Identifying the preferred subset of enzymatic profiles in nonlinear kinetic metabolic models via multiobjective global optimization and pareto filters

Optimization models in metabolic engineering and systems biology focus typically on optimizing a unique criterion, usually the synthesis rate of a metabolite of interest or the rate of growth. Connectivity and non-linear regulatory effects, however, make it necessary to consider multiple objectives in order to identify useful strategies that balance out different metabolic issues. This is a fundamental aspect, as optimization of maximum yield in a given condition may involve unrealistic values in other key processes. Due to the difficulties associated with detailed non-linear models, analysis using stoichiometric descriptions and linear optimization methods have become rather popular in systems biology. However, despite being useful, these approaches fail in capturing the intrinsic nonlinear nature of the underlying metabolic systems and the regulatory signals involved. Targeting more complex biological systems requires the application of global optimization methods to non-linear representations. In this work we address the multi-objective global optimization of metabolic networks that are described by a special class of models based on the power-law formalism: the generalized mass action (GMA) representation. Our goal is to develop global optimization methods capable of efficiently dealing with several biological criteria simultaneously. In order to overcome the numerical difficulties of dealing with multiple criteria in the optimization, we propose a heuristic approach based on the epsilon constraint method that reduces the computational burden of generating a set of Pareto optimal alternatives, each achieving a unique combination of objectives values. To facilitate the post-optimal analysis of these solutions and narrow down their number prior to being tested in the laboratory, we explore the use of Pareto filters that identify the preferred subset of enzymatic profiles. We demonstrate the usefulness of our approach by means of a case study that optimizes the ethanol production in the fermentation of Saccharomyces cerevisiae.

Fórmulas estadísticas de resistencia al flujo para hidráulica fluvial

El empleo en hidráulica en lámina libre de las ecuaciones de resistencia al flujo de Gauckler-Manning o Darcy-Weisbach requiere la determinación de un coeficiente de resistencia; determinación que si bien es suficientemente precisa con un reducido esfuerzo y coste en cauces artificiales, resulta mucho más difícil y cara en ríos. Con objeto de eliminar la necesidad de una estimación independiente del coeficiente de resistencia se han desarrollado estadísticamente una serie de ecuaciones para flujo permanente y uniforme en ríos, en las que se prescinde de dicho coeficiente. El presente artículo pretende ser una revisión de las fórmulas de este último tipo más difundidas en la práctica de la hidráulica fluvial.

Influencia de la información territorial en la simulación hidrológica. Aplicación a la cuenca de Canalda (El Solsonés)

La modelización hidrológica de cuencas requiere datos del territorio para hacer una correcta parametrización del modelo. La escala de entrada (grado de generalización) de los datos influirá en los cálculos de la escorrentía superficial realizados en la simulación. HEC-1 es un modelo empírico de simulación hidrológica de cuencas de amplia difusión. En la actualidad, se encuentra disponible conjuntamente con el programa informático WMS (Watershed Modeling System), que dispone de diferentes herramientas que facilitan el procesamiento de los datos del territorio. El modelo HEC-1 se ha aplicado a la cuenca de Canalda de 66 km2 (El Solsonés, Lleida) para conocer la influencia de generalizar los parámetros de entrada (usos y tipos de suelos y división en subcuencas) en el cálculo de la escorrentía superficial. Para aplicar el modelo ha sido necesario hacer un reconocimiento y estudio de los suelos de la cuenca, con énfasis especial en las propiedades físicas, la distribución y extensión de los suelos, obteniendo el mapa de suelos de la cuenca a escala 1:50.000. El proceso de generalización de los datos de entrada se ha efectuado con la escala base 1:50.000, realizando otras simulaciones a las escalas 1:100.000 y 1:200.000. En las simulaciones practicadas se obseva que el grado de generalización de los datos de entrada tiene efecto en el hidrograma de salida de la cuenca; al generalizar los datos a las escalas mencionadas se aprecia un retardo en el hidrograma y una reducción de la aportación total y del caudal punta.

Is the matching function Cobb-Douglas?

[cat] Estudiem les propietats teòriques que una funció d.emparellament ha de satisfer per tal de representar un mercat laboral amb friccions dins d'un model d'equilibri general amb emparellament aleatori. Analitzem el cas Cobb-Douglas, CES i altres formes funcionals per a la funció d.emparellament. Els nostres resultats estableixen restriccions sobre els paràmetres d'aquests formes funcionals per assegurar que l.equilibri és interior. Aquestes restriccions aporten raons teòriques per escollir entre diverses formes funcionals i permeten dissenyar tests d'error d'especificació de model en els treballs empírics.

Is the matching function Cobb-Douglas?

[cat] Estudiem les propietats teòriques que una funció d.emparellament ha de satisfer per tal de representar un mercat laboral amb friccions dins d'un model d'equilibri general amb emparellament aleatori. Analitzem el cas Cobb-Douglas, CES i altres formes funcionals per a la funció d.emparellament. Els nostres resultats estableixen restriccions sobre els paràmetres d'aquests formes funcionals per assegurar que l.equilibri és interior. Aquestes restriccions aporten raons teòriques per escollir entre diverses formes funcionals i permeten dissenyar tests d'error d'especificació de model en els treballs empírics.

Modelling the Evolution and Spread of HIV Immune Escape Mutants.

During infection with human immunodeficiency virus (HIV), immune pressure from cytotoxic T-lymphocytes (CTLs) selects for viral mutants that confer escape from CTL recognition. These escape variants can be transmitted between individuals where, depending upon their cost to viral fitness and the CTL responses made by the recipient, they may revert. The rates of within-host evolution and their concordant impact upon the rate of spread of escape mutants at the population level are uncertain. Here we present a mathematical model of within-host evolution of escape mutants, transmission of these variants between hosts and subsequent reversion in new hosts. The model is an extension of the well-known SI model of disease transmission and includes three further parameters that describe host immunogenetic heterogeneity and rates of within host viral evolution. We use the model to explain why some escape mutants appear to have stable prevalence whilst others are spreading through the population. Further, we use it to compare diverse datasets on CTL escape, highlighting where different sources agree or disagree on within-host evolutionary rates. The several dozen CTL epitopes we survey from HIV-1 gag, RT and nef reveal a relatively sedate rate of evolution with average rates of escape measured in years and reversion in decades. For many epitopes in HIV, occasional rapid within-host evolution is not reflected in fast evolution at the population level.

How to introduce connectance in a frame of an expression for diversity

Systems made of parts that are totally connected do not work, neither ecosys- tems nor artifacts. Relative connectance is inversely related to diversity, and both magnitudes can find a common frame of expression, in which some constant expressing the constraints of any organization might be embodied. If S is Simp- son's index, the expression (1 - S)IS as a measure of diversity offers some advantages or, at least, helps further reasoning. Such expression is the ratio between total interspecific possible interactions and possible intraspecific inter- actions.

Variación regional del coeficiente de atenuación de las ondas Rayleigh en el escudo europeo

A partir del análisis del modo fundamental de las ondas Rayleigh generadas por tres terremotos situados en las Azores, Sicilia y el Mar Negro se obtiene la variación regional del coeficiente de atenuación en el escudo europeo para un intervalo de periodos de 15-80 s. El método de análisis ha consistido en comparar los espectros de amplitudes observados con los calculados teóricamente. Para el calculo de estos últimos se ha utilizado un nuevo método consistente en calcular la función global de la fuente a partir de un proceso de mínimos cuadrados. Los resultados son los siguientes.

Anàlisis del modelo de la telaraña en contexto de incertidumbre

In the present work the behavior of a model acquaintance of market is analyzed with an only one, in that is considered that the parameters that tie the variables that it incorporates the pattern come expressed through uncertain magnitudes. The objective of the study consists on the analysis of the balance from the hypotheses of established uncertainties

Movilidad intergeneracional y emparejamiento selectivo en España

This paper examines the role of assortative mating in the intergenerational economic mobility in Spain. Sons and daughters usually marry individuals with similar characteristics, which may lower mobility. Our empirical strategy employs the Two-sample two-stage least squares estimator to estimate the intergenerational income elasticity in absence of data for two generations not residing in the same household. Our findings suggest that assortative mating plays an important role in the intergenerational transmission process. On average about 50 per 100 of the covariance between parents’ income and child family’s incomecan be accounted for by the person the child is married to

Progress in front propagation research

We review the progress in the field of front propagation in recent years. We survey many physical, biophysical and cross-disciplinary applications, including reduced-variable models of combustion flames, Reid's paradox of rapid forest range expansions, the European colonization of North America during the 19th century, the Neolithic transition in Europe from 13 000 to 5000 years ago, the description of subsistence boundaries, the formation of cultural boundaries, the spread of genetic mutations, theory and experiments on virus infections, models of cancer tumors, etc. Recent theoretical advances are unified in a single framework, encompassing very diverse systems such as those with biased random walks, distributed delays, sequential reaction and dispersion, cohabitation models, age structure and systems with several interacting species. Directions for future progress are outlined

Language extinction and linguistic fronts

Language diversity has become greatly endangered in the past centuries owing to processes of language shift from indigenous languages to other languages that are seen as socially and economically more advantageous, resulting in the death or doom of minority languages. In this paper, we define a new language competition model that can describe the historical decline of minority languages in competition with more advantageous languages. We then implement this non-spatial model as an interaction term in a reactiondiffusion system to model the evolution of the two competing languages. We use the results to estimate the speed at which the more advantageous language spreads geographically, resulting in the shrinkage of the area of dominance of the minority language. We compare the results from our model with the observed retreat in the area of influence of the Welsh language in the UK, obtaining a good agreement between the model and the observed data

A measure of stability as a criterion for the verification and analysis of simulation models

The aim of this study is to define a new statistic, PVL, based on the relative distance between the likelihood associated with the simulation replications and the likelihood of the conceptual model. Our results coming from several simulation experiments of a clinical trial show that the PVL statistic range can be a good measure of stability to establish when a computational model verifies the underlying conceptual model. PVL improves also the analysis of simulation replications because only one statistic is associated with all the simulation replications. As well it presents several verification scenarios, obtained by altering the simulation model, that show the usefulness of PVL. Further simulation experiments suggest that a 0 to 20 % range may define adequate limits for the verification problem, if considered from the viewpoint of an equivalence test.

Desenvolupament d'una app

El TFM ha consistit en participar i conèixer de prop tots el passos de desenvolupament d’una aplicació: elaboració d’un guió, realització de la part gràfica, programació i màrqueting. Per aquest motiu he realitzat unes hores de pràctiques a l'empresa Factoria Interactive SL. Durant aquest periòde vaig realitzar diversos guions per diferents apps relacionades amb continguts matemàtics i vaig participar en el programació de l'app "Dress up". I l'últim pas va consistir en penjar l'app a la botiga de Google Play. Per poder accedir a l'aplicació cal seguir el següent enllaç de Google Play: https://play.google.com/store/apps/details?id=eu.lafactoria.dressup&hl=es

L’aprenentatge de càlcul mental a través de jocs a un aula d’educació primària

Aquest treball es basa en identificar les estratègies de càlcul mental que fan servir alumnes de quart de primària. Aquesta identificació es realitza a partir de la resolució d’operacions per part dels alumnes i el seu posterior anàlisi. A partir de les estratègies que hagin sorgit, es realitzarà una intervenció didàctica basada en jocs matemàtics per tal de descobrir i treballar noves estratègies matemàtiques. Finalment, amb una nova prova es comprovarà si els nens i nenes coneixen i apliquen diferents estratègies pel càlcul mental. Amb aquesta intervenció es pretén comprovar si a partir de jocs els nens i nenes milloren les estratègies de càlcul mental.