The effects of intrinsic noise on the behaviour of bistable cell regulatory systems under quasi-steady state conditions

We analyse the effect of intrinsic fluctuations on the properties of bistable stochastic systems with time scale separation operating under1 quasi-steady state conditions. We first formulate a stochastic generalisation of the quasi-steady state approximation based on the semi-classical approximation of the partial differential equation for the generating function associated with the Chemical Master Equation. Such approximation proceeds by optimising an action functional whose associated set of Euler-Lagrange (Hamilton) equations provide the most likely fluctuation path. We show that, under appropriate conditions granting time scale separation, the Hamiltonian can be re-scaled so that the set of Hamilton equations splits up into slow and fast variables, whereby the quasi-steady state approximation can be applied. We analyse two particular examples of systems whose mean-field limit has been shown to exhibit bi-stability: an enzyme-catalysed system of two mutually-inhibitory proteins and a gene regulatory circuit with self-activation. Our theory establishes that the number of molecules of the conserved species are order parameters whose variation regulates bistable behaviour in the associated systems beyond the predictions of the mean-field theory. This prediction is fully confirmed by direct numerical simulations using the stochastic simulation algorithm. This result allows us to propose strategies whereby, by varying the number of molecules of the three conserved chemical species, cell properties associated to bistable behaviour (phenotype, cell-cycle status, etc.) can be controlled.Comment: 33 pages, 9 figures, accepted for publication in the Journal of Chemical Physic

An in-depth view of the microscopic dynamics of Ising spin glasses at fixed temperature

Using the dedicated computer Janus, we follow the nonequilibrium dynamics of the Ising spin glass in three dimensions for eleven orders of magnitude. The use of integral estimators for the coherence and correlation lengths allows us to study dynamic heterogeneities and the presence of a replicon mode and to obtain safe bounds on the Edwards-Anderson order parameter below the critical temperature. We obtain good agreement with experimental determinations of the temperature-dependent decay exponents for the thermoremanent magnetization. This magnitude is observed to scale with the much harder to measure coherence length, a potentially useful result for experimentalists. The exponents for energy relaxation display a linear dependence on temperature and reasonable extrapolations to the critical point. We conclude examining the time growth of the coherence length, with a comparison of critical and activated dynamics.Comment: 38 pages, 26 figure

Matching microscopic and macroscopic responses in glasses

We first reproduce on the Janus and Janus II computers a milestone experiment that measures the spin-glass coherence length through the lowering of free-energy barriers induced by the Zeeman effect. Secondly we determine the scaling behavior that allows a quantitative analysis of a new experiment reported in the companion Letter [S. Guchhait and R. Orbach, Phys. Rev. Lett. 118, 157203 (2017)]. The value of the coherence length estimated through the analysis of microscopic correlation functions turns out to be quantitatively consistent with its measurement through macroscopic response functions. Further, non-linear susceptibilities, recently measured in glass-forming liquids, scale as powers of the same microscopic length.Comment: 6 pages, 4 figure

The Mpemba effect in spin glasses is a persistent memory effect

The Mpemba effect occurs when a hot system cools faster than an initially colder one, when both are refrigerated in the same thermal reservoir. Using the custom built supercomputer Janus II, we study the Mpemba effect in spin glasses and show that it is a non-equilibrium process, governed by the coherence length \xi of the system. The effect occurs when the bath temperature lies in the glassy phase, but it is not necessary for the thermal protocol to cross the critical temperature. In fact, the Mpemba effect follows from a strong relationship between the internal energy and \xi that turns out to be a sure-tell sign of being in the glassy phase. Thus, the Mpemba effect presents itself as an intriguing new avenue for the experimental study of the coherence length in supercooled liquids and other glass formers.Comment: Version accepted for publication in PNAS. 6 pages, 7 figure

The Spin Glass Phase in the Four-State, Three-Dimensional Potts Model

We perform numerical simulations, including parallel tempering, on the Potts glass model with binary random quenched couplings using the JANUS application-oriented computer. We find and characterize a glassy transition, estimating the location of the transition and the value of the critical exponents. We show that there is no ferromagnetic transition in a large temperature range around the glassy critical temperature. We also compare our results with those obtained recently on the "random permutation" Potts glass.Comment: 7 pages and 3 figures. Corrected minor typo

The three dimensional Ising spin glass in an external magnetic field: the role of the silent majority

We perform equilibrium parallel-tempering simulations of the 3D Ising Edwards-Anderson spin glass in a field. A traditional analysis shows no signs of a phase transition. Yet, we encounter dramatic fluctuations in the behaviour of the model: Averages over all the data only describe the behaviour of a small fraction of it. Therefore we develop a new approach to study the equilibrium behaviour of the system, by classifying the measurements as a function of a conditioning variate. We propose a finite-size scaling analysis based on the probability distribution function of the conditioning variate, which may accelerate the convergence to the thermodynamic limit. In this way, we find a non-trivial spectrum of behaviours, where a part of the measurements behaves as the average, while the majority of them shows signs of scale invariance. As a result, we can estimate the temperature interval where the phase transition in a field ought to lie, if it exists. Although this would-be critical regime is unreachable with present resources, the numerical challenge is finally well posed.Comment: 42 pages, 19 figures. Minor changes and added figure (results unchanged

Nature of the spin-glass phase at experimental length scales

We present a massive equilibrium simulation of the three-dimensional Ising spin glass at low temperatures. The Janus special-purpose computer has allowed us to equilibrate, using parallel tempering, L=32 lattices down to T=0.64 Tc. We demonstrate the relevance of equilibrium finite-size simulations to understand experimental non-equilibrium spin glasses in the thermodynamical limit by establishing a time-length dictionary. We conclude that non-equilibrium experiments performed on a time scale of one hour can be matched with equilibrium results on L=110 lattices. A detailed investigation of the probability distribution functions of the spin and link overlap, as well as of their correlation functions, shows that Replica Symmetry Breaking is the appropriate theoretical framework for the physically relevant length scales. Besides, we improve over existing methodologies to ensure equilibration in parallel tempering simulations.Comment: 48 pages, 19 postscript figures, 9 tables. Version accepted for publication in the Journal of Statistical Mechanic

Critical parameters of the three-dimensional Ising spin glass

We report a high-precision finite-size scaling study of the critical behavior of the three-dimensional Ising Edwards-Anderson model (the Ising spin glass). We have thermalized lattices up to L=40 using the Janus dedicated computer. Our analysis takes into account leading-order corrections to scaling. We obtain Tc = 1.1019(29) for the critical temperature, \nu = 2.562(42) for the thermal exponent, \eta = -0.3900(36) for the anomalous dimension and \omega = 1.12(10) for the exponent of the leading corrections to scaling. Standard (hyper)scaling relations yield \alpha = -5.69(13), \beta = 0.782(10) and \gamma = 6.13(11). We also compute several universal quantities at Tc.Comment: 9 pages, 5 figure

Thermodynamic glass transition in a spin glass without time-reversal symmetry

Spin glasses are a longstanding model for the sluggish dynamics that appears at the glass transition. However, spin glasses differ from structural glasses for a crucial feature: they enjoy a time reversal symmetry. This symmetry can be broken by applying an external magnetic field, but embarrassingly little is known about the critical behaviour of a spin glass in a field. In this context, the space dimension is crucial. Simulations are easier to interpret in a large number of dimensions, but one must work below the upper critical dimension (i.e., in d<6) in order for results to have relevance for experiments. Here we show conclusive evidence for the presence of a phase transition in a four-dimensional spin glass in a field. Two ingredients were crucial for this achievement: massive numerical simulations were carried out on the Janus special-purpose computer, and a new and powerful finite-size scaling method.Comment: 10 pages, 6 figure

Janus II: a new generation application-driven computer for spin-system simulations

This paper describes the architecture, the development and the implementation of Janus II, a new generation application-driven number cruncher optimized for Monte Carlo simulations of spin systems (mainly spin glasses). This domain of computational physics is a recognized grand challenge of high-performance computing: the resources necessary to study in detail theoretical models that can make contact with experimental data are by far beyond those available using commodity computer systems. On the other hand, several specific features of the associated algorithms suggest that unconventional computer architectures, which can be implemented with available electronics technologies, may lead to order of magnitude increases in performance, reducing to acceptable values on human scales the time needed to carry out simulation campaigns that would take centuries on commercially available machines. Janus II is one such machine, recently developed and commissioned, that builds upon and improves on the successful JANUS machine, which has been used for physics since 2008 and is still in operation today. This paper describes in detail the motivations behind the project, the computational requirements, the architecture and the implementation of this new machine and compares its expected performances with those of currently available commercial systems.Comment: 28 pages, 6 figure