80 research outputs found
Deciphering exome sequencing data: Bringing mitochondrial DNA variants to light
The expanding use of exome sequencing (ES) in diagnosis generates a huge amount of data, including untargeted mitochondrial DNA (mtDNA) sequences. We developed a strategy to deeply study ES data, focusing on the mtDNA genome on a large unspecific cohort to increase diagnostic yield. A targeted bioinformatics pipeline assembled mitochondrial genome from ES data to detect pathogenic mtDNA variants in parallel with the "in-house" nuclear exome pipeline. mtDNA data coming from off-target sequences (indirect sequencing) were extracted from the BAM files in 928 individuals with developmental and/or neurological anomalies. The mtDNA variants were filtered out based on database information, cohort frequencies, haplogroups and protein consequences. Two homoplasmic pathogenic variants (m.9035T>C and m.11778G>A) were identified in 2 out of 928 unrelated individuals (0.2%): the m.9035T>C (MT-ATP6) variant in a female with ataxia and the m.11778G>A (MT-ND4) variant in a male with a complex mosaic disorder and a severe ophthalmological phenotype, uncovering undiagnosed Leber\u27s hereditary optic neuropathy (LHON). Seven secondary findings were also found, predisposing to deafness or LHON, in 7 out of 928 individuals (0.75%). This study demonstrates the usefulness of including a targeted strategy in ES pipeline to detect mtDNA variants, improving results in diagnosis and research, without resampling patients and performing targeted mtDNA strategies
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
Low Q^2 Jet Production at HERA and Virtual Photon Structure
The transition between photoproduction and deep-inelastic scattering is
investigated in jet production at the HERA ep collider, using data collected by
the H1 experiment. Measurements of the differential inclusive jet
cross-sections dsigep/dEt* and dsigmep/deta*, where Et* and eta* are the
transverse energy and the pseudorapidity of the jets in the virtual
photon-proton centre of mass frame, are presented for 0 < Q2 < 49 GeV2 and 0.3
< y < 0.6. The interpretation of the results in terms of the structure of the
virtual photon is discussed. The data are best described by QCD calculations
which include a partonic structure of the virtual photon that evolves with Q2.Comment: 20 pages, 5 Figure
Hadron Production in Diffractive Deep-Inelastic Scattering
Characteristics of hadron production in diffractive deep-inelastic
positron-proton scattering are studied using data collected in 1994 by the H1
experiment at HERA. The following distributions are measured in the
centre-of-mass frame of the photon dissociation system: the hadronic energy
flow, the Feynman-x (x_F) variable for charged particles, the squared
transverse momentum of charged particles (p_T^{*2}), and the mean p_T^{*2} as a
function of x_F. These distributions are compared with results in the gamma^* p
centre-of-mass frame from inclusive deep-inelastic scattering in the
fixed-target experiment EMC, and also with the predictions of several Monte
Carlo calculations. The data are consistent with a picture in which the
partonic structure of the diffractive exchange is dominated at low Q^2 by hard
gluons.Comment: 16 pages, 6 figures, submitted to Phys. Lett.
A Search for Selectrons and Squarks at HERA
Data from electron-proton collisions at a center-of-mass energy of 300 GeV
are used for a search for selectrons and squarks within the framework of the
minimal supersymmetric model. The decays of selectrons and squarks into the
lightest supersymmetric particle lead to final states with an electron and
hadrons accompanied by large missing energy and transverse momentum. No signal
is found and new bounds on the existence of these particles are derived. At 95%
confidence level the excluded region extends to 65 GeV for selectron and squark
masses, and to 40 GeV for the mass of the lightest supersymmetric particle.Comment: 13 pages, latex, 6 Figure
Measurement of D* Meson Cross Sections at HERA and Determination of the Gluon Density in the Proton using NLO QCD
With the H1 detector at the ep collider HERA, D* meson production cross
sections have been measured in deep inelastic scattering with four-momentum
transfers Q^2>2 GeV2 and in photoproduction at energies around W(gamma p)~ 88
GeV and 194 GeV. Next-to-Leading Order QCD calculations are found to describe
the differential cross sections within theoretical and experimental
uncertainties. Using these calculations, the NLO gluon momentum distribution in
the proton, x_g g(x_g), has been extracted in the momentum fraction range
7.5x10^{-4}< x_g <4x10^{-2} at average scales mu^2 =25 to 50 GeV2. The gluon
momentum fraction x_g has been obtained from the measured kinematics of the
scattered electron and the D* meson in the final state. The results compare
well with the gluon distribution obtained from the analysis of scaling
violations of the proton structure function F_2.Comment: 27 pages, 9 figures, 2 tables, submitted to Nucl. Phys.
Measurement of Leading Proton and Neutron Production in Deep Inelastic Scattering at HERA
Deep--inelastic scattering events with a leading baryon have been detected by
the H1 experiment at HERA using a forward proton spectrometer and a forward
neutron calorimeter. Semi--inclusive cross sections have been measured in the
kinematic region 2 <= Q^2 <= 50 GeV^2, 6.10^-5 <= x <= 6.10^-3 and baryon p_T
<= MeV, for events with a final state proton with energy 580 <= E' <= 740 GeV,
or a neutron with energy E' >= 160 GeV. The measurements are used to test
production models and factorization hypotheses. A Regge model of leading baryon
production which consists of pion, pomeron and secondary reggeon exchanges
gives an acceptable description of both semi-inclusive cross sections in the
region 0.7 <= E'/E_p <= 0.9, where E_p is the proton beam energy. The leading
neutron data are used to estimate for the first time the structure function of
the pion at small Bjorken--x.Comment: 30 pages, 9 figures, 2 tables, submitted to Eur. Phys.
DEVELOPMENT of the MODEL of GALACTIC INTERSTELLAR EMISSION for STANDARD POINT-SOURCE ANALYSIS of FERMI LARGE AREA TELESCOPE DATA
Most of the celestial \u3b3 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\ub0 and we observe an enhanced emission toward their base extending in the north and south Galactic directions and located within \u2dc4\ub0 of the Galactic Center
Charmonium Production in Deep Inelastic Scattering at HERA
The electroproduction of J/psi and psi(2S) mesons is studied in elastic, quasi-elastic and inclusive reactions for four momentum transfers 2 Q^2 80 GeV^2 and photon-proton centre of mass energies 25 W 180 GeV. The data were taken with the H1 detector at the electron proton collider HERA in the years 1995 to 1997. The total virtual photon-proton cross section for elastic J/psi production is measured as a function of Q^2 and W. The dependence of the production rates on the square of the momentum transfer from the proton (t) is extracted. Decay angular distributions are analysed and the ratio of the longitudinal and transverse cross sections is derived. The ratio of the cross sections for quasi-elastic psi(2S) and J/psi meson production is measured as a function of Q^2. The results are discussed in terms of theoretical models based upon perturbative QCD. Differential cross sections for inclusive and inelastic production of J/psi mesons are determined and predictions within two theoretical frameworks are compared with the data, the non-relativistic QCD factorization approach including colour octet and colour singlet contributions, and the model of Soft Colour Interactions
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
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