Observed NO/NO_2 Ratios in the Upper Troposphere Imply Errors in NO-NO_2-O_3 Cycling Kinetics or an Unaccounted NO_x Reservoir

Observations from the SEAC^4RS aircraft campaign over the southeast United States in August–September 2013 show NO/NO_2 concentration ratios in the upper troposphere that are approximately half of photochemical equilibrium values computed from Jet Propulsion Laboratory (JPL) kinetic data. One possible explanation is the presence of labile NO_x reservoir species, presumably organic, decomposing thermally to NO_2 in the instrument. The NO_2 instrument corrects for this artifact from known labile HNO_4 and CH_3O_2NO_2 NO_x reservoirs. To bridge the gap between measured and simulated NO_2, additional unaccounted labile NO_x reservoir species would have to be present at a mean concentration of ~40 ppt for the SEAC^4RS conditions (compared with 197 ppt for NOx). An alternative explanation is error in the low‐temperature rate constant for the NO + O_3 reaction (30% 1‐σ uncertainty in JPL at 240 K) and/or in the spectroscopic data for NO_2 photolysis (20% 1‐σ uncertainty). Resolving this discrepancy is important for understanding global budgets of tropospheric oxidants and for interpreting satellite observations of tropospheric NO_2 columns

Observed NO/NO2 Ratios in the Upper Troposphere Imply Errors in NO-NO2-O3 Cycling Kinetics or an Unaccounted NOx Reservoir

Observations from the SEAC4RS aircraft campaign over the southeast United States in August-September 2013 show NO/NO2 concentration ratios in the upper troposphere that are approximately half of photochemical equilibrium values computed from Jet Propulsion Laboratory (JPL) kinetic data. One possible explanation is the presence of labile NOx reservoir species, presumably organic, decomposing thermally to NO2 in the instrument. The NO2 instrument corrects for this artifact from known labile HNO4 and CH3O2NO2 NOx reservoirs. To bridge the gap between measured and simulated NO2, additional unaccounted labile NOx reservoir species would have to be present at a mean concentration of ~40 ppt for the SEAC4RS conditions (compared with 197 ppt for NOx). An alternative explanation is error in the low-temperature rate constant for the NO + O3 reaction (30% 1-σ uncertainty in JPL at 240 K) and/or in the spectroscopic data for NO2 photolysis (20% 1-σ uncertainty). Resolving this discrepancy is important for understanding global budgets of tropospheric oxidants and for interpreting satellite observations of tropospheric NO2 columns

Observed NO/NO_2 Ratios in the Upper Troposphere Imply Errors in NO-NO_2-O_3 Cycling Kinetics or an Unaccounted NO_x Reservoir

Observations from the SEAC^4RS aircraft campaign over the southeast United States in August–September 2013 show NO/NO_2 concentration ratios in the upper troposphere that are approximately half of photochemical equilibrium values computed from Jet Propulsion Laboratory (JPL) kinetic data. One possible explanation is the presence of labile NO_x reservoir species, presumably organic, decomposing thermally to NO_2 in the instrument. The NO_2 instrument corrects for this artifact from known labile HNO_4 and CH_3O_2NO_2 NO_x reservoirs. To bridge the gap between measured and simulated NO_2, additional unaccounted labile NO_x reservoir species would have to be present at a mean concentration of ~40 ppt for the SEAC^4RS conditions (compared with 197 ppt for NOx). An alternative explanation is error in the low‐temperature rate constant for the NO + O_3 reaction (30% 1‐σ uncertainty in JPL at 240 K) and/or in the spectroscopic data for NO_2 photolysis (20% 1‐σ uncertainty). Resolving this discrepancy is important for understanding global budgets of tropospheric oxidants and for interpreting satellite observations of tropospheric NO_2 columns

Novel Systems Physiology Instrumentation: Addressing Limitations in Heart Failure Reseearch

Heart disease remains the leading cause of death in the United States, but technology (e.g., pacemakers, defibrillators, and imaging systems) has dramatically lowered mortality associated with heart disease. In basic research science, integrative approaches with different tools have been crucial to understanding the multifactorial nature of heart disease from the individual protein to the organ level. Despite available technology, important limitations still exist in our ability to phenotype heart disease and to characterize failures in therapeutic intervention. One specific area of cardiology with insufficient tools for basic research and clinical applications is heart failure. Heart failure is one of the most common and costly cardiac diseases in developing and industrialized countries. Despite its important public health implications, no definitive cure exists for heart failure patients. An important reason for this is a wide array of symptoms in heart failure: loss of cardiac contractility, ventricular chamber dilation, increased valvular resistance, impaired fluid homeostasis, and increased incidence of sudden cardiac death due to arrhythmias. This complex pathology makes treating and studying the failing heart particularly difficult. Recently, systems physiology (i.e., understanding interactions between mechanical, electrical, and metabolic systems in the heart) has become a popular meme in heart failure research. If systems physiology is to revolutionize heart failure research, new tools are necessary to address critical limitations in cardiology from bench-top to bedside. In this dissertation, I introduce and evaluate novel tools for addressing limitations in heart failure research in three specific areas: animal models of heart failure, imaging technology for electromechanical mapping, and treatment of arrhythmias associated with heart failure. First, I present a miniature, implantable pacemaker for mice as a tool for investigating pacing-induced heart failure and cardiac memory. In previous studies, reliable, chronic pacing in mice has been limited to a maximum of one week. Here, I demonstrate 30 days of in vivo pacing in mice with a novel, wirelessly powered and controlled pacemaker. Long-term pacing in genetically-modified mouse models will yield a critical tool for the association of genes/proteins with specific disease mechanisms in heart failure. Second, I show the development and application of a structured light imaging system for description of whole-heart mechanical mapping in the beating heart. The high temporal (&g;667 FPS) and spatial resolution (87 μm in-plane, 10 μm depth) of this structured light imaging system enables dynamic assessment of both rhythmic and arrhythmic contraction without gating to the cardiac cycle, a feature presently impossible with current technology. Additionally, I present a novel method for tracking epicardial displacement on a pixel-by-pixel basis without the use of fiducial markers. By combining structured light with optical mapping of fluorescent dyes, imaging of excitation-contraction-metabolic coupling of healthy and failing hearts can be performed at unprecedented spatio-temporal resolution. In the final chapter of this dissertation, I evaluate potential mechanisms of failure for High Intensity Focused Ultrasound (HIFU) ablation in cardiac tissue. HIFU ablation offers a unique opportunity to develop effective strategies for noninvasive or minimally invasive treatment of atrial fibrillation and other arrhythmias. Despite its promises, current HIFU technology has failed to demonstrate high standards of safety and efficacy. Here, I identify three potential mechanisms that may be responsible for the failure of current HIFU technology: acoustic cavitation, acoustic radiation force, and discontinuous linear lesions. Improving our understanding of these mechanisms and their role in the creation of transmural lesions will facilitate the development of new HIFU technologies that would improve patient outcomes. Specifically, this research underscores the critical need for real time feedback to monitor thermal deposition in 3D space and acoustic pressure

Measuring Dynamic 3D Micro-Structures Using a Superfast Digital Binary Phase-Shifting Technique

Binary phase-shifting in digital fringe projection has demonstrated significant merit over conventional sinusoidal phases-shifting methods in terms of measurement speed and simplicity. This paper will show that compared to conventional sinusoidal methods, binary defocusing 1) can better resolve 3D micro-structures; and 2) can achieve kilo-Hz 3D shape measurement rates. These features are critical for measuring dynamically deformable objects, such as the beating heart.</jats:p

Mapping cardiac surface mechanics with structured light imaging

Cardiovascular disease often manifests as a combination of pathological electrical and structural heart remodeling. The relationship between mechanics and electrophysiology is crucial to our understanding of mechanisms of cardiac arrhythmias and the treatment of cardiac disease. While several technologies exist for describing whole heart electrophysiology, studies of cardiac mechanics are often limited to rhythmic patterns or small sections of tissue. Here, we present a comprehensive system based on ultrafast three-dimensional (3-D) structured light imaging to map surface dynamics of whole heart cardiac motion. Additionally, we introduce a novel nonrigid motion-tracking algorithm based on an isometry-maximizing optimization framework that forms correspondences between consecutive 3-D frames without the use of any fiducial markers. By combining our 3-D imaging system with nonrigid surface registration, we are able to measure cardiac surface mechanics at unprecedented spatial and temporal resolution. In conclusion, we demonstrate accurate cardiac deformation at over 200,000 surface points of a rabbit heart recorded at 200 frames/s and validate our results on highly contrasting heart motions during normal sinus rhythm, ventricular pacing, and ventricular fibrillation. </jats:p

Processing and analysis of cardiac optical mapping data obtained with potentiometric dyes

Optical mapping has become an increasingly important tool to study cardiac electrophysiology in the past 20 years. Multiple methods are used to process and analyze cardiac optical mapping data, and no consensus currently exists regarding the optimum methods. The specific methods chosen to process optical mapping data are important because inappropriate data processing can affect the content of the data and thus alter the conclusions of the studies. Details of the different steps in processing optical imaging data, including image segmentation, spatial filtering, temporal filtering, and baseline drift removal, are provided in this review. We also provide descriptions of the common analyses performed on data obtained from cardiac optical imaging, including activation mapping, action potential duration mapping, repolarization mapping, conduction velocity measurements, and optical action potential upstroke analysis. Optical mapping is often used to study complex arrhythmias, and we also discuss dominant frequency analysis and phase mapping techniques used for the analysis of cardiac fibrillation. </jats:p

Media 3: 3D absolute shape measurement of live rabbit hearts with a superfast two-frequency phase-shifting technique

Originally published in Optics Express on 11 March 2013 (oe-21-5-5822

Media 1: 3D absolute shape measurement of live rabbit hearts with a superfast two-frequency phase-shifting technique

Originally published in Optics Express on 11 March 2013 (oe-21-5-5822

Media 2: 3D absolute shape measurement of live rabbit hearts with a superfast two-frequency phase-shifting technique

Originally published in Optics Express on 11 March 2013 (oe-21-5-5822