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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. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- 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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| 9. |
- Goedecke, Julia H, et al.
(författare)
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Reduced gluteal expression of adipogenic and lipogenic genes in black south african women is associated with obesity-related insulin resistance
- 2011
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - Philadelphia : Lippincott Williams & Wilkins. - 0021-972X .- 1945-7197. ; 96:12, s. E2029-E2033
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Tidskriftsartikel (refereegranskat)abstract
- Context: Black South African women are less insulin sensitive than their White counterparts, despite less central and greater peripheral fat deposition. We hypothesized that this paradox may be explained, in part, by differences in the adipogenic capacity of sc adipose tissue (SAT). Objective: Our objective was to measure adipogenic and lipogenic gene expression in abdominal and gluteal SAT depots and determine their relationships with insulin sensitivity (S(I)) in South African women. Participants and Design: Fourteen normal-weight [body mass index (BMI) <25 kg/m(2)] Black, 13 normal-weight White, 14 obese (BMI >30 kg/m(2)) Black, and 13 obese White premenopausal South African women participated in this cross-sectional study.Main outcomes:S(I) (frequently sampled iv glucose tolerance test) in relation to expression of adipogenic and lipogenic genes in abdominal and gluteal SAT depots. Results: With increasing BMI, Black women had less visceral fat (P = 0.03) and more abdominal (P = 0.017) and gynoid (P = 0.041) SAT but had lower S(I) (P < 0.01) than White women. The expression of adipogenic and lipogenic genes was proportionately lower with obesity in Black but not White women in the gluteal and deep SAT depots (P < 0.05 for ethnicity × BMI effect). In Black women only, the expression of these genes correlated positively with S(I) (all P < 0.05), independently of age and fat mass. Conclusions: Obese Black women have reduced SAT expression of adipogenic and lipogenic genes compared with White women, which associates with reduced S(I). These findings suggest that obesity in Black women impairs SAT adipogenesis and storage, potentially leading to insulin resistance and increased risk of type 2 diabetes.
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| 15. |
- Rennie, JM, et al.
(författare)
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Characterisation of neonatal seizures and their treatment using continuous EEG monitoring: a multicentre experience
- 2019
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Ingår i: Archives of disease in childhood. Fetal and neonatal edition. - : BMJ. - 1468-2052 .- 1359-2998. ; 104:5, s. F493-F501
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this multicentre study was to describe detailed characteristics of electrographic seizures in a cohort of neonates monitored with multichannel continuous electroencephalography (cEEG) in 6 European centres.MethodsNeonates of at least 36 weeks of gestation who required cEEG monitoring for clinical concerns were eligible, and were enrolled prospectively over 2 years from June 2013. Additional retrospective data were available from two centres for January 2011 to February 2014. Clinical data and EEGs were reviewed by expert neurophysiologists through a central server.ResultsOf 214 neonates who had recordings suitable for analysis, EEG seizures were confirmed in 75 (35%). The most common cause was hypoxic-ischaemic encephalopathy (44/75, 59%), followed by metabolic/genetic disorders (16/75, 21%) and stroke (10/75, 13%). The median number of seizures was 24 (IQR 9–51), and the median maximum hourly seizure burden in minutes per hour (MSB) was 21 min (IQR 11–32), with 21 (28%) having status epilepticus defined as MSB>30 min/hour. MSB developed later in neonates with a metabolic/genetic disorder. Over half (112/214, 52%) of the neonates were given at least one antiepileptic drug (AED) and both overtreatment and undertreatment was evident. When EEG monitoring was ongoing, 27 neonates (19%) with no electrographic seizures received AEDs. Fourteen neonates (19%) who did have electrographic seizures during cEEG monitoring did not receive an AED.ConclusionsOur results show that even with access to cEEG monitoring, neonatal seizures are frequent, difficult to recognise and difficult to treat.Oberservation study numberNCT02160171
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