Identifying quantitative operation principles in metabolic pathways: a systematic method for searching feasible enzyme activity patterns leading to cellular adaptive responses

Background: Optimization methods allow designing changes in a system so that specific goals are attained. These techniques are fundamental for metabolic engineering. However, they are not directly applicable for investigating the evolution of metabolic adaptation to environmental changes. Although biological systems have evolved by natural selection and result in well-adapted systems, we can hardly expect that actual metabolic processes are at the theoretical optimum that could result from an optimization analysis. More likely, natural systems are to be found in a feasible region compatible with global physiological requirements. Results: We first present a new method for globally optimizing nonlinear models of metabolic pathways that are based on the Generalized Mass Action (GMA) representation. The optimization task is posed as a nonconvex nonlinear programming (NLP) problem that is solved by an outer- approximation algorithm. This method relies on solving iteratively reduced NLP slave subproblems and mixed-integer linear programming (MILP) master problems that provide valid upper and lower bounds, respectively, on the global solution to the original NLP. The capabilities of this method are illustrated through its application to the anaerobic fermentation pathway in Saccharomyces cerevisiae. We next introduce a method to identify the feasibility parametric regions that allow a system to meet a set of physiological constraints that can be represented in mathematical terms through algebraic equations. This technique is based on applying the outer-approximation based algorithm iteratively over a reduced search space in order to identify regions that contain feasible solutions to the problem and discard others in which no feasible solution exists. As an example, we characterize the feasible enzyme activity changes that are compatible with an appropriate adaptive response of yeast Saccharomyces cerevisiae to heat shock Conclusion: Our results show the utility of the suggested approach for investigating the evolution of adaptive responses to environmental changes. The proposed method can be used in other important applications such as the evaluation of parameter changes that are compatible with health and disease states.

Operational Cost Reduction in WDM Networks using Lighttours

Wavelength division multiplexing (WDM) networks have been adopted as a near-future solution for the broadband Internet. In previous work we proposed a new architecture, named enhanced grooming (G+), that extends the capabilities of traditional optical routes (lightpaths). In this paper, we compare the operational expenditures incurred by routing a set of demands using lightpaths with that of lighttours. The comparison is done by solving an integer linear programming (ILP) problem based on a path formulation. Results show that, under the assumption of single-hop routing, almost 15% of the operational cost can be reduced with our architecture. In multi-hop routing the operation cost is reduced in 7.1% and at the same time the ratio of operational cost to number of optical-electro-optical conversions is reduced for our architecture. This means that ISPs could provide the same satisfaction in terms of delay to the end-user with a lower investment in the network architecture

G+: Enhanced Traffic Grooming in WDM Mesh Networks using Lighttours

In this article, a new technique for grooming low-speed traffic demands into high-speed optical routes is proposed. This enhancement allows a transparent wavelength-routing switch (WRS) to aggregate traffic en route over existing optical routes without incurring expensive optical-electrical-optical (OEO) conversions. This implies that: a) an optical route may be considered as having more than one ingress node (all inline) and, b) traffic demands can partially use optical routes to reach their destination. The proposed optical routes are named "lighttours" since the traffic originating from different sources can be forwarded together in a single optical route, i.e., as taking a "tour" over different sources towards the same destination. The possibility of creating lighttours is the consequence of a novel WRS architecture proposed in this article, named "enhanced grooming" (G+). The ability to groom more traffic in the middle of a lighttour is achieved with the support of a simple optical device named lambda-monitor (previously introduced in the RingO project). In this article, we present the new WRS architecture and its advantages. To compare the advantages of lighttours with respect to classical lightpaths, an integer linear programming (ILP) model is proposed for the well-known multilayer problem: traffic grooming, routing and wavelength assignment The ILP model may be used for several objectives. However, this article focuses on two objectives: maximizing the network throughput, and minimizing the number of optical-electro-optical conversions used. Experiments show that G+ can route all the traffic using only half of the total OEO conversions needed by classical grooming. An heuristic is also proposed, aiming at achieving near optimal results in polynomial time

New delay-dependent stability criteria for uncertain neutral systems with mixed time-varying delays and nonlinear perturbations

The problem of stability analysis for a class of neutral systems with mixed time-varying neutral, discrete and distributed delays and nonlinear parameter perturbations is addressed. By introducing a novel Lyapunov-Krasovskii functional and combining the descriptor model transformation, the Leibniz-Newton formula, some free-weighting matrices, and a suitable change of variables, new sufficient conditions are established for the stability of the considered system, which are neutral-delay-dependent, discrete-delay-range dependent, and distributeddelay-dependent. The conditions are presented in terms of linear matrix inequalities (LMIs) and can be efficiently solved using convex programming techniques. Two numerical examples are given to illustrate the efficiency of the proposed method

Measuring and explaining farm inefficiency in a panel data set of mixed farms

This paper aims to estimate a translog stochastic frontier production function in the analysis of a panel of 150 mixed Catalan farms in the period 1989-1993, in order to attempt to measure and explain variation in technical inefficiency scores with a one-stage approach. The model uses gross value added as the output aggregate measure. Total employment, fixed capital, current assets, specific costs and overhead costs are introduced into the model as inputs. Stochasticfrontier estimates are compared with those obtained using a linear programming method using a two-stage approach. The specification of the translog stochastic frontier model appears as an appropriate representation of the data, technical change was rejected and the technical inefficiency effects were statistically significant. The mean technical efficiency in the period analyzed was estimated to be 64.0%. Farm inefficiency levels were found significantly at 5%level and positively correlated with the number of economic size units.

Mixed Hodge structures and vector bundles on the projective Plane I

We describe an equivalence of categories between the category of mixed Hodge structures and a category of vector bundles on the toric complex projective plane which verify some semistability condition. We then apply this correspondence to define an invariant which generalises the notion of R-split mixed Hodge structure and compute extensions in the category of mixed Hodge structures in terms of extensions of the corresponding vector bundles. We also give a relative version of this correspondence and apply it to define stratifications of the bases of the variations of mixed Hodge structure.

A proposal for a new specification for a conditionally heteroskedastic variance model: the Quadratic Moving-Average Conditional Heteroskedasticity and an application to the D. Mark-U.S. dollar Exchange Rate

Ever since the appearance of the ARCH model [Engle(1982a)], an impressive array of variance specifications belonging to the same class of models has emerged [i.e. Bollerslev's (1986) GARCH; Nelson's (1990) EGARCH]. This recent domain has achieved very successful developments. Nevertheless, several empirical studies seem to show that the performance of such models is not always appropriate [Boulier(1992)]. In this paper we propose a new specification: the Quadratic Moving Average Conditional heteroskedasticity model. Its statistical properties, such as the kurtosis and the symmetry, as well as two estimators (Method of Moments and Maximum Likelihood) are studied. Two statistical tests are presented, the first one tests for homoskedasticity and the second one, discriminates between ARCH and QMACH specification. A Monte Carlo study is presented in order to illustrate some of the theoretical results. An empirical study is undertaken for the DM-US exchange rate.

Optimal regulation of specialized medical care in a mixed system

We study the optimal public intervention in setting minimum standards of formation for specialized medical care. The abilities the physicians obtain by means of their training allow them to improve their performance as providers of cure and earn some monopoly rents.. Our aim is to characterize the most efficient regulation in this field taking into account different regulatory frameworks. We find that the existing situation in some countries, in which the amount of specialization is controlled, and the costs of this process of specialization are publicly financed, can be supported as the best possible intervention.

The third order Melnikov function of a quadratic center under quadratic perturbation

We study quadratic perturbations of the integrable system (1+x)dH; where H =(x²+y²)=2: We prove that the first three Melnikov functions associated to the perturbed system give rise at most to three limit cycles.

Quadratic perturbations of a quadratic reversible Lotka-Volterra System

"Vegeu el resum a l'inici del document del fitxer adjunt."

Characterisation of neutron spectra in mixed high energy fields in lineal accelerators: response functions validation

Actualment, la resposta de la majoria d’instrumentació operacional i dels dosímetres personals utilitzats en radioprotecció per a la dosimetria neutrònica és altament dependent de l’energia dels espectres neutrònics a analitzar, especialment amb camps neutrònics amb una important component intermitja. En conseqüència, la interpretació de les lectures d’aquests aparells es complicada si no es té un coneixement previ de la distribució espectral de la fluència neutrònica en els punts d’interès. El Grup de Física de les Radiacions de la Universitat Autònoma de Barcelona (GFR-UAB) ha desenvolupat en els últims anys un espectròmetre de neutrons basat en un Sistema d’Esferes Bonner (BSS) amb un contador proporcional d’3He com a detector actiu. Els principals avantatges dels espectròmetres de neutrons per BSS són: la seva resposta isotròpica, la possibilitat de discriminar la component neutrònica de la gamma en camps mixtos, i la seva alta sensibilitat neutrònica als nivells de dosi analitzats. Amb aquestes característiques, els espectròmetres neutrònics per BSS compleixen amb els estándards de les últimes recomanacions de la ICRP i poden ser utilitzats també en el camp de la dosimetria neutrònica per a la mesura de dosis en el rang d’energia que va dels tèrmics fins als 20 MeV, en nou ordres de magnitud. En el marc de la col•laboració entre el GFR - UAB i el Laboratorio Nazionale di Frascati – Istituto Nazionale di Fisica Nucleare (LNF-INFN), ha tingut lloc una experiència comparativa d’espectrometria per BSS amb els feixos quasi monoenergètics de 2.5 MeV i 14 MeV del Fast Neutron Generator de l’ENEA. En l’exercici s’ha determinat l’espectre neutrònic a diferents distàncies del blanc de l’accelerador, aprofitant el codi FRUIT recentment desenvolupat pel grup LNF. Els resultats obtinguts mostren una bona coherència entre els dos espectròmetres i les dades mesurades i simulades.

Pure motives, mixed motives and extensions of motives associated to singular surfaces

We first recall the construction of the Chow motive modelling intersection cohomology of a proper surface X and study its fundamental properties. Using Voevodsky's category of effective geometrical motives, we then study the motive of the exceptional divisor D in a non-singular blow-up of X. If all geometric irreducible components of D are of genus zero, then Voevodsky's formalism allows us to construct certain one-extensions of Chow motives, as canonical subquotients of the motive with compact support of the smooth part of X. Specializing to Hilbert-Blumenthal surfaces, we recover a motivic interpretation of a recent construction of A. Caspar.

Algebraic properties of isochronous centers of polynomial quadratic-like Hamiltonian systems

Projecte de recerca elaborat a partir d’una estada a la School of Mathematics and Statistics de la University of Plymouth, United Kingdom, entre abril juliol del 2007.Aquesta investigació és encara oberta i la memòria que presento constitueix un informe de la recerca que estem duent a terme actualment. En aquesta nota estudiem els centres isòcrons dels sistemes Hamiltonians analítics, parant especial atenció en el cas polinomial. Ens centrem en els anomenats quadratic-like Hamiltonian systems. Diverses propietats dels centres isòcrons d'aquest tipus de sistemes van ser donades a [A. Cima, F. Mañosas and J. Villadelprat, Isochronicity for several classes of Hamiltonian systems, J. Di®erential Equations 157 (1999) 373{413]. Aquell article estava centrat principalment en el cas en que A; B i C fossin funcions analítiques. El nostre objectiu amb l'estudi que estem duent a terme és investigar el cas en el que aquestes funcions són polinomis. En aquesta nota formulem una conjectura concreta sobre les propietats algebraiques que venen forçades per la isocronia del centre i provem alguns resultats parcials.

A mixed finite element method for nonlinear diffusion equations

We propose a mixed finite element method for a class of nonlinear diffusion equations, which is based on their interpretation as gradient flows in optimal transportation metrics. We introduce an appropriate linearization of the optimal transport problem, which leads to a mixed symmetric formulation. This formulation preserves the maximum principle in case of the semi-discrete scheme as well as the fully discrete scheme for a certain class of problems. In addition solutions of the mixed formulation maintain exponential convergence in the relative entropy towards the steady state in case of a nonlinear Fokker-Planck equation with uniformly convex potential. We demonstrate the behavior of the proposed scheme with 2D simulations of the porous medium equations and blow-up questions in the Patlak-Keller-Segel model.

A mixed splicing procedure for economic time series

This note develops a flexible methodology for splicing economic time series that avoids the extreme assumptions implicit in the procedures most commonly used in the literature. It allows the user to split the required correction to the older of the series being linked between its levels and growth rates on the basis what he knows or conjectures about the persistence of the factors that account for the discrepancy between the two series that emerges at their linking point. The time profile of the correction is derived from the assumption that the error in the older series reflects the inadequate coverage of emerging sectors or activities that grow faster than the aggregate.