A Markovian decision model of adaptive cancer treatment and quality of life.

This paper develops and analyzes a Markov chain model for the treatment of cancer. Cancer therapy is modeled as the patient's Markov Decision Problem, with the objective of maximizing the patient's discounted expected quality of life years. Patients make decisions on the duration of therapy based on the progression of the disease as well as their own preferences. We obtain a powerful analytic decision tool through which patients may select their preferred treatment strategy. We illustrate the tradeoffs patients in a numerical example and calculate the value lost to a cohort in suboptimal strategies. In a second model patients may make choices to include drug holidays. By delaying therapy, the patient temporarily forgoes the gains of therapy in order to delay its side effects. We obtain an analytic tool that allows numerical approximations of the optimal times of delay.

Synchronization of cyclic power grids: Equilibria and stability of the synchronous state.

Synchronization is essential for the proper functioning of power grids; we investigate the synchronous states and their stability for cyclic power grids. We calculate the number of stable equilibria and investigate both the linear and nonlinear stabilities of the synchronous state. The linear stability analysis shows that the stability of the state, determined by the smallest nonzero eigenvalue, is inversely proportional to the size of the network. We use the energy barrier to measure the nonlinear stability and calculate it by comparing the potential energy of the type-1 saddles with that of the stable synchronous state. We find that the energy barrier depends on the network size (N) in a more complicated fashion compared to the linear stability. In particular, when the generators and consumers are evenly distributed in an alternating way, the energy barrier decreases to a constant when N approaches infinity. For a heterogeneous distribution of generators and consumers, the energy barrier decreases with N. The more heterogeneous the distribution is, the stronger the energy barrier depends on N. Finally, we find that by comparing situations with equal line loads in cyclic and tree networks, tree networks exhibit reduced stability. This difference disappears in the limit of N→∞. This finding corroborates previous results reported in the literature and suggests that cyclic (sub)networks may be applied to enhance power transfer while maintaining stable synchronous operation.

Force spectroscopy of polymer desorption: theory and molecular dynamics simulations.

Forced detachment of a single polymer chain, strongly adsorbed on a solid substrate, is investigated by two complementary methods: a coarse-grained analytical dynamical model, based on the Onsager stochastic equation, and Molecular Dynamics (MD) simulations with a Langevin thermostat. The suggested approach makes it possible to go beyond the limitations of the conventional Bell-Evans model. We observe a series of characteristic force spikes when the pulling force is measured against the cantilever displacement during detachment at constant velocity vc (displacement control mode) and find that the average magnitude of this force increases as vc increases. The probability distributions of the pulling force and the end-monomer distance from the surface at the moment of the final detachment are investigated for different adsorption energies ε and pulling velocities vc. Our extensive MD simulations validate and support the main theoretical findings. Moreover, the simulations reveal a novel behavior: for a strong-friction and massive cantilever the force spike pattern is smeared out at large vc. As a challenging task for experimental bio-polymer sequencing in future we suggest the fabrication of a stiff, super-light, nanometer-sized AFM probe.

Stackelberg evolutionary game theory: how to manage evolving systems.

Stackelberg evolutionary game (SEG) theory combines classical and evolutionary game theory to frame interactions between a rational leader and evolving followers. In some of these interactions, the leader wants to preserve the evolving system (e.g. fisheries management), while in others, they try to drive the system to extinction (e.g. pest control). Often the worst strategy for the leader is to adopt a constant aggressive strategy (e.g. overfishing in fisheries management or maximum tolerable dose in cancer treatment). Taking into account the ecological dynamics typically leads to better outcomes for the leader and corresponds to the Nash equilibria in game-theoretic terms. However, the leader's most profitable strategy is to anticipate and steer the eco-evolutionary dynamics, leading to the Stackelberg equilibrium of the game. We show how our results have the potential to help in fields where humans try to bring an evolutionary system into the desired outcome, such as, among others, fisheries management, pest management and cancer treatment. Finally, we discuss limitations and opportunities for applying SEGs to improve the management of evolving biological systems. This article is part of the theme issue 'Half a century of evolutionary games: a synthesis of theory, application and future directions'.

Long time evolution of atherosclerotic plaques.

The evolution of atherosclerosis in general, and the influence of wall shear stress on the growth of atherosclerotic plaques in particular, is an intricate phenomenon which is still only partly understood. We therefore propose a qualitative mathematical model which consists of a number of ordinary differential equations for the concentrations of the most relevant constituents of the atherosclerotic plaque. These equations were studied both for the case that the wall shear stress is a parameter (model A), and for the case in which the plaque evolution is coupled to the blood flow (model B) which results in a time dependent wall shear stress. We find that both models exhibit a class of marginally stable equilibria, all reflecting states in which the plaque only grows for a short period of time after a perturbation. The uncoupled model A, however, shows bi-stability between this class of equilibria and another equilibrium state in which the plaque experiences unlimited growth in time, if the LDL cholesterol intake exceeds a threshold value. In model B the bi-stability vanishes, but we find that there is still a critical value of the LDL cholesterol intake beyond which the lumen radius drastically decreases. We show that this decrease is quite sensitive to the value of the wall shear stress.

Fisheries management as a Stackelberg Evolutionary Game: Finding an evolutionarily enlightened strategy.

Fish populations subject to heavy exploitation are expected to evolve over time smaller average body sizes. We introduce Stackelberg evolutionary game theory to show how fisheries management should be adjusted to mitigate the potential negative effects of such evolutionary changes. We present the game of a fisheries manager versus a fish population, where the former adjusts the harvesting rate and the net size to maximize profit, while the latter responds by evolving the size at maturation to maximize the fitness. We analyze three strategies: i) ecologically enlightened (leading to a Nash equilibrium in game-theoretic terms); ii) evolutionarily enlightened (leading to a Stackelberg equilibrium) and iii) domestication (leading to team optimum) and the corresponding outcomes for both the fisheries manager and the fish. Domestication results in the largest size for the fish and the highest profit for the manager. With the Nash approach the manager tends to adopt a high harvesting rate and a small net size that eventually leads to smaller fish. With the Stackelberg approach the manager selects a bigger net size and scales back the harvesting rate, which lead to a bigger fish size and a higher profit. Overall, our results encourage managers to take the fish evolutionary dynamics into account. Moreover, we advocate for the use of Stackelberg evolutionary game theory as a tool for providing insights into the eco-evolutionary consequences of exploiting evolving resources.

Classification of link-breaking and link-creation updating rules in susceptible-infected-susceptible epidemics on adaptive networks.

In the classical susceptible-infected-susceptible (SIS) model, a disease or infection spreads over a given, mostly fixed graph. However, in many real complex networks, the topology of the underlying graph can change due to the influence of the dynamical process. In this paper, besides the spreading process, the network adaptively changes its topology based on the states of the nodes in the network. An entire class of link-breaking and link-creation mechanisms, which we name Generalized Adaptive SIS (G-ASIS), is presented and analyzed. For each instance of G-ASIS using the complete graph as initial network, the relation between the epidemic threshold and the effective link-breaking rate is determined to be linear, constant, or unknown. Additionally, we show that there exist link-breaking and link-creation mechanisms for which the metastable state does not exist. We confirm our theoretical results with several numerical simulations.

Dynamic heterogeneity in hydrogen-bonded polymers.

We report on neutron spin echo experiments on hydrogen-bonded polymers and compare the experimentally found dynamical structure factor with theoretical predictions. Surprisingly, we find that in the melt phase the expected scaling of the Rouse dynamics is not satisfied. We propose an explanation based upon the large spatial volume occupied by the connecting groups. When the effects of these bulky groups on the local friction are taken into account, the usual scaling behavior is restored.

Self-consistent dynamics of wall slip.

A simple molecular model is studied to explain wall slip in a polymer melt. We consider a tube model for tethered chains in which the most important relaxation mechanisms: convective constraint release and chain stretching (retraction), are incorporated. Furthermore, we take the interactions between tethered chains and bulk flow self-consistently into account. Numerical simulations show that our model exhibits an entanglement-disentanglement transition, leading to a jump in the slip velocity which increases with the number of entanglements and the grafting density. The wall shear stress is found to be a nonmonotonic function of the slip and plate velocity, yielding the possibility of hysteresis and spurt instabilities. In a simplified version of the model we show via an analytical approach that the stick-slip transition is asymmetrical: the transition from stick to slip is much faster than the slip to stick transition. Our analysis reveals the existence of a dimensionless parameter that determines the time scale of the dynamics for the slowing down of the bulk flow. The relative rate at which relaxation of the tethered chains and slowing down of the bulk take place, seems to be quintessential for the slip behavior of the melt.

Polymer translocation through a nanopore: a showcase of anomalous diffusion.

We investigate the translocation dynamics of a polymer chain threaded through a membrane nanopore by a chemical potential gradient that acts on the chain segments inside the pore. By means of diverse methods (scaling theory, fractional calculus, and Monte Carlo and molecular dynamics simulations), we demonstrate that the relevant dynamic variable, the transported number of polymer segments, s(t), displays an anomalous diffusive behavior, both with and without an external driving force being present. We show that in the absence of drag force the time tau, needed for a macromolecule of length N to thread from the cis into the trans side of a cell membrane, scales as tauN(2/alpha) with the chain length. The anomalous dynamics of the translocation process is governed by a universal exponent alpha= 2/(2nu + 2 - gamma(1)), which contains the basic universal exponents of polymer physics, nu (the Flory exponent) and gamma(1) (the surface entropic exponent). A closed analytic expression for the probability to find s translocated segments at time t in terms of chain length N and applied drag force f is derived from the fractional Fokker-Planck equation, and shown to provide analytic results for the time variation of the statistical moments and . It turns out that the average translocation time scales as tau proportional, f(-1)N(2/alpha-1). These results are tested and found to be in perfect agreement with extensive Monte Carlo and molecular dynamics computer simulations.

End-evaporation dynamics revisited.

We present analytical results on the so-called end-evaporation kinetics in equilibrium polymeric systems following a temperature jump (T jump). A T jump prepares the system with a nonequilibrium length distribution, after which it relaxes back to its equilibrium state. Starting from a master equation, we develop a mean-field analytical theory based on a generating function approach, which allows explicit approximate expressions for the monomer and dimer concentrations to be derived in a discrete setting; the concentrations of the other chains as well as the average chain length were shown to be entirely expressible in terms of the monomer and dimer concentrations. We find that the calculated monomer and dimer concentrations as well as the average chain length are in good agreement with numerical simulation results and do not suffer from some of the defects of earlier continuum theories. Furthermore, the relaxation was shown to take place in three different stages. The first stage comprises the very fast relaxation of the monomers to almost their equilibrium concentration; the other polymer chains have hardly relaxed. During the second stage, which is highly nonlinear, a redistribution of material at practically constant monomer density takes place. Only in the final stage of the relaxation process the chain concentrations approach their true equilibrium values. In this stage there are only very small shifts in the concentrations of chains, which are governed by extremely slow "indirect" monomer-mediated processes.