1,721,748 research outputs found

    A novel prophylactic strategy to minimize stem cell transplantation-related complications

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    Hematopoietic stem cell transplantation (HSCT) is a curative treatment and sometimes is the only option for patients with hematological malignancies and some types of solid tumors. It is also the first-line treatment for several severe genetic and metabolic disorders. The annual numbers of HSCT are continuously increasing, among which around 40% are allogeneic transplantations. However, the survival and life quality of those patients are largely compromised by transplantation-related complications, including acute graft-versus-host disease (aGvHD) and cardiovascular diseases. Oxidative stress is ubiquitously implied in the pathogenesis of these conditions and can thus serve as a treatment target. The present thesis provides a systematic investigation of a new prophylactic strategy employing antioxidants to combat HSCT-related complications.Using a mouse model, we found that the onset of aGvHD is associated with intensive renal injury manifested by neutrophil gelatinase-associated lipocalin upregulation, hetero-lysosomes accumulation in the renal proximal tubular epithelial cells, and especially αKlotho depletion and increased circulatory FGF23. These findings suggest the important role of oxidative stress in the pathogenesis of aGvHD. Thereafter, two antioxidants N-acetylcysteine (NAC) and Nacetylcysteine amide (NACA) were investigated thoroughly in respect of their therapeutic potentials.In order to compare the pharmacokinetic-pharmacodynamic properties and the mechanisms of action of NACA and NAC, we developed a new liquid chromatography-mass spectrometry method that could quantify both compounds in biological samples. We found that in relation to NAC, NACA has a higher oral bioavailability and superior capability to replenish glutathione.In the aGvHD mouse model, NACA, but not NAC, was shown to ameliorate disease burden and prolong survival. Mechanistic studies demonstrated that the protective role of NACA was mediated by its antioxidative, anti-inflammatory and immuno-modulatory effects. Importantly, NACA did not negatively affect the engraftment efficiency in transplanted mice.In addition to the prophylactic ability against aGvHD, NACA also exhibited a cardioprotective effect. We observed that NACA significantly attenuated the endothelial injuries induced by cyclophosphamide treatment. NACA preserved the integrity of the vascular endothelium in vivo, while reduced intracellular oxidative stress and cell death in vitro. Moreover, NACA assisted in maintaining the endothelial hemostasis and angiogenesis. Yet, NAC was relatively less efficient compared to NACA.Taken together, the results obtained in the present thesis provide experimental evidence that the novel antioxidant, NACA, is a promising candidate for prophylaxis of HSCT-related complications. Further investigations are warranted to optimize the treatment regimen and to evaluate the influence of NACA on the clinical outcome of HSCT.List of scientific papersI. Risul Amin, Rui He, Dhanu Gupta, Mikhail Burmakin, Dara K. Mohammad, Joseph W. DePierre, Behnam Sadeghi, Hannes Olauson, Annika Wernerson, MD, Samir El-Andaloussi, Moustapha Hassan, Manuchehr Abedi-Valugerdi. The kidney injury casued by the onset of acute graft-versus-host disease is associated with down-regulation of αKlotho. International Immunopharmacology. 2020, 78: 106042. https://doi.org/10.1016/j.intimp.2019.106042 II. Rui He, Wenyi Zheng, Tobias Ginman, Håkan Ottosson, Svante Norgren, Ying Zhao, Moustapha Hassan. Pharmacokinetic profile of N-acetylcysteine amide and its main metabolite in mice using new analytical method. European Journal of Pharmaceutical Sciences. 2020, 143: 105158. https://doi.org/10.1016/j.ejps.2019.105158 III. Rui He, Wenyi Zheng, Kicky Rozing, Xiaoli Li, Yikai Yin, Weiying Zhou, Samir EL Andaloussi, Svante Norgren, Ying Zhao, Moustapha Hassan. The Role of N-acetylcysteine Amide in Acute Graft-versus-host Disease Mouse Model. [Submitted]IV. Rui He, Wenyi Zheng, Terra Slof, Eva Wärdell, Agneta Månsson-Broberg, Svante Norgren, Ying Zhao, Moustapha Hassan. N-acetylcysteine Amide Alleviates Cyclophosphamide-induced Endothelial Damage. [Manuscript]</p

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    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

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    “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

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    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

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    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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    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 Under Sail The Imagination of Jack London, 1893-1902

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    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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