On the noise-induced passage through an unstable periodic orbit II: General case

Consider a dynamical system given by a planar differential equation, which exhibits an unstable periodic orbit surrounding a stable periodic orbit. It is known that under random perturbations, the distribution of locations where the system's first exit from the interior of the unstable orbit occurs, typically displays the phenomenon of cycling: The distribution of first-exit locations is translated along the unstable periodic orbit proportionally to the logarithm of the noise intensity as the noise intensity goes to zero. We show that for a large class of such systems, the cycling profile is given, up to a model-dependent change of coordinates, by a universal function given by a periodicised Gumbel distribution. Our techniques combine action-functional or large-deviation results with properties of random Poincar\'e maps described by continuous-space discrete-time Markov chains.Comment: 44 pages, 4 figure

The effect of additive noise on dynamical hysteresis

We investigate the properties of hysteresis cycles produced by a one-dimensional, periodically forced Langevin equation. We show that depending on amplitude and frequency of the forcing and on noise intensity, there are three qualitatively different types of hysteresis cycles. Below a critical noise intensity, the random area enclosed by hysteresis cycles is concentrated near the deterministic area, which is different for small and large driving amplitude. Above this threshold, the area of typical hysteresis cycles depends, to leading order, only on the noise intensity. In all three regimes, we derive mathematically rigorous estimates for expectation, variance, and the probability of deviations of the hysteresis area from its typical value.Comment: 30 pages, 5 figure

Metastability in Interacting Nonlinear Stochastic Differential Equations II: Large-N Behaviour

We consider the dynamics of a periodic chain of N coupled overdamped particles under the influence of noise, in the limit of large N. Each particle is subjected to a bistable local potential, to a linear coupling with its nearest neighbours, and to an independent source of white noise. For strong coupling (of the order N^2), the system synchronises, in the sense that all oscillators assume almost the same position in their respective local potential most of the time. In a previous paper, we showed that the transition from strong to weak coupling involves a sequence of symmetry-breaking bifurcations of the system's stationary configurations, and analysed in particular the behaviour for coupling intensities slightly below the synchronisation threshold, for arbitrary N. Here we describe the behaviour for any positive coupling intensity \gamma of order N^2, provided the particle number N is sufficiently large (as a function of \gamma/N^2). In particular, we determine the transition time between synchronised states, as well as the shape of the "critical droplet", to leading order in 1/N. Our techniques involve the control of the exact number of periodic orbits of a near-integrable twist map, allowing us to give a detailed description of the system's potential landscape, in which the metastable behaviour is encoded

Beyond the Fokker-Planck equation: Pathwise control of noisy bistable systems

We introduce a new method, allowing to describe slowly time-dependent Langevin equations through the behaviour of individual paths. This approach yields considerably more information than the computation of the probability density. The main idea is to show that for sufficiently small noise intensity and slow time dependence, the vast majority of paths remain in small space-time sets, typically in the neighbourhood of potential wells. The size of these sets often has a power-law dependence on the small parameters, with universal exponents. The overall probability of exceptional paths is exponentially small, with an exponent also showing power-law behaviour. The results cover time spans up to the maximal Kramers time of the system. We apply our method to three phenomena characteristic for bistable systems: stochastic resonance, dynamical hysteresis and bifurcation delay, where it yields precise bounds on transition probabilities, and the distribution of hysteresis areas and first-exit times. We also discuss the effect of coloured noise.Comment: 37 pages, 11 figure

Mixed-mode oscillations and interspike interval statistics in the stochastic FitzHugh-Nagumo model

We study the stochastic FitzHugh-Nagumo equations, modelling the dynamics of neuronal action potentials, in parameter regimes characterised by mixed-mode oscillations. The interspike time interval is related to the random number of small-amplitude oscillations separating consecutive spikes. We prove that this number has an asymptotically geometric distribution, whose parameter is related to the principal eigenvalue of a substochastic Markov chain. We provide rigorous bounds on this eigenvalue in the small-noise regime, and derive an approximation of its dependence on the system's parameters for a large range of noise intensities. This yields a precise description of the probability distribution of observed mixed-mode patterns and interspike intervals.Comment: 36 page

Activation of Toll-like receptors nucleates assembly of the MyDDosome signaling hub.

Infection and tissue damage induces assembly of supramolecular organizing centres (SMOCs)), such as the Toll-like receptor (TLR) MyDDosome, to co-ordinate inflammatory signaling. SMOC assembly is thought to drive digital all-or-none responses, yet TLR activation by diverse microbes induces anything from mild to severe inflammation. Using single-molecule imaging of TLR4-MyDDosome signaling in living macrophages, we find that MyDDosomes assemble within minutes of TLR4 stimulation. TLR4/MD2 activation leads only to formation of TLR4/MD2 heterotetramers, but not oligomers, suggesting a stoichiometric mismatch between activated receptors and MyDDosomes. The strength of TLR4 signalling depends not only on the number and size of MyDDosomes formed but also how quickly these structures assemble. Activated TLR4, therefore, acts transiently nucleating assembly of MyDDosomes, a process that is uncoupled from receptor activation. These data explain how the oncogenic mutation of MyD88 (L265P) assembles MyDDosomes in the absence of receptor activation to cause constitutive activation of pro-survival NF-κB signalling