Cesar Nieto - Academia.edu (original) (raw)

Papers by Cesar Nieto

Research paper thumbnail of Comparative analysis of noise-attenuation mechanisms in gene expression: From single cells to cell populations

Negative feedback regulation is a well-known motif for suppressing deleterious fluctuations in ge... more Negative feedback regulation is a well-known motif for suppressing deleterious fluctuations in gene product levels. We systematically compare two scenarios where negative feedback is either implemented in the protein production rate (regulated synthesis) or in the protein degradation rate (regulated degradation). Our results show that while in lownoise regimes both schemes are identical, they begin to show remarkable differences in high-noise regimes. Analytically solving for the probability distributions of the protein levels reveals that regulated synthesis is a better strategy to suppress random fluctuations while also minimizing protein levels dipping below a threshold. In contrast, regulated degradation is preferred if the goal is to minimize protein levels going beyond a threshold. Finally, we compare and contrast these distributions not only in a single cell over time but also in an expanding cell population where these effects can be buffered or exacerbated due to the coupli...

Research paper thumbnail of Optimal network transmission to minimize state-estimation error and channel usage

2022 26th International Conference on System Theory, Control and Computing (ICSTCC)

Research paper thumbnail of Quantifying noise modulation from coupling of stochastic expression to cellular growth: An analytical approach

The overexpression of many proteins can often have a detrimental impact on cellular growth. This ... more The overexpression of many proteins can often have a detrimental impact on cellular growth. This expression-growth coupling leads to positive feedback - any increase of intracellular protein concentration reduces the growth rate of cell size expansion that in turn enhances the concentration via reduced dilution. We investigate how such feedback amplifies intrinsic stochasticity in gene expression to drive a skewed distribution of the protein concentration. Our results provide an exact solution to this distribution by analytically solving the Chapman-Kolmogorov equation, and we use it to quantify the enhancement of noise/skewness as a function of expression-growth coupling. This analysis has important implications for the expression of stress factors, where high levels provide protection from stress, but come at the cost of reduced cellular proliferation. Finally, we connect these analytical results to the case of an actively degraded gene product, where the degradation machinery is ...

Research paper thumbnail of Modeling cell size regulation under complex and dynamic environments

In nature, cells face changes in environmental conditions that can modify their growth rate. In t... more In nature, cells face changes in environmental conditions that can modify their growth rate. In these dynamic environments, recent experiments found changes in cell size regulation. Currently, there are few clues about the origin of these cell size changes. In this work, we model cell division as a stochastic process that occurs at a rate proportional to the size. We propose that this rate is zero if the cell is smaller than a minimum size. We show how this model predicts some of the properties found in cell size regulation. For example, among our predictions, we found that the mean cell size is an exponential function of the growth rate under steady conditions. We predict that cells become smaller and the way the division strategy changes during dynamic nutrient depletion. Finally, we use the model to predict cell regulation in an arbitrary complex dynamic environment.

Research paper thumbnail of Feedback strategies for threshold crossing of protein levels at a prescribed time

2022 30th Mediterranean Conference on Control and Automation (MED)

Research paper thumbnail of The role of division stochasticity on the robustness of bacterial size dynamics

Variables of bacterial division such as size at birth, growth rate, division time, and the positi... more Variables of bacterial division such as size at birth, growth rate, division time, and the position of the septal ring, all vary from cell to cell. Currently, it is unknown how these random fluctuations can combine to produce a robust mechanism of homeostasis. To address this question, we studied the dynamics of the cell division process from both experimental and theoretical perspectives. Our model predicts robustness in division times as sustained oscillations in metrics of the cell size distribution, such as the mean, variability, and the cell size autocorrelation function. These oscillations do not get damped, even considering stochasticity in division timing and the cell size at the beginning of the experiment. Damping appears just after inducing stochasticity in either the septum position or the growth rate. We compare the predictions of the full model with the size dynamics of E. coli bacteria growing in minimal media using either glucose or glycerol as carbon sources. We obs...

Research paper thumbnail of Cell size regulation and proliferation fluctuations in single-cell derived colonies

Exponentially growing cells regulate their size by controlling their timing of division. Since tw... more Exponentially growing cells regulate their size by controlling their timing of division. Since two daughter cells are born as a result of this cell splitting, cell size regulation has a direct connection with cell proliferation dynamics. Recent models found more clues about this connection by suggesting that division occurs at a size-dependent rate. In this article, we propose a framework that couples the stochastic transient dynamics of both the cell size and the number of cells in the initial expansion of a single-cell-derived colony. We describe the population from the two most common perspectives. The first is known as Single Lineage: where only one cell is followed in each colony, and the second is Population Snapshots: where all cells in different colonies are followed. At a low number of cells, we propose a third perspective; Single Colony, where one tracks only cells with a common ancestor. We observe how the statistics of these three approaches are different at low numbers ...

Research paper thumbnail of Boundary integral method for Stokes flow with linear slip flow conditions in curved surfaces

Mesh Reduction Methods, 2009

The no slip boundary condition is traditionally used to predict velocity fields in macro scale fl... more The no slip boundary condition is traditionally used to predict velocity fields in macro scale flows. When the scale of the problem is about the size of the mean free path of particles, it is necessary to consider that the flow slips over the solid surfaces and the boundary condition must be changed to improve the description of the flow behaviour with continuous governing fluid flow equations. Navier's slip boundary condition states that the relative velocity of the fluid respect to the wall is directly proportionally to the local tangential shear stress. The proportionally constant is called the slip length, which represent the hypothetical distance at the wall needed to satisfy the condition of no-slip flow. Some works have misused boundary conditions derived from Navier's work to model slip flow behaviour for example by employing expressions, for diagonal and curved surfaces, that were derived for flat infinite surfaces aligned with coordinate axes. In this work, the creeping flow of a Newtonian fluid under linear slip conditions is simulated for the cases of a Slit and a Couette mixer by means of the Boundary Element Method (BEM). In the evaluation of such flows, different magnitudes of slip length from 0 (no slip) to 1.0 are analysed in an effort to understand the effect of the slip boundary condition on the physical behaviour of the simulation system. Analytic solutions for both geometries under slip flow are used to estimate L2 norm error, which is below 0.25% for Couette flow and 1.25% for Slit flow, validating the approximation applied.

Research paper thumbnail of Regulatory strategies to schedule threshold crossing of protein levels at a prescribed time

The timing of diverse cellular processes is based on the instant when the concentration of regula... more The timing of diverse cellular processes is based on the instant when the concentration of regulatory proteins crosses a critical threshold level. Hence, noise mechanisms inherent to these protein synthesis pathways drive statistical fluctuations in such events’ timing. How to express proteins ensuring both the threshold crossing at a prescribed time and minimal timing fluctuations? To find this optimal strategy, we formulate a model where protein molecules are synthesized in random bursts of gene activity. The burst frequency depends on the protein level creating a feedback loop, and cellular growth dilutes protein concentration between consecutive bursts. Counterintuitively, our analysis shows that positive feedback in protein production is best for minimizing variability in threshold-crossing times. We analytically predict the optimal feedback strength in terms of the dilution rate. As a corollary to our result, a no-feedback strategy emerges as the optimal strategy in the absenc...

Research paper thumbnail of Continuous rate modeling of bacterial stochastic size dynamics

Physical Review E, 2021

Bacterial division is an inherently stochastic process with effects on fluctuations of protein co... more Bacterial division is an inherently stochastic process with effects on fluctuations of protein concentration and phenotype variability. Current modeling tools for the stochastic short-term cell-size dynamics are scarce and mainly phenomenological. Here we present a general theoretical approach based on the Chapman-Kolmogorov equation incorporating continuous growth and division events as jump processes. This approach allows us to include different division strategies, noisy growth, and noisy cell splitting. Considering bacteria synchronized from their last division, we predict oscillations in both the central moments of the size distribution and its autocorrelation function. These oscillations, barely discussed in past studies, can arise as a consequence of the discrete time displacement invariance of the system with a period of one doubling time, and they do not disappear when including stochasticity on either division times or size heterogeneity on the starting population but only after inclusion of noise in either growth rate or septum position. This result illustrates the usefulness of having a solid mathematical description that explicitly incorporates the inherent stochasticity in various biological processes, both to understand the process in detail and to evaluate the effect of various sources of variability when creating simplified descriptions.

Research paper thumbnail of Division stochasticity can be transmitted to protein expression through chromosome replication

Stochastic fluctuations (noise) are a fundamental characteristic of protein production. Some sour... more Stochastic fluctuations (noise) are a fundamental characteristic of protein production. Some sources of this stochasticity are still under debate. In this work, we explore how these fluctuations can originate from the stochasticity on division events. To do that, we consider the classical gene expression model with chromosome replication following the known Helmstetter & Cooper model. This model predicts intervals of the cell cycle where bacteria can have more than one copy of a particular gene. Considering the transcription rate as proportional to the number of chromosomes and division based on a continuous rate model, we explore how stochasticity in division or equivalently in cell size, could be transmitted to gene expression. Our simulations suggest that division can be an important source of such fluctuations only if chromosomes are replicating, otherwise, this noise is not well transmitted. This effect happens even if replication is deterministic. This work can be helpful for ...

Research paper thumbnail of Noise signature in added size suggests bacteria target a commitment size to enable division

ABSTRACTRecent experiments suggested that sizer-like division strategy, a deviation from the adde... more ABSTRACTRecent experiments suggested that sizer-like division strategy, a deviation from the adder paradigm might be produced by additional degradation events of cell division machinery molecules. We revisited single cell size data from a recently microfluidics setup using the above model. We observed that such additional degradation process, although reproduces size observations in the mean sense, it is unable to capture cell size fluctuations. We further extended recently proposed power law models to include commitment size. Our proposal is in agreement of both mean and fluctuation profiles seen in experiments. Our approach suggests further uses of noise profiles on dissecting cell size regulatory mechanisms.SIGNIFICANCEWe contrast cell division models against bacteria cell size data in minimal media. Our results seems to support the idea that division starts once bacteria meet a given commitment size.

Research paper thumbnail of Continuous Rate Modelling of bacterial stochastic size dynamics

Bacterial division is an inherently stochastic process. However, theoretical tools to simulate an... more Bacterial division is an inherently stochastic process. However, theoretical tools to simulate and study the stochastic transient dynamics of cell-size are scarce. Here, we present a general theoretical approach based on the Chapman-Kolmogorov formalism to describe these stochastic dynamics including continuous growth and division events as jump processes. Using this approach, we analyze the effect of different sources of noise on the dynamics of the size distribution. Oscillations in the distribution central moments were found as consequence of the discrete translation invariance of the system with period of one doubling time, these oscillations are found in both the central moments of the size distribution and the auto-correlation function and do not disappear including stochasticity on division times or size heterogeneity on the population but only after include noise in either growth rate or septum position.

Research paper thumbnail of PyEcoLib: a python library for simulating E. coli stochastic size dynamics

Recent studies describe bacterial division as a jump process triggered when it reaches a fixed nu... more Recent studies describe bacterial division as a jump process triggered when it reaches a fixed number of stochastic discrete events at a rate depending on the cell-size. This theoretical approach enabled the computation of stochastic cell-size transient dynamics with arbitrary precision, with the possibility of being coupled to other continuous processes as gene expression. Here we synthesize most of this theory in the tool PyEcoLib, a python-based library to estimate bacterial cell size stochastic dynamics including continuous growth and division events. In this library, we include examples predicting statistical properties seen in experiments.

Research paper thumbnail of Correlation between protein concentration and bacterial cell size can reveal mechanisms of gene expression

Physical Biology, 2020

Classically, gene expression is modeled as a chemical process with reaction rates dependent on th... more Classically, gene expression is modeled as a chemical process with reaction rates dependent on the concentration of the reactants (typically, DNA loci, plasmids, RNA, enzymes, etc). Other variables like cell size are in general ignored. Size dynamics can become an important variable due to the low number of many of these reactants, imperfectly symmetric cell partitioning and molecule segregation. In this work we measure the correlation between size and protein concentration by observing the gene expression of the RpOD gene from a low-copy plasmid in Escherichia coli during balanced growth in different media. A positive correlation was found, and we used it to examine possible models of cell size dynamics and plasmid replication. We implemented a previously developed model describing the full gene expression process including transcription, translation, loci replication, cell division and molecule segregation. By comparing with the observed correlation, we determine that the transcri...

Research paper thumbnail of Efficient computation of stochastic cell-size transient dynamics

BMC Bioinformatics, 2019

Background How small, fast-growing bacteria ensure tight cell-size distributions remains elusive.... more Background How small, fast-growing bacteria ensure tight cell-size distributions remains elusive. High-throughput measurement techniques have propelled efforts to build modeling tools that help to shed light on the relationships between cell size, growth and cycle progression. Most proposed models describe cell division as a discrete map between size at birth and size at division with stochastic fluctuations assumed. However, such models underestimate the role of cell size transient dynamics by excluding them. Results We propose an efficient approach for estimation of cell size transient dynamics. Our technique approximates the transient size distribution and statistical moment dynamics of exponential growing cells following an adder strategy with arbitrary precision. Conclusions We approximate, up to arbitrary precision, the distribution of division times and size across time for the adder strategy in rod-shaped bacteria cells. Our approach is able to compute statistical moments li...

Research paper thumbnail of Stochasticity in bacterial division control: Preliminary consequences for protein concentration

The stochastic nature of protein concentration inside cells can have important consequences in th... more The stochastic nature of protein concentration inside cells can have important consequences in their physiology and population fitness. Classical models of gene expression consider these processes as first-order reactions with little dependence with the cell size. However, the concentrations of the relevant molecules depends directly on the cellular volume. Here we model the cell size dynamics as exponential growth followed by division with occurrence rate proportional to the size. This framework, together with known models of chromosome replication and both protein and mRNA synthesis, lets us predict relationships between cell size and both protein number and concentration. As a main result, we find that protein production strategies (constant rate or rate proportional to either chromosome number, cell size or chromosome number times cell size) can be experimentally distinguished from the correlation between protein concentration and cell size.

Research paper thumbnail of Critical Sources of Aerodynamic Resistance in a Medium Distance Urban Train: a CFD approach

Revista Guillermo de Ockham, 2013

How to cite Complete issue More information about this article Journal's homepage in redalyc.org ... more How to cite Complete issue More information about this article Journal's homepage in redalyc.org Scientific Information System Network of Scientific Journals from Latin America, the Caribbean, Spain and Portugal Non-profit academic project, developed under the open access initiative

Research paper thumbnail of A Conceptual Design of Energy Exchange System for Recovery of Residual Heat Using Aluminum Foams

Procedia Materials Science, 2014

ABSTRACT Open cell aluminum foams have been recently studied for its use in heat exchangers, heat... more ABSTRACT Open cell aluminum foams have been recently studied for its use in heat exchangers, heat sink and electronics cooling. In this paper, a conceptual design of a heat energy exchange recovering system for residual heat at low temperatures is studies for its potential industrial application. Experimental samples were produced by infiltration process using vacuum pressure. Samples with different pore sizes of 0.5, 1.0 and 2.0 mm were obtained. The samples dimensions were 50 mm x 50 mm x 5 mm and the material was characterized by structure analysis and fluid flow (pressure drop) and heat transfer measurements under transitory and steady state conditions. The experimentation carried on in regards of the fluid flow and heat transfer properties, shown that these two properties are extremely dependent on the pore size of the aluminum foam. In this preliminary study, the thermo-physical characteristics of the aluminum foams useful for energy exchange system in recuperating of residual heat (heat transfer efficiency, transfer time, amount of heat transferred and pressure drop generated), had been presented and used to create a conceptual design. From the tested parameters, the best foam structure and some process parameters have been established for a conceptual design a heat exchanger for a heat recovery system.

Research paper thumbnail of Boundary elements solution of stokes flow between curved surfaces with nonlinear slip boundary condition

Numerical Methods for Partial Differential Equations, 2012

ABSTRACT

Research paper thumbnail of Comparative analysis of noise-attenuation mechanisms in gene expression: From single cells to cell populations

Negative feedback regulation is a well-known motif for suppressing deleterious fluctuations in ge... more Negative feedback regulation is a well-known motif for suppressing deleterious fluctuations in gene product levels. We systematically compare two scenarios where negative feedback is either implemented in the protein production rate (regulated synthesis) or in the protein degradation rate (regulated degradation). Our results show that while in lownoise regimes both schemes are identical, they begin to show remarkable differences in high-noise regimes. Analytically solving for the probability distributions of the protein levels reveals that regulated synthesis is a better strategy to suppress random fluctuations while also minimizing protein levels dipping below a threshold. In contrast, regulated degradation is preferred if the goal is to minimize protein levels going beyond a threshold. Finally, we compare and contrast these distributions not only in a single cell over time but also in an expanding cell population where these effects can be buffered or exacerbated due to the coupli...

Research paper thumbnail of Optimal network transmission to minimize state-estimation error and channel usage

2022 26th International Conference on System Theory, Control and Computing (ICSTCC)

Research paper thumbnail of Quantifying noise modulation from coupling of stochastic expression to cellular growth: An analytical approach

The overexpression of many proteins can often have a detrimental impact on cellular growth. This ... more The overexpression of many proteins can often have a detrimental impact on cellular growth. This expression-growth coupling leads to positive feedback - any increase of intracellular protein concentration reduces the growth rate of cell size expansion that in turn enhances the concentration via reduced dilution. We investigate how such feedback amplifies intrinsic stochasticity in gene expression to drive a skewed distribution of the protein concentration. Our results provide an exact solution to this distribution by analytically solving the Chapman-Kolmogorov equation, and we use it to quantify the enhancement of noise/skewness as a function of expression-growth coupling. This analysis has important implications for the expression of stress factors, where high levels provide protection from stress, but come at the cost of reduced cellular proliferation. Finally, we connect these analytical results to the case of an actively degraded gene product, where the degradation machinery is ...

Research paper thumbnail of Modeling cell size regulation under complex and dynamic environments

In nature, cells face changes in environmental conditions that can modify their growth rate. In t... more In nature, cells face changes in environmental conditions that can modify their growth rate. In these dynamic environments, recent experiments found changes in cell size regulation. Currently, there are few clues about the origin of these cell size changes. In this work, we model cell division as a stochastic process that occurs at a rate proportional to the size. We propose that this rate is zero if the cell is smaller than a minimum size. We show how this model predicts some of the properties found in cell size regulation. For example, among our predictions, we found that the mean cell size is an exponential function of the growth rate under steady conditions. We predict that cells become smaller and the way the division strategy changes during dynamic nutrient depletion. Finally, we use the model to predict cell regulation in an arbitrary complex dynamic environment.

Research paper thumbnail of Feedback strategies for threshold crossing of protein levels at a prescribed time

2022 30th Mediterranean Conference on Control and Automation (MED)

Research paper thumbnail of The role of division stochasticity on the robustness of bacterial size dynamics

Variables of bacterial division such as size at birth, growth rate, division time, and the positi... more Variables of bacterial division such as size at birth, growth rate, division time, and the position of the septal ring, all vary from cell to cell. Currently, it is unknown how these random fluctuations can combine to produce a robust mechanism of homeostasis. To address this question, we studied the dynamics of the cell division process from both experimental and theoretical perspectives. Our model predicts robustness in division times as sustained oscillations in metrics of the cell size distribution, such as the mean, variability, and the cell size autocorrelation function. These oscillations do not get damped, even considering stochasticity in division timing and the cell size at the beginning of the experiment. Damping appears just after inducing stochasticity in either the septum position or the growth rate. We compare the predictions of the full model with the size dynamics of E. coli bacteria growing in minimal media using either glucose or glycerol as carbon sources. We obs...

Research paper thumbnail of Cell size regulation and proliferation fluctuations in single-cell derived colonies

Exponentially growing cells regulate their size by controlling their timing of division. Since tw... more Exponentially growing cells regulate their size by controlling their timing of division. Since two daughter cells are born as a result of this cell splitting, cell size regulation has a direct connection with cell proliferation dynamics. Recent models found more clues about this connection by suggesting that division occurs at a size-dependent rate. In this article, we propose a framework that couples the stochastic transient dynamics of both the cell size and the number of cells in the initial expansion of a single-cell-derived colony. We describe the population from the two most common perspectives. The first is known as Single Lineage: where only one cell is followed in each colony, and the second is Population Snapshots: where all cells in different colonies are followed. At a low number of cells, we propose a third perspective; Single Colony, where one tracks only cells with a common ancestor. We observe how the statistics of these three approaches are different at low numbers ...

Research paper thumbnail of Boundary integral method for Stokes flow with linear slip flow conditions in curved surfaces

Mesh Reduction Methods, 2009

The no slip boundary condition is traditionally used to predict velocity fields in macro scale fl... more The no slip boundary condition is traditionally used to predict velocity fields in macro scale flows. When the scale of the problem is about the size of the mean free path of particles, it is necessary to consider that the flow slips over the solid surfaces and the boundary condition must be changed to improve the description of the flow behaviour with continuous governing fluid flow equations. Navier's slip boundary condition states that the relative velocity of the fluid respect to the wall is directly proportionally to the local tangential shear stress. The proportionally constant is called the slip length, which represent the hypothetical distance at the wall needed to satisfy the condition of no-slip flow. Some works have misused boundary conditions derived from Navier's work to model slip flow behaviour for example by employing expressions, for diagonal and curved surfaces, that were derived for flat infinite surfaces aligned with coordinate axes. In this work, the creeping flow of a Newtonian fluid under linear slip conditions is simulated for the cases of a Slit and a Couette mixer by means of the Boundary Element Method (BEM). In the evaluation of such flows, different magnitudes of slip length from 0 (no slip) to 1.0 are analysed in an effort to understand the effect of the slip boundary condition on the physical behaviour of the simulation system. Analytic solutions for both geometries under slip flow are used to estimate L2 norm error, which is below 0.25% for Couette flow and 1.25% for Slit flow, validating the approximation applied.

Research paper thumbnail of Regulatory strategies to schedule threshold crossing of protein levels at a prescribed time

The timing of diverse cellular processes is based on the instant when the concentration of regula... more The timing of diverse cellular processes is based on the instant when the concentration of regulatory proteins crosses a critical threshold level. Hence, noise mechanisms inherent to these protein synthesis pathways drive statistical fluctuations in such events’ timing. How to express proteins ensuring both the threshold crossing at a prescribed time and minimal timing fluctuations? To find this optimal strategy, we formulate a model where protein molecules are synthesized in random bursts of gene activity. The burst frequency depends on the protein level creating a feedback loop, and cellular growth dilutes protein concentration between consecutive bursts. Counterintuitively, our analysis shows that positive feedback in protein production is best for minimizing variability in threshold-crossing times. We analytically predict the optimal feedback strength in terms of the dilution rate. As a corollary to our result, a no-feedback strategy emerges as the optimal strategy in the absenc...

Research paper thumbnail of Continuous rate modeling of bacterial stochastic size dynamics

Physical Review E, 2021

Bacterial division is an inherently stochastic process with effects on fluctuations of protein co... more Bacterial division is an inherently stochastic process with effects on fluctuations of protein concentration and phenotype variability. Current modeling tools for the stochastic short-term cell-size dynamics are scarce and mainly phenomenological. Here we present a general theoretical approach based on the Chapman-Kolmogorov equation incorporating continuous growth and division events as jump processes. This approach allows us to include different division strategies, noisy growth, and noisy cell splitting. Considering bacteria synchronized from their last division, we predict oscillations in both the central moments of the size distribution and its autocorrelation function. These oscillations, barely discussed in past studies, can arise as a consequence of the discrete time displacement invariance of the system with a period of one doubling time, and they do not disappear when including stochasticity on either division times or size heterogeneity on the starting population but only after inclusion of noise in either growth rate or septum position. This result illustrates the usefulness of having a solid mathematical description that explicitly incorporates the inherent stochasticity in various biological processes, both to understand the process in detail and to evaluate the effect of various sources of variability when creating simplified descriptions.

Research paper thumbnail of Division stochasticity can be transmitted to protein expression through chromosome replication

Stochastic fluctuations (noise) are a fundamental characteristic of protein production. Some sour... more Stochastic fluctuations (noise) are a fundamental characteristic of protein production. Some sources of this stochasticity are still under debate. In this work, we explore how these fluctuations can originate from the stochasticity on division events. To do that, we consider the classical gene expression model with chromosome replication following the known Helmstetter & Cooper model. This model predicts intervals of the cell cycle where bacteria can have more than one copy of a particular gene. Considering the transcription rate as proportional to the number of chromosomes and division based on a continuous rate model, we explore how stochasticity in division or equivalently in cell size, could be transmitted to gene expression. Our simulations suggest that division can be an important source of such fluctuations only if chromosomes are replicating, otherwise, this noise is not well transmitted. This effect happens even if replication is deterministic. This work can be helpful for ...

Research paper thumbnail of Noise signature in added size suggests bacteria target a commitment size to enable division

ABSTRACTRecent experiments suggested that sizer-like division strategy, a deviation from the adde... more ABSTRACTRecent experiments suggested that sizer-like division strategy, a deviation from the adder paradigm might be produced by additional degradation events of cell division machinery molecules. We revisited single cell size data from a recently microfluidics setup using the above model. We observed that such additional degradation process, although reproduces size observations in the mean sense, it is unable to capture cell size fluctuations. We further extended recently proposed power law models to include commitment size. Our proposal is in agreement of both mean and fluctuation profiles seen in experiments. Our approach suggests further uses of noise profiles on dissecting cell size regulatory mechanisms.SIGNIFICANCEWe contrast cell division models against bacteria cell size data in minimal media. Our results seems to support the idea that division starts once bacteria meet a given commitment size.

Research paper thumbnail of Continuous Rate Modelling of bacterial stochastic size dynamics

Bacterial division is an inherently stochastic process. However, theoretical tools to simulate an... more Bacterial division is an inherently stochastic process. However, theoretical tools to simulate and study the stochastic transient dynamics of cell-size are scarce. Here, we present a general theoretical approach based on the Chapman-Kolmogorov formalism to describe these stochastic dynamics including continuous growth and division events as jump processes. Using this approach, we analyze the effect of different sources of noise on the dynamics of the size distribution. Oscillations in the distribution central moments were found as consequence of the discrete translation invariance of the system with period of one doubling time, these oscillations are found in both the central moments of the size distribution and the auto-correlation function and do not disappear including stochasticity on division times or size heterogeneity on the population but only after include noise in either growth rate or septum position.

Research paper thumbnail of PyEcoLib: a python library for simulating E. coli stochastic size dynamics

Recent studies describe bacterial division as a jump process triggered when it reaches a fixed nu... more Recent studies describe bacterial division as a jump process triggered when it reaches a fixed number of stochastic discrete events at a rate depending on the cell-size. This theoretical approach enabled the computation of stochastic cell-size transient dynamics with arbitrary precision, with the possibility of being coupled to other continuous processes as gene expression. Here we synthesize most of this theory in the tool PyEcoLib, a python-based library to estimate bacterial cell size stochastic dynamics including continuous growth and division events. In this library, we include examples predicting statistical properties seen in experiments.

Research paper thumbnail of Correlation between protein concentration and bacterial cell size can reveal mechanisms of gene expression

Physical Biology, 2020

Classically, gene expression is modeled as a chemical process with reaction rates dependent on th... more Classically, gene expression is modeled as a chemical process with reaction rates dependent on the concentration of the reactants (typically, DNA loci, plasmids, RNA, enzymes, etc). Other variables like cell size are in general ignored. Size dynamics can become an important variable due to the low number of many of these reactants, imperfectly symmetric cell partitioning and molecule segregation. In this work we measure the correlation between size and protein concentration by observing the gene expression of the RpOD gene from a low-copy plasmid in Escherichia coli during balanced growth in different media. A positive correlation was found, and we used it to examine possible models of cell size dynamics and plasmid replication. We implemented a previously developed model describing the full gene expression process including transcription, translation, loci replication, cell division and molecule segregation. By comparing with the observed correlation, we determine that the transcri...

Research paper thumbnail of Efficient computation of stochastic cell-size transient dynamics

BMC Bioinformatics, 2019

Background How small, fast-growing bacteria ensure tight cell-size distributions remains elusive.... more Background How small, fast-growing bacteria ensure tight cell-size distributions remains elusive. High-throughput measurement techniques have propelled efforts to build modeling tools that help to shed light on the relationships between cell size, growth and cycle progression. Most proposed models describe cell division as a discrete map between size at birth and size at division with stochastic fluctuations assumed. However, such models underestimate the role of cell size transient dynamics by excluding them. Results We propose an efficient approach for estimation of cell size transient dynamics. Our technique approximates the transient size distribution and statistical moment dynamics of exponential growing cells following an adder strategy with arbitrary precision. Conclusions We approximate, up to arbitrary precision, the distribution of division times and size across time for the adder strategy in rod-shaped bacteria cells. Our approach is able to compute statistical moments li...

Research paper thumbnail of Stochasticity in bacterial division control: Preliminary consequences for protein concentration

The stochastic nature of protein concentration inside cells can have important consequences in th... more The stochastic nature of protein concentration inside cells can have important consequences in their physiology and population fitness. Classical models of gene expression consider these processes as first-order reactions with little dependence with the cell size. However, the concentrations of the relevant molecules depends directly on the cellular volume. Here we model the cell size dynamics as exponential growth followed by division with occurrence rate proportional to the size. This framework, together with known models of chromosome replication and both protein and mRNA synthesis, lets us predict relationships between cell size and both protein number and concentration. As a main result, we find that protein production strategies (constant rate or rate proportional to either chromosome number, cell size or chromosome number times cell size) can be experimentally distinguished from the correlation between protein concentration and cell size.

Research paper thumbnail of Critical Sources of Aerodynamic Resistance in a Medium Distance Urban Train: a CFD approach

Revista Guillermo de Ockham, 2013

How to cite Complete issue More information about this article Journal's homepage in redalyc.org ... more How to cite Complete issue More information about this article Journal's homepage in redalyc.org Scientific Information System Network of Scientific Journals from Latin America, the Caribbean, Spain and Portugal Non-profit academic project, developed under the open access initiative

Research paper thumbnail of A Conceptual Design of Energy Exchange System for Recovery of Residual Heat Using Aluminum Foams

Procedia Materials Science, 2014

ABSTRACT Open cell aluminum foams have been recently studied for its use in heat exchangers, heat... more ABSTRACT Open cell aluminum foams have been recently studied for its use in heat exchangers, heat sink and electronics cooling. In this paper, a conceptual design of a heat energy exchange recovering system for residual heat at low temperatures is studies for its potential industrial application. Experimental samples were produced by infiltration process using vacuum pressure. Samples with different pore sizes of 0.5, 1.0 and 2.0 mm were obtained. The samples dimensions were 50 mm x 50 mm x 5 mm and the material was characterized by structure analysis and fluid flow (pressure drop) and heat transfer measurements under transitory and steady state conditions. The experimentation carried on in regards of the fluid flow and heat transfer properties, shown that these two properties are extremely dependent on the pore size of the aluminum foam. In this preliminary study, the thermo-physical characteristics of the aluminum foams useful for energy exchange system in recuperating of residual heat (heat transfer efficiency, transfer time, amount of heat transferred and pressure drop generated), had been presented and used to create a conceptual design. From the tested parameters, the best foam structure and some process parameters have been established for a conceptual design a heat exchanger for a heat recovery system.

Research paper thumbnail of Boundary elements solution of stokes flow between curved surfaces with nonlinear slip boundary condition

Numerical Methods for Partial Differential Equations, 2012

ABSTRACT