In biomechanics, local phenomena, such as tissue perfusion, are strictly related to the global features of the surrounding blood circulation. In this paper, we propose a heterogeneous model where a local, accurate, 3D description of tissue perfusion by means of fluid flows through deformable porous media equations is coupled with a systemic, 0D, lumped model of the remainder of the circulation, where the fluid flow through a vascular network is described via its analog with a current flowing through an electric circuit. This represents a multiscale strategy, which couples an initial boundary value problem to be used in a specific tissue region with an initial value problem in the surrounding circulatory system. This PDE/ODE coupling leads to interface conditions enforcing the continuity of mass and the balance of stresses across models at different scales, and careful consideration is taken to address this interface mismatch. The resulting system involves PDEs of mixed type with interface conditions depending on nonlinear ODEs. A new result on local existence of solutions for this multiscale interface coupling is provided in this article.
The distinct timescales of synaptic plasticity and neural activity dynamics play an important role in the brain's learning and memory systems. Activity-dependent plasticity reshapes neural circuit architecture, determining spontaneous and stimulus-encoding spatiotemporal patterns of neural activity. Neural activity bumps maintain short term memories of continuous parameter values, emerging in spatially-organized models with short term excitation and long-range inhibition. Previously, we demonstrated nonlinear Langevin equations derived using an interface method accurately describe the dynamics of bumps in continuum neural fields with separate excitatory/inhibitory populations. Here we extend this analysis to incorporate effects of slow short term plasticity that modifies connectivity described by an integral kernel. Linear stability analysis adapted to these piecewise smooth models with Heaviside firing rates further indicate how plasticity shapes bumps' local dynamics. Facilitation (depression), which strengthens (weakens) synaptic connectivity originating from active neurons, tends to increase (decrease) stability of bumps when acting on excitatory synapses. The relationship is inverted when plasticity acts on inhibitory synapses. Multiscale approximations of the stochastic dynamics of bumps perturbed by weak noise reveal the plasticity variables evolve to slowly diffusing and blurred versions of that arising in the stationary solution. Nonlinear Langevin equations associated with bump positions or interfaces coupled to slowly evolving projections of plasticity variables accurately describe the wandering of bumps underpinned by these smoothed synaptic efficacy profiles.
We present a novel weak formulation and discretization for discovering governing equations from noisy measurement data. This method of learning differential equations from data fits into a new class of algorithms that replace pointwise derivative approximations with linear transformations and variance reduction techniques. Compared to the standard SINDy algorithm presented in [S. L. Brunton, J. L. Proctor, and J. N. Kutz, Proc. Natl. Acad. Sci. USA, 113 (2016), pp. 3932-3937], our so-called weak SINDy (WSINDy) algorithm allows for reliable model identification from data with large noise (often with ratios greater than 0.1) and reduces the error in the recovered coefficients to enable accurate prediction. Moreover, the coefficient error scales linearly with the noise level, leading to high-accuracy recovery in the low-noise regime. Altogether, WSINDy combines the simplicity and efficiency of the SINDy algorithm with the natural noise reduction of integration, as demonstrated in [H. Schaeffer and S. G. McCalla, Phys. Rev. E, 96 (2017), 023302], to arrive at a robust and accurate method of sparse recovery.
We present the first mathematical model of flow-mediated primary hemostasis in an extravascular injury which can track the process from initial deposition to occlusion. The model consists of a system of ordinary differential equations (ODEs) that describe platelet aggregation (adhesion and cohesion), soluble-agonist-dependent platelet activation, and the flow of blood through the injury. The formation of platelet aggregates increases resistance to flow through the injury, which is modeled using the Stokes-Brinkman equations. Data from analogous experimental (microfluidic flow) and partial differential equation models informed parameter values used in the ODE model description of platelet adhesion, cohesion, and activation. This model predicts injury occlusion under a range of flow and platelet activation conditions. Simulations testing the effects of shear and activation rates resulted in delayed occlusion and aggregate heterogeneity. These results validate our hypothesis that flow-mediated dilution of activating chemical adenosine diphosphate hinders aggregate development. This novel modeling framework can be extended to include more mechanisms of platelet activation as well as the addition of the biochemical reactions of coagulation, resulting in a computationally efficient high throughput screening tool of primary and secondary hemostasis.
The mechanism of gas transport across cell membranes remains a topic of considerable interest, particularly regarding the extent to which lipids vs. specific membrane proteins provide conduction pathways. Studies of transmembrane (CO2) transport often rely on data collected under controlled conditions, using pH-sensitive microelectrodes at the extracellular surface to record changes due to extracellular CO2 diffusion and reactions. Although recent detailed computational models can predict a qualitatively correct behavior, a mismatch between the dynamical ranges of the predicted and observed pH curves raises the question whether the discrepancy may be due to a bias introduced by the pH electrode itself. More specifically, it is reasonable to ask whether bringing the electrode tip near or in contact with the membrane creates a local microenvironment between the electrode tip and the membrane, so that the measured data refer to the microenvironment rather than to the free surface. Here, we introduce a detailed computational model, designed to address this question. We find that, as long as a zone of free diffusion exists between the tip and the membrane, the microenvironment behaves effectively as the free membrane. However, according to our model, when the tip contacts the membrane, partial quenching of extracellular diffusion by the electrode rim leads to a significant increase in the pH dynamics under the electrode, matching values measured in physiological experiments. The computational schemes for the model predictions are based on semi-discretization by a finite-element method, and an implicit-explicit time integration scheme to capture the different time scales of the system.
