1,721,141 research outputs found
Alcaloides de la iboga: modificaciones estructurales y evaluación de su potencial antidepresivo
No full textLa ibogaina es un alcaloide monoterpeno indólico (MIA), clasificado como un psicodélico del tipo oneirogénico (generador de sueños). Es el constituyente mayoritario del extracto de la corteza de raíz de Tabernanthe iboga, un arbusto de la región de África central, donde es utilizado de forma sacramental por la población bwiti hace al menos ciento cincuenta años. El interés moderno que justifica el amplio estudio sobre la neurofarmacología de este alcaloide, esta fundado en la descripción de su actividad antiadictiva. Estudios observacionales indican que: tras una única administración de altas dosis de ibogaina, individuos que padecen trastorno por uso problemático de sustancias (principalmente a opioides), presentan una marcada reducción del síndrome de abstinencia (withdrawal) y conducta de búsqueda de sustancia (craving). La investigación clínica se limitó a estudios de fase 1 y 2, mostrando eficacia, pero advirtiendo problemas de seguridad. Existen antecedentes que muestran que ibogaína puede promover la aparición de arritmias ventriculares y eventuales fatalidades, que han sido atribuidas a la inhibición del canal de potasio Herg, responsable de la repolarización de células del miocardio. Existe una amplia discusión en la literatura entorno a la elucidación del mecanismo de acción de ibogaina; no se ha definido un receptor del sistema nervioso central único que explique su actividad biológica. Se hipotetiza un mecanismo de acción polifarmacológico, ya que el alcaloide presenta actividad micromolar por receptores nicotínicos, opioides, glutamatérgicos, sigma y transportadores de monoaminas. Además, al igual que otros psicofélicos, ibogaina genera eventos de plasticidad neuronal mediados el aumento en la expresión de factores neurotróficos, lo que podría explicar sus efectos duraderos, incluso luego de su eliminación del organismo.En modelos de comportamiento animal para depresión mayor, se describió recientemente, un efecto tipo-antidepresivo de ibogaina, que resulta más potente y rápido que aquel observado para fluoxetina, un conocido antidepresivo de amplia distribución en la clínica. Este hecho, sumado a la conocida capacidad de ibogaína de inhibir el transportador recaptador de serotonina humano (hSERT) de forma no competitiva, siguieren que los efectos antiadictivos de la ibogaína podrían estar relacionados a un fuerte efecto antidepresivo inducido por la sustancia. Esto inspiró la propuesta del proyecto de química medicinal abordado en la siguiente tesis doctoral, donde nos propusimos basarnos en la estructura de la ibogaína para la preparación de nuevas moléculas con potencial antidepresivo. Para ello, llevamos a cabo la obtención de análogos de ibogaina mediante una estrategia semisintética, lo que demandó la optimización y escalado de un proceso de extracción de alcaloides de la iboga desde la corteza de raíz de Voacanga africana (Apocynaceae); la evaluación in vitro de los compuestos sintetizados como inhibidores de hSERT y otros transportadores de monoaminas; y por último, la evaluación in vitro de la actividad inhibitoria del canal hERG, para los análogos más prometedores.INTRODUCCIÓN -- ANTECEDENTES -- Ibogaína -- Origen e historia -- Evidencia preclínica y clínica de sus efectos antiadictivos -- Farmacología y mecanismo de acción -- Toxicidad -- Depresión e hipótesis monoaminérgica -- Bases neurobiológicas de la depresión -- Ibogaína y SERT -- Desarrollos de química medicinal -- Análogos de estructura completa -- Derivados simplificados -- Desarrollos de química medicinal -- Análogos de estructura completa -- Derivados simplificados -- Química de los alcaloides de la iboga -- Modificaciones estructurales sobre el producto natural -- Fuentes naturales de alcaloides de la iboga y origen biosintético -- OBJETIVOS Y ESTRATEGIA METODOLÓGICA -- RESULTADOS Y DISCUSIÓN -- Obtención de alcaloides de la corteza de raíz de Voacanga africana -- Optimización de la extracción a escala de laboratorio -- Ruptura de alcaloides bis-indólicos -- Modificaciones estructurales del esqueleto de alcaloides de la iboga -- Modificaciones en N1, C10 y C16 -- Reacciones de oxidación en C3, N4 y C7. -- Análogos funcionalizados en la cadena etílica lateral (C18 y C19 -- Evaluación biológica de alcaloides semisintéticos de la iboga -- Inhibición de transportadores de monoaminas -- Sobre el mecanismo de acción antidepresivo de ibogaína y noribogaína -- Inhibición del canal de potasio hERG -- CONCLUSIONES Y PERSPECTIVAS FUTURAS -- Voacanga africana como fuente viable de alcaloides de la iboga -- Construcción de una biblioteca de análogos -- Establecimiento de una línea de producción de ibogaína y noribogaína -- Estudio de reactividad comparada entre ibogaína y voacangina -- Determinación de la configuración absoluta de 32b -- Síntesis total de análogos con modificados en la cadena etílica -- Nuevos inhibidores no-competitivos de SERT y VMAT2 -- Evaluación preliminar de la cardiotoxicidad por inhibición hERG -- EXPERIMENTAL -- Obtención de alcaloides de la corteza de Voacanga africana -- Procedimientos de síntesis y caracterización de compuestos -- Cálculos computacionales -- Caracterización biológica de análogos de ibogain
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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