CAREER: Integrated Research and Education in Nonlinear Dynamics in Biological Systems

这项教师早期职业发展(Career)项目的研究计划是开发一个全面的计算和分析框架，用于在系统水平上了解导致致命心脏疾病(如室颤和房颤)的心律紊乱的非线性动力学。该项目的具体研究目标包括：1)开发简化模型以准确描述心肌细胞的动力学；2)开发多尺度计算方法来研究扩展的心肌组织的动力学；3)通过理论分析和数值模拟发展对心律失常的系统水平的理解。本研究旨在对心律失常的诊断和治疗产生影响。室颤导致心源性猝死，这是工业化世界的主要死亡原因。在美国，每年有超过35万人死于心脏性猝死。房颤是中风的主要原因，65岁以上的美国人中有五分之一会受到影响。从这项研究中获得的对心脏动力学的更好的理解最终可能会通过其医学意义产生更广泛的社会影响。拟议的研究活动还将支持生物医学工程、生命科学和数学领域的新的跨学科合作。振荡和节律现象普遍存在于许多生物过程中，如昼夜节律、新陈代谢和大脑活动。由于它们的非线性、多尺度的复杂性，这些系统违背了基于传统简化论者的方法的理解，在传统的简化论者的方法中，人们试图通过将已经单独检查的所有组成部分组合在一起来理解系统的行为。该项目中开发的计算和分析方法为促进对这些非线性过程的系统级理解提供了有用的工具。该项目的教育计划立志于培养将非线性思维引入生物医学研究的下一代科学家。大学生和毕业生不熟悉非线性现象及其数学表示。缺乏非线性分析知识使学生对现实世界中的问题和生物医学研究中固有的非线性思维缺乏准备。拟议工作的各个方面将用于加强生物系统中非线性动力学的研究生和本科生教育。将开发一个推广计划，让K-12学生接触到数学建模对生物医学研究的兴奋和重要性。此外，这项研究将被用来促进工科新生和代表性不足的群体更高的保留率。

The research program of this faculty early career development (CAREER) project is to develop a comprehensive computation and analysis framework for system-level understanding of nonlinear dynamics of heart rhythm disorders that lead to fatal cardiac diseases such as ventricular fibrillation and atrial fibrillation. The specific research objectives of this project include: 1) developing simplified models to accurately describe the dynamics of cardiac myocytes; 2) developing multiscale computational methods to study dynamics of extended cardiac tissue; and 3) developing system-level understanding of cardiac arrhythmias using theoretical analysis and numerical simulation. This research aims to impact the diagnosis and treatment of cardiac arrhythmias. Ventricular fibrillation induces sudden cardiac death, a leading cause of death in the industrialized world. Sudden cardiac death kills more than 350,000 people each year in the United States. Atrial fibrillation is the leading cause of stroke, which will affect one-fifth of Americans over 65. Improved understanding of cardiac dynamics gained from this research may eventually have a broader social impact through its medical implications. The proposed research activities will also support new cross-disciplinary collaborations in the areas of biomedical engineering, life science, and mathematics. Oscillatory and rhythmic phenomena are common in many biological processes, such as circadian cycle, metabolism, and brain activity. Because of their nonlinear, multiscale complexities, these systems defy understanding based on the conventional reductionist's approach, in which one attempts to understand a system's behavior by putting together all the constituent pieces that have been examined separately. The computational and analytical methods developed in this project provide useful tools to advance system-level understanding of these nonlinear processes. The education plan of this project aspires to train the next generation of scientists who bring nonlinear thinking into biomedical research. College students and graduates are not familiar with nonlinear phenomena and their mathematical representations. The lack of knowledge in nonlinear analysis leaves the students unprepared for real-world problems and nonlinear thinking inherent in biomedical research. Various aspects of the proposed work will be used to enhance graduate and undergraduate education in nonlinear dynamics in biological systems. An outreach program will be developed to expose K-12 students to the excitement and importance of mathematical modeling for biomedical research. In addition, the research will be used to promote higher retention rates among engineering freshmen and underrepresented groups.