554 research outputs found

    The Obama Paradox: Policy Success, Political Failure

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    The presidency of Barack Obama presents us with a paradox, in that it was both a policy success and a political failure, two states that seemingly contradict with one another. His presidency is considered a policy success due to its ability to successfully pass many key pieces of legislation, despite several challenges. On the other hand, Obama\u27s presidency is also considered a political failure primarily due to the election of Donald J. Trump, someone who is not an ally to the Obama administration and has worked to undo Obama\u27s accomplishments as president in nearly every area. Today, Obama\u27s legacy as president continues to play a large impact on American politics given the high stakes nature of the current 2020 presidential election and the strong connection that both candidates running has with President Obama. As a result, examining Obama\u27s presidency and the impact it left behind is more important than ever. This research takes into consideration the large amount of literature on the paradox and evaluates several arguments by a variety of authors in four different areas of the Obama presidency to determine the strength of these arguments

    Oligodendroglioma cells lack glutamine synthetase and are auxotrophic for glutamine, but do not depend on glutamine anaplerosis for growth

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    In cells derived from several types of cancer, a transcriptional program drives high consumption of glutamine (Gln), which is used for anaplerosis, leading to a metabolic addiction for the amino acid. Low or absent expression of Glutamine Synthetase (GS), the only enzyme that catalyzes de novo Gln synthesis, has been considered a marker of Gln-addicted cancers. In this study, two human cell lines derived from brain tumors with oligodendroglioma features, HOG and Hs683, have been shown to be GS-negative. Viability of both lines depends from extracellular Gln with EC of 0.175 ± 0.056 mM (Hs683) and 0.086 ± 0.043 mM (HOG), thus suggesting that small amounts of extracellular Gln are sufficient for OD cell growth. Gln starvation does not significantly affect the cell content of anaplerotic substrates, which, consistently, are not able to rescue cell growth, but causes hindrance of the Wnt/β-catenin pathway and protein synthesis attenuation, which is mitigated by transient GS expression. Gln transport inhibitors cause partial depletion of intracellular Gln and cell growth inhibition, but do not lower cell viability. Therefore, GS-negative human oligodendroglioma cells are Gln-auxotrophic but do not use the amino acid for anaplerosis and, hence, are not Gln addicted, exhibiting only limited Gln requirements for survival and growth

    Activity Following Total Hip Arthroplasty: Which Patients Are Active, and Is Being Active Safe?

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    BACKGROUND Younger and physically active patients demand a return to sport after total hip arthroplasty (THA). However, because of the risk of implant wear and loosening, high-impact activities are often not recommended. The current study evaluates predictive factors and revision rates in patients with higher activity levels. METHODS This retrospective study included 4152 hips in 3828 patients aged 45-75 that underwent primary THA for primary osteoarthritis between 2009 and 2019 with a minimum follow-up of 2 years. Pain and Lower Extremity Activity Scale (LEAS) were assessed before and 2 years after surgery. Activity was classified as low (LEAS 1-6), moderate (LEAS 7-13), or high (LEAS 14-18). RESULTS Pain and LEAS improved from preoperative to 2-years postoperative (p < 0.001). The activity level was low in 6.2%, moderate in 52.9%, and high in 40.9% of the patients. Younger age, lower BMI, ASA, and CCI, male sex, and higher preoperative LEAS correlated with higher activity at 2 years (p < 0.001). The predicted revision-free survival rates between the activity groups were better for more highly active patients (p < 0.001). CONCLUSIONS High physical activity 2 years following THA, with participating in sports like jogging several times a week, did not increase the risk of revision surgery. THA patients should not be prevented from a highly active lifestyle

    Contingency Games for Multi-Agent Interaction

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    Contingency planning, wherein an agent generates a set of possible plans conditioned on the outcome of an uncertain event, is an increasingly popular way for robots to act under uncertainty. In this work, we take a game-theoretic perspective on contingency planning which is tailored to multi-agent scenarios in which a robot's actions impact the decisions of other agents and vice versa. The resulting contingency game allows the robot to efficiently coordinate with other agents by generating strategic motion plans conditioned on multiple possible intents for other actors in the scene. Contingency games are parameterized via a scalar variable which represents a future time at which intent uncertainty will be resolved. Varying this parameter enables a designer to easily adjust how conservatively the robot behaves in the game. Interestingly, we also find that existing variants of game-theoretic planning under uncertainty are readily obtained as special cases of contingency games. Lastly, we offer an efficient method for solving N-player contingency games with nonlinear dynamics and non-convex costs and constraints. Through a series of simulated autonomous driving scenarios, we demonstrate that plans generated via contingency games provide quantitative performance gains over game-theoretic motion plans that do not account for future uncertainty reduction

    Experimental Zika Virus Infection in the Pregnant Common Marmoset Induces Spontaneous Fetal Loss and Neurodevelopmental Abnormalities.

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    During its most recent outbreak across the Americas, Zika virus (ZIKV) was surprisingly shown to cause fetal loss and congenital malformations in acutely and chronically infected pregnant women. However, understanding the underlying pathogenesis of ZIKV congenital disease has been hampered by a lack of relevant in vivo experimental models. Here we present a candidate New World monkey model of ZIKV infection in pregnant marmosets that faithfully recapitulates human disease. ZIKV inoculation at the human-equivalent of early gestation caused an asymptomatic seroconversion, induction of type I/II interferon-associated genes and proinflammatory cytokines, and persistent viremia and viruria. Spontaneous pregnancy loss was observed 16-18 days post-infection, with extensive active placental viral replication and fetal neurocellular disorganization similar to that seen in humans. These findings underscore the key role of the placenta as a conduit for fetal infection, and demonstrate the utility of marmosets as a highly relevant model for studying congenital ZIKV disease and pregnancy loss

    Species at Risk (SPEAR) index indicates effects of insecticides on stream invertebrate communities in soy production regions of the Argentine Pampas

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    We investigated relationships among insecticides and aquatic invertebrate communities in 22 streams of two soy production regions of the Argentine Pampas over three growing seasons. Chlorpyrifos, endosulfan, cypermethrin, and lambda-cyhalothrin were the insecticides most frequently detected in stream sediments. The Species at Risk (SPEAR) pesticide bioassessment index (SPEARpesticides) was adapted and applied to evaluate relationships between sediment insecticide toxic units (TUs) and invertebrate communities associated with both benthic habitats and emergent vegetation habitats. SPEARpesticides was the only response metric that was significantly correlated with total insecticide TU values for all three averaged data sets, consistently showing a trend of decreasing values with increasing TU values (r2 = 0.35 to 0.42, p-value = 0.001 to 0.03). Although pyrethroids were the insecticides that contributed the highest TU values, toxicity calculated based on all insecticides was better at predicting changes in invertebrate communities than toxicity of pyrethroids alone. Crustaceans, particularly the amphipod Hyalella spp., which are relatively sensitive to pesticides, played a large role in the performance of SPEARpesticides, and the relative abundance of all crustaceans also showed a significant decreasing trend with increasing insecticide TUs for two of three data sets (r2 = 0.30 to 0.57, p-value = 0.003 to 0.04) examined. For all data sets, total insecticide TU was the most important variable in explaining variance in the SPEARpesticides index. The present study was the first application of the SPEAR index in South America, and the first one to use it to evaluate effects of pesticides on invertebrate communities associated with aquatic vegetation. Although the SPEAR index was developed in Europe, it performed well in the Argentine Pampas with only minor modifications, and would likely improve in performance as more data are obtained on traits of South American taxa, such as pesticide sensitivity and generation time.Instituto de Limnología "Dr. Raúl A. Ringuelet

    Species at Risk (SPEAR) index indicates effects of insecticides on stream invertebrate communities in soy production regions of the Argentine Pampas

    Get PDF
    We investigated relationships among insecticides and aquatic invertebrate communities in 22 streams of two soy production regions of the Argentine Pampas over three growing seasons. Chlorpyrifos, endosulfan, cypermethrin, and lambda-cyhalothrin were the insecticides most frequently detected in stream sediments. The Species at Risk (SPEAR) pesticide bioassessment index (SPEARpesticides) was adapted and applied to evaluate relationships between sediment insecticide toxic units (TUs) and invertebrate communities associated with both benthic habitats and emergent vegetation habitats. SPEARpesticides was the only response metric that was significantly correlated with total insecticide TU values for all three averaged data sets, consistently showing a trend of decreasing values with increasing TU values (r2 = 0.35 to 0.42, p-value = 0.001 to 0.03). Although pyrethroids were the insecticides that contributed the highest TU values, toxicity calculated based on all insecticides was better at predicting changes in invertebrate communities than toxicity of pyrethroids alone. Crustaceans, particularly the amphipod Hyalella spp., which are relatively sensitive to pesticides, played a large role in the performance of SPEARpesticides, and the relative abundance of all crustaceans also showed a significant decreasing trend with increasing insecticide TUs for two of three data sets (r2 = 0.30 to 0.57, p-value = 0.003 to 0.04) examined. For all data sets, total insecticide TU was the most important variable in explaining variance in the SPEARpesticides index. The present study was the first application of the SPEAR index in South America, and the first one to use it to evaluate effects of pesticides on invertebrate communities associated with aquatic vegetation. Although the SPEAR index was developed in Europe, it performed well in the Argentine Pampas with only minor modifications, and would likely improve in performance as more data are obtained on traits of South American taxa, such as pesticide sensitivity and generation time.Instituto de Limnología "Dr. Raúl A. Ringuelet

    Development of a robust and convenient dual-reporter high-throughput screening assay for SARS-CoV-2 antiviral drug discovery.

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    Massive efforts on both vaccine development and antiviral research were launched to combat the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We contributed, amongst others, by the development of a high-throughput screening (HTS) antiviral assay against SARS-CoV-2 using a fully automated, high-containment robot system. Here, we describe the development of this novel, convenient and phenotypic dual-reporter virus-cell-based high-content imaging assay using the A549+hACE2+TMPRSS2_mCherry reporter lung carcinoma cell line and an ancestral SARS-CoV-2_Wuhan_mNeonGreen reporter virus. Briefly, by means of clonal selection, a host cell subclone was selected that (i) efficiently supports replication of the reporter virus with high expression, upon infection, of the NeonGreen fluorescent reporter protein, (ii) that is not affected by virus-induced cytopathogenic effects and, (iii) that expresses a strong fluorescent mCherry signal in the nucleus. The selected clone matched these criteria with an infection rate on average of 75% with limited cell death. The average (R)Z'-factors of the assay plates were all >0.8, which indicates a robust assay suitable for HTS purposes. A selection of reference compounds that inhibits SARS-CoV-2 replication in vitro were used to validate this novel dual-reporter assay and confirms the data reported in the literature. This assay is a convenient and powerful tool for HTS of large compound libraries against SARS-CoV-2
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