1,721,104 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
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
Using rapid diagnostic tests as a source of viral RNA for dengue serotyping by RT-PCR - a novel epidemiological tool
Background Dengue virus infection causes major public health problems in tropical and subtropical areas. In many endemic areas, including the Lao PDR, inadequate access to laboratory facilities is a major obstacle to surveillance and study of dengue epidemiology. Filter paper is widely used for blood collection for subsequent laboratory testing for antibody and nucleic acid detection. For the first time, we demonstrate that dengue viral RNA can be extracted from dengue rapid diagnostic tests (RDT) and then submitted to real-time RT-PCR for serotyping. Methodology/Principal Findings We evaluated the Standard Diagnostics (SD) Bioline Dengue Duo RDT, a commonly used test in dengue endemic areas. First, using the QIAamp RNA kit, dengue RNA was purified from the sample pad of the NS1 RDT loaded with virus isolates of the four serotypes, then quantified by RT-PCR. We observed greater recovery of virus, with a mean of 27 times more RNA recovered from RDT, than from filter paper. Second, we evaluated dengue NS1 RDTs from patients at Mahosot Hospital, Vientiane, (99 patients) and from rural Salavan Provincial Hospital (362 patients). There was good agreement between dengue RT-PCR from NS1 RDT with RT-PCR performed on RNA extracted from patient sera, either using RDT loaded with blood (82.8% and 91.4%, in Vientiane and Salavan, respectively) or serum (91.9% and 93.9%). There was 100% concordance between RDT and serum RT-PCR of infecting dengue serotype. Conclusions/Significance Therefore, the collection of NS1 positive RDTs, which do not require cold storage, may be a novel approach for dengue serotyping by RT-PCR and offers promising prospects for the collection of epidemiological data from previously inaccessible tropical areas to aid surveillance and public health interventions
Variations on the Author
“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
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
Investigating viral glycosylation pathways for drug and vaccine development
Glycosylation is the most common protein co- and post-translational modification. It has crucial functions for glycoprotein folding, structure, trafficking, localisation and stability. Glycosylation is not only critical for eukaryotic cell function but vital for many enveloped viruses which have evolved to exploit the host cell glycosylation pathway in order to fold their proteins correctly and coat many of their surface proteins with glycans that can contribute to viral pathogenesis. Vaccines often focus on the viral fusion glycoproteins that protrude from the virion envelope as they are among the most immunogenic biomolecules and can elicit a humoral immune response. A robust vaccine antigen needs to mimic viral glycosylation to produce an appropriate and strong B-cell response, as many neutralising antibodies incorporate glycans as part of their binding epitopes, and other epitopes are shielded by sugars and inducing antibodies against those would lead to a less relevant antibody response.
The current COVID-19 pandemic has highlighted the urgent need for vaccines and antiviral drugs. The principal topic of my DPhil centres on addressing these needs for viral infection. Chapter 4 focuses on the site-specific glycosylation occupancy, and N- and O-glycan structures attached to virion derived SARS-CoV-2 spike glycoproteins. This glycan signature was compared to a stabilised prefusion trimeric spike, to a monomeric subunit of spike (S1) and to an antigen of a non-stabilised vaccine candidate, revealing subunit shedding of the S1 glycoprotein for the vaccine candidate. Whether or not monomeric S1 shedding has an effect on the vaccine antibody response or could be implicated in the observed rare side effects, remains to be investigated but evidence from other studies implicates this occurrence as detrimental in animal models.
The COVID-19 pandemic highlighted again the lack of broad-spectrum antivirals available to patients before thorough investigation of an emergent virus, such as its genome or target host receptor. Chapter 5 discusses the establishment of a medium-throughput drug screening platform against SARS-CoV-2. FDA-approved compounds were prioritised and triaged within the screen for clinical committees such as the UK steering group for therapeutics for COVID-19. Compounds of a global anti-COVID-19 effort called the “Moonshot project” targeting the main protease of SARS-CoV-2 were also screened and promising compounds were progressed further to produce a specific direct-acting SARS-CoV-2 antiviral compound. Iminosugars, which inhibit N-linked glycan processing enzymes such as endoplasmic reticulum alpha-glucosidase I and II of the glycoprotein quality control pathway, constituted one of the two most promising groups of drugs in this antiviral cellular screen that have not entered clinical trials yet.
The second part of this thesis focuses on ER alpha-glucosidase I as a key antiviral target to develop a broad-spectrum antiviral. Previously, it had been observed that a single high-dose treatment with the iminosugar MON-DNJ led to long-lasting antiviral effects in lethal dengue mouse models via alpha-glucosidase I inhibition. In Chapter 6 the mechanism of action was investigated in an in cellulo model recapitulating the in vivo data. This led to preliminary results and the hypothesis that the unfolded protein response might play a fundamental role in activating the apoptosis pathway in dengue-infected and high-dose treated cells alone. This warrants further investigation in a more relevant cell type, precipitating the development of the human induced pluripotent stem cell knockouts of the unfolded protein response constituents. This chapter also describes how I produced these cells.
An important factor that warrants consideration is that inhibition of the alpha-glucosidases in the ER by iminosugars as glucose mimetics can lead to unintended side-effects as many host enzymes can recognise glucose molecules. In Chapter 7, I describe attempts towards identification of a specific alpha-glucosidase I inhibitor. X-ray crystallisation of ER alpha-glucosidase I with the iminosugar NB-DNJ bound in the active site, led to one crystal which was analysed, but the crystallisation process was not reproducible enough to be useful for fragment or drug screening. Further methods such as thermal shift assay screening of 1600 FDA-approved compounds did not reveal any compounds that bound to the soluble enzyme. Screening of a library of 2.9 billion DNA-tagged molecules against the soluble enzyme found 937 potential binders. This needs further validation to establish the binding mode and inhibitory activity.
Overall, this thesis describes the unique influence of glycan analysis in the rational design of vaccines and how subtle changes in glycosylation help interpret large-scale changes in the structure of an antigen, or the foundation for a totally new type of broad-spectrum antiviral that functions through inhibiting the host glycosylation pathway – collectively these outputs will help preparedness for future pandemics
Dispelling the Myths Behind First-author Citation Counts
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
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
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