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Cellular Potts models are broadly applied across developmental biology and cancer research. We overcome limitations of the traditional approach, which reinterprets a modified Metropolis sampling as ad hoc dynamics, by introducing a physical timescale through Poissonian kinetics and by applying principles of stochastic thermodynamics to separate thermal and relaxation effects from athermal noise and nonconservative forces. Our method accurately describes cell-sorting dynamics in mouse-embryo development and identifies the distinct contributions of nonequilibrium processes, e.g., cell growth and active fluctuations.

The self-organization of cells into complex tissues relies on a tight coordination of cell behavior. Identifying the cellular processes driving tissue growth is key to understanding the emergence of tissue forms and devising targeted therapies for aberrant growth, such as in cancer. Inferring the mode of tissue growth, whether it is driven by cells on the surface or by cells in the bulk, is possible in cell culture experiments but difficult in most tissues in living organisms (in vivo). Genetic tracing experiments, where a subset of cells is labeled with inheritable markers, have become important experimental tools to study cell fate in vivo. Here we show that the mode of tissue growth is reflected in the size distribution of the progeny of marked cells. To this end, we derive the clone size distributions using analytical calculations in the limit of negligible cell migration and cell death, and we test our predictions with an agent-based stochastic sampling technique. We show that for surface-driven growth the clone size distribution takes a characteristic power-law form with an exponent determined by fluctuations of the tissue surface. Our results propose a possible way of determining the mode of tissue growth from genetic tracing experiments.

In open water, social fish gather to form schools, in which fish generally align with each other. In this work, we study how this social behavior evolves when perturbed by artificial obstacles. We measure the behavior of a group of zebrafish in the presence of a periodic array of pillars. When the pillar density is low, the fish regroup with a typical interdistance and a well-polarized state with parallel orientations, similarly to their behavior in open-water conditions. Above a critical density of pillars, their social interactions, which are mostly based on vision, are screened and the fish spread randomly through the aquarium, orienting themselves along the free axes of the pillar lattice. The abrupt transition from natural to artificial orientation happens when the pillar interdistance is comparable to the social distance of the fish, i.e., their most probable interdistance. We develop a stochastic model of the relative orientation between fish pairs, taking into account alignment, antialignment, and tumbling, from a distribution biased by the environment. This model provides a good description of the experimental probability distribution of the relative orientation between the fish and captures the behavioral transition. Using the model to fit the experimental data provides qualitative information on the evolution of cognitive parameters, such as the alignment or the tumbling rates, as the pillar density increases. At high pillar density, we find that the artificial environment imposes its geometrical constraints to the fish school, drastically increasing the tumbling rate.

Phenotypic switching plays a crucial role in cell fate determination across various organisms. Recent experimental findings highlight the significance of protein compartmentalization via liquid-liquid phase separation in influencing such decisions. However, the precise mechanism through which phase separation regulates phenotypic switching remains elusive. To investigate this, we established a mathematical model that couples a phase separation process and a gene expression process with feedback. We used the chemical master equation theory and mean-field approximation to study the effects of phase separation on the gene expression products. We found that phase separation can cause bistability and bimodality. Furthermore, phase separation can control the bistable properties of the system, such as bifurcation points and bistable ranges. On the other hand, in stochastic dynamics, the droplet phase exhibits double peaks within a more extensive phase separation threshold range than the dilute phase, indicating the pivotal role of the droplet phase in cell fate decisions. These findings propose an alternative mechanism that influences cell fate decisions through the phase separation process. As phase separation is increasingly discovered in gene regulatory networks, related modeling research can help build biomolecular systems with desired properties and offer insights into explaining cell fate decisions.

During electrochemical signal transmission through synapses, triggered by an action potential (AP), a stochastic number of synaptic vesicles (SVs), called the "quantal content," release neurotransmitters in the synaptic cleft. It is widely accepted that the quantal content probability distribution is a binomial based on the number of ready-release SVs in the presynaptic terminal. But the latter number itself fluctuates due to its stochastic replenishment, hence the actual distribution of quantal content is unknown. We show that exact distribution of quantal content can be derived for general stochastic AP inputs in the steady state. For fixed interval AP train, we prove that the distribution is a binomial, and corroborate our predictions by comparison with electrophysiological recordings from MNTB-LSO synapses of juvenile mice. For a Poisson train, we show that the distribution is nonbinomial. Moreover, we find exact moments of the quantal content in the Poisson and other general cases, which may be used to obtain the model parameters from experiments.

Many physical and biological systems rely on the progression of material through multiple independent stages. In viral replication, for example, virions enter a cell to undergo a complex process comprising several disparate stages before the eventual accumulation and release of replicated virions. While such systems may have some control over the internal dynamics that make up this progression, a challenge for many is to regulate behavior under what are often highly variable external environments acting as system inputs. In this work, we study a simple analog of this problem through a linear multicompartment model subject to a stochastic input in the form of a mean-reverting Ornstein-Uhlenbeck process, a type of Gaussian process. By expressing the system as a multidimensional Gaussian process, we derive several closed-form analytical results relating to the covariances and autocorrelations of the system, quantifying the smoothing effect discrete compartments afford multicompartment systems. Semianalytical results demonstrate that feedback and feedforward loops can enhance system robustness, and simulation results probe the intractable problem of the first passage time distribution, which has specific relevance to eventual cell lysis in the viral replication cycle. Finally, we demonstrate that the smoothing seen in the process is a consequence of the discreteness of the system, and does not manifest in systems with continuous transport. While we make progress through analysis of a simple linear problem, many of our insights are applicable more generally, and our work enables future analysis into multicompartment processes subject to stochastic inputs.

Genomic regions can acquire heritable epigenetic states through unique histone modifications, which lead to stable gene expression patterns without altering the underlying DNA sequence. However, the relationship between chromatin conformational dynamics and epigenetic stability is poorly understood. In this paper, we propose kinetic models to investigate the dynamic fluctuations of histone modifications and the spatial interactions between nucleosomes. Our model explicitly incorporates the influence of chemical modifications on the structural stability of chromatin and the contribution of chromatin contacts to the cooperative nature of chemical reactions. Through stochastic simulations and analytical theory, we have discovered distinct steady-state outcomes in different kinetic regimes, resembling a dynamical phase transition. Importantly, we have validated that the emergence of this transition, which occurs on biologically relevant timescales, is robust against variations in model design and parameters. Our findings suggest that the viscoelastic properties of chromatin and the timescale at which it transitions from a gel-like to a liquidlike state significantly impact dynamic processes that occur along the one-dimensional DNA sequence.

By diversifying, cells in a clonal population can together overcome the limits of individuals. Diversity in single-cell growth rates allows the population to survive environmental stresses, such as antibiotics, and grow faster than the undiversified population. These functional cell-cell variations can arise stochastically, from noise in biochemical reactions, or deterministically, by asymmetrically distributing damaged components. While each of the mechanisms is well understood, the effect of the combined mechanisms is unclear. To evaluate the contribution of the deterministic component we developed a mathematical model by mapping the growing population to the Ising model. To analyze the combined effects of stochastic and deterministic contributions we introduced the analytical results of the Ising-mapping into an Euler-Lotka framework. Model results, confirmed by simulations and experimental data, show that deterministic cell-cell variations increase near-linearly with stress. As a consequence, we predict that the gain in population doubling time from cell-cell variations is primarily stochastic at low stress but may cross over to deterministic at higher stresses. Furthermore, we find that while the deterministic component minimizes population damage, stochastic variations antagonize this effect. Together our results may help identifying stress-tolerant pathogenic cells and thus inspire novel antibiotic strategies.

The COVID-19 pandemic has underscored the importance of understanding, forecasting, and avoiding infectious processes, as well as the necessity for understanding the diffusion and acceptance of preventative measures. Simple contagions, like virus transmission, can spread with a single encounter, while complex contagions, such as preventive social measures (e.g., wearing masks, social distancing), may require multiple interactions to propagate. This disparity in transmission mechanisms results in differing contagion rates and contagion patterns between viruses and preventive measures. Furthermore, the dynamics of complex contagions are significantly less understood than those of simple contagions. Stochastic models, integrating inherent variability and randomness, offer a way to elucidate complex contagion dynamics. This paper introduces a stochastic model for both simple and complex contagions and assesses its efficacy against ensemble simulations for homogeneous and heterogeneous threshold configurations. The model provides a unified framework for analyzing both types of contagions, demonstrating promising outcomes across various threshold setups on Erds-Rényi graphs.

Statistically inferred neuronal connections from observed spike train data are often skewed from ground truth by factors such as model mismatch, unobserved neurons, and limited data. Spike train covariances, sometimes referred to as "functional connections," are often used as a proxy for the connections between pairs of neurons, but reflect statistical relationships between neurons, not anatomical connections. Moreover, covariances are not causal: spiking activity is correlated in both the past and the future, whereas neurons respond only to synaptic inputs in the past. Connections inferred by maximum likelihood inference, however, can be constrained to be causal. However, we show in this work that the inferred connections in spontaneously active networks modeled by stochastic leaky integrate-and-fire networks strongly correlate with the covariances between neurons, and may reflect noncausal relationships, when many neurons are unobserved or when neurons are weakly coupled. This phenomenon occurs across different network structures, including random networks and balanced excitatory-inhibitory networks. We use a combination of simulations and a mean-field analysis with fluctuation corrections to elucidate the relationships between spike train covariances, inferred synaptic filters, and ground-truth connections in partially observed networks.

Complex molecular details of transcriptional regulation can be coarse-grained by assuming that reaction waiting times for promoter-state transitions, the mRNA synthesis, and the mRNA degradation follow general distributions. However, how such a generalized two-state model is analytically solved is a long-standing issue. Here we first present analytical formulas of burst-size distributions for this model. Then, we derive an iterative equation for the mRNA moment-generating function, by which mRNA raw and binomial moments of any order can be conveniently calculated. The analytical results obtained in the special cases of phase-type waiting-time distributions not only provide insights into the mechanisms of complex transcriptional regulations but also bring conveniences for experimental data-based statistical inferences.

Ultimately, the eventual extinction of any biological population is an inevitable outcome. While extensive research has focused on the average time it takes for a population to go extinct under various circumstances, there has been limited exploration of the distributions of extinction times and the likelihood of significant fluctuations. Recently, Hathcock and Strogatz [D. Hathcock and S. H. Strogatz, Phys. Rev. Lett. 128, 218301 (2022)0031-900710.1103/PhysRevLett.128.218301] identified Gumbel statistics as a universal asymptotic distribution for extinction-prone dynamics in a stable environment. In this study we aim to provide a comprehensive survey of this problem by examining a range of plausible scenarios, including extinction-prone, marginal (neutral), and stable dynamics. We consider the influence of demographic stochasticity, which arises from the inherent randomness of the birth-death process, as well as cases where stochasticity originates from the more pronounced effect of random environmental variations. Our work proposes several generic criteria that can be used for the classification of experimental and empirical systems, thereby enhancing our ability to discern the mechanisms governing extinction dynamics. Employing these criteria can help clarify the underlying mechanisms driving extinction processes.

The telegraph model is the standard model of stochastic gene expression, which can be solved exactly to obtain the distribution of mature RNA numbers per cell. A modification of this model also leads to an analytical distribution of nascent RNA numbers. These solutions are routinely used for the analysis of single-cell data, including the inference of transcriptional parameters. However, these models neglect important mechanistic features of transcription elongation, such as the stochastic movement of RNA polymerases and their steric (excluded-volume) interactions. Here we construct a model of gene expression describing promoter switching between inactive and active states, binding of RNA polymerases in the active state, their stochastic movement including steric interactions along the gene, and their unbinding leading to a mature transcript that subsequently decays. We derive the steady-state distributions of the nascent and mature RNA numbers in two important limiting cases: constitutive expression and slow promoter switching. We show that RNA fluctuations are suppressed by steric interactions between RNA polymerases, and that this suppression can in some instances even lead to sub-Poissonian fluctuations; these effects are most pronounced for nascent RNA and less prominent for mature RNA, since the latter is not a direct sensor of transcription. We find a relationship between the parameters of our microscopic mechanistic model and those of the standard models that ensures excellent consistency in their prediction of the first and second RNA number moments over vast regions of parameter space, encompassing slow, intermediate, and rapid promoter switching, provided the RNA number distributions are Poissonian or super-Poissonian. Furthermore, we identify the limitations of inference from mature RNA data, specifically showing that it cannot differentiate between highly distinct RNA polymerase traffic patterns on a gene.

We develop a finite-cell model of tumor natural selection dynamics to investigate the stochastic fluctuations associated with multiple rounds of adaptive chemotherapy. The adaptive cycles are designed to avoid chemoresistance in the tumor by managing the ecological mechanism of competitive release of a resistant subpopulation. Our model is based on a three-component evolutionary game played among healthy (H), sensitive (S), and resistant (R) populations of N cells, with a chemotherapy control parameter, C(t), which we use to dynamically impose selection pressure on the sensitive subpopulation to slow tumor growth and manage competitive release of the resistant population. The adaptive chemoschedule is designed based on the deterministic (N→∞) adjusted replicator dynamical system, then implemented using the finite-cell stochastic frequency dependent Moran process model (N=10K-50K) to ascertain the cumulative effect of the stochastic fluctuations on the efficacy of the adaptive schedules over multiple rounds. We quantify the stochastic fixation probability regions of the R and S populations in the HSR trilinear phase plane as a function of the control parameter C∈[0,1], showing that the size of the R region increases with increasing C. We then implement an adaptive time-dependent schedule C(t) for the stochastic model and quantify the variances (using principal component coordinates) associated with the evolutionary cycles over multiple rounds of adaptive therapy. The variances increase subquadratically through several rounds before the evolutionary cycle begins to break down. Despite this, we show the stochastic adaptive schedules are more effective at delaying resistance than standard maximum tolerated dose and low-dose metronomic schedules. The simplified low-dimensional model provides some insights on how well multiple rounds of adaptive therapies are likely to perform over a range of tumor sizes (i.e., different values of N) if the goal is to maintain a sustained balance among competing subpopulations of cells to avoid chemoresistance via competitive release in a stochastic environment.

The assumption of constant population size is central in population genetics. It led to a large body of results that is robust to modeling choices and that has proven successful to understand evolutionary dynamics. In reality, allele frequencies and population size are both determined by the interaction between a population and the environment. Relaxing the constant-population assumption has two big drawbacks. It increases the technical difficulty of the analysis, and it requires specifying a mechanism for the saturation of the population size, possibly making the results contingent on model details. Here we develop a framework that encompasses a great variety of systems with an arbitrary mechanism for population growth limitation. By using techniques based on scale separation for stochastic processes, we are able to calculate analytically properties of evolutionary trajectories, such as the fixation probability. Remarkably, these properties assume a universal form with respect to our framework, which depends on only three parameters related to the intergeneration timescale, the invasion fitness, and the carrying capacity of the strains. In other words, different systems, such as Lotka-Volterra or a chemostat model (contained in our framework), share the same evolutionary outcomes after a proper remapping of their parameters. An important and surprising consequence of our results is that the direction of selection can be inverted, with a population evolving to reach lower values of invasion fitness.

Generalization is one of the most important problems in deep learning, where there exist many low-loss solutions due to overparametrization. Previous empirical studies showed a strong correlation between flatness of the loss landscape at a solution and its generalizability, and stochastic gradient descent (SGD) is crucial in finding the flat solutions. To understand the effects of SGD, we construct a simple model whose overall loss landscape has a continuous set of degenerate (or near-degenerate) minima and the loss landscape for a minibatch is approximated by a random shift of the overall loss function. By direct simulations of the stochastic learning dynamics and solving the underlying Fokker-Planck equation, we show that due to its strong anisotropy the SGD noise introduces an additional effective loss term that decreases with flatness and has an overall strength that increases with the learning rate and batch-to-batch variation. We find that the additional landscape-dependent SGD loss breaks the degeneracy and serves as an effective regularization for finding flat solutions. As a result, the flatness of the overall loss landscape increases during learning and reaches a higher value (flatter minimum) for a larger SGD noise strength before the noise strength reaches a critical value when the system fails to converge. These results, which are verified in realistic neural network models, elucidate the role of SGD for generalization, and they may also have important implications for hyperparameter selection for learning efficiently without divergence.

First-passage properties of continuous stochastic processes confined in a one-dimensional interval are well described. However, for jump processes (discrete random walks), the characterization of the corresponding observables remains elusive, despite their relevance in various contexts. Here we derive exact asymptotic expressions for the leftward, rightward, and complete exit-time distributions from the interval [0,x] for symmetric jump processes starting from x_{0}=0, in the large x and large time limit. We show that both the leftward probability F_{[under 0]̲,x}(n) to exit through 0 at step n and rightward probability F_{0,[under x]̲}(n) to exit through x at step n exhibit a universal behavior dictated by the large-distance decay of the jump distribution parametrized by the Levy exponent μ. In particular, we exhaustively describe the n≪(x/a_{μ})^{μ} and n≫(x/a_{μ})^{μ} limits and obtain explicit results in both regimes. Our results finally provide exact asymptotics for exit-time distributions of jump processes in regimes where continuous limits do not apply.

The Ornstein-Uhlenbeck process is interpreted as Brownian motion in a harmonic potential. This Gaussian Markov process has a bounded variance and admits a stationary probability distribution, in contrast to the standard Brownian motion. It also tends to a drift towards its mean function, and such a process is called mean reverting. Two examples of the generalized Ornstein-Uhlenbeck process are considered. In the first one, we study the Ornstein-Uhlenbeck process on a comb model, as an example of the harmonically bounded random motion in the topologically constrained geometry. The main dynamical characteristics (as the first and the second moments) and the probability density function are studied in the framework of both the Langevin stochastic equation and the Fokker-Planck equation. The second example is devoted to the study of the effects of stochastic resetting on the Ornstein-Uhlenbeck process, including stochastic resetting in the comb geometry. Here the nonequilibrium stationary state is the main question in task, where the two divergent forces, namely, the resetting and the drift towards the mean, lead to compelling results in the cases of both the Ornstein-Uhlenbeck process with resetting and its generalization on the two-dimensional comb structure.

Purkinje cells exhibit a reduction of the mean firing rate at intermediate-noise intensities, which is somewhat reminiscent of the response enhancement known as "stochastic resonance" (SR). Although the comparison with the stochastic resonance ends here, the current phenomenon has been given the name "inverse stochastic resonance" (ISR). Recent research has demonstrated that the ISR effect, like its close relative "nonstandard SR" [or, more correctly, noise-induced activity amplification (NIAA)], has been shown to stem from the weak-noise quenching of the initial distribution, in bistable regimes where the metastable state has a larger attraction basin than the global minimum. To understand the underlying mechanism of the ISR and NIAA phenomena, we study the probability distribution function of a one-dimensional system subjected to a bistable potential that has the property of symmetry, i.e., if we change the sign of one of its parameters, we can obtain both phenomena with the same properties in the depth of the wells and the width of their basins of attraction subjected to Gaussian white noise with variable intensity. Previous work has shown that one can theoretically determine the probability distribution function using the convex sum between the behavior at small and high noise intensities. To determine the probability distribution function more precisely, we resort to the "weighted ensemble Brownian dynamics simulation" model, which provides an accurate estimate of the probability distribution function for both low and high noise intensities and, most importantly, for the transition of both behaviors. In this way, on the one hand, we show that both phenomena emerge from a metastable system where, in the case of ISR, the global minimum of the system is in a state of lower activity, while in the case of NIAA, the global minimum is in a state of increased activity, the importance of which does not depend on the width of the basins of attraction. On the other hand, we see that quantifiers such as Fisher information, statistical complexity, and especially Shannon entropy fail to distinguish them, but they show the existence of the mentioned phenomena. Thus, noise management may well be a mechanism by which Purkinje cells find an efficient way to transmit information in the cerebral cortex.

Linear diffusions are used to model a large number of stochastic processes in physics, including small mechanical and electrical systems perturbed by thermal noise, as well as Brownian particles controlled by electrical and optical forces. Here we use techniques from large deviation theory to study the statistics of time-integrated functionals of linear diffusions, considering three classes of functionals or observables relevant for nonequilibrium systems which involve linear or quadratic integrals of the state in time. For these, we derive exact results for the scaled cumulant generating function and the rate function, characterizing the fluctuations of observables in the long-time limit, and study in an exact way the set of paths or effective process that underlies these fluctuations. The results give a complete description of how fluctuations arise in linear diffusions in terms of effective forces that remain linear in the state or, alternatively, in terms of fluctuating densities and currents that solve Riccati-type equations. We illustrate these results using two common nonequilibrium models, namely, transverse diffusions in two dimensions involving a nonconservative rotating force, and two interacting particles in contact with heat baths at different temperatures.

Despite the huge number of neurons composing a brain network, ongoing activity of local cell assemblies is intrinsically stochastic. Fluctuations in their instantaneous rate of spike firing ν(t) scale with the size of the assembly and persist in isolated networks, i.e., in the absence of external sources of noise. Although deterministic chaos due to the quenched disorder of the synaptic couplings underlies this seemingly stochastic dynamics, an effective theory for the network dynamics of a finite assembly of spiking neurons is lacking. Here, we fill this gap by extending the so-called population density approach including an activity- and size-dependent stochastic source in the Fokker-Planck equation for the membrane potential density. The finite-size noise embedded in this stochastic partial derivative equation is analytically characterized leading to a self-consistent and nonperturbative description of ν(t) valid for a wide class of spiking neuron networks. Power spectra of ν(t) are found in excellent agreement with those from detailed simulations both in the linear regime and across a synchronization phase transition, when a size-dependent smearing of the critical dynamics emerges.

While changes in resonant Raman scattering measurements are commonly used to measure the effect of chemical functionalization on single-walled carbon nanotubes, the precise effects of functionalization on these spectra have yet to be clearly identified. In this density functional theory study, we explore the effects of functionalization on both the nanotube resonance energy and frequency shifts in radial breathing mode. Charge transfer effects cause a shift in the first Van Hove singularity spacings, and hence resonance excitation energy, and lead to a decrease in the radial breathing mode frequency, notably when the Fermi level decreases. By varying stochastically the effective mass of carbon atoms in the tube, we simulate the mass effect of functionalization on breathing mode frequency. Finally, full density functional calculations are performed for different nanotubes with varying functional group distribution and concentration using fluorination and hydrogenation, allowing us to determine overall effect on radial breathing mode and charge transfer. The results concur well with experiment, and we discuss the importance when using Raman spectroscopy to interpret experimental functionalization treatments. [ABSTRACT FROM AUTHOR]

We show that the steady-state entropy production rate of a stochastic process is inversely proportional to the minimal time needed to decide on the direction of the arrow of time. Here we apply Wald's sequential probability ratio test to optimally decide on the direction of time's arrow in stationary Markov processes. Furthermore, the steady-state entropy production rate can be estimated using mean first-passage times of suitable physical variables. We derive a first-passage time fluctuation theorem which implies that the decision time distributions for correct and wrong decisions are equal. Our results are illustrated by numerical simulations of two simple examples of nonequilibrium processes. [ABSTRACT FROM AUTHOR]

A predator-prey model of dual populations with stochastic oscillators is presented. A linear cross-coupling between the two populations is introduced following the coupling between the motions of a Wilberforce pendulum in two dimensions: one in the longitudinal and the other in torsional plain. Within each population a Kuramoto-type competition between the phases is assumed. Thus, the synchronization state of the whole system is controlled by these two types of competitions. The results of the numerical simulations show that by adding the linear cross-coupling interactions predator-prey oscillations between the two populations appear, which results in self-regulation of the system by a transfer of synchrony between the two populations. The model represents several important features of the dynamical interplay between the drift wave and zonal flow turbulence in magnetically confined plasmas, and a novel interpretation of the coupled dynamics of drift wave-zonal flow turbulence using synchronization of stochastic oscillator is discussed. [ABSTRACT FROM AUTHOR]

The finest state-space resolution that can be achieved in a physical dynamical system is limited by the presence of noise. In the weak-noise approximation, the stochastic neighborhoods of deterministic periodic orbits can be computed from distributions stationary under the action of a local Fokker-Planck operator and its adjoint. We derive explicit formulas for widths of these distributions in the case of chaotic dynamics, when the periodic orbits are hyperbolic. The resulting neighborhoods form a basis for functions on the attractor. The global stationary distribution, needed for calculation of long-time expectation values of observables, can be expressed in this basis. [ABSTRACT FROM AUTHOR]

We study the activation process in large assemblies of type II excitable units whose dynamics is influenced by two independent noise terms. The mean-field approach is applied to explicitly demonstrate that the assembly of excitable units can itself exhibit macroscopic excitable behavior. In order to facilitate the comparison between the excitable dynamics of a single unit and an assembly, we introduce three distinct formulations of the assembly activation event. Each formulation treats different aspects of the relevant phenomena, including the thresholdlike behavior and the role of coherence of individual spikes. Statistical properties of the assembly activation process, such as the mean time-to-first pulse and the associated coefficient of variation, are found to be qualitatively analogous for all three formulations, as well as to resemble the results for a single unit. These analogies are shown to derive from the fact that global variables undergo a stochastic bifurcation from the stochastically stable fixed point to continuous oscillations. Local activation processes are analyzed in the light of the competition between the noise-led and the relaxation-driven dynamics. We also briefly report on a system-size antiresonant effect displayed by the mean time-to-first pulse. [ABSTRACT FROM AUTHOR]

We consider the coaction of two distinct noise sources on the activation process of a single excitable unit and two interacting excitable units, which are mathematically described by the Fitzhugh-Nagumo equations. We determine the most probable activation paths around which the corresponding stochastic trajectories are clustered. The key point lies in introducing appropriate boundary conditions that are relevant for a class II excitable unit, which can be immediately generalized also to scenarios involving two coupled units. We analyze the effects of the two noise sources on the statistical features of the activation process, in particular demonstrating how these are modified due to the linear or nonlinear form of interactions. Universal properties of the activation process are qualitatively discussed in the light of a stochastic bifurcation that underlies the transition from a stochastically stable fixed point to continuous oscillations. [ABSTRACT FROM AUTHOR]

We study the effects of uniform time delays on the extreme fluctuations in stochastic synchronization and coordination problems with linear couplings in complex networks. We obtain the average size of the fluctuations at the nodes from the behavior of the underlying modes of the network. We then obtain the scaling behavior of the extreme fluctuations with system size, as well as the distribution of the extremes on complex networks, and compare them to those on regular one-dimensional lattices. For large complex networks, when the delay is not too close to the critical one, fluctuations at the nodes effectively decouple, and the limit distributions converge to the Fisher-Tippett-Gumbel density. In contrast, fluctuations in low-dimensional spatial graphs are strongly correlated, and the limit distribution of the extremes is the Airy density. Finally, we also explore the effects of nonlinear couplings on the stability and on the extremes of the synchronization landscapes. [ABSTRACT FROM AUTHOR]

Randomness is ubiquitous in nature. From single-molecule biochemical reactions to macroscale biological systems, stochasticity permeates individual interactions and often regulates emergent properties of the system. While such systems are regularly studied from a modeling viewpoint using stochastic simulation algorithms, numerous potential analytical tools can be inherited from statistical and quantum physics, replacing randomness due to quantum fluctuations with low-copy-number stochasticity. Nevertheless, classical studies remained limited to the abstract level, demonstrating a more general applicability and equivalence between systems in physics and biology rather than exploiting the physics tools to study biological systems. Here the Fock space representation, used in quantum mechanics, is combined with the symbolic algebra of creation and annihilation operators to consider explicit solutions for the chemical master equations describing small, well-mixed, biochemical, or biological systems. This is illustrated with an exact solution for a Michaelis-Menten single enzyme interacting with limited substrate, including a consideration of very short time scales, which emphasizes when stiffness is present even for small copy numbers. Furthermore, we present a general matrix representation for Michaelis-Menten kinetics with an arbitrary number of enzymes and substrates that, following diagonalization, leads to the solution of this ubiquitous, nonlinear enzyme kinetics problem. For this, a flexible symbolic maple code is provided, demonstrating the prospective advantages of this framework compared to stochastic simulation algorithms. This further highlights the possibilities for analytically based studies of stochastic systems in biology and chemistry using tools from theoretical quantum physics. [ABSTRACT FROM AUTHOR]

The calculation of the steady-state probability density for multidimensional stochastic systems that do not obey detailed balance is a difficult problem. Here we present the analytical derivation of the stationary joint and various marginal probability densities for a stochastic neuron model with adaptation current. Our approach assumes weak noise but is valid for arbitrary adaptation strength and time scale. The theory predicts several effects of adaptation on the statistics of the membrane potential of a tonically firing neuron: (i) a membrane potential distribution with a convex shape, (ii) a strongly increased probability of hyperpolarized membrane potentials induced by strong and fast adaptation, and (iii) a maximized variability associated with the adaptation current at a finite adaptation time scale. [ABSTRACT FROM AUTHOR]

Markov processes restarted or reset at random times to a fixed state or region in space have been actively studied recently in connection with random searches, foraging, and population dynamics. Here we study the large deviations of time-additive functions or observables of Markov processes with resetting. By deriving a renewal formula linking generating functions with and without resetting, we are able to obtain the rate function of such observables, characterizing the likelihood of their fluctuations in the long-time limit. We consider as an illustration the large deviations of the area of the Ornstein-Uhlenbeck process with resetting. Other applications involving diffusions, random walks, and jump processes with resetting or catastrophes are discussed. [ABSTRACT FROM AUTHOR]

We numerically demonstrate the dynamic stabilization of a strongly interacting many-body bosonic system which can be realized by coupled ultracold atom-molecule gases. The system is initialized to an unstable equilibrium state corresponding to a saddle point in the classical phase space, where subsequent free evolution gives rise to atom-molecule conversion. To control and stabilize the system, periodic modulation is applied that suddenly shifts the relative phase between the atomic and the molecular modes and limits their further interconversion. The stability diagram for the range of modulation amplitudes and periods that stabilize the dynamics is given. The validity of the phase diagram obtained from the time-average calculation is discussed by using the orbit tracking method, and the difference in contrast with the maximum absolute deviation analysis is shown as well. A brief quantum analysis shows that quantum fluctuations can put serious limitations on the applicability of the mean-field results. [ABSTRACT FROM AUTHOR]

We study the thermostatistics of a damped bimodal particle, i.e., a particle of mass m subject to a work reservoir that is analytically represented by the telegraph noise. Because of the colored nature of the noise, it does not fit the Lévy-Itô class of stochastic processes, making this system an instance of a nonequilibrium system in contact with a non-Gaussian external reservoir. We obtain the statistical description of the position and velocity, namely in the stationary state, as well as the (time-dependent) statistics of the energy fluxes in the system considering no constraints on the telegraph noise features. With that result we are able to give an account of the statistical properties of the large deviations of the injected and dissipated power that can change from sub-Gaussianity to super-Gaussianity depending on the color of the noise. By properly defining an effective temperature for this system, T, we are capable of obtaining an equivalent entropy production-exchange rate equal to the ratio between the dissipation of the medium, γ, and the mass of the particle, m, a relation that concurs with the case of a standard thermal reservoir at temperature, T = T. [ABSTRACT FROM AUTHOR]

A zero-dimensional system that is affected by field-dependent fluctuations evolves toward the field's values in which the fluctuations' effect is minimized. For a high enough noise intensity, it causes an exchange of roles between the stable and unstable state. In this paper, we report symmetry breaking in two stable states, but one of them stabilized by the fluctuations while exchanging its role with a previously stable state. [ABSTRACT FROM AUTHOR]

We calculate the reaction rate for stochastically gated ligands diffusing in a two-dimensional and a three-dimensional bounded domain with a single small target. Each ligand independently switches between an open and a closed state according to a two-state Markov process; a reaction between ligand and target can only occur when the former is an open state. In the large-time limit the reaction-rate is an exponentially decaying function of time, whose rate of decay is given by the principal eigenvalue of the Laplacian. We calculate the principal eigenvalue using matched asymptotics and determine the leading-order reduction in the reaction rate due to stochastic gating. We also develop a probabilistic interpretation of the reaction rate in terms of the first-passage time density to the target. [ABSTRACT FROM AUTHOR]

The likelihood that a mutant fixates in the wild population, i.e., fixation probability, has been intensively studied in evolutionary game theory, where individuals' fitness is frequency dependent. However, it is of limited interest when it takes long to take over. Thus the speed of evolution becomes an important issue. In general, it is still unclear how fixation times are affected by the population structure, although the fixation times have already been addressed in the well-mixed populations. Here we theoretically address this issue by pair approximation and diffusion approximation on regular graphs. It is shown (i) that under neutral selection, both unconditional and conditional fixation time are shortened by increasing the number of neighbors; (ii) that under weak selection, for the simplified prisoner's dilemma game, if benefit-to-cost ratio exceeds the degree of the graph, then the unconditional fixation time of a single cooperator is slower than that in the neutral case; and (iii) that under weak selection, for the conditional fixation time, limited neighbor size dilutes the counterintuitive stochastic slowdown which was found in well-mixed populations. Interestingly, we find that all of our results can be interpreted as that in the well-mixed population with a transformed payoff matrix. This interpretation is also valid for both death-birth and birth-death processes on graphs. This interpretation bridges the fixation time in the structured population and that in the well-mixed population. Thus it opens the avenue to investigate the challenging fixation time in structured populations by the known results in well-mixed populations. [ABSTRACT FROM AUTHOR]

We investigate three-dimensional O(N) spin models driven with a uniform velocity over a random field. Within a spin-wave approximation, it is shown that in the strong driving regime the model with N = 2 exhibits a quasi-long-range order in which the spatial correlation function decays in a power-law form. Furthermore, for the cases that N = 2 and 3, we numerically demonstrate a nonequilibrium phase transition between the quasi-long-range order phase and the disordered phase, which turns out to resemble the Kosterlitz-Thouless transition in the two-dimensional pure XY model in equilibrium. [ABSTRACT FROM AUTHOR]

We analyze the performance of quantum annealing as a heuristic optimization method to find the absolute minimum of various continuous models, including landscapes with only two wells and also models with many competing minima and with disorder. The simulations performed using a projective quantum Monte Carlo (QMC) algorithm are compared with those based on the finite-temperature path-integral QMC technique and with classical annealing. We show that the projective QMC algorithm is more efficient than the finite-temperature QMC technique, and that both are inferior to classical annealing if this is performed with appropriate long-range moves. However, as the difficulty of the optimization problem increases, classical annealing loses efficiency, while the projective QMC algorithm keeps stable performance and is finally the most effective optimization tool. We discuss the implications of our results for the outstanding problem of testing the efficiency of adiabatic quantum computers using stochastic simulations performed on classical computers. [ABSTRACT FROM AUTHOR]

We have studied Markov processes on denumerable state space and continuous time. We found that all these processes are connected via gauge transformations. We have used this result before as a method to resolve equations, included the case in a previous work in which the sample space is time-dependent [Phys. Rev. E 90, 022125 (2014)]. We found a general solution through dilation of the state space, although the prior probability distribution of the states defined in this new space takes smaller values with respect to that in the initial problem. The gauge (local) group of dilations modifies the distribution on the dilated space to restore the original process. In this work, we show how the Markov process in general could be linked via gauge (local) transformations, and we present some illustrative examples for this result. [ABSTRACT FROM AUTHOR]

Recovering a stochastic process from noisy ensembles of single-particle trajectories is resolved here using the coarse-grained Langevin equation as a model. The massive redundancy contained in single-particle tracking data allows recovering local parameters of the underlying physical model. We use several parametric and nonparametric estimators to compute the first and second moments of the process, to recover the local drift, its derivative, and the diffusion tensor, and to deconvolve the instrumental from the physical noise. We use numerical simulations to also explore the range of validity for these estimators. The present analysis allows defining what can exactly be recovered from statistics of super-resolution microscopy trajectories used for characterizing molecular trafficking underlying cellular functions. [ABSTRACT FROM AUTHOR]

The stochastic simulation algorithm (SSA) and the corresponding Monte Carlo (MC) method are among the most common approaches for studying stochastic processes. They relies on knowledge of interevent probability density functions (PDFs) and on information about dependencies between all possible events. Analytical representations of a PDF are difficult to specify in advance, in many real life applications. Knowing the shapes of PDFs, and using experimental data, different optimization schemes can be applied in order to evaluate probability density functions and, therefore, the properties of the studied system. Such methods, however, are computationally demanding, and often not feasible. We show that, in the case where experimentally accessed properties are directly related to the frequencies of events involved, it may be possible to replace the heavy Monte Carlo core of optimization schemes with an analytical solution. Such a replacement not only provides a more accurate estimation of the properties of the process, but also reduces the simulation time by a factor of order of the sample size (at least ≈104). The proposed analytical approach is valid for any choice of PDF. The accuracy, computational efficiency, and advantages of the method over MC procedures are demonstrated in the exactly solvable case and in the evaluation of branching fractions in controlled radical polymerization (CRP) of acrylic monomers. This polymerization can be modeled by a constrained stochastic process. Constrained systems are quite common, and this makes the method useful for various applications. [ABSTRACT FROM AUTHOR]

An alternative application of duality relations of stochastic processes is demonstrated. Although conventional usages of the duality relations need analytical solutions for the dual processes, here I employ numerical solutions of the dual processes and investigate the usefulness. As a demonstration, estimation problems of hidden variables in stochastic differential equations are discussed. Employing algebraic probability theory, a little complicated birth-death process is derived from the stochastic differential equations, and an estimation method based on the ensemble Kaiman filter is proposed. As a result, the possibility for making faster computational algorithms based on the duality concepts is shown. [ABSTRACT FROM AUTHOR]

To understand methodological features of the detrended fluctuation analysis (DFA) using a higher-order polynomial fitting, we establish the direct connection between DFA and Fourier analysis. Based on an exact calculation of the single-frequency response of the DFA, the following facts are shown analytically: (1) in the analysis of stochastic processes exhibiting a power-law scaling of the power spectral density (PSD), S(f) ~ f-β, a higher-order detrending in the DFA has no adverse effect in the estimation of the DFA scaling exponent a, which satisfies the scaling relation α = (β + 1)/2; (2) the upper limit of the scaling exponents detectable by the DFA depends on the order of polynomial fit used in the DFA, and is bounded by m + 1, where m is the order of the polynomial fit; (3) the relation between the time scale in the DFA and the corresponding frequency in the PSD are distorted depending on both the order of the DFA and the frequency dependence of the PSD. We can improve the scale distortion by introducing the corrected time scale in the DFA corresponding to the inverse of the frequency scale in the PSD. In addition, our analytical approach makes it possible to characterize variants of the DFA using different types of detrending. As an application, properties of the detrending moving average algorithm are discussed. [ABSTRACT FROM AUTHOR]

Two types of random evolution processes are studied for ensembles of the standard map with driving parameter K that determines its degree of stochasticity. For one type of process the parameter K is chosen at random from a Gaussian distribution and is then kept fixed, while for the other type it varies from step to step. In addition, noise that can be arbitrarily weak is added. The ensemble average and the average over noise of the diffusion coefficient are calculated for both types of processes. These two types of processes are relevant for two types of experimental situations as explained in the paper. Both types of processes destroy fine details of the dynamics, and the second process is found to be more effective in destroying the fine details. We hope that this work is a step in the efforts for developing a statistical theory for systems with mixed phase space (regular in some parts and chaotic in other parts). [ABSTRACT FROM AUTHOR]

We generalize the description of the dynamics of the order book of financial markets in terms of a Brownian particle embedded in a fluid of incoming, exiting, and annihilating particles by presenting a model of the velocity on each side (buy and sell) independently. The improved model builds on the time-averaged number of particles in the inner layer and its change per unit time, where the inner layer is revealed by the correlations between price velocity and change in the number of particles (limit orders). This allows us to introduce the Knudsen number of the financial Brownian particle motion and its asymmetric version (on the buy and sell sides). Not being considered previously, the asymmetric Knudsen numbers are crucial in finance in order to detect asymmetric price changes. The Knudsen numbers allows us to characterize the conditions for the market dynamics to be correctly described by a continuous stochastic process. Not questioned until now for large liquid markets such as the USD-JPY and EUR-USD exchange rates, we show that there are regimes when the Knudsen numbers are so high that discrete particle effects dominate, such as during market stresses and crashes. We document the presence of imbalances of particles depletion rates on the buy and sell sides that are associated with high Knudsen numbers and violent directional price changes. This indicator can detect the direction of the price motion at the early stage while the usual volatility risk measure is blind to the price direction. [ABSTRACT FROM AUTHOR]

The activity of pancreatic β cells can be described by biological networks of coupled nonlinear oscillators that, via electrochemical synchronization, release insulin in response to augmented glucose levels. In this work, we analyze the emergent behavior of regular and percolated β-cells clusters through a stochastic mathematical model where "functional" networks arise. We show that the emergence and robustness of the synchronized dynamics depend both on intrinsic and extrinsic parameters. In particular, cellular noise level, glucose concentration, network spatial architecture, and cell-to-cell coupling strength are the key factors for the generation of a rhythmic and robust activity. Their role in the functional network topology associated with β-cells clusters is analyzed and discussed. [ABSTRACT FROM AUTHOR]

We describe the lifetimes associated with the stochastic evolution from an unstable uniform state to a patterned one when the time evolution of the field is controlled by a nonlocal Fisher equation. A small noise is added to the evolution equation to define the lifetimes and to calculate the mean first-passage time of the stochastic field through a given threshold value, before the patterned steady state is reached. In order to obtain analytical results we introduce a stochastic multiscale perturbation expansion. This multiscale expansion can also be used to tackle multiplicative stochastic partial differential equations. A critical slowing down is predicted for the marginal case when the Fourier phase of the unstable initial condition is null. We carry out Monte Carlo simulations to show the agreement with our theoretical predictions. Analytic results for the bifurcation point and asymptotic analysis of traveling wave-front solutions are included to get insight into the noise-induced transition phenomena mediated by invading fronts. [ABSTRACT FROM AUTHOR]

We present theoretical calculations of the ensemble-averaged (or effective or coherent) wave field propagating in a heterogeneous medium considered as one realization of a random process. In the literature, it is usually assumed that heterogeneity can be accounted for by a random scalar function of the space coordinates, termed the potential. Physically, this amounts to replacing the constant wave speed in Helmholtz' equation by a space-dependent speed. In the case of acoustic waves, we show that this approach leads to incorrect results for the scattering mean free path, no matter how weak the fluctuations. The detailed calculation of the coherent wave field must take into account both a scalar and an operator part in the random potential. When both terms have identical amplitudes, the correct value for the scattering mean free paths is shown to be more than 4 times smaller (13/3, precisely) in the low-frequency limit, whatever the shape of the correlation function. Based on the diagrammatic approach of multiple scattering, theoretical results are obtained for the self-energy and mean free path within Bourret's and on-shell approximations. They are confirmed by numerical experiments. [ABSTRACT FROM AUTHOR]

Neurons communicate with each other dynamically; how such communications lead to consciousness remains unclear. Here, we present a theoretical model to understand the dynamic nature of sensory activity and information integration in a hierarchical network, in which edges are stochastically defined by a single parameter p representing the percolation probability of information transmission. We validate the model by comparing the transmitted and original signal distributions, and we show that a basic version of this model can reproduce key spectral features clinically observed in electroencephalographic recordings of transitions from conscious to unconscious brain activities during general anesthesia. As p decreases, a steep divergence of the transmitted signal from the original was observed, along with a loss of signal synchrony and a sharp increase in information entropy in a critical manner; this resembles the precipitous loss of consciousness during anesthesia. The model offers mechanistic insights into the emergence of information integration from a stochastic process, laying the foundation for understanding the origin of cognition. [ABSTRACT FROM AUTHOR]