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排序方式: 共有1160条查询结果,搜索用时 1 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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D. Dietrich ÖVE H. Reiter Th. Sauter H. -J. Schweinzer 《e & i Elektrotechnik und Informationstechnik》1997,114(5):225-230
The past decade may be regarded as the phase of the fundamental developments in fieldbus systems that were based on the OSI model. Today we are entering a second stage. It is the objective of this issue to present the current state and where the further developments will lead to. This introductory article is intended to give an overview on the subject. 相似文献
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M. Muhr ÖVE S. Pack ÖVE H. Haidvogl F. Kreyca 《e & i Elektrotechnik und Informationstechnik》1997,114(11):680-686
Recently appeared defects on high voltage cables have required an urgent evaluation of the impact of lightning strikes necessary. In some cases overvoltages between the copper wire screen of the cable and earth may appear which cause damages of the cablesheath. Field measurements with a classification of the voltage impulses at the copper wire screen have been made to evaluate the number of events. Additionally a numerical model was developed to study the effects of atmospheric discharges on underground cables with emphasis to the influence on the cablesheath. This numeric method was also applied to estimate the effectiveness of different protection arrangements. This contribution presents evaluation methods for overvoltages of cables and a model used firstly for calculating the stress caused by differential voltages and secondly to determinate the influence of protection measures. 相似文献
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The mechanical properties of totally ischemic hearts of inbred albino rats were studied. The ischemic myocardium was found to be more sensitive to cyclic loads. Energy deficient contracture of cardiomyocytes is a factor which increases the resistance of the myocardium to mechanical effects. 相似文献
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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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