1,721,088 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
Mathematical Modeling of the \u3ci\u3eCandida albicans\u3c/i\u3e Yeast to Hyphal Transition Reveals Novel Control Strategies
Get PDFCandida albicans, an opportunistic fungal pathogen, is a significant cause of human infections, particularly in immunocompromised individuals. Phenotypic plasticity between two morphological phenotypes, yeast and hyphae, is a key mechanism by which C. albicans can thrive in many microenvironments and cause disease in the host. Understanding the decision points and key driver genes controlling this important transition and how these genes respond to different environmental signals is critical to understanding how C. albicans causes infections in the host. Here we build and analyze a Boolean dynamical model of the C. albicans yeast to hyphal transition, integrating multiple environmental factors and regulatory mechanisms. We validate the model by a systematic comparison to prior experiments, which led to agreement in 17 out of 22 cases. The discrepancies motivate alternative hypotheses that are testable by follow-up experiments. Analysis of this model revealed two time-constrained windows of opportunity that must be met for the complete transition from the yeast to hyphal phenotype, as well as control strategies that can robustly prevent this transition. We experimentally validate two of these control predictions in C. albicans strains lacking the transcription factor UME6 and the histone deacetylase HDA1, respectively. This model will serve as a strong base from which to develop a systems biology understanding of C. albicans morphogenesis
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
Logical modelling of mesoderm differentiation in Drosophila melanogaster
No full textAu cours des dernières décennies, les approches expérimentales nous ont permis d'obtenir des informations importantes en biologie du développement et nous ont conduit à la définition de réseaux complexes de régulation contrôlant les processus développementaux. Actuellement, notre compréhension de ces réseaux est entravée par leur complexité même. La modélisation mathématique est de plus en plus utilisée pour intégrer les voies de régulation et prévoir les effets de perturbations génétiques. Durant ma thèse, je me suis intéressée à la différentiation du mésoderme chez Drosophila melanogaster. Elle commence par la spécification du mésoderme en 4 différents tissus: le muscle viscéral, le coeur, le muscle somatique et le corps gras. La formation de ces tissus se traduit par une organisation segmentale répétitive le long du mésoderme. Mon premier but était de construire un modèle qui récapitule la spécification de ces quatre tissus entre les stades 8 et 10. Par la suite, je me suis concentrée sur le développement du coeur dans le but de proposer un modèle de régulation de la diversification des cellules cardiaques contractiles (cardioblastes) entre les stade 10 et 12. Afin de comprendre ces processus complémentaires, j'ai été amené à modéliser les voies de signalisation qui jouent un rôle important dans le développement du mésoderme et des cardioblastes. Je me suis appuyée sur des données génétiques et des analyses haut-débit publiées (HhIP-chip, ChIP-seq et transcriptome) pour déterminer et annoter des graphes de régulation complet pour chacun de ces réseaux ou voies.During the past decades, experimental approaches have allowed us to gain important insights in developmental biology, and led to the delineation of complex regulatory networks controlling developmental processes. Currently, our understanding of these networks is hindered by their sheer complexity. Mathematical modelling is increasingly used to integrate regulatory pathways and predict the effects of genetic perturbations. My thesis focuses on the development of the specification of the mesoderm in Drosophila melanogaster. Its development results in the formation of different tissues segmentally iterated: the visceral muscle, the heart, the somatic muscle, and the fat body. My first goal was to build a network model recapitulating the specification of these 4 mesodermal tissues during stages 8 to 10. Then, focusing on heart development, my second aim was to build a network model recapitulating contractile cardiac cell (cardioblast) diversification during stages 10 to 12. To understand these complementary processes, I was further led to model the signalling pathways that play important roles in mesoderm and cardioblast development. I rely on a combination of published genetic data and high- throughput analyses (ChIP-chip, ChiP-seq, transcriptome) to delineate and annotate comprehensive regulatory graphs for each of these networks or pathways. Using a logical formalism and the GINsim software, I have further defined logical rules enabling the simulation of wild type and mutant behaviours for each of this networks or pathways. By and large, my model simulations recapitulate all relevant published data
Transcriptional Dynamics Reveal Critical Roles for Non-coding RNAs in the Immediate-Early Response
Get PDFThe immediate-early response mediates cell fate in response to a variety of extracellular stimuli and is dysregulated in many cancers. However, the specificity of the response across stimuli and cell types, and the roles of non-coding RNAs are not well understood. Using a large collection of densely-sampled time series expression data we have examined the induction of the immediate-early response in unparalleled detail, across cell types and stimuli. We exploit cap analysis of gene expression (CAGE) time series datasets to directly measure promoter activities over time. Using a novel analysis method for time series data we identify transcripts with expression patterns that closely resemble the dynamics of known immediate-early genes (IEGs) and this enables a comprehensive comparative study of these genes and their chromatin state. Surprisingly, these data suggest that the earliest transcriptional responses often involve promoters generating non-coding RNAs, many of which are produced in advance of canonical protein-coding IEGs. IEGs are known to be capable of induction without de novo protein synthesis. Consistent with this, we find that the response of both protein-coding and non-coding RNA IEGs can be explained by their transcriptionally poised, permissive chromatin state prior to stimulation. We also explore the function of non-coding RNAs in the attenuation of the immediate early response in a small RNA sequencing dataset matched to the CAGE data: We identify a novel set of microRNAs responsible for the attenuation of the IEG response in an estrogen receptor positive cancer cell line. Our computational statistical method is well suited to meta-analyses as there is no requirement for transcripts to pass thresholds for significant differential expression between time points, and it is agnostic to the number of time points per dataset.</p
Integrative modelling and analysis of MAPK network deregulations in human cancers
No full textLe réseau des MAPK est composé de pathways de signalisation fermement entrecroisés impliqués dans le cancer. Toutefois, les mécanismes précis qui sous-tendent son influence sur l'équilibre entre la prolifération et la mort cellulaire demeurent insaisissablesDes données publiques ont été intégrés dans une carte de réactions détaillée, représentant l'influence du réseau des MAPKs sur la décision du destin cellulaire. Cette carte a ensuite été utilisée pour des analyses informatiques spécifiquesTout d'abord, les dynamiques du réseau des MAPKs dans les cancers de la vessie ont été analysés.Un modèle Booléen a été construit, représentant la réponse du réseau aux inputs d'intérêt.Les résultats de simulations systématiques ont été trouvés globalement cohérents avec des données publiques, et ont permis de déchiffrer les principaux événements qui sous-tendent les différents comportements observés dans le cancerEnsuite, la carte a été exploitée pour réanalyser des données publiques d'expression de gènes, avec l'objectif d'identifier les principaux acteurs de la transduction des signaux prolifératifs, dans des types cellulaires spécifiques.Des analyses du réseaux et des calculs statistiques ont conduit à l'identification de régions dérégulées dans le réseau des MAPKs, et à la délinéation de points d'intervention optimales dans cinq stades du cancer de la vessie et dans quatre sous-types de lymphome TL'ensemble de ces résultats a conduit à la formulation de nouvelles hypothèses concernant le fonctionnement du réseau des MAPKs dans différents états pathologiques, et à la sélection de composants cibles qui pourraient être envisagées pour le développement de nouveaux traitementsMAPK network consists of tightly interconnected signalling pathways. Although several studies established the involvement of this network in cancer deregulations, the precise mechanisms underlying its influence on the balance between cell proliferation and death remain elusive.Public data were integrated into a detailed reaction map, accounting for the influence of MAPK network on cell fate decision. This map was then used for computational analyses addressing specific cancer-related questions.First, the dynamics of MAPK network in bladder cancers were analysed. A Boolean model was built, accounting for the response of the network to selected inputs. The results of systematic simulations were found globally coherent with published data. Based on in silico experiments, the main events underlying different observed cancer cell behaviours were then deciphered.Next, the MAPK reaction map was exploited to reanalyse public high-throughput gene expression data. The goal was to identify key actors for the transduction of proliferative signals, in specific cell types. Network analyses and statistical computations led to the identification of deregulated MAPK network regions, and to the delineation of optimal intervention points aimed at blocking the proliferative signals transduced from such regions. This approach was used to study five different tumour stages and four different subtypes of T-cell lymphoma.Altogether, these results led to the formulation of novel hypotheses concerning the functioning of MAPK network in different pathological conditions, and to the selection of target components that might be considered for the development of novel treatments
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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