An improved multi-parametric programming algorithm for flux balance analysis of metabolic networks

Flux balance analysis has proven an effective tool for analyzing metabolic networks. In flux balance analysis, reaction rates and optimal pathways are ascertained by solving a linear program, in which the growth rate is maximized subject to mass-balance constraints. A variety of cell functions in response to environmental stimuli can be quantified using flux balance analysis by parameterizing the linear program with respect to extracellular conditions. However, for most large, genome-scale metabolic networks of practical interest, the resulting parametric problem has multiple and highly degenerate optimal solutions, which are computationally challenging to handle. An improved multi-parametric programming algorithm based on active-set methods is introduced in this paper to overcome these computational difficulties. Degeneracy and multiplicity are handled, respectively, by introducing generalized inverses and auxiliary objective functions into the formulation of the optimality conditions. These improvements are especially effective for metabolic networks because their stoichiometry matrices are generally sparse; thus, fast and efficient algorithms from sparse linear algebra can be leveraged to compute generalized inverses and null-space bases. We illustrate the application of our algorithm to flux balance analysis of metabolic networks by studying a reduced metabolic model of Corynebacterium glutamicum and a genome-scale model of Escherichia coli. We then demonstrate how the critical regions resulting from these studies can be associated with optimal metabolic modes and discuss the physical relevance of optimal pathways arising from various auxiliary objective functions. Achieving more than five-fold improvement in computational speed over existing multi-parametric programming tools, the proposed algorithm proves promising in handling genome-scale metabolic models.Comment: Accepted in J. Optim. Theory Appl. First draft was submitted on August 4th, 201

Inhomogeneous Neutrino Degeneracy and Big Bang Nucleosynthesis

We examine Big Bang nucleosynthesis (BBN) in the case of inhomogenous neutrino degeneracy, in the limit where the fluctuations are sufficiently small on large length scales that the present-day element abundances are homogeneous. We consider two representive cases: degeneracy of the electron neutrino alone, and equal chemical potentials for all three neutrinos. We use a linear programming method to constrain an arbitrary distribution of the chemical potentials. For the current set of (highly-restrictive) limits on the primordial element abundances, homogeneous neutrino degeneracy barely changes the allowed range of the baryon-to-photon ratio. Inhomogeneous degeneracy allows for little change in the lower bound on the baryon-to-photon ratio, but the upper bound in this case can be as large as 1.1 \times 10^{-8} (only electron neutrino degeneracy) or 1.0 \times 10^{-9} (equal degeneracies for all three neutrinos). For the case of inhomogeneous neutrino degeneracy, we show that there is no BBN upper bound on the neutrino energy density, which is bounded in this case only by limits from structure formation and the cosmic microwave background.Comment: 6 pages, no figure

Phase Transitions of the Typical Algorithmic Complexity of the Random Satisfiability Problem Studied with Linear Programming

Here we study the NP-complete $K$-SAT problem. Although the worst-case complexity of NP-complete problems is conjectured to be exponential, there exist parametrized random ensembles of problems where solutions can typically be found in polynomial time for suitable ranges of the parameter. In fact, random $K$-SAT, with $\alpha=M/N$ as control parameter, can be solved quickly for small enough values of $\alpha$. It shows a phase transition between a satisfiable phase and an unsatisfiable phase. For branch and bound algorithms, which operate in the space of feasible Boolean configurations, the empirically hardest problems are located only close to this phase transition. Here we study $K$-SAT ($K=3,4$) and the related optimization problem MAX-SAT by a linear programming approach, which is widely used for practical problems and allows for polynomial run time. In contrast to branch and bound it operates outside the space of feasible configurations. On the other hand, finding a solution within polynomial time is not guaranteed. We investigated several variants like including artificial objective functions, so called cutting-plane approaches, and a mapping to the NP-complete vertex-cover problem. We observed several easy-hard transitions, from where the problems are typically solvable (in polynomial time) using the given algorithms, respectively, to where they are not solvable in polynomial time. For the related vertex-cover problem on random graphs these easy-hard transitions can be identified with structural properties of the graphs, like percolation transitions. For the present random $K$-SAT problem we have investigated numerous structural properties also exhibiting clear transitions, but they appear not be correlated to the here observed easy-hard transitions. This renders the behaviour of random $K$-SAT more complex than, e.g., the vertex-cover problem.Comment: 11 pages, 5 figure

Partial Identification in Matching Models for the Marriage Market

We study partial identification of the preference parameters in models of one-to-one matching with perfectly transferable utilities, without imposing parametric distributional restrictions on the unobserved heterogeneity and with data on one large market. We provide a tractable characterisation of the identified set, under various classes of nonparametric distributional assumptions on the unobserved heterogeneity. Using our methodology, we re-examine some of the relevant questions in the empirical literature on the marriage market which have been previously studied under the Multinomial Logit assumption