258 research outputs found

    Reassessing the History of U.S. Hazardous Waste Disposal Policy - Problem Definition, Expert Knowledge and Agenda-Setting

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    The authors show that in the 1940\u27s technical consensus began to develop about the effects of land-based waste disposal on groundwater degradation. They go on to explain why this understanding was only slowly reflected in federal legislation

    Characterization of Cre recombinase activity for in vivo targeting of adipocyte precursor cells.

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    The increased incidence of obesity and metabolic disease underscores the importance of elucidating the biology of adipose tissue development. The recent discovery of cell surface markers for prospective identification of adipose precursor cells (APCs) in vivo will greatly facilitate these studies, yet tools for specifically targeting these cells in vivo have not been identified. Here, we survey three transgenic mouse lines, Fabp4-Cre, PdgfRĪ±-Cre, and Prx1-Cre, precisely assessing Cre-mediated recombination in adipose stromal populations and mature tissues. Our data provide key insights into the utility of these tools to modulate gene expression in adipose tissues. In particular, Fabp4-Cre is not effective to target APCs, nor is its activity restricted to these cells. PdgfRĪ±-Cre directs recombination in the vast majority of APCs, but also targets other populations. In contrast, adipose expression of Prx1-Cre is chiefly limited to subcutaneous inguinal APCs, which will be valuable for dissection of APC functions among adipose depots

    Assessing Dimensions of the Security-Liberty Trade-off in the United States

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    The trade-off between security and liberty has been a leading frame for understanding public opinion about domestic surveillance policies. Most of the empirical work explicitly examining whether individuals meet the trade-off frameworkā€™s core attitudinal assumptions comes from European studies. This study uses a survey of US residents to assess the veracity of the assumptions embedded in the trade-off framework, namely whether domestic counterterrorism policies are simultaneously viewed as improving security and decreasing liberty. We find that the vast majority of US respondents do not meet the basic attitudinal assumptions of the trade-off frame. Next, we evaluate the source of these attitudes with a focus on whether attitudes toward surveillance policies merely relate to core political values or whether they also depend on the messages from political leaders. We find that both political values and opinion leadership shape these attitudes. Finally, because general attitudes towards surveillance and privacy often fail to have practical implications, we assess whether these attitudes matter for understanding the structure of policy support. Our results show that heightened terrorism threat positively associates with increased support for counterterrorism policies only when people believe these policies are effective security tools

    QES-Fire: A dynamically coupled fast-response wildfire model

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    A microscale wildfire model, QES-Fire, that dynamically couples the fire front to microscale winds was developed using a simplified physics rate of spread (ROS) model, a kinematic plume-rise model and a mass-consistent wind solver. The model is three-dimensional and couples fire heat fluxes to the wind field while being more computationally efficient than other coupled models. The plume-rise model calculates a potential velocity field scaled by the ROS model\u27s fire heat flux. Distinct plumes are merged using a multiscale plume-merging methodology that can efficiently represent complex fire fronts. The plume velocity is then superimposed on the ambient winds and the wind solver enforces conservation of mass on the combined field, which is then fed into the ROS model and iterated on until convergence. QES-Fire\u27s ability to represent plume rise is evaluated by comparing its results with those from an atmospheric large-eddy simulation (LES) model. Additionally, the model is compared with data from the FireFlux II field experiment. QES-Fire agrees well with both the LES and field experiment data, with domain-integrated buoyancy fluxes differing by less than 17% between LES and QES-Fire and less than a 10% difference in the ROS between QES-Fire and FireFlux II data

    LARP7 is a stable component of the 7SK snRNP while P-TEFb, HEXIM1 and hnRNP A1 are reversibly associated

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    Regulation of the elongation phase of RNA polymerase II transcription by P-TEFb is a critical control point for gene expression. The activity of P-TEFb is regulated, in part, by reversible association with one of two HEXIMs and the 7SK snRNP. A recent proteomics survey revealed that P-TEFb and the HEXIMs are tightly connected to two previously-uncharacterized proteins, the methyphosphate capping enzyme, MEPCE, and a La-related protein, LARP7. Glycerol gradient sedimentation analysis of lysates from cells treated with P-TEFb inhibitors, suggested that the 7SK snRNP reorganized such that LARP7 and 7SK remained associated after P-TEFb and HEXIM1 were released. Immunodepletion of LARP7 also depleted most of the 7SK regardless of the presence of P-TEFb, HEXIM or hnRNP A1 in the complex. Small interfering RNA knockdown of LARP7 in human cells decreased the steady-state level of 7SK, led to an initial increase in free P-TEFb and increased Tat transactivation of the HIV-1 LTR. Knockdown of LARP7 or 7SK ultimately caused a decrease in total P-TEFb protein levels. Our studies have identified LARP7 as a 7SK-binding protein and suggest that free P-TEFb levels are determined by a balance between release from the large form and reduction of total P-TEFb

    The Drosophila 7SK snRNP and the essential role of dHEXIM in development

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    Regulation of the positive transcription elongation factor, P-TEFb, plays a major role in controlling mammalian transcription and this is accomplished in part by controlled release of P-TEFb from the 7SK snRNP that sequesters the kinase in an inactive state. We demonstrate here that a similar P-TEFb control system exists in Drosophila. We show that an RNA previously suggested to be a 7SK homolog is, in fact, associated with P-TEFb, through the action of a homolog of the human HEXIM1/2 proteins (dHEXIM). In addition, a Drosophila La related protein (now called dLARP7) is shown to be the functional homolog of human LARP7. The Drosophila 7SK snRNP (d7SK snRNP) responded to treatment of cells with P-TEFb inhibitors and to nuclease treatment of cell lysates by releasing P-TEFb. Supporting a critical role for the d7SK snRNP in Drosophila development, dLARP7 and dHEXIM were found to be ubiquitously expressed throughout embryos and tissues at all stages. Importantly, knockdown of dHEXIM was embryonic lethal, and reduction of dHEXIM in specific tissues led to serious developmental defects. Our results suggest that regulation of P-TEFb by the d7SK snRNP is essential for the growth and differentiation of tissues required during Drosophila development
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