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Impact of Interfacial Chemistry on Corrosion, Sensing, and Catalytic Properties of Materials
Get PDFInterfaces are critical for the development of new technologies spanning applications from energy to sensing. Here, electrochemical and spectroscopic investigations of interfacial chemistry reveal how the sensitivity of chemical vapor sensors can be tuned, how stoichiometry and electrolysis affect the chemical state of a Mn-based oxygen evolution catalyst, and how the presence of barrier protection layers affects the stability of photoanodes in alkaline solution. Additionally, an in-depth discussion of x-ray photoelectron spectroscopy gives advice and insight into this surface-sensitive technique and several practical examples are discussed
Uncovering Mechanisms of Host Recognition, Host Finding and Host Specificity
Get PDFInsect diversification is thought to have been catalyzed by widespread specialization on novel hosts—a process underlying exceptional radiations of phytophagous beetles, lepidopterans, parasitoid wasps, and inordinate lineages of symbionts, predators, and other trophic specialists. The fidelity of such interspecies partnerships is often posited to arise from sensory tuning to host-derived cues, a model supported by studies of neural function in host-specific model species. Abundant literature on parasites also suggest that extrinsic factors, namely dispersal mechanisms and aggressiveness/acceptance from novel hosts, externally enforces host specificity. Here, I first review what is known about host specificity, why it arises and how it is controlled, and then explore how these factors influence the biology of myrmecophiles, the intimate symbiotic associates of ants. I then test the mechanisms of host specificity by investigating the chemosensory basis of symbiotic interactions between a myrmecophile rove beetle and its single, natural host ant species. I show that host cues trigger analogous behaviors in both the ant and myrmecophile. Cuticular hydrocarbons—the ant's nestmate recognition pheromones—elicit partner recognition in the myrmecophile and execution of ant grooming behavior that achieves chemical mimicry. The myrmecophile also follows host trail pheromones, permitting inter-colony dispersal. Remarkably, however, the myrmecophile performs these same adaptive behaviors with non-host ants separated by up to ~100-million years and shows minimal preference for its natural host over non-host ant species. Experimentally validated agent-based modelling supports a scenario in which specificity is enforced by physiological constraints on dispersal, and negative fitness interactions with alternative hosts, rather than via sensory tuning. Infrequent realization of latent compatibilities of specialists with alternative hosts may facilitate host switching, and the persistence and diversification of seemingly specialized clades over deep time
Intermolecular and Intramolecular Stable Isotope Studies in Alanine
Get PDFIn Chapter 1 of this thesis, we give an introduction to this body of work, providing some background for context.
In Chapter 2, we present a set of theoretical predictions for the carbon isotope distribution between equilibrated carbon sites of alanine and pyruvate. We start with the simplest possible theoretical treatment, and work progressively through higher levels of theory, showing consistency in the direction and magnitude of expected fractionation across these treatments.
In Chapter 3, we present our experimental work to confirm the predictions made in Chapter 2 by measuring the δ13C of the α carbon site in alanine that has undergone equilibration with the analogous carbon site in pyruvate via the alanine transaminase enzyme (ALT).
In Chapter 4, we describe the process that led to our (re)discovery of β-hydrogen-deuterium exchange in amino acids catalyzed by transaminases. We then provide a literature review on the small body of historical work on this system, which took place primarily during the 1960s and 70s. This literature summary provides the background necessary for the reader to appreciate our experimental work presented in the next chapter.
In Chapter 5, we present novel 1H NMR and 13C NMR experimental observations of intermolecular hydrogen isotope exchange between water and the α and β carbon sites of alanine, as well as intramolecular hydrogen isotope exchange between the α and β carbons, all of which is catalyzed by alanine transaminase (ALT). These experiments track the abundances of eight isotopically distinct alanine species varying in their position and/or number of hydrogen isotopes over a series of reactions differing in initial alanine isotopic composition and initial water isotopic composition. With the data collected we are able to determine up to thirteen rate constants and ten equilibrium constants describing the transfer of hydrogen and deuterium amongst these eight isotopic variants and water, as well as the thermodynamic equilibrium constants between them.</p
Tools for Noninvasive Imaging and Control of Engineered Bacteria In Vivo
Get PDFGenetically engineered bacteria are promising new cell-based diagnostic and therapeutic agents due to their ability to sense and respond to unique signals, access and interface with hard-to-reach areas of the body, and deliver therapeutics directly to these areas. However, currently tools to noninvasively monitor and control their activity in vivo are limited. Optical imaging methods, which are based on fluorescent and luminescent reporter genes, and optogenetics, which are based on light-activated proteins, are widely used in cell culture and rodent studies. However, these optical methods suffer from the poor penetration depth of light in tissue which limits their use in larger animals or humans. On the other hand, nuclear imaging methods such as PET and SPECT have good imaging depth but rely on radioactive tracers whose synthesis can be complex and exposes patients to radiation. Here I present tools for imaging and control of bacteria that based on non-ionizing forms of energy that easily penetrate tissue: sound waves and magnetic fields.
The first two parts of my thesis focuses on imaging bacteria in vivo with ultrasound, which is a widely available imaging modality that does not use ionizing radiation and has tissue penetration depth of several centimeters. Bacteria can be imaged with ultrasound by expressing acoustic reporter genes (ARGs) which result in the production of gas vesicles (GVs), air-filled protein nanostructures that aquatic microbes use to regulate their buoyancy. However, the first-generation acoustic reporter genes expressed too poorly under in vivo conditions to enable ultrasound imaging of bacteria in therapeutically relevant contexts. Here, we present a new and improved ARG construct that produces high levels of robust gas vesicle expression in the probiotic bacterium E. coli Nissle (EcN), enabling ultrasound imaging of these cells with high sensitivity. This second-generation ARG construct, bARGSer, uses genes derived from Serratia sp. ATCC 39006 and was optimized for plasmid-based expression in EcN. We demonstrate that with bARGSer, we can visualize the spatial distribution of engineered EcN after they home to and colonize tumors upon systemic administration. We also demonstrate that the engineered EcN can be imaged with ultrasound when colonizing the gastrointestinal tract of mice after sensing dietary sugars as well as biomarkers of inflammation. By enabling monitoring of the precise spatial location of engineered probiotic bacteria inside the body, this technology could greatly improve the development and eventual clinical use of this emerging class of microbial cell-based theranostics.
The last part of my thesis focuses on control of bacteria in vivo with magnetic fields. Many bacteria have limited ability to selectively colonize specific targeted regions of the GI tract due to a lack of external control over their location and persistence. Magnetic fields are well suited to provide such control due to their ability to freely penetrate biological tissues, but they are difficult to apply with enough strength to directly manipulate magnetically labeled cells within deep tissue or viscous environments such as in the GI tract. Here, we show that ingestible micron-sized magnetic particles, combined with an externally applied magnetic field, act as in vivo magnetic field gradient amplifiers, enabling the trapping and retention of orally administered probiotic E. coli within the mouse GI tract. This technology improves the ability of these probiotic agents to accumulate at specific locations and stably colonize without antibiotic treatment. By enhancing the ability of GI-targeted cellular agents to be at the right place at the right time, cellular localization assisted by magnetic particles (CLAMP) adds external physical control to an important emerging class of biotherapeutics.</p
Perturbing the Genome: From Bench to Biophysics
Get PDFIn single-cell genomics, we can simultaneously assay hundreds of thousands of cells, their molecular contents, and how they respond to perturbation, from genetic knockouts to environmental changes. This thesis focuses on how to merge experimental and computational techniques to generate and analyze large-scale perturbation data for high-resolution systems biology. Beginning at the bench, we demonstrate how combining large-scale cell atlas surveys with multi-condition experimentation can illuminate the diversity of cell types across whole organisms and cellular strategies in response to environmental changes and perturbations. We then investigate the limitations of current practice in exploratory analysis, and strategies for determining preservation or distortion of biological insight by these data transformation and dimensionality reduction techniques. To address these limitations, we demonstrate how stochastic biophysical models can rewrite the way we interpret complex perturbation data, taking greater advantage of the diverse molecular measurements to develop biological hypotheses about DNA and RNA regulation in cellular function, development, and disease.</p
Topics in Gravitational Wave Physics: Lensing, Detection with Astrometry and Dark Siren Hubble Measurement
Get PDFIn this thesis, we study several subjects in gravitational wave (GW) physics, including gravitational wave lensing, detection with astrometry data and dark siren measurement of cosmological parameters.
We investigate various lensing features and their detection prospects in third-generation gravitational-wave networks. Firstly, we focus on type II lensed images which are Hilbert transforms of regular images. We compute the waveform mismatch and quantify the distinguishable fraction given Bayes factor thresholds over a range of binary mass ratio and redshifted mass. We make forecast on the detectable and distinguishable type II images in aLIGO Voyager, Cosmic Explorer and Einstein Telescope. This work shows that a significant number of type II images can be distinguished from waveforms alone, and this strategy can contribute to future pipelines for more accurate GW event inference.
We further model relativistic lensing in a large-inclination hierarchical triple system with a central Kerr supermassive black hole. We combine the elliptical integral formalism and optical scalar formalism to study image location and magnification. By analyzing the repeated lensing signature observed by the Decihertz Gravitational-wave Observatory, we examine the importance of relativistic images in detecting the presence of lensing or specifically the lens spin. We compute the detectable effective volume and estimate the upper limit for expected number of such events. This work demonstrates that lensing with relativistic images is a fruitful avenue where decihertz observation contributes to studies on intermediate-mass binary black holes and their galactic environment.
GW detection with astrometry was proposed as an alternative strategy that uses stellar astrometry data for GW measurement with flexible frequency coverage. We point out that surveys providing relative astrometry only can also be sensitive to GWs. We apply this method to the Roman Space Telescope Galactic Bulge Time Domain survey and make sensitivity forecast for both monochromatic GWs from supermassive binary black holes and stochastic GW background. We clarify the survey requirements and technical challenges for GW detection, and show that Roman will enable microhertz GW measurement for local sources. We also present on-going work to develop a data-processing pipeline to use Kepler archival data to search for GWs.
With increasing number of events in GW catalog, the GW source population offers a unique perspective into cosmology and astrophysics. In the last chapter, we use a Fisher information formalism to quantify the astrophysical model error tolerance of GW dark siren measurement on cosmological parameters. We generate galaxy catalog based on realistic survey and population parameters, and we apply expected GW uncertainties in third-generation ground-based networks. Based on simulation results, we study dominating error factors and make suggestions to dark siren selection strategy given different total error requirements.</p
Exploring Nature’s Fingerprints with Isotopic Distributions
Get PDFThis thesis examines the measurement and interpretation of isotopic distributions and the application of these techniques to forensic questions. Stable isotope abundances are a powerful tool for examining a compound’s history. However, their use is complicated by the fact that 1) isotope substitutions can occur at many positions of a molecule, resulting in a combinatorial increase in possible combinations of isotopes (or isotopologues) with molecule size, and 2) it is difficult to experimentally distinguish between isotopologues, so observational data averages over many isotopologues with distinct properties and histories. We here develop experimental and theoretical strategies to address these questions via observations of the isotopic distributions of small organic compounds obtained by Orbitrap mass spectrometry. In Chapter II, we develop mathematical procedures for manipulating and tracking isotopologues through various experimental designs, allowing us to make precise statements about how observable quantities are affected by underlying physical and chemical processes. Chapters III and IV explore corresponding experimental methods: Chapter III presents a sample introduction technique for the long duration observations required to measure rare, multiply substituted isotopologues, while Chapter IV applies these to observe 146 isotopic properties of methionine, a model analyte. We then explore the use of these Orbitrap methods to applied science problems. In Chapter V, we characterize the 13C and 2H enrichment of methylphosphonic acid, a breakdown product of sarin precursors, and examine the signatures of its synthesis methods. In Chapter VI, we apply these techniques to extraterrestrial, abiotic syntheses of nucleobases, focusing on the chemistry of adenine. These results are interpreted in the context of proposed extraterrestrial syntheses of adenine and other purine nucleobases and used to predict the isotopic distributions of these compounds.</p
Freeze-Cast Porous Ceramics: Tailoring Chemistry and Porosity for Functionality
Get PDFPorous ceramics have been created and utilized in applications ranging from the automotive industry to biomedical research, with the chemical and pore characteristics of these ceramic structures crucial to their function and design. In this work, these intertwined factors are explored for a variety of applications by controlling the chemistry through precursor preparation and heat treatments, and the porosity controlled through freeze casting, a tunable and facile pore-forming technique yielding a range of pore sizes and morphologies. First, shape memory and superelastic behaviors in ceria-doped zirconia are observed by creating porous honeycomb structures that can accommodate the volume change of the martensitic transformation enabling such performance. By controlling dopant concentration, powder morphology, and freezing rate, the martensitic transformation is tracked over multiple cycles and collection volumes in these bulk-scale, polycrystalline zirconia ceramics. Next, transparent porous model sediments are created through heat treatments of freeze-cast synthetic cryolite (Na3AlF6) powder. Fluorescent beads the same size as many bacterial cells are visualized in a range of pore morphologies over both depth and time, and these porous ceramics are deployed in a sedimentary environment and the imaging of the microbial communities contained within and are found to colonize the porous cryolite structures. Alternate porous habitats for bacterial colonization are further created using materials such as iron oxides and carbon nanotubes to produce structures that can act both as electron acceptors and as microbial habitats. Finally, thermally anisotropic Si-based porous ceramics are developed with a potential use in optical devices. Using two contrasting preceramic polymers and both traditional and UV-assisted freeze-casting techniques, porous SiOC is produced from preceramic polymers with differing carbon contents. Together, these examples explore how the chemistry and porosity of porous ceramics can be manipulated to affect the chemical, optical, mechanical, and thermal properties of ceramic structures to best suit the intended function
Seismic Thermometry of the North Pacific and Equatorial Indian Oceans
Get PDFThe ocean absorbs the majority of excess heat in the climate system. Ocean mixing is also critical in setting Earth's thermal inertia. Over the course of the past few decades, conventional observations like Argo floats have drastically improved the coverage of the global ocean. However, their temporal and spatial resolutions are still limited. Resolving trends and patterns of temperature variations in the ocean under climate change remains a challenging sampling problem. This dissertation seeks to reduce such sampling errors by developing seismic thermometry. It is an acoustic method that measures large-scale ocean temperature changes using sound waves generated by repeating earthquakes. The chapters in this thesis attempt to combine physical understanding with statistical analysis to improve and implement seismic thermometry in several ways. First, acoustic waves generated by earthquakes along the Japan Trench and received at Wake Island are used to constrain temperature variation in the Kuroshio Extension region. An inversion that combines these measurements for the time and azimuth dependence of the range-averaged deep temperatures reveals lateral and temporal variations due to Kuroshio Extension meanders, mesoscale eddies, and decadal water mass rearrangements. Second, a comprehensive covariance structure is proposed to represent variabilities due to stochastic mesoscale, regional trend, and large-scale seasonality. It demonstrates statistical consistency between conventional float data and seismic measurements, and shows quantitatively that seismic thermometry reduces basin-scale temperature uncertainty when combined with conventional measurements. Finally, seismic data are compared with ocean models in the equatorial Indian Ocean to study the vertical structure of biweekly Yanai waves. The comparison indicates qualitative agreements in biweekly variations, and regression analysis confirms their origin as west-propagating Yanai waves. Yet quantitative differences in the biweekly variance magnitude demand further calibrations in both models and the seismic inversion
Dissecting and Reconstructing the Cosmic Infrared Background with Spaceborne Experiments
Get PDFThe utilization of several tracers of large-scale structure has led to important advancements in our understanding of the history of the Universe, in both characterizing cosmological initial conditions and late-time astrophysics. With the onset of dramatic changes in data volume and quality through existing and near-future experiments, methodologies that harness the information content in imaging and spectroscopic datasets while mitigating systematic effects will have larger impacts than ever before. In this thesis, we present a variety of analysis techniques for galaxy surveys of discrete objects and diffuse light measurements that are demonstrated on both synthetic and real datasets.
In Chapter 2, we develop techniques for measurement of near-infrared extragalactic background light (EBL) anisotropies, focusing on imager data from the Cosmic Infrared Background ExpeRiment (CIBER). Through improvements in methodology and data quality, we present fluctuation measurements in Chapter 3 that are five to ten times more sensitive on several arcminute to degree scales than existing studies, with clear detection of diffuse anisotropies exceeding those from the Poisson noise of individual stars and galaxies. In Chapter 4, we present a new suite of empirically-based galaxy simulations which we use to examine the diversity of galaxies that will be observed with SPHEREx, NASA's upcoming MIDEX mission. We then develop and apply redshift estimation techniques to synthetic SPHEREx observations generated from these simulations, demonstrating the ability to measure the distances to several hundred million galaxies over the full sky. In Chapter 5, we describe a formalism for modeling point-like and diffuse signals in astronomical images, which can be used for robust photometry in the presence of diffuse contaminants, extraction of diffuse signals in the presence of point source contaminants, and more general component separation. In Chapter 6 we apply this modeling framework to Herschel-SPIRE observations of galaxy cluster RX J1347.5-1145, measuring the diffuse thermal Sunyaev-Zel'dovich (tSZ) effect at high significance and using relativistic corrections of the tSZ spectrum to constrain the intra-cluster medium temperature, for which we find consistent estimates with independent X-ray measurements.</p