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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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目的: 建立快速灵敏的LC-MS/MS法测定人血浆中阿莫西林浓度,并用于两种阿莫西林胶囊的一致性评价。方法: 采用岛津公司LCMS-8060型LC-MS/MS仪,以MRM模式测定阿莫西林(m/z 366.00/114.00)的浓度,d4-阿莫西林作内标(m/z 370.10/114.05),离子源为ESI源。色谱柱选用Waters ACQUITY BEH C18(2.1×50 mm,1.7 μm),梯度洗脱。血浆样本加入内标,经甲醇沉淀蛋白后取上清液进样检测。结果: 所建方法经验证,其线性、准确度、精密度、最低定量限、提取回收率、特异性、基质效应、稳定性等各项指标均符合CFDA的指导原则及最新核查标准要求,并较文献报道中的方法有处理简单、灵敏度高、色谱峰形好的优点。结论: 所建方法快速、灵敏,适用于人血浆中阿莫西林浓度的检测。用于一致性评价的样本实测,两种制剂生物等效。 相似文献
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Baizhan Li Chenqiu Du Hong Liu Wei Yu Jie Zheng Meilan Tan Zhenxing Jin Wenjie Li Jing Wu Lu Chen Runming Yao 《Indoor air》2019,29(2):308-319
The extensive research interests in environmental temperature can be linked to human productivity / performance as well as comfort and health; while the mechanisms of physiological indices responding to temperature variations remain incompletely understood. This study adopted a physiological sensory nerve conduction velocity (SCV) as a temperature‐sensitive biomarker to explore the thermoregulatory mechanisms of human responding to annual temperatures. The measurements of subjects’ SCV (over 600 samples) were conducted in a naturally ventilated environment over all four seasons. The results showed a positive correlation between SCV and annual temperatures and a Boltzmann model was adopted to depict the S‐shaped trend of SCV with operative temperatures from 5°C to 40°C. The SCV increased linearly with operative temperatures from 14.28°C to 20.5°C and responded sensitively for 10.19°C‐24.59°C, while tended to be stable beyond that. The subjects’ thermal sensations were linearly related to SCV, elaborating the relation between human physiological regulations and subjective thermal perception variations. The findings reveal the body SCV regulatory characteristics in different operative temperature intervals, thereby giving a deeper insight into human autonomic thermoregulation and benefiting for built environment designs, meantime minimizing the temperature‐invoked risks to human health and well‐being. 相似文献
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Neural Processing Letters - The beta processes (BP) is a powerful nonparametric tool in feature learning, which is often used as the prior of Bernoulli process for choosing features from a feature... 相似文献
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Zhen Wu Jing Yao Pengfei Zhu Fusheng Yang Xiangyu Meng Sandra Kurko Zaoxiao Zhang 《International Journal of Hydrogen Energy》2021,46(19):11183-11198
Advanced biogas power generation technology has been attracting attentions, which contributes to the waste disposal and the mitigation of greenhouse gas emissions. This work proposes and models a novel biogas-fed hybrid power generation system consisting of solid oxide fuel cell, water gas shift reaction, thermal swing adsorption and proton exchange membrane fuel cell (SOFC-WGS-TSA-PEMFC). The thermodynamic, exergetic, and thermo-economic analyses of this hybrid system for power generation were conducted to comprehensively evaluate its performance. It was found that the novel biogas-fed hybrid system has a gross energy conversion efficiency of 68.63% and exergy efficiency of 65.36%, indicating high efficiency for this kind of hybrid power technology. The market sensitivity analysis showed that the hybrid system also has a low sensitivity to market price fluctuation. Under the current subsidy level for the distributed biogas power plant, the levelized cost of energy can be lowered to 0.02942 $/kWh for a 1 MW scale system. Accordingly, the payback period and annual return on investment can reach 1.4 year and about 20%, respectively. These results reveal that the proposed hybrid system is promising and economically feasible as a distributed power plant, especially for the small power scale (no more than 2 MW). 相似文献
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In the early design stage, automotive modeling should both meet the requirements of aesthetics and engineering. Therefore, a vehicle CAD (computer aided design) model that can be easily adjusted by feedbacks is necessary. Based on CE-Bézier surface, this paper presents a set of algorithms for parametric segmentation and fairing surface generation in a car model. This model is defined by a simplified automotive template and relevant control points, shape parameters and segmentation parameters, which can be modified to alter the car form efficiently. With this model and the corresponding adjustment method, more than fifty various vehicle models are established in this research according to different parameters. And two methods for calculating similarity index between car models are constructed, which are suitable for brand design trend analysis and modelling design decisionmaking. 相似文献