No Arabic abstract
Ageing of lithium-ion batteries results in irreversible reduction in performance. Intrinsic variability between cells, caused by manufacturing differences, occurs throughout life and increases with age. Researchers need to know the minimum number of cells they should test to give an accurate representation of population variability, since testing many cells is expensive. In this paper, empirical capacity versus time ageing models were fitted to various degradation datasets for commercially available cells assuming the model parameters could be drawn from a larger population distribution. Using a hierarchical Bayesian approach, we estimated the number of cells required to be tested. Depending on the complexity, ageing models with 1, 2 or 3 parameters respectively required data from at least 9, 11 or 13 cells for a consistent fit. This implies researchers will need to test at least these numbers of cells at each test point in their experiment to capture manufacturing variability.
As a concrete setting where stochastic partial differential equations (SPDEs) are able to model real phenomena, we propose a stochastic Meinhardt model for cell repolarisation and study how parameter estimation techniques developed for simple linear SPDE models apply in this situation. We establish the existence of mild SPDE solutions and we investigate the impact of the driving noise process on pattern formation in the solution. We then pursue estimation of the diffusion term and show asymptotic normality for our estimator as the space resolution becomes finer. The finite sample performance is investigated for synthetic and real data.
Cell detection and counting in the image-based ELISPOT and Fluorospot immunoassays is considered a bottleneck. The task has remained hard to automatize, and biomedical researchers often have to rely on results that are not accurate. Previously proposed solutions are heuristic, and data-based solutions are subject to a lack of objective ground truth data. In this paper, we analyze a partial differential equations model for ELISPOT, Fluorospot, and assays of similar design. This leads us to a mathematical observation model for the images generated by these assays. We use this model to motivate a methodology for cell detection. Finally, we provide a real-data example that suggests that this cell detection methodology and a human expert perform comparably.
Mapping of the forces on biomolecules in cell membranes has spurred the development of effective labels, e.g. organic fluorophores and nanoparticles, to track trajectories of single biomolecules. Standard methods use particular statistics, namely the mean square displacement, to analyze the underlying dynamics. Here, we introduce general inference methods to fully exploit information in the experimental trajectories, providing sharp estimates of the forces and the diffusion coefficients in membrane microdomains. Rapid and reliable convergence of the inference scheme is demonstrated on trajectories generated numerically. The method is then applied to infer forces and potentials acting on the receptor of the $epsilon$-toxin labeled by lanthanide-ion nanoparticles. Our scheme is applicable to any labeled biomolecule and results show show its general relevance for membrane compartmentation.
There are many mathematical models of biochemical cell signaling pathways that contain a large number of elements (species and reactions). This is sometimes a big issue for identifying critical model elements and describing the model dynamics. Thus, techniques of model reduction can be used as a mathematical tool in order to minimize the number of variables and parameters. In this thesis, we review some well-known methods of model reduction for cell signaling pathways. We have also developed some approaches that provide us a great step forward in model reduction. The techniques are quasi steady state approximation (QSSA), quasi equilibrium approximation (QEA), lumping of species and entropy production analysis. They are applied on protein translation pathways with microRNA mechanisms, chemical reaction networks, extracellular signal regulated kinase (ERK) pathways, NFkB signal transduction pathways, elongation factors EFTu and EFTs signaling pathways and Dihydrofolate reductase (DHFR) pathways. The main aim of this thesis is to reduce the complex cell signaling pathway models. This provides one a better understanding of the dynamics of such models and gives an accurate approximate solution. Results show that there is a good agreement between the original models and the simplified models.
Cells grown in culture act as a model system for analyzing the effects of anticancer compounds, which may affect cell behavior in a cell cycle position-dependent manner. Cell synchronization techniques have been generally employed to minimize the variation in cell cycle position. However, synchronization techniques are cumbersome and imprecise and the agents used to synchronize the cells potentially have other unknown effects on the cells. An alternative approach is to determine the age structure in the population and account for the cell cycle positional effects post hoc. Here we provide a formalism to use quantifiable age distributions from live cell microscopy experiments to parameterize an age-structured model of cell population response.