Corona, Jet, and Relativistic Line Models for Suzaku/RXTE/Chandra-HETG Observations of the Cygnus X-1 Hard State

Using Suzaku and the Rossi X-ray Timing Explorer, we have conducted a series of four simultaneous observations of the galactic black hole candidate Cyg X-1 in what were historically faint and spectrally hard low states. Additionally, all of these observations occurred near superior conjunction with our line of sight to the X-ray source passing through the dense phases of the focused wind from the mass donating secondary. One of our observations was also simultaneous with observations by the Chandra-High Energy Transmission Grating. These latter spectra are crucial for revealing the ionized absorption due to the secondary's focused wind. Such absorption is present and must be accounted for in all four spectra. These simultaneous data give an unprecedented view of the 0.8-300 keV spectrum of Cyg X-1, and hence bear upon both corona and X-ray emitting jet models of black hole hard states. Three models fit the spectra well: coronae with thermal or mixed thermal/non-thermal electron populations, and jets. All three models require a soft component that we fit with a low temperature disk spectrum with an inner radius of only a few tens of GM/c^2. All three models also agree that the known spectral break at 10\,keV is not solely due to the presence of reflection, but each gives a different underlying explanation for the augmentation of this break. Thus whereas all three models require that there is a relativistically broadened Fe line, the strength and inner radius of such a line is dependent upon the specific model, {thus making premature line-based estimates of the black hole spin in the Cyg X-1 system. We look at the relativistic line in detail, accounting for the narrow Fe emission and ionized absorption detected by HETG. Although the specific relativistic parameters of the line are continuum-dependent, none of the broad line fits allow for an inner disk radius that is >40 GM/c^2.Comment: 22 pages, 16 figures. Uses emulateapj style. Final three tables inserted as a figure to avoid issues with astro-ph's version of latex mangling the use of lscape. To be published in the Astrophysical Journal, January, 201

The rocket experiment demonstration of a soft x-ray polarimeter (REDSoX Polarimeter)

The Rocket Experiment Demonstration of a Soft X-ray Polarimeter (REDSoX Polarimeter) is a sounding rocket instrument that can make the first measurement of the linear X-ray polarization of an extragalactic source in the 0.2-0.8 keV band as low as 10%. We employ multilayer-coated mirrors as Bragg reflectors at the Brewster angle. By matching the dispersion of a spectrometer using replicated optics from MSFC and critical angle transmission gratings from MIT to three laterally graded multilayer mirrors (LGMLs), we achieve polarization modulation factors over 90%. We present a novel arrangement of gratings, designed optimally for the purpose of polarimetry with a converging beam. The entrance aperture is divided into six equal sectors; pairs of blazed gratings from opposite sectors are oriented to disperse to the same LGML. The LGML position angles are 120 degrees to each other. CCD detectors then measure the intensities of the dispersed spectra after reflection and polarizing by the LGMLs, giving the three Stokes parameters needed to determine a source's linear polarization fraction and orientation. A current grant is funding further development to improve the LGMLs. Sample gratings for the project have been fabricated at MIT and the development team continues to improve them under separate funding. Our technological approach is the basis for a possible orbital missio

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

The hedgehog receptor Patched1 regulates myeloid and lymphoid progenitors by distinct cell-extrinsic mechanisms

Hedgehog (Hh) ligands bind to the Patched1 (Ptch1) receptor, relieving repression of Smoothened, which leads to activation of the Hh signaling pathway. Using conditional Ptch1 knockout mice, the aim of this study was to determine the effects of activating the Hh signaling pathway in hematopoiesis. Surprisingly, hematopoietic-specific deletion of Ptch1 did not lead to activation of the Hh signaling pathway and, consequently, had no phenotypic effect. In contrast, deletion of Ptch1 in nonhematopoietic cells produced 2 distinct hematopoietic phenotypes. First, activation of Hh signaling in epithelial cells led to apoptosis of lymphoid progenitors associated with markedly elevated levels of circulating thymic stromal lymphopoietin. Second, activation of Hh signaling in the bone marrow cell niche led to increased numbers of lineage-negative c-kit+ Sca-1+ bone marrow cells and mobilization of myeloid progenitors associated with a marked loss of osteoblasts. Thus, deletion of Ptch1 leads to hematopoietic effects by distinct cell-extrinsic mechanisms rather than by direct activation of the Hh signaling pathway in hematopoietic cells. These findings have important implications for therapeutics designed to activate the Hh signaling pathway in hematopoietic cells including hematopoietic stem cells

Correction: Molecular Subsets in the Gene Expression Signatures of Scleroderma Skin

Background: Scleroderma is a clinically heterogeneous disease with a complex phenotype. The disease is characterized by vascular dysfunction, tissue fibrosis, internal organ dysfunction, and immune dysfunction resulting in autoantibody production. Methodology and Findings: We analyzed the genome-wide patterns of gene expression with DNA microarrays in skin biopsies from distinct scleroderma subsets including 17 patients with systemic sclerosis (SSc) with diffuse scleroderma (dSSc), 7 patients with SSc with limited scleroderma (lSSc), 3 patients with morphea, and 6 healthy controls. 61 skin biopsies were analyzed in a total of 75 microarray hybridizations. Analysis by hierarchical clustering demonstrates nearly identical patterns of gene expression in 17 out of 22 of the forearm and back skin pairs of SSc patients. Using this property of the gene expression, we selected a set of ‘intrinsic’ genes and analyzed the inherent data-driven groupings. Distinct patterns of gene expression separate patients with dSSc from those with lSSc and both are easily distinguished from normal controls. Our data show three distinct patient groups among the patients with dSSc and two groups among patients with lSSc. Each group can be distinguished by unique gene expression signatures indicative of proliferating cells, immune infiltrates and a fibrotic program. The intrinsic groups are statistically significant (p , 0.001) and each has been mapped to clinical covariates of modified Rodnan skin score, interstitial lung disease, gastrointestinal involvement, digital ulcers, Raynaud’s phenomenon and disease duration. We report a 177-gene signature that is associated with severity of skin disease in dSSc. Conclusions and Significance: Genome-wide gene expression profiling of skin biopsies demonstrates that the heterogeneity in scleroderma can be measured quantitatively with DNA microarrays. The diversity in gene expression demonstrates multiple distinct gene expression programs in the skin of patients with scleroderma