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排序方式: 共有2566条查询结果,搜索用时 15 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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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
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OBJECTIVE: To study the effects of an aldose reductase inhibitor (ARI-509, Wyeth-Ayerst, Princeton, NJ) and aminoguanidine (AMG), agents that have been reported to prevent or delay diabetic retinopathy, on retinal vascular abnormalities and the immunocytochemical expression in the retina of vascular endothelial growth factor (VEGF) in rats maintained for up to 2 years on a 50% galactose diet. METHODS: Albino rats were placed on a control diet, a diet containing 50% galactose, or the 50% galactose diet containing either ARI-509 or AMG. Treatment with ARI-509 or AMG was initiated at the beginning of the experiment or after 12 months of galactose feeding. After 22 to 24 months, the rats were killed and the retinal vasculature from half of one eye was isolated by trypsin-elastase digestion for semiquantitative evaluation of retinal vascular lesions. The other half of the retina was prepared for immunocytochemistry and stained for the presence of VEGF, factor VIII, vimentin, and glial fibrillary acidic protein. Red blood cells, sciatic nerves, and a portion of the retina from the second eye were assayed for glucose, galactose, fructose, sorbitol, galactitol, and myo-inositol. Red blood cells were also assayed for galactosylated hemoglobin. RESULTS: Galactose-fed animals developed a vascular retinopathy characterized by severe cellular loss in the retinal capillaries and intensification of periodic acid-Schiff staining of the vascular basement membranes. Some animals also displayed dilation and hypercellularity of vessels in the posterior retina. These changes were substantially reduced in animals receiving ARI-509 from the beginning of the galactose diet, but were unaffected in all of the other treatment groups. None of the rats receiving ARI-509 or AMG treatment, whether initiated from the onset or after 12 months of galactosemia, demonstrated VEGF immunoreactivity. With the exception of the animals receiving ARI-509 from the beginning of the experiment, all of the galactose-fed animals developed dense cataracts within 6 weeks of the beginning of the galactose diet. Galactitol levels in animals receiving ARI-509 were 86% to 93% lower in red blood cells, retina, and sciatic nerve than those in the other galactose-fed groups. CONCLUSIONS: Although ARI-509 and AMG have different abilities to delay or prevent the diabetic-like retinopathy in galactosemic rats, even when substantial retinal microvascular acellularity occurs, both drugs prevent the immunocytochemical expression of VEGF. These results suggest that factors other than hypoxia may be responsible for VEGF expression in the retina, and that aldose reductase inhibitors and AMG have potential roles in preventing such expression and, thus, perhaps preventing retinal neovascularization. 相似文献
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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
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Bound-state beta decay of highly ionized atoms 总被引:1,自引:0,他引:1
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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
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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
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The occurrence of fungi was investigated in the gut of 200 common garden lizards (Agama agama). The most important pathogenic fungus isolated was Basidiobolus haptosporus, an aetiological agent of subcutaneous zygomycosis. It was recovered from the intestinal contents of 112 (56%) lizards. Other important fungi isolated included Aspergillus spp. in 24 (12%) lizards, Candida spp. in 12 (6%), Penicillium spp. in 12 (6%) and Fusarium spp. in 12 (6%). Mucor spp. were isolated from eight (4%) male lizards only. Agamid lizards are plentiful in rural and urban areas of Nigeria. As they live in close vicinity to man, they are likely to play an important role in the spread of disease that may be caused by these fungi and its transmission to man. None of the animals investigated that yielded fungal cultures revealed any external fungal infection. 相似文献
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