Polymorphism at High Molecular Weight Glutenin Subunits and Morphological Diversity of Aegilops geniculata Roth Collected in Algeria

A collection of 35 accessions of the tetraploid wild wheat Aegilops geniculata Roth (MM, UU) sampled in northern Algeria was evaluated for morphological and biochemical variability. Morphological and ecological analyses based on morphological traits and bioclimatic parameters, respectively, were assessed using principal component analysis (PCA). Accessions were differentiated by width characters, namely spike’s width, and a weak relationship between morphological traits and ecological parameters was found. Polymorphism of high molecular weight (HMW) glutenin subunits was carried on by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Among accessions analyzed, 27 alleles were identified at the two loci Glu-M1 and Glu-U1: resulting in twenty-nine patterns and a nomenclature was proposed. Two alleles at the Glu-U1 locus expressed a new subunit with a slightly slower mobility than subunit 8. These results provide new information regarding the genetic variability of HMW glutenin subunits, as well as their usefulness in cultivated wheat quality improvement

Constraints on Dark Matter Annihilation in Clusters of Galaxies with the Fermi Large Area Telescope

Nearby clusters and groups of galaxies are potentially bright sources of high-energy gamma-ray emission resulting from the pair-annihilation of dark matter particles. However, no significant gamma-ray emission has been detected so far from clusters in the first 11 months of observations with the Fermi Large Area Telescope. We interpret this non-detection in terms of constraints on dark matter particle properties. In particular for leptonic annihilation final states and particle masses greater than ~200 GeV, gamma-ray emission from inverse Compton scattering of CMB photons is expected to dominate the dark matter annihilation signal from clusters, and our gamma-ray limits exclude large regions of the parameter space that would give a good fit to the recent anomalous Pamela and Fermi-LAT electron-positron measurements. We also present constraints on the annihilation of more standard dark matter candidates, such as the lightest neutralino of supersymmetric models. The constraints are particularly strong when including the fact that clusters are known to contain substructure at least on galaxy scales, increasing the expected gamma-ray flux by a factor of ~5 over a smooth-halo assumption. We also explore the effect of uncertainties in cluster dark matter density profiles, finding a systematic uncertainty in the constraints of roughly a factor of two, but similar overall conclusions. In this work, we focus on deriving limits on dark matter models; a more general consideration of the Fermi-LAT data on clusters and clusters as gamma-ray sources is forthcoming.Comment: accepted to JCAP, Corresponding authors: T.E. Jeltema and S. Profumo, minor revisions to be consistent with accepted versio

The On-orbit Calibrations for the Fermi Large Area Telescope

The Large Area Telescope (LAT) on--board the Fermi Gamma ray Space Telescope began its on--orbit operations on June 23, 2008. Calibrations, defined in a generic sense, correspond to synchronization of trigger signals, optimization of delays for latching data, determination of detector thresholds, gains and responses, evaluation of the perimeter of the South Atlantic Anomaly (SAA), measurements of live time, of absolute time, and internal and spacecraft boresight alignments. Here we describe on orbit calibration results obtained using known astrophysical sources, galactic cosmic rays, and charge injection into the front-end electronics of each detector. Instrument response functions will be described in a separate publication. This paper demonstrates the stability of calibrations and describes minor changes observed since launch. These results have been used to calibrate the LAT datasets to be publicly released in August 2009.Comment: 60 pages, 34 figures, submitted to Astroparticle Physic

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

The 2009 december gamma-ray flare of 3C 454.3: The multifrequency campaign

During the month of 2009 December, the blazar 3C 454.3 became the brightest gamma-ray source in the sky, reaching a peak flux F 2000 × 10 -8 photons cm-2 s-1 for E > 100 MeV. Starting in 2009 November intensive multifrequency campaigns monitored the 3C 454 gamma-ray outburst. Here, we report on the results of a two-month campaign involving AGILE, INTEGRAL, Swift/XRT, Swift/BAT, and Rossi XTE for the high-energy observations and Swift/UVOT, KANATA, Goddard Robotic Telescope, and REM for the near-IR/optical/UV data. GASP/WEBT provided radio and additional optical data. We detected a long-term active emission phase lasting 1 month at all wavelengths: in the gamma-ray band, peak emission was reached on 2009 December 2-3. Remarkably, this gamma-ray super-flare was not accompanied by correspondingly intense emission in the optical/UV band that reached a level substantially lower than the previous observations in 2007-2008. The lack of strong simultaneous optical brightening during the super-flare and the determination of the broadband spectral evolution severely constrain the theoretical modeling. We find that the pre- and post-flare broadband behavior can be explained by a one-zone model involving synchrotron self-Compton plus external Compton emission from an accretion disk and a broad-line region. However, the spectra of the 2009 December 2-3 super-flare and of the secondary peak emission on 2009 December 9 cannot be satisfactorily modeled by a simple one-zone model. An additional particle component is most likely active during these states. © 2010. The American Astronomical Society. All rights reserved

Multiwavelength observations of a TeV-Flare from W comae

We report results from an intensive multiwavelength campaign on the intermediate-frequency-peaked BL Lacertae object W Com (z = 0.102) during a strong outburst of very high energy gamma-ray emission in 2008 June. The very high energy gamma-ray signal was detected by VERITAS on 2008 June 7-8 with a flux F(>200 GeV) =(5.7 0.6) × 10-11 cm-2 s -1, about three times brighter than during the discovery of gamma-ray emission from W Com by VERITAS in 2008 March. The initial detection of this flare by VERITAS at energies above 200 GeV was followed by observations in high-energy gamma rays (AGILE; E γ≥ 100 MeV), X-rays (Swift and XMM-Newton), and at UV, and ground-based optical and radio monitoring through the GASP-WEBT consortium and other observatories. Here we describe the multiwavelength data and derive the spectral energy distribution of the source from contemporaneous data taken throughout the flare. © 2009. The American Astronomical Society. All rights reserved

Multi-wavelength observations of blazar AO 0235+164 in the 2008-2009 flaring state

The blazar AO 0235+164 (z = 0.94) has been one of the most active objects observed by Fermi Large Area Telescope (LAT) since its launch in Summer 2008. In addition to the continuous coverage by Fermi, contemporaneous observations were carried out from the radio to γ-ray bands between 2008 September and 2009 February. In this paper, we summarize the rich multi-wavelength data collected during the campaign (including F-GAMMA, GASP-WEBT, Kanata, OVRO, RXTE, SMARTS, Swift, and other instruments), examine the cross-correlation between the light curves measured in the different energy bands, and interpret the resulting spectral energy distributions in the context of well-known blazar emission models. We find that the γ-ray activity is well correlated with a series of near-IR/optical flares, accompanied by an increase in the optical polarization degree. On the other hand, the X-ray light curve shows a distinct 20 day high state of unusually soft spectrum, which does not match the extrapolation of the optical/UV synchrotron spectrum. We tentatively interpret this feature as the bulk Compton emission by cold electrons contained in the jet, which requires an accretion disk corona with an effective covering factor of 19% at a distance of 100 R g. We model the broadband spectra with a leptonic model with external radiation dominated by the infrared emission from the dusty torus. © 2012. The American Astronomical Society. All rights reserved

The spectral energy distribution of fermi bright blazars

We have conducted a detailed investigation of the broadband spectral properties of the γ-ray selected blazars of the Fermi LAT Bright AGN Sample (LBAS). By combining our accurately estimated Fermi γ-ray spectra with Swift, radio, infra-red, optical, and other hard X-ray/γ-ray data, collected within 3 months of the LBAS data taking period, we were able to assemble high-quality and quasi-simultaneous spectral energy distributions (SED) for 48 LBAS blazars. The SED of these γ-ray sources is similar to that of blazars discovered at other wavelengths, clearly showing, in the usual log ν-log ν Fν representation, the typical broadband spectral signatures normally attributed to a combination of low-energy synchrotron radiation followed by inverse Compton emission of one or more components. We have used these SED to characterize the peak intensity of both the low- and the high-energy components. The results have been used to derive empirical relationships that estimate the position of the two peaks from the broadband colors (i.e., the radio to optical, αro, and optical to X-ray, αox, spectral slopes) and from the γ-ray spectral index. Our data show that the synchrotron peak frequency (νSpeak) is positioned between 1012.5 and 1014.5 Hz in broad-lined flat spectrum radio quasars (FSRQs) and between 10 13 and 1017 Hz in featureless BL Lacertae objects. We find that the γ-ray spectral slope is strongly correlated with the synchrotron peak energy and with the X-ray spectral index, as expected at first order in synchrotron-inverse Compton scenarios. However, simple homogeneous, one-zone, synchrotron self-Compton (SSC) models cannot explain most of our SED, especially in the case of FSRQs and low energy peaked (LBL) BL Lacs. More complex models involving external Compton radiation or multiple SSC components are required to reproduce the overall SED and the observed spectral variability. While more than 50% of known radio bright high energy peaked (HBL) BL Lacs are detected in the LBAS sample, only less than 13% of known bright FSRQs and LBL BL Lacs are included. This suggests that the latter sources, as a class, may be much fainter γ-ray emitters than LBAS blazars, and could in fact radiate close to the expectations of simple SSC models. We categorized all our sources according to a new physical classification scheme based on the generally accepted paradigm for Active Galactic Nuclei and on the results of this SED study. Since the LAT detector is more sensitive to flat spectrum γ-ray sources, the correlation between νSpeak and γ-ray spectral index strongly favors the detection of high energy peaked blazars, thus explaining the Fermi overabundance of this type of sources compared to radio and EGRET samples. This selection effect is similar to that experienced in the soft X-ray band where HBL BL Lacs are the dominant type of blazars. © 2010 The American Astronomical Society

Insights into the high-energy γ-ray emission of Markarian 501 from extensive multifrequency observations in the Fermi era

We report on the γ-ray activity of the blazar Mrk 501 during the first 480 days of Fermi operation. We find that the average Large Area Telescope (LAT) γ-ray spectrum of Mrk 501 can be well described by a single power-law function with a photon index of 1.78 ± 0.03. While we observe relatively mild flux variations with the Fermi-LAT (within less than a factor of two), we detect remarkable spectral variability where the hardest observed spectral index within the LAT energy range is 1.52 ± 0.14, and the softest one is 2.51 ± 0.20. These unexpected spectral changes do not correlate with the measured flux variations above 0.3 GeV. In this paper, we also present the first results from the 4.5 month long multifrequency campaign (2009 March 15-August 1) on Mrk 501, which included the Very Long Baseline Array (VLBA), Swift, RXTE, MAGIC, and VERITAS, the F-GAMMA, GASP-WEBT, and other collaborations and instruments which provided excellent temporal and energy coverage of the source throughout the entire campaign. The extensive radio to TeV data set from this campaign provides us with the most detailed spectral energy distribution yet collected for this source during its relatively low activity. The average spectral energy distribution of Mrk 501 is well described by the standard one-zone synchrotron self-Compton (SSC) model. In the framework of this model, we find that the dominant emission region is characterized by a size ≲0.1 pc (comparable within a factor of few to the size of the partially resolved VLBA core at 15-43 GHz), and that the total jet power (≃1044 erg s-1) constitutes only a small fraction (∼10-3) of the Eddington luminosity. The energy distribution of the freshly accelerated radiating electrons required to fit the time-averaged data has a broken power-law form in the energy range 0.3 GeV-10 TeV, with spectral indices 2.2 and 2.7 below and above the break energy of 20 GeV. We argue that such a form is consistent with a scenario in which the bulk of the energy dissipation within the dominant emission zone of Mrk 501 is due to relativistic, proton-mediated shocks. We find that the ultrarelativistic electrons and mildly relativistic protons within the blazar zone, if comparable in number, are in approximate energy equipartition, with their energy dominating the jet magnetic field energy by about two orders of magnitude. © 2011. The American Astronomical Society

Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6, OPRM1, and COMT genotype and select opioid therapy

First published: 02 January 2021Opioids are mainly used to treat both acute and chronic pain. Several opioids are metabolized to some extent by CYP2D6 (codeine, tramadol, hydrocodone, oxycodone and methadone). Polymorphisms in CYP2D6 have been studied for an association with the clinical effect and safety of these drugs. Other genes which have been studied for their association with opioid clinical effect or adverse events include OPRM1 (mu receptor) and COMT (catechol-O-methyltransferase). This guideline updates and expands the 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and codeine therapy and includes a summation of the evidence describing the impact of CYP2D6, OPRM1 and COMT on opioid analgesia and adverse events. We provide therapeutic recommendations for the use of CYP2D6 genotype results for prescribing codeine and tramadol and describe the limited and/or weak data for CYP2D6 and hydrocodone, oxycodone and methadone and for OPRM1 and COMT for clinical use.Kristine R. Crews, Andrew A. Monte, Rachel Huddart, Kelly E. Caudle, Evan D. Kharasch, Andrea Gaedigk ... et al