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排序方式: 共有469条查询结果,搜索用时 125 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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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
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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
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Antiplasticization is applicable to polymers which contain rigid, polar groups and stiff chains, such as many bisphenol polycarbonates and polyesters, 2,2,4,4-tetramethyl-1,3-cyclobutanediol polycarbonates and polyesters, cellulose triacetate, and a commercial poly(sulfone ether). The stiffness, hardness, and tensile strength of these polymers are increased by antiplasticizers, and the elongation, impact strength, and heat-distortion temperature are decreased. The stiffness of antiplasticized polymers can be further increased by crystallization. A clear, hard, stiff, tough, self-extinguishing molding plastic with good electrical properties and improved resistance to stress cracking is obtained by antiplasticizing bisphenol A polycarbonate with 20% Aroclor 5460. 相似文献