solveME: fast and reliable solution of nonlinear ME models.

BackgroundGenome-scale models of metabolism and macromolecular expression (ME) significantly expand the scope and predictive capabilities of constraint-based modeling. ME models present considerable computational challenges: they are much (>30 times) larger than corresponding metabolic reconstructions (M models), are multiscale, and growth maximization is a nonlinear programming (NLP) problem, mainly due to macromolecule dilution constraints.ResultsHere, we address these computational challenges. We develop a fast and numerically reliable solution method for growth maximization in ME models using a quad-precision NLP solver (Quad MINOS). Our method was up to 45 % faster than binary search for six significant digits in growth rate. We also develop a fast, quad-precision flux variability analysis that is accelerated (up to 60× speedup) via solver warm-starts. Finally, we employ the tools developed to investigate growth-coupled succinate overproduction, accounting for proteome constraints.ConclusionsJust as genome-scale metabolic reconstructions have become an invaluable tool for computational and systems biologists, we anticipate that these fast and numerically reliable ME solution methods will accelerate the wide-spread adoption of ME models for researchers in these fields

Three Puzzles on Mathematics, Computation, and Games

In this lecture I will talk about three mathematical puzzles involving mathematics and computation that have preoccupied me over the years. The first puzzle is to understand the amazing success of the simplex algorithm for linear programming. The second puzzle is about errors made when votes are counted during elections. The third puzzle is: are quantum computers possible?Comment: ICM 2018 plenary lecture, Rio de Janeiro, 36 pages, 7 Figure

C++ Standard Template Library by template specialized containers

The C++ Standard Template Library is the flagship example for libraries based on the generic programming paradigm. The usage of this library is intended to minimize the number of classical C/C++ errors, but does not warrant bug-free programs. Furthermore, many new kinds of errors may arise from the inaccurate use of the generic programming paradigm, like dereferencing invalid iterators or misunderstanding remove-like algorithms. In this paper we present some typical scenarios that may cause runtime or portability problems. We emit warnings and errors while these risky constructs are used. We also present a general approach to emit "customized" warnings. We support the so-called "believe-me marks" to disable warnings. We present another typical usage of our technique, when classes become deprecated during the software lifecycle

Optimal Pavement Design and Rehabilitation Planning Using a Mechanistic-Empirical Approach

This paper presents the development of a pavement design and rehabilitation optimization decision-making framework based on Mechanistic-Empirical (ME) roughness transfer models. The AASHTOWare Pavement ME Design (the software of Pavement ME Design) is used to estimate pavement deterioration based on the combined effects of permanent deformation, fatigue, and thermal cracking. The optimization problem is first formulated into a mixed-integer nonlinear programming model to address the predominant trade-off between agency and user costs. To deal with the complexity associated with the pavement roughness transfer functions in the software and to use the roughness values as input to the optimization framework, a dynamic programming subroutine is developed for determining the optimal rehabilitation timing and asphalt concrete design thickness. An application of the proposed model is demonstrated in a case study. Managerial insights from a series of sensitivity analyses on different unit user cost values and model comparisons are presented

DATA CONFESSION in the PORTUGUESE EDM REGION

A dual profit model is used to characterize the Entre Douro e Minho (EDM) region agriculture. The data comes from budgets for twelve representative farms. Positive Mathematical Programming (PMP) is applied. First, shadow prices of fixed inputs are obtained for each farm from a linear program (LP) forcing base year (1994) net output and fixed input allocations. Second, the Maximum Entropy (ME) technique is used to recover the restricted profit functions. The model purely reproduces observed net output and fixed input data. A short run profit function is derived for the region from aggregation of the model. The corresponding long run profit function is also derived. The profit model reveals an inelastic response to prices in the short run, and a more elastic response in the long run. Nitrogen and water appear as complements. The inelasticity of nitrogen response to its own price precludes taxing nitrogen to control its use. In contrast, pricing water is an effective strategy, not only to control water use but also nitrogen use. The Water Framework Directive (WFD) recommends both strategies.water, agricultural economics, elasticities, positive mathematical programming, maximum entropy

Object-oriented programming with mixins in Ada

Recently, I wrote a paper discussing the lack of 'true' object-oriented programming language features in Ada 83, why one might desire them in Ada, and how they might be added in Ada 9X. The approach I took in this paper was to build the new object-oriented features of Ada 9X as much as possible on the basic constructs and philosophy of Ada 83. The object-oriented features proposed for Ada 9X, while different in detail, are based on the same kind of approach. Further consideration of this approach led me on a long reflection on the nature of object-oriented programming and its application to Ada. The results of this reflection, presented in this paper, show how a fairly natural object-oriented style can indeed be developed even in Ada 83. The exercise of developing this style is useful for at least three reasons: (1) it provides a useful style for programming object-oriented applications in Ada 83 until new features become available with Ada 9X; (2) it demystifies many of the mechanisms that seem to be 'magic' in most object-oriented programming languages by making them explicit; and (3) it points out areas that are and are not in need of change in Ada 83 to make object-oriented programming more natural in Ada 9X. In the next four sections I will address in turn the issues of object-oriented classes, mixins, self-reference and supertyping. The presentation is through a sequence of examples. This results in some overlap with that paper, but all the examples in the present paper are written entirely in Ada 83. I will return to considerations for Ada 9X in the last section of the paper

Clinical interpretation of health and the human spirit for occupation .

In reading and contemplating Yenca\u27s (1998) article, I was immediately struck by the utility of the ideas she offers on a number of clinical fronts. We are presented with occupation-based strategies that are directly applicable to our work with patients and program development; we can make use of the language and ideas that are offered as a way to begin talking to one another (therapist to therapist) in clinical settings about occupation; and we are given the opportunity to think about the contribution, value, and efficacy of occupation and how we might convert those ideas into clinically based research actions. This last point is especially useful given Yerxa\u27s powerful view of the complex and compelling human and person issues that are looming on the horizon (achieving healthfulness, finding valued substitutes for work). In response to these person dilemmas of the future, it is exciting to consider what kinds of new treatment approaches, programming ideas, and research questions might be most appropriate for us to develop on me basis of our understanding of the importance of occupation to health

A Primer on Marginal Effects—Part II: Health Services Research Applications

Marginal analysis evaluates changes in a regression function associated with a unit change in a relevant variable. The primary statistic of marginal analysis is the marginal effect (ME). The ME facilitates the examination of outcomes for defined patient profiles or individuals while measuring the change in original units (e.g., costs, probabilities). The ME has a long history in economics; however, it is not widely used in health services research despite its flexibility and ability to provide unique insights. This article, the second in a two-part series, discusses practical issues that arise in the estimation and interpretation of the ME for a variety of regression models often used in health services research. Part one provided an overview of prior studies discussing ME followed by derivation of ME formulas for various regression models relevant for health services research studies examining costs and utilization. The current article illustrates the calculation and interpretation of ME in practice and discusses practical issues that arise during the implementation, including: understanding differences between software packages in terms of functionality available for calculating the ME and its confidence interval, interpretation of average marginal effect versus marginal effect at the mean, and the difference between ME and relative effects (e.g., odds ratio). Programming code to calculate ME using SAS, STATA, LIMDEP, and MATLAB are also provided. The illustration, discussion, and application of ME in this two-part series support the conduct of future studies applying the concept of marginal analysis