1,720,968 research outputs found
Alcoholic liver disease: contribution of hypoxia signaling and transiational relevance in a humanized liver mouse model
No full textTesis doctoral presentada para lograr el título de Doctorado en Biomedicina por la Universidad de Barcelona, Facultad de Medicina y Ciencias de la Salud.--2021-12-16.--Excelente Cum LaudeALD is a major concern worldwide as it is one of the most prevalent liver diseases in Europe and USA (Blachier et al., 2013; Pimpin et al., 2018; Rehm et al., 2013). In addition, despite most patients with alcoholic fatty liver and early stages of alcoholic steatohepatitis (ASH) can recover after cessation of drinking, current treatment for more advanced stages as alcoholic cirrhosis and alcoholic hepatitis (AH) is limited and have undergone a minimal innovation with respect to the first description of the potential benefits of corticosteroid therapy. Thus, the recommendation for patients with advanced ALD is currently liver transplantation (Sanyal et al., 2018), suggesting the urgent need for new therapeutic targets. Although the main features of the different stages of the disease have been described, several underlying mechanisms still remain unknown, which could be the key for developing new therapies. For instance, the role of hypoxic pathway in ALD is still controversial, as opposite roles for the master regulator of hypoxia (HIF-1α) have been described using the same experimental model of ALD (Nath et al., 2011; Nishiyama et al., 2011).
In this doctoral thesis hepatocyte specific deletion of VHL has been used as a model to stabilize HIF-α and study its contribution to acute-on-chronic model of ALD. In this context, a synergistic effect of VHL deletion and ethanol intake has been characterized, in which livers presented severe steatosis and fibrosis, as well as increased cholesterol trafficking to mitochondria, which completely impaired mitochondrial respiration. Our results suggest the direct implication of hypoxic pathway in fibrosis, fat accumulation and cholesterol transport with a subsequent impact in respiration decline, proposing a new mechanistic pathway for the metabolic switch in hypoxic environment and progression to more severe stages of ALD.
ALD is studied using a wide variety of models that are performed mainly in rodents. However, the animal models that are used to study many aspects of human disease cannot replicate some very important features of human biology. To overcome this limitation, previous reports used human knock-in models with the expression of human genes (as CYP2E1 (Lu et al., 2010) and CIDEC (Xu et al., 2015) in ALD. Although these models have been useful, these reports only apply to the impact of a single gene. Therefore, we approached this issue using a humanized model with humanized mice. The humanization process takes advantage of immune deficient mice, creating chimeric animals that harbor human tissues and cells, including hepatocytes. In this regard, the “humanized liver” model can be used to mimic human metabolism in the liver and further study the human disease in a more physiological environment, which allows us to compare the differences in ALD to murine versus humanized livers.
Our results in this doctoral thesis suggest a clear difference between hepatocytes from different species. In fact, human hepatocytes displayed basal reduced expression of ER stress or oxidative stress markers compared to murine hepatocytes, as well as an increased antioxidant defense (GSH). Despite this, we observed an enhanced susceptibility of human hepatocytes upon acute-on-chronic model of alcohol intake compared to murine hepatocytes as all stress parameters significantly induced, whereas only a slight increase was observed in murine hepatocytes. Overall, this doctoral thesis presents new insights of the differences between species upon the same insult, increasing the awareness on the research of ALD using rodents as animal models
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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