101 research outputs found

    Mutational processes molding the genomes of 21 breast cancers

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    All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed "kataegis," was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed

    Superluminous supernovae from the Dark Energy Survey

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    We present a sample of 21 hydrogen-free superluminous supernovae (SLSNe-I) and one hydrogen-rich SLSN (SLSN-II) detected during the five-year Dark Energy Survey (DES). These SNe, located in the redshift range 0.220 < z < 1.998, represent the largest homogeneously selected sample of SLSN events at high redshift. We present the observed g, r, i, z light curves for these SNe, which we interpolate using Gaussian processes. The resulting light curves are analysed to determine the luminosity function of SLSNe-I, and their evolutionary timescales. The DES SLSN-I sample significantly broadens the distribution of SLSN-I light-curve properties when combined with existing samples from the literature. We fit a magnetar model to our SLSNe, and find that this model alone is unable to replicate the behaviour of many of the bolometric light curves. We search the DES SLSN-I light curves for the presence of initial peaks prior to the main light-curve peak. Using a shock breakout model, our Monte Carlo search finds that 3 of our 14 events with pre-max data display such initial peaks. However, 10 events show no evidence for such peaks, in some cases down to an absolute magnitude of<−16, suggesting that such features are not ubiquitous to all SLSN-I events. We also identify a red pre-peak feature within the light curve of one SLSN, which is comparable to that observed within SN2018bsz

    The first Hubble diagram and cosmological constraints using superluminous supernovae

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    This paper has gone through internal review by the DES collaboration. It has Fermilab preprint number 19-115-AE and DES publication number 13387. We acknowledge support from EU/FP7- ERC grant 615929. RCN would like to acknowledge support from STFC grant ST/N000688/1 and the Faculty of Technology at the University of Portsmouth. LG was funded by the European Union’s Horizon 2020 Framework Programme under the Marie Skłodowska- Curie grant agreement no. 839090. This work has been partially supported by the Spanish grant PGC2018-095317-B-C21 within the European Funds for Regional Development (FEDER). Funding for the DES Projects has been provided by the U.S. Department of Energy, the U.S. National Science Foundation, the Ministry of Science and Education of Spain, the Science and Technology Facilities Council of the United Kingdom, the Higher Education Funding Council for England, the National Center for Supercomputing Applications at the University of Illinois at Urbana-Champaign, the Kavli Institute of Cosmological Physics at the University of Chicago, the Center for Cosmology and Astro-Particle Physics at the Ohio State University, the Mitchell Institute for Fundamental Physics and Astronomy at Texas A&M University, Financiadora de Estudos e Projetos, Fundac¸ ˜ao Carlos Chagas Filho de Amparo `a Pesquisa do Estado do Rio de Janeiro, Conselho Nacional de Desenvolvimento Cient´ıfico e Tecnol´ogico and the Minist´erio da Ciˆencia, Tecnologia e Inovac¸ ˜ao, the Deutsche Forschungsgemeinschaft, and the Collaborating Institutions in the Dark Energy Survey. The Collaborating Institutions are Argonne National Laboratory, the University of California at Santa Cruz, the University of Cambridge, Centro de Investigaciones Energ´eticas, Medioambientales y Tecnol ´ogicas-Madrid, the University of Chicago, University College London, the DES-Brazil Consortium, the University of Edinburgh, the Eidgen¨ossische Technische Hochschule (ETH) Z¨urich, Fermi NationalAccelerator Laboratory, theUniversity of Illinois atUrbana- Champaign, the Institut de Ci`encies de l’Espai (IEEC/CSIC), the Institut de F´ısica d’Altes Energies, Lawrence Berkeley National Laboratory, the Ludwig-Maximilians Universit¨at M¨unchen and the associated Excellence Cluster Universe, the University of Michigan, the National Optical Astronomy Observatory, the University of Nottingham, The Ohio State University, the University of Pennsylvania, the University of Portsmouth, SLAC National Accelerator Laboratory, Stanford University, the University of Sussex, Texas A&M University, and the OzDES Membership Consortium. Based in part on observations at Cerro Tololo Inter-American Observatory, National Optical Astronomy Observatory, which is operated by the Association of Universities for Research in Astronomy (AURA) under a cooperative agreement with the National Science Foundation. The DES data management system is supported by the National Science Foundation under grant numbers AST-1138766 and AST-1536171. The DES participants from Spanish institutions are partially supported by MINECO under grants AYA2015- 71825, ESP2015-66861, FPA2015-68048, SEV-2016-0588, SEV- 2016-0597, and MDM-2015-0509, some of which include ERDF funds from the European Union. IFAE is partially funded by the CERCA program of the Generalitat de Catalunya. Research leading to these results has received funding from the European Research Council under the European Union Seventh Framework Programme (FP7/2007-2013) including ERC grant agreements 240672, 291329, and 306478.We acknowledge support from the Australian Research Council Centre of Excellence for All-skyAstrophysics (CAASTRO), through project number CE110001020, and the Brazilian Instituto Nacional de Ciˆencia e Tecnologia (INCT) e-Universe (CNPq grant 465376/2014-2). This paper has been authored by Fermi Research Alliance, LLC under Contract No.DE-AC02-07CH11359 with theU.S.Department of Energy, Office of Science, Office of High Energy Physics. The United States Government retains and the publisher, by accepting the paper for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this paper, or allow others to do so, for United States Government purposes.We present the first Hubble diagram of superluminous supernovae (SLSNe) out to a redshift of two, together with constraints on the matter density, M, and the dark energy equation-of-state parameter, w(≡p/ρ). We build a sample of 20 cosmologically useful SLSNe I based on light curve and spectroscopy quality cuts. We confirm the robustness of the peak–decline SLSN I standardization relation with a larger data set and improved fitting techniques than previous works. We then solve the SLSN model based on the above standardization via minimization of the χ2 computed from a covariance matrix that includes statistical and systematic uncertainties. For a spatially flat cold dark matter ( CDM) cosmological model, we find M = 0.38+0.24 −0.19, with an rms of 0.27 mag for the residuals of the distance moduli. For a w0waCDM cosmological model, the addition of SLSNe I to a ‘baseline’ measurement consisting of Planck temperature together with Type Ia supernovae, results in a small improvement in the constraints of w0 and wa of 4 per cent.We present simulations of future surveys with 868 and 492 SLSNe I (depending on the configuration used) and show that such a sample can deliver cosmological constraints in a flat CDM model with the same precision (considering only statistical uncertainties) as current surveys that use Type Ia supernovae, while providing a factor of 2–3 improvement in the precision of the constraints on the time variation of dark energy, w0 and wa. This paper represents the proof of concept for superluminous supernova cosmology, and demonstrates they can provide an independent test of cosmology in the high-redshift (z > 1) universe.EU/FP7-ERC grant 615929STFC grant ST/N000688/1Faculty of Technology at the University of PortsmouthEuropean Union’s Horizon 2020 Framework Programme under the Marie Skłodowska- Curie grant agreement no. 839090Spanish grant PGC2018-095317-B-C21 within the European Funds for Regional Development (FEDER)U.S. Department of EnergyU.S. National Science FoundationMinistry of Science and Education of SpainScience and Technology Facilities Council of the United KingdomHigher Education Funding Council for EnglandNational Center for Supercomputing Applications at the University of Illinois at Urbana-Champaign,Kavli Institute of Cosmological Physics at the University of ChicagoCenter for Cosmology and Astro-Particle Physics at the Ohio State UniversityMitchell Institute for Fundamental Physics and Astronomy at Texas A&M University, Financiadora de Estudos e Projetos, Fundacão Carlos Chagas Filho de Amparo `a Pesquisa do Estado do Rio de Janeiro, Conselho Nacional de Desenvolvimento Científico e Tecnológico and the Ministério da Ciencia, Tecnologia e InovacãoDeutsche ForschungsgemeinschaftCollaborating Institutions in the Dark Energy Survey.National Science Foundation under grant numbers AST-1138766 and AST-1536171.T MINECO under grants AYA2015- 71825, ESP2015-66861, FPA2015-68048, SEV-2016-0588, SEV- 2016-0597, and MDM-2015-0509, some of which include ERDF funds from the European Union.CERCA program of the Generalitat de Catalunya.European Research Council under the European Union Seventh Framework Programme (FP7/2007-2013) including ERC grant agreements 240672, 291329, and 306478.Australian Research Council Centre of Excellence for All-skyAstrophysics (CAASTRO), through project number CE110001020Brazilian Instituto Nacional de Ciˆencia e Tecnologia (INCT) e-Universe (CNPq grant 465376/2014-2)Fermi Research Alliance, LLC under Contract No.DE-AC02-07CH11359 with theU.S.Department of Energy, Office of Science, Office of High Energy Physic

    First cosmology results using type Ia supernovae from the Dark Energy Survey: constraints on cosmological parameters

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    We present the first cosmological parameter constraints using measurements of type Ia supernovae (SNe Ia) from the Dark Energy Survey Supernova Program (DES-SN). The analysis uses a subsample of 207 spectroscopically confirmed SNe Ia from the first three years of DES-SN, combined with a low-redshift sample of 122 SNe from the literature. Our "DES-SN3YR" result from these 329 SNe Ia is based on a series of companion analyses and improvements covering SN Ia discovery, spectroscopic selection, photometry, calibration, distance bias corrections, and evaluation of systematic uncertainties. For a flat LCDM model we find a matter density Omega_m = 0.331 +_ 0.038. For a flat wCDM model, and combining our SN Ia constraints with those from the cosmic microwave background (CMB), we find a dark energy equation of state w = -0.978 +_ 0.059, and Omega_m = 0.321 +_ 0.018. For a flat w0waCDM model, and combining probes from SN Ia, CMB and baryon acoustic oscillations, we find w0 = -0.885 +_ 0.114 and wa = -0.387 +_ 0.430. These results are in agreement with a cosmological constant and with previous constraints using SNe Ia (Pantheon, JLA)

    Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study

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    A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4

    Dynamic assessment precursors: Soviet ideology, and Vygotsky

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    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

    The first Hubble diagram and cosmological constraints using superluminous supernovae

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    We present the first Hubble diagram of superluminous supernovae (SLSNe) out to a redshift of two, together with constraints on the matter density, ΩM, and the dark energy equation-of-state parameter, w(≡p/ρ). We build a sample of 20 cosmologically useful SLSNe I based on light curve and spectroscopy quality cuts. We confirm the robustness of the peak–decline SLSN I standardization relation with a larger data set and improved fitting techniques than previous works. We then solve the SLSN model based on the above standardization via minimization of the χ2 computed from a covariance matrix that includes statistical and systematic uncertainties. For a spatially flat Λ cold dark matter (ΛCDM) cosmological model, we find ΩM=0.38+0.24−0.19⁠, with an rms of 0.27 mag for the residuals of the distance moduli. For a w0waCDM cosmological model, the addition of SLSNe I to a ‘baseline’ measurement consisting of Planck temperature together with Type Ia supernovae, results in a small improvement in the constraints of w0 and wa of 4 per cent. We present simulations of future surveys with 868 and 492 SLSNe I (depending on the configuration used) and show that such a sample can deliver cosmological constraints in a flat ΛCDM model with the same precision (considering only statistical uncertainties) as current surveys that use Type Ia supernovae, while providing a factor of 2–3 improvement in the precision of the constraints on the time variation of dark energy, w0 and wa. This paper represents the proof of concept for superluminous supernova cosmology, and demonstrates they can provide an independent test of cosmology in the high-redshift (z > 1) universe.</p

    Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

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    To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely
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