1,721,199 research outputs found
Étude de la variabilité naturelle du système immunitaire pour déterminer les réponses cytokiniques
No full textLes cytokines sont des initiateurs et des régulateurs essentiels des réponses immunitaires et coordonnent la réponse contre les agents pathogènes et les tumeurs. Elles présentent donc un grand potentiel en tant que cibles pour de nouvelles stratégies diagnostiques et thérapeutiques. L'IL-12p70 est une cytokine hétérodimérique pro-inflammatoire qui régule à la fois l'immunité innée et l'immunité adaptative et joue un rôle central dans les réponses Th1. Malgré son rôle essentiel dans l'immunité, nous avons observé des réponses IL-12p70 très variables chez les 1000 donneurs sains de la cohorte Milieu Intérieur. De plus, cette réponse perturbée a été observée à des fréquences significativement plus élevées chez les patients atteints de tuberculose (TB) ou d'hépatite C (HCV). Nous avons appliqué une approche de biologie des systèmes dans la cohorte Milieu Intérieur pour disséquer cette voie chez les donneurs sains et potentiellement fournir de nouvelles informations sur la pathogénie de certaines maladies. Après stimulation du sang total des 1000 donneurs de la cohorte Milieu Intérieur avec LPS, 28 % des donneurs sécrètent une faible quantité d'IL-12p70. Ayant identifié par cytométrie de flux que les monocytes et les cellules dendritiques sont les principaux producteurs d'IL-12p70 dans le sang, nous avons confirmé que les différences cellulaires n'étaient pas responsables de la variabilité observée chez les donneurs sains. En revanche, l'analyse génétique et épigénétique de la cohorte a révélé de nouvelles associations avec les niveaux d'IL-12p70 sécrété sous stimulation LPS. Une analyse cinétique détaillée a permis de définir que la sécrétion d’IFNβ, agissant par le biais de la voie de signalisation IFNAR1, détermine la sécrétion d’IL-12p70. L'induction de l'IL-12p70 par IFNβ via l'activation du récepteur TLR4 par LPS est modifiée chez les patients infectés par HCV qui ne répondent au traitement basée sur la prise d’IFNα. L'ensemble de ces résultats contribue à une meilleure compréhension de la réponse immunitaire de l'IL-12p70 lors d'une infection bactérienne chez les individus sains et malades.Cytokines are essential instigators and regulators of immune responses and coordinate the response against pathogens and tumors. Therefore, they hold great potential as targets for new diagnostic and therapeutic strategies. IL-12p70 is a heterodimeric pro- inflammatory cytokine which regulates both innate and adaptive immunity and has a central role in Th1 responses. Despite its essential role in immunity, we have observed highly variable IL-12p70 responses in the 1,000 healthy donors of the Milieu Interieur cohort. Furthermore, this perturbed response was observed at significantly higher frequencies in patients chronically infected with tuberculosis (TB) or chronic hepatitis C (HCV). We have applied a systems biological approach in the Milieu Interieur cohort to dissect this perturbed pathway in healthy donors and potentially provide new insights into disease pathogenesis. Following whole blood LPS stimulation using a highly standardized approach from 1,000 healthy donors of the cohort, 28% of these donors failed to secrete IL-12p70. Having identified by flow cytometry that monocytes and dendritic cells are the main IL-12p70 producers in whole blood, we confirmed that cellular differences were not responsible for the observed variability in healthy donors. In contrast, genetic and epigenetic analysis of the healthy population cohort revealed novel associations with IL-12p70 levels. A detailed kinetic analysis allowed to define that early IFNβ secretion determines variable downstream IL-12p70 responses, acting through IFNAR1 signaling. The induction of IL-12p70 by IFNβ through TLR4 activation was altered in HCV infected patients who did not respond to the IFNα-based therapy. All together, these results contribute to a better understanding of IL-12p70 immune response upon bacterial infection both in health and diseases
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Standardized Immunomonitoring: Separating the Signals from the Noise
No full textInternational audienceClassical immunoassays are routinely performed in the clinic for disease diagnosis and monitoring. Recent advances in phenotyping technologies offer huge potential in expanding the breadth of immune response monitoring. Challenges remain, however, in translating many of these tools to routine clinical practice. This Opinion focuses on two strategies that may advance the clinical adoption of immune-based biomarkers: protein-based assays employing digital readouts can reduce nonspecific signals that limit more classical assays; and approaches that stimulate immune responses in more standardized ways can help to reveal disease-specific immune response signatures by elevating the signal above the background. The integration of such immune response phenotypes is a critical step for the increased implementation of precision medicine-based strategies
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
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