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

A Pseudo-Inverse for Nonlinear Operators

The Moore-Penrose inverse is widely used in physics, statistics and various fields of engineering. Among other characteristics, it captures well the notion of inversion of linear operators in the case of overcomplete data. In data science, nonlinear operators are extensively used. In this paper we define and characterize the fundamental properties of a pseudo-inverse for nonlinear operators. The concept is defined broadly. First for general sets, and then a refinement for normed spaces. Our pseudo-inverse for normed spaces yields the Moore-Penrose inverse when the operator is a matrix. We present conditions for existence and uniqueness of a pseudo-inverse and establish theoretical results investigating its properties, such as continuity, its value for operator compositions and projection operators, and others. Analytic expressions are given for the pseudo-inverse of some well-known, non-invertible, nonlinear operators, such as hard- or soft-thresholding and ReLU. Finally, we analyze a neural layer and discuss relations to wavelet thresholding and to regularized loss minimization

An exercise in welfare economics (III)

Welfare Economics

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel.In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime: we compute the two-point correlation functions for the linearized Einstein tensor and for the metric perturbations. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a quasi-static black hole.Comment: 75 pages, no figures, submitted to Living Reviews in Relativit

Mixed-integer Nonlinear Optimization: a hatchery for modern mathematics

The second MFO Oberwolfach Workshop on Mixed-Integer Nonlinear Programming (MINLP) took place between 2nd and 8th June 2019. MINLP refers to one of the hardest Mathematical Programming (MP) problem classes, involving both nonlinear functions as well as continuous and integer decision variables. MP is a formal language for describing optimization problems, and is traditionally part of Operations Research (OR), which is itself at the intersection of mathematics, computer science, engineering and econometrics. The scientific program has covered the three announced areas (hierarchies of approximation, mixed-integer nonlinear optimal control, and dealing with uncertainties) with a variety of tutorials, talks, short research announcements, and a special "open problems'' session

Sparse representations and harmonic wavelets for stochastic modeling and analysis of diverse structural systems and related excitations

In this thesis, novel analytical and computational approaches are proposed for addressing several topics in the field of random vibration. The first topic pertains to the stochastic response determination of systems with singular parameter matrices. Such systems appear, indicatively, when a redundant coordinate modeling scheme is adopted. This is often associated with computational cost-efficient solution frameworks and modeling flexibility for treating complex systems. Further, structures are subject to environmental excitations, such as ground motions, that typically exhibit non-stationary characteristics. In this regard, aiming at a joint time-frequency analysis of the system response a recently developed generalized harmonic wavelet (GHW)-based solution framework is employed in conjunction with tools originated form the generalized matrix inverse theory. This leads to a generalization of earlier excitation-response relationships of random vibration theory to account for systems with singular matrices. Harmonic wavelet-based statistical linearization techniques are also extended to nonlinear multi-degree-of-freedom (MDOF) systems with singular matrices. The accuracy of the herein proposed framework is further improved by circumventing previous “local stationarity” assumptions about the response. Furthermore, the applicability of the method is extended beyond redundant coordinate modeling applications. This is achieved by a formulation which accounts for generally constrained equations of motion pertaining to diverse engineering applications. These include, indicatively, energy harvesters with coupled electromechanical equations and oscillators subject to non-white excitations modeled via auxiliary filter equations. The second topic relates to the probabilistic modeling of excitation processes in the presence of missing data. In this regard, a compressive sampling methodology is developed for incomplete wind time-histories reconstruction and extrapolation in a single spatial dimension, as well as for related stochastic field statistics estimation. An alternative methodology based on low rank matrices and nuclear norm minimization is also developed for wind field extrapolation in two spatial dimensions. The proposed framework can be employed for monitoring of wind turbine systems utilizing information from a few measured locations as well as in the context of performance-based design optimization of structural systems. Lastly, the problem of with data-driven sparse identification methods of nonlinear dynamics is considered. In particular, utilizing measured responses a Bayesian compressive sampling technique is developed for determining the governing equations of stochastically excited structural systems exhibiting diverse nonlinear behaviors and also endowed with fractional derivative elements. Compared to alternative state-of-the-art schemes that yield deterministic estimates for the identified model, the herein developed methodology exhibits additional sparsity promoting features and is capable of quantifying the uncertainty associated with the model estimates. This provides a quantifiable degree of confidence when employing the proposed framework as a predictive tool

Robust Controller Design for Stochastic Nonlinear Systems via Convex Optimization

This paper presents ConVex optimization-based Stochastic steady-state Tracking Error Minimization (CV-STEM), a new state feedback control framework for a class of Ito stochastic nonlinear systems and Lagrangian systems. Its strength lies in computing the control input by an optimal contraction metric, which greedily minimizes an upper bound of the steady-state mean squared tracking error of the system trajectories. Although the problem of minimizing the bound is nonlinear, its equivalent convex formulation is proposed utilizing state-dependent coefficient parameterizations of the nonlinear system equation. It is shown using stochastic incremental contraction analysis that the CV-STEM provides a sufficient guarantee for exponential boundedness of the error for all time with L₂-robustness properties. For the sake of its sampling-based implementation, we present discrete-time stochastic contraction analysis with respect to a state- and time-dependent metric along with its explicit connection to continuous-time cases. We validate the superiority of the CV-STEM to PID, H∞, and given nonlinear control for spacecraft attitude control and synchronization problems

accuracy: Tools for Accurate and Reliable Statistical Computing

Most empirical social scientists are surprised that low-level numerical issues in software can have deleterious effects on the estimation process. Statistical analyses that appear to be perfectly successful can be invalidated by concealed numerical problems. We have developed a set of tools, contained in accuracy, a package for R and S-PLUS, to diagnose problems stemming from numerical and measurement error and to improve the accuracy of inferences. The tools included in accuracy include a framework for gauging the computational stability of model results, tools for comparing model results, optimization diagnostics, and tools for collecting entropy for true random numbers generation.