Constraint-based metabolic models can be used to investigate the intracellular physiology of microorganisms. These models couple genes to reactions, and typically seek to predict metabolite fluxes that optimize some biologically important metric. Classical techniques, like Flux Balance Analysis (FBA), formulate the metabolism of a microbe as an optimization problem where growth rate is maximized. While FBA has found widespread use, it often leads to thermodynamically infeasible solutions that contain internal cycles (loops). To address this shortcoming, Loopless-Flux Balance Analysis (ll-FBA) seeks to predict flux distributions that do not contain these loops. ll-FBA is a disjunctive program, usually reformulated as a mixed-integer program, and is challenging to solve for biological models that often contain thousands of reactions and metabolites. In this paper, we compare various reformulations of ll-FBA and different solution approaches. Overall, the combinatorial Benders' decomposition is the most promising of the tested approaches with which we could solve most instances. However, the model size and numerical instability pose a challenge to the combinatorial Benders' method.

Frank-Wolfe (FW) algorithms have emerged as an essential class of methods for constrained optimization, especially on large-scale problems. In this article, we summarize the algorithmic design choices and progress made in the last years of the development of FrankWolfe.jl, a Julia package gathering high-performance implementations of state-of-the-art FW variants. We review key use cases of the library in the recent literature, which match its original dual purpose: first, becoming the de-facto toolbox for practitioners applying FW methods to their problem, and second, offering a modular ecosystem to algorithm designers who experiment with their own variants and implementations of algorithmic blocks. Finally, we demonstrate the performance of several FW variants on important problem classes in several experiments, which we curated in a separate repository for continuous benchmarking.