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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Perturbations in Boolean Networks

Ghanbarnejad, Fakhteh 27 September 2012 (has links) (PDF)
Boolean networks are coarse-grained models of the regulatory dynamics that controls the survival and proliferation of a living cell. The dynamics is time- and state-discrete. This Boolean abstraction assumes that small differences in concentration levels are irrelevant; and the binary distinction of a low or a high concentration of each biomolecule is sufficient to capture the dynamics. In this work, we briefly introduce the gene regulatory models, where with the advent of system-specific Boolean models, new conceptual questions and analytical and numerical challenges arise. In particular, the response of the system to external intervention presents a novel area of research. Thus first we investigate how to quantify a node\\\'s individual impact on dynamics in a more detailed manner than an averaging against all eligible perturbations. Since each node now represents a specific biochemical entity, it is the subject of our interest. The prediction of nodes\\\' dynamical impacts from the model may be compared to the empirical data from biological experiments. Then we develop a hybrid model that incorporates both continuous and discrete random Boolean networks to compare the reaction of the dynamics against small as well as flip perturbations in different regimes. We show that the chaotic behaviour disappears in high sensitive Boolean ensembles with respect to continuous small fluctuations in contrast to the flipping. Finally, we discuss the role of distributing delays in stabilizing of the Boolean dynamics against noise. These studies are expected to trigger additional experiments and lead to improvement of models in gene regulatory dynamics.
2

Perturbations in Boolean Networks

Ghanbarnejad, Fakhteh 14 September 2012 (has links)
Boolean networks are coarse-grained models of the regulatory dynamics that controls the survival and proliferation of a living cell. The dynamics is time- and state-discrete. This Boolean abstraction assumes that small differences in concentration levels are irrelevant; and the binary distinction of a low or a high concentration of each biomolecule is sufficient to capture the dynamics. In this work, we briefly introduce the gene regulatory models, where with the advent of system-specific Boolean models, new conceptual questions and analytical and numerical challenges arise. In particular, the response of the system to external intervention presents a novel area of research. Thus first we investigate how to quantify a node\\\''s individual impact on dynamics in a more detailed manner than an averaging against all eligible perturbations. Since each node now represents a specific biochemical entity, it is the subject of our interest. The prediction of nodes\\\'' dynamical impacts from the model may be compared to the empirical data from biological experiments. Then we develop a hybrid model that incorporates both continuous and discrete random Boolean networks to compare the reaction of the dynamics against small as well as flip perturbations in different regimes. We show that the chaotic behaviour disappears in high sensitive Boolean ensembles with respect to continuous small fluctuations in contrast to the flipping. Finally, we discuss the role of distributing delays in stabilizing of the Boolean dynamics against noise. These studies are expected to trigger additional experiments and lead to improvement of models in gene regulatory dynamics.
3

Physical Aspects of Min Oscillations in Escherichia Coli

Meacci, Giovanni 25 January 2007 (has links) (PDF)
The subject of this thesis is the generation of spatial temporal structures in living cells. Specifically, we studied the Min-system in the bacterium Escherichia coli. It consists of the MinC, the MinD, and the MinE proteins, which play an important role in the correct selection of the cell division site. The Min-proteins oscillate between the two cell poles and thereby prevent division at these locations. In this way, E. coli divides at the center, producing two daughter cells of equal size, providing them with the complete genetic patrimony. Our goal is to perform a quantitative study, both theoretical and experimental, in order to reveal the mechanism underlying the Min-oscillations. Experimentally, we characterize theMin-system, measuring the temporal period of the oscillations as a function of the cell length, the time-averaged protein distributions, and the in vivo Min-protein mobility by means of different fluorescence microscopy techniques. Theoretically, we discuss a deterministic description based on the exchange of Minproteins between the cytoplasm and the cytoplasmic membrane and on the aggregation current induced by the interaction between membrane-bound proteins. Oscillatory solutions appear via a dynamic instability of the homogenous protein distributions. Moreover, we perform stochastic simulations based on a microscopic description, whereby the probability for each event is calculated according to the corresponding probability in the master equation. Starting from this microscopic description, we derive Langevin equations for the fluctuating protein densities which correspond to the deterministic equations in the limit of vanishing noise. Stochastic simulations justify this deterministic model, showing that oscillations are resistant to the perturbations induced by the stochastic reactions and diffusion. Predictions and assumptions of our theoretical model are compatible with our experimental findings. Altogether, these results enable us to propose further experiments in order to quantitatively compare the different models proposed so far and to test our model with even higher precision. They also point to the necessity of performing such an analysis through single cell measurements.
4

Physical Aspects of Min Oscillations in Escherichia Coli

Meacci, Giovanni 20 December 2006 (has links)
The subject of this thesis is the generation of spatial temporal structures in living cells. Specifically, we studied the Min-system in the bacterium Escherichia coli. It consists of the MinC, the MinD, and the MinE proteins, which play an important role in the correct selection of the cell division site. The Min-proteins oscillate between the two cell poles and thereby prevent division at these locations. In this way, E. coli divides at the center, producing two daughter cells of equal size, providing them with the complete genetic patrimony. Our goal is to perform a quantitative study, both theoretical and experimental, in order to reveal the mechanism underlying the Min-oscillations. Experimentally, we characterize theMin-system, measuring the temporal period of the oscillations as a function of the cell length, the time-averaged protein distributions, and the in vivo Min-protein mobility by means of different fluorescence microscopy techniques. Theoretically, we discuss a deterministic description based on the exchange of Minproteins between the cytoplasm and the cytoplasmic membrane and on the aggregation current induced by the interaction between membrane-bound proteins. Oscillatory solutions appear via a dynamic instability of the homogenous protein distributions. Moreover, we perform stochastic simulations based on a microscopic description, whereby the probability for each event is calculated according to the corresponding probability in the master equation. Starting from this microscopic description, we derive Langevin equations for the fluctuating protein densities which correspond to the deterministic equations in the limit of vanishing noise. Stochastic simulations justify this deterministic model, showing that oscillations are resistant to the perturbations induced by the stochastic reactions and diffusion. Predictions and assumptions of our theoretical model are compatible with our experimental findings. Altogether, these results enable us to propose further experiments in order to quantitatively compare the different models proposed so far and to test our model with even higher precision. They also point to the necessity of performing such an analysis through single cell measurements.

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