Molecular pathogenesis of apolipoprotein E-mediated amyloidosis in late-onset Alzheimer’s disease

Apolipoprotein E (apoE) ɛ4 allele is a genetic risk factor for late-onset familial and sporadic Alzheimer’s disease (AD). In the central nervous system, apoE is secreted mainly by astrocytes as a constituent of high-density lipoproteins. A recent study using apoE knockout mice provided strong evidence that apoE promotes cerebral deposition of amyloid β protein (Aβ). However, no clear explanation of the pathogenesis of apoE-induced AD has been provided. Here we discuss two possible mechanisms by which apoE might enhance Aβ deposition. One is the intracellular pathway in which apoE is internalized by neurons and induces lysosomal accumulation of Aβ and amyloidogenic APP (amyloid precursor protein) fragments, leading to neuronal death. The other is the extracellular pathway in which apoE-containing lipoproteins are trapped by Aβ1–42 deposits mobilizing soluble Aβ peptides and consequently enlarge amyloid plaques. These two mechanisms may operate at different stages of AD pathogenesis and suggest a chaperone-like function for the apoE molecule. Received 4 February 1999; received after revision 9 April 1999; accepted 23 April 1999     

七绝、文人竹枝词与客家山歌

七绝,本为来自民间的七言诗,经永明体而为近体诗之一种诗体;竹枝词,本为巴渝民歌,自刘禹锡以降．历代文人多有仿作,所仿作者为文人竹枝词;而客家山歌,则是自明清客家民系形成以来,至今犹传承于客地的鲜活民歌。从这三种诗歌中,可发现雅俗文学之间的交融、碰撞而嬗变的文学雅俗互动的有趣轨迹。     

额田王咏秋风歌之语象溯源

古代中日两国吟咏爱情的诗歌中，“秋风”一词时有所见。从日本最早的古典和歌大成《万叶集》中所记载的、由女歌人额田王所咪的“思近江天皇咏秋风歌”可知，它与中国六朝闺怨诗既有联系又有区别，“秋风”语象在当时的中日诗歌中具有不同的意蕴。     

Klein-Weyl's program and the ontology of gauge and quantum systems

We distinguish two orientations in Weyl's analysis of the fundamental role played by the notion of symmetry in physics, namely an orientation inspired by Klein's Erlangen program and a phenomenological-transcendental orientation. By privileging the former to the detriment of the latter, we sketch a group(oid)-theoretical program—that we call the Klein-Weyl program—for the interpretation of both gauge theories and quantum mechanics in a single conceptual framework. This program is based on Weyl's notion of a “structure-endowed entity” equipped with a “group of automorphisms”. First, we analyze what Weyl calls the “problem of relativity” in the frameworks provided by special relativity, general relativity, and Yang-Mills theories. We argue that both general relativity and Yang-Mills theories can be understood in terms of a localization of Klein's Erlangen program: while the latter describes the group-theoretical automorphisms of a single structure (such as homogenous geometries), local gauge symmetries and the corresponding gauge fields (Ehresmann connections) can be naturally understood in terms of the groupoid-theoretical isomorphisms in a family of identical structures. Second, we argue that quantum mechanics can be understood in terms of a linearization of Klein's Erlangen program. This stance leads us to an interpretation of the fact that quantum numbers are “indices characterizing representations of groups” ((Weyl, 1931a), p.xxi) in terms of a correspondence between the ontological categories of identity and determinateness.     

4-Hydroxynonenal-modified amyloid-beta peptide inhibits the proteasome: possible importance in Alzheimer's disease

The amyloid β-peptide (Aβ) is a 4-kDa species derived from the amyloid precursor protein, which accumulates in the brains of patients with Alzheimer’s disease. Although we lack full understanding of the etiology and pathogenesis of selective neuron death, considerable data do imply roles for both the toxic Aβ and increased oxidative stress. Another significant observation is the accumulation of abnormal, ubiquitin-conjugated proteins in affected neurons, suggesting dysfunction of the proteasome proteolytic system in these cells. Recent reports have indicated that Aβ can bind and inhibit the proteasome, the major cytoslic protease for degrading damaged and ubiquitin-conjugated proteins. Earlier results from our laboratory showed that moderately oxidized proteins are preferentially recognized and degraded by the proteasome; however, severely oxidized proteins cannot be easily degraded and, instead, inhibit the proteasome. We hypothesized that oxidatively modified Aβ might have a stronger (or weaker) inhibitory effect on the proteasome than does native Aβ. We therefore also investigated the proteasome inhibitory action of Aβ _1–40 (a peptide comprising the first 40 residues of Aβ) modified by the intracellular oxidant hydrogen peroxide, and by the lipid peroxidation product 4-hydroxynonenal (HNE). H₂O₂ modification of Aβ _1–40 generates a progressively poorer inhibitor of the purified human 20S proteasome. In contrast, HNE modification of Aβ _1–40 generates a progressively more selective and efficient inhibitor of the degradation of fluorogenic peptides and oxidized protein substrates by human 20S proteasome. This interaction may contribute to certain pathological manifestations of Alzheimer’s disease Received 26 September 2000; accepted 26 September 2000     

二阶退化双曲型方程的第二类广义Darboux问题

A.V.Bitsadze在文[1]中提出和研究了二阶一致线性双曲型方程uxx-uyy+aux+by+cu+d=0(A)的第一类和第二类Darboux问题.本文的目的是讨论二阶退化双曲型方程第二类广义Darboux问题和斜微商问题解的表示式,并证明这些问题解的存在唯一性。本文使用不同于[1]中的方法,但类似于[1]中的方程(A),根据本文中的结果,我们可以解决广义Chaplygin方程在一般区域上的Frankl问题.     

儿童连身裤结构参数与人体运动适应性研究

采用人体体表描线法对8～9岁男童进行皮肤变化率的测量实验,通过测量人体动、静态6种动作下的皮肤变化率,得出影响儿童连身裤设计的结构参数,即背长、胸围、臀围、立裆及它们的取值范围.     

一种新型的智能式体液粘弹性检测系统

介绍了一种体液粘弹性自动检测系统。该系统在ｆ＝１￣１０Ｈｚ的振荡频率范围内，流体的复粘度的粘性分量和弹性分量的变化比较平缓。     

两类熵密度规划的对偶规划和最优性条件

基于广义的Fenchel对偶定理及其相应的Kuhn-Tucker条件,给出了带有二次约束和熵密度约束的二次规划问题和熵密度问题的对偶规划,强对偶定理以及Kuhn-Tucker条件。     

基于虚拟仪器的锅炉运行参数监测系统设计

针对传统锅炉运行参数监测系统监测点分散、节点数据共享及一体化管理难度大等问题,构建了基于虚拟仪器的锅炉运行参数监测系统,该系统以MSP430F149单片机为控制器的测量节点,构建了CAN总线网络,配置了CAN-以太网转换器将总线数据传输至局域网,采用了基于Lab View的上位机监控软件优化人机界面,实现了对锅炉运行系统的多参数、一体化实时监控和故障预警。