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排序方式: 共有6045条查询结果,搜索用时 31 毫秒
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Dr. Yahu A. Liu Dr. Qihui Jin Qiang Ding Dr. Xueshi Hao Tingting Mo Shanshan Yan Dr. Yefen Zou Dr. Zhihong Huang Xiaoyue Zhang Wenqi Gao Dr. Tom Y.-H. Wu Chun Li Dr. Badry Bursalaya Dr. Michael Di Donato Dr. You-Qing Zhang Lisa Deaton Dr. Weijun Shen Dr. Brandon Taylor Anwesh Kamireddy Dr. George Harb Dr. Jing Li Dr. Yong Jia Dr. Andrew M. Schumacher Dr. Bryan Laffitte Dr. Richard Glynne Dr. Shifeng Pan Dr. Peter McNamara Dr. Valentina Molteni Dr. Jon Loren 《ChemMedChem》2020,15(16):1562-1570
Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation. 相似文献
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为提高生产效率、改变原来通过车削加工汽车悬架球头拉杆的方式,提出了一种球头拉杆的多工位冷镦成形工艺。基于DEFORM-3D软件建立了有限元模型,对球头拉杆的塑性成形过程进行了仿真,研究了预成形凸模入模角α、预成形凹模圆角R1、终成形凹模圆角R2以及终成形凹模入模角β等工艺参数对球头拉杆成形的影响,并进行了正交试验,以模具在球头拉杆成形过程中所受载荷及工件损伤值为优化目标,获得了合理的工艺参数组合。结果表明:在保证工件成形质量及模具寿命的前提下,当预成形凸模入模角α为30°、预成形凹模圆角R1为12 mm、终成形凹模圆角R2为3 mm、终成形凹模入模角β为60°时,模具载荷及工件损伤有显著的降低。采用优化后的参数进行试模生产,工件成形质量较好,验证了模拟结果的可信性,能够有效地指导工艺设计人员的设计工作。 相似文献
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以合肥市为例,选取人均水资源量、年产水模数、人均供水量、植被覆盖率、日生活用水量、万元GDP用水量、万元工业增加值需水量、人口密度、城市化率、农田灌溉定额、水资源开发利用率、人均GDP、污水排放达标率、水功能区达标率、生态用水率15个指标,在建立合肥市水资源承载力评价指标体系及等级标准体系的基础上,构建模糊分析模型并借助Matlab工具计算隶属度、确定指标权重,进而计算2013~2017年水资源承载等级,获得了合肥市水资源承载力情况,计算结果对合肥市水资源开发利用具有一定的参考意义。 相似文献
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Zhao-Hua Mo Rui Yang Song Hong Yi-Xian Wu 《International Journal of Hydrogen Energy》2018,43(3):1790-1804
Introducing graphene into polymer matrix is an effective way to enhance performances of anion exchange membrane (AEM). However, utilizing the advantages of graphene by physical approach is limited due to the weak interface interaction between graphene and polymer matrix. Herein, we report an effective strategy to covalently bond graphene with polymer matrix to improve the interface interaction and further to improve the properties of AEM. A series of cross-linked quaternized graphene-based hybrid AEM were fabricated by covalently bonding poly (vinylbenzyl chloride) grafted graphene (GN-g-PVBC) copolymer with chloromethyl functionalized poly (styrene-b-isobutylene-b-styrene) (SIBS) through the cross-linker (N,N,N′,N′-tetramethyl-1,6-hexanediamine) by in-situ synthetic approach. The interface interaction between graphene and QSIBS is greatly enhanced according to micromorphology characterization of the hybrid membrane. The cross-linked quaternized hybrid AEM containing 0.55 wt% of GN-g-PVBC exhibits obviously improved dynamical mechanical properties (storage modulus: 418 MPa), ion conductivity (1.81 × 102 S cm?1), methanol barrier property (5.19 × 10?7 cm2 s?1), selectivity (3.49 × 104 S s cm?3) at 60 °C and especially a comparably excellent chemical stability to that of Nafion 115 due to the enhanced interface interaction between graphene and the polymer matrix. 相似文献
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This paper is prepared in honour of Professor E.T. Brown for his outstanding contributions to rock mechanics and geotechnical engineering and also for his personal influence on the first author's research career in geomechanics and geotechnical engineering. As a result, we have picked a topic that reflects two key research areas in which Professor E.T. Brown has made seminal contributions over a long and distinguished career. These two areas are concerned with the application of the critical state concept to modelling geomaterials and the analysis of underground excavation or tunnelling in geomaterials.Partially due to Professor Brown's influence, the first author has also been conducting research in these two areas over many years. In particular, this paper aims to describe briefly the development of a unified critical state model for geomaterials together with an application to cavity contraction problems and tunnelling in soils. 相似文献
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材料的总体一次薄膜应力强度许用值(Smt)是高温反应堆设备结构设计力学分析的重要判定依据,但美国机械工程师协会(ASME)的规范和法国《快堆核岛机械设备设计和建造规范》(RCC-MR)给出的最长30万小时的Smt不能满足长寿期反应堆的设计要求。本文基于ASME规范给出的30万小时许用应力、预计最小断裂应力及断裂应力系数等材料蠕变性能数据,采用Larson-Miller外推模型成功获得了50万小时长寿期的316不锈钢母材和焊缝的长时蠕变性能,可满足长寿期反应堆的设计要求。 相似文献
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