Universality in stochastic exponential growth.
TL;DR: This model, the stochastic Hinshelwood cycle (SHC), is an autocatalytic reaction cycle in which each molecular species catalyzes the production of the next, and it is described how more complex reaction networks can reduce to such a cycle.
Abstract: Recent imaging data for single bacterial cells reveal that their mean sizes grow exponentially in time and that their size distributions collapse to a single curve when rescaled by their means. An analogous result holds for the division-time distributions. A model is needed to delineate the minimal requirements for these scaling behaviors. We formulate a microscopic theory of stochastic exponential growth as a Master Equation that accounts for these observations, in contrast to existing quantitative models of stochastic exponential growth (e.g., the Black-Scholes equation or geometric Brownian motion). Our model, the stochastic Hinshelwood cycle (SHC), is an autocatalytic reaction cycle in which each molecular species catalyzes the production of the next. By finding exact analytical solutions to the SHC and the corresponding first passage time problem, we uncover universal signatures of fluctuations in exponential growth and division. The model makes minimal assumptions, and we describe how more complex reaction networks can reduce to such a cycle. We thus expect similar scalings to be discovered in stochastic processes resulting in exponential growth that appear in diverse contexts such as cosmology, finance, technology, and population growth.
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28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
TL;DR: It is shown that the relative standard deviation associated with the FPT of an optimally restarted process, i.e., one that is restarted at a constant (nonzero) rate which brings the mean FPT to a minimum, is always unity.
Abstract: Stochastic restart may drastically reduce the expected run time of a computer algorithm, expedite the completion of a complex search process, or increase the turnover rate of an enzymatic reaction. These diverse first-passage-time (FPT) processes seem to have very little in common but it is actually quite the other way around. Here we show that the relative standard deviation associated with the FPT of an optimally restarted process, i.e., one that is restarted at a constant (nonzero) rate which brings the mean FPT to a minimum, is always unity. We interpret, further generalize, and discuss this finding and the implications arising from it.
228 citations
TL;DR: The experimental and theoretical analysis reveals a simple physical principle governing these complex biological processes: a single temperature-dependent scale of cellular time governs the stochastic dynamics of growth and division in balanced growth conditions.
Abstract: Uncovering the quantitative laws that govern the growth and division of single cells remains a major challenge. Using a unique combination of technologies that yields unprecedented statistical precision, we find that the sizes of individual Caulobacter crescentus cells increase exponentially in time. We also establish that they divide upon reaching a critical multiple (≈1.8) of their initial sizes, rather than an absolute size. We show that when the temperature is varied, the growth and division timescales scale proportionally with each other over the physiological temperature range. Strikingly, the cell-size and division-time distributions can both be rescaled by their mean values such that the condition-specific distributions collapse to universal curves. We account for these observations with a minimal stochastic model that is based on an autocatalytic cycle. It predicts the scalings, as well as specific functional forms for the universal curves. Our experimental and theoretical analysis reveals a simple physical principle governing these complex biological processes: a single temperature-dependent scale of cellular time governs the stochastic dynamics of growth and division in balanced growth conditions.
218 citations
Cites background or methods from "Universality in stochastic exponent..."
...A key result of the model is that, asymptotically, fluctuations in all chemicals in the SHC (Fig....
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...To enable comparison with our data, we derived the equivalent Langevin description from the Master equation for the SHC....
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...To this end, we recently generalized the model by assuming that the reactions in the cycle have exponential waiting-time distributions and showed analytically that its dynamics reduces to those of a single composite stochastic variable (48)....
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...The fact that effective activation energies for population growth are generally in the range of individual enzyme-catalyzed reactions’ (45) suggests that the SHC applies broadly....
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...2), governs stochastic division dynamics (48)....
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TL;DR: It is argued that for S. cerevisiae the "volume increment" is not added from birth to division, but rather between two budding events, suggesting a common strategy for cell size control with bacteria.
192 citations
Cites background from "Universality in stochastic exponent..."
...This assumption is supported by precise measurements of cell mass [1] as well as optical measurements of cell volume both in bacteria [14, 17, 18] and budding yeast [19], and an appealing model for its theoretical basis was recently proposed [20]....
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...[20] Iyer-Biswas, S, Crooks, G....
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TL;DR: A striking finding is presented showing that a bacterial population grows faster on average than its constituent cells, and an empirical growth law is identified that constrains the maximal growth rate of Escherichia coli.
Abstract: Cellular populations in both nature and the laboratory are composed of phenotypically heterogeneous individuals that compete with each other resulting in complex population dynamics. Predicting population growth characteristics based on knowledge of heterogeneous single-cell dynamics remains challenging. By observing groups of cells for hundreds of generations at single-cell resolution, we reveal that growth noise causes clonal populations of Escherichia coli to double faster than the mean doubling time of their constituent single cells across a broad set of balanced-growth conditions. We show that the population-level growth rate gain as well as age structures of populations and of cell lineages in competition are predictable. Furthermore, we theoretically reveal that the growth rate gain can be linked with the relative entropy of lineage generation time distributions. Unexpectedly, we find an empirical linear relation between the means and the variances of generation times across conditions, which provides a general constraint on maximal growth rates. Together, these results demonstrate a fundamental benefit of noise for population growth, and identify a growth law that sets a “speed limit” for proliferation.
152 citations
References
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28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
TL;DR: In this article, a simulation algorithm for the stochastic formulation of chemical kinetics is proposed, which uses a rigorously derived Monte Carlo procedure to numerically simulate the time evolution of a given chemical system.
Abstract: There are two formalisms for mathematically describing the time behavior of a spatially homogeneous chemical system: The deterministic approach regards the time evolution as a continuous, wholly predictable process which is governed by a set of coupled, ordinary differential equations (the “reaction-rate equations”); the stochastic approach regards the time evolution as a kind of random-walk process which is governed by a single differential-difference equation (the “master equation”). Fairly simple kinetic theory arguments show that the stochastic formulation of chemical kinetics has a firmer physical basis than the deterministic formulation, but unfortunately the stochastic master equation is often mathematically intractable. There is, however, a way to make exact numerical calculations within the framework of the stochastic formulation without having to deal with the master equation directly. It is a relatively simple digital computer algorithm which uses a rigorously derived Monte Carlo procedure to numerically simulate the time evolution of the given chemical system. Like the master equation, this “stochastic simulation algorithm” correctly accounts for the inherent fluctuations and correlations that are necessarily ignored in the deterministic formulation. In addition, unlike most procedures for numerically solving the deterministic reaction-rate equations, this algorithm never approximates infinitesimal time increments df by finite time steps At. The feasibility and utility of the simulation algorithm are demonstrated by applying it to several well-known model chemical systems, including the Lotka model, the Brusselator, and the Oregonator.
10,275 citations
01 Jan 1950
TL;DR: A First Course in Probability (8th ed.) by S. Ross is a lively text that covers the basic ideas of probability theory including those needed in statistics.
Abstract: Office hours: MWF, immediately after class or early afternoon (time TBA). We will cover the mathematical foundations of probability theory. The basic terminology and concepts of probability theory include: random experiments, sample or outcome spaces (discrete and continuous case), events and their algebra, probability measures, conditional probability A First Course in Probability (8th ed.) by S. Ross. This is a lively text that covers the basic ideas of probability theory including those needed in statistics. Theoretical concepts are introduced via interesting concrete examples. In 394 I will begin my lectures with the basics of probability theory in Chapter 2. However, your first assignment is to review Chapter 1, which treats elementary counting methods. They are used in applications in Chapter 2. I expect to cover Chapters 2-5 plus portions of 6 and 7. You are encouraged to read ahead. In lectures I will not be able to cover every topic and example in Ross, and conversely, I may cover some topics/examples in lectures that are not treated in Ross. You will be responsible for all material in my lectures, assigned reading, and homework, including supplementary handouts if any.
10,221 citations
TL;DR: Bacterial growth is considered as a method for the study of bacterial physiology and biochemistry, with the interpretation of quantitative data referring to bacterial growth limited to populations considered genetically homogeneous.
Abstract: The study of the growth of bacterial cultures does not constitute a specialized subject or branch of research: it is the basic method of Microbiology. It would be a foolish enterprise, and doomed to failure, to attempt reviewing briefly a \"subject\" which covers actually our whole discipline. Unless, of course, we considered the formal laws of growth for their own sake, an approach which has repeatedly proved sterile. In the present review we shall consider bacterial growth as a method for the study of bacterial physiology and biochemistry. More precisely, we shall concern ourselves with the quantitative aspects of the method, with the interpretation of quantitative data referring to bacterial growth. Furthermore, we shall considerz exclusively the positive phases of growth, since the study of bacterial \"death,\" i.e., of the negative phases of growth, involves distinct problems and methods. The discussion will be limited to populations considered genetically homogeneous. The problems of mutation and selection in growing cultures have been excellently dealt with in recent review articles by Delbriick (1) and Luria (2). No attempt is made at reviewing the literature on a subject which, as we have just seen, is not really a subject at all. The papers and results quoted have been selected as illustrations of the points discussed.
4,104 citations