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Träfflista för sökning "WFRF:(Sehgal N.) "

Sökning: WFRF:(Sehgal N.)

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1.
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2.
  • Drlica-Wagner, A., et al. (författare)
  • SEARCH FOR GAMMA-RAY EMISSION FROM DES DWARF SPHEROIDAL GALAXY CANDIDATES WITH FERMI-LAT DATA
  • 2015
  • Ingår i: Astrophysical Journal Letters. - 2041-8205. ; 809:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Due to their proximity, high dark-matter (DM) content, and apparent absence of non-thermal processes, Milky Way dwarf spheroidal satellite galaxies (dSphs) are excellent targets for the indirect detection of DM. Recently, eight new dSph candidates were discovered using the first year of data from the Dark Energy Survey (DES). We searched for gamma-ray emission coincident with the positions of these new objects in six years of Fermi Large Area Telescope data. We found no significant excesses of gamma-ray emission. Under the assumption that the DES candidates are dSphs with DM halo properties similar to the known dSphs, we computed individual and combined limits on the velocity-averaged DM annihilation cross section for these new targets. If the estimated DM content of these dSph candidates is confirmed, they will constrain the annihilation cross section to lie below the thermal relic cross section for DM particles with masses less than or similar to 20 GeV annihilating via the b (b) over bar or pi(+)pi(-) channels.
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3.
  • Schofield, James P. R., et al. (författare)
  • Stratification of asthma phenotypes by airway proteomic signatures
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - Elsevier. - 0091-6749 .- 1097-6825. ; 144:1, s. 70-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies.
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4.
  • Ackermann, M., et al. (författare)
  • Dark matter constraints from observations of 25 Milky Way satellite galaxies with the Fermi Large Area Telescope
  • 2014
  • Ingår i: Fermi-LAT Collaboration.
  • Tidskriftsartikel (refereegranskat)abstract
    • The dwarf spheroidal satellite galaxies of the Milky Way are some of the most dark-matter-dominated objects known. Due to their proximity, high dark matter content, and lack of astrophysical backgrounds, dwarf spheroidal galaxies are widely considered to be among the most promising targets for the indirect detection of dark matter via gamma rays. Here we report on.-ray observations of 25 Milky Way dwarf spheroidal satellite galaxies based on 4 years of Fermi Large Area Telescope (LAT) data. None of the dwarf galaxies are significantly detected in. rays, and we present.-ray flux upper limits between 500 MeV and 500 GeV. We determine the dark matter content of 18 dwarf spheroidal galaxies from stellar kinematic data and combine LAT observations of 15 dwarf galaxies to constrain the dark matter annihilation cross section. We set some of the tightest constraints to date on the annihilation of dark matter particles with masses between 2 GeV and 10 TeV into prototypical standard model channels. We find these results to be robust against systematic uncertainties in the LAT instrument performance, diffuse.-ray background modeling, and assumed dark matter density profile.
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5.
  • Ackermann, M., et al. (författare)
  • Dark matter constraints from observations of 25 Milky Way satellite galaxies with the Fermi Large Area Telescope
  • 2014
  • Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 89:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The dwarf spheroidal satellite galaxies of the Milky Way are some of the most dark-matter-dominated objects known. Due to their proximity, high dark matter content, and lack of astrophysical backgrounds, dwarf spheroidal galaxies are widely considered to be among the most promising targets for the indirect detection of dark matter via gamma rays. Here we report on.-ray observations of 25 Milky Way dwarf spheroidal satellite galaxies based on 4 years of Fermi Large Area Telescope (LAT) data. None of the dwarf galaxies are significantly detected in. rays, and we present.-ray flux upper limits between 500 MeV and 500 GeV. We determine the dark matter content of 18 dwarf spheroidal galaxies from stellar kinematic data and combine LAT observations of 15 dwarf galaxies to constrain the dark matter annihilation cross section. We set some of the tightest constraints to date on the annihilation of dark matter particles with masses between 2 GeV and 10 TeV into prototypical standard model channels. We find these results to be robust against systematic uncertainties in the LAT instrument performance, diffuse.-ray background modeling, and assumed dark matter density profile.
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6.
  • Ackermann, M., et al. (författare)
  • SEARCH FOR DARK MATTER SATELLITES USING FERMI-LAT
  • 2012
  • Ingår i: Astrophysical Journal. - 0004-637X. ; 747:2, s. 121
  • Tidskriftsartikel (refereegranskat)abstract
    • Numerical simulations based on the ACDM model of cosmology predict a large number of as yet unobserved Galactic dark matter satellites. We report the results of a Large Area Telescope (LAT) search for these satellites via the gamma-ray emission expected from the annihilation of weakly interacting massive particle (WIMP) dark matter. Some dark matter satellites are expected to have hard gamma-ray spectra, finite angular extents, and a lack of counterparts at other wavelengths. We sought to identify LAT sources with these characteristics, focusing on gamma-ray spectra consistent with WIMP annihilation through the b (b) over bar channel. We found no viable dark matter satellite candidates using one year of data, and we present a framework for interpreting this result in the context of numerical simulations to constrain the velocity-averaged annihilation cross section for a conventional 100 GeV WIMP annihilating through the b (b) over bar channel.
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7.
  • Ackermann, M., et al. (författare)
  • Searching for Dark Matter Annihilation from Milky Way Dwarf Spheroidal Galaxies with Six Years of Fermi Large Area Telescope Data
  • 2015
  • Ingår i: Physical Review Letters. - 0031-9007. ; 115:23
  • Tidskriftsartikel (refereegranskat)abstract
    • The dwarf spheroidal satellite galaxies (dSphs) of the Milky Way are some of the most dark matter (DM) dominated objects known. We report on gamma-ray observations of Milky Way dSphs based on six years of Fermi Large Area Telescope data processed with the new PASS8 event-level analysis. None of the dSphs are significantly detected in gamma rays, and we present upper limits on the DM annihilation cross section from a combined analysis of 15 dSphs. These constraints are among the strongest and most robust to date and lie below the canonical thermal relic cross section for DM of mass less than or similar to 100 GeV annihilating via quark and tau-lepton channels.
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8.
  • Coelho, Teresa, et al. (författare)
  • Safety and efficacy of RNAi therapy for transthyretin amyloidosis
  • 2013
  • Ingår i: The New England journal of medicine. - 1533-4406. ; 369:9, s. 819-29
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Transthyretin amyloidosis is caused by the deposition of hepatocyte-derived transthyretin amyloid in peripheral nerves and the heart. A therapeutic approach mediated by RNA interference (RNAi) could reduce the production of transthyretin. METHODS: We identified a potent antitransthyretin small interfering RNA, which was encapsulated in two distinct first- and second-generation formulations of lipid nanoparticles, generating ALN-TTR01 and ALN-TTR02, respectively. Each formulation was studied in a single-dose, placebo-controlled phase 1 trial to assess safety and effect on transthyretin levels. We first evaluated ALN-TTR01 (at doses of 0.01 to 1.0 mg per kilogram of body weight) in 32 patients with transthyretin amyloidosis and then evaluated ALN-TTR02 (at doses of 0.01 to 0.5 mg per kilogram) in 17 healthy volunteers. RESULTS: Rapid, dose-dependent, and durable lowering of transthyretin levels was observed in the two trials. At a dose of 1.0 mg per kilogram, ALN-TTR01 suppressed transthyretin, with a mean reduction at day 7 of 38%, as compared with placebo (P=0.01); levels of mutant and nonmutant forms of transthyretin were lowered to a similar extent. For ALN-TTR02, the mean reductions in transthyretin levels at doses of 0.15 to 0.3 mg per kilogram ranged from 82.3 to 86.8%, with reductions of 56.6 to 67.1% at 28 days (P<0.001 for all comparisons). These reductions were shown to be RNAi-mediated. Mild-to-moderate infusion-related reactions occurred in 20.8% and 7.7% of participants receiving ALN-TTR01 and ALN-TTR02, respectively. CONCLUSIONS: ALN-TTR01 and ALN-TTR02 suppressed the production of both mutant and nonmutant forms of transthyretin, establishing proof of concept for RNAi therapy targeting messenger RNA transcribed from a disease-causing gene. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov numbers, NCT01148953 and NCT01559077.).
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9.
  • Hellgren, Olof, et al. (författare)
  • Global phylogeography of the avian malaria pathogen Plasmodium relictum based on MSP1 allelic diversity
  • 2015
  • Ingår i: Ecography. - Wiley-Blackwell. - 1600-0587. ; 38:8, s. 842-850
  • Tidskriftsartikel (refereegranskat)abstract
    • Knowing the genetic variation that occurs in pathogen populations and how it is distributed across geographical areas is essential to understand parasite epidemiology, local patterns of virulence, and evolution of host-resistance. In addition, it is important to identify populations of pathogens that are evolutionarily independent and thus free' to adapt to hosts and environments. Here, we investigated genetic variation in the globally distributed, highly invasive avian malaria parasite Plasmodium relictum, which has several distinctive mitochondrial haplotyps (cyt b lineages, SGS1, GRW11 and GRW4). The phylogeography of P. relictum was accessed using the highly variable nuclear gene merozoite surface protein 1 (MSP1), a gene linked to the invasion biology of the parasite. We show that the lineage GRW4 is evolutionarily independent of GRW11 and SGS1 whereas GRW11 and SGS1 share MSP1 alleles and thus suggesting the presence of two distinct species (GRW4 versus SGS1 and GRW11). Further, there were significant differences in the global distribution of MSP1 alleles with differences between GRW4 alleles in the New and the Old World. For SGS1, a lineage formerly believed to have both tropical and temperate transmission, there were clear differences in MSP1 alleles transmitted in tropical Africa compared to the temperate regions of Europe and Asia. Further, we highlight the occurrence of multiple MSP1 alleles in GRW4 isolates from the Hawaiian Islands, where the parasite has contributed to declines and extinctions of endemic forest birds since it was introduced. This study stresses the importance of multiple independent loci for understanding patterns of transmission and evolutionary independence across avian malaria parasites.
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10.
  • Journeau, C., et al. (författare)
  • Safest roadmap for corium experimental research in Europe
  • 2018
  • Ingår i: ASCE-ASME Journal of Risk and Uncertainty in Engineering Systems, Part B: Mechanical Engineering. - ASME Press. - 2332-9017. ; 4:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe accident facilities for European safety targets (SAFEST) is a European project networking the European experimental laboratories focused on the investigation of a nuclear power plant (NPP) severe accident (SA) with reactor core melting and formation of hazardous material system known as corium. The main objective of the project is to establish coordinated activities, enabling the development of a common vision and severe accident research roadmaps for the next years, and of the management structure to achieve these goals. In this frame, a European roadmap on severe accident experimental research has been developed to define research challenges to contribute to further reinforcement of Gen II and III NPP safety. The roadmap takes into account different SA phenomena and issues identified and prioritized in the analyses of severe accidents at commercial NPPs and in the results of the recent European stress tests carried out after the Fukushima accident. Nineteen relevant issues related to reactor core meltdown accidents have been selected during these efforts. These issues have been compared to a survey of the European SA research experimental facilities and corium analysis laboratories. Finally, the coherence between European infrastructures and R&D needs has been assessed and a table linking issues and infrastructures has been derived. The comparison shows certain important lacks in SA research infrastructures in Europe, especially in the domains of core late reflooding impact on source term, reactor pressure vessel failure and molten core release modes, spent fuel pool (SFP) accidents, as well as the need for a large-scale experimental facility operating with up to 500 kg of chemically prototypic corium melt.
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