5,349 research outputs found

    The Role of the Basic Health Program in the Coverage Continuum: Opportunities, Risks and Considerations for States

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    Outlines issues for offering subsidized coverage to those eligible for insurance exchange subsidies by using federal dollars that would otherwise go to those subsidies, including continuity of coverage, impact on exchanges, and financial feasibility

    Cross-Product Extensions of the Gene Ontology

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    The Gene Ontology is being normalized and extended to include computable logical definitions. These definitions are partitioned into mutually exclusive cross-product sets, many of which reference other OBO Foundry ontologies. The results can be used to reason over the ontology, and to make cross-ontology queries

    Why Stay? A Phenomenological Look at Special Education Teacher Retention

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    This phenomenological study examined the teaching experiences of veteran special education teachers (SETs) and why they chose to remain in a special education teaching setting. Guided by Bronfenbrenner’s ecological systems framework, veteran SETs were interviewed and asked to describe the experiences and situations that have influenced their decision to remain in special education. Three themes and two sub-categories emerged as their motivation for persevering: (A) a calling from above, (B) standing up for the underdog, (b) personally committed to my kids, my babies, (C) beating the bushes with the apathetic, (c) against my ethical judgment. Specific information related to these themes is reported with implications for hiring practices of special education teachers and future special education teacher retention/attrition research

    Identification of early gene expression changes in primary cultured neurons treated with topoisomerase I poisons.

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    Topoisomerase 1 (TOP1) poisons like camptothecin (CPT) are currently used in cancer chemotherapy but these compounds can have damaging, off-target effects on neurons leading to cognitive, sensory and motor deficits. To understand the molecular basis for the enhanced sensitivity of neurons to CPT, we examined the effects of compounds that inhibit TOP1-CPT, actinomycin D (ActD) and β-lapachone (β-Lap)-on primary cultured rat motor (MN) and cortical (CN) neurons as well as fibroblasts. Neuronal cells expressed higher levels of Top1 mRNA than fibroblasts but transcript levels are reduced in all cell types after treatment with CPT. Microarray analysis was performed to identify differentially regulated transcripts in MNs in response to a brief exposure to CPT. Pathway analysis of the differentially expressed transcripts revealed activation of ERK and JNK signaling cascades in CPT-treated MNs. Immediate-early genes like Fos, Egr-1 and Gadd45b were upregulated in CPT-treated MNs. Fos mRNA levels were elevated in all cell types treated with CPT; Egr-1, Gadd45b and Dyrk3 transcript levels, however, increased in CPT-treated MNs and CNs but decreased in CPT-treated fibroblasts. These transcripts may represent new targets for the development of therapeutic agents that mitigate the off-target effects of chemotherapy on the nervous system

    Boolean intervals in the weak Bruhat order of a finite Coxeter group

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    Given a Coxeter group WW with Coxeter system (W,S)(W,S), where SS is finite. We provide a complete characterization of Boolean intervals in the weak order of WW uniformly for all Coxeter groups in terms of independent sets of the Coxeter graph. Moreover, we establish that the number of Boolean intervals of rank kk in the weak order of WW is ik(ΓW)W/2k{i_k(\Gamma_W)\cdot|W|}\,/\,2^{k}, where ΓW\Gamma_W is the Coxeter graph of WW and ik(ΓW)i_k(\Gamma_W) is the number of independent sets of size kk of ΓW\Gamma_W when WW is finite. Specializing to AnA_n, we recover the characterizations and enumerations of Boolean intervals in the weak order of AnA_n given in arXiv:2306.14734. We provide the analogous results for types CnC_n and DnD_n, including the related generating functions and additional connections to well-known integer sequences

    Risk of hospitalisation or death in households with a case of COVID-19 in England: an analysis using the HOSTED dataset

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    Objective: To determine whether household contacts of confirmed cases of COVID-19 have an increased risk of hospitalisation or death. Methods: We used the HOSTED dataset of index cases of COVID-19 in England between June and November 2020, linked to Secondary Uses Service data on hospital episodes and Office for National Statistics’ mortality data. Multivariable logistic regression models of the odds of household contacts being hospitalised or dying within six weeks of an index case, adjusted for case type, age, sex and calendar month were calculated. Excess risk was determined by comparing the first six weeks after the index case with 6-12 weeks after the index case in a survival analysis framework. Results: Index cases were more likely to be hospitalised or die than either secondary cases or non-cases, having adjusted for age and sex. There was an increased risk of hospitalisation for non-cases (adjusted hazard ratio (aHR) 1.10 (95% CI 1.04, 1.16)) and of death (aHR 1.57 (95% CI 1.14, 2.16)) in the first six weeks after an index case, compared to 6-12 weeks after. Conclusion: Risks of hospitalisation and mortality are predictably higher in cases compared to non-cases. The short-term increase in risks for non-case contacts following diagnosis of the index case may suggest incomplete case ascertainment among contacts, although this was relatively small

    Analysis of Oligomerization Properties of Heme a Synthase Provides Insights into Its Function in Eukaryotes

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    Heme a is an essential cofactor for function of cytochrome c oxidase in the mitochondrial electron transport chain. Several evolutionarily conserved enzymes have been implicated in the biosynthesis of heme a, including the heme a synthase Cox15. However, the structure of Cox15 is unknown, its enzymatic mechanism and the role of active site residues remain debated, and recent discoveries suggest additional chaperone-like roles for this enzyme. Here, we investigated Cox15 in the model eukaryote Saccharomyces cerevisiae via several approaches to examine its oligomeric states and determine the effects of active site and human pathogenic mutations. Our results indicate that Cox15 exhibits homotypic interactions, forming highly stable complexes dependent upon hydrophobic interactions. This multimerization is evolutionarily conserved and independent of heme levels and heme a synthase catalytic activity. Four conserved histidine residues are demonstrated to be critical for eukaryotic heme a synthase activity and cannot be substituted with other heme-ligating amino acids. The 20-residue linker region connecting the two conserved domains of Cox15 is also important; removal of this linker impairs both Cox15 multimerization and enzymatic activity. Mutations of COX15 causing single amino acid conversions associated with fatal infantile hypertrophic cardiomyopathy and the neurological disorder Leigh syndrome result in impaired stability (S344P) or catalytic function (R217W), and the latter mutation affects oligomeric properties of the enzyme. Structural modeling of Cox15 suggests these two mutations affect protein folding and heme binding, respectively. We conclude that Cox15 multimerization is important for heme a biosynthesis and/or transfer to maturing cytochrome c oxidase
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