Showing papers by "University of Michigan published in 2013"
TL;DR: This work presents an improved method for sequencing variable regions within the 16S rRNA gene using Illumina's MiSeq platform, which is currently capable of producing paired 250-nucleotide reads and demonstrates that it can provide data that are at least as good as that generated by the 454 platform while providing considerably higher sequencing coverage for a fraction of the cost.
Abstract: Rapid advances in sequencing technology have changed the experimental landscape of microbial ecology. In the last 10 years, the field has moved from sequencing hundreds of 16S rRNA gene fragments per study using clone libraries to the sequencing of millions of fragments per study using next-generation sequencing technologies from 454 and Illumina. As these technologies advance, it is critical to assess the strengths, weaknesses, and overall suitability of these platforms for the interrogation of microbial communities. Here, we present an improved method for sequencing variable regions within the 16S rRNA gene using Illumina's MiSeq platform, which is currently capable of producing paired 250-nucleotide reads. We evaluated three overlapping regions of the 16S rRNA gene that vary in length (i.e., V34, V4, and V45) by resequencing a mock community and natural samples from human feces, mouse feces, and soil. By titrating the concentration of 16S rRNA gene amplicons applied to the flow cell and using a quality score-based approach to correct discrepancies between reads used to construct contigs, we were able to reduce error rates by as much as two orders of magnitude. Finally, we reprocessed samples from a previous study to demonstrate that large numbers of samples could be multiplexed and sequenced in parallel with shotgun metagenomes. These analyses demonstrate that our approach can provide data that are at least as good as that generated by the 454 platform while providing considerably higher sequencing coverage for a fraction of the cost.
5,417 citations
TL;DR: Although not yet providing compelling mechanical strength or electrical or thermal conductivities for many applications, CNT yarns and sheets already have promising performance for applications including supercapacitors, actuators, and lightweight electromagnetic shields.
Abstract: Worldwide commercial interest in carbon nanotubes (CNTs) is reflected in a production capacity that presently exceeds several thousand tons per year. Currently, bulk CNT powders are incorporated in diverse commercial products ranging from rechargeable batteries, automotive parts, and sporting goods to boat hulls and water filters. Advances in CNT synthesis, purification, and chemical modification are enabling integration of CNTs in thin-film electronics and large-area coatings. Although not yet providing compelling mechanical strength or electrical or thermal conductivities for many applications, CNT yarns and sheets already have promising performance for applications including supercapacitors, actuators, and lightweight electromagnetic shields.
4,596 citations
University of Illinois at Urbana–Champaign1, Joint Institute for the Study of the Atmosphere and Ocean2, Cooperative Institute for Research in Environmental Sciences3, University of Leeds4, University of Oslo5, United States Environmental Protection Agency6, University of Michigan7, Pacific Northwest National Laboratory8, German Aerospace Center9, United States Department of Energy10, Max Planck Society11, University of Tokyo12, National Oceanic and Atmospheric Administration13, Forschungszentrum Jülich14, Norwegian Meteorological Institute15, Indian Institute of Technology Bombay16, China Meteorological Administration17, Peking University18, Met Office19, Desert Research Institute20, Clarkson University21, Stanford University22, European Centre for Medium-Range Weather Forecasts23, International Institute of Minnesota24, Goddard Institute for Space Studies25, Yale University26, University of Washington27, University of California, Irvine28
TL;DR: In this paper, the authors provided an assessment of black-carbon climate forcing that is comprehensive in its inclusion of all known and relevant processes and that is quantitative in providing best estimates and uncertainties of the main forcing terms: direct solar absorption; influence on liquid, mixed phase, and ice clouds; and deposition on snow and ice.
Abstract: Black carbon aerosol plays a unique and important role in Earth's climate system. Black carbon is a type of carbonaceous material with a unique combination of physical properties. This assessment provides an evaluation of black-carbon climate forcing that is comprehensive in its inclusion of all known and relevant processes and that is quantitative in providing best estimates and uncertainties of the main forcing terms: direct solar absorption; influence on liquid, mixed phase, and ice clouds; and deposition on snow and ice. These effects are calculated with climate models, but when possible, they are evaluated with both microphysical measurements and field observations. Predominant sources are combustion related, namely, fossil fuels for transportation, solid fuels for industrial and residential uses, and open burning of biomass. Total global emissions of black carbon using bottom-up inventory methods are 7500 Gg yr−1 in the year 2000 with an uncertainty range of 2000 to 29000. However, global atmospheric absorption attributable to black carbon is too low in many models and should be increased by a factor of almost 3. After this scaling, the best estimate for the industrial-era (1750 to 2005) direct radiative forcing of atmospheric black carbon is +0.71 W m−2 with 90% uncertainty bounds of (+0.08, +1.27) W m−2. Total direct forcing by all black carbon sources, without subtracting the preindustrial background, is estimated as +0.88 (+0.17, +1.48) W m−2. Direct radiative forcing alone does not capture important rapid adjustment mechanisms. A framework is described and used for quantifying climate forcings, including rapid adjustments. The best estimate of industrial-era climate forcing of black carbon through all forcing mechanisms, including clouds and cryosphere forcing, is +1.1 W m−2 with 90% uncertainty bounds of +0.17 to +2.1 W m−2. Thus, there is a very high probability that black carbon emissions, independent of co-emitted species, have a positive forcing and warm the climate. We estimate that black carbon, with a total climate forcing of +1.1 W m−2, is the second most important human emission in terms of its climate forcing in the present-day atmosphere; only carbon dioxide is estimated to have a greater forcing. Sources that emit black carbon also emit other short-lived species that may either cool or warm climate. Climate forcings from co-emitted species are estimated and used in the framework described herein. When the principal effects of short-lived co-emissions, including cooling agents such as sulfur dioxide, are included in net forcing, energy-related sources (fossil fuel and biofuel) have an industrial-era climate forcing of +0.22 (−0.50 to +1.08) W m−2 during the first year after emission. For a few of these sources, such as diesel engines and possibly residential biofuels, warming is strong enough that eliminating all short-lived emissions from these sources would reduce net climate forcing (i.e., produce cooling). When open burning emissions, which emit high levels of organic matter, are included in the total, the best estimate of net industrial-era climate forcing by all short-lived species from black-carbon-rich sources becomes slightly negative (−0.06 W m−2 with 90% uncertainty bounds of −1.45 to +1.29 W m−2). The uncertainties in net climate forcing from black-carbon-rich sources are substantial, largely due to lack of knowledge about cloud interactions with both black carbon and co-emitted organic carbon. In prioritizing potential black-carbon mitigation actions, non-science factors, such as technical feasibility, costs, policy design, and implementation feasibility play important roles. The major sources of black carbon are presently in different stages with regard to the feasibility for near-term mitigation. This assessment, by evaluating the large number and complexity of the associated physical and radiative processes in black-carbon climate forcing, sets a baseline from which to improve future climate forcing estimates.
4,591 citations
TL;DR: Screening and intervention can prevent chronic kidney disease, and where management strategies have been implemented the incidence of end-stage kidney disease has been reduced, but awareness of the disorder remains low in many communities and among many physicians.
3,207 citations
European Institute of Oncology1, Harvard University2, University of Sydney3, Institut Jules Bordet4, Kantonsspital St. Gallen5, University of St. Gallen6, Loyola University Chicago7, Institut Gustave Roussy8, Karolinska Institutet9, University of Bordeaux10, University of Geneva11, University of Pittsburgh12, University of Copenhagen13, University of Newcastle14, Medical University of Vienna15, University of Toronto16, University of Michigan17, Memorial Sloan Kettering Cancer Center18, Mayo Clinic19, Gdańsk Medical University20, University of Gothenburg21, Baylor College of Medicine22, University of North Carolina at Chapel Hill23, Université libre de Bruxelles24, Netherlands Cancer Institute25, Fudan University26, Kyoto University27, King's College London28, University of Göttingen29, Emory University30
TL;DR: The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy.
2,831 citations
Johns Hopkins University1, University of Utah2, University of Rochester3, The Royal Marsden NHS Foundation Trust4, National Institutes of Health5, Stanford University6, Washington University in St. Louis7, Ontario Institute for Cancer Research8, University of Sydney9, St. Jude Medical Center10, University of Toronto11, Mayo Clinic12, American Society of Clinical Oncology13, University of Southern California14, North Carolina State University15, Indiana University16, University of Milan17, University of Michigan18
TL;DR: The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patients with invasive breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive).
Abstract: Purpose.—To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in b...
2,817 citations
Radboud University Nijmegen Medical Centre1, University of Michigan2, Radboud University Nijmegen3, University of Toronto4, McGill University5, University of Basel6, University of Florence7, Auckland City Hospital8, University of Pittsburgh9, Charité10, University of California, Los Angeles11, University College London12, University of Zurich13, University of Paris14, Marche Polytechnic University15, University of Texas Health Science Center at Houston16, Newcastle University17, University of Pécs18, Georgetown University19, Istanbul University20, Medical University of Białystok21, University of Giessen22, Seconda Università degli Studi di Napoli23, University College Dublin24, Stanford University25, University of Colorado Denver26, National Health Service27, Medical College of Wisconsin28, University of Alabama at Birmingham29, University of Manchester30, Rutgers University31, Thomas Jefferson University32, Amgen33, University of Toledo34, Boston University35, Medical University of South Carolina36, University of Pennsylvania37, Northwestern University38
TL;DR: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria and should allow for more patients to be classified correctly as having the disease.
Abstract: OBJECTIVE: The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. METHODS: Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by 1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and 2) validating against the combined view of a group of experts on a set of cases with or without SSc. RESULTS: It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, 7 additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud's phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. CONCLUSION: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.
2,743 citations
Cristen J. Willer1, Ellen M. Schmidt1, Sebanti Sengupta1, Gina M. Peloso2 +316 more•Institutions (87)
TL;DR: It is found that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index.
Abstract: Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
2,585 citations
Florey Institute of Neuroscience and Mental Health1, University of Calgary2, Boston Medical Center3, University of Zurich4, University of Missouri–Kansas City5, University of Oslo6, International Olympic Committee7, University of Toronto8, University of Michigan9, Vanderbilt University Medical Center10, University of Washington11, University of North Carolina at Chapel Hill12, University of British Columbia13, Burke Rehabilitation Hospital14, Cornell University15, University of Ottawa16, Medical College of Wisconsin17, Monash University18, University of New South Wales19, University of Melbourne20, McMaster University21, University of Medicine and Dentistry of New Jersey22, Princeton University23
TL;DR: The 4th International Conference on Concussion in Sport held in Zurich, November 2012 was attended by Paul McCrory, Willem H Meeuwisse, Mark Aubry, Jiří Dvořák, Ruben J Echemendia, Lars Engebretsen, Karen Johnston, Jeffrey S Kutcher, Martin Raftery, Allen Sills and Kathryn Schneider.
2,293 citations
Florey Institute of Neuroscience and Mental Health1, University of Calgary2, Boston University3, University of Missouri–Kansas City4, International Olympic Committee5, University of Michigan6, Veterans Health Administration7, University of North Carolina at Chapel Hill8, University of British Columbia9, Medical College of Wisconsin10, University of Melbourne11, McMaster University12, Rutgers University13
TL;DR: This paper is a revision and update of the recommendations developed following the 1st (Vienna 2001), 2nd (Prague 2004) and 3rd (Zurich 2008) International Consensus Conferences on Concussions in Sport and is based on the deliberations at the 4th International Conference on Concussion in Sport held in Zurich, November 2012.
Abstract: The new 2012 Zurich Consensus statement is designed to build on the principles outlined in the previous documents and to develop further conceptual understanding of this problem using a formal consensus-based approach. A detailed description of the consensus process is outlined at the end of this document under the Background section. This document is developed primarily for use by physicians and healthcare professionals who are involved in the care of injured athletes, whether at the recreational, elite or professional level.
2,269 citations
TL;DR: The fit of integration describes the extent the qualitative and quantitative findings cohere and can help health services researchers leverage the strengths of mixed methods.
Abstract: Mixed methods research offers powerful tools for investigating complex processes and systems in health and health care. This article describes integration principles and practices at three levels in mixed methods research and provides illustrative examples. Integration at the study design level occurs through three basic mixed method designs—exploratory sequential, explanatory sequential, and convergent—and through four advanced frameworks—multistage, intervention, case study, and participatory. Integration at the methods level occurs through four approaches. In connecting, one database links to the other through sampling. With building, one database informs the data collection approach of the other. When merging, the two databases are brought together for analysis. With embedding, data collection and analysis link at multiple points. Integration at the interpretation and reporting level occurs through narrative, data transformation, and joint display. The fit of integration describes the extent the qualitative and quantitative findings cohere. Understanding these principles and practices of integration can help health services researchers leverage the strengths of mixed methods.
TL;DR: Empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
Abstract: Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
California Institute of Technology1, University of California, Berkeley2, Lawrence Livermore National Laboratory3, Technical University of Denmark4, Columbia University5, Goddard Space Flight Center6, INAF7, SLAC National Accelerator Laboratory8, McGill University9, Hoffmann-La Roche10, University of Toulouse11, Inter-University Centre for Astronomy and Astrophysics12, Durham University13, Sonoma State University14, Roma Tre University15, Santa Cruz Institute for Particle Physics16, Georgia Institute of Technology17, Pontifical Catholic University of Chile18, Pennsylvania State University19, Harvard University20, Massachusetts Institute of Technology21, University of Cambridge22, Virginia Tech23, Los Alamos National Laboratory24, Quest University25, University of Michigan26, Weizmann Institute of Science27, North Carolina State University28, Willamette University29, University of Concepción30, Yale University31
TL;DR: The Nuclear Spectroscopic Telescope Array (NuSTAR) as discussed by the authors is the first focusing high-energy X-ray telescope in orbit, which operates in the band from 3 to 79 keV.
Abstract: The Nuclear Spectroscopic Telescope Array (NuSTAR) mission, launched on 2012 June 13, is the first focusing high-energy X-ray telescope in orbit. NuSTAR operates in the band from 3 to 79 keV, extending the sensitivity of focusing far beyond the ~10 keV high-energy cutoff achieved by all previous X-ray satellites. The inherently low background associated with concentrating the X-ray light enables NuSTAR to probe the hard X-ray sky with a more than 100-fold improvement in sensitivity over the collimated or coded mask instruments that have operated in this bandpass. Using its unprecedented combination of sensitivity and spatial and spectral resolution, NuSTAR will pursue five primary scientific objectives: (1) probe obscured active galactic nucleus (AGN) activity out to the peak epoch of galaxy assembly in the universe (at z ≾ 2) by surveying selected regions of the sky; (2) study the population of hard X-ray-emitting compact objects in the Galaxy by mapping the central regions of the Milky Way; (3) study the non-thermal radiation in young supernova remnants, both the hard X-ray continuum and the emission from the radioactive element ^(44)Ti; (4) observe blazars contemporaneously with ground-based radio, optical, and TeV telescopes, as well as with Fermi and Swift, to constrain the structure of AGN jets; and (5) observe line and continuum emission from core-collapse supernovae in the Local Group, and from nearby Type Ia events, to constrain explosion models. During its baseline two-year mission, NuSTAR will also undertake a broad program of targeted observations. The observatory consists of two co-aligned grazing-incidence X-ray telescopes pointed at celestial targets by a three-axis stabilized spacecraft. Deployed into a 600 km, near-circular, 6° inclination orbit, the observatory has now completed commissioning, and is performing consistent with pre-launch expectations. NuSTAR is now executing its primary science mission, and with an expected orbit lifetime of 10 yr, we anticipate proposing a guest investigator program, to begin in late 2014.
Radboud University Nijmegen1, University of Michigan2, University of Toronto3, McGill University4, University of Basel5, University of Florence6, Auckland City Hospital7, University of Pittsburgh8, Complutense University of Madrid9, Charité10, University of California, Los Angeles11, University College London12, University of Zurich13, University of Paris14, Marche Polytechnic University15, University of Texas Health Science Center at Houston16, Newcastle University17, University of Pécs18, Georgetown University19, Istanbul University20, Medical University of Białystok21, University of Giessen22, Seconda Università degli Studi di Napoli23, University College Dublin24, Stanford University25, University of Colorado Denver26, Amgen27, Medical College of Wisconsin28, University of Alabama at Birmingham29, University of Manchester30, National Health Service31, Rutgers University32, Thomas Jefferson University33, University of Toledo34, Boston University35, University of Pennsylvania36, Medical University of South Carolina37, Northwestern University38, University of Western Ontario39
TL;DR: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria and should allow for more patients to be classified correctly as having the disease.
Abstract: Objective The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. Methods Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by (1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and (2) validating against the combined view of a group of experts on a set of cases with or without SSc. Results It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, seven additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud9s phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. Conclusions The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.
TL;DR: The Quantum Toolbox in Python as mentioned in this paper has been updated with new features, enhanced performance, and made changes in the API for improved functionality and consistency within the package, as well as increased compatibility with existing conventions used in other scientific software packages for Python.
TL;DR: Data suggest that, through recruitment of tumor-infiltrating immune cells, fusobacteria generate a proinflammatory microenvironment that is conducive for colorectal neoplasia progression, and this work finds that F.nucleatum does not exacerbate colitis, enteritis, or inflammation-associated intestinal carcinogenesis.
University of Oklahoma1, University of Washington2, University of Nebraska Medical Center3, Johns Hopkins University4, Northwestern University5, University of Colorado Boulder6, University of Colorado Hospital7, University of Michigan8, University of Virginia9, West Virginia University10, Emory University11, Rush University Medical Center12
TL;DR: These guidelines were developed jointly by the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America, the Surgical Infection Society (SIS), and the Society for Healthcare Epidemiology of America (SHEA).
Abstract: These guidelines were developed jointly by the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), the Surgical Infection Society (SIS), and the Society for Healthcare Epidemiology of America (SHEA). This work represents an update to the
TL;DR: Understanding the interaction of the microbiota with pathogens and the host might provide new insights into the pathogenesis of disease, as well as novel avenues for preventing and treating intestinal and systemic disorders.
Abstract: The mammalian intestine is colonized by trillions of microorganisms, most of which are bacteria that have co-evolved with the host in a symbiotic relationship. The collection of microbial populations that reside on and in the host is commonly referred to as the microbiota. A principal function of the microbiota is to protect the intestine against colonization by exogenous pathogens and potentially harmful indigenous microorganisms via several mechanisms, which include direct competition for limited nutrients and the modulation of host immune responses. Conversely, pathogens have developed strategies to promote their replication in the presence of competing microbiota. Breakdown of the normal microbial community increases the risk of pathogen infection, the overgrowth of harmful pathobionts and inflammatory disease. Understanding the interaction of the microbiota with pathogens and the host might provide new insights into the pathogenesis of disease, as well as novel avenues for preventing and treating intestinal and systemic disorders.
Pacific Northwest National Laboratory1, California Institute of Technology2, Princeton University3, Humboldt University of Berlin4, Pennsylvania State University5, Brookhaven National Laboratory6, University of California, Riverside7, University of Illinois at Urbana–Champaign8, University of California, Berkeley9, United States Department of Energy10, University of Toronto11, University of Michigan12, University of Amsterdam13, Utah State University14, Max Planck Society15, Louisiana State University16
TL;DR: Providing a future energy supply that is secure and CO_2-neutral will require switching to nonfossil energy sources such as wind, solar, nuclear, and geothermal energy and developing methods for transforming the energy produced by these new sources into forms that can be stored, transported, and used upon demand.
Abstract: Two major energy-related problems confront the world in the
next 50 years. First, increased worldwide competition for
gradually depleting fossil fuel reserves (derived from past
photosynthesis) will lead to higher costs, both monetarily and politically. Second, atmospheric CO_2 levels are at their highest recorded level since records began. Further increases are predicted to produce large and uncontrollable impacts on the world climate. These projected impacts extend beyond climate to ocean acidification, because the ocean is a major sink for atmospheric CO2.1 Providing a future energy supply that is secure and CO_2-neutral will require switching to nonfossil energy sources such as wind, solar, nuclear, and geothermal energy and developing methods for transforming the energy produced by these new sources into forms that can be stored, transported, and used upon demand.
TL;DR: In the second edition of Multilevel Analysis, Tom A. B. Snijders & Roel J. Bosker present a meta-modelling framework called “Smart Modeling” that automates the very labor-intensive and therefore time-heavy and therefore expensive and expensive process of designing and implementing multilevel models.
Abstract: Tom A. B. Snijders & Roel J. Bosker. Los Angeles, CA: Sage, 2012, 354 pp. $45.00 (softcover). In the second edition of Multilevel Analysis: An Introduction to Basic and Advanced Multilevel Modeling...
TL;DR: In this article, the three major materials challenges for the current and next generation of water-cooled fission reactors are centered on two structural materials aging degradation issues (corrosion and stress corrosion cracking of structural materials and neutron-induced embrittlement of reactor pressure vessels), along with improved fuel system reliability and accident tolerance issues.
Panos Deloukas1, Stavroula Kanoni1, Christina Willenborg2, Martin Farrall3 +201 more•Institutions (64)
TL;DR: An association analysis in CAD cases and controls identifies 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants strongly associated with CAD at a 5% false discovery rate (FDR).
Abstract: Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.
TL;DR: These results provide a unifying model for the activation of the NLRP3 inflammasome in which a drop in cytosolic K⁺ is the common step that is necessary and sufficient for caspase-1 activation.
TL;DR: Hybrid quantum circuits combine two or more physical systems, with the goal of harnessing the advantages and strengths of the different systems in order to better explore new phenomena and potentially bring about novel quantum technologies as discussed by the authors.
Abstract: Hybrid quantum circuits combine two or more physical systems, with the goal of harnessing the advantages and strengths of the different systems in order to better explore new phenomena and potentially bring about novel quantum technologies. This article presents a brief overview of the progress achieved so far in the field of hybrid circuits involving atoms, spins, and solid-state devices (including superconducting and nanomechanical systems). How these circuits combine elements from atomic physics, quantum optics, condensed matter physics, and nanoscience is discussed, and different possible approaches for integrating various systems into a single circuit are presented. In particular, hybrid quantum circuits can be fabricated on a chip, facilitating their future scalability, which is crucial for building future quantum technologies, including quantum detectors, simulators, and computers.
TL;DR: Huygens' principle is applied to develop designer surfaces that provide extreme control of electromagnetic wave fronts across electrically thin layers to find a wide range of applications over the entire electromagnetic spectrum including single-surface lenses, polarization controlling devices, stealth technologies, and perfect absorbers.
Abstract: Huygens' principle is a well-known concept in electromagnetics that dates back to 1690. Here, it is applied to develop designer surfaces that provide extreme control of electromagnetic wave fronts across electrically thin layers. These reflectionless surfaces, referred to as metamaterial Huygens' surfaces, provide new beam shaping, steering, and focusing capabilities. The metamaterial Huygens' surfaces are realized with two-dimensional arrays of polarizable particles that provide both electric and magnetic polarization currents to generate prescribed wave fronts. A straightforward design methodology is demonstrated and applied to develop a beam-refracting surface and a Gaussian-to-Bessel beam transformer. Metamaterial Huygens' surfaces could find a wide range of applications over the entire electromagnetic spectrum including single-surface lenses, polarization controlling devices, stealth technologies, and perfect absorbers.
TL;DR: Early diagnosis of PAH remains difficult, and screening programs in asymptomatic patients are feasible only in high-risk populations, particularly in patients with systemic sclerosis, for whom recent data suggest that a combination of clinical assessment and pulmonary function testing has a higher predictive value than echocardiography alone.
TL;DR: Reducing dopant volume is found to be as important as optimizing carrier concentration when maximizing ZT in OSCs, and this stands in sharp contrast to ISCs, for which these parameters have trade-offs.
Abstract: The conversion efficiency of heat to electricity in thermoelectric materials depends on both their thermopower and electrical conductivity. It is now reported that, unlike their inorganic counterparts, organic thermoelectric materials show an improvement in both these parameters when the volume of dopant elements is minimized; furthermore, a high conversion efficiency is achieved in PEDOT:PSS blends.
University of Michigan1, University of Toronto2, Princeton University3, ETH Zurich4, Stowers Institute for Medical Research5, Utrecht University6, Netherlands Cancer Institute7, Radboud University Nijmegen8, Université de Montréal9, University of Zurich10, Austrian Academy of Sciences11, National University of Singapore12, University of Kansas13, University of Southampton14, Case Western Reserve University15
TL;DR: The contaminant repository for affinity purification (the CRAPome) is presented and its use for scoring protein-protein interactions is described and aggregating negative controls from multiple AP-MS studies can increase coverage and improve the characterization of background associated with a given experimental protocol.
Abstract: Affinity purification coupled with mass spectrometry (AP-MS) is a widely used approach for the identification of protein-protein interactions. However, for any given protein of interest, determining which of the identified polypeptides represent bona fide interactors versus those that are background contaminants (for example, proteins that interact with the solid-phase support, affinity reagent or epitope tag) is a challenging task. The standard approach is to identify nonspecific interactions using one or more negative-control purifications, but many small-scale AP-MS studies do not capture a complete, accurate background protein set when available controls are limited. Fortunately, negative controls are largely bait independent. Hence, aggregating negative controls from multiple AP-MS studies can increase coverage and improve the characterization of background associated with a given experimental protocol. Here we present the contaminant repository for affinity purification (the CRAPome) and describe its use for scoring protein-protein interactions. The repository (currently available for Homo sapiens and Saccharomyces cerevisiae) and computational tools are freely accessible at http://www.crapome.org/.
TL;DR: It is shown that eIF2α-phosphorylation-attenuated protein synthesis, and not Atf4 mRNA translation, promotes cell survival, and suggesting that limiting protein synthesis will be therapeutic for diseases caused by protein misfolding in the ER.
Abstract: Protein misfolding in the endoplasmic reticulum (ER) leads to cell death through PERK-mediated phosphorylation of eIF2α, although the mechanism is not understood. ChIP-seq and mRNA-seq of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), key transcription factors downstream of p-eIF2α, demonstrated that they interact to directly induce genes encoding protein synthesis and the unfolded protein response, but not apoptosis. Forced expression of ATF4 and CHOP increased protein synthesis and caused ATP depletion, oxidative stress and cell death. The increased protein synthesis and oxidative stress were necessary signals for cell death. We show that eIF2α-phosphorylation-attenuated protein synthesis, and not Atf4 mRNA translation, promotes cell survival. These results show that transcriptional induction through ATF4 and CHOP increases protein synthesis leading to oxidative stress and cell death. The findings suggest that limiting protein synthesis will be therapeutic for diseases caused by protein misfolding in the ER.
Duke University1, University of Melbourne2, Université de Montréal3, Royal College of Surgeons in Ireland4, University of Pennsylvania5, University of Washington6, Emory University7, Cincinnati Children's Hospital Medical Center8, Royal Children's Hospital9, Imperial College London10, New York University11, University of California, San Francisco12, University of Liverpool13, Royal Melbourne Hospital14, Columbia University15, Harvard University16, Vanderbilt University17, Cleveland Clinic18, Yeshiva University19, Mayo Clinic20, University of Pittsburgh21, University of Minnesota22, University of Virginia23, Saint Barnabas Medical Center24, University of Michigan25, Kaiser Permanente26, University of Chicago27, University of Texas Health Science Center at Houston28, Johns Hopkins University29, Children's Hospital Oakland Research Institute30, Boston Children's Hospital31, Oregon Health & Science University32, Cornell University33, United States Department of Veterans Affairs34, Washington University in St. Louis35
TL;DR: In this paper, a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms and Lennox-Gastaut syndrome (n = 115) was performed.
Abstract: Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox-Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the ∼4,000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 × 10(-3)). Among these are GABRB3, with de novo mutations in four patients, and ALG13, with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 × 10(-10) and P = 7.8 × 10(-12), respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P < 10(-8)), as has been reported previously for autism spectrum disorders.