1,720,954 research outputs found
Molecular simulation studies of extrinsic and intrinsic mechanism of permeation block in eukaryotic potassium channels
Full text linkIon channels are an extremely important class of proteins. They are crucial to every aspect of life, including sensory perception, movement, thought and memory, and heartbeat. Potassium (K+) channels are the most abundant type of ion channel. Mutations in these proteins are linked to a wide array of neurological, cardiovascular, and metabolic diseases in humans. Research into the molecular mechanisms of these proteins is necessary to understand the origin of these diseases and to identify potential therapeutic strategies. This thesis is specifically focused on investigating intrinsic and extrinsic mechanisms of blocking ion permeation in three distinct K+ channels using Molecular dynamics simulations: human TMEM175, which is key in lysosomal homeostasis; Shaker from Drosophila melanogaster, a prototypical member of the family of eukaryotic voltage-gated K+ channels and important in neuronal function; and Kv2.1 from Rattus norvegicus, another member of the family of voltage-gated K+ channels and also crucial for neuronal function. Investigating the mechanism of inhibition for a known inhibitor, 4-aminopyridine (4-AP) of the non-canonical TMEM175, we learn that 4-AP is recognized by TMEM175 in both a dynamic and specific manner and inhibits permeation in an electrostatic as well as steric manner. We also investigate the recently solved structure of C-type inactivated Shaker and learn that dilation of the filter through repositioning of crucial neighboring residues causes inhibition of rapid ion permeation. Finally, we compare RY785, a potent and specific inhibitor of Kv2.1, to a well characterized inhibitor tetraethylammonium (TEA), and discover that while TEA occludes the pore, RY785 still allows for permeation indicating RY785 facilitates channel closing suggesting an allosteric mechanism of inhibition. The insights gained into mechanisms of intrinsic and extrinsic inhibition can not only aid in the development of more targeted therapeutic approaches and novel drugs for these specific K+ channels but can contribute to a broader understanding of the mechanisms of inhibition and inactivation in other K+ channels, as well as, ion channels in general
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
Molecular simulation studies of extrinsic and intrinsic mechanism of permeation block in eukaryotic potassium channels
Full text linkIon channels are an extremely important class of proteins. They are crucial to every aspect of life, including sensory perception, movement, thought and memory, and heartbeat. Potassium (K+) channels are the most abundant type of ion channel. Mutations in these proteins are linked to a wide array of neurological, cardiovascular, and metabolic diseases in humans. Research into the molecular mechanisms of these proteins is necessary to understand the origin of these diseases and to identify potential therapeutic strategies. This thesis is specifically focused on investigating intrinsic and extrinsic mechanisms of blocking ion permeation in three distinct K+ channels using Molecular dynamics simulations: human TMEM175, which is key in lysosomal homeostasis; Shaker from Drosophila melanogaster, a prototypical member of the family of eukaryotic voltage-gated K+ channels and important in neuronal function; and Kv2.1 from Rattus norvegicus, another member of the family of voltage-gated K+ channels and also crucial for neuronal function. Investigating the mechanism of inhibition for a known inhibitor, 4-aminopyridine (4-AP) of the non-canonical TMEM175, we learn that 4-AP is recognized by TMEM175 in both a dynamic and specific manner and inhibits permeation in an electrostatic as well as steric manner. We also investigate the recently solved structure of C-type inactivated Shaker and learn that dilation of the filter through repositioning of crucial neighboring residues causes inhibition of rapid ion permeation. Finally, we compare RY785, a potent and specific inhibitor of Kv2.1, to a well characterized inhibitor tetraethylammonium (TEA), and discover that while TEA occludes the pore, RY785 still allows for permeation indicating RY785 facilitates channel closing suggesting an allosteric mechanism of inhibition. The insights gained into mechanisms of intrinsic and extrinsic inhibition can not only aid in the development of more targeted therapeutic approaches and novel drugs for these specific K+ channels but can contribute to a broader understanding of the mechanisms of inhibition and inactivation in other K+ channels, as well as, ion channels in general
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
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