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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
161

Autonomous or assisted deployment by mobile robots of wireless sensor networks : coverage and connectivity issues / Déploiement autonome ou assisté par des robots mobiles d'un réseau de capteurs sans fil : couverture et connectivité

Khoufi Saadallah, Ines 30 September 2015 (has links)
Les réseaux de capteurs sans fil sont déployés pour assurer la surveillance de phénomènes physiques. La précision de l’information recueillie dépend fortement des positions des capteurs déployés. Ces positions doivent satisfaire les exigences de l’application en termes de couverture et de connectivité. Par conséquent, les algorithmes de déploiement sont nécessaires pour déterminer les positions optimales des capteurs. Cette thèse se concentre sur le déploiement de capteurs sans fil, d’une part lorsque ces noeuds sont capables de se positionner de manière autonome, et d’autre part lorsque leur déploiement est assisté par des robots mobiles. Dans les deux cas, ce déploiement doit, non seulement répondre aux exigences de l’application en termes de couverture et connectivité, mais aussi minimiser le nombre de capteurs nécessaires tout en satisfaisant diverses contraintes (e.g. obstacles, énergie, connectivité tolérant les défaillances). Nous avons proposé des algorithmes de déploiement autonome qui évitent les oscillations des noeuds : ADVFA, GDVFA et OA-DVFA pour surveiller des zones 2D et 3D-DVFA pour surveiller un espace 3D. Lorsque le déploiement est assisté par robots mobiles, nous avons proposé deux approches pour optimiser la durée du déploiement. La première se base sur la théorie de jeux pour optimiser la durée des trajectoires de deux robots (TRDS) et la deuxième se base sur l'optimisation multi-objectifs avec un nombre de robots supérieur ou égale à 2 (MRDS). Les objectifs à satisfaire sont : optimiser la durée de la trajectoire la plus longue, équilibrer les durées des trajectoires des robots et minimiser le nombre de robots utilisés, en évitant les obstacles. / Wireless sensor networks are deployed to monitor physical phenomena. The accuracy of information collected depends on sensor node positions. These positions must meet the application requirements in terms of coverage and connectivity. Therefore, deployment algorithms are necessary to determine the optimal positions of sensor nodes. This thesis focuses on the deployment of wireless sensor nodes, first when these nodes are autonomous, and secondly when they are static and the deployment is assisted by mobile robots. In both cases, this deployment must not only meet the application requirements in terms of coverage and connectivity, but also minimize the number of sensors needed while satisfying various constraints (e.g. obstacles, energy, fault-tolerant connectivity). We proposed autonomous deployment algorithms that avoid node oscillations: ADVFA, GDVFA and OA-DVFA to monitor 2D areas and 3D-DVFA to monitor a 3D space. In case of a deployment assisted by mobile robots, we proposed two approaches to optimize the deployment duration. The first one is based on game theory to optimize the length of the paths of two robots (TRDS) and the second is based on the multi-objective optimization, with a number of robots greater than or equal to 2 (MRDS). The objectives to be met are: optimizing the duration of the longest tour duration, balancing the durations of the robot tours and minimizing the number of robots used, while bypassing obstacles.
162

Bio-Inspired Evolutionary Algorithms for Multi-Objective Optimization Applied to Engineering Applications

DeBruyne, Sandra, DeBruyne January 2018 (has links)
No description available.
163

PHYSICS-BASED MODELLING AND SIMULATION FRAMEWORK FOR MULTI-OBJECTIVE OPTIMIZATION OF LITHIUM-ION CELLS IN ELECTRIC VEHICLE APPLICATIONS

Ashwin Pramod Gaonkar (12469470) 27 April 2022 (has links)
<p>  </p> <p>In the last years, lithium-ion batteries (LIBs) have become the most important energy storage system for consumer electronics, electric vehicles, and smart grids. The development of lithium-ion batteries (LIBs) based on current practice allows an energy density increase estimated at 10% per year. However, the required power for portable electronic devices is predicted to increase at a much faster rate, namely 20% per year. Similarly, the global electric vehicle battery capacity is expected to increase from around 170 GWh per year today to 1.5 TWh per year in 2030--this is an increase of 125% per year. Without a breakthrough in battery design technology, it will be difficult to keep up with the increasing energy demand. To that end, a design methodology to accelerate the LIB development is needed. This can be achieved through the integration of electro-chemical numerical simulations and machine learning algorithms.</p> <p><br></p> <p>To help this cause, this study develops a design methodology and framework using Simcenter Battery Design Studio® (BDS) and Bayesian optimization for design and optimization of cylindrical cell type 18650. The materials of the cathode are Nickel-Cobalt-Aluminum (NCA)/Nickel-Manganese-Cobalt-Aluminum (NMCA), anode is graphite, and electrolyte is Lithium hexafluorophosphate (LiPF6). Bayesian optimization has emerged as a powerful gradient-free optimization methodology to solve optimization problems that involve the evaluation of expensive black-box functions. The black-box functions are simulations of the cyclic performance test in Simcenter Battery Design Studio. </p> <p>The physics model used for this study is based on full system model described by Fuller and Newman. It uses Butler-Volmer Equation for ion-transportation across an interface and solvent diffusion model (Ploehn Model) for Aging of Lithium-Ion Battery Cells. The BDS model considers effects of SEI, cell electrode and microstructure dimensions, and charge-discharge rates to simulate battery degradation. Two objectives are optimized: maximization of the specific energy and minimization of the capacity fade. We perform global sensitivity analysis and see that thickness and porosity of the coating of the LIB electrodes that affect the objective functions the most. As such the design variables selected for this study are thickness and porosity of the electrodes. The thickness is restricted to vary from 22 micron to 240 microns and the porosity varies from 0.22 to 0.54. </p> <p>Two case studies are carried out using the above-mentioned objective functions and parameters. In the first study, cycling tests of 18650 NCA cathode Li-ion cells are simulated. The cells are charged and discharged using a constant 0.2C rate for 500 cycles. In the second case study a cathode active material more relevant to the electric vehicle industry, Nickel-Manganese-Cobalt-Aluminum (NMCA), is used. Here, the cells are cycled for 5 different charge-discharge scenarios to replicate charge-discharge scenario that an EVs battery module experiences. The results show that the design and optimization methodology can identify cells to satisfy the design objective that extend and improve the pareto front outside the original sampling plan for several practical charge-discharge scenarios which maximize energy density and minimize capacity fade. </p>
164

Transition Towards Fixed-Line Autonomous Bus Transportation Systems

Hatzenbühler, Jonas January 2020 (has links)
In the last years the steady development of autonomous driving technology has enabled the deployment of more mature autonomous vehicles. These vehicles have been applied in several pilot projects worldwide, most commonly in the form of small buses. At the same time, the amount of people traveling in especially urban areas is continuously growing, resulting in more trips in the transportation system. An efficient transportation system is therefore required to serve the growing passenger demand. Autonomous buses (AB) are assumed to have lower operational costs and with that public transport (PT) systems can potentially be designed more efficiently to facilitate the increased demand better. In this study, an AB specific simulation-based optimization framework is proposed which allows analyzing the impacts AB have on line-based PT systems. The thesis focuses on the transition from existing PT systems towards line-based PT systems operated partially or exclusively by AB. Existing work on PT service design is extended so that realistic AB systems can be investigated. This is achieved by (i) using AB specific operator cost formulations, (ii) integrating infrastructure costs required for AB operations, (iii) utilizing a dynamic, stochastic and schedule-based passenger assignment model for the simulation of PT networks and by (iv) formulating a multi-objective optimization problem allowing to investigate the stakeholder-specific impacts of AB. In Paper I the effects of AB, concerning service frequency and vehicle capacity, on fixed-line PT networks are investigated. Among other metrics, the changes are evaluated based on differences in level of service and passenger flow. Additionally, the sequential introduction of AB in existing PT systems is studied. The framework addresses a case study in Kista, Sweden. The study confirmed the initial hypothesis that the deployment of AB leads to an increase in service frequency and a marginal reduction in vehicle capacity. Furthermore, it could be seen that the deployment of AB increases the passenger load on AB lines and that passengers can shift from other PT modes towards the AB services. Paper II incorporates a multi-objective heuristic optimization algorithm in the simulation framework. The study investigates changes in transport network design based on the deployment of AB. The differences in user-focused and operator-focused network design are analyzed and the impact of AB on these is quantified. This study is applied to a case study in Barkarby, Sweden where a full-sized, line-based PT network is designed to exclusively operate AB. Among other findings, we show that the autonomous technology reduces the number of served bus stops and reduces the total PT network size. Additionally, average passenger waiting time can be reduced when deploying AB on user-focused PT networks, which in turn leads to a further reduction of user cost. / De senaste årens framsteg inom autonom körteknik har lett till mer mogna autonoma fordon. Dessa fordon har setts tillämpas i flera pilotprojekt över hela världen, oftast i form av små bussar. Samtidigt växer mängden människor som reser, särskilt i stadsområden, kontinuerligt vilket resulterar i fler resor i transportsystemet. Därför krävs ett effektivt transportsystem för att tillgodose det växande antalet passagerare. Autonoma bussar (AB) antas ha lägre driftskostnader och därmed kan system för kollektivtrafik (public transport, PT) potentiellt utformas mer effektivt för att underlätta den ökade efterfrågan bättre. I denna studie föreslås ett AB-specifikt simuleringsbaserat optimeringsramverk som gör det möjligt att analysera effekterna AB har på linjebaserade PT-system. Avhandlingen fokuserar på övergången från befintliga PT-system till linjebaserade PT-system som delvis eller uteslutande drivs av AB. Befintligt arbete med PT-tjänstdesign utvidgas så att realistiska AB-system kan undersökas. Detta uppnås genom att (i) använda AB-specifika operatörskostnadsformuleringar, (ii) integrera infrastrukturkostnader som krävs för AB-verksamhet, (iii) använda en dynamisk, stokastisk och schemabaserad modell för att tilldela passagerare vid simulering av PT-nät samt genom att (iv) formulera ett multifunktionellt optimeringsproblem som gör det möjligt att undersöka AB: s intressespecifika effekter. I artikel I undersöks effekterna av AB, med avseende på servicefrekvens och fordonskapacitet, på fasta linjer i PT-nät. Förändringar utvärderas bland annat utifrån skillnader i servicenivå och passagerarflöde. Dessutom studeras den sekventiella introduktionen av AB i befintliga PT-system. Det föreslagna ramverket tillämpas på en fallstudie i Kista, Sverige. Studien bekräftade den initiala hypotesen att utplaceringen av AB leder till en ökning av servicefrekvensen och en marginell minskning av fordonens kapacitet. Vidare kunde man se att utplaceringen av AB ökar passagerarbelastningen på AB-linjer och att passagerare kan skifta från andra PT-former mot AB-tjänsterna. Artikel II integrerar en multifunktionell heuristisk optimeringsalgoritm i ramverket för simuleringen. Studien undersöker förändringar i transportnätverkets design baserat på implementeringen av AB. Skillnaderna i användarfokuserad och operatörsfokuserad nätverksdesign analyseras och AB: s inverkan på dessa kvantifieras. Denna studie tillämpas på en fallstudie i Barkarby, Sverige, där ett fullstort linjebaserat PT-nät är utformat för att exklusivt driva AB. Vi visar bland annat att den autonoma tekniken reducerar antalet använda busshållplatser och reducerar den totala PT-nätstorleken. Dessutom kan implementeringen av AB på användarfokuserade PT-nät ytterligare förbättra servicenivån främst genom att minska den genomsnittliga väntetiden per passagerare.
165

Use of Approximate Triple Modular Redundancy for Fault Tolerance in Digital Circuits

Albandes, Iuri 26 November 2018 (has links)
La triple redundancia modular (TMR) es una técnica bien conocida de mitigación de fallos que proporciona una alta protección frente a fallos únicos pero con un gran coste en términos de área y consumo de potencia. Por esta razón, la redundancia parcial se suele aplicar para aligerar estos sobrecostes. En este contexto, la TMR aproximada (ATMR), que consisten en la implementación de la redundancia triple con versiones aproximadas del circuito a proteger, ha surgido en los últimos años como una alternativa a la replicación parcial, con la ventaja de obtener mejores soluciones de compromiso entre la cobertura a fallos y los sobrecostes. En la literatura ya han sido propuestas varias técnicas para la generación de circuitos aproximados, cada una con sus pros y sus contras. Este trabajo realiza un estudio de la técnica ATMR, evaluando el coste-beneficio entre el incremento de recursos (área) y la cobertura frente a fallos. La primera contribución es una nueva aproximación ATMR donde todos los módulos redundantes son versiones aproximadas del diseño original, permitiendo la generación de circuitos ATMR con un sobrecoste de área muy reducido, esta técnica se denomina Full-ATMR (ATMR completo o FATMR). El trabajo también presenta una segunda aproximación para implementar la ATMR de forma automática combinando una biblioteca de puertas aproximadas (ApxLib) y un algoritmo genético multi-objetivo (MOOGA). El algoritmo realiza una búsqueda ciega sobre el inmenso espacio de soluciones, optimizando conjuntamente la cobertura frente a fallos y el sobrecoste de área. Los experimentos comparando nuestra aproximación con las técnicas del estado del arte muestran una mejora de los trade-offs para diferentes circuitos de prueba (benchmark).
166

Multiobjective Coordination Models For Maintenance And Service Parts Inventory Planning And Control

Martinez, Oscar 01 January 2008 (has links)
In many equipment-intensive organizations in the manufacturing, service and particularly the defense sectors, service parts inventories constitute a significant source of tactical and operational costs and consume a significant portion of capital investment. For instance, the Defense Logistics Agency manages about 4 million consumable service parts and provides about 93% of all consumable service parts used by the military services. These items required about US$1.9 billion over the fiscal years 1999-2002. During the same time, the US General Accountability Office discovered that, in the United States Navy, there were about 3.7 billion ship and submarine parts that were not needed. The Federal Aviation Administration says that 26 million aircraft parts are changed each year. In 2002, the holding cost of service parts for the aviation industry was estimated to be US$50 billion. The US Army Institute of Land Warfare reports that, at the beginning of the 2003 fiscal year, prior to Operation Iraqi Freedom the aviation service parts alone was in excess of US$1 billion. This situation makes the management of these items a very critical tactical and strategic issue that is worthy of further study. The key challenge is to maintain high equipment availability with low service cost (e.g., holding, warehousing, transportation, technicians, overhead, etc.). For instance, despite reporting US$10.5 billion in appropriations spent on purchasing service parts in 2000, the United States Air Force (USAF) continues to report shortages of service parts. The USAF estimates that, if the investment on service parts decreases to about US$5.3 billion, weapons systems availability would range from 73 to 100 percent. Thus, better management of service parts inventories should create opportunities for cost savings caused by the efficient management of these inventories. Unfortunately, service parts belong to a class of inventory that continually makes them difficult to manage. Moreover, it can be said that the general function of service parts inventories is to support maintenance actions; therefore, service parts inventory policies are highly related to the resident maintenance policies. However, the interrelationship between service parts inventory management and maintenance policies is often overlooked, both in practice and in the academic literature, when it comes to optimizing maintenance and service parts inventory policies. Hence, there exists a great divide between maintenance and service parts inventory theory and practice. This research investigation specifically considers the aspect of joint maintenance and service part inventory optimization. We decompose the joint maintenance and service part inventory optimization problem into the supplier s problem and the customer s problem. Long-run expected cost functions for each problem that include the most common maintenance cost parameters and service parts inventory cost parameters are presented. Computational experiments are conducted for a single-supplier two-echelon service parts supply chain configuration varying the number of customers in the network. Lateral transshipments (LTs) of service parts between customers are not allowed. For this configuration, we optimize the cost functions using a traditional, or decoupled, approach, where each supply chain entity optimizes its cost individually, and a joint approach, where the cost objectives of both the supplier and customers are optimized simultaneously. We show that the multiple objective optimization approach outperforms the traditional decoupled optimization approach by generating lower system-wide supply chain network costs. The model formulations are extended by relaxing the assumption of no LTs between customers in the supply chain network. Similar to those for the no LTs configuration, the results for the LTs configuration show that the multiobjective optimization outperforms the decoupled optimization in terms of system-wide cost. Hence, it is economically beneficial to jointly consider all parties within the supply network. Further, we compare the model configurations LTs versus no LTs, and we show that using LTs improves the overall savings of the system. It is observed that the improvement is mostly derived from reduced shortage costs since the equipment downtime is reduced due to the proximity of the supply. The models and results of this research have significant practical implications as they can be used to assist decision-makers to determine when and where to pre-position parts inventories to maximize equipment availability. Furthermore, these models can assist in the preparation of the terms of long-term service agreements and maintenance contracts between original equipment manufacturers and their customers (i.e., equipment owners and/or operators), including determining the equitable allocation of all system-wide cost savings under the agreement.
167

The Development of a Multiple-Objective Optimization Tool to Reduce Greenhouse Gas Emissions of a Microgrid: A Case Study using University of Cincinnati’s Combined Heat and Power Microgrid

Swikert, Montine January 2022 (has links)
No description available.
168

A Multi-Objective Genetic Algorithm to Solve Single Machine Scheduling Problems Using a Fuzzy Fitness Function

Allard, David M. 24 July 2007 (has links)
No description available.
169

Shape and Structural Optimization of Flapping Wings

Stewart, Eric C. 11 January 2014 (has links)
This dissertation presents shape and structural optimization studies on flapping wings for micro air vehicles. The design space of the optimization includes the wing planform and the structural properties that are relevant to the wing model being analyzed. The planform design is parameterized using a novel technique called modified Zimmerman, which extends the concept of Zimmerman planforms to include four ellipses rather than two. Three wing types are considered: rigid, plate-like deformable, and membrane. The rigid wing requires no structural design variables. The structural design variables for the plate-like wing are the thickness distribution polynomial coefficients. The structural variables for the membrane wing control the in-plane distributed forces which modulate the structural deformation of the wing. The rigid wing optimization is performed using the modified Zimmerman method to describe the wing. A quasi-steady aerodynamics model is used to calculate the thrust and input power required during the flapping cycle. An assumed inflow model is derived based on lifting-line theory and is used to better approximate the effects of the induced drag on the wing. A multi-objective optimization approach is used since more than one aspect is considered in flapping wing design. The the epsilon-constraint approach is used to calculate the Pareto optimal solutions that maximize the cycle-average thrust while minimizing the peak input power and the wing mass. An aeroelastic model is derived to calculate the aerodynamic performance and the structural response of the deformable wings. A linearized unsteady vortex lattice method is tightly coupled to a linear finite element model. The model is cost effective and the steady-state solution is solved by inverting a matrix. The aeroelastic model is used to maximize the thrust produced over one flapping cycle while minimizing the input power. / Ph. D.
170

A systems engineering approach to model, tune and test synthetic gene circuits

Boada Acosta, Yadira Fernanda 16 November 2018 (has links)
La biología sintética se define como la ingeniería de la biología: el (re)diseño y construcción de nuevas partes, dispositivos y sistemas biológicos para realizar nuevas funciones con fines útiles, que se basan en principios elucidados de la biología y la ingeniería. Para facilitar la construcción rápida, reproducible y predecible de estos sistemas biológicos a partir de conjuntos de componentes es necesario desarrollar nuevos métodos y herramientas. La tesis plantea la optimización multiobjetivo como el marco adecuado para tratar los problemas comunes que surgen en el diseño racional y el ajuste óptimo de los circuitos genéticos sintéticos. Utilizando un enfoque clásico de ingeniería de sistemas, la tesis se centra principalmente en: i) el modelado de circuitos genéticos sintéticos basado en los primeros principios, ii) la estimación de parámetros de modelos a partir de datos experimentales y iii) el ajuste basado en modelos para lograr el desempeño deseado de los circuitos. Se han utilizado dos circuitos genéticos sintéticos de diferente naturaleza y con diferentes objetivos y problemas: un circuito de realimentación de tipo 1 incoherente (I1-FFL) que exhibe la importante propiedad biológica de adaptación, y un circuito de detección de quorum sensing y realimentación (QS/Fb) que comprende dos bucles de realimentación entrelazados -uno intracelular y uno basado en la comunicación de célula a célula- diseñado para regular el nivel medio de expresión de una proteína de interés mientras se minimiza su varianza a través de la población de células. Ambos circuitos han sido analizados in silico e implementados in vivo. En ambos casos, se han desarrollado modelos de estos circuitos basado en primeros principios. Se presta especial atención a ilustrar cómo obtener modelos de orden reducido susceptibles de estimación de parámetros, pero manteniendo el significado biológico. La estimación de los parámetros del modelo a partir de los datos experimentales se considera en diferentes escenarios, tanto utilizando modelos determinísticos como estocásticos. Para el circuito I1-FFL se consideran modelos determinísticos. Aquí, la tesis plantea la utilización de modelos locales utilizando la optimización multiobjetivo para realizar la estimación de parámetros del modelo bajo escenarios con estructura de modelo incompleta. Para el circuito QS/Fb, una estructura controlada por realimentación, el problema tratado es la falta de excitabilidad de las señales. La tesis propone una metodología de estimación en dos etapas utilizando modelos estocásticos. La metodología permite utilizar datos de curso temporal promediados de la población y mediciones de distribución en estado estacionario para una sola célula. El ajuste de circuitos basado en modelos para lograr un desempeño deseado también se aborda mediante la optimización multiobjetivo. Para el circuito QS/Fb se realiza un análisis estocástico completo. La tesis aborda cómo tener en cuenta correctamente tanto el ruido intrínseco como el extrínseco, las dos principales fuentes de ruido en los circuitos genéticos. Se analiza el equilibrio entre ambas fuentes de ruido y el papel que desempeñan en el bucle de realimentación intracelular, y en la realimentación extracelular de toda la población. La principal conclusión es que la compleja interacción entre ambos canales de realimentación obliga al uso de la optimización multiobjetivo para el adecuado ajuste del circuito. En esta tesis además del uso adecuado de herramientas de optimización multiobjetivo, la principal preocupación es cómo derivar directrices para el ajuste in silico de parámetros de circuitos que puedan aplicarse de forma realista in vivo en un laboratorio estándar. Como alternativa al análisis de sensibilidad de parámetros clásico, la tesis propone el uso de técnicas de clustering a lo largo de los frentes de Pareto, relacionando el compr / La biologia sintètica es defineix com l'enginyeria de la biologia: el (re) disseny i construcció de noves parts, dispositius i sistemes biològics per a realitzar noves funcions útils que es basen a principis elucidats de la biologia i l'enginyeria. Per facilitar la construcció ràpida, reproduïble i predictible de aquests sistemes biològics a partir de conjunts de components és necessari desenvolupar nous mètodes i eines. La tesi planteja la optimització multiobjectiu com el marc adequat per a tractar els problemes comuns que apareixen en el disseny racional i l' ajust òptim dels circuits genètics sintètics. Utilitzant un enfocament clàssic d'enginyeria de sistemes, la tesi es centra principalment en: i) el modelatge de circuits genètics sintètics basat en primers principis, ii) l' estimació de paràmetres de models a partir de dades experimentals i iii) l' ajust basat en models per aconseguir el rendiment desitjat dels circuits. S'han utilitzat dos circuits genètics sintètics de diferent naturalesa i amb diferents objectius i problemes: un circuit de prealimentació de tipus 1 incoherent (I1-FFL) que exhibeix la important propietat biològica d'adaptació, i un circuit de quorum sensing i realimentació (QS/Fb) que comprèn dos bucles de realimentació entrellaçats -un intracel·lular i un basat en la comunicació de cèl·lula a cèl·lula- dis-senyat per regular el nivell mitjà d'expressió normal d'una proteïna d'interès mentre es minimitza la seua variació al llarg de la població de cèl·lules. Els dos circuits han estat analitzats in silico i implementats in vivo. En tots dos casos, s'han desenvolupat models basats en primers principis d'aquests circuits. Després es presta especial atenció a delinear com obtenir models d'ordre reduït susceptibles de estimació de paràmetres, però mantenint el significat biològic. L' estimació dels paràmetres del model a partir de les dades experimentals es considera en diferents escenaris, tant utilitzant models determinístics com estocàstics. Per al circuit I1-FFL es consideren models determinístics. La tesi planteja la utilització de models locals utilitzant la optimització multiobjectiu per realitzar l'estimació de parametres del model sota escenaris amb estructura de model incompleta (dinàmica no modelada). Per al circuit de QS/Fb, una estructura controlada per realimentació, el problema tractat és la manca d'excitabilitat dels senyals. La tesi proposa una metodologia de estimació en dues etapes utilitzant models estocàstics. La metodologia permet utilitzar dades de curs temporal promediats de la població i mesures de distribució en estat estacionari d'una sola una cèl·lula. L' ajust de circuits basat en models per aconseguir el rendiment desitjat dels circuits també s' aborda mitjançant la optimització multiobjectiu. Per al circuit QS/Fb, es fa un anàlisi estocàstic complet. La tesi aborda com tenir en compte correctament tant el soroll intrínsec com l' extrínsec, les dues principals fonts de soroll en els circuits genètics sintètics. S' analitza l'equilibri entre dues fonts de soroll i el paper que exerceixen en el bucle de realimentació intracel·lular, les i en la realimentació extracel·lular de tota la població. La principal conclusió es que la complexa interacció entre els dos canals de realimentació fa necessari l' ús de la optimització multiobjectiu per al adequat ajust del circuit. En aquesta tesi, a més de l'ús adequat d'eines d'optimització multiobjectiu, la principal preocupació és com derivar directives per al ajust in silico de paràmetres de circuits que puguin aplicar-se de forma realista en viu en un laboratori estàndard. Així, com a alternativa a l'anàlisi de sensibilitat de paràmetres clàssic, la tesi proposa l'ús de l' tècniques de l'agrupació al llarg dels fronts de Pareto, relacionant el compromís de dessempeny amb les regions en l'espai d'paràmetres. / Synthetic biology is defined as the engineering of biology: the deliberate (re)design and construction of novel biological and biologically based parts, devices and systems to perform new functions for useful purposes, that draws on principles elucidated from biology and engineering. Methods and tools are needed to facilitate fast, reproducible and predictable construction of biological systems from sets of biological components. This thesis raises multi-objective optimization as the proper framework to deal with common problems arising in rational design and optimal tuning of synthetic gene circuits. Using a classical systems engineering approach, the thesis mainly addresses: i) synthetic gene circuit modeling based on first principles, ii) model parameters estimation from experimental data and iii) model-based tuning to achieve desired circuit performance. Two gene synthetic circuits of different nature and with different goals and inherent problems have been used throughout the thesis: an Incoherent type 1 feedforward circuit (I1-FFL) that exhibits the important biological property of adaptation, and a Quorum sensing/Feedback circuit (QS/Fb) comprising two intertwined feedback loops -an intracellular one and a cell-to-cell communication-based one-- designed to regulate the mean expression level of a protein of interest while minimizing its variance across the population of cells. Both circuits have been analyzed in silico and implemented in vivo. In both cases, circuit modeling based on first principles has been carried out. Then, special attention is paid to illustrate how to obtain reduced order models amenable for parameters estimation yet keeping biological significance. Model parameters estimation from experimental data is considered in different scenarios, both using deterministic and stochastic models. For the I1-FFL circuit, deterministic models are considered. In this case, the thesis raises ensemble modeling using multi-objective optimization to perform model parameters estimation under scenarios with incomplete model structure (unmodeled dynamics). For the QS/Fb gene circuit, a feedback controlled structure, the lack of excitability of the signals is the problem addressed. The thesis proposes a two-stage estimation methodology using stochastic models. The methodology allows using population averaged time-course data and steady state distribution measurements at the single-cell level. Model-based circuit tuning to achieve desired circuit performance is also addressed using multi-objective optimization. First, for the QS/Fb feedback control circuit, a complete stochastic analysis is performed. Here, the thesis addresses how to correctly take into account both intrinsic and extrinsic noise, the two main sources of noise in gene synthetic circuits. The trade-off between both sources of noise, and the role played by in the intracellular single-cell feedback loop and the extracellular population-wide feedback is analyzed. The main conclusion being that the complex interplay between both feedback channels compel the use of multi-objective optimization for proper tuning of the circuit to achieve desired performance. Thus, the thesis wraps up all the previous results and uses them to address circuit tuning for desired performance. Here, besides the proper use of multi-objective optimization tools, the main concern is how to derive guidelines for circuit parameters tuning in silico that can realistically be applied in vivo in a standard laboratory. Thus, as an alternative to classical parameters sensitivity analysis, the thesis proposes the use of clustering techniques along the optimal Pareto fronts relating the performance trade-offs with regions in the circuits parameters space. / This work has been partially supported by the Spanish Government (CICYT DPI2014- 55276-C5-1) and the European Union (FEDER). The author was recipient of the grant Formación de Personal Investigador by the Universitat Politècnica de València, subprogram 1 (FPI/2013-3242). She was also recipient of the competitive grants for pre-doctoral stays Erasmus Student Placement-European Programme 2015, and FPI Mobility program 2016 of the Universitat Politècnica de València. She also received the competitive grant for a pre-doctoral stay Becas de movilidad para Jóvenes Profesores e Investigadores 2016, Programa de Becas Iberoamérica of the Santander Bank. / Boada Acosta, YF. (2018). A systems engineering approach to model, tune and test synthetic gene circuits [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/112725

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