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Multiscale Modeling and Parallel Simulations of Blood Flow in Cerebral Malaria an

脑疟疾血流的多尺度建模和并行模拟

基本信息

批准号：
8065374
负责人：
George Karniadakis
金额：
$ 58.36万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8065374
关键词：
Adhesions Adhesives Affect Algorithms Anemia Animal Model Binding Biochemical Biological Models Biomechanics Biophysics Blood capillaries Blood flow Brain Capsid Proteins Cell Adhesion Cell Adhesion Process Cell Aggregation Cell membrane Cell model Cell surface Cells Cephalic Cereals Cerebral Malaria Clinical Code Complex Computer Systems Coupled Cytoskeleton Data Development Diabetes Mellitus Diffusion Disease Documentation Elliptocytosis found Endothelial Cells Equation Erythrocytes Falciparum Malaria Future Generations Glycocalyx Goals Health Hematocrit procedure Hematological Disease Hemoglobin High Performance Computing Human In Vitro Individual Intercellular adhesion molecule 1 Laboratories Lasers Lead Length Ligands Link Liquid substance Malaria Measurement Measures Mechanics Mediating Methodology Methods Metric Microcirculation Microfluidic Microchips Microfluidics Microscopy Mining Minor Modeling Molecular Monitor Motion Nanotechnology Nutrient Obstruction Online Systems Optics Organ Oxygen Pharmaceutical Preparations Phase Physiological Preparation Procedures Process Property Proteins Reaction Recording of previous events Recovery Resources Rheology Schools Severity of illness Shapes Sickle Cell Sickle Hemoglobin Signal Pathway Simulate Site Software Tools Spectrin Staging Symptoms System Techniques Testing Time Tissues Transport Reaction Trees Uncertainty Validation Width Work abstracting adhesion process arteriole base cancer cell capillary computer code computing resources design flexibility laser tweezer molecular dynamics multi-scale modeling nanoscale oxygen transport parallel computing particle polymerization pressure programs receptor repository research study response sensor simulation software repository theories three-dimensional modeling tool venule working group

项目摘要

DESCRIPTION (provided by applicant): Project Summary/Abstract The objective of this project is to develop a unified and validated multiscale modeling methodology for two diseases with serious hematological disorders: celebral malaria (CM) and sickle-cell (SS) anemia. The common clinical symptom of both diseases is obstruction in the microcirculation caused primarily by loss of deformability of red blood cells (RBCs) and increased cytoadhesion. Both diseases are characterized by multiscale phenomena, spanning at least four orders of magnitude in length scale with corresponding disparity in the temporal scale. Moreover, the local vaso-oclusions occurring in CM and SS strongly affect blood flow and oxygen transport at the global organ scale as well. Building on recent progress in modeling RBCs at the spectrin level and cell-aggregation processes and taking advantage of available petaflop-level computing resources, we propose a parallel multiscale methodology to model CM and SS and use it as a predictive tool for quantitatively assessing the severity of these diseases. This will form a general simulation platform for adding further complexity in future studies, e.g., incorporating more biochemical details or studying other hemolytic disorders. Predictability of multiscale models requires quantifying uncertainty, and, to this end, we will incorporate polynomial chaos methods to model and propagate parametric uncertainties through the multiscale system. In addition, to validate the new methodology, microfluidic experiments, optical tweezers measurements and 3D phase microscopy will be used to test different aspects of the conceptual and numerical modeling under different conditions. The specific contributions of this project include: (1) Development of fine- and coarse-grained RBC models in CM (cytoskeleton dynamics) and SS (oxygen transport and polymerization) using molecular dynamics (MD), partial differential equations (PDEs), and mean-field theory. (2) Characterization of infected RBCs and sickle cells at different developmental stages using optical non-invasive means. (3) Modeling of flow and rheology in small vessels. Flow modeling will be based on the "triple-decker"1 - a new algorithm that we have developed for interfacing seamlessly MD, mesoscopic dynamics, and the Navier-Stokes equations. For mesoscopic dynamics we will employ the dissipative particle dynamics (DPD) method, a particularly effective simulation approach for complex fluids. We plan to disseminate our models and software tools, including the general-purpose triple-decker algorithm, via web-based repositories, existing public openware sites, summer schools, and through the MSM consortium. 1 http://www.cfm.brown.edu/crunch/IMAG/FedosovK08.pdf PUBLIC HEALTH RELEVANCE: We propose to develop a unified multiscale modeling methodology for two diseases with serious hematological disorders: celebral malaria (CM) and sickle-cell (SS) anemia. We will model the increase in stiffness of the deformable red blood cells and the adhesion processes involved and correspondingly blood flow in capillaries and arterioles, modeling multiscale phenomena across more than four orders of magnitude in spatio-temporal scales.

描述（由申请人提供）：项目摘要/摘要该项目的目标是针对两种严重血液疾病疾病开发统一且经过验证的多尺度建模方法：疟疾（CM）和镰状细胞（SS）贫血。这两种疾病的共同临床症状是主要由红细胞（RBC）变形能力丧失和细胞粘附增加引起的微循环阻塞。这两种疾病都具有多尺度现象的特点，在长度尺度上跨越至少四个数量级，在时间尺度上也有相应的差异。此外，CM和SS中发生的局部血管闭塞也强烈影响全球器官尺度的血流和氧气输送。基于血影蛋白水平和细胞聚集过程中红细胞建模的最新进展，并利用可用的 petaflop 级计算资源，我们提出了一种并行多尺度方法来建模 CM 和 SS，并将其用作定量评估这些疾病严重程度的预测工具。这将形成一个通用模拟平台，以增加未来研究的复杂性，例如纳入更多生化细节或研究其他溶血性疾病。多尺度模型的可预测性需要量化不确定性，为此，我们将结合多项式混沌方法来建模并通过多尺度系统传播参数不确定性。此外，为了验证新方法，将使用微流体实验、光镊测量和 3D 相位显微镜来测试不同条件下概念和数值模型的不同方面。该项目的具体贡献包括：（1）利用分子动力学（MD）、偏微分方程（PDE）和平均场理论开发CM（细胞骨架动力学）和SS（氧传输和聚合）中的细粒度和粗粒度RBC模型。 (2) 使用光学非侵入性手段表征不同发育阶段的感染红细胞和镰状细胞。 (3) 小血管中的流动和流变学建模。流动建模将基于“三层”1 - 我们开发的一种新算法，用于无缝连接MD、介观动力学和纳维-斯托克斯方程。对于介观动力学，我们将采用耗散粒子动力学（DPD）方法，这是一种对复杂流体特别有效的模拟方法。我们计划通过基于网络的存储库、现有的公共开放软件网站、暑期学校以及 MSM 联盟来传播我们的模型和软件工具，包括通用三层算法。 1 http://www.cfm.brown.edu/crunch/IMAG/FedosovK08.pdf 公共健康相关性：我们建议针对两种严重血液疾病的疾病开发统一的多尺度建模方法：疟疾（CM）和镰状细胞（SS）贫血。我们将模拟可变形红细胞硬度的增加以及所涉及的粘附过程以及相应的毛细血管和小动脉中的血流，模拟时空尺度上超过四个数量级的多尺度现象。