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1.
Tumor progression to a metastatic and ultimately lethal stage relies on a tumor-supporting microenvironment that is generated by reciprocal communication between tumor and stromal host cells. The tumor–stroma crosstalk is instructed by the genetic alterations of the tumor cells—the most frequent being mutations in the gene Tumor protein p53 (TP53) that are clinically correlated with metastasis, drug resistance and poor patient survival. The crucial mediators of tumor–stroma communication are tumor-derived extracellular vesicles (EVs), in particular exosomes, which operate both locally within the primary tumor and in distant organs, at pre-metastatic niches as the future sites of metastasis. Here, we review how wild-type and mutant p53 proteins control the secretion, size, and especially the RNA and protein cargo of tumor-derived EVs. We highlight how EVs extend the cell-autonomous tumor suppressive activity of wild-type p53 into the tumor microenvironment (TME), and how mutant p53 proteins switch EVs into oncogenic messengers that reprogram tumor–host communication within the entire organism so as to promote metastatic tumor cell dissemination.  相似文献   
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This paper analyses the characteristics of software houses as service providers. The tasks of internal IT-services are determined from these characteristics and a reporting system for the IT-controlling is outlined. The concept results from the analysis of one of the 25 largest German software houses. The paper concludes with a case study of the fiscal year 2000 IT-controlling report of the above-mentioned firm.  相似文献   
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Two experiments explore whether synchrony between peak circadian arousal periods and time of testing influences inhibitory efficiency for younger and older adults. Experiment 1 assesses inhibitory control over no-longer-relevant thoughts, and Experiment 2 assesses control over unwanted but strong responses, as well as performance on neuropsychological tasks that index frontal function. Inhibitory control is greatest at optimal times for both age groups and is generally greater for younger than for older adults. Performance on 2 neuropsychological measures (Stroop and Trails) also changes over the day, at least for older adults, and is correlated with inhibitory indexes, suggesting that for older adults changes in inhibition may be mediated by circadian variations in frontal functioning. By contrast, access to well-learned responses is not vulnerable to synchrony or age effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
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This article reviews a number of case studies involving hydrogen-assisted cracking in steels. Before the case studies are presented, the current state of understanding of hydrogen-assisted cracking is briefly reviewed. At present there are two leading approaches to the development of a mechanism of hydrogen-assisted cracking, one based upon bond weakening, and the other upon strain localization. As the case studies illustrate, hydrogen-assisted cracking can lead to failures in perhaps unexpected circumstances. The need for the wider dissemination of information about hydrogen cracking to design engineers is indicated.  相似文献   
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On-line NMR spectroscopy can beneficially be applied to studies of supercritical and near-critical fluids as an alternative to optical spectroscopy. Up to now high pressure NMR experiments are predominantly accomplished using custom made NMR batch reactors. The authors present a novel high pressure cell with displacement plunger for on-line NMR experiments on compressible fluids which can be used in conjunction with commercially available SCF NMR flow probes. The on-line technique offers advantages compared to stopped flow techniques such as enhanced control of mixture composition and reaction parameters as well as the facility of engagement into the reaction. The new apparatus is used for NMR studies on hydrogen bonding of methanol in near critical and supercritical carbon dioxide up to 403 K and 35 MPa for which data on the chemical shift of the hydroxyl group and methyl group are reported and interpreted.  相似文献   
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With the increasing use of electric motors in automobiles—in some cases as many as 100 electric motors per vehicle—alternatives to ferrite magnetic materials are under consideration. If more powerful magnetic materials could be implemented, size reductions in these motors could result in curb weight reductions that lead to improved fuel economy. NdFeB magnets are attractive as potential replacement materials, due to their higher flux density and thus smaller required size; however, high material costs have limited their implementation. To investigate the economic competitiveness of alternative magnetic materials, technical cost models (TCMs) were developed and used to examine the manufacturing economics related to the production of both NdFeB and ferrite magnets. Results from the TCMs are used to identify the cost drivers and opportunities for cost reductions. Subsequent investigations will include effects on vehicle fuel efficiency, and the environmental impact of magnet manufacture and disposal.  相似文献   
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