1,721,118 research outputs found
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
Innate-like functions of natural killer T cell subsets result from highly divergent gene programs
No full textNatural killer T cells (NKT cells) have stimulatory or inhibitory effects on the immune response that can be attributed in part to the existence of functional subsets of NKT cells. These subsets have been characterized only on the basis of the differential expression of a few transcription factors and cell-surface molecules. Here we have analyzed purified populations of thymic NKT cell subsets at both the transcriptomic level and epigenomic level and by single-cell RNA sequencing. Our data indicated that despite their similar antigen specificity, the functional NKT cell subsets were highly divergent populations with many gene-expression and epigenetic differences. Therefore, the thymus 'imprints' distinct gene programs on subsets of innate-like NKT cells that probably impart differences in proliferative capacity, homing, and effector functions.</p
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
Design of NKT-cell activators: Structure and function of a microbial glycosphingolipid bound to mouse CD1d
No full textCrystal structure of mouse CD1d bound to the self ligand phosphatidylcholine: A molecular basis for NKT cell activation
No full textNKT cells are immunoregulatory lymphocytes whose activation is triggered by the recognition of lipid Ags in the context of the CD1d molecules by the TCR. In this study we present the crystal structure to 2.8 Å of mouse CD1d bound to phosphatidylcholine. The interactions between the ligand acyl chains and the CD1d molecule define the structural and chemical requirements for the binding of lipid Ags to CD1d. The orientation of the polar headgroup toward the C terminus of the α1 helix provides a rationale for the structural basis for the observed Vα chain bias in invariant NKT cells. The contribution of the ligand to the protein surface suggests a likely mode of recognition of lipid Ags by the NKT cell TCR.</p
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Multi-layered study of T cells in inflammatory bowel disease pathogenesis
Get PDFInflammatory bowel disease (IBD) is a complicated disease characterized by an inflammation of the gastrointestinal (GI) tract, but the mechanism remains unknown. Among all the immune cells, T cells showed strong association with IBD pathogenesis. In this thesis, we studied how T cells contribute to IBD through genetics and pathogenic transcriptomic programs. Genome wide association studies (GWAS) identify a site near the metabolism gene laccase domain containing 1 (LACC1) as a risk for Crohn’s disease (CD). We previously found in populations that the Crohn’s disease risk allele correlates with decreased LACC1 expression in T lymphocytes. Despite this, the mechanism by which T cell gene expression is affected, and a link to T cell function and inflammatory disease, remained unknown. Here we identified sites in the promoter region in a haploblock that influenced LACC1 gene expression. Direct association of disease-risk variants with lower LACC1 mRNA was confirmed by comparing transcript quantity of the alleles in LACC1 heterozygous human CD4+ T cells. Using gene editing, we validated the role of this LACC1 region in gene expression in T cells. Human CD4+ T cells with LACC1 gene knockdown showed altered metabolism and reduced regulatory T cell differentiation. Overall, our study connects a disease GWAS hit by linking promoter region alterations specifically to changes in T cell metabolism and function. In the other part of the thesis, to identify the pathogenic T cell subsets, we compared T cells from the inflamed and non-involved tissues of active UC patients, with T cells from healthy donors and remission patients whose UC symptoms were temporarily suppressed by medications. Single-cell RNA seq analysis indicated that CD4 and CD8 T cells from inflamed tissues both showed increased IL17A-expressing cells (TH17/TC17), and TCF7-expressing stem-like T cells, which all showed more activation and pro-inflammatory features. RNA velocity and TCR analyses implied that the pathogenic TH17/TC17 cells subsets were derived from TCF7-expressing stem-like T cells, thus we hypothesized that stemness program is critical for the disease development. To validate the idea, we adaptively transferred Bcl6-deficient T cells, whose stemness program was impaired, into Rag1-/- mice to induce colitis. Compared to WT T cells, Bcl6-deficient T cells induced much less severe colitis with lower expansion and lower pathogenic TH17/TC17 populations, which showed high TFH gene signatures. In summary, our study unveiled the novel stem-like T cells in colitis, which could lead to new therapies to the disease
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Intestinal CD4 Cytotoxic T Lymphocytes are Generated during Steady State and Confer Protective Immunity during Infection
Get PDFDuring steady state, CD4 T helper (Th) cells reprogram to cytotoxic T lymphocytes (CTLs) in the small intestinal epithelium. In the present study, CD4 CTLs were evaluated for their potential to promote tolerance during steady state as well as their ability to fend off enteric pathogens during infection. The CD4 T cell adoptive transfer model of colitis was used to determine if CTLs may represent a strategy of avoiding CD4 Th-mediated inflammation. Using both an in vitro differentiation model as well as transgenic models, where CD4 T cell fates are forced into predetermined phenotypes, the conversion of Th to CTL was found to mitigate disease pathology and promote tolerogenic conditions.
After defining the role of CD4 T cells during steady state, we then assessed the ability of CD4 CTLs to respond to enteric pathogens. Pre-existing CD4 CTLs were found to have the capacity to kill Salmonella enterica-infected cells, thereby preserving the integrity of the barrier and preventing bacterial dissemination. Furthermore, we identified IL-15/IL-15Ra complex trans-presentation as a mechanism of inciting CD4 CTLs to become active killers. Functionally, CD4 CTLs represent a strategy of the immune system to fortify the epithelium with quiescent but primed CTLs that can provide rapid immunity during enteric infection. The generation of CD4 CTLs during steady state and their functional relevance during infection is a novel strategy of mucosal immunity that can be defined as ‘protective tolerance’
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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