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  • 11
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    RNA splicing is a primary link between genetic variation and disease (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-04-30
    Description: Noncoding variants play a central role in the genetics of complex traits, but we still lack a full understanding of the molecular pathways through which they act. We quantified the contribution of cis-acting genetic effects at all major stages of gene regulation from chromatin to proteins, in Yoruba lymphoblastoid cell lines (LCLs). About ~65% of expression quantitative trait loci (eQTLs) have primary effects on chromatin, whereas the remaining eQTLs are enriched in transcribed regions. Using a novel method, we also detected 2893 splicing QTLs, most of which have little or no effect on gene-level expression. These splicing QTLs are major contributors to complex traits, roughly on a par with variants that affect gene expression levels. Our study provides a comprehensive view of the mechanisms linking genetic variation to variation in human gene regulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Yang I -- van de Geijn, Bryce -- Raj, Anil -- Knowles, David A -- Petti, Allegra A -- Golan, David -- Gilad, Yoav -- Pritchard, Jonathan K -- R01MH084703/MH/NIMH NIH HHS/ -- R01MH101825/MH/NIMH NIH HHS/ -- U01HG007036/HG/NHGRI NIH HHS/ -- U54CA149145/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):600-4. doi: 10.1126/science.aad9417. Epub 2016 Apr 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Stanford University, Stanford, CA, USA. ; Department of Human Genetics, University of Chicago, Chicago, IL, USA. ; Department of Computer Science, Stanford University, Stanford, CA, USA. Department of Radiology, Stanford University, Stanford, CA, USA. ; Genome Institute, Washington University in St. Louis, St. Louis, MO, USA. ; Department of Human Genetics, University of Chicago, Chicago, IL, USA. gilad@uchicago.edu pritch@stanford.edu. ; Department of Genetics, Stanford University, Stanford, CA, USA. Department of Biology, Stanford University, Stanford, CA, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. gilad@uchicago.edu pritch@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27126046" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Chromatin/metabolism ; *Gene Expression Regulation ; *Genetic Variation ; Genome-Wide Association Study ; Humans ; Immune System Diseases/*genetics ; Lymphocytes/immunology ; Phenotype ; Polymorphism, Single Nucleotide ; *Quantitative Trait Loci ; RNA Splicing/*genetics
    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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  • 12
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    An orthopoxvirus-based vaccine reduces virus excretion after MERS-CoV infection in dromedary camels (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-12-19
    Description: Middle East respiratory syndrome coronavirus (MERS-CoV) infections have led to an ongoing outbreak in humans, which was fueled by multiple zoonotic MERS-CoV introductions from dromedary camels. In addition to the implementation of hygiene measures to limit further camel-to-human and human-to-human transmissions, vaccine-mediated reduction of MERS-CoV spread from the animal reservoir may be envisaged. Here we show that a modified vaccinia virus Ankara (MVA) vaccine expressing the MERS-CoV spike protein confers mucosal immunity in dromedary camels. Compared with results for control animals, we observed a significant reduction of excreted infectious virus and viral RNA transcripts in vaccinated animals upon MERS-CoV challenge. Protection correlated with the presence of serum neutralizing antibodies to MERS-CoV. Induction of MVA-specific antibodies that cross-neutralize camelpox virus would also provide protection against camelpox.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haagmans, Bart L -- van den Brand, Judith M A -- Raj, V Stalin -- Volz, Asisa -- Wohlsein, Peter -- Smits, Saskia L -- Schipper, Debby -- Bestebroer, Theo M -- Okba, Nisreen -- Fux, Robert -- Bensaid, Albert -- Solanes Foz, David -- Kuiken, Thijs -- Baumgartner, Wolfgang -- Segales, Joaquim -- Sutter, Gerd -- Osterhaus, Albert D M E -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):77-81. doi: 10.1126/science.aad1283. Epub 2015 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Viroscience, Erasmus Medical Center, Rotterdam, Netherlands. b.haagmans@erasmusmc.nl gerd.sutter@lmu.de albert.osterhaus@tiho-hannover.de. ; Department of Viroscience, Erasmus Medical Center, Rotterdam, Netherlands. ; German Centre for Infection Research (DZIF), Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-Universitat Munchen, Munich, Germany. ; Department of Pathology, University of Veterinary Medicine, Hannover, Germany. ; Institut de Recerca i Tecnologia Agroalimentaries (IRTA), Centre de Recerca en Sanitat Animal [CReSA, IRTA-Universitat Autonoma de Barcelona (UAB)], Campus de la UAB, 08193 Bellaterra, Spain. ; UAB, CReSA, (IRTA-UAB), Campus de la UAB, 08193 Bellaterra, Spain. Departament de Sanitat i Anatomia Animals, Facultat de Veterinaria, UAB, 08193 Bellaterra, Spain. ; German Centre for Infection Research (DZIF), Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-Universitat Munchen, Munich, Germany. b.haagmans@erasmusmc.nl gerd.sutter@lmu.de albert.osterhaus@tiho-hannover.de. ; Department of Viroscience, Erasmus Medical Center, Rotterdam, Netherlands. Artemis One Health, Utrecht, Netherlands. Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine, Hannover, Germany. b.haagmans@erasmusmc.nl gerd.sutter@lmu.de albert.osterhaus@tiho-hannover.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26678878" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Neutralizing/blood/immunology ; Antibodies, Viral/blood/immunology ; Camels/*virology ; Coronavirus Infections/*prevention & control/*veterinary ; Disease Outbreaks/*prevention & control ; Humans ; Middle East Respiratory Syndrome Coronavirus/*physiology ; RNA, Viral/immunology ; Spike Glycoprotein, Coronavirus/genetics/*immunology ; Vaccinia virus/genetics/*immunology ; Viral Vaccines/*immunology ; Virus Shedding/immunology
    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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  • 13
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    Influence of Processing on the Microstructure and Mechanical Properties of a NbAl3-Base Alloy (1992)
    In:  Other Sources
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    Publication Date: 2011-12-07
    Description: Induction melting and rapid solidification processing, followed by grinding to 75-micron powder and P/M consolidation, have been used to produce a multiphase, NbAl3-based, oxidation-resistant alloy of Nb-67Al-7Cr-0.5Y-0.25W composition whose strength and ductility are significantly higher than those of the induction-melted alloy at test temperatures of up to 1200 K. Attention is given to the beneficial role of microstructural refinement; the major second phase, AlNbCr, improves both oxidation resistance and mechanical properties.
    Keywords: METALLIC MATERIALS
    Type: Journal of Materials Research (ISSN 0884-2914); 7; 7, Ju
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  • 14
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    Effect of oxidation on the mechanical properties of a NbAl3 alloy at intermediate temperatures (1992)
    In:  Other Sources
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    Publication Date: 2011-08-24
    Description: The effect of environment on the mechanical properties of an Nb-67Al-7Cr-0.25W-0.5Y alloy was investigated experimentally in the temperature range 800-1200 K. It is found that the severity of environmental attack in the alloy is determined by both matrix plasticity and oxidation kinetics. The former determines the ability of the matrix to accommodate the localized stresses generated during deformation and oxidation, while the latter governs the rate of formation of a protective oxide scale. The environmental degradation of the alloy can thus be reduced or eliminated by increasing atomic mobility.
    Keywords: METALLIC MATERIALS
    Type: Journal of Materials Research (ISSN 0884-2914); 7; 12; p. 3219-3234.
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  • 15
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    Correlation of deformation mechanisms with the tensile and compressive behavior of NiAl and NiAl(Zr) intermetallic alloys (1992)
    In:  Other Sources
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    Publication Date: 2011-08-24
    Description: To identify the mechanisms controlling strength and ductility in powder-extruded NiAl and NiAl + 0.05 at. pct Zr, tensile and compressive testing was performed from 300 to 1300 K for several grain sizes. Grain size refinement significantly increased yield stress in both alloys and, in some cases, slightly lowered the ductile-to-brittle transition temperature (DBTT), although no room-temperature tensile ductility was observed even in the finest grain size specimens. The small Zr addition increased the DBTT and changed the low-temperature fracture mode from intergranular in NiAl to a combination of intergranular and transgranular in the Zr-doped alloy. Scanning electron microscopy of compression specimens deformed at room temperature revealed the presence of grain-boundary cracks in both alloys. These cracks were due to the incompatibility of strain in the polycrystalline material, owing to the lack of five independent slip systems. The tendency to form grain-boundary cracks, in addition to the low fracture stress of these alloys, contributed to the lack of tensile ductility at low temperatures.
    Keywords: METALLIC MATERIALS
    Type: Metallurgical Transactions A - Physical Metallurgy and Materials Science (ISSN 0360-2133); 23A; 5, Ma
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  • 16
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    Deformation behavior of a Ni-30Al-20Fe-0.05Zr intermetallic alloy in the temperature range 300 to 1300 K (1992)
    In:  Other Sources
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    Publication Date: 2011-12-09
    Description: The deformation properties of an extruded Ni-30Al-20Fe-0.05Zr (at. pct) alloy in the temperature range 300-1300 K were investigated under initial tensile strain rates that varied between 10 exp -6 and 10 exp -3/sec and in constant load compression creep between 1073 and 1300 K. Three deformation regimes were observed: region I, occurring between 400 and 673 K, which consisted of an athermal regime of less than 0.3 percent tensile ductility; region II, between 673 and 1073, where exponential creep was dominant; and region III, between 1073 and 1300 K, where a significant improvement in tensile ductility was observed.
    Keywords: METALLIC MATERIALS
    Type: Metallurgical Transactions A - Physical Metallurgy and Materials Science (ISSN 0360-2133); 23A; 6, Ju
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  • 17
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    Grain boundary sliding behaviour of copper and alpha brass at intermediate temperatures (1991)
    In:  Other Sources
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    Publication Date: 2011-08-19
    Description: The role of grain boundary sliding in copper and Cu-30 pct Zn in the temperature range 0.50-0.72 Tm, where Tm is the absolute melting point of the material, is examined. First, sliding data obtained on these materials are presented. The results indicate that the stress exponent for sliding is similar to that for lattice deformation, while the activation energy for sliding varies between 0.5 and 1.6 of the activation energy for creep. Several models proposed for grain boundary sliding are discussed, and it is shown that they do not account for the observed results on copper and alpha brass. A phenomenological model is proposed, where it is assumed that grain boundary sliding results from the glide of dislocations on secondary slip planes.
    Keywords: METALLIC MATERIALS
    Type: Journal of Materials Science (ISSN 0022-2461); 26; 1000-100
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  • 18
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    Observations on the brittle to ductile transition temperatures of B2 nickel aluminides with and without zirconium (1989)
    In:  Other Sources
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    Publication Date: 2011-08-19
    Description: The effect of a zirconium addition (0.05 at. pct) to a stoichiometric NiAl alloy on the brittle-to-ductile transition temperature (BDTT) of this alloy was investigated. Constant velocity tensile tests were conducted to fracture between 300 and 1100 K under initial strain rate 0.00014/sec, and the true stress and true strain values were determined from plots of load vs time after subtracting the elastic strain. The inelastic strain was measured under a traveling microscope. Microstructural characterization of as-extruded and fractured specimens was carried out by SEM and TEM. It was found that, while the addition of 0.05 at. pct Zr strengthened the NiAl alloy, it increased its BDTT; this shift in the BDTT could not be attributed either to variations in grain size or to impurity contents. Little or no room-temperature ductility was observed for either alloy.
    Keywords: METALLIC MATERIALS
    Type: Scripta Metallurgica (ISSN 0036-9748); 23; 2049-205
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  • 19
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    Slow strain rate 1200-1400 K compressive properties of NiAl-1Hf (1991)
    In:  Other Sources
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    Publication Date: 2011-08-24
    Description: Compression tests are conducted on NiAl-1Hf to assess the elevated-temperature creep behavior of this precipitation-hardened aluminide. While the strength is high under fast strain rates (more than 10 exp -5/s), under slower conditions the alloy is weak. Thus, it is unlikely that effective creep resistance can be obtained in NiAl through small Hf additions.
    Keywords: METALLIC MATERIALS
    Type: Materials Letters (ISSN 0167-577X); 11; 267-272
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  • 20
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    Apparent activation volume for creep of copper and alpha brass at intermediate temperatures (1989)
    In:  Other Sources
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    Publication Date: 2011-08-19
    Description: Experimental measurements of the apparent activation volume for creep, V-asterisk, of Cu and Cu-30 pct Zn conducted at intermediate temperatures showed two types of strain dependencies. At the lower temperatures and higher stresses, V-asterisk decreased with increasing creep strain, while at higher temperatures and lower stresses, V-asterisk was essentially independent of strain. The low temperature-high stress behavior for Cu and Cu-30 pct Zn was found to be consistent with the dominance of a dislocation intersection mechanism. The high temperature-low stress data for the pure metals suggest that the rate-controlling process involves the nonconservative motion of jogs on screw dislocations. For the latter conditions, an additional contribution from solute drag-limited dislocation glide also appears to be important in governing the creep behavior of the alloy.
    Keywords: METALLIC MATERIALS
    Type: Journal of Materials Science (ISSN 0022-2461); 24; 3196-320
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