4,308 research outputs found

    Genetic basis of octanoic acid resistance in drosophila sechellia: functional analysis of a fine-mapped region

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    Masters thesisDrosophila sechellia is a species of fruit fly endemic to the Seychelles islands, which are located northeast of Madagascar off the coast of Africa. Unlike its generalist sister species D. simulans and D. mauritiana, and their closest relative D. melanogaster, D. sechellia evolved to specialize on a single plant species, Morinda citrifolia. Specialization on M. citrifolia is surprising because the fruit of the plant contains toxic compounds, primarily octanoic acid (OA), that are lethal to all Drosophila species except D. sechellia. Although the ecological and behavioral adaptations to this toxic fruit are known, the genetic basis for the evolutionary changes in OA resistance is not. Prior work showed that a genomic region on chromosome 3R, containing 18 genes, contributes to OA tolerance. To determine which gene(s) in this region might be involved in the evolution of OA resistance, I knocked-down expression of each gene in D. melanogaster with RNA interference (RNAi) (i) ubiquitously throughout development, (ii) during the adult stage, and (iii) within specific tissues in D. melanogaster. RNAi knockdown flies were tested for resistance to OA using the mixed effects Cox regression model. I found that knock-down of three neighboring genes, Osiris 6, Osiris 7, and Osiris 8, increased OA sensitivity. Tissue specific knockdowns, however, showed that decreasing expression of these genes in the fat body and salivary glands increases OA tolerance. I show that both Osi6/7 are highly expressed during the first 24 hours of development and that exposure to different stressors induces expression in adults. Although Osi6/7 have no coding change, RNA-seq data shows derived lower expression of these genes in D. sechellia; Osi8 has two derived coding changes in D. sechellia. This study sheds light on the genetic basis of ecological adaptation to a toxic host within Drosophila, and insect-host specialization more broadly.http://deepblue.lib.umich.edu/bitstream/2027.42/113257/1/MSThesis2015_AndradeLopez.pdf-1Description of MSThesis2015_AndradeLopez.pdf : Thesis tex

    Bayesian Probabilistic Power Flow Analysis Using Jacobian Approximate Bayesian Computation

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    A probabilistic power flow (PPF) study is an essential tool for the analysis and planning of a power system when specific variables are considered as random variables with particular probability distributions. The most widely used method for solving the PPF problem is Monte Carlo simulation (MCS). Although MCS is accurate for obtaining the uncertainty of the state variables, it is also computationally expensive, since it relies on repetitive deterministic power flow solutions. In this paper, we introduce a different perspective for the PPF problem. We frame the PPF as a probabilistic inference problem, and instead of repetitively solving optimization problems, we use Bayesian inference for computing posterior distributions over state variables. Additionally, we provide a likelihood-free method based on the Approximate Bayesian Computation philosophy, that incorporates the Jacobian computed from the power flow equations. Results in three different test systems show that the proposed methodologies are competitive alternatives for solving the PPF problem, and in some cases, they allow for reduction in computation time when compared to MCS

    Accurate calibration of the four-detector photopolarimeter with imperfect polarizing optical elements

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    The first three columns of the instrument matrix A of the four-detector photopolarimeter (FDP) are determined by Fourier analysis of the output current vector I(P) as a function of the azimuth angle P of the incident linearly polarized light. Therefore 12 of the 16 elements of A are measured free of the imperfections of the (absent) quarter-wave retarder (QWR). The effect of angular beam deviation by the polarizer is compensated for by taking the average, (1/2) [I(P) + I(P + 180°)], of the FDP output at 180°-apart, optically equivalent, angular positions of the polarizer. The remaining fourth column of A is determined by the FDP’s response to the right- and left-handed circular polarization states. Because these states are impossible to generate with an imperfect QWR, a novel procedure is developed. In particular, the response of the FDP to the unattainable right- or left-handed circular polarization state is found by taking the average of the responses of the FDP to an elliptical near-circular state and that state rotated in azimuth by 90°. This calibration scheme is applied to measure A of our prototype FDP of four Si detectors at λ = 632.8 nm. A is determined, in external and internal reference frames, free of imperfections in the polarizing optical elements. The FDP, with its uncontaminated A matrix, is used subsequently to evaluate the imperfections of the QWR with the help of an appropriate model

    Efficient modeling of latent information in supervised learning using Gaussian processes

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    Often in machine learning, data are collected as a combination of multiple conditions, e.g., the voice recordings of multiple persons, each labeled with an ID. How could we build a model that captures the latent information related to these conditions and generalize to a new one with few data? We present a new model called Latent Variable Multiple Output Gaussian Processes (LVMOGP) that allows to jointly model multiple conditions for regression and generalize to a new condition with a few data points at test time. LVMOGP infers the posteriors of Gaussian processes together with a latent space representing the information about different conditions. We derive an efficient variational inference method for LVMOGP for which the computational complexity is as low as sparse Gaussian processes. We show that LVMOGP significantly outperforms related Gaussian process methods on various tasks with both synthetic and real data

    Physically-inspired Gaussian process models for post-transcriptional regulation in Drosophila

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    The regulatory process of Drosophila is thoroughly studied for understanding a great variety of biological principles. While pattern-forming gene networks are analysed in the transcription step, post-transcriptional events (e.g. translation, protein processing) play an important role in establishing protein expression patterns and levels. Since the post-transcriptional regulation of Drosophila depends on spatiotemporal interactions between mRNAs and gap proteins, proper physically-inspired stochastic models are required to study the link between both quantities. Previous research attempts have shown that using Gaussian processes (GPs) and differential equations lead to promising predictions when analysing regulatory networks. Here we aim at further investigating two types of physically-inspired GP models based on a reaction-diffusion equation where the main difference lies in where the prior is placed. While one of them has been studied previously using protein data only, the other is novel and yields a simple approach requiring only the differentiation of kernel functions. In contrast to other stochastic frameworks, discretising the spatial space is not required here. Both GP models are tested under different conditions depending on the availability of gap gene mRNA expression data. Finally, their performances are assessed on a high-resolution dataset describing the blastoderm stage of the early embryo of Drosophila melanogaster

    Prevención cardiovascular y de la osteoporosis con terapia hormonal sustitutiva

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    Se recomienda actualmente que todo médico -sea cual sea su especialidad- aproveche la oportunidad que supone la atención clínica a cualquier mujer postmenopáusica o que se halle en torno a la menopausia para aconsejarle acerca de los beneficios y riesgos que supone la terapia hormonal sustitutiva (THS) con estrógenos y progesterona. Una vez que sea adecuadamente informada de estos beneficios y riesgos, debe ser la propia mujer quien decida si va a iniciar o no esta terapia, teniendo en cuenta no sólo su propio perfil de riesgo sino también sus preferencias. Los beneficios más claros se refieren a la reducción del riesgo de osteoporosis y de fracturas, así como al control y prevención de algunos síntomas frecuentes en la menopausia. Para prevenir la osteoporosis se requiere un uso continuado de IaTHS. También existen cada vez más argumentos que sugieren una reducción del riesgo de un primer episodio coronario. No obstante, no hay pruebas de que laTHS sea útil en la prevención secundaria de la cardiopatía isquémica o aporte alguna protección frente a los accidentes cerebrovasculares. Las desventajas más importantes de la THS se refieren a un mayor riesgo de hiperplasia de endometrio y de cáncer endometrial cuando se usan estrógenos solos, sin combinarlos con progestágenos. También existe un pequeño incremento del riesgo de cáncer de mama cuando se prolonga la THS, también cuando se asocian progestágenos

    Fabrication of chromium carbide cermets by electric resistance sintering process: Processing, microstructure and mechanical properties

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    Chromium carbide-based cermets are suitable for use in abrasive and corrosive environments. This work presents the fabrication of chromium carbide-based cermets by a very fast sintering process: Electric Resistance Sintering. The thermal cycle duration was less than 1 s and without protective atmosphere. Two different compositions were studied: Cr3C2-25NiCr (wt%) and WC-20Cr3C2-7Ni (wt%). Microstructure and crystallographic phases of the initial powders and sintered materials are presented. In addition, hardness and toughness were characterized and compared to conventional materials. One important issue of ERS is the size and homogeneity of the pieces. This work presents the also the fabrication of a mining wear piece and some aspects about scaling up.This work is financially supported by the European Institute of Innovation and Technology (EIT Raw Materials), a body of European Union (Horizon 2020 Framework Programme) under the project FASTRAM

    Differential hypertrophic effects of cardiotrophin-1 on adult cardiomyocytes from normotensive and spontaneously hypertensive rats

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    Cardiotrophin-1 (CT-1) produces longitudinal elongation of neonatal cardiomyocytes, but its effects in adult cardiomyocytes are not known. Recent observations indicate that CT-1 may be involved in pressure overload left ventricular hypertrophy (LVH). We investigated whether the hypertrophic effects of CT-1 are different in cardiomyocytes isolated from adult normotensive and spontaneously hypertensive rats (SHR). Hypertrophy was evaluated by planimetry and confocal microscopy, contractile proteins were quantified by Western blotting and real-time RT-PCR, and intracellular pathways were analyzed with specific chemical inhibitors. CT-1 increased c-fos and ANP expression (p<0.01) and cell area (p<0.01) in cardiomyocytes from both rat strains. In Wistar cells, CT-1 augmented cell length (p<0.01) but did not modify either the transverse diameter or cell depth. In SHR cells, CT-1 increased cell length (p<0.05), cell width (p<0.01) and cell depth, augmented the expression of myosin light chain-2v (MLC-2v) and skeletal alpha-actin (p<0.01) and enhanced MLC-2v phosphorylation (p<0.01). The blockade of gp130 or LIFR abolished CT-1-induced growth in the two cell types. All distinct effects observed in cardiomyocytes from SHR were mediated by STAT3. Baseline angiotensinogen expression was higher in SHR cells, and CT-1 induced a 1.7-fold and 3.2-fold increase of angiotensinogen mRNA in cardiomyocytes from Wistar rats and SHR respectively. In addition, AT1 blockade inhibited the specific effects of CT-1 in SHR cells. Finally, ex vivo determinations revealed that adult SHR exhibited enhanced myocardial CT-1 (mRNA and protein, p<0.01), increased cell width (p<0.01) and concentric LVH compared with pre-hypertensive SHR. These findings reveal a specific cell-broadening effect of CT-1 in cardiomyocytes from adult SHR and suggest that the hypertensive phenotype of these cells may influence the hypertrophic effects of CT-1, probably by means of an exaggerated induction of angiotensinogen expression. We suggest that CT-1 might facilitate LVH in genetic hypertension through a cross-talk with the renin-angiotensin system
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