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排序方式: 共有8373条查询结果,搜索用时 15 毫秒
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Viktoria M. S. Kjær Loukas Ieremias Dr. Viktorija Daugvilaite Dr. Michael Lückmann Prof. Thomas M. Frimurer Prof. Trond Ulven Prof. Mette M. Rosenkilde Dr. Jon Våbenø 《ChemMedChem》2021,16(17):2623-2627
The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca2+ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch. 相似文献
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Madhu Ramesh Dr. Pushparathinam Gopinath Prof. Thimmaiah Govindaraju 《Chembiochem : a European journal of chemical biology》2020,21(8):1052-1079
The global burden of Alzheimer's disease (AD) is growing. Valiant efforts to develop clinical candidates for treatment have continuously met with failure. Currently available palliative treatments are temporary and there is a constant need to search for reliable disease pathways, biomarkers and drug targets for developing diagnostic and therapeutic tools to address the unmet medical needs of AD. Challenges in drug-discovery efforts raise further questions about the strategies of current conventional diagnosis; drug design; and understanding of disease pathways, biomarkers and targets. In this context, post-translational modifications (PTMs) regulate protein trafficking, function and degradation, and their in-depth study plays a significant role in the identification of novel biomarkers and drug targets. Aberrant PTMs of disease-relevant proteins could trigger pathological pathways, leading to disease progression. Advancements in proteomics enable the generation of patterns or signatures of such modifications, and thus, provide a versatile platform to develop biomarkers based on PTMs. In addition, understanding and targeting the aberrant PTMs of various proteins provide viable avenues for addressing AD drug-discovery challenges. This review highlights numerous PTMs of proteins relevant to AD and provides an overview of their adverse effects on the protein structure, function and aggregation propensity that contribute to the disease pathology. A critical discussion offers suggestions of methods to develop PTM signatures and interfere with aberrant PTMs to develop viable diagnostic and therapeutic interventions in AD. 相似文献
5.
为解决共享交通下的共乘用户群体发现效率低、准确率不高问题,依据R-树原理建立GeoOD-Tree索引,并在此基础上提出以最大化共乘率为目标的群体发现策略。首先,对原始时空轨迹数据进行特征提取与标定处理,挖掘有效出行起讫点(OD)轨迹;其次,针对用户起讫点轨迹的特征,建立GeoOD-Tree索引进行有效的存储管理;最后,给出以最大化共乘行程为目标的群体发现模型,并运用K最近邻(KNN)查询对搜索空间剪枝压缩,提高群体发现效率。采用西安市近12000辆出租车营运轨迹数据,选取动态时间规整(DTW)等典型算法与所提算法在查询效率与准确率上进行性能对比分析。与DTW算法相比,所提算法的准确率提高了10.12%,查询效率提高了约15倍。实验结果表明提出的群体发现策略能有效提高共乘用户群体发现的准确率和效率,可有效提升共乘出行方式的出行率。 相似文献
6.
介绍了高压变频调速变压器及高压变频器系统的基本原理及结构,详细论述了系统各组成部分的功能,并进行了举例说明。 相似文献
7.
Hai Huang Haichao An Haibo Ma Shenyan Chen 《International journal for numerical methods in engineering》2019,117(3):291-315
This work presents an engineering method for optimizing structures made of bars, beams, plates, or a combination of those components. Corresponding problems involve both continuous (size) and discrete (topology) variables. Using a branched multipoint approximate function, which involves such mixed variables, a series of sequential approximate problems are constructed to make the primal problem explicit. To solve the approximate problems, genetic algorithm (GA) is utilized to optimize discrete variables, and when calculating individual fitness values in GA, a second-level approximate problem only involving retained continuous variables is built to optimize continuous variables. The solution to the second-level approximate problem can be easily obtained with dual methods. Structural analyses are only needed before improving the branched approximate functions in the iteration cycles. The method aims at optimal design of discrete structures consisting of bars, beams, plates, or other components. Numerical examples are given to illustrate its effectiveness, including frame topology optimization, layout optimization of stiffeners modeled with beams or shells, concurrent layout optimization of beam and shell components, and an application in a microsatellite structure. Optimization results show that the number of structural analyses is dramatically decreased when compared with pure GA while even comparable to pure sizing optimization. 相似文献
8.
从生产安全运行的管理要求;电压压降和电流的限制及信号的衰减;网络运行时间的要求;系统设计的影响;备用能力的考虑等各个方面,结合上海赛科聚苯乙烯项目的具体设计,分析隔爆条件下FF现场总线的H1网段负载能力的设计,以供大家探讨。 相似文献
9.
Depending on whether bidirectional links or unidirectional links are used for communications, the network topology under a
given range assignment is either an undirected graph referred to as the bidirectional topology, or a directed graph referred
to as the unidirectional topology. The Min-Power Bidirectional (resp., Unidirectional) k-Node Connectivity problem seeks a range assignment of minimum total power subject to the constraint that the produced bidirectional
(resp. unidirectional) topology is k-vertex connected. Similarly, the Min-Power Bidirectional (resp., Unidirectional) k-Edge Connectivity problem seeks a range assignment of minimum total power subject to the constraint the produced bidirectional
(resp., unidirectional) topology is k-edge connected.
The Min-Power Bidirectional Biconnectivity problem and the Min-Power Bidirectional Edge-Biconnectivity problem have been studied
by Lloyd et al. [23]. They show that range assignment based the approximation algorithm of Khuller and Raghavachari [18],
which we refer to as Algorithm KR, has an approximation ratio of at most 2(2 – 2/n)(2 + 1/n) for Min-Power Bidirectional Biconnectivity, and range assignment based on the approximation algorithm of Khuller and Vishkin [19],
which we refer to as Algorithm KV, has an approximation ratio of at most 8(1 – 1/n) for Min-Power Bidirectional Edge-Biconnectivity.
In this paper, we first establish the NP-hardness of Min-Power Bidirectional (Edge-) Biconnectivity. Then we show that Algorithm KR has an approximation ratio of at most 4 for both Min-Power Bidirectional Biconnectivity and Min-Power Unidirectional Biconnectivity,
and Algorithm KV has an approximation ratio of at most 2k for both Min-Power Bidirectional k-Edge Connectivity and Min-Power Unidirectional k-Edge Connectivity. We also propose a new simple constant-approximation algorithm for both Min-Power Bidirectional Biconnectivity
and Min-Power Unidirectional Biconnectivity. This new algorithm applies only to Euclidean instances, but is best suited for
distributed implementation.
A preliminary version of this work appeared in the proceedings of the 2nd International Conference on AD-HOC Network and Wireless
(Adhoc-Now 2003).
Research performed in part while visiting the Max-Plank-Institut fur Informatik.
Gruia Calinescu is an Assistant Professor of Computer Science at the Illinois Institute of Technology since 2000. He held postdoc or visiting
researcher positions at DIMACS, University of Waterloo, and Max-Plank Institut fur Informatik. Gruia has a Diploma from University
of Bucharest and a Ph.D. from Georgia Insitute of Technology. His research interests are in the area of algorithms.
Peng-Jun Wan has joined the Computer Science Department at Illinois Institute of Technology in 1997 and has been an Associate Professor
since 2004. He received his Ph.D. in Computer Science from University of Minnesota in 1997, M.S. in Operations Research and
Control Theory from Chinese Academy of Science in 1993, and B.S. in Applied Mathematics from Tsinghua University in 1990.
His research interests include optical networks and wireless networks. 相似文献
10.
无线网状网及相关标准 总被引:1,自引:0,他引:1
赵广元 《电信工程技术与标准化》2006,19(7):28-32
简要描述了无线网状网(Wireless Mesh Networks)拓朴、网络架构和协议,分析了其优点,对相关标准作了介绍和比较. 相似文献