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    Human hepatocytes in three-dimensional culture on Innovative biopolymeric scaffolds as a useful system for in vitro toxicology tests

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    P 1.6 HUMAN HEPATOCY TES IN THREE- DIMENSIONAL CULTURE ON INNOVATIVE BIOPOLYMERIC SCAFFOLDS AS AN USEFUL SYSTEM FOR IN VITRO TOXICOLOGY TESTS Stampella A. (a), Massimi M. (b), Barbetta A. (c), Rizzitelli G. (c), Dentini M. (c), Conti Devirgiliis L. (a) (a) Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Rome, Italy (b) Department of Basic and Applied Biology, University of L’Aquila, L’Aquila, Italy (c) Department of Chemistry, Sapienza University of Rome, Rome, Italy Many innovative biomaterials have recently be developed as scaffolds to replace physiological matrix components and their im provement has led to significant advances in culture techniques in terms of cell survival, quantitative expansion, maintenance of differentiated phenotype and specific cell functions. A key point in achieving these goals has been to maintain a three-dimensional culture and the typical cyto-architecture of the tissue by improving the extracellular matrix geometry and by promoting cell-cell contacts and reciprocal adhesions. These bio-artificial systems represent a real hope as functional substitutes for damaged organs and tissues and have provoked a great interest in the field of regenerative medicine. Concerning hepatocyte cultures, since the liver is the main organ involved in detoxification processes and in the defence of organisms against harmful molecules, in addition to their biomedical applications, these systems can be utilized as invaluable tool for toxicology tests for analyzing the effects on metabolism of new drugs, or for screening potentially toxic substances. The aim of our research was to identify the most suitable biomaterial for the technological applications with hepatocytes. Since the possibility to improve the performance of thes e systems depends strongly on the methods used to create the scaffolds, here we analyzed porous matrices made of gelatin or blends of gelatin and glycosaminoglycans, obtained with different methods for the culture of the C3A cell line, considered a good model of human hepatocytes. Scaffolds were obtained using either a concentrated emulsi on-templating technique known as High Internal Phase Emulsion (HIPE) or a gas foaming technique; the latter method uses an inert gas instead of the internal liquid phase toluene, avoiding the use of organic solvent and allowing the creation of scaffolds with la rger pores and interconnections. Cell viability was analysed using MTS and LDH assays; ultrastructural morphology and three-dimensional cell organization into the scaffold were assessed by SEM; albumin and urea secretion, as the main metabolic markers of hepatocyte functions, were monitored using, respectively, an ELISA kit and a colorimetric assay. Finally Cytochrome P450-3A4 activity was quantified by a luminescent method. Values of activity of this important enzyme of the detoxification system, obtained in the absence or in the pr esence of specific inducing molecules, were compared between the different culture conditions

    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

    Satisfactory performance of hepatocytes in three-dimensional culture on innovative biopolymeric scaffolds

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    The introduction in recent years of innovative biomaterials as scaffolds to replace physiological matrix components has led to significant advances in culture techniques, in terms of cell survival, quantitative expansion, maintenance of differentiated phenotype and specific functions of cells. ese bio-artificial tissues can be used as functional substitutes for damaged organs, as models to study complex biological processes, or for tissue-specific toxicology tests. e aim of our research was to identify the most suitable biomaterial for technological applications with hepatocytes, e.g. tissue therapy, cellular transplantation, metabolic analysis of new drugs or screening for potentially toxic substances. Since the possibility to improve the performance of these systems depends strongly on the methods used to create the scaffolds, here we analyzed porous matrices made of gelatin or blends of gelatin and glycosaminoglycans, obtained with different methods for the culture of the C3A cell line, considered a good model of human hepatocytes. Scaffolds were obtained using either a concentrated emulsion-templating technique known as high internal phase emulsion (HIPE) or a gas foaming technique; the latter method uses an inert gas instead of the internal liquid phase toluene, avoiding the use of organic solvent and allowing the creation of scaffolds with larger pores and interconnections. By analyzing cell adhesion, viability, ultrastructural morphology, production of albumin and urea and induction of cytochrome P450-3A4 as the main metabolic markers of hepatocyte functions, it was possible to compare the performances of matrices prepared with the different methods. Taken together our results suggest that the morphology of the scaffolds (surface porosity, void/ interconnection size) is less crucial than the utilization of potentially harmful molecules during their creation

    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

    Dielectric characterization of Hepatocytes in suspension and embedded into two different polymeric scaffolds

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    The dielectric and conductometric properties of hepatocytes in two different environments (in aqueous suspension and embedded into polymeric scaffolds) have been investigated in the frequency range from 10 kHz to 2 GHz, where the interfacial electrical polarization gives rise to marked dielectric relaxation effects. We analyzed the dielectric behavior of hepatocytes in complete medium aqueous suspensions in the light of effective medium approximation for heterogeneous systems and hepatocytes cultured into two different highly porous and interconnected polymeric structures. In the former case, we have evaluated the passive electrical parameters associated with both the plasmatic and nuclear membrane, finding a general agreement with the values reported elsewhere, based on a partially different analysis of the experimental spectra. In the latter case, we have evaluated the cell growth into two different polymeric scaffolds made of alginate and gelatin with a similar pore distribution and similar inter-connectivity. Based on a qualitative analysis of the dielectric spectra, we were able to provide evidence that alginate scaffolds allow an overall survival of cells better than gelatin scaffold can do. These indications, confirmed by biological tests on cell viability, suggest that hepatocytes embedded in alginate scaffolds are able to perform liver specific functions even over on extended period of time

    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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