The kinetic uncertainty relation (KUR) is a trade-off relation between the precision of an observable and the mean dynamical activity in a fixed time interval for a time-homogeneous and continuous-time Markov chain. In this letter, we derive the KUR on the first passage time for the time-integrated current from the information inequality at stopping times. The relation shows that the precision of the first passage time is bounded from above by the mean number of jumps up to that time. We apply our result to simple systems and demonstrate that the activity constraint gives a tighter bound than the thermodynamic uncertainty relation in the regime far from equilibrium.
A Universal Control Budget for First-Passage Kinetics
Center for Systems Biology Dresden（德累斯顿系统生物学中心）；Max Planck Institute for the Physics of Complex Systems（马克斯·普朗克复杂系统物理研究所）；Max Planck Institute of Molecular Cell Biology and Genetics（马克斯·普朗克分子细胞生物学与遗传学研究所）；Department of Physics, Graduate School of Science, The University of Tokyo（东京大学理学研究科物理学系）
We consider the first-passage problem for $N$ identical independent particles that are initially released uniformly in a finite domain $Ω$ and then diffuse toward a reactive area $Γ$, which can be part of the outer boundary of $Ω$ or a reaction centre in the interior of $Ω$. For both cases of perfect and partial reactions, we obtain the explicit formulas for the first two moments of the fastest first-passage time (fFPT), i.e., the time when the first out of the $N$ particles reacts with $Γ$. Moreover, we investigate the full probability density of the fFPT. We discuss a significant role of the…
DNA replication fidelity is a critical issue in molecular biology. Biochemical experiments have provided key insights on the mechanism of fidelity control by DNAP in the past decades, whereas systematic theoretical studies on this issue began only recently. Because of the underlying difficulties of mathematical treatment, comprehensive surveys on the template-specific replication kinetics are still rare. Here we proposed a first-passage approach to address this problem, in particular the positional fidelity, for complicated processes with high-order neighbor effects. Under biologically-relevan…
Markov processes are widely used models for investigating kinetic networks. Here we collate and present a variety of results pertaining to kinetic network models, in a unified framework. The aim is to lay out explicit links between several important quantities commonly studied in the field, including mean first passage times (MFPTs), correlation functions and the Kemeny constant, and highlight some of the subtleties which are often overlooked in the literature, while providing new insights. Results include (i) a simple physical interpretation of the Kemeny constant, (ii) a recipe to infer equi…
The first passage statistics of a continuous time random walker with Poisson distributed jumps on one and two dimensional infinite lattices is investigated. An exact expression for the probability of first return to the origin in one dimension is derived for a symmetric random walker as well as a biased random walker. The Laplace transform of the occupation probability of a site for a symmetric random walker on a two dimensional lattice is identified with the lattice Green's function for a square lattice. This allows computation of the exact first passage distribution to any arbitrary site on …
Many out of equilibrium phenomena, such as diffusion-limited reactions or target search processes, are controlled by first-passage events. So far the general determination of the mean first-passage time (FPT) to a target in confinement has left aside aging processes, involved in contexts as varied as glassy dynamics, tracer diffusion in biological membranes or transport of cold atoms in optical lattices. Here we consider general non-Markovian scale-invariant processes in arbitrary dimension, displaying aging, and demonstrate that all the moments of the FPT obey universal scalings with the conf…
Persistence, defined as the probability that a fluctuating signal has not reached a threshold up to a given observation time, plays a crucial role in the theory of random processes. It quantifies the kinetics of processes as varied as phase ordering, reaction diffusion or interface relaxation dynamics. The fact that persistence can decay algebraically with time with non trivial exponents has triggered a number of experimental and theoretical studies. However, general analytical methods to calculate persistence exponents cannot be applied to the ubiquitous case of non-Markovian systems relaxing…
Reliable ligand discrimination in stochastic multistep kinetic proofreading: First passage time vs. product counting strategies
Department of Computational Medicine, University of California, Los Angeles（加州大学洛杉矶分校计算医学系）；Department of Mathematics, University of California, Los Angeles（加州大学洛杉矶分校数学系）
The classical theory of chemical reactions can be understood in terms of diffusive barrier crossing, where the rate of a reaction is determined by the inverse of the mean first passage time (FPT) to cross a free energy barrier. Whenever a few reaction events suffice to trigger a response or the energy barriers are not high, the mean first passage time alone does not suffice to characterize the kinetics, i.e., the kinetics do not occur on a single time-scale. Instead, the full statistics of the FPT are required. We present a spectral representation of the FPT statistics that allows us to unders…
Active Brownian Dynamics in Channels: First-Passage and Spatiotemporal Properties via Siegmund Duality
Max-Planck-Institut für Physik komplexer Systeme（马克斯·普朗克复杂系统物理研究所）；Center for Systems Biology Dresden（德累斯顿系统生物学中心）；Cluster of Excellence, Physics of Life, TU Dresden（德累斯顿工业大学生命物理卓越集群）
How much time does it take for a fluctuating system, such as a polymer chain, to reach a target configuration that is rarely visited -- typically because of a high energy cost ? This question generally amounts to the determination of the first-passage time statistics to a target zone in phase space with lower occupation probability. Here, we present an analytical method to determine the mean first-passage time of a generic non-Markovian random walker to a rarely visited threshold, which goes beyond existing weak-noise theories. We apply our method to polymer systems, to determine (i) the first…
Influence of probability density function of the passage time in the method of non-equilibrium statistical operator on non-equilibrium properties of the system
Thermodynamics with thermodynamic variable first-passage time. II. Dynamics of explosive boiling of superheated liquid, critical indices, fractional calculus
Institute for Nuclear Research, pr. Nauki, 47 Kiev, Ukraine（乌克兰国家核科学研究所）
Levy walks (LWs) define a fundamental class of finite velocity stochastic processes that can be introduced as a special case of continuous time random walks. Alternatively, there is a hyperbolic representation of them in terms of partial probability density waves. Using the latter framework we explore the impact of aging on LWs, which can be viewed as a specific initial preparation of the particle ensemble with respect to an age distribution. We show that the hyperbolic age formulation is suitable for a simple integral representation in terms of linear Volterra equations for any initial prepar…
The escape from a given domain is one of the fundamental problems in statistical physics and the theory of stochastic processes. Here, we explore properties of the escape of an inertial particle driven by Lévy noise from a bounded domain, restricted by two absorbing boundaries.Presence of two absorbing boundaries assures that the escape process can be characterized by the finite mean first passage time. The detailed analysis of escape kinetics shows that properties of the mean first passage time for the integrated Ornstein--Uhlenbeck process driven by Lévy noise are closely related to properti…
Stochastic synthesis-degradation processes: first-passage properties and connections with resetting
Pritzker School of Molecular Engineering, University of Chicago（芝加哥大学普里茨克分子工程学院）；Instituto de Física, Universidad Nacional Autónoma de México（墨西哥国立自治大学物理研究所）
For two molecules to react they first have to meet. Yet, reaction times are rarely on par with the first-passage times that govern such molecular encounters. A prime reason for this discrepancy is stochastic transitions between reactive and non-reactive molecular states, which results in effective gating of product formation and altered reaction kinetics. To better understand this phenomenon we develop a unifying approach to gated reactions on networks. We first show that the mean and distribution of the gated reaction time can always be expressed in terms of ungated first-passage and return t…
The first-passage time (FPT), i.e., the moment when a stochastic process reaches a given threshold value for the first time, is a fundamental mathematical concept with immediate applications. In particular, it quantifies the statistics of instances when biomolecules in a biological cell reach their specific binding sites and trigger cellular regulation. Typically, the first-passage properties are given in terms of mean first-passage times. However, modern experiments now monitor single-molecular binding-processes in living cells and thus provide access to the full statistics of the underlying …
The statistics of first-passage times of random walks to target sites has proved to play a key role in determining the kinetics of space exploration in various contexts. In parallel, the number of distinct sites visited by a random walker and related observables have been introduced to characterize the geometry of space exploration. Here, we address the question of the joint distribution of the first-passage time to a target and the number of distinct sites visited when the target is reached, which fully quantifies the coupling between kinetics and geometry of search trajectories. Focusing on …
Relaxation and first passage processes are the pillars of kinetics in condensed matter, polymeric and single-molecule systems. Yet, an explicit connection between relaxation and first passage time-scales so far remained elusive. Here we prove a duality between them in the form of an interlacing of spectra. In the basic form the duality holds for reversible Markov processes to effectively one-dimensional targets. The exploration of a triple-well potential is analyzed to demonstrate how the duality allows for an intuitive understanding of first passage trajectories in terms of relaxational eigen…
The first-passage time (FPT), defined as the time a random walker takes to reach a target point in a confining domain, is a key quantity in the theory of stochastic processes. Its importance comes from its crucial role to quantify the efficiency of processes as varied as diffusion-limited reactions, target search processes or spreading of diseases. Most methods to determine the FPT properties in confined domains have been limited to Markovian (memoryless) processes. However, as soon as the random walker interacts with its environment, memory effects can not be neglected. Examples of non Markov…
When does a diffusing particle reach its target for the first time? This first-passage time (FPT) problem is central to the kinetics of molecular reactions in chemistry and molecular biology. Here we explain the behavior of smooth FPT densities, for which all moments are finite, and demonstrate universal yet generally non-Poissonian long-time asymptotics for a broad variety of transport processes. While Poisson-like asymptotics arise generically in the presence of an effective repulsion in the immediate vicinity of the target, a time-scale separation between direct and reflected indirect traje…
Understanding current fluctuations is of fundamental importance and paves the way for the development of practical applications. According to the thermodynamic and kinetic uncertainty relations, the precision of currents can be constrained solely by total entropy production or dynamical activity. In this study, we derive a tighter bound on the precision of currents in terms of both thermodynamic and kinetic quantities, demonstrating that these quantities jointly constrain current fluctuations. The thermodynamic and kinetic uncertainty relations become particular cases of our result in asymptot…
Kinetic Turnover in the Early-Stage Nucleation of Multi-Shell Condensed Clusters
Department of Chemistry, The Hong Kong University of Science and Technology（香港科技大学化学系）；IAS Center for AI for Scientific Discoveries, The Hong Kong University of Science and Technology（香港科技大学人工智能科学发现国际高等研究院中心）
Text-book concepts of diffusion- versus kinetic-control are well-defined for reaction-kinetics involving macroscopic concentrations of diffusive reactants that are adequately described by rate-constants -- the inverse of the mean-first-passage-time to the reaction-event. In contradistinction, an open important question is whether the mean-first-passage-time alone is a sufficient measure for biochemical reactions that involve nanomolar reactant concentrations. Here, using a simple yet generic, exactly-solvable model we study the conspiratory effect of diffusion and chemical reaction-limitations…
Theory of stochastic processes provides theoretical tools which can be efficiently used to explore properties of noise induced escape kinetics. Since noise facilitated escape over the potential barrier resembles free climbing, one can use the first passage time theory in analysis of rock climbing. We perform the analysis of the mean first passage time in order to answer the question regarding the optimal, i.e., resulting in the fastest climbing, rope length. It is demonstrated that there is a discrete set of favorable rope lengths assuring shortest climbing times, as they correspond to local m…
We investigate the kinetics and the free energy landscape of the crystallization of hard spheres from a supersaturated metastable liquid though direct simulations and forward flux sampling. In this first paper, we describe and test two different ways to reconstruct the free energy barriers from the sampled steady state probability distribution of cluster sizes without sampling the equilibrium distribution. The first method is based on mean first passage times, the second on splitting probabilities. We verify both methods for a single particle moving in a double-well potential. For the nucleati…
