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.     

A Strategy for Discovering Heterochiral Bioactive Peptides by Using the OB2nP Library and SPOTs Method

d -Amino acid containing peptides are promising as drug lead compounds because of their expected higher stability in vivo. A heterochiral random peptide library called the one-bead–2ⁿ-peptide (OB2ⁿP) library, which can display 2ⁿ peptide diastereomers per bead, has been developed. Through screening of the OB2ⁿP library and subsequent binding assay among the peptide diastereomers synthesized in parallel by means of the SPOTs method, new heterochiral mimotopes for the anti-β-endorphin monoclonal antibody have been obtained. One mimotope was a new ligand for the μ-opioid receptor. The screening strategy enabled d -amino acid containing drug leads to be obtained efficiently by expanding searchable chemical space without increasing the experimental scale.     

网络匿名扫描系统设计及优化

针对网络扫描工具在进行扫描时面临的溯源问题，提出了一种匿名网络扫描系统。首先将匿名系统与网络扫描工具结合以实现匿名扫描；然后在现有匿名系统的基础上实现了该系统的本地私有化；接着通过流量分析发现，Nmap的多进程扫描因为代理链的原因会变成单进程扫描而导致其扫描扫描性能较低；最后提出了一种基于多Namp进程并发的性能优化方案，将总体扫描任务分割为多个扫描任务，并分配给多个单独的Nmap进程并行运行。实验结果表明，该性能优化方案的扫描时延接近正常扫描情况下的时延，达到了提高匿名扫描系统性能的目的。因此，该优化后的网络匿名扫描系统在阻碍溯源的同时提升了扫描效率。     

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。     

Small-Molecule Inhibition of Glucose Transporters GLUT-1–4

Glucose addiction is observed in cancer and other diseases that are associated with hyperproliferation. The development of compounds that restrict glucose supply and decrease glycolysis has great potential for the development of new therapeutic approaches. Addressing facilitative glucose transporters (GLUTs), which are often upregulated in glucose-dependent cells, is therefore of particular interest. This article reviews a selection of potent, isoform-selective GLUT inhibitors and their biological characterization. Potential therapeutic applications of GLUT inhibitors in oncology and other diseases that are linked to glucose addiction are discussed.     

折臂式随车起重机转台的拓扑优化设计

为了使折臂式随车起重机转台在最大应力不超过材料许用应力的前提下实现轻量化设计的目的,通过ADAMS软件仿真确定其极限工况,对转台进行静力学分析及拓扑优化。通过拓扑优化得到了理想的材料分布。基于优化结果调整转台结构,并对改进后的转台进行静力学分析。结果表明,优化后的转台能够满足实际的使用需求。同时,转台质量降低了12%,证明了优化设计的有效性和可行性,并为折臂式随车起重机的相关设计提供了一定的借鉴。     

Void region restriction for additive manufacturing via a diffusion physics approach

A longstanding challenge in additive manufacturing (AM), the presence of void regions in additively manufactured components, causes two main issues: the enclosing of build material powder in powder bed fusion techniques and limiting tool access in critical post-processing operations to remove sacrificial support structures. As topology optimization has embraced and overcome many of the obstacles of incorporating AM constraints into the underlying numerical optimization statement, there exist few solutions that directly address this fundamental void region issue. By developing computationally efficient and effective solutions to this problem, the integration of these two advanced technologies can be fully realized. Drawing on inspiration from the principles of diffusion physics, a particle diffusion void restriction (PDVR) method is presented in this work that is capable of encouraging the optimization scheme to generate final designs that are fully accessible. Additionally, this method empowers the user to choose the type of post-processing method to clear support material (eg, three-axis or five-axis milling operations, number and orientation of part set-ups) and, therefore, quantify the level of costs associated with the post-processing operation. The PDVR optimization framework is demonstrated on multiple two- and three-dimensional test problems, with physically manufactured examples depicting the real-world benefits this method admits.     

Role of Post-translational Modifications in Alzheimer's Disease

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.     

浅谈高压变频调速变压器及高压变频系统结构

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。