Reusing simulation experiments for model composition and extension

This thesis aims to reuse simulation experiments to support developing models via model reuse, with a focus on validating the resulting model. Individual models are annotated with their simulation experiments. Upon reuse of those models for building new ones, the associated simulation experiments are also reused and executed with the new model, to inspect whether the key behavior exhibited by the original models is preserved or not in the new model. Hence, the changes of model behavior resulting from the model reuse are revealed, and insights into validity of the new model are provided

Toward guiding simulation experiments

To face the variety of simulation experiment methods, tools are needed that allow their seamless integration, guide the user through the steps of an experiment, and support him in selecting the most suitable method for the task at hand. This work presents techniques for facing such challenges. To guide users through the experiment process, six typical tasks have been identified for structuring the experiment workflow. The M&S framework JAMES II and its plug-in system is exploited to integrate various methods. Finally, an approach for automatic selection and use of such methods is realized

Domain-specific languages for modeling and simulation

Simulation models and simulation experiments are increasingly complex. One way to handle this complexity is developing software languages tailored to specific application domains, so-called domain-specific languages (DSLs). This thesis explores the potential of employing DSLs in modeling and simulation. We study different DSL design and implementation techniques and illustrate their benefits for expressing simulation models as well as simulation experiments with several examples.Simulationsmodelle und -experimente werden immer komplexer. Eine Möglichkeit, dieser Komplexität zu begegnen, ist, auf bestimmte Anwendungsgebiete spezialisierte Softwaresprachen, sogenannte domänenspezifische Sprachen (\emph{DSLs, domain-specific languages}), zu entwickeln. Die vorliegende Arbeit untersucht, wie DSLs in der Modellierung und Simulation eingesetzt werden können. Wir betrachten verschiedene Techniken für Entwicklung und Implementierung von DSLs und illustrieren ihren Nutzen für das Ausdrücken von Simulationsmodellen und -experimenten anhand einiger Beispiele

Simulator adaptation at runtime for component-based simulation software

Component-based simulation software can provide many opportunities to compose and configure simulators, resulting in an algorithm selection problem for the user of this software. This thesis aims to automate the selection and adaptation of simulators at runtime in an application-independent manner. Further, it explores the potential of tailored and approximate simulators - in this thesis concretely developed for the modeling language ML-Rules - supporting the effectiveness of the adaptation scheme.Komponenten-basierte Simulationssoftware kann viele Möglichkeiten zur Komposition und Konfiguration von Simulatoren bieten und damit zu einem Konfigurationsproblem für Nutzer dieser Software führen. Das Ziel dieser Arbeit ist die Entwicklung einer generischen und automatisierten Auswahl- und Adaptionsmethode für Simulatoren. Darüber hinaus wird das Potential von spezifischen und approximativen Simulatoren anhand der Modellierungssprache ML-Rules untersucht, welche die Effektivität des entwickelten Adaptionsmechanismus erhöhen können

Advances in modelling of epithelial to mesenchymal transition

Epithelial to Mesenchymal Transition (EMT) is a cellular transformation process that is employed repeatedly and ubiquitously during vertebrate morphogenesis to build complex tissues and organs. Cellular transformations that occur during cancer cell invasion are phenotypically similar to developmental EMT, and involve the same molecular signalling pathways. EMT processes are diverse, but are characterised by: a loss of cell-cell adhesion; a gain in cell-matrix adhesion; an increase in cell motility; the secretion of proteases that degrade basement membrane proteins; an increased resistance to apoptosis; a loss of polarisation; increased production of extracellular matrix components; a change from a rounded to a fibroblastic morphology; and an invasive phenotype. This thesis focuses explicitly on endocardial EMT, which is the EMT that occurs during vertebrate embryonic heart development. The embryonic heart initially forms as a tube, with myocardium externally, endocardium internally, with these tissue layers separated by a thick extracellular matrix termed the cardiac jelly. Some of the endocardial cells in specific regions of the embryonic heart tube undergo EMT and invade the cardiac jelly. This causes cellularised swellings inside the embryonic heart tube termed the endocardial cushions. The emergence of the four chambered double pump heart of mammals involves a complex remodelling that the endocardial cushions play an active role in. Even while heart remodelling is taking place, the heart tube is operating as a single-circulation pump, and the endocardial cushions are performing a valve-like function that is critical to the survival of the embryo (Nomura-Kitabayashi et al. 2009). As the endocardial cushions grow and remodel, they become the valve leaflets of the foetal heart. The endocardial cushions also contribute tissue to the septa (walls) of the heart. Their correct formation is thus essential to the development of a fully functional, fully divided, double-pump system. It has been shown that genetic mutations that cause impaired endocardial EMT lead to the development of a range of congenital heart defects (Fischer et al. 2007). An extensive review is conducted of existing experimental investigations into endocardial EMT. The information extracted from this review is used to develop a multiscale conceptual model of endocardial EMT, including the major protein signalling pathways involved, and the cellular phenotypes that they induce or inhibit. After considering the requirements for computational simulations of EMT, and reviewing the various techniques and simulation packages available for multi-cell modelling, cellular Potts modelling is selected as having the most appropriate combination of features. The open source simulation platform Compucell3D is selected for model development, due to the flexibility, range of features provided and an existing implementation of multiscale models; that include subcellular models of reaction pathways. Based on the conceptual model of endocardial EMT, abstract computational simulations of key aspects are developed, in order to investigate qualitative behaviour under different simulated conditions. The abstract simulations include a 2D multiscale model of Notch signalling lateral induction, which is the mechanism by which the embryonic heart tube is patterned into cushion and non-cushion forming regions. Additionally, a 3D simulation is used to investigate the possible role of contact-inhibited mitosis, upregulated by the VEGF protein, in maintaining an epithelial phenotype. One particular in vitro investigation of endocardial EMT (Luna-Zurita et al. 2010) is used to develop quantitative simulations. The quantitative data used for fitting the simulations consist of cell shape metrics that are derived from simple processing of the imaging results. Single cell simulations are used to investigate the relationship between cell motility and cell shape in the cellular Potts model. The findings are then implemented in multi-cell models, in order to investigate the relationship between cell-cell adhesion, cell-matrix adhesion, cell motility and cell shape during EMT

Integrating knowledge about complex adaptive systems: insights from modelling the Eastern Baltic cod

Currently, the Eastern Baltic cod (EBC) is in continuing decline. Supporting management efforts to assist in its recovery will require a functional understanding of the dynamics of the EBC and the Baltic ecosystem. However, aquatic environments are challenging to research as they are elusive, encompass many scientific disciplines and are complex adaptive systems. This thesis explores how modelling and simulation methods can be applied and adapted to meet the specific needs of fisheries biologies’ current challenges regarding the EBC and potentially those of other stocks in similar situations.Aktuell verschlechtert sich der Zustand des Ostdorsches anhaltend und unterstützende Bewirtschaftungsmaßnahmen zu identifizieren erfordert ein funktionales Verständnis des Bestands und des Ökosystems Ostsee. Die Erforschung aquatischer Systeme ist jedoch schwierig: sie sind flüchtig, umfassen eine Vielzahl an Disziplinen und sind komplexe adaptiver Systeme. Diese Arbeit untersucht, wie Modellierungs- und Simulationsmethoden angewendet und angepasst werden können, um den Anforderungen der Fischereibiologie beim Ostdorsch und potentiell bei anderer Bestände in ähnlichen Situationen zu begegnen

Whole-Body Regeneration

This Open Access volume provides a comprehensive overview of the latest tools available to scientists to study the many facets of whole-body regeneration (WBR). The chapters in this book are organized into six parts. Part One provides a historical overview on the study of the WBR phenomena focusing on the primary challenges of this research. Parts Two and Three explore a series of non-vertebrate zoological contexts that provide experimental models for WBR, showing how they can be approached with cellular tools. Parts Four, Five, and Six discuss the future advancements of WBR, reporting about the cutting-edge techniques in genetics and omics used to dissect the underlying mechanisms of WBR, and systems biology approaches to reach a synthetic view of WBR. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and thorough, Whole-Body Regeneration: Methods and Protocols is a valuable resource for scientists and researchers who want to learn more about this important and developing field

Whole-Body Regeneration

This Open Access volume provides a comprehensive overview of the latest tools available to scientists to study the many facets of whole-body regeneration (WBR). The chapters in this book are organized into six parts. Part One provides a historical overview on the study of the WBR phenomena focusing on the primary challenges of this research. Parts Two and Three explore a series of non-vertebrate zoological contexts that provide experimental models for WBR, showing how they can be approached with cellular tools. Parts Four, Five, and Six discuss the future advancements of WBR, reporting about the cutting-edge techniques in genetics and omics used to dissect the underlying mechanisms of WBR, and systems biology approaches to reach a synthetic view of WBR. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and thorough, Whole-Body Regeneration: Methods and Protocols is a valuable resource for scientists and researchers who want to learn more about this important and developing field