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Sökning: WFRF:(Jakob Robert) > (2020-2022) > (2021)

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  • Kurilshikov, Alexander, et al. (författare)
  • Large-scale association analyses identify host factors influencing human gut microbiome composition
  • 2021
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 53:2, s. 156-165
  • Tidskriftsartikel (refereegranskat)abstract
    • To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) < P < 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
  • Pihl, Erik, et al. (författare)
  • Ten New Insights in Climate Science 2020 : A Horizon Scan
  • 2021
  • Ingår i: Global Sustainability. - : Cambridge University Press. - 2059-4798. ; 4:e5, s. 1-18
  • Forskningsöversikt (refereegranskat)abstract
    • Non-technical summary: We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding of Earth's sensitivity to carbon dioxide, finds that permafrost thaw could release more carbon emissions than expected and that the uptake of carbon in tropical ecosystems is weakening. Adverse impacts on human society include increasing water shortages and impacts on mental health. Options for solutions emerge from rethinking economic models, rights-based litigation, strengthened governance systems and a new social contract. The disruption caused by COVID-19 could be seized as an opportunity for positive change, directing economic stimulus towards sustainable investments. Technical summary: A synthesis is made of ten fields within climate science where there have been significant advances since mid-2019, through an expert elicitation process with broad disciplinary scope. Findings include: (1) a better understanding of equilibrium climate sensitivity; (2) abrupt thaw as an accelerator of carbon release from permafrost; (3) changes to global and regional land carbon sinks; (4) impacts of climate change on water crises, including equity perspectives; (5) adverse effects on mental health from climate change; (6) immediate effects on climate of the COVID-19 pandemic and requirements for recovery packages to deliver on the Paris Agreement; (7) suggested long-term changes to governance and a social contract to address climate change, learning from the current pandemic, (8) updated positive cost-benefit ratio and new perspectives on the potential for green growth in the short- A nd long-term perspective; (9) urban electrification as a strategy to move towards low-carbon energy systems and (10) rights-based litigation as an increasingly important method to address climate change, with recent clarifications on the legal standing and representation of future generations. Social media summary Stronger permafrost thaw, COVID-19 effects and growing mental health impacts among highlights of latest climate science.
  • Stein, Robert, et al. (författare)
  • A tidal disruption event coincident with a high-energy neutrino
  • 2021
  • Ingår i: Nature Astronomy. - : Springer Science and Business Media LLC. - 2397-3366. ; :5, s. 510-518
  • Tidskriftsartikel (refereegranskat)abstract
    • Cosmic neutrinos provide a unique window into the otherwise hidden mechanism of particle acceleration in astrophysical objects. The IceCube Collaboration recently reported the likely association of one high-energy neutrino with a flare from the relativistic jet of an active galaxy pointed towards the Earth. However a combined analysis of many similar active galaxies revealed no excess from the broader population, leaving the vast majority of the cosmic neutrino flux unexplained. Here we present the likely association of a radio-emitting tidal disruption event, AT2019dsg, with a second high-energy neutrino. AT2019dsg was identified as part of our systematic search for optical counterparts to high-energy neutrinos with the Zwicky Transient Facility. The probability of finding any coincident radio-emitting tidal disruption event by chance is 0.5%, while the probability of finding one as bright in bolometric energy flux as AT2019dsg is 0.2%. Our electromagnetic observations can be explained through a multizone model, with radio analysis revealing a central engine, embedded in a UV photosphere, that powers an extended synchrotron-emitting outflow. This provides an ideal site for petaelectronvolt neutrino production. Assuming that the association is genuine, our observations suggest that tidal disruption events with mildly relativistic outflows contribute to the cosmic neutrino flux. The tidal disruption event AT2019dsg is probably associated with a high-energy neutrino, suggesting that such events can contribute to the cosmic neutrino flux. The electromagnetic emission is explained in terms of a central engine, a photosphere and an extended synchrotron-emitting outflow.
  • van Velzen, Sjoert, et al. (författare)
  • Seventeen Tidal Disruption Events from the First Half of ZTF Survey Observations : Entering a New Era of Population Studies
  • 2021
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 908:1
  • Tidskriftsartikel (refereegranskat)abstract
    • While tidal disruption events (TDEs) have long been heralded as laboratories for the study of quiescent black holes, the small number of known TDEs and uncertainties in their emission mechanism have hindered progress toward this promise. Here we present 17 new TDEs that have been detected recently by the Zwicky Transient Facility along with Swift UV and X-ray follow-up observations. Our homogeneous analysis of the optical/UV light curves, including 22 previously known TDEs from the literature, reveals a clean separation of light-curve properties with spectroscopic class. The TDEs with Bowen fluorescence features in their optical spectra have smaller blackbody radii, lower optical luminosities, and higher disruption rates compared to the rest of the sample. The small subset of TDEs that show only helium emission lines in their spectra have the longest rise times, the highest luminosities, and the lowest rates. A high detection rate of Bowen lines in TDEs with small photometric radii could be explained by the high density that is required for this fluorescence mechanism. The stellar debris can provide a source for this dense material. Diffusion of photons through this debris may explain why the rise and fade timescale of the TDEs in our sample are not correlated. We also report, for the first time, the detection of soft X-ray flares from a TDE on similar to day timescales. Based on the fact that the X-ray flares peak at a luminosity similar to the optical/UV blackbody luminosity, we attribute them to brief glimpses through a reprocessing layer that otherwise obscures the inner accretion flow.
  • Beck, Lisa J., et al. (författare)
  • Differing Mechanisms of New Particle Formation at Two Arctic Sites
  • 2021
  • Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 48:4
  • Tidskriftsartikel (refereegranskat)abstract
    • New particle formation in the Arctic atmosphere is an important source of aerosol particles. Understanding the processes of Arctic secondary aerosol formation is crucial due to their significant impact on cloud properties and therefore Arctic amplification. We observed the molecular formation of new particles from low-volatility vapors at two Arctic sites with differing surroundings. In Svalbard, sulfuric acid (SA) and methane sulfonic acid (MSA) contribute to the formation of secondary aerosol and to some extent to cloud condensation nuclei (CCN). This occurs via ion-induced nucleation of SA and NH3 and subsequent growth by mainly SA and MSA condensation during springtime and highly oxygenated organic molecules during summertime. By contrast, in an ice-covered region around Villum, we observed new particle formation driven by iodic acid but its concentration was insufficient to grow nucleated particles to CCN sizes. Our results provide new insight about sources and precursors of Arctic secondary aerosol particles.
  • Bejanyan, Nelli, et al. (författare)
  • Myeloablative Conditioning for Allogeneic Transplantation Results in Superior Disease-Free Survival for Acute Myelogenous Leukemia and Myelodysplastic Syndromes with Low/Intermediate but not High Disease Risk Index : A Center for International Blood and Marrow Transplant Research Study
  • 2021
  • Ingår i: Transplantation and Cellular Therapy. - : ELSEVIER SCIENCE INC. - 2666-6375 .- 2666-6367. ; 27:1, s. 68.e1-68.e9
  • Tidskriftsartikel (refereegranskat)abstract
    • Compared with reduced-intensity conditioning (RIC), myeloablative conditioning (MAC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, disease-specific risk factors in AML/MDS can further inform when MAC and RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the Disease Risk Index (DRI) in 4387 adults (age 40 to 65 years) to identify the impact of conditioning intensity. In the low/ intermediate-risk DRI cohort, RIC was associated with lower nonrelapse mortality (NRM) (hazard ratio [HR],.74; 95% confidence interval [CI],.62 to.88; P <.001) but significantly greater relapse risk (HR, 1.54; 95% CI, 1.35 to 1.76; P <.001) and thus inferior disease-free survival (DFS) (HR, 1.19; 95% CI, 1.07 to 1.33; P =.001). In the high/ very high-risk DRI cohort, RIC was associated with marginally lower NRM (HR,.83; 95% CI,.68 to 1.00; P =.051) and significantly higher relapse risk (HR, 1.23; 95% CI, 1.08 to 1.41; P =.002), leading to similar DFS using either RIC or MAC. These data support MAC over RIC as the preferred conditioning intensity for patients with AML/MDS with low/intermediate-risk DRI, but with a similar benefit as RIC in high/very high-risk DRI. Novel MAC regimens with less toxicity could benefit all patients, but more potent antineoplastic approaches are needed for the high/ very-high risk DRI group.
  • De Rezende, Susanna F., et al. (författare)
  • Automating algebraic proof systems is NP-hard
  • 2021
  • Ingår i: STOC 2021 - Proceedings of the 53rd Annual ACM SIGACT Symposium on Theory of Computing. - New York, NY, USA : Association for Computing Machinery (ACM). - 0737-8017. - 9781450380539 ; , s. 209-222
  • Konferensbidrag (refereegranskat)abstract
    • We show that algebraic proofs are hard to find: Given an unsatisfiable CNF formula F, it is NP-hard to find a refutation of F in the Nullstellensatz, Polynomial Calculus, or Sherali-Adams proof systems in time polynomial in the size of the shortest such refutation. Our work extends, and gives a simplified proof of, the recent breakthrough of Atserias and Müller (JACM 2020) that established an analogous result for Resolution.
  • De Rezende, Susanna F., et al. (författare)
  • Nullstellensatz Size-Degree Trade-offs from Reversible Pebbling
  • 2021
  • Ingår i: Computational Complexity. - : Birkhäuser Verlag. - 1016-3328 .- 1420-8954. ; 30:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We establish an exactly tight relation between reversiblepebblings of graphs and Nullstellensatz refutations of pebbling formulas,showing that a graph G can be reversibly pebbled in time t and space s if and only if there is a Nullstellensatz refutation of the pebbling formulaover G in size t + 1 and degree s (independently of the field in whichthe Nullstellensatz refutation is made). We use this correspondenceto prove a number of strong size-degree trade-offs for Nullstellensatz,which to the best of our knowledge are the first such results for thisproof system.
  • Hagsäter, S Melker, et al. (författare)
  • A Complex Impact of Systemically Administered 5-HT2A Receptor Ligands on Conditioned Fear
  • 2021
  • Ingår i: International Journal of Neuropsychopharmacology. - : Oxford University Press (OUP). - 1461-1457 .- 1469-5111. ; 24:9, s. 749-757
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Though drugs binding to serotonergic 5-HT2A receptors have long been claimed to influence human anxiety, it remains unclear if this receptor subtype is best described as anxiety promoting or anxiety dampening. Whereas conditioned fear expressed as freezing in rats is modified by application of 5-HT2A-acting drugs locally into different brain regions, reports on the effect of systemic administration of 5-HT2A receptor agonists and 5-HT2A antagonists or inverse agonists on this behavior remain sparse. Methods: We assessed the possible impact of systemic administration of 5-HT2A receptor agonists, 5-HT2A receptor inverse agonists, and a selective serotonin reuptake inhibitor (SSRI)-per se or in combination-on the freezing displayed by male rats when re-exposed to a conditioning chamber in which they received foot shocks 7 days earlier. Results: The 5-HT2A receptor agonists psilocybin and 25CN-NBOH induced a reduction in conditioned fear that was countered by pretreatment with 5-HT2A receptor inverse agonist MDL 100907. While both MDL 100907 and another 5-HT2A receptor inverse agonist, pimavanserin, failed to impact freezing per se, both compounds unmasked a robust fear-reducing effect of an SSRI, escitalopram, which by itself exerted no such effect. Conclusions: The results indicate that 5-HT2A receptor activation is not a prerequisite for normal conditioned freezing in rats but that this receptor subtype, when selectively over-activated prior to expression, exerts a marked fear-reducing influence. However, in the presence of an SSRI, the 5-HT2A receptor, on the contrary, appears to counter an anti-freezing effect of the enhanced extracellular serotonin levels following reuptake inhibition.
  • Ostaszewski, Marek, et al. (författare)
  • COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms
  • 2021
  • Ingår i: Molecular Systems Biology. - : WILEY. - 1744-4292 .- 1744-4292. ; 17:10
  • Tidskriftsartikel (refereegranskat)abstract
    • We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.
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