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1.
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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Wan Huan Wang Hui Scotney Bryan Liu Jun Ng Wing W. Y. 《Multimedia Tools and Applications》2020,79(39-40):29327-29352
Multimedia Tools and Applications - In many real-world classification problems there exist multiple subclasses (or clusters) within a class; in other words, the underlying data distribution is... 相似文献
4.
Rats given medial frontal lesions on Postnatal Day 1 or Day 10 were trained on the Morris water task on Days 19–21 or Days 56–58. The operated groups were equally impaired at the water task on Days 19–21, but the Day 10 rats had recovered by 56 days. Dendritic arborization and spine density were analyzed in parietal layer II–III pyramidal cells. At Day 60, but not at Day 22, the Day 10 animals had more dendritic spines per unit dendritic length than did the controls or Day 1 rats. Thus, there was functional recovery rather than sparing after frontal lesions at 10 days, and the recovery was correlated with an increase in dendritic spines. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
5.
Oleg A. Mezentsev Rixin Zhu Richard E. DeVor Shiv G. Kapoor William A. Kline 《International Journal of Machine Tools and Manufacture》2002,42(4)
A model-based method for fault detection in tapping based on torque and radial forces is proposed. The method allows the identification of faults typical of a tapping operation including axial misalignment, tap runout, tooth breakage both singly and together. The validation experiments have been run on aluminum 356 workpieces for different combinations of process faults. Results have shown that the model predictions are in good agreement with the experimental radial force and torque signals under various fault conditions. 相似文献
6.
Amanda Alliband Daniel W. Lenz Laura E. Stevenson Travis Whitmer Rex Cash Dennis Burns Sarah Hall William T.K. Stevenson 《Progress in Organic Coatings》2008
A model has been proposed to explain the failure of the original BMS10-39 epoxy paint on upper vertical surfaces in B-52 fuel tanks. The model involves interaction of the paint with DIEGME, a fuel system ice inhibitor (FSII) in jet fuel, that is distilled from the liquid fuel. In this communication, distillation experiments used to support the model are refined to better match the mass transfer of vapor from fuel in a B-52 fuel tank at close to room temperature. The interaction of these lower temperature distillates with the paint affirms the earlier model. On the basis of these experiments it is proposed that paint failure may be controlled or eliminated by reducing the level of DIEGME in the fuel. Proposed changes in military jet fuel composition are detailed. 相似文献
7.
Osemwengie Iyoha Bret Howard Bryan Morreale Richard Killmeyer Robert Enick 《Topics in Catalysis》2008,49(1-2):97-107
The hydrogen permeance of 1 mm-thick Pd80wt%Cu foils was measured in the presence of equimolar mixtures of H2 with CO, CO2 or H2O over the temperature and total pressure ranges of 623–1,173 K and 0.62–2.86 MPa, respectively. In all cases, permeance losses at 623 and 738 K were very modest. At higher temperatures, more significant decreases in membrane permeance were observed with the highest reduction of about 50% occurring when macroscopic carbon deposition occurred on the membrane surface during H2–CO exposure at 908 K. The more worrisome effects of exposure to these gases, however, were the micron-scale surface defects observed at 908 and 1,038 K. Although the 1 mm thick disk membranes retained their mechanical integrity, such defects could cause catastrophic failure of ultra-thin, Pd–Cu membranes (1–5 μm thick) deposited on porous substrates. 相似文献
8.
几乎是摩尔定律的必然结果: 明年,微机将具有更多功能,软件开发团队也会有更宏大的构想.可惜,输出针脚的数量并未增加.找到一个多余输出端口用于诊断、测试或标准I/O都是很困难的.图1中的单一针脚"总线"以简单的附加硬件可提供无数的并行输出.带有RC低通滤波器的微机输出,控制串/并转换器HC164. 相似文献
9.
Here, we describe the development of a reacting flow multi-species/combustion methodology, implemented as an extension to the differential reduced ejector analysis (DREA) computer program [Mathematical and computer modeling, vol. 31, 2000, p. 21; Appl. Math. Model. 25 (2001) 427; Comput. Math. Appl. 43(10–11); NASA Contractor Report, 1998]. Use of the single fluid IVP solver framework that was developed for the original DREA model has been directly coupled into the combustion formulation. With these modifications, the analysis has an elementary single step reaction Fuel+Oxidizer→Product combustion capability. Though approximate in nature, the simplicity and efficiency of the DREA formulation make it suitable for its original niche, namely design and preliminary design environments where more complex and expensive models may be inappropriate. 相似文献
10.
Dopaminergic blocking agents have been known to suppress intracranial self-stimulation, but whether the suppression results from a reduction in the rewarding value of stimulation or from motor deficits has remained controversial. We have resolved this controversy by developing an operant technique minimally dependent on motor activity; rats were trained to perform a bar-holding response for 3s or to produce hippocampal theta waves for 3s when the bar was retracted. Decamethonium bromide (a muscle relaxant) reduced bar holding without affecting theta production for brain stimulation. Pimozide (a dopaminergic blocking-agent) reduced both bar holding and theta production for stimulation, though rats were still capable of making the theta response at a rate comparable to the preinjection rate. Dopaminergic blocking at low doses reduces the rewarding value of brain stimulation at the level of the lateral hypothalamus. The method described in this report has wide applicability. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献