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251.
Purification and cloning of amyloid precursor protein beta-secretase from human brain 总被引:40,自引:0,他引:40
Sinha S Anderson JP Barbour R Basi GS Caccavello R Davis D Doan M Dovey HF Frigon N Hong J Jacobson-Croak K Jewett N Keim P Knops J Lieberburg I Power M Tan H Tatsuno G Tung J Schenk D Seubert P Suomensaari SM Wang S Walker D Zhao J McConlogue L John V 《Nature》1999,402(6761):537-540
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. 相似文献
252.
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. 总被引:226,自引:0,他引:226
L A Donehower M Harvey B L Slagle M J McArthur C A Montgomery J S Butel A Bradley 《Nature》1992,356(6366):215-221
Mutations in the p53 tumour-suppressor gene are the most frequently observed genetic lesions in human cancers. To investigate the role of the p53 gene in mammalian development and tumorigenesis, a null mutation was introduced into the gene by homologous recombination in murine embryonic stem cells. Mice homozygous for the null allele appear normal but are prone to the spontaneous development of a variety of neoplasms by 6 months of age. These observations indicate that a normal p53 gene is dispensable for embryonic development, that its absence predisposes the animal to neoplastic disease, and that an oncogenic mutant form of p53 is not obligatory for the genesis of many types of tumours. 相似文献
253.
254.
Imran Sadiq Shahzad Naseem Saira Riaz S. Sajjad Hussain Muhammad Naeem Ashiq Mazhar Rana 《自然科学进展(英文版)》2018,28(4):478-482
Rare earth Dy~(3+)and divalent Mn~(2+)elements substituting W-type hexagonal ferrites Ba_(1-x)Dy_xZn_2Fe_(16-y)Mn_yO_(27)(x=0,0.02,0.06,0.1 and y=0,0.1,0.3,0.5)were prepared by sol-gel method.The thermo-gravimetric analysis(TGA)and differential scanning calorimetry(DSC)was carried out to find the temperature at which single phase can be obtained.XRD patterns indicate the presence of the single phase for all the synthesized samples with the absence of any extra peak due to unreacted material and secondary phases.The occurrence of absorption bands at low wave numbers(563 and 446 cm~(-1)),can be assigned to the stretching vibration of metal and oxygen ions in FTIR spectra,which also confirms the single hexagonal phase for prepared material.The grains are of platelet like structure,which enhances the microwave absorption properties of hexagonal ferrites.The synthesized material exhibits the minimum reflection loss of-20.9 dB at 11.8 GHz frequency,which reflects the applications of this material in super high frequency devices.The microwave conductivity of the material increases with frequency. 相似文献
255.
Volatility models such as GARCH, although misspecified with respect to the data‐generating process, may well generate volatility forecasts that are unconditionally unbiased. In other words, they generate variance forecasts that, on average, are equal to the integrated variance. However, many applications in finance require a measure of return volatility that is a non‐linear function of the variance of returns, rather than of the variance itself. Even if a volatility model generates forecasts of the integrated variance that are unbiased, non‐linear transformations of these forecasts will be biased estimators of the same non‐linear transformations of the integrated variance because of Jensen's inequality. In this paper, we derive an analytical approximation for the unconditional bias of estimators of non‐linear transformations of the integrated variance. This bias is a function of the volatility of the forecast variance and the volatility of the integrated variance, and depends on the concavity of the non‐linear transformation. In order to estimate the volatility of the unobserved integrated variance, we employ recent results from the realized volatility literature. As an illustration, we estimate the unconditional bias for both in‐sample and out‐of‐sample forecasts of three non‐linear transformations of the integrated standard deviation of returns for three exchange rate return series, where a GARCH(1, 1) model is used to forecast the integrated variance. Our estimation results suggest that, in practice, the bias can be substantial. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
256.
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. 相似文献
257.
研究在转杯纺加捻区中加装阻扭件,然后选用相同的棉条纺制不同捻系数的转杯纱(加装阻扭件和不加装阻扭件)和环锭纱,并测试其成纱的强伸性能、表面形态和扭转性能.测试结果表明,加装阻扭件的转杯纱可以适当改善转杯纺的加捻效果,进而适当提高了转杯纱的成纱强力. 相似文献
258.
A microRNA component of the p53 tumour suppressor network 总被引:5,自引:0,他引:5
259.
Windows环境下蒙古文复杂文本处理的研究 总被引:1,自引:0,他引:1
简要介绍了复杂文本和Uniscribe布局引擎,然后介绍一种基于Uniscribe的蒙古文Unicode文本的解释算法,解决Windows环境下字处理软件不支持蒙古文国际标准编码的问题.该算法具有较好的通用性,能够有效处理多种复杂文本语言,在蒙古文字处理软件MWord中的应用说明了该算法的有效性. 相似文献
260.
Biodiesel fuel is found to be a promising alter- native for the petroleum diesel based on the results published by the researchers for a decade. Biodiesel fuel is renewable and non degradable fuel. Many countries use biodiesel fuel for automotives to meet the crisis due to the depletion of the petroleum fuel and to meet the stringent emission norms. Various researches have been carried out with different bio- diesel fuels with vegetable oil as the source and appreciable results were reported. Few biodiesel fuels which have been already tested are Jatropha, Pongamia, Mahua, neem, cotton seed, etc. In this experimental work, Adelfa biodiesel blend is used as the test fuel. The emission and performance charac- teristics were compared with three other different biodiesel fuel blends. Appreciable results imply that Adelfa biodiesel (Nerium oil methyl ester) can be a futuristic biodiesel fuel, which has a good compatibility with the direct injection (DI) diesel engine without any major modification. Moreover, Adelfa can be cultivated in a non agricultural land with fewer sources of water. It is widely spread over all major countries of Asia. Experimental investigations have been carried out on a single cylinder DI diesel engine with standard engine speci- fications. In this experimental work, various Adelfa biodiesel blends is compared with reference fuel (diesel) to choose the best blend which gives a closer performance to diesel. The comparative analysis with other biodiesel fuels has also been done and results have been discussed. 相似文献