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31.
32.
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
33.
针对传统隐伏型导水地质裂缝勘探方法存在勘测精度较差的问题,提出电磁精细探测法探析隐伏型导水地质裂缝。依照屏蔽系数、实测场强和理论场强数据绘制综合曲线图,通过该图获取隐伏型导水地质裂缝所处位置几何阴影范围,采用层析成像法得到网格化的工作面,获取隐伏型导水地质图像。通过图像直接观测隐伏型导水地质工作面裂缝所处位置,在此基础上,观测四个电磁场分量,采用正交电磁场分量计算介质视电阻率,依据计算视电阻率数值和视电阻率分布状态研究裂缝发育情况和裂缝富水程度。结果表明:采用该方法能较为精准地获取隐伏型导水地质裂缝位置。通过裂缝位置进一步检测出隐伏型导水地质裂缝最大发育高度为63.5 m。当视电阻数值不断增加时,隐伏型导水地质裂缝和裂缝富水性逐渐减小,与实际情况较为相符,说明该种方法探析效果较好。 相似文献
34.
In this research, the three‐dimensional structural and colorimetric modeling of three‐dimensional woven fabrics was conducted for accurate color predictions. One‐hundred forty single‐ and double‐layered woven samples in a wide range of colors were produced. With the consideration of their three‐dimensional structural parameters, three‐dimensional color prediction models, K/S‐, R‐, and L*a*b*‐based models, were developed through the optimization of previous two‐dimensional models which have been reported to be the three most accurate models for single‐layered woven structures. The accuracy of the new three‐dimensional models was evaluated by calculating the color differences ΔL*, ΔC*, Δh°, and ΔECMC(2:1) between the measured and the predicted colors of the samples, and then the error values were compared to those of the two‐dimensional models. As a result, there has been an overall improvement in color predictions of all models with a decrease in ΔECMC(2:1) from 10.30 to 5.25 units on average after the three‐dimensional modeling. 相似文献
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Functional expression and synergistic cooperation of xylan‐degrading enzymes from Hypocrea orientalis and Aspergillus niger 下载免费PDF全文
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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
39.
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
40.
Steffen Vojacek Lukas Schulig Nathalie Wössner Norman Geist Prof. Dr. Walter Langel Prof. Dr. Manfred Jung Prof. Dr. Dennis Schade Prof. Dr. Andreas Link 《ChemMedChem》2019,14(8):853-864
Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp3 hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC50 value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling. 相似文献