1,720,960 research outputs found
Assessment of AN2-73, a Putative Sigma 1 Receptor (S1R) Agonist in a Model of Infantile Spasms
No full textInfantile spasms represent a devastating epilepsy syndrome during early life (incidence of IS is 1:3,200-3,400 live births). The syndrome consists of a triad of spasms (stretch-like seizures) in clusters, electroencephalogram pattern of hypsarrhythmia and neurobehavioral regress. Current Food and Drug Administration approved medications (adrenocorticotropic hormone and vigabatrin) are not completely effective (40% of patients do not respond to the treatments) and have side effects that may severely affect quality of life or even be life-threatening. Therefore, new improved treatments for infantile spasms are needed.
Sigma-1 receptor is a specific protein found at the mitochondrion-endoplasmic reticulum junction. Activation of sigma-1 receptor can modulate cellular properties in multiple ways. Though, the exact mechanisms of sigma-1 receptor action are still not well understood, sigma-1 receptors play important roles in neuronal physiology and are involved in the cell protective mechanisms in neurodegenerative disorders. Studies show that many sigma-1 receptor agonists have anticonvulsant effects in multiple models of acutely induced seizures. We used a biological model of infantile spasms developed in rats consisting of prenatal betamethasone exposure and postnatal trigger of spasms by N-methyl-D-aspartate. This model has been developed in our laboratory, repeatedly validated and reproduced in five independent laboratories worldwide. We primarily tested a sigma 1 receptor agonist, ANAVEX®2-73, as a potential infantile spasms treatment but also included additional sigma-1 receptor agonists to determine whether this class of small molecules may offer a new treatment approach for infantile spasms.
ANAVEX®2-73 was applied in both acute and chronic settings in postnatal day 12-15 rats. In the acute experiment, the drug was administered as a single pretreatment before a single trigger of spasms. In the chronic experiment, the drug administration was randomized in a prospective trial over several days with repeated treatments initiated only after the first bout of spasms. The results indicate that ANAVEX®2-73 has strong activity against the spasms in both approaches. However, while testing this drug together with commercially available sigma-1 receptor antagonist, there was no loss of effect. Similarly, a commercially available sigma-1 receptor agonist (PRE-084) was ineffective in the model. Both these failures indicate that either ANAVEX®2-73 is using different conformational states of sigma-1 receptor in comparison to PRE-084 leading to activation of different cellular effectors, or, the ANAVEX®2-73 has additional effects outside sigma-1 receptor domain.
In the animals undergoing treatment in the chronic model, we further investigated whether introduction of ANAVEX®2-73 affects animal behaviors (as a rat correlate of human neurodevelopment). In the studies we found that those animals experiencing spasms are less fearful and explore an open space more than naïve animals. Treatment with ANAVEX®2-73 however did not change this behavior.
As neurodevelopmental and learning problems observed in infants with infantile spasms may be the result of impaired neuronal plasticity, specifically long-term potentiation after the spasms, we also investigated hippocampal long-term potentiation in the stratum radiatum of CA1 and dentate gyrus molecular layers. The spasms with NMDA in our infantile spasms model caused impairments of long term potentiation in the dentate gyrus but not in the CA1 hippocampal region during adolescence (25 to 30 days old rats). ANAVEX®2-73 recovered the lost plasticity in the dentate gyrus.
Our data indicate that ANAVEX®2-73 significantly suppresses spasms in our animal model of infantile spasms. Whether this effect also includes additional S1R agonists or is due to cholinergic effects of ANAVEX®2-73 is yet to be determined. Spasms elicited changes in behavior of the rats such as anxiolytic effects seen as loss of fear in open space. Interestingly, ANAVEX®2-73 was able to recover some impairments in the long-term potentiation despite not affecting behavioral outcome. It is possible that a longer period of behavioral follow-up would return positive results with ANAVEX®2-73 treatment
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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