1,721,017 research outputs found
INVESTIGATION OF THE ROLE OF ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS IN INFLAMMATORY DISEASES THROUGH THE DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF NEW HETEROCYCLIC DERIVATIVES
Get PDFLa ricerca sviluppata con il presente progetto di Dottorato è rivolta all’approfondimento del ruolo del recettore nicotinico alfa7 nella cascata infiammatoria colinergica attraverso la progettazione, la sintesi e la valutazione farmacologica di nuovi derivati eterociclici in grado di interagire e attivare selettivamente questo sottotipo recettoriale. A tale scopo, sono stati progettati nuovi modulatori allosterici positivi (PAMs) o agonisti silenti del recettore nicotinico alfa7. Per ottenere i nuovi PAMs, caratterizzati da migliore potenza e selettività, è stato applicato l’approccio di ibridizzazione molecolare ai due PAMs di tipo I, il 5-idrossindolo (5-HI) e la genisteina. Il nucleo eteroaromatico del 5-HI è stato connesso a un anello benzenico variamente funzionalizzato sfruttando due diversi posizioni di connessione, l’azoto indolico e il carbonio in posizione 2, e sono state pertanto ottenute due serie parallele di composti. Inoltre, l’attivazione del recettore alfa7 è stata studiata attraverso la preparazione di agonisti silenti, in grado di trasmettere il segnale recettoriale con un meccanismo indipendente dall’apertura del canale e dal passaggio della corrente ionica. Con l’intento di chiarire il modello farmacoforico di tali nuovi agonisti alfa7 e di approfondirne il profilo farmacologico, tre serie di derivati sono state progettate e sintetizzate. La prima comprende derivati strutturalmente correlati al diEPP, recentemente emerso come agonista silente del recettore alfa7. Le altre due serie di composti sono state progettate inserendo il nucleo azabiciclico chinuclidinico, legato in forma spirociclica all’anello Delta2-isossazolinico o connesso a un eterociclo 1,2,4-ossadiazolico, per valutare l’importanza del centro basico quale requisito fondamentale nel modello farmacoforico noto. Il profilo farmacologico dei nuovi derivati è stato studiato in saggi elettrofisiologici su oociti di Xenopus che esprimono il recettore umano alfa7. Nella serie dei derivati del 5-idrossindolo, tre composti hanno mostrato un’attività allosterica positiva migliore rispetto al composto di riferimento. L’indagine farmacologica sui potenziali agonisti silenti è tuttora in corso. Attualmente sono disponibili i dati preliminari solo per la serie dei diEPP derivati e quattro composti si sono rivelati caratterizzati da un agonismo silente fino a 46 volte maggiore rispetto al composto parente.The current PhD research project aimed at investigating the role of the alpha7 nAChRs in the cholinergic inflammatory cascade through the design, synthesis and pharmacological evaluation of novel heterocyclic ligands targeting and selectively activating this receptor subtype. To this purpose, new sets of compounds acting as positive allosteric modulators (PAMs) or silent agonists were planned. In order to achieve new alpha7 PAMs endowed with enhanced allosteric activity and selectivity, the molecular hybridization approach was applied to the type I PAMs, 5-hydroxyindole (5-HI) and genistein. Therefore, the heteroaromatic nucleus of 5-HI was connected to a variable substituted phenyl ring by exploring two different positions of linking, the nitrogen and the adjacent carbon atom in position 2, thus obtaining two parallel series of target compounds. In addition, the alpha7 nAChR activation was investigated through compounds characterized by the silent agonism profile, an emerging mode of signal transduction of the alpha7 receptor not involving ion-channel current signaling. To shed light on this new mechanism of alpha7 receptor activation and to clarify the peculiar pharmacological profile of silent agonism in the modulation of inflammatory conditions, three different series of new potential silent derivatives were designed and synthesized. Moreover, the new compounds aimed at elucidating the pharmacophoric requirements for alpha7 nAChR silent agonism. In particular, a first series was obtained by modifying the diEPP compound, a recently emerged alpha7 silent agonist, whereas the other two sets of derivatives were planned to evaluate the pharmacophoric positive center by selecting the azabicyclic quinuclidine nucleus which was inserted as a spirocyclic-Delta2-isoxazoline scaffold or connected to a 1,2,4-oxadiazole heterocyclic system. Electrophysiological assays in Xenopus oocytes expressing human alpha7 nAChRs were performed to investigate the pharmacological profile of the novel derivatives. Within the 5-HI series, three compounds displayed enhanced alpha7 PAM activity compared to the parent compound. As far as concern the alpha7 nAChR silent signaling transduction, many target derivatives are still under investigation. The data so far available highlighted four diEPP analogues endowed with a very promising silent agonism profile which appear to be up to 46-fold greater compared to the reference compound
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
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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