3 resultados para within-host modelling

em Nottingham eTheses


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We study the growth of a tissue construct in a perfusion bioreactor, focussing on its response to the mechanical environment. The bioreactor system is modelled as a two-dimensional channel containing a tissue construct through which a flow of culture medium is driven. We employ a multiphase formulation of the type presented by G. Lemon, J. King, H. Byrne, O. Jensen and K. Shakesheff in their study (Multiphase modelling of tissue growth using the theory of mixtures. J. Math. Biol. 52(2), 2006, 571–594) restricted to two interacting fluid phases, representing a cell population (and attendant extracellular matrix) and a culture medium, and employ the simplifying limit of large interphase viscous drag after S. Franks in her study (Mathematical Modelling of Tumour Growth and Stability. Ph.D. Thesis, University of Nottingham, UK, 2002) and S. Franks and J. King in their study Interactions between a uniformly proliferating tumour and its surrounding: Uniform material properties. Math. Med. Biol. 20, 2003, 47–89). The novel aspects of this study are: (i) the investigation of the effect of an imposed flow on the growth of the tissue construct, and (ii) the inclusion of a chanotransduction mechanism regulating the response of the cells to the local mechanical environment. Specifically, we consider the response of the cells to their local density and the culture medium pressure. As such, this study forms the first step towards a general multiphase formulation that incorporates the effect of mechanotransduction on the growth and morphology of a tissue construct. The model is analysed using analytic and numerical techniques, the results of which illustrate the potential use of the model to predict the dominant regulatory stimuli in a cell population.

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Planar cell polarity (PCP) occurs in the epithelia of many animals and can lead to the alignment of hairs, bristles and feathers; physiologically, it can organise ciliary beating. Here we present two approaches to modelling this phenomenon. The aim is to discover the basic mechanisms that drive PCP, while keeping the models mathematically tractable. We present a feedback and diffusion model, in which adjacent cell sides of neighbouring cells are coupled by a negative feedback loop and diffusion acts within the cell. This approach can give rise to polarity, but also to period two patterns. Polarisation arises via an instability provided a sufficiently strong feedback and sufficiently weak diffusion. Moreover, we discuss a conservative model in which proteins within a cell are redistributed depending on the amount of proteins in the neighbouring cells, coupled with intracellular diffusion. In this case polarity can arise from weakly polarised initial conditions or via a wave provided the diffusion is weak enough. Both models can overcome small anomalies in the initial conditions. Furthermore, the range of the effects of groups of cells with different properties than the surrounding cells depends on the strength of the initial global cue and the intracellular diffusion.

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Multi-agent systems offer a new and exciting way of understanding the world of work. We apply agent-based modeling and simulation to investigate a set of problems in a retail context. Specifically, we are working to understand the relationship between people management practices on the shop-floor and retail performance. Despite the fact we are working within a relatively novel and complex domain, it is clear that using an agent-based approach offers great potential for improving organizational capabilities in the future. Our multi-disciplinary research team has worked closely with one of the UK’s top ten retailers to collect data and build an understanding of shop-floor operations and the key actors in a department (customers, staff, and managers). Based on this case study we have built and tested our first version of a retail branch agent-based simulation model where we have focused on how we can simulate the effects of people management practices on customer satisfaction and sales. In our experiments we have looked at employee development and cashier empowerment as two examples of shop floor management practices. In this paper we describe the underlying conceptual ideas and the features of our simulation model. We present a selection of experiments we have conducted in order to validate our simulation model and to show its potential for answering “what-if” questions in a retail context. We also introduce a novel performance measure which we have created to quantify customers’ satisfaction with service, based on their individual shopping experiences.