Interval and Possibilistic Methods for Constraint-Based Metabolic Models

This thesis is devoted to the study and application of constraint-based metabolic models. The objective was to find simple ways to handle the difficulties that arise in practice due to uncertainty (knowledge is incomplete, there is a lack of measurable variables, and those available are imprecise). With this purpose, tools have been developed to model, analyse, estimate and predict the metabolic behaviour of cells. The document is structured in three parts. First, related literature is revised and summarised. This results in a unified perspective of several methodologies that use constraint-based representations of the cell metabolism. Three outstanding methods are discussed in detail, network-based pathways analysis (NPA), metabolic flux analysis (MFA), and flux balance analysis (FBA). Four types of metabolic pathways are also compared to clarify the subtle differences among them. The second part is devoted to interval methods for constraint-based models. The first contribution is an interval approach to traditional MFA, particularly useful to estimate the metabolic fluxes under data scarcity (FS-MFA). These estimates provide insight on the internal state of cells, which determines the behaviour they exhibit at given conditions. The second contribution is a procedure for monitoring the metabolic fluxes during a cultivation process that uses FS-MFA to handle uncertainty. The third part of the document addresses the use of possibility theory. The main contribution is a possibilistic framework to (a) evaluate model and measurements consistency, and (b) perform flux estimations (Poss-MFA). It combines flexibility on the assumptions and computational efficiency. Poss-MFA is also applied to monitoring fluxes and metabolite concentrations during a cultivation, information of great use for fault-detection and control of industrial processes. Afterwards, the FBA problem is addressed.Llaneras Estrada, F. (2011). Interval and Possibilistic Methods for Constraint-Based Metabolic Models [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/10528Palanci

Safety Related Misconceptions and Self-Reported BehavioralAdaptations Associated With Advanced In-Vehicle Systems: Lessons Learned From Early Technology Adopters

Early adopters of advanced in-vehicle technologies (Adaptive Cruise Control, night vision, park aid, and navigation systems) were interviewed in an effort to assess the extent to which drivers come to understand the performance capabilities and limitations of these types of advanced systems, and to understand how systems are influencing driver behavior (modifying behavior in potentially positive or negative ways). Despite access to a wide array of information about their in-vehicle system, responses to knowledge-based questions about the systems themselves suggest that key information was not necessarily acquired nor understood by a large number of drivers. Many drivers held misconceptions about the performance capabilities of their advanced systems, suggesting that drivers’ mental models of how these systems function and perform do not always match reality. For example, 99% of ACC system owners did not know that the system ignores stopped vehicles. Similarly, 41% of park aid system owners did not know that the system warning is tied solely on the distance to objects and does not take into account their closing speed. Self-reported data also provided evidence of behavioral adaptations. Results suggest that additional efforts are needed to increase driver understanding of how these systems operate, particularly for safety-related aspects

Design and evaluation of a conversational agent to support focused knowledge work

The rise of social networks and the increase of notifications we receive on our phones has had a negative impact on the way people work. Distractions have become a more serious problem on such times when productivity is the center of attention of many project managers. This project has analyzed this issue, and proposed a modern and flexible solution based on a conversational agent. It has implemented and evaluated a mobile application designed to support focused work, obtaining results that suggest the validation and effectiveness of a work assistant to increase productivity and well-being

La asistencia psiquiátrica como productora de subnormalidad

Abstract not availabl

Which Metabolic Pathways Generate and Characterize the Flux Space? A Comparison among Elementary Modes, Extreme Pathways and Minimal Generators

Important efforts are being done to systematically identify the relevant pathways in a metabolic network. Unsurprisingly, there is not a unique set of network-based pathways to be tagged as relevant, and at least four related concepts have been proposed: extreme currents, elementary modes, extreme pathways, and minimal generators. Basically, there are two properties that these sets of pathways can hold: they can generate the flux space—if every feasible flux distribution can be represented as a nonnegative combination of flux through them—or they can comprise all the nondecomposable pathways in the network. The four concepts fulfill the first property, but only the elementary modes fulfill the second one. This subtle difference has been a source of errors and misunderstandings. This paper attempts to clarify the intricate relationship between the network-based pathways performing a comparison among them

Aproximación teórica a la traducción y la autotraducción. A propósito de las literaturas catalana y española

Theories about translation and self-translation between Catalan and Spanish literatures during Franco’s dictatorship are strictly subject to cultural and linguistic dispositions imposed by Franco’s regime from its victory. The explicit banning of any publication in Catalan, as well as the feeble slots opened with the pass of the decades, explicitly marks the evolution of translation and self-translation between both literatures. The goal of this article is to examine from a theoretical point of view, based on the Polysystem Theory and P. Casanova’s approach, the relation between both literatures through translation and self-translation, especially during Franco’s dictatorship, which lasted more than thirty years.Las premisas teóricas a propósito de la traducción y la autotraducción entre las literaturas catalana y española durante el régimen franquista están estrechamente sujetas a las disposiciones lingüísticas y culturales que la dictadura impuso desde el mismo momento de su victoria. La prohibición explícita de cualquier publicación en lengua catalana, así como las tímidas ranuras que se fueron abriendo con el paso de las décadas marcan claramente el devenir de la traducción y la autotraducción entre las dos literaturas. El objetivo de este trabajo es revisar desde un punto de vista teórico, partiendo de la teoría de los polisistemas y los planteamientos de P. Casanova, la relación entre ambas literaturas a través de la traducción y la autotraducción, especialmente durante los más de treinta años de dictadura franquista

Validation of a constraint-based model of Pichia pastoris metabolism under data scarcity

<p>Abstract</p> <p>Background</p> <p>Constraint-based models enable structured cellular representations in which intracellular kinetics are circumvented. These models, combined with experimental data, are useful analytical tools to estimate the state exhibited (the phenotype) by the cells at given pseudo-steady conditions.</p> <p>Results</p> <p>In this contribution, a simplified constraint-based stoichiometric model of the metabolism of the yeast <it>Pichia pastoris</it>, a workhorse for heterologous protein expression, is validated against several experimental available datasets. Firstly, maximum theoretical growth yields are calculated and compared to the experimental ones. Secondly, possibility theory is applied to quantify the consistency between model and measurements. Finally, the biomass growth rate is excluded from the datasets and its prediction used to exemplify the capability of the model to calculate non-measured fluxes.</p> <p>Conclusions</p> <p>This contribution shows how a small-sized network can be assessed following a rational, quantitative procedure even when measurements are scarce and imprecise. This approach is particularly useful in lacking data scenarios.</p

A possibilistic framework for constraint-based metabolic flux analysis

<p>Abstract</p> <p>Background</p> <p>Constraint-based models allow the calculation of the metabolic flux states that can be exhibited by cells, standing out as a powerful analytical tool, but they do not determine which of these are likely to be existing under given circumstances. Typical methods to perform these predictions are (a) flux balance analysis, which is based on the assumption that cell behaviour is optimal, and (b) metabolic flux analysis, which combines the model with experimental measurements.</p> <p>Results</p> <p>Herein we discuss a possibilistic framework to perform metabolic flux estimations using a constraint-based model and a set of measurements. The methodology is able to handle inconsistencies, by considering sensors errors and model imprecision, to provide rich and reliable flux estimations. The methodology can be cast as linear programming problems, able to handle thousands of variables with efficiency, so it is suitable to deal with large-scale networks. Moreover, the possibilistic estimation does not attempt necessarily to predict the actual fluxes with precision, but rather to exploit the available data – even if those are scarce – to distinguish possible from impossible flux states in a gradual way.</p> <p>Conclusion</p> <p>We introduce a possibilistic framework for the estimation of metabolic fluxes, which is shown to be flexible, reliable, usable in scenarios lacking data and computationally efficient.</p

In-Vehicle Navigation Systems: Interface Characteristics and Industry Trends

A review and inventory of in-vehicle navigation systems was conducted in order to better understand the current state of practice and trends relating to their design and implementation. The review focused on human factors characteristics and interface features using accepted human factors practices, principles, and guidelines as a basis for assessing likely impacts on driver distraction. The inventory examined market-ready in-vehicle products, and identified a range of interface design features, noting aspects and dimensions that have implications for potential driver distraction. Results indicated that devices tend to incorporate a large number of features and options, making it a potential challenge for drivers to learn all of the capabilities of a system and resulting in lengthy manuals. Although devices also tended to provide large amounts of information, some designs may allow for increased information presentation without necessarily sacrificing performance. Warnings or cautions against interacting with systems while driving were common; however, relatively few systems disable equipment when vehicles are in operation