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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.
21

Weighted Branching Automata / Combining Concurrency and Weights / Gewichtete verzweigende Automaten

Meinecke, Ingmar 05 November 2005 (has links) (PDF)
Eine der stärksten Erweiterungen der klassischen Theorie formaler Sprachen und Automaten ist die Einbeziehung von Gewichten oder Vielfachheiten aus einem Halbring. Diese Dissertation untersucht gewichtete Automaten über Strukturen mit Nebenläufigkeit. Wir erweitern die Arbeit von Lodaya und Weil und erhalten so ein Modell gewichteter verzweigender Automaten, in dem die Berechnung des Gewichts einer parallelen Komposition anders als die einer sequentiellen Komposition gehandhabt wird. Die von Lodaya und Weil eingeführten Automaten modellieren Nebenläufigkeit durch Verzweigen. Ein verzweigender Automat ist ein endlicher Automat mit drei verschiedenen Typen von Transitionen. Sequentielle Transitionen überführen durch Ausführen eines Ereignisses einen Zustand in einen anderen. Dagegen sind Gabel- und Binde-Transitionen für das Verzweigen verantwortlich. Läufe dieser Automaten werden beschrieben durch sequentiell-parallele posets, kurz sp-posets. Alle Transitionen des Automaten werden in unserem Modell mit Gewichten versehen. Neben dem Nichtdeterminismus und der sequentiellen Komposition wollen wir nun auch die parallele Komposition quantitativ behandeln. Dafür benötigen wir eine Gewichtsstruktur mit einer Addition, einer sequentiellen und einer parallelen Multiplikation. Solch eine Struktur, genannt Bihalbring, besteht damit de facto aus zwei Halbringen mit derselben additiven Struktur. Weiterhin muss die parallele Multiplikation kommutativ sein. Das Verhalten eines gewichteten verzweigenden Automaten ist dann eine Funktion, die jeder sp-poset ein Element eines Bihalbrings zuordnet. Das Hauptresultat charakterisiert das Verhalten dieser Automaten im Sinne von Kleenes und Schützenbergers Sätzen über das Zusammenfallen der Klassen der erkennbaren und der rationalen Sprachen bzw. formalen Potenzreihen. Darüber hinaus untersuchen wir den Abschluss dieser Verhalten unter allen rationalen Operationen und unter dem Hadamard-Produkt. Letztlich diskutieren wir Zusammenhänge zwischen Reihen und Sprachen im Rahmen verzweigender Automaten. / One of the most powerful extensions of classical formal language and automata theory is the consideration of weights or multiplicities from a semiring. This thesis investigates weighted automata over structures incorporating concurrency. Extending work by Lodaya and Weil, we propose a model of weighted branching automata in which the calculation of the weight of a parallel composition is handled differently from the calculation of the weight of a sequential composition. The automata as proposed by Lodaya and Weil model concurrency by branching. A branching automaton is a finite-state device with three different types of transitions. Sequential transitions transform a state into another one by executing an action. In contrast, fork and join transitions are responsible for branching. Executions of such systems can be described by sequential-parallel posets, or sp-posets for short. In the model considered here all kinds of transitions are equipped with weights. Beside non-determinism and sequential composition we would like to deal with the parallel composition in a quantitative way. Therefore, we are in need of a weight structure equipped with addition, a sequential, and, moreover, a parallel multiplication. Such a structure, called a bisemiring, is actually composed of two semirings with the same additive structure. Moreover, the parallel multiplication has to be commutative. Now, the behavior of a weighted branching automaton is a function that associates with every sp-poset an element from the bisemiring. The main result characterizes the behavior of these automata in the spirit of Kleene's and Schützenberger's theorems about the coincidence of recognizable and rational languages, and formal power series, respectively. Moreover, we investigate the closure of behaviors under all rational operations and under Hadamard-product. Finally, we discuss connections between series and languages within our setting.
22

Lattice-gas cellular automata for the analysis of cancer invasion / Zelluläre Gitter-Gas Automaten Modelle für die Analyse von Tumorinvasion

Hatzikirou, Haralambos 16 July 2009 (has links) (PDF)
Cancer cells display characteristic traits acquired in a step-wise manner during carcinogenesis. Some of these traits are autonomous growth, induction of angiogenesis, invasion and metastasis. In this thesis, the focus is on one of the latest stages of tumor progression, tumor invasion. Tumor invasion emerges from the combined effect of tumor cell-cell and cell-microenvironment interactions, which can be studied with the help of mathematical analysis. Cellular automata (CA) can be viewed as simple models of self-organizing complex systems in which collective behavior can emerge out of an ensemble of many interacting "simple" components. In particular, we focus on an important class of CA, the so-called lattice-gas cellular automata (LGCA). In contrast to traditional CA, LGCA provide a straightforward and intuitive implementation of particle transport and interactions. Additionally, the structure of LGCA facilitates the mathematical analysis of their behavior. Here, the principal tools of mathematical analysis of LGCA are the mean-field approximation and the corresponding Lattice Boltzmann equation. The main objective of this thesis is to investigate important aspects of tumor invasion, under the microscope of mathematical modeling and analysis: Impact of the tumor environment: We introduce a LGCA as a microscopic model of tumor cell migration together with a mathematical description of different tumor environments. We study the impact of the various tumor environments (such as extracellular matrix) on tumor cell migration by estimating the tumor cell dispersion speed for a given environment. Effect of tumor cell proliferation and migration: We study the effect of tumor cell proliferation and migration on the tumor’s invasive behavior by developing a simplified LGCA model of tumor growth. In particular, we derive the corresponding macroscopic dynamics and we calculate the tumor’s invasion speed in terms of tumor cell proliferation and migration rates. Moreover, we calculate the width of the invasive zone, where the majority of mitotic activity is concentrated, and it is found to be proportional to the invasion speed. Mechanisms of tumor invasion emergence: We investigate the mechanisms for the emergence of tumor invasion in the course of cancer progression. We conclude that the response of a microscopic intracellular mechanism (migration/proliferation dichotomy) to oxygen shortage, i.e. hypoxia, maybe responsible for the transition from a benign (proliferative) to a malignant (invasive) tumor. Computing in vivo tumor invasion: Finally, we propose an evolutionary algorithm that estimates the parameters of a tumor growth LGCA model based on time-series of patient medical data (in particular Magnetic Resonance and Diffusion Tensor Imaging data). These parameters may allow to reproduce clinically relevant tumor growth scenarios for a specific patient, providing a prediction of the tumor growth at a later time stage. / Krebszellen zeigen charakteristische Merkmale, die sie in einem schrittweisen Vorgang während der Karzinogenese erworben haben. Einige dieser Merkmale sind autonomes Wachstum, die Induktion von Angiogenese, Invasion und Metastasis. Der Schwerpunkt dieser Arbeit liegt auf der Tumorinvasion, einer der letzten Phasen der Tumorprogression. Die Tumorinvasion ensteht aus der kombinierten Wirkung von den Wechselwirkungen Tumorzelle-Zelle und Zelle-Mikroumgebung, die mit die Hilfe von mathematischer Analyse untersucht werden können. Zelluläre Automaten (CA) können als einfache Modelle von selbst-organisierenden komplexen Systemen betrachtet werden, in denen kollektives Verhalten aus einer Kombination von vielen interagierenden "einfachen" Komponenten entstehen kann. Insbesondere konzentrieren wir uns auf eine wichtige CA-Klasse, die sogenannten Zelluläre Gitter-Gas Automaten (LGCA). Im Gegensatz zu traditionellen CA bieten LGCA eine einfache und intuitive Umsetzung der Teilchen und Wechselwirkungen. Zusätzlich erleichtert die Struktur der LGCA die mathematische Analyse ihres Verhaltens. Die wichtigsten Werkzeuge der mathematischen Analyse der LGCA sind hier die Mean-field Approximation und die entsprechende Lattice - Boltzmann - Gleichung. Das wichtigste Ziel dieser Arbeit ist es, wichtige Aspekte der Tumorinvasion unter dem Mikroskop der mathematischen Modellierung und Analyse zu erforschen: Auswirkungen der Tumorumgebung: Wir stellen einen LGCA als mikroskopisches Modell der Tumorzellen-Migration in Verbindung mit einer mathematischen Beschreibung der verschiedenen Tumorumgebungen vor. Wir untersuchen die Auswirkungen der verschiedenen Tumorumgebungen (z. B. extrazellulären Matrix) auf die Migration von Tumorzellen dürch Schätzung der Tumorzellen-Dispersionsgeschwindigkeit in einem gegebenen Umfeld. Wirkung von Tumor-Zellenproliferation und Migration: Wir untersuchen die Wirkung von Tumorzellenproliferation und Migration auf das invasive Verhalten der Tumorzellen durch die Entwicklung eines vereinfachten LGCA Tumorwachstumsmodells. Wir leiten die entsprechende makroskopische Dynamik und berechnen die Tumorinvasionsgeschwindigkeit im Hinblick auf die Tumorzellenproliferation- und Migrationswerte. Darüber hinaus berechnen wir die Breite der invasiven Zone, wo die Mehrheit der mitotischer Aktivität konzentriert ist, und es wird festgestellt, dass diese proportional zu den Invasionsgeschwindigkeit ist. Mechanismen der Tumorinvasion Entstehung: Wir untersuchen Mechanismen, die für die Entstehung von Tumorinvasion im Verlauf des Krebs zuständig sind. Wir kommen zu dem Schluss, dass die Reaktion eines mikroskopischen intrazellulären Mechanismus (Migration/Proliferation Dichotomie) zu Sauerstoffmangel, d.h. Hypoxie, möglicheweise für den Übergang von einem gutartigen (proliferative) zu einer bösartigen (invasive) Tumor verantwortlich ist. Berechnung der in-vivo Tumorinvasion: Schließlich schlagen wir einen evolutionären Algorithmus vor, der die Parameter eines LGCA Modells von Tumorwachstum auf der Grundlage von medizinischen Daten des Patienten für mehrere Zeitpunkte (insbesondere die Magnet-Resonanz-und Diffusion Tensor Imaging Daten) ermöglicht. Diese Parameter erlauben Szenarien für einen klinisch relevanten Tumorwachstum für einen bestimmten Patienten zu reproduzieren, die eine Vorhersage des Tumorwachstums zu einem späteren Zeitpunkt möglich machen.
23

Tracking of individual cell trajectories in LGCA models of migrating cell populations

Mente, Carsten 22 May 2015 (has links) (PDF)
Cell migration, the active translocation of cells is involved in various biological processes, e.g. development of tissues and organs, tumor invasion and wound healing. Cell migration behavior can be divided into two distinct classes: single cell migration and collective cell migration. Single cell migration describes the migration of cells without interaction with other cells in their environment. Collective cell migration is the joint, active movement of multiple cells, e.g. in the form of strands, cohorts or sheets which emerge as the result of individual cell-cell interactions. Collective cell migration can be observed during branching morphogenesis, vascular sprouting and embryogenesis. Experimental studies of single cell migration have been extensive. Collective cell migration is less well investigated due to more difficult experimental conditions than for single cell migration. Especially, experimentally identifying the impact of individual differences in cell phenotypes on individual cell migration behavior inside cell populations is challenging because the tracking of individual cell trajectories is required. In this thesis, a novel mathematical modeling approach, individual-based lattice-gas cellular automata (IB-LGCA), that allows to investigate the migratory behavior of individual cells inside migrating cell populations by enabling the tracking of individual cells is introduced. Additionally, stochastic differential equation (SDE) approximations of individual cell trajectories for IB-LGCA models are constructed. Such SDE approximations allow the analytical description of the trajectories of individual cells during single cell migration. For a complete analytical description of the trajectories of individual cell during collective cell migration the aforementioned SDE approximations alone are not sufficient. Analytical approximations of the time development of selected observables for the cell population have to be added. What observables have to be considered depends on the specific cell migration mechanisms that is to be modeled. Here, partial integro-differential equations (PIDE) that approximate the time evolution of the expected cell density distribution in IB-LGCA are constructed and coupled to SDE approximations of individual cell trajectories. Such coupled PIDE and SDE approximations provide an analytical description of the trajectories of individual cells in IB-LGCA with density-dependent cell-cell interactions. Finally, an IB-LGCA model and corresponding analytical approximations were applied to investigate the impact of changes in cell-cell and cell-ECM forces on the migration behavior of an individual, labeled cell inside a population of epithelial cells. Specifically, individual cell migration during the epithelial-mesenchymal transition (EMT) was considered. EMT is a change from epithelial to mesenchymal cell phenotype which is characterized by cells breaking adhesive bonds with surrounding epithelial cells and initiating individual migration along the extracellular matrix (ECM). During the EMT, a transition from collective to single cell migration occurs. EMT plays an important role during cancer progression, where it is believed to be linked to metastasis development. In the IB-LGCA model epithelial cells are characterized by balanced cell-cell and cell-ECM forces. The IB-LGCA model predicts that the balance between cell-cell and cell-ECM forces can be disturbed to some degree without being accompanied by a change in individual cell migration behavior. Only after the cell force balance has been strongly interrupted mesenchymal migration behavior is possible. The force threshold which separates epithelial and mesenchymal migration behavior in the IB-LGCA has been identified from the corresponding analytical approximation. The IB-LGCA model allows to obtain quantitative predictions about the role of cell forces during EMT which in the context of mathematical modeling of EMT is a novel approach.
24

Topological Conjugacies Between Cellular Automata

Epperlein, Jeremias 19 December 2017 (has links) (PDF)
We study cellular automata as discrete dynamical systems and in particular investigate under which conditions two cellular automata are topologically conjugate. Based on work of McKinsey, Tarski, Pierce and Head we introduce derivative algebras to study the topological structure of sofic shifts in dimension one. This allows us to classify periodic cellular automata on sofic shifts up to topological conjugacy based on the structure of their periodic points. We also get new conjugacy invariants in the general case. Based on a construction by Hanf and Halmos, we construct a pair of non-homeomorphic subshifts whose disjoint sums with themselves are homeomorphic. From this we can construct two cellular automata on homeomorphic state spaces for which all points have minimal period two, which are, however, not topologically conjugate. We apply our methods to classify the 256 elementary cellular automata with radius one over the binary alphabet up to topological conjugacy. By means of linear algebra over the field with two elements and identities between Fibonacci-polynomials we show that every conjugacy between rule 90 and rule 150 cannot have only a finite number of local rules. Finally, we look at the sequences of finite dynamical systems obtained by restricting cellular automata to spatially periodic points. If these sequences are termwise conjugate, we call the cellular automata conjugate on all tori. We then study the invariants under this notion of isomorphism. By means of an appropriately defined entropy, we can show that surjectivity is such an invariant.
25

Weighted Branching Automata: Combining Concurrency and Weights

Meinecke, Ingmar 14 December 2004 (has links)
Eine der stärksten Erweiterungen der klassischen Theorie formaler Sprachen und Automaten ist die Einbeziehung von Gewichten oder Vielfachheiten aus einem Halbring. Diese Dissertation untersucht gewichtete Automaten über Strukturen mit Nebenläufigkeit. Wir erweitern die Arbeit von Lodaya und Weil und erhalten so ein Modell gewichteter verzweigender Automaten, in dem die Berechnung des Gewichts einer parallelen Komposition anders als die einer sequentiellen Komposition gehandhabt wird. Die von Lodaya und Weil eingeführten Automaten modellieren Nebenläufigkeit durch Verzweigen. Ein verzweigender Automat ist ein endlicher Automat mit drei verschiedenen Typen von Transitionen. Sequentielle Transitionen überführen durch Ausführen eines Ereignisses einen Zustand in einen anderen. Dagegen sind Gabel- und Binde-Transitionen für das Verzweigen verantwortlich. Läufe dieser Automaten werden beschrieben durch sequentiell-parallele posets, kurz sp-posets. Alle Transitionen des Automaten werden in unserem Modell mit Gewichten versehen. Neben dem Nichtdeterminismus und der sequentiellen Komposition wollen wir nun auch die parallele Komposition quantitativ behandeln. Dafür benötigen wir eine Gewichtsstruktur mit einer Addition, einer sequentiellen und einer parallelen Multiplikation. Solch eine Struktur, genannt Bihalbring, besteht damit de facto aus zwei Halbringen mit derselben additiven Struktur. Weiterhin muss die parallele Multiplikation kommutativ sein. Das Verhalten eines gewichteten verzweigenden Automaten ist dann eine Funktion, die jeder sp-poset ein Element eines Bihalbrings zuordnet. Das Hauptresultat charakterisiert das Verhalten dieser Automaten im Sinne von Kleenes und Schützenbergers Sätzen über das Zusammenfallen der Klassen der erkennbaren und der rationalen Sprachen bzw. formalen Potenzreihen. Darüber hinaus untersuchen wir den Abschluss dieser Verhalten unter allen rationalen Operationen und unter dem Hadamard-Produkt. Letztlich diskutieren wir Zusammenhänge zwischen Reihen und Sprachen im Rahmen verzweigender Automaten. / One of the most powerful extensions of classical formal language and automata theory is the consideration of weights or multiplicities from a semiring. This thesis investigates weighted automata over structures incorporating concurrency. Extending work by Lodaya and Weil, we propose a model of weighted branching automata in which the calculation of the weight of a parallel composition is handled differently from the calculation of the weight of a sequential composition. The automata as proposed by Lodaya and Weil model concurrency by branching. A branching automaton is a finite-state device with three different types of transitions. Sequential transitions transform a state into another one by executing an action. In contrast, fork and join transitions are responsible for branching. Executions of such systems can be described by sequential-parallel posets, or sp-posets for short. In the model considered here all kinds of transitions are equipped with weights. Beside non-determinism and sequential composition we would like to deal with the parallel composition in a quantitative way. Therefore, we are in need of a weight structure equipped with addition, a sequential, and, moreover, a parallel multiplication. Such a structure, called a bisemiring, is actually composed of two semirings with the same additive structure. Moreover, the parallel multiplication has to be commutative. Now, the behavior of a weighted branching automaton is a function that associates with every sp-poset an element from the bisemiring. The main result characterizes the behavior of these automata in the spirit of Kleene's and Schützenberger's theorems about the coincidence of recognizable and rational languages, and formal power series, respectively. Moreover, we investigate the closure of behaviors under all rational operations and under Hadamard-product. Finally, we discuss connections between series and languages within our setting.
26

Kompatibilitätsanalyse dynamischen Verhaltens von integrierten Automobil-Steuergeräten

Glockner, Matthias, Fuchs, Maximilian, Macht, Michael 08 June 2007 (has links)
In Premium-Fahrzeugen werden derzeit ca. 60-70 Steuergeräte (SG) verbaut. Steuergeräte sind „eingebettete Systeme“ und stellen die zentralen Rechen- und Steuereinheiten für die elektrischen und elektronischen Systeme im Fahrzeug dar. Mit Hilfe der Steuergeräte, die über Bus-Systeme (z.B. CAN-Bus) miteinander vernetzt sind, können komplexe Funktionen realisiert werden. Das Motor- Steuergerät ist eines der bekanntesten. Der steigende Innovationsgrad im Elektrik- / Elektronik- Umfeld zwingt die Autohersteller, in immer kürzeren Zeitabständen, neue Steuergeräte mit höherer Rechenleistung und neuen Funktionen zu entwickeln. Aufgrund der steigenden Anzahl von Steuergeräten, spielt deren Rückwärtskompatibilität eine immer wichtigere Rolle.
27

Structural distortions in molecular-based quantum cellular automata: a minimal model based study

Santana Bonilla, Alejandro, Gutierrez, Rafael, Medrano Sandonas, Leonardo, Nozaki, Daijiro, Bramanti, Alessandro Paolo, Cuniberti, Gianaurelio 10 January 2020 (has links)
Molecular-based quantum cellular automata (m-QCA), as an extension of quantum-dot QCAs, offer a novel alternative in which binary information can be encoded in the molecular charge configuration of a cell and propagated via nearest-neighbor Coulombic cell–cell interactions. Appropriate functionality of m-QCAs involves a complex relationship between quantum mechanical effects, such as electron transfer processes within the molecular building blocks, and electrostatic interactions between cells. The influence of structural distortions of single m-QCA are addressed in this paper within a minimal model using an diabatic-to-adiabatic transformation. We show that even small changes of the classical square geometry between driver and target cells, such as those induced by distance variations or shape distortions, can make cells respond to interactions in a far less symmetric fashion, modifying and potentially impairing the expected computational behavior of the m-QCA.
28

Tracking of individual cell trajectories in LGCA models of migrating cell populations

Mente, Carsten 20 April 2015 (has links)
Cell migration, the active translocation of cells is involved in various biological processes, e.g. development of tissues and organs, tumor invasion and wound healing. Cell migration behavior can be divided into two distinct classes: single cell migration and collective cell migration. Single cell migration describes the migration of cells without interaction with other cells in their environment. Collective cell migration is the joint, active movement of multiple cells, e.g. in the form of strands, cohorts or sheets which emerge as the result of individual cell-cell interactions. Collective cell migration can be observed during branching morphogenesis, vascular sprouting and embryogenesis. Experimental studies of single cell migration have been extensive. Collective cell migration is less well investigated due to more difficult experimental conditions than for single cell migration. Especially, experimentally identifying the impact of individual differences in cell phenotypes on individual cell migration behavior inside cell populations is challenging because the tracking of individual cell trajectories is required. In this thesis, a novel mathematical modeling approach, individual-based lattice-gas cellular automata (IB-LGCA), that allows to investigate the migratory behavior of individual cells inside migrating cell populations by enabling the tracking of individual cells is introduced. Additionally, stochastic differential equation (SDE) approximations of individual cell trajectories for IB-LGCA models are constructed. Such SDE approximations allow the analytical description of the trajectories of individual cells during single cell migration. For a complete analytical description of the trajectories of individual cell during collective cell migration the aforementioned SDE approximations alone are not sufficient. Analytical approximations of the time development of selected observables for the cell population have to be added. What observables have to be considered depends on the specific cell migration mechanisms that is to be modeled. Here, partial integro-differential equations (PIDE) that approximate the time evolution of the expected cell density distribution in IB-LGCA are constructed and coupled to SDE approximations of individual cell trajectories. Such coupled PIDE and SDE approximations provide an analytical description of the trajectories of individual cells in IB-LGCA with density-dependent cell-cell interactions. Finally, an IB-LGCA model and corresponding analytical approximations were applied to investigate the impact of changes in cell-cell and cell-ECM forces on the migration behavior of an individual, labeled cell inside a population of epithelial cells. Specifically, individual cell migration during the epithelial-mesenchymal transition (EMT) was considered. EMT is a change from epithelial to mesenchymal cell phenotype which is characterized by cells breaking adhesive bonds with surrounding epithelial cells and initiating individual migration along the extracellular matrix (ECM). During the EMT, a transition from collective to single cell migration occurs. EMT plays an important role during cancer progression, where it is believed to be linked to metastasis development. In the IB-LGCA model epithelial cells are characterized by balanced cell-cell and cell-ECM forces. The IB-LGCA model predicts that the balance between cell-cell and cell-ECM forces can be disturbed to some degree without being accompanied by a change in individual cell migration behavior. Only after the cell force balance has been strongly interrupted mesenchymal migration behavior is possible. The force threshold which separates epithelial and mesenchymal migration behavior in the IB-LGCA has been identified from the corresponding analytical approximation. The IB-LGCA model allows to obtain quantitative predictions about the role of cell forces during EMT which in the context of mathematical modeling of EMT is a novel approach.
29

Topological Conjugacies Between Cellular Automata

Epperlein, Jeremias 21 April 2017 (has links)
We study cellular automata as discrete dynamical systems and in particular investigate under which conditions two cellular automata are topologically conjugate. Based on work of McKinsey, Tarski, Pierce and Head we introduce derivative algebras to study the topological structure of sofic shifts in dimension one. This allows us to classify periodic cellular automata on sofic shifts up to topological conjugacy based on the structure of their periodic points. We also get new conjugacy invariants in the general case. Based on a construction by Hanf and Halmos, we construct a pair of non-homeomorphic subshifts whose disjoint sums with themselves are homeomorphic. From this we can construct two cellular automata on homeomorphic state spaces for which all points have minimal period two, which are, however, not topologically conjugate. We apply our methods to classify the 256 elementary cellular automata with radius one over the binary alphabet up to topological conjugacy. By means of linear algebra over the field with two elements and identities between Fibonacci-polynomials we show that every conjugacy between rule 90 and rule 150 cannot have only a finite number of local rules. Finally, we look at the sequences of finite dynamical systems obtained by restricting cellular automata to spatially periodic points. If these sequences are termwise conjugate, we call the cellular automata conjugate on all tori. We then study the invariants under this notion of isomorphism. By means of an appropriately defined entropy, we can show that surjectivity is such an invariant.
30

Lattice-gas cellular automata for the analysis of cancer invasion

Hatzikirou, Haralambos 10 July 2009 (has links)
Cancer cells display characteristic traits acquired in a step-wise manner during carcinogenesis. Some of these traits are autonomous growth, induction of angiogenesis, invasion and metastasis. In this thesis, the focus is on one of the latest stages of tumor progression, tumor invasion. Tumor invasion emerges from the combined effect of tumor cell-cell and cell-microenvironment interactions, which can be studied with the help of mathematical analysis. Cellular automata (CA) can be viewed as simple models of self-organizing complex systems in which collective behavior can emerge out of an ensemble of many interacting "simple" components. In particular, we focus on an important class of CA, the so-called lattice-gas cellular automata (LGCA). In contrast to traditional CA, LGCA provide a straightforward and intuitive implementation of particle transport and interactions. Additionally, the structure of LGCA facilitates the mathematical analysis of their behavior. Here, the principal tools of mathematical analysis of LGCA are the mean-field approximation and the corresponding Lattice Boltzmann equation. The main objective of this thesis is to investigate important aspects of tumor invasion, under the microscope of mathematical modeling and analysis: Impact of the tumor environment: We introduce a LGCA as a microscopic model of tumor cell migration together with a mathematical description of different tumor environments. We study the impact of the various tumor environments (such as extracellular matrix) on tumor cell migration by estimating the tumor cell dispersion speed for a given environment. Effect of tumor cell proliferation and migration: We study the effect of tumor cell proliferation and migration on the tumor’s invasive behavior by developing a simplified LGCA model of tumor growth. In particular, we derive the corresponding macroscopic dynamics and we calculate the tumor’s invasion speed in terms of tumor cell proliferation and migration rates. Moreover, we calculate the width of the invasive zone, where the majority of mitotic activity is concentrated, and it is found to be proportional to the invasion speed. Mechanisms of tumor invasion emergence: We investigate the mechanisms for the emergence of tumor invasion in the course of cancer progression. We conclude that the response of a microscopic intracellular mechanism (migration/proliferation dichotomy) to oxygen shortage, i.e. hypoxia, maybe responsible for the transition from a benign (proliferative) to a malignant (invasive) tumor. Computing in vivo tumor invasion: Finally, we propose an evolutionary algorithm that estimates the parameters of a tumor growth LGCA model based on time-series of patient medical data (in particular Magnetic Resonance and Diffusion Tensor Imaging data). These parameters may allow to reproduce clinically relevant tumor growth scenarios for a specific patient, providing a prediction of the tumor growth at a later time stage. / Krebszellen zeigen charakteristische Merkmale, die sie in einem schrittweisen Vorgang während der Karzinogenese erworben haben. Einige dieser Merkmale sind autonomes Wachstum, die Induktion von Angiogenese, Invasion und Metastasis. Der Schwerpunkt dieser Arbeit liegt auf der Tumorinvasion, einer der letzten Phasen der Tumorprogression. Die Tumorinvasion ensteht aus der kombinierten Wirkung von den Wechselwirkungen Tumorzelle-Zelle und Zelle-Mikroumgebung, die mit die Hilfe von mathematischer Analyse untersucht werden können. Zelluläre Automaten (CA) können als einfache Modelle von selbst-organisierenden komplexen Systemen betrachtet werden, in denen kollektives Verhalten aus einer Kombination von vielen interagierenden "einfachen" Komponenten entstehen kann. Insbesondere konzentrieren wir uns auf eine wichtige CA-Klasse, die sogenannten Zelluläre Gitter-Gas Automaten (LGCA). Im Gegensatz zu traditionellen CA bieten LGCA eine einfache und intuitive Umsetzung der Teilchen und Wechselwirkungen. Zusätzlich erleichtert die Struktur der LGCA die mathematische Analyse ihres Verhaltens. Die wichtigsten Werkzeuge der mathematischen Analyse der LGCA sind hier die Mean-field Approximation und die entsprechende Lattice - Boltzmann - Gleichung. Das wichtigste Ziel dieser Arbeit ist es, wichtige Aspekte der Tumorinvasion unter dem Mikroskop der mathematischen Modellierung und Analyse zu erforschen: Auswirkungen der Tumorumgebung: Wir stellen einen LGCA als mikroskopisches Modell der Tumorzellen-Migration in Verbindung mit einer mathematischen Beschreibung der verschiedenen Tumorumgebungen vor. Wir untersuchen die Auswirkungen der verschiedenen Tumorumgebungen (z. B. extrazellulären Matrix) auf die Migration von Tumorzellen dürch Schätzung der Tumorzellen-Dispersionsgeschwindigkeit in einem gegebenen Umfeld. Wirkung von Tumor-Zellenproliferation und Migration: Wir untersuchen die Wirkung von Tumorzellenproliferation und Migration auf das invasive Verhalten der Tumorzellen durch die Entwicklung eines vereinfachten LGCA Tumorwachstumsmodells. Wir leiten die entsprechende makroskopische Dynamik und berechnen die Tumorinvasionsgeschwindigkeit im Hinblick auf die Tumorzellenproliferation- und Migrationswerte. Darüber hinaus berechnen wir die Breite der invasiven Zone, wo die Mehrheit der mitotischer Aktivität konzentriert ist, und es wird festgestellt, dass diese proportional zu den Invasionsgeschwindigkeit ist. Mechanismen der Tumorinvasion Entstehung: Wir untersuchen Mechanismen, die für die Entstehung von Tumorinvasion im Verlauf des Krebs zuständig sind. Wir kommen zu dem Schluss, dass die Reaktion eines mikroskopischen intrazellulären Mechanismus (Migration/Proliferation Dichotomie) zu Sauerstoffmangel, d.h. Hypoxie, möglicheweise für den Übergang von einem gutartigen (proliferative) zu einer bösartigen (invasive) Tumor verantwortlich ist. Berechnung der in-vivo Tumorinvasion: Schließlich schlagen wir einen evolutionären Algorithmus vor, der die Parameter eines LGCA Modells von Tumorwachstum auf der Grundlage von medizinischen Daten des Patienten für mehrere Zeitpunkte (insbesondere die Magnet-Resonanz-und Diffusion Tensor Imaging Daten) ermöglicht. Diese Parameter erlauben Szenarien für einen klinisch relevanten Tumorwachstum für einen bestimmten Patienten zu reproduzieren, die eine Vorhersage des Tumorwachstums zu einem späteren Zeitpunkt möglich machen.

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