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21.
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.  相似文献   
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Reverberation is significant in shallow water and produces obvious notches in OBC spec-tra. It also degrades the quality of sections and increases the difficulty of processing and interpretation. This ...  相似文献   
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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.  相似文献   
26.
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.  相似文献   
27.
以玉林高中生物教师为研究对象,通过问卷调查法和个人访谈法对高中生物教师队伍的基本结构、生物教师配备、工作量、任职、收入、科研水平和进修培训等情况进行了调查,分析得出了影响高中生物教师发展的不利因素:(1)教师队伍结构不合理;(2)公立和私立学校、城市和乡镇学校,在师资配备、教师培养、待遇等方面的投入存在着较大的差距;(3)高中生物教师工作量较大、得到发展的机会较少;(4)教学资金投入不足,不利于教学工作的开展.文中结合新形势下对高中生物教师的要求,提出了一些促进高中生物教师发展的对策,以求为有关部门有效地优化高中生物教师队伍、合理利用和分配教师资源提供理论依据和实践参考.  相似文献   
28.
三门峡水库电站运行调度的优化研究   总被引:2,自引:0,他引:2  
三门峡水库泥沙淤积严重,使其枢纽的各项技术指标经常变化,为其调度运行带来极大困难。为此,充分考虑三门峡水电站运行过程中的各种约束条件,分别采用动态规划和遗传算法给出了电站优化调度模型,建立了该电站的运行调度系统。经过水库1991年—2000年实际来水和控制运行的月报资料的模拟验证,结果表明,该系统可平均增加发电量约12.9%,使电站能更合理地进行管理调度。而且,通过对随机模拟的长序列入库月径流过程的模拟调度,建议了三门峡水电站具体的管理调度运行方式。  相似文献   
29.
Reconsideration on Homogeneous Quadratic Riemann Boundary Value Problem   总被引:1,自引:0,他引:1  
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.  相似文献   
30.
“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。  相似文献   
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