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排序方式: 共有141条查询结果,搜索用时 312 毫秒
61.
登陆火星或月球时,释放降落伞后进入推进阶段,通过轴向推力倾斜实现水平方向运动,能够与速度矢量(重力)的相反方向一致或与需要的加速度方向保持一致.后一种策略能实现精确着陆,在该策略下,倾斜角(俯仰角和偏转角)与水平加速度成正比.这种策略并未采用以水平加速度为姿态控制目标的递阶导航与控制方案,而是基于角加速度对位置作用的四阶动力学特性设计了一个独特的控制系统.除去倾斜角的非线性因素(垂直制动规定的轴向推力)后,系统综合动力学方程能够实现(准)输入-状态线性化.论文同时表明:一方面,基于参考轨迹(倾斜角和位置)的控制器设计仅能实现部分输入-状态线性化;另一方面,系统的内部稳定性可以证明.即使存在不可镇定的外部干扰动力学模态时,仍能确保系统稳定性.蒙特卡洛仿真验证了闭环控制策略的有效性. 相似文献
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Chen Z Cheng K Walton Z Wang Y Ebi H Shimamura T Liu Y Tupper T Ouyang J Li J Gao P Woo MS Xu C Yanagita M Altabef A Wang S Lee C Nakada Y Peña CG Sun Y Franchetti Y Yao C Saur A Cameron MD Nishino M Hayes DN Wilkerson MD Roberts PJ Lee CB Bardeesy N Butaney M Chirieac LR Costa DB Jackman D Sharpless NE Castrillon DH Demetri GD Jänne PA Pandolfi PP Cantley LC Kung AL Engelman JA Wong KK 《Nature》2012,483(7391):613-617
Targeted therapies have demonstrated efficacy against specific subsets of molecularly defined cancers. Although most patients with lung cancer are stratified according to a single oncogenic driver, cancers harbouring identical activating genetic mutations show large variations in their responses to the same targeted therapy. The biology underlying this heterogeneity is not well understood, and the impact of co-existing genetic mutations, especially the loss of tumour suppressors, has not been fully explored. Here we use genetically engineered mouse models to conduct a 'co-clinical' trial that mirrors an ongoing human clinical trial in patients with KRAS-mutant lung cancers. This trial aims to determine if the MEK inhibitor selumetinib (AZD6244) increases the efficacy of docetaxel, a standard of care chemotherapy. Our studies demonstrate that concomitant loss of either p53 (also known as Tp53) or Lkb1 (also known as Stk11), two clinically relevant tumour suppressors, markedly impaired the response of Kras-mutant cancers to docetaxel monotherapy. We observed that the addition of selumetinib provided substantial benefit for mice with lung cancer caused by Kras and Kras and p53 mutations, but mice with Kras and Lkb1 mutations had primary resistance to this combination therapy. Pharmacodynamic studies, including positron-emission tomography (PET) and computed tomography (CT), identified biological markers in mice and patients that provide a rationale for the differential efficacy of these therapies in the different genotypes. These co-clinical results identify predictive genetic biomarkers that should be validated by interrogating samples from patients enrolled on the concurrent clinical trial. These studies also highlight the rationale for synchronous co-clinical trials, not only to anticipate the results of ongoing human clinical trials, but also to generate clinically relevant hypotheses that can inform the analysis and design of human studies. 相似文献
63.
Paolo Fornaro 《Journal of forecasting》2016,35(6):477-492
In this paper, I use a large set of macroeconomic and financial predictors to forecast US recession periods. I adopt Bayesian methodology with shrinkage in the parameters of the probit model for the binary time series tracking the state of the economy. The in‐sample and out‐of‐sample results show that utilizing a large cross‐section of indicators yields superior US recession forecasts in comparison to a number of parsimonious benchmark models. Moreover, the data‐rich probit model gives similar accuracy to the factor‐based model for the 1‐month‐ahead forecasts, while it provides superior performance for 1‐year‐ahead predictions. Finally, in a pseudo‐real‐time application for the Great Recession, I find that the large probit model with shrinkage is able to pick up the recession signals in a timely fashion and does well in comparison to the more parsimonious specification and to nonparametric alternatives. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
64.
The generation of specialized neural cells in the developing and postnatal central nervous system is a highly regulated process, whereby neural stem cells divide to generate committed neuronal progenitors, which then withdraw from the cell cycle and start to differentiate. Cell cycle checkpoints play a major role in regulating the balance between neural stem cell expansion and differentiation. Loss of tumor suppressors involved in checkpoint control can lead to dramatic alterations of neurogenesis, thus contributing to neoplastic transformation. Here we summarize and critically discuss the existing literature on the role of tumor suppressive pathways and their regulatory networks in the control of neurogenesis and transformation. 相似文献
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Colaluca IN Tosoni D Nuciforo P Senic-Matuglia F Galimberti V Viale G Pece S Di Fiore PP 《Nature》2008,451(7174):76-80
NUMB is a cell fate determinant, which, by asymmetrically partitioning at mitosis, controls cell fate choices by antagonising the activity of the plasma membrane receptor of the NOTCH family. NUMB is also an endocytic protein, and the NOTCH-NUMB counteraction has been linked to this function. There might be, however, additional functions of NUMB, as witnessed by its proposed role as a tumour suppressor in breast cancer. Here we describe a previously unknown function for human NUMB as a regulator of tumour protein p53 (also known as TP53). NUMB enters in a tricomplex with p53 and the E3 ubiquitin ligase HDM2 (also known as MDM2), thereby preventing ubiquitination and degradation of p53. This results in increased p53 protein levels and activity, and in regulation of p53-dependent phenotypes. In breast cancers there is frequent loss of NUMB expression. We show that, in primary breast tumour cells, this event causes decreased p53 levels and increased chemoresistance. In breast cancers, loss of NUMB expression causes increased activity of the receptor NOTCH. Thus, in these cancers, a single event-loss of NUMB expression-determines activation of an oncogene (NOTCH) and attenuation of the p53 tumour suppressor pathway. Biologically, this results in an aggressive tumour phenotype, as witnessed by findings that NUMB-defective breast tumours display poor prognosis. Our results uncover a previously unknown tumour suppressor circuitry. 相似文献
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Rainville S Thompson JK Myers EG Brown JM Dewey MS Kessler EG Deslattes RD Börner HG Jentschel M Mutti P Pritchard DE 《Nature》2005,438(7071):1096-1097
One of the most striking predictions of Einstein's special theory of relativity is also perhaps the best known formula in all of science: E=mc(2). If this equation were found to be even slightly incorrect, the impact would be enormous--given the degree to which special relativity is woven into the theoretical fabric of modern physics and into everyday applications such as global positioning systems. Here we test this mass-energy relationship directly by combining very accurate measurements of atomic-mass difference, Delta(m), and of gamma-ray wavelengths to determine E, the nuclear binding energy, for isotopes of silicon and sulphur. Einstein's relationship is separately confirmed in two tests, which yield a combined result of 1-Delta(mc2)/E=(-1.4+/-4.4)x10(-7), indicating that it holds to a level of at least 0.00004%. To our knowledge, this is the most precise direct test of the famous equation yet described. 相似文献
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