Metastability and low lying spectra in reversible Markov chains

We study a large class of reversible Markov chains with discrete state space and transition matrix $P_N$. We define the notion of a set of {\it metastable points} as a subset of the state space \G_N such that (i) this set is reached from any point x\in \G_N without return to x with probability at least $b_N$, while (ii) for any two point x,y in the metastable set, the probability $T^{-1}_{x,y}$ to reach y from x without return to x is smaller than $a_N^{-1}\ll b_N$. Under some additional non-degeneracy assumption, we show that in such a situation: \item{(i)} To each metastable point corresponds a metastable state, whose mean exit time can be computed precisely. \item{(ii)} To each metastable point corresponds one simple eigenvalue of $1-P_N$ which is essentially equal to the inverse mean exit time from this state. The corresponding eigenfunctions are close to the indicator function of the support of the metastable state. Moreover, these results imply very sharp uniform control of the deviation of the probability distribution of metastable exit times from the exponential distribution.Comment: 44pp, AMSTe

Metastability in stochastic dynamics of disordered mean-field models

We study a class of Markov chains that describe reversible stochastic dynamics of a large class of disordered mean field models at low temperatures. Our main purpose is to give a precise relation between the metastable time scales in the problem to the properties of the rate functions of the corresponding Gibbs measures. We derive the analog of the Wentzell-Freidlin theory in this case, showing that any transition can be decomposed, with probability exponentially close to one, into a deterministic sequence of ``admissible transitions''. For these admissible transitions we give upper and lower bounds on the expected transition times that differ only by a constant. The distribution rescaled transition times are shown to converge to the exponential distribution. We exemplify our results in the context of the random field Curie-Weiss model.Comment: 73pp, AMSTE

The K-process on a tree as a scaling limit of the GREM-like trap model

We introduce trap models on a finite volume $k$-level tree as a class of Markov jump processes with state space the leaves of that tree. They serve to describe the GREM-like trap model of Sasaki and Nemoto. Under suitable conditions on the parameters of the trap model, we establish its infinite volume limit, given by what we call a $K$-process in an infinite $k$-level tree. From this we deduce that the $K$-process also is the scaling limit of the GREM-like trap model on extreme time scales under a fine tuning assumption on the volumes.Comment: Published in at http://dx.doi.org/10.1214/13-AAP937 the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org

Convergence to extremal processes in random environments and extremal ageing in SK models

This paper extends recent results on aging in mean field spin glasses on short time scales, obtained by Ben Arous and Gun [2] in law with respect to the environment, to results that hold almost surely, respectively in probability, with respect to the environment. It is based on the methods put forward in Gayrard [8,9] and naturally complements Bovier and Gayrard [6].Comment: Revised version contains minor change

Dynamic phase diagram of the REM

By studying the two-time overlap correlation function, we give a comprehensive analysis of the phase diagram of the Random Hopping Dynamics of the Random Energy Model (REM) on time-scales that are exponential in the volume. These results are derived from the convergence properties of the clock process associated to the dynamics and fine properties of the simple random walk in the $n$-dimensional discrete cube.Comment: This paper is in large part based on the unpublished work arXiv:1008.3849. In particular, the analysis of the overlap correlation function is new as well as the study of the high temperature and short time-scale transition line between aging and stationarit

Infinitely many states and stochastic symmetry in a Gaussian Potts-Hopfield model

We study a Gaussian Potts-Hopfield model. Whereas for Ising spins and two disorder variables per site the chaotic pair scenario is realized, we find that for q-state Potts spins [{q(q-1} \over 2]-tuples occur. Beyond the breaking of a continous stochastic symmetry, we study the fluctuations and obtain the Newman-Stein metastate description for our model.Comment: latex, 17 page

Universality of REM-like aging in mean field spin glasses

Aging has become the paradigm to describe dynamical behavior of glassy systems, and in particular spin glasses. Trap models have been introduced as simple caricatures of effective dynamics of such systems. In this Letter we show that in a wide class of mean field models and on a wide range of time scales, aging occurs precisely as predicted by the REM-like trap model of Bouchaud and Dean. This is the first rigorous result about aging in mean field models except for the REM and the spherical model.Comment: 4 page

Pharmacokinetics of Quinacrine Efflux from Mouse Brain via the P-glycoprotein Efflux Transporter

The lipophilic cationic compound quinacrine has been used as an antimalarial drug for over 75 years but its pharmacokinetic profile is limited. Here, we report on the pharmacokinetic properties of quinacrine in mice. Following an oral dose of 40 mg/kg/day for 30 days, quinacrine concentration in the brain of wild-type mice was maintained at a concentration of ∼1 µM. As a substrate of the P-glycoprotein (P-gp) efflux transporter, quinacrine is actively exported from the brain, preventing its accumulation to levels that may show efficacy in some disease models. In the brains of P-gp–deficient Mdr10/0 mice, we found quinacrine reached concentrations of ∼80 µM without any signs of acute toxicity. Additionally, we examined the distribution and metabolism of quinacrine in the wild-type and Mdr10/0 brains. In wild-type mice, the co-administration of cyclosporin A, a known P-gp inhibitor, resulted in a 6-fold increase in the accumulation of quinacrine in the brain. Our findings argue that the inhibition of the P-gp efflux transporter should improve the poor pharmacokinetic properties of quinacrine in the CNS