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  • 1
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    Efficient estimation of nonparametric genetic risk function with censored data (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-21
    Description: With the discovery of an increasing number of causal genes for complex human disorders, it is crucial to assess the genetic risk of disease onset for individuals who are carriers of these causal mutations and to compare the distribution of the age-at-onset for such individuals with the distribution for noncarriers. In many genetic epidemiological studies that aim to estimate causal gene effect on disease, the age-at-onset of disease is subject to censoring. In addition, the mutation carrier or noncarrier status of some individuals may be unknown, due to the high cost of in-person ascertainment by collecting DNA samples or because of the death of older individuals. Instead, the probability of such individuals’ mutation status can be obtained from various other sources. When mutation status is missing, the available data take the form of censored mixture data. Recently, various methods have been proposed for risk estimation using such data, but none is efficient for estimating a nonparametric distribution. We propose a fully efficient sieve maximum likelihood estimation method, in which we estimate the logarithm of the hazard ratio between genetic mutation groups using B-splines, while applying nonparametric maximum likelihood estimation to the reference baseline hazard function. Our estimator can be calculated via an expectation-maximization algorithm which is much faster than existing methods. We show that our estimator is consistent and semiparametrically efficient and establish its asymptotic distribution. Simulation studies demonstrate the superior performance of the proposed method, which is used to estimate the distribution of the age-at-onset of Parkinson's disease for carriers of mutations in the leucine-rich repeat kinase 2, LRRK2, gene.
    Print ISSN: 0006-3444
    Electronic ISSN: 1464-3510
    Topics: Biology , Mathematics , Medicine
    Published by Oxford University Press
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  • 2
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    Thermal conductivity of IPA-CuCl_{3}: Evidence for ballistic magnon transport and the limited applicability of the Bose-Einstein condensation model (2015)
    American Physical Society (APS)
    Details
    Publication Date: 2015-04-18
    Description: Author(s): Z. Y. Zhao, B. Tong, X. Zhao, L. M. Chen, J. Shi, F. B. Zhang, J. D. Song, S. J. Li, J. C. Wu, H. S. Xu, X. G. Liu, and X. F. Sun The heat transport of the spin-gapped material (CH 3 ) 2 CHNH 3 CuCl 3 (IPA-CuCl 3 ), a candidate quantum magnet with Bose-Einstein condensation (BEC), is studied at ultralow temperatures and in high magnetic fields. Due to the presence of the spin gap, the zero-field thermal conductivity (κ) is purely phono... [Phys. Rev. B 91, 134420] Published Fri Apr 17, 2015
    Keywords: Magnetism
    Print ISSN: 1098-0121
    Electronic ISSN: 1095-3795
    Topics: Physics
    Published by American Physical Society (APS)
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  • 3
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    Geochronology and geochemistry of basalts from the Karamay ophiolitic melange in West Junggar (NW China): Implications for Devonian-Carboniferous intra-oceanic accretionary tectonics of the southern Altaids (2013)
    Geological Society of America (GSA)
    Details
    Publication Date: 2013-02-28
    Description: New laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS) U-Pb zircon ages and geochemical data are reported for the Karamay ophiolitic mélange in the West Junggar area at the southwestern margin of the Altaids (or Central Asian orogenic belt), northwestern China. The data were used to identify the petrogenesis of the mélange, and to evaluate its tectonic significance. In addition, this study aimed to assess the possible presence of Devonian mantle plume in the region. The Karamay ophiolitic mélange crops out at the boundary of the Junggar Basin but is partly hidden by Mesozoic sediments, with an exposure area of ~40 km 2 . The site contains ultramafic rocks, cumulates, gabbros, pillow lavas, abyssal radiolarian cherts, turbidites, and tuffs, which show typical block-in-matrix structures. Zircon U-Pb analyses from the basalt and gabbro by LA-ICP-MS yielded weighted mean ages of 395 ± 3 Ma and 387 ± 8 Ma, respectively. These ages suggest a Middle Devonian emplacement. All basalts bear the signature of ocean-island basalt (OIB) and are characterized by alkaline compositions with high concentrations of Na 2 O + K 2 O (3.7–8.5 wt%) and TiO 2 (1.5–3.1 wt%); large ion lithophile element and light rare earth element enrichment and heavy rare earth element depletion; very weak or no Eu anomalies (Eu/Eu* = 0.9–1.0); and no obvious Nb, Ta, or Ti negative anomalies. We propose that these basaltic rocks were derived from mantle plume–related magmatism associated with the evolution of the Paleoasian oceanic system. The enriched mantle source could have contained 2%–5% garnet and ~3% spinel. The rocks also display strong geochemical similarities with the Xigaze seamount basalts, which formed in intra-oceanic settings. Compared to the basalts, the gabbros display mid-ocean-ridge-basalt–type tholeiitic basalt features, derived from a depleted mantle source with the addition of fluids from a subducted slab within a suprasubduction-zone environment. These observations are supported by previous work, and they indicate Devonian mantle plume–related magmatism within the Paleoasian Ocean. However, as these rocks are mainly parts of accretionary complexes, whether the Karamay and Darbut ophiolitic mélange formed in a single belt remains equivocal, and further work is required to resolve this issue. Thus, there was a complex evolution by subduction-accretion processes from the Devonian to the Carboniferous before final amalgamation and docking to the northern Siberian block.
    Print ISSN: 0016-7606
    Electronic ISSN: 1943-2674
    Topics: Geosciences
    Published by Geological Society of America (GSA)
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  • 4
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    Ebola virus disease in Sierra Leone [Medical Sciences] (2016)
    National Academy of Sciences
    Details
    Publication Date: 2016-04-20
    Description: Sierra Leone is the most severely affected country by an unprecedented outbreak of Ebola virus disease (EVD) in West Africa. Although successfully contained, the transmission dynamics of EVD and the impact of interventions in the country remain unclear. We established a database of confirmed and suspected EVD cases from May...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 5
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    Cryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals nucleated polymerization (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-10-10
    Description: The NLR family apoptosis inhibitory proteins (NAIPs) bind conserved bacterial ligands, such as the bacterial rod protein PrgJ, and recruit NLR family CARD-containing protein 4 (NLRC4) as the inflammasome adapter to activate innate immunity. We found that the PrgJ-NAIP2-NLRC4 inflammasome is assembled into multisubunit disk-like structures through a unidirectional adenosine triphosphatase polymerization, primed with a single PrgJ-activated NAIP2 per disk. Cryo-electron microscopy (cryo-EM) reconstruction at subnanometer resolution revealed a ~90 degrees hinge rotation accompanying NLRC4 activation. Unlike in the related heptameric Apaf-1 apoptosome, in which each subunit needs to be conformationally activated by its ligand before assembly, a single PrgJ-activated NAIP2 initiates NLRC4 polymerization in a domino-like reaction to promote the disk assembly. These insights reveal the mechanism of signal amplification in NAIP-NLRC4 inflammasomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640189/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640189/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Liman -- Chen, Shuobing -- Ruan, Jianbin -- Wu, Jiayi -- Tong, Alexander B -- Yin, Qian -- Li, Yang -- David, Liron -- Lu, Alvin -- Wang, Wei Li -- Marks, Carolyn -- Ouyang, Qi -- Zhang, Xinzheng -- Mao, Youdong -- Wu, Hao -- 1DP1HD087988/DP/NCCDPHP CDC HHS/ -- AI100645/AI/NIAID NIH HHS/ -- K99 AI108793/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Oct 23;350(6259):404-9. doi: 10.1126/science.aac5789. Epub 2015 Oct 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA. ; Center for Quantitative Biology, Peking-Tsinghua Joint Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, China. Department of Cancer Immunology and Virology, Intel Parallel Computing Center for Structural Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. ; Department of Cancer Immunology and Virology, Intel Parallel Computing Center for Structural Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. ; Center for Nanoscale Systems, Harvard University, Cambridge, MA 02138, USA. ; Center for Quantitative Biology, Peking-Tsinghua Joint Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, China. ; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. ; Center for Quantitative Biology, Peking-Tsinghua Joint Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, China. Department of Cancer Immunology and Virology, Intel Parallel Computing Center for Structural Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. wu@crystal.harvard.edu youdong_mao@dfci.harvard.edu. ; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA. wu@crystal.harvard.edu youdong_mao@dfci.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26449474" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 6
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    Chromatin binding and regulation of MLL5 [Biochemistry] (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-07-10
    Description: The human mixed-lineage leukemia 5 (MLL5) protein mediates hematopoietic cell homeostasis, cell cycle, and survival; however, the molecular basis underlying MLL5 activities remains unknown. Here, we show that MLL5 is recruited to gene-rich euchromatic regions via the interaction of its plant homeodomain finger with the histone mark H3K4me3. The 1.48-Å...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 7
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    CPG2 links F-actin to synaptic GluR endocytosis [Neuroscience] (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-11-20
    Description: A key neuronal mechanism for adjusting excitatory synaptic strength is clathrin-mediated endocytosis of postsynaptic glutamate receptors (GluRs). The actin cytoskeleton is critical for clathrin-mediated endocytosis, yet we lack a mechanistic understanding of its interaction with the endocytic process and how it may be regulated. Here we show that F-actin in...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    Modulation of the sis gene transcript during endothelial cell differentiation in vitro (1985)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1985-05-17
    Description: Endothelial cells, which line the interior walls of blood vessels, proliferate at the site of blood vessel injury. Knowledge of the factors that control the proliferation of these cells would help elucidate the role of endothelial cells in wound healing, tumor growth, and arteriosclerosis. In vitro, endothelial cells organize into viable, three-dimensional tubular structures in environments that limit cell proliferation. The process of endothelial cell organization was found to result in decreased levels of the sis messenger RNA transcript and increased levels of the messenger RNA transcript for fibronectin. This situation was reversed on transition from the organized structure to a proliferative monolayer. These results suggest a reciprocity for two biological response modifiers involved in the regulation of endothelial cell proliferation and differentiation in vitro.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jaye, M -- McConathy, E -- Drohan, W -- Tong, B -- Deuel, T -- Maciag, T -- 14147/PHS HHS/ -- 310765/PHS HHS/ -- 4807/PHS HHS/ -- etc. -- New York, N.Y. -- Science. 1985 May 17;228(4701):882-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3890179" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Differentiation ; Cell Division ; Cells, Cultured ; Culture Media ; Endothelial Growth Factors ; Endothelium/*cytology/metabolism ; Extracellular Matrix/metabolism ; Fibronectins/biosynthesis/genetics ; *Gene Expression Regulation ; Growth Substances/pharmacology ; Humans ; Platelet-Derived Growth Factor/*genetics ; RNA, Messenger/*genetics ; *Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 9
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    Vegetation history and dynamics in the middle reach of the Yangtze River during the last 1500 years revealed by sedimentary records from Taibai Lake, China (2012)
    Sage
    In: Holocene
    Details
    Publication Date: 2012-12-21
    Description: Pollen and charcoal records of a 150 cm long lake sediment core from Taibai Lake in the middle reach of the Yangtze River reveal seven major changes in regional vegetation over the last 1500 years. During the period c . ad 480–710, evergreen broadleaved forest dominated by Castanopsis/Lithocarpus and evergreen oaks occurred in the Taibai Lake catchment. From c . ad 710 to 1050, the vegetation shifted to a mixed conifer and broadleaved forest, with Pinus expanding at the expense of Castanopsis/Lithocarpus . Between c . ad 1050 and 1320, evergreen broadleaved forest reoccupied the studied area. From c . ad 1320 to 1650, the area of primary forest decreased markedly with synchronous reduction in broadleaved trees and Pinus . Between c . ad 1650 and 1740, the biomass declined rapidly, while secondary Pinus forest began to expand. During c . ad 1740–1950, forest extent increased slightly compared with the previous stage, but the landscape was still secondary forest with the minimum proportion of broadleaved trees. After c . ad 1950, the biomass in the surrounding area was very low, with vegetation types similar to that at present (secondary Pinus forest and mixed conifer and broadleaved forest). A detrended correspondence analysis (DCA) with 125 samples and 34 main pollen types is used to separate human and climatic impacts on vegetation. Then, the pollen assemblage, DCA, charcoal record, and magnetic susceptibility are combined to discuss the key factors inducing these vegetation changes. The vegetation changes were mainly controlled by the climatic changes, with the weak impacts of human activities before c . ad 1320. Since then, the intensity of human influences on vegetation increased gradually, entering a transitional period of main controlling factors of vegetation changes from nature to human activities. After c . ad 1740, the vegetation changes were chiefly controlled by human activities, and the climatic signal was weak.
    Print ISSN: 0959-6836
    Electronic ISSN: 1477-0911
    Topics: Geography , Geosciences
    Published by Sage
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  • 10
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    Low-temperature thermal conductivity of Dy_{2} Ti_{2} O_{7} and Yb_{2} Ti_{2} O_{7} single crystals (2015)
    American Physical Society (APS)
    Details
    Publication Date: 2015-09-05
    Description: Author(s): S. J. Li, Z. Y. Zhao, C. Fan, B. Tong, F. B. Zhang, J. Shi, J. C. Wu, X. G. Liu, H. D. Zhou, X. Zhao, and X. F. Sun We study the low-temperature thermal conductivity ( κ ) of Dy 2 Ti 2 O 7 and Yb 2 Ti 2 O 7 single crystals in magnetic fields up to 14 T along the [111], [100], and [110] directions. For Dy 2 Ti 2 O 7 we find experimentally that (i) the low- T κ ( H ) isotherms exhibit not only the steplike decreases at the low-field ( &l… [Phys. Rev. B 92, 094408] Published Fri Sep 04, 2015
    Keywords: Magnetism
    Print ISSN: 1098-0121
    Electronic ISSN: 1095-3795
    Topics: Physics
    Published by American Physical Society (APS)
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