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461.
The iron-chalcogenide high temperature superconductor Fe(Se,Te) (FST) has been reported to exhibit complex magnetic ordering and nontrivial band topology which ...  相似文献   
462.
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   
463.
The p53 tumour suppressor gene   总被引:266,自引:0,他引:266  
A J Levine  J Momand  C A Finlay 《Nature》1991,351(6326):453-456
The cell cycle is composed of a series of steps which can be negatively or positively regulated by various factors. Chief among the negative regulators is the p53 protein. Alteration or inactivation of p53 by mutation, or by its interactions with oncogene products of DNA tumour viruses, can lead to cancer. These mutations seem to be the most common genetic change in human cancers.  相似文献   
464.
Two defining functional features of ion channels are ion selectivity and channel gating. Ion selectivity is generally considered an immutable property of the open channel structure, whereas gating involves transitions between open and closed channel states, typically without changes in ion selectivity. In store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels, the molecular mechanism of channel gating by the CRAC channel activator, stromal interaction molecule 1 (STIM1), remains unknown. CRAC channels are distinguished by a very high Ca(2+) selectivity and are instrumental in generating sustained intracellular calcium concentration elevations that are necessary for gene expression and effector function in many eukaryotic cells. Here we probe the central features of the STIM1 gating mechanism in the human CRAC channel protein, ORAI1, and identify V102, a residue located in the extracellular region of the pore, as a candidate for the channel gate. Mutations at V102 produce constitutively active CRAC channels that are open even in the absence of STIM1. Unexpectedly, although STIM1-free V102 mutant channels are not Ca(2+)-selective, their Ca(2+) selectivity is dose-dependently boosted by interactions with STIM1. Similar enhancement of Ca(2+) selectivity is also seen in wild-type ORAI1 channels by increasing the number of STIM1 activation domains that are directly tethered to ORAI1 channels, or by increasing the relative expression of full-length STIM1. Thus, exquisite Ca(2+) selectivity is not an intrinsic property of CRAC channels but rather a tuneable feature that is bestowed on otherwise non-selective ORAI1 channels by STIM1. Our results demonstrate that STIM1-mediated gating of CRAC channels occurs through an unusual mechanism in which permeation and gating are closely coupled.  相似文献   
465.
466.
主要利用φ混合序列的矩不等式和随机变量的截尾技术,在适当的矩条件下,研究了φ混合序列的完全矩收敛性。本文的结果推广了独立序列和已有文献关于φ混合序列的相应结果,同时也将φ混合序列的完全收敛性改进到完全矩收敛性。  相似文献   
467.
In this study, plasma nitriding was used to fabricate a hard protective layer on AISI P20 steel, at three process temperatures (450°C, 500°C, and 550°C) and over a range of time periods (2.5, 5, 7.5, and 10 h), and at a fixed gas N2:H2 ratio of 75vol%:25vol%. The morphology of samples was studied using optical microscopy and scanning electron microscopy, and the formed phase of each sample was determined by X-ray diffraction. The elemental depth profile was measured by energy dispersive X-ray spectroscopy, wavelength dispersive spectroscopy, and glow dispersive spectroscopy. The hardness profile of the samples was identified, and the microhardness profile from the surface to the sample center was recorded. The results show that ε-nitride is the dominant species after carrying out plasma nitriding in all strategies and that the plasma nitriding process improves the hardness up to more than three times. It is found that as the time and temperature of the process increase, the hardness and hardness depth of the diffusion zone considerably increase. Furthermore, artificial neural networks were used to predict the effects of operational parameters on the mechanical properties of plastic mold steel. The plasma temperature, running time of imposition, and target distance to the sample surface were all used as network inputs; Vickers hardness measurements were given as the output of the model. The model accurately reproduced the experimental outcomes under different operational conditions; therefore, it can be used in the effective simulation of the plasma nitriding process in AISI P20 steel.  相似文献   
468.
Reducing the dimensions of electrode materials from the micron to the nanoscale can have a profound influence on their properties and hence on the performance of electrochemical devices,e.g.Li-ion batteries,that employ such electrodes.TiO2(B) has received growing interest as a possible anode for Li-ion batteries in recent years.It offers the possibility of higher energy storage compared with the commercialized Li4Ti5O12.Bulk,nanowire,nanotube,and nanoparticle morphologies have been prepared and studied.However,to date these materials have not be compared in one article.In the current review we first summarize the different synthesis methods for the preparation of nanostructured TiO2(B);then present the effects of size and shape on the electrochemical properties.Finally TiO2(B) with nanometer dimensions exhibit a higher capacity to store Li,regardless of rate,due to structural distortions inherent at the nanoscale.  相似文献   
469.
HIV preferentially infects HIV-specific CD4+ T cells   总被引:34,自引:0,他引:34  
HIV infection is associated with the progressive loss of CD4(+) T cells through their destruction or decreased production. A central, yet unresolved issue of HIV disease is the mechanism for this loss, and in particular whether HIV-specific CD4(+) T cells are preferentially affected. Here we show that HIV-specific memory CD4(+) T cells in infected individuals contain more HIV viral DNA than other memory CD4(+) T cells, at all stages of HIV disease. Additionally, following viral rebound during interruption of antiretroviral therapy, the frequency of HIV viral DNA in the HIV-specific pool of memory CD4(+) T cells increases to a greater extent than in memory CD4(+) T cells of other specificities. These findings show that HIV-specific CD4(+) T cells are preferentially infected by HIV in vivo. This provides a potential mechanism to explain the loss of HIV-specific CD4(+) T-cell responses, and consequently the loss of immunological control of HIV replication. Furthermore, the phenomenon of HIV specifically infecting the very cells that respond to it adds a cautionary note to the practice of structured therapy interruption.  相似文献   
470.
土壤微生物群落及其活性与植被的关系   总被引:12,自引:0,他引:12  
植被通过影响土壤环境,从而影响到土壤微生物群落的结构和多样性.受植被影响的土壤环境中土壤微生物群落的多样性比不受植被影响或者没有植被的土壤环境中的微生物群落的多样性要高很多,不受植被影响的表面以下土壤环境中的微生物群落具有显著的优势OTU种群,而表层土壤环境中没有显著的优势OTU种群.植被对微生物的影响同时也表现在对生命物质DNA的影响,即有植被的土壤环境中的微生物DNA具有更高的活性,其基因在克隆过程中更容易被转移,获得更多的克隆细胞和种群.  相似文献   
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