1. |
- Ackermann, M., et al.
(författare)
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Fermi-LAT Observations of the Gamma-Ray Burst GRB 130427A
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 343:6166, s. 42-47
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Tidskriftsartikel (refereegranskat)abstract
- The observations of the exceptionally bright gamma-ray burst (GRB) 130427A by the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope provide constraints on the nature of these unique astrophysical sources. GRB 130427A had the largest fluence, highest-energy photon (95 GeV), longest gamma-ray duration (20 hours), and one of the largest isotropic energy releases ever observed from a GRB. Temporal and spectral analyses of GRB 130427A challenge the widely accepted model that the nonthermal high-energy emission in the afterglow phase of GRBs is synchrotron emission radiated by electrons accelerated at an external shock.
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2. |
- Preece, R., et al.
(författare)
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The First Pulse of the Extremely Bright GRB 130427A : A Test Lab for Synchrotron Shocks
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 343:6166, s. 51-54
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Tidskriftsartikel (refereegranskat)abstract
- Gamma-ray burst (GRB) 130427A is one of the most energetic GRBs ever observed. The initial pulse up to 2.5 seconds is possibly the brightest well-isolated pulse observed to date. A fine time resolution spectral analysis shows power-law decays of the peak energy from the onset of the pulse, consistent with models of internal synchrotron shock pulses. However, a strongly correlated power-law behavior is observed between the luminosity and the spectral peak energy that is inconsistent with curvature effects arising in the relativistic outflow. It is difficult for any of the existing models to account for all of the observed spectral and temporal behaviors simultaneously.
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3. |
- Ackermann, M., et al.
(författare)
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Multiwavelength observations of GRB 110731A : GeV emission from onset to afterglow
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 763:2, s. 71-
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Tidskriftsartikel (refereegranskat)abstract
- We report on the multiwavelength observations of the bright, long gamma-ray burst GRB 110731A, by the Fermi and Swift observatories, and by the MOA and GROND optical telescopes. The analysis of the prompt phase reveals that GRB 110731A shares many features with bright Large Area Telescope bursts observed by Fermi during the first three years on-orbit: a light curve with short time variability across the whole energy range during the prompt phase, delayed onset of the emission above 100 MeV, extra power-law component and temporally extended high-energy emission. In addition, this is the first GRB for which simultaneous GeV, X-ray, and optical data are available over multiple epochs beginning just after the trigger time and extending for more than 800 s, allowing temporal and spectral analysis in different epochs that favor emission from the forward shock in a wind-type medium. The observed temporally extended GeV emission is most likely part of the high-energy end of the afterglow emission. Both the single-zone pair transparency constraint for the prompt signal and the spectral and temporal analysis of the forward-shock afterglow emission independently lead to an estimate of the bulk Lorentz factor of the jet Γ ∼ 500-550.
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4. |
- Ackermann, M., et al.
(författare)
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THE FIRST FERMI-LAT GAMMA-RAY BURST CATALOG
- 2013
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 209:1
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Tidskriftsartikel (refereegranskat)abstract
- In three years of observations since the beginning of nominal science operations in 2008 August, the Large Area Telescope (LAT) on board the Fermi Gamma-Ray Space Telescope has observed high-energy (greater than or similar to 20 MeV) gamma-ray emission from 35 gamma-ray bursts (GRBs). Among these, 28 GRBs have been detected above 100 MeV and 7 GRBs above similar to 20 MeV. The first Fermi-LAT catalog of GRBs is a compilation of these detections and provides a systematic study of high-energy emission from GRBs for the first time. To generate the catalog, we examined 733 GRBs detected by the Gamma-Ray Burst Monitor (GBM) on Fermi and processed each of them using the same analysis sequence. Details of the methodology followed by the LAT collaboration for the GRB analysis are provided. We summarize the temporal and spectral properties of the LAT-detected GRBs. We also discuss characteristics of LAT-detected emission such as its delayed onset and longer duration compared with emission detected by the GBM, its power-law temporal decay at late times, and the fact that it is dominated by a power-law spectral component that appears in addition to the usual Band model.
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5. |
- Ackermann, M., et al.
(författare)
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Constraining The High-Energy Emission From Gamma-Ray Bursts With Fermi
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 754:2, s. 121-
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Tidskriftsartikel (refereegranskat)abstract
- We examine 288 gamma-ray bursts (GRBs) detected by the Fermi Gamma-ray Space Telescope's Gamma-ray Burst Monitor (GBM) that fell within the field of view of Fermi's Large Area Telescope (LAT) during the first 2.5 years of observations, which showed no evidence for emission above 100 MeV. We report the photon flux upper limits in the 0.1-10 GeV range during the prompt emission phase as well as for fixed 30 s and 100 s integrations starting from the trigger time for each burst. We compare these limits with the fluxes that would be expected from extrapolations of spectral fits presented in the first GBM spectral catalog and infer that roughly half of the GBM-detected bursts either require spectral breaks between the GBM and LAT energy bands or have intrinsically steeper spectra above the peak of the nu F-nu spectra (E-pk). In order to distinguish between these two scenarios, we perform joint GBM and LAT spectral fits to the 30 brightest GBM-detected bursts and find that a majority of these bursts are indeed softer above E-pk than would be inferred from fitting the GBM data alone. Approximately 20% of this spectroscopic subsample show statistically significant evidence for a cutoff in their high-energy spectra, which if assumed to be due to gamma gamma attenuation, places limits on the maximum Lorentz factor associated with the relativistic outflow producing this emission. All of these latter bursts have maximum Lorentz factor estimates that are well below the minimum Lorentz factors calculated for LAT-detected GRBs, revealing a wide distribution in the bulk Lorentz factor of GRB outflows and indicating that LAT-detected bursts may represent the high end of this distribution.
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6. |
- Ackermann, M., et al.
(författare)
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Fermi Detection of γ-Ray Emission from the M2 Soft X-Ray Flare on 2010 June 12
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 745:2, s. 144-
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Tidskriftsartikel (refereegranskat)abstract
- The Geostationary Operational Environmental Satellite (GOES) M2-class solar flare, SOL2010-06-12T00: 57, was modest in many respects yet exhibited remarkable acceleration of energetic particles. The flare produced an similar to 50 s impulsive burst of hard X-and gamma-ray emission up to at least 400 MeV observed by the Fermi Gamma-ray Burst Monitor and Large Area Telescope experiments. The remarkably similar hard X-ray and high-energy gamma-ray time profiles suggest that most of the particles were accelerated to energies greater than or similar to 300 MeV with a delay of similar to 10 s from mildly relativistic electrons, but some reached these energies in as little as similar to 3 s. The gamma-ray line fluence from this flare was about 10 times higher than that typically observed from this modest GOES class of X-ray flare. There is no evidence for time-extended >100 MeV emission as has been found for other flares with high-energy gamma-rays.
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7. |
- Axelsson, Magnus, et al.
(författare)
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GRB110721A : AN EXTREME PEAK ENERGY AND SIGNATURES OF THE PHOTOSPHERE
- 2012
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Ingår i: Astrophysical Journal Letters. - 2041-8205. ; 757:2
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Tidskriftsartikel (refereegranskat)abstract
- GRB110721A was observed by the Fermi Gamma-ray Space Telescope using its two instruments, the Large Area Telescope (LAT) and the Gamma-ray Burst Monitor (GBM). The burst consisted of one major emission episode which lasted for similar to 24.5 s (in the GBM) and had a peak flux of (5.7 +/- 0.2) x 10(-5) erg s(-1) cm(-2). The time-resolved emission spectrum is best modeled with a combination of a Band function and a blackbody spectrum. The peak energy of the Band component was initially 15 +/- 2 MeV, which is the highest value ever detected in a GRB. This measurement was made possible by combining GBM/BGO data with LAT Low Energy events to achieve continuous 10-100 MeV coverage. The peak energy later decreased as a power law in time with an index of -1.89 +/- 0.10. The temperature of the blackbody component also decreased, starting from similar to 80 keV, and the decay showed a significant break after similar to 2 s. The spectrum provides strong constraints on the standard synchrotron model, indicating that alternative mechanisms may give rise to the emission at these energies.
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8. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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11. |
- Curtis, Bruce A., et al.
(författare)
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Algal genomes reveal evolutionary mosaicism and the fate of nucleomorphs
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7427, s. 59-65
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Tidskriftsartikel (refereegranskat)abstract
- Cryptophyte and chlorarachniophyte algae are transitional forms in the widespread secondary endosymbiotic acquisition of photosynthesis by engulfment of eukaryotic algae. Unlike most secondary plastid-bearing algae, miniaturized versions of the endosymbiont nuclei (nucleomorphs) persist in cryptophytes and chlorarachniophytes. To determine why, and to address other fundamental questions about eukaryote-eukaryote endosymbiosis, we sequenced the nuclear genomes of the cryptophyte Guillardia theta and the chlorarachniophyte Bigelowiella natans. Both genomes have >21,000 protein genes and are intron rich, and B. natans exhibits unprecedented alternative splicing for a single-celled organism. Phylogenomic analyses and subcellular targeting predictions reveal extensive genetic and biochemical mosaicism, with both host-and endosymbiont-derived genes servicing the mitochondrion, the host cell cytosol, the plastid and the remnant endosymbiont cytosol of both algae. Mitochondrion-to-nucleus gene transfer still occurs in both organisms but plastid-to-nucleus and nucleomorph-to-nucleus transfers do not, which explains why a small residue of essential genes remains locked in each nucleomorph.
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12. |
- Gruber, D, et al.
(författare)
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Fermi/GBM observations of the ultra-long GRB 091024. A burst with an optical flash
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 528:A15
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Tidskriftsartikel (refereegranskat)abstract
- Aims: In this paper we examine gamma-ray and optical data of GRB 091024, a gamma-ray burst (GRB) with an extremely long duration of T90 $\approx$ 1020 s, as observed with the Fermi Gamma-ray Burst Monitor (GBM). Methods: We present spectral analysis of all three distinct emission episodes using data from Fermi/GBM. Because of the long nature of this event, many ground-based optical telescopes slewed to its location within a few minutes and thus were able to observe the GRB during its active period. We compare the optical and gamma-ray light curves. Furthermore, we estimate a lower limit on the bulk Lorentz factor from the variability and spectrum of the GBM light curve and compare it with that obtained from the peak time of the forward shock of the optical afterglow. Results: From the spectral analysis we note that, despite its unusually long duration, this burst is similar to other long GRBs, i.e. there is spectral evolution (both the peak energy and the spectral index vary with time) and spectral lags are measured. We find that the optical light curve is highly anti-correlated to the prompt gamma-ray emission, with the optical emission reaching the maximum during an epoch of quiescence in the prompt emission. We interpret this behavior as the reverse shock (optical flash), expected in the internal-external shock model of GRB emission but observed only in a handful of GRBs so far. The lower limit on the initial Lorentz factor deduced from the variability time scale (Γmin = 195_-110+90) is consistent within the error to the one obtained using the peak time of the forward shock (Γ0 = 120) and is also consistent with Lorentz factors of other long GRBs.
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13. |
- Gruber, D, et al.
(författare)
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Rest-frame properties of 32 gamma-ray bursts observed by the Fermi Gamma-ray Burst Monitor
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 531:A20
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Tidskriftsartikel (refereegranskat)abstract
- Aims: In this paper we study the main spectral and temporal properties of gamma-ray bursts (GRBs) observed by Fermi/GBM. We investigate these key properties of GRBs in the rest-frame of the progenitor and test for possible intra-parameter correlations to better understand the intrinsic nature of these events. Methods: Our sample comprises 32 GRBs with measured redshift that were observed by GBM until August 2010. 28 of them belong to the long-duration population and 4 events were classified as short/hard bursts. For all of these events we derive, where possible, the intrinsic peak energy in the νFν spectrum (Ep,rest), the duration in the rest-frame, defined as the time in which 90% of the burst fluence was observed (T90,rest) and the isotropic equivalent bolometric energy (Eiso). Results: The distribution of Ep,rest has mean and median values of 1.1 MeV and 750 keV, respectively. A log-normal fit to the sample of long bursts peaks at ~800 keV. No high-Ep population is found but the distribution is biased against low Ep values. We find the lowest possible Ep that GBM can recover to be $\approx$ 15 keV. The T90,rest distribution of long GRBs peaks at ~10 s. The distribution of Eiso has mean and median values of 8.9 × 1052 erg and 8.2 × 1052 erg, respectively. We confirm the tight correlation between Ep,rest and Eiso (Amati relation) and the one between Ep,rest and the 1-s peak luminosity (Lp) (Yonetoku relation). Additionally, we observe a parameter reconstruction effect, i.e. the low-energy power law index α gets softer when Ep is located at the lower end of the detector energy range. Moreover, we do not find any significant cosmic evolution of neither Ep,rest nor T90,rest.
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14. |
- Burgess, J. M., et al.
(författare)
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Time-resolved analysis of fermi gamma-ray bursts with fast- and slow-cooled synchrotron photon models
- 2014
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 784:1, s. 17-
-
Tidskriftsartikel (refereegranskat)abstract
- Time-resolved spectroscopy is performed on eight bright, long gamma-ray bursts (GRBs) dominated by single emission pulses that were observed with the Fermi Gamma-Ray Space Telescope. Fitting the prompt radiation of GRBs by empirical spectral forms such as the Band function leads to ambiguous conclusions about the physical model for the prompt radiation. Moreover, the Band function is often inadequate to fit the data. The GRB spectrum is therefore modeled with two emission components consisting of optically thin non-thermal synchrotron radiation from relativistic electrons and, when significant, thermal emission from a jet photosphere, which is represented by a blackbody spectrum. To produce an acceptable fit, the addition of a blackbody component is required in five out of the eight cases. We also find that the low-energy spectral index a is consistent with a synchrotron component with a = -0.81 +/- 0.1. This value lies between the limiting values of a = -2/3 and a = -3/2 for electrons in the slow-and fast-cooling regimes, respectively, suggesting ongoing acceleration at the emission site. The blackbody component can be more significant when using a physical synchrotron model instead of the Band function, illustrating that the Band function does not serve as a good proxy for a non-thermal synchrotron emission component. The temperature and characteristic emission-region size of the blackbody component are found to, respectively, decrease and increase as power laws with time during the prompt phase. In addition, we find that the blackbody and non-thermal components have separate temporal behaviors as far as their respective flux and spectral evolutions.
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19. |
- Jackson, Lisa A., et al.
(författare)
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Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in adults 70 years of age and older previously vaccinated with 23-valent pneumococcal polysaccharide vaccine
- 2013
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 31:35, s. 3585-3593
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Tidskriftsartikel (refereegranskat)abstract
- Background: The currently recommended single dose of the 23-valent pneumococcal free polysaccharide vaccine (PPSV23) for adults 65 years of age and older does not provide extended protection into older age. This reflects a significant unmet medical need for alternative strategies to protect older adults against pneumococcal infection, which may be met by the 13-valent polysaccharide conjugate vaccine (PCV13). Methods: We performed a randomized, modified double-blind trial in 936 adults aged 70 years and older who had previously received PPSV23 at least 5 years before study entry and were now vaccinated with PCV13 or PPSV23. At 1 year after enrollment, all subjects received a follow-on dose of PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured before and at 1 month after each vaccination. Results: Following the enrollment vaccination, OPA titers were significantly greater in the PCV13 group compared to the PPSV23 group for 10 of the 12 serotypes common to both vaccines and to serotype 6A which is unique to PCV13. Responses were noninferior for the other 2 common serotypes. Responses to PCV13 given at 1 year were generally lower in the group that received PPSV23 at enrollment. Conclusion: In adults aged 70 years and older previously vaccinated with PPSV23, PCV13 was significantly more immunogenic than PPSV23 for most of the common serotypes and for serotype 6A. The OPA responses after a follow-on dose of PCV13 one year later indicate that a prior dose of PPSV23, but not PCV13, diminishes the response to the subsequent administration of PCV13.
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20. |
- Leymarie, N., et al.
(författare)
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Interlaboratory Study on Differential Analysis of Protein Glycosylation by Mass Spectrometry: The ABRF Glycoprotein Research Multi-Institutional Study 2012
- 2013
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476. ; 12:10, s. 2935-2951
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Tidskriftsartikel (refereegranskat)abstract
- One of the principal goals of glycoprotein research is to correlate glycan structure and function. Such correlation is necessary in order for one to understand the mechanisms whereby glycoprotein structure elaborates the functions of myriad proteins. The accurate comparison of glycoforms and quantification of glycosites are essential steps in this direction. Mass spectrometry has emerged as a powerful analytical technique in the field of glycoprotein characterization. Its sensitivity, high dynamic range, and mass accuracy provide both quantitative and sequence/structural information. As part of the 2012 ABRF Glycoprotein Research Group study, we explored the use of mass spectrometry and ancillary methodologies to characterize the glycoforms of two sources of human prostate specific antigen (PSA). PSA is used as a tumor marker for prostate cancer, with increasing blood levels used to distinguish between normal and cancer states. The glycans on PSA are believed to be biantennary N-linked, and it has been observed that prostate cancer tissues and cell lines contain more antennae than their benign counterparts. Thus, the ability to quantify differences in glycosylation associated with cancer has the potential to positively impact the use of PSA as a biomarker. We studied standard peptide-based proteomics/glycomics methodologies, including LC-MS/MS for peptide/glycopeptide sequencing and label-free approaches for differential quantification. We performed an interlaboratory study to determine the ability of different laboratories to correctly characterize the differences between glycoforms from two different sources using mass spectrometry methods. We used clustering analysis and ancillary statistical data treatment on the data sets submitted by participating laboratories to obtain a consensus of the glycoforms and abundances. The results demonstrate the relative strengths and weaknesses of top-down glycoproteomics, bottom-up glycoproteomics, and glycomics methods. T6G 2G2, Canada. [Cipollo, John F.; An, Yanming] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20993 USA. [Desaire, Heather; Go, Eden P.] Univ Kansas, Lawrence, KS 66045 USA. [Goldman, Radoslav; Pompach, Petr; Sanda, Miloslav] Georgetown Univ, Dept Oncol, Washington, DC [Halim, Adnan; Larson, Goran; Nilsson, Jonas] Univ Gothenburg, Sahlgrenska Acad, Dept Clin Chem & [Hensbergen, Paul J.; Wuhrer, Manfred] Leiden Univ, Med Ctr, Biomol Mass Spectrometry Unit, NL- [Jabs, Wolfgang; Marx, Kristina; Resemann, Anja; Schweiger-Hufnagel, Ulrike; Suckau, Detlev] Bruker [Ly, Mellisa; Staples, Gregory O.] Agilent Technol, Agilent Labs, Santa Clara, CA 95051 USA. [Mechref, Yehia; Song, Ehwang] Texas Tech Univ, Dept Chem & Biochem, Lubbock, TX 79409 USA. [Nyalwidhe, Julius O.; Watson, Megan] Eastern Virginia Med Sch, Leroy T Canoles Jr Canc Res Ctr, Dept [Packer, Nicolle H.; Thaysen-Andersen, Morten] Macquarie Univ, Dept Chem & Biomol Sci, Biomol [Sihlbom, Carina] Gothenburg Univ, Prote Core Facil, Gothenburg, Sweden. [Tang, Haixu] Indiana Univ, Sch Informat, Bloomington, IN 47405 USA. [Valmuv, Leena] Finnish Red Cross Blood Serv, Helsinki 00310, Finland. [Wada, Yoshinao] Osaka Med Ctr Maternal & Child Hlth, Res Inst, Izumi Ku, Osaka 5941101, Japan.
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21. |
- Maxwell, Christopher A., et al.
(författare)
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Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer
- 2011
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
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25. |
- Cheng, QF, et al.
(författare)
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A role for factor XIIa-mediated factor XI activation in thrombus formation in vivo
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 116:19, s. 3981-3989
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Tidskriftsartikel (refereegranskat)abstract
- Mice lacking factor XII (fXII) or factor XI (fXI) are resistant to experimentally–induced thrombosis, suggesting fXIIa activation of fXI contributes to thrombus formation in vivo. It is not clear whether this reaction has relevance for thrombosis in pri mates. In 2 carotid artery injury models (FeCl3 and Rose Bengal/laser), fXII-deficient mice are more resistant to thrombosis than fXI- or factor IX (fIX)–deficient mice, raising the possibility that fXII and fXI function in distinct pathways. Antibody 14E11 binds fXI from a variety of mammals and interferes with fXI activation by fXIIa in vitro. In mice, 14E11 prevented arterial occlusion induced by FeCl3 to a similar degree to total fXI deficiency. 14E11 also had a modest beneficial effect in a tissue factor–induced pulmonary embolism model, indicating fXI and fXII contribute to thrombus formation even when factor VIIa/tissue factor initiates thrombosis. In baboons, 14E11 reduced platelet-rich thrombus growth in collagen-coated grafts inserted into an arteriovenous shunt. These data support the hypothesis that fXIIa-mediated fXI activation contributes to thrombus formation in rodents and primates. Since fXII deficiency does not impair hemostasis, targeted inhibition of fXI activation by fXIIa may be a useful antithrombotic strategy associated with a low risk of bleeding complications.
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26. |
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27. |
- Goldstein, Adam, et al.
(författare)
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The Fermi GBM Gamma-Ray Burst Spectral Catalog : The First Two Years
- 2012
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 199:1
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Tidskriftsartikel (refereegranskat)abstract
- We present systematic spectral analyses of gamma-ray bursts (GRBs) detected by the Fermi Gamma-Ray Burst Monitor (GBM) during its first two years of operation. This catalog contains two types of spectra extracted from 487 GRBs, and by fitting four different spectral models, this results in a compendium of over 3800 spectra. The models were selected based on their empirical importance to the spectral shape of many GRBs, and the analysis performed was devised to be as thorough and objective as possible. We describe in detail our procedure and criteria for the analyses, and present the bulk results in the form of parameter distributions. This catalog should be considered an official product from the Fermi GBM Science Team, and the data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center.
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28. |
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29. |
- Matafonov, A, et al.
(författare)
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Factor XII inhibition reduces thrombus formation in a primate thrombosis model
- 2014
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 123:11, s. 1739-1746
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Tidskriftsartikel (refereegranskat)abstract
- Factor XII can contribute to thrombus formation in human and nonhuman primate blood. An antibody that blocks factor XII activation (15H8) produces an antithrombotic effect in a primate thrombosis model.
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31. |
- Silfverdal, Sven Arne, et al.
(författare)
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13-Valent pneumococcal conjugate vaccine (PCV13) in children partially immunized with 7-valent pneumococcal conjugate vaccine (PCV7): A phase 3, open-label trial
- 2013
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 31:9, s. 1284-1292
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Tidskriftsartikel (refereegranskat)abstract
- Background: As 13-valent pneumococcal conjugate vaccine (PCV13) is introduced, children who began vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) may complete their vaccination with PCV13. This open-label phase 3 study evaluated immunogenicity and safety of PCV13 in Swedish infants and toddlers previously given 1 or 2 doses of PCV7 during infancy. Methods: Healthy infants previously given PCV7 at ages 3 months (group 1; n = 118) or 3 and 5 months (group 2; n = 116) received PCV13 at ages 5 (group 1) and 12 months (both groups). IgG responses were assessed 1 month after each PCV13 dose and before the 12-month dose. Local reactions and systemic events were collected for 7 days postvaccination. Other adverse events were also collected. Results: Post-5-month dose, IgG geometric mean concentrations (GMCs) in group 1 were 1.56-4.70 mu g/ml for most PCV7 serotypes except 6B (0.40 mu g/ml) and 23F (0.57 mu g/ml) and 0.72-1.88 mu g/ml for most of the 6 additional serotypes, except 6A (0.28 mu g/ml). Post-12-month dose, IgG GMCs for the PCV7 serotypes were 2.93-9.63 mu g/ml (group 1) and 3.33-9.30 mu g/ml (group 2); and for the 6 additional serotypes, 1.85-14.65 mu g/ml (group 1) and 1.34-13.16 mu g/ml (group 2). GMCs increased by >4-fold in both groups from pre- to post-12-month dose. Proportions of subjects in group 1 with pneumococcal serotype-specific IgG concentrations >= 0.35 mu g/ml (WHO-designated postprimary reference antibody level) post-5-month dose were 92.2-99.1% for most PCV7 serotypes except 6B (53.0%) and 23F (62.6%) and 80.9-100.0% for most of the 6 additional serotypes except 6A (36.8%). Local reactions and fever were mostly mild or moderate. Conclusions: PCV13 was immunogenic and safe in infants and toddlers previously partially immunized with PCV7. Even a single dose in an infant or toddler induces an immune response to the 6 additional serotypes. (C) 2013 Published by Elsevier Ltd.
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32. |
- Tierney, D, et al.
(författare)
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Anomalies in low-energy gamma-ray burst spectra with the Fermi Gamma-ray Burst Monitor
- 2013
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 550
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Tidskriftsartikel (refereegranskat)abstract
- Context: A Band function has become the standard spectral function used to describe the prompt emission spectra of gamma-ray bursts (GRBs). However, deviations from this function have previously been observed in GRBs detected by BATSE and in individual GRBs from the Fermi era.Aims: We present a systematic and rigorous search for spectral deviations from a Band function at low energies in a sample of the first two years of high fluence, long bursts detected by the Fermi Gamma-ray Burst Monitor (GBM). The sample contains 45 bursts with a fluence greater than 2 × 10-5 erg/cm2 (10-1000 keV).Methods: An extrapolated fit method is used to search for low-energy spectral anomalies, whereby a Band function is fit above a variable low-energy threshold and then the best fit function is extrapolated to lower energy data. Deviations are quantified by examining residuals derived from the extrapolated function and the data and their significance is determined via comprehensive simulations which account for the instrument response. This method was employed for both time-integrated burst spectra and time-resolved bins defined by a signal-to-noise ratio of 25σ and 50σ.Results: Significant deviations are evident in 3 bursts (GRB 081215A, GRB 090424 and GRB 090902B) in the time-integrated sample (~7%) and 5 bursts (GRB 090323, GRB 090424, GRB 090820, GRB 090902B and GRB 090926A) in the time-resolved sample (~11%).Conclusions: The advantage of the systematic, blind search analysis is that it can demonstrate the requirement for an additional spectral component without any prior knowledge of the nature of that extra component. Deviations are found in a large fraction of high fluence GRBs; fainter GRBs may not have sufficient statistics for deviations to be found using this method.
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33. |
- von Kienlin, Andreas, et al.
(författare)
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The Second Fermi GBM Gamma-Ray Burst Catalog : The First Four Years
- 2014
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Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 211:1
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Tidskriftsartikel (refereegranskat)abstract
- This is the second of a series of catalogs of gamma-ray bursts (GRBs) observed with the Fermi Gamma-ray Burst Monitor (GBM). It extends the first two-year catalog by two more years, resulting in an overall list of 953 GBM triggered GRBs. The intention of the GBM GRB catalog is to provide information to the community on the most important observables of the GBM detected GRBs. For each GRB the location and main characteristics of the prompt emission, the duration, peak flux and fluence are derived. The latter two quantities are calculated for the 50-300 keV energy band, where the maximum energy release of GRBs in the instrument reference system is observed and also for a broader energy band from 10-1000 keV, exploiting the full energy range of GBMs low-energy detectors. Furthermore, information is given on the settings and modifications of the triggering criteria and exceptional operational conditions during years three and four in the mission. This second catalog is an official product of the Fermi GBM science team, and the data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center.
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34. |
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35. |
- Burgess, J Michael, et al.
(författare)
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Constraints on the Synchrotron Shock Model for the Fermi GRB 090820A Observed by Gamma-Ray Burst Monitor
- 2011
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 741:1
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Tidskriftsartikel (refereegranskat)abstract
- Discerning the radiative dissipation mechanism for prompt emission in gamma-ray bursts (GRBs) requires detailed spectroscopic modeling that straddles the vF(v) peak in the 100 keV-1 MeV range. Historically, empirical fits such as the popular Band function have been employed with considerable success in interpreting the observations. While extrapolations of the Band parameters can provide some physical insight into the emission mechanisms responsible for GRBs, these inferences do not provide a unique way of discerning between models. By fitting physical models directly, this degeneracy can be broken, eliminating the need for empirical functions; our analysis here offers a first step in this direction. One of the oldest, and leading, theoretical ideas for the production of the prompt signal is the synchrotron shock model. Here we explore the applicability of this model to a bright Fermi gamma-ray burst monitor (GBM) burst with a simple temporal structure, GRB 090820A. Our investigation implements, for the first time, thermal and non-thermal synchrotron emissivities in the RMFIT forward-folding spectral analysis software often used in GBM burst studies. We find that these synchrotron emissivities, together with a blackbody shape, provide at least as good a match to the data as the Band GRB spectral fitting function. This success is achieved in both time-integrated and time-resolved spectral fits.
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36. |
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37. |
- Guiriec, Sylvain, et al.
(författare)
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Detection of a thermal spectral component in the prompt emission of GRB 100724B
- 2011
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Ingår i: ASTROPHYSICAL JOURNAL LETTERS. - 2041-8205. ; 727:2, s. L33-
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Tidskriftsartikel (refereegranskat)abstract
- Observations of GRB 100724B with the Fermi Gamma-Ray Burst Monitor find that the spectrum is dominated by the typical Band functional form, which is usually taken to represent a non-thermal emission component, but also includes a statistically highly significant thermal spectral contribution. The simultaneous observation of the thermal and non-thermal components allows us to confidently identify the two emission components. The fact that these seem to vary independently favors the idea that the thermal component is of photospheric origin while the dominant non-thermal emission occurs at larger radii. Our results imply either a very high efficiency for the non-thermal process or a very small size of the region at the base of the flow, both quite challenging for the standard fireball model. These problems are resolved if the jet is initially highly magnetized and has a substantial Poynting flux.
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38. |
- Guiriec, Sylvain, et al.
(författare)
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Time-resolved Spectroscopy of the Three Brightest and Hardest Short Gamma-ray Bursts Observed with the Fermi Gamma-ray Burst Monitor
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 725:1, s. 225-241
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Tidskriftsartikel (refereegranskat)abstract
- From 2008 July to 2009 October, the Gamma-ray Burst Monitor (GBM) on board the Fermi Gamma-ray Space Telescope has detected 320 gamma-ray bursts (GRBs). About 20% of these events are classified as short based on their T90 duration below 2 s. We present here for the first time time-resolved spectroscopy at timescales as short as 2 ms for the three brightest short GRBs observed with GBM. The time-integrated spectra of the events deviate from the Band function, indicating the existence of an additional spectral component, which can be fit by a power law with index ∼-1.5. The time-integrated Epeak values exceed 2 MeV for two of the bursts and are well above the values observed in the brightest long GRBs. Their Epeak values and their low-energy power-law indices (a) confirm that short GRBs are harder than long ones. We find that short GRBs are very similar to long ones, but with light curves contracted in time and with harder spectra stretched toward higher energies. In our time-resolved spectroscopy analysis, we find that the Epeak values range from a few tens of keV up to more than 6MeV. In general, the hardness evolutions during the bursts follow their flux/intensity variations, similar to long bursts. However, we do not always see the Epeak leading the light-curve rises and confirm the zero/short average light-curve spectral lag below 1 MeV, already established for short GRBs. We also find that the time-resolved low-energy power-law indices of the Band function mostly violate the limits imposed by the synchrotron models for both slow and fast electron cooling and may require additional emission processes to explain the data. Finally, we interpreted these observations in the context of the current existing models and emission mechanisms for the prompt emission of GRBs.
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39. |
- Karlsson, Per, 1963, et al.
(författare)
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Patterns and risk factors for locoregional failures after mastectomy for breast cancer: an International Breast Cancer Study Group report
- 2012
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 23:11, s. 2852-2858
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Tidskriftsartikel (refereegranskat)abstract
- Rates and risk factors of local, axillary and supraclavicular recurrences can guide patient selection and target for postmastectomy radiotherapy (PMRT). Local, axillary and supraclavicular recurrences were evaluated in 8106 patients enrolled in 13 randomized trials. Patients received chemotherapy and/or endocrine therapy and mastectomy without radiotherapy. Median follow-up was 15.2 years. Ten-year cumulative incidence for chest wall recurrence of > 15% was seen in patients aged < 40 years (16.1%), with >= 4 positive nodes (16.5%) or 0-7 uninvolved nodes (15.1%); for supraclavicular failures > 10%: >= 4 positive nodes (10.2%); for axillary failures of > 5%: aged < 40 years (5.1%), unknown primary tumor size (5.2%), 0-7 uninvolved nodes (5.2%). In patients with 1-3 positive nodes, 10-year cumulative incidence for chest wall recurrence of > 15% were age < 40, peritumoral vessel invasion or 0-7 uninvolved nodes. Age, number of positive nodes and number of uninvolved nodes were significant parameters for each locoregional relapse site. PMRT to the chest wall and supraclavicular fossa is supported in patients with >= 4 positive nodes. With 1-3 positive nodes, chest wall PMRT may be considered in patients aged < 40 years, with 0-7 uninvolved nodes or with vascular invasion. The findings do not support PMRT to the dissected axilla.
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40. |
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41. |
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42. |
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43. |
- Paciesas, William S, et al.
(författare)
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The Fermi GBM Gamma-Ray Burst Catalog : The First Two Years
- 2012
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 199:1
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Tidskriftsartikel (refereegranskat)abstract
- The Fermi Gamma-ray Burst Monitor (GBM) is designed to enhance the scientific return from Fermi in studying gamma-ray bursts (GRBs). In its first two years of operation GBM triggered on 491 GRBs. We summarize the criteria used for triggering and quantify the general characteristics of the triggered GRBs, including their locations, durations, peak flux, and fluence. This catalog is an official product of the Fermi GBM science team, and the data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center.
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44. |
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45. |
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46. |
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47. |
- Sitch, S., et al.
(författare)
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Trends and drivers of regional sources and sinks of carbon dioxide over the past two decades
- 2013
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Ingår i: Biogeosciences Discussions. - : Copernicus GmbH. - 1810-6277. ; 10, s. 20113-20177
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Abstract. The land and ocean absorb on average over half of the anthropogenic emissions of carbon dioxide (CO2) every year. These CO2 "sinks" are modulated by climate change and variability. Here we use a suite of nine Dynamic Global Vegetation Models (DGVMs) and four Ocean Biogeochemical General Circulation Models (OBGCMs) to quantify the global and regional climate and atmospheric CO2 – driven trends in land and oceanic CO2 exchanges with the atmosphere over the period 1990–2009, attribute these trends to underlying processes, and quantify the uncertainty and level of model agreement. The models were forced with reconstructed climate fields and observed global atmospheric CO2; Land Use and Land Cover Changes are not included for the DGVMs. Over the period 1990–2009, the DGVMs simulate a mean global land carbon sink of −2.4 ± 0.7 Pg C yr−1 with a small significant trend of −0.06 ± 0.03 Pg C yr−2 (increasing sink). Over the more limited period 1990–2004, the ocean models simulate a mean ocean sink of –2.2 ± 0.2 Pg C yr–1 with a trend in the net C uptake that is indistinguishable from zero (−0.01 ± 0.02 Pg C yr−2). The two ocean models that extended the simulations until 2009 suggest a slightly stronger, but still small trend of −0.02 ± 0.01 Pg C yr−2. Trends from land and ocean models compare favourably to the land greenness trends from remote sensing, atmospheric inversion results, and the residual land sink required to close the global carbon budget. Trends in the land sink are driven by increasing net primary production (NPP) whose statistically significant trend of 0.22 ± 0.08 Pg C yr−2 exceeds a significant trend in heterotrophic respiration of 0.16 ± 0.05 Pg C yr−2 – primarily as a consequence of wide-spread CO2 fertilisation of plant production. Most of the land-based trend in simulated net carbon uptake originates from natural ecosystems in the tropics (−0.04 ± 0.01 Pg C yr−2), with almost no trend over the northern land region, where recent warming and reduced rainfall offsets the positive impact of elevated atmospheric CO2 on carbon storage. The small uptake trend in the ocean models emerges because climate variability and change, and in particular increasing sea surface temperatures, tend to counteract the trend in ocean uptake driven by the increase in atmospheric CO2. Large uncertainty remains in the magnitude and sign of modelled carbon trends in several regions, and on the influence of land use and land cover changes on regional trends.
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48. |
- Ungerstedt, J. S., et al.
(författare)
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Autologous hematopoietic stem cell transplantation in multiple myeloma and lymphoma : an analysis of factors influencing stem cell collection and hematological recovery
- 2012
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 29:3, s. 2191-2199
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Tidskriftsartikel (refereegranskat)abstract
- Autologous stem cell transplantation is standard treatment for newly diagnosed younger patients with multiple myeloma and for relapsed or refractory Hodgkin or non-Hodgkin lymphoma. Patient characteristics influencing the yield from stem cell collection and time from transplant to platelet recovery were retrospectively analyzed in 630 consecutive patients, attempting to define adequate amounts of CD34+ cells to collect and reinfuse; 509/630 patients (81%) mobilized the requested CD34+ cell number. Factors influencing the harvest yield were age (PÂ <Â 0.001) and gender, where 85% of men and 78% of women (PÂ <Â 0.02) attained the requested stem cell amount. Time to platelet recovery was significantly faster for multiple myeloma patients compared to all other diagnoses (14.6Â days compared to 19.8, PÂ <Â 0.0001). Multiple myeloma patients were older than lymphoma patients but received stem cell transplant up-front as opposed to second line therapy for other patient groups. Multivariate analysis revealed that the most important factor influencing platelet recovery was diagnosis, followed by the amount of reinfused CD34+ cells (PÂ <Â 0.001, PÂ <Â 0.05). Blood group O+ had the fastest platelet recovery, whereas blood group A harvested the highest cell amounts. In conclusion, we demonstrate a significant importance of the number of reinfused CD34+ cells on the time to platelet recovery.
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49. |
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