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The focus of this paper is to develop a new partial differential equation model for the pattern formation of the human pathogen Staphylococcus aureus, starting from a newly developed model of selected gene regulation mechanisms. In our model, we do not only account for the bacteria densities and nutrient concentrations, but also for the quorum sensing and biofilm components, since they enable bacteria to coordinate their behavior and provide the environment in which the colony grows. To this end, we model the relevant gene regulation systems using ordinary differential equations and therefrom derive our evolution equations for quorum sensing and biofilm environment by time-scale arguments. Furthermore, we compare and validate our model and the corresponding simulation results with biological real data observations of Staphylococcus aureus mutant colony growth in the laboratory. We show that we are able to adequately display the qualitative biological features of pattern formation in selected mutants, using the parameter changes indicated by the gene regulation mechanisms. [ABSTRACT FROM AUTHOR]

A continuum hypothesis-based model is developed for the simulation of the contraction of burns in order to gain new insights into which elements of the healing response might have a substantial influence on this process. Tissue is modeled as a neo-Hookean solid. Furthermore, (myo)fibroblasts, collagen molecules, and a generic signaling molecule are selected as model components. An overview of the custom-made numerical algorithm is presented. Subsequently, good agreement is demonstrated with respect to variability in the evolution of the surface area of burns over time between the outcomes of computer simulations and measurements obtained in an experimental study. In the model this variability is caused by varying the values for some of its parameters simultaneously. A factorial design combined with a regression analysis are used to quantify the individual contributions of these parameter value variations to the dispersion in the surface area of healing burns. The analysis shows that almost all variability in the surface area can be explained by variability in the value for the myofibroblast apoptosis rate and, to a lesser extent, the value for the collagen molecule secretion rate. This suggests that most of the variability in the evolution of the surface area of burns over time in the experimental study might be attributed to variability in these two rates. Finally, a probabilistic analysis is used in order to investigate in more detail the effect of variability in the values for the two rates on the healing process. Results of this analysis are presented and discussed. [ABSTRACT FROM AUTHOR]

An association of stenotic internal jugular veins (IJVs) to anomalous cerebral venous hemodynamics and Multiple Sclerosis has been recently hypothesized. In this work, we set up a computational framework to assess the relevance of IJV stenoses through numerical simulation, combining medical imaging, patient-specific data and a mathematical model for venous occlusions. Coupling a three-dimensional description of blood flow in IJVs with a reduced one-dimensional model for major intracranial veins, we are able to model different anatomical configurations, an aspect of importance to understand the impact of IJV stenosis in intracranial venous haemodynamics. We investigate several stenotic configurations in a physiologic patient-specific regime, quantifying the effect of the stenosis in terms of venous pressure increase and wall shear stress patterns. Simulation results are in qualitative agreement with reported pressure anomalies in pathological cases. Moreover, they demonstrate the potential of the proposed multiscale framework for individual-based studies and computer-aided diagnosis. [ABSTRACT FROM AUTHOR]

Erythropoiesis, the process of red blood cell production, occurs mainly in the bone marrow. The functional unit of mammalian erythropoiesis, the erythroblastic island, consists of a central macrophage surrounded by adherent erythroid progenitor cells (CFU-E/Pro-EBs) and their differentiating progeny, the erythroblasts. Central macrophages display on their surface or secrete various growth or inhibitory factors that influence the fate of the surrounding erythroid cells. CFU-E/Pro-EBs have three possible fates: (a) expansion of their numbers without differentiation, (b) differentiation into reticulocytes that are released into the blood, (c) death by apoptosis. CFU-E/Pro-EB fate is under the control of a complex molecular network, that is highly dependent upon environmental conditions in the erythroblastic island. In order to assess the functional role of space coupled with the complex network behavior in erythroblastic islands, we developed hybrid discrete-continuous models of erythropoiesis. A model was developed in which cells are considered as individual physical objects, intracellular regulatory networks are modeled with ordinary differential equations and extracellular concentrations by partial differential equations. We used the model to investigate the impact of an important difference between humans and mice in which mature late-stage erythroblasts produce the most Fas-ligand in humans, whereas early-stage erythroblasts produce the most Fas-ligand in mice. Although the global behaviors of the erythroblastic islands in both species were similar, differences were found, including a relatively slower response time to acute anemia in humans. Also, our modeling approach was very consistent with in vitro culture data, where the central macrophage in reconstituted erythroblastic islands has a strong impact on the dynamics of red blood cell production. The specific spatial organization of erythroblastic islands is key to the normal, stable functioning of mammalian erythropoiesis, both in vitro and in vivo. Our model of a simplified molecular network controlling cell decision provides a realistic functional unit of mammalian erythropoiesis that integrates multiple microenvironmental influences within the erythroblastic island with those of circulating regulators of erythropoiesis, such as EPO and glucocorticosteroids, that are produced at remote sites. [ABSTRACT FROM AUTHOR]