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    Adverse outcome pathway for benzene induced toxicity through reverse causal reasoning and network perturbation analysis

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    Trabalho de Projeto do Mestrado Integrado em Engenharia Biomédica apresentado à Faculdade de Ciências e TecnologiaThe increase and improvement in molecular profiling technologies have enabled the acquisition of large datasets consisting of measurements for many molecular entities. These datasets allow an understanding of molecular profiles of, for example, a disease, drug and compounds action, or toxicity. Furthermore, gene expression profiling experiments usually produce extensive lists of differential expressed genes that characterize the comparison between the two states in the study, such as disease versus healthy or treatment versus control. In this study two approaches are used to interpret these lists, take out relevant and reliable hypotheses and quantify biological network perturbations: Reverse Causal Reasoning (RCR) and Network Perturbation Analysis (NPA); towards exploring the full potential of these datasets. The RCR and NPA methods are implemented and tested on the transcriptome of benzene-exposed individuals to propose a hypothesis of biological processes alterations. Several proposed altered biological mechanisms are in agreement with literature evidence, meaning that this approach can be a valuable tool for understanding mechanisms associated with benzene exposure. While some of them have not been studied and false positives are a possibility, this approach indicates possible candidates, that have not been verified by the literature as potential future directions in research.The increase and improvement in molecular profiling technologies have enabled the acquisition of large datasets consisting of measurements for many molecular entities. These datasets allow an understanding of molecular profiles of, for example, a disease, drug and compounds action, or toxicity. Furthermore, gene expression profiling experiments usually produce extensive lists of differential expressed genes that characterize the comparison between the two states in the study, such as disease versus healthy or treatment versus control.In this study two approaches are used to interpret these lists, take out relevant and reliable hypotheses and quantify biological network perturbations: Reverse Causal Reasoning (RCR) and Network Perturbation Analysis (NPA); towards exploring the full potential of this datasets. The RCR and NPA methods are implemented and tested on the transcriptome of benzene-exposed individuals to propose a hypothesis of biological processes alterations.Several proposed altered biological mechanisms are in agreement with literature evidence, meaning that this approach can be a valuable tool for understanding mechanisms associated with benzene exposure. While some of them have not been studied and false positives are a possibility, this approach indicates possible candidates, that have not been verified by the literature as potential future directions in research

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    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

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    “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

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    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

    Dispelling the Myths Behind First-author Citation Counts

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    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

    Author Index

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    Applications of evidence synthesis in chemical health risk assessment

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    This thesis aimed to combine all available evidence within and across evidence streams, i.e. evidence synthesis, to strengthen chemical risk assessment. The evidence considered was published data of the following evidence streams: epidemiologic studies, molecular epidemiology studies, animal studies and mechanistic assays. For the purpose of evidence synthesis, advanced statistical and biological informed tools and approaches were used including meta-analysis, meta-regression, text mining, systematic reviews, systems biology, physiological based kinetic (PBK) models, and Bayesian inference. Most work performed in this thesis is on two exemplary data rich chemicals: benzene and diisocyanates. The case-studies of this thesis illustrate that human biomonitoring studies can be a valuable source of information for both enhancing exposure assessment and hazard characterization. Tooling such as text mining and network visualization tools can help to make evidence identification for hazard identification more efficient. And evidence from human (epidemiology and biomonitoring) and animal studies can also be combined together, but this does require a large number of assumptions. The chapters in this thesis demonstrate that a wide range of interdisciplinary approaches are required to be able to integrate data, for it to become optimally useful for chemical risk assessment. The methods and tooling in this thesis are mostly applied to chemicals for which a large amount of data is known. In the Discussion chapter of this thesis, suggestions are given for approaches that can be used for chemicals for which only little information is known, possibly in conjunction with the new scientific approaches described in the other Chapters of this Thesis

    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    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
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