1,720,981 research outputs found
Synthesis of new fluorescent nucleosides
No full textLes travaux présentés dans ce manuscrit de thèse décrivent la conception et l’étude de nucléosides fluorescents originaux pour la détection de processus biologiques. Dans un premier temps, la synthèse et la diversification du bicycle 1,6-naphthyridin-7(6H)-one sont présentés, démontrant l’intérêt de cette plateforme synthétique. Puis, une étude des propriétés photophysiques de ces structures a été menée afin d’évaluer leur potentiel en tant que nucléobases fluorescentes artificielles. La liaison de ces structures à un ribose a permis l’obtention des nucléosides fluorescents artificiels correspondant. Dans un second temps, la structure hétérocyclique 3-(3-phenyl-1H-1,2,4-triazol-5-yl)pyridin-2(1H)-one a également été étudiée et a permis l’accès à une deuxième famille de nucléosides fluorescents.The work presented in this manuscript describes the design and study of novel fluorescent nucleosides for the detection of biological processes. First, the synthesis and diversification of the 1,6-naphthyridin-7(6H)-one bicycle is presented, demonstrating the interest of this synthetic platform. Then, a study of the photophysical properties of these structures was conducted in order to evaluate their potential as artificial fluorescent nucleobases. The linkage of these structures to a ribose afforded the corresponding artificial fluorescent nucleosides. In a second step, the heterocyclic structure 3-(3-phenyl-1H-1,2,4-triazol-5-yl)pyridin-2(1H)-one was also studied and allowed access to a second family of fluorescent nucleosides
Fluorescent Heterocycles for detection of carbonylated proteins associated to ageing and inflammation
No full textLes travaux présentés dans ce manuscrit décrivent la synthèse de nouvelles sondes fluorescentes pour le marquage des protéines carbonylées. Dans une première partie, la synthèse de nouvelles molécules fluorescentes à base 1,2,4-triazoles 1,3,5-trisubstitués est décrite à partir des 4H-pyrido[e][1,3]oxazin-4-ones. L’étude photophysique des 1,2,4- triazoles dans plusieurs solvants a permis de mettre en évidence un mécanisme de fluorescence de type ESIPT induisant un large déplacement de Stokes (jusqu’à 250 nm). La deuxième partie de ce manuscrit est consacrée à la synthèse de nouveaux BODIPY avec une fonction hydrazide. Enfin, la dernière partie décrit les applications de ces nouveaux BODIPY en tant que marqueurs des protéines carbonylées, utilisable avec la 2D-Oxi DIGE, la microscopie à fluorescence et la cytométrie en flux.The works presented in this manuscript describe the synthesis of new fluorescent probes for protein labelling. In a first part, the synthesis of new fluorescent molecules 1,2,4-triazoles based 1,3,5-trisubstituted is described from 4H-pyrido[e][1,3]oxazin-4-ones. The photophysical study of 1,2,4-triazoles in several solvents allowed to highlight a fluorescence ESIPT type mechanism leadingto a wide Stokes’shift (close to 250 nm). The second part of this manuscript is dedicated to the synthesis of new BODIPY with a hydrazide function. Finally, the last part describes the applications of these new BODIPY as fluorescent probes for carbonylated proteins labelling, used in 2D - Oxi DIGE, fluorescence microscopy and flow cytometry
Synthèse Asymétrique de Diaryls [c,e] Azépines à partir d’o-Hydroxy-a-Alkylbenzylamines.
No full textSCGCDIPLOMES; GR - 53 263; Université de Genève, dpt chimie organique; . Consultable sur demande à la Bibliothèque de l'EPFL / Offered in consultation at the EPFL library
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
Rational design, synthesis and pharmacological evaluation of Kallikrein 8 (neuropsin) : therapeutic applications for Alzheimer’s disease and associated dementias
No full textLa maladie d’Alzheimer est une maladie neurogénédérative progressive. Cependant, il n’existe pas à ce jour de traitement ni de diagnostic pré-mortem. L’un des enjeux de la recherche sur cette maladie est de la diagnostiquer avant l’apparition de symptômes irréversibles et donc de prévenir sa progression. Une nouvelle hypothèse serait que la kallicréine 8 (KLK8) ou neuropsine, une protéase à sérine majeure du système nerveux central, serait impliquée dans le développement de différentes voies physiopathologiques associées à la maladie. Cependant, malgré l’intérêt croissant pour cette cible, aucun inhibiteur thérapeutique potentiel n’avait été identifié au début du travail de thèse. Par ailleurs, la dyshoméostasie du fer est également une caractéristique clé des maladies neurodégénératives, telle que la maladie d'Alzheimer. Après un criblage initial à large spectre, nous avons découvert deux séries de composés chimiques, les 1,2,4-triazoles et les N,N,N-triacylamines, qui inhibent la KLK8. Nous avons entrepris de concevoir et synthétiser de façon rationnelle les premiers inhibiteurs organiques de la KLK8 à l’aide de pharmacomodulations puis de caractériser leur mécanisme d'inhibition. Pour chaque série, une étude de relation structure-activité a été réalisée dans l’objectif d’optimiser le pouvoir inhibiteur, et la sélectivité des inhibiteurs envers d'autres protéases à sérine a été également évaluée. Ainsi, les N,N,N-triacylamines démontrent une très bonne affinité envers la KLK8 tandis que les dérivés du Déférasirox inhibent certes la KLK8 avec une affinité modérée mais présentent simultanément des propriétés de chélation avec le fer. En conclusion, ce travail de thèse a permis d’identifier deux séries chimiques constituant les premiers inhibiteurs rapportés de la KLK8 et une base pour l’optimisation de nouvelles générations de composés multifonctionnels.Alzheimer’s disease is a progressive neurodegenerative disease. However, to date, there is no treatment or pre-mortem diagnosis. One of the challenges of research into this disease is to diagnose it before the apparition of irreversible symptoms, and thus prevent its progression. A new hypothesis is that kallikrein 8 (KLK8) or neuropsin, a major serine protease of the central nervous system, is involved in the development of various pathophysiological pathways associated with Alzheimer's disease. However, despite growing interest in this target, no potential therapeutic inhibitor had been identified at the beginning of the thesis. Iron dyshomeostasis is also a key feature of neurodegenerative diseases such as Alzheimer's. After an initial broad-spectrum screening, we identified two series of chemical compounds, 1,2,4-triazoles and N,N,N-triacylamines, which efficiently inhibit KLK8. We set out to rationally design and synthesize the first organic KLK8 inhibitors using pharmacomodulations, and then to characterize their mechanism of inhibition. For each series, a structure-activity relationship study was carried out with the aim of optimizing inhibitory potency, and the inhibitors' selectivity towards other serine proteases was also assessed. Hence, N,N,N-triacylamines showed very good affinity towards KLK8, while derived from deferasirox inhibited KLK8 with moderate affinity, but simultaneously exhibited iron chelation properties. In conclusion, this thesis work has identified two original chemical series constituting the first reported KLK8 inhibitors and a basis for the optimization of new generations of multifunctional compounds
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
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