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111.
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
112.
Yang Yang Yibei Zhou Juan Ren Qiaoji Zheng Kwok Ho Lam Dunmin Lin 《Journal of the European Ceramic Society》2018,38(2):557-566
Perovskite ferroelectrics possess the fascinating piezoelectric properties near a morphotropic phase boundary, attributing to a low energy barrier that the results in structural instability and easy polarization rotation. In this work, a new lead-free system of (1-x)BaTiO3-xCaHfO3 was designed, and characterized by a coexistence of ferroelectric rhombohedral-orthorhombic-tetragonal (R-O-T) phases. With the increase amount of CaHfO3 (x), a stable coexistence region of three ferroelectric phases (R-O-T) exists at 0.06 ≤ x ≤ 0.08. Both large piezoelectric coefficient (d33~400 pC/N), inverse piezoelectric coefficient (d33*~547 pm/V) and planar electromechanical coupling factor (kp~58.2%) can be achieved for the composition with x = 0.08 near the coexistence of three ferroelectric phases. Our results show that the materials with the composition located at a region where the three ferroelectric R-O-T phases coexist would have the lowest energy barrier and thus greatly promote the polarization rotation, resulting in a strong piezoelectric response. 相似文献
113.
Tian Xiaoying Peng Hui Luo Xuguang Nie Shiyuan Zhou Feng Peng Xiaoyan 《International Journal of Control, Automation and Systems》2020,18(4):897-910
International Journal of Control, Automation and Systems - There is a class of typical nonlinear industrial process, which can be characterized by a first-order inertia plus pure delay model in an... 相似文献
114.
刘家山排土场为民采排弃形成,已经出现大规模滑坡。为了保证上下游生产生活设施的安全,依据现场实际情况,结合现场调查,提出了削坡处理的方案。经过治理后,刘家山排土场平稳地渡过了雨季,目前处于稳定状态,达到了治理目的。 相似文献
115.
The Caputo and Caputo–Fabrizio derivative are applied to study a second‐grade nanofluid over a vertical plate. A comparative analysis is presented to study the unsteady free convection of a second‐grade nanofluid with a new time–space fractional heat conduction. The governing equations with mixed time–space fractional derivatives are non‐dimensionalized and solved numerically, and a comparison between the Caputo and the Caputo–Fabrizio models is made. It is found that the temperature is higher for the Caputo–Fabrizio fractional model than the Caputo model, but the higher velocity only exists near the vertical plate for the Caputo–Fabrizio model than the Caputo model. Moreover, the velocity for the Caputo model will exceed the Caputo–Fabrizio model as y evolves. 相似文献
116.
文章中主要采用有机溶剂萃取法(OSE)对高浓度石油污染土壤进行修复,经过精馏操作,有效回收原油,建立脱附等温曲线,研究了石油污染物在土壤-有机溶剂两相间的迁移规律。 相似文献
117.
118.
Yingchao Hu Wenqiang Liu Yuandong Yang Xianliang Tong Qianjun Chen Zijian Zhou 《Ceramics International》2018,44(14):16668-16677
Li4SiO4 sorbents for high-temperature CO2 removal have drawn extensive attention owing to their potential application in carbon capture and storage (CCS). The major challenge in the application lies in the poor CO2 capture performance under realistic conditions of low CO2 concentrations, owing to the dense structure and poor porosity. In this work, Li4SiO4 sorbents were prepared with porous micromorphologies and large contact areas using a variety of organometallic Li-precursors, achieving fast CO2 sorption kinetics, high capacity and excellent cyclic stability at a low CO2 concentration (15?vol%). It was found that a high conversion of ~?74% was maintained for pure Li4SiO4 even after 100 sorption/desorption cycles. Moreover, by doping with Na2CO3 to reduce the CO2 diffusion resistance, the conversion of the sorbent was further enhanced to 93.2%. The enhancement mechanism of alkali carbonate have been proven here to be ascribed to the formation of the eutectic melt of Li/Na carbonates, the existence and function of which has been confirmed in this study. 相似文献
119.
由于AD HOC网络自身的特点,其网络管理很多方面与固定网络不同,如移动性管理和体系结构管理等。讨论了AD HOC网络管理的各个方面,并列举了各个方面的设计思路和已有的相关算法的简介。 相似文献
120.
聚烯烃催化剂硅胶载体的制备和表征 总被引:3,自引:0,他引:3
采用并流共沉淀法制备了适用于聚烯烃催化剂的硅胶载体,为减少颗粒的聚集,在制备过程中添加一种表面活性剂。利用透射电子显微镜(TEM)、比表面积测定(BET)和X射线粉末衍射(XRD)法对制备的硅胶载体进行了表征;考察了在制备硅胶载体过程中原料硅酸钠溶液的浓度、溶液pH以及焙烧温度对产物硅胶载体的物理性能的影响。实验结果表明,硅酸钠溶液的浓度影响硅胶的初始粒子的大小,溶液pH直接影响硅酸钠的水解速率,焙烧温度影响硅胶的孔结构和比表面积。当硅酸钠溶液的浓度为0.2mol/L、溶液pH为8-9、反应温度为70℃、焙烧温度为700℃时,硅胶载体的BET比表面积为242.22m2/g、最可几孔径为16.45 nm、堆密度为0.492 1g/mL,与进口硅胶(Silica Gel 955)的物理性能相近。 相似文献