Clinical exome performance for reporting secondary genetic findings.

BACKGROUND : Reporting clinically actionable incidental genetic findings in the course of clinical exome testing is recommended by the American College of Medical Genet- ics and Genomics (ACMG). However, the performance of clinical exome methods for reporting small subsets of genes has not been previously reported. METHODS : In this study, 57 exome data sets performed as clinical (n ! 12) or research (n ! 45) tests were retrospec- tively analyzed. Exome sequencing data was examined for adequacy in the detection of potentially pathogenic variant locations in the 56 genes described in the ACMG incidental findings recommendation. All exons of the 56 genes were examined for adequacy of sequencing coverage. In addition, nucleotide positions annotated in HGMD (Human Gene Mutation Database) were examined. RESULTS : The 56 ACMG genes have 18336 nucleotide variants annotated in HGMD. None of the 57 exome data sets possessed a HGMD variant. The clinical exome test had inadequate coverage for " 50% of HGMD vari- ant locations in 7 genes. Six exons from 6 different genes had consistent failure across all 3 test methods; these exons had high GC content (76%–84%). CONCLUSIONS : The use of clinical exome sequencing for the interpretation and reporting of subsets of genes requires recognition of the substantial possibility of inadequate depth and breadth of sequencing coverage at clinically relevant locations. Inadequate depth of coverage may contribute to false-negative clinical ex- ome results

Gamma-Rays Produced in Cosmic-Ray Interactions and the TeV-band Spectrum of RX J1713.7-3946

We employ the Monte Carlo particle collision code DPMJET3.04 to determine the multiplicity spectra of various secondary particles (in addition to $\pi^0$'s) with $\gamma$'s as the final decay state, that are produced in cosmic-ray ($p$'s and $\alpha$'s) interactions with the interstellar medium. We derive an easy-to-use $\gamma$-ray production matrix for cosmic rays with energies up to about 10 PeV. This $\gamma$-ray production matrix is applied to the GeV excess in diffuse Galactic $\gamma$-rays observed by EGRET, and we conclude the non-$\pi^0$ decay components are insufficient to explain the GeV excess, although they have contributed a different spectrum from the $\pi^0$-decay component. We also test the hypothesis that the TeV-band $\gamma$-ray emission of the shell-type SNR RX J1713.7-3946 observed with HESS is caused by hadronic cosmic rays which are accelerated by a cosmic-ray modified shock. By the $\chi^2$ statistics, we find a continuously softening spectrum is strongly preferred, in contrast to expectations. A hardening spectrum has about 1% probability to explain the HESS data, but then only if a hard cutoff at 50-100 TeV is imposed on the particle spectrum.Comment: 3 pages; 4 figures; Contribution to the First GLAST Symposium, Standord, 200

Generalised additive dependency inflated models including aggregated covariates

Let us assume that X, Y and U are observed and that the conditional mean of U given X and Y can be expressed via an additive dependency of X, λ(X)Y and X + Y for some unspecified function . This structured regression model can be transferred to a hazard model or a density model when applied on some appropriate grid, and has important forecasting applications via structured marker dependent hazards models or structured density models including age-period-cohort relationships. The structured regression model is also important when the severity of the dependent variable has a complicated dependency on waiting times X, Y and the total waiting time X+Y . In case the conditional mean of U approximates a density, the regression model can be used to analyse the age-period-cohort model, also when exposure data are not available. In case the conditional mean of U approximates a marker dependent hazard, the regression model introduces new relevant age-period-cohort time scale interdependencies in understanding longevity. A direct use of the regression relationship introduced in this paper is the estimation of the severity of outstanding liabilities in non-life insurance companies. The technical approach taken is to use B-splines to capture the underlying one-dimensional unspecified functions. It is shown via finite sample simulation studies and an application for forecasting future asbestos related deaths in the UK that the B-spline approach works well in practice. Special consideration has been given to ensure identifiability of all models considered

Performance of a prototype active veto system using liquid scintillator for a dark matter search experiment

We report the performance of an active veto system using a liquid scintillator with NaI(Tl) crystals for use in a dark matter search experiment. When a NaI(Tl) crystal is immersed in the prototype detector, the detector tags 48% of the internal K-40 background in the 0-10 keV energy region. We also determined the tagging efficiency for events at 6-20 keV as 26.5 +/- 1.7% of the total events, which corresponds to 0.76 +/- 0.04 events/keV/kg/day. According to a simulation, approximately 60% of the background events from U, Th, and K radioisotopes in photomultiplier tubes are tagged at energies of 0-10 keV. Full shielding with a 40-cm-thick liquid scintillator can increase the tagging efficiency for both the internal K-40 and external background to approximately 80%.Comment: Submitted to Nuclear Instruments and Methods in Physics Research Section

Epitaxial Growth of an n-type Ferromagnetic Semiconductor CdCr2Se4 on GaAs(001) and GaP(001)

We report the epitaxial growth of CdCr2Se4, an n-type ferromagnetic semiconductor, on both GaAs and GaP(001) substrates, and describe the structural, magnetic and electronic properties. Magnetometry data confirm ferromagnetic order with a Curie temperature of 130 K, as in the bulk material. The magnetization exhibits hysteretic behavior with significant remanence, and an in-plane easy axis with a coercive field of ~125 Oe. Temperature dependent transport data show that the films are semiconducting in character and n-type as grown, with room temperature carrier concentrations of n ~ 1 x 10^18 cm-3.Comment: 12 pages, 3 figure

Mixed finite element domain decomposition for nonlinear parabolic problems

AbstractFully discrete mixed finite element method is considered to approximate the solution of a nonlinear second-order parabolic problem. A massively parallel iterative procedure based on domain decomposition technique is presented to solve resulting nonlinear algebraic equations. Robin type boundary conditions are used to transmit information between subdomains. The convergence of the iteration for each time step is demonstrated. Optimal-order error estimates are also derived. Numerical examples are given