Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity.

Most monogenic cases of obesity in humans have been linked to mutations in genes encoding members of the leptin-melanocortin pathway. Specifically, mutations in MC4R, the melanocortin-4 receptor gene, account for 3-5% of all severe obesity cases in humans1-3. Recently, ADCY3 (adenylyl cyclase 3) gene mutations have been implicated in obesity4,5. ADCY3 localizes to the primary cilia of neurons 6 , organelles that function as hubs for select signaling pathways. Mutations that disrupt the functions of primary cilia cause ciliopathies, rare recessive pleiotropic diseases in which obesity is a cardinal manifestation 7 . We demonstrate that MC4R colocalizes with ADCY3 at the primary cilia of a subset of hypothalamic neurons, that obesity-associated MC4R mutations impair ciliary localization and that inhibition of adenylyl cyclase signaling at the primary cilia of these neurons increases body weight. These data suggest that impaired signaling from the primary cilia of MC4R neurons is a common pathway underlying genetic causes of obesity in humans

Simulating the High Energy Gamma-ray sky seen by the GLAST Large Area Telescope

This paper presents the simulation of the GLAST high energy gamma-ray telescope. The simulation package, written in C++, is based on the Geant4 toolkit, and it is integrated into a general framework used to process events. A detailed simulation of the electronic signals inside Silicon detectors has been provided and it is used for the particle tracking, which is handled by a dedicated software. A unique repository for the geometrical description of the detector has been realized using the XML language and a C++ library to access this information has been designed and implemented. A new event display based on the HepRep protocol was implemented. The full simulation was used to simulate a full week of GLAST high energy gamma-ray observations. This paper outlines the contribution developed by the Italian GLAST software group.Comment: 6 pages, 4 figures, to be published in the Proceedings of the 6th International Symposium ''Frontiers of Fundamental and Computational Physics'' (FFP6), Udine (Italy), Sep. 26-29, 200

Measurement of the branching ratio of the decay Ξ0→Σ+μ−νˉμ\Xi^{0}\rightarrow \Sigma^{+} \mu^{-} \bar{\nu}_{\mu}

From the 2002 data taking with a neutral kaon beam extracted from the CERN-SPS, the NA48/1 experiment observed 97 $\Xi^{0}\rightarrow \Sigma^{+} \mu^{-} \bar{\nu}_{\mu}$ candidates with a background contamination of $30.8 \pm 4.2$ events. From this sample, the BR($\Xi^{0}\rightarrow \Sigma^{+} \mu^{-} \bar{\nu}_{\mu}$) is measured to be $(2.17 \pm 0.32_{\mathrm{stat}}\pm 0.17_{\mathrm{syst}})\times10^{-6}$

Fermi-LAT Study of Gamma-ray Emission in the Direction of Supernova Remnant W49B

We present an analysis of the gamma-ray data obtained with the Large Area Telescope (LAT) onboard the Fermi Gamma-ray Space Telescope in the direction of SNR W49B (G43.3-0.2). A bright unresolved gamma-ray source detected at a significance of 38 sigma is found to coincide with SNR W49B. The energy spectrum in the 0.2-200 GeV range gradually steepens toward high energies. The luminosity is estimated to be 1.5x10^{36} (D/8 kpc)^2 erg s^-1 in this energy range. There is no indication that the gamma-ray emission comes from a pulsar. Assuming that the SNR shell is the site of gamma-ray production, the observed spectrum can be explained either by the decay of neutral pi mesons produced through the proton-proton collisions or by electron bremsstrahlung. The calculated energy density of relativistic particles responsible for the LAT flux is estimated to be remarkably large, U_{e,p}>10^4 eV cm^-3, for either gamma-ray production mechanism.Comment: 9 pages, 10 figure

Search for Early Gamma-ray Production in Supernovae Located in a Dense Circumstellar Medium with the Fermi LAT

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 time scale of several months. We perform the first systematic search for gamma-ray emission in Fermi LAT data in the energy range from 100 MeV to 300 GeV from the ensemble of 147 SNe Type IIn exploding in 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 (PTF10aaxf), 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 95% confidence level (CL) for the source SN 2010jl (PTF10aaxf).Comment: Accepted for publication in ApJ. Corresponding author: A. Franckowiak ([email protected]), updated author list and acknowledgement

GeV Gamma-ray Flux Upper Limits from Clusters of Galaxies

The detection of diffuse radio emission associated with clusters of galaxies indicates populations of relativistic leptons infusing the intracluster medium. Those electrons and positrons are either injected into and accelerated directly in the intracluster medium, or produced as secondary pairs by cosmic-ray ions scattering on ambient protons. Radiation mechanisms involving the energetic leptons together with decay of neutral pions produced by hadronic interactions have the potential to produce abundant GeV photons. Here, we report on the search for GeV emission from clusters of galaxies using data collected by the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope (Fermi) from August 2008 to February 2010. Thirty-three galaxy clusters have been selected according to their proximity and high mass, X-ray flux and temperature, and indications of non-thermal activity for this study. We report upper limits on the photon flux in the range 0.2-100 GeV towards a sample of observed clusters (typical values 1-5 x 10^-9 ph cm^-2 s^-1) considering both point-like and spatially resolved models for the high-energy emission, and discuss how these results constrain the characteristics of energetic leptons and hadrons, and magnetic fields in the intracluster medium. The volume-averaged relativistic-hadron-to-thermal energy density ratio is found to be < 5-10% in several clusters.Comment: 9 pages, 3 tables, 1 figure, accepted for publication in ApJ Letter

Detection of 16 Gamma-Ray Pulsars Through Blind Frequency Searches Using the Fermi LAT

Pulsars are rapidly-rotating, highly-magnetized neutron stars emitting radiation across the electromagnetic spectrum. Although there are more than 1800 known radio pulsars, until recently, only seven were observed to pulse in gamma rays and these were all discovered at other wavelengths. The Fermi Large Area Telescope makes it possible to pinpoint neutron stars through their gamma-ray pulsations. We report the detection of 16 gamma-ray pulsars in blind frequency searches using the LAT. Most of these pulsars are coincident with previously unidentified gamma-ray sources, and many are associated with supernova remnants. Direct detection of gamma-ray pulsars enables studies of emission mechanisms, population statistics and the energetics of pulsar wind nebulae and supernova remnants.Comment: Corresponding authors: Michael Dormody, Paul S. Ray, Pablo M. Saz Parkinson, Marcus Ziegle

Gamma-Ray Emission Concurrent with the Nova in the Symbiotic Binary V407 Cygni

Novae are thermonuclear explosions on a white dwarf surface fueled by mass accreted from a companion star. Current physical models posit that shocked expanding gas from the nova shell can produce X-ray emission but emission at higher energies has not been widely expected. Here, we report the Fermi Large Area Telescope detection of variable gamma-ray (0.1-10 GeV) emission from the recently-detected optical nova of the symbiotic star V407 Cygni. We propose that the material of the nova shell interacts with the dense ambient medium of the red giant primary, and that particles can be accelerated effectively to produce pi0 decay gamma-rays from proton-proton interactions. Emission involving inverse Compton scattering of the red giant radiation is also considered and is not ruled out.Comment: 38 pages, includes Supplementary Online Material; corresponding authors: C.C. Cheung, A.B. Hill, P. Jean, S. Razzaque, K.S. Woo

Observations of Milky Way Dwarf Spheroidal galaxies with the Fermi-LAT detector and constraints on Dark Matter models

We report on the observations of 14 dwarf spheroidal galaxies with the Fermi Gamma-Ray Space Telescope taken during the first 11 months of survey mode operations. The Fermi telescope provides a new opportunity to test particle dark matter models through the expected gamma-ray emission produced by pair annihilation of weakly interacting massive particles (WIMPs). Local Group dwarf spheroidal galaxies, the largest galactic substructures predicted by the cold dark matter scenario, are attractive targets for such indirect searches for dark matter because they are nearby and among the most extreme dark matter dominated environments. No significant gamma-ray emission was detected above 100 MeV from the candidate dwarf galaxies. We determine upper limits to the gamma-ray flux assuming both power-law spectra and representative spectra from WIMP annihilation. The resulting integral flux above 100 MeV is constrained to be at a level below around 10^-9 photons cm^-2 s^-1. Using recent stellar kinematic data, the gamma-ray flux limits are combined with improved determinations of the dark matter density profile in 8 of the 14 candidate dwarfs to place limits on the pair annihilation cross-section of WIMPs in several widely studied extensions of the standard model. With the present data, we are able to rule out large parts of the parameter space where the thermal relic density is below the observed cosmological dark matter density and WIMPs (neutralinos here) are dominantly produced non-thermally, e.g. in models where supersymmetry breaking occurs via anomaly mediation. The gamma-ray limits presented here also constrain some WIMP models proposed to explain the Fermi and PAMELA e^+e^- data, including low-mass wino-like neutralinos and models with TeV masses pair-annihilating into muon-antimuon pairs. (Abridged)Comment: 25 pages, 4 figures, accepted to ApJ, Corresponding authors: J. Cohen-Tanugi, C. Farnier, T.E. Jeltema, E. Nuss, and S. Profum

Detection of the Small Magellanic Cloud in gamma-rays with Fermi/LAT

The flux of gamma rays with energies >100MeV is dominated by diffuse emission from CRs illuminating the ISM of our Galaxy through the processes of Bremsstrahlung, pion production and decay, and inverse-Compton scattering. The study of this diffuse emission provides insight into the origin and transport of CRs. We searched for gamma-ray emission from the SMC in order to derive constraints on the CR population and transport in an external system with properties different from the Milky Way. We analysed the first 17 months of continuous all-sky observations by the Large Area Telescope of the Fermi mission to determine the spatial distribution, flux and spectrum of the gamma-ray emission from the SMC. We also used past radio synchrotron observations of the SMC to study the population of CR electrons specifically. We obtained the first detection of the SMC in high-energy gamma rays, with an integrated >100MeV flux of (3.7 +/-0.7) x10e-8 ph/cm2/s, with additional systematic uncertainty of <16%. The emission is steady and from an extended source ~3{\deg} in size. It is not clearly correlated with the distribution of massive stars or neutral gas, nor with known pulsars or SNRs, but a certain correlation with supergiant shells is observed. The observed flux implies an upper limit on the average CR nuclei density in the SMC of ~15% of the value measured locally in the Milky Way. The population of high-energy pulsars of the SMC may account for a substantial fraction of the gamma-ray flux, which would make the inferred CR nuclei density even lower. The average density of CR electrons derived from radio synchrotron observations is consistent with the same reduction factor but the uncertainties are large. From our current knowledge of the SMC, such a low CR density does not seem to be due to a lower rate of CR injection and rather indicates a smaller CR confinement volume characteristic size.Comment: 14 pages, 6 figures, accepted for publication in A&