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Farshid Jafarpour

Publications and source records attributed to Farshid Jafarpour.

13 recordsLinked to original sources

Physical limits to concentration and gradient sensing by perfect monitors

Cells often estimate chemical concentrations from only a few diffusing molecules, whose stochastic motion limits sensing precision. We consider a perfect monitoring instrument that records the instantaneous molecular density throughout a finite region without perturbing the concentration field or distinguishing molecular identities. The standard Berg-Purcell estimator weights all positions uniformly. Here we derive the optimal spatial weighting within a large class of unbiased estimators for both concentration and gradient sensing. Variance minimization maps to an electrostatic problem. Surprisingly, although the instrument monitors the entire volume, the optimal estimator assigns all weight to its boundary, reducing the uncertainty in both concentration and gradient sensing. We extend the results to arbitrary geometries and spatial dimensions.

physics.bio-ph

Probing the Critical Point (CritPt) of AI Reasoning: a Frontier Physics Research Benchmark

While large language models (LLMs) with reasoning capabilities are progressing rapidly on high-school math competitions and coding, can they reason effectively through complex, open-ended challenges found in frontier physics research? And crucially, what kinds of reasoning tasks do physicists want LLMs to assist with? To address these questions, we present the CritPt (Complex Research using Integrated Thinking - Physics Test, pronounced "critical point"), the first benchmark designed to test LLMs on unpublished, research-level reasoning tasks that broadly covers modern physics research areas, including condensed matter, quantum physics, atomic, molecular & optical physics, astrophysics, high energy physics, mathematical physics, statistical physics, nuclear physics, nonlinear dynamics, fluid dynamics and biophysics. CritPt consists of 71 composite research challenges designed to simulate full-scale research projects at the entry level, which are also decomposed to 190 simpler checkpoint tasks for more fine-grained insights. All problems are newly created by 50+ active physics researchers based on their own research. Every problem is hand-curated to admit a guess-resistant and machine-verifiable answer and is evaluated by an automated grading pipeline heavily customized for advanced physics-specific output formats. We find that while current state-of-the-art LLMs show early promise on isolated checkpoints, they remain far from being able to reliably solve full research-scale challenges: the best average accuracy among base models is only 5.7%, achieved by GPT-5 (high), moderately rising to around 10% when equipped with coding tools. Through the realistic yet standardized evaluation offered by CritPt, we highlight a large disconnect between current model capabilities and realistic physics research demands, offering a foundation to guide the development of scientifically grounded AI tools.

cs.AI

Optimal information transmission in a sequential model for cell division

In proliferating cell populations, adaptive changes to biochemical reactions can change a cell's division time, which in turn can change the population size. However, biochemical reactions are subject to noise, and therefore the conditions for optimal information transmission from the molecular to the population scale are poorly understood. Here, we model cell proliferation as a Bellman-Harris branching process with age-dependent division times. We identify a class of division time distributions, built from a series of Markovian steps, for which the population size distribution at all times is hierarchically calculable. We use this feature to characterize the amount of influence that a given reaction step has on the population size via the mutual information. We find that information transmission is optimal for a characteristic number of steps until division: too few and the population size is unpredictable; too many and any given step has vanishing influence on the population size. Our work reveals the potential tradeoffs involved in adaptive decision making at the sub-cellular, cellular and population scales.

physics.bio-ph

Size-structured populations with growth fluctuations: Feynman--Kac formula and decoupling

We study a size-structured population model in which individual cells grow at a rate determined by a fluctuating internal variable (e.g., gene expression levels). Many previous models of phenotypically heterogeneous populations can be viewed as special cases of this model, and it has previously been observed that the internal variable decouples from cell size under certain conditions. In this work, we generalize these results and connect them to the Feynman-Kac formula, which yields relationships between the lineage dynamics and population distribution in branching processes. To this end, we derive conditions for decoupling, both in the lineage and population ensemble. When decoupling occurs in both ensembles, the size dynamics can be transformed, via a random time change, into a growth-homogeneous process, and expectations can be evaluated through an exponential tilting procedure that follows from the Feynman-Kac formula. We further characterize weaker, ensemble-specific forms of decoupling that hold in either the lineage or the population ensemble, but not both. We provide a more general interpretation of tilted expectations in terms of the mass-weighted phenotype distribution

cond-mat.stat-mech

Exactly Solvable Population Model with Square-Root Growth Noise and Cell-Size Regulation

Stochastic exponential growth is nearly ubiquitous across cellular life, but how its microscopic noise structure shapes population growth remains poorly understood. Here, we introduce an exactly solvable population model in which cells grow exponentially with fluctuations that scale with the square root of cell size, and divide according to general size-control mechanisms. Our first result is that the population growth rate is exactly equal to the mean single-cell growth rate, for all noise strengths and for all division and size-regulation schemes that maintain size homeostasis. Thus square-root growth noise does not affect long-term fitness, in sharp contrast to models with size-independent stochastic growth rates. Second, we derive an exact solution for the steady-state distribution of cell sizes in the population and show that it is broadened by growth fluctuations. Third, the mean-rescaled population size $N_t/\langle N_t \rangle$ converges to a stationary compound Poisson-exponential distribution that depends only on growth noise. This distribution, and hence the long-time shape of population-size fluctuations, is unchanged by division-size noise or asymmetric partitioning. These results identify Feller-type exponential growth with square-root noise as an exactly solvable benchmark for stochastic growth in size-controlled populations and provide concrete signatures that distinguish it from models with size-independent growth-rate noise.

q-bio.PE

Competition between transient oscillations and early stochasticity in exponentially growing populations

It has been recently shown that the exponential growth rate of a population of bacterial cells starting from a single cell shows transient oscillations due to early synchronized bursts of division. These oscillations are enhanced by cell size regulation and contain information about single-cell growth statistics. Here, we report a phase transition in these oscillations as a function of growth rate variability. Below the transition point, these oscillations become asymptotically deterministic and can be measured experimentally, while above the transition point, the stochasticity in population growth dominates the oscillations and masks all the information about single cell growth statistics. The analytically calculated transition point, which roughly corresponds to $13\%$ variability in single-cell growth rate, falls within physiologically relevant parameters. Additionally, we show that the oscillations can stochastically emerge even when the initial state contains multiple cells with out-of-phase division cycles. We show that the amplitude and the phase of these oscillations are stochastic and would vary across repeated measurements with the same initial conditions. We provide analytic expressions as well as numerical estimates for the typical oscillation amplitude and the number of generations before the amplitude falls below a given measurement threshold for E. coli in multiple growth conditions.

q-bio.PE

Asymptotic decoupling of population growth rate and cell size distribution

The rate at which individual bacterial cells grow depends on the concentrations of cellular components such as ribosomes and proteins. These concentrations continuously fluctuate over time and are inherited from mother to daughter cells, leading to correlations between the growth rates of cells across generations. Division sizes of cells are also stochastic and correlated across generations due to a phenomenon known as cell size regulation. Fluctuations and correlations from both growth and division processes affect the population dynamics of an exponentially growing culture. Here, we provide analytic solutions for the population dynamics of cells with continuously fluctuating growth rates coupled with a generic model of cell-size regulation. We show that in balanced growth, the effects of growth and division processes decouple; the population growth rate only depends on the single-cell growth rate process, and the population cell size distribution only depends on the model of division and cell size regulation. The population growth rate is always higher than the average single-cell growth rate, and the difference increases with growth rate variability and its correlation time. This difference also sets the timescale for the population to reach its steady state. We provide analytical solutions for oscillations in population growth rate and traveling waves in size distribution during this approach to the steady state.

q-bio.PE

Cell size regulation induces sustained oscillations in the population growth rate

We study the effect of correlations in generation times on the dynamics of population growth of microorganisms. We show that any non-zero correlation that is due to cell-size regulation, no matter how small, induces long-term oscillations in the population growth rate. The population only reaches its steady state when we include the often-neglected variability in the growth rates of individual cells. We discover that the relaxation time scale of the population to its steady state is determined by the distribution of single-cell growth rates and is surprisingly independent of details of the division process such as the noise in the timing of division and the mechanism of cell-size regulation. We validate the predictions of our model using existing experimental data and propose an experimental method to measure single-cell growth variability by observing how long it takes for the population to reach its steady state or balanced growth.

q-bio.PE

Bridging the time scales of single-cell and population dynamics

How are granular details of stochastic growth and division of individual cells reflected in smooth deterministic growth of population numbers? We provide an integrated, multiscale perspective of microbial growth dynamics by formulating a data-validated theoretical framework that accounts for observables at both single-cell and population scales. We derive exact analytical complete time-dependent solutions to cell-age distributions and population growth rates as functionals of the underlying interdivision time distributions, for symmetric and asymmetric cell division. These results provide insights into the surprising implications of stochastic single-cell dynamics for population growth. Using our results for asymmetric division, we deduce the time to transition from the reproductively quiescent (swarmer) to replication-competent (stalked) stage of the {\em Caulobacter crescentus} lifecycle. Remarkably, population numbers can spontaneously oscillate with time. We elucidate the physics leading to these population oscillations. For {\em C. crescentus} cells, we show that a simple measurement of the population growth rate, for a given growth condition, is sufficient to characterize the condition-specific cellular unit of time, and thus yields the mean (single-cell) growth and division timescales, fluctuations in cell division times, the cell age distribution, and the quiescence timescale.

q-bio.QM

Phenomenology of stochastic exponential growth

Stochastic exponential growth is observed in a variety of contexts, including molecular autocatalysis, nuclear fission, population growth, inflation of the universe, viral social media posts, and financial markets. Yet literature on modeling the phenomenology of these stochastic dynamics has predominantly focused on one model, Geometric Brownian Motion (GBM), which can be described as the solution of a Langevin equation with linear drift and linear multiplicative noise. Using recent experimental results on stochastic exponential growth of individual bacterial cell sizes, we motivate the need for a more general class of phenomenological models of stochastic exponential growth, which are consistent with the observation that the mean-rescaled distributions are approximately stationary at long times. We show that this behavior is not consistent with GBM, instead it is consistent with power law multiplicative noise with positive fractional powers. Therefore, we consider this general class of phenomenological models for stochastic exponential growth, provide analytical solutions, and identify the important dimensionless combination of model parameters which determines the shape of the mean-rescaled distribution. We also provide a prescription for robustly inferring model parameters from experimentally observed stochastic growth trajectories.

cond-mat.stat-mech

Biological timekeeping in the presence of stochasticity

Causal ordering of key events in the cell cycle is essential for proper functioning of an organism. Yet, it remains a mystery how a specific temporal program of events is maintained despite ineluctable stochasticity in the biochemical dynamics which dictate timing of cellular events. We propose that if a change of cell fate is triggered by the {\em time-integral} of the underlying stochastic biochemical signal, rather than the original signal, then a dramatic improvement in temporal specificity results. Exact analytical results for stochastic models of hourglass-timers and pendulum-clocks, two important paradigms for biological timekeeping, elucidate how temporal specificity is achieved through time-integration. En route, we introduce a natural representation for time-integrals of stochastic processes, provide an analytical prescription for evaluating corresponding first-passage-time distributions, and uncover a mechanism by which a population of identical cells can spontaneously bifurcate into subpopulations of early and late responders, depending on hierarchy of timescales in the dynamics. Moreover, our approach reveals how time-integration of stochastic signals may be realized biochemically, through a simple chemical reaction scheme.

q-bio.MN

Giant amplification of noise in fluctuation-induced pattern formation

The amplitude of fluctuation-induced patterns might be expected to be proportional to the strength of the driving noise, suggesting that such patterns would be difficult to observe in nature. Here, we show that a large class of spatially-extended dynamical systems driven by intrinsic noise can exhibit giant amplification, yielding patterns whose amplitude is comparable to that of deterministic Turing instabilities. The giant amplification results from the interplay between noise and non-orthogonal eigenvectors of the linear stability matrix, yielding transients that grow with time, and which, when driven by the ever-present intrinsic noise, lead to persistent large amplitude patterns. This mechanism provides a robust basis for fluctuation-induced biological pattern formation based on the Turing mechanism, without requiring fine tuning of diffusion constants.

cond-mat.stat-mech

A noise-induced mechanism for biological homochirality of early life self-replicators

The observed single-handedness of biological amino acids and sugars has long been attributed to autocatalysis. However, the stability of homochiral states in deterministic autocatalytic systems relies on cross inhibition of the two chiral states, an unlikely scenario for early life self-replicators. Here, we present a theory for a stochastic individual-level model of autocatalysis due to early life self-replicators. Without chiral inhibition, the racemic state is the global attractor of the deterministic dynamics, but intrinsic multiplicative noise stabilizes the homochiral states, in both well-mixed and spatially-extended systems. We conclude that autocatalysis is a viable mechanism for homochirality, without imposing additional nonlinearities such as chiral inhibition.

q-bio.PE