Discovery of GPR183 Agonists Based on an Antagonist Scaffold

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.     

共享交通的时空轨迹检索与群体发现

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。     

An engineering method for complex structural optimization involving both size and topology design variables

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.     

FF现场总线的网段负载能力的设计及计算

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。     

Range Assignment for Biconnectivity and k-Edge Connectivity in Wireless Ad Hoc Networks

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.     

A Bluetooth Based Sensor Network for Civil Infrastructure Health Monitoring

Communicating with sensors has long been limited either to wired connections or to proprietary wireless communication protocols. Using a ubiquitous and inexpensive wireless communication technology to create Sensor Area Networks (SANs) will accelerate the extensive deployment of sensor technology. Bluetooth, an emerging, worldwide standard for inexpensive, local wireless communication is a viable choice for SANs because of its inherent support for some of the important requirements – low power, small form factor, low cost and sufficient communication range. In this paper we outline an approach, centered on the Bluetooth technology, to support a sensor network composed of fixed wireless sensors for health monitoring of highways, bridges and other civil infrastructures. We present a topology formation scheme that not only takes into account the traffic generated by different sensors but also the associated link strengths, buffer capacities and energy availability. The algorithm makes no particular assumptions as to the placement of nodes, and not all nodes need to be in radio proximity of each other. The output is a tree shaped scatternet rooted at the sensor hub (data logger) that is balanced in terms of traffic carried on each of the links. We also analyze the scheduling, routing and healing aspects of the resulting sensor-net topology.     

A Multilayer Optical Packet Switching Network Based on the Kautz Graph and Optical Passive Star Couplers

The multihop optical network is the most appropriate solution to satisfy the increasing applications of Internet services. This paper extends the regular Kautz graph to one with multiple layers in order to produce more architectural variations. The connectivity between adjacent layers utilizes the systematic connection patterns of a regular Kautz graph. A routing algorithm based on its property is presented. Optical passive star (OPS) couplers are adopted to implement our new topologies. Three scheduling criteria that can solve the contention problem in the intermediate nodes are evaluated and compared in terms of their capability to improve the accessibility.     

Topology optimization of trusses using genetic algorithm,force method and graph theory

In this article size/topology optimization of trusses is performed using a genetic algorithm (GA), the force method and some concepts of graph theory. One of the main difficulties with optimization with a GA is that the parameters involved are not completely known and the number of operations needed is often quite high. Application of some concepts of the force method, together with theory of graphs, make the generation of a suitable initial population well‐matched with critical paths for the transformation of internal forces feasible. In the process of optimization generated topologically unstable trusses are identified without any matrix manipulation and highly penalized. Identifying a suitable range for the cross‐section of each member for the ground structure in the list of profiles, the length of the substrings representing the cross‐sectional design variables are reduced. Using a contraction algorithm, the length of the strings is further reduced and a GA is performed in a smaller domain of design space. The above process is accompanied by efficient methods for selection, and by using a suitable penalty function in order to reduce the number of numerical operations and to increase the speed of the optimization toward a global optimum. The efficiency of the present method is illustrated using some examples, and compared to those of previous studies. Copyright © 2003 John Wiley & Sons, Ltd.     

大规模数据库中的知识获取

一、前言数据是知识的潭泉,拥有大量的数据与拥有许多有用的知识完全是两回事.为了有效地利用大量的公共数据,必须更好地理解这些数据,并从其中快速、准确地发现知识.这里所说的知识是指大量数据中存在的规律性(r egularity)或不同属性值之间所存在的[I F THEN〕规则.将所获取的知识附加于仅由事实数据(fact data)构成的传统数据库上,既可强化数据库的查询能力,又可给数据库提供推理能力,