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Evolution of the Seminal O'Hara Rudy Model to More Accurately Simulate the Electrophysiology of Human Ventricular Cardiomyocytes
No full textThe aim of our work consists in developing a new model of the human ventricular cardiomyocyte, based on the O'Hara-Rudy model (ORd), to improve, in particular, the action potential duration (APD) dependence on the extracellular Ca2+ concentration (Cao). Moreover, the new model reproduces all the available experimental data on APD rate dependence, APD restitution, drug block effects, etc., when the experimental extracellular ionic concentrations are carefully reproduced in simulationsThe main differences between our and the ORd model are: a novel Markovian formulation for the L-type Ca2+ current; the Markovian rapid delayed rectifier K+ current formulation published by Li et al.; a new formulation of the Ca2+ release from the sarcoplasmic reticulum. Several model parameters were modifiedOur BS (Bartolucci-Severi) model successfully improved the ORd, one of the most detailed, used and influent models in computational cardiology, by reproducing the APD-Cao relationship while keeping all the original model features tested in the appropriate experimentally-matched conditions. Furthermore, the BS was suitability as baseline for the generation of in silico populations of models and for reproducing cardiac abnormalities such as early afterdepolarizations
A synthetic molecular tool for post-transcriptional control of gene expression in E. coli
No full textSimulation of the Effects of Extracellular Calcium Changes Leads to a Novel Computational Model of Human Ventricular Action Potential With a Revised Calcium Handling
Get PDFThe importance of electrolyte concentrations for cardiac function is well established. Electrolyte variations can lead to arrhythmias onset, due to their important role in the action potential (AP) genesis and in maintaining cell homeostasis. However, most of the human AP computer models available in literature were developed with constant electrolyte concentrations, and fail to simulate physiological changes induced by electrolyte variations. This is especially true for Ca2+, even in the O’Hara-Rudy model (ORd), one of the most widely used models in cardiac electrophysiology. Therefore, the present work develops a new human ventricular model (BPS2020), based on ORd, able to simulate the inverse dependence of AP duration (APD) on extracellular Ca2+ concentration ([Ca2+]o), and APD rate dependence at 4 mM extracellular K+. The main changes needed with respect to ORd are: (i) an increased sensitivity of L-type Ca2+ current inactivation to [Ca2+]o; (ii) a single compartment description of the sarcoplasmic reticulum; iii) the replacement of Ca2+ release. BPS2020 is able to simulate the physiological APD-[Ca2+]o relationship, while also retaining the well-reproduced properties of ORd (APD rate dependence, restitution, accommodation and current block effects). We also used BPS2020 to generate an experimentally-calibrated population of models to investigate: (i) the occurrence of repolarization abnormalities in response to hERG current block; (ii) the rate adaptation variability; (iii) the occurrence of alternans and delayed after-depolarizations at fast pacing. Our results indicate that we successfully developed an improved version of ORd, which can be used to investigate electrophysiological changes and pro-arrhythmic abnormalities induced by electrolyte variations and current block at multiple rates and at the population level
Optimization of the O'Hara-Rudy Model of Human Ventricular Action Potential with Respect to Electrolyte Concentrations and Rate Dependence
No full textThe 'Comprehensive In vitro Proarrhythmia Assay' (CiPA) initiative proposes a new mechanistic, model-informed, approach to cardiac safety assessment of new drugs, an approach made possible by a deeper understanding of the ionic currents that play a role in QTc prolongation and in the development of torsades de pointes (TdP). In defining a new paradigm in the field of cardiac safety the proarrhythmic risk would be primarily assessed using preclinical in vitro and in silico human models. In this scenario the best cellular computer model(s) would have to be selected and if necessary improved. The aim of this study has been the upgrade of the most updated human ventricular cell model in order to: 1) correct its response to [Ca2+]°changes; 2) replicate the steady state action potential duration (APD) rate dependency and 3) the S1S2 APD restitution. The presented model has been validated against the same experimental data used for the original one, in order to verify its consistency and enforce its integration in the use of in silico models for predicting clinical risk of drug-induced arrhythmias
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
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
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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