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Developing Dalotia coriaria, the Greenhouse Rove Beetle, as a Novel Model Organism
Get PDFThis thesis deals with the development of Dalotia coriaria, the greenhouse rove beetle, as a novel model organism. A fundamental characteristic of metazoan life is inter-species interactions. Chapter 1 explores why there is a need for Dalotia as a new model organism to study these interspecies interactions in ways that are intractable with current established models. It also explores the life history characteristics of Dalotia that make it amenable to development as a novel model organism as well as the need for genetic access in order to successfully make Dalotia an established laboratory model organism.
Chapter 2 explores how I have solved the husbandry techniques required for genetic manipulations in Dalotia. These include the ability to collect large amounts of early embryos, mount embryos on slides, micro inject embryos, raise single housed larvae to adulthood, and set up one-on-one adult crosses.
Chapter 3 explores how I have developed the Piggybac transposon system to successfully knock in trans-genes into the Dalotia genome. It also shows how I have developed the UAS Gal4Δ binary expression system to work in Dalotia, allowing for controlled high expression of inserted trans-genes.
Chapter 4 explores how I have developed the CRISPR Cas9 system to successfully perform targeted germline point mutations in the Dalotia genome. It also shows how I have developed fast and accurate genotyping techniques for producing and maintaining homozygous stocks of mutant Dalotia for long periods of time. The appendices of this thesis include step-by-step protocols that allow for reproduction of all of the husbandry and genetic manipulation techniques covered in Chapters 2-4.
Lastly, Chapter 5 of this thesis explores olfactory receptor guided behaviors in Dalotia. I use RNA Smartseq techniques to produce a map of chemoreceptors across the Dalotia body. I also use the Dalotia CRISPR Cas9 protocol I developed to produce a homozygous line of olfactory receptor-deficient Dalotia by knocking out the olfactory receptor co-receptor. I show that the line of olfactory receptor-deficient Dalotia are incapable of olfaction, and then explore how it affects their defensive behavior when interacting with ants. These interactions are studied in a free moving arena and in a tethered beetle on the ball setup using machine learning to analyze pose.</p
The Hemodynamics of Native and Surgical Aortic Valves with Regards to Wall Shear Stress and Residence Time
Get PDFCardiovascular diseases are the leading causes of illness and death all around the world. The third most common cardiovascular disease is aortic stenosis (AS). AS is most commonly characterized as a stiffening of the native trileaflet aortic valve, which impedes blood flow into the aorta and puts extra stress on the heart. The aorta is the main artery that supplies oxygenated blood to the body. AS has been widely studied in the past. However, there has been little work in understanding the complex effects that non uniform stiffening of the aortic valve can have on the hemodynamics inside the aorta.
The most effective treatment for AS is to replace the stiffened valve with a prosthetic valve. Care must be taken to ensure that the replacement actually performs better hemodynamically. A major metric for prosthetic valve performance is the transvalvular pressure drop which is a measure of how much pressure, and energy, is lost as the heart pumps blood through the valve. Generally speaking, larger valves exhibit a smaller pressure drop because they restrict the flow to a lesser degree. This phenomenon has led to a trend for surgeons to implant the largest prosthetic valve possible, and in some cases, to expanding the aorta to fit even larger valves. However, there has been relatively little work done on determining the effects of valve oversizing on the blood flow inside the Aorta.
The aims of this study were two-fold. First, a model of AS was tested inside an in vitro aortic simulator in order to identify how different individual leaflet stiffnesses would affect blood flow. Digital particle image velocimetry (DPIV) was used to measure velocity profiles inside a model aorta. The DPIV results were used to estimate the wall shear stress and blood residence time. Our analysis suggests that leaflet asymmetry greatly affects the amount of WSS by vectoring the systolic jet and that stiffened leaflets have an increased residence time. This study indicates that valve leaflets with different stiffness conditions can have a more significant impact on wall shear stress than stenosis caused by the uniform increase in all three leaflets (and the subsequent increased systolic velocity) alone. Second, the experimental apparatus was used to test different prosthetic valve sizes and valve mounting methods in order to identify how they affected residence time inside the sinus bulge. Dye residence experiments and DPIV were used to measure fluid stasis in several different combinations of prosthetic valve sizes, sinus sizes, and valve mounting methods. Our results indicate that valve to sinus sizing and mounting method is very important and can lead to greatly increased residence time and thrombosis risk. We have also identified a metric that can predict the threshold at which valves become oversized
Maternally Inherited siRNAs Initiate piRNA Cluster Formation
Get PDFPIWI-interacting RNAs (piRNAs) guide repression of transposable elements in germlines of animals to protect genome integrity. In Drosophila, the majority of piRNAs are produced from heterochromatic genomic loci, called piRNA clusters, that act as repositories of information about genome invaders. piRNA generation by dual-strand clusters depends on the chromatin-bound Rhino-Deadlock-Cutoff (RDC) complex, a complex specifically enriched on a dual-strand cluster, which is deposited on clusters guided by piRNAs, forming a feed-forward loop in which piRNAs promote their own biogenesis. However, this rises a fundamental question about how piRNA clusters are formed initially before cognate piRNAs are present.
Here we report the spontaneous de novo formation of a Rhino-dependent piRNA cluster from repetitive transgenic sequences. We show that cluster formation occurs gradually over several generations and requires continuous trans-generational transmission of small RNAs from mothers to their progeny. Importantly, we discovered that maternally-supplied siRNAs are responsible for triggering de novo cluster activation in progeny. In contrast, the siRNA pathway is dispensable for piRNA cluster function and maintenance after its establishment. These results revealed an unexpected cross-talk between the siRNA and piRNA pathways and suggested a mechanism for de novo formation of piRNA clusters triggered by production of siRNAs.</p
Probing Solid-Earth, Ocean, and Structural Dynamics with Distributed Fiber-Optic Sensing
Get PDFObservational geophysics conventionally relies on point sensors to document and monitor Earth’s dynamic processes, from locating earthquakes and imaging subsurface structure with seismometers to forecasting coastal wave heights and detecting tsunamis with buoys. Distributed acoustic sensing (DAS) offers a fundamentally different paradigm: distributed instead of point sensing. DAS converts fiber-optic cables into dense arrays of broadband, linear strainmeters, with spatial resolution as fine as one meter and temporal resolution up to several thousand samples per second. The first four chapters of this thesis concern ocean-bottom DAS, repurposing pre-existing telecommunications and power cables as distributed seafloor sensing networks for seismology and physical oceanography. In Chapter 2, we analyze one of the first ocean-bottom DAS datasets, demonstrating that seismic and ocean waves observed on the same array are related by a classic theory of double-frequency microseism generation. We also extract the principal body-wave phases of a M8.2 deep earthquake, demonstrating the earthquake detection capabilities of DAS even in a shallow water environment. In Chapter 3, we apply ambient noise interferometry to a one-hour of ocean-bottom DAS data and derive a shallow shear-wave velocity model. We also isolate spurious arrivals in noise cross-correlations associated with nearby offshore wind turbines, suggesting potential for remote monitoring. In Chapter 4, we adapt ambient noise interferometry to the ocean surface gravity wavefield, and estimate the tidal current velocity along a short cable segment in the Strait of Gibraltar with a waveform stretching method. In Chapter 5, we explore the application of DAS as a temperature sensor at long periods, documenting temperature signals up to 4 K associated with internal wave and boundary layer dynamics. We demonstrate that while ocean-bottom DAS exhibits sufficient strain sensitivity to record seafloor geodetic processes, oceanic temperature transients may overprint such signals. The last part of this thesis concerns a different frontier in geophysical instrumentation: long time-series. With a 20-year continuous record of ambient vibrations from a single accelerometer located on the ninth floor of a concrete building, we document long-term, passive changes in the building’s natural frequencies as well as complex, time-dependent nonlinear elasticity during earthquakes
Towards High-Accuracy Simulations of Strongly Correlated Materials Using Tensor Networks
Get PDFAccurate and verifiable computation of the properties of real materials with strong electron correlation has been a long-standing challenge in the fields of chemistry, physics, and material science. Most existing algorithms suffer from either approximations that are too inaccurate, or fundamental computational complexity that is too high. In studies of simplified models of strongly-correlated materials, tensor network algorithms have demonstrated the potential to overcome these limitations. This thesis describes our research efforts to develop new algorithms for two-dimensional (2D) tensor networks that extend their range of applicability beyond simple models and toward simulations of realistic materials.
We begin by describing three algorithms for projected entangled-pair states (PEPS, a type of 2D tensor network) that address three of their major limitations: numerical stability, long-range interactions, and computational efficiency of operators. We first describe (Ch. 2) a technique for converting a PEPS into a canonical form. By generalizing the QR matrix factorization to entire columns of a PEPS, we approximately generate a PEPS with analogous properties to the well-studied canonical 1D tensor network. This connection enables enhanced numerical stability and ground state optimization protocols. Next, we describe (Ch. 3) a technique to efficiently represent physically realistic long-range interactions between particles in a 2D tensor network operator, a projected entangled-pair operator (PEPO). We express the long-range interaction as a linear combination of correlation functions of an auxiliary system with only nearest-neighbor interactions. This allows us to represent long-range pairwise interactions with linear scaling in the system size. The third algorithm we present (Ch. 4) is a method to rewrite the 2D PEPO in terms of a set of quasi-1D tensor network operators, by exploiting intrinsic redundancies in the PEPO representation. We also report an on-the-fly contraction algorithm using these operators that allows for a significant reduction in computational complexity, enabling larger scale simulations of more complex problems.
We then move on to describe (Ch. 5) an extensive study of a "synthetic 2D material"---a two-dimensional square array of ultracold Rydberg atoms---enabled by some of the new algorithms. We investigate the ground state quantum phases of this system in the bulk and on large finite arrays directly comparable to recent quantum simulation experiments. We find a greatly altered phase diagram compared to earlier numerical and experimental studies, and in particular, we uncover an unexpected entangled nematic phase that appears in the absence of geometric frustration.
Finally, we finish by describing (Ch. 6) a somewhat unrelated, but topically similar project in which we investigate the feasibility of laser cooling small molecules with two metal atoms to ultracold temperatures. We study in detail the properties of the molecules YbCCCa and YbCCAl for application in precision measurement experiments.</p
Shock Compression of Body-Centered Cubic Metals from the Atomistic to Continuum Scale: Iron and Molybdenum
Get PDFFundamental understanding of material behavior under extreme conditions is crucial for designing high strength, light weight, and high temperature resistance materials, and for modeling planetary physics problems such as behavior of the core and impact phenomena. Under extreme conditions, materials not only exhibit a different mechanical, thermal, and failure response but can also undergo structural changes, such as phase transformations, which significantly alters their material properties. This motivates studying their dynamic response and developing constitutive models for applications such as hypersonics, high speed manufacturing, impact and blast of structures, aircraft and spacecraft shielding, meteorite impact, and collision of planets. Despite the importance, experimental investigations of shock induced phase transitions, inelastic material behavior, and elastic-plastic anisotropy under multi-axial stress states and at microscopic length scales of metals still remains largely unexplored. Thus, the focus of this thesis is on the shock compression behavior of body-centered cubic (BCC) metals, specifically iron and molybdenum, under compression-shear loading and at the atomistic-continuum spatial scales. In particular, the role of solid-solid phase transformation of body-centered cubic (BCC) iron on material strength and the orientation dependence of single crystal molybdenum on its elastic-plastic transition is investigated.
Iron in its high pressure hexagonal close-packed (HCP) ϵ-phase is critical in geological and planetary applications such as inner cores of rocky planets and hypervelocity impacts of asteroids, and meteorites. Thus, understanding plasticity behavior of iron under these condensed matter states is important to develop more accurate models for such applications and to understand deformation mechanisms of inner planetary cores. Because the ϵ-phase is unstable, iron reverts to its ambient α-phase (BCC) upon release making it difficult to probe the strength behavior using conventional methods. Additionally, solid-solid phase transformations provide a unique opportunity to study material strength as they are crucial for expanding the design space for various load-bearing applications. In the first part of the thesis, the pressure dependent dynamic strength behavior of both the ambient BCC α-phase and high-pressure HCP ϵ-phase of iron at strain rates on the order of 1 X 10⁵ s⁻¹ and pressures up to 42 GPa is investigated. Pressure shear plate impact experiments are conducted using a sandwich configuration to decouple the effect of pressure and shear thereby allowing to probe shear strength once the sample reaches an equilibrated state of pressure but prior to release. The strength of the ϵ-phase is observed to be more than double the strength of α-phase possibly due to microstructural evolution during phase transformation. Additionally, the evolution of yield properties with pressure, temperature, and strain is presented for the first time, enabling more accurate modeling of extreme deformation phenomena associated with iron-rich celestial bodies such as planetary collisions.
Molybdenum, its alloys, and other body-centered cubic (BCC) refractory metals are critical in geological and planetary applications such as structural properties of terrestrial planetary composition, formation of the earth-moon system, and hypervelocity impacts of rocky planets. Additionally, the high temperature specific strength, creep resistance, and ductility of BCC refractory metals make them ideal for aerospace and armor/anti-armor applications. Under high strain-rate inelastic loadings, the macroscopic response of these metals is often influenced by the atomistic mechanisms including dislocation motion and deformation twinning. Current material models rely on investigations that involve continuum measurements followed by postmortem microstructural analysis of recovered samples. However, these may not reflect the material behavior during the passage of the shock wave and, thus, requires real-time in-situ atomistic characterization to link the microstructure to macroscopic response. In the second part of the thesis, plate impact experiments coupled with both laser interferometry continuum measurements and in-situ dynamic Laue x-ray diffraction (XRD), at the Advanced Photon Source (APS), are conducted on single crystal molybdenum. Here, the role of crystal orientation, either [100] or [111], on deformation mechanisms during the elastic-plastic transition and the steady state response is explored at pressures ranging from 9-19 GPa. Complementary simulation methodology is developed to analyze the evolution of the Laue diffraction spots captured during impact. By extracting the lattice strain and stresses from XRD images, dislocation slip along [110]〈111〉 and [112]〈111〉 is found to be the probable deformation mechanism during compression with negligible anisotropy observed at the Hugoniot state. For the first time, real-time evidence of molybdenum undergoing deformation twinning along [112̅]〈111〉 during shock release beyond a critical pressure of 16 GPa irrespective of the loading orientation is presented.</p
Droplet Control in Aqueous and Hydrocarbon Fluids: Long, End-Associative Polymers Dictate Fluid Behavior Under Elongational Flows
Get PDFModifying elongational flows seen in sprayed mists, turbulent flows, and droplet spreading and retraction following impact, is of interest in diverse industries, including agriculture and aviation. Long flexible polymers (with fully extended lengths 1 to 10 µm) modify the elongational flow behavior of a fluid to which they are added. At low concentrations (1 to 10% of their overlap concentrations), their effect is mild under shear flow (shear viscosity increases < 50%), but dramatic under elongational flows (extensional viscosity increases ≥ 300).
These long polymers are not widely used in practice because they degrade under strong flows, such as passing through pumps and filters, that typically precede spray. Pairwise end-associative polymers can overcome this limitation. Pulling apart non-covalent associative bonds under such strong flow conditions relieves the tension along the polymer backbone. The pairwise end-associative polymers that are effective in mist control and drag reduction are individually short enough to avoid chain scission in flows that would break long covalent polymers, yet long enough that 6 to 8 associative polymers connected end-to-end create supermolecules that are as effective as their long covalent counterparts.
This thesis systematically compares the effect of long covalent and long end-associative polymers on the fluid’s extensional flow properties and the polymers' performance in controlling droplet impact and spray breakup. To measure the elongational flow properties, I implemented and enhanced the Dripping onto Substrate Extensional Rheometry (DoSER) technique (Chapter 2) and applied it to long covalent polymers (Chapter 3) and to end-to-end associative polymers (Chapter 4). Preparing solutions in which the polymers negligibly affect the interfacial tension (< 10%) allows us to explore the relationship between extensional flow properties and droplet impact (Chapter 5) and spray (Chapter 6).
By combining the quantitative measurements of extensional viscosity and extensional relaxation time with the corresponding behavior in impact and spray, I correlate the structure of polymers to the solution behavior in droplet rebound and spray breakup. This work has the potential to reduce pesticide contamination of soil, water, and air from agricultural sprays and fire hazard associated with hydrocarbon lubricants.</p
Expanding Adeno-Associated Viral Capsid Engineering to Multiple Variable Regions for Diversified Tropism
Get PDFAdeno-associated virus research is critical for the advancement of gene therapy and treatment of myriad debilitating genetic disorders. Targeted delivery of genetic components to a tissue or cell population remains a bottleneck for gene therapy, but the selection of AAV capsids through directed evolution can yield vectors that target desired tissues or cells. This thesis details the engineering of the AAV capsid to acquire desired tropism, namely reduction in liver transduction or increased transduction of the lung. Chapter I chronicles the history of AAV engineering, provides useful information about the AAV capsid proteins, and describes how AAV has been engineered for altered tropism in works preceding this thesis. Chapter II describes the development of AAV9.452sub.LUNG1, an AAV variant that is enriched in the lung of mice after systemic injection. Chapter III details the engineering of variants with attenuated tropism in the liver while maintaining previously acquired brain transduction after systemic injection. Two of these variants, AAV.CAP-B10 and AAV.CAP-B22, display similar tropism in the marmoset after systemic injection. Chapter IV describes the parallel engineering of prominent variable regions of the AAV capsid. Overall, the work presented in this thesis expands the toolbox available for gene therapy and represents an advancement of methods for AAV capsid engineering.</p
Ultrafast Dynamics of Photo-Doped Mott Antiferromagnets
Get PDFStrong coupling between spin and charge degrees of freedom in two-dimensional spin-1/2 Mott antiferromagnets (AFMs) creates a rich platform to study quantum many-body physics. For decades, the consequences of these interactions have been intensely studied in thermal equilibrium, where the introduction of charge carriers through chemical doping has been shown to generate a vibrant phase diagram rich with unconventional types of charge, spin, and orbital ordering. In recent years, however, attention has grown to include the study of these materials as they are driven far from equilibrium using intense pulses of light produced by femtosecond laser sources. In addition to fundamental interest in the resultant dynamics, recent experimental and theoretical studies have suggested that driven Mott insulators can host states of matter that cannot be accessed in thermal equilibrium.
While many driving protocols have been developed---spanning from the selective excitation of bosonic modes to photon-dressing via coherent time-periodic driving---the simplest conceptual approach to engineering Mott insulators with light is known as photo-doping. In this procedure, the material is impulsively driven resonantly with a transition from a filled band to an empty band, transiently producing charge carriers. Given the impact of chemical doping in thermal equilibrium, photo-doping has garnered interest as an important tool in the study of driven Mott insulators. Early successes in the study of photo-doped Mott AFMs include the observation of ultrafast demagnetization and the prediction of non-thermal magnetic states, charge density waves, and superconductivity. Photo-doping thus holds promise to generate an out-of-equilibrium phase diagram that is equally rich to that found in equilibrium.
Yet, many open questions about the basic properties of photo-doped Mott insulators remain unresolved. Whether charge instabilities exist as a result of interactions between the photo-dopants has yet to be examined. Moreover, while theoretical studies have suggested that antiferromagnetic correlations can enhance attractive interactions between photo-dopants, evidence of the resultant bound states remain elusive. Even the light-matter interactions that generate the photo-dopants are in need of investigation, as the fate of a Mott insulator driven by strong electric fields remains a fundamental open theoretical and experimental problem.
In this thesis, I present a series of experiments designed to answer each of these questions. After describing the properties of Mott insulators in Chapter 1, I present the experimental details of the tools that enable these studies in Chapter 2. Taking a multi-messenger approach to ultrafast spectroscopy, a suite of ultrafast probes simultaneously track the spin and charge degrees of freedom to paint a holistic picture of the out-of-equilibrium state. In Chapter 3, I use ultrafast THz conductivity to establish the existence of an insulating photo-excited fluid of Hubbard excitons (HEs), which are bound states that are thought to form as a result of attractive spin-mediated interactions. This magnetic binding mechanism is studied in more detail in Chapter 4 by examining the properties of these HEs in the magnetic critical region of several materials that lie in different magnetic universality classes. In Chapter 5, I study the effects of HE formation on the ultrafast demagnetization that is known to occur following photo-doping. Finally, I turn my attention towards the photo-dopant generation mechanism in Chapter 6, exploring the effects of strong electric field driving in Mott insulators. I find signatures of the so-called Keldysh crossover from a multiphoton-absorption- to a quantum-tunneling-dominated pair production regime. Altogether, this work establishes photo-doped Mott insulators as a rich playground to engineer non-equilibrium phases of matter and study quantum many-body dynamics.</p
High Energy Transients Powered by Black Holes
Get PDFThe accretion of matter onto black holes heats the surrounding materials to extremely high temperatures and drives outflows, producing a sudden and intense emission of light. Some of the most well-known examples include gamma-ray bursts, X-ray binaries (XRBs), and tidal disruption events (TDEs). In recent years, modern wide-field time domain sky surveys, such as the optical Zwicky Transient Facility (ZTF) and the Spektrum-Roentgen-Gamma (SRG) X-ray satellite, have opened up the discovery space of fast-evolving transients and enabled population analysis. In this thesis, I conducted a series of observational studies to understand the inner workings, environments, and demographics of high-energy transients powered by black holes.
The first part of my thesis presents detailed studies on AT2019wey and AT2020mrf --- two transients discovered by SRG. First, I established that AT2019wey is a Galactic XRB with a low-mass companion star, and provided evidence that its central compact object is a black hole. Next, I demonstrated that AT2020mrf is a massive star explosion likely powered by fall-back accretion onto a newly formed black hole (with a rapidly spinning magnetar as an alternative power source). My work supports the idea that luminous fast blue optical transients form a rare class of engine-driven stellar explosions.
The second part of my thesis concerns TDEs. I contributed to the discovery of two X-ray bright TDEs (AT2021ehb and AT2022cmc) and led comprehensive follow-up campaigns to track their long-term evolution. In both objects, using the NuSTAR and NICER X-ray telescopes, I identified novel TDE spectral features, which probe massive black hole accretion and jet launching. Additionally, using ZTF, I constructed the largest flux-limited sample of 33 TDEs, which enabled robust estimates of the optical TDE luminosity functions, host galaxy preference, and the black hole mass function. The emerging functional forms resulting from the large sample size represent significant advancements. My work lays a foundation for both TDE population studies with future sky surveys and theoretical inquiries.</p