Evolutionary Epidemiology Consequences of Trait-Dependent Control of Heterogeneous Parasites.

AbstractDisease control can induce both demographic and evolutionary responses in host-parasite systems. Foreseeing the outcome of control therefore requires knowledge of the eco-evolutionary feedback between control and system. Previous work has assumed that control strategies have a homogeneous effect on the parasite population. However, this is not true when control targets those traits that confer to the parasite heterogeneous levels of resistance, which can additionally be related to other key parasite traits through evolutionary trade-offs. In this work, we develop a minimal model coupling epidemiological and evolutionary dynamics to explore possible trait-dependent effects of control strategies. In particular, we consider a parasite expressing continuous levels of a trait-determining resource exploitation and a control treatment that can be either positively or negatively correlated with that trait. We demonstrate the potential of trait-dependent control by considering that the decision maker may want to minimize both the damage caused by the disease and the use of treatment, due to possible environmental or economic costs. We identify efficient strategies showing that the optimal type of treatment depends on the amount applied. Our results pave the way for the study of control strategies based on evolutionary constraints, such as collateral sensitivity and resistance costs, which are receiving increasing attention for both public health and agricultural purposes.

Redundancy-selection trade-off in phenotype-structured populations.

Realistic fitness landscapes generally display a redundancy-fitness trade-off: highly fit trait configurations are inevitably rare, while less fit trait configurations are expected to be more redundant. The resulting sub-optimal patterns in the fitness distribution are typically described by means of effective formulations, where redundancy provided by the presence of neutral contributions is modelled implicitly, e.g. with a bias of the mutation process. However, the extent to which effective formulations are compatible with explicitly redundant landscapes is yet to be understood, as well as the consequences of a potential miss-match. Here we investigate the effects of such trade-off on the evolution of phenotype-structured populations, characterised by continuous quantitative traits. We consider a typical replication-mutation dynamics, and we model redundancy by means of two dimensional landscapes displaying both selective and neutral traits. We show that asymmetries of the landscapes will generate neutral contributions to the marginalised fitness-level description, that cannot be described by effective formulations, nor disentangled by the full trait distribution. Rather, they appear as effective sources, whose magnitude depends on the geometry of the landscape. Our results highlight new important aspects on the nature of sub-optimality. We discuss practical implications for rapidly mutant populations such as pathogens and cancer cells, where the qualitative knowledge of their trait and fitness distributions can drive disease management and intervention policies.

Ghost-patterning and non-patterning in a draining film model.

Patterns can form when the uniform state of any system is unstable so that some non-uniform motif grows in amplitude. Here, we identify an alternative way to form non-trivial structures, which we call "ghost-patterns". Ghost-patterns emerge from noisy initial conditions when all non-uniform modes decay in amplitude except for one non-trivial motif which fails to decay. Hence, in seeking structured states, it is not necessary to find positive growth rates. We demonstrate ghost-patterns in an idealized non-equilibrium model intended to emulate draining thin-film suspensions.

Classical XY model with conserved angular momentum is an archetypal non-Newtonian fluid.

We find that the classical one-dimensional XY model, with angular-momentum-conserving Langevin dynamics, mimics the non-Newtonian flow regimes characteristic of soft matter when subjected to counterrotating boundaries. An elaborate steady-state phase diagram has continuous and first-order transitions between states of uniform flow, shear-banding, solid-fluid coexistence and slip planes. Results of numerical studies and a concise mean-field constitutive relation offer a paradigm for diverse nonequilibrium complex fluids.

Measuring local volume fraction, long-wavelength correlations, and fractionation in a phase-separating polydisperse fluid.

We dynamically simulate fractionation (partitioning of particle species) during spinodal gas-liquid separation of a size-polydisperse colloid, using polydispersity up to ~40% and a skewed parent size distribution. We introduce a novel coarse-grained Voronoi method to minimise size bias in measuring local volume fraction, along with a variety of spatial correlation functions which detect fractionation without requiring a clear distinction between the phases. These can be applied whether or not a system is phase separated, to determine structural correlations in particle size, and generalise easily to other kinds of polydispersity (charge, shape, etc.). We measure fractionation in both mean size and polydispersity between the phases, its direction differing between model interaction potentials which are identical in the monodisperse case. These qualitative features are predicted by a perturbative theory requiring only a monodisperse reference as input. The results show that intricate fractionation takes place almost from the start of phase separation, so can play a role even in nonequilibrium arrested states. The methods for characterisation of inhomogeneous polydisperse systems could in principle be applied to experiment as well as modelling.

Effects of orientational order on modulated cylindrical interfaces.

Cylindrical interfaces occur in sheared or deformed emulsions and as biological or technological lipid monolayer or bilayer tubules. Like the corresponding spherical droplets and vesicles, these cylinderlike surfaces may host orientational order with n-fold rotational symmetry, for example in the positions of lipid molecules or of spherical nanoparticles. We examine how that order interacts with and induces shape modulations of cylindrical interfaces. While on spherical droplets 2n topological defects necessarily exist and can induce icosahedral droplet shapes, the cylindrical topology is compatible with a defect-free patterning. Nevertheless, once a modulation is introduced by a mechanism such as spontaneous curvature, nontrivial patterns of order, including ones with excess defects, emerge and have nonlinear effects on the shape of the tube. By examining the equilibrium energetics of the system analytically and with a lattice-based Markov chain Monte Carlo simulation, we predict low-temperature morphologies of modulated cylindrical interfaces hosting orientational order. A shape modulation induces a banded pattern of alternatingly isotropic and ordered interfacial material. Furthermore, cylindrical systems can be divided into type I, without defects, and type II, which go through a spectrum of defect states with up to 4n excess defects. The character of the curvature-induced shape transition from unmodulated to modulated cylinders is continuous or discontinuous accordingly.

Direct conversion of rheological compliance measurements into storage and loss moduli.

We remove the need for Laplace/inverse-Laplace transformations of experimental data, by presenting a direct and straightforward mathematical procedure for obtaining frequency-dependent storage and loss moduli [G'(omega) and G''(omega), respectively], from time-dependent experimental measurements. The procedure is applicable to ordinary rheological creep (stress-step) measurements, as well as all microrheological techniques, whether they access a Brownian mean-square displacement, or a forced compliance. Data can be substituted directly into our simple formula, thus eliminating traditional fitting and smoothing procedures that disguise relevant experimental noise.

The self-assembly, elasticity, and dynamics of cardiac thin filaments.

Solutions of intact cardiac thin filaments were examined with transmission electron microscopy, dynamic light scattering (DLS), and particle-tracking microrheology. The filaments self-assembled in solution with a bell-shaped distribution of contour lengths that contained a population of filaments of much greater length than the in vivo sarcomere size ( approximately 1 mum) due to a one-dimensional annealing process. Dynamic semiflexible modes were found in DLS measurements at fast timescales (12.5 ns-0.0001 s). The bending modulus of the fibers is found to be in the range 4.5-16 x 10(-27) Jm and is weakly dependent on calcium concentration (with Ca2+ > or = without Ca2+). Good quantitative agreement was found for the values of the fiber diameter calculated from transmission electron microscopy and from the initial decay of DLS correlation functions: 9.9 nm and 9.7 nm with and without Ca2+, respectively. In contrast, at slower timescales and high polymer concentrations, microrheology indicates that the cardiac filaments act as short rods in solution according to the predictions of the Doi-Edwards chopsticks model (viscosity, eta approximately c(3), where c is the polymer concentration). This differs from the semiflexible behavior of long synthetic actin filaments at comparable polymer concentrations and timescales (elastic shear modulus, G' approximately c(1.4), tightly entangled) and is due to the relative ratio of the contour lengths ( approximately 30). The scaling dependence of the elastic shear modulus on the frequency (omega) for cardiac thin filaments is G' approximately omega(3/4 +/- 0.03), which is thought to arise from flexural modes of the filaments.

Properties of a nonequilibrium heat bath.

At equilibrium, a fluid element, within a larger heat bath, receives random impulses from the bath. Those impulses, which induce stochastic transitions in the system (the fluid element), respect the principle of detailed balance, because the bath is also at equilibrium. Under continuous shear, the fluid element adopts a nonequilibrium steady state. Because the surrounding bath of fluid under shear is also in a nonequilibrium steady state, the system receives stochastic impulses with a nonequilibrium distribution. Those impulses no longer respect detailed balance, but are nevertheless constrained by rules. The rules in question, which are applicable to a wide subclass of driven steady states, were recently derived [R. M. L. Evans, Phys. Rev. Lett. 92, 150601 (2004); J. Phys A 38, 293 (2005)] using information-theoretic arguments. In the present paper, we provide a more fundamental derivation, based on the uncontroversial, non-Bayesian interpretation of probabilities as simple ratios of countable quantities. We apply the results to some simple models of interacting particles, to investigate the nature of forces that are mediated by a nonequilibrium noise source such as a fluid under shear.

Pay-off scarcity causes evolution of risk-aversion and extreme altruism.

All organisms descend from populations with limited resources, so it is clear why evolution should select strategies that win resources at the expense of competitors. Less obvious is how altruistic behaviours evolve, whereby an individual helps others despite expense to itself. Modelling simple agents using evolutionary game theory, it is shown that steady states of extreme altruism can evolve when pay-offs are very rare compared with death. In these states, agents give away most of their wealth. A new theorem for general evolutionary models shows that, when pay-offs are rare, evolution no longer selects strategies to maximize income (average pay-off), but to minimize the risk of missing-out entirely on a rare resource. Principles revealed by the model are widely applicable, where the game represents rare life-changing events: disasters or gluts.

Validation of the Jarzynski relation for a system with strong thermal coupling: an isothermal ideal gas model.

We revisit the paradigm of an ideal gas under isothermal conditions. A moving piston performs work on an ideal gas in a container that is strongly coupled to a heat reservoir. The thermal coupling is modeled by stochastic scattering at the boundaries. In contrast to recent studies of an adiabatic ideal gas with a piston [R.C. Lua and A.Y. Grosberg, J. Phys. Chem. B 109, 6805 (2005); I. Bena, Europhys. Lett. 71, 879 (2005)], the container and piston stay in contact with the heat bath during the work process. Under this condition the heat reservoir as well as the system depend on the work parameter lambda and microscopic reversibility is broken for a moving piston. Our model is thus not included in the class of systems for which the nonequilibrium work theorem has been derived rigorously either by Hamiltonian [C. Jarzynski, J. Stat. Mech. (2004) P09005] or stochastic methods [G.E. Crooks, J. Stat. Phys. 90, 1481 (1998)]. Nevertheless the validity of the nonequilibrium work theorem is confirmed both numerically for a wide range of parameter values and analytically in the limit of a very fast moving piston, i.e., in the far nonequilibrium regime.

Numerical comparison of a constrained path ensemble and a driven quasisteady state.

We investigate the correspondence between a nonequilibrium ensemble defined via the distribution of phase-space paths of a Hamiltonian system and a system driven into a steady state by nonequilibrium boundary conditions. To discover whether the nonequilibrium path ensemble adequately describes the physics of a driven system, we measure transition rates in a simple one-dimensional model of rotors with Newtonian dynamics and purely conservative interactions. We compare those rates with known properties of the nonequilibrium path ensemble. In doing so, we establish effective protocols for the analysis of transition rates in nonequilibrium quasisteady states. Transition rates between potential wells and also between phase-space elements are studied and found to exhibit distinct properties, the more coarse-grained potential wells being effectively further from equilibrium. In all cases the results from the boundary-driven system are close to the path-ensemble predictions, but the question of equivalence of the two remains open.

Spinodal fractionation in a polydisperse square-well fluid.

Using kinetic Monte Carlo simulation, we model gas-liquid spinodal decomposition in a size-polydisperse square well fluid, representing a "near-monodisperse" colloidal dispersion. We find that fractionation (demixing) of particle sizes between the phases begins asserting itself shortly after the onset of phase ordering. Strikingly, the direction of size fractionation can be reversed by a seemingly trivial choice between two interparticle potentials which, in the monodisperse case, are identical--we rationalize this in terms of a perturbative, equilibrium theory of polydispersity. Furthermore, our quantitative results show that kinetic Monte Carlo simulation can provide detailed insight into the role of fractionation in real colloidal systems.

Statistical mechanics far from equilibrium: prediction and test for a sheared system.

We report the application of a far-from-equilibrium statistical-mechanical theory to a nontrivial system with Newtonian interactions in continuous boundary-driven flow. By numerically time stepping the force-balance equations of a one-dimensional model fluid we measure occupancies and transition rates in simulation. The high-shear-rate simulation data reproduce the predicted invariant quantities, thus supporting the theory that a class of nonequilibrium steady states of matter, namely, sheared complex fluids, is amenable to statistical treatment from first principles.

Measuring storage and loss moduli using optical tweezers: broadband microrheology.

We present an experimental procedure to perform broadband microrheological measurements with optical tweezers. A generalized Langevin equation is adopted to relate the time-dependent trajectory of a particle in an imposed flow to the frequency-dependent moduli of the complex fluid. This procedure allows us to measure the material linear viscoelastic properties across the widest frequency range achievable with optical tweezers.

Invariant quantities in shear flow.

The dynamics of systems out of thermal equilibrium is usually treated on a case-by-case basis without knowledge of fundamental and universal principles. We address this problem for a class of driven steady states, namely, those mechanically driven at the boundaries such as complex fluids under shear. From a nonequilibrium counterpart to detailed balance (NCDB) we derive a remarkably simple set of invariant quantities which remain unchanged when the system is driven. These new nonequilibrium relations are both exact and valid arbitrarily far from equilibrium. Furthermore, they enable the systematic calculation of transition rates in driven systems with state spaces of arbitrary connectivity.

Dynamics of semiflexible polymer solutions in the highly entangled regime.

We present experimental evidence that the effective medium approximation (EMA), [D. C. Morse, Phys. Rev. E 63, 031502 (2001)], provides the correct scaling law of the plateau modulus G0 proportional variantrho4/3Lp(-1/3) (with rho the contour length per unit volume and Lp the persistence length) of semiflexible polymer solutions, in the highly entangled regime. Competing theories, including a binary collision approximation (BCA), instead predict G0 proportional, variantrho7/5Lp(-1/5). We have tested both predictions using F-actin solutions which permit experimental control of Lp independently of other parameters. A combination of video particle tracking microrheology and dynamic light scattering yields independent measurements of G0 and Lp, respectively. Thus we can distinguish between the two proposed laws, in contrast to previous experimental studies focused on the (less discriminating) concentration dependence.

Pattern formation in draining thin film suspensions.

We demonstrate the emergence of complexity from remarkably simple and ubiquitous systems: draining thin-film suspensions exhibiting a striking transition between two classes of self-organizing patterns. Vertical channels form when attractive forces lead to transient gelation, while horizontal bands result from granular mixtures. We propose an explanation whereby the generic physical mechanisms require only the existence of viscous and excluded-volume couplings among the particles, solvent, and substrate. System-specific, small inhomogeneities trigger large-scale pattern formation, through collective dynamics, where jamming plays a crucial role. Our results shed light on emergent complexity in bio- and geophysical processes and have implications for coatings and food industries.

The internal dynamic modes of charged self-assembled peptide fibrils.

Photon correlation spectroscopy is used to study the internal dynamics of self-assembled charged peptide fibrils. Short neutral and charged polymeric aggregates have diffusive modes due to whole macromolecular motion. For long semiflexible fibrils the logarithm of the intermediate scattering function follows a q(2)t(3/4) scaling at long times consistent with a Kratky-Porod free energy and preaveraged Oseen hydrodynamics. Persistence lengths on the order of micrometers are calculated for the peptide fibrils consistent with estimates from the liquid-crystalline phase behavior. Fibril diameters (5-35 nm) calculated from the initial decay of the correlation functions are in agreement with transmission electron microscopy measurements.

Rules for transition rates in nonequilibrium steady states.

Just as transition rates in a canonical ensemble must respect the principle of detailed balance, constraints exist on transition rates in driven steady states. I derive those constraints, by maximum information-entropy inference, and apply them to the steady states of driven diffusion and a sheared lattice fluid. The resulting ensemble can potentially explain nonequilibrium phase behavior and, for steady shear, gives rise to stress-mediated long-range interactions.