Rice University Electronic Theses and Dissertations

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Rice University makes all graduate theses and dissertations (1916-present) available online at no cost to end users. Occasionally a thesis or dissertation may be be missing from the repository. If you are unable to find a specific dissertation, please let us know and we will attempt to make it available through the repository, provided that the author has not elected for it to be embargoed.

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Seismic Retrofitting of Low-Rise Reinforced Concrete (RC) Structures: a Multi-Faceted Evaluation
(2024-04-23) Laguerre, Marc-Ansy; Desroches, Reginald; Padgett, Jamie; Duno-Gottberg, Luis; Duenas-Osorio, Leonardo
The threat of seismic activity is a major concern for countries worldwide, and many have invested significant resources into researching the seismic retrofit of reinforced concrete (RC) structures. As a result, building codes and retrofit strategies have been enhanced to strengthen vulnerable structures. However, Haiti remains a country with limited knowledge about the vulnerability of RC buildings to seismic events and retrofitting solutions. This study aims to address this knowledge gap by conducting a comprehensive analysis of Haitian RC structures and evaluating multiple retrofit methods to enhance their seismic performance. This study examines the retrofitting of RC buildings in Haiti using deterministic and probabilistic approaches, followed by a Life-Cycle Cost-Benefit (LCCB) analysis to determine the optimal techniques. The study first analyzes Haitian construction norms and practices before selecting building prototypes: R1 (residential 1-story), R2 (residential 2-story), NR2 (non-residential 2-story), and NR3 (non-residential 3-story). These prototypes' columns and beams are designed according to the BAEL (Beton Aux Etats Limites) guidelines, a French construction code widely used for engineered buildings in Haiti before 2010. For the deterministic analysis, a two-phase numerical modeling method is used. Initially, continuum-based finite element models on LS-DYNA are used to validate and derive hysteretic curves of the column joints. Following this, a macroscopic model, which is calibrated from the results from LS-DYNA, is used for non-linear time history analysis of the building's 2D frames using OpenSees. Five retrofit strategies are then added to the original frames: RC shear walls (used for non-residential models), steel braces (used for residential models), buckling-restrained braces (used for non-residential models), prestressed tendons (used for residential models), and RC jackets (used for all models). These retrofits were designed such that the frames do not reach the life safety (LS) objectives of FEMA for a hazard of the return period of 2475 years. A total of 10 ground motions, which include motion recorded in Haiti, are chosen to run the time history analysis and evaluate the retrofit methods' efficiency. It was observed that the using of RC jackets with each of the global retrofits is able to enhance the building's performance to meet chosen performance objectives. This research also assessed retrofitting solutions through probabilistic analysis, generating fragility curves. Initially, empirical fragility curves were derived using post-earthquake data and the shakemap from Haiti's 2021 earthquake, confirming the high vulnerability of Haitian RC buildings. Analytical fragility curves were subsequently developed for the four models representing these structures. Using continuum-based models on LS-DYNA, four damage states (minor, moderate, severe, and collapse) were used and investigated through pushover analyses. The results were then used for a multiple linear regression to predict the drift limit states. A probabilistic seismic demand regression was further derived via time history analysis on a 2D OpenSees model. The resulting analytical fragility curves revealed that incorporating RC jackets and a global retrofit substantially improved building resilience. Finally, a LCCB analysis was conducted to assess the financial implications of the retrofits. By integrating hazard and fragility data with the estimated costs for building repair, replacement, and retrofitting, the benefit of implementing the retrofits was evaluated. The analysis revealed that retrofitting with RC jackets offers significant benefits. However, these benefits are notably higher when RC jackets are combined with steel braces in residential buildings, and with shear walls in non-residential buildings, thus optimizing the structural resilience and financial viability of the retrofitting strategies.
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Unsettling Frontiers, Futures and Democracy: Alaska and Beyond
(2024-04-19) Haver, Maureen Siobhan; Boyer, Dominic
Alaska is frequently imagined by the Lower 48 as the Last Frontier, a vast pristine wilderness, and an essential component to United States energy independence. Alaska is also warming at twice the rate of the rest of the United States and is a contested site for oil and gas development in the Arctic. With over 222 million acres of land controlled by federal government—Alaska represents a third of all federal land holdings, reflecting the legacies of settler colonialism, the conservation movement, and resource extraction while raising questions about the future of decarbonization and decolonization amidst the climate crisis and Indigenous-led movements for sovereignty, climate justice, and land (Byrd 2011; Waziyatawin 2012; Estes 2019; Dhillon 2022). Through anthropological ethnography in Alaska and multidisciplinary research, this dissertation brings together climate, energy, and settler colonial studies to examine how the U.S. settler colonial project as a process of internal expansion enacted through reiterative and theoretical frontiers formed settler identities, notions of democracy and populism, and understandings of nature vis- à-vis resource abundance and extraction and the wilderness that impact the broader fights over public lands—which should also be understood as unceded Indigenous lands—decolonization, climate change, and energy transition.
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Encapsulated Cell Systems for Treating Inflammatory Diseases
(2024-04-19) Aghlara-Fotovat, Samira; Veiseh, Omid; Ghanta, Ravi K
In response to pathogens and trauma, host immune cells interact bi-directionally with their local environment to receive and deposit molecular signals, which orchestrate cellular activation, proliferation, differentiation, and function to maintain healthy tissue homeostasis. While our immune system functions as a vigilant safeguard against environmental threats, instances of immune dysregulation may occur, leading to uncontrolled responses. In these conditions, it is essential to restore balance to the body through modulation of the immune system and the ECM. Cell-based therapeutics have significant potential in locally monitoring and treating inflammatory diseases, however, their widespread use is hindered by recognition and elimination by the host. Thus, novel technologies that can improve the viability and function of cell-based therapies have significant potential in improving translation. Here, we aim to utilize biomaterial encapsulation as a tool for improving the delivery of cell-based therapeutics for local immunomodulation in various inflammatory diseases including myocardial infarct, acute respiratory distress syndrome, neural inflammation, inflammatory bowel disease.
Flow Analysis of Vibration Modes in Turbocharger Turbines
(2024-04-19) Pritchard, Noah; Tezduyar, Tayfun E
The purpose of this research is to help understand the influence of time-dependent fluid dynamics forces on the fatigue failure of turbomachinery blades. To that end, we conduct computational flow analysis of a turbocharger turbine with 13 rotor blades and 14 stator blades for precomputed time-dependent blade deformation patterns. The flow analysis is carried out for the rotor vibration modes corresponding to a set of natural frequencies lower than but close to the frequency associated with the upper end of the turbine operation range. The core computational method is the Space–Time Variational Multiscale (ST-VMS) method. The ST-VMS serves as a moving mesh method. That enables mesh-resolution control near the rotor surfaces and high-resolution boundary-layer representation. The core method is complemented with the “ST-SI-IGA,” which is the synthesis of the ST Slip Interface (ST-SI) method and ST Isogeometric Analysis (ST-IGA). The ST-SI enables the use of ST-VMS as a moving-mesh method even with the inner mesh rotating with the rotor. The ST-IGA with IGA basis functions in space brings superior accuracy to the geometry representation and flow solution. The ST-IGA with IGA basis functions in time enables higher-accuracy representation of the rotor motion and blade deformations.
Performing with a Personal Musical Identity: An Examination of Musicians' Distinctive Personalities in Performances of Bach's Solo Violin Sonatas and Partitas
(2024-04-19) Park, Samuel; Barnett, Gregory
Teaching and performing Bach’s Solo Sonatas and Partitas for Solo Violin is a major challenge in American violin pedagogy today. A significant reason for this can be traced historically to the mid-20th-century, when performances influenced by modernist ideology became prevalent in the classical music world. Under this influence, musicians search for objective measures to define proper performance practice of musical works, including fidelity to the notated score or to a historically informed recreation of Bach’s Sonatas and Partitas (S&Ps, hereafter). Modernist performance and pedagogy are not only established on a misleading premise that textually literal and historically accurate recreations of pieces are true to a composer’s intentions, but they have also led to complaints of uniformity and blandness of violin performances. These complaints persist to this day. In this thesis, I analyze how violinists can make interpretative decisions in the S&Ps based on their own identifiable musical personality. In highlighting the vast musical possibilities featured in a variety of S&P interpretations, I hope that the violinist reader will be inspired to implement their own personality into Bach’s S&Ps instead of feeling compelled to attribute their interpretative choices to an objective criteria such as text-fidelity or historical accuracy. In advocating for future performances based on the performer’s own unique musical inspirations, I also hope that we will further contribute to a more diverse ecosystem of violin playing today. Toward this objective, I examine cellist Pablo Casals, a Romantic, early-20th-century trailblazer of Bach’s solo string works. Utilizing Romantic string techniques such as flexible rubato and a wide range of intonation, articulation, and dynamic contrasts, he is able to channel his deep empathy, shaped by his humanitarian convictions, into distinct human emotions through Bach’s music. Then, I compare four violinists, ranging from the mid-20th-century to today, who present contrasting interpretations of the S&Ps: Yehudi Menuhin, Nathan Milstein, Christian Tetlzaff, and Shunske Sato. I demonstrate how they also utilize similar Romantic, early-20th-century string techniques to highlight their own personally identifiable music philosophies.
Advancing Control Over Two-dimensional Noble Metal Nanoparticle Self-assembly
(2024-04-19) Kress, Rachael Nicole; Jones, Matthew R
Self-assembly is utilized by many natural processes to make large-scale complex structures and materials from much smaller, simpler components. These structures are stable without the continuous influx of energy. It is a “bottom-up” approach that is not restricted by scale and is therefore a very promising approach for the fabrication and manufacturing of both new synthetic materials or mimics of biological materials. This is especially true in the field of nanomaterials. Objects that exist on the nanoscale often have unique and interesting properties that are dependent on their size, which makes them very appealing for a variety of applications. Most of these applications depend on arranging nanoparticles into very specific patterns on a large scale. Currently, many of the fabrication techniques that excel in terms of order and control, such as lithography-based techniques, lack scalability. Self-assembly is one conceivable pathway for achieving a high degree of control in a scalable manufacturing process. In this thesis, I present investigations into two different nanoparticle two-dimensional (2D) self-assembly systems, which advance our understanding of the principles that govern them and provide the groundwork for further exploration into these systems. In Chapter 1, I discuss the basic principles of self-assembly at the nano-length scale. This discussion includes highlighting the most common forces used to drive self-assembly, and how different components of a nanoparticle system can be used to alter those forces. I also provide additional analysis on the specific challenges and merits of 2D self-assembly as compared to 3D self-assembly. Chapter 2 is a commentary that provides a structure and language for discussing interparticle interactions and how self-assembly systems can carry the information that directs them. The terms valency, directionality, and specificity are used to describe the type and degree of information that is encoded into a system. In Chapter 3, I present an investigation into the role of DNA flexibility during the DNA-mediated 2D self-assembly of gold nanospheres. Introducing an “ambidextrous” design of the sticky end of the DNA strands directing the self-assembly, I was able to deconvolute the particle-particle interactions and the particle-surface interactions in a 2D system. This revealed that the system favored softer, more flexible particle-particle interactions but harder, more energetically stable particle-substrate interactions. I performed additional experimentation and analysis that suggests the preference for hard particle-substrate interactions is most likely a result of having faster kinetics under those circumstances, while the softer particle-particle interaction is more strongly dictated by the ability of softer ligand shells to overcome lattice defects. The final chapter presents a second 2D self-assembly system in which cubes and orthocentric bitetrahedra are co-assembled into two distinct superstructures based on the size and sharpness of both shapes. While this project is still in its infancy, the initial work for determining a standard and the boundary conditions for each of the different elements of the system is present. In this chapter, I also discuss the promising initial results and the future experiments needed to resolve standing questions and to quantify my observations. Self-assembly is a simple and universal principle that governs many of the most complex materials in our lives. Understanding and applying it, however, is anything but simple. The discussions, observations, and results presented in this thesis add to the growing body of knowledge about this ubiquitous process so that it may one day be utilized with accuracy and efficiency in the fabrication of complex materials and structures.
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Phase behavior, flow dynamics, and solution processing of boron nitride nanotubes and carbon nanotubes
(2024-04-19) Ginestra, Cedric; Pasquali, Matteo
Carbon nanotubes (CNTs) have the potential to combat climate change by displacing innately high CO2-intensive materials like metals and carbon fiber, through synthesis of CNTs by natural gas pyrolysis and solution fiber spinning. Despite having been synthesized shortly after CNTs, structurally similar boron nitride nanotubes (BNNTs) are at a somewhat nascent technological phase, marred by stagnation from early technical obstacles. Continued improvements to BNNT synthesis and purification are still required to produce high aspect ratio, pure BNNTs. In this work, we process the first BNNT liquid crystalline solutions into neat BNNT structures using scalable methods. We find that high material purity is required to achieve the liquid crystalline phase preferred for solution processing of rigid rods into macroscopic objects, such as films and fibers. We find that BNNT fiber properties are ~10x lower than expected from results obtained with early CNT fibers composed of similar aspect ratio nanotubes, and we attribute this performance gap to low BNNT purity, which leads to poor solution quality. To better understand the behavior of nematic nanotubes, we study solutions of CNTs and BNNTs using quantitative polarized optical microscopy (Q-POM) and find that the purity of different BNNT grades might possibly be determined semi-quantitatively by measuring the birefringence intensities of these solutions. If so, this approach will significantly enhance the optimization of future BNNT purification with corresponding advancements expected in macroscopic material performance. By QPOM of BNNT and long CNT solutions, we show that flow-induced alignment created by sample preparation does not relax on experimental timescales due to low rotational diffusivity - this behavior is distinct from solutions of short CNTs, which lose their flow-induced order on relatively short time scales, manifesting as a reduction in birefringence intensity. The existence of a pseudo-equilibrium for long CNTs is of particular importance for materials characterization, because the isotropic-nematic phase transition concentration (commonly measured by POM) is used to estimate CNT aspect ratios and predict CNT fiber performance. We find POM to be ill-suited to determine this transition concentration for long CNTs and recommend against using these POM-based measurements to inform changes in CNT synthesis or fiber spinning processes.
Overparameterization and double descent in PCA, GANs, and Diffusion models
(2024-04-19) Luzi, Lorenzo; Baraniuk, Richard G
This PhD thesis constitutes a synthesis of my doctoral work, which addresses various aspects of study related to generative modeling with a particular focus on overparameterization. Using a novel method we call pseudo-supervision, we investigate approaches toward characterization of overparameterization behaviors, including double descent, of GANs as well as PCA-like problems. Extending pseudo-supervision to diffusion models, we see that it can be used to create an inductive bias; we demonstrate that this allows us to train our model with lower generalization error and faster convergence time compared to the baseline. I additionally introduce a novel method called Boomerang to extend our study of diffusion models, showing that they can be used for local sampling in image manifolds. Finally, in an approach we titled WaM, I extend FID to include non-Gaussian distributions by using a Gaussian mixture model and a bound on the 2-Wasserstein metric for Gaussian mixture models to define a metric on non-Gaussian features.
Evaluation of the Hemodynamic Response of Heartbeat Synchronized Speed Modulation using a Continuous Flow Left Ventricular Assist Device
(2024-04-19) Kiang, Simon; Cavallaro, Joseph R
Heart disease is the leading cause of death in the United States. Left ventricular assist devices (LVAD) have been shown to be effective for treating late-stage congestive heart failure as bridge to transplant, and destination therapies. Continuous flow LVADs are currently the most clinically used however, continuous flow veers away from the naturally physiological pulsatile flow of the heart and circulatory system. This causes complications including but not limited to internal bleeding, and increased chance of thrombosis and stroke. An artificial pulsatile flow can be created with a continuous flow LVAD by increasing and decreasing its speed. Synchronizing this speed changes to the heart’s rhythm will result in flow and pressure closer to the physiological norm. This thesis covers the hemodynamic response of heartbeat synchronized speed modulation in simulation, and experimentally using a Frank-Starling controlled mock circulatory loop.
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The Microbiome in its Entirety: Community-Oriented Computational Tools for Deciphering Metagenomic Diversity
(2024-04-19) Curry, Kristen; Treangen, Todd J
Microbiome. An ecosystem composed of microscopic organisms. Although unseen by the naked eye, these communities can have powerful impacts on their hosts and surrounding environments. Yet, we are just beginning to crack the surface as to who these tiny critters are, how they are surviving, and what their overarching purpose is in the tree of life. This thesis presents software methods developed to improve understanding of these communities by leveraging the advent of high-throughput sequencing and viewing each ecosystem holistically, motivated by the intention of improving upon methods for gut microbiome analysis in concussion recovery. We dive into three computational tools developed for improvement of understanding the diversity within microbial communities: Emu for taxonomic community profiling, Rhea for structural variant detection, and Kiwi for P4 phage satellite detection. Each of these algorithms was designed with the view of the microbiome as a single evolving entity, rather than a sum of unique individuals. Viewing microbiomes through this lens and incorporating computer science theories in expectation-maximization, graph motifs extraction, and sub-string minimizers allowed us to develop software for each of these concepts that showed improvement upon existing methods.
Aluminum Nitride Memristors: The Fabrication and Analysis of a Next Generation Processor
(2024-04-21) Attarwala, Ali; Spanos, Pol D; Ghorbel, Fathi; Tang, Ming
This thesis details the experimental development of memristors with an Aluminum Nitride (AlN) insulative layer that can switch its resistance by adjusting its phase. Upon conducting an exhaustive literature review, the opportunity to study the ferroelectric properties of AlN in a resistive switching setting came about. The experimental study starts by detailing the fabrication of memristors utilizing atomic layer deposition (ALD) and electrode deposition. To study the characteristics of the device, relevant AlN memristor samples underwent a full electrical characterization. While there were some interesting results, the current-voltage (I-V) data did not match the expected behavior and results. To further investigate the data, transmission electron microscopy (TEM) analysis was conducted to look inside the device at the nanometer scale. The TEM data highlights the difficulties of memristor fabrication and processing. The experimental process provided insight into the behavior of the ferroelectric properties of AlN suggesting resistive switching applications. However, further exploration of the fabrication and processing of AlN in memristors is required, before any industrial applications are pursued.
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An Approach Towards Sustainable Synthesis of MXene and High-Performance Cementitious Composites
(2024-04-19) Jayanthi Harikrishnan, VJ; Ajayan, Pulickel M; Vajtai, Robert
This thesis investigates innovative methods for synthesizing MXenes and enhancing cementitious materials to meet the critical need for sustainable manufacturing and improved mechanical properties in structural materials. Central to this research is the advancement in material science across two key areas: the development of environmentally friendly synthesis methods and the adoption of efficient manufacturing strategies to create advanced cement structures. A significant emphasis is placed on pushing the boundaries of material performance, sustainability, and synthesis techniques. For example, we explore modified approaches to MXene synthesis and the development of reinforced cementitious composites through the integration of nanotechnology and cutting-edge 3D printing technologies. The initial three chapters primarily concentrate on sustainable synthesis strategies for MXenes, including the exploration of alternatives to traditional hydrofluoric acid (HF) for removing aluminum (Al) from the MAX-phase. Due to HF's high toxicity and associated health and safety risks, we investigate the use of ammonium fluoride (NH4F) as a safe alternative. Our findings, supported by various analytical techniques, confirm NH4F's effectiveness in Al removal and in the production of 2D MXene flakes. Additionally, we explore a novel non-fluoride-based chemical method using iron chloride (FeCl2) as an etchant, which plays a dual role in etching and intercalating, leading to the production of high-quality Fe intercalated MXene flakes. Through detailed analysis, we evaluate the crystallinity, chemical composition, surface morphology, and defects of the MXene flakes produced by these new techniques. This part of the thesis not only aims to mitigate the environmental impact associated with MXene production due to HF use, but also to enhance their surface chemistry adaptability, broadening their application potential. Furthermore, the thesis chapters provide fundamental and an in-depth analysis of MXenes, in addition to highlighting the efficacy of these innovative synthesis techniques in maintaining the structural integrity and desired features of MXenes. The latter chapters, specifically chapters four and five, focus on enhancing the mechanical properties of cementitious materials by leveraging the unique properties of nanoparticles and the advancements in multi-material 3D printing. This section demonstrates significant improvements in compressive strength, toughness, and thermal management by incorporating hexagonal boron nitride (h-BN) into cement matrices. Additionally, it examines the application of direct ink writing (DIW) in creating reinforced cement and polyvinyl alcohol (PVA) structures, aiming to boost their impact resistance and energy absorption capabilities. Overall, this thesis offers a comprehensive overview of the synthesis, chemistry, and technologies involved in developing advanced materials with wide-ranging applications. For instance, the synthesized MXenes could be applied in electromagnetic interference shielding, catalysis, sensors, and flexible electronics. Conversely, the nanofiller and polymer-reinforced cement structures have potential applications in environments subjected to extreme thermal and mechanical stresses
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Modeling human gastrulation at the extraemrbyonic-embryonic border
(2024-04-19) Kong, Xiangyu; Warmflash, Aryeh
Human gastrulation has long been a fascinating process that developmental biology tries to understand. Due to a lack of sample accessibility and ethical concerns, the answers to some basic questions like what signaling is initiating this process still elude us. In the past decade, several in vitro models were developed to answer such questions using human pluripotent stem cells (hPSCs), such as 2D and 3D human gastruloids. We gained a lot of insight into fate patterning, morphogenesis, and the mechanism driving them by studying these in vitro models. Compared to in vivo studies, these in vitro models provide us with better flexibility for experimental manipulation and scalability. However, the current in vitro models for human gastrulation are initiated by adding exogenous signaling molecules, by sticking to these systems, we risk missing some of the detailed dynamics during the process. It has long been hypothesized that the fate patterning during gastrulation is induced by signaling molecules secreted from the neighboring extraembryonic tissues, however, such inducing potency has yet to be reliably demonstrated in a human model. We developed a simple experimental model that juxtaposes extraembryonic and embryonic cells side by side to recreate a boundary to directly observe the interactions between them. We found that when hPSCs are juxtaposed against amnion-like cells (AMLCs), cells near the border recapitulating several aspects of gastrulation including…. We were able to capture this patterned differentiation and the underlying signaling in time. Studying the connection between said fate patterning and underlying signals grants us further insights into human gastrulation that have not been revealed in previous studies conducted on other model organisms or alternative gastrulation models. This demonstrates the potential of the juxtaposition model for studying the native signaling events between different cell populations.
Cages of Jade
(2024-04-18) Gonzalez Soledad, Ethan; Jalbert, Pierre
As a result of the Chinese exclusion act, San Francisco Bay’s Angel Island acted as an immigration station for mostly Chinese immigrants in the beginning of the 20th century. Those held at the station would spend weeks, months, and even years on the island in horrible living conditions before being released or sent back to their origins. There are many poems written on the walls describing the sense of despair, loneliness, anxiety, and boredom which people faced during their stay. The title of my orchestral piece, “Cages of Jade,” comes from one of these poems. Through my piece for full symphony orchestra, I sought to portray the journey of this author from their arrival at the station to their eventual release into the US.
Essays in Industrial Organization
(2024-04-18) Lu, Sen; Fox, Jeremy
This dissertation consists of two chapters on the partial identification in empirical industrial organization. Chapter 1: Game-theoretic entry models usually impose strong restrictions on the predetermined information structure of the game. This paper introduces a new method for the identification and inference of payoff parameters in static entry games, while being agnostic about the latent information structure. I examine a static entry game, assuming that all potential entrants are symmetric. I introduce a modification of Bergemann and Morris's (2016) solution concept, Bayes Correlated Equilibrium (BCE), which I refer to as Symmetric BCE, and provide a tractable and sharp characterization of the identified set of payoff parameters. I apply the method to driving schools, investigating the impact of the number of operating firms on the profitability of potential entrants. I conduct two counterfactual experiments to evaluate the effects on the number of operating firms: firstly, a simulation of market size reduction, and secondly, amplifying the market size effect by 30%. The empirical results indicate that the new, robust method still provides informative insights. Moreover, using the notion of Symmetric BCE, as opposed to BCE, reduces the computational burden, making identification and inference feasible even with a moderate number of players. Chapter 2: This paper proposes a new approach to partial identification of the semi-parametric multinomial choices model in a panel data setting, where the analyst uses covariate data on a subset of choices. This multinomial choice model allows for an arbitrary joint distribution of choice specific unobservables, so IIA-like property is not assumed. I show that the within-group comparison proposed by Pakes and Porter(2024) can be modified to account for the observation structure. I show that the new within-group comparison leads to a set of conditional moment inequalities. My main finding shows that the set of conditional moment inequalities characterizes the sharp identified set of the index parameters. In Monte Carlo simulations, the finite sample performance is presented.
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Molecular coarse-graining for classical and quantum systems
(2024-04-19) Zaporozhets, Iryna; Kolomeisky, Anatoly; Clementi, Cecilia
Understanding the intricate molecular mechanisms underlying biological processes is crucial for tackling multiple biomedical challenges. Molecular dynamics serves as a "computational microscope", offering insights into biomolecular processes with unparalleled spatial and temporal resolution. Yet capturing these processes on biologically relevant scales poses significant computational challenges, especially when additional phenomena, such as nuclear quantum effects (NQEs), must be considered. However, many processes of interest can be described by a smaller set of collective variables instead of the intractably large number of degrees of freedom arising in atomistic simulation. The idea behind coarse-graining is to integrate out the irrelevant degrees of freedom and model the target system at a lower resolution while preserving the target properties. This thesis contributes to the development and application of coarse-grained models to increase the computational efficiency of biomolecular simulation and extend the range of molecular processes that can be investigated computationally. First, we applied a structure-based coarse-grained model combined with all-atom simulations to elucidate the helix formation mechanism following the chromophore isomerization in cyanobacteriochrome Slr1393-g3. Our findings indicate a destabilization of the helical state in the 15-Z configuration compared to the 15-E configuration, which has implications for future experimental investigations. This project also highlights the need for improved coarse-grained models. Second, the ODEM optimization framework was used to parameterize protein structure-based models using experimental data. The results suggest that incorporating many-body terms to describe nonbonded interactions is crucial to accurately reproduce the protein thermodynamics. This result underscores the importance of using neural networks' potential in approximating coarse-grained force-fields for future research. Next, a combination of coarse-graining, path integral quantum mechanics, and machine learning was used to develop potentials that incorporate NQEs into all-atom simulation at the cost of classical molecular dynamics. We developed separate models to approximate quantum dynamics and quantum statistics, which demonstrated good performance when applied to test systems. These approaches have the potential to obtain an accurate incorporation of NQEs in biomolecular simulation. Finally, we discuss how the developed approaches contribute to the bigger goal of effective and accurate methods for computational elucidation of biomolecular processes.
Understanding the Mechanisms of DNA Polymerases and Nucleases with Time-Resolved X-ray Crystallography
(2024-04-18) Chang, Caleb; Gao, Yang
Divalent metal ions, especially Mg2+, play pivotal roles in an enzyme’s ability to manipulate the highly stable structure of DNA. DNA and RNA polymerases, as well as numerous nucleases are clear examples of such enzymes, and are integral to critical cellular functions. Thus, these proteins represent important drug targets for various diseases and biotechnological tools for genome editing. Understanding the molecular mechanism of Mg2+-promoted DNA synthesis and cleavage is crucial for engineering and efficiently targeting of these enzymes. Time-resolved X-ray crystallography enables the visualization of catalytic processes and aids in dissecting catalytic molecular mechanisms. This technique tracks active conformations and intermediate states during catalysis by initiating chemical reactions in protein crystals synchronously via light activation or substrate diffusion. In my thesis work, I applied diffusion-based time-resolved crystallography to investigate two representative enzymes: DNA polymerase η, which is a Y-family DNA polymerase that participates during DNA replication to bypass bulky DNA lesions; and I-PpoI endonuclease, which is one-metal dependent His-Me nuclease that has an active site homologous to the HNH active site of the Cas9 nuclease. In elucidating the catalytic mechanism of DNA polymerases, wild-type and mutant variants of DNA polymerase η were generated and analyzed using kinetic assays. Over 100 crystal structures of DNA polymerase η complexed with a wide variety of deoxyribonucleotides, ribonucleotides, and nucleoside analogue drugs were determined with resolutions ranging from 1.4 to 2.8 Å, providing high-resolution visualization of canonical DNA synthesis and polymerase targeting. The structural alignments revealed the essential role of the third divalent metal ion and the dynamics of the primer end, including the sugar ring, correlated to substrate discrimination and efficient chemistry. Similarly, I tracked the reaction process of I-PpoI with kinetic assays and time-resolved crystallography. More than 40 crystal structures of I-PpoI at various pH and metal ion concentrations were determined. The intermediate structures revealed the involvement of one and only one divalent metal ion in DNA hydrolysis. DNA cleavage assays unveiled several possible deprotonation pathways for the nucleophilic water molecule. Importantly, metal ion binding and water deprotonation were found to be highly correlated during catalysis. These results offer mechanistic insights that can be instrumental in enhancing the bioengineering and targeting of polymerases and nucleases.
High-Purity 2D Perovskite Thin Films: Role of Solvent Interactions for Solution-Processed Optoelectronic Materials
(2024-04-18) Khalili Samani, Mohammad Hossein; Marciel, Amanda B
Perovskite solar cells have emerged as a hot topic in recent years with their promise of a cheaper and more efficient alternative to conventional silicon solar cells. While 3D perovskites have demonstrated impressive performance in solar cells, their long-term stability remains to be a challenge. This has led to exploration of 2D perovskites, which offer improved stability due to their unique atomic structure. In this thesis, we address several factors impacting stability, phase purity, and device performance of 2D perovskite systems. Firstly, we present a new synthetic route to produce single n–valued parent crys- tals. The phase selective method involves precrystallization of parent crystals with a single phase structure, that upon dissolution, yield memory seeds for a patterned growth and nucleation of thin films. Our analyses showed the parent crystals are 100% phase pure and resulting thin films have upwards of 90% phase purity with minor undesired n–phases. We monitored the seeds and growth process by dynamic light scattering and optical microscopy techniques, and fabricated devices with high stability and efficiencies (> 17%). Next, we probe the mechanism by which memory seeds interact with processing solvents of varying propertie, including polar, hydrogen bonding, van der Waals inter- actions to deepen our understanding of the dissolution process of phase-pure parent crystals. We leveraged dynamic light scattering, microscopy, and spectroscopy tech- niques to monitor different steps of film formation. Our study demonstrates that solvents exhibiting high propensity for hydrogen bonding and diminished dispersion forces promote the formation of thin films with superior phase purity and the tar- geted out-of-plane orientation. Conversely, solvents with dominant dispersion forces and a diminished capacity for hydrogen bonding lead to the formation of thin films exhibiting poor phase purity, diminished excitonic peak intensities, and an undesired in-plane orientation. Lastly, we increased device efficiency by employing lithium-doped nickel oxide (Li-doped NiOX) as the hole transport layer (HTL). This Li-doped HTL not only improves the physical characteristics of the 2D perovskite film structure, crystal formation, and alignment, but also optimizes the energy levels within the device, leading to efficient charge extraction. Furthermore, the resulting 2D perovskite solar cells with Li-doped NiOX demonstrate excellent stability under light exposure. In summary, this thesis presents works on improving stability, efficiency, and life-time of solar cell devices based on 2D metal halide perovskites. This goal has been achieved by engineering of different steps leading to the device fabrication, such as optimization of crystal synthesis, solvent-perovskite interactions, and transport layer engineering of the device module.
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Engineering chromatin modifiers as biological discovery tools and epigenome editors
(2024-04-19) Goell, Jacob; Hilton, Isaac
Epigenetics is the study of heritable traits driven by alterations in the genome that occur on top of the DNA sequences encoding our genome. These features include histone and DNA modifications, chromatin architecture, and transcription factors that enable the emergence of cell types and a diversity of traits that are responsive to external stimuli. The study of the epigenome has thus been important for understanding basic biology and human disease. Until the emergence of CRISPR/Cas systems for programmable gene/epigenome editing, the field of epigenetics relied heavily on observational studies and genome-wide correlations to reach conclusions on the role epigenetic features play. The rapid adoption of CRISPR-based tools allowed for the targeted modification of DNA and deposition of precise epigenetic modifications through the fusion of chromatin-modifying factors to a catalytically inactivated version of a CRISPR system. While promising in its use for both basic and translational applications, the field still requires improved tools and a better understanding of their function to address inherent toxicity and off-targeting concerns, especially with respect to histone acylation, a modification linked to gene activation. Using the widely adopted epigenome editing effector domain and histone acyltransferase, p300, I address these concerns by (1) engineering mutations into p300 to alter its acylation deposition profile and cytotoxicity and (2) applying multi-omics and functional genomics methods to characterize these effectors for off-targets and benchmark their utility in a non-coding enhancer mapping screen.
Advancing Four-Dimensional Scanning Transmission Electron Microscopy for the Strain Analysis of Deformed Thin Films
(2024-04-19) Mireles, Adan Joel; Han, Yimo
This study presents significant advancements in Four-Dimensional Scanning Transmission Electron Microscopy (4D-STEM) for analyzing strain and crystal orientation in thin films by introducing three novel methods. First, we developed an area-selective filtering technique that leverages unsupervised learning to reduce noise in 4D-STEM datasets. This approach achieved up to a 70% noise reduction for WS2-WSe2 superlattice data. Second, we introduce a strain correction method tailored for buckled two-dimensional materials. Guided by kinematical diffraction simulations, this method produces surface morphology maps that enable surface tilt and strain decoupling. Its application to MoSe2-MoS2 heterojunction data successfully reduced compressive strain measurements from an overestimated 6.5% to a more accurate ~1.5%. Lastly, we present a technique for precisely mapping crystal orientation in thin films. This technique was effectively applied to a gold nanoplate using a combination of 4D-STEM data, abTEM multislice simulations, and electron tomography validation. These advancements significantly improve the accuracy of strain measurements and crystallographic analysis, thereby enhancing our understanding of deformed nanofilms and expanding the capabilities of 4D-STEM for future materials science research.

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