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排序方式: 共有535条查询结果,搜索用时 463 毫秒
1.
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
2.
Locke Davenport Huyer Serena Mandla Yufeng Wang Scott B. Campbell Bess Yee Christian Euler Benjamin F. Lai A. Dawn Bannerman Dawn S. Y. Lin Miles Montgomery Kayla Nemr Timothy Bender Slava Epelman Radhakrishnan Mahadevan Milica Radisic 《Advanced functional materials》2021,31(6):2003341
Itaconate (ITA) is an emerging powerhouse of innate immunity with therapeutic potential that is limited in its ability to be administered in a soluble form. A library of polyester materials that incorporate ITA into polymer backbones resulting in materials with inherent immunoregulatory behavior is developed. Harnessing hydrolytic degradation release from polyester backbones, ITA polymers result in the mechanism specific immunoregulatory properties on macrophage polarization in vitro. In a functional assay, the polymer-released ITA inhibits bacterial growth on acetate. Translation to an in vivo model of biomaterial associated inflammation, intraperitoneal injection of ITA polymers demonstrate a rapid resolution of inflammation in comparison to a control polymer silicone, demonstrating the value of sustained biomimetic presentation of ITA. 相似文献
3.
Yu Yang Hugo Bender Kai Arstila Bart Swinnen Bert Verlinden Ingrid De Wolf 《Microelectronics Reliability》2008,48(8-9):1517-1520
Focused ion beam (FIB) and nano-probing were applied for failure analysis of three-dimensional stacked circuits with copper through-silicon-vias between the stacked chips. The failure analysis was done after high temperature storage and thermal cycling tests. Passive voltage contrast in FIB allowed to pinpoint the open sites. FIB cross-sections showed the presence of opens at the bottom of the copper vias. The failure cause was suspected to be an interlayer particle, which was confirmed by optical profilometry. Nano-probing was used on another sample to pinpoint the failure location through the measurement of the local resistance within the daisy chains. The failure was traced out to be related with surface contamination. 相似文献
4.
Materials Science - Results are presented on the tendency to stress corrosion cracking in NACE solution for welded joints in tube steel with sulfur contents from 0.002 to 0.028%. Threshold stresses... 相似文献
5.
Christiane Bender 《Industry and innovation》1996,3(2):153-162
The Paper develops a critique of industrial restructuring measures from the perspective of social innovation theory. Three kinds of industrial restructure are discussed: business process re-engineering; computer-integrated manufacturing; and lean production. The paper argues that the dominant approaches to these restructuring initiatives are socially deficient in that they do not draw on the full potential of the workforce. 相似文献
6.
Barium strontium titanate glass-ceramics were successfully produced with one major crystalline phase when Al2O3 was added to the melt. A dielectric constant of 1000 and a breakdown strength of 800 kV/cm was achieved; however the energy
density was only measured to be 0.3–0.9 J/cm3. These energy density values were lower than anticipated due to the presence of dendrites and pores in the microstructure.
Using BaF2 as a refining agent improved the microstructure and doubled the energy density for BST 80/20 samples. However, no refining
agent reduced the increasing amount of hysteresis that developed with increasing applied electric field. This phenomenon is
believed to be due to interfacial polarization. 相似文献
7.
Discusses the impact of asthma on children's educational experiences. Respiratory arrest or hypoxia may lead to neuropsychological changes in a few cases, and some medications may produce mild, temporary changes, affecting learning and classroom performance. For most asthmatic children, their illness does not result in permanent brain function changes that compromise their educational adaptation and performance. Increased school absence, stress of chronic illness, isolation from peers, diminished physical activities, reduced adult expectations and self esteem, and depression can compromise children's academic adaptation and progress. Co-occurrence of factors like severe illness, poverty, and family dysfunction may increase the risk for educational and psychosocial impairment. Systematic and comprehensive education of asthmatic patients, their parents, and school personnel is crucial to improving the control of asthma and activity level. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
8.
JB Bender S Sreevatsan RA Robinson D Otterby 《Canadian Metallurgical Quarterly》1997,80(11):3064-3067
As part of a total mixed ration, two rumen-fistulated dairy cows were fed meat and bone meal that had been artificially contaminated with Salmonella spp. Samples from the rumen, feces, and milk were taken 3 d/wk and cultured for salmonella. Rectal temperatures and rumen pH were also measured at the time of sample collection. Over the 2-mo study, salmonella were intermittently recovered from rumen contents, from feces, and from necropsy specimens of rumen contents, cecal contents, and mesenteric lymph nodes. No excretion of salmonella in milk was detected. An elevated rumen pH was associated with increased isolation of salmonella. No clinical illness was observed for either cow. Meat and bone meal that has been contaminated with low concentrations of salmonella is unlikely to result in clinical illness in healthy adult lactating cows. However, dairy producers should continue to be concerned about feed biosecurity and water contamination of animal by-products to prevent and control contamination by salmonella. 相似文献
9.
Interactive rigid body simulation is an important part of many modern computer tools, which no authoring tool nor game engine can do without. Such high‐performance computer tools open up new possibilities for changing how designers, engineers, modelers and animators work with their design problems. This paper is a self contained state‐of‐the‐art report on the physics, the models, the numerical methods and the algorithms used in interactive rigid body simulation all of which have evolved and matured over the past 20 years. Furthermore, the paper communicates the mathematical and theoretical details in a pedagogical manner. This paper is not only a stake in the sand on what has been done, it also seeks to give the reader deeper insights to help guide their future research. 相似文献
10.
Thomas W. Coyle William S. Coblenz Barry A. Bender 《Journal of the American Ceramic Society》1988,71(2):88-C-
The fracture and transformation behavior of tetragonal polycrystalline ZrO2 alloys containing 18 mol% CeO2 (Ce-TZP) was investigated. In the absence of applied stress the tetragonal phase was found to be stable in large-grained (>30 μm) samples at room temperature. The monoclinic phase was detected in regions of high residual stress near hardness indentations although no evidence of a wake of monoclinic phase along the fracture surface was observed. The fracture toughness increased from 4 to 7 MPa · m1/2 as density and/or grain size increased. It is proposed that the relatively high toughness of these materials is due to the occurrence of stress-driven tetragonal-to-monoclinic transformation near the crack tip, which reverses when the crack has passed. 相似文献