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排序方式: 共有6908条查询结果,搜索用时 15 毫秒
1.
Dr. Maria L. Di Paolo Dr. Michael S. Christodoulou Dr. Alessandra M. Calogero Dr. Luca Pinzi Prof. Giulio Rastelli Prof. Daniele Passarella Prof. Graziella Cappelletti Prof. Lisa Dalla Via 《ChemMedChem》2019,14(18):1641-1652
A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (Ki) values in the sub-micromolar range and a good selectivity index (Ki MAO-A/Ki MAO-B>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity. 相似文献
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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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Alan Bivens Rashim Gupta Ingo McLean Boleslaw Szymanski Jerome White 《International Journal of Network Management》2004,14(2):131-146
Rapid growth of computer network sizes and uses necessitate analysis of network application middleware in terms of its scalability as well as performance. In this paper we analyze a distributed network management middleware based on agents that can be dispatched to locations where they can execute close to the managed nodes. The described middleware operates between the network protocol layer and the application layer and uses standard TCP protocol and SNMP probes to interface the network. By aggregating requests from many users into a single agent, our system allows multiple managers to probe problem areas with minimal management traffic overhead. We discuss and quantify the benefits of the described middleware by implementing real‐time network managers using our system. The main result of this paper is a comparison of scalability and efficiency of our agent‐based management middleware and traditional SNMP‐based data collection. To this end, we measured traffic in both real and simulated networks. In the latter case, we designed, used and described here a method of separating simulated application flow into separate subflows to simplify design of simulations. Copyright © 2004 John Wiley & Sons, Ltd. 相似文献
4.
Thomas S. Lowry John C. Bright Murray E. Close Christina A. Robb Paul A. White Stewart G. Cameron 《国际水资源开发杂志》2003,19(4):579-592
The primary objective of this project is to identify gaps, whether real or perceived, that hinder effective groundwater management in New Zealand. These gaps show as gaps in information, gaps in implementation, gaps in technological and management tools, and gaps in understanding of fundamental processes. The secondary objective is to propose a management strategy to close the identified gaps. Several methods are used to meet these objectives: surveys distributed to selected staff in each regional council; the review of various written reports; the analysis of land-use databases; and private consultation within each regional council. Results show that groundwater management in New Zealand is generally reactionary with the main gaps being in strategic planning and national guidelines. Most gaps appear to be predominantly information and implementation issues. In some cases there are gaps in the understanding of fundamental processes within an aquifer system, including the long-term effects of land-use on groundwater quality. An adaptive management approach is suggested as a means of closing these gaps. 相似文献
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Dual command travel times and miniload system throughput with turnover-based storage 总被引:2,自引:0,他引:2
Byung Chun Park Robert D. Foley John A. White Edward H. Frazelle 《IIE Transactions》2003,35(4):343-355
We analyze travel times for automated storage/retrieval systems. In particular, we apply our travel time model to turnover-based storage systems and determine the mean and variance of dual command travel times. We present detailed numerical results for selected rack shape factors and ABC inventory profiles. We then investigate the effect of alternative rack configurations on travel time performance measures. We also show how to determine the throughput of miniload systems with turnover-based storage and exponentially distributed pick times. 相似文献
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Twenty-six patients with an intracardiac myxoma underwent surgical resection at our institution from 1977 through 1992. Left atrial myxoma was diagnosed in 22 patients, left ventricular in 1, right atrial in 2, and right ventricular in 1. Six patients were asymptomatic; preoperative symptoms included dyspnea, arrhythmias, embolic episodes, and syncope. The diagnosis was established with transthoracic echocardiography in all cases but one. Surgery was performed in all cases with the aid of cardiopulmonary bypass with moderate hypothermia and cold crystalloid cardioplegia. One patient with a left ventricular myxoma died in a comatose state during the immediate postoperative period. Long-term clinical and echocardiographic evaluation was performed in 19 patients; results were excellent (all the patients were in New York Heart Association functional class I or II), and no recurrences were documented. The clinical characteristics, diagnostic methods, and surgical approach are presented and discussed. 相似文献
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McIntyre Christa K.; Marriott Lisa K.; Gold Paul E. 《Canadian Metallurgical Quarterly》2003,117(2):320
The present experiment examined the relationship between release of acetylcholine (ACh) in the amygdala and performance on a hippocampus-dependent spatial working memory task. Using in vivo microdialysis, the authors measured ACh release in rats during testing on a spontaneous alternation task. Amygdala ACh release was positively correlated with performance on the hippocampus-dependent task. These findings suggest that activation of the amygdala promotes processing in other neural systems important for learning and memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献