Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs

Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs. We further characterized the early dynamics of LILRB2 and MHC-I expression by showing that SIVmac251 infection of macaques promotes coordinated up-regulation of LILRB2 and MHC-I on cDCs and monocytes/macrophages, from blood and lymph nodes. Orientation towards the LILRB2/MHC-I inhibitory axis starts from the first days of infection and is transiently induced in the entire cDC population in acute phase. Analysis of the factors involved indicates that HIV-1 replication, TLR7/8 triggering, and treatment by IL-10 or type I IFNs increase LILRB2 expression. Finally, enhancement of the LILRB2/MHC-I inhibitory axis is specific to HIV-1 and SIVmac251 infections, as expression of LILRB2 on cDCs decreased in naturally controlled chikungunya virus infection of macaques. Altogether, our data reveal a unique up-regulation of LILRB2 and its MHC-I ligands on cDCs in the early phase of SIV/HIV infection, which may account for immune dysregulation at a critical stage of the anti-viral response.     

文化线路遗产旅游体验影响因素研究——以丝绸之路为例

通过文献分析法以及访谈法拟定和选取了文化线路遗产旅游体验测评的潜变量和相应的测量变量,并基于陕西,甘肃两地丝绸之路世界遗址点景区的游客调研数据对丝绸之路文化线路遗产旅游体验评价维度进行验证性因子分析,构建了丝绸之路旅游体验影响因素的二阶五因素结构模型。结果显示:影响丝绸之路文化线路遗产旅游体验的因素并非是由资源主导,而是综合因素共同导向;遗产地旅游设施服务水平、遗产资源品质、遗产解说、活动参与感知以及遗产地环境氛围均显著影响旅游者体验质量,且以旅游设施服务能力的影响程度最大。     

EVOKE: A Value-Driven Concept Selection Method for Early System Design

The development of new technologically advanced products requires the contribution from a range of skills and disciplines, which are often difficult to find within a single company or organization. Requirements establishment practices in Systems Engineering (SE), while ensuring coordination of activities and tasks across the supply network, fall short when it comes to facilitate knowledge sharing and negotiation during early system design. Empirical observations show that when system-level requirements are not available or not mature enough, engineers dealing with the development of long lead-time sub-systems tend to target local optima, rather than opening up the design space. This phenomenon causes design teams to generate solutions that do not embody the best possible configuration for the overall system. The aim of this paper is to show how methodologies for value-driven design may address this issue, facilitating early stage design iterations and the resolution of early stage design trade-offs. The paper describes how such methodologies may help gathering and dispatching relevant knowledge about the ‘design intent’ of a system to the cross-functional engineering teams, so to facilitate a more concurrent process for requirement elicitation in SE. The paper also describes EVOKE (Early Value Oriented design exploration with KnowledgE maturity), a concept selection method that allows benchmarking design options at sub-system level on the base of value-related information communicated by the system integrators. The use of EVOKE is exemplified in an industrial case study related to the design of an aero-engine component. EVOKE’s ability to raise awareness on the value contribution of early stage design concepts in the SE process has been further verified with industrial practitioners in ad-hoc design episodes.     

The expansion of GPCR transactivation-dependent signalling to include serine/threonine kinase receptors represents a new cell signalling frontier

G protein-coupled receptor (GPCR) signalling is mediated through transactivation-independent signalling pathways or the transactivation of protein tyrosine kinase receptors and the recently reported activation of the serine/threonine kinase receptors, most notably the transforming growth factor-β receptor family. Since the original observation of GPCR transactivation of protein tyrosine kinase receptors, there has been considerable work on the mechanism of transactivation and several pathways are prominent. These pathways include the “triple membrane bypass” pathway and the generation of reactive oxygen species. The recent recognition of GPCR transactivation of serine/threonine kinase receptors enormously broadens the GPCR signalling paradigm. It may be predicted that the transactivation of serine/threonine kinase receptors would have mechanistic similarities with transactivation of tyrosine kinase pathways; however, initial studies suggest that these two transactivation pathways are mechanistically distinct. Important questions are the relative importance of tyrosine and serine/threonine transactivation pathways, the contribution of transactivation to overall GPCR signalling, mechanisms of transactivation and the range of cell types in which this phenomenon occurs. The ultimate significance of transactivation-dependent signalling remains to be defined but it appears to be prominent and if so will represent a new cell signalling frontier.     

环境规制政策与公共健康——基于环境污染的中介效应检验

为了探究环境规制政策对于环境污染及公共健康的影响,本文基于我国1978至2013年颁布的976条环境规制政策,利用从政策属性力度、政策内容力度两个维度对我国环境规制政策进行量化的数据,构建了针对环境规制政策效果的计量模型,通过将中介效应检验方法引入环境健康经济学分析,检验了环境污染对环境规制政策与公共健康的中介效应.研究结果表明:环境规制政策对公共健康具有促进作用;我国总体的环境规制政策对于防治环境污染产生了一定程度的积极效果;环境规制政策通过对环境污染显著的部分中介效应进而对公共健康产生了促进作用.本研究基于总体环境规制政策文献量化角度考察的"政策-环境-健康"三维动态关系结果,阐明了环境规制政策、环境污染以及公共健康三者的影响传输路径,对于有效评估环境规制政策效果,保障环境质量以及公共健康的可持续提升具有理论借鉴价值.     

中国大气颗粒物污染与致癌研究进展

 室外空气污染和污染空气中的颗粒物是一类致癌物，而近年中国的大气颗粒物污染仍然维持在较高浓度水平。通过综述中国近年大气颗粒物污染现状和开展的颗粒物致癌机制研究，分析中国研究中颗粒物有关实验动物致癌性的证据和颗粒物致癌的人群流行病学线索，阐述大气颗粒物与癌症的关系，提出中国亟需开展相关研究。     

Reconsideration on Homogeneous Quadratic Riemann Boundary Value Problem

The homogeneous quadratic Riemann boundary value problem (1) with Hoelder continuous coefficients for the normal case was considered by the author in 1997. But the solutions obtained there are incomplete. Here its general method of solution is obtained.     

"数字电路与系统"多媒体双语教学的体会

“数字电路与系统”具有实践性和离散性等特点;采用多媒体与板书相结合的方法克服多媒体的局限性,发扬板书的优势,取长补短;加强与学生的交流,创建和谐、有序、兴趣盎然的教学氛围。     

高校图书馆数字化与现代化服务

互联网改变了图书馆的运作方式，网络已成为高校图书馆信息采集、存储和传播的主要途径。介绍了高校图书馆数字化与现代化服务的主要内容，对高校图书馆数字化与现代化服务的功能与特点、技术关键、对策与措施及发展趋势进行了深入的探讨。     

Abrupt climate change：Debate or action

Global abrupt climate changes have been documented by various climate records, including ice cores, ocean sediment cores, lake sediment cores, cave deposits, loess deposits and pollen records. The climate system prefers to be in one of two stable states, i.e. interstadial or stadial conditions, but not in between. The transition between two states has an abrupt character. Abrupt climate changes are, in general, synchronous in the northern hemisphere and tropical regions. The timescale for abrupt climate changes can be as short as a decade. As the impacts may be potentially serious, we need to take actions such as reducing CO2 emissions to the atmosphere.