1,721,004 research outputs found
Design of a multi-analysis and real time multi-organ-on-chip in the context of blood sugar regulation and type 2 diabetes
No full textDepuis 4 décennies, un modèle intermédiaire entre les traditionnelles approches in vivo et in vitro émerge : les Systèmes MicroPhysiologiques (SMP). Ils sont construits pour recréer différents niveaux de physiologie humaine, du simple organe à leurs interactions. Ils améliorent l’environnement de culture grâce à des microstructures accueillant des modèles d’architecture 3D et multicellulaire, et intègrent des microcapteurs monitorant l’activité cellulaire et leur environnement.Ce nouvel outil d’investigation est d’intérêt pour la recherche fondamentale sur les maladies comme le diabète. Dans le cas de cette maladie incurable, la régulation du glucose sanguin, résultant d’interactions complexes entre les îlots pancréatiques, le foie, les adipocytes et les muscles, est altérée. Un Multi-Organe-sur-Puce (MOsP) est un SMP pouvant reproduire ces interactions, et représente donc un modèle pertinent pour la recherche sur le diabète. En effet, la régulation inter-organe n’est pas entièrement reproduite par les modèles in vitro usuels, et requiert de multiples capteurs, ce qui est éthiquement et techniquement impossible in vivo. Dans le contexte du diabète, il n’existe aucun MOsPs reproduisant l’action des îlots sur les muscles, malgré l’importance des muscles squelettiques dans la régulation glycémique.Cette thèse propose une méthodologie pour construire un MOsP étudiant les interactions d’îlot à muscle dans la régulation glycémique. Les 3 objectifs du MOsP étaient : atteindre des concentrations physiologiques d’insuline grâce à des îlots sécrétant en réponse à une élévation physiologique de glucose, induisant une prise de glucose mesurable par les muscles, et monitorer l’expérience en direct. Pour cela, les investigations ont été menées avec une approche interdisciplinaire, utilisant et confrontant des résultats venant d’expériences biologiques in vitro et de simulations modélisant la biologie et la physique.Ce manuscrit détaille les étapes de la méthodologie, et délivre différents designs pour progressivement construire un MOsP comprenant: une puce microfluidique contenant les cellules et un capteur de glucose connecté directement au flux. Les principales découvertes ont été :- Un milieu et procédure de co-culture entre îlots primaires et LHCN-M2 myotubes ont été démontrés.- Un substrat de culture commun de type MicroElectrodes Array a été trouvé.- Des îlots ont été cultivés en puce microfluidique, et ont présenté une sécrétion d’insuline en réponse au glucose durant des expériences en fluidique. Des myotubes ont pu se différentier en puce, et ont présenté une prise de glucose basale (insuline indépendant).- Une stratégie in vitro-in silico pour dimensionner le MOsP a été développée et implémentée. Un modèle in silico simplifié d’îlot a été développé pour rapidement explorer 2 designs de puce. Des expériences in vitro correspondantes, de sécrétion d’insuline, ont été menées et confrontées aux expériences in silico. Les résultats ont soulevé l’hypothèse que les îlots n’avaient pas une fonctionnalité optimale dans nos petits volumes de culture. La même constatation a été faite concernant les myotubes, où la prise de glucose insuline dépendante a été démontrée en macro volumes, mais en micro volumes, la réponse observée (uniquement à concentration physiologique d’insuline) doit être reproduite avec des expériences plus robustes pour démontrer leur présence.- Un capteur de glucose compatible avec le système microfluidique a été caractérisé à l’aide d’expériences in vitro et in silico.- Un multi-potentiostat a été développé dans la perspective de futures mesures électrochimiques multiples et intégrées.Les bases et perspectives présentées ici permettront d’achever le MOsP îlot-muscle par de futurs travaux. La méthodologie peut aussi être réutilisée pour l’ajout de nouveaux organes (foie, adipocytes) complétant le MOsP, qui permettra de mieux comprendre les dérégulations intervenant dans le diabète de type 2.Over the past 4 decades, an intermediate model between the traditional in vivo and in vitro approaches has emerged: the MicroPhysiological Systems (MPS). MPS are designed to recapitulate different levels of human physiology, from the single organ to organs crosstalk. They upgrade the culture environment by patterning microstructures hosting 3D and multicellular architecture models and integrate microsensors monitoring cell activity and environment.This new investigation tool is of interest in fundamental research on diseases such as diabetes. In this incurable disease, blood glucose regulation, resulting from a complex organs interplay between the pancreatic islets, the liver, the adipocytes and the muscles, is impaired. A Multi-Organ-on-a-Chip (MOoC) is a MPS that can recapitulate these organs crosstalk and represents a relevant model for diabetes research. Indeed, inter-organ regulations are not recapitulated by usual in vitro models, and deciphering these interactions requires multiple sensors, which is not ethically and technically possible in vivo. In the context of diabetes, MOoCs reproducing the islets to skeletal muscles communication do not exist so far, despite the importance of the skeletal muscles impact on blood glucose, under islets action.In this thesis, we propose a methodology to design a MOoC deciphering islets to muscles interactions in blood glucose regulation. The MOoC objectives were to: (i) attain physiological insulin concentration secreted by islets in response to physiological glucose elevation, (ii) that induces a measurable glucose uptake by the muscle cells, (iii) monitor online relevant parameters. To that end, the investigations were conducted with an interdisciplinary approach, using and confronting results from both in vitro biological experiments and in silico modelling of biology and physics.This manuscript details the methodology steps, delivering different designs for progressive validation toward a complete MOoC that comprises a microfluidic chip with cells and an online glucose sensor. During the MOoC construction, our main findings were the following:- A co-culture medium and procedure for primary islets and LHCN-M2 myotubes were demonstrated.- A common MicroElectrodes Array-based substrate was found suited for co-culture in a single microfluidic chip.- Islets were cultured in microfluidic chips, and presented an insulin secretory response to glucose during fluidic experiments. Myotubes were successfully differentiated in microfluidic chips, and presented a measurable basal (insulin-independent) glucose uptake.- An in silico and in vitro informed MOoC scaling strategy was developed and implemented. A simplified in silico islet model was developed to rapidly explore chip designs. Corresponding in vitro insulin secretion experiments were conducted and confronted to the in silico experiments. Results raised the hypothesis that islets function was sub optimal when cultured in our low volume. Similar observation was made concerning myotubes scaling, where insulin-dependent glucose uptake was demonstrated in macro volumes experiments, but in micro volumes, the observed insulin response (only at physiological insulin concentration) has to be further repeated with improved experiments to explicitly demonstrate its presence.- A glucose biosensor compatible with microfluidic was characterized under different injection protocols, using in vitro and in silico experiments.- A multi-potentiostat was developed in the perspective of multiple and integrated electrochemical sensing in the MOoC.From the grounds and perspectives presented in this thesis, future work can be conducted to further complete this islet-muscle MOoC. The methodology can be re-used and extended in the perspective of adding new organs (liver, adipocytes) in this MOoC in order to better address the interorgan crosstalk deregulations in type 2 diabetes pathophysiology
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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