@phdthesis{Schwetlick2023, author = {Schwetlick, Lisa}, title = {Data assimilation for neurocognitive models of eye movement}, doi = {10.25932/publishup-59828}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-598280}, school = {Universit{\"a}t Potsdam}, pages = {x, 209}, year = {2023}, abstract = {Visual perception is a complex and dynamic process that plays a crucial role in how we perceive and interact with the world. The eyes move in a sequence of saccades and fixations, actively modulating perception by moving different parts of the visual world into focus. Eye movement behavior can therefore offer rich insights into the underlying cognitive mechanisms and decision processes. Computational models in combination with a rigorous statistical framework are critical for advancing our understanding in this field, facilitating the testing of theory-driven predictions and accounting for observed data. In this thesis, I investigate eye movement behavior through the development of two mechanistic, generative, and theory-driven models. The first model is based on experimental research regarding the distribution of attention, particularly around the time of a saccade, and explains statistical characteristics of scan paths. The second model implements a self-avoiding random walk within a confining potential to represent the microscopic fixational drift, which is present even while the eye is at rest, and investigates the relationship to microsaccades. Both models are implemented in a likelihood-based framework, which supports the use of data assimilation methods to perform Bayesian parameter inference at the level of individual participants, analyses of the marginal posteriors of the interpretable parameters, model comparisons, and posterior predictive checks. The application of these methods enables a thorough investigation of individual variability in the space of parameters. Results show that dynamical modeling and the data assimilation framework are highly suitable for eye movement research and, more generally, for cognitive modeling.}, language = {en} } @phdthesis{Schindler2023, author = {Schindler, Daniel}, title = {Mathematical modeling and simulation of protrusion-driven cell dynamics}, doi = {10.25932/publishup-61327}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-613275}, school = {Universit{\"a}t Potsdam}, pages = {VI, 161}, year = {2023}, abstract = {Amoeboid cell motility takes place in a variety of biomedical processes such as cancer metastasis, embryonic morphogenesis, and wound healing. In contrast to other forms of cell motility, it is mainly driven by substantial cell shape changes. Based on the interplay of explorative membrane protrusions at the front and a slower-acting membrane retraction at the rear, the cell moves in a crawling kind of way. Underlying these protrusions and retractions are multiple physiological processes resulting in changes of the cytoskeleton, a meshwork of different multi-functional proteins. The complexity and versatility of amoeboid cell motility raise the need for novel computational models based on a profound theoretical framework to analyze and simulate the dynamics of the cell shape. The objective of this thesis is the development of (i) a mathematical framework to describe contour dynamics in time and space, (ii) a computational model to infer expansion and retraction characteristics of individual cell tracks and to produce realistic contour dynamics, (iii) and a complementing Open Science approach to make the above methods fully accessible and easy to use. In this work, we mainly used single-cell recordings of the model organism Dictyostelium discoideum. Based on stacks of segmented microscopy images, we apply a Bayesian approach to obtain smooth representations of the cell membrane, so-called cell contours. We introduce a one-parameter family of regularized contour flows to track reference points on the contour (virtual markers) in time and space. This way, we define a coordinate system to visualize local geometric and dynamic quantities of individual contour dynamics in so-called kymograph plots. In particular, we introduce the local marker dispersion as a measure to identify membrane protrusions and retractions in a fully automated way. This mathematical framework is the basis of a novel contour dynamics model, which consists of three biophysiologically motivated components: one stochastic term, accounting for membrane protrusions, and two deterministic terms to control the shape and area of the contour, which account for membrane retractions. Our model provides a fully automated approach to infer protrusion and retraction characteristics from experimental cell tracks while being also capable of simulating realistic and qualitatively different contour dynamics. Furthermore, the model is used to classify two different locomotion types: the amoeboid and a so-called fan-shaped type. With the complementing Open Science approach, we ensure a high standard regarding the usability of our methods and the reproducibility of our research. In this context, we introduce our software publication named AmoePy, an open-source Python package to segment, analyze, and simulate amoeboid cell motility. Furthermore, we describe measures to improve its usability and extensibility, e.g., by detailed run instructions and an automatically generated source code documentation, and to ensure its functionality and stability, e.g., by automatic software tests, data validation, and a hierarchical package structure. The mathematical approaches of this work provide substantial improvements regarding the modeling and analysis of amoeboid cell motility. We deem the above methods, due to their generalized nature, to be of greater value for other scientific applications, e.g., varying organisms and experimental setups or the transition from unicellular to multicellular movement. Furthermore, we enable other researchers from different fields, i.e., mathematics, biophysics, and medicine, to apply our mathematical methods. By following Open Science standards, this work is of greater value for the cell migration community and a potential role model for other Open Science contributions.}, language = {en} }