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Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 13 new celiac disease risk loci reaching genome-wide significance, bringing the number of known loci (including the HLA locus) to 40. We found multiple independent association signals at over one-third of these loci, a finding that is attributable to a combination of common, low-frequency and rare genetic variants. Compared to previously available data such as those from HapMap3, our dense genotyping in a large sample collection provided a higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions. In particular, 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements. Altogether, we define the complex genetic architecture of the risk regions of and refine the risk signals for celiac disease, providing the next step toward uncovering the causal mechanisms of the disease.  相似文献   
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Tarruell L  Greif D  Uehlinger T  Jotzu G  Esslinger T 《Nature》2012,483(7389):302-305
Dirac points are central to many phenomena in condensed-matter physics, from massless electrons in graphene to the emergence of conducting edge states in topological insulators. At a Dirac point, two energy bands intersect linearly and the electrons behave as relativistic Dirac fermions. In solids, the rigid structure of the material determines the mass and velocity of the electrons, as well as their interactions. A different, highly flexible means of studying condensed-matter phenomena is to create model systems using ultracold atoms trapped in the periodic potential of interfering laser beams. Here we report the creation of Dirac points with adjustable properties in a tunable honeycomb optical lattice. Using momentum-resolved interband transitions, we observe a minimum bandgap inside the Brillouin zone at the positions of the two Dirac points. We exploit the unique tunability of our lattice potential to adjust the effective mass of the Dirac fermions by breaking inversion symmetry. Moreover, changing the lattice anisotropy allows us to change the positions of the Dirac points inside the Brillouin zone. When the anisotropy exceeds a critical limit, the two Dirac points merge and annihilate each other-a situation that has recently attracted considerable theoretical interest but that is extremely challenging to observe in solids. We map out this topological transition in lattice parameter space and find excellent agreement with ab initio calculations. Our results not only pave the way to model materials in which the topology of the band structure is crucial, but also provide an avenue to exploring many-body phases resulting from the interplay of complex lattice geometries with interactions.  相似文献   
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The International Union for Conservation of Nature and Natural Resources red-lists a number of ant species. One species is Anergates atratulus (Schenck, 1852), a rarely collected social parasite introduced from Europe. The known distribution in North America is along the Atlantic seaboard. This note reports a huge range expansion in North America, to include Colorado. This finding is important because it provides useful information about the conservation and dispersal patterns of a rare, introduced, socially parasitic ant species.  相似文献   
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电磁干扰(EMI)是瞬时功能故障的主要来源之一,原因是电源供电线上的噪声注入引起了VDD和GND的额定值的波动.介绍了一种新的方法来增强片上系统(SoC)关于电源和接地电压瞬变时的信号完整性,并且这种方法完全符合IEC 61000-4-29 标准.其基本思想是设计和IEC 61000-4-29兼容的集成电路,通过局部和动态地将时钟占空比去适应传播延迟的变化和扰动的逻辑路径.当无法满足时,该方法导致暂时把集成电路的工作频率减小到满足该标准的最小值.根据异常电网活动,时钟占空比调制(CDCM)是通过使用正和/或负边沿时钟展宽逻辑(CSL)块来实现的.基于这个概念,在尽可能保持时钟高速频率的同时,数字电路对于电源供电线上波动的耐受性将会更强.该方法可被视作一种在线提供动态自适应同步的监视技术.通过SPICE模拟,实验结果表明此方法的有效性.  相似文献   
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Summary Perfusion of the isolated rat heart at constant heart rate and coronary flow with the inhibitor of cyclic nucleotide phosphodiesterase, pentoxifylline (10–4 moles/l), produced no significant effect on the maximum rate and the peak of contraction, but increased the maximum rate of relaxation. cAMP level and cAMP-dependent protein kinase activity were increased in the absence of changes in cGMP. The results were identical in hearts of reserpinized rats.This work was supported by grants from the Consejo Nacional de Investigaciones Cientificas y Técnicas and the Comisión de Investigaciones Científicas. Buenos Aires, Argentina.We thank Hoechst Laboratories for the partial support and Mrs Alicia R. Ramirez and María Prinzo for the excellent technical assistance.  相似文献   
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Alcohol is an important risk factor for upper aerodigestive cancers and is principally metabolized by alcohol dehydrogenase (ADH) enzymes. We have investigated six ADH genetic variants in over 3,800 aerodigestive cancer cases and 5,200 controls from three individual studies. Gene variants rs1229984 (ADH1B) and rs1573496 (ADH7) were significantly protective against aerodigestive cancer in each individual study and overall (P = 10(-10) and 10(-9), respectively). These effects became more apparent with increasing alcohol consumption (P for trend = 0.0002 and 0.065, respectively). Both gene effects were independent of each other, implying that multiple ADH genes may be involved in upper aerodigestive cancer etiology.  相似文献   
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