242 research outputs found

    Governing the Alien Threat : A Multilevel Analysis of Punitiveness Toward Non-Citizen Federal Drug Offenders Across Time and Place

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    Though frequently disadvantaged across a plethora of various institutions throughout history, noncitizens have become increasingly targeted with recent political rhetoric refocusing on immigration as a threat to homeland security. The latent effects of this renewed political platform has been a heightened awareness of the “immigration threat” that has infiltrated the criminal justice system. Previous research has found that citizenship status is related to sentencing outcomes despite the identification of this variable as extralegal by the USSC, though research remains largely divided on the extent and manifestation of this disparity. Furthermore, only a very few of these studies have examined potential mediating and moderating effects within noncitizens. Because political rhetoric emphasizes “illegal immigrants from Mexico,” ethnicity, country of origin, and documentation status are likely to influence sentencing outcomes. This dissertation is the first known study to control for each of these potential mediators in the analysis of noncitizen federal sentencing disparities. Because the emphasis on foreign populations is not immutable but rather fluctuates according to the existing sociocultural context, aggregated sentencing data fails to acknowledge nuanced patterns of disadvantage, often masking disparities. This study is among the first to examine the effects of citizenship status on federal sentencing outcomes over time and across districts and is the first study to do so while controlling for spatial autocorrelation. Multilevel modeling techniques are employed to examine cases nested within sentencing districts. A queen contiguity spatial weight matrix is included to control for geographic proximity. Finally, a series of growth models are used to examine longitudinal patterns in sentencing outcomes across districts over time. The results of this study support the contention that noncitizens receive more severe sentencing outcomes across numerous outcomes including incarceration, prison alternatives for eligible offenders, sentence length, and departures. Ethnicity, country of origin, and documentation status were also frequently found to be significant predictors of sentencing severity though fail to explain citizenship effects in their entirety. Sentencing outcomes have fluctuated over time, with sentencing outcomes demonstrating increased severity. Furthermore, variations in district caseloads and offender demographics demonstrate unique effects on noncitizen sentencing outcomes, though not always in the anticipated direction

    Wireline Coring and Analysis under Pressure: Recent Use and Future Developments of the HYACINTH System

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    The pressure of the deep sea and of deep earth formations has subtle effects on all aspects of physics, chemistry, and biology. Core material recovered under pressure, using pressure cores, can be subjected to sophisticated laboratory analyses that are not feasible in situ. Though many fields of study might benefit from pressurized cores, most obviously, any investigation on gas- or gas-hydrate-rich formations on land or under the sea certainly requires pressure coring

    Reducing Burnout in Nursing: Implementation of a Mindfulness-Based Intervention

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    Objective: To decrease nursing burnout in a rural hospital setting. Background: Burnout increases the rate of turnover, lowers patient satisfaction scores, and increases costs. An estimated 15.6% of nurses are experiencing burnout at an annual cost of 9 billion dollars for hospitals. Local Problem: A rural hospital in Tennessee without a burnout reduction program available to staff. Methods: The Iowa Model Revised was utilized to implement a mindfulness-based stress reduction program. Invention/Measurements: The Palouse mindfulness-based stress reduction program was utilized for this evidence-based practice project. The online course spans eight weeks and includes videos, reading materials, and worksheets. The program takes approximately 50 hours to complete. The Copenhagen Burnout Inventory measured burnout pre-implementation and post-implementation. Results: Paired t-tests were performed to compare pre-implementation burnout and post-implementation burnout. Participants had a statistically significant improvement in burnout in all three areas measured by the Copenhagen Burnout Inventory: personal (p=.014), work related (p=.024), and client related (p=.008). Nine participants completed the pre-implementation and post-implementation surveys. Of those nine, 66% completed at least half of the content in the program. Conclusion: The use of a mindfulness-based stress reduction program resulted in a statistically significant decrease in burnout amongst nurses in this setting

    Designed ankyrin repeat proteins for detecting prostate-specific antigen expression in vivo

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    Late-stage prostate cancer often acquires resistance to conventional chemotherapies and transforms into a hormone-refractory, drug-resistant, and non-curative disease. Developing non-invasive tools to detect the biochemical changes that correlate with drug efficacy and reveal the onset of drug resistance would have important ramifications in managing the treatment regimen for individual patients. Here, we report the selection of new Designed Ankyrin Repeat Proteins (DARPins) that show high affinity toward prostate-specific antigen (PSA), a biomarker used in clinical monitoring of prostate cancer. Ribosome display and in vitro screening tools were used to select PSA-binding DARPins based on their binding affinity, selectivity, and chemical constitution. Surface plasmon resonance measurements demonstrated that the four lead candidates bind to PSA with nanomolar affinity. DARPins were site-specifically functionalised at a unique C-terminal cysteine with a hexadentate aza-nonamacrocyclic chelate (NODAGA) for subsequent radiolabelling with the positron-emitting radionuclide 68^{68}Ga. [68^{68}Ga]GaNODAGA-DARPins showed high stability toward transchelation and were stable in human serum for >2 h. Radioactive binding assays using streptavidin-loaded magnetic beads confirmed that the functionalisation and radiolabelling did not compromise the specificity of [68^{68}Ga]GaNODAGA-DARPins toward PSA. Biodistribution experiments in athymic nude mice bearing subcutaneous prostate cancer xenografts derived from the LNCaP cell line revealed that three of the four [68^{68}Ga]GaNODAGA-DARPins displayed specific tumour-binding in vivo. For DARPin-6, tumour-uptake in the normal group reached 4.16 ± 0.58% ID g−1^{-1} (n = 3; 2 h post-administration) and was reduced by ∌50% by competitive binding with a low molar activity formulation (blocking group: 2.47 ± 0.42% ID g−1^{-1}; n = 3; P value = 0.018). Collectively, the experimental results support the future development of new PSA-specific imaging agents for potential use in monitoring the efficacy of androgen receptor (AR)-targeted therapies

    Quantification of gas hydrate saturation and morphology based on a generalized effective medium model

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    Highlights ‱ A modified cementation theory is developed by introducing generalized pressure-dependent normalized contact-cemented radii. ‱ A generalized effective medium model is proposed to merge the effective medium theory and cementation theory. ‱ Modeling and inversion schemes are proposed to quantify hydrate saturation and morphology from laboratory and well-log data. ‱ Hydrates mainly grow as matrix-supporting form (~54%) in sands and as pore-filling form (~59%) in clay-rich marine sediments. Abstract Numerous models have been developed for prediction of gas hydrate saturation based on the microstructural relationship between gas hydrates and sediment grains. However, quantification of hydrate saturation and morphology from elastic properties has been hindered by failing to account for complex hydrate distributions. Here, we develop a generalized effective medium model by applying the modified Hashin-Shtrikman bounds to a newly developed cementation theory. This model is validated by experimental data for synthetic methane and tetrahydrofuran hydrates. Good comparison of model predictions with experimental measurements not only reveals its ability to merge the results of contact cementation theory and effective medium theory, but also indicates its feasibility for characterizing complex morphologies. Moreover, the results of inverting acoustic measurements quantitatively confirm that for synthetic samples in “excess-gas” condition gas hydrates mainly occur as a hybrid-cementing morphology with a low percentage of pore-filling morphology, whereas for pressure-core hydrate-bearing sediments in natural environments they exist as matrix-supporting and pore-filling morphologies with a very low percentage of hybrid-cementing morphology. The hydrate saturations estimated from sonic and density logs in several regions including northern Cascadia margin (Integrated Ocean Drilling Program Expedition 311, Hole U1326D and Hole U1327E), Alaska North Slope (Mount Elbert test well) and Mackenzie Delta (Mallik 5L-38), are comparable to the referenced hydrate saturations derived from core data and resistivity, and/or nuclear magnetic resonance log data, confirming validity and applicability of our model. Furthermore, our results indicate that ~8% hybrid-cementing, ~33% matrix-supporting and ~59% pore-filling hydrates may coexist in the fine-grained and clay-rich marine sediments on the northern Cascadia margin, whereas ~10% hybrid-cementing, ~54% matrix-supporting and ~36% pore-filling hydrates may coexist in the coarse-grained and sand-dominated terrestrial sediments of the Alaska North Slope and Mackenzie Delta

    Suitability of the height above nearest drainage (HAND) model for flood inundation mapping in data-scarce regions: a comparative analysis with hydrodynamic models

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    Unprecedented floods from extreme rainfall events worldwide emphasize the need for flood inundation mapping for floodplain management and risk reduction. Access to flood inundation maps and risk evaluation tools remains challenging in most parts of the world, particularly in rural regions, leading to decreased flood resilience. The use of hydraulic and hydrodynamic models in rural areas has been hindered by excessive data and computational requirements. In this study, we mapped the flood inundation in Huron Creek watershed, Michigan, USA for an extreme rainfall event (1000-year return period) that occurred in 2018 (Father’s Day Flood) using the Height Above Nearest Drainage (HAND) model and a synthetic rating curve developed from LIDAR DEM. We compared the flood inundation extent and depth modeled by the HAND with flood inundation characteristics predicted by two hydrodynamic models, viz., HEC-RAS 2D and SMS-SRH 2D. The flood discharge of the event was simulated using the HEC-HMS hydrologic model. Results suggest that, in different channel segments, the HAND model produces different degrees of concurrence in both flood inundation extent and depth when compared to the hydrodynamic models. The differences in flood inundation characteristics produced by the HAND model are primarily due to the uncertainties associated with optimal parameter estimation of the synthetic rating curve. Analyzing the differences between the HAND and hydrodynamic models also highlights the significance of terrain characteristics in model predictions. Based on the comparable predictive capability of the HAND model to map flood inundation areas during extreme rainfall events, we demonstrate the suitability of the HAND-based approach for mitigating flood risk in data-scarce, rural regions

    Ancient expansion of the Hox cluster in Lepidoptera generated four homeobox genes implicated in extra-embryonic tissue formation

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    Gene duplications within the conserved Hox cluster are rare in animal evolution, but in Lepidoptera an array of divergent Hox-related genes (Shx genes) has been reported between pb and zen. Here, we use genome sequencing of five lepidopteran species (Polygonia c-album, Pararge aegeria, Callimorpha dominula, Cameraria ohridella, Hepialus sylvina) plus a caddisfly outgroup (Glyphotaelius pellucidus) to trace the evolution of the lepidopteran Shx genes. We demonstrate that Shx genes originated by tandem duplication of zen early in the evolution of large clade Ditrysia; Shx are not found in a caddisfly and a member of the basally diverging Hepialidae (swift moths). Four distinct Shx genes were generated early in ditrysian evolution, and were stably retained in all descendent Lepidoptera except the silkmoth which has additional duplications. Despite extensive sequence divergence, molecular modelling indicates that all four Shx genes have the potential to encode stable homeodomains. The four Shx genes have distinct spatiotemporal expression patterns in early development of the Speckled Wood butterfly (Pararge aegeria), with ShxC demarcating the future sites of extraembryonic tissue formation via strikingly localised maternal RNA in the oocyte. All four genes are also expressed in presumptive serosal cells, prior to the onset of zen expression. Lepidopteran Shx genes represent an unusual example of Hox cluster expansion and integration of novel genes into ancient developmental regulatory networks

    Charting the Chemical and Mechanistic Scope of Light-Triggered Protein Ligation

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    The creation of discrete, covalent bonds between a protein and a functional molecule like a drug, fluorophore, or radiolabeled complex is essential for making state-of-the-art tools that find applications in basic science and clinical medicine. Photochemistry offers a unique set of reactive groups that hold potential for the synthesis of protein conjugates. Previous studies have demonstrated that photoactivatable desferrioxamine B (DFO) derivatives featuring a para-substituted aryl azide (ArN3ArN_3) can be used to produce viable zirconium-89-radiolabeled monoclonal antibodies (89Zr−mAbs^{89}Zr-mAbs) for applications in noninvasive diagnostic positron emission tomography (PET) imaging of cancers. Here, we report on the synthesis, 89Zr^{89}Zr-radiochemistry, and light-triggered photoradiosynthesis of 89Zr^{89}Zr-labeled human serum albumin (HSA) using a series of 14 different photoactivatable DFO derivatives. The photoactive groups explore a range of substituted, and isomeric ArN3ArN_3 reagents, as well as derivatives of benzophenone, a para-substituted trifluoromethyl phenyl diazirine, and a tetrazole species. For the compounds studied, efficient photochemical activation occurs inside the UVA-to-visible region of the electromagnetic spectrum (∌365–450 nm) and the photochemical reactions with HSA in water were complete within 15 min under ambient conditions. Under standardized experimental conditions, photoradiosynthesis with compounds 1–14 produced the corresponding 89ZrDFO−PEG3−HSA^{89}ZrDFO-PEG_{3}-HSA conjugates with decay-corrected isolated radiochemical yields between 18.1 ± 1.8% and 62.3 ± 3.6%. Extensive density functional theory (DFT) calculations were used to explore the reaction mechanisms and chemoselectivity of the light-induced bimolecular conjugation of compounds 1–14 to protein. The photoactivatable DFO-derivatives operate by at least five distinct mechanisms, each producing a different type of bioconjugate bond. Overall, the experimental and computational work presented here confirms that photochemistry is a viable option for making diverse, functionalized protein conjugates
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