3,534 research outputs found

    Theoretical investigation of the lowest five ionization potentials of uranium

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    Quantum mechanical determination of lowest five ionization potentials of uraniu

    The causal effect of red blood cell folate on genome-wide methylation in cord blood: a Mendelian randomization approach

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    Background: Investigation of the biological mechanism by which folate acts to affect fetal development can inform appraisal of expected benefits and risk management. This research is ethically imperative given the ubiquity of folic acid fortified products in the US. Considering that folate is an essential component in the one-carbon metabolism pathway that provides methyl groups for DNA methylation, epigenetic modifications provide a putative molecular mechanism mediating the effect of folic acid supplementation on neonatal and pediatric outcomes. Results: In this study we use a Mendelian Randomization Unnecessary approach to assess the effect of red blood cell (RBC) folate on genome-wide DNA methylation in cord blood. Site-specific CpG methylation within the proximal promoter regions of approximately 14,500 genes was analyzed using the Illumina Infinium Human Methylation27 Bead Chip for 50 infants from the Epigenetic Birth Cohort at Brigham and Women’s Hospital in Boston. Using methylenetetrahydrofolate reductase genotype as the instrument, the Mendelian Randomization approach identified 7 CpG loci with a significant (mostly positive) association between RBC folate and methylation level. Among the genes in closest proximity to this significant subset of CpG loci, several enriched biologic processes were involved in nucleic acid transport and metabolic processing. Compared to the standard ordinary least squares regression method, our estimates were demonstrated to be more robust to unmeasured confounding. Conclusions: To the authors’ knowledge, this is the largest genome-wide analysis of the effects of folate on methylation pattern, and the first to employ Mendelian Randomization to assess the effects of an exposure on epigenetic modifications. These results can help guide future analyses of the causal effects of periconceptional folate levels on candidate pathways

    Ageing effects around the glass and melting transitions in poly(dimethylsiloxane) visualized by resistance measurements

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    The process of ageing in rubbers requires monitoring over long periods (days to years). To do so in non-conducting rubbers, small amounts of carbon-black particles were dispersed in a fractal network through the rubber matrix, to make the rubber conducting without modifying its properties. Continuous monitoring of the resistance reveals the structural changes around the glass and melting transitions and especially details about the hysteresis and ageing processes. We illustrate the method for the semicrystalline polymer poly(dimethylsiloxane) (PDMS).Comment: 4 pages, 4 figure

    A COCRIAÇÃO DE VALOR NO ENSINO SUPERIOR PRIVADO: UM ESTUDO DE CASO NO CURSO DE ADMINISTRAÇÃO DA FACULDADE CAPIVARI - FUCAP

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    O ambiente organizacional está em um momento de grande complexidade e dinamismo, por isso encontrar formas de gerar vantagem competitiva pode ser fator determinante entre sucesso e fracasso organizacional. Embora já existam vários estudos sobre cocriação de valor, o tema ainda continua a ser uma “caixa preta” a ser explorada, e essencial para o desenvolvimento das instituições. Segundo Chandler e Vargo (2011), a cocriação de valor continua a ser um tema relevante para pesquisas, pois é preciso integrar passado e futuro para alcançar maiores níveis de crescimento organizacional. Diante disso, este estudo teve como objetivo identificar os benefícios da cocriação de valor em um curso de Administração da Faculdade Capivari. Para alcançar os objetivos a que se propôs este trabalho, optou-se pela revisão sistemática, utilizando os pressupostos epistemológicos na compreensão de seu desenvolvimento, contando com a utilização de técnicas que estão vinculadas ao paradigma interpretativista. Para a realização da pesquisa foram feitas entrevistas com docentes e discentes do Curso de Administração da Faculdade Capivari, resultando na identificação de maior produtividade no processo de ensino e aprendizagem e aumento na satisfação do alunado a partir da utilização da cocriação de valor na condução das decisões do curso

    Pyrosequencing Evaluation of Widely Available Bisulfite Conversion Methods: Considerations for Application

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    Introduction: Bisulfite treatment of DNA introduces methylation-dependent sequence changes through selective chemical conversion of nonmethylated cytosine to uracil and serves as pretreatment step for the majority of DNA methylation analysis methods. Methods: We have evaluated the conversion performance of five of the most commonly used bisulfite treatment kits [MethylDetector (Active Motif), Epitect+ (Qiagen), Zymo Methylation, Zymo Gold and Zymo Lightning (all from Zymo Research)] by pyrosequencing four different regions with variable methylation levels, including: a repetitive element (ALUSX), a gene with low levels of methylation (IL6ST), an imprinted gene expected to be approximately 50% methylated (IGF2), and a fully methylated gene (ST3GAL2). In addition, we have studied the influence of duration (3 vs. 16 h) and type (fixed temperature vs. cycling program) of incubation protocol on the conversion efficiency of each evaluated kit. Results: All kits produced similar conversion rates of ALUSX, IGF2 and ST3GAL2, while the conversion of the low methylated IL6ST gene was variable between kits. The Zymo kits were highly consistent in their performance even when different protocols of incubation were applied, generating full conversion at the low methylated gene IL6; this was not true for the MethylDetector and Epitect+ kits. However, long-cycling incubation could produce similar conversion rates for the same locus in combination with Active Motif and Qiagen kits. Conclusions: The selection of a long-cycling protocol during conversion permits standardization of protocols, improving the reproducibility of methylation estimates across laboratories for gene-specific, genome-wide and bisulfite-based sequencing analyses

    Interactions of the drug amphotericin B with phospholipid membranes containing or not ergosterol: new insight into the role of ergosterol

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    AbstractAmphotericin B (AmB) is an amphipathic polyene antibiotic which permeabilizes ergosterol-containing membranes, supposedly by formation of pores. In water, AmB forms chiral aggregates, modelled as stacks of planar dimers in which the joined polyene chains in each dimer turn round, from one dimer to the following in these stacks, by forming a helical array. Studies of the binding of AmB with L-dipalmitoylphosphatidylcholine (L-DPPC) and L-dilauroylphosphatidylcholine (L-DLPC) bilayers disclose the main following results. (1) An inversion of the helicity of the L-DPPC-bound AmB aggregates, when the L-DPPC bilayers are in the gel phase, is inferred from the evolution of the circular dichroism spectra of AmB+L-DPPC mixtures. (2) An AmB-induced gel-to-subgel transformation of L-DPPC bilayers, in the previous mixtures, is revealed by a differential scanning calorimetry study. (3) The role played by ergosterol in the location of phospholipid-bound AmB aggregates with respect to a phospholipid bilayer is directly demonstrated from atomic force microscopy observations of mica-supported AmB+L-DLPC mixtures, in the presence or absence of ergosterol. While in the absence of ergosterol AmB aggregates remained at the surface of the bilayer, in the presence of ergosterol they appeared embedded within this bilayer and became hollow-centered. As such an embedding in the hydrophobic core of a bilayer requires a rearrangement of the aggregates with respect to their architecture in water, this rearrangement is held responsible for the hollowing of aggregates. The hollow-centered sublayer-embedded AmB aggregates are thought to be the precursors of the formation of AmB pores

    An Estimate of the Vibrational Frequencies of Spherical Virus Particles

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    The possible normal modes of vibration of a nearly spherical virus particle are discussed. Two simple models for the particle are treated, a liquid drop model and an elastic sphere model. Some estimates for the lowest vibrational frequency are given for each model. It is concluded that this frequency is likely to be of the order of a few GHz for particles with a radius of the order of 50 nm.Comment: 6 pages, 1 figur
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