Cells need to adapt to dynamic environments. Yeast that fail to cope with dynamic changes in the abundance of glucose can undergo growth arrest. We show that this failure is caused by imbalanced reactions in glycolysis, the essential pathway in energy metabolism in most organisms. The imbalance arises largely from the fundamental design of glycolysis, making this state of glycolysis a generic risk. Cells with unbalanced glycolysis coexisted with vital cells. Spontaneous, nongenetic metabolic variability among individual cells determines which state is reached and, consequently, which cells survive. Transient ATP (adenosine 5'-triphosphate) hydrolysis through futile cycling reduces the probability of reaching the imbalanced state. Our results reveal dynamic behavior of glycolysis and indicate that cell fate can be determined by heterogeneity purely at the metabolic level.

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381We consider a model for non-static groundwater flow where the saturation-pressure relation is extended by a dynamic term. This approach, together with a convective term due to gravity, results in a pseudo-parabolic Burgers type equation. We give a rigorous study of global travelling-wave solutions, with emphasis on the role played by the dynamic term and the appearance of fronts.

Specific product formation rates and cellular growth rates are important maximization targets in biotechnology and microbial evolution. Maximization of a specific rate (i.e. a rate expressed per unit biomass amount) requires the expression of particular metabolic pathways at optimal enzyme concentrations. In contrast to the prediction of maximal product yields, any prediction of optimal specific rates at the genome scale is currently computationally intractable, even if the kinetic properties of all enzymes are available. In the present study, we characterize maximal-specific-rate states of metabolic networks of arbitrary size and complexity, including genome-scale kinetic models. We report that optimal states are elementary flux modes, which are minimal metabolic networks operating at a thermodynamically-feasible steady state with one independent flux. Remarkably, elementary flux modes rely only on reaction stoichiometry, yet they function as the optimal states of mathematical models incorporating enzyme kinetics. Our results pave the way for the optimization of genome-scale kinetic models because they offer huge simplifications to overcome the concomitant computational problems. Database The mathematical model described here has been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at

The harmonic map heat flow is a model for nematic liquid crystals and also has origins in geometry. We present an analysis of the asymptotic behaviour of singularities arising in this flow for a special class of solutions which generalises a known (radially symmetric) reduction. Specifically, the rate at which blowup occurs is investigated in settings with certain symmetries using the method of matched asymptotic expansions. We identify a range of blowup scenarios in both finite and infinite time, including degenerate cases.

We consider non-negative solutions on the half-line of the thin film equation h t + (h n h xxx) x = 0, which arises in lubrication models for thin viscous films, spreading droplets and Hele-Shaw cells. We present a discussion of the boundary conditions at x = 0 on the basis of formal and modelling arguments when x = 0 is an edge over which fluid can drain. We apply this discussion to define some similarity solutions of the first and the second kind. Depending on the boundary conditions, we introduce mass-preserving solutions of the first kind (0 < n < 3), 'anomalous dipoles' of the second kind (0 < n < 2, n = 1) and a standard dipole solution of the first kind for n = 1. For solutions of the first kind we prove results on existence, uniqueness and asymptotic behaviour, both at x = 0 and at the free boundary. For solutions of the second kind we briefly present some qualitative properties.

Abstract. We derive the asymptotic behaviour of the ground states of a system of two coupled semilinear Poisson equations with a strongly indefinite variational structure in the critical Sobolev growth case.

Every solution of a linear elliptic equation on a bounded domain may be considered as an equilibrium of a free boundary problem. The free boundary problem consists of the corresponding parabolic equation on a variable unknown domain with free boundary conditions prescribing both Dirichlet and Neumann data. We establish a rigorous stability analysis of such equilibria, including the construction of stable and unstable manifolds. For this purpose we transform the free boundary problem to a fully nonlinear and nonlocal parabolic problem on a fixed domain with fully nonlinear lateral boundary conditions and we develop the general theory for such problems. As an illustration we give two examples, the second being the focussing flame problem in combustion theory. Academic Press