Modelling T-cell memory by genetic marking of memory T cells in vivo.

Immunological memory is the ability of the immune system to respond with enhanced vigour to pathogens that have been encountered in the past. Following infection or immunization, most effector T cells undergo apoptotic cell death, but a small fraction of these cells, proportional to the early antigen load and initial clonal burst size, persist in the host as a stable pool of memory T cells. The existence of immunological memory has been recognized for over 2,000 years, but our understanding of this phenomenon is limited, primarily because memory lymphocytes cannot be unequivocally identified as they lack specific, permanent markers. Here we have developed a transgenic mouse model system whereby memory T cells and their precursors can be irreversibly marked with a reporter gene and thus can be unambiguously identified. Adoptive transfer of marked CD8+ T cells specific for lymphocytic choriomeningitis virus protected naive recipients following viral challenge, demonstrating that we have marked memory T cells. We also show that cytotoxic effector lymphocytes that develop into memory T cells can be identified in the primary response.     

Reciprocal interactions of the intestinal microbiota and immune system

The emergence of the adaptive immune system in vertebrates set the stage for evolution of an advanced symbiotic relationship with the intestinal microbiota. The defining features of specificity and memory that characterize adaptive immunity have afforded vertebrates the mechanisms for efficiently tailoring immune responses to diverse types of microbes, whether to promote mutualism or host defence. These same attributes can put the host at risk of immune-mediated diseases that are increasingly linked to the intestinal microbiota. Understanding how the adaptive immune system copes with the remarkable number and diversity of microbes that colonize the digestive tract, and how the system integrates with more primitive innate immune mechanisms to maintain immune homeostasis, holds considerable promise for new approaches to modulate immune networks to treat and prevent disease.     

A component of innate immunity prevents bacterial biofilm development

Antimicrobial factors form one arm of the innate immune system, which protects mucosal surfaces from bacterial infection. These factors can rapidly kill bacteria deposited on mucosal surfaces and prevent acute invasive infections. In many chronic infections, however, bacteria live in biofilms, which are distinct, matrix-encased communities specialized for surface persistence. The transition from a free-living, independent existence to a biofilm lifestyle can be devastating, because biofilms notoriously resist killing by host defence mechanisms and antibiotics. We hypothesized that the innate immune system possesses specific activity to protect against biofilm infections. Here we show that lactoferrin, a ubiquitous and abundant constituent of human external secretions, blocks biofilm development by the opportunistic pathogen Pseudomonas aeruginosa. This occurs at lactoferrin concentrations below those that kill or prevent growth. By chelating iron, lactoferrin stimulates twitching, a specialized form of surface motility, causing the bacteria to wander across the surface instead of forming cell clusters and biofilms. These findings reveal a specific anti-biofilm defence mechanism acting at a critical juncture in biofilm development, the time bacteria stop roaming as individuals and aggregate into durable communities.     

防空战略势函数的PDG模型

基于对防空战略作战势的认识，引入了描述防空战略势的势函数的PDG模型，该模型具有便于进行防空战略体系优势分析的特点。并对防空战略体系的优势建设进行了初步分析和探讨。     

The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens.

Macrophages orchestrate innate immunity by phagocytosing pathogens and coordinating inflammatory responses. Effective defence requires the host to discriminate between different pathogens. The specificity of innate immune recognition in Drosophila is mediated by the Toll family of receptors; Toll mediates anti-fungal responses, whereas 18-wheeler mediates anti-bacterial defence. A large number of Toll homologues have been identified in mammals, and Toll-like receptor 4 is critical in responses to Gram-negative bacteria. Here we show that Toll-like receptor 2 is recruited specifically to macrophage phagosomes containing yeast, and that a point mutation in the receptor abrogates inflammatory responses to yeast and Gram-positive bacteria, but not to Gram-negative bacteria. Thus, during the phagocytosis of pathogens, two classes of innate immune receptors cooperate to mediate host defence: phagocytic receptors, such as the mannose receptor, signal particle internalization, and the Toll-like receptors sample the contents of the vacuole and trigger an inflammatory response appropriate to defence against the specific organism.     

对保障律师参与刑事诉讼权利问题的探讨

保障律师辩护是完善辩护制度的重要内容，而在现实中律师行使辩护权存在诸多问题。律师辩护权难以有效保障与我国的律师环境恶劣密切相关，进一步改善辩护律师的执业环境，逐步完善刑事诉讼结构，强化律师的诉讼保障，是解决这一问题的关键。     

略论假想防卫及其过当

大陆法系对属于违法性阻却事由的错误的假想防卫及其过当存在着极为复杂的理论和激烈的争论,属于事实错误的假想防卫只可能是疏忽大意的过失犯罪或者意外事件,而行为人对其过当部分也正如对防卫过当一样不可能存在故意。     

Generalization in vision and motor control

Learning is more than memory. It is not simply the building of a look-up table of labelled images, or a phone-directory-like list of motor acts and the corresponding sequences of muscle activation. Central to learning and intelligence is the ability to predict, that is, to generalize to new situations, beyond the memory of specific examples. The key to generalization, in turn, is the architecture of the system, more than the rules of synaptic plasticity. We propose a specific architecture for generalization for both the motor and the visual systems, and argue for a canonical microcircuit underlying visual and motor learning.     

试论我国审前准备程序的构建

20世纪90年代,中国实行的＂一步到庭＂产生了很多问题,由于开庭审理前没有进行争点整理和证据固定,很容易造成案件多次开庭审理,严重影响了司法效率。结合我国的具体国情,以我国民事诉讼目的为出发点和归宿,在现阶段采取以偏向职权主义诉讼模式,辅之以当事人主义诉讼模式的特点为基本思路,增加答辩和证据制度,在一定情况下发挥法官的释明权,构建中国特色的审前准备程序。     

北京电网集控型防误系统建设研究

本文针对北京电网集控站现有运行模式,提出北京电网集控型防误系统建设方案,对集控型防误系统建设需求作了详细分析,提出了北京电网集控型防误系统所需特点,重点讨论了集控站防误系统建设方案中的组网模式、五防操作模式以及防误系统功能的设计方案,为保证北京电网电力设备的安全稳定运行提供了思路。     

Viral immune modulators perturb the human molecular network by common and unique strategies

Viruses must enter host cells to replicate, assemble and propagate. Because of the restricted size of their genomes, viruses have had to evolve efficient ways of exploiting host cell processes to promote their own life cycles and also to escape host immune defence mechanisms. Many viral open reading frames (viORFs) with immune-modulating functions essential for productive viral growth have been identified across a range of viral classes. However, there has been no comprehensive study to identify the host factors with which these viORFs interact for a global perspective of viral perturbation strategies. Here we show that different viral perturbation patterns of the host molecular defence network can be deduced from a mass-spectrometry-based host-factor survey in a defined human cellular system by using 70 innate immune-modulating viORFs from 30 viral species. The 579 host proteins targeted by the viORFs mapped to an unexpectedly large number of signalling pathways and cellular processes, suggesting yet unknown mechanisms of antiviral immunity. We further experimentally verified the targets heterogeneous nuclear ribonucleoprotein?U, phosphatidylinositol-3-OH kinase, the WNK (with-no-lysine) kinase family and USP19 (ubiquitin-specific peptidase 19) as vulnerable nodes in the host cellular defence system. Evaluation of the impact of viral immune modulators on the host molecular network revealed perturbation strategies used by individual viruses and by viral classes. Our data are also valuable for the design of broad and specific antiviral therapies.     

一种基于VxWorks的内存管理封装层的设计与实现

根据特定应用领域对商用嵌入式操作系统进行封装是很有必要的．通信类产品应用程序的内存管理往往对性能与安全有特殊的要求,本文在VxWorks提供的内存管理功能的基础上给出了一种封装方案：使用块内存与堆内存两种分配与释放方式提高内存管理性能,增加调试信息;通过“加墙”或“加页”两种方式实现内存保护,使封装后的VxWorks更适合通信产品应用领域的软件开发．     

Optogenetic stimulation of a hippocampal engram activates fear memory recall

A specific memory is thought to be encoded by a sparse population of neurons. These neurons can be tagged during learning for subsequent identification and manipulation. Moreover, their ablation or inactivation results in reduced memory expression, suggesting their necessity in mnemonic processes. However, the question of sufficiency remains: it is unclear whether it is possible to elicit the behavioural output of a specific memory by directly activating a population of neurons that was active during learning. Here we show in mice that optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behaviour. We labelled a population of hippocampal dentate gyrus neurons activated during fear learning with channelrhodopsin-2 (ChR2) and later optically reactivated these neurons in a different context. The mice showed increased freezing only upon light stimulation, indicating light-induced fear memory recall. This freezing was not detected in non-fear-conditioned mice expressing ChR2 in a similar proportion of cells, nor in fear-conditioned mice with cells labelled by enhanced yellow fluorescent protein instead of ChR2. Finally, activation of cells labelled in a context not associated with fear did not evoke freezing in mice that were previously fear conditioned in a different context, suggesting that light-induced fear memory recall is context specific. Together, our findings indicate that activating a sparse but specific ensemble of hippocampal neurons that contribute to a memory engram is sufficient for the recall of that memory. Moreover, our experimental approach offers a general method of mapping cellular populations bearing memory engrams.     

不安抗辩权制度评析

不安抗辩权制度是我国新合同法确立的一项重要法律制度，它的设立是我国立法的一大进步，其对合同的正确履行和社会经济生活、市场交换秩序都有重要的意义，但在实践中不安抗辩权制度仍然存在一定的缺陷，对此本文提出探讨性的意见及对策。     

强制辩护制度探究

刑事诉讼中的辩护权是被追诉人的一项基本权利,辩护权行使的充分与否,不仅关涉被追诉人的切身利益,更影响着司法的公正性和公信力。现阶段我国刑事案件辩护率低且逐年下降,辩护人的缺席导致控辩力量对比失衡,控辩平等对抗近乎空谈,被告人的正当权益屡遭侵害,冤假错案时有发生。为突破这一困境,提高刑事案件审判水平,借鉴引入强制辩护制度尤为重要,通过强制辩护制度,制衡控方公权力行使,规范刑事诉讼活动,切实维护刑事被追诉人的基本权利,对我国刑事诉讼法的发展具有重要意义。     

紫外线(UV)-B辐射增强对植物影响的研究进展

紫外线—B辐射增强时生物和生态系统的影响是目前科学研究的热点之一，本文从植物的生理活动、蛋白质和DNA分子、防御反应等几个方面对植物受到紫外线—B辐射增强的影响进行了综述，并论述了在紫外线—B辐射下植物产生的一些防御反应。     

Calmodulin interacts with MLO protein to regulate defence against mildew in barley

In plants, defence against specific isolates of a pathogen can be triggered by the presence of a corresponding race-specific resistance gene, whereas resistance of a more broad-spectrum nature can result from recessive, presumably loss-of-regulatory-function, mutations. An example of the latter are mlo mutations in barley, which have been successful in agriculture for the control of powdery mildew fungus (Blumeria graminis f. sp. hordei; Bgh). MLO protein resides in the plasma membrane, has seven transmembrane domains, and is the prototype of a sequence-diversified family unique to plants, reminiscent of the seven-transmembrane receptors in fungi and animals. In animals, these are known as G-protein-coupled receptors and exist in three main families, lacking sequence similarity, that are thought to be an example of molecular convergence. MLO seems to function independently of heterotrimeric G proteins. We have identified a domain in MLO that mediates a Ca2+-dependent interaction with calmodulin in vitro. Loss of calmodulin binding halves the ability of MLO to negatively regulate defence against powdery mildew in vivo. We propose a sensor role for MLO in the modulation of defence reactions.     

“制贼”与“防夷”——以清代前期广东海防为中心的考察

清代前期,广东沿海构建了严密的海防体系,部署了星罗棋布的海防军队,并采取了一系列意在＂制贼＂的措施,＂防夷＂意识也逐渐萌动。但是,由于统治者一贯的自大和对外界的茫然无知,未能顺应时代的要求做出积极反应。清代前期,在以＂防＂为主的思想指导下,以＂禁＂为基本特征的海防实践,对我国海防事业的发展产生了消极影响,最终失职于海防重责。     

局部开发人防坑道为主扇性能测试系统

根据人防工程与煤矿巷道的相似性，详细论述了局部改造人防坑道为主扇性能测试系统的实施方法及应用效果。     

防空战略作战的势战律建模研究

基于对防空战略作战势战律的认识 ,首次引入了防空战略体系的势函数的概念 ,建立了势的比较、等势面、势的发展等概念 ,提出了势的规划问题。并结合模型对防空战略作战体系建设得到了一些非常有益的启示。