VictorJuiz/thesis huggingface dataset:
Glucose-6-phosphate dehydrogenase in health and disease and a therapeutic strategy for glucose-6-phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, is critical for a variety of cellular processes and mutations in the G6PD gene can cause G6PD deficiency -- a genetic trait present in ~300-500 million people worldwide. Currently, G6PD deficiency is most known for causing hemolytic anemia; however, it has been associated with other chronic disorders and there are no therapeutics for G6PD deficiency. Here, the role of G6PD in health and disease, past treatment strategies, and potential pharmacological pathways and drug targets are discussed. The lack of therapeutics and drug discovery efforts for G6PD deficiency motivated our lab to conduct a high throughput screen where we identified a small molecule activator of G6PD, which works by stabilizing the structural NADP+ and dimer. My work aimed to understand how loss of structural NADP+ binding affected the homo-oligomeric properties and function of G6PD and whether oligomer stabilization could be used as a therapeutic strategy for G6PD deficiency. Here, I found that loss of structural NADP+ induces structural changes in the G6PD dimer, which prevents tetramer formation. By introducing non-native cysteines at the oligomeric interfaces of G6PD, I found that the tetramer is the more active and stable form of wild type G6PD. Furthermore, I found that stabilization of the dimer and tetramer improved activity for select G6PD variants and that favoring the tetramer stabilized the enzyme to a greater extent than the dimer. Since enzyme activity and stability are major determinants of pathogenicity, my study suggests a small molecule which stabilizes the tetramer may be beneficial for treatment of G6PD deficiency related disorders and encourages the pursuit of such novel compounds. Foreseeable challenges and future research directions pertaining to these findings conclude my dissertation

Keywords: Chemical and Systems Biology.
Advisor: Mochly-Rosen Daria
Chen James Kenneth
Jarosz Daniel
Wakatsuki Soichi
A goal-driven approach to systems neuroscience

Humans and animals exhibit a range of interesting behaviors in dynamic environments, and it is unclear how our brains actively reformat this dense sensory information to enable these behaviors. Experimental neuroscience is undergoing a revolution in its ability to record and manipulate hundreds to thousands of neurons while an animal is performing a complex behavior. As these paradigms enable unprecedented access to the brain, a natural question that arises is how to distill these data into interpretable insights about how neural circuits give rise to intelligent behaviors. The classical approach in systems neuroscience has been to ascribe well-defined operations to individual neurons and provide a description of how these operations combine to produce a circuit-level theory of neural computations. While this approach has had some success for small-scale recordings with simple stimuli, designed to probe a particular circuit computation, often times these ultimately lead to disparate descriptions of the same system across stimuli. Perhaps more strikingly, many response profiles of neurons are difficult to succinctly describe in words, suggesting that new approaches are needed in light of these experimental observations. In this thesis, we offer a different definition of interpretability that we show has promise in yielding unified structural and functional models of neural circuits, and describes the evolutionary constraints that give rise to the response properties of the neural population, including those that have previously been difficult to describe individually. Specifically, our approach is to "reverse engineer" neural circuits by simulating the evolutionary process to build in-silico neural networks that are subject to the combined interaction of three types of constraints: the "task", expressed as an objective function to be maximized or minimized given a data stream; the network "architecture", expressed as the connections through which inputs flow; and the "learning rule", expressed as synaptic weight updates. This joint set of constraints is an interpretable hypothesis for the evolutionary design principles that enable a biological circuit to perform its computations, and crucially, the set of combinations of these constraints gives rise to multiple hypotheses that will be quantitatively evaluated against high-throughput neural and behavioral recordings. We demonstrate the utility of this framework across multiple brain areas and species to study the roles of recurrent processing in the primate ventral visual pathway; mouse visual processing; heterogeneity in rodent medial entorhinal cortex; and facilitating biological learning

Advisor: Ganguli Surya
Yamins Daniel
Baccus Stephen A.
Druckmann Shaul
Sussillo David
Goldi-ox : mixing metals and valences in halide perovskites

Throughout my PhD, I have explored and expanded the vast and diverse class of metal-halide perovskites. These extended semiconducting solids can be prepared by aqueous syntheses at near-ambient temperatures and offer myriad applications, the most prominent of which is as high-efficiency solar absorbers in photovoltaic cells. My work has focused on understanding and controlling the optical and electronic effects of combining different metals and distinct oxidation states of the same metal in both known and novel halide perovskites. The perovskite Cs2AgBiBr6 represents one promising nontoxic alternative to the toxic Pb-based perovskites, such as (CH3NH3)PbI3, but it has a large bandgap energy that makes it impractical for use as a high-efficiency single-junction solar absorber. I showed that mixing Sn into Cs2AgBiBr6 reduced the bandgap in a fully nontoxic composition. Using a host of experimental techniques complemented by calculations, I uncovered the structural, electronic, and optical consequences of the complex mechanism of Sn substitution in Cs2AgBiBr6. This study demonstrated the ability to tune the electronic structure of perovskites by mixing metals in a nontoxic composition, opening the door to a wider diversity of methods to manipulate the electronic structures of perovskites. I expanded the family of halide perovskites by discovering and characterizing the new family of gold-cage perovskites, an unprecedented structure with no known analog. This structure, with the general formula Cs8AuIII4MIIIX23 (M = In3+, Sb3+, Bi3+; X = Cl-, Br-, I-), combines zero- and three-dimensional sublattices and features ordering of the homovalent Au3+ and M3+ metals, a rare phenomenon only observed in one other halide perovskite. Furthermore, I demonstrated that the visible light absorption could be tuned across a wide range by changing the M3+ metal and by mixing in Au1+. This work added a new member to the impressive array of halide-perovskite structures and demonstrated tunability of the electronic structure, thereby helping to solidify the promise of studying unique perovskite structures. I further diversified halide perovskites with new structure types that stabilize unusual oxidation states of metals in well-defined mixed-valence solids that are stable to ambient conditions. In addition to rigorously confirming the oxidation state assignments using a slew of characterization techniques, I investigated the optical, electronic transport, and magnetic properties of these unique perovskites. This work expands the small family of mixed-valence 3D halide perovskites to bolster the promise of novel perovskite architectures to incorporate new metals and metals with unusual oxidation states

Keywords: Chemistry.
Advisor: Karunadasa Hemamala
Chidsey Christopher E. D. (Christopher Elisha Dunn)
Kanan Matthew William
Graph algorithms for systems design

Graphs are a powerful tool for data and system representation. Many types of complex and highly structured data can be represented using graphs, such as social networks, computer networks, and molecules. Graphs can also be used to represent computer systems, such as distributed storage networks and peer-to-peer communication networks. In this dissertation, we discuss approaches to processing graph data at scale and using graphs to design better systems. We first discuss two methods of processing graph data at scale. While they are extremely powerful, graph datasets pose unique challenges for their processing and storage. Graph Neural Networks (GNNs) are an effective method of applying deep learning to graph structured data. However, training GNNs can be extremely expensive to compute because of the interconnected and highly structured nature of graphs. We study methods for hierarchical aggregation, an approach to improving the efficiency of training GNNs. Another approach to understanding graph datasets is to examine frequencies of small, repeated patterns, called motifs. We propose the Temporal Activity State Block Model, an efficient analytical model for computing expected motif frequencies in temporal graphs, which have the added complexity of edges arriving over large timespans. We next cover two methods of applying graphs to design better systems. In a distributed storage system, it is often necessary to store data with redundancy in case a server fails, and the design of where and how frequently to create such redundancy can be represented as a graph problem. Fractional repetition (FR) codes are an approach to this designed to maximize storage capacity while ensuring failed nodes can be replaced by sending replacement data from the surviving nodes. We present load-balanced fractional repetition codes which are a strengthening of FR codes with additional guarantees about how efficiently failed nodes can be replaced. We next consider the problem of sending messages efficiently in a peer-to-peer network. The problem can be characterized by a graph representing which peers have data that another peer wants. Index coding is a method for designing efficient communication from a central server to a set of receivers. We adapt this approach to the peer-to-peer model and introduce and study embedded index coding

Advisor: Leskovec Jurij
Wootters Mary
Charikar Moses
Gut microbial metabolism of specialized compounds from dietary plants

Plants are prolific chemists and synthesize a plethora of compounds with diverse bioactivities. We encounter these specialized molecules with every meal through the consumption of plant-based foods. While a diet rich in plants has been shown through epidemiological studies to be protective against chronic diseases like diabetes and cardiovascular disease, the molecular components of plants responsible for these benefits are still unknown. A major challenge in assessing the health impacts of these compounds is identification of the relevant metabolites that result from their digestion. Just as plants are experts at building complex molecules, gut microbiota are specialists in breaking them down. The gut microbiome has enormous capacity for metabolism and has been shown to metabolize a variety of plant compounds. Here, we describe our efforts towards elucidating the metabolic fates of bioactive compounds from dietary plants following consumption, as mediated by the gut microbiome. We began our studies with cruciferous vegetables, such as cabbage and broccoli. Cruciferous plants produce glucosinolates that can be metabolized by gut bacteria to generate cancer-preventive isothiocyanates. We established the genetic and biochemical basis for activation of glucosinolates by a common human symbiont Bacteroides thetaiotaomicron. Using a genome-wide screen, we identified a gene cluster responsible for isothiocyanate production and demonstrated the importance of these genes in determining host exposure to isothiocyanates. We next turned to Solanaceous plants like potato and tomato. We found steroidal alkaloid aglycones, derived from glycosides made in the plant, to be one of the major classes of compounds that accumulate in systemic circulation following tomato and potato consumption. Furthermore, we showed that host exposure to these compounds is gated by gut microbial metabolism, which is responsible for removing sugar side chain from these molecules and modifying the aglycone core. By surveying metabolism of steroidal glycoalkaloids by intestinal bacteria from human donors, we discovered significant inter-individual variation in the products formed, and a screen of human commensals enabled us to identify specific bacterial strains involved. Finally, we performed preliminary in vitro bioactivity assays and metabolomics analyses with human samples to explore the relevance and effects of this metabolism on host physiology. Taken together, we demonstrate two examples of dietarily abundant plant molecules whose bioactivities and bioavailability are mediated by intestinal microbiota. These studies highlight that, from a common dietary plant input, the gut microbiome can impact divergent health outcomes in the host

Keywords: Chemical Engineering.
Advisor: Sattely Elizabeth
Dodd Dylan
Khosla Chaitan
Hafnium oxide based ferroelectric materials for memory applications

Innovations of memory technologies are essential for addressing the future needs of data processing and storage. The discovery of ferroelectricity in hafnia (HfO2)-based materials has led the re-emergence of ferroelectric memories in advanced semiconductor technologies, with the potential to reshape the technology landscape and to enable novel computing architectures. Ferroelectric HfO2 is promising for non-volatile memories (NVM) due to its ability to scale down to ultra-thin films and very small device dimensions. However, challenges are still present for implementation of ferroelectric HfO2 in commercial products developed for embedded memories, including limited programming cycle endurance and compatibility with the back-end-of-line (BEOL) processing temperature. This dissertation presents innovations at the material and device levels to realize high endurance and low thermal budget ferroelectric memories, followed by advanced material characterizations to probe the mechanisms behind. First, I will demonstrate an experimental investigation of ferroelectricity in CeO2 doped Hf0.5Zr0.5O2 (HZO) thin films.1 I will present an analysis encompassing measurements of switchable polarization, cycling endurance, stress-induced leakage current (SILC) and photoelectric effects to provide a comprehensive understanding of CeO2 doping effects on the conduction mechanism and reliability of CeO2-doped HZO polarization switching. Second, I will report an investigation of the crystal structure of ferroelectric HZO films as a function of atomic layer deposition (ALD) temperature. Our results suggests that optimization of HZO thin film synthesis defined by the ALD deposition temperature not only produces films with the highest ferroelectric polarization, but can achieve this at the low thermal budgets necessary for incorporation of ferroelectric HZO in BEOL devices

Keywords: Electrical Engineering.
Advisor: McIntyre Paul Cameron
Nishi Yoshio
Wong Hon-Sum Philip
Hard and Soft Propaganda: Marketing Autocracy in Contemporary China

Current scholarship has identified distinct styles of propaganda produced by the Chinese government. Huang (2015) describes “hard” propaganda as propaganda designed to signal state capacity rather than persuade; by contrast, Yang (2013) illustrates how “soft” propaganda advances narratives of everyday heroism to deflect from structural critique. However, literature on hard and soft propaganda remains bifurcated, even as both styles rapidly alternate in the Chinese information environment. My thesis offers the first empirical study of hard and soft propaganda, investigating whether distinct styles of propaganda produce different effects, whether propaganda variants interact with one another, and how this might contribute to autocratic resilience. I conduct an original survey experiment with over 650 mainland Chinese participants, who are treated with hard and/or soft propaganda based on the Three Child Policy. I find that citizens are significantly more likely to share and enjoy soft propaganda, and less likely to identify it as “political propaganda” in comparison to hard propaganda. Both hard and soft propaganda encourage citizens to seek redress through official channels, while soft propaganda also stirs an entrepreneurial response. Though hard and soft propaganda create political backlash, exposure to both varieties also makes it more difficult for participants to identify soft propaganda as political propaganda, and easier for participants to identify hard propaganda as political propaganda. I conclude that hard and soft propaganda result in distinct effects, and that a diverse informational strategy may reinforce autocracy over time.

Keywords: Propaganda
Propaganda, Chinese
China
Three Child Policy
One Child Policy
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Thesis
Advisor: Pan Jennifer
Hardware-efficient designs for quantum error correction

Quantum error correction (QEC) protects the quantum information against various dissipation processes. The experimental implementation of QEC is still challenging, despite significant efforts and progress in recent years. For example, the standard qubit-based QEC requires a large overhead in the qubit counts with a high hardware complexity. In this dissertation, I will present three works towards more hardware-efficient realizations of QEC. First, I will talk about an experiment on the quantum parametric oscillator, where the generated cat states are potentially useful as bosonic qubits. Next, I will propose a Floquet qubit design in superconducting circuits that has a mechanical analog of Kapitza's pendulum. The qubit subspace is protected autonomously with an engineered cooling process. Finally, I will describe a numerical framework for automatically discovering autonomous QEC schemes

Keywords: Applied Physics.
Advisor: Safavi-Naeini Amir H.
Mabuchi Hideo
Schleier-Smith Monika
Have low interest rates affected the contribution decisions of public pension funds in the United States?

Low interest rates increase the liabilities of public pension funds by raising the costs of paying fixed future benefits. In response to this it is expected that contributions would increase. In this paper, it is found that public pension funds in the United States are not accounting for interest rates when making contribution decisions. Instead, it seems as though the duration of the pension fund liabilities on which zero coupon treasury yield curve rates are calculated is of greater importance. Public pension funds are seemingly concerned relatively more by the length of their amortization period to catch up on missed contributions, with increases in contributions occurring for low durations and decreases in contributions occurring for high durations.

Keywords: Public pensions, Interest rates, Pension contributions, Duration of pension liabilities
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Thesis
Advisor: Rauh Joshua D.
HE ĀNUENUE PIʻO I LUNA O KOʻOLAUPOKO: Ethnography of Koʻolaupoko as a Native Hawaiian Cultural Complex of Resilience

Measuring the health, vibrance, and the body politic of Indigenous communities is a task best approached by nuance and complexity. This paper strategically envisions pathways of Native Hawaiian resilience and revival through the community, identity, tradition, and landmarks of the district of Koʻolaupoko on the Eastern side of Oʻahu, a place where settler colonialism, development, and Indigeneity come into conflict with one another. This paper fortifies and campaigns for the assessment and value of Indigenous community and cultural health via the vibrance of ancestral pathways. These pathways manifest as links between two physical spaces, humans and natural phenomena, ancestors and grandchildren, heavens and earth, spirits and materials. This paper shows that pathways continue to thrive and be reawakened by Native Hawaiians who inhabit these lands through physical presence, genealogical connection, and participation in local lineages of Indigenous knowledge.

Keywords: Indigenous peoples > Civil rights
Native Hawaiians
Native language and education
Indigenous peoples
Oahu
Hawaii > Kailua (Oahu)
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Thesis
Advisor: Ebron Paulla
Heavy Minerals from barite-rich sandstone beds in the Mapepe Formation, Barberton Greenstone Belt, South Africa

Heavy mineral deposits in the Fig Tree Group Mapepe Formation in the Barberton Greenstone Belt are composed largely of detrital barite sand but also contain detrital chromite and zircon. This study presents geochemical chromite data, primarily Cr# (Cr/(Cr+AL))*100, and geochronological zircon data and compare these with published and unpublished data from source rock areas. Cr# data from source rock areas suggest aeolian processes could have transported grains prior to Fig Tree Group time. Mapepe Formation detrital zircons and chromites combined suggest these barite sandstones sourced chromite grains mainly from Onverwacht Group Mendon and Kromberg Formation komatiitic flows and zircon grains from Hooggenoeg Formation felsic rocks (H6), and that uplift was able to erode 3-4 km into underlying rock.

Keywords: Byerly, Benjamin L.
Africa > Barberton Greenstone Belt (Eswatini and South Africa)
Chromite
Zircon
Komatiite
Africa > Fig Tree Group (Eswatini and South Africa)
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Thesis
Here to stay : queer homemaking in German literature, 1980-2000

This dissertation considers portrayals and practices of homemaking in queer German literary writing from the 1980s and 1990s. I term this genre the 'literature of partial discrimination', referring to legal changes in 1968/69 that partially decriminalised consensual sex between adult men and thus changed their status as citizens. In the fictionalised, semi-autobiographical texts that are the focus of my study, establishing a home -- often, but not always, within a domestic space -- emerges as crucial to the formation of queer identity. The queer literary corpus uncovers some of the affective, emotional and subjective elements of queer life and experience that are elided from the public histories of homosexuality that have constituted much of the scholarly work in the field. Chapter one reads two texts by Ronald M Schernikau -- kleinstadtnovelle (1980) and so schön (1999) -- arguing that they offer a queer utopian blueprint for non-heteronormative homemaking in West Berlin. Chapter two is situated on the other side of the Berlin Wall and examines Ulrich Berkes' Eine schlimme Liebe (1987); here I argue that Berkes' text is a quiet but radical call for acceptance of queerness in the German Democratic Republic. Chapter three remains East and reads three texts exploring queer female embodiment and desire: Waldtraut Lewin's Dich hat Amor gewiß... (1983), Gabriele Eckart's Der Seidelstein (1986) and Sonja Voß-Scharfenberg's Abseits (1990). These texts show the potentiality for queer female homemaking but also the very real constraints on these practices, constraints engendered by the patriarchal hegemonic nature of both private and public spheres in East Germany. This dissertation reads these literary works in their socio-historic context, and argues that literature as historical source material has the potential to disrupt dominant historiographies of post-war Germany

Keywords: German Studies.
Advisor: Daub Adrian 
Eshel Amir
Starkey Kathryn