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Mycobacterium marinum (Mm), a genetically similar bacterium to Mycobacterium tuberculosis, affects a number of fish industries (fisheries, aquaculture, aquariums and research stocks) on a comparable scale to tuberculosis (TB) in humans. Because of this, and the practical advantages of working with animal models as opposed to humans, Mm infections in recently established fish models provide a unique opportunity for the study of mycobacterial infections. We derive a model of transmission dynamics of Mm in fish, which either involves consumption of an infected host or a source of bacteria to ensure "activation" into a highly infectious state. We derive a model of transmission within a food web, in which infected fish behavior is structured by infection severity. This is a key component as chronic (seemingly asymptomatic) infection is prominent in both fish and human TB. We illustrate, via a novel numerical scheme, that this model can be used to reproduce experimental settings. We further argue that the framework developed herein is a useful tool to address key questions such as design in experimental settings and potential control strategies in large-scale situations. [ABSTRACT FROM AUTHOR]

Abstract: CFSE analysis of a proliferating cell population is a popular tool for the study of cell division and divisionlinked changes in cell behavior. Recently Banks et al. (2011), Luzyanina et al. (2009), Luzyanina et al. (2007), a partial differential equation (PDE) model to describe lymphocyte dynamics in a CFSE proliferation assay was proposed. We present a significant revision of this model which improves the physiological understanding of several parameters. Namely, the parameter used previously as a heuristic explanation for the dilution of CFSE dye by cell division is replaced with a more physical component, cellular autofluorescence. The rate at which label decays is also quantified using a Gompertz decay process. We then demonstrate a revised method of fitting the model to the commonly used histogram representation of the data. It is shown that these improvements result in a model with a strong physiological basis which is fully capable of replicating the behavior observed in the data. [Copyright &y& Elsevier]

Abstract: The design and evaluation of epidemiological control strategies is central to public health policy. While inverse problem methods are routinely used in many applications, this remains an area in which their use is relatively rare, although their potential impact is great. We describe methods particularly relevant to epidemiological modeling at the population level. These methods are then applied to the study of pneumococcal vaccination strategies as a relevant example which poses many challenges common to other infectious diseases. We demonstrate that relevant yet typically unknown parameters may be estimated, and show that a calibrated model may used to assess implemented vaccine policies through the estimation of parameters if vaccine history is recorded along with infection and colonization information. Finally, we show how one might determine an appropriate level of refinement or aggregation in the age-structured model given age-stratified observations. These results illustrate ways in which the collection and analysis of surveillance data can be improved using inverse problem methods. [Copyright &y& Elsevier]

Abstract: It is well-established that the binding of N-formyl peptides to the N-formyl peptide receptor on neutrophils can be described by a kinetic scheme that involves two ligand-bound receptor states, both a low affinity ligand–receptor complex and a high affinity ligand–receptor complex, and that the rate constants describing ligand–receptor binding and receptor affinity state interconversion are ligand-specific. Here we examine whether differences due to these rate constants, i.e. differences in the numbers and lifetimes of particular receptor states, are correlated with neutrophil responses, namely actin polymerization and oxidant production. We find that an additional receptor state, one not discerned from kinetic binding assays, is required to account for these responses. This receptor state is interpreted as the number of low affinity bound receptors that are capable of activating G proteins; in other words, the accumulation of these active receptors correlates with the extent of both responses. Furthermore, this analysis allows for the quantification of a parameter that measures the relative strength of a ligand to bias the receptor into the active conformation. A model with this additional receptor state is sufficient to describe response data when two ligands (agonist/agonist or agonist/antagonist pairs) are added simultaneously, suggesting that cells respond to the accumulation of active receptors regardless of the identity of the ligand(s). [Copyright &y& Elsevier]

The goal of this study was to elucidate the relationships between early ligand binding/receptor processing events and cellular responses for the N-formyl peptide receptor system on human neutrophils as a model of a GPCR system in a physiologically relevant context. Binding kinetics of N-formyl-methionyl-leucyl-phenylalanyl-phenylalanyl-lysine-fluorescein and N-formyl-valyl-leucyl-phenylalanyl-lysine fluorescein to the N-formyl peptide receptor on human neutrophils were characterized and combined with previously published binding data for four other ligands. Binding was best fit by an interconverting two-receptor state model that included a low affinity receptor state that converted to a high affinity state. Response behaviors elicited at 37 °C by the six different agonists for the N-formyl peptide receptor were measured. Dose response curves for oxidant production, actin polymerization, and G-protein activation were obtained for each ligand; whereas all ligands showed equal efficacy for all three responses, the ED50 values varied as much as 7000-fold. The level of agonism and rank order of potencies of ligands for actin and oxidant responses were the same as for the G-protein activation assay, suggesting that the differences in abilities of ligands to mediate responses were determined upstream of G-protein activation at the level of ligand-receptor interactions. The rate constants governing ligand binding and receptor affinity conversion were ligand-dependent. Analysis of the forward and reverse rate constants governing binding to the proposed signaling receptor state showed that it was of a similar energy for all six ligands, suggesting the hypothesis that ligand efficacy is dictated by the energy state of this ligand-receptor complex. However, the interconverting two-receptor state model was not sufficient to predict response potency, suggesting the presence of receptor states not discriminated by the binding data. [ABSTRACT FROM AUTHOR]

We present a second-order high-resolution finite difference scheme to approximate the solution of a mathematical model of the transmission dynamics ofMycobacterium marinum(Mm) in an aquatic environment. This work extends the numerical theory and continues the preliminary studies on the model first developed in Acklehet al.[Structured models for the spread of Mycobacterium marinum: foundations for a numerical approximation scheme, Math. Biosci. Eng. 11 (2014), pp. 679–721]. Numerical simulations demonstrating the accuracy of the method are presented, and we compare this scheme to the first-order scheme developed in Acklehet al.[Structured models for the spread of Mycobacterium marinum: foundations for a numerical approximation scheme, Math. Biosci. Eng. 11 (2014), pp. 679–721] to show that the first-order method requires significantly more computational time to provide solutions with a similar accuracy. We also demonstrated that the model can be a tool to understand surprising or nonintuitive phenomena regarding competitive advantage in the context of biologically realistic growth, birth and death rates. [ABSTRACT FROM AUTHOR]

We present a second-order high-resolution finite difference scheme to approximate the solution of a mathematical model of the transmission dynamics of Mycobacterium marinum (Mm) in an aquatic environment. This work extends the numerical theory and continues the preliminary studies on the model first developed in Ackleh et al. [Structured models for the spread of Mycobacterium marinum: foundations for a numerical approximation scheme, Math. Biosci. Eng. 11 (2014), pp. 679-721]. Numerical simulations demonstrating the accuracy of the method are presented, and we compare this scheme to the first-order scheme developed in Ackleh et al. [Structured models for the spread of Mycobacterium marinum: foundations for a numerical approximation scheme, Math. Biosci. Eng. 11 (2014), pp. 679-721] to show that the firstorder method requires significantly more computational time to provide solutions with a similar accuracy. We also demonstrated that the model can be a tool to understand surprising or nonintuitive phenomena regarding competitive advantage in the context of biologically realistic growth, birth and death rates. [ABSTRACT FROM AUTHOR]

Abstract: We present a general class of cell population models that can be used to track the proliferation of cells which have been labeled with a fluorescent dye. The mathematical models employ fluorescence intensity as a structure variable to describe the evolution in time of the population density of proliferating cells. While cell division is a major component of changes in cellular fluorescence intensity, models developed here also address overall label degradation. [ABSTRACT FROM AUTHOR]