55 research outputs found

    Fractional Entropy Based Active Contour Segmentation of Cell Nuclei in Actin-Tagged Confocal Microscopy Images

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    In the framework of cell structure characterization for predictive oncology, we propose in this paper an unsupervised statistical region based active contour approach integrating an original fractional entropy measure for single channel actin tagged fluorescence confocal microscopy image segmentation. Following description of statistical based active contour segmentation and the mathematical definition of the proposed fractional entropy descriptor, we demonstrate comparative segmentation results between the proposed approach and standard Shannon’s entropy obtained for nuclei segmentation. We show that the unsupervised proposed statistical based approach integrating the fractional entropy measure leads to very satisfactory segmentation of the cell nuclei from which shape characterization can be subsequently used for the therapy progress assessment

    Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities

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    Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

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    The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 x 10(-8)) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.Peer reviewe

    Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

    Get PDF
    The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30-80%, depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures: word reading, nonword reading, spelling, phoneme awareness, and nonword repetition, in samples of 13,633 to 33,959 participants aged 5-26 years. We identified genome-wide significant association with word reading (rs11208009, p=1.098 x 10-8) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP-heritability, accounting for 13-26% of trait variability. Genomic structural equation modelling revealed a shared genetic factor explaining most variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis of multivariate GWAS results with neuroimaging traits identified association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain, and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide new avenues for deciphering the biological underpinnings of uniquely human traits

    Etude de la formation d'agrégats multicellulaires de carcinomes ovariens et du remodelage du microenvironnement tumoral

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    Les adénocarcinomes ovariens dérivent de la transformation maligne de l épithélium ovarien de surface, et se développent et se propagent au sein de différents microenvironnements. Les cellules transformées peuvent s exfolier à partir de la surface de l ovaire et former des agrégats multicellulaires appelés sphéroïdes . Leur dissémination implique l interaction physique des cellules cancéreuses ovariennes entre elles, leur permettant de survivre en suspension au sein de l ascite, mais également, l interaction des cellules avec un microenvironnement matriciel lors de leur réimplantation sur le tissu sain. Le travail de thèse contribue à une meilleure compréhension des mécanismes moléculaires impliqués lors des interactions au sein d agrégats multicellulaires tumoraux ainsi que lors de leur implantation. Le rôle du système adhésif composé de la vitronectine et de son récepteur, les intégrines av, ainsi que celui de la fibronectine ont plus particulièrement été appréhendé.The ovarian adenocarcinomas derive from the malignant process of the epithelium ovarian surface, and develop and propagate within various microenvironments. The transformed cells can exfoliate from the ovarian surface form multicellular aggregates called spheroids . Their dissemination involves the physical interaction of the ovarian cancer cells between them, allowing them to survive in suspension within the ascite, but also, the interaction of cells with a matrix microenvironment during their reimplantation on healthy tissue. The work of this thesis contributes to a better understanding of the molecular mechanisms involved during the interactions within tumoral multicellular aggregates as well as during their dissemination. The role of the adhesive system consisted of the vitronectine and his receptor, integrin av, as well as that of the fibronectine were more particularly studied.CERGY PONTOISE-BU Saint-Martin (951272103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF
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