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| 3. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 4. |
- Bousquet, J, et al.
(författare)
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Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
- 2020
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Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
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Tidskriftsartikel (refereegranskat)abstract
- There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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- van Bragt, JJMH, et al.
(författare)
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Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
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| 6. |
- Abdalla, H., et al.
(författare)
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An extreme particle accelerator in the Galactic plane : HESS J1826-130
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 644, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- The unidentified very-high-energy (VHE; E > 0.1 TeV) gamma -ray source, HESS J1826-130, was discovered with the High Energy Stereoscopic System (HESS) in the Galactic plane. The analysis of 215 h of HESS data has revealed a steady gamma -ray flux from HESS J1826-130, which appears extended with a half-width of 0.21 degrees +/- 0.02 (stat)degrees stat degrees +/- 0.05 (sys)degrees sys degrees . The source spectrum is best fit with either a power-law function with a spectral index Gamma = 1.78 +/- 0.10(stat) +/- 0.20(sys) and an exponential cut-off at 15.2 (+5.5)(-3.2) -3.2+5.5 TeV, or a broken power-law with Gamma (1) = 1.96 +/- 0.06(stat) +/- 0.20(sys), Gamma (2) = 3.59 +/- 0.69(stat) +/- 0.20(sys) for energies below and above E-br = 11.2 +/- 2.7 TeV, respectively. The VHE flux from HESS J1826-130 is contaminated by the extended emission of the bright, nearby pulsar wind nebula, HESS J1825-137, particularly at the low end of the energy spectrum. Leptonic scenarios for the origin of HESS J1826-130 VHE emission related to PSR J1826-1256 are confronted by our spectral and morphological analysis. In a hadronic framework, taking into account the properties of dense gas regions surrounding HESS J1826-130, the source spectrum would imply an astrophysical object capable of accelerating the parent particle population up to greater than or similar to 200 TeV. Our results are also discussed in a multiwavelength context, accounting for both the presence of nearby supernova remnants, molecular clouds, and counterparts detected in radio, X-rays, and TeV energies.
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| 7. |
- Abdalla, H., et al.
(författare)
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Detection of very-high-energy gamma-ray emission from the colliding wind binary eta Car with HESS
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 635, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Aims. Colliding wind binary systems have long been suspected to be high-energy (HE; 100 MeV < E < 100 GeV) gamma-ray emitters. eta Car is the most prominent member of this object class and is confirmed to emit phase-locked HE gamma rays from hundreds of MeV to 100 GeV energies. This work aims to search for and characterise the very-high-energy (VHE; E >100 GeV) gamma-ray emission from eta Car around the last periastron passage in 2014 with the ground-based High Energy Stereoscopic System (H.E.S.S.).Methods. The region around eta Car was observed with H.E.S.S. between orbital phase p = 0.78-1.10, with a closer sampling at p approximate to 0.95 and p approximate to 1.10 (assuming a period of 2023 days). Optimised hardware settings as well as adjustments to the data reduction, reconstruction, and signal selection were needed to suppress and take into account the strong, extended, and inhomogeneous night sky background (NSB) in the eta Car field of view. Tailored run-wise Monte-Carlo simulations (RWS) were required to accurately treat the additional noise from NSB photons in the instrument response functions.Results. H.E.S.S. detected VHE gamma-ray emission from the direction of eta Car shortly before and after the minimum in the X-ray light-curve close to periastron. Using the point spread function provided by RWS, the reconstructed signal is point-like and the spectrum is best described by a power law. The overall flux and spectral index in VHE gamma rays agree within statistical and systematic errors before and after periastron. The gamma-ray spectrum extends up to at least 400 GeV. This implies a maximum magnetic field in a leptonic scenario in the emission region of 0.5 Gauss. No indication for phase-locked flux variations is detected in the H.E.S.S. data.
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| 8. |
- Abdalla, H., et al.
(författare)
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Probing the Magnetic Field in the GW170817 Outflow Using HESS Observations
- 2020
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Ingår i: Astrophysical Journal Letters. - : Institute of Physics Publishing (IOPP). - 2041-8205 .- 2041-8213. ; 894:2, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- The detection of the first electromagnetic counterpart to the binary neutron star (BNS) merger remnant GW170817 established the connection between short gamma-ray bursts and BNS mergers. It also confirmed the forging of heavy elements in the ejecta (a so-called kilonova) via the r-process nucleosynthesis. The appearance of nonthermal radio and X-ray emission, as well as the brightening, which lasted more than 100 days, were somewhat unexpected. Current theoretical models attempt to explain this temporal behavior as either originating from a relativistic off-axis jet or a kilonova-like outflow. In either scenario, there is some ambiguity regarding how much energy is transported in the nonthermal electrons versus the magnetic field of the emission region. Combining the Very Large Array (radio) and Chandra (X-ray) measurements with observations in the GeV-TeV domain can help break this ambiguity, almost independently of the assumed origin of the emission. Here we report for the first time on deep H.E.S.S. observations of GW170817/GRB 170817A between 124 and 272 days after the BNS merger with the full H.E.S.S. array of telescopes, as well as on an updated analysis of the prompt (<5 days) observations with the upgraded H.E.S.S. phase-I telescopes. We discuss implications of the H.E.S.S. measurement for the magnetic field in the context of different source scenarios.
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| 9. |
- Abdalla, H., et al.
(författare)
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Very high energy gamma-ray emission from two blazars of unknown redshift and upper limits on their distance
- 2020
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 494:4, s. 5590-5602
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Tidskriftsartikel (refereegranskat)abstract
- We report on the detection of very high energy (VHE; E > 100 GeV) gamma-ray emission from the BL Lac objects KUV 00311-1938 and PKS 1440-389 with the High Energy Stereoscopic System (H.E.S.S.). H.E.S.S. observations were accompanied or preceded by multiwavelength observations with Fermi/LAT, XRT and UVOT onboard the Swift satellite, and ATOM. Based on an extrapolation of the Fermi/LAT spectrum towards the VHE gamma-ray regime, we deduce a 95 per cent confidence level upper limit on the unknown redshift of KUV 00311-1938 of z < 0.98 and of PKS 1440-389 of z < 0.53. When combined with previous spectroscopy results, the redshift of KUV 00311-1938 is constrained to 0.51 <= z < 0.98 and of PKS 1440-389 to 0.14 (sic) z < 0.53.
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| 10. |
- Abdallah, H., et al.
(författare)
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Search for dark matter signals towards a selection of recently detected DES dwarf galaxy satellites of the Milky Way with HESS
- 2020
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Ingår i: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 102:6, s. 1-20
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Tidskriftsartikel (refereegranskat)abstract
- Dwarf spheroidal galaxy satellites of the Milky Way are prime targets for indirect detection of dark matter with gamma rays due to their proximity, high dark matter content, and absence of nonthermal emission processes. Recently, the Dark Energy Survey (DES) revealed the existence of new ultrafaint dwarf spheroidal galaxies in the southern-hemisphere sky, therefore ideally located for ground-based observations with the imaging atmospheric Cherenkov telescope array H.E.S.S. We present a search for very-high-energy (E greater than or similar to 100 GeV) gamma-ray emission using H.E.S.S. observations carried out recently towards Reticulum II, Tucana II, Tucana III, Tucana IV, and Grus II satellites. No significant very-high-energy gamma-ray excess is found from the observations on any individual object nor in the combined analysis of all the datasets. Using the most recent modeling of the dark matter distribution in the dwarf galaxy halo, we compute for the first time on DES satellites individual and combined constraints from Cherenkov telescope observations on the annihilation cross section of dark matter particles in the form of Weakly Interacting Massive Particles. The combined 95% C.L. observed upper limits reach similar or equal to 1 x 10(-23) cm(3) s(-1) in the W+W- channel and 4 x 10(-26) cm(3) s(-1) in the gamma gamma channels for a dark matter mass of 1.5 TeV. The H.E.S.S. constraints well complement the results from Fermi-LAT, HAWC, MAGIC, and VERITAS and are currently the most stringent in the gamma gamma channels in the multi-GeV/multi-TeV mass range.
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