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Infectious diseases caused by bacteria, fungi, viruses and parasites have affected humans historically. Infectious diseases remain a major cause of premature death and a public health concern globally with increased mortality and significant economic burden. Unvaccinated individuals, people with suppressed and compromised immune systems are at higher risk of suffering from infectious diseases. In spite of significant advancements in infectious diseases research, the control or treatment process faces challenges. The mucosal immune system plays a crucial role in safeguarding the body from harmful pathogens, while being constantly exposed to the environment. To develop treatment options for infectious diseases, it is vital to understand the immune responses that occur during infection. The two infectious diseases presented here are: i) Helicobacter pylori infection and ii) human immunodeficiency (HIV) and human papillomavirus (HPV) co-infection. H pylori, is a bacterium that colonizes the stomach and causes gastric cancer in 1-2% but is beneficial for protection against allergies and gastroesophageal diseases. An estimated 85% of H pylori colonized individuals show no detrimental effects. HIV is a virus that causes AIDS, one of the deadliest and most persistent epidemics. HIV-infected patients are at an increased risk of co-infection with HPV, and report an increased incidence of oral cancer. The goal of this thesis is to elucidate the host immune responses in infectious diseases via the use of computational and mathematical models. First, the thesis reviews the need for computational and mathematical models to study the immune responses in the course of infectious diseases. Second, it presents a novel sensitivity analysis method that identifies important parameters in a hybrid (agent-based/equation-based) model of H. pylori infection. Third, it introduces a novel model representing the HIV/HPV coinfection and compares the simulation results with a clinical study. Fourth, it discusses the need of advanced modeling technologies to achieve a personalized systems wide approach and the challenges that can be encountered in the process. Taken together, the work in this dissertation presents modeling approaches that could lead to the identification of host immune factors in infectious diseases in a predictive and more resource-efficient manner. / Doctor of Philosophy / Infectious diseases caused by bacteria, fungi, viruses and parasites have affected humans historically. Infectious diseases remain a major cause of premature death and a public health concern globally with increased mortality and significant economic burden. These infections can occur either via air, travel to at-risk places, direct person-to-person contact with an infected individual or through water or fecal route. Unvaccinated individuals, individuals with suppressed and compromised immune system such as that in HIV carriers are at higher risk of getting infectious diseases. In spite of significant advancements in infectious diseases research, the control and treatment of these diseases faces numerous challenges. The mucosal immune system plays a crucial role in safeguarding the body from harmful pathogens, while being exposed to the environment, mainly food antigens. To develop treatment options for infectious diseases, it is vital to understand the immune responses that occur during infection. In this work, we focus on gut immune system that acts like an ecosystem comprising of trillions of interacting cells and molecules, including membars of the microbiome. The goal of this dissertation is to develop computational models that can simulate host immune responses in two infectious diseases- i) Helicobacter pylori infection and ii) human immunodeficiency virus (HIV)-human papilloma virus (HPV) co-infection. Firstly, it reviews the various mathematical techniques and systems biology based methods. Second, it introduces a "hybrid" model that combines different mathematical and statistical approaches to study H. pylori infection. Third, it highlights the development of a novel HIV/HPV coinfection model and compares the results from a clinical trial study. Fourth, it discusses the challenges that can be encountered in adapting machine learning based computational technologies. Taken together, the work in this dissertation presents modeling approaches that could lead to the identification of host immune factors in infectious diseases in a predictive and more resourceful way.

Made available in DSpace on 2016-04-27T16:58:29Z (GMT). No. of bitstreams: 1 Nelson Dias Leme.pdf: 5327513 bytes, checksum: 4de15af5883da758e73a3351fa8b55d1 (MD5) Previous issue date: 2007-10-17 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This work aims to contribute to the investigation of the impact of a constructionist approach to the use of electronic spreadsheets on the teaching and learning of topics related to Financial Mathematics. To this end, a teaching experiment was designed which involved students in the construction of their own formulas, using spreadsheets, for calculating interests and future values of investments, under regimes of both simple and compound rates. The constructionist conceptions of Papert provided a theoretical base for the development of the activities. The methodology adopted for the study was modelled according to the design-based research methodologies. Two phases of experimentation were elaborated. The first phase involves students initiating their studies in Financial Mathematics in working on a set of activities with spreadsheets, and then completing a series of paper and pencil tasks. In the second phase, to provide a basis for comparing the approach adopted with the more usual practice of giving students previously defined formulae for calculating interest, the paper and pencil task were also administered to a group of students who has previously studied Financial Mathematics. The analysis of data followed the cycle of description-execution-reflectiondebugging- description described by Valente. According to these analyses, the formulae constructed by the students and implemented on the computer served as computational models providing feedback and enabling simulations of various possible situations. This in turn allowed students to engage in a cycle of expression, evaluation and reflection of the mathematical domain in question / O objetivo deste trabalho é colaborar na investigação do impacto da abordagem construcionista e das potencialidades das planilhas eletrônicas no ensino-aprendizagem de conteúdos da Matemática Financeira. Para alcançar o objetivo proposto, foi elaborado um experimento de ensino envolvendo alunos na construção de suas próprias fórmulas, usando planilhas eletrônicas, para o cálculo dos juros e do montante, nos regimes dos juros simples e compostos. Para o desenvolvimento das atividades buscamos referência na concepção construcionista de Seymour Papert (1994). A metodologia empregada neste trabalho está baseada no design-based research methodologies . Metodologia de Pesquisa Baseada em Design. Foram desenvolvidas duas fases de experimentação. A primeira fase envolveu um grupo de alunos iniciantes seus em estudos de Matemática Financeira, em um conjunto de atividades com planilhas eletrônicas e, em uma série de tarefas em papel e lápis. Na segunda fase para comparar com o desempenho do primeiro grupo, foram aplicadas as atividades com papel e lápis a um grupo de alunos que já concluiu seus estudos de Matemática Financeira e que vivenciou uma abordagem de ensino onde as fórmulas não foram construídas. A análise empregou o ciclo descrição-execução-reflexão-depuraçãodescrição de Valente (2002). Segundo nossas análises, as fórmulas deduzidas e implementadas no computador são modelos computacionais que possibilitam o feedback e a simulação, favorecendo o envolvimento dos aprendizes no ciclo básico de expressão, avaliação e reflexão sobre o domínio considerado

Submitted by Cláudia Bueno (claudiamoura18@gmail.com) on 2016-10-25T17:23:14Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação_Geovanne_Furriel - 2016.pdf: 10594556 bytes, checksum: e02146f1c9d65005e1bc2e584ca3d281 (MD5) / Approved for entry into archive by Cláudia Bueno (claudiamoura18@gmail.com) on 2016-10-25T17:24:42Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação_Geovanne_Furriel - 2016.pdf: 10594556 bytes, checksum: e02146f1c9d65005e1bc2e584ca3d281 (MD5) / Made available in DSpace on 2016-10-25T17:24:42Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação_Geovanne_Furriel - 2016.pdf: 10594556 bytes, checksum: e02146f1c9d65005e1bc2e584ca3d281 (MD5) Previous issue date: 2016-08-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The purpose of this work is to present the development of automatic instrument for measuring soil compaction through penetration resistance. Commonly, this measurement is performed by load cells. In the proposed methodology and apparatus, the penetration resistance is directly measured by the current applied to the motor that performs penetration of the rod into the soil, thus replacing the load cell. The collected data are stored in Datalogger and further processed in order to enable analysis and the generation of maps of the surface with soil compaction values up to a certain depth. The presented results indicate greater precision and control of the fundamental parameters of data acquisition / O objetivo deste trabalho é apresentar o desenvolvimento de aparelho automático para medição da compactação do solo através da resistência a penetração. Comumente, esta aferição é realizada por células de carga. Na metodologia e aparelho proposto, a resistência à penetração será medida diretamente pela corrente aplicada ao motor que realiza a penetração da haste no solo, em substituição da célula de carga. Os dados coletados são armazenados em Datalogger e posteriormente tratados de forma que possibilite a análise e a geração de mapas do terreno com valores da compactação do solo até determinada profundidade. Os resultados apresentados indicam maior precisão em relação ao método utilizado e controle sobre os parâmetros fundamentais da coleta de dados.

Submitted by Erika Demachki (erikademachki@gmail.com) on 2017-01-02T20:08:50Z No. of bitstreams: 2 Dissertação - Geovanne Pereira Furriel - 2016.pdf: 10594556 bytes, checksum: e02146f1c9d65005e1bc2e584ca3d281 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-01-03T09:57:56Z (GMT) No. of bitstreams: 2 Dissertação - Geovanne Pereira Furriel - 2016.pdf: 10594556 bytes, checksum: e02146f1c9d65005e1bc2e584ca3d281 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-01-03T09:57:56Z (GMT). No. of bitstreams: 2 Dissertação - Geovanne Pereira Furriel - 2016.pdf: 10594556 bytes, checksum: e02146f1c9d65005e1bc2e584ca3d281 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-08-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The purpose of this work is to present the development of automatic instrument for measuring soil compaction through penetration resistance. Commonly, this measurement is performed by load cells. In the proposed methodology and apparatus, the penetration resistance is directly measured by the current applied to the motor that performs penetration of the rod into the soil, thus replacing the load cell. The collected data are stored in Datalogger and further processed in order to enable analysis and the generation of maps of the surface with soil compaction values up to a certain depth. The presented results indicate greater precision and control of the fundamental parameters of data acquisition. / O objetivo deste trabalho é apresentar o desenvolvimento de aparelho automático para medição da compactação do solo através da resistência a penetração. Comumente, esta aferição é realizada por células de carga. Na metodologia e aparelho proposto, a resistência à penetração será medida diretamente pela corrente aplicada ao motor que realiza a penetração da haste no solo, em substituição da célula de carga. Os dados coletados são armazenados em Datalogger e posteriormente tratados de forma que possibilite a análise e a geração de mapas do terreno com valores da compactação do solo até determinada profundidade. Os resultados apresentados indicam maior precisão em relação ao método utilizado e controle sobre os parâmetros fundamentais da coleta de dados.

Submitted by isabela.moljf@hotmail.com (isabela.moljf@hotmail.com) on 2017-02-13T14:23:53Z No. of bitstreams: 1 evelynaparecidadeoliveira.pdf: 4026204 bytes, checksum: c1b720f3501ffcd12b38f9d4c877dfa9 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-02-13T16:49:50Z (GMT) No. of bitstreams: 1 evelynaparecidadeoliveira.pdf: 4026204 bytes, checksum: c1b720f3501ffcd12b38f9d4c877dfa9 (MD5) / Made available in DSpace on 2017-02-13T16:49:50Z (GMT). No. of bitstreams: 1 evelynaparecidadeoliveira.pdf: 4026204 bytes, checksum: c1b720f3501ffcd12b38f9d4c877dfa9 (MD5) Previous issue date: 2016-04-01 / O desgaste do dente, que se manifesta com uma grande variedade de graus ou níveis, é uma das anomalias dentárias comumente encontradas em diversas populações. A modelagem computacional do problema de contato oclusal pode ajudar na compreensão das interações entre os dentes, que gera concentrações de tensões. A abordagem utilizada para simular o contato entre as superfícies ásperas, dadas as funções de densidade de probabilidade das alturas das asperezas, consiste em discretizá-las em vários intervalos, de modo que cada um deles represente uma aspereza principal. As deformações das asperezas principais são analisadas e, utilizando técnicas de homogeneização, é possível estabelecer a relação entre as respostas que ocorrem em microescala e as respostas esperadas na macroescala. Neste trabalho, foi criada uma rotina para geração numérica de superfícies, um script acoplado ao programa de elementos finitos, Abaqus, para análise dos microcontatos, e, finalmente, um código para o procedimento de homogeneização e análise paramétrica das medidas de rugosidade. Na estimativa da dureza superficial, verificou-se que a curvatura média das asperezas exerce maior influência. Os parâmetros que mais influenciam nas forças e áreas de contato são o coeficiente de achatamento (kurtosis), cujo aumento leva ao decaimento dessas grandezas, seguido da rugosidade média quadrática, que, por sua vez, tem uma relação diretamente proporcional com a carga e consequentemente com a área de contato. / Tooth wear, which manifests with a great variety of degrees or levels, is one of the dental abnormalities commonly found in different populations. The computational modelling of the occlusal contact problem can help the comprehension of any interaction between teeth generating stress concentration. The approach used in this work to simulate contact between rough surfaces, given the probability density functions of asperities, consists in discretizing them in several intervals, so that each one represents a main asperity. The deformations of the main asperities are analyzed and, using homogenization techniques, it is possible to developed the relationship among the responses occurred in micro-scale and the predicted responses in macro-scale. In this work a routine has been established for numerical generation of surfaces, a script as well as has been coupled to the finite element program Abaqus, for analysis of the micro-contacts, and, finally, a code for homogenization and parametric analysis of the roughness measure. In the estimate of the surface hardness it was found that the mean curvature of the asperities exerts the largest influence. The parameters that influence the forces and contact areas are the flattening coefficient (kurtosis), which when increases leads to decay of these greatness, followed by the mean square roughness, which, in turn, has a direct proportional relationship with the strength and consequently with the contact area.

Dissimilarity plays a very important role in object recognition. But, finding perceptual dissimilarity between objects is non-trivial as it is not equivalent to the pixel dissimilarity between the objects (For example, two white noise images appear very similar even when they have different intensity values at every corresponding pixel). However, visual search allows us to reliably measure perceptual dissimilarity between a pair of objects. When the target object is dissimilar to the distracter, visual search becomes easy and it will be difficult otherwise. Even though we can measure perceptual dissimilarity between objects, we still do not understand either the underlying mechanisms or the visual features involved in the computation of dissimilarities. For this thesis, I have explored perceptual dissimilarity in two studies – by looking at known simple features and understanding how they combine, and using computational models to understand or discover complex features. In the first study, we looked at how dissimilarity between two simple objects with known features can be predicted using dissimilarities between individual features. Specifically, we investigated how search for targets differing in multiple features (intensity, length, orientation) from the distracters is related to searches for targets differing in each of the individual features. We found that multiple feature dissimilarities could be predicted as a linear combination of individual feature dissimilarities. Also, we demonstrated for the first time that Aspect ratio of the object emerges as a novel feature in visual search. This work has been published in the Journal of Vision (Pramod & Arun, 2014). Having established in the first study that simple features combine linearly, we devised a second study to investigate dissimilarities in complex shapes. Since it is known that shape is one of the salient and complex features in object representation, we chose silhouettes of animals and abstract objects to explore the nature of dissimilarity computations. We conducted visual search using pairs of these silhouettes on humans to get an estimate of perceptual dissimilarity. We then used various computational models of shape representation (like Fourier Descriptors, Curvature Scale Space, HMAX model etc) to see how well they can predict the observed dissimilarities. We found that many of these computational models were able to predict the perceptual dissimilarities of a large number of object pairs. However, we also observed many cases where computational models failed to predict perceptual dissimilarities. The manuscript related to this study is under preparation.

Jazz improvisation provides a case context for examining information in music; entropy provides a means for representing music for retrieval. Entropy measures are shown to distinguish between different improvisations on the same theme, thus demonstrating their potential for representing jazz information for analysis and retrieval. The calculated entropy measures are calibrated against human representation by means of a case study of an advanced jazz improvisation course, in which synonyms for "entropy" are frequently used by the instructor. The data sets are examined for insights in music information retrieval, music information behavior, and music representation.

During tissue invasion individual tumor cells exhibit two interconvertible migration modes, namely mesenchymal and amoeboid migration. The cellular microenvironment triggers the switch between both modes, thereby allowing adaptation to dynamic conditions. It is, however, unclear if this amoeboid-mesenchymal migration plasticity contributes to a more effective tumor invasion. We address this question with a mathematical model, where the amoeboid-mesenchymal migration plasticity is regulated in response to local extracellular matrix resistance. Our numerical analysis reveals that extracellular matrix structure and presence of a chemotactic gradient are key determinants of the model behavior. Only in complex microenvironments, if the extracellular matrix is highly heterogeneous and a chemotactic gradient directs migration, the amoeboid-mesenchymal migration plasticity allows a more widespread invasion compared to the non-switching amoeboid and mesenchymal modes. Importantly, these specific conditions are characteristic for in vivo tumor invasion. Thus, our study suggests that in vitro systems aiming at unraveling the underlying molecular mechanisms of tumor invasion should take into account the complexity of the microenvironment by considering the combined effects of structural heterogeneities and chemical gradients on cell migration.

[ES] La fibrilación auricular es la arritmia cardíaca más común. Durante la fibrilación auricular, el sustrato auricular sufre una serie de cambios o remodelados a nivel eléctrico y estructural. La remodelación eléctrica se caracteriza por la alteración de una serie de canales iónicos, lo que cambia la morfología del potential de transmembrana conocido como potencial de acción. La remodelación estructural es un proceso complejo que involucra la interacción de varios procesos de señalización, interacción celular y cambios en la matriz extracelular. Durante la remodelación estructural, los fibroblastos que abundan en el tejido cardíaco, comienzan a diferenciarse en miofibroblastos que son los encargados de mantener la estructura de la matriz extracelular depositando colágeno. Además, la señalización paracrina de los miofibroblastos afecta a los canales iónicos de los miocitos circundantes. Se utilizaron modelos computacionales muy detallados a diferentes escalas para estudiar la remodelación estructural inducida a nivel celular y tisular. Se realizó una adaptación de un modelo de fibroblastos humanos a nivel celular para reproducir la electrofisiología de los miofibroblastos durante la fibrilación auricular. Además, se evaluó la exploración de la interacción del calcio en la electrofisiología de los miofibroblastos ajustando el canal de calcio a los datos experimentales. A nivel tisular, se estudió la infiltración de miofibroblastos para cuantificar el aumento de vulnerabilidad a una arritmia cardíaca. Los miofibroblastos cambian la dinámica de la reentrada. Una baja densidad de miofibroblastos permite la propagación a través del área fibrótica y crea puntos de salida de actividad focal y roturas de ondas dentro de esta área. Además, las composiciones de fibrosis juegan un papel clave en la alteración del patrón de propagación. La alteración del patrón de propagación afecta a los electrogramas recogidos en la superficie del tejido. La morfología del electrograma se alteró dependiendo de la disposición y composición del tejido fibrótico. Se combinaron modelos detallados de tejido cardíaco con modelos realistas de los catéteres de mapeo disponibles comercialmente para comprender las señales registradas clínicamente. Se generó un modelo de ruido a partir de señales clínicas para reproducir los artefactos de señal en el modelo. Se utilizaron electrogramas de modelos de dos dominios altamente detallados para entrenar un algoritmo de aprendizaje automático para caracterizar el sustrato fibrótico auricular. Las características que cuantifican la complejidad de las señales fueron extraídas para identificar la densidad fibrótica y la transmuralidad fibrótica. Posteriormente, se generaron mapas de fibrosis utilizando el registro del paciente como prueba de concepto. El mapa de fibrosis proporciona información sobre el sustrato fibrótico sin utilizar un valor único de corte de 0,5 milivoltios. Además, utilizando la medición del flujo de información como la entropía de transferencia combinada con gráficos dirigidos, en este estudio, se siguió la dirección de propagación del frente de onda. La transferencia de entropía con gráficos dirigidos proporciona información crucial durante la electrofisiología para comprender la dinámica de propagación de ondas durante la fibrilación auricular. En conclusión, esta tesis presenta un estudio in silico multiescala que proporciona información sobre los mediadores celulares responsables de la remodelación de la matriz extracelular y su electrofisiología. Además, proporciona una configuración realista para crear datos in silico que pueden ser usados para aplicaciones clínicas y servir de soporte al tratamiento de ablación. / [CA] La fibril·lació auricular és l'arrítmia cardíaca més freqüent, en la qual el substrat auricular patix una sèrie de remodelacions elèctriques i estructurals. La remodelació de tipus elèctric es caracteritza per l'alteració d'un conjunt de canals iònics que modifica la morfologia del voltatge transmembrana, conegut com a potencial d'acció. La remodelació estructural és un fenomen complex que implica la relació entre diversos processos de senyalització, interaccions cel·lulars i canvis en la matriu extracel·lular. Durant la remodelació estructural, els abundants fibroblasts presents en el teixit cardíac comencen a diferenciar-se en miofibroblasts, els quals s'encarreguen de mantenir l'estructura de la matriu extracel·lular dipositant-hi col·lagen. A més, la senyalització paracrina dels miofibroblasts amb els miòcits circumdants també afectarà els canals iònics. Es van utilitzar models computacionals molt detallats a diferents escales per estudiar la remodelació estructural induïda a nivell tissular i cel·lular. Es va fer una adaptació a nivell cel·lular d'un model de fibroblasts humans per reproduir-hi l'electrofisiologia dels miofibroblasts durant la fibril·lació auricular. A més, l'exploració de la interacció del calci amb l'electrofisiologia dels miofibroblasts va ser avaluada mitjançant l'adequació del canal de calci a les dades experimentals. A nivell tissular es va estudiar la infiltració de miofibroblasts per tal de quantificar l'augment de vulnerabilitat que això conferia per patir una arrítmia cardíaca. Els miofibroblasts canvien la dinàmica de la reentrada, i presentar-ne una baixa densitat permet la propagació a través de la zona fibròtica, tot creant punts de sortida d'activitat focal i trencaments d'ones dins d'aquesta àrea. A més, les composicions de fibrosi tenen un paper clau en l'alteració del patró de propagació, afectant els electrogrames recollits en la superfície del teixit. La morfologia dels electrogrames es va veure alterada en funció de la disposició i la composició del teixit fibròtic. Per comprendre els senyals clínicament registrats es van combinar models detallats de teixits cardíacs amb models realistes dels catèters de cartografia disponibles comercialment. Es va generar un model de soroll a partir de senyals clínics per reproduir-hi els artefactes de senyal. Es van utilitzar electrogrames de models de bidominis molt detallats per entrenar un algoritme d'aprenentatge automàtic destinat a caracteritzar el substrat fibròtic auricular. Les característiques que quantifiquen la complexitat dels senyals van ser extretes per identificar la densitat i transmuralitat fibròtica. Posteriorment, es van generar mapes de fibrosi mitjançant la gravació del pacient com a prova de concepte. El mapa de fibrosi proporciona informació sobre el substrat fibròtic sense utilitzar un sol valor de tensió de tall de 0,5 mV. A més, utilitzant la mesura del flux d'informació com l'entropia de transferència combinada amb gràfics dirigits, en aquest estudi es va fer un seguiment de la direcció de propagació de l'ona. L'entropia de transferència amb gràfics dirigits proporciona informació crucial durant l'electrofisiologia per entendre la dinàmica de propagació d'ones durant la fibril·lació auricular. En conclusió, aquesta tesi presenta un estudi multi-escala in silico que proporciona informació sobre els mediadors cel·lulars responsables de la remodelació de la matriu extracel·lular i la seva electrofisiologia. A més, proporciona una configuració realista per crear dades in silico que es poden traduir a aplicacions clíniques que puguen donar suport al tractament de l'ablació. / [EN] Atrial fibrillation is the most common cardiac arrhythmia. During atrial fibrillation, the atrial substrate undergoes a series of electrical and structural remodeling. The electrical remodeling is characterized by the alteration of specific ionic channels, which changes the morphology of the transmembrane voltage known as action potential. Structural remodeling is a complex process involving the interaction of several signalling pathways, cellular interaction, and changes in the extracellular matrix. During structural remodeling, fibroblasts, abundant in the cardiac tissue, start to differentiate into myofibroblasts, which are responsible for maintaining the extracellular matrix structure by depositing collagen. Additionally, myofibroblasts paracrine signalling with surrounding myocytes will also affect ionic channels. Highly detailed computational models at different scales were used to study the effect of structural remodeling induced at the cellular and tissue levels.At the cellular level, a human fibroblast model was adapted to reproduce the myofibroblast electrophsyiology during atrial fibrillation. Additionally, the calcium handling in myofibroblast electrophysiology was assessed by fitting calcium ion channel to experimental data. At the tissue level, myofibroblasts infiltration was studied to quantify the increase of vulnerability to cardiac arrhythmia. Myofibroblasts alter the dynamics of reentry. A low density of myofibroblasts allows the propagation through the fibrotic area and creates focal activity exit points and wave breaks inside this area. Moreover, fibrosis composition plays a key role in the alteration of the propagation pattern. The alteration of the propagation pattern affects the electrograms computed at the surface of the tissue. Electrogram morphology was altered depending on the arrangement and composition of the fibrotic tissue. Detailed cardiac tissue models were combined with realistic models of the commercially available mapping catheters to understand the clinically recorded signals. A noise model from clinical signals was generated to reproduce the signal artifacts in the model. Electrograms from highly detailed bidomain models were used to train a machine learning algorithm to characterize the atrial fibrotic substrate. Features that quantify the complexity of the signals were extracted to identify fibrotic density and fibrotic transmurality. Subsequently, fibrosis maps were generated using patient recordings as a proof of concept. Fibrosis map provides information about the fibrotic substrate without using a single cut-off voltage value of 0.5 mV. Furthermore, in this study, using information theory measurements such as transfer entropy combined with directed graphs, the wave propagation direction was tracked. Transfer entropy with directed graphs provides crucial information during electrophysiology to understand wave propagation dynamics during atrial fibrillation. In conclusion, this thesis presents a multiscale in silico study atrial fibrillation mechanisms providing insight into the cellular mediators responsible for the extracellular matrix remodeling and its electrophysiology. Additionally, it provides a realistic setup to create in silico data that can be translated to clinical applications that could support ablation treatment. / Sánchez Arciniegas, JP. (2021). A Multiscale in Silico Study to Characterize the Atrial Electrical Activity of Patients With Atrial Fibrillation. A Translational Study to Guide Ablation Therapy [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/171456