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.     

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.     

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.     

含PM-映射的变分不等式

文章在自反Banach空间中，利用锐角原理讨论了含PM-映射的变分不等式解的存在性问题。     

编队协同对地攻防对抗多级动态决策方法研究

针对编队协同对地攻击的攻防对抗系统的强对抗性、多目标性和多层次性,运用军事对抗的动态状态空间模型,建立了主从递阶互动决策模型——Nash-Stackelberg-Nash决策模型,重点解决军事对抗中寻求多级动态决策的联合最优策略问题。仿真结果表明,该决策模型应用于编队协同对地攻防对抗决策系统,良好的解决了两级对抗动态决策问题,并达到了较好的作战效果,能够为作战对抗提供有力的战场分析依据。     

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.     

The Optimal Solution of the Model with Physical and Human Capital Adjustment Costs

We prove that the model with physical and human capital adjustment costs has optimal solution when the production function is increasing return and the structure of vetor fields of the model changes substantially when the prodution function from decreasing return turns to increasing return. And it is shown that the economy is improved when the coefficients of adjustment costs become small.     

城市土地规划的优化方法研究

以多目标决策理论、组合优化理论以及预测科学技术为依据 ,首先建立了土地功能配置模型 ,帮助规划师对各种不同功能土地的片面布置进行分析 ,从而找到最合理的城市土地布局 ;然后以遗传算法作为优化工具 ,对建立的模型进行了优化。     

AC单兵喷射器的技术分析

文章详细介绍了AC单兵喷射器的设计原理，技术参数及性能特点。