1,720,959 research outputs found

    Implication des facteurs transcriptionnels Slug et Snail dans les carcinomes du sein in-vivo et dans des modèles 3D : Localisation fonctionnelle et lien à la progression tumoral sous traitement

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    L'émergence de la plasticité et de la résistance parmi les cellules tumorales sous traitement est un problème essentiel pour la thérapie. Parmi les mécanismes impliqués, les voies contrôlant la plasticité cellulaire paraissent incontournables avec l'activation de gènes tels que Slug et Snail. Pour analyser leurs rôles nous avons généré des modèles 3D pertinents et originaux, permettant l'analyse dynamique des cellules tumorales dans un environnement contrôlé. Nous avons d'abord étudié extensivement l'organisation tumorale et le profil d'expression de Slug et Snail dans les divers types de cancers du sein, à partir d'une cohorte de 656 tumeurs organisées en micro tissus sur lames multi-échantillons. Cette analyse topologique nous a permis de mieux comprendre les liens entre gènes, fonctions invasives et proliférations. Basé sur ces résultats, nous avons développé deux types de modèles 3D.Le premier, est analytique. Dans ce modèle, nous pouvons suivre la réponse des cellules tumorales, leur morphogenèse, leur plasticité, leur capacité à migrer et leur éventuelle résistance après une à deux semaines de traitements avec ou sans la présence de cellules stromales et immunitaires compétentes. Le second modèle, en collaboration avec la startup Okomera est destiné au criblage haut débit à partir de micro-puits permettant la croissance de 150 agrégats par puce. Nous l'avons adapté avec un protocole destiné à une utilisation préclinique pour fournir en une semaine un tableau des résistances aux traitements avec des combinaisons utilisés par les cliniciens. Ces deux modèles sont la base de deux publications publiées. L'une pour l'utilisation préclinique, l'autre s'attachant aux mécanismes d'émergence des résistances.The emergence of plasticity and resistance among tumor cells under treatment is a key issue for therapy. Among the mechanisms involved, the pathways controlling cellular plasticity seem unavoidable, with the activation of genes such as Slug and Snail. To analyze their roles, we have generated relevant and original 3D models, enabling dynamic analysis of tumor cells in a controlled environment. We began by extensively studying tumor organization and the expression profile of Slug and Snail in various types of breast cancer, based on a cohort of 656 tumors organized as microtissues on multisample slides. This topological analysis enabled us to better understand the links between genes, invasive functions, and proliferation. Based on these results, we have developed two types of 3D model.The first is analytical. In this model, we can monitor tumor cell response, morphogenesis, plasticity, migratory capacity and resistance after one to two weeks of treatment, with or without the presence of competent stromal and immune cells. The second model, in collaboration with the startup Okomera, is designed for high- throughput screening using microwells capable of growing 150 aggregates per chip. We have adapted it with a protocol designed for preclinical use, to provide in a week's time a picture of resistance to treatments with combinations used by clinicians. These two models are the basis of two published publications. One for preclinical use, the other focusing on the mechanisms of resistance emergence

    Implication des facteurs transcriptionnels Slug et Snail dans les carcinomes du sein in-vivo et dans des modèles 3D : Localisation fonctionnelle et lien à la progression tumoral sous traitement

    No full text
    The emergence of plasticity and resistance among tumor cells under treatment is a key issue for therapy. Among the mechanisms involved, the pathways controlling cellular plasticity seem unavoidable, with the activation of genes such as Slug and Snail. To analyze their roles, we have generated relevant and original 3D models, enabling dynamic analysis of tumor cells in a controlled environment. We began by extensively studying tumor organization and the expression profile of Slug and Snail in various types of breast cancer, based on a cohort of 656 tumors organized as microtissues on multisample slides. This topological analysis enabled us to better understand the links between genes, invasive functions, and proliferation. Based on these results, we have developed two types of 3D model.The first is analytical. In this model, we can monitor tumor cell response, morphogenesis, plasticity, migratory capacity and resistance after one to two weeks of treatment, with or without the presence of competent stromal and immune cells. The second model, in collaboration with the startup Okomera, is designed for high- throughput screening using microwells capable of growing 150 aggregates per chip. We have adapted it with a protocol designed for preclinical use, to provide in a week's time a picture of resistance to treatments with combinations used by clinicians. These two models are the basis of two published publications. One for preclinical use, the other focusing on the mechanisms of resistance emergence.L'émergence de la plasticité et de la résistance parmi les cellules tumorales sous traitement est un problème essentiel pour la thérapie. Parmi les mécanismes impliqués, les voies contrôlant la plasticité cellulaire paraissent incontournables avec l'activation de gènes tels que Slug et Snail. Pour analyser leurs rôles nous avons généré des modèles 3D pertinents et originaux, permettant l'analyse dynamique des cellules tumorales dans un environnement contrôlé. Nous avons d'abord étudié extensivement l'organisation tumorale et le profil d'expression de Slug et Snail dans les divers types de cancers du sein, à partir d'une cohorte de 656 tumeurs organisées en micro tissus sur lames multi-échantillons. Cette analyse topologique nous a permis de mieux comprendre les liens entre gènes, fonctions invasives et proliférations. Basé sur ces résultats, nous avons développé deux types de modèles 3D.Le premier, est analytique. Dans ce modèle, nous pouvons suivre la réponse des cellules tumorales, leur morphogenèse, leur plasticité, leur capacité à migrer et leur éventuelle résistance après une à deux semaines de traitements avec ou sans la présence de cellules stromales et immunitaires compétentes. Le second modèle, en collaboration avec la startup Okomera est destiné au criblage haut débit à partir de micro-puits permettant la croissance de 150 agrégats par puce. Nous l'avons adapté avec un protocole destiné à une utilisation préclinique pour fournir en une semaine un tableau des résistances aux traitements avec des combinaisons utilisés par les cliniciens. Ces deux modèles sont la base de deux publications publiées. L'une pour l'utilisation préclinique, l'autre s'attachant aux mécanismes d'émergence des résistances

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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