Journal of theoretical biology
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A detailed computational model is developed to simulate oxygen transport from a three-dimensional (3D) microvascular network to the surrounding tissue in the presence of hemoglobin-based oxygen carriers. The model accounts for nonlinear O(2) consumption, myoglobin-facilitated diffusion and nonlinear oxyhemoglobin dissociation in the RBCs and plasma. It also includes a detailed description of intravascular resistance to O(2) transport and is capable of incorporating realistic 3D microvascular network geometries. ⋯ Sample results in a microvascular network show an enhancement of diffusive shunting between arterioles, venules and capillaries and a decrease in hemoglobin's effectiveness for tissue oxygenation when its affinity for O(2) is decreased. Model simulations suggest that microvascular network anatomy can affect the optimal hemoglobin affinity for reducing tissue hypoxia. O(2) transport simulations in realistic representations of microvascular networks should provide a theoretical framework for choosing optimal parameter values in the development of hemoglobin-based blood substitutes.
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We present a simplified dynamical model of immune response to uncomplicated influenza A virus (IAV) infection, which focuses on the control of the infection by the innate and adaptive immunity. Innate immunity is represented by interferon-induced resistance to infection of respiratory epithelial cells and by removal of infected cells by effector cells (cytotoxic T-cells and natural killer cells). Adaptive immunity is represented by virus-specific antibodies. ⋯ We find that for small initial viral load the disease progresses through an asymptomatic course, for intermediate value it takes a typical course with constant duration and severity of infection but variable onset, and for large initial viral load the disease becomes severe. This behavior is robust to a wide range of parameter values. The absence of antibody response leads to recurrence of disease and appearance of a chronic state with nontrivial constant viral load.
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Brain hypothermia treatment (BHT) is an intensive care characterized by simultaneous managements of various vital signs, such as intracranial temperature (ICT) and pressure (ICP), of the severe neuropatient. Medical treatments including therapeutic ambient cooling and diuresis are separately carried out based on the experience of the medical staff involved in the clinical management of various pathophysiological processes, such as thermodynamics, hemodynamics and pharmacokinetics. However, no special attention has been paid to the interactions among these subsystems in therapeutic hypothermia because of the lack of theoretical knowledge. ⋯ Decoupling control simulation indicates that ICT and ICP of the integrated model, representing a patient under BHT, can be simultaneously regulated by a single PID controller for ambient cooling and another for diuresis. The proposed decoupler effectively establishes hypothermic decompression, reduces the dosage of diuretic and improves ICP management. Theoretical analyses of the integrated model and decoupling control of ICT and ICP provide insights into the intensive care of various pathophysiological processes in patients undergoing BHT.
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The consequences of regulatory T cell (Treg) inhibition of interleukine 2 secretion is examined by mathematical modelling. We demonstrate that cytokine dependent growth exhibits a quorum T cell population threshold that determines if immune responses develop on activation. ⋯ Thus Treg induced secretion inhibition can provide a mechanism for tissue specific regulation of the balance between suppression (control) and immune responses, a balance that can be varied at the local tissue level through the regulation of the local active Treg population size. However, nonspecific inhibition is prone to escape of initially controlled autoimmune T cells through cross reactivity to pathogens and bystander proliferation on unrelated immune responses.
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Punishment is an important mechanism promoting the evolution of altruism among non-relatives. We investigate the coevolution of altruism and punitive behavior, considering four possible strategies: the altruist punisher (AP, a cooperator who punishes defectors), the altruist non-punisher (AN, a pure cooperator), the selfish punisher (SP, a defector who punishes defectors), and the selfish non-punisher (SN, a pure defector). The SP uses a paradoxical strategy as it punishes other defectors. ⋯ In both the viability and fertility models of a lattice-structured population, SP promotes the spread of AP. In contrast, AN discourages the evolution of AP. These results can be understood that punishment is a form of spite behavior, paying a cost to reduce the fitness of the opponents, and that different models give different magnitude of advantage to spite behavior.