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  • 1
    Publication Date: 2011-10-14
    Description: The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering approximately 4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for approximately 60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3207357/" 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/PMC3207357/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lindblad-Toh, Kerstin -- Garber, Manuel -- Zuk, Or -- Lin, Michael F -- Parker, Brian J -- Washietl, Stefan -- Kheradpour, Pouya -- Ernst, Jason -- Jordan, Gregory -- Mauceli, Evan -- Ward, Lucas D -- Lowe, Craig B -- Holloway, Alisha K -- Clamp, Michele -- Gnerre, Sante -- Alfoldi, Jessica -- Beal, Kathryn -- Chang, Jean -- Clawson, Hiram -- Cuff, James -- Di Palma, Federica -- Fitzgerald, Stephen -- Flicek, Paul -- Guttman, Mitchell -- Hubisz, Melissa J -- Jaffe, David B -- Jungreis, Irwin -- Kent, W James -- Kostka, Dennis -- Lara, Marcia -- Martins, Andre L -- Massingham, Tim -- Moltke, Ida -- Raney, Brian J -- Rasmussen, Matthew D -- Robinson, Jim -- Stark, Alexander -- Vilella, Albert J -- Wen, Jiayu -- Xie, Xiaohui -- Zody, Michael C -- Broad Institute Sequencing Platform and Whole Genome Assembly Team -- Baldwin, Jen -- Bloom, Toby -- Chin, Chee Whye -- Heiman, Dave -- Nicol, Robert -- Nusbaum, Chad -- Young, Sarah -- Wilkinson, Jane -- Worley, Kim C -- Kovar, Christie L -- Muzny, Donna M -- Gibbs, Richard A -- Baylor College of Medicine Human Genome Sequencing Center Sequencing Team -- Cree, Andrew -- Dihn, Huyen H -- Fowler, Gerald -- Jhangiani, Shalili -- Joshi, Vandita -- Lee, Sandra -- Lewis, Lora R -- Nazareth, Lynne V -- Okwuonu, Geoffrey -- Santibanez, Jireh -- Warren, Wesley C -- Mardis, Elaine R -- Weinstock, George M -- Wilson, Richard K -- Genome Institute at Washington University -- Delehaunty, Kim -- Dooling, David -- Fronik, Catrina -- Fulton, Lucinda -- Fulton, Bob -- Graves, Tina -- Minx, Patrick -- Sodergren, Erica -- Birney, Ewan -- Margulies, Elliott H -- Herrero, Javier -- Green, Eric D -- Haussler, David -- Siepel, Adam -- Goldman, Nick -- Pollard, Katherine S -- Pedersen, Jakob S -- Lander, Eric S -- Kellis, Manolis -- 095908/Wellcome Trust/United Kingdom -- GM82901/GM/NIGMS NIH HHS/ -- R01 HG003474/HG/NHGRI NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- U54 HG003067-09/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Oct 12;478(7370):476-82. doi: 10.1038/nature10530.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. kersli@broadinstitute.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21993624" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Disease ; *Evolution, Molecular ; Exons/genetics ; Genome/*genetics ; Genome, Human/*genetics ; Genomics ; Health ; Humans ; Mammals/*genetics ; Molecular Sequence Annotation ; Phylogeny ; RNA/classification/genetics ; Selection, Genetic/genetics ; Sequence Alignment ; Sequence Analysis, DNA
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 57 (1990), S. 1254-1256 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Ultraclean, integrated metal-oxide-semiconductor oxide fabrication has been investigated for the first time by combining (i) surface cleaning in inert ambient, (ii) wafer transfer through ultrahigh vacuum, and (iii) thermal oxidation in an ultrahigh vacuum-based reactor. Device quality oxide structures are obtained (evidenced by dielectric breakdown characteristics for Al gate capacitors) under suitable conditions, while under other circumstances chemical mechanisms severely degrade electrical performance; even in ultraclean environments, impurity-related Si etching reactions before oxidation degrade oxide quality, but this can be avoided by appropriate use of passivating oxide films which prevent roughness associated with etching.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    [S.l.] : International Union of Crystallography (IUCr)
    Acta crystallographica 44 (1988), S. 965-975 
    ISSN: 1600-5724
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: Progress in introducing high-resolution electron microscopy at controlled elevated temperatures is described. Initial work involved the study of dynamic events in materials like cadmium telluride which can be heated to a sufficient degree by the imaging beam. However, for reproducible experiments the temperature must be carefully controlled and measured, and this involves a heating specimen holder. Results achieved recently this way on a variety of substances including CdTe, GaAs, Si, GaAs-Ti, GaAs-Ni, Si- Mo and Si-Ti, are reported. To derive information pertinent to bulk behavior both the manner of an in situ reaction and its kinetics should be compared with those for specimens prepared from macroscopic materials treated ex situ. For interface reactions in semiconductor materials it is found that events typical of the bulk can be recorded under high-resolution conditions in a large proportion of cases.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Propellants, Explosives, Pyrotechnics 3 (1978), S. 159-162 
    ISSN: 0721-3115
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The preparation and properties of silver fulminate have been examined to assess its potential for use as a primary explosive. It is an extremely effective detonant but does not appear promising as a stab-sensitive material. It is concluded that its extreme sensitiveness and the hazards and difficulties associated with its preparation render it unsuitable for military applications. It does find commercial use in the manufacture of toys and crackers when it is normally handled exclusively in small quantities and in the wet state.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: We demonstrate that depositing Ta diffusion barriers under ultra-high vacuum conditions without in situ oxygen dosing allows for variations both in microstructure and in the concentration of chemical impurities that severely degrade barrier performance. The effects of deposition pressure, in situ oxygen dosing at interfaces, hydrogen and oxygen contamination, and microstructure on diffusion barrier performance to Cu diffusion for electron-beam deposited Ta are presented. 20 nm of Ta diffusion barrier followed by a 150 nm Cu conductor were deposited under ultra-high vacuum (UHV, deposition pressure of 1×10−9 to 5 ×10−8 Torr) and high vacuum (HV, deposition pressure of 1×10−7 to 5×10−6 Torr) conditions onto 〈100〉 Si. In situ resistance furnace measurements, Auger compositional depth profiling, secondary ion mass spectrometry, and forward recoil detection along with scanning and transmission electron microscopy were used to determine the electrical, chemical, and structural changes that occurred in thin-film Ta diffusion barriers upon annealing. Undosed HV deposited Ta barriers failed from 560 to 630 °C, while undosed UHV barriers failed from 310 to 630 °C. For UHV Ta barriers, in situ oxygen dosing during deposition at the Cu/Ta interface increased the failure temperatures by 30–250 °C and decreased the range of failure temperatures to 570–630 °C. Undosed UHV Ta barriers have no systematic relationship between failure temperature and deposition pressure, although correlations between breakdown temperature, oxygen and hydrogen concentrations, and microstructural variations were measured.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The addition of 0.4–8.6 at. % Co to Cu thin films strongly influences the temperature evolution of microstructure, stress, and resistivity. For concentrations near 1 at. % Co in coevaporated Cu-Co on oxidized Si, normal grain growth begins at about 75 °C, about 50 °C lower than in pure Cu. There is an abrupt decrease in resistivity and stress at a temperature which increases with Co content from 120 °C (0% Co) to 250 °C (8.6 at. % Co), and coincides with precipitation of Co within Cu grains. A dramatic change in texture is observed in both coevaporated and electroplated Cu-Co films upon annealing above 250 °C. As-deposited films have a three-component texture of (111) fiber, (200) fiber, and random but annealed films have a dominant (200) fiber texture. This "cube'' texture differs from the dominant (111) texture of annealed pure Cu, and appears to be coupled to an abnormal grain growth process since many grains are observed to be larger than ten times the film thickness. It is proposed that segregation of Co to external surfaces or to Cu grain boundaries may favor this (200) texture by selectively affecting grain-boundary mobility or the surface energy driven grain growth.
    Type of Medium: Electronic Resource
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  • 7
    Publication Date: 2018-03-25
    Description: Objective To determine whether adults with normoglycaemia, impaired fasting glucose (IFG) and diabetes differed according to the incidence, rate, length and primary reasons for hospital admission. Design Retrospective cohort study. Setting Barwon Statistical Division, Geelong, Australia. Participants Cohort included 971 men and 924 women, aged 20+ years, participating in the Geelong Osteoporosis Study. Glycaemic status was assessed at cohort entry using fasting plasma glucose, use of antihyperglycaemic medication and/or self-report. Primary and secondary outcome measures Primary outcome measure was any admission to the major tertiary public hospital in the study region over the follow-up period. Secondary outcome measures were admission rate and length (days). Results Over a median follow-up of 7.4 years (IQR 5.3–9.6), participants with diabetes, compared with those with normoglycaemia, were two times as likely to be hospitalised (OR 2.07, 95% CI 1.42 to 3.02), had a higher admission rate (incidence rate ratio 1.61, 95% CI 1.17 to 2.23) and longer hospital stay (third quartile difference 7.7, 95% CI 1.3 to 14.1 and ninth decile difference 16.2, 95% CI 4.2 to 28.3). IFG group was similar to normoglycaemia for the incidence, rate and length of admission. Cardiovascular disease-related diagnoses were the most common primary reasons for hospitalisation across all glycaemic categories. Conclusions Our results show increased incidence, rate and length of all-cause hospital admission in adults with diabetes as compared with normoglycaemia; however, we did not detect any associations for IFG. Interventions should focus on preventing IFG-to-diabetes progression and reducing cardiovascular risk in IFG and diabetes.
    Keywords: Open access, Diabetes and Endocrinology
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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