Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration.

Data visualization is an essential component of genomic data analysis. However, the size and diversity of the data sets produced by today's sequencing and array-based profiling methods present major challenges to visualization tools. The Integrative Genomics Viewer (IGV) is a high-performance viewer that efficiently handles large heterogeneous data sets, while providing a smooth and intuitive user experience at all levels of genome resolution. A key characteristic of IGV is its focus on the integrative nature of genomic studies, with support for both array-based and next-generation sequencing data, and the integration of clinical and phenotypic data. Although IGV is often used to view genomic data from public sources, its primary emphasis is to support researchers who wish to visualize and explore their own data sets or those from colleagues. To that end, IGV supports flexible loading of local and remote data sets, and is optimized to provide high-performance data visualization and exploration on standard desktop systems. IGV is freely available for download from http://www.broadinstitute.org/igv, under a GNU LGPL open-source license

GBM heterogeneity as a function of variable epidermal growth factor receptor variant III activity.

Abnormal activation of the epidermal growth factor receptor (EGFR) due to a deletion of exons 2-7 of EGFR (EGFRvIII) is a common alteration in glioblastoma (GBM). While this alteration can drive gliomagenesis, tumors harboring EGFRvIII are heterogeneous. To investigate the role for EGFRvIII activation in tumor phenotype we used a neural progenitor cell-based murine model of GBM driven by EGFR signaling and generated tumor progenitor cells with high and low EGFRvIII activation, pEGFRHi and pEGFRLo. In vivo, ex vivo, and in vitro studies suggested a direct association between EGFRvIII activity and increased tumor cell proliferation, decreased tumor cell adhesion to the extracellular matrix, and altered progenitor cell phenotype. Time-lapse confocal imaging of tumor cells in brain slice cultures demonstrated blood vessel co-option by tumor cells and highlighted differences in invasive pattern. Inhibition of EGFR signaling in pEGFRHi promoted cell differentiation and increased cell-matrix adhesion. Conversely, increased EGFRvIII activation in pEGFRLo reduced cell-matrix adhesion. Our study using a murine model for GBM driven by a single genetic driver, suggests differences in EGFR activation contribute to tumor heterogeneity and aggressiveness

The ``Outside-In'' Outburst of HT Cassiopeiae

We present results from photometric observations of the dwarf nova system HT Cas during the eruption of November 1995. The data include the first two--colour observations of an eclipse on the rise to outburst. They show that during the rise to outburst the disc deviates significantly from steady state models, but the inclusion of an inner-disc truncation radius of about 4 $R_{wd}$ and a ``flared'' disc of semi-opening angle of $10^{\circ}$ produces acceptable fits. The disc is found to have expanded at the start of the outburst to about $0.41R_{L1}$, as compared to quiescent measurements. The accretion disc then gradually decreases in radius reaching $<0.32R_{L1}$ during the last stages of the eruption. Quiescent eclipses were also observed prior to and after the eruption and a revised ephemeris is calculated.Comment: 9 pages, 11 figures, to appear in MNRA

Structure formation by cosmic strings with a cosmological constant

Final published version.Comment: 4 Page

Independent Ion Migration in Suspensions of Strongly Interacting Charged Colloidal Spheres

We report on sytematic measurements of the low frequency conductivity in aequous supensions of highly charged colloidal spheres. System preparation in a closed tubing system results in precisely controlled number densities between 1E16/m3 and 1E19/m^3 (packing fractions between 1E-7 and 1E-2) and electrolyte concentrations between 1E-7 and 1E-3 mol/l. Due to long ranged Coulomb repulsion some of the systems show a pronounced fluid or crystalline order. Under deionized conditions we find s to depend linearily on the packing fraction with no detectable influence of the phase transitions. Further at constant packing fraction s increases sublinearily with increasing number of dissociable surface groups N. As a function of c the conductivity shows pronounced differences depending on the kind of electrolyte used. We propose a simple yet powerful model based on independent migration of all species present and additivity of the respective conductivity contributions. It takes account of small ion macro-ion interactions in terms of an effectivly transported charge. The model successfully describes our qualitatively complex experimental observations. It further facilitates quantitative estimates of conductivity over a wide range of particle and experimental parameters.Comment: 32 pages, 17 figures, 2 tables, Accepted by Physical Review

Is there Evidence for Flat Cores in the Halos of Dwarf Galaxies?: The Case of NGC 3109 and NGC 6822

Two well studied dwarf galaxies -- NGC 3109 and NGC 6822 -- present some of the strongest observational support for a flat core at the center of galactic dark matter (DM) halos. We use detailed cosmologically motivated numerical models to investigate the systematics and the accuracy of recovering parameters of the galaxies. Some of our models match the observed structure of the two galaxies remarkably well. Our analysis shows that the rotation curves of these two galaxies are instead quite compatible with their DM halos having steep cuspy density profiles. The rotation curves in our models are measured using standard observational techniques. The models reproduce the rotation curves of both galaxies, the disk surface brightness profiles as well as the profile of isophotal ellipticity and position angle. The models are centrally dominated by baryons; however, the dark matter component is globally dominant. The simulated disk mass is marginally consistent with a stellar mass-to-light ratio in agreement with the observed colors. We show that non-circular motions combined with gas pressure support and projection effects results in a large underestimation of the circular velocity in the central $\sim 1$ kpc region, creating the illusion of a constant density core. Although the systematic effects mentioned above are stronger in barred systems, they are also present in axisymetric disks. Our results strongly suggest that there is no contradiction between the observed rotation curves in dwarf galaxies and the cuspy central dark matter density profiles predicted by Cold Dark Matter models.Comment: Accepted for publication in the ApJ. New discussion, figures and one appendix. High resolution version at:http://www.astro.washington.edu/octavio/N3109_paper.ps.g

Resolved Mid-IR Emission in the Narrow Line Region of NGC 4151

We present subarcsecond resolution mid infrared images of NGC 4151 at 10.8 micron and 18.2 micron. These images were taken with the University of Florida mid-IR camera/spectrometer OSCIR at the Gemini North 8-m telescope. We resolve emission at both 10.8 micron and 18.2 micron extending ~ 3.5" across at a P.A. of ~ 60 degrees. This coincides with the the narrow line region of NGC 4151 as observed in [OIII] by the Hubble Space Telescope. The most likely explanation for this extended mid-IR emission is dust in the narrow line region heated by a central engine. We find no extended emission associated with the proposed torus and place an upper limit on its mid-IR size of less than or equal to ~ 35 pc.Comment: accepted for publication in the Astrophysical Journal, 19 pages including 5 figure

Effect of Hydrologic Restoration on the Habitat of The Cape Sable Seaside Sparrow, Annual Report of 2003-2004

Following on our previous year’s work on ‘Effect of hydrologic restoration on the habitat of the Cape Sable seaside sparrow (CSSS)’, we presented first year results at the Cape Sable seaside sparrow – fire planning workshop at Everglades National Park in December 2003. Later, with almost the same set of crews as in the previous year, we started field work in the first week of January and continued till May 26, 2004. Protocols for sampling topography and vegetation in 2004 were identical to the previous year. In the early season, we completed topographic surveys along two remaining transects, B and E (~16.5 km), and vegetation surveys along three transects, D, E and F (~10.8 km), leaving only the vegetation sampling on transects B and C to be completed in 2005. During April and May, vegetation sampling was completed at 230 census sites, making the total of 409 CSSS census sites for which we have complete vegetation data. We updated data sets from both 2003 and 2004, and analyzed them together using cluster analysis, ordination, weighted-averaging regression and analysis of variance, as we had in 2003. Additionally, we used logistic regression to examine the effect of vegetation structural parameters on the recent occurrence of CSSS. We also analyzed vegetation observations recorded by the sparrow census team in 1981 and annually between 1992 and 2004 to assess historical patterns of vegetation change in CSSS habitat

Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium

D2 autoreceptors regulate dopamine release throughout the brain. Two isoforms of the D2 receptor, D2S and D2L, are expressed in midbrain dopamine neurons. Differential roles of these isoforms as autoreceptors are poorly understood. By virally expressing the isoforms in dopamine neurons of D2 receptor knockout mice, this study assessed the calcium-dependence and drug-induced plasticity of D2S and D2L receptor-dependent G protein-coupled inwardly rectifying potassium (GIRK) currents. The results reveal that D2S, but not D2L receptors, exhibited calcium-dependent desensitization similar to that exhibited by endogenous autoreceptors. Two pathways of calcium signaling that regulated D2 autoreceptor-dependent GIRK signaling were identified, which distinctly affected desensitization and the magnitude of D2S and D2L receptor-dependent GIRK currents. Previous in vivo cocaine exposure removed calcium-dependent D2 autoreceptor desensitization in wild type, but not D2S-only mice. Thus, expression of D2S as the exclusive autoreceptor was insufficient for cocaine-induced plasticity, implying a functional role for the co-expression of D2S and D2L autoreceptors