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| 7. |
- Sampson, Joshua N., et al.
(author)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Journal article (peer-reviewed)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 9. |
- Allaria, E., et al.
(author)
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Highly coherent and stable pulses from the FERMI seeded free-electron laser in the extreme ultraviolet
- 2012
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In: Nature Photonics. - 1749-4885. ; 6:10, s. 699-704
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Journal article (peer-reviewed)abstract
- Free-electron lasers (FELs) are promising devices for generating light with laser-like properties in the extreme ultraviolet and X-ray spectral regions. Recently, FELs based on the self-amplified spontaneous emission (SASE) mechanism have allowed major breakthroughs in diffraction and spectroscopy applications, despite the relatively large shot-to-shot intensity and photon-energy fluctuations and the limited longitudinal coherence inherent in the SASE mechanism. Here, we report results on the initial performance of the FERMI seeded FEL, based on the high-gain harmonic generation configuration, in which an external laser is used to initiate the emission process. Emission from the FERMI FEL-1 source occurs in the form of pulses carrying energy of several tens of microjoules per pulse and tunable throughout the 65 to 20 nm wavelength range, with unprecedented shot-to-shot wavelength stability, low-intensity fluctuations, close to transform-limited bandwidth, transverse and longitudinal coherence and full control of polarization.
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| 10. |
- Donnarumma, I., et al.
(author)
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Multiwavelength Observations of 3C 454.3. II. The AGILE 2007 December Campaign
- 2009
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In: Astrophysical Journal Letters. - 2041-8205. ; 707:2, s. 1115-1123
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Journal article (peer-reviewed)abstract
- We report on the second Astrorivelatore Gamma a Immagini Leggero (AGILE) multiwavelength campaign of the blazar 3C 454.3 during the first half of 2007 December. This campaign involved AGILE, Spitzer, Swift, Suzaku, the Whole Earth Blazar Telescope (WEBT) consortium, the Rapid Eye Mount (REM), and the Multicolor Imaging Telescopes for Survey and Monstrous Explosions (MITSuME) telescopes, offering a broadband coverage that allowed for a simultaneous sampling of the synchrotron and inverse Compton (IC) emissions. The two-week AGILE monitoring was accompanied by radio to optical monitoring by WEBT and REM, and by sparse observations in mid-infrared and soft/ hard X-ray energy bands performed by means of Target of Opportunity observations by Spitzer, Swift, and Suzaku, respectively. The source was detected with an average flux of similar to 250 x 10(-8) photons cm(-2) s(-1) above 100 MeV, typical of its flaring states. The simultaneous optical and gamma-ray monitoring allowed us to study the time lag associated with the variability in the two energy bands, resulting in a possible <= one-day delay of the gamma-ray emission with respect to the optical one. From the simultaneous optical and gamma-ray fast flare detected on December 12, we can constrain the delay between the gamma-ray and optical emissions within 12 hr. Moreover, we obtain three spectral energy distributions (SEDs) with simultaneous data for 2007 December 5, 13, and 15, characterized by the widest multifrequency coverage. We found that a model with an external Compton on seed photons by a standard disk and reprocessed by the broad-line regions does not describe in a satisfactory way the SEDs of 2007 December 5, 13, and 15. An additional contribution, possibly from the hot corona with T = 10(6) K surrounding the jet, is required to account simultaneously for the softness of the synchrotron and the hardness of the IC emissions during those epochs.
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| 11. |
- Feroci, M., et al.
(author)
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Monitoring the hard X-ray sky with SuperAGILE
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 510, s. A9-
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Journal article (peer-reviewed)abstract
- Context SuperAGILE is the hard X-ray monitor of the AGILE gamma ray mission, in orbit since 23 April 2007. It is an imaging experiment based on a set of four independent silicon strip detectors, equipped with one-dimensional coded masks, operating in the nominal energy range 18-60 keV. Aims. The main goal of SuperAGILE is the observation of cosmic sources simultaneously with the main gamma-ray AGILE experiment, the Gamma Ray Imaging Detector (GRID). Given its similar to steradian-wide field of view and its similar to 15 mCrab day-sensitivity, SuperAGILE is also well suited to the long-term monitoring of Galactic compact objects and the detection of bright transients. Methods. The SuperAGILE detector properties and design allow for a 6 arcmin angular resolution in each of the two independent orthogonal projections of the celestial coordinates. Photon by photon data are continuously available by means of experiment telemetry, and are used to derive images and fluxes of individual sources, with integration times depending on the source intensity and position in the field of view. Results. We report on the main scientific results achieved by SuperAGILE over its first two years in orbit, until April 2009. The scientific observations started in mid-July 2007, with the science verification phase, continuing during the complete AGILE Cycle 1 and the first similar to half of Cycle 2. Despite the largely non-uniform sky coverage, due to the pointing strategy of the AGILE mission, a few tens of Galactic sources were monitored, sometimes for unprecedently long continuous periods, leading to the detection also of several bursts and outbursts. Approximately one gamma ray burst per month was detected and localized, allowing for prompt multi-wavelength observations. A few extragalactic sources in bright states were occasionally detected as well. The light curves of sources measured by SuperAGILE are made publicly available on the web in almost real-time. To enable a proper scientific use of these, we provide the reader with the relevant scientific and technical background.
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| 12. |
- Longo, F., et al.
(author)
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Upper limits on the high-energy emission from gamma-ray bursts observed by AGILE-GRID
- 2012
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 547, s. A95-
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Journal article (peer-reviewed)abstract
- Context. The detection and the characterization of the highenergy emission component from individual gamma-ray bursts (GRBs) is one of the key science objectives of the currently operating gamma-ray satellite AGILE, launched in April 2007. In its first two years of operation AGILE detected three GRBs with photons of energy larger than 30 MeV. One more GRB was detected in AGILE third operation year, while operating in spinning mode. Aims. For the 64 other GRBs localized during the period July 2007 to October 2009 in the field of view of the AGILE Gamma-Ray Imaging Detector (GRID), but not detected by this instrument, we estimate the count and flux upper limits on the GRB high energy emission in the AGILE-GRID energy band (30 MeV-3 GeV). Methods. To calculate the count upper limits, we adopted a Bayesian approach. The flux upper limits are derived using several assumptions on the high-energy spectral behavior. For 28 GRBs with available prompt spectral information, a flux upper limit and the comparison with the expected flux estimated from spectral extrapolation of the Band spectrum to the 30 MeV-3 GeV band are provided. Moreover, upper limits on the flux under the assumption of an extra power law component dominating the 30 MeV-3 GeV band are calculated for all GRBs and considering four different values for the spectral photon index. Finally, we performed a likelihood upper limit on the possible delayed emission up to 1 h after the GRB. Results. The estimated flux upper limits range between 1 × 10 -4 and ∼2 × 10 -2 photons cm -2 s -1 and generally lie above the flux estimated from the extrapolation of the prompt emission in the 30 MeV-3 GeV band. A notable case is GRB 080721, where the AGILE-GRID upper limit suggests a steeper spectral index or the presence of a cut-off in the high energy part of the Band prompt spectrum. The four GRBs detected by AGILE-GRID show high-energy (30 MeV-3 GeV) to low-energy (1 keV-10 MeV) fluence ratios similar to those estimated in this paper for the 64 GRBs without GRID detection, favoring the possibility that AGILE-GRID detected only high-fluence, hard GRBs. From the flux upper limits derived in this work we put some constraint on high-energy radiation from the afterglow emission and from synchrotron self Compton emission in internal shocks.
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| 13. |
- Pellizzoni, A., et al.
(author)
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Detection of Gamma-Ray Emission from the Vela Pulsar Wind Nebula with AGILE
- 2010
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 327:5966, s. 663-665
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Journal article (peer-reviewed)abstract
- Pulsars are known to power winds of relativistic particles that can produce bright nebulae by interacting with the surrounding medium. These pulsar wind nebulae are observed by their radio, optical, and x-ray emissions, and in some cases also at TeV (teraelectron volt) energies, but the lack of information in the gamma-ray band precludes drawing a comprehensive multiwavelength picture of their phenomenology and emission mechanisms. Using data from the AGILE satellite, we detected the Vela pulsar wind nebula in the energy range from 100 MeV to 3 GeV. This result constrains the particle population responsible for the GeV emission and establishes a class of gamma-ray emitters that could account for a fraction of the unidentified galactic gamma-ray sources.
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| 14. |
- Pittori, C., et al.
(author)
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First AGILE catalog of high-confidence gamma-ray sources
- 2009
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 506:3, s. 1563-1574
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Journal article (peer-reviewed)abstract
- We present the first catalog of high-confidence gamma-ray sources detected by the AGILE satellite during observations performed from July 9, 2007 to June 30, 2008. Cataloged sources were detected by merging all the available data over the entire time period. AGILE, launched in April 2007, is an ASI mission devoted to gamma-ray observations in the 30 MeV-50 GeV energy range, with simultaneous X-ray imaging capability in the 18-60 keV band. This catalog is based on Gamma-Ray Imaging Detector (GRID) data for energies greater than 100 MeV. For the first AGILE catalog, we adopted a conservative analysis, with a high-quality event filter optimized to select gamma-ray events within the central zone of the instrument field of view (radius of 40 degrees). This is a significance-limited (4 sigma) catalog, and it is not a complete flux-limited sample due to the non-uniform first-year AGILE sky coverage. The catalog includes 47 sources, 21 of which are associated with confirmed or candidate pulsars, 13 with blazars (7 FSRQ, 4 BL Lacs, 2 unknown type), 2 with HMXRBs, 2 with SNRs, 1 with a colliding-wind binary system, and 8 with unidentified sources.
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| 15. |
- Tavani, M., et al.
(author)
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Detection of Gamma-Ray Emission from the Eta-Carinae Region
- 2009
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In: ASTROPHYSICAL JOURNAL LETTERS. - 2041-8205. ; 698:2, s. L142-L146
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Journal article (peer-reviewed)abstract
- We present the results of extensive observations by the gamma-ray AGILE satellite of the Galactic region hosting the Carina nebula and the remarkable colliding wind binary Eta Carinae (eta Car) during the period 2007 July-2009 January. We detect a gamma-ray source (1AGL J1043-5931) consistent with the position of eta Car. If 1AGL J1043-5931 is associated with the Car system, our data provide the long sought first detection above 100 MeV of a colliding wind binary. The average gamma-ray flux above 100 MeV and integrated over the preperiastron period 2007 July-2008 October is F(gamma) = (37 +/- 5) x 10(-8) ph cm(-2) s(-1) corresponding to an average gamma-ray luminosity of L(gamma) = 3.4 x 10(34) erg s(-1) for a distance of 2.3 kpc. We also report a two-day gamma-ray flaring episode of 1AGL J1043-5931 on 2008 October 11-13 possibly related to a transient acceleration and radiation episode of the strongly variable shock in the system.
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| 16. |
- Ankowski, A., et al.
(author)
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Energy reconstruction of electromagnetic showers from Ν0 decays with the ICARUS T600 liquid argon TPC
- 2010
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In: Acta Physica Polonica, Series B.. - 1509-5770 .- 0587-4254. ; 41:1, s. 103-125
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Journal article (peer-reviewed)abstract
- We discuss the ICARUS T600 detector capabilities in electromagnetic shower reconstruction through the analysis of a sample of 212 events, coming from the 2001 Pavia surface test run, of hadronic interactions leading to the production of π 0 mesons. Methods of shower energy and shower direction measurements were developed and the invariant mass of the photon pairs was reconstructed. The (γγ) invariant mass was found to be consistent with the value of the π 0 mass. The resolution of the reconstructed π 0 mass was found to be equal to 27.3%. An improved analysis, carried out in order to clean the full event sample from the events measured in the crowded environment, mostly due to the trigger conditions, gave a π 0 mass resolution of 16.1%, significantly better than the one evaluated for the full event sample. The trigger requirement of the coincidence of at least four photo-multiplier signals favored the selection of events with a strong pile up of cosmic ray tracks and interactions. Hence a number of candidate π 0 events were heavily contaminated by other tracks and had to be rejected. Monte Carlo simulations of events with π 0 production in hadronic and neutrino interactions confirmed the validity of the shower energy and shower direction reconstruction methods applied to the real data.
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| 17. |
- Ankowski, A, et al.
(author)
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Energy reconstruction of electromagnetic showers from π0 decays with the ICARUS T600 liquid argon TPC
- 2010
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In: Acta Physica Polonica B. - : Jagellonian University. - 0587-4254 .- 1509-5770. ; 41:1, s. 103-125
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Journal article (peer-reviewed)abstract
- We discuss the ICARUS T600 detector capabilities in electromagnetic shower reconstruction through the analysis of a sample of 212 events, coming from the 2001 Pavia surface test run, of hadronic interactions leading to the production of π0 mesons. Methods of shower energy and shower direction measurements were developed and the invariant mass of the photon pairs was reconstructed. The (γ,γ) invariant mass was found to be consistent with the value of the π0 mass. The resolution of the reconstructed π0 mass was found to be equal to 27.3%. An improved analysis, carried out in order to clean the full event sample from the events measured in the crowded environment, mostly due to the trigger conditions, gave a π0 mass resolution of 16.1%, significantly better than the one evaluated for the full event sample. The trigger requirement of the coincidence of at least four photo-multiplier signals favored the selection of events with a strong pile up of cosmic ray tracks and interactions. Hence a number of candidate π0 events were heavily contaminated by other tracks and had to be rejected. Monte Carlo simulations of events with π0 production in hadronic and neutrino interactions confirmed the validity of the shower energy and shower direction reconstruction methods applied to the real data.
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| 18. |
- Chen, A. W., et al.
(author)
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Calibration of AGILE-GRID with in-flight data and Monte Carlo simulations
- 2013
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 558, s. A37-
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Journal article (peer-reviewed)abstract
- Context. AGILE is a γ-ray astrophysics mission which has been in orbit since 23 April 2007 and continues to operate reliably. The γ-ray detector, AGILE-GRID, has observed Galactic and extragalactic sources, many of which were collected in the first AGILE Catalog. Aims. We present the calibration of the AGILE-GRID using in-flight data and Monte Carlo simulations, producing instrument response functions (IRFs) for the effective area (A eff), energy dispersion probability (EDP), and point spread function (PSF), each as a function of incident direction in instrument coordinates and energy. Methods. We performed Monte Carlo simulations at different γ-ray energies and incident angles, including background rejection filters and Kalman filter-based γ-ray reconstruction. Long integrations of in-flight observations of the Vela, Crab and Geminga sources in broad and narrow energy bands were used to validate and improve the accuracy of the instrument response functions. Results. The weighted average PSFs as a function of spectra correspond well to the data for all sources and energy bands. Conclusions. Changes in the interpolation of the PSF from Monte Carlo data and in the procedure for construction of the energy-weighted effective areas have improved the correspondence between predicted and observed fluxes and spectra of celestial calibration sources, reducing false positives and obviating the need for post-hoc energy-dependent scaling factors. The new IRFs have been publicly available from the AGILE Science Data Center since November 25, 2011, while the changes in the analysis software will be distributed in an upcoming release.
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| 19. |
- Cozen, W., et al.
(author)
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A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus
- 2014
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3856-
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Journal article (peer-reviewed)abstract
- Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR) = 0.81, 95% confidence interval (95% CI) = 0.76-0.86, P-combined 3.5 x 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B-and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.
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| 20. |
- Marisaldi, M., et al.
(author)
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Detection of terrestrial gamma ray flashes up to 40 MeV by the AGILE satellite
- 2010
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In: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 115:3, s. A00E13-
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Journal article (peer-reviewed)abstract
- We report the detection by the Astrorivelatore Gamma a Immagini Leggero (AGILE) satellite of terrestrial gamma ray flashes (TGFs) obtained with the minicalorimeter (MCAL) detector operating in the energy range 0.3-100 MeV. We select events typically lasting a few milliseconds with spectral and directional selections consistent with the TGF characteristics previously reported by other space missions. During the period 1 June 2008 to 31 March 2009 we detect 34 high-confidence events showing millisecond durations and a geographical distribution peaked over continental Africa and Southeast Asia. For the first time, AGILE-MCAL detects photons associated with TGF events up to 40 MeV. We determine the cumulative spectral properties of the spectrum in the range 0.5-40 MeV, which can be effectively described by a Bremsstrahlung spectrum. We find that both the TGF cumulative spectral properties and their geographical distribution are in good agreement with the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) results.
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| 21. |
- Tavani, M., et al.
(author)
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Direct Evidence for Hadronic Cosmic-Ray Acceleration in the Supernova Remnant IC 443
- 2010
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In: The Astrophysical Journal. Letters. - 2041-8205. ; 710:2, s. L151-L155
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Journal article (peer-reviewed)abstract
- The supernova remnant (SNR) IC 443 is an intermediate-age remnant well known for its radio, optical, X-ray, and gamma-ray energy emissions. In this Letter, we study the gamma-ray emission above 100 MeV from IC 443 as obtained by the AGILE satellite. A distinct pattern of diffuse emission in the energy range 100 MeV-3 GeV is detected across the SNR with its prominent maximum (source "A") localized in the northeastern shell with a flux F = (47 +/- 10) x 10(-8) photons cm(-2) s(-1) above 100 MeV. This location is the site of the strongest shock interaction between the SNR blast wave and the dense circumstellar medium. Source "A" is not coincident with the TeV source located 0.4. away and associated with a dense molecular cloud complex in the SNR central region. From our observations, and from the lack of detectable diffuse TeV emission from its northeastern rim, we demonstrate that electrons cannot be the main emitters of gamma rays in the range 0.1-10 GeV at the site of the strongest SNR shock. The intensity, spectral characteristics, and location of the most prominent gamma-ray emission together with the absence of cospatial detectable TeV emission are consistent only with a hadronic model of cosmic-ray acceleration in the SNR. A high-density molecular cloud (cloud "E") provides a remarkable "target" for nucleonic interactions of accelerated hadrons; our results show enhanced gamma-ray production near the molecular cloud/shocked shell interaction site. IC 443 provides the first unambiguous evidence of cosmic-ray acceleration by SNRs.
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| 22. |
- Apponi, A., et al.
(author)
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Heisenberg's uncertainty principle in the PTOLEMY project : A theory update
- 2022
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In: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 106:5
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Journal article (peer-reviewed)abstract
- We discuss the consequences of the quantum uncertainty on the spectrum of the electron emitted by the beta-processes of a tritium atom bound to a graphene sheet. We analyze quantitatively the issue recently raised by Cheipesh, Cheianov, and Boyarsky [Phys. Rev. D 104, 116004 (2021)], and discuss the relevant timescales and the degrees of freedom that can contribute to the intrinsic spread in the electron energy. We perform careful calculations of the potential between tritium and graphene with different coverages and geometries. With this at hand, we propose possible avenues to mitigate the effect of the quantum uncertainty.
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| 23. |
- Berndt, Sonja I., et al.
(author)
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Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P = 2.55 x 10(-11)), 6p25.2 (rs73718779, SERPINB6, P = 1.97 x 10(-8)) and 3q28 (rs9815073, LPP, P = 3.62 x 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P = 1.00 x 10(-11)) in the combined analysis. We find suggestive evidence (P<5 x 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P = 7.19 x 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P = 2.12 x 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.
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| 24. |
- Giuliani, A., et al.
(author)
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AGILE Detection of Delayed Gamma-ray Emission From the Short Gamma-Ray Burst GRB 090510
- 2010
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In: Astrophysical Journal Letters. - 2041-8205. ; 708:2, s. L84-L88
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Journal article (peer-reviewed)abstract
- Short gamma-ray bursts (GRBs), typically lasting less than 2 s, are a special class of GRBs of great interest. We report the detection by the AGILE satellite of the short GRB 090510 which shows two clearly distinct emission phases: a prompt phase lasting similar to 200 ms and a second phase lasting tens of seconds. The prompt phase is relatively intense in the 0.3-10 MeV range with a spectrum characterized by a large peak/cutoff energy near 3 MeV; in this phase, no significant high-energy gamma-ray emission is detected. At the end of the prompt phase, intense gamma-ray emission above 30 MeV is detected showing a power-law time decay of the flux of the type t(-1.3) and a broadband spectrum remarkably different from that of the prompt phase. It extends from sub-MeV to hundreds of MeV energies with a photon index alpha similar or equal to 1.5. GRB 090510 provides the first case of a short GRB with delayed gamma-ray emission. We present the timing and spectral data of GRB 090510 and briefly discuss its remarkable properties within the current models of gamma-ray emission of short GRBs.
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| 25. |
- Betti, M. G., et al.
(author)
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Neutrino physics with the PTOLEMY project : active neutrino properties and the light sterile case
- 2019
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In: Journal of Cosmology and Astroparticle Physics. - : IOP PUBLISHING LTD. - 1475-7516. ; :7
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Journal article (peer-reviewed)abstract
- The PTOLEMY project aims to develop a scalable design for a Cosmic Neutrino Background (CNB) detector, the first of its kind and the only one conceived that can look directly at the image of the Universe encoded in neutrino background produced in the first second after the Big Bang. The scope of the work for the next three years is to complete the conceptual design of this detector and to validate with direct measurements that the non-neutrino backgrounds are below the expected cosmological signal. In this paper we discuss in details the theoretical aspects of the experiment and its physics goals. In particular, we mainly address three issues. First we discuss the sensitivity of PTOLEMY to the standard neutrino mass scale. We then study the perspectives of the experiment to detect the CNB via neutrino capture on tritium as a function of the neutrino mass scale and the energy resolution of the apparatus. Finally, we consider an extra sterile neutrino with mass in the eV range, coupled to the active states via oscillations, which has been advocated in view of neutrino oscillation anomalies. This extra state would contribute to the tritium decay spectrum, and its properties, mass and mixing angle, could be studied by analyzing the features in the beta decay electron spectrum.
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| 26. |
- Del Monte, E., et al.
(author)
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The observation of GRBs with AGILE and the interesting cases of GRB 090618 and GRB 100724B
- 2011
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In: AIP Conf. Proc.. - : AIP. - 9780735409163 ; , s. 209-212
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Conference paper (peer-reviewed)abstract
- The AGILE satellite, in orbit since 2007, is localizing about 0.5 GRBs per month with the hard X-ray Imager superagile (18-60 keV) and is detecting around 1 GRB per week with the non-imaging Minicalorimeter (0.35 - 100 MeV). Up to now the AGILE Gamma Ray Imaging Detector firmly detected four GRBs in the energy band between 20 MeV and few GeV. In this presentation we review the status of the GRBs observation with AGILE, we discuss the upper limits in the gamma-ray band of the non-detected events and we show some interesting bursts, especially GRB 090618 (bright in soft and hard-X rays, optical and radio but lacking GeV emission) and GRB 100724B (with a bright GeV emission simultaneous to hard-X rays without delayed onset).
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| 27. |
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| 28. |
- Rubbia, C, et al.
(author)
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Underground operation of the ICARUS T600 LAr-TPC : first results
- 2011
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In: Journal of Instrumentation. ; 6:07
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Journal article (peer-reviewed)abstract
- Important open questions are still present in fundamental Physics and Cosmology, like the nature of Dark Matter, the matter-antimatter asymmetry and the validity of the Standard Model of particle interactions. Addressing these questions requires a new generation of massive particle detectors to explore the subatomic and astrophysical worlds. ICARUS T600 is the first large mass (760 tons) example of a new generation of detectors able to combine the imaging capabilities of the old famous “bubble chamber” with the excellent energy measurement of huge electronic detectors. ICARUS T600 now operates at the Gran Sasso underground laboratory and is used to study cosmic rays, neutrino oscillations and the proton decay. The potential for doing physics of this novel telescope is presented through a few examples of neutrino interactions reconstructed with unprecedented detail. Detector design and early operation are also reported.
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| 29. |
- Apponi, A., et al.
(author)
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Implementation and optimization of the PTOLEMY transverse drift electromagnetic filter
- 2022
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In: Journal of Instrumentation. - : IOP Publishing Ltd. - 1748-0221. ; 17:5
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Journal article (peer-reviewed)abstract
- The PTOLEMY transverse drift filter is a new concept to enable precision analysis of the energy spectrum of electrons near the tritium beta-decay endpoint. This paper details the implementation and optimization methods for successful operation of the filter for electrons with a known pitch angle. We present the first demonstrator that produces the required magnetic field properties with an iron return-flux magnet. Two methods for the setting of filter electrode voltages are detailed. The challenges of low-energy electron transport in cases of low field are discussed, such as the growth of the cyclotron radius with decreasing magnetic field, which puts a ceiling on filter performance relative to fixed filter dimensions. Additionally, low pitch angle trajectories are dominated by motion parallel to the magnetic field lines and introduce non-adiabatic conditions and curvature drift. To minimize these effects and maximize electron acceptance into the filter, we present a three-potential-well design to simultaneously drain the parallel and transverse kinetic energies throughout the length of the filter. These optimizations are shown, in simulation, to achieve low-energy electron transport from a 1 T iron core (or 3 T superconducting) starting field with initial kinetic energy of 18.6 keV drained to < 10 eV (< 1 eV) in about 80 cm. This result for low field operation paves the way for the first demonstrator of the PTOLEMY spectrometer for measurement of electrons near the tritium endpoint to be constructed at the Gran Sasso National Laboratory (LNGS) in Italy.
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| 30. |
- Berndt, Sonja, I, et al.
(author)
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Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
- 2022
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In: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:12, s. 2835-2844
-
Journal article (peer-reviewed)abstract
- Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
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| 31. |
- Berndt, Sonja I., et al.
(author)
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Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:8, s. 868-U202
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 x 10(-14)), 18q21.33 (BCL2, P = 7.76 x 10(-11)), 11p15.5 (C11orf21, P = 2.15 x 10(-10)), 4q25 (LEF1, P = 4.24 x 10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10(-9)), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10(-8)), 18q21.32 (PMAIP1, P = 2.51 x 10(-8)), 15q15.1 (BMF, P = 2.71 x 10(-10)) and 2p22.2 (QPCT, P = 1.68 x 10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10(-8)) and 5p15.33 (TERT, P = 1.92 x 10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
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| 32. |
- Betti, M. G., et al.
(author)
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A design for an electromagnetic filter for precision energy measurements at the tritium endpoint
- 2019
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In: Progress in Particle and Nuclear Physics. - : Elsevier BV. - 0146-6410 .- 1873-2224. ; 106, s. 120-131
-
Research review (peer-reviewed)abstract
- We present a detailed description of the electromagnetic filter for the PTOLEMY project to directly detect the Cosmic Neutrino Background (CNB). Starting with an initial estimate for the orbital magnetic moment, the higher-order drift process of E x B is configured to balance the gradient-B drift motion of the electron in such a way as to guide the trajectory into the standing voltage potential along the mid-plane of the filter. As a function of drift distance along the length of the filter, the filter zooms in with exponentially increasing precision on the transverse velocity component of the electron kinetic energy. This yields a linear dimension for the total filter length that is exceptionally compact compared to previous techniques for electromagnetic filtering. The parallel velocity component of the electron kinetic energy oscillates in an electrostatic harmonic trap as the electron drifts along the length of the filter. An analysis of the phase-space volume conservation validates the expected behavior of the filter from the adiabatic invariance of the orbital magnetic moment and energy conservation following Liouville's theorem for Hamiltonian systems.
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| 33. |
- Conde, Lucia, et al.
(author)
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Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:8, s. 661-664
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Journal article (peer-reviewed)abstract
- To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)).
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| 34. |
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| 35. |
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| 36. |
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| 37. |
- Din, Lennox, et al.
(author)
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Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes
- 2019
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In: Genetic Epidemiology. - : WILEY. - 0741-0395 .- 1098-2272. ; 43:7, s. 844-863
-
Journal article (peer-reviewed)abstract
- Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p =.0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.
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| 38. |
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| 39. |
- Pearce, Neil E, et al.
(author)
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IARC Monographs : 40 Years of Evaluating Carcinogenic Hazards to Humans
- 2015
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In: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 507-514
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' failures to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.OBJECTIVES: The authors of this paper are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We have examined here criticisms of the IARC classification process to determine the validity of these concerns. We review the history of IARC evaluations and describe how the IARC evaluations are performed.DISCUSSION: We conclude that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various discipline and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.
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| 40. |
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| 41. |
- Skibola, Christine F, et al.
(author)
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Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region.
- 2014
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 95:4, s. 462-471
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [ORper-allele] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (ORper-allele = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.
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| 42. |
- Hensiek, A E, et al.
(author)
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Familial effects on the clinical course of multiple sclerosis.
- 2007
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In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 1526-632X .- 0028-3878. ; 68:5, s. 376-83
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Familial factors influence susceptibility to multiple sclerosis (MS) but it is unknown whether there are additional effects on the natural history of the disease. METHOD: We evaluated 1,083 families with > or =2 first-degree relatives with MS for concordance of age at onset, clinical course, and disease severity and investigated transmission patterns of these clinical features in affected parent-child pairs. RESULTS: There is concordance for age at onset for all families (correlation coefficient 0.14; p < 0.001), as well as for affected siblings (correlation coefficient 0.15; p < 0.001), and affected parent-child pairs (correlation coefficient 0.12; p = 0.03) when each is evaluated separately. Concordance for year of onset is present among affected siblings (correlation coefficient 0.18; p < 0.001) but not the parent-child group (correlation coefficient 0.08; p = 0.15). The clinical course is similar between siblings (kappa 0.12; p < 0.001) but not affected parents and their children (kappa -0.04; p = 0.09). This influence on the natural history is present in all clinical subgroups of relapsing-remitting, and primary and secondary progressive MS, reflecting a familial effect on episodic and progressive phases of the disease. There is no concordance for disease severity within any of the considered family groups (correlation coefficients: all families analyzed together, 0.02, p = 0.53; affected sibling group, 0.02, p = 0.61; affected parent-child group, 0.02, p = 0.69). Furthermore, there are no apparent transmission patterns of any of the investigated clinical features in affected parent-child pairs and no evidence for anticipation or effects of genetic loading. CONCLUSION: Familial factors do not significantly affect eventual disease severity. However, they increase the probability of a progressive clinical course, either from onset or after a phase of relapsing remitting disease. The familial effect is more likely to reflect genetic than environmental conditions. The results are relevant for counseling patients and have implications for the design of studies seeking to identify factors that influence the natural history of the disease.
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| 43. |
- Law, PJ, et al.
(author)
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Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
- 2017
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8, s. 14175-
-
Journal article (peer-reviewed)abstract
- Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.
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| 44. |
- Percetti, M., et al.
(author)
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TWNK in Parkinson's Disease: A Movement Disorder and Mitochondrial Disease Center Perspective Study
- 2022
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In: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 37:9, s. 1938-1943
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Journal article (peer-reviewed)abstract
- Background Parkinsonian features have been described in patients harboring variants in nuclear genes encoding for proteins involved in mitochondrial DNA maintenance, such as TWNK. Objectives The aim was to screen for TWNK variants in an Italian cohort of Parkinson's disease (PD) patients and to assess the occurrence of parkinsonism in patients presenting with TWNK-related autosomal dominant progressive external ophthalmoplegia (TWNK-adPEO). Methods Genomic DNA of 263 consecutively collected PD patients who underwent diagnostic genetic testing was analyzed with a targeted custom gene panel including TWNK, as well as genes causative of monogenic PD. Genetic and clinical data of 18 TWNK-adPEO patients with parkinsonism were retrospectively analyzed. Results Six of 263 PD patients (2%), presenting either with isolated PD (n = 4) or in combination with bilateral ptosis (n = 2), carried TWNK likely pathogenic variants. Among 18 TWNK-adPEO patients, 5 (28%) had parkinsonism. Conclusions We show candidate TWNK variants occurring in PD without PEO. This finding will require further confirmatory studies. (c) 2022 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
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| 45. |
- Wang, Sophia S., et al.
(author)
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HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes
- 2018
-
In: Cancer Research. - 0008-5472 .- 1538-7445. ; 78:14, s. 4086-4096
-
Journal article (peer-reviewed)abstract
- A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06-1.60; OR MZL = 1.45, 95% CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24-3.55; OR MZL = 2.10, 95% CI = 0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma.
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| 46. |
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| 47. |
- Campus, G., et al.
(author)
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Fluoride Concentration from Dental Sealants: A Randomized Clinical Trial
- 2013
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In: Journal of Dental Research. - : SAGE Publications. - 0022-0345 .- 1544-0591. ; 92:S7
-
Journal article (peer-reviewed)abstract
- A randomized clinical trial was performed in schoolchildren (6-7 yrs) to evaluate fluoride concentration in interproximal fluid after the placement of 3 different sealants. The sample consisted of 2,776 children randomly divided: 926 in the high-viscosity Glass-ionomer Cement group (GIC group), 923 in the fluoride Resin-based group (fluoride-RB group), and 927 in the no-fluoride Resin-based group (RB group). In total, 2,640 children completed the trial. Sealants were applied following manufacturer's instructions. Interproximal fluid samples were collected at baseline and 2, 7, and 21 days after application of sealants, by insertion of a standardized paperpoint into the interproximal mesial space of the sealed tooth for 15 seconds. Fluoride concentration was evaluated by means of a fluoride ion-selective electrode. At 2 days after sealant application, fluoride concentration was significantly higher in GIC and fluoride-RB groups compared with that in the RB group (p < .01). Mean fluoride concentrations after 7 days were 2.54 (SE 0.68) ppm, 0.85 (SE 0.26) ppm, and 0.53 (SE 0.11) ppm for the three groups, respectively. After 21 days, fluoride concentration in the GIC group remained higher than that in the other two groups. High-viscosity GIC sealants increased the fluoride concentrations in interproximal fluid more than did a Resin-based sealant containing fluoride (ClinicalTrials.gov NCT01588210).
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| 48. |
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| 49. |
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| 50. |
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