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61.
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
62.
豫西熊耳山雷门沟钼矿床位于东秦岭多金属成矿带东段,是已探明的超大型斑岩型钼矿,前人研究程度高、地质成果丰硕,但对矿床开采技术条件方面研究较少。本次通过地质调查工程、水文地质试验等方法,从水文地质角度,对雷门沟钼矿床水文地质条件进行研究,填补了该方面的空白,丰富了研究成果;采用水文地质比拟法预测未来矿坑最大排水量2613 m3/d,经实践检验结果较为可靠;总结的采坑排水量预测方法、含水层特点、矿床充水因素以及防治水措施,以期对该区域水文地质工作具有参考价值。 相似文献
63.
Thermal barrier coatings (TBCs) produced by electron beam physical vapor deposition (EB-PVD) or plasma spray (PS) usually suffer from molten calcium-magnesium-alumino-silicate (CMAS) attack. In this study, columnar structured YSZ coatings were fabricated by plasma spray physical vapor deposition (PS-PVD). The coatings were CMAS-infiltrated at 1250?°C for short terms (1, 5, 30?min). The wetting and spreading dynamics of CMAS melt on the coating surface was in-situ investigated using a heating microscope. The results indicate that the spreading evolution of CMAS melt can be described in terms of two stages with varied time intervals and spreading velocities. Besides, the PS-PVD columnar coating (~100?μm thick) was fully penetrated by CMAS melt within 1?min. After the CMAS attack for 30?min, the original feathered-YSZ grains (tetragonal phase) in both PS-PVD and EB-PVD coatings were replaced by globular shaped monoclinic ZrO2 grains in the interaction regions. 相似文献
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65.
Qun Ren Haijun Su Jun Zhang Haifang Liu Weidan Ma Guangrao Fan Di Zhao Min Guo Lin Liu Hengzhi Fu 《Ceramics International》2019,45(6):6632-6638
Directionally solidified microstructures of Al2O3-Er3Al5O12 eutectic and off-eutectic in situ composite ceramics were explored under abrupt-change pulling rate conditions. Corresponding temperature distributions and interface locations were studied. In eutectic composition, fluctuation of eutectic spacing occurred when the pulling rate increased abruptly. A gradually increase or abrupt increase in eutectic spacing was observed when the pulling rate decreased abruptly. In hypoeutectic and hypereutectic compositions, formation of the primary phases were suppressed when the pulling rate increased abruptly from 10?µm/s to 100?µm/s, while primary phases precipitated when the pulling rate decreased abruptly from 100?µm/s to 10?µm/s. The interface altitude decreased after the pulling rate increased abruptly, but increased after the pulling rate decreased abruptly. The liquid composition restriction (around the eutectic composition) at the eutectic interface plays an important role in the suppression of the primary dendrite and coupled eutectic oxides can be obtained in off-eutectic compositions even under higher solidification rate conditions. 相似文献
66.
This paper discusses the compressive performance of perforated brick masonry after fire exposure. Compressive strength tests of the mortar, clay perforated brick, and perforated brick masonry specimens were performed in accordance with ISO834 fire tests of different durations. The temperature distribution of the masonry materials and specimens was simulated using the finite element software ABAQUS, with the thermal parameters of masonry materials recommended by European standard Eurocode 6 and related literature. The compressive strength reduction factors of mortar and clay perforated brick exposed to different fire durations were calculated via the layered method suggested by European standard Eurocode 1. In addition, the compressive strength reduction factors after cooldown were obtained from the experimental data of the masonry materials, and by considering further reductions in the compressive strength after cooling from high temperatures. Experimental data of the masonry specimens were compared with the numerical results obtained using the reduction factors proposed in this work. The comparison revealed an overall acceptable approximation. Thus, the method presented in this paper can be used to evaluate the residual capacity of masonry structures after fire. 相似文献
67.
测向误差的减小一直以来都是无线电测向精度提高的一个难点,对于不同的测向体制所采用的减小测向误差的方法都不尽相同。本文主要介绍的是相关干涉仪测向体制的基本原理以及通过内插法的应用来减小测向误差的方法。 相似文献
68.
69.
为研究古建筑木结构透榫节点的M-θ力学模型,在分析透榫节点构造特征与受力机理的基础上,建立其数值模型,用透榫节点的试验数据验证了该数值模型的正确性,并分析了节点缝隙、木材横纹弹性模量和大榫头长度对透榫节点受弯承载力的影响。根据受力分析结果,建立以弹性点、屈服点与极限点为特征点的三折线多参数M-θ力学模型,其结果与多数的试验结果基本吻合,并将该力学模型应用于木构架的受力分析。研究结果表明:透榫节点的滞回耗能能力强,节点的变形主要集中在榫头处。当榫头与卯口之间的缝隙增大时,节点的受弯承载力降低。随木材横纹弹性模量的提高和大榫头长度的增加,节点的受弯承载力有一定提高。文章建立的M-θ力学模型能较好反映透榫节点的受力过程,适用于木构架的受力分析,其荷载 位移骨架曲线与试验结果基本吻合。研究成果可为古建筑木结构的维修与保护提供参考。 相似文献
70.