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。     

Role of Nd-Ni on structural,spectral and dielectric properties of strontium-barium based nano-sized X-type ferrites

The influence of neodymium and nickel substitution on structural and dielectric parameters was investigated in strontium-barium X-type hexagonal ferrites having composition SrBaCu_2?xNi_xNd_yFe_28?yO₄₆ (x = 0, 0.2, 0.4, 0.6, 0.8, 1 and y = 0, 0.02, 0.04, 0.06, 0.08, 0.1). Sol-gel method was employed for synthesizing these hexagonal ferrites. The XRD plots of all studied materials which were annealed at 1250 °C show single phase characteristics. Lattice parameter ‘c’ increased as a consequence of larger radius of rare earth ion (Nd³⁺) as compared to (Fe³⁺), while lattice parameter ‘a’ showed very small variation. The cell volume was obtained in the range 2508.32–2523.75 (ų). The inclusion of Nd-Ni also affected X-ray density, bulk density and porosity. The FTIR spectroscopy indicated the particular absorption peaks of hexagonal ferrites and it was performed in the range of 500–700 cm^?1. On account of Nd-Ni doping, the dielectric constant, dielectric loss and AC-conductivity showed decreasing trend. The occupancy of Nd³⁺ ions at octahedral site impedes the valence alternation of Fe³⁺; therefore there was decrease in dielectric permittivity. Ac conductivity has been decreased from 9.14 to 6.49 (Ω cm)^?1 at frequency of 2.7 GHz. The Cole-Cole plots of synthesized materials noticeably revealed grain boundary contribution. The appearance of single semi-circle in impedance Cole-Cole graphs confirms the exceptional role of grain boundaries in the conduction process. The considerably lower dielectric parameters of investigated nano X-type ferrites propose their feasibility for high-frequency applications (phase shifters, dielectric resonators, stealth technology etc).     

Tuning of ferrimagnetic nature and hyperfine interaction of Ni2+ doped cobalt ferrite nanoparticles for power transformer applications

Ferrites may contain single domain particles which gets converted into super-paramagnetic state near critical size. To explore the existence of these characteristic feature of ferrites, we have performed magnetization(M-H loop) and Mössbauer spectroscopic studies of Ni²⁺ substitution effect in Co_1-xNi_xFe₂O₄ (where x?=?0, 0.25, 0.5, 0.75 and 1) nanoparticles were fabricated by solution combustion route using mixture of carbamide and glucose as fuels for the first time. As prepared samples exhibit spinel cubic structure with lattice parameters which decreases linearly with increase in Ni²⁺ concentration. The M-H loops reveals that saturation magnetization(M_s), coercive field(H_c) remanence magnetization(M_r) and magnetron number(η_B) decreases significantly with increasing Ni²⁺ substitution. The variation of saturation magnetization has been explained on the basis of Neel's molecular field theory. The coercive field(H_c) is found strongly dependent on the concentration of Ni²⁺ and decrease of coercivity suggests that the particles have single domain and exhibits superparamagnetic behavior. The Mössbauer spectroscopy shows two ferrimagnetically relaxed Zeeman sextets distribution at room temperature. The dependence of Mössbauer parameters such as isomer shift, quadru pole splitting, line width and hyperfine magnetic field on Ni²⁺ concentration have been discussed. Hence our results suggest that synthesized materials are potential candidate for power transformer application.     

DSR的一种自适应路由自动缩短机制

动态源路由协议是无线自组织网络众多路由协议中被广泛关注的一种按需路由协议，目前，关于该协议的优化措施有很多。本文先分析了动态源路由协议的一种优化机制——路由自动缩短，该机制能动态缩短处于工作状态路由的跳数，但不保证缩短路由的质量，在此基础上，提出一种自适应路由自动缩短机制，新机制既可缩短路由．又能保证缩短路由质量．理论分析及仿真结果表明，自适应路由缩短机制的各项性能优于原路由缩短机制。     

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…     

对地域通信网呼损的研究与仿真

本文通过对具有迂回路由的地域通信网呼损的研究与计算机仿真,得出迂回路由的存在使呼损大为降低的结论,从而增加了地域通信网的抗毁性能。     

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,     

新型实用布线算法──L─M算法

本文提出新型布线算法，集李氏迷宫法与线搜索法的长处为一体，以饱和带法进行动态排序，以线搜索法确定借孔位置，然后用李氏法进行单层布线，获得最佳路径，从而达到线型好，布通率高的效果。