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Sökning: WFRF:(Fitzpatrick N)

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  • Abazov, V. M., et al. (författare)
  • The upgraded DO detector
  • 2006
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 565:2, s. 463-537
  • Tidskriftsartikel (refereegranskat)abstract
    • The DO experiment enjoyed a very successful data-collection run at the Fermilab Tevatron collider between 1992 and 1996. Since then, the detector has been upgraded to take advantage of improvements to the Tevatron and to enhance its physics capabilities. We describe the new elements of the detector, including the silicon microstrip tracker, central fiber tracker, solenoidal magnet, preshower detectors, forward muon detector, and forward proton detector. The uranium/liquid -argon calorimeters and central muon detector, remaining from Run 1, are discussed briefly. We also present the associated electronics, triggering, and data acquisition systems, along with the design and implementation of software specific to DO.
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  • Fenstermacher, M.E., et al. (författare)
  • DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
  • 2022
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
  • Tidskriftsartikel (refereegranskat)abstract
    • DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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6.
  • Davies, G., et al. (författare)
  • Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
  • 2018
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
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  • Ackermann, M., et al. (författare)
  • Fermi-LAT Observations of the Gamma-Ray Burst GRB 130427A
  • 2014
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 343:6166, s. 42-47
  • 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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10.
  • Ackermann, M., et al. (författare)
  • THE FIRST FERMI-LAT GAMMA-RAY BURST CATALOG
  • 2013
  • Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 209:1
  • 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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  • Ackermann, M., et al. (författare)
  • Constraining The High-Energy Emission From Gamma-Ray Bursts With Fermi
  • 2012
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 754:2, s. 121-
  • 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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15.
  • Preece, R., et al. (författare)
  • The First Pulse of the Extremely Bright GRB 130427A : A Test Lab for Synchrotron Shocks
  • 2014
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 343:6166, s. 51-54
  • 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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  • Racusin, J. L., et al. (författare)
  • SEARCHING THE GAMMA-RAY SKY FOR COUNTERPARTS TO GRAVITATIONAL WAVE SOURCES : FERMI GAMMA-RAY BURST MONITOR. AND LARGE AREA TELESCOPE OBSERVATIONS OF LVT151012 AND GW151226
  • 2017
  • Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 835:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the Fermi Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) observations of the LIGO binary black hole merger event GW151226 and candidate LVT151012. At the time of the LIGO triggers on LVT151012 and GW151226, GBM was observing 68% and 83% of the localization regions, and LAT was observing 47% and 32%, respectively. No candidate electromagnetic counterparts were detected by either the GBM or LAT. We present a detailed analysis of the GBM and LAT data over a range of timescales from seconds to years, using automated pipelines and new techniques for characterizing the flux upper bounds across large areas of the sky. Due to the partial GBM and LAT coverage of the large LIGO localization regions at the trigger times for both events, differences in source distances and masses, as well as the uncertain degree to which emission from these sources could be beamed, these non-detections cannot be used to constrain the variety of theoretical models recently applied to explain the candidate GBM counterpart to GW150914.
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17.
  • Axelsson, Magnus, et al. (författare)
  • GRB110721A : AN EXTREME PEAK ENERGY AND SIGNATURES OF THE PHOTOSPHERE
  • 2012
  • Ingår i: Astrophysical Journal Letters. - 2041-8205. ; 757:2
  • 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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  • Wrzosek-Lipska, K., et al. (författare)
  • Electromagnetic properties of low-lying states in neutron-deficient Hg isotopes : Coulomb excitation of 182Hg, 184Hg, 186Hg and 188Hg
  • 2019
  • Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 55:8
  • Tidskriftsartikel (refereegranskat)abstract
    • The neutron-deficient mercury isotopes serve as a classical example of shape coexistence, whereby at low energy near-degenerate nuclear states characterized by different shapes appear. The electromagnetic structure of even-mass 182-188 Hg isotopes was studied using safe-energy Coulomb excitation of neutron-deficient mercury beams delivered by the REX-ISOLDE facility at CERN. The population of 01,2+, 21,2+ and 41+ states was observed in all nuclei under study. Reduced E2 matrix elements coupling populated yrast and non-yrast states were extracted, including their relative signs. These are a sensitive probe of shape coexistence and may be used to validate nuclear models. The experimental results are discussed in terms of mixing of two different configurations and are compared with three different model calculations: the Beyond Mean Field model, the Interacting Boson Model with configuration mixing and the General Bohr Hamiltonian. Partial agreement with experiment was observed, hinting to missing ingredients in the theoretical descriptions.
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  • Bauer, C., et al. (författare)
  • Prolate shape of Ba-140 from a first combined Doppler-shift and Coulomb-excitation measurement at the REX-ISOLDE facility
  • 2012
  • Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 86:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Quadrupole moments of excited nuclear states are important observables for geometrically interpreting nuclear structure in terms of deformed shapes, although data are scarce and sometimes ambiguous, in particular, in neutron-rich nuclides. Purpose: A measurement was performed for determining the spectroscopic quadrupole moment of the 2(1)(+) state of Ba-140 in order to clarify the character of quadrupole deformation (prolate or oblate) of the state in its yrast sequence of levels. Method: We have utilized a new combined technique of lifetime measurement at REX-ISOLDE and MINIBALL using the Doppler-shift attenuation method (DSAM) and a reorientation analysis of Coulomb-excitation yields. Results: On the basis of the new lifetime of tau(2(1)(+)) = 10.4(-0.8)(+2.2) ps the electric quadrupole moment was determined to be Q(2(1)(+)) = -0.52(34) eb, indicating a predominant prolate deformation. Conclusions: This finding is in agreement with beyond-mean-field calculations using the Gogny D1S force and with results from the Monte Carlo shell-model approach.
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  • Bree, N, et al. (författare)
  • Shape Coexistence in the Neutron-Deficient Even-Even Hg182-188 Isotopes Studied via Coulomb Excitation.
  • 2014
  • Ingår i: Physical Review Letters. - 1079-7114. ; 112:16
  • Tidskriftsartikel (refereegranskat)abstract
    • Coulomb-excitation experiments to study electromagnetic properties of radioactive even-even Hg isotopes were performed with 2.85 MeV/nucleon mercury beams from REX-ISOLDE. Magnitudes and relative signs of the reduced E2 matrix elements that couple the ground state and low-lying excited states in Hg182-188 were extracted. Information on the deformation of the ground and the first excited 0+ states was deduced using the quadrupole sum rules approach. Results show that the ground state is slightly deformed and of oblate nature, while a larger deformation for the excited 0+ state was noted in Hg182,184. The results are compared to beyond mean field and interacting-boson based models and interpreted within a two-state mixing model. Partial agreement with the model calculations was obtained. The presence of two different structures in the light even-mass mercury isotopes that coexist at low excitation energy is firmly established.
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  • Kröll, T., et al. (författare)
  • Transfer Reactions on Neutron-rich Nuclei at REX-ISOLDE
  • 2009
  • Ingår i: AIP Conference Proceedings. - 1551-7616 .- 0094-243X. ; 1165, s. 363-368 461
  • Konferensbidrag (refereegranskat)abstract
    • We report on one- and two-neutron transfer reactions to study the single-particle properties of nuclei at the border of the "island of inversion". The (d,p)- and (t,p)-reactions in inverse kinematics on the neutron-rich isotope Mg-30, delivered as radioactive beam by the REX-ISOLDE facility, have been investigated. The outgoing protons have been detected and identified by a newly built array of Si detectors. The gamma-decay of excited states has been detected in coincidence by the MINIBALL array. First results for Mg-31 and from the search for the second, spherical, 0(+) state in Mg-32 are presented.
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26.
  • Callaway, EM, et al. (författare)
  • A multimodal cell census and atlas of the mammalian primary motor cortex
  • 2021
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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  • Davies, G., et al. (författare)
  • Genetic contributions to variation in general cognitive function : a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)
  • 2015
  • Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 20:2, s. 183-192
  • Tidskriftsartikel (refereegranskat)abstract
    • General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health-and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N = 53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P = 3.93 x 10(-9), MIR2113; rs17522122, P = 2.55 x 10(-8), AKAP6; rs10119, P = 5.67 x 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P = 1x10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N = 6617) and the Health and Retirement Study (N = 5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e. = 5%) and 28% (s.e. = 7%), respectively. Using polygenic prediction analysis, similar to 1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N = 5487; P = 1.5 x 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.
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29.
  • Santangelo, James S., et al. (författare)
  • Global urban environmental change drives adaptation in white clover
  • 2022
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
  • Tidskriftsartikel (refereegranskat)abstract
    • Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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  • Clément, E., et al. (författare)
  • Low-energy Coulomb excitation of Sr 96,98 beams
  • 2016
  • Ingår i: Physical Review C - Nuclear Physics. - 0556-2813. ; 94:5, s. 054326-
  • Tidskriftsartikel (refereegranskat)abstract
    • The structure of neutron-rich Sr96,98 nuclei was investigated by low-energy safe Coulomb excitation of radioactive beams at the REX-ISOLDE facility, CERN, with the MINIBALL spectrometer. A rich set of transitional and diagonal E2 matrix elements, including those for non-yrast structures, has been extracted from the differential Coulomb-excitation cross sections. The results support the scenario of a shape transition at N=60, giving rise to the coexistence of a highly deformed prolate and a spherical configuration in Sr98, and are compared to predictions from several theoretical calculations. The experimental data suggest a significant contribution of the triaxal degree of freedom in the ground state of both isotopes. In addition, experimental information on low-lying states in Rb98 has been obtained.
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32.
  • Clément, E, et al. (författare)
  • Spectroscopic Quadrupole Moments in ^{96,98}Sr: Evidence for Shape Coexistence in Neutron-Rich Strontium Isotopes at N=60.
  • 2016
  • Ingår i: Physical Review Letters. - 1079-7114. ; 116:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Neutron-rich ^{96,98}Sr isotopes have been investigated by safe Coulomb excitation of radioactive beams at the REX-ISOLDE facility. Reduced transition probabilities and spectroscopic quadrupole moments have been extracted from the differential Coulomb excitation cross sections. These results allow, for the first time, the drawing of definite conclusions about the shape coexistence of highly deformed prolate and spherical configurations. In particular, a very small mixing between the coexisting states is observed, contrary to other mass regions where strong mixing is present. Experimental results have been compared to beyond-mean-field calculations using the Gogny D1S interaction in a five-dimensional collective Hamiltonian formalism, which reproduce the shape change at N=60.
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33.
  • Grenda, R., et al. (författare)
  • A prospective, randomized, multicenter trial of tacrolimus-based therapy with or without basiliximab in pediatric renal transplantation
  • 2006
  • Ingår i: American journal of transplantation. - : Elsevier BV. - 1600-6135. ; 6:7, s. 1666-72
  • Tidskriftsartikel (refereegranskat)abstract
    • In a 6-month, multicenter, randomized, controlled, open-label, parallel-group trial, we investigated the efficacy and safety of adding basiliximab to a standard tacrolimus-based regimen in pediatric renal transplant recipients. Patients < 18 years received tacrolimus/azathioprine/steroids (TAS, n = 93) or tacrolimus/azathioprine/steroids/basiliximab (TAS + B, n = 99). Target tacrolimus levels were 10-20 ng/mL between days 0-21 and 5-15 ng/mL thereafter. Steroid dosing was identical in both groups. Basiliximab was administered at 10 mg (patients < 40 kg) or 20 mg (patients > or = 40 kg) within 4 h of reperfusion; the same dose was repeated on day 4. Biopsy-proven acute rejection rates were 20.4% (TAS) and 19.2% (TAS + B); steroid-resistant acute rejection rates were 3.2% and 3.0%, respectively. Patient survival was 100%; graft survival rates were 95% in both arms. The nature and incidence of adverse events were similar in both arms except toxic nephropathy and abdominal pain, which were significantly higher in the TAS + B arm (14.1% vs. 4.3%; p = 0.03 and 11.1% vs. 2.2%; p = 0.02; respectively). Median serum creatinine concentrations at 6 months were 86 micromol/L in the TAS and 91 micromol/L in the TAS + B arm; glomerular filtration rate was 79.4 and 77.6 (mL/min/1.73 m2), respectively. Adding basiliximab to a tacrolimus-based regimen is safe in pediatric patients, but does not improve clinical efficacy.
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35.
  • Li, W, et al. (författare)
  • Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY 2 TRIAL
  • 2020
  • Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 6:1, s. 63-
  • Tidskriftsartikel (refereegranskat)abstract
    • Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype.
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36.
  • Patel, Riyaz S., et al. (författare)
  • Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
  • 2019
  • Ingår i: Circulation. - 2574-8300. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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37.
  • Patel, Riyaz S., et al. (författare)
  • Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
  • 2019
  • Ingår i: Circulation. - 2574-8300. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
  •  
38.
  • Ammerlaan, H S M, et al. (författare)
  • Secular Trends in Nosocomial Bloodstream Infections : Antibiotic-Resistant Bacteria Increase the Total Burden of Infection
  • 2013
  • Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP): Policy A1. - 1058-4838 .- 1537-6591. ; 56:6, s. 798-805
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. It is unknown whether rising incidence rates of nosocomial bloodstream infections (BSIs) caused by antibiotic-resistant bacteria (ARB) replace antibiotic-susceptible bacteria (ASB), leaving the total BSI rate unaffected.Methods. We investigated temporal trends in annual incidence densities (events per 100 000 patient-days) of nosocomial BSIs caused by methicillin-resistant Staphylococcus aureus (MRSA), ARB other than MRSA, and ASB in 7 ARB-endemic and 7 ARB-nonendemic hospitals between 1998 and 2007.Results. 33 130 nosocomial BSIs (14% caused by ARB) yielded 36 679 microorganisms. From 1998 to 2007, the MRSA incidence density increased from 0.2 to 0.7 (annual increase, 22%) in ARB-nonendemic hospitals, and from 3.1 to 11.7 (annual increase, 10%) in ARB-endemic hospitals (P = .2), increasing the incidence density difference between ARB-endemic and ARB-nonendemic hospitals from 2.9 to 11.0. The non-MRSA ARB incidence density increased from 2.8 to 4.1 (annual increase, 5%) in ARB-nonendemic hospitals, and from 1.5 to 17.4 (annual increase, 22%) in ARB-endemic hospitals (P < .001), changing the incidence density difference from −1.3 to 13.3. Trends in ASB incidence densities were similar in both groups (P = .7). With annual increases of 3.8% and 5.4% of all nosocomial BSIs in ARB-nonendemic and ARB-endemic hospitals, respectively (P < .001), the overall incidence density difference of 3.8 increased to 24.4.Conclusions.  Increased nosocomial BSI rates due to ARB occur in addition to infections caused by ASB, increasing the total burden of disease. Hospitals with high ARB infection rates in 2005 had an excess burden of BSI of 20.6 per 100 000 patient-days in a 10-year period, mainly caused by infections with ARB.
  •  
39.
  • Boyle, P, et al. (författare)
  • Need for global action for cancer control
  • 2008
  • Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology. - : Elsevier BV. - 1569-8041. ; 19:9, s. 1519-1521
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
40.
  • Burgess, J. Michael, et al. (författare)
  • AN OBSERVED CORRELATION BETWEEN THERMAL AND NON-THERMAL EMISSION IN GAMMA-RAY BURSTS
  • 2014
  • Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 784:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent observations by the Fermi Gamma-ray Space Telescope have confirmed the existence of thermal and non-thermal components in the prompt photon spectra of some gamma-ray bursts (GRBs). Through an analysis of six bright Fermi GRBs, we have discovered a correlation between the observed photospheric and non-thermal gamma-ray emission components of several GRBs using a physical model that has previously been shown to be a good fit to the Fermi data. From the spectral parameters of these fits we find that the characteristic energies, E-p and kT, of these two components are correlated via the relation E-p proportional to T-alpha which varies from GRB to GRB. We present an interpretation in which the value of the index alpha indicates whether the jet is dominated by kinetic or magnetic energy. To date, this jet composition parameter has been assumed in the modeling of GRB outflows rather than derived from the data.
  •  
41.
  • Burgess, J Michael, et al. (författare)
  • Constraints on the Synchrotron Shock Model for the Fermi GRB 090820A Observed by Gamma-Ray Burst Monitor
  • 2011
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 741:1
  • 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.
  •  
42.
  • Connaughton, V, et al. (författare)
  • Localization of Gamma-Ray Bursts Using the Fermi Gamma-Ray Burst Monitor
  • 2015
  • Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 216:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The Fermi Gamma-ray Burst Monitor (GBM) has detected over 1400 gamma-ray bursts (GRBs) since it began science operations in 2008 July. We use a subset of over 300 GRBs localized by instruments such as Swift, the Fermi Large Area Telescope, INTEGRAL, and MAXI, or through triangulations from the InterPlanetary Network, to analyze the accuracy of GBM GRB localizations. We find that the reported statistical uncertainties on GBM localizations, which can be as small as 1°, underestimate the distance of the GBM positions to the true GRB locations and we attribute this to systematic uncertainties. The distribution of systematic uncertainties is well represented (68% confidence level) by a 3.°7 Gaussian with a non-Gaussian tail that contains about 10% of GBM-detected GRBs and extends to approximately 14°. A more complex model suggests that there is a dependence of the systematic uncertainty on the position of the GRB in spacecraft coordinates, with GRBs in the quadrants on the Y axis better localized than those on the X axis.
  •  
43.
  • Das, Yadunandan B., et al. (författare)
  • The influence of temperature on deformation-induced martensitic transformation in 301 stainless steel
  • 2018
  • Ingår i: Materials Science and Technology. - : Taylor & Francis Group. - 0267-0836 .- 1743-2847. ; 34:17, s. 2114-2125
  • Tidskriftsartikel (refereegranskat)abstract
    • Deformation-induced martensitic transformations are increasingly being used to create desirable mechanical properties in steels. Here, the kinetics of the deformation-induced martensitic transformation is investigated at 300, 263, 223, 173 and 100 K using in situ neutron diffraction during tensile loading. The results from these experiments show a distinct change in the transformation behaviour between 300 K and the tests conducted at 263 K and below, causing a difference in martensite structure. The difference in transformation kinetics is correlated to the suppression of slip at low temperatures, as evidenced using diffraction peak intensity analysis for different grain families and corroborated using transmission electron microscopy. A direct correlation between the deformation-induced martensite fraction and the work-hardening rate is shown.
  •  
44.
  • Escott-Price, Valentina, et al. (författare)
  • Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
  •  
45.
  • Feng, Shaohong, et al. (författare)
  • Dense sampling of bird diversity increases power of comparative genomics
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
  • Tidskriftsartikel (refereegranskat)abstract
    • Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
  •  
46.
  • Fitzpatrick, J L, et al. (författare)
  • Female-mediated causes and consequences of status change in a social fish.
  • 2008
  • Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 275:1637
  • Tidskriftsartikel (refereegranskat)abstract
    • In highly social species, dominant individuals often monopolize reproduction, resulting in reproductive investment that is status dependent. Yet, for subordinates, who typically invest less in reproduction, social status can change and opportunities to ascend to dominant social positions are presented suddenly, requiring abrupt changes in behaviour and physiology. In this study, we examined male reproductive anatomy, physiology and behaviour following experimental manipulations of social status in the cooperatively breeding cichlid fish, Neolamprologus pulcher. This unusual fish species lives in permanent social groups composed of a dominant breeding pair and 1-20 subordinates that form a linear social dominance hierarchy. By removing male breeders, we created 18 breeding vacancies and thus provided an opportunity for subordinate males to ascend in status. Dominant females play an important role in regulating status change, as males successfully ascended to breeder status only when they were slightly larger than the female breeder in their social group. Ascending males rapidly assumed behavioural dominance, demonstrated elevated gonadal investment and androgen concentrations compared with males remaining socially subordinate. Interestingly, to increase gonadal investment ascending males appeared to temporarily restrain somatic growth. These results highlight the complex interactions between social status, reproductive physiology and group dynamics, and underscore a convergent pattern of reproductive investment among highly social, cooperative species.
  •  
47.
  • Fitzpatrick, John M., et al. (författare)
  • Optimizing treatment for men with advanced prostate cancer : expert recommendations and the multidisciplinary approach
  • 2008
  • Ingår i: Critical reviews in oncology/hematology. - : Elsevier BV. - 1040-8428 .- 1879-0461. ; 68:Suppl.1, s. S9-S22
  • Forskningsöversikt (refereegranskat)abstract
    • A multidisciplinary panel of 20 international experts, including urologists, radiation oncologists, and medical oncologists, convened during the Advanced Prostate Cancer Multidisciplinary Team meeting in Rome, Italy, in January 2007, to discuss the multidisciplinary team approach and current patterns of care for patients with hormone-refractory prostate cancer (HRPC). During the meeting, the experts discussed several definitions currently used in prostate cancer management, including those for senior adult patients. In addition, the panel reviewed a series of patient case studies in order to provide feedback on current treatment practices and to identify possible strategies for best practice. It was stressed that treatment decisions for senior adult patients should not be based solely on patient age. Additionally, although historically treatment decisions for advanced prostate cancer have focused on palliative care, given the survival benefit associated with docetaxel-based chemotherapy across patient subgroups, more men are likely to be offered chemotherapy for advanced-stage disease in the future.
  •  
48.
  • Gale, S. J., et al. (författare)
  • Band termination spectroscopy in 157Er
  • 1995
  • Ingår i: Journal of Physics G: Nuclear and Particle Physics. - 0954-3899. ; 21:2, s. 193-213
  • Tidskriftsartikel (refereegranskat)abstract
    • The level scheme of 157Er has been extended from a spin region where the nucleus behaves as a prolate rotor to a region where the spin is produced by the alignment of all or most of the available valence nucleons along the symmetry axis of a weakly deformed oblate shape. The level scheme was established at high spin using up to four-fold gamma -ray coincidences detected in the Eurogam spectrometer following the reaction 114Cd( 48Ca,5n)157Er at a bombarding energy of 210 MeV. Particularly favoured states have been established at IK=69/2+, 81/2+, 71/2+, 77/2-, 87-/2 and 89-/2. Specific single-particle configurations are assigned to these special states by comparison with cranked Nilsson-Strutinsky calculations. These states are related to structures observed in the neighbouring nuclei 158Er and 157Ho. These data provide the spectrum of single-particle states for the lowest lying valence orbitals above the 146Gd closed core.
  •  
49.
  • Goldstein, Adam, et al. (författare)
  • The Fermi GBM Gamma-Ray Burst Spectral Catalog : The First Two Years
  • 2012
  • Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 199:1
  • 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.
  •  
50.
  • Gruber, D, et al. (författare)
  • Rest-frame properties of 32 gamma-ray bursts observed by the Fermi Gamma-ray Burst Monitor
  • 2011
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 531:A20
  • 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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