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.     

Sustainability of ride-hailing services in China’s mobility market: A simulation model of socio-technical system transition

As a symbol of sharing economy, ride-hailing services have spread to Asia, where various forms of services have been established according to the existing socio-technical regimes, including legal, policy, and environmental concerns. China, in particular, has accepted ride-hailing services by revising existing institutions. This study analyzes China’s acceptance of ride-hailing services in the socio-technical system context set up for legacy services. Simulation modeling, combined with transition theory and an agent-based model, is used to analyze the data. This study calculates consumer disutility based on mobility market share, reflecting consumer preference, and predicts the sustainability of ride-hailing services. The simulation results conclude that legalization and socio-technical context are of importance for sustainable mobility.     

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.     

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。     

Liner services network design and fleet deployment with empty container repositioning

Transportation demand of shipping container fluctuates due to the seasonality of international trade, thus, every 3–6 months, the liner company has to alter its current liner shipping service network, redeploy ships and design cargo routes with the objective of minimizing the total cost. To solve the problem, the paper presents a mixed integer linear program model. The proposed model incorporates several relevant constraints, such as weekly frequency, the transshipment of cargo between two or more service routes, and transport time. Extensive numerical experiments based on realistic date of Asia–Europe–Oceania shipping operations show that the proposed model can solve real-case problems efficiently by CPLEX. The results demonstrate that the model can reduce ship’s capacity consumption and raise ships’ capacity utilization.     

Quantum computation based bundling optimization for combinatorial auction in freight service procurements

Combinatorial auction is a useful trade manner for transportation service procurements in e-marketplaces. To enhance the competition of combinatorial auction, a novel auction mechanism of two-round bidding with bundling optimization is proposed. As the recommended the auction mechanism, the shipper/auctioneer integrates the objects into several bundles based on the bidding results of first round auction. Then, carriers/bidders bid for the object bundles in second round. The bundling optimization is described as a multi-objective model with two criteria on price complementation and combination consistency. A Quantum Evolutionary Algorithm (QEA) with β-based rotation gate and the encoding scheme based on non-zero elements in complementary coefficient matrix is developed for the model solution. Comparing with a Contrast Genetic Algorithm, QEA can achieve better computational performances for small and middle size problems.     

Research on Circular Area Search algorithm of multi-robot service based on SOA cloud platform

Considering autonomous mobile robots with a variety of specific functions as a kind of service, when there are many types and quantities of services and the density of regional services is large, proposing an algorithm of Circular Area Search (CAS) because of the problem of multi-robot service scheduling in various areas. Firstly, Django is used as the web framework to build the Service-Oriented Architecture (SOA) multi-robot service cloud platform, which is the basic platform for multi-service combination. Then, the service type, the latitude and longitude and the scoring parameters of the service are selected as the service search metrics to design the CAS algorithm that based on the existing service information registered in MySQL and the Gaode Map for screening optimal service, and then providing the service applicant with the best service. Finally, the service applicant applies for the self-driving tour service as an example to perform performance simulation test on the proposed CAS algorithm. The results show that the CAS algorithm of the multi-robot service cloud platform proposed in this paper is practical compared to the global search. And compared with the Greedy Algorithm experiment, the service search time is reduced about 58% compared with the Greedy Algorithm, which verifies the efficiency of CAS algorithm.     

Effective Location Based Services with Dynamic Data Management in Mobile Environments

With the proliferation of mobile computing technologies, location based services have been identified as one of the most promising target application. We classify mobile information service domains based on feature characteristics of the information sources and different patterns of mobile information access. By carefully examining the service requirements, we identify the dynamic data management problem that must be addressed for effective location based services in mobile environments. We then devise a general architecture and cost model for servicing both location independent and location dependent data. Based on the architecture and cost model, we propose a set of dynamic data management strategies that employs judicious caching, proactive server pushing and neighborhood replication to reduce service cost and improve response time under changing user mobility and access patterns. Detail behavior analysis helps us in precisely capturing when and how to apply these strategies. Simulation results suggest that different strategies are effective for different types of data in response to different patterns of movement and information access. Shiow-yang Wu is an associate professor of the Department of Computer Science and Information Engineering at National Dong Hwa University, Hualien, Taiwan, R.O.C. He received the BS and MS degrees in computer engineering from National Chiao Tung University, Hsinchu, Taiwan, ROC, and the PhD degree in computer science from the University of Texas at Austin in 1984, 1986, and 1995, respectively. His research interests include data/knowledge bases, mobile computing, distributed processing, intelligence information systems, and electronic commerce. Kun-Ta Wu was born in Taipei, Taiwan, R.O.C., in 1976. He received the B.S. degree in computer science from Soochow University, Taipei, Taiwan, R.O.C., in 1999 and the M.S. degree in computer science and information engineering from National Dong Hwa University, Hualien, Taiwan, R.O.C., in 2001. Currently, he is an Assistant Researcher in the Domestic Division at Science and Technology Information Center, National Science Council, R.O.C., as a member of Information Gathering and Analysis Group of National Information and Communication Security Taskforce. His research interests include mobile computing, wireless network and information security.     

全球宽带电话市场分析

近两年．IP电话又叫网络电话的发展受到全球的关注。随着宽带接入的发展，基于宽带接入提供的网络电话具有了更大的生命力。从宽带电话的经营模式出发，探究这类业务的出现时现有话音业务市场的影响，进而分析这类业务的发展前景。