We derive an Itô stochastic differential equation for entropy production in nonequilibrium Langevin processes. Introducing a random-time transformation, entropy production obeys a one-dimensional drift-diffusion equation, independent of the underlying physical model. This transformation allows us to identify generic properties of entropy production. It also leads to an exact uncertainty equality relating the Fano factor of entropy production and the Fano factor of the random time, which we also generalize to non-steady-state conditions.

Cells are the basic units of all living matter which harness the flow of energy to drive the processes of life. While the biochemical networks involved in energy transduction are well-characterized, the energetic costs and constraints for specific cellular processes remain largely unknown. In particular, what are the energy budgets of cells? What are the constraints and limits energy flows impose on cellular processes? Do cells operate near these limits, and if so how do energetic constraints impact cellular functions? Physics has provided many tools to study nonequilibrium systems and to define physical limits, but applying these tools to cell biology remains a challenge. Physical bioenergetics, which resides at the interface of nonequilibrium physics, energy metabolism, and cell biology, seeks to understand how much energy cells are using, how they partition this energy between different cellular processes, and the associated energetic constraints. Here we review recent advances and discuss open questions and challenges in physical bioenergetics.

In ecology, species can mitigate their extinction risks in uncertain environments by diversifying individual phenotypes. This observation is quantified by the theory of bet-hedging, which provides a reason for the degree of phenotypic diversity observed even in clonal populations. Bet-hedging in well-mixed populations is rather well understood. However, many species underwent range expansions during their evolutionary history, and the importance of phenotypic diversity in such scenarios still needs to be understood. In this paper, we develop a theory of bet-hedging for populations colonizing new, unknown environments that fluctuate either in space or time. In this case, we find that bet-hedging is a more favorable strategy than in well-mixed populations. For slow rates of variation, temporal and spatial fluctuations lead to different outcomes. In spatially fluctuating environments, bet-hedging is favored compared to temporally fluctuating environments. In the limit of frequent environmental variation, no opportunity for bet-hedging exists, regardless of the nature of the environmental fluctuations. For the same model, bet-hedging is never an advantageous strategy in the well-mixed case, supporting the view that range expansions strongly promote diversification. These conclusions are robust against stochasticity induced by finite population sizes. Our findings shed light on the importance of phenotypic heterogeneity in range expansions, paving the way to novel approaches to understand how biodiversity emerges and is maintained. Ecological populations are often exposed to unpredictable and variable environmental conditions. A number of strategies have evolved to cope with such uncertainty. One of them is stochastic phenotypic switching, by which some individuals in the community are enabled to tackle adverse conditions, even at the price of reducing overall growth in the short term. In this paper, we study the effectiveness of these “bet-hedging” strategies for a population in the process of colonizing new territory. We show that bet-hedging is more advantageous when the environment varies spatially rather than temporally, and infrequently rather than frequently.

Thermodynamic observables of mesoscopic systems can be expressed as integrated empirical currents. Their fluctuations are bound by thermodynamic uncertainty relations. We introduce the hyperaccurate current as the integrated empirical current with the least fluctuations in a given nonequilibrium system. For steady-state systems described by overdamped Langevin equations, we derive an equation for the hyperaccurate current by means of a variational principle. We show that the hyperaccurate current coincides with the entropy production if and only if the latter saturates the thermodynamic uncertainty relation, and it can be substantially more precise otherwise. The hyperaccurate current can be used to improve estimates of entropy production from experimental data.

Lower bounds on fluctuations of thermodynamic currents depend on the nature of time, discrete or continuous. To understand the physical reason, we compare current fluctuations in discrete-time Markov chains and continuous-time master equations. We prove that current fluctuations in the master equations are always more likely, due to random timings of transitions. This comparison leads to a mapping of the moments of a current between discrete and continuous time. We exploit this mapping to obtain uncertainty bounds. Our results reduce the quests for uncertainty bounds in discrete and continuous time to a single problem.

Summary: The estimation of a density profile from experimental data points is a challenging problem, which is usually tackled by plotting a histogram. Prior assumptions on the nature of the density, from its smoothness to the specification of its form, allow the design of more accurate estimation procedures, such as maximum likelihood. Our aim is to construct a procedure that makes no explicit assumptions, but still providing an accurate estimate of the density. We introduce the self-consistent estimate: the power spectrum of a candidate density is given, and an estimation procedure is constructed on the assumption, to be released a posteriori, that the candidate is correct. The self-consistent estimate is defined as a prior candidate density that precisely reproduces itself. Our main result is to derive the exact expression of the self-consistent estimate for any given data set, and to study its properties. Applications of the method require neither priors on the form of the density nor the subjective choice of parameters. A cut-off frequency, akin to a bin size or a kernel bandwidth, emerges naturally from the derivation. We apply the self-consistent estimate to artificial data generated from various distributions and show that it reaches the theoretical limit for the scaling of the square error with the size of the data set.