate dosage selection to optimize inhibition of the drug target and correlation of target inhibition with disease treatment efficacy. This information is crucial for successful evaluation of drug candidates in clinical trials. Based on the pyridine carboxamide scaffold of a novel solvent-accessible pocket (SAP) series of covalent irreversible Btk inhibitors, we successfully developed a potent and selective affinity-based biotinylated probe 12 (2-[(4-{4-[5-(1-{5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamido}-3,6,9,12-tetraoxapentadecan-15-amido)pentanoyl]piperazine-1-carbonyl}phenyl)amino]-6-[1-(prop-2-enoyl)piperidin-4-yl]pyridine-3-carboxamide). Compound 12 has been used in Btk occupancy assays for preclinical studies to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon. 相似文献
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Yan T Wong Norbert Dommel Philip Preston Luke E Hallum Torsten Lehmann Nigel H Lovell Gregg J Suaning 《IEEE transactions on neural systems and rehabilitation engineering》2007,15(3):425-434
A neurostimulator application-specific integrated circuit (ASIC) with scalable circuitry that can stimulate 14 channels, has been developed for an epi-retinal vision prosthesis. This ASIC was designed to allow seven identical units to be connected to control up to 98 channels, with the ability to stimulate 14 electrodes simultaneously. The neurostimulator forms part of a vision prosthesis, designed to restore vision to patients who have lost their sight due to retinal diseases such as retinitis pigmentosa and macular degeneration. For charge balance, the neurostimulator was designed to stimulate with current sources and sinks operating together, and with the ability to drive a hexagonal mosaic of electrodes to reduce the electrical crosstalk that occurs when multiple bipolar stimulation sites are active simultaneously. A hexagonal mosaic of electrodes surrounds each stimulation site and has been shown to effectively isolate each site, increasing the ability to inject localized independent charge into multiple regions simultaneously. 相似文献
5.
GL Anderson KN Caldwell LR Beuchat PL Williams 《Canadian Metallurgical Quarterly》2003,66(9):1543-1549
Free-living nematodes may harbor, protect, and disperse bacteria, including those ingested and passed in viable form in feces. These nematodes are potential vectors for human pathogens and may play a role in foodborne diseases associated with fruits and vegetables eaten raw. In this study, we evaluated the associations between a free-living soil nematode, Caenorhabditis elegans, and Escherichia coli, an avirulent strain of Salmonella Typhimurium, Listeria welshimeri, and Bacillus cereus. On an agar medium, young adult worms quickly moved toward colonies of all four bacteria; over 90% of 3-day-old adult worms entered colonies within 16 min after inoculation. After 48 h, worms moved in and out of colonies of L. welshimeri and B. cereus but remained associated with E. coli and Salmonella Typhimurium colonies for at least 96 h. Young adult worms fed on cells of the four bacteria suspended in K medium. Worms survived and reproduced with the use of nutrients derived from all test bacteria, as determined for eggs laid by second-generation worms after culturing for 96 h. Development was slightly slower for worms fed gram-positive bacteria than for worms fed gram-negative bacteria. Worms that fed for 24 h on bacterial lawns formed on tryptic soy agar dispersed bacteria over a 3-h period when they were transferred to a bacteria-free agar surface. The results of this study suggest that C. elegans and perhaps other free-living nematodes are potential vectors for both gram-positive and gram-negative bacteria, including foodborne pathogens in soil. 相似文献
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Alexander A. Kortt J. Bruce Caldwell 《Journal of the science of food and agriculture》1985,36(9):863-870
The acidic and basic lectins of the winged bean were isolated from seed extracts by affinity chromatography on lactose-Sepharose 6B and melibiose Bio-Gel P150, respectively. The lectins isolated from six varieties of Psophocarpus tetragonolobus, collected from different regions of south-east Asia, showed no significant differences in their properties; their subunit Mr and amino acid compositions were the same as those of the acidic and basic lectins isolated by non-affinity methods. On isoelectric focusing the affinity purified acidic lectins showed two major protein components (isolectins) while the affinity purified basic lectins had four protein components. The acidic lectins showed a preference for β-D-galactosides and they agglutinated trypsinised human type A, B and O erythrocytes but not trypsinised rabbit erythrocytes. The basic lectins showed a preference for α-D-galactosides and they agglutinated trypsinised rabbit and human type A and B erythrocytes but not trypsinised human type O erythrocytes. 相似文献
8.
Les Hatton Andy Wright Stuart Smith Gregg Parkes Paddy Bennett Robert Laws 《Software》1988,18(4):301-329
The portability of software has become a major commercial issue in recent times. Such portability does not come easily, as few if any computer languages are really portable in practice. An additional complicating factor, especially in the commercial environment, is that the resulting software must be efficient. This paper describes the design and successful implementation of a 500,000+ line portable FORTRAN 77 package for the processing of seismic data. The package exhibits demonstrably high efficiency on a wide variety of machines from minicomputers to the largest supercomputers. Experiences gained during this exercise throw much light on the integration of the various thought processes which occur during the software engineering cycle, especially the notion of locality. 相似文献
9.
Reports the death of Martin Deutsch (1926-2002) and notes his contributions to the field of developmental psychology. Deutsch believed that environmental influences were critical for cognitive development during children's early years and that it was possible to design programs that would provide some of those experiences for children. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
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M Albert C Athanassopoulos LB Auerbach D Bauer R Bolton B Boyd RL Burman I Cohen DO Caldwell BD Dieterle JB Donahue AM Eisner A Fazely FJ Federspiel GT Garvey RM Gunasingha V Highland J Hill R Imlay K Johnston WC Louis A Lu AK Mann J Margulies K McIlhany W Metcalf RA Reeder V Sandberg M Schillaci D Smith I Stancu W Strossman MK Sullivan GJ VanDalen W Vernon YX Wang DH White D Whitehouse D Works Y Xiao S Yellin 《Canadian Metallurgical Quarterly》1995,51(3):R1065-R1069