Defining G protein-coupled receptor peptide ligand expressomes and signalomes in human and mouse islets

Introduction

Islets synthesise and secrete numerous peptides, some of which are known to be important regulators of islet function and glucose homeostasis. In this study, we quantified mRNAs encoding all peptide ligands of islet G protein-coupled receptors (GPCRs) in isolated human and mouse islets and carried out in vitro islet hormone secretion studies to provide functional confirmation for the species-specific role of peptide YY (PYY) in mouse islets.

Materials and methods

GPCR peptide ligand mRNAs in human and mouse islets were quantified by quantitative real-time PCR relative to the reference genes ACTB, GAPDH, PPIA, TBP and TFRC. The pathways connecting GPCR peptide ligands with their receptors were identified by manual searches in the PubMed, IUPHAR and Ingenuity databases. Distribution of PYY protein in mouse and human islets was determined by immunohistochemistry. Insulin, glucagon and somatostatin secretion from islets was measured by radioimmunoassay.

Results

We have quantified GPCR peptide ligand mRNA expression in human and mouse islets and created specific signalomes mapping the pathways by which islet peptide ligands regulate human and mouse GPCR signalling. We also identified species-specific islet expression of several GPCR ligands. In particular, PYY mRNA levels were ~ 40,000-fold higher in mouse than human islets, suggesting a more important role of locally secreted Pyy in mouse islets. This was confirmed by IHC and functional experiments measuring insulin, glucagon and somatostatin secretion.

Discussion

The detailed human and mouse islet GPCR peptide ligand atlases will allow accurate translation of mouse islet functional studies for the identification of GPCR/peptide signalling pathways relevant for human physiology, which may lead to novel treatment modalities of diabetes and metabolic disease.

     

An Economic Model-Based Matching Approach Between Buyers and Sellers Through a Broker in an Open E-Marketplace

A broker in an open e-marketplace enables buyers and sellers to do business with each other. Although a broker plays an important role in e-marketplaces, theory and guidelines for matching between buyers and sellers in multi-attribute exchanges are limited. Therefore, a challenge for a broker’s responsibility is how to maximize a buyer’s total satisfaction degree as its goals under the consideration of trade-off between a buyer’s buying quantity and price paid to a seller, and other attributes. To solve this challenge, this paper proposes an economic model-based matching approach between a buyer’s requirements and a seller’s offers. The major contributions of this paper are that (i) a broker can model a seller’s price policy as per a buyer’s buying quantity through communication between a broker and a seller; (ii) due to each buyer’s different quantity demand, a broker models a buyer’s satisfaction degree as per a buyer’s buying quantity based on communication between a broker and a buyer; and (iii) to carry out a broker’s matching processes, an objective function and a set of constraints are generated to help a broker to maximize a buyer’s total satisfaction degree. Experimental results demonstrate the good performance of the proposed approach.     

冻结黏土的强度与变形特性及参数研究

为了更全面地分析冻土的强度与变形特性,以皖北某矿取样的原状黏土为研究对象,进行不同温度(-5℃、-10℃、-15℃)下的单轴抗压强度试验和三轴剪切强度试验.试验结果表明,在试验温度下,试样单轴抗压强度的应力-应变曲线为应变软化型;试验条件下,冻土三轴剪切应力-应变曲线可以用双曲线模型描述.随着温度的降低,冻土的单轴抗压强度和弹性模量均增加.初始弹性模量和极限偏应力均与围压呈正相关,与温度呈负相关.冻土的抗剪强度随围压增加而增大,随温度增加而减小.通过冻土三轴试验得到的抗剪强度指标推算单轴抗压强度,可以为人工冻结法施工提供理论依据.     

部件寿命服从威布尔分布时典型系统的寿命与剩余寿命估计

在实际工程中,对系统寿命以及剩余寿命的估计非常重要。在已知系统中部件寿命与可靠度的前提下,关于如何快速得到系统级寿命与剩余寿命的相关研究比较缺乏。针对这一问题,首先研究了可靠度、寿命以及剩余寿命的关系,进一步假设部件寿命服从同一威布尔分布,根据部件的寿命与可靠度函数,推导得到串联、并联和表决系统寿命与剩余寿命期望的封闭表达式,并给出了相应的计算方法。对于冷备系统,当部件寿命服从同一指数分布时,推得了系统寿命及剩余寿命期望的封闭表达式,而当部件寿命服从同一威布尔分布时,给出了系统寿命与剩余寿命的数值计算方法。仿真试验证明本文所提出的方法是准确高效的。最后,以卫星中的动量轮r/n(G)表决系统为例开展了实例研究,证明了该方法在工程实践中的有效性。     

Hierarchical Community Detection Based on Partial Matrix Convergence Using Random Walks

Random walks are a standard tool for modeling the spreading process in social and biological systems.But in the face of large-scale networks,to achieve convergence,iterative calculation of the transition matrix in random walk methods consumes a lot of time.In this paper,we propose a three-stage hierarchical community detection algorithm based on Partial Matrix Approximation Convergence(PMAC) using random walks.First,this algorithm identifies the initial core nodes in a network by classical measurement and then utilizes the error function of the partial transition matrix convergence of the core nodes to determine the number of random walks steps.As such,the PMAC of the core nodes replaces the final convergence of all the nodes in the whole matrix.Finally,based on the approximation convergence transition matrix,we cluster the communities around core nodes and use a closeness index to merge two communities.By recursively repeating the process,a dendrogram of the communities is eventually constructed.We validated the performance of the PMAC by comparing its results with those of two representative methods for three real-world networks with different scales.     

乡村振兴绩效评价:意义、维度与路径

2018年,中共中央、国务院印发《中国乡村振兴战略规划(2018-2022年)》,全面部署和布局乡村振兴战略.文章基于政府绩效评价的理念和方法,构建乡村振兴绩效评价指标体系,明确评价维度,为实现乡村振兴、城乡融合发展提供价值导向、度量体系和动力工具.该评价维度包涵资源投入、过程监管、目标实现情况和社会满意度四个方面.文章指出,相关单位以绩效评价推进乡村振兴时应注重顶层设计,强化部门协同,构建评价体系,引入第三方评价主体,凸显农民获得感.     

等候区手术患者家属的心理影响因素及干预措施

目的:探讨等候区手术患者家属的心理影响因素及其干预措施.方法:通过临床护理实践及查阅相关文献进行总结分析.结果:影响因素及其干预措施包括详解病情及手术风险性;对手术环境及术中情况的告知;完善急诊手术患者家属心理干预;根据不同文化水平进行健康宣教;尽量以病情为主,设计最经济有效的治疗方案;提高医护人员从业技能及道德品质.结论:对等候区手术患者家属进行积极有效的心理干预,可很大程度上减轻患者家属的焦虑程度,缓和医患关系,一定程度上提升了医疗质量.     

数字量子模拟已经应用到两费米子体系了（英文）

In a recent work,a group of researchers led by Gui-Lu Long of Tsinghua University proposed a digital quantum simulation algorithm for the dynamics of interacting quantum systems in real space.They experimentally implemented the algorithm to simulate the dynamics of two interacting fermions using a nuclear magnetic resonance(NMR)setup[1].     

基于计算实验的流感大流行预防策略

流感是人类健康的重大威胁之一.为探索预防新型流感大流行的有效策略,建立了北京市计算流行病模型,评估了边境口岸检疫,病例治疗,病例隔离,社会关系抗病毒预防以及免疫接种措施对四种新型流感大流行的预防效能.结果表明:边境口岸检疫对于预防新型流感大流行的作用非常有限;积极的病例治疗可预防传播能力类似于2009年A(H1N1)的新型流感大流行;高强度的病例治疗和病例隔离可预防传播能力类似于1957年A(H2N2)的新型流感大流行;对于传播能力类似于1918年A(H1N1)的新型流感,在高强度病例治疗和病例隔离的基础上须对病例的社会关系进行抗病毒预防才有可能预防大流行;而对于具有超级传播能力的新型流感(R_03.3),必须依靠有效的广谱疫苗才能预防大流行.研究结果对于进一步完善我国应对流感大流行的应急准备与处置计划具有参考价值.     

考虑交付质量和交付期约束的移动应用供应链决策与协调

针对由ERP厂商、APP厂商与客户企业组成的移动应用供应链,考虑客户企业对软件质量与交付时间存在约束,ERP厂商的售前服务会影响软件开发质量等问题,构建了基于软件质量与交付时间的收益模型,分析了分散与集中决策下双方的最优决策策略以及APP厂商的售后维护成本分担比例与应急成本对双方决策水平的影响,比较了两种决策下对应的合作绩效,提出了双向成本分担与提前交付奖励的供应链协调策略.研究表明:随客户企业的质量感知度增大,ERP厂商通过适当延长交付时间产生的质量改进效应大于延长交付期产生的负效应,使总效应增加;当客户企业的交付期敏感程度小于临界值时,ERP厂商可通过交付高质量软件产品提高自身利润,当交付期敏感程度大于临界值时,可通过提前交付提高自身利润;通过对供应链进行协调,可使原本因无法满足客户企业对质量与交付期的要求而使双方放弃合作的情形变得可合作,使原本可合作时双方的合作绩效与利润更高;当APP厂商独自承担售后维护成本时,实施供应链协调产生的价值大于双方共同承担时对应的值.