1,720,956 research outputs found
CARDIAC PACEMAKING: PATHOPHYSIOLOGY AND PHARMACOLOGY OF THE IF CURRENT
Get PDFDuring my Ph.D. I focussed my experiments on the investigation of physiopathological and pharmacological role of the cardiac sinoatrial If since it has a key role in the generation and modulation of cardiac pacemaker activity.
The identification of pharmacological agents able to reduce sinus heart rate has a strong interest in the clinic since they could be useful in the treatment of ischemic heart disease. Despite longstanding and intense investigation at present there is only one such agent (ivabradine) that has reached therapeutic application since all other compounds tested have shown undesired side-effects. I therefore investigated the effect of Tong Mai Yan Xin (TMYX), a drug currently used in China as a cardiac regulator of both brady- and tachy-cardic condition. Electrophysiological experiments performed on rabbit SA node cells have shown a dose-dependent slowing effect of TMYX on pacemaking rate, associated with a reduction of the early part of the pacemaker depolarization and with a moderate prolongation of APD50. The investigation of the effects of TMYX on the If current, the major contributor of diastolic depolarization phase, has revealed a dual effect: TMYX causes a leftward-shift of the activation current curve and an increase of the channel conductance. At physiological potential the bradycardic action (leftward shift) strongly prevails, thus confirming the effect on the spontaneous automaticity observed in SA node cells.
The effect of TMYX was also evaluated in freely moving mice implanted with ECG transmitters. Preliminary experiments surprisingly show an increment of heart rate after the i.p. injection of the drug, while when TMYX was delivered during pharmacological blockade of only sympathetic or both sympathetic and parasympathetic autonomic system, a deep bradycardia was observed.
Given the importance of the If current in the pacemaking process, it is important characterize the functional role of mutations in the HCN4 channels, the molecular constituent of If current, that are associated with clinically relevant modification of heart rate. So far all mutations reported in the literature are associated with tachycardic conditions. During my study I had the opportunity to investigate the properties of the R524Q mutation which is located in the first portion of C-linker, a region connecting the S6 transmembrane domain to the CNBD; this mutation cosegregates in familial members affected by inappropriate sinus tachycardia.
Electrophysiological analysis carried out on HEK 293 cells showed an increment of cAMP sensitivity in the R524Q channels resulting in a rightward shift of the activation curve that mimic the effect of β-adrenergic stimulation. When transfected with mutant rather than wild-type HCN channels newborn ventricular myocytes, an excitable cellular model used to test the effect of mutations on spontaneous rate, showed a faster pacemaking rate.
Finally I carried out some experiments to test the quantitative relevance of the If current during pacemaking. The study was carried out by means of an indirect approach based on mathematical models of SA node action potentials combined with the dynamic-clamp technique. I compared the models developed by Maltsev-Lakatta and Severi-DiFrancesco. Both these formulations describe the SA node automaticity, but they have differences in quantitative contribution of If current. My experiments allowed to validate the Severi-DiFrancesco model, that is associate with a higher contribution of If current during the diastolic depolarization than Maltsev-Lakatta formulation.
In conclusion, using independent and separate approaches, my experiments confirm that alterations of the amount of the If current flowing during the diastolic depolarization leads to robust effect on automaticity of the SA node
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
- …
