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  • 1
    Publication Date: 2010-05-15
    Description: Tibetans have lived at very high altitudes for thousands of years, and they have a distinctive suite of physiological traits that enable them to tolerate environmental hypoxia. These phenotypes are clearly the result of adaptation to this environment, but their genetic basis remains unknown. We report genome-wide scans that reveal positive selection in several regions that contain genes whose products are likely involved in high-altitude adaptation. Positively selected haplotypes of EGLN1 and PPARA were significantly associated with the decreased hemoglobin phenotype that is unique to this highland population. Identification of these genes provides support for previously hypothesized mechanisms of high-altitude adaptation and illuminates the complexity of hypoxia-response pathways in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simonson, Tatum S -- Yang, Yingzhong -- Huff, Chad D -- Yun, Haixia -- Qin, Ga -- Witherspoon, David J -- Bai, Zhenzhong -- Lorenzo, Felipe R -- Xing, Jinchuan -- Jorde, Lynn B -- Prchal, Josef T -- Ge, RiLi -- 1P01CA108671-01A2/CA/NCI NIH HHS/ -- DK069513/DK/NIDDK NIH HHS/ -- GM059290/GM/NIGMS NIH HHS/ -- HL50077/HL/NHLBI NIH HHS/ -- R00 HG005846/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2010 Jul 2;329(5987):72-5. doi: 10.1126/science.1189406. Epub 2010 May 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Eccles Institute of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20466884" target="_blank"〉PubMed〈/a〉
    Keywords: *Acclimatization ; *Altitude ; Asian Continental Ancestry Group/genetics ; Ethnic Groups/genetics ; Female ; Genetic Association Studies ; Genetic Variation ; Genome, Human ; Haplotypes ; Hemoglobins/*analysis ; Humans ; Hypoxia-Inducible Factor 1/metabolism ; Hypoxia-Inducible Factor-Proline Dioxygenases ; Linear Models ; Male ; *Oxygen ; PPAR alpha/*genetics ; Phenotype ; Polymorphism, Single Nucleotide ; Procollagen-Proline Dioxygenase/*genetics ; *Selection, Genetic ; Signal Transduction ; Tibet
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2016-05-25
    Description: We study nonparametric maximum likelihood estimation for the distribution of spherical radii using samples containing a mixture of one-dimensional, two-dimensional biased and three-dimensional unbiased observations. Since direct maximization of the likelihood function is intractable, we propose an expectation-maximization algorithm for implementing the estimator, which handles an indirect measurement problem and a sampling bias problem separately in the E- and M-steps, and circumvents the need to solve an Abel-type integral equation, which creates numerical instability in the one-sample problem. Extensions to ellipsoids are studied and connections to multiplicative censoring are discussed.
    Print ISSN: 0006-3444
    Electronic ISSN: 1464-3510
    Topics: Biology , Mathematics , Medicine
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  • 3
    Publication Date: 2016-04-21
    Description: The identification of genes with specific patterns of change (e.g. down-regulated and methylated) as phenotype drivers or samples with similar profiles for a given gene set as drivers of clinical outcome, requires the integration of several genomic data types for which an ‘integrate by intersection’ (IBI) approach is often applied. In this approach, results from separate analyses of each data type are intersected, which has the limitation of a smaller intersection with more data types. We introduce a new method, GISPA (Gene Integrated Set Profile Analysis) for integrated genomic analysis and its variation, SISPA (Sample Integrated Set Profile Analysis) for defining respective genes and samples with the context of similar, a priori specified molecular profiles. With GISPA, the user defines a molecular profile that is compared among several classes and obtains ranked gene sets that satisfy the profile as drivers of each class. With SISPA, the user defines a gene set that satisfies a profile and obtains sample groups of profile activity. Our results from applying GISPA to human multiple myeloma (MM) cell lines contained genes of known profiles and importance, along with several novel targets, and their further SISPA application to MM coMMpass trial data showed clinical relevance.
    Keywords: Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 4
    Publication Date: 2017-12-01
    Description: Competing inhomogeneous orders are a central feature of correlated electron materials, including the high-temperature superconductors. The two-dimensional Hubbard model serves as the canonical microscopic physical model for such systems. Multiple orders have been proposed in the underdoped part of the phase diagram, which corresponds to a regime of maximum numerical difficulty. By combining the latest numerical methods in exhaustive simulations, we uncover the ordering in the underdoped ground state. We find a stripe order that has a highly compressible wavelength on an energy scale of a few kelvin, with wavelength fluctuations coupled to pairing order. The favored filled stripe order is different from that seen in real materials. Our results demonstrate the power of modern numerical methods to solve microscopic models, even in challenging settings.
    Keywords: Physics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2015-07-29
    Description: Interconnection networks are a significant consideration for high-performance computing and the datacenter. However, interflow interference seriously impacts the communication performance and even causes disastrous congestion. The paper reports a virtual channel (VC)-sharing scheme that is aimed to separate VCs into many groups, and assign them to data flows based on the destination address. The technique can effectively isolate various traffics into separate VCs groups such that heavy loads have a lesser influence on the other normal traffics. As a consequence, we achieve a slimming congestion tree. In the proposal, the routing algorithm is a two-stage selection that includes the port selection and the VC group selection, respectively. Each of them has an independently selecting algorithm so that routing algorithm is a combined tactic by Cartesian product. The experiment represents that our scheme has excellent performance on adversarial traffics. Using our scheme, the growth curve is linear and slow after crossing the saturation point. For benign traffic patterns, our scheme does not effect any oblivious change on the communication performance when the system receives a lower injection rate.
    Print ISSN: 0010-4620
    Electronic ISSN: 1460-2067
    Topics: Computer Science
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