Alfons Georgius Hoekstra

University of Amsterdam | UVA · Department of Computational Science

Uncertainty quantification (UQ) is a key component when using computational models that involve uncertainties, e.g. in decision-making scenarios. In this work, we present uncertainty quantification patterns (UQPs) that are designed to support the analysis of uncertainty in coupled multi-scale and multi-domain applications. UQPs provide the basic bu...

The influence of the flow environment on platelet aggregation is not fully understood in high-shear thrombosis. The objective of this study is to investigate the role of a high shear rate in initial platelet aggregation. The haemodynamic conditions in a microfluidic device are studied using cell-based blood flow simulations. The results are compare...

The influence of the flow environment on platelet aggregation is not fully understood in high-shear thrombosis. The objective of this study is to investigate the role of a high shear rate in initial platelet aggregation. The haemodynamic conditions in a microfluidic device are studied using cell-based blood flow simulations. The results are compare...

Endothelial cells (ECs) play a major role in the healing process following angioplasty to inhibit excessive neointima. This makes the process of EC healing after injury, in particular EC migration in a stented vessel, important for recovery of normal vessel function. In that context, we present a novel particle-based model of EC migration and valid...

Computer simulations were performed to study the transport of red blood cells and platelets in high shear flows, mimicking earlier published in vitro experiments in microfluidic devices with high affinity for platelet aggregate formation. The goal is to understand and predict where thrombus formation starts. Additionally, the need of cell-based mod...

New applications that can exploit emerging exascale computing resources efficiently, while providing meaningful scientific results, are eagerly anticipated. Multi-scale models, especially multi-scale applications, will assuredly run at the exascale. We have established that a class of multi-scale applications implementing the heterogeneous multi-sc...

[Background] Coronary artery restenosis is an important side effect of percutaneous coronary intervention. Computational models can be used to better understand this process. We report on an approach for validation of an in silico 3D model of in-stent restenosis in porcine coronary arteries and illustrate this approach by comparing the modelling re...

We explore the efficiency of a semi-intrusive uncertainty quantification (UQ) method for multiscale models as proposed by us in an earlier publication. We applied the multiscale metamodelling UQ method to a two-dimensional multiscale model for the wound healing response in a coronary artery after stenting (in-stent restenosis). The results obtained...

We describe our Multiscale Computing Patterns software for High Performance Multiscale Computing. Following a short review of Multiscale Computing Patterns, this paper introduces the Multiscale Computing Patterns Software, which consists of description, optimisation and execution components. First, the description component translates the task grap...

We study the effect of pulsatile flow on the transport of red blood cells (RBCs) and platelets into aneurysm geometries with varying dome-to-neck aspect ratios (AR). We use a validated two-dimensional lattice Boltzmann model for blood plasma with a discrete element method for both RBCs and platelets coupled by the immersed boundary method. Flow vel...

The non-homogeneous distribution of computational costs is often challenging to handle in highly parallel applications. Using a methodology based on fractional overheads, we studied the fractional load imbalance overhead in a high-performance biofluid simulation aiming to accurately resolve blood flow on a cellular level. In general, the concentrat...

The immersed-boundary lattice-Boltzmann method (IB-LBM) is increasingly being used in simulations of dense suspensions. These systems are computationally very expensive and can strongly benefit from lower resolutions that still maintain the desired accuracy for the quantities of interest. IB-LBM has a number of free parameters that have to be defin...

Modeling of fluid mechanics for the vascular system is of great value as a source of knowledge about development, progression, and treatment of cardiovascular disease. Full three-dimensional simulation of blood flow in the whole human body is a hard computational problem. We discuss parallel decomposition of blood flow simulation as a graph partiti...

Multiscale Modelling and Simulation (MMS) is a cornerstone in the today’s research in computational science. Simulations containing multiple models, with each model operating at a different temporal or spatial scale, are a challenging setting that frequently require innovative approaches in areas such as scale bridging, code deployment, error quant...

This discussion paper introduces the concept of the Virtual Artery as a multiscale model for arterial physiology and pathologies at the physics–chemistry–biology (PCB) interface. The cellular level is identified as the mesoscopic level, and we argue that by coupling cell-based models with other relevant models on the macro- and microscale, a versat...

We expect that multiscale simulations will be one of the main high performance computing workloads in the exascale era. We propose multiscale computing patterns as a generic vehicle to realise load balanced, fault tolerant and energy aware high performance multiscale computing. Multiscale computing patterns should lead to a separation of concerns,...

The transport of cells and substances in dense suspensions like blood heavily depends on the microstructure and the dynamics arising from their interactions with red blood cells (RBCs). Computer simulations are used to probe into the detailed transport-related characteristics of a blood-like suspension, for a wide range of volume fractions and shea...

Modelling and simulation of multiscale systems constitutes a grand challenge in computational science, and is widely applied in fields ranging from the physical sciences and engineering to the life sciences and the socio-economic domain. To adequately simulate numerous intertwined processes characterized by different spatial and temporal scales (of...

Nano- and microscale flow phenomena turn out to be highly non-trivial for simulation and require the use of heterogeneous modeling approaches. While the continuum Navier-Stokes equations and related boundary conditions quickly break down at those scales, various direct simulation methods and hybrid models have been applied, such as Molecular Dynami...

Several clinical studies and their meta-analysis suggest that developed collateral vessels in the heart correlate to an increased risk of in-stent restenosis. The possible physiological interaction between the collateral development and in-stent restenosis is investigated in this study. Based on existing publications, a hypothesis is suggested that...

Systems medicine is the application of systems biology concepts, methods, and tools to medical research and practice. It aims to integrate data and knowledge from different disciplines into biomedical models and simulations for the understanding, prevention, cure, and management of complex diseases. Complex diseases arise from the interactions amon...

The Fisher-Rao metric from Information Geometry is related to phase transition phenomena in classical statistical mechanics. Several studies propose to extend the use of Information Geometry to study more general phase transitions in complex systems. However, it is unclear whether the Fisher-Rao metric does indeed detect these more general transiti...

We report and address the errors in the analysis of the weighted discretization in Section 2F of [J. Opt. Soc. Am. A 23, 2578–2591 (2006)]

A detailed comparison between the finite element method (FEM) and the lattice-Boltzmann method (LBM) is presented. As a realistic test case, three-dimensional fluid flow simulations in an SMRX static mixer were performed. The SMRX static mixer is a piece of equipment with excellent mixing performance and it is used as a highly efficient chemical re...

Blood is a dense suspension of deformable red blood cells (RBCs) and its complex behavior, in terms of rheology and transport, can be attributed to their high concentration and mechanical properties. Studying the microstructure and the transport mechanisms of such dense suspensions is important in understanding the behavior of blood and can aid in...

Excessive migration and proliferation of smooth muscle cells (SMCs) has been observed as a major factor contributing to the development of in-stent restenosis after coronary stenting. Building upon the results from in vivo experiments, we formulated a hypothesis that the speed of the initial tissue re-growth response is determined by the early migr...

The Fisher Information matrix is a widely used measure for applications ranging from statistical inference, information geometry, experiment design, to the study of criticality in biological systems. Yet there is no commonly accepted non-parametric algorithm to estimate it from real data. In this rapid communication we show how to accurately estima...

We present performance results from ficsion, a general purpose parallel suspension solver, employing the Immersed-Boundary lattice-Boltzmann method (IB-LBM). ficsion is build on top of the open-source LBM framework Palabos, making use of its data structures and their inherent parallelism. We describe in brief the implementation and present weak and...

Many rheological properties of blood, along with transport properties of blood cells can be captured by means of modeling blood through its main constituents, red blood cells (RBCs) and plasma. In the current work, we present a fully resolved two-dimensional model for blood suspension flow, employing a discrete element model (DEM) for RBCs and coup...

We present the Multiscale Coupling Library and Environment: MUSCLE 2. This multiscale component-based execution environment has a simple to use Java, C++, C, Python and Fortran API, compatible with MPI, OpenMP and threading codes. We demonstrate its local and distributed computing capabilities and compare its performance to MUSCLE 1, file copy, MPI...

The immersed boundary method (IBM) [1] is increasingly used for dealing with the fluid-structure interactions in suspension simulations. Not much is known on the influence of basic IBM parameters like the interpolation kernel φ and the number of vertices N v [2, 3] on the dynamics and the interactions of suspended particles. We investigate their in...

Multiscale systems that are characterized by a great range of spatial–temporal scales arise widely in many scientific domains. These range from the study of protein conformational dynamics to multiphase processes in, for example, granular media or haemodynamics, and from nuclear reactor physics to astrophysics. Despite the diversity in subject area...

We argue that, despite the fact that the field of multiscale modelling and simulation has enjoyed significant success within the past decade, it still holds many open questions that are deemed important but so far have barely been explored. We believe that this is at least in part due to the fact that the field has been mainly developed within disc...

Multiscale simulations model phenomena across natural scales using monolithic or component-based code, running on local or distributed resources. In this work, we investigate the performance of distributed multiscale computing of component-based models, guided by six multiscale applications with different characteristics and from several discipline...

We review a methodology to design, implement and execute multi-scale and multi-science numerical simulations. We identify important ingredients of multi-scale modelling and give a precise definition of them. Our framework assumes that a multi-scale model can be formulated in terms of a collection of coupled single-scale submodels. With concepts suc...

The implantation of stents has been used to treat coronary artery stenosis for several decades. Although stenting is successful in restoring the vessel lumen and is a minimally invasive approach, the long-term outcomes are often compromised by in-stent restenosis (ISR). Animal models have provided insights into the pathophysiology of ISR and are wi...

This manual describes the open-source code ADDA, which simulates elastic light scattering from finite 3D objects of arbitrary shape and composition, either in free space or near the plane surface. Besides standard sequential execution, ADDA can run on a multiprocessor system, using MPI (message passing interface), parallelizing a single DDA calcula...

Re-establishing a functional endothelium following endovascular treatment is an important factor in arresting neointimal proliferation. In this study, both histology (in vivo) and computational simulations (in silico) are used to evaluate neointimal growth patterns within coronary arteries along the axial direction of the stent. Comparison of the g...

We introduce a software tool to simulate multiscale models: the Multiscale Coupling Library and Environment 2 (MUSCLE 2). MUSCLE 2 is a component-based modeling tool inspired by the multiscale modeling and simulation framework, with an easy-to-use API which supports Java, C++, C, and Fortran. We present MUSCLE 2's runtime features, such as its dist...

Treatment of stenosed coronary arteries by balloon angioplasty and stenting results in arterial injury including severe damage to the endothelium at the site of treatment and initiates a complex cascade of inflammatory processes that may lead to the development of in-stent restenosis (ISR). Many clinical and biological factors involved in the progr...

In tissue engineering (TE), scaffolds are widely used to provide a suitable and native-like environment for cell growth, organization, and proliferation. Microstructure of TE scaffolds is fundamental to the cell attachment and in-depth penetration, in conjunction with biological factors as cell seeding and nutrients supply. In particular, several s...

Multiscale simulations are essential in the biomedical domain to accurately model human physiology. We present a modular approach for designing, constructing and executing multiscale simulations on a wide range of resources, from laptops to petascale supercomputers, including combinations of these. Our work features two multiscale applications, in-...

Despite the importance of platelets in the formation of a thrombus, their transport in complex flows has not yet been studied in detail. In this paper we simulated red blood cells and platelets to explore their transport behaviour in aneurysmal geometries. We considered two aneurysms with different aspect ratios (AR = 1.0, 2.0) in the presence of f...

Inherently complex problems from many scientific disciplines require a multiscale modeling approach. Yet its practical contents remain unclear and inconsistent. Moreover, multiscale models can be very computationally expensive, and may have potential to be executed on distributed infrastructure. In this paper we propose firm foundations for multisc...

Nature is observed at all scales; with multiscale modeling, scientists bring together several scales for a holistic analysis of a phenomenon. The models on these different scales may require significant but also heterogeneous computational resources, creating the need for distributed multiscale computing. A particularly demanding type of multiscale...

The understanding of biological processes, e.g. related to cardio-vascular disease and treatment, can significantly be improved by numerical simulation. In this paper, we present an approach for a multiscale simulation environment, applied for the prediction of in-stent re-stenos is. Our focus is on the coupling of distributed, heterogeneous hardwa...

In several disciplines, a multiscale approach is being used to model complex natural processes yet a principled background to multiscale modeling is not clear. Additionally, some multiscale models requiring distributed resources to be computed in an acceptable timeframe, while no standard framework for distributed multiscale computing is place. In...

The macroscopically emergent rheology of suspensions is dictated by details of fluid-particle and particle-particle interactions. For systems where the typical spatial scale on the particle level is much smaller than that of macroscopic properties, the scales can be split. We present a heterogeneous multiscale method (HMM) approach to modeling susp...

In this paper we present three dimensional cellular automata models for tumour growth, with a focus on the tumour’s natural shrinkage caused by the removal of the dead cells’ mortal remains. The significance of this phenomenon for the resulting volume of the in silico tumour is shown. Two algorithms are presented, one using the chain shifting appro...

The Complex Automata (CxA) methodology offers a new framework to develop multiscale and multiscience numerical simulations. The CxA approach assumes that a multiscale model can be formulated in terms of several coupled single-scale submodels. With concepts such as the scale separation map, the generic submodel execution loop and the coupling templa...

Neointimal hyperplasia, a process of smooth muscle cell re-growth, is the result of a natural wound healing response of the injured artery after stent deployment. Excessive neointimal hyperplasia following coronary artery stenting results in in-stent restenosis (ISR). Regardless of recent developments in the field of coronary stent design, ISR rema...

The emergence of multicore architectures and the chip industry’s plan to roll out hundreds of cores per die sometime in the near future might have triggered the evolution of von Neumann architectures towards a parallel processing paradigm. The capability to have hundreds of cores per die is exciting, but how optimally we are able to utilize such...

Optical Models of White Blood Cells Direct and Inverse Light-Scattering Problems for White Blood Cells Experimental Measurement of Light Scattering by White Blood Cells

In-stent restenosis, the maladaptive response of a blood vessel to injury caused by the deployment of a stent, is a multiscale system involving a large number of biological and physical processes. We describe a Complex Automata model for in-stent restenosis, coupling bulk flow, drug diffusion, and smooth muscle cell models, all operating on differe...

The open-source code ADDA is described, which implements the discrete dipole approximation (DDA), a method to simulate light scattering by finite 3D objects of arbitrary shape and composition. Besides standard sequential execution, ADDA can run on a multiprocessor distributed-memory system, parallelizing a single DDA calculation. Hence the size par...

ADDA is an open-source parallel implementation of the discrete dipole approximation (DDA), capable of simulating light scattering by particles of arbitrary shape and composition in a wide range of particle sizes. It is used by more than 50 researchers worldwide. At the ASI we will present a poster, describing features of ADDA version 1.0, which is...

Plasmon resonance in metal nanoparticles has gained increasing interest in recent years due to its ability to concentrate electromagnetic energy into subwavelength regions. One of the commonly used methods to simulate interaction of light with nanoparticles is the discrete dipole approximation (DDA). Agreement between the DDA simulations and experi...

Microparticles and exosomes are cell-derived microvesicles present in body fluids that play a role in coagulation, inflammation, cellular homeostasis and survival, intercellular communication, and transport. Despite increasing scientific and clinical interest, no standard procedures are available for the isolation, detection and characterization of...

We compared three formulations of the discrete dipole approximation (DDA) for simulation of light scattering by particles with refractive indices m=10+10i , 0.1+i , and 1.6+0.01i . These formulations include the filtered coupled dipoles (FCD), the lattice dispersion relation (LDR) and the radiative reaction correction. We compared the number of ite...

We describe a method to obtain the fraction of poorly deformable red blood cells in a blood sample from the intensity pattern in an ektacytometer. In an ektacytometer red blood cells are transformed into ellipsoids by a shear flow between two transparent cylinders. The intensity pattern, due to a laser beam that is sent through the suspension, is p...

>>> The best seller in the field - over 30k ebooks sold as 2018. <<< From the Back Cover: Deeply rooted in fundamental research in Mathematics and Computer Science, Cellular Automata (CA) are recognized as an intuitive modeling paradigm for Complex Systems. Already very basic CA, with extremely simple micro dynamics such as the Game of Life, show...

Cellular Automata (CA) are generally acknowledged to be a powerful way to describe and model natural phenomena [1–3]. There are even tempting claims that nature itself is one big (quantum) information processing system, e.g. [4], and that CA may actually be nature’s way to do this processing [5–7]. We will not embark on this philosophical road, but...

..... The INTRODUCTION into the one of the best selling book in the field (over 30k ebooks sold) ..... Abstract: Since the sixteenth century there have been two main paradigms in the methodology of doing science. The first one is referred to as “the experimental” paradigm. During an experiment we observe, measure, and quantify natural phenomena in...