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Archetypes of Femininity in Shakespeare's Tragedies
No full textShakespeare’s works are renowned for the insight they present on the human condition. While his tragedies are defined by the journeys and suffering of male protagonists, the females of these tragedies contribute greatly to plot and character development. Though all the main female characters in Shakespeare’s tragedies die—or suffer fates worse than death—we can classify them in three types: villains, the perfect victims and tragic heroines. This classification, based on shared traits and outcomes, provides insight on the roles these women’s lives and deaths serve in the tragedies
Visualizing Small Proteins with the cryoEM Platform and The Structure of the Vibrio cholerae Type IV Competence Pilus Secretin PilQ
Get PDFSolving protein structures by single-particle cryoelectron microscopy (cryo-EM) has become a crucial tool in structural biology. While exciting progress is being made toward the visualization of small macromolecules, the median protein size in both eukaryotes and bacteria is still beyond the reach of cryo-EM. To overcome this problem, we implemented a platform strategy in which a small protein target was rigidly attached to a large, symmetric base via a selectable adapter. Of our seven designs, the best construct used a designed ankyrin repeat protein (DARPin) rigidly fused to tetrameric rabbit muscle aldolase through a helical linker. The DARPin retained its ability to bind its target: GFP. We solved the structure of this complex to 3.0 Å resolution overall, with 5-8 Å resolution in the GFP region. As flexibility in the DARPin position limited the overall resolution of the target, we describe strategies to rigidify this element.
Natural competence is the process by which bacteria take up genetic material from their environment and integrate it into their genome using homologous recombination. In Vibrio cholerae, the Type IV competence pilus is thought to mediate DNA uptake by binding DNA and retracting back toward the cell. How the DNA enters the periplasm is unclear. One hypothesis suggests that the DNA-bound Type IV competence pilus retracts completely so that the DNA would pass through the outer membrane secretin pore (PilQ). PilQ is a 870 kDa outer membrane pore with C14 symmetry. Here, we purify the V. cholerae PilQ secretin from V. cholerae cells in amphipols for single particle cryogenic electron microscopy (cryoEM). We solve the structure to 3.0 Å and provide insight on the channel DNA may traverse through during uptake.</p
Dynamics of an Arched Magnetically-Twisted Current-Carrying Plasma
Get PDFExperimental and numerical studies of a dense magnetically-twisted plasma and their applications to solar plasmas are the subject of this dissertation. In the corona, plasma lies in a low-beta, high Lundquist number regime, meaning that it is magnetically dominated and the magnetic fields are well frozen into the plasma. Understanding the dynamics of these plasmas help us predict and prevent damage from future catastrophic solar eruption events. In situ measurements from satellite and ground-based observation provide limited information that is not controllable nor reproducible. The research objective in this thesis is to produce a miniature-scaled plasma with the same dimensionless parameters as the space plasmas. Along with numerical simulation, theoretical study, and observational data, the laboratory plasma can give novel insights into the physics of solar plasma.
First, an experimental dip on a flux rope, previously thought to be caused by a kink instability, is discussed and explained. We find that the apex cusp is in fact caused by the differential acceleration due to a non-uniform density. The pileup density results from a nonlinear interaction of the neutral gas. This result introduces a new method to impose effective gravity on the arched plasma and explains the suppression of kink instability. Second, a model for a morphology of CME and its shock driving mechanism is investigated. In the experiment, the chamber is prefilled with neutral gas, leading to an observation of a density cavity. Because the plasma is flux conserving, injecting a current into the plasma induces an opposite eddy current in front of the flux rope. The two opposing currents repel and leave a low density region in between. This feature is often observed in CMEs. We propose this mechanism to be the model of the CME 3-part structure formation. The opposite eddy current acts as a current piston driving an MHD perturbation/shock, which is often observed on the sun as an EUV wave.
A Magnetic Rayleigh-Taylor instability has been observed in the arched plasma loop. For the first time, the magnetic effect of the MRT instability is shown when the wavelength observed depends on the initial magnetic field initially injected into the system. In several years of working with the experiment in the Bellan plasma group, I designed and constructed several diagnostics, such as Langmuir probes, magnetic probes, and a coded aperture camera. Together with fast multi-images camera and spectroscopy techniques, plasma parameters are measured and compared to verify the models.
The 3D MHD numerical simulation was performed using the supercomputer from the Los Alamos National Laboratory. The initial condition and injection routines were modified to appropriately replicate the experiment. The code has been significant in improving our understanding of the physical phenomena we observed in the experiment. We attain a proper initial distribution of the mass density and the initial and injected current density. In addition to simulating an arched flux rope experiment, we use this tool to replicate MHD instabilities detected in the astrophysical jet experiment. Specifically, both a sausage-to-kink and kink-to-Rayleigh-Taylor instability have been reproduced using the numerical simulation. Each process thins the plasma current channel to be below the ion skin depth. The kinetic effect then gives rise to magnetic reconnection. An anomalous resistivity is added to simulate this process.
In conclusion, an interdisciplinary approach, through experimental, numerical, observational, and theoretical studies, is presented. It improves our understanding of the underlying mechanism for solar eruptions. A magnetically-twisted current-carrying flux rope, once formed, could exhibit dips and cavity. Its evolution could a drive shock and instabilities, which ultimately cause particle acceleration.</p
Photoacoustic Tomography: From Bench to Bedside
Get PDFPhotoacoustic imaging (PAI) is an emerging imaging modality that shows great potential for preclinical research and clinical practice. As a hybrid technique, PAI uniquely combines the advantages of optical excitation and of acoustic detection. Optical absorption provides a rich contrast mechanism from either endogenous chromophores or exogenous contrast agents. Because ultrasound scatters much less than light in tissue, PAI generates high-resolution images in both the optical ballistic and diffusive regimes, overcoming the limitations imposed by light scattering in deep biological tissues. PAI has led to a variety of exciting discoveries and applications from laboratory research to clinical patient care.
To translate photoacoustic technology from the bench to the bedside, this thesis focuses on efforts to increase the imaging depth, provide clinically useful information (i.e., relevant imaging contrast), reduce system size, and improve system reliability. Assisted by powerful pulsed lasers and advanced data acquisition circuits, modern PAI has achieved applications such as functional imaging of the whole rat brain, revealing detailed angiography and functional connectivity at high spatiotemporal resolution. The advancement of deep imaging in small animal PAI has been transferred to human breast and brain imaging, showing early promise for clinical practice. To further extend the imaging depth and provide dielectric imaging contrast, microwave-based thermoacoustic tomography has been demonstrated in vivo. To map further physiological contrasts, spectroscopic PAI has been performed to image the oxygenation states of hemoglobin and myoglobin. In addition to the effort towards deep penetration and multiple contrasts, benchtop photoacoustic microscopy has been minimized to a handheld probe for human skin imaging. As a rapidly evolving imaging technology, PAI is being translated from the bench to the bedside and promises exciting and useful clinical applications.</p
Collection of Solved Nonlinear Problems for Remote Shaping and Patterning of Liquid Structures on Flat and Curved Substrates by Electric and Thermal Fields
Get PDF There has been significant interest during the past decade in developing methods for remote manipulation and shaping of soft matter such as polymer melts or liquid metals to pattern films at the micro- and nanoscale. The appeal of low-cost fabrication of micro-optical devices for beam shaping or metallic films to produce high order cuspidal arrays for antireflective or self-cleaning coatings has driven considerable interest in the fundamentals associated with film shaping and liquid curvature. Physicists and applied mathematicians have uncovered new rich ground in examining the complex behavior of high order, nonlinear partial differential equations describing the motion and response of liquid structures driven to redistribute and reorganize by externally applied thermal and electric fields. For the problems relevant to this thesis, which focuses on liquid structures at small scales, the applied fields induce surface forces which act only at the moving interface. Because the surface-to-volume ratios tend to be very large however, the corresponding forces are considerable in magnitude and dominate the formation and growth processes described. In all cases examined, once the driving forces are removed and the operating temperatures dropped below the melting point, the patterned films and liquid shapes rapidly solidify in place, leaving behind structures with molecularly smooth surfaces, an especially advantageous feature for micro-optical applications.
The first part of this thesis examines the nonlinear dynamics of free surface films in the long wavelength limit coating either a flat or curved substrate. We examine the long wavelength limit in which inertial forces are suppressed in comparison to viscous forces such that the system reacts instantaneously to interfacial forces acting in the direction normal to the moving interface, such as capillary and Maxwell forces, or in the direction parallel to the moving interface, such as thermocapillary forces. In the first example, we demonstrate by analytic and numerical means how a system designed to incur large runaway thermocapillary forces can pattern films with conic cusps whose tips undergo self-focused sharpening through a novel self-similar process. This finding expands the known categories of flows that can generate cusp-like shapes and introduces a new lithographic method for remote, one-step fabrication of cuspidal microarrays. We next examine a lithographic technique known as Electrohydrodynamic Lithography in which remote patterned electric field distributions projected onto the surface of a dielectric film generate Maxwell stresses which cause growth and accumulation toward regions of highest field gradients. Here we solve the inverse problem associated with the governing fourth-order nonlinear interface equation by appealing to a control-theoretical approach. This approach reveals the optimal electrode topography required to generate precise complex liquid patterns within a given time interval. Numerical implementation of this algorithm yields high fidelity pattern replication by essentially incorporating proximity corrections which quench undesirable interference effects of material waves. We then extend the long wavelength analysis to a liquid layer coating a curved manifold and demonstrate how a desired film shape can be obtained by novel application of the Helmholtz minimum dissipation principle. We illustrate this solution method by deriving the nonlocal tensorial partial differential equation for the evolution of a slender, perfectly conducting or insulating liquid film supported on a curved electrode. Finite element simulations demonstrate the complex shapes which can result, including formation of liquid accumulation sites and flow instabilities not accessible to films supported on a planar substrate.
The second part of this thesis focuses exclusively on geometric singularities which result from nonlinear effects caused by the coupling of capillary and Maxwell forces in perfectly conducting liquids. Here, we do not restrict ourselves to the long wavelength approximation but instead examine systems with comparable lateral and transverse dimensions. We probe the energy stability of such systems using a convective Lagrangian approach. The exact variational characterization of equilibrium shapes and their stability is derived in the most general form without restriction to coordinate system or shape deformations. This formulation unmasks several terms, typically not evident in calculations restricted to normal deformations of an electrified spherical drop. Our result provides new insights into the energy stability of equilibrium shapes that do not necessarily have constant interface curvature or uniform surface charge distribution. We then turn attention to the classical problem of a conical meniscus produced in an electrified liquid body. The analysis by G. I. Taylor (1963) first determined that the hydrostatic equilibrium shape for a liquid body subject only to capillary and Maxwell forces is given by a cone with an opening angle of 98.6°. However, the fact that such a cone represents an unsteady configuration is often ignored. We revisit the inviscid analysis by Zubarev (2001) who proposed that conic cusps in perfectly conductive liquid evolve through a time-dependent self-similar process. Using the unsteady Bernoulli's equation, he analyzed the force balance at the moving interface and obtained an asymptotically correct self-similar solution dominated by a sink flow far from the evolving apex whose streamlines orient nearly parallel to the moving surface. In addition to the sink flow our analysis, supported by accurate, high resolution numerical solutions of the boundary integral equations, independently reveals a two-parameter family of non-spherically symmetric self-similar solutions whose velocity streamlines intercept the conic surface at an angle. This new family of solutions not only properly account for the interplay between capillary, Maxwell and inertial forces but generate advancing and recoiling type interface shapes, which substantially alter current understanding of the formation and acceleration of dynamic cones. </p
Investigations of Different Methods to Promote Drug Mixing in the Eye
Get PDFAge-related macular degeneration (AMD) is the leading cause of central vision loss in the developed world. In the case of wet AMD, it can be managed through serial intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents. However, sometimes the treatment is ineffective. Given that half-life time of the drug is limited, one possible cause of the ineffective treatment is inefficient drug mixing in the eye. Here, we focus on the understanding of drug mixing in vitreous chamber and parameters that could potentially influence mixing profiles. Both movement-driven method and thermal-driven method are explored. The in-vitro study outcomes will not only be useful for achieving fundamental understandings of fluid dynamics in the eye, but also helpful in developing a better strategy for intravitreal injection and improving the quality of care for patients
Topology Optimization and Failure Analysis of Deployable Thin Shells with Cutouts
Get PDFShell structures with cutouts are widely used in architectural and engineering applications. For thin, lightweight, and deployable space structures, cutouts are cleverly positioned to fold and store the structure in a small volume. To maintain shape accuracy, these structures must fold without becoming damaged and must be stiff in their deployed configurations. Intuitive designs often fail to satisfy these two requirements. This research proposes solutions to the topology optimization of composite, thin shell structures with cutouts.
A novel optimization algorithm was developed that makes no assumptions on the initial number, shape, and location of cutouts on deployable thin shells. The algorithm uses a density-based approach, which distributes the material within the structure by assigning a density parameter to discretized locations. This parametrization of the design domain allows for the finding of new features and the connectivity of the domain, thus providing a completely general formulation to the optimization problem. The goal is to study the effects of volume and stress constraints imposed in a deformed configuration of thin shell structures. While classical topology optimization studies focus on finding solutions to linear problems, this method is applicable to geometrically nonlinear problems and implements stress constraints in the deformed, and hence most stressed, configuration of these shells. A mathematical formulation of the optimization problem and interpolation schemes for stiffness tensor, volume, and stress are presented. A sensitivity analysis of objective function, volume, and stress constraints is provided. Finally, solutions for a thin plate and a tape spring are proposed.
Density-based methods are computationally expensive when applied to large structures and complex shapes because of the large number of design variables. To address these challenges, two optimization methods that provide more specific solutions to the problem of composite, deployable shells are proposed. The first method uses level sets to parametrize the cutouts, thereby restricting the design space and simultaneously limiting the number of design variables. This greatly reduces the computational cost. Using this approach, successful solutions are found for stiff, composite, thin shells with complex shapes that can fold without becoming damaged. The second method uses a spline representation of the contour of a single cutout on the shell, thus performing fine tuning of the shape of the cutout. Modeling techniques that simulate localized strain and experimental methods for studying the quasi-static folding of these composite shells are developed. A laminate failure criterion suitable for thin, plain-weave composites is used in simulations to predict the onset of failure in folded shells. Numerical results are validated with folding experiments that demonstrated good agreement with numerical solutions.
Lastly, it was discovered that many of the best performing solutions have multiple closely spaced cutouts, as opposed to current designs for deployable space structures that have fewer large cutouts. This leads to the formation of small strips of material between cutouts. Hence, the behavior of thin, plain-weave composite material was characterized and the first study on size-scaling effects at small length scales (≤ 15 mm) in this type of material was performed. Size-scaling effects on stiffness and strength shown in this study were introduced in numerical simulations of deployable thin shells. The study demonstrates that the prediction of the onset of failure in folded shells strongly depends on these size effects. Numerical predictions are corroborated by an experimental investigation of localized damage in thin strips of material forming between cutouts. Deployable shells resulting from the optimization studies are built and tested and localized damage is measured via digital volume correlation techniques.</p
Ultraviolet Radiation of Hypervelocity Stagnation Flows and Shock/Boundary-Layer Interactions
Get PDFShock/boundary-layer interactions can induce flow distortion, create flow separation with loss of control authority, and result in high thermal loads. Correct prediction of the flow structure and heating loads is vital for vehicle survival. However, a recent NATO workshop revealed severe underprediction of thermal loads and discrepancies in the location of separation by simulations of high enthalpy air flows. Due to the coupling between thermochemistry and fluid mechanics, a substantial effort has been placed on the development and validation of thermochemical models. As a result, there is a need for experimental data that are more than mean flow surface measurements.
Spatially resolved emission spectra are collected in the post-shock regime of hypervelocity flow over a circular cylinder and a 30-55 degree double wedge. The Hypervelocity Expansion Tube (HET) is used to generate high Mach number, high enthalpy flow (Mach numbers 5 - 7, h₀ = 4 - 8 MJ/kg) with minimal freestream dissociation. The NO γ band (A²Σ⁺ - X²Π) emission is measured in the ultraviolet range of 210-250 nm at downstream locations behind shock waves. Excitation temperatures are extracted from the NO γ emission from spectrum fitting. The result is a temperature relaxation profile that quantifies the state thermal non-equilibrium. Profiles of vibrational band intensity as a function of streamwise distance are used as direct measurements of chemical non-equilibrium in the flow.
Cylinder experiments are performed with varying freestream total enthalpy, Mach number, and test gas O₂ mole fraction to examine changes in relaxation profile. Schlieren images are used to accurately measure standoff distance. Temperature measurements are compared against a zero-dimensional state-to-state model. Strategies for spectrum fitting are presented for cases where the gas is not optically thin and for radiation containing multiple electronic states. For freestream mixtures with reduced oxygen mole fraction, an electronic excitation temperature is required to describe the radiation of the NO γ, β (B²Π - X²Π), and δ (C²Π - X²Π) transitions. The creation of electronically excited NO is discussed in the context of measured vibrational band intensities and computed NO(A) number density profiles using a two-temperature reactive Landau-Teller model.
Emission spectra are collected in the post bow shock and reattachment shock region of hypervelocity flow over a double wedge. High speed schlieren imaging is performed to investigate facility startup effects and for tracking features in a shock/boundary-layer interaction. Detector exposures occur at select times throughout the flow development process to study temporal changes in thermal and chemical non-equilibrium. Time evolution of temperatures at strategic locations of the flow is obtained from spectrum fitting. Two-temperature calculations of the oblique shock system are compared against the emission results. Radiation data are discussed in the context of recent simulation efforts.</p
Using Graviton EFT and Massive Gravity to Compute Gravitational Potentials for Black Hole Inspirals
Get PDFThis year, the LIGO detectors entered their third observing run and have been detecting black hole interactions with increasing precision and sensitivity. These detections have opened up a new way to compare the predictions of Einsteinian gravity with more exotic models. One of these models, massive gravity, is a concrete toy to use in testing these predictions. This project uses ideas from EFT and standard techniques from quantum field theory to calculate scattering amplitudes for scalar particles interacting via gravitons. We first calculated amplitudes up to the 1-looplevel assuming the standard massless graviton and then assuming a massive graviton. We then mapped these amplitudes to gravitational potentials for black holes. Future work will include looking at the different predictions of these two theories (massless and massive gravitons), and comparing them to black hole inspiral data to determine if the massive graviton theory could be a legitimate contender as a model for gravity
Mechanistic Insights for Magnetic Imaging and Control of Cellular Function
Get PDFThe vast biomolecular toolkit for optical imaging and control of cellular function has revolutionized the study of in vitro samples and superficial tissues in living organisms but leaves deep tissue unexplored. To look deeper in tissue and observe system-level biological function in large organisms requires a modality that exploits a more penetrant form of energy than visible light. Magnetic imaging with MRI reveals the previously unseen, with endogenous tissue contrast and practically infinite penetration depth. While these clear advantages have made MRI a cornerstone of modern medical imaging, the sparse library of molecular agents for MRI have severely limited its utility for studies of cellular function in vivo. The development of new molecular agents for MRI has suffered from a lack of tools to study the connection between changes in the microscale cellular environment and the corresponding millimeter-scale MRI contrast. Bridging this gap requires revisiting the mechanistic underpinnings of MRI contrast, casting aside some of the simplifications that smooth over sub-voxel heterogeneity that is rich with information pertinent to the underlying cell state.
Here, we will demonstrate theoretical, computational, and experimental connections between subtle changes in microscale cellular environment and resultant MRI contrast. After reviewing some foundational principles of MRI physics in the first chapter, the second chapter of the thesis will explore computational models that have significantly enhanced the development of genetically encoded agents for MRI, including the first genetically encoded contrast agent for diffusion weighted imaging. By improving the efficacy of these genetically encoded agents, we unlock MRI reporter genes for in vivo studies of cellular dynamics much in the same way that the engineering of Green Fluorescent Protein has dramatically improved in vitro studies of cellular function.
In the third chapter, we introduce our study that maps microscale magnetic fields in cells and tissues and connects those magnetic fields to MRI contrast. Such a connection has previously been experimentally intractable due to the lack of methods to resolve small magnetic perturbations with microscale resolution. To overcome this challenge, we leverage nitrogen vacancy diamond magnetometry to optically probe magnetic fields in cells with sub-micron resolution and nanotesla sensitivity, together with iterative localization of field sources and Monte Carlo simulation of nuclear spins to predict the corresponding MRI contrast. We demonstrate the utility of this technology in an in vitro model of macrophage iron uptake and histological samples from a mouse model of hepatic iron overload. In addition, we show that this technique can follow dynamic changes in the magnetic field occurring during contrast agent endocytosis by living cells. This approach bridges a fundamental gap between an MRI voxel and its microscopic constituents and provides a new capability for noninvasive imaging of opaque tissues.
In the fourth chapter, we focus on the use of magnetic fields to perturb, rather than image, biological function. Recent suggestions of nanoscale heat confinement on the surface of synthetic and biogenic magnetic nanoparticles during heating by radiofrequency alternating magnetic fields have generated intense interest due to the potential utility of this phenomenon in non-invasive control of biomolecular and cellular function. However, such confinement would represent a significant departure from classical heat transfer theory. We present an experimental investigation of nanoscale heat confinement on the surface of several types of iron oxide nanoparticles commonly used in biological research, using an all-optical method devoid of potential artifacts present in previous studies. By simultaneously measuring the fluorescence of distinct thermochromic dyes attached to the particle surface or dissolved in the surrounding fluid during radiofrequency magnetic stimulation, we found no measurable difference between the nanoparticle surface temperature and that of the surrounding fluid for three distinct nanoparticle types. Furthermore, the metalloprotein ferritin produced no temperature increase on the protein surface, nor in the surrounding fluid. Experiments mimicking the designs of previous studies revealed potential sources of artifacts. These findings inform the use of magnetic nanoparticle hyperthermia in engineered cellular and molecular systems and can help direct future resources towards tractable avenues of magnetic control of cellular function.</p