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1.
国际空间站和欧洲核子中心的大型强子对撞机 (LHC)计划目前都面临资金上的窘境 ;……除了对项目 (尤其是耗资巨大的项目 )预算的科学化 ,管理的科学化在其中尤显重要 相似文献
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The ability to improve out-of-sample forecasting performance by combining forecasts is well established in the literature. This paper advances this literature in the area of multivariate volatility forecasts by developing two combination weighting schemes that exploit volatility persistence to emphasise certain losses within the combination estimation period. A comprehensive empirical analysis of the out-of-sample forecast performance across varying dimensions, loss functions, sub-samples and forecast horizons show that new approaches significantly outperform their counterparts in terms of statistical accuracy. Within the financial applications considered, significant benefits from combination forecasts relative to the individual candidate models are observed. Although the more sophisticated combination approaches consistently rank higher relative to the equally weighted approach, their performance is statistically indistinguishable given the relatively low power of these loss functions. Finally, within the applications, further analysis highlights how combination forecasts dramatically reduce the variability in the parameter of interest, namely the portfolio weight or beta. 相似文献
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Thomas Söderqvist Adam Bencard Camilla Mordhorst 《Studies in history and philosophy of science》2009,40(4):431-438
The acquisition and display of material artefacts is the raison d’être of museums. But what constitutes a museum artefact? Contemporary medicine (biomedicine) is increasingly producing artefacts that do not fit the traditional museological understanding of what constitutes a material, tangible artefact. Museums today are therefore caught in a paradox. On the one hand, medical science and technologies are having an increasing pervasive impact on the way contemporary life is lived and understood and is therefore a central part of the contemporary world. On the other hand, the objects involved in medical diagnostics and therapies are becoming increasingly invisible and intangible and therefore seem to have no role to play as artefacts in a museum context. Consequently, museums are at risk of becoming alienated from an increasingly important part of contemporary society. This essay elaborates the paradox by employing Gumbrecht’s (2004) distinction between ‘presence’ and ‘meaning’. 相似文献
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The strength of network biology lies in its ability to derive cell biological information without a priori mechanistic or molecular knowledge. It is shown here how a careful understanding of a given biological pathway can refine an interactome approach. This permits the elucidation of additional design principles and of spatio-temporal dynamics behind pathways, and aids in experimental design and interpretation. 相似文献
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Wertz IE Kusam S Lam C Okamoto T Sandoval W Anderson DJ Helgason E Ernst JA Eby M Liu J Belmont LD Kaminker JS O'Rourke KM Pujara K Kohli PB Johnson AR Chiu ML Lill JR Jackson PK Fairbrother WJ Seshagiri S Ludlam MJ Leong KG Dueber EC Maecker H Huang DC Dixit VM 《Nature》2011,471(7336):110-114
Microtubules have pivotal roles in fundamental cellular processes and are targets of antitubulin chemotherapeutics. Microtubule-targeted agents such as Taxol and vincristine are prescribed widely for various malignancies, including ovarian and breast adenocarcinomas, non-small-cell lung cancer, leukaemias and lymphomas. These agents arrest cells in mitosis and subsequently induce cell death through poorly defined mechanisms. The strategies that resistant tumour cells use to evade death induced by antitubulin agents are also unclear. Here we show that the pro-survival protein MCL1 (ref. 3) is a crucial regulator of apoptosis triggered by antitubulin chemotherapeutics. During mitotic arrest, MCL1 protein levels decline markedly, through a post-translational mechanism, potentiating cell death. Phosphorylation of MCL1 directs its interaction with the tumour-suppressor protein FBW7, which is the substrate-binding component of a ubiquitin ligase complex. The polyubiquitylation of MCL1 then targets it for proteasomal degradation. The degradation of MCL1 was blocked in patient-derived tumour cells that lacked FBW7 or had loss-of-function mutations in FBW7, conferring resistance to antitubulin agents and promoting chemotherapeutic-induced polyploidy. Additionally, primary tumour samples were enriched for FBW7 inactivation and elevated MCL1 levels, underscoring the prominent roles of these proteins in oncogenesis. Our findings suggest that profiling the FBW7 and MCL1 status of tumours, in terms of protein levels, messenger RNA levels and genetic status, could be useful to predict the response of patients to antitubulin chemotherapeutics. 相似文献
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Harvey R. Brown Wayne Myrvold Jos Uffink 《Studies in History and Philosophy of Science Part B: Studies in History and Philosophy of Modern Physics》2009,40(2):174-191
A comparison is made of the traditional Loschmidt (reversibility) and Zermelo (recurrence) objections to Boltzmann's H-theorem, and its simplified variant in the Ehrenfests’ 1912 wind-tree model. The little-cited 1896 (measure-theoretic) objection of Zermelo (similar to an 1889 argument due to Poincaré) is also analysed. Significant differences between the objections are highlighted, and several old and modern misconceptions concerning both them and the H-theorem are clarified. We give particular emphasis to the radical nature of Poincaré's and Zermelo's attack, and the importance of the shift in Boltzmann's thinking in response to the objections taken together. 相似文献