Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro

The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC₅₀) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC₅₀ shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development.     

基于改进NSGA-Ⅱ算法的乙烯裂解炉操作优化

现有的乙烯裂解炉优化通常只针对两个目标函数即产物乙烯和丙烯的收率，并且采用遗传算法的收敛效果一般，故提出一种基于改进NSGA-Ⅱ算法来研究一个多目标运行的解决方案，以此来解决乙烯裂解炉的固定周期操作优化问题，即在增大产物乙烯和丙烯收率的同时减少原料以及蒸汽流量来提高整体运行状况。把具体问题量化为数学模型，分析了原料气烃比、原料流量、出口温度对乙烯和丙烯收率的影响。实验结果表明，相较于原有操作条件，提出的优化方案具有良好的可行性。     

An effective coding approach for multiobjective integrated resource selection and operation sequences problem

In this paper, we consider an integrated Resource Selection and Operation Sequences (iRS/OS) problem in Intelligent Manufacturing System (IMS). Several kinds of objectives are taken into account, in which the makespan for orders should be minimized; workloads among machine tools should be balanced; the total transition times between machines in a local plant should also be minimized. To solve this multiobjective iRS/OS model, a new two vectors-based coding approach has been proposed to improve the efficiency by designing a chromosome containing two kinds of information, i.e., operation sequences and machine selection. Using such kind of chromosome, we adapt multistage operation-based Genetic Algorithm (moGA) to find the Pareto optimal solutions. Moreover a special technique called left-shift hillclimber has been used as one kind of local search to improve the efficiency of our algorithm. Finally, the experimental results of several iRS/OS problems indicate that our proposed approach can obtain best solutions. Further more comparing with previous approaches, moGA performs better for finding Pareto solutions. Received: May 2005/Accepted: December 2005     

基于进化算法的常减压装置模拟

提出了基于优选优生进化算法（Select—best and prepotency evolution algorithm，SPEA）的常减压装置模拟方法。以各塔的温度分布为目标，基于生产过程和分析数据，采用SPEA确定各塔板Murphree效率，从而精确描述各塔板平衡偏离程度。在实际应用中，获得具有良好精度的常减压装置模型。系统分析了SPEA算法的关键参数——优选领域大小与计算复杂性及寻优性能之间的关系，结果显示其取值为群体规模的10％最为合适。     

法国电信集团运营模式研究

中国电信企业经过多年的高速发展，逐渐步入成熟期，增长率下降、利润降低将是必然趋势，因此目前亟需探索新的运营模式，向综合型全业务电信运营商的方向发展。法国电信集团历史悠久，市场转型起步早．其发展经验有许多地方值得借鉴，包括法国电信集团具有特色的品牌战咯、灵活的经营模式、为企业提供全方位服务的经营手段。中国电信企业应积极开展全业务经营，加快发展企业网市场，完善合作运营模式，争取早日走向世界。     

一种智能型的PCB产业需求预测方法

目前需求预测在整个印制电路板产业的生产活动控制中正扮演着越来越重要的角色。分析了影响印制电路板需求的因素和现有的预测方法,提出了一种适用于PCB产业需求预测的有效方法——遗传/BP—神经网络。实验表明该方法能够进一步改善印制电路板预测的准确度和减少生产成本的消耗。     

基于形态学top-hat算子的多传感器图像融合

本文根据形态学top-hat算子能够提取图像中极大值与极小值区域的特点,将其应用于多传感器图像融合的两个重要领域——多聚焦图像融合和高分辨、多光谱图像融合.实验中将本文方法与Laplacian塔型变换、子波变换、主分量分析等方法进行了比较,结果表明本文所提的基于top-hat算子的融合方法具有优越的性能,拓广了top-hat算子的应用范围.     

遗传算法在GSM移动通信网络频率规划中的应用

应用遗传算法设计和开发了针对爱立信GSM900系统的频率规划软件。在设计中，采用了交叉点存储、变异回退以及分割分步降维的方法，从而提高遗传算法的执行速度。     

An Improved Immune Genetic Algorithm for Solving the Optimization Problems of Computer Communication Networks

1　IntroductionIndesigningacomputercommunicationnet work ,thenetworkaveragedelayisanimportantpa rameterinthenetworkperformance .Inthispaper,weonlyconsiderM /M/1networks,whichmeansthatthemessageprocessingtimeisaprobabilisticdensityfunctionwithnegativepower,thegroupar rivalandsendingisofPoissiondistributionwithasinglequeue .Supposethatthenetworktopologicalstructureandtheestimatesoftheexternaltrafficrequirementsaregiven ,howtoselecttheoptimalroutestobeusedbythecommunicatingnodesinthenetworksoast…     

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.