Showing papers by "University of Bonn published in 2015"
Alexander A. Aarts, Joanna E. Anderson1, Christopher J. Anderson2, Peter Raymond Attridge3 +287 more•Institutions (116)
TL;DR: A large-scale assessment suggests that experimental reproducibility in psychology leaves a lot to be desired, and correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.
Abstract: Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.
5,532 citations
University Hospital Bonn1, University of California, Riverside2, Harvard University3, Case Western Reserve University4, University of Illinois at Chicago5, European Institute6, VA Palo Alto Healthcare System7, Stanford University8, Spanish National Research Council9, Cleveland Clinic Lerner Research Institute10, Hong Kong University of Science and Technology11, University of California, Los Angeles12, University of Southern Denmark13, University of Cambridge14, Ikerbasque15, University of Manchester16, University of the Basque Country17, RIKEN Brain Science Institute18, University of Eastern Finland19, University of Massachusetts Medical School20, University of Bonn21, Center of Advanced European Studies and Research22, University of Southern California23, University of South Florida24, Duke University25, Southampton General Hospital26, University of Southampton27, Moorgreen Hospital28, Louisiana State University29, Imperial College London30, Centre national de la recherche scientifique31, Karolinska Institutet32, Max Planck Society33, University of Tübingen34, University of Groningen35, University of Colorado Denver36, Douglas Mental Health University Institute37
TL;DR: Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction.
Abstract: Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.
3,947 citations
TL;DR: No associations with mortality were found with any circulating miRNAs studied and these results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.
Abstract: Introduction
The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals.
Materials and Methods
A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed.
Results
None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count.
Discussion
No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.
3,094 citations
TL;DR: An overview of the DBpedia community project is given, including its architecture, technical implementation, maintenance, internationalisation, usage statistics and applications, including DBpedia one of the central interlinking hubs in the Linked Open Data (LOD) cloud.
Abstract: The DBpedia community project extracts structured, multilingual knowledge from Wikipedia and makes it freely available on the Web using Semantic Web and Linked Data technologies. The project extracts knowledge from 111 different language editions of Wikipedia. The largest DBpedia knowledge base which is extracted from the English edition of Wikipedia consists of over 400 million facts that describe 3.7 million things. The DBpedia knowledge bases that are extracted from the other 110 Wikipedia editions together consist of 1.46 billion facts and describe 10 million additional things. The DBpedia project maps Wikipedia infoboxes from 27 different language editions to a single shared ontology consisting of 320 classes and 1,650 properties. The mappings are created via a world-wide crowd-sourcing effort and enable knowledge from the different Wikipedia editions to be combined. The project publishes releases of all DBpedia knowledge bases for download and provides SPARQL query access to 14 out of the 111 language editions via a global network of local DBpedia chapters. In addition to the regular releases, the project maintains a live knowledge base which is updated whenever a page in Wikipedia changes. DBpedia sets 27 million RDF links pointing into over 30 external data sources and thus enables data from these sources to be used together with DBpedia data. Several hundred data sets on the Web publish RDF links pointing to DBpedia themselves and make DBpedia one of the central interlinking hubs in the Linked Open Data (LOD) cloud. In this system report, we give an overview of the DBpedia community project, including its architecture, technical implementation, maintenance, internationalisation, usage statistics and applications.
2,856 citations
Kavli Institute for Theoretical Physics1, University of Bonn2, University of California, Berkeley3, University of California, Santa Barbara4, University of Nice Sophia Antipolis5, Arizona State University6, Netherlands Institute for Space Research7, University of Wisconsin-Madison8, University of Alabama9
TL;DR: Modules for Experiments in Stellar Astrophysics (MESA) as discussed by the authors can now simultaneously evolve an interacting pair of differentially rotating stars undergoing transfer and loss of mass and angular momentum, greatly enhancing the prior ability to model binary evolution.
Abstract: We substantially update the capabilities of the open-source software instrument Modules for Experiments in Stellar Astrophysics (MESA). MESA can now simultaneously evolve an interacting pair of differentially rotating stars undergoing transfer and loss of mass and angular momentum, greatly enhancing the prior ability to model binary evolution. New MESA capabilities in fully coupled calculation of nuclear networks with hundreds of isotopes now allow MESA to accurately simulate advanced burning stages needed to construct supernova progenitor models. Implicit hydrodynamics with shocks can now be treated with MESA, enabling modeling of the entire massive star lifecycle, from pre-main sequence evolution to the onset of core collapse and nucleosynthesis from the resulting explosion. Coupling of the GYRE non-adiabatic pulsation instrument with MESA allows for new explorations of the instability strips for massive stars while also accelerating the astrophysical use of asteroseismology data. We improve treatment of mass accretion, giving more accurate and robust near-surface profiles. A new MESA capability to calculate weak reaction rates "on-the-fly" from input nuclear data allows better simulation of accretion induced collapse of massive white dwarfs and the fate of some massive stars. We discuss the ongoing challenge of chemical diffusion in the strongly coupled plasma regime, and exhibit improvements in MESA that now allow for the simulation of radiative levitation of heavy elements in hot stars. We close by noting that the MESA software infrastructure provides bit-for-bit consistency for all results across all the supported platforms, a profound enabling capability for accelerating MESA's development.
2,166 citations
TL;DR: The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance, as well as several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors.
Abstract: Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. We developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. Here we report a new antibiotic that we term teixobactin, discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.
1,964 citations
TL;DR: MCC950 treatment rescued neonatal lethality in a mouse model of CAPS and was active in ex vivo samples from individuals with Muckle–Wells syndrome, and is a potential therapeutic for NLRP3-associated syndromes, and a tool for further study of theNLRP3 inflammasome in human health and disease.
Abstract: The NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is a component of the inflammatory process, and its aberrant activation is pathogenic in inherited disorders such as cryopyrin-associated periodic syndrome (CAPS) and complex diseases such as multiple sclerosis, type 2 diabetes, Alzheimer's disease and atherosclerosis. We describe the development of MCC950, a potent, selective, small-molecule inhibitor of NLRP3. MCC950 blocked canonical and noncanonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibited activation of NLRP3 but not the AIM2, NLRC4 or NLRP1 inflammasomes. MCC950 reduced interleukin-1β (IL-1β) production in vivo and attenuated the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis. Furthermore, MCC950 treatment rescued neonatal lethality in a mouse model of CAPS and was active in ex vivo samples from individuals with Muckle-Wells syndrome. MCC950 is thus a potential therapeutic for NLRP3-associated syndromes, including autoinflammatory and autoimmune diseases, and a tool for further study of the NLRP3 inflammasome in human health and disease.
1,798 citations
TL;DR: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels.
Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.
1,567 citations
University of Cologne1, Stanford University2, University of Ulsan3, Hanyang University4, Vancouver General Hospital5, University of Bonn6, University of North Carolina at Chapel Hill7, University of Rostock8, Epigenomics AG9, University of Tsukuba10, University Hospital Heidelberg11, Heidelberg University12, Schiller International University13, University of Zurich14, Vanderbilt University15, University of Belgrade16, Peter MacCallum Cancer Centre17, Casa Sollievo della Sofferenza18, University of Liverpool19, University of Zagreb20, Charité21, Oslo University Hospital22, VU University Medical Center23, Uppsala University24, Haukeland University Hospital25, Max Planck Society26, Memorial Sloan Kettering Cancer Center27, French Institute of Health and Medical Research28
TL;DR: This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
Abstract: We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Δex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
1,504 citations
University of Florida1, University of Bonn2, Institut national de la recherche agronomique3, Blaise Pascal University4, Stanford University5, Prince of Songkla University6, Agricultural Research Service7, University of Arizona8, International Maize and Wheat Improvement Center9, Kansas State University10, International Water Management Institute11, Washington State University12, Michigan State University13, CGIAR14, University of Leeds15, Counterintelligence Field Activity16, Spanish National Research Council17, University of Tübingen18, University of Guelph19, Texas A&M University20, University of Maryland, College Park21, Aarhus University22, Potsdam Institute for Climate Impact Research23, Indian Agricultural Research Institute24, Goddard Institute for Space Studies25, Rothamsted Research26, University of Hohenheim27, Wageningen University and Research Centre28, Chinese Academy of Sciences29, Commonwealth Scientific and Industrial Research Organisation30, China Agricultural University31, Nanjing Agricultural University32
TL;DR: The authors systematically tested 30 different wheat crop models of the Agricultural Model Intercomparison and Improvement Project against field experiments in which growing season mean temperatures ranged from 15 degrees C to 32 degrees C, including experiments with artificial heating.
Abstract: Crop models are essential tools for assessing the threat of climate change to local and global food production(1). Present models used to predict wheat grain yield are highly uncertain when simulating how crops respond to temperature(2). Here we systematically tested 30 different wheat crop models of the Agricultural Model Intercomparison and Improvement Project against field experiments in which growing season mean temperatures ranged from 15 degrees C to 32 degrees C, including experiments with artificial heating. Many models simulated yields well, but were less accurate at higher temperatures. The model ensemble median was consistently more accurate in simulating the crop temperature response than any single model, regardless of the input information used. Extrapolating the model ensemble temperature response indicates that warming is already slowing yield gains at a majority of wheat-growing locations. Global wheat production is estimated to fall by 6% for each degrees C of further temperature increase and become more variable over space and time.
1,461 citations
Kavli Institute for Theoretical Physics1, University of Bonn2, University of California, Berkeley3, University of California, Santa Barbara4, University of Nice Sophia Antipolis5, Arizona State University6, Netherlands Institute for Space Research7, University of Wisconsin-Madison8, University of Alabama9
TL;DR: Modules for Experiments in Stellar Astrophysics (MESA) as discussed by the authors can now simultaneously evolve an interacting pair of differentially rotating stars undergoing transfer and loss of mass and angular momentum, greatly enhancing the prior ability to model binary evolution.
Abstract: We substantially update the capabilities of the open-source software instrument Modules for Experiments in Stellar Astrophysics (MESA). MESA can now simultaneously evolve an interacting pair of differentially rotating stars undergoing transfer and loss of mass and angular momentum, greatly enhancing the prior ability to model binary evolution. New MESA capabilities in fully coupled calculation of nuclear networks with hundreds of isotopes now allow MESA to accurately simulate advanced burning stages needed to construct supernova progenitor models. Implicit hydrodynamics with shocks can now be treated with MESA, enabling modeling of the entire massive star lifecycle, from pre-main sequence evolution to the onset of core collapse and nucleosynthesis from the resulting explosion. Coupling of the GYRE non-adiabatic pulsation instrument with MESA allows for new explorations of the instability strips for massive stars while also accelerating the astrophysical use of asteroseismology data. We improve treatment of mass accretion, giving more accurate and robust near-surface profiles. A new MESA capability to calculate weak reaction rates "on-the-fly" from input nuclear data allows better simulation of accretion induced collapse of massive white dwarfs and the fate of some massive stars. We discuss the ongoing challenge of chemical diffusion in the strongly coupled plasma regime, and exhibit improvements in MESA that now allow for the simulation of radiative levitation of heavy elements in hot stars. We close by noting that the MESA software infrastructure provides bit-for-bit consistency for all results across all the supported platforms, a profound enabling capability for accelerating MESA's development.
TL;DR: A mechanism where host-microbe interactions augment barrier function in the distal gut is highlighted, where the influences of butyrate are lost in cells lacking HIF, thus linkingbutyrate metabolism to stabilized HIF and barrier function.
TL;DR: This work comprehensively map myeloid progenitor subpopulations by transcriptional sorting of single cells from the bone marrow, showing unexpected transcriptional priming toward seven differentiation fates but no progenitors with a mixed state.
National Center for Atmospheric Research1, University of Graz2, Lawrence Berkeley National Laboratory3, Centre national de la recherche scientifique4, ETH Zurich5, University of Bonn6, University of Giessen7, University of Trier8, Katholieke Universiteit Leuven9, Pacific Northwest National Laboratory10
TL;DR: This study aims to provide a common basis for CPM climate simulations by giving a holistic review of the topic, and presents the consolidated outcome of studies that addressed the added value of CPMClimate simulations compared to LSMs.
Abstract: Regional climate modeling using convection-permitting models (CPMs; horizontal grid spacing 10 km). CPMs no longer rely on convection parameterization schemes, which had been identified as a major source of errors and uncertainties in LSMs. Moreover, CPMs allow for a more accurate representation of surface and orography fields. The drawback of CPMs is the high demand on computational resources. For this reason, first CPM climate simulations only appeared a decade ago. In this study, we aim to provide a common basis for CPM climate simulations by giving a holistic review of the topic. The most important components in CPMs such as physical parameterizations and dynamical formulations are discussed critically. An overview of weaknesses and an outlook on required future developments is provided. Most importantly, this review presents the consolidated outcome of studies that addressed the added value of CPM climate simulations compared to LSMs. Improvements are evident mostly for climate statistics related to deep convection, mountainous regions, or extreme events. The climate change signals of CPM simulations suggest an increase in flash floods, changes in hail storm characteristics, and reductions in the snowpack over mountains. In conclusion, CPMs are a very promising tool for future climate research. However, coordinated modeling programs are crucially needed to advance parameterizations of unresolved physics and to assess the full potential of CPMs.
Boston Children's Hospital1, German Cancer Research Center2, University of Texas MD Anderson Cancer Center3, St. Jude Children's Research Hospital4, University of Toronto5, Max Planck Society6, Heidelberg University7, University of Utah8, Tel Aviv University9, University of Colorado Denver10, University of Bern11, Masaryk University12, University of Texas Health Science Center at San Antonio13, University of California, San Francisco14, New York University15, University of Cambridge16, University of Hamburg17, University of Bonn18
TL;DR: The molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next World Health Organization classification of CNS tumors.
TL;DR: Large sequencing data sets of clinically informative samples enable the discovery of novel genes associated with cancer, the network of relationships between the driver events, and their impact on disease relapse and clinical outcome.
Abstract: Which genetic alterations drive tumorigenesis and how they evolve over the course of disease and therapy are central questions in cancer biology Here we identify 44 recurrently mutated genes and 11 recurrent somatic copy number variations through whole-exome sequencing of 538 chronic lymphocytic leukaemia (CLL) and matched germline DNA samples, 278 of which were collected in a prospective clinical trial These include previously unrecognized putative cancer drivers (RPS15, IKZF3), and collectively identify RNA processing and export, MYC activity, and MAPK signalling as central pathways involved in CLL Clonality analysis of this large data set further enabled reconstruction of temporal relationships between driver events Direct comparison between matched pre-treatment and relapse samples from 59 patients demonstrated highly frequent clonal evolution Thus, large sequencing data sets of clinically informative samples enable the discovery of novel genes associated with cancer, the network of relationships between the driver events, and their impact on disease relapse and clinical outcome
TL;DR: In this paper, the authors conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts.
Abstract: The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
German Cancer Research Center1, University Hospital Heidelberg2, Heidelberg University3, Ludwig Maximilian University of Munich4, University of Würzburg5, University of Bonn6, University of Bergen7, Medical University of Vienna8, Max Planck Society9, University of Tübingen10, University of Calgary11
TL;DR: It is shown that many tumour cells in astrocytomas extend ultra-long membrane protrusions, and use these distinct tumour microtubes as routes for brain invasion, proliferation, and to interconnect over long distances, which develops functional multicellular network structures.
Abstract: Astrocytic brain tumours, including glioblastomas, are incurable neoplasms characterized by diffusely infiltrative growth. Here we show that many tumour cells in astrocytomas extend ultra-long membrane protrusions, and use these distinct tumour microtubes as routes for brain invasion, proliferation, and to interconnect over long distances. The resulting network allows multicellular communication through microtube-associated gap junctions. When damage to the network occurred, tumour microtubes were used for repair. Moreover, the microtube-connected astrocytoma cells, but not those remaining unconnected throughout tumour progression, were protected from cell death inflicted by radiotherapy. The neuronal growth-associated protein 43 was important for microtube formation and function, and drove microtube-dependent tumour cell invasion, proliferation, interconnection, and radioresistance. Oligodendroglial brain tumours were deficient in this mechanism. In summary, astrocytomas can develop functional multicellular network structures. Disconnection of astrocytoma cells by targeting their tumour microtubes emerges as a new principle to reduce the treatment resistance of this disease.
TL;DR: It is demonstrated that the microbiota-associated metabolites taurine, histamine, and spermine shape the host-microbiome interface by co-modulating NLRP6 inflammasome signaling, epithelial IL-18 secretion, and downstream anti-microbial peptide (AMP) profiles.
TL;DR: In this paper, the branching fraction ratio R(D)(()*()) of (B) over bar → D-(*())tau(-)(nu)over bar (tau) relative to (B), where l = e or mu, was measured using the full Belle data sample.
Abstract: We report a measurement of the branching fraction ratios R(D)(()*()) of (B) over bar -> D-(*())tau(-)(nu) over bar (tau) relative to (B) over bar -> D-(*())l(-)(nu) over barl (where l = e or mu) using the full Belle data sample of 772 x 10(6)B (B) over bar pairs collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. The measured values are R(D) = 0.375 +/- 0.064(stat) +/- 0.026(syst) and R(D*) = 0.293 +/- 0.038 (stat) +/- 0.015 (syst). The analysis uses hadronic reconstruction of the tag-side B meson and purely leptonic t decays. The results are consistent with earlier measurements and do not show a significant deviation from the standard model prediction.
Max Planck Society1, University College London2, University of Bonn3, Centre national de la recherche scientifique4, University of Maryland, College Park5, University of Toulouse6, ETH Zurich7, Spanish National Research Council8, University of California, Irvine9, Tel Aviv University10, University of Arizona11
TL;DR: In this paper, the scaling relations of molecular gas depletion timescale (t depl) and gas to stellar mass ratio (M mol gas/M* ) of 500 star-forming galaxies near the star formation "main-sequence" with redshift, specific star-formation rate (sSFR), and stellar mass (M* ).
Abstract: We combine molecular gas masses inferred from CO emission in 500 star-forming galaxies (SFGs) between z = 0 and 3, from the IRAM-COLDGASS, PHIBSS1/2, and other surveys, with gas masses derived from Herschel far-IR dust measurements in 512 galaxy stacks over the same stellar mass/redshift range. We constrain the scaling relations of molecular gas depletion timescale (t depl) and gas to stellar mass ratio (M mol gas/M* ) of SFGs near the star formation "main-sequence" with redshift, specific star-formation rate (sSFR), and stellar mass (M* ). The CO- and dust-based scaling relations agree remarkably well. This suggests that the CO → H2 mass conversion factor varies little within ±0.6 dex of the main sequence (sSFR(ms, z, M *)), and less than 0.3 dex throughout this redshift range. This study builds on and strengthens the results of earlier work. We find that t depl scales as (1 + z)–0.3 × (sSFR/sSFR(ms, z, M *))–0.5, with little dependence on M *. The resulting steep redshift dependence of M mol gas/M * ≈ (1 + z)3 mirrors that of the sSFR and probably reflects the gas supply rate. The decreasing gas fractions at high M* are driven by the flattening of the SFR-M * relation. Throughout the probed redshift range a combination of an increasing gas fraction and a decreasing depletion timescale causes a larger sSFR at constant M *. As a result, galaxy integrated samples of the M mol gas-SFR rate relation exhibit a super-linear slope, which increases with the range of sSFR. With these new relations it is now possible to determine M mol gas with an accuracy of ±0.1 dex in relative terms, and ±0.2 dex including systematic uncertainties.
Harvard University1, Niigata University2, University of California, San Francisco3, Duke University4, University of Bonn5, Heidelberg University6, University of Texas MD Anderson Cancer Center7, University of Colorado Denver8, Queen's University9, University of Groningen10, Henry Ford Health System11, University of California, Irvine12, University of Western Ontario13, Stanford University14, University of Maryland, Baltimore15, University of Virginia16, University of Turin17, Cleveland Clinic18, Erasmus University Rotterdam19
TL;DR: Recommendations for standard response and progression criteria for the assessment of brain metastases in clinical trials are presented and hopefully facilitate the development of novel approaches to this difficult problem by providing more uniformity.
Abstract: CNS metastases are the most common cause of malignant brain tumours in adults. Historically, patients with brain metastases have been excluded from most clinical trials, but their inclusion is now becoming more common. The medical literature is difficult to interpret because of substantial variation in the response and progression criteria used across clinical trials. The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group is an international, multidisciplinary effort to develop standard response and progression criteria for use in clinical trials of treatment for brain metastases. Previous efforts have focused on aspects of trial design, such as patient population, variations in existing response and progression criteria, and challenges when incorporating neurological, neuro-cognitive, and quality-of-life endpoints into trials of patients with brain metastases. Here, we present our recommendations for standard response and progression criteria for the assessment of brain metastases in clinical trials. The proposed criteria will hopefully facilitate the development of novel approaches to this difficult problem by providing more uniformity in the assessment of CNS metastases across trials.
TL;DR: It is indicated that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders.
Abstract: Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.
TL;DR: This work used direct intracranial electroencephalogram recordings from human epilepsy patients during natural sleep to test the assumption that SOs, spindles and ripples are functionally coupled in the hippocampus, and found thatSpindles were modulated by the up-state of SOs.
Abstract: During systems-level consolidation, mnemonic representations initially reliant on the hippocampus are thought to migrate to neocortical sites for more permanent storage, with an eminent role of sleep for facilitating this information transfer. Mechanistically, consolidation processes have been hypothesized to rely on systematic interactions between the three cardinal neuronal oscillations characterizing non-rapid eye movement (NREM) sleep. Under global control of de- and hyperpolarizing slow oscillations (SOs), sleep spindles may cluster hippocampal ripples for a precisely timed transfer of local information to the neocortex. We used direct intracranial electroencephalogram recordings from human epilepsy patients during natural sleep to test the assumption that SOs, spindles and ripples are functionally coupled in the hippocampus. Employing cross-frequency phase-amplitude coupling analyses, we found that spindles were modulated by the up-state of SOs. Notably, spindles were found to in turn cluster ripples in their troughs, providing fine-tuned temporal frames for the hypothesized transfer of hippocampal memory traces.
TL;DR: The open government data life-cycle is described and a discussion on publishing and consuming processes required within open governmentData initiatives is focused on, and guidelines for publishing data are provided and an integrated overview is provided.
Memorial Sloan Kettering Cancer Center1, University of Ulsan2, Johns Hopkins University3, Emory University4, University of Glasgow5, Utrecht University6, Jichi Medical University7, Japanese Foundation for Cancer Research8, Technische Universität München9, Dartmouth College10, University of Bonn11, Kyoto University12, University of Paris13, University of Düsseldorf14
TL;DR: International experts met to discuss recent advances and to revise the 2004 recommendations for assessing and reporting precursor lesions to invasive carcinomas of the pancreas, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasms (IPMN), mucinous cystic neoplasm, and other lesions.
Abstract: International experts met to discuss recent advances and to revise the 2004 recommendations for assessing and reporting precursor lesions to invasive carcinomas of the pancreas, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm, and other lesions. Consensus recommendations include the following: (1) To improve concordance and to align with practical consequences, a 2-tiered system (low vs. high grade) is proposed for all precursor lesions, with the provision that the current PanIN-2 and neoplasms with intermediate-grade dysplasia now be categorized as low grade. Thus, "high-grade dysplasia" is to be reserved for only the uppermost end of the spectrum ("carcinoma in situ"-type lesions). (2) Current data indicate that PanIN of any grade at a margin of a resected pancreas with invasive carcinoma does not have prognostic implications; the clinical significance of dysplasia at a margin in a resected pancreas with IPMN lacking invasive carcinoma remains to be determined. (3) Intraductal lesions 0.5 to 1 cm can be either large PanINs or small IPMNs. The term "incipient IPMN" should be reserved for lesions in this size with intestinal or oncocytic papillae or GNAS mutations. (4) Measurement of the distance between an IPMN and invasive carcinoma and sampling of intervening tissue are recommended to assess concomitant versus associated status. Conceptually, concomitant invasive carcinoma (in contrast with the "associated" group) ought to be genetically distinct from an IPMN elsewhere in the gland. (5) "Intraductal spread of invasive carcinoma" (aka, "colonization") is recommended to describe lesions of invasive carcinoma invading back into and extending along the ductal system, which may morphologically mimic high-grade PanIN or even IPMN. (6) "Simple mucinous cyst" is recommended to describe cysts >1 cm having gastric-type flat mucinous lining at most minimal atypia without ovarian-type stroma to distinguish them from IPMN. (7) Human lesions resembling the acinar to ductal metaplasia and atypical flat lesions of genetically engineered mouse models exist and may reflect an alternate pathway of carcinogenesis; however, their biological significance requires further study. These revised recommendations are expected to improve our management and understanding of precursor lesions in the pancreas.
TL;DR: The new composite scheme (termed PBEh-3c) represents the next member in a hierarchy of "low-cost" electronic structure approaches, mainly free of BSSE and account for most interactions in a physically sound and asymptotically correct manner, and is suggested as a robust "high-speed" computational tool in theoretical chemistry and physics.
Abstract: A density functional theory (DFT) based composite electronic structure approach is proposed to efficiently compute structures and interaction energies in large chemical systems. It is based on the well-known and numerically robust Perdew-Burke-Ernzerhoff (PBE) generalized-gradient-approximation in a modified global hybrid functional with a relatively large amount of non-local Fock-exchange. The orbitals are expanded in Ahlrichs-type valence-double zeta atomic orbital (AO) Gaussian basis sets, which are available for many elements. In order to correct for the basis set superposition error (BSSE) and to account for the important long-range London dispersion effects, our well-established atom-pairwise potentials are used. In the design of the new method, particular attention has been paid to an accurate description of structural parameters in various covalent and non-covalent bonding situations as well as in periodic systems. Together with the recently proposed three-fold corrected (3c) Hartree-Fock method, the new composite scheme (termed PBEh-3c) represents the next member in a hierarchy of "low-cost" electronic structure approaches. They are mainly free of BSSE and account for most interactions in a physically sound and asymptotically correct manner. PBEh-3c yields good results for thermochemical properties in the huge GMTKN30 energy database. Furthermore, the method shows excellent performance for non-covalent interaction energies in small and large complexes. For evaluating its performance on equilibrium structures, a new compilation of standard test sets is suggested. These consist of small (light) molecules, partially flexible, medium-sized organic molecules, molecules comprising heavy main group elements, larger systems with long bonds, 3d-transition metal systems, non-covalently bound complexes (S22 and S66×8 sets), and peptide conformations. For these sets, overall deviations from accurate reference data are smaller than for various other tested DFT methods and reach that of triple-zeta AO basis set second-order perturbation theory (MP2/TZ) level at a tiny fraction of computational effort. Periodic calculations conducted for molecular crystals to test structures (including cell volumes) and sublimation enthalpies indicate very good accuracy competitive to computationally more involved plane-wave based calculations. PBEh-3c can be applied routinely to several hundreds of atoms on a single processor and it is suggested as a robust "high-speed" computational tool in theoretical chemistry and physics.
TL;DR: A systematic review of approaches for assessing the quality of Linked Data, which unify and formalize commonly used terminologies across papers related to data quality and provides a comprehensive list of 18 quality dimensions and 69 metrics.
Abstract: The development and standardization of semantic web technologies has resulted in an unprecedented volume of data being published on the Web as Linked Data (LD). However, we observe widely varying data quality ranging from extensively curated datasets to crowdsourced and extracted data of relatively low quality. In this article, we present the results of a systematic review of approaches for assessing the quality of LD. We gather existing approaches and analyze them qualitatively. In particular, we unify and formalize commonly used terminologies across papers related to data quality and provide a comprehensive list of 18 quality dimensions and 69 metrics. Additionally, we qualitatively analyze the 30 core approaches and 12 tools using a set of attributes. The aim of this article is to provide researchers and data curators a comprehensive understanding of existing work, thereby encouraging further experimentation and development of new approaches focused towards data quality, specifically for LD.
TL;DR: A combination of all inclusive deep inelastic cross sections previously published by the H1 and ZEUS collaborations at HERA for neutral and charged current scattering for zero beam polarisation is presented in this paper.
Abstract: A combination is presented of all inclusive deep inelastic cross sections previously published by the H1 and ZEUS collaborations at HERA for neutral and charged current $e^{\pm}p$ scattering for zero beam polarisation. The data were taken at proton beam energies of 920, 820, 575 and 460 GeV and an electron beam energy of 27.5 GeV. The data correspond to an integrated luminosity of about 1 fb$^{-1}$ and span six orders of magnitude in negative four-momentum-transfer squared, $Q^2$, and Bjorken $x$. The correlations of the systematic uncertainties were evaluated and taken into account for the combination. The combined cross sections were input to QCD analyses at leading order, next-to-leading order and at next-to-next-to-leading order, providing a new set of parton distribution functions, called HERAPDF2.0. In addition to the experimental uncertainties, model and parameterisation uncertainties were assessed for these parton distribution functions. Variants of HERAPDF2.0 with an alternative gluon parameterisation, HERAPDF2.0AG, and using fixed-flavour-number schemes, HERAPDF2.0FF, are presented. The analysis was extended by including HERA data on charm and jet production, resulting in the variant HERAPDF2.0Jets. The inclusion of jet-production cross sections made a simultaneous determination of these parton distributions and the strong coupling constant possible, resulting in $\alpha_s(M_Z)=0.1183 \pm 0.0009 {\rm(exp)} \pm 0.0005{\rm (model/parameterisation)} \pm 0.0012{\rm (hadronisation)} ^{+0.0037}_{-0.0030}{\rm (scale)}$. An extraction of $xF_3^{\gamma Z}$ and results on electroweak unification and scaling violations are also presented.
TL;DR: The state of the art of critical eCB functions in peripheral organs is reviewed to establish consensus views on the relevance of the peripheral ECS for human health and disease pathogenesis, as well as highlighting emerging challenges and therapeutic hopes.