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21.
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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Yong Pan Chen Zhu Wen Bin Zeng Pei Fu Chi Chen Bao Ming Xu Zhong Feng Gao 《Chembiochem : a European journal of chemical biology》2021,22(24):3431-3436
Rapid and sensitive point-of-care testing (POCT) is an extremely critical mission in practical applications, especially for rigorous military medicine, home health care, and in the third world. Here, we report a visual POCT method for adenosine triphosphate (ATP) detection based on Taylor rising in the corner of quadratic geometries between two rod surfaces. We discuss the principle of Taylor rising, demonstrating that it is significantly influenced by contact angle, surface tension, and density of the sample, which are controlled by ATP-dependent rolling circle amplification (RCA). In the presence of ATP, RCA reaction effectively suppresses Taylor-rising behavior, due to the increased contact angle, density, and decreased surface tension. Without addition of ATP, untriggered RCA reaction is favorable for Taylor rising, resulting in a significant height. With this proposed method, visual sensitive detection of ATP without the aid of other instruments is realized with only a 5 μL droplet, which has good selectivity and a low detection limit (17 nM). Importantly, this visual method provides a promising POCT tool for user-friendly molecular diagnostics. 相似文献
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Understanding semantic word shifts in scientific domains is essential for facilitating interdisciplinary communication. Using a data set of published papers in the field of information retrieval (IR), this paper studies the semantic shifts of words in IR based on mining per-word topic distribution over time. We propose that semantic word shifts not only occur over time, but also over topics. The shifts are examined from two perspectives, the topic-level and the context-level. According to the over-time word-topic distribution, stable words and unstable words are recognized. The diverging and converging trends in the unstable type reveal characteristics of the topic evolution process. The context-level shifts are further detected by similarities between word vectors. Our work associates semantic word shifts with the evolving of topics, which facilitates a better understanding of semantic word shifts from both topics and contexts. 相似文献
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热轧态中锰TRIP钢首先经650 ℃退火2 h,随后在550 ℃进行等温时效热处理,采用场发射扫描电镜(FE-SEM)研究该钢中P的偏聚和时效析出行为的变化情况。结果表明,中锰TRIP钢中P在晶界的偏聚是一种非平衡偏聚现象,临界时间约为50 h,与理论计算结果48 h较为吻合。在局部偏聚区域内,C与P存在共偏聚的关系,即P偏聚量高的地方,C含量也高。而合金元素Nb具有抑制P偏聚的效果,在20~70 h时效时间内,可以相对降低6.57%~19.5%的最大P偏聚量。根据电子背散射衍射(EBSD)菊池线分析,P偏聚量低于2.28at%时,P为固溶状态,高于2.28at.%时,P为析出状态。 相似文献
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Natural Computing - The fiber stretching process plays the key role in the process of fiber production and its effects is measured by the stretching ratio. The stretching ratio is determined by the... 相似文献
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针对目标探测类空间红外相机大范围成像、高灵敏度探测、高精度定位等应用需求,文中提出采用像方远心光路和低温光学技术结合的解决方案,设计了物方视场角8°×8°、入瞳口径265 mm、工作温度200 K的像方远心折射式光学系统。镜头最大口径280 mm,采用多级分散的弹性支撑设计,解决大口径低温透镜装框、透镜组件支撑和镜头整体安装各环节的热应力卸载问题。在保证高刚度和低漏热的情况下,使低温下透镜的热应力对镜头能量集中度的影响降低到可接受范围内。镜头完成装调及室温下像质确认后,进行了力学振动试验,并将其制冷到200 K水平测试像质,测试结果表明,镜头能量集中度达到轴上75%,边缘视场72%。 相似文献
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