Showing papers by "University of California, Irvine published in 2012"
TL;DR: STRUCTURE HARVESTER is presented, a web-based program for collating results generated by the program STRUCTURE, which provides a fast way to assess and visualize likelihood values across multiple values of K and hundreds of iterations for easier detection of the number of genetic groups that best fit the data.
Abstract: We present STRUCTURE HARVESTER (available at http://taylor0.biology.ucla.edu/structureHarvester/
), a web-based program for collating results generated by the program STRUCTURE. The program provides a fast way to assess and visualize likelihood values across multiple values of K and hundreds of iterations for easier detection of the number of genetic groups that best fit the data. In addition, STRUCTURE HARVESTER will reformat data for use in downstream programs, such as CLUMPP.
9,960 citations
TL;DR: In this article, a search for the Standard Model Higgs boson in proton-proton collisions with the ATLAS detector at the LHC is presented, which has a significance of 5.9 standard deviations, corresponding to a background fluctuation probability of 1.7×10−9.
9,282 citations
Tohoku University1, University of Zurich2, Lawrence Berkeley National Laboratory3, Stanford University4, College of William & Mary5, University of Genoa6, University of Urbino7, CERN8, Budker Institute of Nuclear Physics9, University of California, Irvine10, Cornell University11, Argonne National Laboratory12, ETH Zurich13, Tata Institute of Fundamental Research14, Hillsdale College15, Spanish National Research Council16, Ohio State University17, University of Notre Dame18, Kent State University19, University of California, San Diego20, University of California, Berkeley21, University of Minnesota22, University of Alabama23, University of Helsinki24, Los Alamos National Laboratory25, California Institute of Technology26, George Washington University27, Syracuse University28, Lawrence Livermore National Laboratory29, Oklahoma State University–Stillwater30, University of Washington31, Max Planck Society32, Boston University33, University of California, Los Angeles34, Royal Holloway, University of London35, Université Paris-Saclay36, Fermilab37, University of Pennsylvania38, University of Illinois at Urbana–Champaign39, University of Bristol40, University of Tokyo41, University of Delaware42, Carnegie Mellon University43, University of California, Santa Cruz44, Karlsruhe Institute of Technology45, Heidelberg University46, Florida State University47, Carleton University48, University of Mainz49, University of Edinburgh50, Brookhaven National Laboratory51, Durham University52, University of Lausanne53, Massachusetts Institute of Technology54, University of Southampton55, Nagoya University56, University of Oxford57, Northwestern University58, University of British Columbia59, Columbia University60, Lund University61, University of Sheffield62, University of California, Santa Barbara63, Iowa State University64, University of Alberta65, University of Cambridge66
TL;DR: The Particle Data Group's biennial review as mentioned in this paper summarizes much of particle physics, using data from previous editions, plus 2658 new measurements from 644 papers, and lists, evaluates, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons.
Abstract: This biennial Review summarizes much of particle physics. Using data from previous editions, plus 2658 new measurements from 644 papers, we list, evaluate, and average measured properties of gauge bosons, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics. Among the 112 reviews are many that are new or heavily revised including those on Heavy-Quark and Soft-Collinear Effective Theory, Neutrino Cross Section Measurements, Monte Carlo Event Generators, Lattice QCD, Heavy Quarkonium Spectroscopy, Top Quark, Dark Matter, V-cb & V-ub, Quantum Chromodynamics, High-Energy Collider Parameters, Astrophysical Constants, Cosmological Parameters, and Dark Matter. A booklet is available containing the Summary Tables and abbreviated versions of some of the other sections of this full Review. All tables, listings, and reviews (and errata) are also available on the Particle Data Group website: http://pdg.lbl.gov.
4,465 citations
Cold Spring Harbor Laboratory1, University of California, Irvine2, California Institute of Technology3, Florida State University College of Arts and Sciences4, Yale University5, Wellcome Trust Sanger Institute6, Norwegian University of Science and Technology7, Affymetrix8, University of North Carolina at Chapel Hill9, University of Lausanne10, University of Geneva11, Genome Institute of Singapore12, Stanford University13, Pompeu Fabra University14
TL;DR: Evidence that three-quarters of the human genome is capable of being transcribed is reported, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs that prompt a redefinition of the concept of a gene.
Abstract: Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.
4,450 citations
Daniel J. Klionsky1, Fábio Camargo Abdalla2, Hagai Abeliovich3, Robert T. Abraham4 +1284 more•Institutions (463)
TL;DR: These guidelines are presented for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
4,316 citations
16 Jun 2012
TL;DR: It is shown that tree-structured models are surprisingly effective at capturing global elastic deformation, while being easy to optimize unlike dense graph structures, in real-world, cluttered images.
Abstract: We present a unified model for face detection, pose estimation, and landmark estimation in real-world, cluttered images. Our model is based on a mixtures of trees with a shared pool of parts; we model every facial landmark as a part and use global mixtures to capture topological changes due to viewpoint. We show that tree-structured models are surprisingly effective at capturing global elastic deformation, while being easy to optimize unlike dense graph structures. We present extensive results on standard face benchmarks, as well as a new “in the wild” annotated dataset, that suggests our system advances the state-of-the-art, sometimes considerably, for all three tasks. Though our model is modestly trained with hundreds of faces, it compares favorably to commercial systems trained with billions of examples (such as Google Picasa and face.com).
2,340 citations
Allen Institute for Brain Science1, University of Edinburgh2, Radboud University Nijmegen3, University of California, Irvine4, Centre for Addiction and Mental Health5, University of Maryland, Baltimore6, University of Washington7, University of California, Los Angeles8, Georgetown University9, Icahn School of Medicine at Mount Sinai10, University of Oxford11, California Institute of Technology12
TL;DR: A transcriptional atlas of the adult human brain is described, comprising extensive histological analysis and comprehensive microarray profiling of ∼900 neuroanatomically precise subdivisions in two individuals, to form a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function.
Abstract: Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ~900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography—the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function.
2,204 citations
TL;DR: In this article, a review of recent advances in the condensed matter search for Majorana fermions is presented, which has led many in the field to believe that this quest may soon bear fruit.
Abstract: The 1937 theoretical discovery of Majorana fermions-whose defining property is that they are their own anti-particles-has since impacted diverse problems ranging from neutrino physics and dark matter searches to the fractional quantum Hall effect and superconductivity. Despite this long history the unambiguous observation of Majorana fermions nevertheless remains an outstanding goal. This review paper highlights recent advances in the condensed matter search for Majorana that have led many in the field to believe that this quest may soon bear fruit. We begin by introducing in some detail exotic 'topological' one- and two-dimensional superconductors that support Majorana fermions at their boundaries and at vortices. We then turn to one of the key insights that arose during the past few years; namely, that it is possible to 'engineer' such exotic superconductors in the laboratory by forming appropriate heterostructures with ordinary s-wave superconductors. Numerous proposals of this type are discussed, based on diverse materials such as topological insulators, conventional semiconductors, ferromagnetic metals and many others. The all-important question of how one experimentally detects Majorana fermions in these setups is then addressed. We focus on three classes of measurements that provide smoking-gun Majorana signatures: tunneling, Josephson effects and interferometry. Finally, we discuss the most remarkable properties of condensed matter Majorana fermions-the non-Abelian exchange statistics that they generate and their associated potential for quantum computation.
2,156 citations
University of Washington1, Paris Diderot University2, Lawrence Berkeley National Laboratory3, New York University4, University of Utah5, Apache Corporation6, Autonomous University of Madrid7, Yale University8, University of Barcelona9, Harvard University10, Aix-Marseille University11, Princeton University12, Carnegie Mellon University13, Ohio State University14, University of Portsmouth15, University of California, Irvine16, University College London17, University of Valencia18, Max Planck Society19, Leibniz Institute for Astrophysics Potsdam20, Institut d'Astrophysique de Paris21, Spanish National Research Council22, Columbia University23, University of California, Berkeley24, Drexel University25, Korea Institute for Advanced Study26, Institute for the Physics and Mathematics of the Universe27, Abastumani Astrophysical Observatory28, Pennsylvania State University29, University of California, San Diego30, University of Wisconsin-Madison31, Open University32, Case Western Reserve University33
TL;DR: In this paper, the authors present a measurement of the cosmic distance scale from detections of the baryon acoustic oscillations in the clustering of galaxies from the Baryon Oscillation Spectroscopic Survey (BOSS), which is part of the Sloan Digital Sky Survey III (SDSS-III).
Abstract: We present a one per cent measurement of the cosmic distance scale from the detections of the baryon acoustic oscillations in the clustering of galaxies from the Baryon Oscillation Spectroscopic Survey (BOSS), which is part of the Sloan Digital Sky Survey III (SDSS-III). Our results come from the Data Release 11 (DR11) sample, containing nearly one million galaxies and covering approximately $8\,500$ square degrees and the redshift range $0.2
2,040 citations
TL;DR: The analyses clearly show that the ecosystem consequences of local species loss are as quantitatively significant as the direct effects of several global change stressors that have mobilized major international concern and remediation efforts.
Abstract: Evidence is mounting that extinctions are altering key processes important to the productivity and sustainability of Earth’s ecosystems 1–4 . Further species loss will accelerate change in ecosystem processes 5–8 , but it is unclear how these effects compare to the direct effects of other forms of environmental change that are both driving diversity loss and altering ecosystem function. Here we use a suite of meta-analyses of published data to show that the effects of species loss on productivity and decomposition—two processes important in all ecosystems—are of comparable magnitude to the effects of many other global environmental changes. In experiments, intermediate levels of species loss (21–40%) reduced plant production by 5–10%, comparable to previously documented effects of ultraviolet radiation and climate warming. Higher levels of extinction (41–60%) had effects rivalling those of ozone, acidification, elevated CO2 and nutrient pollution. At intermediate levels, species loss generally had equal or greater effects on decomposition than did elevated CO2 and nitrogen addition. The identity of species lost also had a large effect on changes in productivity and decomposition, generating a wide range of plausible outcomes for extinction. Despite the need for more studies on interactive effects of diversity loss and environmental changes, our analyses clearly show that the ecosystem consequences of local species loss are as quantitatively significant as the direct effects of several global change stressors that have mobilized major international concern and remediation efforts 9 .
1,858 citations
Christopher P. Ahn1, Rachael Alexandroff2, Carlos Allende Prieto3, Scott F. Anderson4 +256 more•Institutions (65)
TL;DR: In this paper, the authors presented the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS) for the Sloan Digital Sky Survey III (SDSS-III) dataset.
Abstract: The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median z ~ 0.52), 102,100 new quasar spectra (median z ~ 2.32), and 90,897 new stellar spectra, along with the data presented in previous data releases. These spectra were obtained with the new BOSS spectrograph and were taken between 2009 December and 2011 July. In addition, the stellar parameters pipeline, which determines radial velocities, surface temperatures, surface gravities, and metallicities of stars, has been updated and refined with improvements in temperature estimates for stars with T eff -0.5. DR9 includes new stellar parameters for all stars presented in DR8, including stars from SDSS-I and II, as well as those observed as part of the SEGUE-2. The astrometry error introduced in the DR8 imaging catalogs has been corrected in the DR9 data products. The next data release for SDSS-III will be in Summer 2013, which will present the first data from the APOGEE along with another year of data from BOSS, followed by the final SDSS-III data release in 2014 December.
TL;DR: The Drosophila melanogaster Genetic Reference Panel is described, a community resource for analysis of population genomics and quantitative traits, which reveals reduced polymorphism in centromeric autosomal regions and the X chromosomes, evidence for positive and negative selection, and rapid evolution of the X chromosome.
Abstract: A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics.
University of Michigan1, Boston University2, National Research Council3, Johns Hopkins University4, University of Washington5, University of Pennsylvania6, Brown University7, University of Hasselt8, University of Minnesota9, Torcuato di Tella University10, Rutgers University11, Johnson & Johnson12, University of California, Irvine13
TL;DR: Methods for preventing missing data and, failing that, dealing with data that are missing in clinical trials are reviewed.
Abstract: Missing data in clinical trials can have a major effect on the validity of the inferences that can be drawn from the trial. This article reviews methods for preventing missing data and, failing that, dealing with data that are missing.
TL;DR: This review paper highlights recent advances in the condensed matter search for Majorana that have led many in the field to believe that this quest may soon bear fruit and discusses the most remarkable properties of condensed matter Majorana fermions-the non-Abelian exchange statistics that they generate and their associated potential for quantum computation.
Abstract: The 1937 theoretical discovery of Majorana fermions--whose defining property is that they are their own anti-particles--has since impacted diverse problems ranging from neutrino physics and dark matter searches to the fractional quantum Hall effect and superconductivity. Despite this long history the unambiguous observation of Majorana fermions nevertheless remains an outstanding goal. This review article highlights recent advances in the condensed matter search for Majorana that have led many in the field to believe that this quest may soon bear fruit. We begin by introducing in some detail exotic `topological' one- and two-dimensional superconductors that support Majorana fermions at their boundaries and at vortices. We then turn to one of the key insights that arose during the past few years; namely, that it is possible to `engineer' such exotic superconductors in the laboratory by forming appropriate heterostructures with ordinary s-wave superconductors. Numerous proposals of this type are discussed, based on diverse materials such as topological insulators, conventional semiconductors, ferromagnetic metals, and many others. The all-important question of how one experimentally detects Majorana fermions in these setups is then addressed. We focus on three classes of measurements that provide smoking-gun Majorana signatures: tunneling, Josephson effects, and interferometry. Finally, we discuss the most remarkable properties of condensed matter Majorana fermions--the non-Abelian exchange statistics that they generate and their associated potential for quantum computation.
University of Michigan1, University of California, Los Angeles2, University of Rochester3, Boston Medical Center4, New York University5, Oklahoma Medical Research Foundation6, University of California, San Diego7, University of Otago8, Paris Diderot University9, University of Alabama at Birmingham10, University of Auckland11, Emory University12, Veterans Health Administration13, University of California, Irvine14, University of Florida15, Cleveland Clinic16, University of Pennsylvania17, Harvard University18
TL;DR: DINESH KHanNA, JOHN D. FITZGERALD, PUJA P. KHANNA, SANGMEE BAE, MANJIT K. SINGH, TUHINA NEOGI, MICHAEL H. PILLINGER, JOAN MERILL, SUSAN LEE, SHRADDHA PRAKASH, MARIAN KALDAS, MANEESH GOGIA, FERNANDO PEREZ-RUI
Abstract: DINESH KHANNA, JOHN D. FITZGERALD, PUJA P. KHANNA, SANGMEE BAE, MANJIT K. SINGH, TUHINA NEOGI, MICHAEL H. PILLINGER, JOAN MERILL, SUSAN LEE, SHRADDHA PRAKASH, MARIAN KALDAS, MANEESH GOGIA, FERNANDO PEREZ-RUIZ, WILL TAYLOR, FREDERIC LIOTE, HYON CHOI, JASVINDER A. SINGH, NICOLA DALBETH, SANFORD KAPLAN, VANDANA NIYYAR, DANIELLE JONES, STEVEN A. YAROWS, BLAKE ROESSLER, GAIL KERR, CHARLES KING, GERALD LEVY, DANIEL E. FURST, N. LAWRENCE EDWARDS, BRIAN MANDELL, H. RALPH SCHUMACHER, MARK ROBBINS, NEIL WENGER, AND ROBERT TERKELTAUB
TL;DR: This perspective reviews some recent progress and ongoing challenges in density functional theory.
Abstract: Density functional theory (DFT) is an incredible success story. The low computational cost, combined with useful (but not yet chemical) accuracy, has made DFT a standard technique in most branches of chemistry and materials science. Electronic structure problems in a dazzling variety of fields are currently being tackled. However, DFT has many limitations in its present form: too many approximations, failures for strongly correlated systems, too slow for liquids, etc. This perspective reviews some recent progress and ongoing challenges.
University of Leeds1, Jet Propulsion Laboratory2, University of Colorado Boulder3, Technical University of Denmark4, Durham University5, University of Texas at Austin6, Ohio State University7, University College London8, Technische Universität München9, Lamont–Doherty Earth Observatory10, Johns Hopkins University Applied Physics Laboratory11, Newcastle University12, University of Tasmania13, Utrecht University14, University of Kansas15, Swansea University16, Goddard Space Flight Center17, University of Ottawa18, University of California, Irvine19, University of Bristol20, British Antarctic Survey21, University of Innsbruck22, Delft University of Technology23
TL;DR: There is good agreement between different satellite methods—especially in Greenland and West Antarctica—and that combining satellite data sets leads to greater certainty, and the mass balance of Earth’s polar ice sheets is estimated by combining the results of existing independent techniques.
Abstract: We combined an ensemble of satellite altimetry, interferometry, and gravimetry data sets using common geographical regions, time intervals, and models of surface mass balance and glacial isostatic adjustment to estimate the mass balance of Earth’s polar ice sheets. We find that there is good agreement between different satellite methods—especially in Greenland and West Antarctica—and that combining satellite data sets leads to greater certainty. Between 1992 and 2011, the ice sheets of Greenland, East Antarctica, West Antarctica, and the Antarctic Peninsula changed in mass by –142 ± 49, +14 ± 43, –65 ± 26, and –20 ± 14 gigatonnes year−1, respectively. Since 1992, the polar ice sheets have contributed, on average, 0.59 ± 0.20 millimeter year−1 to the rate of global sea-level rise.
TL;DR: It is proposed that four processes — selection, drift, dispersal and mutation — create and maintain microbial biogeographic patterns on inseparable ecological and evolutionary scales.
Abstract: Recently, microbiologists have established the existence of biogeographic patterns among a wide range of microorganisms. The focus of the field is now shifting to identifying the mechanisms that shape these patterns. Here, we propose that four processes — selection, drift, dispersal and mutation — create and maintain microbial biogeographic patterns on inseparable ecological and evolutionary scales. We consider how the interplay of these processes affects one biogeographic pattern, the distance-decay relationship, and review evidence from the published literature for the processes driving this pattern in microorganisms. Given the limitations of inferring processes from biogeographic patterns, we suggest that studies should focus on directly testing the underlying processes.
TL;DR: Crizotinib is well tolerated with rapid, durable responses in patients with ALK-positive NSCLC and there seems to be potential for ongoing benefit after initial disease progression in this population, but a more formal definition of ongoing benefit in this context is needed.
Abstract: Summary Background ALK fusion genes occur in a subset of non-small-cell lung cancers (NSCLCs). We assessed the tolerability and activity of crizotinib in patients with NSCLC who were prospectively identified to have an ALK fusion within the first-in-man phase 1 crizotinib study. Methods In this phase 1 study, patients with ALK -positive stage III or IV NSCLC received oral crizotinib 250 mg twice daily in 28-day cycles. Endpoints included tumour responses, duration of response, time to tumour response, progression-free survival (PFS), overall survival at 6 and 12 months, and determination of the safety and tolerability and characterisation of the plasma pharmacokinetic profile of crizotinib after oral administration. Responses were analysed in evaluable patients and PFS and safety were analysed in all patients. This study is registered with ClinicalTrials.gov, number NCT00585195. Findings Between Aug 27, 2008, and June 1, 2011, 149 ALK -positive patients were enrolled, 143 of whom were included in the response-evaluable population. 87 of 143 patients had an objective response (60·8%, 95% CI 52·3–68·9), including three complete responses and 84 partial responses. Median time to first documented objective response was 7·9 weeks (range 2·1–39·6) and median duration of response was 49·1 weeks (95% CI 39·3–75·4). The response rate seemed to be largely independent of age, sex, performance status, or line of treatment. Median PFS was 9·7 months (95% CI 7·7–12·8). Median overall survival data are not yet mature, but estimated overall survival at 6 and 12 months was 87·9% (95% CI 81·3–92·3) and 74·8% (66·4–81·5), respectively. 39 patients continued to receive crizotinib for more than 2 weeks after progression because of perceived ongoing clinical benefit from the drug (12 for at least 6 months from the time of their initial investigator-defined disease progression). Overall, 144 (97%) of 149 patients experienced treatment-related adverse events, which were mostly grade 1 or 2. The most common adverse events were visual effects, nausea, diarrhoea, constipation, vomiting, and peripheral oedema. The most common treatment-related grade 3 or 4 adverse events were neutropenia (n=9), raised alanine aminotransferase (n=6), hypophosphataemia (n=6), and lymphopenia (n=6). Interpretation Crizotinib is well tolerated with rapid, durable responses in patients with ALK -positive NSCLC. There seems to be potential for ongoing benefit after initial disease progression in this population, but a more formal definition of ongoing benefit in this context is needed. Funding Pfizer.
University College London1, University of Cambridge2, University of California, Irvine3, University of Maryland, College Park4, University of Oxford5, Smithsonian Institution6, University of Greifswald7, Max Planck Society8, Imperial College London9, Harvard University10, University of East Anglia11, Mississippi State University12, University of Texas at Austin13, Commonwealth Scientific and Industrial Research Organisation14, University of Paris15, University of Hawaii16, California Academy of Sciences17, Williams College18, Yale University19, University of Puerto Rico20, Johns Hopkins University21, North Carolina State University22, University of Bristol23, University of Edinburgh24, Baylor College of Medicine25, Del Rosario University26, University of Exeter27, Boston University28
TL;DR: It is inferred that closely related Heliconius species exchange protective colour-pattern genes promiscuously, implying that hybridization has an important role in adaptive radiation.
Abstract: Sequencing of the genome of the butterfly Heliconius melpomene shows that closely related Heliconius species exchange protective colour-pattern genes promiscuously.
TL;DR: An overview of the concepts of stability that are relevant for microbial communities is provided, and thoughts about the unique insights that systems perspectives – informed by meta-omics data – may provide about microbial community stability are concluded.
Abstract: Microbial communities are at the heart of all ecosystems, and yet microbial community behavior in disturbed environments remains difficult to measure and predict. Understanding the drivers of microbial community stability, including resistance (insensitivity to disturbance) and resilience (the rate of recovery after disturbance) is important for predicting community response to disturbance. Here, we provide an overview of the concepts of stability that are relevant for microbial communities. First, we highlight insights from ecology that are useful for defining and measuring stability. To determine whether general disturbance responses exist for microbial communities, we next examine representative studies from the literature that investigated community responses to press (long-term) and pulse (short-term) disturbances in a variety of habitats. Then we discuss the biological features of individual microorganisms, of microbial populations, and of microbial communities that may govern overall community stability. We conclude with thoughts about the unique insights that systems perspectives - informed by meta-omics data - may provide about microbial community stability.
National Institutes of Health1, University of Pittsburgh2, Bayer Corporation3, CHDI Foundation4, Cornell University5, Rockefeller University6, Alzheimer's Drug Discovery Foundation7, University of Massachusetts Medical School8, University of Nebraska Medical Center9, American Medical Association10, Michigan State University11, University of Rochester12, University of Melbourne13, Stanford University14, American Association for the Advancement of Science15, Harvard University16, Hoffmann-La Roche17, University of California, Los Angeles18, University of Edinburgh19, University of California, San Francisco20, Amyotrophic Lateral Sclerosis Therapy Development Institute21, University of California, Irvine22, Food and Drug Administration23
TL;DR: The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data.
Abstract: The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data. We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators, reviewers, funding agencies and journal editors. Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress.
TL;DR: In this article, a design of multiphase supramolecular thermoplastic elastomers that combine high modulus and toughness with spontaneous healing capability is presented. But, unlike previous self-healing polymers, this new system spontaneously selfheals as a single component solid material at ambient conditions.
Abstract: The development of polymers that can spontaneously repair themselves after mechanical damage would significantly improve the safety, lifetime, energy efficiency and environmental impact of man-made materials. Most approaches to self-healing materials require the input of external energy, healing agents, solvent or plasticizer. Despite intense research in this area, the synthesis of a stiff material with intrinsic self-healing ability remains a key challenge. Here, we show a design of multiphase supramolecular thermoplastic elastomers that combine high modulus and toughness with spontaneous healing capability. The designed hydrogen-bonding brush polymers self-assemble into a hard-soft microphase-separated system, combining the enhanced stiffness and toughness of nanocomposites with the self-healing capability of dynamic supramolecular assemblies. In contrast to previous self-healing polymers, this new system spontaneously self-heals as a single-component solid material at ambient conditions, without the need for any external stimulus, healing agent, plasticizer or solvent.
TL;DR: The full scope of the human and mouse chemokine superfamilies and their relationships are updated and several important roles that homeostatic chemokines play in the immune system are summarized.
University of Sussex1, Jet Propulsion Laboratory2, California Institute of Technology3, European Space Agency4, Ames Research Center5, University of Edinburgh6, Paris Diderot University7, Imperial College London8, University of Paris-Sud9, Aix-Marseille University10, Cornell University11, Spanish National Research Council12, University of La Laguna13, Complutense University of Madrid14, UK Astronomy Technology Centre15, University of Colorado Boulder16, University of California, Irvine17, Goddard Space Flight Center18, University of Nottingham19, Cardiff University20, University of Padua21, Institut d'Astrophysique de Paris22, University of Cambridge23, University of British Columbia24, European Space Research and Technology Centre25, University of Manchester26, University College London27, University of Lethbridge28, Rutherford Appleton Laboratory29, University of Oxford30, Commonwealth Scientific and Industrial Research Organisation31, University of Hertfordshire32, Harvard University33
TL;DR: The Herschel Multi-tiered Extragalactic Survey (HerMES) is a legacy program designed to map a set of nested fields totalling ∼380deg^2 as mentioned in this paper.
Abstract: The Herschel Multi-tiered Extragalactic Survey (HerMES) is a legacy programme designed to map a set of nested fields totalling ∼380 deg^2. Fields range in size from 0.01 to ∼20 deg^2, using the Herschel-Spectral and Photometric Imaging Receiver (SPIRE) (at 250, 350 and 500 μm) and the Herschel-Photodetector Array Camera and Spectrometer (PACS) (at 100 and 160 μm), with an additional wider component of 270 deg^2 with SPIRE alone. These bands cover the peak of the redshifted thermal spectral energy distribution from interstellar dust and thus capture the reprocessed optical and ultraviolet radiation from star formation that has been absorbed by dust, and are critical for forming a complete multiwavelength understanding of galaxy formation and evolution.
The survey will detect of the order of 100 000 galaxies at 5σ in some of the best-studied fields in the sky. Additionally, HerMES is closely coordinated with the PACS Evolutionary Probe survey. Making maximum use of the full spectrum of ancillary data, from radio to X-ray wavelengths, it is designed to facilitate redshift determination, rapidly identify unusual objects and understand the relationships between thermal emission from dust and other processes. Scientific questions HerMES will be used to answer include the total infrared emission of galaxies, the evolution of the luminosity function, the clustering properties of dusty galaxies and the properties of populations of galaxies which lie below the confusion limit through lensing and statistical techniques.
This paper defines the survey observations and data products, outlines the primary scientific goals of the HerMES team, and reviews some of the early results.
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TL;DR: A detailed analysis of a robust tensor power method is provided, establishing an analogue of Wedin's perturbation theorem for the singular vectors of matrices, and implies a robust and computationally tractable estimation approach for several popular latent variable models.
Abstract: This work considers a computationally and statistically efficient parameter estimation method for a wide class of latent variable models---including Gaussian mixture models, hidden Markov models, and latent Dirichlet allocation---which exploits a certain tensor structure in their low-order observable moments (typically, of second- and third-order). Specifically, parameter estimation is reduced to the problem of extracting a certain (orthogonal) decomposition of a symmetric tensor derived from the moments; this decomposition can be viewed as a natural generalization of the singular value decomposition for matrices. Although tensor decompositions are generally intractable to compute, the decomposition of these specially structured tensors can be efficiently obtained by a variety of approaches, including power iterations and maximization approaches (similar to the case of matrices). A detailed analysis of a robust tensor power method is provided, establishing an analogue of Wedin's perturbation theorem for the singular vectors of matrices. This implies a robust and computationally tractable estimation approach for several popular latent variable models.
TL;DR: It is suggested that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia.
Abstract: Cannabidiol is a component of marijuana that does not activate cannabinoid receptors, but moderately inhibits the degradation of the endocannabinoid anandamide. We previously reported that an elevation of anandamide levels in cerebrospinal fluid inversely correlated to psychotic symptoms. Furthermore, enhanced anandamide signaling let to a lower transition rate from initial prodromal states into frank psychosis as well as postponed transition. In our translational approach, we performed a double-blind, randomized clinical trial of cannabidiol vs amisulpride, a potent antipsychotic, in acute schizophrenia to evaluate the clinical relevance of our initial findings. Either treatment was safe and led to significant clinical improvement, but cannabidiol displayed a markedly superior sideeffect profile. Moreover, cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement. The results suggest that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia. Translational Psychiatry (2012) 2, e94; doi:10.1038/tp.2012.15; published online 20 March 2012
16 Jun 2012
TL;DR: This work presents a novel dataset and novel algorithms for the problem of detecting activities of daily living in firstperson camera views, and develops novel representations including temporal pyramids and composite object models that exploit the fact that objects look different when being interacted with.
Abstract: We present a novel dataset and novel algorithms for the problem of detecting activities of daily living (ADL) in firstperson camera views. We have collected a dataset of 1 million frames of dozens of people performing unscripted, everyday activities. The dataset is annotated with activities, object tracks, hand positions, and interaction events. ADLs differ from typical actions in that they can involve long-scale temporal structure (making tea can take a few minutes) and complex object interactions (a fridge looks different when its door is open). We develop novel representations including (1) temporal pyramids, which generalize the well-known spatial pyramid to approximate temporal correspondence when scoring a model and (2) composite object models that exploit the fact that objects look different when being interacted with. We perform an extensive empirical evaluation and demonstrate that our novel representations produce a two-fold improvement over traditional approaches. Our analysis suggests that real-world ADL recognition is “all about the objects,” and in particular, “all about the objects being interacted with.”
TL;DR: Property intrinsic to early-stage neurons can overcome the inhibitory milieu of the injured adult spinal cord to mount remarkable axonal growth, resulting in formation of new relay circuits that significantly improve function.
TL;DR: The pervasive presence of epistasis among beneficial mutations was inferred, which shaped adaptive trajectories into at least two distinct pathways involving mutations either in the RNA polymerase complex or the termination factor rho.
Abstract: To estimate the number and diversity of beneficial mutations, we experimentally evolved 115 populations of Escherichia coli to 42.2°C for 2000 generations and sequenced one genome from each population. We identified 1331 total mutations, affecting more than 600 different sites. Few mutations were shared among replicates, but a strong pattern of convergence emerged at the level of genes, operons, and functional complexes. Our experiment uncovered a set of primary functional targets of high temperature, but we estimate that many other beneficial mutations could contribute to similar adaptive outcomes. We inferred the pervasive presence of epistasis among beneficial mutations, which shaped adaptive trajectories into at least two distinct pathways involving mutations either in the RNA polymerase complex or the termination factor rho.