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排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
992.
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
993.
994.
Bulge is a defect that causes geometrical inaccuracy and premature failure in the innovative incremental sheet forming (ISF) process. This study has two-fold objectives: (1) knowing the bulging behavior of a Cu clad tri-layered steel sheet as a function of forming conditions, and (2) analyzing the bending effect on bulging in an attempt to identify the associated mechanism. A series of ISF tests and bending analysis are performed to realize these objectives. From the cause-effect analysis, it is found that bulge formation in the layered sheet is sensitive to forming conditions in a way that bulging can be minimized utilizing annealed material and performing ISF with larger tool diameter and step size. The bending under tension analysis reveals that the formation of bulge is an outgrowth of bending moment that the forming tool applies on the sheet during ISF. Furthermore, the magnitude of bending moment depending upon the forming conditions varies from 0.046 to 10.24 N·m/m and causes a corresponding change in the mean bulge height from 0.07 to 0.91 mm. The bending moment governs bulging in layered sheet through a linear law. These findings lead to a conclusion that the bulge defect can be overcome by controlling the bending moment and the formula proposed can be helpful in this regards. 相似文献
995.
996.
Differences between oculomotor and perceptual artifacts for temporally limited head mounted displays
Alexander Goettker Kevin J. MacKenzie T. Scott Murdison 《Journal of the Society for Information Display》2020,28(6):509-519
We used perceptual and oculomotor measures to understand the negative impacts of low (phantom array) and high (motion blur) duty cycles with a high‐speed, AR‐likehead‐mounted display prototype. We observed large intersubject variability for the detection of phantom array artifacts but a highly consistent and systematic effect on saccadic eye movement targeting during low duty cycle presentations. This adverse effect on saccade endpoints was also related to an increased error rate in a perceptual discrimination task, showing a direct effect of display duty cycle on the perceptual quality. For high duty cycles, the probability of detecting motion blur increased during head movements, and this effect was elevated at lower refresh rates. We did not find an impact of the temporal display characteristics on compensatory eye movements during head motion (e.g., VOR). Together, our results allow us to quantify the tradeoff of different negative spatiotemporal impacts of user movements and make subsequent recommendations for optimized temporal HMD parameters. 相似文献
997.
Park Sangwon Nam Hyunbin Na Youngsang Kim Hyoungseop Moon Younghoon Kang Namhyun 《Metals and Materials International》2020,26(5):641-649
Metals and Materials International - This study investigated the influence of the initial grain size on the plastic deformation and tunnel defects that occurred from friction stir welding of... 相似文献
998.
Dr. Manuel Nieto-Domínguez Dr. Pablo I. Nikel 《Chembiochem : a European journal of chemical biology》2020,21(18):2551-2571
The diversity of life relies on a handful of chemical elements (carbon, oxygen, hydrogen, nitrogen, sulfur and phosphorus) as part of essential building blocks; some other atoms are needed to a lesser extent, but most of the remaining elements are excluded from biology. This circumstance limits the scope of biochemical reactions in extant metabolism – yet it offers a phenomenal playground for synthetic biology. Xenobiology aims to bring novel bricks to life that could be exploited for (xeno)metabolite synthesis. In particular, the assembly of novel pathways engineered to handle nonbiological elements (neometabolism) will broaden chemical space beyond the reach of natural evolution. In this review, xeno-elements that could be blended into nature's biosynthetic portfolio are discussed together with their physicochemical properties and tools and strategies to incorporate them into biochemistry. We argue that current bioproduction methods can be revolutionized by bridging xenobiology and neometabolism for the synthesis of new-to-nature molecules, such as organohalides. 相似文献
999.
The present study focuses on the sintering of silicon carbide-based ceramics (SiC) by liquid phase sintering (LPS) followed by characterization of the produced ceramics. AlN/Re2O3 mixtures were used as additives in the LPS process. In the first step, the LPS-SiC materials were produced in a graphite resistance furnace in the form of discs at different temperatures. The conditions with the best results regarding real density and relative density were taken as reference for sintering in the form of prismatic bars. In the second step, these samples were evaluated regarding fracture toughness (KIC), by the Single Edge V Notch Beam – SEVNB – method, and flexural strength. KIC behavior was evaluated according to the depth and curvature radius of the notches. Reliable KIC values were presented when the ceramic displayed a small curvature radius at the notch tip. When the radius was large, it did not maintain the square root singularity of the notch tip. Tests were carried out to determine KIC values in atmospheric air and water. KIC results were lower in water than air, with a decrease ranging between 2.56% and 11.26%. The observations indicated a direct grain size correlation between KIC values and fracture strength of the SiC ceramics. 相似文献
1000.
This study aims to evaluate the tribological behaviour of 3Y-TZP/Ta (20 vol%) ceramic-metal composites and 3Y-TZP monolithic ceramic prepared by spark plasma sintering (SPS) against ultrahigh molecular weight polyethylene (UHMWPE). According to the results of pin (UHMWPE)-on-flat wear test under dry conditions, the UHMWPE – 3Y-TZP/Ta system exhibited lower volume loss and friction coefficient than the UHMWPE – monolithic ceramic combination due to the presence of an autolubricating layer that provides sufficient lubrication for reducing the friction. Owing to the lubrication of the liquid media, under wet conditions obtained using simulated body fluid (SBF), similar behaviour is observed in both cases. Additionally, the ceramic and biocomposite materials were subjected to a low temperature degradation (LTD) process (often referred to as “ageing”) to evaluate the changes in the tribological behaviour after this treatment. In this particular case, the wear properties of the UHMWPE-biocomposite system were found to be less influenced by ageing in contrast to the case of the UHMWPE-zirconia monolithic material. In addition to their exceptional mechanical performance, 3Y-TZP/Ta composites also showed high resistance to low temperature degradation and good tribological properties, making them promising candidates for biomedical applications, especially for orthopaedic implants. 相似文献