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Mechanical Investigations: Experimental Fracture Techniques and Frozen Small-Molecule Organics
Get PDFFracture of architected lattices: Three-dimensional diamond, kagome, and octet lattices were prepared for validation of a standard compact tension fracture experiment at two different length scales. Solid polymer lattices were written via two-photon lithography at the microscale, and solid polymer lattices are printed via digital light processing at the macroscale. Several of the macrolattices were pyrolyzed into carbon lattices to yield a brittle material for testing. The scaling laws of fracture toughness with relative density are explored, and this offers one of the first experimental studies of a fully 3D kagome lattice.
Mechanical properties of solid benzene: We explore the mechanical properties and deformation of 10 um-sized cuboid-shaped solid benzene crystals made by freezing directly onto a liquid-nitrogen-cooled sample stage and compressed quasi-statically to 10% strain at 125 K with an in-situ nanomechanical instrument inside a Scanning Electron Microscope (SEM). Cryo-Transmission Electron Microscopy (cryo-TEM) and diffraction of frozen benzene confirms the orthorhombic crystal structure of benzene. Compressive contact pressure-strain response generated from load-displacement data suggests the deformation mechanism to occur via densification, with a loading modulus of 9 GPa, slightly larger than that of other small molecules composed of aromatic rings, such as naphthalene and biphenyl. Molecular dynamics (MD) simulations of experimentally equivalent compressions of 10-30 nm benzene samples of the same crystal structure and geometry along the principal lattice directions at 10-30 K suggest densification could, initially, occur by local amorphization of the compressed region. The discovered deformation mechanism, stiffness, and strength of benzene at 125 K can inform our understanding of geological processes on cold planetary bodies. For example, the surface of Saturn’s moon Titan is teeming with solid organics at an ambient temperature of 95 K; this work will have significant impact on designing in-situ sampling tools for future missions to Titan and to substantiate speculative surface compositions.</p
Molecular Mechanisms Underlying Cardiac Neural Crest Development in Avian Embryos
Get PDFThe neural crest is a multipotent, vertebrate-specific stem cell population that gives rise to diverse cell types in the developing embryo, including craniofacial cartilage, enteric ganglia, and cardiac septa. Neural crest cells that originate from a given axial level in the embryo give rise to a characteristic array of progeny and follow distinct pathways from those arising at other levels. One of these subpopulations, called the cardiac neural crest, originates in the dorsal hindbrain and migrates into the developing heart, where it forms the aorticopulmonary septum, cardiac ganglion, and part of the interventricular septum. Mutations in or loss of these cells causes heart defects that are among the most common birth defects in the general population. For my thesis, I sought to identify the mechanisms that underlie the formation of neural crest cells, and confer cardiac neural crest cells with their unique developmental potential.
To enable interrogation of epistatic relationships between key neural crest genes during neural crest induction and crest specification, I first optimized the CRISPR-Cas9 system for genome editing in gastrula and neurula-stage chicken embryos. I then further improved the CRISPR toolbox by devising an all-in-one single-plasmid strategy that harnesses the self-cleavage properties of ribozymes for the simultaneous delivery of Cas9, gRNAs, and fluorescent reporters in transfected cells. This has enabled live tracking of wildtype and mutant neural crest cells as they migrate to their terminal locations.
Prior to their induction at the neural plate border, precursors in the neural plate border are transcriptionally primed toward multiple cell fates, including neural tube, neural crest, epidermis, and placode. While this priming has been thought to involve epigenetic regulation, chromatin remodeler genes have been overlooked in the context of neural crest formation given their concomitant expression in surrounding cell types. By combining single-cell transcriptional profiling of the early chick embryonic hindbrain with temporally-controlled knockouts, I uncovered a novel bimodal mechanism whereby the chromatin remodeler gene Hmga1 first regulates Pax7-dependent neural crest induction at the neural plate border, and later modulates Wnt signaling in the dorsal neural tube to control neural crest delamination. These results established Hmga1 as a direct regulator of neural crest induction and emigration.
Finally, given that amongst distinct neural crest subpopulations designated as cranial, cardiac/vagal, and trunk, only cardiac crest has the ability to contribute to heart development, and that neither trunk nor cranial neural crest subpopulations can rescue the loss of cardiac crest, I investigated the genetic logic that imbues cardiac crest with its unique ability to form cardiovascular derivatives. To this end, I combined surgical ablations, bulk and single-cell transcriptional profiling, RNA labeling, CRISPR-Cas9-mediated gene editing, transcription factor binding motif mutation analysis, and transgenic tissue grafting approaches to uncover and characterize a cardiac-neural-crest-specific subcircuit comprised of the transcription factors Sox8, Tgif1, and Ets1. I demonstrated that ectopic expression of this subcircuit in trunk neural crest cells reprogrammed them towards a cardiac-crest-like fate, and transplanting these reprogrammed cells in place of ablated cardiac crest restored cardiac-crest-like migration patterns and rescued outflow tract septation defects.
Taken together, my thesis work has not only built a genome engineering toolbox for a key model system in developmental biology, but has also expanded our understanding of the genetic circuits that govern the formation of the cardiac neural crest and underlie its unique ability to contribute to the heart.</p
The Relevance of Jazz in Modern Historiography
No full text[Introduction] Power and information often go hand in hand. Those who have the power to shape the world around them exercise that power to affect how they are viewed, and their ability to control cultural narratives in this way cements their power. Disempowered minorities are not only oppressed but suppressed, either circumstantially (through limited access to education and academia) or directly (through propaganda and silencing). When studying African American history, it becomes especially important to include as many perspectives as possible because of the systemic silencing and misinformation that these people have faced for centuries. In their article "Why Jazz Still Matters," historian Dr. Gerald Early and ethnomusicologist Dr. Ingrid Monson argue that jazz, both as a set of musical forms and a broader culture surrounding them, provides an insightful perspective on the oft-overlooked lives of society's oppressed peoples. While not traditionally viewed as a historical record, jazz has preserved generations of emotions and stories within its complex forms and expressions. Referencing the ideas of some of the most influential figures in jazz, the authors draw connections between the music stylings of jazz and the values that it encouraged
Enhanced Noninvasive Imaging of Acoustic Biomolecules
Get PDFThe extensive scientific interest in cellular and biomolecular processes is due in large part to the importance of such processes deep inside living organisms, in the context of both health and disease. However, most methods for imaging cellular processes such as gene expression have relied on fluorescent proteins and other optical reporters that, while providing a direct optical readout of the biomolecular environment in cells readily exposed to light, have greatly limited performance in large animals due to the poor penetration of visible light beyond 1 mm of biological tissue. In contrast, ultrasound is widely used to noninvasively image tissue deep inside living organisms but has rarely been used to investigate cellular function due a lack of acoustic reporters whose production and properties are coupled to biomolecular events. Recently, the first acoustic reporter genes (ARGs) were developed for ultrasound imaging of a unique class of air-filled protein nanostructures known as gas vesicles, or GVs, which scatter sound waves when expressed in bacterial and mammalian cells. ARGs allow gene expression to be visualized with ultrasound similar to how green fluorescent protein (GFP) allowed gene expression to be visualized with light. However, ARGs will have limited utility in practical applications involving living organisms without ultrasound imaging methods providing the specificity to reliably distinguish GVs from surrounding tissue and the sensitivity to detect GVs at low concentrations.
In this thesis, we present two novel ultrasound imaging methods that exploit the unique nonlinear physical properties of gas vesicles to enhance image quality in situations that pose challenges for conventional imaging methods. In Chapter 1, we address the problem of distinguishing GVs from tissue with cross-Amplitude Modulation (xAM), an ultrasound pulse sequence that uses X-waves to isolate the signal generated by reversible buckling of the GV shell while cancelling scattering and artifacts from tissue. In Chapter 2, we present an application of xAM to imaging of dynamic biomolecular processes. We show that, when GVs are engineered such that buckling is induced by enzyme activity, xAM can visualize enzymatic processes deep inside living animals. In Chapter 3, we address the problem of detecting very low concentrations of ARG-expressing cells with Burst Ultrasound Reconstructed with Signal Templates (BURST), an imaging method that exploits the strong, transient signals generated during sudden GV collapse under acoustic pressure by unmixing the temporal dynamics of such signals from background scattering. BURST imaging improves cellular sensitivity by more than 1000-fold and, in dilute cell suspensions, enables the detection of gene expression in individual bacteria and mammalian cells. In Chapter 4, we present an application of an early formulation of BURST to imaging gene expression in mammalian cells. We use this imaging method to visualize vascularization patterns in tumors containing mammalian cells expressing acoustic reporter genes.</p
Theoretical, Computational, and Experimental Characterization of Nematic Elastomers
Get PDFNematic elastomers are programmable soft materials that display large, reversible, and predictable deformation under an external stimulus such as a change in temperature or light. They are composed of a lightly crosslinked polymer network with stiff, rod-like liquid crystal molecules incorporated within the polymer chains. In thermotropic nematic elastomers, the liquid crystals undergo a continuous and reversible phase transition between the randomly oriented isotropic state and the highly oriented nematic state. Further, there is a direct thermo-mechanical coupling between the underlying temperature-responsive orientational order of the liquid crystal molecules and the macroscopic shape change of the surrounding elastomer chains. Finally, these materials display an unusually soft behavior. These remarkable properties make them promising materials for applications in aerospace as deployable structures and skins, in biomedical engineering as a soft pump, and in communications as the actuation mechanism in a reconfigurable antenna. Motivated by these applications, this thesis discusses the theoretical, computational, and experimental characterization of nematic elastomers.
We begin by investigating an example of actuation that takes advantage of the programmable, soft nature of these materials as well as instabilities associated with large deformation. We outline the multi-stable equilibrium solutions to a cylindrical balloon subjected to internal inflation, the material's microstructure formation due to this deformation, and its use as a soft pump with large ejection fraction, which involves a snap-through instability. Then we extend the Agostiniani-DeSimone-Dolzmann relaxed energy to a generalized Mooney-Rivlin constitutive relation and study four examples of Ericksen's universal deformations -- the inflation of cylindrical and spherical balloons, the cavitation of a disk, and the bending of a block.
We then move beyond the modeling of ideal materials and present a new constitutive relation for isotropic-genesis polydomain nematic elastomers. It is based on internal variables that describe the fine-scale domain patterns and evolve according to a kinetic process with dissipation. We discuss the model's implementation in the commercial finite-element software, ABAQUS, and study the problem of torsion of a cylinder. We identify an interesting instability at large torsional strains as a result of the Poynting effect. Finally, we present the design of a thermo-mechanical tensile setup and the experimental results for strain-rate dependence and temperature-dependence of samples that we synthesize in-house.</p
Light Induced Dynamics in Quantum Matter
Get PDFThis thesis presents studies of different schemes to probe and manipulate quantum matter using light with an aim to discover novel routes to efficiently control the properties of quantum materials. A special focus is placed on developing new schemes utilizing light-matter interactions (1) to modify exchange interactions in magnetic insulators, and (2) to probe and modify band topology in quantum matter.
In part II, new schemes are presented to probe local band topology of Bloch bands. First, we study the effects of time-dependent band topology on adiabatic evolution of a Bloch wavepacket. We find that it results in an electric-field analog in semi-classical equation of motion, and can be demonstrated in a honeycomb lattice by varying the sublattice offset energy. We then extend these methods to include non-adiabatic processes, and found interesting connections between the anomalous drift during band excitation and a quantum geometric quantity known as shift-vector. We generalize the concept of shift-vector to include different kinds of band transition protocols beyond light-induced dipole transitions. The idea of electric-field analog and the shift-vector are then combined to develop a novel charge pumping scheme. Motivated by these interesting consequences of band topology in non-adiabatic processes, we study shift-current response in moiré materials, and find that the highly topological nature of flat bands along with their very large unit cells significantly enhances these shift-vector related effects. This response also displays a strong dependence on interaction-induced changes in the band structure and quantum geometric quantities. These results suggest that shift-current response can possibly serve as a very reliable probe for interactions in twisted bilayer graphene. In addition to studying consequences of band topology on single-particle transport, we also consider Berry curvature effects on exciton transport. We find that the non-trivial band topology of underlying electron and hole bands allows us to manipulate excitons with a uniform electric field. We examine the conditions necessary to observe such transport and propose that transition metal dichalcogenide heterobilayers with moiré structure can prove an ideal platform for these effects.
In part III, we propose novel drive protocols based on manipulating orbital and lattice degrees of freedom in quantum materials with light. We found that light induced changes in orbital hybridization and their electronic energies results in a significant change in exchange interactions in quantum magnets. We also accounted for the role of ligands in periodically driven quantum magnets, and found that the predictions made by the minimal model based on direct-hopping can be wrong in certain regimes of drive parameters. This understanding of light induced modifications in ligand-mediated exchange interactions was used to explain the phase shift observed in coherent phonon oscillations of CrSiTe₃ upon the onset of short-range spin correlations. We also demonstrate that light induced coherent lattice vibrations can provide a new route to realize space-time symmetry protected topological phases. Our results suggest that manipulating additional degrees of freedom (not included in commonly employed minimal models of periodically driven systems) with light can provide novel routes for ultrafast control of quantum materials.</p
Developing Multivalent Nanoparticle Vaccines Against Current and Future Viruses
Get PDFThe 1918-1919 flu pandemic resulted in an estimated 50 to 100 million deaths worldwide, making it the deadliest pandemic in modern history. It was caused by a new influenza virus that likely spilled over from birds and reassorted with a human influenza virus. Since the human population was immunologically naïve to this virus, transmission and lethality was much higher than for seasonal influenza outbreaks. Numerous pandemic influenza viruses emerged within the next century, with none causing the same amount of carnage. There is likely to be future influenza pandemics, with wild migratory birds being carriers of a wide swath of different influenza A viruses. Zoonotic transmission of Avian influenza has taken place with limited human to human transmission. There is evidence showing that the barrier of human transmissibility by some of these avian viruses is not very high, and therefore emergence into humans is possible, with most if not all of the population immunologically naïve. The humoral immune response to influenza is defined by the imprinting of the antibody response to immunodominant epitopes. Such responses can impair immunity, providing less adequate protection against seasonal and pandemic infections, as well as poorer immunity induced by seasonal vaccines. There are instances where imprinting can be advantageous and even offer protection against pandemic or avian viruses, particularly when conserved epitopes to the HA stalk are exploited. Manipulating the antibody response to recognizing conserved stalk epitopes on influenza HA is therefore a strategy being used for universal influenza vaccines. In the second Chapter of this thesis, a mosaic nanoparticle immunization strategy for inducing breadth of antibody responses against HA will be described. This strategy involves the co-display of HAs from up to eight different strains on a particle platform. Although the breadth of antibody responses elicited by immunization of these particles was limited, this work provides insight into the antigenicity of such particles, and a possible alternative to current influenza vaccines.
Approximately 100 years after the 1918-1919 flu pandemic, a deadly SARS-like coronavirus, known as SARS-CoV-2, emerged in the human population resulting in a currently ongoing pandemic. This came less than two decades after the small but deadly SARS outbreak, essentially a warning call for this class of coronaviruses. Other SARS-like coronavirus strains in bats have been identified and shown to be human tropic, though resulting in an attenuated infection. Some of these viruses can infect via hACE2 but there are others that may use an unknown receptor for entry into VERO cells as well as human cell lines. There is evidence that the major barrier to zoonosis is protease compatibility, which could be gained through recombination events or errors during replication. Therefore, future SARS-like coronaviruses (sarbecovirus) may emerge in humans, seeding future outbreaks. The antibody response to SARS-CoV-2 is robust and protective. Furthermore, there is the presence of conserved epitopes particularly on the RBD that can be targeted by antibodies that are cross-neutralizing against many SARS-like coronaviruses. Exploiting these cross-reactive epitopes is one strategy that can be used for developing a universal coronavirus vaccine. In Chapter 3 of this thesis, a similar mosaic nanoparticle immunization strategy will be described, that attempts to elicit cross-reactive antibodies against the SARS-like coronavirus family. The mosaic nanoparticles co-display the RBDs of eight different sarbecovirus strains including SARS-CoV-2. Immunization with these mosaic-RBD nanoparticles elicited polyclonal antibody responses that were cross-reactive as well as cross-neutralizing against sarbecoviruses strains both present and not present on the particles.</p
Life Without Cortex: Subcortical Circuits in Naturalistic Behaviors
Get PDFA major goal of neuroscience is to understand the neural circuits underlying animal behavior. Many contemporary studies focus on behavioral tasks which do not reflect realistic conditions, such as mapping an arbitrary sensory stimulus to motor output. Given that the brain evolved within the context of the natural environment, it is more likely that these circuits were optimized for naturalistic behaviors such as avoiding predators, hunting, and social interactions with conspecifics. Many of these naturalistic behaviors predate the great expansion of the neocortex in mammals, as they are crucial for the survival of any animal. Using a mutant mouse model and surgical techniques, we show that the evolutionarily ancient subcortical circuits of mice are sufficient for sensory processing, stimulus discrimination, and exhibiting robust innate defensive behaviors in a predator avoidance assay. Furthermore, these animals are capable of navigating a complex labyrinth, which challenges long-held beliefs that learning and memory require the neocortex and the hippocampus. Our results emphasize the significant capacity of subcortical circuits in behaviors necessary for survival and illustrate the importance of using naturalistic behaviors to probe brain function
Ahab’s Solipsism and the Illusion of Self-Reliance: The Career of Herman Melville
No full text[Introduction] What’s eating moody Ahab? In Herman Melville’s Moby Dick, Ahab is obsessed with hunting the white whale and cannot rest until he gets his revenge. His monomania germinates before the start of the novel, when a misadventure with Moby Dick results in a cruel disfigurement. Ahab cannot fathom any explanation for his lost leg except that the whale must be composed of pure malice—he places “the sum of all the general rage and hate felt by his whole race from Adam down” (Melville 182) onto Moby Dick’s white hump, personifying the whale as the supreme evil of the world. Ahab then believes that he must be the one to take down the wicked whale. He becomes a man of absolutes, of black and white, and his world closes in until the only certainties are himself and the wicked whale. As a reaction to transcendentalism, Melville has the vengeful Ahab follow much of Emerson’s “Self-Reliance” advice, often too literally. Rather than becoming truly self-reliant or competent, Ahab instead becomes more selfdeluded, more reliant on others, and loses touch with humanity. On the other hand, through Ishmael and Queequeg, Melville shows how transcendentalism can be used in non-problematic ways to lead meaningful lives, and these characters can be seen as foils to Ahab. Ahab often takes Emerson’s transcendentalist advice to an extreme, creating an image of toxic self-reliance that morphs into solipsism; Ahab then dangerously perpetuates his narcissism through self-idolatry, and, by viewing the ship as his personal stage, eventually leads everyone—except Ishmael—to their demise
Interior and Orbital Dynamics at the Innermost and Outermost Reaches of Planetary Systems
Get PDFIn contrast to the canonical planets of our solar system, with semimajor axes in the familiar range of ~ 0.3–30 au, exoplanets have been detected at considerably shorter and longer distances from their host stars. These planets, at the innermost and outermost reaches of planetary systems, have challenged many hitherto foundational ideas of planetary formation and evolution that were based solely on knowledge of our own solar system. This thesis addresses some of the emergent puzzles posed by the orbital and interior dynamics of planets orbiting very close and far away from their stars.
Chapters II-III consider the origins of planets on very short-period orbits. Two and a half decades ago, the discovery of the first hot Jupiter marked the dawn of exoplanet detections around sunlike stars. The existence of these extremely irradiated Jovian planets (orbital periods ≾ 5 days) runs in stark contrast to the utter absence of material orbiting interior to Mercury in our own solar system. This striking discrepancy between the close-in planetary content of observed systems and our own — together with the notion that, interior to the "snow lines" of stars at stello-centric radii of several au, water ice is not available to contribute to the accretion of the several Earth-mass cores necessary for runaway core accretion — has led to many works aiming to explain how Jovian-mass (≳ 0.1MJ) planets can migrate inward to become hot Jupiters after forming beyond the snow lines of their stars. One such migration mechanism, known as high-eccentricity migration, occurs when a Jovian planet is excited to extremely high eccentricity such that it experiences significant tidal dissipation at perihelion passage, promoting orbital decay to a short-period orbit. For cases such as the massive (~ 9MJ), eccentric (e ~ 0.5) hot Jupiter HAT-P-2b — for which the exterior perturber is characterized — the eccentric orbital state encodes information about the tidal history of the planet. In Chapter II, I outline a method for constraining the tidal dissipation rate in eccentric hot Jupiters such as HAT-P-2b and its analogues. In Chapter III, I consider the opposite limit of possibilities: local conglomeration. While observations of highly eccentric, tidally unstable hot Jupiters imply some hot Jupiters must form through high-eccentricity migration, I present a -2/7 power law prediction which naturally follows from a basic picture of viscous accretion and inner magnetic truncation of protoplanetary disks. This power law, combined with simple tidal corrections, agrees well with the observed period-mass distribution of hot Jupiters, possibly lending new credence to the hypothesis that hot Jupiters predominantly form in situ, near their observed close-in positions.
Next, with Chapter IV, we move on from the inner regions of planetary systems to address the interior dynamics of our furthest observed solar system planets, Uranus and Neptune. The so-called "ice giants" present a major challenge to interior modeling efforts due not only to a relative lack of spacecraft coverage compared to other solar system planets, but also because of a compositional degeneracy which inherently arises from their intermediate densities. An especially confounding issue surrounding these planets has been the extremely low heat flux of Uranus compared to Neptune. Chapter IV addresses these challenges with the application of novel thermodynamic constraints that follow in the case where hydrogen and water are taken to be immiscible major constituents. As discussed in Chapter IV, this model framework can satisfy the observed masses, radii, and gravitational harmonics of these planets — without being at odds with observations of the magnetic fields. Importantly, as Chapter IV shows, hydrogen-water immiscibility in the deep interiors of Uranus and Neptune can offer a natural explanation for the disparate heat fluxes — but characteristically similar magnetic fields — of Uranus and Neptune.
Following this discussion of the outermost directly observed planets in our solar system, Chapters V-VI delve into the orbital dynamics of planets on extremely wide (hundred-au) orbits, with a specific emphasis on the hypothesized Planet Nine. In our own solar system, the existence of a massive planet on such a wide orbit, with considerable eccentricity (e ≳ 0.1) and inclination (i ~ 20°), has been proposed to explain several dynamical features of the outer solar system. In Chapter V, I describe how this very distant planet could affect the dynamics down to the innermost reaches of the solar system, through secular modulation of the so-called "invariable" plane of the canonical planets, relative to the solar spin axis. Next, in Chapter VI, I numerically derive a prior distribution for the relative occupation of individual mean-motion resonances with this planet by eccentric small bodies, showing that assumption of low-order resonances with observed objects is not a viable means to determine the current true anomaly of Planet Nine.
Finally, in Chapter VII, concluding remarks are given, and the findings of this work are discussed in relation to the ongoing exploration of related topics in planetary system dynamics.</p