1,720,958 research outputs found
Estudio de marcadores de disfunción endotelial en el síndrome metabólico : evaluación de la vía RhoA/ROCK como posible eje de señalización
Tesis (Doctor en Ciencias Médicas)--Pontificia Universidad Católica de Chile, 2015El Síndrome Metabólico (SM) es un agregado de condiciones cardio-metabólicas que en cronicidad involucra patologías tales como la obesidad, diabetes e hipertensión arterial (HTA), aumentando considerablemente el riesgo de desarrollar enfermedades cardiovasculares (ECV). La aterosclerosis es el denominador común de las patologías que desencadenan los eventos cardiovasculares y la disfunción endotelial (DE) es la alteración base del proceso aterosclerótico. La prevalencia mundial del SM ha aumentado progresivamente, alcanzando alrededor del 25% de la población adulta. Existen datos clínicos de una población mas joven que califica para SM por mostrar un aumento de la circunferencia de la cintura y sobrepeso junto con niveles elevados de triglicéridos plasmáticos. En este grupo de sujetos jóvenes con SM se desconoce la presencia de marcadores de daño endotelial e inflamatorios similares a los que presentan pacientes adultos sobre 50 años con diabetes tipo 2 e hipertensión. En este último grupo de adultos, se han reportado niveles elevados de citoquinas inflamatorias tales como IL-6, de ácidos grasos, específicamente el ácido palmítico (AP), hiper-insulinemia y alteraciones relacionadas con DE y, solo en un reporte, se ha mencionado la sobre-activación de la vía RhoA/ROCK.En base a lo expuesto planteamos como hipótesis que: IL-6, insulina y AP son moléculas que se encuentran elevadas en sujetos con SM sin diabetes tipo 2 o hipertensión arterial, y pueden inducir DE mediada por la activación de RhoA/ROCK. Para poner a prueba nuestro postulado propusimos tres estrategias que involucran estudios ex–vivo, in–vitro e in–vivo. Los estudios ex–vivo se realizaron en sujetos adultos jóvenes que consultaron por sobrepeso pero calificaron para SM por presentar aumento del contorno de cintura y dislipidemia. Nuestros resultados mostraron que el grupo de sujetos evaluado tiene, además de niveles de LDL-c elevados y HDL-c bajos, altos niveles de IL-6, insulina y AP, aumento de marcadores de DE tales como MCP-1, sICAM-1, aumento de marcadores de estrés oxidativo (AOPP y TBARS), menor biodisponibilidad de óxido nítrico (ON) y una sobre activación de RhoA/ROCK en leucocitos en comparación a sujetos sanos. Aunque dentro de rango normales, se encontró además, mayores niveles plasmáticos de ácido úrico, menores niveles creatinina y un moderado estado de hiper-coagulabilidad en comparación con individuos controles.El estudio in-vitro se llevó a cabo en células endoteliales de cordón umbilical estimuladas con concentración similares a las encontradas en sujetos con SM de IL-6, insulina y AP, con el objetivo de evaluar la participación de RhoA/ROCK en el daño endotelial inducido por estas moléculas. Los resultados mostraron que la combinación de IL-6, insulina y AP activa la vía RhoA/ROCK y altera la señalización de Akt y ERK. Adicionalmente, se reducen los niveles de ON y la actividad de eNOS, junto a un aumento de los niveles de marcadores de estrés oxidativo. Se observaron cambios en la estructura de actina y de VEcaderina y alteraciones en la citoarquitectura de la monocapa celular, acompañado de un aumento de la actividad de MMP9 intracelular. La triple estimulación aumentó la adhesión plaquetaria, la actividad pro-coagulante, la liberación de Factor de Von Willenbrand (FVW), MCP-1, siCAM-1, E-selectina y la acumulación intracelular de lípidos. Todas estas alteraciones a excepción de los niveles de FVW y la actividad pro-coagulante parecen ser mediadas por la sobre-activación de RhoA/ROCK ya que se evitaron al adicionar el inhibidor Y-27632.La participación de RhoA/ROCK en relación a características de SM se evaluó en un modelo de ratas alimentadas con una dieta rica en AP por 14 semanas con y sin la administración de Fasudil, un inhibidor de RhoA/ROCK, por las dos últimas semanas. Los resultados muestran que la dieta alta en grasa indujo características SM tales como: sobrepeso, mayor circunferencia abdominal y dislipidemia. A las 14 semanas de dieta los animales tuvieron presión sistólica elevada, altos niveles de triglicéridos, colesterol y glicemia, en comparación a los animales controles pero dentro de los rangos de normalidad. La dieta alta en grasa indujo además altos niveles de insulina, IL-6, aumento de tejido adiposo extra-peritoneal, marcadores de estrés oxidativo (TBARS y AOPP), siCAM-1, sCD40L, ácido úrico y niveles reducidos de ON. La administración de Fasudil por dos semanas, revirtió las alteraciones observadas. El análisis de las aortas de los animales alimentados con dieta rica en AP muestra una mayor infiltración grasa y un aumento de la actividad de RhoA/ROCK, de E-selectina, una disminución de la actividad de Akt, eNOS y de los niveles de Nrf2 comparados con las aortas de los animales alimentados con dieta control. Los animales tratados con Fasudil mostraron una reducción de las alteraciones mencionadas. A pesar de la presencia de alteraciones metabólicas, la dieta alta en grasa no indujo diabetes ni HTA en los animales durante el periodo estudiado.Consideramos que los resultados de esta tesis entregan evidencias sobre la participación de RhoA/ROCK en las alteraciones relacionadas a la DE asociadas a SM y demuestra el rol del AP, IL-6 e insulina como componentes que, al estar elevados en pacientes con SM, promueven DE. Adicionalmente, creemos que los resultados obtenidos entregan información relevante para sujetos jóvenes con SM que, por no mostrar síntomas relacionadas con patologías tales como diabetes tipo 2 o hipertensión, desconocen que ya presentan signos relacionados con mayor riesgo cardiovascular
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
We 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
We 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.
Author-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
In 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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