Digital Commons Network^™

Identifying Structures For Ion Channel Kinetic Models, Kathryn Mangold

McKelvey School of Engineering Graduate Student Theses & Dissertations

Voltage-gated ion channels carry transmembrane current and underlie the voltages changes seen during the action potential. The ion channels open and close precisely, or gate, in response to voltage to create the specific cellular action potential waveform. The first models of voltage-gated ion channels gating dynamics were described by Hodgkin and Huxley when studying the neuronal action potential in the squid giant axon. While the probabilistic gating variables cleverly imagined by Hodgkin and Huxley to describe channel gating are still used today to describe cardiac ionic currents, Markov (or state-dependent) models provide a more accurate representation of channel dynamics. As …

Laser Stimulated Dynamic Thermal Imaging System For Tumor Detection, Hongyu Meng

McKelvey School of Engineering Graduate Student Theses & Dissertations

Laser stimulated dynamic thermal imaging system for tumor detectionby Hongyu Meng Doctor of Philosophy in Biomedical Engineering Washington University in St. Louis, 2021 Professor Samuel Achilefu, Chair Recent advances in infrared sensor technology have enabled the rapid application of thermal imaging in materials science, security and medicine. Relying on the infrared characteristics of living systems, thermal imaging has been used to generate individual heat maps, detect inflammation and tumor. As an imaging system, thermal imaging has the advantages of portability, real-time, non-invasive, and non-contact. But the low specificity of thermal imaging hinders its wide clinical application.

Unfortunately, label-free DTI is …

Electrodeless Electrochemistry Enabled By Nonthermal Plasma, Harold Oldham

McKelvey School of Engineering Graduate Student Theses & Dissertations

The increasing availability and decreasing cost of electricity generated by renewable resources have motivated research into electrified chemical processing, whereby electrical energy is used to drive chemical transformations. Electricity-intensive processing techniques such as electrochemistry using solid electrodes has attracted attention in this context for the synthesis of organic compounds, such as high-value pharmaceuticals and renewable chemical production. Selective chemical transformations are achieved in conventional aqueous electrochemical systems by using external circuitry to bias solid electrodes, allowing for the preferential transfer of electrons between the electrode-liquid interface. Despite having the ability to promote controlled electrochemical reactions, configurations using solid electrodes are …

Acoustic Radiation Force And Its Application For Cell Manipulation And Ion Channels Activation, Xiangjun Peng

McKelvey School of Engineering Graduate Student Theses & Dissertations

Sound is a stress wave that carries energy and momentum flux. Scattered sound waves can generate acoustic radiation force that can be used to manipulate particles or cells. This dissertation demonstrates the physics behind cell manipulation by ultrasound. The work begins with a detailed analysis of the mechanics of using standing surface acoustic waves to fabricate acoustic tweezers for contactless particle manipulation using acoustic radiation force. Models to design and analyze acoustic radiation force have traditionally relied on plane wave theories that cannot predict how standing surface acoustic waves can levitate cells in the direction perpendicular to the substrate. We …

Hyperlocal Air Quality Exposure Assessment To Support Health Studies, Pradeep Prathibha

McKelvey School of Engineering Graduate Student Theses & Dissertations

Hyperlocal air pollution exposure is driven by local emission sources, meteorology, and the built environment, with traffic-related emissions modulating primary and secondary pollutant concentrations against a variable background of similar contaminants from other sources. Recent studies show that intra-urban air quality has temporally persistent patterns that sharply vary 5-8 times within a city block; currently, regulatory ambient air quality monitoring (2-5 fixed-site monitors per 1000 km2 in U.S. census urban areas) cannot capture exposure at this spatial resolution. This dissertation aims to advance methods relying on fixed-site and mobile measurements using high-time resolution aerosol instruments as well as low-cost sensors …

Quantifying Components Of Protein Translation And Metabolite Heterogeneity In Isogenic Microbial Populations, Alexander Schmitz

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cell-to-cell variation in gene expression and metabolite levels have a significant impact on ensemble productivity of microbial bioproduction. New metabolic engineering tools and approaches are needed that consider cell cultures as an amalgam of uniquely behaving individuals to improve the slow commercialization of metabolically engineered systems. Stochastic cellular process including gene expression, metabolism, and growth lead to phenotypic variation between genetically identical cells. Understanding and the ability to control microbial phenotypic variation is key to improving microbial bioproduction metrics. During protein translation, codon usage strongly influences ensemble gene expression but the effect on the variation of gene expression was not …

Zebrafish Models Of Katp Channelopathies, Soma S. Singareddy

McKelvey School of Engineering Graduate Student Theses & Dissertations

Much work has been carried out to understand the composition, structure, and function of ATP-sensitive potassium (KATP) channels in mammalian tissues, as well as the molecular basis of the channelopathies that result from loss-of-function or gain-of-function mutations in these channels. These studies have also highlighted that the available pharmacology to treat such diseases is limited. To overcome such limitations, a better understanding of the tissue specificity of expression, the exact mechanisms linking the molecular dysfunction to the development of complex pathophysiology, the potential for reducing cross-reactivity of drugs, and ultimately more specific therapies are needed. The work described in this …

Macrophage-Based Immunotherapies For The Treatment Of Multiple Myeloma, Jennifer Sun

McKelvey School of Engineering Graduate Student Theses & Dissertations

Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow (BM) and represents the second most common hematologic malignancy in the world. Despite an array of novel therapy approvals, MM remains to be incurable. Most patients ultimately relapse and become refractory to previous treatments, which lowers the median survival to only 5–15 months. Recently, cancer immunotherapy has gained attention as a promising approach to enhance the body’s natural immune responses to fight cancer. Currently, immunotherapies in MM have largely focused on engaging the T cells; however, many are challenged by insufficient responses, high cost, and/or extensive adverse …

Anion Exchange Membranes In Electrochemical Energy Systems, Yunzhu Zhang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Non-CO2-emitting sources of renewable energy, such as solar and wind, have become quite popular in recent years, and their electricity generation cost at scale has become comparable with that of gas- and coal-fired power plants. However, their intermittent output makes the resultant electricity hard to dispatch in a reliable manner in the absence of grid-scale electrical energy storage (EES) technologies. Redox-flow batteries (RFBs) are promising devices for medium- to large-scale electric energy storage. They are safe, reliable, and portable, and are designed with decoupled power and energy modules, which makes it easy and cost-effective to scale their output to meet …

Short-Term Memory And Olfactory Signal Processing, Lijun Zhang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Modern neural recording methodologies, including multi-electrode and optical recordings, allow us to monitor the large population of neurons with high temporal resolution. Such recordings provide rich datasets that are expected to understand better how information about the external world is internally represented and how these representations are altered over time. Achieving this goal requires the development of novel pattern recognition methods and/or the application of existing statistical methods in novel ways to gain insights into basic neural computational principles. In this dissertation, I will take this data-driven approach to dissect the role of short-term memory in olfactory signal processing in …

Racial/Ethnic Differences In The Relationship Between Wealth And Health, Sicong Sun

Brown School Graduate Student Theses and Dissertations

Racial wealth inequity is one of the most pressing social and economic issues in the United States, historically and contemporarily. Primarily due to unequal distribution of opportunity for economic advancement and mobility in addition to the accumulation of historic disadvantage endured by Black and Latinx Americans, U.S. racial wealth inequity leads to substantial racial health disparities. It is widely acknowledged that socioeconomic position (SEP) is a fundamental cause of disease and health disparities. Centering around three key constructs—race/ethnicity, wealth, and health—this dissertation had two overarching aims: (a) to investigate the relationship between wealth and health, delineating the effects of wealth …

A Study On The Hormonal Regulation And Novel Role Of Na+ Leak Channel, Non-Selective (Nalcn) In Human Myometrial Smooth Muscle Cells, Chinwendu Amazu

Arts & Sciences Graduate Student Theses and Dissertations

During pregnancy, the uterus transitions from a quiescent state to an excitable, highly contractile state to deliver the fetus. Two important contributors essential for this transition are progesterone (P4) and estrogen (E2), which promote quiescence or contraction, respectively, by acting on the myometrial smooth muscle cells (MSMCs). While these hormones regulate uterine contractions, it is unclear how they affect electrical activity of MSMCs, which underlies uterine contractile activity. Our lab recently identified Na+ leak channel, non-selective (NALCN) as a component of the leak current in human MSMCs and showed that mice lacking NALCN in the uterus have dysfunctional labor. In …

Quantitative Characterization Of Microbial Ecologies In Dysbiosis And Infection, Eric Keen

Arts & Sciences Graduate Student Theses and Dissertations

In 1973, Theodosius Dobzhansky famously wrote that nothing in biology makes sense except in the light of evolution. Today, nearly 50 years later, little in microbiology – or in biology, for that matter – makes sense except in the light of genomics. Microbial genomics populates the field with innumerable testable hypotheses for evaluation in vitro and in vivo, allows us to monitor microbial populations in real time and at a massive scale, and underpins our approach to entire domains of microbiology, including microbial evolution. In this Thesis, I present three studies from my graduate research united by their common theme …

La Esfera Lúdica: Entretenimiento Popular En El Espacio Público Urbano Del Río De La Plata, 1870-1933, Maria Soledad Mocchi Radichi

Arts & Sciences Graduate Student Theses and Dissertations

In this dissertation, I focus on popular ludic and cultural practices that shaped the urban spaces of Uruguay and Argentina at the end of the nineteenth century and the beginning of the twentieth. I argue that by inhabiting the public sphere in close dialogue with modernization and urbanization, popular entertainment became a main protagonist within everyday life. Cultural practices such as carnival, theater, soccer, radio, and cinema, presented intersections between each other. These intersections generated what I term the ludic urban sphere, to underscore not just the overwhelming presence of play and entertainment as central elements in the urban landscape, …

Computational Methods For Analysis Of Data For Conformational And Phase Equilibria Of Disordered Proteins, Jared Michael M Lalmansingh

Arts & Sciences Graduate Student Theses and Dissertations

Intrinsically disordered proteins and regions (IDPs / IDRs) are a class of proteins with diverse conformational heterogeneity that do not fold into a tertiary structure due to the lack of a native structural state. Consequently, disordered proteins are remarkably flexible and exhibit multivalent properties that enable them to adopt myriad functional roles within the cell such as: signaling transduction, transcription, enzymatic catalysis, translation, and many more. Due to their multivalency, some IDPs undergo monomeric and heterotypic interactions which can drive phase separation. Such IDPs can form membraneless organelles with specific regulatory roles within the cell which include, but are not …

Petrology, Geochemistry, And Experimental Studies Of Mafic Enclaves And Amphibole At Shiveluch Volcano, Kamchatka, Andrea Elizabeth Goltz

Arts & Sciences Graduate Student Theses and Dissertations

This thesis connects mineralogical, chemical, and physical observables in quenched mafic inclusions from Shiveluch Volcano in Kamchatka and high pressure and temperature experiments to elucidate the water content of primitive magmas at Shiveluch, the timing of magmatic recharge events relative to eruption, and the petrogenetic history of andesites erupted at Shiveluch. Using the petrology of basaltic andesite mafic inclusions erupted from Shiveluch, in Chapter 2, the water content of primitive magmas at Shiveluch is found to be 8-10 wt%, which is two to three times higher than the global average determined by other methods, and the temperature of primitive magmas …

Satirizing Empire: Comparing Ancient China And Rome, Di Wang

Arts & Sciences Graduate Student Theses and Dissertations

Comparative scholars of the ancient Mediterranean and East Asian worlds have recently taken a serious interest in the unprecedented and simultaneous emergence of two classical empires: Rome and China. The trend, invigorated by the contemporary geopolitical development of China’s rise as a world empire challenging the post-World War II Western hegemony, has yielded new insights into the many divergences and convergences of the world’s two most enduring political and cultural systems. However, preoccupied with describing the political, cultural institutions and grand narratives of empire, scholarship has largely ignored the detractors of empire, whose ingenious expressions are as enduring as these …

Using Single-Particle Fluorescence Microscopy To Elucidate The Role Of Structural Distortions And Defects In The Chemical Reactivity And Photophysics Of Cesium Lead Halide Perovskite Nanocrystals, Dong Wang

Arts & Sciences Graduate Student Theses and Dissertations

Colloidal cesium lead halide perovskite nanocrystals (CsPbX3, X = Cl, Br or I) are attractive for optoelectronic applications due to their unique chemical and physical properties including high photoluminescence quantum yield, tunable bandgaps, high defect tolerance, and low-cost processibility. A facile method to tune the emission wavelength of perovskite nanocrystals is through anion exchange. For light emission applications, it is desirable to prepare CsPbX3 nanocrystals of uniform size and composition. However, the complex reaction kinetics of this chemical transformation may limit the compositional uniformity and color purity of the CsPbX3 nanocrystals produced by anion exchange when the transformation is scaled …

Potassium Isotope Cosmochemistry, Zhen Tian

Arts & Sciences Graduate Student Theses and Dissertations

In Chapter 1, I review the geochemical and cosmochemical properties of potassium (K). Classified as a moderately volatile element, K serves as a robust proxy for understanding the key processes during nebular/planetary evaporation events. I review different mechanisms of volatile depletion among various planetary materials: mass-dependent variations in “nebular” processes; mass-independent variations among different nucleosynthetic sources; or planetary-scale volatile depletion processes. Furthermore, I provide an optimized K purification procedure via ion-exchange chromatography and a high-precision K isotope analysis technique using Neptune plus Multiple Collector Inductively Coupled Plasma Mass Spectrometer (MC-ICPMS) in both “cold plasma” and “dry plasma” methods. I also …

A Continuous Wavelet Representation For Single And Bi-Parameter Calder\'On-Zygmund Operators, Tyler Williams

Arts & Sciences Graduate Student Theses and Dissertations

This thesis develops a novel approach to the representation of singular integral operators of Calder\'on-Zygmund type in terms of continuous model operators, in both the classical and the bi-parametric setting. The representation is realized as a finite sum of averages of wavelet projections of either cancellative or noncancellative type, which are themselves Calder\'on-Zygmund operators. Both properties are out of reach for the established dyadic-probabilistic technique. Unlike their dyadic counterparts, this new representation reflects the additional kernel smoothness of the operator being analyzed. These representation formulas lead naturally to a new family of $T(1)$ theorems on weighted Sobolev spaces whose smoothness …

Evaluating Recognition Memory Models From An Individual Differences Perspective, Kyle Gramer Featherston

Arts & Sciences Graduate Student Theses and Dissertations

Although recognition memory models have been thoroughly compared in various recognition memory paradigms, the relative reliability and validity of their parameters have not been thoroughly assessed using an individual differences approach. In two studies, I evaluated three models: the dual-process signal detection (DPSD) model, the continuous dual process (CDP) model, and the unequal variance signal detection (UVSD) model. In Study 1, participants performed a remember-know procedure that also included confidence ratings. When model parameters were estimated twice in the same individual, both key parameters from the DPSD model were reliable within an individual, whereas the CDP version of familiarity was …

Process Information And Creative Mindsets: An Examination Of Their Role In The Evaluation Of Creativity, Brendon Michael Cummiskey

Arts & Sciences Graduate Student Theses and Dissertations

Evaluating creativity is a key role for any organization interested in innovation and how that evaluation occurs has been a focal point of researchers. Although creativity scholars have made strides in understanding creativity evaluations, questions remain about the role that process information plays in the evaluation. While most creativity research involves some type of outcome, such as an idea or product, the evaluators often have no description of the creator’s work process or any understanding of the idea or product’s creation. In this dissertation, I build upon the existing evaluation literature and critically examine how process information may influence the …

The Effects Of Molecular Chaperone Modulation On Protein Folding, Prion Formation, And Prion Propagation In Saccharomyces Cerevisiae, Leeran Blythe Dublin Ryan

Arts & Sciences Graduate Student Theses and Dissertations

Proper and efficient protein folding is vital for cell survival. Many factors affect protein folding fidelity and prion formation, including molecular chaperone availability and activity. Research has shown that modulating chaperone availability and function can affect protein misfolding and aggregation, as well as de novo prion formation and propagation. However, the factors involved and underlying mechanisms influencing prion formation and protein folding are largely unknown. The following work aims to elucidate these areas. The Nascent Polypeptide-Associated Complex (NAC) is the first point of chaperone contact for nascent polypeptides. Previous work has shown that disruption of the NAC leads to improved …

Deconvolving Genomic Regulatory Heterogeneity With Self-Reporting Transposons, Arnav Moudgil

Arts & Sciences Graduate Student Theses and Dissertations

A cell’s identity is a function of the genes expressed in that cell, which are in turn regulated by transcription factors. Over the last decade, single-cell RNA sequencing (RNA-seq) has emerged as a powerful class of techniques to characterize cellular diversity in heterogeneous tissues. These methods barcode transcripts by their cell-of-origin and assign them to specific genes. The resulting high-dimensional data are further processed to reveal clusters of cells sharing transcriptional states. Annotating these clusters, based on either known or discovered marker genes, offers a glimpse into the dynamic composition of an organ or biological process. While single-cell RNA-seq excels …

Surveillance And Dynamics Of Bacteria And Resistance Genes In Humans And Hospitals, Alaric Wences D'Souza

Arts & Sciences Graduate Student Theses and Dissertations

Bacteria live in, on, and around us. These bacteria affect human health through beneficial commensal interactions that promote normal development and through harmful infections or perturbations leading to disease. Understanding the prevalence, spread, and resilience of these bacteria in humans and human environments is critical to clinical medicine and epidemiology. I investigated environmental and human resident bacteria to understand dynamics in bacterial communities and how these dynamics may impact human health.Hospitals are one critical location of human-bacterial interactions. Bacteria can contaminate hospital surfaces from patients or environmental sources and subsequently transmit from surfaces to vulnerable patients. I analyzed bacteria from …

Electro-Organic Chemistry: An Alternative Pathway To Handle Redox Organic Reactions, Tiandi Wu

Arts & Sciences Graduate Student Theses and Dissertations

Electrochemistry provides an alternative pathway to handle redox organic reactions, especially for certain chemical process that can be only achieved through electrochemical process. Herein, there research projects are introduced to enrich the whole synthetic community, including an anodic oxidative cyclization studies to develop methodology on heterocyclic ring skeleton constructions, an electroreduction pathway exploration to more effectively obtain hydrazine from nitroso compounds, as well as a study in paired electrolysis process on which both anode and cathode are simultaneously employed to maximize overall atom and energy efficiency. Future directions on these projects are also demonstrated at the end of each chapters..

Iron And Manganese Oxidation By Oxyhalogen Species: Implications For Paleoenvironmental Reconstruction On Mars, Kaushik Mitra

Arts & Sciences Graduate Student Theses and Dissertations

As the nearest planetary neighbor with potential earlier habitable conditions, Mars is replete with minerals that hold clues to its past chemistry and evolution of the aqueous systems. Oxidized iron (Fe) and manganese (Mn) minerals on Mars are geochemical markers of such environments in which they formed and record past pH, redox conditions, and intensity of water-rock interaction. Fe and Mn oxides can therefore be used to reconstruct past Martian environmental conditions from settings where aqueous fluids were active. Various processes that form Fe and Mn oxide minerals on Mars have been previously proposed, including chemical oxidation using molecular oxygen …

On Arousal And The Internal Regulation Of Brain Function: Theory And Evidence Across Modalities And Species, Ryan Raut

Arts & Sciences Graduate Student Theses and Dissertations

The brain is an organ. It is subject to the same physiological regulatory processes that engage the rest of the body’s organs, sculpted over hundreds of millions of years to sustain life so effectively. The central message of this thesis is that the holistic functioning of the brain, rather than operating at some level above or independent from these systemic regulatory processes, is deeply related to them. In short, as our limited attention spans might suggest: brain function is internally regulated. I propose that this internal regulation is a primary function of intrinsic brain activity. Chapter 2 provides a theoretical …

From Inspiration To Actualization: Designing An Mba That Can Deliver The Goods, Rodolfo P. Ang

Journal of Management for Global Sustainability

This invited essay continues the conversation on the International Association of Jesuit Universities’ (IAJU) white paper entitled “An Inspirational Paradigm for Jesuit Business Education.” Mr. Rodolfo P. Ang, one of the members of the Task Force that developed the white paper, talks about his experience of leading the Ateneo de Manila University Graduate School of Business toward the actualization of the paradigm.

A Rapid Screening Method For Ecological Risks Posed By Different Land Use Intensities: Case Study Of Marikina City’S River System, Maria Aileen Leah Guzman, Charlotte Kendra Gotangco Gonzales, Rene Juna Claveria, Philippe Joshua Evardo, Jean Jardeleza Mijares

Journal of Management for Global Sustainability

Land use plays an important role in environmental and sustainability research because of its potential contribution to ecosystem protection or degradation. However, most risk maps used in comprehensive land use planning only identify areas at risk, for example, to various geophysical or climate- and weather-related hazards. It would also be useful to identify land areas that pose a risk to ecological systems. In this study, a simplified method adapted from the source-habitat approach and the relative risk model was used to explore the potential ecological risk of exposure to water pollutants posed by land uses on the river system in …