EAGER: Analysis of cardiac repolarization as a tool for the noninvasive assessment of cardiovascular system exposure to carbon and metallic nanotubes

CBET-1342051这项建议的研究目标是调查心脏复极测量作为非侵入性评估心血管系统暴露于碳和金属纳米管的工具的可行性。为了实现这一目标，具体目标是：(A)对肺暴露于单壁碳和二氧化钛纳米管后的清醒大鼠采用强度控制的多巴酚丁胺运动应激测试，并确定QT/RR滞后值以及QT和RR间期的适应率；(B)使用常见的生物和免疫化学标记物，确定氧化应激、心肌细胞损伤和血管炎症的中毒程度；以及(C)使用电生理学和免疫化学标记物比较不同纳米管暴露于肺的毒性结果之间的关系。这一建议的独特之处在于将理论非线性动力学和实验电生理测量相结合，以评估纳米结构对心脏功能的毒理效应。上述目标的成功实现将对发展强有力的非侵入性监测纳米系统的心脏毒性具有深远的影响。这项提议的教育目标是以有效的方式将新的科学技术融入正式和非正式的教学和推广计划中。我们扩展了一个有三个主要主题的有凝聚力的教育计划：课程开发、指导和外展活动。(A)通过纳入研究成果，改进两门研究生课程：NANO785--纳米生物电子学基础(S.Araamudhan)，NAN740--生物可激发介质中的非线性波(J.Starobin)。(B)研究生和本科生(包括目前在PI工作的少数族裔研究生)在材料、生物电子学、生物学和计算物理方面有大量接触的跨学科领域的参与；(C)NCA&&T；UNG和JSNN当前和未来的推广计划将得到加强(包括NanoDay和K-12纳米技术乐高模块)。智力优势：以前的研究表明，生化和免疫标记物对于识别纳米管引起的氧化应激和血管损伤具有重要意义。然而，这种暴露与非侵入性电生理因素的关联尚不清楚。即使电生理监测心血管系统是最强大的生物医学工具之一，它仍然不适合应用于对公众健康至关重要的环境研究。该项目将为开发对人体心血管系统的毒性影响的新型非侵入性电信号预报器铺平道路。广泛影响：本研究旨在通过培训研究生和本科生，特别是NCA&Amp；T和UNG的少数族裔和女性，增强纳米生物科学新兴跨学科领域的多样性。除了正规教育，它还将丰富与吉尔福德县学校和技术社区学院建立的合作伙伴关系。此外，这项研究的结果将通过正式模式和专门的YouTube频道(JSNN即将推出)向公众广泛传播。

CBET - 1342051The research goal of this proposal is to investigate a feasibility of measurements of cardiac repolarization as a tool for the noninvasive assessment of cardiovascular system exposure to carbon and metallic nanotubes. In pursuit of this goal, the specific objectives are to:(a) employ an intensity-controlled dobutamine exercise stress test for the conscious rats after pulmonary exposure to single-wall carbon and TiO2 nanotubes, and determine values of QT/RR hysteresis and the rates of adaptation of QT and RR intervals, (b) use common bio- and immunochemical markers and determine the degree of toxic levels of oxidative stress, myocyte injury and vascular inflammation, and (c) compare the association of toxic outcomes of pulmonary exposure to different nanotubes using electrophysiological and immunochemical markers. The unique aspect of this proposal is the integration of theoretical nonlinear dynamics and experimental electrophysiological measurements to assess toxicological effects of nanostructures on cardiac function. Successful accomplishment of the above objectives will have far-reaching implications in the development of robust noninvasive monitoring of cardio toxicity of nano-systems. The educational goals of this proposal are to integrate new science and technology into formal and informal teaching and outreach programs in an effective manner. We extend a cohesive educational plan with three major themes: Course development, Mentoring, and Outreach activities. (A) Improve two graduate-level courses: NANO785 - Fundamentals of Nanobioelectronics (S. Aravamudhan), NAN740 - Nonlinear Waves in Biological Excitable Media (J. Starobin), through incorporation of research results. (B) Involvement of graduate and undergraduate students (including minority graduate students, currently working with the PI) in the interdisciplinary fields with significant exposure to materials, bioelectronics, biology and computational physics, (C) Current and future outreach programs at NCA&T, UNCG and JSNN will be strengthened (including NanoDay and K-12 Nanotechnology Lego modules).Intellectual Merit :Previous research demonstrated the importance of biochemical and immunological markers for identifying nanotube induced oxidative stress and vascular damage. However, the association of such exposure with noninvasive electrophysiological factors is not understood. Even if monitoring of cardiovascular system using electrophysiological measurements is one of the most robust biomedical tools it is still not adapted for applications in the environmental studies which is of a critical importance for public health. This project will pave the road for the development of novel non-invasive electrographic predictors of toxic effects on human cardiovascular system.Broader Impacts :This research seeks to enhance diversity in the emerging cross-disciplinary areas of nanobioscience by training graduate and undergraduate students, especially minorities and women in both NCA&T and UNCG. In addition to formal education, it will enrich established partnerships with Guilford County schools and technical community colleges. Also, the results of this research will be widely disseminated to the public through both formal modes and on a dedicated YouTube channel (to be launched soon by JSNN).