The Integrated Film Activated Sludge Process (IFAS) was developed to reduce the cost of additional facilities required to complete year round nitrification in the design of new or retrofit wastewater treatment plants. The purpose of this project was to develop a computer-based mechanistic model, called IFAS, which can be used as a tool by scientists and engineers to optimize their designs and to troubleshoot a full-scale treatment plant. The program also can be employed to assist researchers conducting their studies of IFAS wastewater treatment processes. IFAS enables the steady-state simulation of nitrification-denitrification processes as well as carbonaceous removal in systems utilizing integrated media, but this current version supports only sponge type media. The IFAS program was developed by incorporating empirical equations for integrated biofilm carbonaceous uptake and nitrification developed by Sen and Randall (1995) into the general activated sludge model, developed by the International Association on Water Quality (IAWQ, previously known as IAWRC), plus the biological phosphorus removal model of Wentzel et al (1989). The calibration and evaluation of the IFAS model was performed using existing data from both an IFAS system and a conventional activated sludge bench-scale plant operated over a wide range of Aerobic Mean Cell Residence Times (Aerobic MCRT's). The model developed provides a good fit and a reasonable prediction of the experimental data for both the IFAS and the conventional pilot-scale systems. The phosphorus removal component of the model has not yet been calibrated because of insufficient data and the lack of adequately defined parameters. / Master of Science

Tesis por compendio / [EN] Heart failure, a cardiomyopathy that produces mechanical dysfunction and sudden cardiac death following fatal arrhythmias, is one of the main causes of mortality worldwide that also causes elevated morbidity rates. Current clinical therapies are challenged by the complexity of this cardiac pathology, in which many factors are involved in the electrical instabilities that lead to an altered function. The electrical activity of the heart comprises a wide range of spatial and temporal scales. Ion transport across transmembrane proteins initiate the cellular depolarization that is propagated cell to cell through the myocardium depolarizing and then repolarizing the entire heart in an orchestrated manner. The electrical excitation of cardiomyocytes triggers the cellular contraction, a process in which Ca2+ ions are the main mediators. Ca2+ dynamics plays a relevant role in controlling excitation-contraction coupling and consequently, investigations have focused on Ca2+-handling proteins and the regulation of Ca2+ homeostasis to elucidate the causes of impaired contractility and pro-arrhythmic conditions in cardiac diseases. This thesis takes advantage of the existence of mathematical models with detailed representation of the subcellular processes to perform computational simulations of cardiac electrophysiology and understand the altered mechanisms that govern heart failure, especially those related with intracellular Ca2+ cycling. It is known that failing myocytes undergo a specific remodeling of ion channels and Ca2+-handling proteins that lead to an impaired excitation-contraction coupling. Initially, it was analyzed, in the human action potential model of ventricular myocytes selected for the whole study, the effects of modulating ionic mechanisms on the electrical activity and Ca2+ dynamics. In tissue, heart failure induces additional changes affecting cellular coupling. The development of fibroblasts and impact on myocyte electrophysiology was investigated, including the vulnerability to generate alternans, a common precursor to arrhythmogenesis. Finally, the beta-adrenergic signaling model was integrated with the action potential model because of the electrophysiological modulation exerted by the sympathetic nervous system, which is aggravated under heart failure conditions. Results highlighted the need of studying heart failure therapies on failing cells because of the different response of ion channels and membrane proteins to drugs. Functional Ca2+ proteins were important to maintain Ca2+ homeostasis and to avoid malignant electrical consequences, being SERCA pump the most critical factor. Apart from the electrophysiological remodeling, fibroblast interaction contributed to alter Ca2+ dynamics in myocytes and, when analyzing Ca2+ alternans, spatial electrical discordances predominated in failing tissues. The inclusion of beta-adrenergic stimulation showed that the inotropic response was diminished in heart failure as well as the antiarrhythmic benefits provided by catecholamines in the normal heart. These findings contribute to gain insight into the pathophysiology of heart failure and the development of new pharmacological agents targeted to restore Ca2+ dynamics. The control of intracellular Ca2+ cycling is crucial to ensure both the mechanical force and the electrical activity that lead to a rhythmic contraction of the heart. / [ES] La insuficiencia cardíaca, una cardiomiopatía que provoca disfunción mecánica y muerte súbita tras arritmias cardíacas letales, es una de las principales causas de mortalidad en todo el mundo que además causa tasas de morbilidad elevadas. Las terapias usadas actualmente en la clínica están comprometidas por la complejidad de esta patología cardíaca, ya que son muchos los factores que están implicados en las inestabilidades eléctricas que conllevan a alteraciones funcionales. La actividad eléctrica del corazón abarca un amplio rango escalas espaciales y temporales. El transporte de iones a través de las proteínas transmembrana inicia la despolarización celular que se propaga de célula en célula a través del miocardio, despolarizando y luego repolarizando todo el corazón de manera sincronizada. La excitación eléctrica de los cardiomiocitos desencadena la contracción celular, un proceso en el que los iones de Ca2+ son los principales intermediarios. La dinámica de Ca2+ tiene un papel relevante en el control del acoplamiento excitación-contracción y, como consecuencia, las investigaciones se han centrado en las proteínas que controlan el ciclo del Ca2+ y la regulación homeostática para encontrar las causas que empeoran la contractilidad y conducen a condiciones proarrítmicas en casos de insuficiencia cardíaca. Esta tesis hace uso de la existencia de modelos matemáticos con una representación detallada de los procesos subcelulares para realizar simulaciones computacionales de electrofisiología cardíaca y comprender los mecanismos que están alterados y predominan en insuficiencia cardíaca, especialmente aquellos relacionados con el ciclo intracelular de Ca2+ . Se sabe que los miocitos dañados por insuficiencia cardíaca experimentan un remodelado específico en los canales iónicos y en las proteínas partícipes en el ciclo de Ca2+, ocasionando fallos en el acoplamiento excitación-contracción. Inicialmente, se analizaron, en el modelo de potencial de acción humano de miocitos ventriculares seleccionado para todo el estudio, los efectos de la modulación de los mecanismos iónicos sobre la actividad eléctrica y la dinámica de Ca2+. En los tejidos, la insuficiencia cardíaca induce cambios adicionales que afectan el acoplamiento celular. Se ha investigado la presencia de fibroblastos y su impacto en la electrofisiología de los miocitos, incluida la vulnerabilidad para generar alternantes, un precursor común de la arritmogénesis. Finalmente, se ha incluido el modelo de señalización -adrenérgica integrado con el modelo de potencial de acción debido a la modulación electrofisiológica ejercida por el sistema nervioso simpático, que se agrava en condiciones de insuficiencia cardíaca. Los resultados han destacado la necesidad de estudiar las terapias de insuficiencia cardíaca en células de estos corazones debido a la diferente respuesta de los canales iónicos y las proteínas de membrana a los medicamentos. El buen funcionamiento de las proteínas reguladoras del Ca2+ es importantes para mantener la homeostasis del Ca2+ y evitar consecuencias eléctricas malignas, siendo la bomba SERCA el factor más crítico. Además del remodelado electrofisiológico, la interacción con fibroblastos contribuye a alterar la dinámica de Ca2+ en los miocitos y, al analizar los alternantes de Ca2+, predominan las discordancias eléctricas espaciales en los tejidos de corazones con insuficiencia cardíaca. La inclusión de la estimulación -adrenérgica ha mostrado que la respuesta inotrópica disminuye en insuficiencia cardíaca, así como los beneficios antiarrítmicos proporcionados por las catecolaminas en un corazón normal. Estos hallazgos contribuyen a obtener información sobre la fisiopatología de la insuficiencia cardíaca y el desarrollo de nuevos agentes farmacológicos destinados a restaurar la dinámica de Ca 2+. El control del ciclo de Ca2+ intracelular es crítico para garantizar tanto la fuerza mecánica como la actividad eléctrica que conducen a una contracción rítmica del corazón. / [CA] La insuficiència cardíaca, una cardiomiopatia que provoca disfunció mecànica i mort sobtada després d'arrítmies cardíaques letals, és una de les principals causes de mortalitat a tot el món que a més causa taxes de morbiditat elevades. Les teràpies utilitzades actualment en la clínica estan compromeses per la complexitat d'aquesta patologia cardíaca, ja que són molts els factors que estan implicats en les inestabilitats elèctriques que comporten a alteracions funcionals. L'activitat elèctrica del cor abasta un ampli rang d'escales espacials i temporals. El transport d'ions a través de les proteïnes transmembrana inicia la despolarització cel·lular que es propaga de cèl·lula en cèl·lula a través del miocardi, despolaritzant i després repolaritzant tot el cor de manera sincronitzada. L'excitació elèctrica dels cardiomiòcits desencadena la contracció cel·lular, un procés en el qual els ions de Ca2+ són els principals intermediaris. La dinàmica de Ca2+ té un paper rellevant en el control de l'acoblament excitació-contracció i, com a conseqüència, les investigacions s'han centrat en les proteïnes que controlen el cicle del Ca2+ i la regulació homeostàtica per a trobar les causes que empitjoren la contractilitat i condueixen a condicions proarrítmiques en casos d'insuficiència cardíaca. Aquesta tesi fa ús de l'existència de models matemàtics amb una representació detallada dels processos subcel·lulars per a realitzar simulacions computacionals de l'electrofisiologia cardíaca i comprendre els mecanismes que estan alterats i predominen en insuficiència cardíaca, especialment aquells relacionats amb el cicle intracel·lular de Ca2+. Se sap que els miòcits danyats per insuficiència cardíaca experimenten un remodelat específic en els canals iònics i en les proteïnes partícips en el cicle de Ca2+, ocasionant fallades en l'acoblament excitació-contracció. Inicialment, es van analitzar, en el model de potencial d'acció humà de miòcits ventriculars seleccionat per a tot l'estudi, els efectes de la modulació dels mecanismes iònics sobre l'activitat elèctrica i la dinàmica de Ca2+. En els teixits, la insuficiència cardíaca indueix canvis addicionals que afecten l'acoblament cel·lular. S'ha investigat la presència de fibroblasts i el seu impacte en l'electrofisiologia dels miòcits, inclosa la vulnerabilitat per a generar alternants, un precursor comú de l'arritmogènesi. Finalment, s'ha inclòs el model de senyalització beta-adrenèrgica integrat amb el model de potencial d'acció a causa de la modulació electrofisiològica exercida pel sistema nerviós simpàtic, que s'agreuja en condicions d'insuficiència cardíaca. Els resultats han destacat la necessitat d'estudiar les teràpies d'insuficiència cardíaca en cèl·lules d'aquests cors a causa de la diferent resposta dels canals iònics i les proteïnes de membrana als medicaments. El bon funcionament de les proteïnes reguladores del Ca2+ és importants per a mantindre l'homeòstasi del Ca2+ i evitar conseqüències elèctriques malignes, sent la bomba SERCA el factor més crític. A més del remodelat electrofisiològic, la interacció amb fibroblasts contribueix a alterar la dinàmica de Ca2+ en els miòcits i, en analitzar els alternants de Ca2+, predominen les discordances elèctriques espacials en els teixits de cors amb insuficiència cardíaca. La inclusió de l'estimulació beta-adrenèrgica ha mostrat que la resposta inotròpica disminueix en insuficiència cardíaca, així com els beneficis antiarrítmics proporcionats per les catecolamines en un cor normal. Aquestes troballes contribueixen a obtindre informació sobre la fisiopatologia de la insuficiència cardíaca i el desenvolupament de nous agents farmacològics destinats a restaurar la dinàmica de Ca2+. El control del cicle de Ca2+ intracel·lular és crític per a garantir tant la força mecànica com l'activitat elèctrica per a una contracció rítmica del cor. / Mora Fenoll, MT. (2020). In silico study of calcium handling in the human failing heart [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/153143 / Compendio

Yes / In a hard chromium electroplating process, a heat exchanger is employed to remove the heat produced from the high current intensity in an electroplating bath. Normally, a conventional U shape heat exchanger is installed in the bath but it provides low heat removal. Thus, this study designs a novel W serpentine shape heat exchanger with identical heat transfer area to the conventional one for increasing heat removal performance. The performance of the heat exchange is tested with various flow velocities in a cross-section in range of 1.6 to 2.4 m·s− 1. Mathematical models of this process have been formulated in order to simulate and evaluate the heat exchanger performance. The results show that the developed models give a good prediction of the plating solution and cooling water temperature and the novel heat exchanger provides better results at any flow velocity. In addition, the W serpentine shape heat exchanger has been implemented in a real hard chromium electroplating plant. Actual data collected have shown that the new design gives higher heat removal performance compared with the U shape heat exchanger with identical heat transfer area; it removes more heat out of the process than the conventional one of about 23%.

Wood chemical treatment is an important process in the wood industry, in that such treatment alters the properties of wood so that a variety of wood-based products can be fabricated with enhanced performance. However, wood's complex composition and structure make it difficult to achieve consistent and controllable treatment. An innovative self-flowing process presented for the chemical treatment of wood is inspired by liquid transportation in trees. Effectiveness of the self-flowing process is evaluated and compared to conventional immersion and vacuum wood treatment methods. The self-flowing process allows a more uniform wood treatment compared to that from the immersion and vacuum pressure methods. Lignin content after self-flowing delignification is below 5% with a standard deviation of 0.7, compared to ~20% with a standard deviation of 8 for both immersion and vacuum pressure methods. The self-flowing process allows 100% chemical impregnation depth for the preservation treatment. A mathematical model was developed to simulate the self-flowing process. This model can accurately predict the treatment time required for achieving desired results under various conditions, including temperature, wood density, and liquid properties. This work demonstrates that the self-flowing treatment is a highly efficient, cost-effective, and reliable method in wood preservation and modification industries.

Biofilms are communities of microorganisms that can form in the human microbiome and on medical implants among other locations. These communities provide greater protection for their member cells resulting in an increase in resistance to antibiotic treatment and persistent infections. There are several factors that may contribute to antibiotic resistance of biofilms. These studies were done concurrently with biological experiments to test the hypothesis that dense, rigid structures within the biofilm may be an additional mechanism for protection from antibiotics. A computational tool and workflow was developed to analyze bead movement for the characterization of biofilm biomaterial properties including rigidity. With this tool, the analysis revealed that the amyloid, curli, confers rigidity in biofilms, thereby restricting bead movement. Greater movement of the beads is seen in biofilms lacking curli and biofilms that produced complex heterogeneous rigid structures. A new model was also developed that uses microscopy imaging data to simulate diffusion-reaction of antibiotics within heterogeneous biofilms. This model was used to investigate the effect of the dense, rigid structures on antibiotic treatment through test simulations and simulations using biological imaging data. These studies reveal various properties about the dense, rigid structures that confer protection. / Mathematics

Breakthroughs in molecular and synthetic biology through de novo gene synthesis are stimulating new vaccines, pharmaceutical applications, and functionalized biomaterials, and advancing the knowledge of the function of cells. This evolution in biological processing motivates the study of a class of manufacturing systems, defined here as genetic manufacturing systems, which produce a final product with a genetic construct. Genetic manufacturing systems rely on rare molecular events for success, resulting in waste and repeated work during the deoxyribonucleic acid (DNA) fabrication process. Inspection and real time monitoring strategies are possible as mitigation tools, but it is unclear if these techniques are cost efficient and value added for the successful creation of custom genetic constructs. This work investigates resource allocation strategies for DNA fabrication environments, with an emphasis on inspection allocation. The primary similarities and differences between traditional manufacturing systems and genetic manufacturing systems are described. A serial, multi-stage inspection allocation mathematical model is formulated for a genetic manufacturing system utilizing gene synthesis. Additionally, discrete event simulation is used to evaluate inspection strategies for a fragment synthesis process and multiple fragment assembly operation. Results from the mathematical model and discrete event simulation provide two approaches to determine the appropriate inspection strategies with respect to total cost or total flow time of the genetic manufacturing system. / Ph. D. / Breakthroughs in molecular and synthetic biology through <i>de novo</i> gene synthesis are stimulating new vaccines, pharmaceutical applications, and functionalized biomaterials, and advancing the knowledge of the function of cells. This evolution in biological processing motivates the study of a class of manufacturing systems, defined here as genetic manufacturing systems, which produce a final product with a genetic construct. Genetic manufacturing systems rely on rare molecular events for success, resulting in waste and repeated work during the deoxyribonucleic acid (DNA) fabrication process. Inspection and real time monitoring strategies are possible as mitigation tools, but it is unclear if these techniques are cost efficient and value added for the successful creation of custom genetic constructs. This work investigates resource allocation strategies for DNA fabrication environments, with an emphasis on inspection allocation. The primary similarities and differences between traditional manufacturing systems and genetic manufacturing systems are described. A serial, multi-stage inspection allocation mathematical model is formulated for a genetic manufacturing system utilizing gene synthesis. Additionally, discrete event simulation is used to evaluate inspection strategies for a fragment synthesis process and multiple fragment assembly operation. Results from the mathematical model and discrete event simulation provide two approaches to determine the appropriate inspection strategies with respect to total cost or total flow time of the genetic manufacturing system.

With a continuing and rising demand for hydrocarbons, the energy companies are installing infrastructure ever further offshore, where such infrastructure is often exposed to extreme waves. This thesis explores some aspects of wave-structure interaction, particularly the maximum water surface elevation increase in severe storms due to these local interactions. The effects on wave-structure interactions of column cross-sectional shape are investigated using linear and second-order wave diffraction theory. For multi-column structures, the excitation of locally resonant wave modes (near-trapping) is studied for several column cross-sectional shapes, and a simple method for estimating the surface elevation mode shape is given. The structure of the quadratic transfer functions for second-order sum wave elevation is investigated and an approximation assuming these QTFs are flat perpendicular to the leading diagonal is shown to be adequate for the first few lowest frequency modes. NewWave-type focused wave groups can be used as a more realistic model of extreme ocean waves. A Net Amplification Factor based on the NewWave model is given as an efficient tool for finding the incident frequencies most likely to cause a violent wave-structure interaction and where these violent responses are likely to occur. Statistics are collected from Monte Carlo type simulations of random waves to verify the use of the Net Amplification Factor. Going beyond linear calculations, surface elevation statistics are collected to second-order and a `designer' wave is found to model the most extreme surface elevation responses. A `designer' wave can be identified at required levels of return period to help to understand the relative size of harmonic components in extreme waves. The methods developed with a fixed body are then applied to an identical hull which is freely floating, and the responses between the fixed and moving cases are compared. The vertical heave motion of a semi-submersible in-phase with the incident wave crests is shown to lead to a much lower probability of water-deck impact for the same hull shape restrained vertically. The signal processing methods developed are also applied to a single column to allow comparison with experimental results. Individual harmonic components of the hydrodynamic force are identified up to at least the fifth harmonic. Stokes scaling is shown to hold even for the most violent interactions. It is also shown that the higher harmonic components of the hydrodynamic force can be reconstructed from just the fundamental force time history, and a transfer function in the form of a single phase and an amplitude for each harmonic. The force is also reconstructed well to second-order from the surface elevation time history using diffraction transfer functions. Finally, possible causes of damage to a platform high above mean water level in the North Sea are investigated.

This DPhil project is set in the context of single crystal elasticity-plasticity finite element modelling. Its core objective was to develop and implement a methodology for predicting the evolution of texture in single and dual-phase material systems. This core objective has been successfully achieved. Modelling texture evolution entails essentially modelling large deformations (as accurately as possible) and taking account of the deformation mechanisms that cause texture to change. The most important deformation mechanisms are slip and twinning. Slip has been modelled in this project and care has been taken to explore conditions where it is the dominant deformation mechanism for the materials studied. Modelling slip demands that one also models dislocations since slip is assumed to occur by the movement of dislocations. In this project a model for geometrically necessary dislocations has been developed and validated against experimental measurements. A texture homogenisation technique which relies on interpretation of EBSD data in order to allocate orientation frequencies based on representative area fractions has been developed. This has been coupled with a polycrystal plasticity RVE framework allowing for arbitrarily sized RVEs and corresponding allocation of crystallographic orientation. This has enabled input of experimentally measured initial textures into the CPFE model allowing for comparison of predictions against measured post-deformation textures, with good agreement obtained. The effect of texture on polycrystal physical properties has also been studied. It has been confirmed that texture indeed has a significant role in determining the average physical properties of a polycrystal. The thesis contributes to the following areas of micro-mechanics materials research: (i) 3D small deformation crystal plasticity finite element (CPFE) modelling, (ii) geometrically necessary dislocation modelling, (iii) 3D large deformation CPFE modelling, (iv) texture homogenisation methods, (v) single and dual phase texture evolution modelling, (vi) prediction of polycrystal physical properties, (vii) systematic calibration of the power law for slip based on experimental data, and (viii) texture analysis software development (pole figures and Kearns factors).

Magnetic resonance imaging (MRI) of the liver is an important non-invasive tool for diagnosing liver disease. A key application is dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). With the use of the hepatocyte specific contrast agent (CA) Gd-EOB-DTPA it is now possible to evaluate the liver function. Beyond traditional qualitative evaluation of the DCE-MRI images, parametric quantitative techniques are on the rise which yields more objective evaluations. Systems biology is a gradually expanding field using mathematical modeling to gain deeper mechanistic understanding in complex biological systems. The aim of this thesis to combine these two fields in order to derive a physiologically accurate minimal whole body model that can be used to quantitatively evaluate liver function using clinical DCE-MRI examinations.  The work is based on two previously published sources of data using Gd-EOB-DTPA in healthy humans; i) a region of interest analysis of the liver using DCE-MRI ii) a pre-clinical evaluation of the contrast agent using blood sampling.  The modeling framework consists of a system of ordinary differential equations for the contrast agent dynamics and non-linear models for conversion of contrast agent concentrations to relaxivity values in the DCE-MRI image volumes. Using a χ2-test I have shown that the model, with high probability, can fit the experimental data for doses up to twenty times the clinically used one, using the same parameters for all doses. The results also show that some of the parameters governing the hepatocyte flux of CA can be numerically identifiable. Future applications with the model might be as a basis for regional liver function assessment. This can lead to disease diagnosis and progression evaluation for physicians as well as support for surgeons planning liver resection.

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