1,721,086 research outputs found
The mycosins of pathogenic mycobacteria: digesting the role of conserved proteases in type VII secretion
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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
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
Proteolytic regulation of Cell-Surface Signalling in Pseudomonas bacteria
Get PDFBitter, W. [Promotor]Llamas, M.A. [Copromotor
Improving bladder cancer immunotherapy by tailoring protein secretion in mycobacteria
Get PDFBladder cancer is the 4th to 10th most common cancer worldwide, with non-muscle invasive bladder cancer (NMIBC) counting for 70-75% of cases. Standard treatment of NMIBC includes resection of the tumor followed by intravesical treatment with Mycobacterium bovis BCG (BCG). BCG is a live but attenuated vaccine strain well-known for its use against tuberculosis, an infectious disease caused by Mycobacterium tuberculosis. BCG bacteria induce a local inflammatory response that not only clears the bacterium but also eradicates the remaining tumor cells. Although effective, BCG treatment may still show up to 30% recurrences. The research described in this thesis aims for improvement of bladder cancer treatment. First, since secretion and surface display of (tumor) antigens might improve BCG anti-tumor efficacy, the aim was to enable heterologous secretion in mycobacteria. Mycobacteria use specialized secretion systems to secrete proteins over their unique cell envelope, known as Type VII secretion systems. For heterologous secretion we focused on one of these systems, the ESX-5 system. Model protein OVA was fused to the PE and linker domain of ESX-5 substrate LipY. Screening of an M. marinum error-prone PCR mutant library showed that two mutations in OVA or deletion of the linker domain lead to increased secretion. Thus, the ESX-5 secretion system is suitable for heterologous secretion in mycobacteria but optimization is required for each desired heterologous protein. Second, we focused on the function of ESX-5. Studying the processing of LipY in more detail lead to the discovery of PecA, an ESX-5 dependent secreted aspartic protease that cleaves the PE domain of LipY, other PE_PGRS proteins and itself. Furthermore, deletion of pecA resulted in an attenuated phenotype in zebrafish larvae. Next, we studied the role of ESX-5 in fatty acid uptake. In tuberculosis mycobacteria reside in the lungs inside structures known as granulomas, in which lipids form the main energy source. By screening for transposon mutants showing increased growth on Tween 80 as sole carbon source, two PE proteins, MMAR_0369 and MMAR_4321, were identified to be able to cleave fatty acids. These cutinase-like proteins harbor an α/β hydrolase domain, a domain also predicted for multiple other proteins in M. tuberculosis and M. marinum. Together, these findings demonstrated that PE proteins can have distinctive functions depicted by their C-terminal domains and not by the PE domain by which they are usually categorized. The main aim was to improve bladder cancer immunotherapy. To study anti-tumor activity in vivo we used an orthotopic bladder cancer mouse model. We showed that combining multimodal imaging techniques, e.g. high ultrasound imaging, photoacoustic imaging and bioluminescent imaging, enables longitudinal studies on tumor development in the bladder. The integration of individual strengths enabled sensitive and improved quantification and understanding of tumor biology and ultimately can aid in the discovery and development of new therapeutics. Finally, we tested the hypothesis that anti-tumor activity can be improved by enhancing bacterial binding to the bladder wall. Recently, Salmonella enterica Typhi Ty21a (Ty21a), an oral vaccine strain against typhoid fever, has been shown to be potentially more effective against bladder cancer than BCG. Labeling of Ty21a with adhesion protein FimH resulted in a ~5 fold increased binding to the mouse bladder in vivo. Furthermore, a single bladder cancer mouse study showed a modest increase in median survival for mice treated with FimH-labeled Ty21a. In conclusion, this thesis presents a study on mycobacterial protein secretion in order to improve bladder cancer immunotherapy. We identified novel functions for 3 PE proteins providing more insight into the function of ESX- 5 and its role in virulence. Furthermore, we showed that labeling Ty21a with FimH shows promise for improving bladder cancer treatment
Chaperones and substrate specificity, type VII secretion systems reconnected
Get PDFBitter, W. [Promotor]Houben, E.N.G. [Copromotor
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
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