459 research outputs found

    From Cave Pictures: “The Light Princess” Graphic Comic

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    Use of Solvent Injection Chromatography for Evaluating Extractive Distillation Systems

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    Chemical Engineerin

    An efficient approach to screening epigenome-wide data

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    Screening cytosine-phosphate-guanine dinucleotide (CpG) DNA methylation sites in association with some covariate(s) is desired due to high dimensionality. We incorporate surrogate variable analyses (SVAs) into (ordinary or robust) linear regressions and utilize training and testing samples for nested validation to screen CpG sites. SVA is to account for variations in the methylation not explained by the specified covariate(s) and adjust for confounding effects. To make it easier to users, this screening method is built into a user-friendly R package, ttScreening, with efficient algorithms implemented. Various simulations were implemented to examine the robustness and sensitivity of the method compared to the classical approaches controlling for multiple testing: the false discovery rates-based (FDR-based) and the Bonferroni-based methods. The proposed approach in general performs better and has the potential to control both types I and II errors. We applied ttScreening to 383,998 CpG sites in association with maternal smoking, one of the leading factors for cancer risk

    Sexual dimorphism in glioma glycolysis underlies sex differences in survival

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    The molecular bases for sex differences in cancer remain undefined and how to incorporate them into risk stratification remains undetermined. Given sex differences in metabolism and the inverse correlation between fluorodeoxyglucose (FDG) uptake and survival, we hypothesized that glycolytic phenotyping would improve glioma subtyping. Using retrospectively acquired lower-grade glioma (LGG) transcriptome data from The Cancer Genome Atlas (TCGA), we discovered male-specific decreased survival resulting from glycolytic gene overexpression. Patients within this high-glycolytic group showed significant differences in the presence of key genomic alterations (i.e., 1p/19q codeletion, CIC, EGFR, NF1, PTEN, FUBP1, and IDH mutations) compared with the low-glycolytic group. Although glycolytic stratification defined poor prognostic males independent of grade, histology, TP53, and ATRX mutation status, we unexpectedly found that females with high-glycolytic gene expression and wild-type IDH survived longer than all other wild-type patients. Validation with an independent metabolomics dataset from grade 2 gliomas determined that glycolytic metabolites selectively stratified males and also uncovered a potential sexual dimorphism in pyruvate metabolism. These findings identify a potential synergy between patient sex, tumor metabolism, and genomic alterations in determining outcome for glioma patients

    A persistent major mutation in canonical jasmonate signaling is embedded in an herbivory-elicited gene network

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    When insect herbivores attack plants, elicitors from oral secretions and regurgitants (OS) enter wounds during feeding, eliciting defense responses. These generally require plant jasmonate (JA) signaling, specifically, a jasmonoyl-L-isoleucine (JA-Ile) burst, for their activation and are well studied in the native tobacco Nicotiana attenuata. We used intraspecific diversity captured in a 26-parent MAGIC population planted in nature and an updated genome assembly to impute natural variation in the OS-elicited JA-Ile burst linked to a mutation in the JA-Ile biosynthetic gene NaJAR4. Experiments revealed that NaJAR4 variants were associated with higher fitness in the absence of herbivores but compromised foliar defenses, with two NaJAR homologues (4 and 6) complementing each other spatially and temporally. From decade-long seed collections of natural populations, we uncovered enzymatically inactive variants occurring at variable frequencies, consistent with a balancing selection regime maintaining variants. Integrative analyses of OS-induced transcriptomes and metabolomes of natural accessions revealed that NaJAR4 is embedded in a nonlinear complex gene coexpression network orchestrating responses to OS, which we tested by silencing four hub genes in two connected coexpressed networks and examining their OS-elicited metabolic responses. Lines silenced in two hub genes (NaGLR and NaFB67) co-occurring in the NaJAR4/6 module showed responses proportional to JA-Ile accumulations; two from an adjacent module (NaERF and NaFB61) had constitutively expressed defenses with high resistance. We infer that mutations with large fitness consequences can persist in natural populations due to compensatory responses from gene networks, which allow for diversification in conserved signaling pathways and are generally consistent with predictions of an omnigene model

    Development of the Continuously Variable Volume Reactor for Flow Injection AnalysisDesign, Capabilities and Testing

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    A new apparatus for mixing sample and reagent in flow injection analysis is described. The continuously variable volume reactor (CVVR) replaces the conventional mixing coil in a flow injection manifold to provide mixing and dilution. A linear actuator motor allows control of the chamber volume via Lab VIEW software. The chamber volume can be incremented in steps of 1 uL over the range 68-1704 uL. In addition, the chamber has an integral variable-speed stirring unit that is also under computer control. Experiments were performed to evaluate the dispersion characteristics of this new device, evaluate the volume reproducibility, and understand the mixing characteristics. Use of the chamber is shown in the determination of iron (II) in pond water, and in NIST SRM 1643d with excellent results and a detection limit of 3.7 ug/L iron(II). Advantages of the CVVR and future research activities using the device are discussed

    The Community Mobilization for Preventive Action (COMPACT) project in Zambia: A midline evaluation

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    The Population Council and its partner, Project Concern International, implemented the Community Mobilization for Preventive Action (COMPACT) HIV-prevention program in Zambia. The program works with communities to develop “compacts” through a participatory, community-led process, and assists them in working toward reaching HIV-related “benchmarks,” intended to result in a reduction in HIV-related risk behaviors and harmful norms and ultimately contribute over time to the reduction of HIV incidence. This mid-term evaluation in four of six COMPACT communities indicates that COMPACT is improving some HIV-related behaviors and attitudes, particularly those related to gender norms, multiple sex partnerships, and alcohol abuse. The report concludes that HIV-prevention programs in Zambia must incorporate alcohol risk reduction activities; furthermore, lessons learned from income-generation programs and programs addressing harmful gender norms should be used to strengthen other HIV prevention programs
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