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.

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.

Fronts with continuous waiting-time distributions: Theory and application to virus infections

We generalize to arbitrary waiting-time distributions some results which were previously derived for discrete distributions. We show that for any two waiting-time distributions with the same mean delay time, that with higher dispersion will lead to a faster front. Experimental data on the speed of virus infections in a plaque are correctly explained by the theoretical predictions using a Gaussian delay-time distribution, which is more realistic for this system than the Dirac delta distribution considered previously [J. Fort and V. Méndez, Phys. Rev. Lett.89, 178101 (2002)]

A new distribution on the simplex containing the Dirichlet family

The Dirichlet family owes its privileged status within simplex distributions to easyness of interpretation and good mathematical properties. In particular, we recall fundamental properties for the analysis of compositional data such as closure under amalgamation and subcomposition. From a probabilistic point of view, it is characterised (uniquely) by a variety of independence relationships which makes it indisputably the reference model for expressing the non trivial idea of substantial independence for compositions. Indeed, its well known inadequacy as a general model for compositional data stems from such an independence structure together with the poorness of its parametrisation. In this paper a new class of distributions (called Flexible Dirichlet) capable of handling various dependence structures and containing the Dirichlet as a special case is presented. The new model exhibits a considerably richer parametrisation which, for example, allows to model the means and (part of) the variance-covariance matrix separately. Moreover, such a model preserves some good mathematical properties of the Dirichlet, i.e. closure under amalgamation and subcomposition with new parameters simply related to the parent composition parameters. Furthermore, the joint and conditional distributions of subcompositions and relative totals can be expressed as simple mixtures of two Flexible Dirichlet distributions. The basis generating the Flexible Dirichlet, though keeping compositional invariance, shows a dependence structure which allows various forms of partitional dependence to be contemplated by the model (e.g. non-neutrality, subcompositional dependence and subcompositional non-invariance), independence cases being identified by suitable parameter configurations. In particular, within this model substantial independence among subsets of components of the composition naturally occurs when the subsets have a Dirichlet distribution

Aplicación del DEA en el análisis de beneficios en un sistema integrado verticalmente hacia adelante

En el presente trabajo se diseñan tres modelos DEA a partir de un sistema de producción cuyos componentes están colocados en un arreglo en serie que se integran verticalmente hacia adelante. El primer modelo busca optimizar los beneficios del sistema agregado, así como la mejora de los mismos en cada uno de los subsistemas. En el segundo de los modelos, además del objetivo anterior, se incluyen restricciones de transferencia de los recursos específicos asociados a cada subsistema, y en el tercer modelo se estima el intervalo de variación para los precios de transferencia de los inputs intermedios entre ambos subsistemas. Los modelos han sido programados y simulados en el software GAMS a partir de datos generados por una función de producción Cobb-Douglas para los inputs intermedios y los outputs finales.

La Solvencia financiera del asegurador de vida y su relación con el coste de capital

Esta investigación relaciona el margen de solvencia que normativamente deben acreditar los aseguradores de vida con los recursos propios que cualquier empresa debe poseer para poder ejercer su actividad. Analizaremos la incidencia que la remuneración de esos recursos tiene en la propia actividad de comercialización de los seguros demostrando su relación inversa con el tipo de interés garantizado en los contratos. Analizaremos asimismo la incidencia que los eventuales cambios en los tipos de interés pueden tener en la remuneración que puede ofrecerse a esos recursos y propondremos una ecuación que incorpore todos estos aspectos, comprobando que las relaciones que actualmente ofrece la disciplina académica son casos particulares de la ecuación general, casos que demostraremos que incorporan unas hipótesis implícitas bastante restrictivas.

Single period Markowitz portfolio selection, performance gauging and duality: a variation on Luenberger's shortage function

Markowitz portfolio theory (1952) has induced research into the efficiency of portfolio management. This paper studies existing nonparametric efficiency measurement approaches for single period portfolio selection from a theoretical perspective and generalises currently used efficiency measures into the full mean-variance space. Therefore, we introduce the efficiency improvement possibility function (a variation on the shortage function), study its axiomatic properties in the context of Markowitz efficient frontier, and establish a link to the indirect mean-variance utility function. This framework allows distinguishing between portfolio efficiency and allocative efficiency. Furthermore, it permits retrieving information about the revealed risk aversion of investors. The efficiency improvement possibility function thus provides a more general framework for gauging the efficiency of portfolio management using nonparametric frontier envelopment methods based on quadratic optimisation.

The Cost of ownership in the governance of interfirm collaborations

This paper investigates the selection of governance forms in interfirm collaborations taking into account the predictions from transaction costs and property rights theories. Transaction costs arguments are often used to justify the introduction of hierarchical controls in collaborations, but the ownership dimension of going from “contracts” to “hierarchies” has been ignored in the past and with it the so called “costs of ownership”. The theoretical results, tested with a sample of collaborations in which participate Spanish firms, indicate that the cost of ownership may offset the benefits of hierarchical controls and therefore limit their diffusion. Evidence is also reported of possible complementarities between reputation effects and forms of ownership that go together with hierarchical controls (i.e. joint ventures), in contrast with the generally assumed substitutability between the two.

A Rembrandt is a Rembrandt

As paintings are assets, we propose to model a painting's price dynamics as a diffusion process, i.e., as the financial literature models share prices, but correcting by size. We show that the influence of size on the artwork price diminishes as the paintings gets older because 1) prices incorporate progressively more noise and 2) for high quality artists, the relative importance of size on price decreases as the artist consolidates and authorship gains importance as explanatory variable. Our theoretical results are consistent with data from a sample of 19th- and 20th-century Catalan painters of similar quality. These findings suggest that an artist's quality and antiquity should be taken into account in order to obtain more efficient estimates of parameters in hedonic art market models.

Dynamic matching and bargaining: the role of deadlines

We consider a dynamic model where traders in each period are matched randomly into pairs who then bargain about the division of a fixed surplus. When agreement is reached the traders leave the market. Traders who do not come to an agreement return next period in which they will be matched again, as long as their deadline has not expired yet. New traders enter exogenously in each period. We assume that traders within a pair know each other's deadline. We define and characterize the stationary equilibrium configurations. Traders with longer deadlines fare better than traders with short deadlines. It is shown that the heterogeneity of deadlines may cause delay. It is then shown that a centralized mechanism that controls the matching protocol, but does not interfere with the bargaining, eliminates all delay. Even though this efficient centralized mechanism is not as good for traders with long deadlines, it is shown that in a model where all traders can choose which mechanism to

Scoring rules on dichotomous preferences

In this paper, we study individual incentives to report preferences truthfully for the special case when individuals have dichotomous preferences on the set of alternatives and preferences are aggregated in form of scoring rules. In particular, we show that (a) the Borda Count coincides with Approval Voting on the dichotomous preference domain, (b) the Borda Count is the only strategy-proof scoring rule on the dichotomous preference domain, and (c) if at least three individuals participate in the election, then the dichotomous preference domain is the unique maximal rich domain under which the Borda Count is strategy-proof.

The Instrumental voter goes to the news-agent: demand for information, election closeness, and the media

This paper studies the impact of instrumental voting on information demand and mass media behaviour during electoral campaigns. If voters act instrumentally then information demand should increase with the closeness of an election. Mass media are modeled as profit-maximizing firms that take into account information demand, the value of customers to advertisers and the marginal cost of customers. Information supply should be larger in electoral constituencies where the contest is expected to be closer, there is a higher population density, and customers are on average more profitable for advertisers. The impact of electorate size is theoretically undetermined. These conclusions are then tested with comfortable results on data from the 1997 general election in Britain.

Spatial competition between two candidates of different quality: the effects of candidate ideology and private information

This paper examines competition in a spatial model of two-candidate elections, where one candidate enjoys a quality advantage over the other candidate. The candidates care about winning and also have policy preferences. There is two-dimensional private information. Candidate ideal points as well as their tradeoffs between policy preferences and winning are private information. The distribution of this two-dimensional type is common knowledge. The location of the median voter's ideal point is uncertain, with a distribution that is commonly known by both candidates. Pure strategy equilibria always exist in this model. We characterize the effects of increased uncertainty about the median voter, the effect of candidate policy preferences, and the effects of changes in the distribution of private information. We prove that the distribution of candidate policies approaches the mixed equilibrium of Aragones and Palfrey (2002a), when both candidates' weights on policy preferences go to zero.