Purification and cloning of amyloid precursor protein beta-secretase from human brain

Proteolytic processing of the amyloid precursor protein (APP) generates amyloid beta (Abeta) peptide, which is thought to be causal for the pathology and subsequent cognitive decline in Alzheimer's disease. Cleavage by beta-secretase at the amino terminus of the Abeta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated carboxy-terminal fragment. Cleavage of the C-terminal fragment by gamma-secretase(s) leads to the formation of Abeta. The pathogenic mutation K670M671-->N670L671 at the beta-secretase cleavage site in APP, which was discovered in a Swedish family with familial Alzheimer's disease, leads to increased beta-secretase cleavage of the mutant substrate. Here we describe a membrane-bound enzyme activity that cleaves full-length APP at the beta-secretase cleavage site, and find it to be the predominant beta-cleavage activity in human brain. We have purified this enzyme activity to homogeneity from human brain using a new substrate analogue inhibitor of the enzyme activity, and show that the purified enzyme has all the properties predicted for beta-secretase. Cloning and expression of the enzyme reveals that human brain beta-secretase is a new membrane-bound aspartic proteinase.     

An organic thyristor

Thyristors are a class of nonlinear electronic device that exhibit bistable resistance--that is, they can be switched between two different conductance states. Thyristors are widely used as inverters (direct to alternating current converters) and for the smooth control of power in a variety of applications such as motors and refrigerators. Materials and structures that exhibit nonlinear resistance of this sort are not only useful for practical applications: they also provide systems for exploring fundamental aspects of solid-state and statistical physics. Here we report the discovery of a giant nonlinear resistance effect in the conducting organic salt theta-(BEDT-TTF)2CsCo(SCN)4, the voltage-current characteristics of which are essentially the same as those of a conventional thyristor. This intrinsic organic thyristor works as an inverter, generating an alternating current when a static direct-current voltage is applied. Whereas conventional thyristors consist of a series of diodes (their nonlinearity comes from interface effects at the p-n junctions), the present salt exhibits giant nonlinear resistance as a bulk phenomenon. We attribute the origin of this effect to the current-induced melting of insulating charge-order domains, an intrinsically non-equilibrium phenomenon in the sense that ordered domains are melted by a steady flow.     

形变双奇核1944Au中的强耦合带

利用重离子融合蒸发反应159Tb（29Si,4nγ）194Au布居了形变双奇核184Au的高自旋态,用GASP探测器阵列进行了在束γ实验测量．通过对实验数据的深入分析,新发现了一条可归属于184Au核的强耦合转动带．基于对转动带有效K值的分析以及从实验数据中提取出的带内B（M1）／B（E2）值与理论计算值的比较,建议了转动带的准粒子组态和能级的自旋宇称值．     

SLAC1 is required for plant guard cell S-type anion channel function in stomatal signalling

Stomatal pores, formed by two surrounding guard cells in the epidermis of plant leaves, allow influx of atmospheric carbon dioxide in exchange for transpirational water loss. Stomata also restrict the entry of ozone--an important air pollutant that has an increasingly negative impact on crop yields, and thus global carbon fixation and climate change. The aperture of stomatal pores is regulated by the transport of osmotically active ions and metabolites across guard cell membranes. Despite the vital role of guard cells in controlling plant water loss, ozone sensitivity and CO2 supply, the genes encoding some of the main regulators of stomatal movements remain unknown. It has been proposed that guard cell anion channels function as important regulators of stomatal closure and are essential in mediating stomatal responses to physiological and stress stimuli. However, the genes encoding membrane proteins that mediate guard cell anion efflux have not yet been identified. Here we report the mapping and characterization of an ozone-sensitive Arabidopsis thaliana mutant, slac1. We show that SLAC1 (SLOW ANION CHANNEL-ASSOCIATED 1) is preferentially expressed in guard cells and encodes a distant homologue of fungal and bacterial dicarboxylate/malic acid transport proteins. The plasma membrane protein SLAC1 is essential for stomatal closure in response to CO2, abscisic acid, ozone, light/dark transitions, humidity change, calcium ions, hydrogen peroxide and nitric oxide. Mutations in SLAC1 impair slow (S-type) anion channel currents that are activated by cytosolic Ca2+ and abscisic acid, but do not affect rapid (R-type) anion channel currents or Ca2+ channel function. A low homology of SLAC1 to bacterial and fungal organic acid transport proteins, and the permeability of S-type anion channels to malate suggest a vital role for SLAC1 in the function of S-type anion channels.     

SoC处理器的时钟生成器：电路和体系结构

本书涵盖了面向SoC（System　on　Chip，片上系统）处理器的集成综合器电路设计的论题，采取了一种更为全局的设计观念来考察电路级和体系结构级的设计空间。书中的论述十分广泛，而且包括电路理论和锁相环反馈控制理论的综述。在电路级方面，讨论包括深亚微米数字CMOS过程的低功耗模拟设计、供电噪声效应、设备噪声；在体系结构级方面的论述，涵盖了连续时间和离散时间模型的锁相环分析，以及锁相行为的细节分析。还有一些章节对特定的时钟生成器模块做了电路级和系统结构级的深入描述，其中包括高供电噪声屏蔽的锁相环电路、体系结构和数字锁相环体系结构，考察了为离散时间模拟部件产生低失真采样时钟的方法。这里所说的锁相环包括希格马．代尔塔N分锁相环、直接数字综合（DDS、Direct　Digital　Synthesis）技术和锁相环的非常规应用。本书讨论的面向测试的设计（Dvr、Design　for　Test），其中包括锁相环的精确测量滤波器方法和嵌人式测试（BIST、Built—in—self-test）技术。     

Using Mutual Feedback Chaotic Synchronous Systems

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Integrating complex system dynamics of pandemic influenza with a multi-criteria decision making model for evaluating public health strategies

Recent developments in computational sciences and computer modeling have allowed emergency preparedness exercises to include simulation models as supporting tools.These simulation models are generally built for predicting temporal and geographic patterns of disease spread.However sole use of simulation models in exercise design falls short in terms of incorporating policy decision makers’ preferences into decision-making processes.In this paper,a general framework for exercising public health preparedness plans with a decision support system is presented to integrate estimation of key epidemiological parameters with a system dynamics model of an outbreak.A multi-criteria decision making framework,an Analytical Hierarchy Process model,is then developed and integrated with the simulation model to help public health policy makers prioritize their response goals and evaluate mitigation strategies in a table-top exercise environment.