Showing papers by "University of Wisconsin-Madison published in 2013"
Broad Institute1, Commonwealth Scientific and Industrial Research Organisation2, Massachusetts Institute of Technology3, Hebrew University of Jerusalem4, Science for Life Laboratory5, Pittsburgh Supercomputing Center6, Oklahoma State University–Stillwater7, Griffith University8, University of Wisconsin-Madison9, Dresden University of Technology10, California Institute for Quantitative Biosciences11, Flanders Institute for Biotechnology12, Parco Tecnologico Padano13, United States Department of Agriculture14, Purdue University15, Indiana University16
TL;DR: This protocol provides a workflow for genome-independent transcriptome analysis leveraging the Trinity platform and presents Trinity-supported companion utilities for downstream applications, including RSEM for transcript abundance estimation, R/Bioconductor packages for identifying differentially expressed transcripts across samples and approaches to identify protein-coding genes.
Abstract: De novo assembly of RNA-seq data enables researchers to study transcriptomes without the need for a genome sequence; this approach can be usefully applied, for instance, in research on 'non-model organisms' of ecological and evolutionary importance, cancer samples or the microbiome. In this protocol we describe the use of the Trinity platform for de novo transcriptome assembly from RNA-seq data in non-model organisms. We also present Trinity-supported companion utilities for downstream applications, including RSEM for transcript abundance estimation, R/Bioconductor packages for identifying differentially expressed transcripts across samples and approaches to identify protein-coding genes. In the procedure, we provide a workflow for genome-independent transcriptome analysis leveraging the Trinity platform. The software, documentation and demonstrations are freely available from http://trinityrnaseq.sourceforge.net. The run time of this protocol is highly dependent on the size and complexity of data to be analyzed. The example data set analyzed in the procedure detailed herein can be processed in less than 5 h.
6,369 citations
Stanford University1, Maine Medical Center2, University of California, San Francisco3, Veterans Health Administration4, McGill University5, University of Texas at Austin6, Scripps Health7, Northeastern University8, University of Chicago9, University of Washington10, University of Wisconsin-Madison11, University of Maryland, Baltimore12, University of Cincinnati13, University of Virginia14, Baylor University Medical Center15, Virginia Commonwealth University16, Université de Montréal17, McMaster University18
TL;DR: These guidelines provide a roadmap for developing integrated, evidence-based, and patient-centered protocols for preventing and treating pain, agitation, and delirium in critically ill patients.
Abstract: Objective:To revise the “Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult” published in Critical Care Medicine in 2002.Methods:The American College of Critical Care Medicine assembled a 20-person, multidisciplinary, multi-institutional task f
3,005 citations
Woolcock Institute of Medical Research1, University of Otago2, University of Cape Town3, Boston University4, University of California, San Francisco5, University of Wisconsin-Madison6, Creighton University7, University of Arizona8, University of Newcastle9, Erasmus University Rotterdam10, University of Groningen11, University of Edinburgh12, McMaster University13, Imperial College London14, University of Leicester15, University of Amsterdam16, University of Nevada, Reno17, University of Washington18, University of Aberdeen19, University of Pittsburgh20
TL;DR: This update is a supplement to the previous 2002 IIP classification document and outlines advances in the past decade and potential areas for future investigation.
Abstract: Background: In 2002 the American Thoracic Society/European Respiratory Society (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs) defined seven specific entities, and provided standardized terminology and diagnostic criteria. In addition, the historical “gold standard” of histologic diagnosis was replaced by a multidisciplinary approach. Since 2002 many publications have provided new information about IIPs.Purpose: The objective of this statement is to update the 2002 ATS/ERS classification of IIPs.Methods: An international multidisciplinary panel was formed and developed key questions that were addressed through a review of the literature published between 2000 and 2011.Results: Substantial progress has been made in IIPs since the previous classification. Nonspecific interstitial pneumonia is now better defined. Respiratory bronchiolitis–interstitial lung disease is now commonly diagnosed without surgical biopsy. The clinical course of idiopathic pulmonary fibrosis and nonspecific inte...
2,931 citations
TL;DR: Structural characterization and electrochemical studies confirmed that the nanosheets of the metallic MoS2 polymorph exhibit facile electrode kinetics and low-loss electrical transport and possess a proliferated density of catalytic active sites, which make these metallic nanOSheets a highly competitive earth-abundant HER catalyst.
Abstract: Promising catalytic activity from molybdenum disulfide (MoS2) in the hydrogen evolution reaction (HER) is attributed to active sites located along the edges of its two-dimensional layered crystal structure, but its performance is currently limited by the density and reactivity of active sites, poor electrical transport, and inefficient electrical contact to the catalyst. Here we report dramatically enhanced HER catalysis (an electrocatalytic current density of 10 mA/cm2 at a low overpotential of −187 mV vs RHE and a Tafel slope of 43 mV/decade) from metallic nanosheets of 1T-MoS2 chemically exfoliated via lithium intercalation from semiconducting 2H-MoS2 nanostructures grown directly on graphite. Structural characterization and electrochemical studies confirmed that the nanosheets of the metallic MoS2 polymorph exhibit facile electrode kinetics and low-loss electrical transport and possess a proliferated density of catalytic active sites. These distinct and previously unexploited features of 1T-MoS2 make ...
2,899 citations
TL;DR: Modules for Experiments in Stellar Astrophysics (MESA) as discussed by the authors is an open source software package for modeling the evolution of stellar structures and composition. But it is not suitable for large-scale systems such as supernovae.
Abstract: We substantially update the capabilities of the open source software package Modules for Experiments in Stellar Astrophysics (MESA), and its one-dimensional stellar evolution module, MESA star. Improvements in MESA star's ability to model the evolution of giant planets now extends its applicability down to masses as low as one-tenth that of Jupiter. The dramatic improvement in asteroseismology enabled by the space-based Kepler and CoRoT missions motivates our full coupling of the ADIPLS adiabatic pulsation code with MESA star. This also motivates a numerical recasting of the Ledoux criterion that is more easily implemented when many nuclei are present at non-negligible abundances. This impacts the way in which MESA star calculates semi-convective and thermohaline mixing. We exhibit the evolution of 3-8 M ? stars through the end of core He burning, the onset of He thermal pulses, and arrival on the white dwarf cooling sequence. We implement diffusion of angular momentum and chemical abundances that enable calculations of rotating-star models, which we compare thoroughly with earlier work. We introduce a new treatment of radiation-dominated envelopes that allows the uninterrupted evolution of massive stars to core collapse. This enables the generation of new sets of supernovae, long gamma-ray burst, and pair-instability progenitor models. We substantially modify the way in which MESA star solves the fully coupled stellar structure and composition equations, and we show how this has improved the scaling of MESA's calculational speed on multi-core processors. Updates to the modules for equation of state, opacity, nuclear reaction rates, and atmospheric boundary conditions are also provided. We describe the MESA Software Development Kit that packages all the required components needed to form a unified, maintained, and well-validated build environment for MESA. We also highlight a few tools developed by the community for rapid visualization of MESA star results.
2,761 citations
University of Wisconsin-Madison1, University of Hawaii2, University of Kiel3, Cornell University4, Max Planck Society5, Pasteur Institute6, Stanford University7, University of Helsinki8, University of Würzburg9, University of California, Berkeley10, University of New South Wales11, Harvard University12, California Institute of Technology13, University of Colorado Boulder14, University of Southern California15, University of North Carolina at Chapel Hill16, University of Connecticut17, Duke University18
TL;DR: Recent technological and intellectual advances that have changed thinking about five questions about how have bacteria facilitated the origin and evolution of animals; how do animals and bacteria affect each other’s genomes; how does normal animal development depend on bacterial partners; and how is homeostasis maintained between animals and their symbionts are highlighted.
Abstract: In the last two decades, the widespread application of genetic and genomic approaches has revealed a bacterial world astonishing in its ubiquity and diversity. This review examines how a growing knowledge of the vast range of animal–bacterial interactions, whether in shared ecosystems or intimate symbioses, is fundamentally altering our understanding of animal biology. Specifically, we highlight recent technological and intellectual advances that have changed our thinking about five questions: how have bacteria facilitated the origin and evolution of animals; how do animals and bacteria affect each other’s genomes; how does normal animal development depend on bacterial partners; how is homeostasis maintained between animals and their symbionts; and how can ecological approaches deepen our understanding of the multiple levels of animal–bacterial interaction. As answers to these fundamental questions emerge, all biologists will be challenged to broaden their appreciation of these interactions and to include investigations of the relationships between and among bacteria and their animal partners as we seek a better understanding of the natural world.
2,103 citations
National Center for Atmospheric Research1, Pacific Northwest National Laboratory2, University of Toronto3, Los Alamos National Laboratory4, Cornell University5, University of Wisconsin-Madison6, Lawrence Livermore National Laboratory7, Lawrence Berkeley National Laboratory8, Oak Ridge National Laboratory9, University of Calgary10
TL;DR: The Community Earth System Model (CESM) as discussed by the authors is a community tool used to investigate a diverse set of Earth system interactions across multiple time and space scales, including biogeochemical cycles, a variety of atmospheric chemistry options, the Greenland Ice Sheet, and an atmosphere that extends to the lower thermosphere.
Abstract: The Community Earth System Model (CESM) is a flexible and extensible community tool used to investigate a diverse set of Earth system interactions across multiple time and space scales. This global coupled model significantly extends its predecessor, the Community Climate System Model, by incorporating new Earth system simulation capabilities. These comprise the ability to simulate biogeochemical cycles, including those of carbon and nitrogen, a variety of atmospheric chemistry options, the Greenland Ice Sheet, and an atmosphere that extends to the lower thermosphere. These and other new model capabilities are enabling investigations into a wide range of pressing scientific questions, providing new foresight into possible future climates and increasing our collective knowledge about the behavior and interactions of the Earth system. Simulations with numerous configurations of the CESM have been provided to phase 5 of the Coupled Model Intercomparison Project (CMIP5) and are being analyzed by the broad com...
2,075 citations
Columbia University1, Cambridge University Hospitals NHS Foundation Trust2, University of Wisconsin-Madison3, McGill University4, University of Sheffield5, University of Kentucky6, French Institute of Health and Medical Research7, University of Washington8, Creighton University9, University of Arkansas for Medical Sciences10
TL;DR: The key revisions include omission of terminology used before 1987, recommendations regarding the parameters and technical information that should be included in all histomorphometry articles, recommendations on how to handle dynamic parameters of bone formation in settings of low bone turnover, and updating of references.
Abstract: Before publication of the original version of this report in 1987, practitioners of bone histomorphometry communicated with each other in a variety of arcane languages, which in general were unintelligible to those outside the field. The need for standardization of nomenclature had been recognized for many years,(1) during which there had been much talk but no action. To satisfy this need, B Lawrence Riggs (ASBMR President, 1985 to 1986) asked A Michael Parfitt to convene an ASBMR committee to develop a new and unified system of terminology, suitable for adoption by the Journal of Bone and Mineral Research (JBMR) as part of its Instructions to Authors. The resulting recommendations were published in 1987(2) and were quickly adopted not only by JBMR but also by all respected journals in the bone field. The recommendations improved markedly the ability of histomorphometrists to communicate with each other and with nonhistomorphometrists, leading to a broader understanding and appreciation of histomorphometric data.
In 2012, 25 years after the development of the standardized nomenclature system, Thomas L Clemens (Editor in Chief of JBMR) felt that it was time to revise and update the recommendations. The original committee was reconvened by David W Dempster, who appointed one new member, Juliet E Compston. The original document was circulated to the committee members and was extensively revised according to their current recommendations. The key revisions include omission of terminology used before 1987, recommendations regarding the parameters and technical information that should be included in all histomorphometry articles, recommendations on how to handle dynamic parameters of bone formation in settings of low bone turnover, and updating of references.
2,035 citations
TL;DR: This monograph discusses 10 learning techniques that benefit learners of different ages and abilities and have been shown to boost students’ performance across many criterion tasks and even in educational contexts.
Abstract: Many students are being left behind by an educational system that some people believe is in crisis. Improving educational outcomes will require efforts on many fronts, but a central premise of this monograph is that one part of a solution involves helping students to better regulate their learning through the use of effective learning techniques. Fortunately, cognitive and educational psychologists have been developing and evaluating easy-to-use learning techniques that could help students achieve their learning goals. In this monograph, we discuss 10 learning techniques in detail and offer recommendations about their relative utility. We selected techniques that were expected to be relatively easy to use and hence could be adopted by many students. Also, some techniques (e.g., highlighting and rereading) were selected because students report relying heavily on them, which makes it especially important to examine how well they work. The techniques include elaborative interrogation, self-explanation, summarization, highlighting (or underlining), the keyword mnemonic, imagery use for text learning, rereading, practice testing, distributed practice, and interleaved practice. To offer recommendations about the relative utility of these techniques, we evaluated whether their benefits generalize across four categories of variables: learning conditions, student characteristics, materials, and criterion tasks. Learning conditions include aspects of the learning environment in which the technique is implemented, such as whether a student studies alone or with a group. Student characteristics include variables such as age, ability, and level of prior knowledge. Materials vary from simple concepts to mathematical problems to complicated science texts. Criterion tasks include different outcome measures that are relevant to student achievement, such as those tapping memory, problem solving, and comprehension. We attempted to provide thorough reviews for each technique, so this monograph is rather lengthy. However, we also wrote the monograph in a modular fashion, so it is easy to use. In particular, each review is divided into the following sections: General description of the technique and why it should work How general are the effects of this technique? 2a. Learning conditions 2b. Student characteristics 2c. Materials 2d. Criterion tasks Effects in representative educational contexts Issues for implementation Overall assessment The review for each technique can be read independently of the others, and particular variables of interest can be easily compared across techniques. To foreshadow our final recommendations, the techniques vary widely with respect to their generalizability and promise for improving student learning. Practice testing and distributed practice received high utility assessments because they benefit learners of different ages and abilities and have been shown to boost students' performance across many criterion tasks and even in educational contexts. Elaborative interrogation, self-explanation, and interleaved practice received moderate utility assessments. The benefits of these techniques do generalize across some variables, yet despite their promise, they fell short of a high utility assessment because the evidence for their efficacy is limited. For instance, elaborative interrogation and self-explanation have not been adequately evaluated in educational contexts, and the benefits of interleaving have just begun to be systematically explored, so the ultimate effectiveness of these techniques is currently unknown. Nevertheless, the techniques that received moderate-utility ratings show enough promise for us to recommend their use in appropriate situations, which we describe in detail within the review of each technique. Five techniques received a low utility assessment: summarization, highlighting, the keyword mnemonic, imagery use for text learning, and rereading. These techniques were rated as low utility for numerous reasons. Summarization and imagery use for text learning have been shown to help some students on some criterion tasks, yet the conditions under which these techniques produce benefits are limited, and much research is still needed to fully explore their overall effectiveness. The keyword mnemonic is difficult to implement in some contexts, and it appears to benefit students for a limited number of materials and for short retention intervals. Most students report rereading and highlighting, yet these techniques do not consistently boost students' performance, so other techniques should be used in their place (e.g., practice testing instead of rereading). Our hope is that this monograph will foster improvements in student learning, not only by showcasing which learning techniques are likely to have the most generalizable effects but also by encouraging researchers to continue investigating the most promising techniques. Accordingly, in our closing remarks, we discuss some issues for how these techniques could be implemented by teachers and students, and we highlight directions for future research.
1,989 citations
Kyle S. Dawson1, David J. Schlegel2, Christopher P. Ahn1, Scott F. Anderson3 +181 more•Institutions (51)
TL;DR: The Baryon Oscillation Spectroscopic Survey (BOSS) as discussed by the authors was designed to measure the scale of baryon acoustic oscillations (BAO) in the clustering of matter over a larger volume than the combined efforts of all previous spectroscopic surveys of large-scale structure.
Abstract: The Baryon Oscillation Spectroscopic Survey (BOSS) is designed to measure the scale of baryon acoustic oscillations (BAO) in the clustering of matter over a larger volume than the combined efforts of all previous spectroscopic surveys of large-scale structure. BOSS uses 1.5 million luminous galaxies as faint as i = 19.9 over 10,000 deg2 to measure BAO to redshifts z < 0.7. Observations of neutral hydrogen in the Lyα forest in more than 150,000 quasar spectra (g < 22) will constrain BAO over the redshift range 2.15 < z < 3.5. Early results from BOSS include the first detection of the large-scale three-dimensional clustering of the Lyα forest and a strong detection from the Data Release 9 data set of the BAO in the clustering of massive galaxies at an effective redshift z = 0.57. We project that BOSS will yield measurements of the angular diameter distance dA to an accuracy of 1.0% at redshifts z = 0.3 and z = 0.57 and measurements of H(z) to 1.8% and 1.7% at the same redshifts. Forecasts for Lyα forest constraints predict a measurement of an overall dilation factor that scales the highly degenerate DA (z) and H –1(z) parameters to an accuracy of 1.9% at z ~ 2.5 when the survey is complete. Here, we provide an overview of the selection of spectroscopic targets, planning of observations, and analysis of data and data quality of BOSS.
1,938 citations
Alternatives1, John Innes Centre2, University of Bonn3, University of North Carolina at Chapel Hill4, University of Wisconsin-Madison5, University of Utah6, University of Southern California7, University of Edinburgh8, University of Warwick9, Harvard University10, University College Cork11, University of Queensland12, University of Hertfordshire13, University of Potsdam14, University of California, San Diego15, Goethe University Frankfurt16, University of California, San Francisco17, University of Delaware18, Uppsala University19, Medical University of Vienna20, J. Craig Venter Institute21, University of Hawaii at Manoa22, Leibniz Association23, University of Iowa24, University of Aberdeen25, Georgia Institute of Technology26, University of California, Berkeley27, University of Groningen28, Princeton University29, University of Marburg30, University of Illinois at Urbana–Champaign31, Saarland University32, Norwegian University of Life Sciences33, Massey University34, Toyama Prefectural University35, ETH Zurich36, University of Saskatchewan37, Rutgers University38, Scripps Research Institute39, University of Helsinki40, Texas A&M University41, National Institutes of Health42, Technical University of Berlin43, University of Otago44, University of Cambridge45, University of Alberta46, Michigan State University47, Hofstra University48
TL;DR: This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products.
TL;DR: A revised, error-corrected, and validated assembly of the Nipponbare cultivar of rice was generated using optical map data, re-sequencing data, and manual curation that will facilitate on-going and future research in rice.
Abstract: Rice research has been enabled by access to the high quality reference genome sequence generated in 2005 by the International Rice Genome Sequencing Project (IRGSP). To further facilitate genomic-enabled research, we have updated and validated the genome assembly and sequence for the Nipponbare cultivar of Oryza sativa (japonica group). The Nipponbare genome assembly was updated by revising and validating the minimal tiling path of clones with the optical map for rice. Sequencing errors in the revised genome assembly were identified by re-sequencing the genome of two different Nipponbare individuals using the Illumina Genome Analyzer II/IIx platform. A total of 4,886 sequencing errors were identified in 321 Mb of the assembled genome indicating an error rate in the original IRGSP assembly of only 0.15 per 10,000 nucleotides. A small number (five) of insertions/deletions were identified using longer reads generated using the Roche 454 pyrosequencing platform. As the re-sequencing data were generated from two different individuals, we were able to identify a number of allelic differences between the original individual used in the IRGSP effort and the two individuals used in the re-sequencing effort. The revised assembly, termed Os-Nipponbare-Reference-IRGSP-1.0, is now being used in updated releases of the Rice Annotation Project and the Michigan State University Rice Genome Annotation Project, thereby providing a unified set of pseudomolecules for the rice community. A revised, error-corrected, and validated assembly of the Nipponbare cultivar of rice was generated using optical map data, re-sequencing data, and manual curation that will facilitate on-going and future research in rice. Detection of polymorphisms between three different Nipponbare individuals highlights that allelic differences between individuals should be considered in diversity studies.
University of Adelaide1, University of Wisconsin-Madison2, Ghent University3, University of Canterbury4, University of Geneva5, Humboldt University of Berlin6, University of California, Irvine7, University of Mainz8, University of California, Berkeley9, Ohio State University10, Université libre de Bruxelles11, Ruhr University Bochum12, University of Wuppertal13, University of Maryland, College Park14, University of Kansas15, Lawrence Berkeley National Laboratory16, RWTH Aachen University17, Uppsala University18, University of Alberta19, Stockholm University20, Vrije Universiteit Brussel21, University of Bonn22, École Polytechnique Fédérale de Lausanne23, Georgia Institute of Technology24, Pennsylvania State University25, Technical University of Dortmund26, Southern University and A&M College27
TL;DR: The presence of a high-energy neutrino flux containing the most energetic neutrinos ever observed is revealed, including 28 events at energies between 30 and 1200 TeV, although the origin of this flux is unknown and the findings are consistent with expectations for a neutRino population with origins outside the solar system.
Abstract: We report on results of an all-sky search for high-energy neutrino events interacting within the IceCube neutrino detector conducted between May 2010 and May 2012. The search follows up on the previous detection of two PeV neutrino events, with improved sensitivity and extended energy coverage down to about 30 TeV. Twenty-six additional events were observed, substantially more than expected from atmospheric backgrounds. Combined, both searches reject a purely atmospheric origin for the 28 events at the 4 sigma level. These 28 events, which include the highest energy neutrinos ever observed, have flavors, directions, and energies inconsistent with those expected from the atmospheric muon and neutrino backgrounds. These properties are, however, consistent with generic predictions for an additional component of extraterrestrial origin.
University of Texas MD Anderson Cancer Center1, Cornell University2, Rutgers University3, Barts Health NHS Trust4, University of Wisconsin-Madison5, Jagiellonian University6, Stanford University7, University of Virginia8, Hofstra University9, University of Manchester10, University of Ulm11, Ludwig Maximilian University of Munich12, Medical University of Warsaw13, University of Southampton14, Oregon Health & Science University15, Ohio State University16
TL;DR: Ibrutinib shows durable single-agent efficacy in relapsed or refractory mantle-cell lymphoma and is enrolled into two groups: patients who had previously received at least 2 cycles of bortezomib therapy and those who had received less than 2 complete cycles.
Abstract: rolled into two groups: those who had previously received at least 2 cycles of bor - tezomib therapy and those who had received less than 2 complete cycles of bortezo - mib or had received no prior bortezomib therapy. The primary end point was the overall response rate. Secondary end points were duration of response, progression- free survival, overall survival, and safety. RESULTS The median age was 68 years, and 86% of patients had intermediate-risk or high-risk mantle-cell lymphoma according to clinical prognostic factors. Patients had received a median of three prior therapies. The most common treatment-related adverse events were mild or moderate diarrhea, fatigue, and nausea. Grade 3 or higher hematologic events were infrequent and included neutropenia (in 16% of patients), thrombocytope - nia (in 11%), and anemia (in 10%). A response rate of 68% (75 patients) was observed, with a complete response rate of 21% and a partial response rate of 47%; prior treat - ment with bortezomib had no effect on the response rate. With an estimated median follow-up of 15.3 months, the estimated median response duration was 17.5 months (95% confidence interval (CI), 15.8 to not reached), the estimated median progression- free survival was 13.9 months (95% CI, 7.0 to not reached), and the median overall survival was not reached. The estimated rate of overall survival was 58% at 18 months. CONCLUSIONS Ibrutinib shows durable single-agent efficacy in relapsed or refractory mantle-cell lymphoma. (Funded by Pharmacyclics and others; ClinicalTrials.gov number, NCT01236391.)
TL;DR: Functional human cardiomyocytes differentiated via these protocols may constitute a potential cell source for heart disease modeling, drug screening and cell-based therapeutic applications.
Abstract: The protocol described here efficiently directs human pluripotent stem cells (hPSCs) to functional cardiomyocytes in a completely defined, growth factor- and serum-free system by temporal modulation of regulators of canonical Wnt signaling. Appropriate temporal application of a glycogen synthase kinase 3 (GSK3) inhibitor combined with the expression of β-catenin shRNA or a chemical Wnt inhibitor is sufficient to produce a high yield (0.8-1.3 million cardiomyocytes per cm(2)) of virtually pure (80-98%) functional cardiomyocytes in 14 d from multiple hPSC lines without cell sorting or selection. Qualitative (immunostaining) and quantitative (flow cytometry) characterization of differentiated cells is described to assess the expression of cardiac transcription factors and myofilament proteins. Flow cytometry of BrdU incorporation or Ki67 expression in conjunction with cardiac sarcomere myosin protein expression can be used to determine the proliferative capacity of hPSC-derived cardiomyocytes. Functional human cardiomyocytes differentiated via these protocols may constitute a potential cell source for heart disease modeling, drug screening and cell-based therapeutic applications.
TL;DR: A systematic analysis of the RNA motifs recognized by RNA-binding proteins, encompassing 205 distinct genes from 24 diverse eukaryotes, provides an unprecedented overview of RNA- binding proteins and their targets, and constitute an invaluable resource for determining post-transcriptional regulatory mechanisms in eukARYotes.
Abstract: RNA-binding proteins are key regulators of gene expression, yet only a small fraction have been functionally characterized. Here we report a systematic analysis of the RNA motifs recognized by RNA-binding proteins, encompassing 205 distinct genes from 24 diverse eukaryotes. The sequence specificities of RNA-binding proteins display deep evolutionary conservation, and the recognition preferences for a large fraction of metazoan RNA-binding proteins can thus be inferred from their RNA-binding domain sequence. The motifs that we identify in vitro correlate well with in vivo RNA-binding data. Moreover, we can associate them with distinct functional roles in diverse types of post-transcriptional regulation, enabling new insights into the functions of RNA-binding proteins both in normal physiology and in human disease. These data provide an unprecedented overview of RNA-binding proteins and their targets, and constitute an invaluable resource for determining post-transcriptional regulatory mechanisms in eukaryotes.
TL;DR: Five processes that are essential for adaptive anticipatory responses to future threat uncertainty are identified and it is proposed that alterations in the neural instantiation of these processes result in maladaptive responses to uncertainty in pathological anxiety.
Abstract: Uncertainty about a possible future threat disrupts our ability to avoid it or to mitigate its negative impact and thus results in anxiety. Here, we focus the broad literature on the neurobiology of anxiety through the lens of uncertainty. We identify five processes that are essential for adaptive anticipatory responses to future threat uncertainty and propose that alterations in the neural instantiation of these processes result in maladaptive responses to uncertainty in pathological anxiety. This framework has the potential to advance the classification, diagnosis and treatment of clinical anxiety.
TL;DR: The NBO 6.0 as mentioned in this paper is a new version of the NBO that provides novel "link-free" interactivity with host electronic structure systems, improved search algorithms and labeling conventions, and new analysis options that significantly extend the range of chemical applications.
Abstract: We describe principal features of the newly released version, NBO 6.0, of the natural bond orbital analysis program, that provides novel “link-free” interactivity with host electronic structure systems, improved search algorithms and labeling conventions for a broader range of chemical species, and new analysis options that significantly extend the range of chemical applications. We sketch the motivation and implementation of program changes and describe newer analysis options with illustrative applications. © 2013 Wiley Periodicals, Inc.
TL;DR: This review describes the crystal and electronic structures that are closely related to the photoelectrochemical properties of BiVO(4) and the latest efforts toward addressing these limitations in order to improve the performances of Bi VO(4)-based photoanodes are discussed.
Abstract: Harvesting energy directly from sunlight as nature accomplishes through photosynthesis is a very attractive and desirable way to solve the energy challenge. Many efforts have been made to find appropriate materials and systems that can utilize solar energy to produce chemical fuels. One of the most viable options is the construction of a photoelectrochemical cell that can reduce water to H2 or CO2 to carbon-based molecules. Bismuth vanadate (BiVO4) has recently emerged as a promising material for use as a photoanode that oxidizes water to O2 in these cells. Significant advancement in the understanding and construction of efficient BiVO4-based photoanode systems has been made within a short period of time owing to various newly developed ideas and approaches. In this review, the crystal and electronic structures that are closely related to the photoelectrochemical properties of BiVO4 are described first, and the photoelectrochemical properties and limitations of BiVO4 are examined. Subsequently, the latest efforts toward addressing these limitations in order to improve the performances of BiVO4-based photoanodes are discussed. These efforts include morphology control, formation of composite structures, composition tuning, and coupling oxygen evolution catalysts. The discussions and insights provided in this review reflect the most recent approaches and directions for general photoelectrode developments and they will be directly applicable for the understanding and improvement of other photoelectrode systems.
TL;DR: The term ‘proteoform’ is proposed to be used to designate all of the different molecular forms in which the protein product of a single gene can be found, including changes due to genetic variations, alternatively spliced RNA transcripts and posttranslational modifications.
Abstract: genetic differences and not to variation at the protein level2. The term “protein species” was proposed in 2009 (ref. 2) but does not distinguish between proteins originating from different genes and those originating from a single gene, and thus we find it confusing. A similar issue arises with the term “protein variants.” The UniProt Knowledgebase (a definitive, gene-centric protein database)5 uses the term “isoform” in yet a different manner, one that denotes related forms of protein molecules arising from the same gene by alternative splicing or variable promoter usage (Fig. 1). Such events create a variable set of protein sequences that significantly change the numbering of amino acids for the protein as compared to the canonical sequence. These changes to the base primary sequence are referred to by some as “isoforms” and are denoted in UniProt by a –1, –2 and so on following the accession number (Fig. 1). However, genetic changes (for example, mutations and polymorphisms) are not covered by this terminology and create a conflict with the IUPAC definition of isoform2. Differences in IUPAC and UniProt definitions notwithstanding, the terms “variants” and “isoforms” were intended to describe proteins derived from distinct DNA or RNA; their use to describe modified proteins is confusing. Accordingly, we propose that the term ‘proteoform’ be used to designate all of the different molecular forms in which the protein product of a single gene can be found, including changes due to genetic variations, alternatively spliced RNA transcripts and posttranslational modifications (Fig. 1). Any gene or protein processing events such as those using inteins or RNA-editing mechanisms are now covered cleanly by the term ‘proteoform’. The term should include all post-translational modifications in the PSI-MOD ontology except those classified as reagent-derivatized or isotope-labeled residues (see the Supplementary Note for a precise definition). Products of multigene families should continue to be categorized on the basis of sequence identity (for example, >90%, >99% and so on). The term is compatible with a gene-centric approach for referring to proteins, which we support, because grouping related forms of proteins together even though they are the products of different genes leads to imprecision in protein identification5. We have begun to use the term ‘proteoform’ in our own writing and presentations, and we find it to be intuitive and readily grasped Proteoform: a single term describing protein complexity
Mayo Clinic1, University of Texas MD Anderson Cancer Center2, University of Pittsburgh3, University of Wisconsin-Madison4, Columbia University5, University of Texas Southwestern Medical Center6, Indiana University7, Carolinas Medical Center8, University of Washington9, University of North Carolina at Chapel Hill10, Allegheny General Hospital11, American College of Surgeons Oncology Group12, Rutgers University13
TL;DR: The application of SLN surgery for staging the axilla following chemotherapy for women who initially had node-positive cN1 breast cancer is unclear because of high false-negative results reported in previous studies as mentioned in this paper.
Abstract: IMPORTANCE Sentinel lymph node (SLN) surgery provides reliable nodal staging information with less morbidity than axillary lymph node dissection (ALND) for patients with clinically node-negative (cN0) breast cancer. The application of SLN surgery for staging the axilla following chemotherapy for women who initially had node-positive cN1 breast cancer is unclear because of high false-negative results reported in previous studies.
TL;DR: A bacterial CRISPR RNA/Cas9 system is adapted to precisely engineer the Drosophila genome and it is reported that Cas9-mediated genomic modifications are efficiently transmitted through the germline.
Abstract: We have adapted a bacterial CRISPR RNA/Cas9 system to precisely engineer the Drosophila genome and report that Cas9-mediated genomic modifications are efficiently transmitted through the germline. This RNA-guided Cas9 system can be rapidly programmed to generate targeted alleles for probing gene function in Drosophila.
TL;DR: EBSeq is developed, using the merits of empirical Bayesian methods, for identifying DE isoforms in an RNA-seq experiment comparing two or more biological conditions and proves to be a robust approach for identifying De genes.
Abstract: Motivation: Messenger RNA expression is important in normal development and differentiation, as well as in manifestation of disease. RNA-seq experiments allow for the identification of differentially expressed (DE) genes and their corresponding isoforms on a genome-wide scale. However, statistical methods are required to ensure that accurate identifications are made. A number of methods exist for identifying DE genes, but far fewer are available for identifying DE isoforms. When isoform DE is of interest, investigators often apply gene-level (count-based) methods directly to estimates of isoform counts. Doing so is not recommended. In short, estimating isoform expression is relatively straightforward for some groups of isoforms, but more challenging for others. This results in estimation uncertainty that varies across isoform groups. Count-based methods were not designed to accommodate this varying uncertainty, and consequently, application of them for isoform inference results in reduced power for some classes of isoforms and increased false discoveries for others. Results: Taking advantage of the merits of empirical Bayesian methods, we have developed EBSeq for identifying DE isoforms in an RNA-seq experiment comparing two or more biological conditions. Results demonstrate substantially improved power and performance of EBSeq for identifying DE isoforms. EBSeq also proves to be a robust approach for identifying DE genes. Availability and implementation: An R package containing examples and sample datasets is available at http://www.biostat.wisc.edu/ � kendzior/EBSEQ/.
TL;DR: The panel provides an overview of the SCD standards recommended by the panel (henceforth referred to as the Standards) and adopted in Version 1.0 of the WWC’s official pilot standards.
Abstract: In an effort to responsibly incorporate evidence based on single-case designs (SCDs) into the What Works Clearinghouse (WWC) evidence base, the WWC assembled a panel of individuals with expertise in quantitative methods and SCD methodology to draft SCD standards. In this article, the panel provides an overview of the SCD standards recommended by the panel (henceforth referred to as the Standards) and adopted in Version 1.0 of the WWC’s official pilot standards. The Standards are sequentially applied to research studies that incorporate SCDs. The design standards focus on the methodological soundness of SCDs, whereby reviewers assign the categories of Meets Standards, Meets Standards With Reservations, and Does Not Meet Standards to each study. Evidence criteria focus on the credibility of the reported evidence, whereby the outcome measures that meet the design standards (with or without reservations) are examined by reviewers trained in visual analysis and categorized as demonstrating Strong Evidence, Mod...
TL;DR: Addition of lutein + zeaxanthin, DHA + EPA, or both to the AREDS formulation in primary analyses did not reduce risk of progression to advanced AMD, but because of potential increased incidence of lung cancer in former smokers, luteIn + zexanthin could be an appropriate carotenoid substitute in the ARedS formulation.
Abstract: IMPORTANCE
Oral supplementation with the Age-Related Eye Disease Study (AREDS) formulation (antioxidant vitamins C and E, beta carotene, and zinc) has been shown to reduce the risk of progression to advanced age-related macular degeneration (AMD). Observational data suggest that increased dietary intake of lutein + zeaxanthin (carotenoids), omega-3 long-chain polyunsaturated fatty acids (docosahexaenoic acid [DHA] + eicosapentaenoic acid [EPA]), or both might further reduce this risk.
OBJECTIVES
To determine whether adding lutein + zeaxanthin, DHA + EPA, or both to the AREDS formulation decreases the risk of developing advanced AMD and to evaluate the effect of eliminating beta carotene, lowering zinc doses, or both in the AREDS formulation.
DESIGN, SETTING, AND PARTICIPANTS
The Age-Related Eye Disease Study 2 (AREDS2), a multicenter, randomized, double-masked, placebo-controlled phase 3 study with a 2 × 2 factorial design, conducted in 2006-2012 and enrolling 4203 participants aged 50 to 85 years at risk for progression to advanced AMD with bilateral large drusen or large drusen in 1 eye and advanced AMD in the fellow eye.
INTERVENTIONS
Participants were randomized to receive lutein (10 mg) + zeaxanthin (2 mg), DHA (350 mg) + EPA (650 mg), lutein + zeaxanthin and DHA + EPA, or placebo. All participants were also asked to take the original AREDS formulation or accept a secondary randomization to 4 variations of the AREDS formulation, including elimination of beta carotene, lowering of zinc dose, or both.
MAIN OUTCOMES AND MEASURES
Development of advanced AMD. The unit of analyses used was by eye.
RESULTS
Median follow-up was 5 years, with 1940 study eyes (1608 participants) progressing to advanced AMD. Kaplan-Meier probabilities of progression to advanced AMD by 5 years were 31% (493 eyes [406 participants]) for placebo, 29% (468 eyes [399 participants]) for lutein + zeaxanthin, 31% (507 eyes [416 participants]) for DHA + EPA, and 30% (472 eyes [387 participants]) for lutein + zeaxanthin and DHA + EPA. Comparison with placebo in the primary analyses demonstrated no statistically significant reduction in progression to advanced AMD (hazard ratio [HR], 0.90 [98.7% CI, 0.76-1.07]; P = .12 for lutein + zeaxanthin; 0.97 [98.7% CI, 0.82-1.16]; P = .70 for DHA + EPA; 0.89 [98.7% CI, 0.75-1.06]; P = .10 for lutein + zeaxanthin and DHA + EPA). There was no apparent effect of beta carotene elimination or lower-dose zinc on progression to advanced AMD. More lung cancers were noted in the beta carotene vs no beta carotene group (23 [2.0%] vs 11 [0.9%], nominal P = .04), mostly in former smokers.
CONCLUSIONS AND RELEVANCE
Addition of lutein + zeaxanthin, DHA + EPA, or both to the AREDS formulation in primary analyses did not further reduce risk of progression to advanced AMD. However, because of potential increased incidence of lung cancer in former smokers, lutein + zeaxanthin could be an appropriate carotenoid substitute in the AREDS formulation.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT00345176.
TL;DR: In this paper, a review describes recent groundbreaking results in Si, Si/SiGe, and dopant-based quantum dots, and highlights the remarkable advances in Sibased quantum physics that have occurred in the past few years.
Abstract: This review describes recent groundbreaking results in Si, Si/SiGe, and dopant-based quantum dots, and it highlights the remarkable advances in Si-based quantum physics that have occurred in the past few years. This progress has been possible thanks to materials development of Si quantum devices, and the physical understanding of quantum effects in silicon. Recent critical steps include the isolation of single electrons, the observation of spin blockade, and single-shot readout of individual electron spins in both dopants and gated quantum dots in Si. Each of these results has come with physics that was not anticipated from previous work in other material systems. These advances underline the significant progress toward the realization of spin quantum bits in a material with a long spin coherence time, crucial for quantum computation and spintronics.
Johns Hopkins University1, Princeton University2, Carnegie Institution for Science3, Lawrence Berkeley National Laboratory4, University of California, Santa Cruz5, University of Washington6, University of Utah7, Apache Corporation8, Ohio State University9, Case Western Reserve University10, Fermilab11, University of Pennsylvania12, Massachusetts Institute of Technology13, Spanish National Research Council14, Space Telescope Science Institute15, University of Sussex16, California Institute of Technology17, New York University18, Argonne National Laboratory19, Pennsylvania State University20, University of Wisconsin-Madison21, Ames Research Center22, University of Chicago23
TL;DR: In this article, the design and performance of the multi-object fiber spectrographs for the Sloan Digital Sky Survey (SDSS) and their upgrade for the Baryon Oscillation Spectroscopic Survey (BOSS) were presented.
Abstract: We present the design and performance of the multi-object fiber spectrographs for the Sloan Digital Sky Survey (SDSS) and their upgrade for the Baryon Oscillation Spectroscopic Survey (BOSS). Originally commissioned in Fall 1999 on the 2.5 m aperture Sloan Telescope at Apache Point Observatory, the spectrographs produced more than 1.5 million spectra for the SDSS and SDSS-II surveys, enabling a wide variety of Galactic and extra-galactic science including the first observation of baryon acoustic oscillations in 2005. The spectrographs were upgraded in 2009 and are currently in use for BOSS, the flagship survey of the third-generation SDSS-III project. BOSS will measure redshifts of 1.35 million massive galaxies to redshift 0.7 and Lyα absorption of 160,000 high redshift quasars over 10,000 deg2 of sky, making percent level measurements of the absolute cosmic distance scale of the universe and placing tight constraints on the equation of state of dark energy. The twin multi-object fiber spectrographs utilize a simple optical layout with reflective collimators, gratings, all-refractive cameras, and state-of-the-art CCD detectors to produce hundreds of spectra simultaneously in two channels over a bandpass covering the near-ultraviolet to the near-infrared, with a resolving power R = λ/FWHM ~ 2000. Building on proven heritage, the spectrographs were upgraded for BOSS with volume-phase holographic gratings and modern CCD detectors, improving the peak throughput by nearly a factor of two, extending the bandpass to cover 360 nm < λ < 1000 nm, and increasing the number of fibers from 640 to 1000 per exposure. In this paper we describe the original SDSS spectrograph design and the upgrades implemented for BOSS, and document the predicted and measured performances.
TL;DR: This paper investigates the problem of estimating the frequency components of a mixture of s complex sinusoids from a random subset of n regularly spaced samples and proposes an atomic norm minimization approach to exactly recover the unobserved samples and identify the unknown frequencies.
Abstract: This paper investigates the problem of estimating the frequency components of a mixture of s complex sinusoids from a random subset of n regularly spaced samples. Unlike previous work in compressed sensing, the frequencies are not assumed to lie on a grid, but can assume any values in the normalized frequency domain [0, 1]. An atomic norm minimization approach is proposed to exactly recover the unobserved samples and identify the unknown frequencies, which is then reformulated as an exact semidefinite program. Even with this continuous dictionary, it is shown that O(slog s log n) random samples are sufficient to guarantee exact frequency localization with high probability, provided the frequencies are well separated. Extensive numerical experiments are performed to illustrate the effectiveness of the proposed method.
Lincoln Park Zoo1, University of Maryland, College Park2, University of California, Davis3, University of Vermont4, Rutgers University5, Swedish University of Agricultural Sciences6, Lüneburg University7, University of Queensland8, University of Pretoria9, Commonwealth Scientific and Industrial Research Organisation10, Cornell University11, University of Göttingen12, Simon Fraser University13, University of Wisconsin-Madison14, National Scientific and Technical Research Council15, University of Würzburg16, Michigan State University17, University of Texas at Austin18, Hebrew University of Jerusalem19, University of Reading20, Lund University21, Federal University of Bahia22, University of California, Berkeley23
TL;DR: This synthesis reveals that pollinator persistence will depend on both the maintenance of high-quality habitats around farms and on local management practices that may offset impacts of intensive monoculture agriculture.
Abstract: Bees provide essential pollination services that are potentially affected both by local farm management and the surrounding landscape. To better understand these different factors, we modelled the relative effects of landscape composition (nesting and floral resources within foraging distances), landscape configuration (patch shape, interpatch connectivity and habitat aggregation) and farm management (organic vs. conventional and local-scale field diversity), and their interactions, on wild bee abundance and richness for 39 crop systems globally. Bee abundance and richness were higher in diversified and organic fields and in landscapes comprising more high-quality habitats; bee richness on conventional fields with low diversity benefited most from high-quality surrounding land cover. Landscape configuration effects were weak. Bee responses varied slightly by biome. Our synthesis reveals that pollinator persistence will depend on both the maintenance of high-quality habitats around farms and on local management practices that may offset impacts of intensive monoculture agriculture.
TL;DR: It is concluded that increasing the number of African American/Black physicians could reduce the impact of implicit bias on health care disparities because they exhibit significantly less implicit race bias.
Abstract: Although the medical profession strives for equal treatment of all patients, disparities in health care are prevalent Cultural stereotypes may not be consciously endorsed, but their mere existence influences how information about an individual is processed and leads to unintended biases in decision-making, so called “implicit bias” All of society is susceptible to these biases, including physicians Research suggests that implicit bias may contribute to health care disparities by shaping physician behavior and producing differences in medical treatment along the lines of race, ethnicity, gender or other characteristics We review the origins of implicit bias, cite research documenting the existence of implicit bias among physicians, and describe studies that demonstrate implicit bias in clinical decision-making We then present the bias-reducing strategies of consciously taking patients’ perspectives and intentionally focusing on individual patients’ information apart from their social group We conclude that the contribution of implicit bias to health care disparities could decrease if all physicians acknowledged their susceptibility to it, and deliberately practiced perspective-taking and individuation when providing patient care We further conclude that increasing the number of African American/Black physicians could reduce the impact of implicit bias on health care disparities because they exhibit significantly less implicit race bias