38 research outputs found

    Urban-Rural Differences in School Districts\u27 Local Wellness Policies and Policy Implementation Environments

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    Higher rates of obesity in rural compared to urban districts suggest environmental differences that affect student health. This study examined urban-rural differences in districts\u27 local wellness policies (LWPs) and LWP implementation environments. Cross-sectional data from two assessments in Texas were analyzed. In assessment one, each district\u27s LWP was reviewed to see if 16 goals were included. In assessment two, an audit was conducted to identify the presence of a wellness plan (a document with recommendations for implementing LWPs), triennial LWP assessment, and school health advisory councils (SHACs) on the district website. Rural districts\u27 LWPs had a smaller number of total goals (B = -2.281

    Examination of the specificity of DNA methylation profiling techniques towards 5-methylcytosine and 5-hydroxymethylcytosine

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    DNA cytosine-5 methylation is a well-studied epigenetic pathway implicated in gene expression control and disease pathogenesis. Different technologies have been developed to examine the distribution of 5-methylcytosine (5mC) in specific sequences of the genome. Recently, substantial amounts of 5-hydroxymethylcytosine (5hmC), most likely derived from enzymatic oxidation of 5mC by TET1, have been detected in certain mammalian tissues. Here, we have examined the ability of several commonly used DNA methylation profiling methods to distinguish between 5mC and 5hmC. We show that techniques based on sodium bisulfite treatment of DNA are incapable of distinguishing between the two modified bases. In contrast, techniques based on immunoprecipitation with anti-5mC antibody (methylated DNA immunoprecipitation, MeDIP) or those based on proteins that bind to methylated CpG sequences (e.g. methylated-CpG island recovery assay, MIRA) do not detect 5hmC and are specific for 5mC unless both modified bases occur in the same DNA fragment. We also report that several methyl-CpG binding proteins including MBD1, MBD2 and MBD4 do not bind to sequences containing 5hmC. Selective mapping of 5hmC will require the development of unique tools for the detection of this modified base

    Optimal foreign borrowing: The impact of the planning horizon on the half and full debt cycle

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    Shrimp is one of the predominant causes of food allergy among adults, often presenting with severe reactions. Current in vitro diagnostics are based on quantification of patient specific-IgE (sIgE) to shrimp extract. Tropomyosin is the known major shrimp allergen, but IgE sensitisation to other allergens is poorly characterised. In this study, the binding of IgE to various shrimp allergens, additional to tropomyosin, was investigated using sera from 21 subjects who had clinical reactions to one or more shellfish species. Total shrimp-sIgE was quantified using ImmunoCAP, while allergen-sIgEs were quantified using immunoblotting and mass spectrometry, and immuno-PCR to recombinant shrimp tropomyosin. Sixty-two percent of subjects (13/21) were positive to shrimp by ImmunoCAP. IgE from 43% of subjects (9/21) bound tropomyosin, while an additional 29% of subjects (6/21) demonstrated IgE-binding solely to other shrimp allergens, including sarcoplasmic calcium-binding protein, arginine kinase and hemocyanin. Furthermore, IgE sensitisation to other shrimp allergens was demonstrated in 50% of subjects (4/8) who were ImmunoCAP negative. The lack of standardised shrimp allergens and inadequacy of current extracts for shrimp allergy diagnosis is highlighted by this study. Comprehensive knowledge of less studied allergens and their inclusion in component-resolved diagnostics will improve diagnostic accuracy, benefitting the wider population suffering from shellfish allergy

    Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity

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    The TET family of FE(II) and 2-oxoglutarate-dependent enzymes (Tet1/2/3) promote DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine (5hmC), which they further oxidize into 5-formylcytosine and 5-carboxylcytosine. Tet1 is robustly expressed in mouse embryonic stem cells (mESCs) and has been implicated in mESC maintenance. Here we demonstrate that, unlike genetic deletion, RNAi-mediated depletion of Tet1 in mESCs led to a significant reduction in 5hmC and loss of mESC identity. The differentiation phenotype due to Tet1 depletion positively correlated with the extent of 5hmC loss. Meta-analyses of genomic data sets suggested interaction between Tet1 and leukemia inhibitory factor (LIF) signaling. LIF signaling is known to promote self-renewal and pluripotency in mESCs partly by opposing MAPK/ERK-mediated differentiation. Withdrawal of LIF leads to differentiation of mESCs. We discovered that Tet1 depletion impaired LIF-dependent Stat3-mediated gene activation by affecting Stat3's ability to bind to its target sites on chromatin. Nanog overexpression or inhibition of MAPK/ERK signaling, both known to maintain mESCs in the absence of LIF, rescued Tet1 depletion, further supporting the dependence of LIF/Stat3 signaling on Tet1. These data support the conclusion that analysis of mESCs in the hours/days immediately following efficient Tet1 depletion reveals Tet1's normal physiological role in maintaining the pluripotent state that may be subject to homeostatic compensation in genetic models

    Methalox Propellant for Future Launch Vehicles: A comparative study of methalox, hydrolox and kerolox propellants for future launch vehicles

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    Contrasting experience with Reusable Launch vehicles—Space Shuttle and Falcon 9— has established that potential of reusable launch vehicles to achieve low launch costs is driven by the design choices made. Methalox propellant is one such design choice that has been touted to power future missions and potentially replace traditional propellants — Hydrolox and Kerolox. The high density of methalox compared to hydrolox and improved specific impulse compared to kerolox, potentially make methalox an ideal propellant choice. To justify any new design choice, cost-based analysis is essential, especially given the persisting issue of high launch cost. Additionally, it is essential to benchmark the performance of any new design choice with existing practices, especially when they are expected to replace current practices. For this, a cost based comparative analysis of methalox based launchers with hydrolox and kerolox launchers is performed using a tool capable of launch vehicle design and cost analysis. Rather than designing a tool from scratch, existing First Stage Recovery Tool (FRT), which was developed by M. Rozemeijer to modify and cost existing expendable launchers to include reusability, was extended to include a launch vehicle design module, which was previously lacking. A Multidisciplinary Design Analysis and Optimization (MDAO) methodology was applied for the design module. The design module was developed by verified and validated models implemented from literature for hydrolox, kerolox and methalox propellants and an optimization scheme to minimize for Gross Lift-Off Mass (GLOM). This design module in conjunction with the FRT enables design and costing of expendable and reusable launcher configurations. For the current study, two missions were considered—15600 kg payload to Low Earth Orbit (LEO) and a 5000 kg payload to Geostationary Transfer Orbit (GTO)—for different propellant combination-based launchers. Additionally, different launcher configurations— expendable, reusable via non-propulsive recovery and reusable via propulsive recovery—were considered, enabling cost comparison of propellants for different scenarios. Results indicate that methalox based launchers are cost-effective solution when compared to hydrolox, regardless of mission type or launcher configuration considered in the current study. Compared to kerolox, only a marginal cost benefit can be achieved, for the case of expendable configuration and in combination with kerolox. For reusable configurations, purely methalox shows potential to achieve costs within 10% of kerolox. Sensitivity analysis showed the potential to reduce this gap by including the lower refurbishment requirement of methalox, given low soot formation possibility. Furthermore, it showed the need for a better engine model for methalox, to refine comparison between methalox and kerolox. The tool, however, is not complete and should be extended to include reliability assessment, especially for methalox systems, which are not flight proven unlike hydrolox and kerolox. There also remains issues with the accuracy and uncertainty in certain models, which make the current version suitable only for comparative studies.Aerospace Engineerin

    Crim1–, a regulator of developmental organogenesis

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    The regulation of growth factor localization, availability and activity is critical during embryogenesis to ensure appropriate organogenesis. This process is regulated through the coordinated expression of growth factors and their cognate receptors, as well as via proteins that can bind, sequester or localize growth factors to distinct locations. One such protein is the transmembrane protein Crim1. This protein has been shown to be expressed broadly within the developing embryo, and to regulate organogenesis within the eye, kidney and placenta. Mechanistically, Crim1 has been revealed to mediate organogenesis via its interaction with growth factors including TGFβs, BMPs, VEGFs and PDFGs. More recently, Crim1 has been shown to influence cardiac development, providing further insights into the function of this protein. This review will provide an overview of the role of Crim1 in organogenesis, largely focusing on how this protein regulates growth factor signaling in the nascent heart. Moreover, we will address the challenges ahead relating to further elucidating how Crim1 functions during development
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