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91.
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
92.
乳腺癌一直是全世界范围内威胁妇女健康的恶性疾病, 尽管人们已经进行了大量的研究以减少乳腺癌对人类的危害, 但是乳腺癌仍然是目前导致死亡的恶性肿瘤之一. 乳腺癌的早期发现对于患者的愈后与生存意义重大, 可以明显提高病人生存时间、降低病人的死亡率. 据统计, 在过去的5年里, 早期诊断每年可减少3.2%因乳腺癌死亡的患者. 然而研究表明, 目前常用的乳腺癌诊断技术, 如乳腺X射线摄影和乳房检查均无法诊断出40%的早期乳癌患者和大多数年轻女性的乳腺肿瘤. 因此在乳腺癌临床治疗中, 急需发展新型的高效诊断技术. 相似文献
93.
Receptive field plasticity of neurons in rat auditory cortex 总被引:2,自引:0,他引:2
YANGWenwei GAOLixia SUNXinde 《科学通报(英文版)》2004,49(13):1364-1369
Using conventional electrophysiological technique, we investigated the plasticity of the frequency receptive fields (RF) of auditory cortex (AC) neurons in rats. In the AC, when the frequency difference between conditioning stimulus frequency (CSF) and the best frequency (BF) was in the range of 1--4 kHz, the frequency RF of AC neurons shifted. The smaller the differences between CSF and BF, the higher the probability of the RF shift and the greater the degree of the RF shift. To some extent, the plasticity of RF was dependent on the duration of the session of conditioning stimulus (CS). When the frequency difference between CSF and BF was bigger, the duration of the CS session needed to induce the plasticity was longer. The recovery time course of the frequency RF showed opposite changes after CS cessation.The RF shift could be induced by the frequency that was either higher or lower than the control BF, demonstrating no clear directional preference. The frequency RF of some neurons showed bidirectional shift, and the RF of other neurons showed single directional shift. The results suggest that the frequency RF plasticity of AC neurons could be considered asan ideal model for studying plasticity mechanism. The present study also provides important evidence for further study of learning and memory in auditory system. 相似文献
94.
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
95.
针对电离层延迟会导致GPS单频精密单点定位精度严重缺失的情况,分别探讨了克罗布歇模型、格网模型和历元差分模型,并采用IGS跟踪站数据进行电离层延迟改正。同时根据改正后的单频精密单点定位精度,比较了这三种电离层延迟改正模型的改正效果。结果表明:历元差分模型的改正效果最好,其改正后单频精密单点定位精度可达到厘米级,能较好地符合实际应用要求。 相似文献
96.
Advances and applications of electrohydrodynamics 总被引:1,自引:1,他引:1
CHENXiaopeng CHENGJiusheng YINXiezhen 《科学通报(英文版)》2003,48(11):1055-1063
Electrohydrodynamics (EHD) has been applied in many areas, such as EHD enhanced heat transfer, EHD pump, electrospray mass spectrometry, electrospray nanotechnology, etc. The basic theories underlying these applications and a brief review of the EHD advances are presented in this paper. As electrospray is an important branch of EHD,the applications of electrospray are particularly discussed.Finally, this paper gives some suggestions for the future research and development. 相似文献
97.
During the past several years, the research and development of InP material has made great progress due to serving as the substrate for most optoelectronic devices operating at the communications wavelength of 1.31 and 1.55 μm. At present, InP has become an important semiconductor material together with Si and GaAs. When compared to GaAs, InP has higher electron velocity, higher radiation hardness and better heat-conducting property. The advantage of InP crystal material allows higher frequency operation and lower power requirements. Therefore, InP is widely being used for the manufacture of microwave devices, high-frequency devices and optoelectronic integrated circuits (OEICs) which are indispensable for wireless technology, satellite communications[1—3]. Although n-type and p-type InP can meet actual needs, semi-insulating InP substrates remain to be improved due to their poor uniformity and consistency. For this reason, several possible approaches have been reported to the preparation of SI InP by wafer annealing under different conditions[4—9]. 相似文献
98.
YUWeiping YANGXiaoping WANGGuangming 《科学通报(英文版)》2004,49(14):1446-1449
In the present work, it was studied that nanoosized NiO electrodes doping with C and Co were prepared by electrochemical deposition in an ethanol solution containing nickel nitrate and cobalt nitrate and sintering processes. The capacitance performance of such electrodes was also studied. The results reveal that samples obtained by electrochemical deposition first on a porous nickel cathode in an ethanol solution contain 0.5 mol/L nitrates, in which Ni(NO3)2 and Co(NO3)2 were mixed in a molar proportion of 8 : 2. After sintering at 300℃ for 2 h, they exhibited the best performance. XRD analysis illustrates that the essential phase of the product is NiO doping with certain content of C and Co. The particles of product imaged a spherical morphology with sizes of 20---30 nm in diameter, and with an average crystal size of 4--5 nm. The capacitance measurement of the simulating C/NiO capacitors indicates that a single electrode can reach as high as 410.0 F/g, and still maintain the value of 323 F/g after 30 recycles showed as a stabilized value with increasing recycles, when it was discharged at a current of 5 mA. 相似文献
99.
汽车离合器传动片是离合器传递载荷的重要零件 ,承受复杂载荷 ,而汽车离合器传动片设计方法的研究却不多 笔者分析了汽车离合器传动片工作时的各种受力情况及其变形量的大小 ,给出了传动片设计计算的双端固定梁的力学模型和进行强度、稳定性校核准则 ,并进行了应力和变形试验 ,试验结果与理论计算基本吻合 相似文献
100.
Zhang Hai-long Li Jun Liu Chang-guo Jiang Tian-hua Wei jun School of Civil Engineering Mechanics Huazhong University of Science Technology Wuhan Hubei China 《武汉大学学报:自然科学英文版》2003,8(4):1121-1125
0 IntroductionXiantaoHanjiangRiverHighwayBridgelocatesonnorth westsuburbofXiantaocity ,crossesovertheHanjiangRiv er.Thecable stayedbridgeisasingle towersystemwiththespansof (5 0 + 82 + 180 )m .Thenon symmetricalstructureisusedheresothatthemainpiercankeepoffthemainchannel.Thesectionofthegirderisnotconstantinorderthatthedeadloadcanbeinbalancealthoughthespansaredifferent.Thedeckwidthis 2 3m (notincludingthewidthofthecablelane) ,laterallayoutisthatofdouble directionfour lanewithoutsidewalk ,b… 相似文献