1,720,967 research outputs found
Développement d’un concept innovant de détection et de quantification de la protéine « Multidrug Resistance » P-gp avec les traceurs fluorescents LightSpot® ainsi que d’une nouvelle méthodologie de conservation de sphéroïdes du cancer du sein Triple Négatif dans le milieu synthétique OptiPASS®
No full textCancer drug resistance is a complex biological process representing a major challenge in Oncology for the optimization of cancer treatments. It is the main cause of treatment failure and is frequently associated with a significant risk of tumor relapse or recurrence. In this context, the "Résistance" group, part of the IMoST team (UMR INSERM / UCA 1240) has focused its research works on the study of cancer resistance through the development of in vitro preclinical tools. For this, this group uses Triple Negative Breast Cancer (CSTN) as study model, a breast cancer subtype particularly aggressive and often prone to the development of resistant profiles. One of the main mechanisms involved in cancer resistance is the basal or induced overexpression of transmembrane proteins called MultiDrug Resistance (MDR). These ubiquitous members of the ABC transporters superfamily are involved in the cellular cross-resistance to many cancer treatments, in particular by extracellular efflux of a large panel of xenobiotics. In this context, the “Résistance” group is developing LightSpot® fluorescent probes to detect and quantify the presence of MDR proteins. The first part of this works allowed to validate the use of this type of probes for the detection of cancer resistance established by the Permeability-glycoprotein (P-gp), a major MDR protein. In particular, the LightSpot®-FL-1 probe enables the sensitive and complete detection and quantification of P-gp, on fresh or fixed 2D and 3D cell models. On the other hand, the "Resistance" group is developing models of spheroids, faithfully mimicking the resistance of avascular tumor micro-regions. These 3D cell culture models have a great potential for high-throughput drug screening. Thus, the second part of this works allowed the development of an innovative concept for the preservation of CSTN MDA-MB-231 spheroids, as an alternative to conventional cryopreservation techniques. This concept involves maintaining spheroids for up to 7 days in OptiPASS® medium, in anoxia and at 4 °C. The results have demonstrated that these storage conditions preserved the integrity of various parameters of the spheroids, in particular their growth, their viability and their response to various anticancer drugs. This protocol for the preservation of spheroids will in particular allow to optimize their use, transport, and integration into large drug screening platforms. All of this doctoral research work focused on the development (1) of fluorescent tracers for the detection of MDR proteins and (2) of a spheroid storage protocol, are enhanced by a direct industrial transfer, within the BIORCELL3D consortium. The latter created by the strong public / private collaboration between the "Resistance" group and the BIOPASS and BIOMARQUEURS companies has enabled the development of an important value chain.La résistance des cellules tumorales aux traitements est un processus biologique complexe représentant un défi majeur en Oncologie pour l’optimisation des traitements du cancer. Elle constitue la principale cause d’échec thérapeutique et est souvent associée à un risque important de rechute ou de récidives tumorales. Dans ce contexte, le groupe « Résistance » faisant partie de l’équipe IMoST (UMR INSERM/UCA 1240) a focalisé ses axes de recherche sur l’étude de la résistance tumorale par le développement d’outils précliniques in vitro. Pour ce faire, il utilise le modèle d’étude du Cancer du Sein Triple Négatif (CSTN), un sous-type de cancer du sein particulièrement agressif et souvent sujet au développement de profils résistants. L’un des principaux mécanismes impliqués dans la résistance tumorale est la surexpression basale ou induite de protéines transmembranaires appelées « MultiDrug Resistance » (MDR). Ces membres extrêmement ubiquitaires de la superfamille des transporteurs ABC sont impliqués dans la résistance croisée des cellules aux traitements anticancéreux, notamment par efflux extracellulaire d’un large panel de xénobiotiques. Dans ce cadre, le groupe « Résistance » développe des traceurs fluorescents LightSpot® permettant de détecter et quantifier la présence de protéines MDR. La première partie de ces travaux de thèse ont permis de valider l’utilisation de ce type de traceurs pour la détection de la résistance tumorale instaurée par la Permeability-glycoprotein (P-gp), une protéine MDR majeure. Notamment, le traceur LightSpot®-FL-1 permet de détecter et quantifier de manière sensible et complète la P-gp, sur des modèles cellulaires 2D et 3D, à l’état frais ou fixé. D’autre part le groupe « Résistance » développe des modèles de sphéroïdes, mimant fidèlement la résistance de microrégions tumorales avasculaires. Ces modèles de cultures cellulaires 3D présentent un fort potentiel pour le screening de médicaments à grande échelle. La seconde partie de ces travaux de thèse a permis de développer un concept innovant de préservation de sphéroïdes de CSTN MDA-MB-231, comme alternatif aux techniques conventionnelles de cryopréservation. Ce concept implique de maintenir les sphéroïdes jusqu’à 7 jours dans le milieu OptiPASS®, en anoxie et à 4°C. Les résultats obtenus ont démontré que ces conditions de conservations maintiennent intègres différents paramètres des sphéroïdes, notamment leur croissance, leur viabilité et leur réponse vis-à-vis de différents traitements anticancéreux. Ce protocole de préservation de sphéroïdes pourra notamment permettre d’optimiser leur utilisation, leur transport et leur intégration dans des grandes plateformes de screening médicamenteux. L’ensemble de ces travaux de recherche doctorale focalisés sur le développement (1) de traceurs fluorescents de détection des protéines MDR et (2) d’un protocole de conservation de sphéroïdes, sont valorisés par un transfert industriel direct, au sein du consortium BIORCELL3D. Ce dernier créé par la forte collaboration public/privé entre le groupe de « Résistance » et les sociétés BIOPASS et BIOMARQUEURS a permis l’élaboration d’une importante chaine de valorisation
Development of an innovative concept of detection and quantification of the Multidrug Resistance protein P-gp with LightSpot® fluorescent tracers, and of a new Triple Negative Breast Cancer spheroids preservation methodology in the OptiPASS® synthetic medium
No full textLa résistance des cellules tumorales aux traitements est un processus biologique complexe représentant un défi majeur en Oncologie pour l’optimisation des traitements du cancer. Elle constitue la principale cause d’échec thérapeutique et est souvent associée à un risque important de rechute ou de récidives tumorales. Dans ce contexte, le groupe « Résistance » faisant partie de l’équipe IMoST (UMR INSERM/UCA 1240) a focalisé ses axes de recherche sur l’étude de la résistance tumorale par le développement d’outils précliniques in vitro. Pour ce faire, il utilise le modèle d’étude du Cancer du Sein Triple Négatif (CSTN), un sous-type de cancer du sein particulièrement agressif et souvent sujet au développement de profils résistants. L’un des principaux mécanismes impliqués dans la résistance tumorale est la surexpression basale ou induite de protéines transmembranaires appelées « MultiDrug Resistance » (MDR). Ces membres extrêmement ubiquitaires de la superfamille des transporteurs ABC sont impliqués dans la résistance croisée des cellules aux traitements anticancéreux, notamment par efflux extracellulaire d’un large panel de xénobiotiques. Dans ce cadre, le groupe « Résistance » développe des traceurs fluorescents LightSpot® permettant de détecter et quantifier la présence de protéines MDR. La première partie de ces travaux de thèse ont permis de valider l’utilisation de ce type de traceurs pour la détection de la résistance tumorale instaurée par la Permeability-glycoprotein (P-gp), une protéine MDR majeure. Notamment, le traceur LightSpot®-FL-1 permet de détecter et quantifier de manière sensible et complète la P-gp, sur des modèles cellulaires 2D et 3D, à l’état frais ou fixé. D’autre part le groupe « Résistance » développe des modèles de sphéroïdes, mimant fidèlement la résistance de microrégions tumorales avasculaires. Ces modèles de cultures cellulaires 3D présentent un fort potentiel pour le screening de médicaments à grande échelle. La seconde partie de ces travaux de thèse a permis de développer un concept innovant de préservation de sphéroïdes de CSTN MDA-MB-231, comme alternatif aux techniques conventionnelles de cryopréservation. Ce concept implique de maintenir les sphéroïdes jusqu’à 7 jours dans le milieu OptiPASS®, en anoxie et à 4°C. Les résultats obtenus ont démontré que ces conditions de conservations maintiennent intègres différents paramètres des sphéroïdes, notamment leur croissance, leur viabilité et leur réponse vis-à-vis de différents traitements anticancéreux. Ce protocole de préservation de sphéroïdes pourra notamment permettre d’optimiser leur utilisation, leur transport et leur intégration dans des grandes plateformes de screening médicamenteux. L’ensemble de ces travaux de recherche doctorale focalisés sur le développement (1) de traceurs fluorescents de détection des protéines MDR et (2) d’un protocole de conservation de sphéroïdes, sont valorisés par un transfert industriel direct, au sein du consortium BIORCELL3D. Ce dernier créé par la forte collaboration public/privé entre le groupe de « Résistance » et les sociétés BIOPASS et BIOMARQUEURS a permis l’élaboration d’une importante chaine de valorisation.Cancer drug resistance is a complex biological process representing a major challenge in Oncology for the optimization of cancer treatments. It is the main cause of treatment failure and is frequently associated with a significant risk of tumor relapse or recurrence. In this context, the "Résistance" group, part of the IMoST team (UMR INSERM / UCA 1240) has focused its research works on the study of cancer resistance through the development of in vitro preclinical tools. For this, this group uses Triple Negative Breast Cancer (CSTN) as study model, a breast cancer subtype particularly aggressive and often prone to the development of resistant profiles. One of the main mechanisms involved in cancer resistance is the basal or induced overexpression of transmembrane proteins called MultiDrug Resistance (MDR). These ubiquitous members of the ABC transporters superfamily are involved in the cellular cross-resistance to many cancer treatments, in particular by extracellular efflux of a large panel of xenobiotics. In this context, the “Résistance” group is developing LightSpot® fluorescent probes to detect and quantify the presence of MDR proteins. The first part of this works allowed to validate the use of this type of probes for the detection of cancer resistance established by the Permeability-glycoprotein (P-gp), a major MDR protein. In particular, the LightSpot®-FL-1 probe enables the sensitive and complete detection and quantification of P-gp, on fresh or fixed 2D and 3D cell models. On the other hand, the "Resistance" group is developing models of spheroids, faithfully mimicking the resistance of avascular tumor micro-regions. These 3D cell culture models have a great potential for high-throughput drug screening. Thus, the second part of this works allowed the development of an innovative concept for the preservation of CSTN MDA-MB-231 spheroids, as an alternative to conventional cryopreservation techniques. This concept involves maintaining spheroids for up to 7 days in OptiPASS® medium, in anoxia and at 4 °C. The results have demonstrated that these storage conditions preserved the integrity of various parameters of the spheroids, in particular their growth, their viability and their response to various anticancer drugs. This protocol for the preservation of spheroids will in particular allow to optimize their use, transport, and integration into large drug screening platforms. All of this doctoral research work focused on the development (1) of fluorescent tracers for the detection of MDR proteins and (2) of a spheroid storage protocol, are enhanced by a direct industrial transfer, within the BIORCELL3D consortium. The latter created by the strong public / private collaboration between the "Resistance" group and the BIOPASS and BIOMARQUEURS companies has enabled the development of an important value chain
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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