Discretization of Non-uniform Rational B-Spline (NURBS) Models for Meshless Isogeometric Analysis.

We present an algorithm for fast generation of quasi-uniform and variable-spacing nodes on domains whose boundaries are represented as computer-aided design (CAD) models, more specifically non-uniform rational B-splines (NURBS). This new algorithm enables the solution of partial differential equations within the volumes enclosed by these CAD models using (collocation-based) meshless numerical discretizations. Our hierarchical algorithm first generates quasi-uniform node sets directly on the NURBS surfaces representing the domain boundary, then uses the NURBS representation in conjunction with the surface nodes to generate nodes within the volume enclosed by the NURBS surface. We provide evidence for the quality of these node sets by analyzing them in terms of local regularity and separation distances. Finally, we demonstrate that these node sets are well-suited (both in terms of accuracy and numerical stability) for meshless radial basis function generated finite differences discretizations of the Poisson, Navier-Cauchy, and heat equations. Our algorithm constitutes an important step in bridging the field of node generation for meshless discretizations with isogeometric analysis.

An Efficient High-Order Meshless Method for Advection-Diffusion Equations on Time-Varying Irregular Domains.

We present a high-order radial basis function finite difference (RBF-FD) framework for the solution of advection-diffusion equations on time-varying domains. Our framework is based on a generalization of the recently developed Overlapped RBF-FD method that utilizes a novel automatic procedure for computing RBF-FD weights on stencils in variable-sized regions around stencil centers. This procedure eliminates the overlap parameter δ, thereby enabling tuning-free assembly of RBF-FD differentiation matrices on moving domains. In addition, our framework utilizes a simple and efficient procedure for updating differentiation matrices on moving domains tiled by node sets of time-varying cardinality. Finally, advection-diffusion in time-varying domains is handled through a combination of rapid node set modification, a new high-order semi-Lagrangian method that utilizes the new tuning-free overlapped RBF-FD method, and a high-order time-integration method. The resulting framework has no tuning parameters and has O(N logN) time complexity. We demonstrate high-orders of convergence for advection-diffusion equations on time-varying 2D and 3D domains for both small and large Peclet numbers. We also present timings that verify our complexity estimates. Finally, we utilize our method to solve a coupled 3D problem motivated by models of platelet aggregation and coagulation, once again demonstrating high-order convergence rates on a moving domain.

Pump efficacy in a two-dimensional, fluid-structure interaction model of a chain of contracting lymphangions.

The transport of lymph through the lymphatic vasculature is the mechanism for returning excess interstitial fluid to the circulatory system, and it is essential for fluid homeostasis. Collecting lymphatic vessels comprise a significant portion of the lymphatic vasculature and are divided by valves into contractile segments known as lymphangions. Despite its importance, lymphatic transport in collecting vessels is not well understood. We present a computational model to study lymph flow through chains of valved, contracting lymphangions. We used the Navier-Stokes equations to model the fluid flow and the immersed boundary method to handle the two-way, fluid-structure interaction in 2D, non-axisymmetric simulations. We used our model to evaluate the effects of chain length, contraction style, and adverse axial pressure difference (AAPD) on cycle-mean flow rates (CMFRs). In the model, longer lymphangion chains generally yield larger CMFRs, and they fail to generate positive CMFRs at higher AAPDs than shorter chains. Simultaneously contracting pumps generate the largest CMFRs at nearly every AAPD and for every chain length. Due to the contraction timing and valve dynamics, non-simultaneous pumps generate lower CMFRs than the simultaneous pumps; the discrepancy diminishes as the AAPD increases. Valve dynamics vary with the contraction style and exhibit hysteretic opening and closing behaviors. Our model provides insight into how contraction propagation affects flow rates and transport through a lymphangion chain.

Dissecting Intra-Tumor Heterogeneity by the Analysis of Copy Number Variations in Single Cells: The Neuroblastoma Case Study.

Tumors often show intra-tumor heterogeneity because of genotypic differences between all the cells that compose it and that derive from it. Recent studies have shown significant aspects of neuroblastoma heterogeneity that may affect the diagnostic-therapeutic strategy. Therefore, we developed a laboratory protocol, based on the combination of the advanced dielectrophoresis-based array technology and next-generation sequencing to identify and sort single cells individually and carry out their copy number variants analysis. The aim was to evaluate the cellular heterogeneity, avoiding overestimation or underestimation errors, due to a bulk analysis of the sample. We tested the above-mentioned protocol on two neuroblastoma cell lines, SK-N-BE(2)-C and IMR-32. The presence of several gain or loss chromosomal regions, in both cell lines, shows a high heterogeneity of the copy number variants status of the single tumor cells, even if they belong to an immortalized cell line. This finding confirms that each cell can potentially accumulate different alterations that can modulate its behavior. The laboratory protocol proposed herein provides a tool able to identify prevalent behaviors, and at the same time highlights the presence of particular clusters that deviate from them. Finally, it could be applicable to many other types of cancer.

Hyperviscosity-Based Stabilization for Radial Basis Function-Finite Difference (RBF-FD) Discretizations of Advection-Diffusion Equations.

We present a novel hyperviscosity formulation for stabilizing RBF-FD discretizations of the advectiondiffusion equation. The amount of hyperviscosity is determined quasi-analytically for commonly-used explicit, implicit, and implicit-explicit (IMEX) time integrators by using a simple 1D semi-discrete Von Neumann analysis. The analysis is applied to an analytical model of spurious growth in RBF-FD solutions that uses auxiliary differential operators mimicking the undesirable properties of RBF-FD differentiation matrices. The resulting hyperviscosity formulation is a generalization of existing ones in the literature, but is free of any tuning parameters and can be computed efficiently. To further improve robustness, we introduce a simple new scaling law for polynomial-augmented RBF-FD that relates the degree of polyharmonic spline (PHS) RBFs to the degree of the appended polynomial. When used in a novel ghost node formulation in conjunction with the recently-developed overlapped RBF-FD method, the resulting method is robust and free of stagnation errors. We validate the high-order convergence rates of our method on 2D and 3D test cases over a wide range of Peclet numbers (1-1000). We then use our method to solve a 3D coupled problem motivated by models of platelet aggregation and coagulation, again demonstrating high-order convergence rates.

A Radial Basis Function (RBF)-Finite Difference (FD) Method for Diffusion and Reaction-Diffusion Equations on Surfaces.

In this paper, we present a method based on Radial Basis Function (RBF)-generated Finite Differences (FD) for numerically solving diffusion and reaction-diffusion equations (PDEs) on closed surfaces embedded in ℝ d . Our method uses a method-of-lines formulation, in which surface derivatives that appear in the PDEs are approximated locally using RBF interpolation. The method requires only scattered nodes representing the surface and normal vectors at those scattered nodes. All computations use only extrinsic coordinates, thereby avoiding coordinate distortions and singularities. We also present an optimization procedure that allows for the stabilization of the discrete differential operators generated by our RBF-FD method by selecting shape parameters for each stencil that correspond to a global target condition number. We show the convergence of our method on two surfaces for different stencil sizes, and present applications to nonlinear PDEs simulated both on implicit/parametric surfaces and more general surfaces represented by point clouds.

A study of different modeling choices for simulating platelets within the immersed boundary method.

The Immersed Boundary (IB) method is a widely-used numerical methodology for the simulation of fluid-structure interaction problems. The IB method utilizes an Eulerian discretization for the fluid equations of motion while maintaining a Lagrangian representation of structural objects. Operators are defined for transmitting information (forces and velocities) between these two representations. Most IB simulations represent their structures with piecewise linear approximations and utilize Hookean spring models to approximate structural forces. Our specific motivation is the modeling of platelets in hemodynamic flows. In this paper, we study two alternative representations - radial basis functions (RBFs) and Fourier-based (trigonometric polynomials and spherical harmonics) representations - for the modeling of platelets in two and three dimensions within the IB framework, and compare our results with the traditional piecewise linear approximation methodology. For different representative shapes, we examine the geometric modeling errors (position and normal vectors), force computation errors, and computational cost and provide an engineering trade-off strategy for when and why one might select to employ these different representations.