| 1. |
- 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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| 2. |
- Abdo, A. A., et al.
(författare)
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FERMI LARGE AREA TELESCOPE OBSERVATIONS OF THE VELA PULSAR
- 2009
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 696:2, s. 1084-1093
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Tidskriftsartikel (refereegranskat)abstract
- The Vela pulsar is the brightest persistent source in the GeV sky and thus is the traditional first target for new gamma-ray observatories. We report here on initial Fermi Large Area Telescope observations during verification phase pointed exposure and early sky survey scanning. We have used the Vela signal to verify Fermi timing and angular resolution. The high-quality pulse profile, with some 32,400 pulsed photons at E >= 0.03 GeV, shows new features, including pulse structure as fine as 0.3 ms and a distinct third peak, which shifts in phase with energy. We examine the high-energy behavior of the pulsed emission; initial spectra suggest a phase-averaged power-law index of Gamma = 1.51(-0.04)(+0.05) with an exponential cutoff at E-c = 2.9 +/- 0.1 GeV. Spectral fits with generalized cutoffs of the form e(-(E/Ec)b) require b <= 1, which is inconsistent with magnetic pair attenuation, and thus favor outer-magnetosphere emission models. Finally, we report on upper limits to any unpulsed component, as might be associated with a surrounding pulsar wind nebula.
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| 3. |
- Abdo, A. A., et al.
(författare)
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DISCOVERY OF PULSATIONS FROM THE PULSAR J0205+6449 IN SNR 3C 58 WITH THE FERMI GAMMA-RAY SPACE TELESCOPE
- 2009
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 0004-637X .- 1538-4357. ; 699:2, s. L102-L107
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of gamma-ray pulsations (>= 0.1 GeV) from the young radio and X-ray pulsar PSR J0205 + 6449 located in the Galactic supernova remnant 3C 58. Data in the gamma-ray band were acquired by the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope (formerly GLAST), while the radio rotational ephemeris used to fold gamma-rays was obtained using both the Green Bank Telescope and the Lovell telescope at Jodrell Bank. The light curve consists of two peaks separated by 0.49 +/- 0.01 +/- 0.01 cycles which are aligned with the X-ray peaks. The first gamma-ray peak trails the radio pulse by 0.08 +/- 0.01 +/- 0.01, while its amplitude decreases with increasing energy as for the other gamma-ray pulsars. Spectral analysis of the pulsed gamma-ray emission suggests a simple power law of index -2.1 +/- 0.1 +/- 0.2 with an exponential cutoff at 3.0(-0.7)(+1.1) +/- 0.4 GeV. The first uncertainty is statistical and the second is systematic. The integral gamma-ray photon flux above 0.1 GeV is (13.7 +/- 1.4 +/- 3.0) x 10(-8) cm(-2) s(-1), which implies for a distance of 3.2 kpc and assuming a broad fan-like beam a luminosity of 8.3 x 10(34) erg s(-1) and an efficiency eta of 0.3%. Finally, we report a 95% upper limit on the flux of 1.7 x 10(-8) cm(-2) s(-1) for off-pulse emission from the object.
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| 4. |
- Abdo, A. A., et al.
(författare)
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The first fermi large area telescope catalog of gamma-ray pulsars
- 2010
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 187:2, s. 460-494
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Tidskriftsartikel (refereegranskat)abstract
- The dramatic increase in the number of known gamma-ray pulsars since the launch of the Fermi Gamma-ray Space Telescope (formerly GLAST) offers the first opportunity to study a sizable population of these high-energy objects. This catalog summarizes 46 high-confidence pulsed detections using the first six months of data taken by the Large Area Telescope (LAT), Fermi's main instrument. Sixteen previously unknown pulsars were discovered by searching for pulsed signals at the positions of bright gamma-ray sources seen with the LAT, or at the positions of objects suspected to be neutron stars based on observations at other wavelengths. The dimmest observed flux among these gamma-ray-selected pulsars is 6.0 x 10(-8) ph cm(-2) s(-1) (for E > 100 MeV). Pulsed gamma-ray emission was discovered from 24 known pulsars by using ephemerides (timing solutions) derived from monitoring radio pulsars. Eight of these new gamma-ray pulsars are millisecond pulsars. The dimmest observed flux among the radio-selected pulsars is 1.4 x 10(-8) ph cm(-2) s(-1) (for E > 100 MeV). The remaining six gamma-ray pulsars were known since the Compton Gamma Ray Observatory mission, or before. The limiting flux for pulse detection is non-uniform over the sky owing to different background levels, especially near the Galactic plane. The pulsed energy spectra can be described by a power law with an exponential cutoff, with cutoff energies in the range similar to 1-5 GeV. The rotational energy-loss rate ((E) over dot) of these neutron stars spans five decades, from similar to 3 x 10(33) erg s(-1) to 5 x 10(38) erg s(-1), and the apparent efficiencies for conversion to gammaray emission range from similar to 0.1% to similar to unity, although distance uncertainties complicate efficiency estimates. The pulse shapes show substantial diversity, but roughly 75% of the gamma-ray pulse profiles have two peaks, separated by greater than or similar to 0.2 of rotational phase. For most of the pulsars, gamma-ray emission appears to come mainly from the outer magnetosphere, while polar-cap emission remains plausible for a remaining few. Spatial associations imply that many of these pulsars power pulsar wind nebulae. Finally, these discoveries suggest that gamma-ray-selected young pulsars are born at a rate comparable to that of their radio-selected cousins and that the birthrate of all young gamma-ray-detected pulsars is a substantial fraction of the expected Galactic supernova rate.
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| 5. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 6. |
- Abdo, A. A., et al.
(författare)
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Fermi large area telescope observation of a gamma-ray source at the position of Eta Carinae
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 723:1, s. 649-657
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Tidskriftsartikel (refereegranskat)abstract
- The Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope detected a gamma-ray source that is spatially consistent with the location of Eta Carinae. This source has been persistently bright since the beginning of the LAT survey observations (from 2008 August to 2009 July, the time interval considered here). The gamma-ray signal is detected significantly throughout the LAT energy band (i.e., up to similar to 100 GeV). The 0.1-100 GeV energy spectrum is well represented by a combination of a cutoff power-law model (<10 GeV) and a hard power-law component (>10 GeV). The total flux (>100 MeV) is 3.7(-0.1)(+0.3) x 10(-7) photons s(-1) cm(-2), with additional systematic uncertainties of 10%, and consistent with the average flux measured by AGILE. The light curve obtained by Fermi is consistent with steady emission. Our observations do not confirm the presence of a gamma-ray flare in 2008 October, as reported by Tavani et al., although we cannot exclude that a flare lasting only a few hours escaped detection by the Fermi LAT. We also do not find any evidence for gamma-ray variability that correlates with the large X-ray variability of Eta Carinae observed during 2008 December and 2009 January. We are thus not able to establish an unambiguous identification of the LAT source with Eta Carinae.
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| 7. |
- Bentley, Michael J., et al.
(författare)
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A community-based geological reconstruction of Antarctic Ice Sheet deglaciation since the Last Glacial Maximum
- 2014
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 100, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- A robust understanding of Antarctic Ice Sheet deglacial history since the Last Glacial Maximum is important in order to constrain ice sheet and glacial-isostatic adjustment models, and to explore the forcing mechanisms responsible for ice sheet retreat. Such understanding can be derived from a broad range of geological and glaciological datasets and recent decades have seen an upsurge in such data gathering around the continent and Sub-Antarctic islands. Here, we report a new synthesis of those datasets, based on an accompanying series of reviews of the geological data, organised by sector. We present a series of timeslice maps for 20 ka, 15 ka, 10 ka and 5 ka, including grounding line position and ice sheet thickness changes, along with a clear assessment of levels of confidence. The reconstruction shows that the Antarctic Ice sheet did not everywhere reach the continental shelf edge at its maximum, that initial retreat was asynchronous, and that the spatial pattern of deglaciation was highly variable, particularly on the inner shelf. The deglacial reconstruction is consistent with a moderate overall excess ice volume and with a relatively small Antarctic contribution to meltwater pulse la. We discuss key areas of uncertainty both around the continent and by time interval, and we highlight potential priorities for future work. The synthesis is intended to be a resource for the modelling and glacial geological community.
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| 8. |
- Adrian, Rita, et al.
(författare)
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Lakes as sentinels of climate change
- 2009
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Ingår i: Limnology and Oceanography. - : Wiley. - 0024-3590 .- 1939-5590. ; 54:6(2), s. 2283-2297
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Tidskriftsartikel (refereegranskat)abstract
- While there is a general sense that lakes can act as sentinels of climate change, their efficacy has not been thoroughly analyzed. We identified the key response variables within a lake that act as indicators of the effects of climate change on both the lake and the catchment. These variables reflect a wide range of physical, chemical, and biological responses to climate. However, the efficacy of the different indicators is affected by regional response to climate change, characteristics of the catchment, and lake mixing regimes. Thus, particular indicators or combinations of indicators are more effective for different lake types and geographic regions. The extraction of climate signals can be further complicated by the influence of other environmental changes, such as eutrophication or acidification, and the equivalent reverse phenomena, in addition to other land-use influences. In many cases, however, confounding factors can be addressed through analytical tools such as detrending or filtering. Lakes are effective sentinels for climate change because they are sensitive to climate, respond rapidly to change, and integrate information about changes in the catchment.
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| 9. |
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| 10. |
- Coquery, N, et al.
(författare)
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Locomotion and eating behavior changes in Yucatan minipigs after unilateral radio-induced ablation of the caudate nucleus
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 17082-
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Tidskriftsartikel (refereegranskat)abstract
- The functional roles of the Caudate nucleus (Cd) are well known. Selective Cd lesions can be found in neurological disorders. However, little is known about the dynamics of the behavioral changes during progressive Cd ablation. Current stereotactic radiosurgery technologies allow the progressive ablation of a brain region with limited adverse effects in surrounding normal tissues. This could be of high interest for the study of the modified behavioral functions in relation with the degree of impairment of the brain structures. Using hypofractionated stereotactic radiotherapy combined with synchrotron microbeam radiation, we investigated, during one year after irradiation, the effects of unilateral radio-ablation of the right Cd on the behavior of Yucatan minipigs. The right Cd was irradiated to a minimal dose of 35.5 Gy delivered in three fractions. MRI-based morphological brain integrity and behavioral functions, i.e. locomotion, motivation/hedonism were assessed. We detected a progressive radio-necrosis leading to a quasi-total ablation one year after irradiation, with an additional alteration of surrounding areas. Transitory changes in the motivation/hedonism were firstly detected, then on locomotion, suggesting the influence of different compensatory mechanisms depending on the functions related to Cd and possibly some surrounding areas. We concluded that early behavioral changes related to eating functions are relevant markers for the early detection of ongoing lesions occurring in Cd-related neurological disorders.
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