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Sökning: WFRF:(Schulz Stefan)

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1.
  • Valassi, Andrea, et al. (författare)
  • Challenges in Monte Carlo Event Generator Software for High-Luminosity LHC
  • 2021
  • Ingår i: Computing and Software for Big Science. - : Springer Science and Business Media LLC. - 2510-2044 .- 2510-2036. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We review the main software and computing challenges for the Monte Carlo physics event generators used by the LHC experiments, in view of the High-Luminosity LHC (HL-LHC) physics programme. This paper has been prepared by the HEP Software Foundation (HSF) Physics Event Generator Working Group as an input to the LHCC review of HL-LHC computing, which has started in May 2020.
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2.
  • Jackson, Victoria E, et al. (författare)
  • Meta-analysis of exome array data identifies six novel genetic loci for lung function.
  • 2018
  • Ingår i: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10 -7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs ( SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
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3.
  • Sakornsakolpat, Phuwanat, et al. (författare)
  • Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
  • 2019
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 494-505
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
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4.
  • Shrine, Nick, et al. (författare)
  • New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries
  • 2019
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 481-493
  • Tidskriftsartikel (refereegranskat)abstract
    • Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
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5.
  • Wain, Louise V, et al. (författare)
  • Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
  • 2017
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:3, s. 416-425
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.
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6.
  • Alexander, Stephen P. H., et al. (författare)
  • The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors
  • 2023
  • Ingår i: BRITISH JOURNAL OF PHARMACOLOGY. - : British pharmacological society. - 0007-1188 .- 1476-5381. ; 180
  • Tidskriftsartikel (refereegranskat)abstract
    • The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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7.
  • Christopoulos, Arthur, et al. (författare)
  • THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.
  • 2021
  • Ingår i: British journal of pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 178 Suppl 1
  • Forskningsöversikt (refereegranskat)abstract
    • The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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8.
  • Hedman, Erik, et al. (författare)
  • Sudden gains in internet-based cognitive behaviour therapy for severe health anxiety
  • 2014
  • Ingår i: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 54, s. 22-29
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: A sudden gain is defined as a large and stable individual improvement occurring between two consecutive treatment sessions. Sudden gains have been shown to predict better long-term improvement in several treatment studies, including cognitive behavioural therapy for depression and anxiety disorders, but have not been studied in the treatment of health anxiety or any form of internet-based cognitive behavioural therapy. The aim of this study was to investigate the role of sudden gains in internet-based cognitive behavioural therapy for severe health anxiety.METHOD: We examined the occurrence and significance of sudden gains in measures of health anxiety in 81 participants receiving internet-based cognitive behavioural therapy. We compared patients with sudden gains, patients without sudden gains, and patients with gradual gains.RESULTS: Thirteen participants (16%) experienced one sudden gain in health anxiety with individual sudden gains distributed across the treatment. As expected, patients with a sudden gain showed larger improvements than patients without a sudden gain at post-treatment (d = 1.04) and at one-year follow-up (d = 0.91) on measures of health anxiety.CONCLUSIONS: Consistent with previous studies, sudden gains in internet-based cognitive behavioural therapy are associated with significantly larger and stable treatment effects up to one-year follow-up.
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9.
  • Höche, Stefan, et al. (författare)
  • Simulation of vector boson plus many jet final states at the high luminosity LHC
  • 2019
  • Ingår i: Physical Review D. - 2470-0010. ; 100:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a novel event-generation framework for the efficient simulation of vector boson plus multijet backgrounds at the high-luminosity LHC and at possible future hadron colliders. Message passing interface parallelization of parton-level and particle-level event generation and storage of parton-level event information using the HDF5 data format allow us to obtain leading-order merged Monte Carlo predictions with up to nine jets in the final state. The parton-level event samples generated in this manner correspond to an integrated luminosity of 3 ab-1 and are made publicly available for future phenomenological studies.
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10.
  • Loth, Daan W, et al. (författare)
  • Genome-wide association analysis identifies six new loci associated with forced vital capacity
  • 2014
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46, s. 669-677
  • Tidskriftsartikel (refereegranskat)abstract
    • Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
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11.
  • Mary, Malissa, et al. (författare)
  • Ontological Representation of Laboratory Test Observables: Challenges and Perspectives in the SNOMED CT Observable Entity Model Adoption
  • 2017
  • Ingår i: ARTIFICIAL INTELLIGENCE IN MEDICINE, AIME 2017. - Cham : SPRINGER INTERNATIONAL PUBLISHING AG. - 9783319597584 - 9783319597577 ; , s. 14-23
  • Konferensbidrag (refereegranskat)abstract
    • The emergence of electronic health records has highlighted the need for semantic standards for representation of observations in laboratory medicine. Two such standards are LOINC, with a focus on detailed encoding of lab tests, and SNOMED CT, which is more general, including the representation of qualitative and ordinal test results. In this paper we will discuss how lab observation entries can be represented using SNOMED CT. We use resources provided by the Regenstrief Institute and SNOMED International collaboration, which formalize LOINC terms as SNOMED CT post-coordinated expressions. We demonstrate the benefits brought by SNOMED CT to classify lab tests. We then propose a SNOMED CT based model for lab observation entries aligned with the BioTopLite2 (BTL2) upper level ontology. We provide examples showing how a model designed with no ontological foundation can produce misleading interpretations of inferred observation results. Our solution based on a BTL2 conformant formal interpretation of SNOMED CT concepts allows representing lab test without creating unintended models. We argue in favour of an ontologically explicit bridge between compositional clinical terminologies, in order to safely use their formal representations in intelligent systems.
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12.
  • Meinecke, Christoph R., et al. (författare)
  • Nanolithographic Fabrication Technologies for Network-Based Biocomputation Devices
  • 2023
  • Ingår i: Materials. - : MDPI. - 1996-1944. ; 16:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Network-based biocomputation (NBC) relies on accurate guiding of biological agents through nanofabricated channels produced by lithographic patterning techniques. Here, we report on the large-scale, wafer-level fabrication of optimized microfluidic channel networks (NBC networks) using electron-beam lithography as the central method. To confirm the functionality of these NBC networks, we solve an instance of a classical non-deterministic-polynomial-time complete ("NP-complete") problem, the subset-sum problem. The propagation of cytoskeletal filaments, e.g., molecular motor-propelled microtubules or actin filaments, relies on a combination of physical and chemical guiding along the channels of an NBC network. Therefore, the nanofabricated channels have to fulfill specific requirements with respect to the biochemical treatment as well as the geometrical confienement, with walls surrounding the floors where functional molecular motors attach. We show how the material stack used for the NBC network can be optimized so that the motor-proteins attach themselves in functional form only to the floor of the channels. Further optimizations in the nanolithographic fabrication processes greatly improve the smoothness of the channel walls and floors, while optimizations in motor-protein expression and purification improve the activity of the motor proteins, and therefore, the motility of the filaments. Together, these optimizations provide us with the opportunity to increase the reliability of our NBC devices. In the future, we expect that these nanolithographic fabrication technologies will enable production of large-scale NBC networks intended to solve substantially larger combinatorial problems that are currently outside the capabilities of conventional software-based solvers.
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13.
  • Purrington, Kristen S., et al. (författare)
  • Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer
  • 2014
  • Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 35:5, s. 1012-1019
  • Tidskriftsartikel (refereegranskat)abstract
    • In a genome-wide scan, we show that 30 variants in 25 genomic regions are associated with risk of TN breast cancer. Women carrying many of the risk variants may have 4-fold increased risk relative to women with few variants.Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 x 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 x 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 x 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 x 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.
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14.
  • Sokolowski-Tinten, Klaus, et al. (författare)
  • Short-pulse Laser Induced Transient Structure Formation and Ablation Studied with Time-resolved Coherent XUV-scattering
  • 2010
  • Ingår i: INTERNATIONAL SYMPOSIUM ON HIGH POWER LASER ABLATION 2010. - : AIP. ; , s. 373-379
  • Konferensbidrag (refereegranskat)abstract
    • The structural dynamics of short-pulse laser irradiated surfaces and nano-structures has been studied with nm spatial and ultrafast temporal resolution by means of single-shot coherent XUV-scattering techniques. The experiments allowed us to time-resolve the formation of laser-induced periodic surface structures, and to follow the expansion and disintegration of nano-objects during laser ablation.
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15.
  • Abdalla, H., et al. (författare)
  • Gamma-ray blazar spectra with HESS II mono analysis : The case of PKS2155-304 and PG1553+113
  • 2017
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 600
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The addition of a 28 m Cherenkov telescope (CT5) to the H.E.S.S. array extended the experiment's sensitivity to lower energies. The lowest energy threshold is obtained using monoscopic analysis of data taken with CT5, providing access to gamma-ray energies below 100 GeV for small zenith angle observations. Such an extension of the instrument's energy range is particularly beneficial for studies of active galactic nuclei with soft spectra, as expected for those at a redshift >= 0.5. The high-frequency peaked BL Lac objects PKS 2155-304 (z = 0.116) and PG 1553 + 113 (0.43 < z < 0.58) are among the brightest objects in the gamma-ray sky, both showing clear signatures of gamma-ray absorption at E > 100 GeV interpreted as being due to interactions with the extragalactic background light (EBL). Aims. The aims of this work are twofold: to demonstrate the monoscopic analysis of CT5 data with a low energy threshold, and to obtain accurate measurements of the spectral energy distributions (SED) of PKS 2155-304 and PG 1553 + 113 near their SED peaks at energies approximate to 100 GeV. Methods. Multiple observational campaigns of PKS 2155 304 and PG 1553 + 113 were conducted during 2013 and 2014 using the full H.E.S.S. II instrument (CT1-5). A monoscopic analysis of the data taken with the new CT5 telescope was developed along with an investigation into the systematic uncertainties on the spectral parameters which are derived from this analysis. Results. Using the data from CT5, the energy spectra of PKS 2155 304 and PG 1553 + 113 were reconstructed down to conservative threshold energies of 80 GeV for PKS 2155 304, which transits near zenith, and 110 GeV for the more northern PG 1553 + 113. The measured spectra, well fitted in both cases by a log-parabola spectral model ( with a 5.0 similar to statistical preference for non-zero curvature for PKS 2155 304 and 4.5 sigma for PG 1553+113), were found consistent with spectra derived from contemporaneous Fermi-LAT data, indicating a sharp break in the observed spectra of both sources at E approximate to 100 GeV. When corrected for EBL absorption, the intrinsic H.E.S.S. II mono and Fermi-LAT spectrum of PKS 2155 304 was found to show significant curvature. For PG 1553+113, however, no significant detection of curvature in the intrinsic spectrum could be found within statistical and systematic uncertainties.
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16.
  • Abdo, A. A., et al. (författare)
  • The second Fermi large area telescope catalog of gamma-ray pulsars
  • 2013
  • Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 208:2, s. 17-
  • Tidskriftsartikel (refereegranskat)abstract
    • This catalog summarizes 117 high-confidence ≥0.1 GeV gamma-ray pulsar detections using three years of data acquired by the Large Area Telescope (LAT) on the Fermi satellite. Half are neutron stars discovered using LAT data through periodicity searches in gamma-ray and radio data around LAT unassociated source positions. The 117 pulsars are evenly divided into three groups: millisecond pulsars, young radio-loud pulsars, and young radio-quiet pulsars. We characterize the pulse profiles and energy spectra and derive luminosities when distance information exists. Spectral analysis of the off-peak phase intervals indicates probable pulsar wind nebula emission for four pulsars, and off-peak magnetospheric emission for several young and millisecond pulsars. We compare the gamma-ray properties with those in the radio, optical, and X-ray bands. We provide flux limits for pulsars with no observed gamma-ray emission, highlighting a small number of gamma-faint, radio-loud pulsars. The large, varied gamma-ray pulsar sample constrains emission models. Fermi's selection biases complement those of radio surveys, enhancing comparisons with predicted population distributions.
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17.
  • Acero, F., et al. (författare)
  • Constraints on the galactic population of TeV pulsar wind nebulae using fermi large area telescope observations
  • 2013
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 773:1, s. 77-
  • Tidskriftsartikel (refereegranskat)abstract
    • Pulsar wind nebulae (PWNe) have been established as the most populous class of TeV gamma-ray emitters. Since launch, the Fermi Large Area Telescope (LAT) has identified five high-energy (100 MeV < E < 100 GeV) gamma-ray sources as PWNe and detected a large number of PWN candidates, all powered by young and energetic pulsars. The wealth of multi-wavelength data available and the new results provided by Fermi-LAT give us an opportunity to find new PWNe and to explore the radiative processes taking place in known ones. The TeV gamma-ray unidentified (UNID) sources are the best candidates for finding new PWNe. Using 45 months of Fermi-LAT data for energies above 10 GeV, an analysis was performed near the position of 58 TeV PWNe and UNIDs within 5. of the Galactic plane to establish new constraints on PWN properties and find new clues on the nature of UNIDs. Of the 58 sources, 30 were detected, and this work provides their gamma-ray fluxes for energies above 10 GeV. The spectral energy distributions and upper limits, in the multi-wavelength context, also provide new information on the source nature and can help distinguish between emission scenarios, i.e., between classification as a pulsar candidate or as a PWN candidate. Six new GeV PWN candidates are described in detail and compared with existing models. A population study of GeV PWN candidates as a function of the pulsar/PWN system characteristics is presented.
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18.
  • Acero, F., et al. (författare)
  • DEVELOPMENT OF THE MODEL OF GALACTIC INTERSTELLAR EMISSION FOR STANDARD POINT-SOURCE ANALYSIS OF FERMI LARGE AREA TELESCOPE DATA
  • 2016
  • Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 223:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Most of the celestial. rays detected by the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope originate from the interstellar medium when energetic cosmic rays interact with interstellar nucleons and photons. Conventional point-source and extended-source studies rely on the modeling of this diffuse emission for accurate characterization. Here, we describe the development of the Galactic Interstellar Emission Model (GIEM), which is the standard adopted by the LAT Collaboration and is publicly available. This model is based on a linear combination of maps for interstellar gas column density in Galactocentric annuli and for the inverse-Compton emission produced in the Galaxy. In the GIEM, we also include large-scale structures like Loop. I and the Fermi bubbles. The measured gas emissivity spectra confirm that the cosmic-ray proton density decreases with Galactocentric distance beyond 5 kpc from the Galactic Center. The measurements also suggest a softening of the proton spectrum with Galactocentric distance. We observe that the Fermi bubbles have boundaries with a shape similar to a catenary at latitudes below 20 degrees and we observe an enhanced emission toward their base extending in the north and south Galactic directions and located within similar to 4 degrees of the Galactic Center.
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19.
  • Acero, F., et al. (författare)
  • FERMI LARGE AREA TELESCOPE THIRD SOURCE CATALOG
  • 2015
  • Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 218:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the third Fermi Large Area Telescope (LAT) source catalog (3FGL) of sources in the 100 MeV-300 GeV range. Based on the first 4 yr of science data from the Fermi Gamma-ray Space Telescope mission, it is the deepest yet in this energy range. Relative to the Second Fermi LAT catalog, the 3FGL catalog incorporates twice as much data, as well as a number of analysis improvements, including improved calibrations at the event reconstruction level, an updated model for Galactic diffuse.-ray emission, a refined procedure for source detection, and improved methods for associating LAT sources with potential counterparts at other wavelengths. The 3FGL catalog includes 3033 sources above 4 sigma significance, with source location regions, spectral properties, and monthly light curves for each. Of these, 78 are flagged as potentially being due to imperfections in the model for Galactic diffuse emission. Twenty-five sources are modeled explicitly as spatially extended, and overall 238 sources are considered as identified based on angular extent or correlated variability (periodic or otherwise) observed at other wavelengths. For 1010 sources we have not found plausible counterparts at other wavelengths. More than 1100 of the identified or associated sources are active galaxies of the blazar class; several other classes of non-blazar active galaxies are also represented in the 3FGL. Pulsars represent the largest Galactic source class. From source counts of Galactic sources we estimate that the contribution of unresolved sources to the Galactic diffuse emission is similar to 3% at 1 GeV.
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20.
  • Acero, F., et al. (författare)
  • THE FIRST FERMI LAT SUPERNOVA REMNANT CATALOG
  • 2016
  • Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 224:1
  • Tidskriftsartikel (refereegranskat)abstract
    • To uniformly determine the properties of supernova remnants (SNRs) at high energies, we have developed the first systematic survey at energies from 1 to 100 GeV using data from the Fermi Large Area Telescope (LAT). Based on the spatial overlap of sources detected at GeV energies with SNRs known from radio surveys, we classify 30 sources as likely GeV SNRs. We also report 14 marginal associations and 245 flux upper limits. A mock catalog in which the positions of known remnants are scrambled in Galactic longitude allows us to determine an upper limit of 22% on the number of GeV candidates falsely identified as SNRs. We have also developed a method to estimate spectral and spatial systematic errors arising from the diffuse interstellar emission model, a key component of all Galactic Fermi LAT analyses. By studying remnants uniformly in aggregate, we measure the GeV properties common to these objects and provide a crucial context for the detailed modeling of individual SNRs. Combining our GeV results with multiwavelength (MW) data, including radio, X-ray, and TeV, we demonstrate the need for improvements to previously sufficient, simple models describing the GeV and radio emission from these objects. We model the GeV and MW emission from SNRs in aggregate to constrain their maximal contribution to observed Galactic cosmic rays.
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21.
  • Ackermann, M., et al. (författare)
  • 2FHL : THE SECOND CATALOG OF HARD FERMI-LAT SOURCES
  • 2016
  • Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 222:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a catalog of sources detected above 50 GeV by the Fermi-Large Area Telescope (LAT) in 80 months of data. The newly delivered Pass. 8 event-level analysis allows the detection and characterization of sources in the 50 GeV-2 TeV energy range. In this energy band, Fermi-LAT. has detected 360 sources, which constitute the second catalog of hard Fermi-LAT. sources (2FHL). The improved angular resolution enables the precise localization of point sources (similar to 1.' 7 radius at 68% C.L.) and the detection and characterization of spatially extended sources. We find that 86% of the sources can be associated with counterparts at other wavelengths, of which the majority (75%) are active galactic nuclei and the rest (11%) are Galactic sources. Only 25% of the 2FHL sources have been previously detected by Cherenkov telescopes, implying that the 2FHL provides a reservoir of candidates to be followed up at very high energies. This work closes the energy gap between the observations performed at GeV energies by Fermi-LAT. on orbit and the observations performed at higher energies by Cherenkov telescopes from the ground.
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22.
  • Ackermann, M., et al. (författare)
  • ASSOCIATING LONG-TERM gamma-RAY VARIABILITY WITH THE SUPERORBITAL PERIOD OF LS I+61 degrees 303
  • 2013
  • Ingår i: ASTROPHYSICAL JOURNAL LETTERS. - 2041-8205. ; 773:2, s. L35-
  • Tidskriftsartikel (refereegranskat)abstract
    • Gamma-ray binaries are stellar systems for which the spectral energy distribution (discounting the thermal stellar emission) peaks at high energies. Detected from radio to TeV gamma rays, the gamma-ray binary LS I + 61 degrees 303 is highly variable across all frequencies. One aspect of this system's variability is the modulation of its emission with the timescale set by the similar to 26.4960 day orbital period. Here we show that, during the time of our observations, the gamma-ray emission of LS I + 61 degrees 303 also presents a sinusoidal variability consistent with the previously known superorbital period of 1667 days. This modulation is more prominently seen at orbital phases around apastron, whereas it does not introduce a visible change close to periastron. It is also found in the appearance and disappearance of variability at the orbital period in the power spectrum of the data. This behavior could be explained by a quasi-cyclical evolution of the equatorial outflow of the Be companion star, whose features influence the conditions for generating gamma rays. These findings open the possibility to use gamma-ray observations to study the outflows of massive stars in eccentric binary systems.
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23.
  • Ackermann, M., et al. (författare)
  • Deep view of the Large Magellanic Cloud with six years of Fermi-LAT observations
  • 2016
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 586
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The nearby Large Magellanic Cloud (LMC) provides a rare opportunity of a spatially resolved view of an external star-forming galaxy in gamma-rays. The LMC was detected at 0.1-100 GeV as an extended source with CGRO/EGRET and using early observations with the Fermi-LAT. The emission was found to correlate with massive star-forming regions and to be particularly bright towards 30 Doradus. Aims. Studies of the origin and transport of cosmic rays (CRs) in the Milky Way are frequently hampered by line-of-sight confusion and poor distance determination. The LMC offers a complementary way to address these questions by revealing whether and how the gamma-ray emission is connected to specific objects, populations of objects, and structures in the galaxy. Methods. We revisited the gamma-ray emission from the LMC using about 73 months of Fermi-LAT P7REP data in the 0.2-100 GeV range. We developed a complete spatial and spectral model of the LMC emission, for which we tested several approaches: a simple geometrical description, template-fitting, and a physically driven model for CR-induced interstellar emission. Results. In addition to identifying PSR J0540-6919 through its pulsations, we find two hard sources positionally coincident with plerion N 157B and supernova remnant N 132D, which were also detected at TeV energies with H.E.S.S. We detect an additional soft source that is currently unidentified. Extended emission dominates the total flux from the LMC. It consists of an extended component of about the size of the galaxy and additional emission from three to four regions with degree-scale sizes. If it is interpreted as CRs interacting with interstellar gas, the large-scale emission implies a large-scale population of similar to 1-100 GeV CRs with a density of similar to 30% of the local Galactic value. On top of that, the three to four small-scale emission regions would correspond to enhancements of the CR density by factors 2 to 6 or higher, possibly more energetic and younger populations of CRs compared to the large-scale population. An alternative explanation is that this is emission from an unresolved population of at least two dozen objects, such as pulsars and their nebulae or supernova remnants. This small-scale extended emission has a spatial distribution that does not clearly correlate with known components of the LMC, except for a possible relation to cavities and supergiant shells. Conclusions. The Fermi-LAT GeV observations allowed us to detect individual sources in the LMC. Three of the newly discovered sources are associated with rare and extreme objects. The 30 Doradus region is prominent in GeV gamma-rays because PSR J0540-6919 and N 157B are strong emitters. The extended emission from the galaxy has an unexpected spatial distribution, and observations at higher energies and in radio may help to clarify its origin.
  •  
24.
  • Ackermann, M., et al. (författare)
  • Detection of the Characteristic Pion-Decay Signature in Supernova Remnants
  • 2013
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 339:6121, s. 807-811
  • Tidskriftsartikel (refereegranskat)abstract
    • Cosmic rays are particles (mostly protons) accelerated to relativistic speeds. Despite wide agreement that supernova remnants (SNRs) are the sources of galactic cosmic rays, unequivocal evidence for the acceleration of protons in these objects is still lacking. When accelerated protons encounter interstellar material, they produce neutral pions, which in turn decay into gamma rays. This offers a compelling way to detect the acceleration sites of protons. The identification of pion-decay gamma rays has been difficult because high-energy electrons also produce gamma rays via bremsstrahlung and inverse Compton scattering. We detected the characteristic pion-decay feature in the gamma-ray spectra of two SNRs, IC 443 and W44, with the Fermi Large Area Telescope. This detection provides direct evidence that cosmic-ray protons are accelerated in SNRs.
  •  
25.
  • Ackermann, M., et al. (författare)
  • Fermi establishes classical novae as a distinct class of gamma-ray sources
  • 2014
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 345:6196, s. 554-558
  • Tidskriftsartikel (refereegranskat)abstract
    • A classical nova results from runaway thermonuclear explosions on the surface of a white dwarf that accretes matter from a low-mass main-sequence stellar companion. In 2012 and 2013, three novae were detected in gamma rays and stood in contrast to the first gamma-ray-detected nova V407 Cygni 2010, which belongs to a rare class of symbiotic binary systems. Despite likely differences in the compositions and masses of their white dwarf progenitors, the three classical novae are similarly characterized as soft-spectrum transient gamma-ray sources detected over 2- to 3-week durations. The gamma-ray detections point to unexpected high-energy particle acceleration processes linked to the mass ejection from thermonuclear explosions in an unanticipated class of Galactic gamma-ray sources.
  •  
26.
  • 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.
  •  
27.
  • Ackermann, M., et al. (författare)
  • FERMI LAT STACKING ANALYSIS OF SWIFT LOCALIZED GRBs
  • 2016
  • Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 822:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We perform a comprehensive stacking analysis of data collected by the Fermi. Large Area Telescope (LAT) of gamma-ray bursts (GRBs) localized by the Swift. spacecraft, which were not detected by the LAT but which fell within the instrument's field of view at the time of trigger. We examine a total of 79 GRBs by comparing the observed counts over a range of time intervals to that expected from designated background orbits, as well as by using a joint likelihood technique to model the expected distribution of stacked counts. We find strong evidence for subthreshold emission at MeV to GeV energies using both techniques. This observed excess is detected during intervals that include and exceed the durations typically characterizing the prompt emission observed at keV energies and lasts at least 2700 s after the co-aligned burst trigger. By utilizing a novel cumulative likelihood analysis, we find that although a burst's prompt gamma-ray and afterglow X-ray flux both correlate with the strength of the subthreshold emission, the X-ray afterglow flux measured by Swift's X-ray Telescope at 11 hr post trigger correlates far more significantly. Overall, the extended nature of the subthreshold emission and its connection to the burst's afterglow brightness lend. further support to the external forward shock origin of the late-time emission detected by the LAT. These results suggest that the extended high-energy emission observed by the LAT may be a relatively common feature but remains undetected in a majority of bursts owing. to instrumental threshold effects.
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28.
  • Ackermann, M., et al. (författare)
  • HIGH-ENERGY GAMMA-RAY EMISSION FROM SOLAR FLARES : SUMMARY OF FERMI LARGE AREA TELESCOPE DETECTIONS AND ANALYSIS OF TWO M-CLASS FLARES
  • 2014
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 787:1, s. 15-
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the detections of 18 solar flares detected in high-energy gamma-rays (above 100 MeV) with the Fermi Large Area Telescope (LAT) during its first 4 yr of operation. This work suggests that particle acceleration up to very high energies in solar flares is more common than previously thought, occurring even in modest flares, and for longer durations. Interestingly, all these flares are associated with fairly fast coronal mass ejections (CMEs). We then describe the detailed temporal, spatial, and spectral characteristics of the first two long-lasting events: the 2011 March 7 flare, a moderate (M3.7) impulsive flare followed by slowly varying gamma-ray emission over 13 hr, and the 2011 June 7 M2.5 flare, which was followed by gamma-ray emission lasting for 2 hr. We compare the Fermi LAT data with X-ray and proton data measurements from GOES and RHESSI. We argue that the gamma-rays are more likely produced through pion decay than electron bremsstrahlung, and we find that the energy spectrum of the proton distribution softens during the extended emission of the 2011 March 7 flare. This would disfavor a trapping scenario for particles accelerated during the impulsive phase of the flare and point to a continuous acceleration process at play for the duration of the flares. CME shocks are known for accelerating the solar energetic particles (SEPs) observed in situ on similar timescales, but it might be challenging to explain the production of gamma-rays at the surface of the Sun while the CME is halfway to the Earth. A stochastic turbulence acceleration process occurring in the solar corona is another likely scenario. Detailed comparison of characteristics of SEPs and gamma-ray-emitting particles for several flares will be helpful to distinguish between these two possibilities.
  •  
29.
  • Ackermann, M., et al. (författare)
  • Inferred Cosmic-Ray Spectrum from Fermi Large Area Telescope gamma-Ray Observations of Earth's Limb
  • 2014
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 112:15, s. 151103-
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent accurate measurements of cosmic-ray (CR) species by ATIC-2, CREAM, and PAMELA reveal an unexpected hardening in the proton and He spectra above a few hundred GeV, a gradual softening of the spectra just below a few hundred GeV, and a harder spectrum of He compared to that of protons. These newly discovered features may offer a clue to the origin of high-energy CRs. We use the Fermi Large Area Telescope observations of the gamma-ray emission from Earth's limb for an indirect measurement of the local spectrum of CR protons in the energy range similar to 90 GeV-6 TeV (derived from a photon energy range 15 GeV-1 TeV). Our analysis shows that single power law and broken power law spectra fit the data equally well and yield a proton spectrum with index 2.68 +/- 0.04 and 2.61 +/- 0.08 above similar to 200 GeV, respectively.
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30.
  • Ackermann, M., et al. (författare)
  • Limits on dark matter annihilation signals from the Fermi LAT 4-year measurement of the isotropic gamma-ray background
  • 2015
  • Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :9
  • Tidskriftsartikel (refereegranskat)abstract
    • We search for evidence of dark matter (DM) annihilation in the isotropic gamma-ray background (IGRB) measured with 50 months of Fermi Large Area Telescope (LAT) observations. An improved theoretical description of the cosmological DM annihilation signal, based on two complementary techniques and assuming generic weakly interacting massive particle (WIMP) properties, renders more precise predictions compared to previous work. More specifically, we estimate the cosmologically-induced gamma-ray intensity to have an uncertainty of a factor similar to 20 in canonical setups. We consistently include both the Galactic and extragalactic signals under the same theoretical framework, and study the impact of the former on the IGRB spectrum derivation. We find no evidence for a DM signal and we set limits on the DM-induced isotropic gamma-ray signal. Our limits are competitive for DM particle masses up to tens of TeV and, indeed, are the strongest limits derived from Fermi LAT data at TeV energies. This is possible thanks to the new Fermi LAT IGRB measurement, which now extends up to an energy of 820 GeV. We quantify uncertainties in detail and show the potential this type of search offers for testing the WIMP paradigm with a complementary and truly cosmological probe of DM particle signals.
  •  
31.
  • Ackermann, M., et al. (författare)
  • MULTIWAVELENGTH EVIDENCE FOR QUASI-PERIODIC MODULATION IN THE GAMMA-RAY BLAZAR PG 1553+113
  • 2015
  • Ingår i: Astrophysical Journal Letters. - : Institute of Physics (IOP). - 2041-8205 .- 2041-8213. ; 813:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We report for the first time a gamma-ray and multiwavelength nearly periodic oscillation in an active galactic nucleus. Using the Fermi Large Area Telescope we have discovered an apparent quasi-periodicity in the gamma-ray flux (E > 100 MeV) from the GeV/TeV BL Lac object PG 1553+113. The marginal significance of the 2.18 +/- 0.08 year period gamma-ray cycle is strengthened by correlated oscillations observed in radio and optical fluxes, through data collected in the Owens Valley Radio Observatory, Tuorla, Katzman Automatic Imaging Telescope, and Catalina Sky Survey monitoring programs and Swift-UVOT. The optical cycle appearing in similar to 10 years of data has a similar period, while the 15 GHz oscillation is less regular than seen in the other bands. Further long-term multiwavelength monitoring of this blazar may discriminate among the possible explanations for this quasi-periodicity.
  •  
32.
  • Ackermann, M., et al. (författare)
  • Resolving the Extragalactic gamma-Ray Background above 50 GeV with the Fermi Large Area Telescope
  • 2016
  • Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 116:15
  • Tidskriftsartikel (refereegranskat)abstract
    • The Fermi Large Area Telescope (LAT) Collaboration has recently released a catalog of 360 sources detected above 50 GeV (2FHL). This catalog was obtained using 80 months of data re-processed with Pass 8, the newest event-level analysis, which significantly improves the acceptance and angular resolution of the instrument. Most of the 2FHL sources at high Galactic latitude are blazars. Using detailed Monte Carlo simulations, we measure, for the first time, the source count distribution, dN= dS, of extragalactic.-ray sources at E > 50 GeV and find that it is compatible with a Euclidean distribution down to the lowest measured source flux in the 2FHL (8 x 10(-12) ph cm(-2) s(-1)). We employ a one-point photon fluctuation analysis to constrain the behavior of dN= dS below the source detection threshold. Overall, the source count distribution is constrained over three decades in flux and found compatible with a broken power law with a break flux, Sb, in the range [8 x 10-12; 1.5 x 10-11] ph cm(-2) s(-1) and power-law indices below and above the break of a 2. [1.60; 1.75] and a 1 +/- 2.49 +/- 0.12, respectively. Integration of dN= dS shows that point sources account for at least 86_16 -14 % of the total extragalactic gamma-ray background. The simple form of the derived source count distribution is consistent with a single population (i. e., blazars) dominating the source counts to the minimum flux explored by this analysis. We estimate the density of sources detectable in blind surveys that will be performed in the coming years by the Cherenkov Telescope Array.
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33.
  • Ackermann, M., et al. (författare)
  • SEARCH FOR COSMIC-RAY-INDUCED GAMMA-RAY EMISSION IN GALAXY CLUSTERS
  • 2014
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 787:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Current theories predict relativistic hadronic particle populations in clusters of galaxies in addition to the already observed relativistic leptons. In these scenarios hadronic interactions give rise to neutral pions which decay into gamma rays that are potentially observable with the Large Area Telescope (LAT) on board the Fermi space telescope. We present a joint likelihood analysis searching for spatially extended gamma-ray emission at the locations of 50 galaxy clusters in four years of Fermi-LAT data under the assumption of the universal cosmic-ray (CR) model proposed by Pinzke & Pfrommer. We find an excess at a significance of 2.7 sigma, which upon closer inspection, however, is correlated to individual excess emission toward three galaxy clusters: A400, A1367, and A3112. We discuss these cases in detail and conservatively attribute the emission to unmodeled background systems (for example, radio galaxies within the clusters). Through the combined analysis of 50 clusters, we exclude hadronic injection efficiencies in simple hadronic models above 21% and establish limits on the CR to thermal pressure ratio within the virial radius, R-200, to be below 1.25%-1.4% depending on the morphological classification. In addition, we derive new limits on the gamma-ray flux from individual clusters in our sample.
  •  
34.
  • Ackermann, M., et al. (författare)
  • SEARCH FOR EARLY GAMMA-RAY PRODUCTION IN SUPERNOVAE LOCATED IN A DENSE CIRCUMSTELLAR MEDIUM WITH THE FERMI LAT
  • 2015
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 807:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Supernovae (SNe) exploding in a dense circumstellar medium (CSM) are hypothesized to accelerate cosmic rays in collisionless shocks and emit GeV gamma-rays and TeV neutrinos on a timescale of several months. We perform the first systematic search for gamma-ray emission in Fermi Large Area Telescope data in the energy range from 100 MeV to 300 GeV from the ensemble of 147 SNe Type IIn exploding in a dense CSM. We search for a gamma-ray excess at each SNe location in a one-year time window. In order to enhance a possible weak signal, we simultaneously study the closest and optically brightest sources of our sample in a joint-likelihood analysis in three different time windows (1 year, 6 months, and 3 months). For the most promising source of the sample, SN 2010jl (PTF 10aaxf), we repeat the analysis with an extended time window lasting 4.5 years. We do not find a significant excess in gamma-rays for any individual source nor for the combined sources and provide model-independent flux upper limits for both cases. In addition, we derive limits on the gamma-ray luminosity and the ratio of gamma-ray-to-optical luminosity ratio as a function of the index of the proton injection spectrum assuming a generic gamma-ray production model. Furthermore, we present detailed flux predictions based on multi-wavelength observations and the corresponding flux upper limit at a 95% confidence level (CL) for the source SN 2010jl (PTF 10aaxf).
  •  
35.
  • Ackermann, M., et al. (författare)
  • Search for extended gamma-ray emission from the Virgo Galaxy Cluster with Fermi-LAT
  • 2015
  • Ingår i: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 812:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Galaxy clusters are one of the prime sites to search for dark matter (DM) annihilation signals. Depending on the substructure of the DM halo of a galaxy cluster and the cross sections for DM annihilation channels, these signals might be detectable by the latest generation of gamma-ray telescopes. Here we use three years of Fermi-Large Area Telescope data, which are the most suitable for searching for very extended emission in the vicinity of the nearby Virgo galaxy cluster. Our analysis reveals statistically significant extended emission which can be well characterized by a uniformly emitting disk profile with a radius of 3 degrees that moreover is offset from the cluster center. We demonstrate that the significance of this extended emission strongly depends on the adopted interstellar emission model (IEM) and is most likely an artifact of our incomplete description of the IEM in this region. We also search for and find new point source candidates in the region. We then derive conservative upper limits on the velocity-averaged DM pair annihilation cross section from Virgo. We take into account the potential gamma-ray flux enhancement due to DM sub-halos and its complex morphology as a merging cluster. For DM annihilating into b (b) over bar, assuming a conservative sub-halo model setup, we find limits that are between 1 and 1.5 orders of magnitude above the expectation from the thermal cross section for m(DM) <= 100 GeV. In a more optimistic scenario, we exclude similar to 3 x 10(-26)cm(3)s(-1) for m(DM)less than or similar to 40 GeV for the same channel. Finally, we derive upper limits on the gamma-ray-flux produced by hadronic cosmic-ray interactions in the inter cluster medium. We find that the volume-averaged cosmic-ray-to-thermal pressure ratio is less than similar to 6%.
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36.
  • Ackermann, M., et al. (författare)
  • Search for gamma-ray spectral lines with the Fermi Large Area Telescope and dark matter implications
  • 2013
  • Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:8, s. 082002-
  • Tidskriftsartikel (refereegranskat)abstract
    • Weakly interacting massive particles (WIMPs) are a theoretical class of particles that are excellent dark matter candidates. WIMP annihilation or decay may produce essentially monochromatic gamma rays detectable by the Fermi Large Area Telescope (LAT) against the astrophysical gamma-ray emission of the Galaxy. We have searched for spectral lines in the energy range 5-300 GeV using 3.7 years of data, reprocessed with updated instrument calibrations and an improved energy dispersion model compared to the previous Fermi-LAT Collaboration line searches. We searched in five regions selected to optimize sensitivity to different theoretically motivated dark matter density distributions. We did not find any globally significant lines in our a priori search regions and present 95% confidence limits for annihilation cross sections of self-conjugate WIMPs and decay lifetimes. Our most significant fit occurred at 133 GeV in our smallest search region and had a local significance of 3.3 standard deviations, which translates to a global significance of 1.5 standard deviations. We discuss potential systematic effects in this search, and examine the feature at 133 GeV in detail. We find that the use both of reprocessed data and of additional
  •  
37.
  • 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. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 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.
  •  
38.
  • Ackermann, M., et al. (författare)
  • The Fermi All-Sky Variability Analysis : A List Of Flaring Gamma-Ray Sources And The Search For Transients In Our Galaxy
  • 2013
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 771:1, s. 57-
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper, we present the Fermi All-sky Variability Analysis (FAVA), a tool to systematically study the variability of the gamma-ray sky measured by the Large Area Telescope on board the Fermi Gamma-ray Space Telescope. For each direction on the sky, FAVA compares the number of gamma-rays observed in a given time window to the number of gamma-rays expected for the average emission detected from that direction. This method is used in weekly time intervals to derive a list of 215 flaring gamma-ray sources. We proceed to discuss the 27 sources found at Galactic latitudes smaller than 10 degrees and show that, despite their low latitudes, most of them are likely of extragalactic origin.
  •  
39.
  • Ackermann, M., et al. (författare)
  • THE FIRST FERMI-LAT CATALOG OF SOURCES ABOVE 10 GeV
  • 2013
  • Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 209:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a catalog of gamma-ray sources at energies above 10 GeV based on data from the Large Area Telescope (LAT) accumulated during the first 3 yr of the Fermi Gamma-ray Space Telescope mission. The first Fermi catalog of > 10 GeV sources (1FHL) has 514 sources. For each source we present location, spectrum, a measure of variability, and associations with cataloged sources at other wavelengths. We found that 449 (87%) could be associated with known sources, of which 393 (76% of the 1FHL sources) are active galactic nuclei. Of the 27 sources associated with known pulsars, we find 20 (12) to have significant pulsations in the range > 10 GeV (> 25 GeV). In this work we also report that, at energies above 10 GeV, unresolved sources account for 27% +/- 8% of the isotropic. gamma-ray background, while the unresolved Galactic population contributes only at the few percent level to the Galactic diffuse background. We also highlight the subset of the 1FHL sources that are best candidates for detection at energies above 50-100 GeV with current and future ground-based gamma-ray observatories.
  •  
40.
  • Ackermann, M., et al. (författare)
  • THE SPECTRUM AND MORPHOLOGY OF THE FERMI BUBBLES
  • 2014
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 793:1, s. 64-
  • Tidskriftsartikel (refereegranskat)abstract
    • The Fermi bubbles are two large structures in the gamma-ray sky extending to 55 degrees above and below the Galactic center. We analyze 50 months of Fermi Large Area Telescope data between 100MeV and 500 GeV above 10 degrees in Galactic latitude to derive the spectrum and morphology of the Fermi bubbles. We thoroughly explore the systematic uncertainties that arise when modeling the Galactic diffuse emission through two separate approaches. The gamma-ray spectrum is well described by either a log parabola or a power law with an exponential cutoff. We exclude a simple power law with more than 7 sigma significance. The power law with an exponential cutoff has an index of 1.9 +/- 0.2 and a cutoff energy of 110 +/- 50 GeV. We find that the gamma-ray luminosity of the bubbles is 4.4(-0.9)(+2.4) x 10(37) erg s(-1). We confirm a significant enhancement of gamma-ray emission in the southeastern part of the bubbles, but we do not find significant evidence for a jet. No significant variation of the spectrum across the bubbles is detected. The width of the boundary of the bubbles is estimated to be 3.4(-2.6)(+3.7) deg. Both inverse Compton (IC) models and hadronic models including IC emission from secondary leptons fit the gamma-ray data well. In the IC scenario, synchrotron emission from the same population of electrons can also explain the WMAP and Planck microwave haze with a magnetic field between 5 and 20 mu G.
  •  
41.
  • Ackermann, M., et al. (författare)
  • The spectrum of isotropic diffuse gamma-ray emission between 100 MeV and 820 GeV
  • 2015
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 799:1, s. 86-
  • Tidskriftsartikel (refereegranskat)abstract
    • The gamma-ray sky can be decomposed into individually detected sources, diffuse emission attributed to the interactions of Galactic cosmic rays with gas and radiation fields, and a residual all-sky emission component commonly called the isotropic diffuse gamma-ray background (IGRB). The IGRB comprises all extragalactic emissions too faint or too diffuse to be resolved in a given survey, as well as any residual Galactic foregrounds that are approximately isotropic. The first IGRB measurement with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope (Fermi) used 10 months of sky-survey data and considered an energy range between 200 MeV and 100 GeV. Improvements in event selection and characterization of cosmic-ray backgrounds, better understanding of the diffuse Galactic emission (DGE), and a longer data accumulation of 50 months allow for a refinement and extension of the IGRB measurement with the LAT, now covering the energy range from 100 MeV to 820 GeV. The IGRB spectrum shows a significant high-energy cutoff feature and can be well described over nearly four decades in energy by a power law with exponential cutoff having a spectral index of 2.32 +/- 0.02 and a break energy of (279 +/- 52) GeV using our baseline DGE model. The total intensity attributed to the IGRB is (7.2 +/- 0.6) x 10(-6) cm(-2) s(-1) sr(-1) above 100 MeV, with an additional +15%/-30% systematic uncertainty due to the Galactic diffuse foregrounds.
  •  
42.
  • Ackermann, M., et al. (författare)
  • THE THIRD CATALOG OF ACTIVE GALACTIC NUCLEI DETECTED BY THE FERMI LARGE AREA TELESCOPE
  • 2015
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 810:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The third catalog of active galactic nuclei (AGNs) detected by the Fermi-LAT (3LAC) is presented. It is based on the third Fermi-LAT catalog (3FGL) of sources detected between 100 MeV and 300 GeV with a Test Statistic greater than 25, between 2008 August 4 and 2012 July 31. The 3LAC includes 1591 AGNs located at high Galactic latitudes (vertical bar b vertical bar > 10 degrees), a 71% increase over the second catalog based on 2 years of data. There are 28 duplicate associations, thus 1563 of the 2192 high-latitude gamma-ray sources of the 3FGL catalog are AGNs. Most of them (98%) are blazars. About half of the newly detected blazars are of unknown type, i.e., they lack spectroscopic information of sufficient quality to determine the strength of their emission lines. Based on their gamma-ray spectral properties, these sources are evenly split between flat-spectrum radio quasars (FSRQs) and BL Lacs. The most abundant detected BL Lacs are of the high-synchrotron-peaked (HSP) type. About 50% of the BL Lacs have no measured redshifts. A few new rare outliers (HSP-FSRQs and high-luminosity HSP BL Lacs) are reported. The general properties of the 3LAC sample confirm previous findings from earlier catalogs. The fraction of 3LAC blazars in the total population of blazars listed in BZCAT remains non-negligible even at the faint ends of the BZCAT-blazar radio, optical, and X-ray flux distributions, which hints that even the faintest known blazars could eventually shine in gamma-rays at LAT-detection levels. The energy-flux distributions of the different blazar populations are in good agreement with extrapolation from earlier catalogs.
  •  
43.
  • Ackermann, M., et al. (författare)
  • Updated search for spectral lines from Galactic dark matter interactions with pass 8 data from the Fermi Large Area Telescope
  • 2015
  • Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 91:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Dark matter in the Milky Way may annihilate directly into. rays, producing a monoenergetic spectral line. Therefore, detecting such a signature would be strong evidence for dark matter annihilation or decay. We search for spectral lines in the Fermi Large Area Telescope observations of the Milky Way halo in the energy range 200 MeV-500 GeV using analysis methods from our most recent line searches. The main improvements relative to previous works are our use of 5.8 years of data reprocessed with the Pass 8 event-level analysis and the additional data resulting from the modified observing strategy designed to increase exposure of the Galactic center region. We search in five sky regions selected to optimize sensitivity to different theoretically motivated dark matter scenarios and find no significant detections. In addition to presenting the results from our search for lines, we also investigate the previously reported tentative detection of a line at 133 GeV using the new Pass 8 data.
  •  
44.
  • Adori, Csaba, et al. (författare)
  • Critical role of somatostatin receptor 2 in the vulnerability of the central noradrenergic system : new aspects on Alzheimer's disease
  • 2015
  • Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 129:4, s. 541-563
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease and other age-related neurodegenerative disorders are associated with deterioration of the noradrenergic locus coeruleus (LC), a probable trigger for mood and memory dysfunction. LC noradrenergic neurons exhibit particularly high levels of somatostatin binding sites. This is noteworthy since cortical and hypothalamic somatostatin content is reduced in neurodegenerative pathologies. Yet a possible role of a somatostatin signal deficit in the maintenance of noradrenergic projections remains unknown. Here, we deployed tissue microarrays, immunohistochemistry, quantitative morphometry and mRNA profiling in a cohort of Alzheimer's and age-matched control brains in combination with genetic models of somatostatin receptor deficiency to establish causality between defunct somatostatin signalling and noradrenergic neurodegeneration. In Alzheimer's disease, we found significantly reduced somatostatin protein expression in the temporal cortex, with aberrant clustering and bulging of tyrosine hydroxylase-immunoreactive afferents. As such, somatostatin receptor 2 (SSTR2) mRNA was highly expressed in the human LC, with its levels significantly decreasing from Braak stages III/IV and onwards, i.e., a process preceding advanced Alzheimer's pathology. The loss of SSTR2 transcripts in the LC neurons appeared selective, since tyrosine hydroxylase, dopamine beta-hydroxylase, galanin or galanin receptor 3 mRNAs remained unchanged. We modeled these pathogenic changes in Sstr2 (-/-) mice and, unlike in Sstr1 (-/-) or Sstr4 (-/-) genotypes, they showed selective, global and progressive degeneration of their central noradrenergic projections. However, neuronal perikarya in the LC were found intact until late adulthood (< 8 months) in Sstr2 (-/-) mice. In contrast, the noradrenergic neurons in the superior cervical ganglion lacked SSTR2 and, as expected, the sympathetic innervation of the head region did not show any signs of degeneration. Our results indicate that SSTR2-mediated signaling is integral to the maintenance of central noradrenergic projections at the system level, and that early loss of somatostatin receptor 2 function may be associated with the selective vulnerability of the noradrenergic system in Alzheimer's disease.
  •  
45.
  • Ajello, M., et al. (författare)
  • Impulsive and long duration high-energy gamma-ray emission from the very bright 2012 march 7 solar flares
  • 2014
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 789:1, s. 20-
  • Tidskriftsartikel (refereegranskat)abstract
    • The Fermi Large Area Telescope (LAT) detected gamma-rays up to 4 GeV from two bright X-class solar flares on 2012 March 7, showing both an impulsive and temporally extended emission phases. The gamma-rays appear to originate from the same active region as the X-rays associated with these flares. The >100 MeV gamma-ray flux decreases monotonically during the first hour (impulsive phase) followed by a slower decrease for the next 20 hr. A power law with a high-energy exponential cutoff can adequately describe the photon spectrum. Assuming that the gamma rays result from the decay of pions produced by accelerated protons and ions with a power-law spectrum, we find that the index of that spectrum is similar to 3, with minor variations during the impulsive phase. During the extended phase the photon spectrum softens monotonically, requiring the proton index varying from similar to 4 to >5. The >30 MeV proton flux observed by the GOES satellites also shows a flux decrease and spectral softening, but with a harder spectrum (index similar to 2-3). Based on these observations, we explore the relative merits of prompt or continuous acceleration scenarios, hadronic or leptonic emission processes, and acceleration at the solar corona or by the fast coronal mass ejections. We conclude that the most likely scenario is continuous acceleration of protons in the solar corona that penetrate the lower solar atmosphere and produce pions that decay into gamma rays. However, acceleration in the downstream of the shock cannot be definitely ruled out.
  •  
46.
  • Albrecht, Eva, et al. (författare)
  • Telomere length in circulating leukocytes is associated with lung function and disease
  • 2014
  • Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 43:4, s. 983-992
  • Tidskriftsartikel (refereegranskat)abstract
    • Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in is (FEV1), forced vital capacity (PVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (beta= -0.0452, p= 0.024) as well as COPD (beta= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07 x 10(-7)), FVC (p=2.07 x 10(-5)), and FEV1/FVC (p =5.27 x 10(-3)). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.
  •  
47.
  • Andreasson, Jakob, 1975, et al. (författare)
  • Electron-lattice interactions in the perovskite LaFe0.5Cr0.5O3 characterized by optical spectroscopy and LDA plus U calculations
  • 2009
  • Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X .- 2469-9950 .- 2469-9969. ; 80:7, s. 075103-
  • Tidskriftsartikel (refereegranskat)abstract
    • We use resonance Raman scattering (incident photon energies between 1.8 and 4.13 eV), LDA+U calculations, spectroscopic ellipsometry, and oblique IR reflectivity to characterize the strong electron-phonon interactions in the disordered perovskite LaFe0.5Cr0.5O3. When the photon energy coincides with a Cr to Fe Mott-Hubbard transfer gap around 2.4 eV the electron-phonon interaction is manifested by a Franck-Condon effect with exceptional first-and higher order scattering of a local oxygen breathing mode. At higher incident energies we observe a superposition of Franck-Condon scattering and Frohlich interaction induced infrared active longitudinal optical two-phonon scattering activated mainly by O to Fe charge transfer. Our results establish LaFe0.5Cr0.5O3 as a model compound for research on electron-phonon interactions in strongly correlated complex systems and show that Franck-Condon scattering in complex solids is not limited to Jahn-Teller active compounds.
  •  
48.
  • Aquila, Andrew, et al. (författare)
  • Time-resolved protein nanocrystallography using an X-ray free-electron laser
  • 2012
  • Ingår i: Optics Express. - 1094-4087. ; 20:3, s. 2706-2716
  • Tidskriftsartikel (refereegranskat)abstract
    • We demonstrate the use of an X-ray free electron laser synchronized with an optical pump laser to obtain X-ray diffraction snapshots from the photoactivated states of large membrane protein complexes in the form of nanocrystals flowing in a liquid jet. Light-induced changes of Photosystem I-Ferredoxin co-crystals were observed at time delays of 5 to 10 µs after excitation. The result correlates with the microsecond kinetics of electron transfer from Photosystem I to ferredoxin. The undocking process that follows the electron transfer leads to large rearrangements in the crystals that will terminally lead to the disintegration of the crystals. We describe the experimental setup and obtain the first time-resolved femtosecond serial X-ray crystallography results from an irreversible photo-chemical reaction at the Linac Coherent Light Source. This technique opens the door to time-resolved structural studies of reaction dynamics in biological systems.
  •  
49.
  • Artigas, MS, et al. (författare)
  • Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation
  • 2015
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 8658-
  • Tidskriftsartikel (refereegranskat)abstract
    • Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10−8) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.
  •  
50.
  • Artigas Soler, María, et al. (författare)
  • Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
  • 2011
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
  •  
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