1,720,954 research outputs found
Antiretroviral drug susceptibility of a hinge region variant of HIV-1 subtype C protease
Get PDFA thesis submitted to the Faculty of Science, University of the Witwatersrand,
Johannesburg in fulfilment of the requirements for the degree of Doctor of
Philosophy. Johannesburg, 28 May 2018.Since their discovery, protease inhibitors continue to be an essential component of
antiretroviral treatment for human immunodeficiency virus type 1 (HIV-1). However, the
development of resistance to protease inhibitors remains one of the most significant challenges
in the fight for sustained viral suppression in those infected with HIV-1. Studies show that
specific mutations arising within the HIV-1 gag and protease genes can lead to the
development of resistance. In this research, a South African HIV-1 subtype C Gag-protease
variant (W1201i) was investigated. This variant was considered due to the presence of a
mutation and insertion (N37T↑V), located within the hinge region of the protease enzyme.
Moreover, the variant displayed the following polymorphisms: Q7K, I13V, G16E, M36T,
D60E, Q61E, I62V and M89L. Genotyping of W1201i Gag revealed a previously unreported
MSQAG insertion between the CA/p2 and p2/NC cleavage sites. Additionally, a mutation and
insertion (I372L↑M), and multiple polymorphisms (S369N, S371N, I373M and G377S) were
discovered within the p2/NC cleavage site. Single-cycle phenotypic assays were performed to
determine the drug susceptibility and replication capacity of the variant. The results show that
the mutations present in the N37T↑V protease conferred a replicative advantage and reduced
susceptibility to lopinavir, atazanavir and darunavir. Interestingly, the mutations in W1201i
Gag were found to modulate both replication capacity and protease inhibitor susceptibility.
In silico studies were performed to understand the physical basis for the observed variations.
Molecular dynamics simulations showed that the N37T↑V protease displayed altered dynamics
around the hinge and flap region and highlighted the amino acids responsible for the observed
fluctuations. Furthermore, induced fit docking experiments showed that the variant bound the
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protease inhibitors with fewer favourable chemical interactions than the wild-type protease.
Collectively, these data elucidate the biophysical basis for the selection of hinge region
mutations and insertions by the HI virus and show that protease, as well as Gag, needs to be
evaluated during resistance testing.EM201
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
Iron deficiency in women’s health : an understated burden with serious health consequences
Get PDFThe importance of iron for overall health in humans cannot be overstated and its extremely widespread biological functions include electron transfer, intercellular signalling, catalysis, and oxygen binding and transport. Iron is found in all cells and is required for the synthesis of iron-sulphur clusters and heme proteins like cytochromes c, b5, and P450, myoglobin, neuroglobin and heme-based sensor proteins.1 It is also an enzyme cofactor that is essential for many important biological processes, and studies have shown that up to 6.5% of all human enzymes are iron-dependant.https://www.obstetricsandgynaecologyforum.comam2023Obstetrics and Gynaecolog
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
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