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.     

基于空气质量模拟的江苏省大气污染物排放清单比较研究

大气污染物排放清单是空气质量模拟和空气污染治理的重要依据.本研究比较分析了两套覆盖江苏省的2017年大气污染物排放清单，即分别由上海市环境科学研究院、江苏省环境科学研究院编制的"长三角清单"和"江苏省清单"，并结合区域空气质量模型CMAQ评估不同清单对长三角地区2017年1、4、7、10月的空气质量模拟的影响.清单比较结果表明，除二氧化硫（SO₂）以外，江苏省清单估算的各污染物排放量较长三角清单低.通过与观测数据比较，发现两套清单对SO₂、氮氧化物（NO_x）、臭氧（O₃）和细颗粒物（PM_2.5）的模型模拟性能均较好.江苏省清单与长三角清单两者的模拟结果空间分布接近，其中江苏省清单模拟的PM_2.5和O₃在长三角多数地区略低于长三角清单的模拟结果（1月O₃除外）.江苏省清单与长三角清单均能够用于空气质量模式模拟，可为江苏地区的细颗粒物和光化学烟雾污染的控制策略制定提供参考.     

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。     

Framework to manage multiple goals in community-based energy sharing network in smart grid

Smart grid has opened up a new role of “prosumer” in an energy value network, transforming many conventional energy consumers into prosumers, who not only generate green energy but also share the surplus with utilities and other consumers. The concept of a goal-oriented prosumer community group (PCG) has emerged recently as an effective way to fulfill sustainable energy exchange. Such community-based energy sharing networks comprise multiple irreconcilable objectives such as demand constraints, cost constraints, and income maximization. In many cases, one goal may be achievable only at the expense of other goals. This necessitates the development of an effective framework to manage the multiple goals and reduce the gap with their achievement levels. Therefore, in this research paper, an effective framework is developed to negotiate among the multiple goals and thus to define optimal mutual goals for each PCG in a more sustainable manner using multiple-criteria goal programming techniques. Simulation results are presented to illustrate how the methods work in practical situations, where each of the objective measure is given a target value and the unwanted deviations from this set are minimized in an achievement function.     

Developing social impact assessment guidelines in a pre-existing policy context

Few jurisdictions have translated internationally agreed social impact assessment (SIA) principles into statutory provisions. Governments and regulatory bodies tend to provide developers with high-level frameworks, or require that social impacts be ‘considered’, without specifying how this is to be done. In Australia, this lack of clarity leaves all parties uncertain about requirements for SIA. The New South Wales (NSW) Government’s 2017 release of the SIA guideline for State-significant mining, petroleum and extractive industry development represents an attempt to clarify requirements and provide guidance. In this paper, we describe the process of bringing this guideline to fruition from the perspective of being directly involved in its development, and highlight the challenges involved in integrating leading-practice principles into the state’s pre-existing policy framework. While the guideline represents a significant advance in policy-based SIA guidance, some aspects leave room for improvement. The real test of the guideline’s impact will lie in its influence on SIA practice in NSW, and ultimately in social outcomes for communities affected by resources projects.     

Overlapping Schwarz and Spectral Element Methods for Linear Elasticity and Elastic Waves

The classical overlapping Schwarz algorithm is here extended to the spectral element discretization of linear elastic problems, for both homogeneous and heterogeneous compressible materials. The algorithm solves iteratively the resulting preconditioned system of linear equations by the conjugate gradient or GMRES methods. The overlapping Schwarz preconditioned technique is then applied to the numerical approximation of elastic waves with spectral elements methods in space and implicit Newmark time advancing schemes. The results of several numerical experiments, for both elastostatic and elastodynamic problems, show that the convergence rate of the proposed preconditioning algorithm is independent of the number of spectral elements (scalability), is independent of the spectral degree in case of generous overlap, otherwise it depends inversely on the overlap size. Some results on the convergence properties of the spectral element approximation combined with Newmark schemes for elastic waves are also presented.     

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,     

建设群力新区水系工程的初步设想

就水系工程水源的选择、规划设计要点,提出了初步设想。