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21.
Chiang C Jacobsen JC Ernst C Hanscom C Heilbut A Blumenthal I Mills RE Kirby A Lindgren AM Rudiger SR McLaughlan CJ Bawden CS Reid SJ Faull RL Snell RG Hall IM Shen Y Ohsumi TK Borowsky ML Daly MJ Lee C Morton CC MacDonald ME Gusella JF Talkowski ME 《Nature genetics》2012,44(4):390-7, S1
We defined the genetic landscape of balanced chromosomal rearrangements at nucleotide resolution by sequencing 141 breakpoints from cytogenetically interpreted translocations and inversions. We confirm that the recently described phenomenon of 'chromothripsis' (massive chromosomal shattering and reorganization) is not unique to cancer cells but also occurs in the germline, where it can resolve to a relatively balanced state with frequent inversions. We detected a high incidence of complex rearrangements (19.2%) and substantially less reliance on microhomology (31%) than previously observed in benign copy-number variants (CNVs). We compared these results to experimentally generated DNA breakage-repair by sequencing seven transgenic animals, revealing extensive rearrangement of the transgene and host genome with similar complexity to human germline alterations. Inversion was the most common rearrangement, suggesting that a combined mechanism involving template switching and non-homologous repair mediates the formation of balanced complex rearrangements that are viable, stably replicated and transmitted unaltered to subsequent generations. 相似文献
22.
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
23.
论述了小型实验装置中的低温超导体传热实验所具有的特点、存在的问题以及解决方法。通过对实验装置、测量元件以及测量线路几方面的分析和计算,并根据室温下预试验所取得的结论,合理地设计了测量系统,从而确保了低温超导体传热实验的可靠性和高效率。低温下(HeⅠ,HeⅡs及HeⅡp中)的实验结果证实了理论分析的正确性和室温预试验的必要性。 相似文献
24.
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
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26.
PLETHORA proteins as dose-dependent master regulators of Arabidopsis root development 总被引:1,自引:0,他引:1
Galinha C Hofhuis H Luijten M Willemsen V Blilou I Heidstra R Scheres B 《Nature》2007,449(7165):1053-1057
27.
考虑具有强迫项正负系数的中立型差分方程Δ(xn-γnXn-r) pnXn-r-qnXn-σ=cn,n≥n0,其中cn∈R,γn,qn,pn∈[0, ∞}和r,τ,σ∈{1,2,…},获得了这个方程振动的充分条件。 相似文献
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29.
根据油田内资料欠缺、储层薄、岩性复杂、非均质性强的特点,提出用“动态平移法”进行流体性质识别。实践证明,该方法具有简便易行、精度高、分辨能力强等特点。利用此方法不仅可有效区分油、水、干层,并且可更准确地确定油层分布位置。 相似文献
30.