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211.
提出了可变频时钟写入方法和锁相环倍频时钟写入方法,给出了这两种写入法的读/写电路,并分析了其性能。结果证明,可变频时钟写入方法电路简单,刻写时钟周期短;锁相环倍频时钟写入过程较前者长,但其频率范围容易调整。两者均适合高密度小型温盘的时钟录写。  相似文献   
212.
Extracellular plaques of amyloid-β and intraneuronal neurofibrillary tangles made from tau are the histopathological signatures of Alzheimer's disease. Plaques comprise amyloid-β fibrils that assemble from monomeric and oligomeric intermediates, and are prognostic indicators of Alzheimer's disease. Despite the importance of plaques to Alzheimer's disease, oligomers are considered to be the principal toxic forms of amyloid-β. Interestingly, many adverse responses to amyloid-β, such as cytotoxicity, microtubule loss, impaired memory and learning, and neuritic degeneration, are greatly amplified by tau expression. Amino-terminally truncated, pyroglutamylated (pE) forms of amyloid-β are strongly associated with Alzheimer's disease, are more toxic than amyloid-β, residues 1-42 (Aβ(1-42)) and Aβ(1-40), and have been proposed as initiators of Alzheimer's disease pathogenesis. Here we report a mechanism by which pE-Aβ may trigger Alzheimer's disease. Aβ(3(pE)-42) co-oligomerizes with excess Aβ(1-42) to form metastable low-n oligomers (LNOs) that are structurally distinct and far more cytotoxic to cultured neurons than comparable LNOs made from Aβ(1-42) alone. Tau is required for cytotoxicity, and LNOs comprising 5% Aβ(3(pE)-42) plus 95% Aβ(1-42) (5% pE-Aβ) seed new cytotoxic LNOs through multiple serial dilutions into Aβ(1-42) monomers in the absence of additional Aβ(3(pE)-42). LNOs isolated from human Alzheimer's disease brain contained Aβ(3(pE)-42), and enhanced Aβ(3(pE)-42) formation in mice triggered neuron loss and gliosis at 3 months, but not in a tau-null background. We conclude that Aβ(3(pE)-42) confers tau-dependent neuronal death and causes template-induced misfolding of Aβ(1-42) into structurally distinct LNOs that propagate by a prion-like mechanism. Our results raise the possibility that Aβ(3(pE)-42) acts similarly at a primary step in Alzheimer's disease pathogenesis.  相似文献   
213.
Bone marrow cells regenerate infarcted myocardium   总被引:455,自引:0,他引:455  
Myocardial infarction leads to loss of tissue and impairment of cardiac performance. The remaining myocytes are unable to reconstitute the necrotic tissue, and the post-infarcted heart deteriorates with time. Injury to a target organ is sensed by distant stem cells, which migrate to the site of damage and undergo alternate stem cell differentiation; these events promote structural and functional repair. This high degree of stem cell plasticity prompted us to test whether dead myocardium could be restored by transplanting bone marrow cells in infarcted mice. We sorted lineage-negative (Lin-) bone marrow cells from transgenic mice expressing enhanced green fluorescent protein by fluorescence-activated cell sorting on the basis of c-kit expression. Shortly after coronary ligation, Lin- c-kitPOS cells were injected in the contracting wall bordering the infarct. Here we report that newly formed myocardium occupied 68% of the infarcted portion of the ventricle 9 days after transplanting the bone marrow cells. The developing tissue comprised proliferating myocytes and vascular structures. Our studies indicate that locally delivered bone marrow cells can generate de novo myocardium, ameliorating the outcome of coronary artery disease.  相似文献   
214.
Genome sequencing in microfabricated high-density picolitre reactors   总被引:21,自引:0,他引:21  
The proliferation of large-scale DNA-sequencing projects in recent years has driven a search for alternative methods to reduce time and cost. Here we describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel fibre-optic slide of individual wells and is able to sequence 25 million bases, at 99% or better accuracy, in one four-hour run. To achieve an approximately 100-fold increase in throughput over current Sanger sequencing technology, we have developed an emulsion method for DNA amplification and an instrument for sequencing by synthesis using a pyrosequencing protocol optimized for solid support and picolitre-scale volumes. Here we show the utility, throughput, accuracy and robustness of this system by shotgun sequencing and de novo assembly of the Mycoplasma genitalium genome with 96% coverage at 99.96% accuracy in one run of the machine.  相似文献   
215.
Zinc-aluminum alloys have been used as bearing materials in the past. In recent years, binary Al-Zn alloys and Al-Zn-Cu alloys are being used as an alternative to the Zn-Al alloys for bearing applications. In this study, both binary Al-25Zn and Al-3Cu were prepared using stir casting process. Homogenization of the as-cast alloys was performed at 350℃ for 8 h and then, the alloys were furnace-cooled to 50℃. The homogenization led to the removal of the dendritic structure of the as-cast alloys. After homogenization, wear parameters optimization was carried out using Taguchi technique. For this purpose, L9 orthogonal array was selected, and the control parameters selected are load, velocity, and sliding distance. The optimum parametric condition was obtained using signal-to-noise (S/N) ratio analysis, and specific wear rate (SWR) is the selected response. The "smaller-the-better" is the goal of the experiment for S/N ratio analysis. After the optimization, confirmation tests were carried out using analysis of variance (ANOVA) from the developed regression equation. Finally, wear mechanism studies were conducted using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) images.  相似文献   
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