1,720,973 research outputs found
Bases de la immunodulació micobacteriana per al control de la progressió tumoral
Full text linkEl càncer de bufeta és una patologia que durant els últims anys ha incrementat la seva incidència en la població europea. Afortunadament, les millores en la detecció han comportat una millora en el control d'aquesta i, per tant, en una reducció de les taxes de mortalitat. A grans trets, aquesta patologia es pot classificar en dos grups segons si el tumor ha aconseguit envair o no la capa muscular la bufeta. D'aquesta manera, parlarem de càncer de bufeta no múscul invasiu (NMIBC), en el cas que el tumor no hagi envaït la capa muscular; o de càncer múscul invasiu (MBIC) en el supòsit que aquest ja hagi penetrat la capa muscular. Afortunadament, el NMIBC representa la malignitat de bufeta més comuna amb al voltant del 75% dels diagnòstics. El tractament estàndard del NMIBC consisteix en una resecció transuretral del tumor de la bufeta, que confirma el diagnòstic, seguida d'un règim d'instil·lacions intravesicals del Mycobacterium bovis BCG amb la finalitat d'evitar la recurrència i la progressió d'aquest tumor. No obstant, el 50% de pacients tractats amb el M. bovis BCG pot presentar episodis de recurrència i de progressió del tumor. D'altra banda, al tractar-se d'un patogen atenuat, la seva administració pot comportar complicacions de caràcter local, en aproximadament un 50% dels casos, i de complicacions sistèmiques en un 30% dels pacients sotmesos al tractament intravesical. A més, entre un 1-5% dels pacients pot desenvolupar complicacions severes com infeccions pulmonars o fins i tot sèpsia.
D'altra banda, el mecanisme d'acció del M. bovis BCG continua essent objecte d'estudi. Entre altres aspectes, manquen estudis sobre l'efecte del M. bovis BCG sobre els processos de migració i invasivitat de les cèl·lules tumorals de la bufeta, així com en el potencial immunodulador d'aquest sobre determinats components cel·lulars del microambient tumoral com ara els macròfags.
En aquest treball ens hem proposat demostrar la seguretat i no toxicitat del Mycobacterium. brumae com a alternativa al M. bovis BCG en el tractament del NMIBC una vegada s'ha constatat, prèviament, la resposta immunitària antitumoral que presenta aquest micobacteri. Així doncs, vam infectar per via intravenosa ratolins immunodeprimits amb el M. brumae o el M. bovis BCG i vam estudiar un ampli rang de paràmetres hematològics i bioquímics, així com l'anàlisi histopatològica de múltiples òrgans. Igualment, es va analitzar la seguretat i la no toxicitat del M. brumae en el context de l'administració intravesical d'aquest en ratolins immunocompetents. Finalment, es va comprovar la seguretat d'aquest micobacteri en el model animal de larves de Galleria mellonella.
La segona part de l'estudi va consistir en l'avaluació del paper del M. brumae i el M. bovis BCG davant dels fenòmens de migració i invasivitat cel·lular, així com en el creixement independent a l'ancoratge, presentats per les cèl·lules tumorals de bufeta. A més, es va analitzar si la infecció pel M. brumae i el M. bovis BCG exercien algun efecte sobre la producció de metal·loproteïnases per part de les cèl·lules tumorals de bufeta.
L'últim estudi d'aquesta tesi doctoral va anlitzar el paper dels micobacteris en la modulació de la polarització de macròfags humans. Concretament, es van generar diferents fenotips de macròfags i es va avaluar si la infecció pel M. brumae i el M. bovis BCG podia modular o polaritzar el fenotip d'aquests macròfags i, en el cas de tractar-se de macròfags polaritzats prèviament amb diferents estímuls, de revertir la polarització d'aquests. Per a comprovar la funcionalitat d'aquests fenotips, es va avaluar la seva capacitat d'inhibir la proliferació tumoral, així com la seva implicació en els fenòmens de migració i invasivitat cel·lular de diferents línies tumorals de bufeta.El cáncer de vejiga es una patología que en los últimos años ha incrementado su incidencia en la población europea. Afortunadamente, las mejoras en la detección han comportado una mejora en el control de esta y, por tanto, en una reducción de las tasas de mortalidad. A grandes rasgos, esta patología puede clasificarse en dos grupos según si el tumor ha conseguido invadir o no la capa muscular la vejiga. De esta forma, hablaremos de cáncer de vejiga no músculo invasivo (NMIBC), en caso de que el tumor no haya invadido la capa muscular; o de cáncer músculo invasivo (MBIC) en el supuesto de que éste haya penetrado la capa muscular. Afortunadamente, el NMIBC representa la malignidad de vejiga más común con alrededor del 75% de los diagnósticos. El tratamiento estándar del NMIBC consiste en una resección transuretral del tumor de la vejiga, que confirma el diagnóstico, seguida de un régimen de instilaciones intravesicales del Mycobacterium bovis BCG con el objetivo de evitar la recurrencia y progresión del tumor. Sin embargo, el 50% de pacientes tratados con el M. bovis BCG puede presentar episodios de recurrencia y progresión del tumor. Por otra parte, al tratarse de un patógeno atenuado, su administración puede acarrear complicaciones de carácter local, en aproximadamente un 50% de los casos, y de complicaciones sistémicas en un 30% de los pacientes sometidos al tratamiento intravesical. Además, entre un 1-5% de los pacientes puede desarrollar complicaciones severas como infecciones pulmonares o incluso sepsis.
Por otra parte, el mecanismo de acción del M. bovis BCG sigue siendo objeto de estudio. Entre otros aspectos, carecen estudios sobre el efecto del M. bovis BCG sobre los procesos de migración e invasividad de las células tumorales de la vejiga, así como en el potencial inmunodulador del mismo sobre determinados componentes celulares del microambiente tumoral como los macrófagos.
En este trabajo nos hemos propuesto demostrar la seguridad y la no toxicidad del Mycobacterium. brumae como alternativa al M. bovis BCG en el tratamiento del NMIBC una vez se ha constatado, previamente, la respuesta inmunitaria antitumoral que presenta esta micobacteria. Así pues, infectamos por vía intravenosa ratones inmunodeprimidos con M. brumae o M. bovis BCG y estudiamos un amplio rango de parámetros hematológicos y bioquímicos, así como el análisis histopatológico de múltiples órganos. Asimismo, se analizó la seguridad y no toxicidad del M. brumae en el contexto de la administración intravesical del mismo en ratones inmunocompetentes. Por último, se comprobó la seguridad de esta micobacteria en el modelo animal de larvas de Galleria mellonella.
La segunda parte del estudio consistió en la evaluación del papel del M. brumae y el M. bovis BCG frente a los fenómenos de migración e invasividad celular, así como en el crecimiento independiente al anclaje, presentados por las células tumorales de vejiga. Además, se analizó si la infección por M. brumae y M. bovis BCG ejercía algún efecto sobre la producción de metaloproteínas por parte de las células tumorales de vejiga.
El último estudio de esta tesis doctoral analizó el papel de las micobacterias en la modulación de la polarización de macrófagos humanos. Concretamente, se generaron diferentes fenotipos de macrófagos y se evaluó si la infección por M. brumae y M. bovis BCG podía modular o polarizar el fenotipo de estos macrófagos y, en el caso de tratarse de macrófagos polarizados previamente con distintos estímulos, de revertir la polarización de éstos. Para comprobar la funcionalidad de estos fenotipos, se evaluó su capacidad de inhibir la proliferación tumoral, así como su implicación en los fenómenos de migración e invasividad celular de distintas líneas tumorales de vejiga.Bladder cancer is a disease that has increased its incidence in the European population in recent years. Fortunately, improvements in detection have led to an improvement in cancer control and, therefore, a reduction in mortality rates. Broadly speaking, this pathology can be classified into two major groups depending on whether or not the tumor has managed to invade the muscular layer of the bladder. Thus, we are talking about non-invasive non-muscular bladder cancer (NMIBC), in the case of the tumor has not invaded the muscular layer; or invasive muscle cancer (MBIC) if it has already penetrated the muscle layer. Fortunately, NMIBC represents the most common bladder tumor malignancy with about 75% of total diagnoses. The standard treatment for NMIBC is a transurethral resection of the bladder tumor, which confirms the diagnosis, followed by immunotherapy consisting of a regimen of intravesical instillations of Mycobacterium bovis BCG to prevent recurrence and the progression of this tumor.
However, 50% of patients undergoing treatment with M. bovis BCG may experience episodes of recurrence and progression of the disease. On the other hand, as it is an attenuated pathogen, its administration can lead to local complications in approximately 50% of cases, and systemic complications in approximately 30% of patients undergoing intravesical treatment. In addition, between 1-5% of patients may develop severe complications such as lung infections or even sepsis. On the other hand, the mechanism of action of M. bovis BCG continues to be studied. Among other things, there is a lack of studies on the effect of M. bovis BCG on the processes of migration and invasiveness of bladder tumor cells, as well as the immunomodulatory potential of this mycobacterium on certain cellular components of the bladder, and also the involvement of the tumor microenvironment considering the role of macrophages in such process.
The main objective of this work is to demonstrate the safety and non-toxicity of Mycobacterium brumae as an alternative to M. bovis BCG in the treatment of NMIBC, once the antitumor immune response of this mycobacterium has been established. Thus, we intravenously infected immunocompromised mice with M. brumae or M. bovis BCG and studied/evaluated a wide range of hematologic and biochemical parameters, as well as histopathological analysis of multiple organs. Similarly, the safety and non-toxicity of M. brumae in the context of its intravesical administration to immunocompetent mice were analyzed. Finally, the safety of this mycobacterium was tested in the animal model of Galleria mellonella larvae.
The second part of the study consisted of the evaluation of the role of M. brumae and M. bovis BCG in the phenomena of cell migration and invasiveness, as well as the independent growth in the anchorage, presented by the bladder tumor cells. In addition, it was analyzed whether M. brumae and M. bovis BCG infection had any effect on the production of metalloproteinases by bladder tumor cells.
The latest study in this doctoral dissertation is focused on the role of mycobacteria modulating the polarization of human macrophages. Specifically, different macrophage phenotypes were generated and it was assessed whether M. brumae or M. bovis BCG infection was able to modulate or polarize the phenotype of these macrophages and, in the case of polarized macrophages. previously differentiated with different stimuli, reverse the polarization of this cellular subtype. To test the functionality of these phenotypes, their ability to inhibit tumor proliferation was evaluated, as well as their involvement in the phenomena of migration and cell invasiveness of different bladder tumor lines.Universitat Autònoma de Barcelona. Programa de Doctorat en Microbiologi
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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