1,720,988 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
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
Development of all-in-one CRISPR/Cas9 and CRISPRi AAV constructs to treat autosomal dominant retinitis pigmentosa
Dominant mutations in RHO (rhodopsin) are the most common cause of autosomal dominant retinitis pigmentosa (RHO-adRP). RHO-adRP causes progressive loss of rod cells, followed by cone cells, leading to blindness. This disease is a candidate for CRISPR gene editing, as reduction of mutant rhodopsin is associated with phenotypic rescue. This thesis optimises all-in-one CRISPR/Cas9 and CRISPRi adeno-associated viruses (AAVs) and explores their potential as RHO-adRP gene therapy vectors.
Following construct optimisation in vitro, a CRISPR/Cas9 and CRISPRi plasmid carrying SaCas9 and dSaCas9.KRAB, respectively, were generated. Both demonstrated knock down of endogenously expressed EGFP in a transgenic cell line. For allele-specific knock down of RHO, the CRISPR constructs must target a region unique to the mutant allele. Bioinformatic screening of RHO identified seven non-pathogenic single nucleotide polymorphisms (SNPs) that were targetable with SaCas9. Two of these SNPs could be targeted allele-specifically, with high CRISPR/Cas9 gene disruption and CRISPRi gene repression rates of 38.5-73.2 % and 43.1-65.8 %, respectively. In heterozygous patients, targeting the SNP on the mutant RHO offers a mutation-independent allele-specific targeting strategy.
As a proof-of-concept for targeting rod cells, the AAV were subretinally injected into Nrl-EGFP mice, in whom enhanced green fluorescent protein (EGFP) expression is limited to rod photoreceptors. To restrict Cas9 expression to rods cells only, a novel 154 bp rod cell-specific promoter was identified. This shortened promoter from the PDE6B gene was active in human retinal explants, the human retinoblastoma-derived cell line Y79, and drove strong rod cell-specific expression in mice. The CRISPRi AAV was unable to repress EGFP, despite high transgene expression. The CRISPR/Cas9 AAV however, drove strong EGFP disruption. It produced 4.1 % EGFP indels, resulting in a reduction of EGFP mRNA and fluorescence of 55.3% and 36.5 %, respectively. The all-in-one CRISPR/Cas9 AAV is therefore able to drive strong gene disruption in rod cells in vivo, making it a useful vector for the treatment of RHO-adRP.
This thesis describes in detail the development of these all-in-one CRISPR/Cas9 and CRISPRi AAV vectors from proof-of-concept to in vivo study and advances the potential for using such therapies in future treatments of RHO-adRP
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
AAV2/8 anti-angiogenic gene therapy using single-chain antibodies inhibits murine choroidal neovascularization
While anti-angiogenic therapies for wet age-related macular degeneration (AMD) are effective for many patients, they require multiple injections, are expensive and prone to complications. Gene therapy could be an elegant solution for this problem by providing a long-term source of anti-angiogenic proteins after a single administration. Another potential issue with current therapeutic proteins containing a fragment crystallizable (Fc) domain (such as whole antibodies like bevacizumab) is the induction of an unwanted immune response. In wet AMD a low level of inflammation is already present, so to avoid exacerbation of disease by the therapeutic protein, we propose single-chain fragment variable antibodies (scFv, which lack the Fc domain) as a safer alternative. To investigate the feasibility of this, anti-vascular endothelial growth factor (VEGF) blocking antibodies in two formats were produced and tested in vitro and in vivo. The scFv transgene was then cloned into an adeno-associated virus (AAV) vector.A therapeutic effect in a mouse model of choroidal neovascularization (CNV) was demonstrated with antibodies in both scFv and immunoglobulin G1 (IgG1) formats (p<0.04). Importantly, the scFv anti-VEGF antibody expressed from an AAV vector also had a significant beneficial effect (p=0.02), providing valuable preclinical data for future translation to the clinic
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
Author-wise bibliometric analysis based on entropy.
Author-wise bibliometric analysis based on entropy.</p
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