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Full-Text Articles in Engineering

Single‐Molecule 3d Orientation Imaging Reveals Nanoscale Compositional Heterogeneity In Lipid Membranes, Jin Lu, Hesam Mazidi, Tianben Ding, Oumeng Zhang, Matthew D. Lew Sep 2020

Single‐Molecule 3d Orientation Imaging Reveals Nanoscale Compositional Heterogeneity In Lipid Membranes, Jin Lu, Hesam Mazidi, Tianben Ding, Oumeng Zhang, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

In soft matter, thermal energy causes molecules to continuously translate and rotate, even in crowded environments, thereby impacting the spatial organization and function of most molecular assemblies, such as lipid membranes. Directly measuring the orientation and spatial organization of large collections (>3000 molecules μm−2) of single molecules with nanoscale resolution remains elusive. In this paper, we utilize SMOLM, single‐molecule orientation localization microscopy, to directly measure the orientation spectra (3D orientation plus “wobble”) of lipophilic probes transiently bound to lipid membranes, revealing that Nile red's (NR) orientation spectra are extremely sensitive to membrane chemical composition. SMOLM images resolve …


Pathophysiology And Proteogenomics Of Post-Infectious And Post-Hemorrhagic Hydrocephalus In Infants, Albert M. Isaacs Aug 2020

Pathophysiology And Proteogenomics Of Post-Infectious And Post-Hemorrhagic Hydrocephalus In Infants, Albert M. Isaacs

Arts & Sciences Electronic Theses and Dissertations

Post-infectious (PIH) and post-hemorrhagic (PHH) hydrocephalus occur as sequalae of neonatal sepsis or intraventricular hemorrhage (IVH) of prematurity, respectively. Together, PIH and PHH represent the most common form of infantile hydrocephalus, the most common indication for neurosurgery in children globally, and the leading cause of neurological morbidity and mortality worldwide. The lack of understanding of the pathophysiology of PIH and PHH, particularly with regards to the host central nervous system response to the antecedent infection and hemorrhage, perturbation of differentiating neural stems in the ventricular (VZ) and subventricular (SVZ) zones, and damage to periventricular white matter (PVWM) tracts carrying sensorimotor …


Microrna Gene Expression States Underlying Individual Variation In Aging And Lifespan In Isogenic C. Elegans, Holly Kinser Aug 2020

Microrna Gene Expression States Underlying Individual Variation In Aging And Lifespan In Isogenic C. Elegans, Holly Kinser

McKelvey School of Engineering Theses & Dissertations

Average lifespan differs greatly between species, but lifespan among same-species individuals is also highly variable. While much effort has been devoted to uncovering longevity-associated traits and lifespan-extending perturbations in humans and model organisms, how differences in lifespan arise between individuals is unknown. Studies of human identical twins demonstrate that surprisingly little of the variation in lifespan between individuals can be explained by genetics and shared environment. Furthermore, even genetically identical C. elegans reared in highly homogeneous environments display a degree of variability in lifespan similar to that of outbred human populations. Thus, longevity must be determined at least in part …


Convex Relaxations For Particle-Gradient Flow With Applications In Super-Resolution Single-Molecule Localization Microscopy, Hesam Mazidisharfabadi Aug 2020

Convex Relaxations For Particle-Gradient Flow With Applications In Super-Resolution Single-Molecule Localization Microscopy, Hesam Mazidisharfabadi

McKelvey School of Engineering Theses & Dissertations

Single-molecule localization microscopy (SMLM) techniques have become advanced bioanalytical tools by quantifying the positions and orientations of molecules in space and time at the nanoscale. With the noisy and heterogeneous nature of SMLM datasets in mind, we discuss leveraging particle-gradient flow 1) for quantifying the accuracy of localization algorithms with and without ground truth and 2) as a basis for novel, model-driven localization algorithms with empirically robust performance. Using experimental data, we demonstrate that overlapping images of molecules, a typical consequence of densely packed biological structures, cause biases in position estimates and reconstruction artifacts. To minimize such biases, we develop …


Genetic Interactions And Maternal Genes Modulate Congenital Heart Disease Risk, Ehiole Ogboma Akhirome May 2020

Genetic Interactions And Maternal Genes Modulate Congenital Heart Disease Risk, Ehiole Ogboma Akhirome

Arts & Sciences Electronic Theses and Dissertations

Congenital heart disease (CHD) is the most common congenital anomaly, which makes it a leading cause of infant mortality. Congenital heart defects are a cluster of distinct developmental malformations that affect the vasculature, musculature and organization of the heart, each with varying clinical severity. Although medical and surgical advances have reduced CHD mortality in newborns and children, these patients grow up and many experience serious morbidity and early mortality. The first step toward reducing this burden is to understand the causes of CHD. Surprisingly, environmental insults and de novo mutations are estimated to explain less than one-third of CHD cases. …


Phantoms To Placentas: Mr Methods For Oxygen Quantification, Kelsey Meinerz May 2020

Phantoms To Placentas: Mr Methods For Oxygen Quantification, Kelsey Meinerz

Arts & Sciences Electronic Theses and Dissertations

Molecular oxygen (O2) is vital for efficient energy production and improper oxygenation is a hallmark of disease or metabolic dysfunction. In many pathologies, knowledge of tissue oxygen levels (pO2) could aid in diagnosis and treatment planning. The gold standard for pO2 measures in tissue are implantable probes, which are invasive, require surgery for placement, and are inaccessible to certain regions of the body. Methods for determining pO2 both non-invasively and quantitatively are lacking. The slight paramagnetic nature of O2 provides opportunities to non-invasively characterize pO2 in tissue via magnetic resonance (MR) techniques. As such, O2 can be treated as a …


Joint Estimation Of Perceptual, Cognitive, And Neural Processes, Katherine Heisey May 2020

Joint Estimation Of Perceptual, Cognitive, And Neural Processes, Katherine Heisey

Arts & Sciences Electronic Theses and Dissertations

Humans are remarkable in their ability to perform highly complicated behaviors with ease and little conscious thought. Successful speech comprehension, for example, requires the collaboration of multiple sensory, perceptual, and cognitive processes to focus attention on the speaker, disregard competing cues, correctly process incoming audio stimuli, and attach meaning and context to what is heard. Investigating these phenomena can help unravel crucial aspects of human behavior as well as how the brain works in health and disease. However, traditional methods typically involve isolating individual variables and evaluating their decontextualized contribution to an outcome variable of interest. While rigorous and more …


Transcriptomic Analysis Of Cytokine-Treated Tissue-Engineered Cartilage As An In Vitro Model Of Osteoarthritis, Jiehan Li May 2020

Transcriptomic Analysis Of Cytokine-Treated Tissue-Engineered Cartilage As An In Vitro Model Of Osteoarthritis, Jiehan Li

McKelvey School of Engineering Theses & Dissertations

Osteoarthritis (OA), as the most common form of arthritis and a leading cause of disability worldwide, currently has no disease-modifying drugs. Inflammation plays an important role in cartilage degeneration in OA, and pro-inflammatory cytokines, IL-1β and TNF-α, have been shown to induce degradative changes along with aberrant gene expression in chondrocytes, the only resident cells in cartilage. The goal of this study was to further understand the transcriptomic regulation of tissue-engineered cartilage in response to inflammatory cytokines using an in vitro miPSC model system. We performed RNA sequencing for the IL-1β or TNF-α treated tissue-engineered cartilage derived from murine iPSCs, …