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761.
International Consortium for Blood Pressure Genome-Wide Association Studies Ehret GB Munroe PB Rice KM Bochud M Johnson AD Chasman DI Smith AV Tobin MD Verwoert GC Hwang SJ Pihur V Vollenweider P O'Reilly PF Amin N Bragg-Gresham JL Teumer A Glazer NL Launer L Zhao JH Aulchenko Y Heath S Sõber S Parsa A Luan J Arora P Dehghan A Zhang F Lucas G Hicks AA Jackson AU Peden JF Tanaka T Wild SH Rudan I Igl W Milaneschi Y Parker AN Fava C Chambers JC Fox ER Kumari M Go MJ van der Harst P Kao WH 《Nature》2011,478(7367):103-109
Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140?mm?Hg systolic blood pressure or ≥90?mm?Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention. 相似文献
762.
Cederwall B Moradi FG Bäck T Johnson A Blomqvist J Clément E de France G Wadsworth R Andgren K Lagergren K Dijon A Jaworski G Liotta R Qi C Nyakó BM Nyberg J Palacz M Al-Azri H Algora A de Angelis G Ataç A Bhattacharyya S Brock T Brown JR Davies P Di Nitto A Dombrádi Z Gadea A Gál J Hadinia B Johnston-Theasby F Joshi P Juhász K Julin R Jungclaus A Kalinka G Kara SO Khaplanov A Kownacki J La Rana G Lenzi SM Molnár J Moro R Napoli DR Singh BS Persson A Recchia F Sandzelius M Scheurer JN Sletten G 《Nature》2011,469(7328):68-71
Shell structure and magic numbers in atomic nuclei were generally explained by pioneering work that introduced a strong spin-orbit interaction to the nuclear shell model potential. However, knowledge of nuclear forces and the mechanisms governing the structure of nuclei, in particular far from stability, is still incomplete. In nuclei with equal neutron and proton numbers (N = Z), enhanced correlations arise between neutrons and protons (two distinct types of fermions) that occupy orbitals with the same quantum numbers. Such correlations have been predicted to favour an unusual type of nuclear superfluidity, termed isoscalar neutron-proton pairing, in addition to normal isovector pairing. Despite many experimental efforts, these predictions have not been confirmed. Here we report the experimental observation of excited states in the N = Z = 46 nucleus (92)Pd. Gamma rays emitted following the (58)Ni((36)Ar,2n)(92)Pd fusion-evaporation reaction were identified using a combination of state-of-the-art high-resolution γ-ray, charged-particle and neutron detector systems. Our results reveal evidence for a spin-aligned, isoscalar neutron-proton coupling scheme, different from the previous prediction. We suggest that this coupling scheme replaces normal superfluidity (characterized by seniority coupling) in the ground and low-lying excited states of the heaviest N = Z nuclei. Such strong, isoscalar neutron-proton correlations would have a considerable impact on the nuclear level structure and possibly influence the dynamics of rapid proton capture in stellar nucleosynthesis. 相似文献
763.
研究HMCM-56分子筛上苯酚与异丙醇烷基化反应,探讨了反应条件包括温度,原料配比,催化剂的装填量,空速对催化剂催化性能的影响.通过X射线衍射、研究催化剂的酸性及晶相.得到最佳反应条件:T=220℃,WHSV=3.0h^-1,Catalyst Loading=0.3g,n(IPA)/n(Phenol)=0.8,苯酚的转... 相似文献
764.
765.
全球化伊始,工业文明消解了传统哲学天人合一的理念,由此引发了人口、环境和生态危机。人类必须重估生活方式,从生存论去体悟有机自然。通过溯源可持续设计,其技进于道的变动时空观源自以人为本的文化思想,在卫护人类和自然的循环利用过程中,可持续设计对生态的理性尊重将迎来一种新的文明。 相似文献
766.
以南瓜作为受体,通过种子萌发及幼苗生长试验,初步研究了银胶菊浸提液的化感作用.结果表明:(1)银胶菊浸提液对南瓜种子的萌发具有明显的抑制作用,叶、根、全株浸提液对南瓜种子萌发的抑制效应均随处理浓度的增加而增强;(2)各器官浸提液对南瓜的根长均有一定的促进作用,银胶菊叶、根及全株浸提液对南瓜的苗高具有抑制作用,且抑制作用随处理浓度的增加而增强;(3)叶水浸提液的抑制作用要高于其他部位. 相似文献
767.
Zuber J Shi J Wang E Rappaport AR Herrmann H Sison EA Magoon D Qi J Blatt K Wunderlich M Taylor MJ Johns C Chicas A Mulloy JC Kogan SC Brown P Valent P Bradner JE Lowe SW Vakoc CR 《Nature》2011,478(7370):524-528
Epigenetic pathways can regulate gene expression by controlling and interpreting chromatin modifications. Cancer cells are characterized by altered epigenetic landscapes, and commonly exploit the chromatin regulatory machinery to enforce oncogenic gene expression programs. Although chromatin alterations are, in principle, reversible and often amenable to drug intervention, the promise of targeting such pathways therapeutically has been limited by an incomplete understanding of cancer-specific dependencies on epigenetic regulators. Here we describe a non-biased approach to probe epigenetic vulnerabilities in acute myeloid leukaemia (AML), an aggressive haematopoietic malignancy that is often associated with aberrant chromatin states. By screening a custom library of small hairpin RNAs (shRNAs) targeting known chromatin regulators in a genetically defined AML mouse model, we identify the protein bromodomain-containing 4 (Brd4) as being critically required for disease maintenance. Suppression of Brd4 using shRNAs or the small-molecule inhibitor JQ1 led to robust antileukaemic effects in vitro and in vivo, accompanied by terminal myeloid differentiation and elimination of leukaemia stem cells. Similar sensitivities were observed in a variety of human AML cell lines and primary patient samples, revealing that JQ1 has broad activity in diverse AML subtypes. The effects of Brd4 suppression are, at least in part, due to its role in sustaining Myc expression to promote aberrant self-renewal, which implicates JQ1 as a pharmacological means to suppress MYC in cancer. Our results establish small-molecule inhibition of Brd4 as a promising therapeutic strategy in AML and, potentially, other cancers, and highlight the utility of RNA interference (RNAi) screening for revealing epigenetic vulnerabilities that can be exploited for direct pharmacological intervention. 相似文献
768.
769.
基于von Karman薄板理论和Hamilton原理,运用假设时间模态法,得到了弹性地基上加热圆板非线性轴对称自由振动的常微分控制方程.考虑不可移简支边界条件,采用打靶法得到了一阶屈曲位形下的前3阶振型的数值结果.结果表明:随地基弹性系数增加,热屈曲临界温度增加;在小振幅的情形下,振型对屈曲构型的影响和地基系数对振型... 相似文献
770.
针对常规PDP显示中的低灰度级轮廓问题,提出了一种新的PDP低灰度级图像增强算法.该算法根据PDP线性离散化的显示特点利用图像的表现率动态选择多种子场的编码,减少了图像伽马变化过程中灰度级的细节损失.针对PDP实际输出亮度相对于输入灰度级有反转的现象进行了理论分析和算法处理,消除了低灰度图像灰阶反转的现象.利用误差扩散算法最大限度地重现了图像的细节.实际结果表明该算法能够减少低灰度级轮廓,其显示效果明显优于传统方案. 相似文献