MULTISCALE MODELING ENVIRONMENT FOR TISSUE AND ORGAN BIOPHYSICS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 总体目标是开发和部署新的，网络可访问的，集群使能的，网格感知的软件和数据资源，使生物力学，生物物理学和心血管生理学的研究人员能够进行数值实验，这些实验是：从亚细胞到整个器官尺度的结构整合;跨相互作用的生物过程的功能整合;以及整合来自各种来源，尺度和模式的实验数据。 我们将探索和推进这些综合分析的合成，使研究人员可以开发计算模型，将理论与经验数据在功能和结构上结合起来，以研究实验动机的生物医学假设。为了实现这些目标，我们提出了密切互动的可视化，网格计算和数据集成的核心研究活动的资源。为了将这些发展集中在科学上重要的问题上，我们与研究人员开发了合作项目，这些研究人员正在应用实验和计算方法来了解生理和病理生理过程的细胞和分子机制，这些过程依赖于整个心脏的三维解剖结构，以了解其在体内的表现。 该核心的主要应用将继续是心脏机电特性的计算模型，该模型从单个肌细胞生物物理学到整个心脏生理学进行整合，并在特征良好的动物模型中通过实验测量进行验证。虽然这些多尺度模型的数据组成部分及其实验验证是特定于心脏的，但计算方法和软件更通用。因此，更新的目的和正在开发的新工具的目标用户超出了心脏的生物物理学，扩展到其他生物医学应用，包括软组织生物力学，电生理学，系统生物学和诊断医学成像。 目标1： 集成多尺度模型动态创作的交互式高性能建模环境 目标二： 多尺度模型库与共享框架 目标3： 用于心脏病患者特定诊断和治疗的软件 补充目标D 加快患者特定建模和连续性开发：自NBCR更新提交以来，利用NIH的新投资，帮助建立新兴社区或研究人员 D1.加快开发目标3中建议的针对患者的多尺度建模软件 D2.使用新工具和新的临床数据建立一个去识别化的患者特异性模型数据库，并加快目标2中建议的多尺度模型库和共享框架的开发和发布 D3. GPU技术可加速Continuity中的关键代码

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall objective is to develop and deploy novel, web accessible, cluster-enabled, grid-aware software and data resources that allow investigators in biomechanics, biophysics and cardiovascular physiology to perform numerical experiments that are: structurally integrated from sub-cellular to whole organ scales; functionally integrated across interacting biological processes; and that integrate experimental data from a variety of sources, scales and modalities. We will explore and advance the synthesis of these integrative analyses so that investigators can develop computational models that integrate theory with empirical data both functionally and structurally to investigate experimentally motivated biomedical hypotheses. To achieve these goals, we propose to interact closely with the visualization, grid computing and data integration core research activities of the resource. To focus these developments on scientifically important questions, we have developed collaborative projects with investigators who are applying experimental and computational approaches to understand the cellular and molecular mechanisms of physiological and pathophysiological processes that are dependent on the three-dimensional anatomy of the whole heart for their manifestations in vivo. The primary application of this core will continue to be computational models of cardiac electromechanical properties that integrate from single myocyte biophysics to whole heart physiology and are validated with experimental measurements in well characterized animal models. Whereas the data components of these multiscale models and their experimental validation are specific to the heart, the computational methods and software are more general. Therefore, the aims of the renewal and the targeted users of the new tools under development extend beyond the biophysics of the heart to other biomedical applications including soft tissue biomechanics, electrophysiology, systems biology, and diagnostic medical imaging. Aim 1: Interactive High-Performance Modeling Environment for Dynamic Authoring of Integrative Multi-Scale Models Aim 2: Multi-Scale Model Repository and Sharing Framework Aim 3: Software for Patient-Specific Diagnosis and Treatment of Heart Disease Supplemental Aim D Expediting Patient Specific Modeling and Continuity Development: Capitalizing on new NIH investments since NBCR renewal submission to help build an emerging community or researchers D1. Expedite the development of patient-specific multi-scale modeling software proposed in Aim 3 D2. Develop a database of de-identified patient-specific models using the new tools and newly available clinical data, and to accelerate the development and release of the multi-scale model repository and sharing framework proposed in Aim 2 D3. Harness GPU technology to speed up key codes in Continuity