1,720,958 research outputs found

    Research of drugs against age-related diseases

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    Sarcopenia is a prominent disease in developed societies. It is described as an age-related pathology characterized by a progressive loss of muscle mass and strength. It is the main cause of frailty and disability in the elderly worldwide, affecting up to 50% of 80-year. Currently, no known cure is available for sarcopenia. Our laboratory collaborated with Rejuvenate Biomed, a company specialized in healthy aging, to test the effect of RJx-01, a combination drug, composed of metformin and galantamine, on sarcopenia. Metformin is a drug used against type 2 diabetes. Galantamine is commonly used in the treatment of Alzheimer’s disease. Both drugs have been linked to a decrease in all-cause mortality. The combination of these molecules has been predicted by Rejuvenate Biomed’s proprietary platform CombinAgeTM to have a synergistic effect on sarcopenia. Indeed, RJx-01 has been proven to ameliorate motor symptoms and muscle structure in C. elegans, in aged mice, as well as in inducible muscle specific OPA1 KO mice, a model of precocious aging. We decided to further characterize RJx-01 by testing the drug on murine models for acute disuse skeletal muscle atrophy. As opposed to chronic models of disuse, we aimed at studying the atrophic process during periods of limb immobilization, mimicking the condition of patients wearing casts or dealing with forced bedrest. Before proceeding with the RJx-01 tests, we decided to characterize our own model for unilateral immobilization, consisting in a 3D-printed cast. The mounting procedure is non-invasive, simply requiring a light anesthesia and a few drops of superglue. A 2-weeks period of immobilization produced little to no swelling or skin damage and induces the activation of atrophy-related genes, causing a muscle weight loss, cross-sectional area decrease and reduction of muscle force. The contralateral leg did not show signs of overload or hypertrophy when compared to free roaming littermates, offering a good internal control over the immobilized limb. The unmounting procedure is also simple, only requiring the separation of the two halves of the boot with a specialized scissor. Upon cast removal, mice can immediately reload the previously immobilized hindlimb, recovering the normal 4-legged gait. Therefore, the recovery phase can be studied, with mice effectively recovering muscle mass and force in 3 weeks. We proceeded to test RJx-01 in three groups of wild type mice. We immobilized for 2 weeks a first cohort of aged mice to test the effect of RJx-01 on acute disuse skeletal muscle atrophy as opposed to chronic. We also performed the same experiment in young mice to study possible age-dependent differences in RJx-01. One last cohort of young mice was again immobilized for 2 weeks but allowed to recover for 1 week, to inquire possible effects related to the recovery phase. The preliminary studies showed that RJx-01 treatment resulted in a reduced tendency of percentage muscle loss and had no significant effect on strength after disuse in old mice. In young mice, RJx-01 treatment resulted in a reduced tendency of percentage muscle loss and significantly reduced absolute muscle force loss compared to the untreated group after disuse. RJx-01 had no significant effect on these parameters after one week recovery. Further, we explored the use of C. elegans to study Parkinson’s Disease (PD). Preliminary tests were executed on C. elegans PD models to select a suitable protocol for future drug testing. C. elegans strains expressing human α-synuclein were investigated, monitoring declines in locomotion and survival, and progression of α-synuclein aggregates formation. One strain of YFP-tagged dopaminergic neurons worms was used to study the natural degeneration of dopaminergic neurons during aging, as well as after exposure to a dopaminergic neurons-selective toxin. These tests led to the writing of replicable protocols suitable for drug testing in C. elegans models

    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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