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排序方式: 共有2070条查询结果,搜索用时 31 毫秒
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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3.
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.
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
6.
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
7.
Jon Bryan Burley 《Landscape Research》1992,17(2):74-78
This paper describes the configuration and cultural context of the oldest known designed space in central America, Gheo-Shih, dating from 5,000 - 4,000 BC. This site may have been a ceremonial space, being employed in a similar fashion to ceremonial spaces of Native American cultures from the North American Great Basin. It contains physical features that set precedents and are similar to the geomantic features of later nearby Mesoamerican cultures. 相似文献
8.
Bryan Poulson 《Corrosion Science》2004,46(3):729-753
A simple stress-corrosion cracking (SCC) specimen, suitable for slow strain rate testing and incorporating heat transfer, with an artificial crevice or deposits has been designed and tested. It appears that when the solute level is above a certain value it can concentrate. The kinetics of solute accumulation and the concentration that can be induced in the specimen have been determined. Build up of solute from the ppm level in the bulk environment to the level required to cause cracking can take hours, not days or years. The limiting concentration reached is controlled by thermodynamics, specifically the available superheat. A brief review of relevant literature suggests that this experimental approach to predicting SCC has significant advantages over a modelling or measurement approach. The specimen also lends itself to a monitoring role--a modern version of the Schroeder embrittlement detector. 相似文献
9.
L. Pamela Cook Emeka Nwankwo Gilberto Schleiniger Bryan Wood 《Journal of Engineering Mathematics》2003,45(3-4):269-282
A general formulation for capillary flow of two miscible fluids – one a dilute plug of polymer fluid inserted into a fully developed Poiseuille flow of the other, a Newtonian stream – is examined for its long time behavior. Phenomenologically, the system evolves from an initial state, that of a plug within the boundaries of sharp, well defined fronts inside a Newtonian stream, to a more homogenized state in the very long time scale. This problem was addressed by G.I. Taylor but with regard to a system of two Newtonian fluids, leading to the well-known results commonly described as `Taylor axial dispersion'. In this paper, a general and systematic perturbation analysis is presented from which Taylor's result is recovered as a special case of a more general solution which applies to fluids incorporating elastic properties. In particular, the influence of viscoelasticity and (polymer) diffusivity on the observed pressure profile in the capillary conduit is examined. This effect is clearly separated out for small Peclet number flows using asymptotic and numerical analysis. The results identify the influence of fluid viscosity, elasticity, and diffusivity on the observed pressure profile and form the basis for the improved characterization of polymeric elasticity using capillaries – a finding that is of significant scientific and commercial interest. These results were obtained by the authors as a class of observations resulting from the perturbation analysis of forced-flow capillary devices in viscoelastic fluid property investigation. 相似文献
10.
Deactivation of copper-ion-exchanged hydrogen-mordenite-type zeolite catalyst by SO2 for NO reduction by NH3 was examined in a fixed-bed flow reactor. The deactivation of the catalyst was strongly dependent on reaction temperature. At high reaction temperatures over 300°C, the catalyst did not lose its initial activity up to 50 h of operation, regardless of SO2 feed concentration from 500 to 20,000 ppm. However, at low reaction temperatures near 250°C, apparent deactivation did occur. Changes in the physicochemical properties such as surface area and sulfur content of deactivated catalyst well correlated with catalyst activity, depending upon reaction temperatures. The deactivation was due to pore blocking and/or filling by deactivating agents, which plugged and/or filled the pores of catalyst. The deactivating agents deposited on the catalyst surface were presumed to be (NH4)2SO4 and/or (NH4)HSO4 from the results of TGA and ion-chromatography measurement. 相似文献