Clones assemble! The clonal complexity of blood during ontogeny and disease.

Hematopoietic stem and progenitor cells (HSPCs) govern the daily expansion and turnover of billions of specialized blood cells. Given their clinical utility, much effort has been made toward understanding the dynamics of hematopoietic production from this pool of stem cells. An understanding of hematopoietic stem cell clonal dynamics during blood ontogeny could yield important insights into hematopoietic regulation, especially during aging and repeated exposure to hematopoietic stress-insults that may predispose individuals to the development of hematopoietic disease. Here, we review the current state of research regarding the clonal complexity of the hematopoietic system during embryogenesis, adulthood, and hematologic disease

Alcohol availability and neighborhood poverty and their relationship to binge drinking and related problems among drinkers in committed relationships

The authors examined the relationship of alcohol outlet density (AOD) and neighborhood poverty with binge drinking and alcohol-related problems among drinkers in married and cohabitating relationships and assessed whether these associations differed across sex. A U.S. national population couples survey was linked to U.S. Census data on AOD and neighborhood poverty. The 1,784 current drinkers in the survey reported on their binge drinking, alcohol-related problems, and other covariates. AOD was defined as the number of alcohol outlets per 10,000 persons and was obtained at the zip code level. Neighborhood poverty was as having a low (\u3c20%) or high (≥20%) proportion of residents living in poverty at the census tract level. We used logistic regression for survey data to estimate odds ratios and 95% confidence intervals and tested for differences of associations by sex. Associations of neighborhood poverty with binge drinking were stronger for male than for female drinkers. The association of neighborhood poverty with alcohol-related problems was also stronger for men than for women. We observed no relationships between AOD and binge drinking or alcohol-related problems in this couples survey. Efforts to reduce binge drinking or alcohol-related problems among partners in committed relationships may have the greatest impact if targeted to male drinkers living in high-poverty neighborhoods. Binge drinking and alcohol-related problems, as well as residence in an impoverished neighborhood are risk factors for intimate partner violence (IPV) and other relationship conflicts

Inferring hidden Markov models from noisy time sequences: a method to alleviate degeneracy in molecular dynamics

We present a new method for inferring hidden Markov models from noisy time sequences without the necessity of assuming a model architecture, thus allowing for the detection of degenerate states. This is based on the statistical prediction techniques developed by Crutchfield et al., and generates so called causal state models, equivalent to hidden Markov models. This method is applicable to any continuous data which clusters around discrete values and exhibits multiple transitions between these values such as tethered particle motion data or Fluorescence Resonance Energy Transfer (FRET) spectra. The algorithms developed have been shown to perform well on simulated data, demonstrating the ability to recover the model used to generate the data under high noise, sparse data conditions and the ability to infer the existence of degenerate states. They have also been applied to new experimental FRET data of Holliday Junction dynamics, extracting the expected two state model and providing values for the transition rates in good agreement with previous results and with results obtained using existing maximum likelihood based methods.Comment: 19 pages, 9 figure

Super-critical Accretion Flows around Black Holes: Two-dimensional, Radiation-pressure-dominated Disks with Photon-trapping

The quasi-steady structure of super-critical accretion flows around a black hole is studied based on the two-dimensional radiation-hydrodynamical (2D-RHD) simulations. The super-critical flow is composed of two parts: the disk region and the outflow regions above and below the disk. Within the disk region the circular motion as well as the patchy density structure are observed, which is caused by Kelvin-Helmholtz instability and probably by convection. The mass-accretion rate decreases inward, roughly in proportion to the radius, and the remaining part of the disk material leaves the disk to form outflow because of strong radiation pressure force. We confirm that photon trapping plays an important role within the disk. Thus, matter can fall onto the black hole at a rate exceeding the Eddington rate. The emission is highly anisotropic and moderately collimated so that the apparent luminosity can exceed the Eddington luminosity by a factor of a few in the face-on view. The mass-accretion rate onto the black hole increases with increase of the absorption opacity (metalicity) of the accreting matter. This implies that the black hole tends to grow up faster in the metal rich regions as in starburst galaxies or star-forming regions.Comment: 16 pages, 12 figures, accepted for publication in ApJ (Volume 628, July 20, 2005 issue

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

Design, analysis and test verification of advanced encapsulation systems, phase 2 program results

Optical, electrical isolation, thermal structural, structural deflection, and thermal tests are reported. The utility of the optical, series capacitance, and structural deflection models was verified

Current Status of Simulations

As the title suggests, the purpose of this chapter is to review the current status of numerical simulations of black hole accretion disks. This chapter focuses exclusively on global simulations of the accretion process within a few tens of gravitational radii of the black hole. Most of the simulations discussed are performed using general relativistic magnetohydrodynamic (MHD) schemes, although some mention is made of Newtonian radiation MHD simulations and smoothed particle hydrodynamics. The goal is to convey some of the exciting work that has been going on in the past few years and provide some speculation on future directions.Comment: 15 pages, 14 figures, to appear in the proceedings of the ISSI-Bern workshop on "The Physics of Accretion onto Black Holes" (8-12 October 2012

Particle mass yield in secondary organic aerosol formed by the dark ozonolysis of α-pinene

The yield of particle mass in secondary organic aerosol (SOA) formed by dark ozonolysis was measured for 0.3–22.8 ppbv of reacted α-pinene. Most experiments were conducted using a continuous-flow chamber, allowing nearly constant SOA concentration and chemical composition for several days. For comparison, some experiments were also conducted in batch mode. Reaction conditions were 25°C, 40% RH, dry (NH<sub>4</sub>)SO<sub>4</sub> seed particles, and excess 1-butanol. The organic particle loading was independently measured by an aerosol mass spectrometer and a scanning mobility particle sizer, and the two measurements agreed well. The observations showed that SOA formation occurred for even the lowest reacted α-pinene concentration of 0.3 ppbv. The particle mass yield was 0.09 at 0.15 μg m<sup>−3</sup>, increasing to 0.27 at 40 μg m<sup>−3</sup>. Compared to some results reported in the literature, the yields were 80 to 100% larger for loadings above 2 μg m<sup>−3</sup>. At lower loadings, the yields had an offset of approximately +0.07 from those reported in the literature. To as low as 0.15 μm<sup>−3</sup>, the yield curve had no inflection point toward null yield, implying the formation of one or several products having vapor pressures below this value. These observations of increased yields, especially for low loadings, are potentially important for accurate prediction by chemical transport models of organic particle concentrations in the ambient atmosphere

Cloud droplet activation of mixed organic-sulfate particles produced by the photooxidation of isoprene

The cloud condensation nuclei (CCN) properties of ammonium sulfate particles mixed with organic material condensed during the hydroxyl-radical-initiated photooxidation of isoprene (C<sub>5</sub>H<sub>8</sub>) were investigated in the continuous-flow Harvard Environmental Chamber. CCN activation curves were measured for organic particle mass concentrations of 0.5 to 10.0 μg m<sup>−3</sup>, NO<sub>x</sub> concentrations from under 0.4 ppbv up to 38 ppbv, particle mobility diameters from 70 to 150 nm, and thermodenuder temperatures from 25 to 100 °C. At 25 °C, the observed CCN activation curves were accurately described by a Köhler model having two internally mixed components, namely ammonium sulfate and secondary organic material. The modeled physicochemical parameters of the organic material were equivalent to an effective hygroscopicity parameter κ<sub>ORG</sub> of 0.10±0.03, regardless of the C<sub>5</sub>H<sub>8</sub>:NO<sub>x</sub> concentration ratio for the span of >200:0.4 to 50:38 (ppbv:ppbv). The volatilization curves (i.e., plots of the residual organic volume fraction against temperature) were also similar for the span of investigated C<sub>5</sub>H<sub>8</sub>:NO<sub>x</sub> ratios, suggesting a broad similarity of particle chemical composition. This suggestion was supported by limited variance at 25 °C among the particle mass spectra. For example, the signal intensity at <i>m/z</i> 44 (which can result from the fragmentation of oxidized molecules believed to affect hygroscopicity and CCN properties) varied weakly from 6 to 9% across the range of investigated conditions. In contradistinction to the results for 25 °C, conditioning up to 100 °C in the thermodenuder significantly reduced CCN activity. The altered CCN activity might be explained by chemical reactions (e.g., decomposition or oligomerization) of the secondary organic material at elevated temperatures. The study's results at 25 °C, in conjunction with the results of other chamber and field studies for a diverse range of conditions, suggest that a value of 0.10±0.05 for κ<sub>ORG</sub> is representative of both anthropogenic and biogenic secondary organic material. This finding supports the use of κ<sub>ORG</sub> as a simplified yet accurate general parameter to represent the CCN activation of secondary organic material in large-scale atmospheric and climate models