Eric Lorenz | University of Amsterdam (original) (raw)

Papers by Eric Lorenz

2011 IEEE Seventh International Conference on e-Science Workshops, 2011

The understanding of biological processes, e.g. related to cardio-vascular disease and treatment,... more 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 hardware to take into account the different requirements of the coupled sub-systems concerning computing power. For such a concept, which is an extension of the standard multiscale computing approach, we want to apply the term Distributed Multiscale Computing.

International Journal of Modern Physics C, 2014

Many rheological properties of blood, along with transport properties of blood cells can be captu... more 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°ow, employing a discrete element model (DEM) for RBCs and coupling it to a lattice Boltzmann method (LBM)°uid solver using the immersed boundary method (IBM). We identify an e±cient computationally reduced mesoscopic representation of cells and°ow, still able to recover essential physics and physiological phenomena. Our model is found to agree quantitatively with experimental¯ndings. The Fåhraeus-Lindqvist e®ect and shear thinning is recovered, while the thickness of the cell-free layer (CFL) matches the observations. In addition, we investigate the tank-treading frequency of a single RBC in shear°ow along with the transition from tumbling to tank-treading, also matching experimental data.

Lecture Notes in Computer Science, 2007

Complex Automata were recently proposed as a paradigm to model multi-scale complex systems. The c... more Complex Automata were recently proposed as a paradigm to model multi-scale complex systems. The concept is formalized and the scale separation map is further investigated in relation with its capability to specify the components of Complex Automata. Five classes of scale separation are identified, each potentially giving rise to a specific multiscale modeling paradigm. A number of canonical examples are briefly discussed.

Proceedings - 7th IEEE International Conference on e-Science Workshops, eScienceW 2011, 2011

In several disciplines, a multiscale approach is being used to model complex natural processes ye... more 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 this paper a principled approach to distributed multiscale computing is taken,

Understanding Complex Systems, 2010

Cellular Automata (CA) are generally acknowledged to be a powerful way to describe and model natu... more 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, eg [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 ask ourselves a more mundane question. Can we use CA to model the inherently multi-scale processes in nature and use these models for efficient simulations on digital computers?

Lecture Notes in Computer Science, 2009

In-stent restenosis, the maladaptive response of a blood vessel to injury caused by the deploymen... more In-stent restenosis, the maladaptive response of a blood vessel to injury caused by the deployment of a stent, is a multiscale problem involving a large number of processes. We describe a Complex Automata Model for in-stent restenosis, coupling a bulk flow, drug diffusion, and smooth muscle cell model, all operating on different time scales. Details of the single scale models and of the coupling interfaces are described, together with first simulation results, obtained with a dedicated software environment for Complex Automata simulations. The results show that the model can reproduce growth trends observed in experimental studies.

Interface focus, Jan 6, 2011

Neointimal hyperplasia, a process of smooth muscle cell re-growth, is the result of a natural wou... more 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 remains a significant complication of this interventional therapy. The influence of stent design parameters such as strut thickness, shape and the depth of strut deployment within the vessel wall on the severity of restenosis has already been highlighted but the detail of this influence is unclear. These factors impact on local haemodynamics and vessel structure and affect the rate of neointima formation. This paper presents the first results of a multi-scale model of ISR. The development of the simulated restenosis as a function of stent deployment depth is compared with an in vivo porcine dataset. Moreover, the influence of strut size and sh...

Multiscale Modeling & Simulation, 2011

The macroscopically emergent rheology of suspensions is dictated by details of fluid-particle and... more 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 suspension flow in which at the macroscale the suspension is treated as a non-Newtonian fluid. The local shear-rate and particle volume fraction are input to a simulation of fully resolved suspension microdynamics. With the help of these simulations, the apparent viscosity and shear-induced diffusivities can be computed for a given shear-rate and volume fraction, and are then used to complete the information needed in the constitutional relations on the macroscopic level. On both levels, the lattice-Boltzmann method (LBM) is applied to model the fluid phase and coupled to a Lagrangian model for the advection-diffusion of the solid phase. Down and upward mapping of viscosity and diffusivity related quantities will be discussed, as well as information exchanged between the phases on both scales. Temporal scale splitting between viscous and diffusive dynamics has also been exploited to accelerate the macroscopic equilibration dynamics. Additionionally, Galileian and rotational symmetries allow us to make very efficient use of a database where the results of previous simulations can be stored, again reducing the computational effort by factors of several orders of magnitude. The HMM suspension model is applied to the simulation of a 2-dimensional flow through a straight channel of macroscopic width. The equilibration dynamics of flow and volume fraction profiles and equilibrium profiles of volume fraction, diffusivity, velocity, shear-rate, and viscosity are discussed. We show that the proposed HMM model not only reproduces experimental findings for low Reynolds numbers but also predicts additional dependencies introduced by shear-thickening effects not covered by existing macroscopic suspension flow models.

Procedia Computer Science, 2013

This paper considers a multiscale description of thrombus formation and its simplified numerical ... more This paper considers a multiscale description of thrombus formation and its simplified numerical implementation in the case of cerebral aneurysms. In particular, we extend previously introduced generic 2D models towards 3D patient specific aneurysm geometries. The multiscale amplification method contributes to considerably reducing simulation time. This allows us to achieve a mesh resolution high enough to resolve details of the stent geometry which is triggering flow conditions to induce clotting. Simulation results presented in this paper are qualitatively in a good agreement with clinical observations.

Physical Review E, 2009

Standard methods for lattice Boltzmann simulations of suspended particles, based on the momentum ... more Standard methods for lattice Boltzmann simulations of suspended particles, based on the momentum exchange algorithm, might lack accuracy or violate Galilean invariance in some particular situations. Aiming at simulations of dense suspensions in high-shear flows, we motivate and investigate necessary correction terms. We propose an approach which, combining accurate treatments of fluid-structure interaction and moving boundaries, is able to preserve Galilean invariance in relevant orders and to improve the physical behavior of the system. We validate the approach in a comparison with standard methods in simple test problems.

Physical Review E, 2009

When sheared suspensions are simulated, Lees-Edwards boundary conditions allow more realistic com... more When sheared suspensions are simulated, Lees-Edwards boundary conditions allow more realistic computational setups as they remove the need of a domain bounded by shearing walls ͑as in Couette-type flow͒ which bias typical flow structures. Lees-Edwards boundary conditions therefore allow investigation of pure bulk properties in a quasi-infinite system. In addition, they improve the computational efficiency of the simulations as the whole domain can be used to calculate averages. We propose an implementation of Lees-Edwards boundary conditions for lattice Boltzmann simulations of particulate suspensions, combined with an accurate treatment of fluid-particle interactions. The algorithm is validated using a simple single-particle benchmark and further applied to a fully resolved suspension flow. Shear-thickening behavior, which is prolonged to higher shear rates as compared to Couette flow results, could be observed.

Journal of Parallel and Distributed Computing, 2013

ABSTRACT Inherently complex problems from many scientific disciplines require a multiscale modeli... more ABSTRACT 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 multiscale modeling and distributed multiscale computing. Useful interaction patterns of multiscale models are made predictable with a submodel execution loop (SEL), four coupling templates, and coupling topology properties. We enhance a high-level and well-defined Multiscale Modeling Language (MML) that describes and specifies multiscale models and their computational architecture in a modular way. The architecture is analyzed using directed acyclic task graphs, facilitating validity checking, scheduling distributed computing resources, estimating computational costs, and predicting deadlocks. Distributed execution using the multiscale coupling library and environment (MUSCLE) is outlined. The methodology is applied to two selected applications in nanotechnology and biophysics, showing its capabilities.

Journal of Computational Science, 2011

In-stent restenosis, the maladaptive response of a blood vessel to injury caused by the deploymen... more 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 different time scales. Details of the single scale models and of the coupling interfaces are described, together with first simulation results, obtained with a dedicated software environment for Complex Automata simulations. Preliminary results show that the model can reproduce growth trends observed in experimental studies and facilitate testing of hypotheses concerning the interaction of key factors.

International Journal for Multiscale Computational Engineering, 2007

Complex Automata were recently proposed as a paradigm to model multiscale complex systems. The co... more Complex Automata were recently proposed as a paradigm to model multiscale complex systems. The concept is formalized and the scale separation map is further investigated in relation with its capability to specify the components of Complex Automata. Five classes of scale ...

COAST (Complex Automata Simulation Technique) is a European Union FP6 funded project which has de... more COAST (Complex Automata Simulation Technique) is a European Union FP6 funded project which has developed a methodology for multi-science, multi-scale simulation of complex systems. The resulting framework (MUSCLE: Multiscale Simulation Coupling Library and Environment is now publically available. As an exemplar, MUSCLE has been applied to the model of a complex biomedical pathology, that of in-stent restenosis, resulting in a hierarchical aggregation of coupled cellular automata and agent based models coined "complex automaton". Currently, three simple, single scale models have been coupled to simulate the pathological response of the arterial wall to stent-deployment: an agent based model of smooth muscle cell dynamics (modeling cell cycle and cell-cell interaction), a lattice Boltzmann model of blood flow (defining wall shear stress and oscillatory shear index at the vessel surface) and a finite difference drug diffusion model (defining stent-eluted drug concentrations across the vessel wall). These sub-models operate on distinct temporal scales and can be plotted on a scale separation map. This conceptual tool defines the temporal separation of the processes and the coupling template required for interaction between them [3]. Coupling is implemented using smart conduits and in some situations, mapper agents, which transfer information between models with lattice based domains (blood flow, drug diffusion) to those with continuous domains (smooth muscle behaviour). Here we present preliminary output of a simple 2D model of in-stent restenosis. The present model captures the relationship between degree of stent induced injury and the smooth muscle cell hyperplastic response. The generation of realistic output correlates well with experimental data and paves the way for computer-aided design of stent-based therapies.

Procedia Computer Science, 2012

Nature is observed at all scales; with multiscale modeling, scientists bring together several sca... more 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 models, tightly coupled, brings with it a number of theoretical and practical issues. In this contribution, a tightly coupled model of in-stent restenosis is first theoretically examined for its multiscale merits using the Multiscale Modeling Language (MML); this is aided by a toolchain consisting of MAPPER Memory (MaMe), the Multiscale Application Designer (MAD), and Gridspace Experiment Workbench. It is implemented and executed with the general Multiscale Coupling Library and Environment (MUSCLE). Finally, it is scheduled amongst heterogeneous infrastructures using the QCG-Broker. This marks the first occasion that a tightly coupled application uses distributed multiscale computing in such a general way.

2011 IEEE Seventh International Conference on e-Science Workshops, 2011

The understanding of biological processes, e.g. related to cardio-vascular disease and treatment,... more 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 hardware to take into account the different requirements of the coupled sub-systems concerning computing power. For such a concept, which is an extension of the standard multiscale computing approach, we want to apply the term Distributed Multiscale Computing.

International Journal of Modern Physics C, 2014

Many rheological properties of blood, along with transport properties of blood cells can be captu... more 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°ow, employing a discrete element model (DEM) for RBCs and coupling it to a lattice Boltzmann method (LBM)°uid solver using the immersed boundary method (IBM). We identify an e±cient computationally reduced mesoscopic representation of cells and°ow, still able to recover essential physics and physiological phenomena. Our model is found to agree quantitatively with experimental¯ndings. The Fåhraeus-Lindqvist e®ect and shear thinning is recovered, while the thickness of the cell-free layer (CFL) matches the observations. In addition, we investigate the tank-treading frequency of a single RBC in shear°ow along with the transition from tumbling to tank-treading, also matching experimental data.

Lecture Notes in Computer Science, 2007

Complex Automata were recently proposed as a paradigm to model multi-scale complex systems. The c... more Complex Automata were recently proposed as a paradigm to model multi-scale complex systems. The concept is formalized and the scale separation map is further investigated in relation with its capability to specify the components of Complex Automata. Five classes of scale separation are identified, each potentially giving rise to a specific multiscale modeling paradigm. A number of canonical examples are briefly discussed.

Proceedings - 7th IEEE International Conference on e-Science Workshops, eScienceW 2011, 2011

In several disciplines, a multiscale approach is being used to model complex natural processes ye... more 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 this paper a principled approach to distributed multiscale computing is taken,

Understanding Complex Systems, 2010

Cellular Automata (CA) are generally acknowledged to be a powerful way to describe and model natu... more 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, eg [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 ask ourselves a more mundane question. Can we use CA to model the inherently multi-scale processes in nature and use these models for efficient simulations on digital computers?

Lecture Notes in Computer Science, 2009

In-stent restenosis, the maladaptive response of a blood vessel to injury caused by the deploymen... more In-stent restenosis, the maladaptive response of a blood vessel to injury caused by the deployment of a stent, is a multiscale problem involving a large number of processes. We describe a Complex Automata Model for in-stent restenosis, coupling a bulk flow, drug diffusion, and smooth muscle cell model, all operating on different time scales. Details of the single scale models and of the coupling interfaces are described, together with first simulation results, obtained with a dedicated software environment for Complex Automata simulations. The results show that the model can reproduce growth trends observed in experimental studies.

Interface focus, Jan 6, 2011

Neointimal hyperplasia, a process of smooth muscle cell re-growth, is the result of a natural wou... more 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 remains a significant complication of this interventional therapy. The influence of stent design parameters such as strut thickness, shape and the depth of strut deployment within the vessel wall on the severity of restenosis has already been highlighted but the detail of this influence is unclear. These factors impact on local haemodynamics and vessel structure and affect the rate of neointima formation. This paper presents the first results of a multi-scale model of ISR. The development of the simulated restenosis as a function of stent deployment depth is compared with an in vivo porcine dataset. Moreover, the influence of strut size and sh...

Multiscale Modeling & Simulation, 2011

The macroscopically emergent rheology of suspensions is dictated by details of fluid-particle and... more 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 suspension flow in which at the macroscale the suspension is treated as a non-Newtonian fluid. The local shear-rate and particle volume fraction are input to a simulation of fully resolved suspension microdynamics. With the help of these simulations, the apparent viscosity and shear-induced diffusivities can be computed for a given shear-rate and volume fraction, and are then used to complete the information needed in the constitutional relations on the macroscopic level. On both levels, the lattice-Boltzmann method (LBM) is applied to model the fluid phase and coupled to a Lagrangian model for the advection-diffusion of the solid phase. Down and upward mapping of viscosity and diffusivity related quantities will be discussed, as well as information exchanged between the phases on both scales. Temporal scale splitting between viscous and diffusive dynamics has also been exploited to accelerate the macroscopic equilibration dynamics. Additionionally, Galileian and rotational symmetries allow us to make very efficient use of a database where the results of previous simulations can be stored, again reducing the computational effort by factors of several orders of magnitude. The HMM suspension model is applied to the simulation of a 2-dimensional flow through a straight channel of macroscopic width. The equilibration dynamics of flow and volume fraction profiles and equilibrium profiles of volume fraction, diffusivity, velocity, shear-rate, and viscosity are discussed. We show that the proposed HMM model not only reproduces experimental findings for low Reynolds numbers but also predicts additional dependencies introduced by shear-thickening effects not covered by existing macroscopic suspension flow models.

Procedia Computer Science, 2013

This paper considers a multiscale description of thrombus formation and its simplified numerical ... more This paper considers a multiscale description of thrombus formation and its simplified numerical implementation in the case of cerebral aneurysms. In particular, we extend previously introduced generic 2D models towards 3D patient specific aneurysm geometries. The multiscale amplification method contributes to considerably reducing simulation time. This allows us to achieve a mesh resolution high enough to resolve details of the stent geometry which is triggering flow conditions to induce clotting. Simulation results presented in this paper are qualitatively in a good agreement with clinical observations.

Physical Review E, 2009

Standard methods for lattice Boltzmann simulations of suspended particles, based on the momentum ... more Standard methods for lattice Boltzmann simulations of suspended particles, based on the momentum exchange algorithm, might lack accuracy or violate Galilean invariance in some particular situations. Aiming at simulations of dense suspensions in high-shear flows, we motivate and investigate necessary correction terms. We propose an approach which, combining accurate treatments of fluid-structure interaction and moving boundaries, is able to preserve Galilean invariance in relevant orders and to improve the physical behavior of the system. We validate the approach in a comparison with standard methods in simple test problems.

Physical Review E, 2009

When sheared suspensions are simulated, Lees-Edwards boundary conditions allow more realistic com... more When sheared suspensions are simulated, Lees-Edwards boundary conditions allow more realistic computational setups as they remove the need of a domain bounded by shearing walls ͑as in Couette-type flow͒ which bias typical flow structures. Lees-Edwards boundary conditions therefore allow investigation of pure bulk properties in a quasi-infinite system. In addition, they improve the computational efficiency of the simulations as the whole domain can be used to calculate averages. We propose an implementation of Lees-Edwards boundary conditions for lattice Boltzmann simulations of particulate suspensions, combined with an accurate treatment of fluid-particle interactions. The algorithm is validated using a simple single-particle benchmark and further applied to a fully resolved suspension flow. Shear-thickening behavior, which is prolonged to higher shear rates as compared to Couette flow results, could be observed.

Journal of Parallel and Distributed Computing, 2013

ABSTRACT Inherently complex problems from many scientific disciplines require a multiscale modeli... more ABSTRACT 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 multiscale modeling and distributed multiscale computing. Useful interaction patterns of multiscale models are made predictable with a submodel execution loop (SEL), four coupling templates, and coupling topology properties. We enhance a high-level and well-defined Multiscale Modeling Language (MML) that describes and specifies multiscale models and their computational architecture in a modular way. The architecture is analyzed using directed acyclic task graphs, facilitating validity checking, scheduling distributed computing resources, estimating computational costs, and predicting deadlocks. Distributed execution using the multiscale coupling library and environment (MUSCLE) is outlined. The methodology is applied to two selected applications in nanotechnology and biophysics, showing its capabilities.

Journal of Computational Science, 2011

In-stent restenosis, the maladaptive response of a blood vessel to injury caused by the deploymen... more 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 different time scales. Details of the single scale models and of the coupling interfaces are described, together with first simulation results, obtained with a dedicated software environment for Complex Automata simulations. Preliminary results show that the model can reproduce growth trends observed in experimental studies and facilitate testing of hypotheses concerning the interaction of key factors.

International Journal for Multiscale Computational Engineering, 2007

Complex Automata were recently proposed as a paradigm to model multiscale complex systems. The co... more Complex Automata were recently proposed as a paradigm to model multiscale complex systems. The concept is formalized and the scale separation map is further investigated in relation with its capability to specify the components of Complex Automata. Five classes of scale ...

COAST (Complex Automata Simulation Technique) is a European Union FP6 funded project which has de... more COAST (Complex Automata Simulation Technique) is a European Union FP6 funded project which has developed a methodology for multi-science, multi-scale simulation of complex systems. The resulting framework (MUSCLE: Multiscale Simulation Coupling Library and Environment is now publically available. As an exemplar, MUSCLE has been applied to the model of a complex biomedical pathology, that of in-stent restenosis, resulting in a hierarchical aggregation of coupled cellular automata and agent based models coined "complex automaton". Currently, three simple, single scale models have been coupled to simulate the pathological response of the arterial wall to stent-deployment: an agent based model of smooth muscle cell dynamics (modeling cell cycle and cell-cell interaction), a lattice Boltzmann model of blood flow (defining wall shear stress and oscillatory shear index at the vessel surface) and a finite difference drug diffusion model (defining stent-eluted drug concentrations across the vessel wall). These sub-models operate on distinct temporal scales and can be plotted on a scale separation map. This conceptual tool defines the temporal separation of the processes and the coupling template required for interaction between them [3]. Coupling is implemented using smart conduits and in some situations, mapper agents, which transfer information between models with lattice based domains (blood flow, drug diffusion) to those with continuous domains (smooth muscle behaviour). Here we present preliminary output of a simple 2D model of in-stent restenosis. The present model captures the relationship between degree of stent induced injury and the smooth muscle cell hyperplastic response. The generation of realistic output correlates well with experimental data and paves the way for computer-aided design of stent-based therapies.

Procedia Computer Science, 2012

Nature is observed at all scales; with multiscale modeling, scientists bring together several sca... more 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 models, tightly coupled, brings with it a number of theoretical and practical issues. In this contribution, a tightly coupled model of in-stent restenosis is first theoretically examined for its multiscale merits using the Multiscale Modeling Language (MML); this is aided by a toolchain consisting of MAPPER Memory (MaMe), the Multiscale Application Designer (MAD), and Gridspace Experiment Workbench. It is implemented and executed with the general Multiscale Coupling Library and Environment (MUSCLE). Finally, it is scheduled amongst heterogeneous infrastructures using the QCG-Broker. This marks the first occasion that a tightly coupled application uses distributed multiscale computing in such a general way.