769 research outputs found

    Residential Mobility and the Underclass: Impact of Moving in the \u27Hood

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    Studies of residential mobility amongst disadvantaged populations and juveniles in particular have attracted a great deal of attention with projects such as the Moving to Opportunity Study and policies aimed at reducing concentrated disadvantage by providing alternative housing assistance to low-income families. The results of these studies, however, have been inconclusive and have often not concentrated on the effects of this mobility on a broad spectrum of delinquent behaviors. Previous studies have found that residential mobility negatively affects juveniles, while other studies find that there is little effect after controlling for a wide variety of variables with scant theoretical considerations regarding modeling. This dissertation sought to address these gaps and deficiencies in the literature by examining the effects of residential mobility on a sample of highly impoverished youth by analyzing a variety of delinquent behaviors with theoretically relevant variables in order to better understand the mechanisms driving delinquent behavior. In order to test hypotheses developed from these questions, longitudinal binary and ordinal mixed-effects logit models were utilized on data drawn from the Mobile Youth Survey, which was conducted in areas of extreme poverty. The findings of the current research demonstrated that residential mobility has a weak and inconsistent effect between types of delinquent behavior. Theoretically relevant variables comprised of social bonding and strain constructs were found to mediate the significant relationship for several delinquent outcomes, indicating that these variables play a critical role in predicting delinquent behavior rather than residential mobility. Low correlations between residential mobility and delinquent outcomes indicated that for this particular population, mobility has a differential effect compared to higher socioeconomic groups analyzed in previous studies. Conclusions and implications of the current study suggested that residential mobility is not a particular concern regarding highly impoverished populations. Policies aimed at moving individuals to better neighborhoods would not have a negative effect due to the stress of moving. Addressing strain and the attenuation of social bonds would be more effective at preventing juvenile delinquency even if that means displacement of the individuals into environments that provide opportunities for the creation of stronger social bonds and lessened strain

    Met Receptor Inhibitor SU11274 Localizes in the Endoplasmic Reticulum

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    We discovered that SU11274, a class I c-Met inhibitor, fluoresces when excited by 488 nm laser light and showed rapid specific accumulation in distinct subcellular compartments. Given that SU11274 reduces cancer cell viability, we exploited these newly identified spectral properties to determine SU11274 intracellular distribution and accumulation in human pancreatic cancer cells. The aim of the studies reported here was to identify organelle(s) to which SU11274 is trafficked. We conclude that SU11274 rapidly and predominantly accumulates in the endoplasmic reticulum

    Three-Dimensional Printed Abdominal Imaging Windows for In Vivo Imaging of Deep-Lying Tissues

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    The ability to microscopically image diseased or damaged tissue throughout a longitudinal study in living mice would provide more insight into disease progression than having just a couple of time points to study. In vivo disease development and monitoring provides more insight than in vitro studies as well. In this study, we developed permanent 3D-printed, surgically implantable abdominal imaging windows (AIWs) to allow for longitudinal imaging of deep-lying tissues or organs in the abdominal cavity of living mice. They are designed to prevent organ movement while allowing the animal to behave normally throughout longitudinal studies. The AIW also acts as its own mounting bracket for attaching them to a custom 3D printed microscope mount that attaches to the stage of a microscope and houses the animal inside. During the imaging of the living animal, cellular and macroscopic changes over time in one location can be observed because markers can be used to find the same spot in each imaging session. We were able to deliver cancer cells to the pancreas and use the AIW to image the disease progression. The design of the AIWs can be expanded to include secondary features, such as delivery and manipulation ports and guides, and to make windows for imaging the brain, subcutaneous implants, and mammary tissue. In all, these 3D-printed AIWs and their microscope mount provide a system for enhancing the ability to image and study cellular and disease progression of deep-lying abdominal tissues of living animals during longitudinal studies

    Northern Late Winter Planetary Waves: MRO/MARCI Observations and Mars Climate Model Simulations

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    As does Earth, Mars presents pronounced global atmospheric circulation patterns. Solar differential heating drives mean meridional overturning (Hadley) circulations which are deep and intense, are hemispherically asymmetric, and where a cross-equatorial single cell dominates. Within middle and high latitudes, thermally indirect eddy-driven (Ferrel) circulation cells have been indicated. Differently, however, large-amplitude orography on planetary and continental scales on Mars can force very non-Earth-like hemispheric circulation patterns. Recent observations from the Mars Reconnaissance Orbiter, "Mars Color Imager" (MARCI) instrument are utilized that emphasize water ice clouds in ultra-violet (UV) wavelengths, and these measurements have been binned into "daily global maps" (DGMs) of water-ice cloud optical depth. The presence of large-scale, extratropical quasi-stationary atmospheric wave disturbances in middle and late winter of the northern hemisphere have been found to be present in such DGMs. In combination with such observations, a full-physics Mars global climate model (NASA ARC marsgcm 2.1) is applied to place the observations into context. During late northern winter, it is found that strong, forced Rossby modes (i.e., planetary waves) exist, and with direct correlation to columnintegrated cloud opacity undulating spatial patterns. At this season, zonal wavenumber s = 2 dominates (in contrast to wavenumber s = 1), consistent with MGS/TES analyses at this particular season (Banfield et al., 2003). Large-scale, planetary waves dictate the "coherence" of the northern polar vortex. Fundamentally, such forced planetary waves influence the polar vortex's impermeability (wave-induced) to tracer transport (e.g., dust and water-ice aerosol) and temporal mean water vapor spatial variations. The large-scale dynamical features of such planetary waves will be highlighted and discussed

    Predicting lymphatic filariasis transmission and elimination dynamics using a multi-model ensemble framework

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    Mathematical models of parasite transmission provide powerful tools for assessing the impacts of interventions. Owing to complexity and uncertainty, no single model may capture all features of transmission and elimination dynamics. Multi-model ensemble modelling offers a framework to help overcome biases of single models. We report on the development of a first multi-model ensemble of three lymphatic filariasis (LF) models (EPIFIL, LYMFASIM, and TRANSFIL), and evaluate its predictive performance in comparison with that of the constituents using calibration and validation data from three case study sites, one each from the three major LF endemic regions: Africa, Southeast Asia and Papua New Guinea (PNG). We assessed the performance of the respective models for predicting the outcomes of annual MDA strategies for various baseline scenarios thought to exemplify the current endemic conditions in the three regions. The results show that the constructed multi-model ensemble outperformed the single models when evaluated across all sites. Single models that best fitted calibration data tended to do less well in simulating the out-of-sample, or validation, intervention data. Scenario modelling results demonstrate that the multi-model ensemble is able to compensate for variance between single models in order to produce more plausible predictions of intervention impacts. Our results highlight the value of an ensemble approach to modelling parasite control dynamics. However, its optimal use will require further methodological improvements as well as consideration of the organizational mechanisms required to ensure that modelling results and data are shared effectively between all stakeholders

    Quantum Interference in the Field Ionization of Rydberg Atoms

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    We excite ultracold rubidium atoms in a magneto-optical trap to a coherent superposition of the three |mj | sublevels of the 37d5/2 Rydberg state. After some delay, during which the relative phases of the superposition components can evolve, we apply an electric field pulse to ionize the Rydberg electron and send it to a detector. The electron traverses many avoided crossings in the Stark levels as it ionizes. The net effect of the transitions at these crossings is to mix the amplitudes of the initial superposition into the same final states at ionization. Similar to a Mach-Zehnder interferometer, the three initial superposition components have multiple paths by which they can arrive at ionization and, since the phases of those paths differ, we observe quantum beats as a function of the delay time between excitation and initiation of the ionization pulse. We present a fully quantum-mechanical calculation of the electron’s path to ionization and the resulting interference pattern

    The human RNA polymerase II-associated factor 1 (hPaf1): a new regulator of cell-cycle progression.

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    BACKGROUND: The human PAF (hPAF) complex is part of the RNA polymerase II transcription apparatus and regulates multiple steps in gene expression. Further, the yeast homolog of hPaf1 has a role in regulating the expression of a subset of genes involved in the cell-cycle. We therefore investigated the role of hPaf1 during progression of the cell-cycle. METHODOLOGY/FINDINGS: Herein, we report that the expression of hPaf1, a subunit of the hPAF complex, increases with cell-cycle progression and is regulated in a cell-cycle dependant manner. hPaf1 specifically regulates a subclass of genes directly implicated in cell-cycle progression during G1/S, S/G2, and G2/M. In prophase, hPaf1 aligns in filament-like structures, whereas in metaphase it is present within the pole forming a crown-like structure, surrounding the centrosomes. Moreover, hPaf1 is degraded during the metaphase to anaphase transition. In the nucleus, hPaf1 regulates the expression of cyclins A1, A2, D1, E1, B1, and Cdk1. In addition, expression of hPaf1 delays DNA replication but favors the G2/M transition, in part through microtubule assembly and mitotic spindle formation. CONCLUSION/SIGNIFICANCE: Our results identify hPaf1 and the hPAF complex as key regulators of cell-cycle progression. Mutation or loss of stoichiometry of at least one of the members may potentially lead to cancer development

    The Human RNA Polymerase II-Associated Factor 1 (hPaf1): A New Regulator of Cell-Cycle Progression

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    The human PAF (hPAF) complex is part of the RNA polymerase II transcription apparatus and regulates multiple steps in gene expression. Further, the yeast homolog of hPaf1 has a role in regulating the expression of a subset of genes involved in the cell-cycle. We therefore investigated the role of hPaf1 during progression of the cell-cycle.Herein, we report that the expression of hPaf1, a subunit of the hPAF complex, increases with cell-cycle progression and is regulated in a cell-cycle dependant manner. hPaf1 specifically regulates a subclass of genes directly implicated in cell-cycle progression during G1/S, S/G2, and G2/M. In prophase, hPaf1 aligns in filament-like structures, whereas in metaphase it is present within the pole forming a crown-like structure, surrounding the centrosomes. Moreover, hPaf1 is degraded during the metaphase to anaphase transition. In the nucleus, hPaf1 regulates the expression of cyclins A1, A2, D1, E1, B1, and Cdk1. In addition, expression of hPaf1 delays DNA replication but favors the G2/M transition, in part through microtubule assembly and mitotic spindle formation.Our results identify hPaf1 and the hPAF complex as key regulators of cell-cycle progression. Mutation or loss of stoichiometry of at least one of the members may potentially lead to cancer development

    Effectiveness of a triple-drug regimen for global elimination of lymphatic filariasis : a modelling study

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    Background: Lymphatic filariasis is targeted for elimination as a public health problem by 2020. The principal approach used by current programmes is annual mass drug administration with two pairs of drugs with a good safety profile. However, one dose of a triple-drug regimen (ivermectin, diethylcarbamazine, and albendazole) has been shown to clear the transmissible stage of the helminth completely in treated individuals. The aim of this study was to use modelling to assess the potential value of mass drug administration with the triple-drug regimen for accelerating elimination of lymphatic filariasis in different epidemiological settings. Methods: We used three different transmission models to compare the number of rounds of mass drug administration needed to achieve a prevalence of microfilaraemia less than 1% with the triple-drug regimen and with current two-drug regimens. Findings: In settings with a low baseline prevalence of lymphatic filariasis (5%), the triple-drug regimen reduced the number of rounds of mass drug administration needed to reach the target prevalence by one or two rounds, compared with the two-drug regimen. For areas with higher baseline prevalence (10–40%), the triple-drug regimen strikingly reduced the number of rounds of mass drug administration needed, by about four or five, but only at moderate-to-high levels of population coverage (>65%) and if systematic non-adherence to mass drug administration was low. Interpretation: Simulation modelling suggests that the triple-drug regimen has potential to accelerate the elimination of lymphatic filariasis if high population coverage of mass drug administration can be achieved and if systematic non-adherence with mass drug administration is low. Future work will reassess these estimates in light of more clinical trial data and to understand the effect on an individual country's programme
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