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301.
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   
302.
Inactivation of the apoptosis effector Apaf-1 in malignant melanoma   总被引:47,自引:0,他引:47  
Metastatic melanoma is a deadly cancer that fails to respond to conventional chemotherapy and is poorly understood at the molecular level. p53 mutations often occur in aggressive and chemoresistant cancers but are rarely observed in melanoma. Here we show that metastatic melanomas often lose Apaf-1, a cell-death effector that acts with cytochrome c and caspase-9 to mediate p53-dependent apoptosis. Loss of Apaf-1 expression is accompanied by allelic loss in metastatic melanomas, but can be recovered in melanoma cell lines by treatment with the methylation inhibitor 5-aza-2'-deoxycytidine (5aza2dC). Apaf-1-negative melanomas are invariably chemoresistant and are unable to execute a typical apoptotic programme in response to p53 activation. Restoring physiological levels of Apaf-1 through gene transfer or 5aza2dC treatment markedly enhances chemosensitivity and rescues the apoptotic defects associated with Apaf-1 loss. We conclude that Apaf-1 is inactivated in metastatic melanomas, which leads to defects in the execution of apoptotic cell death. Apaf-1 loss may contribute to the low frequency of p53 mutations observed in this highly chemoresistant tumour type.  相似文献   
303.
At present, high-speed computing capabilities and advanced nonlinear dynamic finite element procedures enable detailed dynamic analysis of cable structures. Although deterministic approaches require considerable analysis time and effort in relation to modeling, running, and data processing, they seem to be the only alternative to obtain high accuracy. Detailed dynamic analysis of cable roof networks is sophisticated and requires advanced modeling expertise. This paper presents a comparison between detailed nonlinear dynamic analysis and a simplified frequency domain approach to estimate the maximum probable response of weakly nonlinear cable roofs. The approach can be considered as alternative to detailed time-domain analysis in the preliminary design phase, or can be used to validate results obtained from more elaborated numerical models. The proposed method is illustrated with two examples of cable net roofs that were also analysed in the time domain.  相似文献   
304.
阐述了人的建模思维机制。引入等价关系和划分作为问题粒度研究的基础,定义了逆商集,使之与商集一起,构成了对问题不同粒度的完整描述,并讨论了粒度的性质,借助拓扑分析,给出了问题可分解、可细化和粗化、细化等一系列定义,在问题簇和模型簇概念的基础上,提出了嵌套式建模(支持)作为面向复杂系统的建模支持方法论,具体给出了其实施步骤,这是一个人机交互的启发式过程,将嵌套式建模与传统式建模作了比较,此外还作了若干说明。  相似文献   
305.
基于换热过程中的损失率能定量地反映该过程中流体的传热与流动的综合性能这一特性,借助换热过程的损失率方程,分析比较了几种流体工质在不同换热方式下的综合特性。比较结果表明,液体(如水)有远优于气体(如空气)的流动与传热的综合性能,且随着流体温度的升高其优势更为明显。同时表明分析法在定量评价换热工质性能的突出特点及工程上的应用价值。  相似文献   
306.
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。  相似文献   
307.
Embryonic stem (ES) cells, the totipotent outgrowths of blastocysts, can be cultured and manipulated in vitro and then returned to the embryonic environment where they develop normally and can contribute to all cell lineages. Maintenance of the stem-cell phenotype in vitro requires the presence of a feeder layer of fibroblasts or of a soluble factor, differentiation inhibitory activity (DIA) produced by a number of sources; in the absence of DIA the ES cells differentiate into a wide variety of cell types. We recently noted several similarities between partially purified DIA and a haemopoietic regulator, myeloid leukaemia inhibitory factor (LIF), a molecule which induces differentiation in M1 myeloid leukaemic cells and which we have recently purified, cloned and characterized. We demonstrate here that purified, recombinant LIF can substitute for DIA in the maintenance of totipotent ES cell lines that retain the potential to form chimaeric mice.  相似文献   
308.
Stem cells, cancer, and cancer stem cells.   总被引:312,自引:0,他引:312  
T Reya  S J Morrison  M F Clarke  I L Weissman 《Nature》2001,414(6859):105-111
Stem cell biology has come of age. Unequivocal proof that stem cells exist in the haematopoietic system has given way to the prospective isolation of several tissue-specific stem and progenitor cells, the initial delineation of their properties and expressed genetic programmes, and the beginnings of their utility in regenerative medicine. Perhaps the most important and useful property of stem cells is that of self-renewal. Through this property, striking parallels can be found between stem cells and cancer cells: tumours may often originate from the transformation of normal stem cells, similar signalling pathways may regulate self-renewal in stem cells and cancer cells, and cancer cells may include 'cancer stem cells' - rare cells with indefinite potential for self-renewal that drive tumorigenesis.  相似文献   
309.
Silicon nitride (Si3N4) ceramics are used in numerous applications because of their superior mechanical properties. Their intrinsically brittle nature is a critical issue, but can be overcome by introducing whisker-like microstructural features. However, the formation of such anisotropic grains is very sensitive to the type of cations used as the sintering additives. Understanding the origin of dopant effects, central to the design of high-performance Si3N4 ceramics, has been sought for many years. Here we show direct images of dopant atoms (La) within the nanometre-scale intergranular amorphous films typically found at grain boundaries, using aberration corrected Z-contrast scanning transmission electron microscopy. It is clearly shown that the La atoms preferentially segregate to the amorphous/crystal interfaces. First-principles calculations confirm the strong preference of La for the crystalline surfaces, which is essential for forming elongated grains and a toughened microstructure. Whereas principles of micrometre-scale structural design are currently used to improve the mechanical properties of ceramics, this work represents a step towards the atomic-level structural engineering required for the next generation of ceramics.  相似文献   
310.
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