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.     

凸曲面平头立铣刀刀位轨迹的计算方法

采用球面刀在三坐标数控机床上加工具有凸曲面工位的零部件时，往往会导致几何形状误差，对此，运用点涉法原理，推导出在凸曲面上确定平头立铣刀五轴和三轴数控联动加工刀位轨迹的计算方法。     

Far-infrared Absorption Spectra and Properties of SnO2 Nanorods

Nanostructured materials have drawn considerable attention because they are promising candidates for nextgeneration electronic and photonic devices with low power consumption[1-5]. A number of methods, such as laser ablation[6], template-induced growth[7], arc discharge [8], vapor transport [9], and molecular-beam epitaxy[10] have been developed to synthesize Si, Ge, MgO,SnO2, GaN, and Ga2O3 nanowires or nanorods[11-15].     

A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage

The p53 gene is frequently inactivated in human cancers. Here we have isolated a p53-inducible gene, p53R2, by using differential display to examine messenger RNAs in a cancer-derived human cell line carrying a highly regulated wild-type p53 expression system. p53R2 contains a p53-binding sequence in intron 1 and encodes a 351-amino-acid peptide with striking similarity to the ribonucleotide reductase small subunit (R2), which is important in DNA synthesis during cell division. Expression of p53R2, but not R2, was induced by ultraviolet and gamma-irradiation and adriamycin treatment in a wild-type p53-dependent manner. Induction of p53R2 in p53-deficient cells caused G2/M arrest and prevented cells from death in response to adriamycin. Inhibition of endogenous p53R2 expression in cells that have an intact p53-dependent DNA damage checkpoint reduced ribonucleotide reductase activity, DNA repair and cell survival after exposure to various genotoxins. Our results indicate that p53R2 encodes a ribonucleotide reductase that is directly involved in the p53 checkpoint for repair of damaged DNA. The discovery of p53R2 clarifies a relationship between a ribonucleotide reductase activity involved in repair of damaged DNA and tumour suppression by p53.     

Experimental validation of inter-subspecific genetic diversity in rice represented by the differences between the DNA sequences of ‘Nipponbare’ and ‘93-11’

The pedigrees of three sequenced rice cultivars were analyzed to show that a majority of the genetic composition of 'Nipponbare' originates from japonica cultivars while the minority originates from indica cultivars. In contrast, '93-11' is derived mainly from indica cultivars with a smaller contribution from japonica cultivars. All ancestors of 'Guang lu ai 4' appeared to be indica lines. A set of molecular markers (46 InDels and 53 SSRs) polymorphic between 'Nipponbare' and '93-11' were examined in 46 typical indica and 47 typical japonica cultivars selected from 443 accessions according to Cheng's index. All cultivars were divided into indica and japonica groups without overlapping when clustered by Cheng's index, InDels and SSRs. Much higher InDel and SSR diversity between groups than within groups implies that the marker polymorphisms between 'Nipponbare' and '93-11' represent a large proportion of inter-subspecific diversity. About 85% of indica cultivars and more than 90% of japonica cultivars were confirmed to have the same PCR banding patterns as '93-11' and 'Nipponbare', respectively. Some polymorphic loci between 'Nipponbare' and '93-11' cannot be validated in other indica and japonica cultivars, either as subspecies-specific but not predominant alleles, or alleles not specific between the two groups. It was concluded that molecular markers developed from sequence polymorphism between 'Nipponbare' and '93-11' often represent inter-subspecific diversity, although some exceptions were sensitive to either particular marker loci or particular cultivars.     

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.     

Direct splitting of water under visible light irradiation with an oxide semiconductor photocatalyst.

The photocatalytic splitting of water into hydrogen and oxygen using solar energy is a potentially clean and renewable source for hydrogen fuel. The first photocatalysts suitable for water splitting, or for activating hydrogen production from carbohydrate compounds made by plants from water and carbon dioxide, were developed several decades ago. But these catalysts operate with ultraviolet light, which accounts for only 4% of the incoming solar energy and thus renders the overall process impractical. For this reason, considerable efforts have been invested in developing photocatalysts capable of using the less energetic but more abundant visible light, which accounts for about 43% of the incoming solar energy. However, systems that are sufficiently stable and efficient for practical use have not yet been realized. Here we show that doping of indium-tantalum-oxide with nickel yields a series of photocatalysts, In(1-x)Ni(x)TaO(4) (x = 0-0.2), which induces direct splitting of water into stoichiometric amounts of oxygen and hydrogen under visible light irradiation with a quantum yield of about 0.66%. Our findings suggest that the use of solar energy for photocatalytic water splitting might provide a viable source for 'clean' hydrogen fuel, once the catalytic efficiency of the semiconductor system has been improved by increasing its surface area and suitable modifications of the surface sites.     

基于多源浮动车数据融合的道路交通运行评估

针对当前出租车浮动车数据覆盖范围和数据质量不足的问题,在现有数据特征分析的基础上引入百度手机导航和公交车浮动车导航数据,面向道路运行评估和拥堵管理提出了基于出行时间的交通运行指数算法和一种基于出租车、百度、公交车多源浮动车数据融合的道路交通运行评估方法,构建了多源数据融合规则和融合算法.以深圳为例进行了融合效果分析,结果表明所提出的多源数据融合方法效果显著,很大程度上提高了融合结果精度、数据覆盖率、数据可靠性和数据样本量,最后提出了主要应用方向和初步应用效果,能够为国内外城市开展交通运行评估工作提供借鉴.     

函数再现机构的可靠性综合

以曲柄滑块机构为例，提出了函数再现机构的可靠性综合方法．首先由机构的允许输出误差应用可靠性概念确定各构件尺寸，然后用概率法分配各构件的尺寸公差．从而使机构具有预定的可靠度．