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51.
To minimize the mass and increase the bearing failure load of composite doublelap bolted joints, a three-step optimization strategy including feasible region reduction, optimization model decoupling and optimization was presented. In feasible region reduction, the dimensions of the feasible design region were reduced by selecting dominant design variables from numerous multilevel parameters by sensitivity analyses, and the feasible regions of variables were reduced by influence mechanism analyses. In model decoupling, the optimization model with a large number of variables was divided into various sub-models with fewer variables by variance analysis. In the third step, the optimization sub-models were solved one by one using a genetic algorithm, and the modified characteristic curve method was adopted as the failure prediction method. Based on the proposed optimization method, optimization of a double-lap single-bolt joint was performed using the ANSYS® code. The results show that the bearing failure load increased by 13.5% and that the mass decreased by 8.7% compared with those of the initial design of the joint, which validated the effectiveness of the three-step optimization strategy.  相似文献   
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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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Abstract

Graphene oxide (GO) was functionalized by polyether amine (PEA) via two methods which were one-pot modification in acetone (GON) and two steps with the intermediate product of GOCO-Cl generated (GONS). There were more PEA successfully grafted onto GO for GONS than GON. The onset polymerization temperatures of the benzoxazine (Bz) composites decreased by the inclusion of 1?wt% of GO, GON or GONS. Thermal stability of the polybenzoxazine (PBz) composites was significantly improved indicated from the increase of weight loss temperature. T10, T20 and T50 values of the composites with GONS were higher than that of the others. Toughness of PBzs may be enhanced by the incorporation of nanofillers, and GONS had stronger interfacial interaction with PBz matrix than GON.  相似文献   
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Porous polyimide (PI) films with low dielectric constants and excellent thermal properties have been a pressing demand for the next generation of high-performance, miniature, and ultrathin microelectronic devices. A series of novel porous PI films containing fluorenyl-adamantane groups were prepared successfully via thermolysis of poly(ethylene glycol) (PEG) added in the PI matrix. The cross-sectional morphologies of porous PI films showed closed pores with diameters ranging from 135 to 158 nm, which were uniform and regular in shape without interconnectivity. These porous PI films exhibited excellent thermal properties with a glass-transition temperature at 376 °C whereas the 5% weight loss temperature in air excess of 405 °C due to enhanced rigidity afforded by fluorenyl-adamantane groups. Accompanied by thermolysis content of PEG increasing from 0 to 20 wt %, the density of porous PI films decreased, and the corresponding porosity grew significantly from 0 to 11.48%. Depending on porosity, the dielectric constant and dielectric loss of porous PI films significantly declined from 2.89 to 2.37 and from 0.050 to 0.021, respectively. These excellent properties benefit the as-prepared porous PI films for application as interlayer dielectrics, integrated circuit chips, or multichip modules in microelectronic fields. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47313.  相似文献   
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The flame front deformation instability of low-velocity filtration combustion within an inert packed bed is studied based on the initial preheating non-uniformity. Based on the experimental phenomena, an initial thermal perturbation model is numerically proposed so as to predict the deformation behaviors of the flame front instabilities. The numerical prediction indicates that the assumption of an initial thermal perturbation is a feasible explanation as the cause of the flame front inclination instability. As the initial thermal perturbation increases, the phenomena of the flame front break and shrinking instabilities could easily occur at high filtration velocity or low equivalence ratio. Moreover, the evolutions of the flame front break rate and the shrinking rate are quantitatively analyzed.  相似文献   
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文章结合广东省惠州东江水利枢纽工程的具体情况,对110 kV变电站进行了优化设计,通过对110 kV变电站采用敞开式布置、主变与GIS同平面布置、主变与GIS采用两层布置的三种不同设备选型及布置方式的技术和经济比较,推荐采用主变与GIS同平面的布置方案.GIS的使用,不仅满足电站运行可靠、灵活及运行维护方便等要求,而且也加快了施工进度,与周围的环境融合在一起,增添了工程的亮点.  相似文献   
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