| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- 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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| 3. |
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| 4. |
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| 5. |
- Abdalla, H., et al.
(författare)
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The starburst galaxy NGC 253 revisited by HESS and Fermi-LAT
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 617
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Tidskriftsartikel (refereegranskat)abstract
- Context. NGC 253 is one of only two starburst galaxies found to emit gamma-rays from hundreds of MeV to multi-TeV energies. Accurate measurements of the very-high-energy (VHE; E> 100 GeV) and high-energy (HE; E > 60 MeV) spectra are crucial to study the underlying particle accelerators, probe the dominant emission mechanism(s) and to study cosmic-ray interaction and transport. Aims. The measurement of the VHE gamma-ray emission of NGC 253 published in 2012 by H.E.S.S. was limited by large systematic uncertainties. Here, the most up to date measurement of the gamma-ray spectrum of NGC 253 is investigated in both HE and VHE gamma-rays. Assuming a hadronic origin of the gamma-ray emission, the measurement uncertainties are propagated into the interpretation of the accelerated particle population. Methods. The data of H.E.S.S. observations are reanalysed using an updated calibration and analysis chain. The improved Fermi-LAT analysis employs more than 8 yr of data processed using pass 8. The cosmic-ray particle population is evaluated from the combined HE-VHE gamma-ray spectrum using NAIMA in the optically thin case. Results. The VHE gamma-ray energy spectrum is best fit by a power-law distribution with a flux normalisation of (1.34 +/- 0.14(stat) +/- 0.27(sys)) x 10(-13) cm(-2) s(-1) TeV-1 at 1 TeV - about 40% above, but compatible with the value obtained in Abramowski et al. (2012). The spectral index Gamma = 2.39 +/- 0.14(stat) +/- 0.25(sys) is slightly softer than but consistent with the previous measurement within systematic errors. In the Fermi energy range an integral flux of F(E > 60 MeV) = (1.56 +/- 0.28(stat) +/- 0.15(sys)) x 10(-8) cm(-2) s(-1) is obtained. At energies above similar to 3 GeV the HE spectrum is consistent with a power-law ranging into the VHE part of the spectrum measured by H.E.S.S. with an overall spectral index Gamma = 2.22 +/- 0.06(stat). Conclusions. Two scenarios for the starburst nucleus are tested, in which the gas in the starburst nucleus acts as either a thin or a thick target for hadronic cosmic rays accelerated by the individual sources in the nucleus. In these two models, the level to which NGC 253 acts as a calorimeter is estimated to a range of f(cal) = 0.1 to 1 while accounting for the measurement uncertainties. The presented spectrum is likely to remain the most accurate measurements until the Cherenkov Telescope Array (CTA) has collected a substantial set of data towards NGC 253.
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| 6. |
- Abdalla, H., et al.
(författare)
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VHE gamma-ray discovery and multiwavelength study of the blazar 1ES 2322-409
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 482:3, s. 3011-3022
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Tidskriftsartikel (refereegranskat)abstract
- A hotspot at a position compatible with the BL. Lac object 1ES 2322-409 was serendipitously detected with H.E.S.S. during observations performed in 2004 and 2006 on the blazar PKS 2316-423. Additional data on 1ES 2322-409 were taken in 2011 and 2012, leading to a total live-time of 22.3 h. Point-like very-high-energy (VHE; E > 100 GeV) gamma-ray emission is detected from a source centred on the IFS 2322-409 position, with an excess of 116.7 events at a significance of 6.0 sigma. The average VHE gamma-ray spectrum is well described with a power law with a photon index Gamma = 3.40 +/- 0.66(stat) +/- 0.20(sys) and an integral flux Phi(E > 200 GeV) = (3.11 +/- 0.71(stat) 0.62(sys)) x 10(-2)cm(-2)s(-1), which corresponds to 1.1 per cent of the Crab nebula flux above 200 GeV. Multiwavelength data obtained with Fermi LAT, Swift XRT and UVOT, RXTE PCA, ATOM, and additional data from WISE, GROND, and Catalina are also used to characterize the broad-band non-thermal emission of lES 2322-409. The multiwavelength behaviour indicates day-scale variability. Swift UVOT and XRT data show strong variability at longer scales. A spectral energy distribution (SED) is built from contemporaneous observations obtained around a high state identified in Swift data. A modelling of the SED is performed with a stationary homogeneous one-zone synchrotronself-Compton leptonic model. The redshift of the source being unknown, two plausible values were tested for the modelling. A systematic scan of the model parameters space is performed, resulting in a well-constrained combination of values providing a good description of the broad-band behaviour of 1ES 2322-409.
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| 7. |
- Abdalla, H., et al.
(författare)
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VHE γ-ray discovery and multiwavelength study of the blazar 1ES 2322−409
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 482:3, s. 3011-3022
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Tidskriftsartikel (refereegranskat)abstract
- A hotspot at a position compatible with the BL. Lac object 1ES 2322-409 was serendipitously detected with H.E.S.S. during observations performed in 2004 and 2006 on the blazar PKS 2316-423. Additional data on 1ES 2322-409 were taken in 2011 and 2012, leading to a total live-time of 22.3 h. Point-like very-high-energy (VHE; E > 100 GeV) gamma-ray emission is detected from a source centred on the IFS 2322-409 position, with an excess of 116.7 events at a significance of 6.0 sigma. The average VHE gamma-ray spectrum is well described with a power law with a photon index Gamma = 3.40 +/- 0.66(stat) +/- 0.20(sys) and an integral flux Phi(E > 200 GeV) = (3.11 +/- 0.71(stat) 0.62(sys)) x 10(-2)cm(-2)s(-1), which corresponds to 1.1 per cent of the Crab nebula flux above 200 GeV. Multiwavelength data obtained with Fermi LAT, Swift XRT and UVOT, RXTE PCA, ATOM, and additional data from WISE, GROND, and Catalina are also used to characterize the broad-band non-thermal emission of lES 2322-409. The multiwavelength behaviour indicates day-scale variability. Swift UVOT and XRT data show strong variability at longer scales. A spectral energy distribution (SED) is built from contemporaneous observations obtained around a high state identified in Swift data. A modelling of the SED is performed with a stationary homogeneous one-zone synchrotronself-Compton leptonic model. The redshift of the source being unknown, two plausible values were tested for the modelling. A systematic scan of the model parameters space is performed, resulting in a well-constrained combination of values providing a good description of the broad-band behaviour of 1ES 2322-409.
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| 8. |
- Mayer, Manuel, et al.
(författare)
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Constraints on particle acceleration in SS433/W50 from MAGIC and HESS observations
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
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Tidskriftsartikel (refereegranskat)abstract
- Context. The large jet kinetic power and non-thermal processes occurring in the microquasar SS 433 make this source a good candidate for a very high-energy (VHE) gamma-ray emitter. Gamma-ray fluxes above the sensitivity limits of current Cherenkov telescopes have been predicted for both the central X-ray binary system and the interaction regions of SS 433 jets with the surrounding W50 nebula. Non-thermal emission at lower energies has been previously reported, indicating that efficient particle acceleration is taking place in the system. Aims. We explore the capability of SS 433 to emit VHE gamma rays during periods in which the expected flux attenuation due to periodic eclipses (P-orb similar to 13.1 days) and precession of the circumstellar disk (P-pre similar to 162 days) periodically covering the central binary system is expected to be at its minimum. The eastern and western SS 433/W50 interaction regions are also examined using the whole data set available. We aim to constrain some theoretical models previously developed for this system with our observations. Methods. We made use of dedicated observations from the Major Atmospheric Gamma Imaging Cherenkov telescopes (MAGIC) and High Energy Spectroscopic System (H.E.S.S.) of SS 433 taken from 2006 to 2011. These observation were combined for the first time and accounted for a total effective observation time of 16.5 h, which were scheduled considering the expected phases of minimum absorption of the putative VHE emission. Gamma-ray attenuation does not affect the jet/medium interaction regions. In this case, the analysis of a larger data set amounting to similar to 40-80 h, depending on the region, was employed. Results. No evidence of VHE gamma-ray emission either from the central binary system or from the eastern/western interaction regions was found. Upper limits were computed for the combined data set. Differential fluxes from the central system are found to be less than or similar to 10(-12)-10(-13) TeV-1 cm(-2) s(-1) in an energy interval ranging from similar to few x 100 GeV to similar to few TeV. Integral flux limits down to similar to 10(-12)-10(-13) ph cm(-2) s(-1) and similar to 10(-13)-10(-14) ph cm(-2) s(-1) are obtained at 300 and 800 GeV, respectively. Our results are used to place constraints on the particle acceleration fraction at the inner jet regions and on the physics of the jet/medium interactions. Conclusions. Our findings suggest that the fraction of the jet kinetic power that is transferred to relativistic protons must be relatively small in SS 433, q(p) <= 2.5 x 10(-5), to explain the lack of TeV and neutrino emission from the central system. At the SS 433/W50 interface, the presence of magnetic fields greater than or similar to 10 mu G is derived assuming a synchrotron origin for the observed X-ray emission. This also implies the presence of high-energy electrons with E-e up to 50 TeV, preventing an efficient production of gamma-ray fluxes in these interaction regions.
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| 9. |
- Abdalla, H., et al.
(författare)
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HESS observations of RX J1713.7-3946 with improved angular and spectral resolution : Evidence for gamma-ray emission extending beyond the X-ray emitting shell
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
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Tidskriftsartikel (refereegranskat)abstract
- Supernova remnants exhibit shock fronts (shells) that can accelerate charged particles up to very high energies. In the past decade, measurements of a handful of shell-type supernova remnants in very high-energy gamma rays have provided unique insights into the acceleration process. Among those objects, RX J1713.7-3946 (also known as G347.3-0.5) has the largest surface brightness, allowing us in the past to perform the most comprehensive study of morphology and spatially resolved spectra of any such very high-energy gamma-ray source. Here we present extensive new H.E.S.S. measurements of RX J1713.7-3946, almost doubling the observation time compared to our previous publication. Combined with new improved analysis tools, the previous sensitivity is more than doubled. The H.E.S.S. angular resolution of 0.048 degrees (0.036 degrees above 2 TeV) is unprecedented in gamma-ray astronomy and probes physical scales of 0.8 (0.6) parsec at the remnant's location. The new H. E. S. S. image of RX J1713.7-3946 allows us to reveal clear morphological di ff erences between X-rays and gamma rays. In particular, for the outer edge of the brightest shell region, we find the first ever indication for particles in the process of leaving the acceleration shock region. By studying the broadband energy spectrum, we furthermore extract properties of the parent particle populations, providing new input to the discussion of the leptonic or hadronic nature of the gamma-ray emission mechanism.
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| 10. |
- Stacchiotti, S., et al.
(författare)
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Epithelioid hemangioendothelioma, an ultra-rare cancer : a consensus paper from the community of experts
- 2021
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 6:3
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Forskningsöversikt (refereegranskat)abstract
- Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.
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