VictorJuiz/thesis huggingface dataset:
Reading at the Opera: Music and Literary Culture in Early Nineteenth-Century Italy

This dissertation emerged out of an archival study of Italian opera libretti published between 1800 and 1835. Many of these libretti, in contrast to their eighteenth-century counterparts, contain lengthy historical introductions, extended scenic descriptions, anthropological footnotes, and even bibliographies, all of which suggest that many operas depended on the absorption of a printed text to inflect or supplement the spectacle onstage. This dissertation thus explores how literature—and, specifically, the act of reading—shaped the composition and early reception of works by Gioachino Rossini, Vincenzo Bellini, Gaetano Donizetti, and their contemporaries. Rather than offering a straightforward comparative study between literary and musical texts, the various chapters track the often elusive ways that literature and music commingle in the consumption of opera by exploring a series of modes through which Italians engaged with their national past. In doing so, the dissertation follows recent, anthropologically inspired studies that have focused on spectatorship, embodiment, and attention. But while these chapters attempt to reconstruct the perceptive filters that educated classes would have brought to the opera, they also reject the historicist fantasy that spectator experience can ever be recovered, arguing instead that great rewards can be found in a sympathetic hearing of music as it appears to us today.

Advisor: Smart, Mary Ann
False Promises: Race, Power, and the Chimera of Indian Assimilation, 1879-1934

False Promises: Race, Power, and the Chimera of Indian Assimilation, 1879-1934, analyzes the punishment of adult Indian women and men at the Carlisle Indian Industrial School (1879-1918) and the Canton Asylum for Insane Indians (1902-1934). While previous boarding school scholarship has focused on the experiences of children, my work finds that as a result of an overlooked policy change, adults eighteen years of age and older, rather than youth, were Carlisle’s demographic majority between 1912-1918. Through an analysis of gendered forms of Indigenous punishment at Carlisle and Canton, this work exposes sites of Indian-white conflict, such as labor and sexuality, that were as integral to the American project of nation-building as was the indoctrination of Indian children in off-reservation boarding schools. By considering two settler institutions alongside one another, I demonstrate punitive connections between those ostensibly distinct facilities, and show how the practice of confining adult Indian people at Carlisle and Canton inaugurated and concretized networks of white racial power in this era./nIn bringing together the fields of Native American history, American studies, and race, gender, and medicine in the Progressive era, my work traces overlapping institutional histories of Native American confinement, punishment, and resistance, and demonstrates patterns of racial prejudice that have ongoing relevance for Indian people in the twenty-first century. This research builds on extant scholarship in Native American history to demonstrate the key role that American institutions played in furthering the subjugation of Indian communities under U.S. settler-colonialism, deputizing white American civilians as the disciplinary agents of Indian people by virtue of proximity to them. This research expands current interpretations of Carlisle as an institution intended solely for the indoctrination of Indian children. Additionally, this work begins to address the neglected history of Indigenous incarceration and elimination at Canton, and the ways in which emergent eugenicist ideologies were operationalized at both of these American facilities. False Promises traces overlapping histories of confinement to reveal how white Americans wielded punishment as a form of racial power held in common over all Indian people, and locates Carlisle and Canton on a historical continuum of policies and practices aimed at the eradication of Indigenous populations.

Advisor: Huhndorf, Shari M
Coronado, Raul
The effect of ubiquitin on protein energy landscapes and consequences for proteasomal degradation

Changes in the cellular environment, such as the hundreds of possible posttranslational modifications, modulate protein energy landscapes to drive important biology, with consequences for signaling, allostery, and other vital processes. The effects of ubiquitination are particularly important because of their potential influence on degradation by the 26S proteasome. Specifically, proteasomal engagement requires unstructured initiation regions that many known proteasome substrates lack. This paradox raises the intriguing possibility that ubiquitin modification itself may induce local or global destabilization, thus revealing the requisite unstructured region for proteasome engagement. However, experimental determination has been hampered by difficulty in producing biophysical quantities of pure, native isopeptide-conjugated ubiquitinated samples. Further, any measured signal must be decoupled between ubiquitin and the substrate protein./nTo assess the energetic effects of ubiquitination and how these manifest at the proteasome, we developed a generalizable strategy to create isopeptide-linked ubiquitin within structured regions of a protein. The effects on the energy landscape vary from negligible to dramatic, depending on the protein and site of ubiquitination. Ubiquitination at sensitive sites destabilizes the native structure and increases the rate of proteasomal degradation. Importantly, in well-folded proteins, ubiquitination can even induce the requisite unstructured regions needed for proteasomal engagement. Our results indicate a biophysical role of site-specific ubiquitination as a potential regulatory strategy for energy-dependent substrate degradation. We further characterize the biophysical mechanism of site-specific destabilization and discover distinct modes of destabilization and stabilizing interactions between ubiquitin and the substrate at different sites.

Advisor: Marqusee, Susan
Cavity Quantum Electrodynamics with a Locally Addressable Quantum Gas

Motivated to develop quantum technologies and to study ever-more complex quantum systems,scientists are developing increasingly sophisticated experimental tools to control and measure quantum samples such as ensembles of ultracold atoms. A high-finesse optical cavity can be used to measure the state of atoms within its photonic mode with precision limited only by quantum uncertainty. Such a cavity can also be used to mediate interactions between different atoms within the cavity mode. High-resolution microscope objectives have been interfaced with ultracold atom experiments to allow researchers to image single atoms within optical lattices, to trap single atoms in microtweezer arrays, and to imprint arbitrary optical patterns onto atomic ensembles. Among other applications, these technologies have allowed researchers to investigate many-body quantum systems, engineer novel interactions, and realize high-fidelity quantum operations./nThis dissertation presents the details of the design, construction, and operation of a new, versatileatomic physics apparatus that combines these two experimental tools. The apparatus includes a high-finesse optical cavity into which atoms are optically transported. In addition, there is a high-numerical-aperture objective aligned to image, with micron-scale resolution, atoms trapped within the center of the optical cavity. We present results demonstrating the capability of this apparatus to deliver and study ultracold atomic samples, ranging from single atoms to Bose-Einstein condensates. We demonstrate a dispersive shift of the cavity resonance due to the presence of atoms in the cavity mode and the trapping and imaging of single atoms in optical microtweezers. We also present an atomic scanning probe microscopy technique with which a single atom in a microtweezer is used to map out the spatial amplitude pattern of an optical cavity mode standing wave by monitoring the position-dependent scattering properties of the atom.

Advisor: Stamper-Kurn, Dan M
A Multi-Study Investigation of Patient Engagement in Psychological Treatment

Patient treatment engagement is a construct composed of two parts: attitudinal engagement and behavioral engagement. Although previous studies have started to demonstrate a relation between treatment engagement and treatment outcome, such research typically has limited long- term follow-up, often focuses on only one treatment or patient population, utilizes varied measures of engagement, and often measures attitudinal or behavioral engagement (but not both). The present study seeks to address these gaps by evaluating treatment engagement across three different interventions and three different patient populations: adults with interepisode bipolar disorder and insomnia (N = 58), adults with depression (N = 48), and adolescents with sleep and circadian problems (N = 176). The first aim was to examine whether attitudinal engagement with treatment—measured as higher credibility/expectancy scores—predicts treatment outcome. The second was to examine whether behavioral engagement with treatment—measured as ratings of adherence by providers—predicts treatment outcome. Results from Study 1 and Study 3 indicate that attitudinal engagement is associated with select measures of treatment outcome. Results from Study 2 suggest that attitudinal engagement is associated with an improvement in symptoms whereas behavioral engagement is associated with improvement in functioning. Overall, results underscore the impact of attitudinal engagement on treatment outcome and highlight important areas for future research.

Advisor: Harvey, Allison G
Statistics, computation, and adaptation in high dimensions

With a focus on designing flexible, tractable, and adaptive methodology for some canonical machine learning tasks, we establish several results for the class of permutation-based models, index models, and Markov reward processes. First, we study permutation-based models in the vector, matrix, and tensor settings, which provide robust representations in "broken-sample" problems and of human-generated data. We design tractable and adaptive methodological solutions for fitting these models that, among other things, narrow statistical computational gaps conjectured in the literature. Second, we study a subclass of index models---widely used in dimensionality reduction and exploratory data analysis---through a computational lens, focusing on avoiding the (statistical) curse of dimensionality and on achieving automatic adaptation to the noise level in the problem. Our perspective yields efficient algorithms for solving these non-convex fitting problems that come with provable guarantees of sample efficiency and adaptation. Finally, we turn to studying some statistical questions in reinforcement learning, focusing in particular on instance-dependent guarantees for the policy evaluation problem. We show that while some algorithms attain the optimal, "local" performance for this problem, other popular methods fall short and must be modified in order to achieve the desired levels of adaptation.

Advisor: Wainwright, Martin J
Courtade, Thomas A
Molecular Sensing and Signaling in Leukocyte-Endothelial Adhesion: From Integrin Activation to Orai Gating

Leukocyte-endothelial adhesion and firm adhesion are chief steps in leukocyte recruitment cascade and immune system response to inflammation. Irregularities in these processes have been related to several human diseases including arthritis, cancer, and atherosclerosis. Given the fundamental importance of integrin activation and Ca2+ signaling in adhesion assembly and strengthening, understanding the molecular mechanisms of kindlin-mediated integrin activation and STIM-mediated Orai gating have potentially important implications in designing new therapeutic interventions. This study employs molecular dynamics and bioinformatic techniques to unravel detailed molecular interactions in these two activation processes./nFirst, we analyzed the effect of kindlin cooperation with talin for integrin activation. Integrins are transmembrane proteins that mediate the signaling between the cytoplasm and extracellular matrix to promote cell adhesion. In order to initiate signaling, integrins must be activated from a low-affinity state to a high-affinity conformation for binding to extracellular molecules. Talin and kindlin are two cytoplasmic proteins that bind to integrin and modulate its affinity for extracellular ligands. Although the molecular details of talin-mediated integrin activation are known, the mechanism of kindlin involvement in this process remains elusive. Here, we carried out, for the first time, a comprehensive molecular dynamics study of integrin activation mediated through simultaneous interaction of talin and kindlin with its b subdomain. We showed that kindlin modifies the molecular mechanisms of inside-out activation by enhancing talin interaction with the membrane proximal region of integrin and decreasing the crossing angle between transmembrane helices of integrin, which eventually results in parallelization of integrin dimer./nSecond, we investigated the molecular details of STIM-Orai interaction and its downstream consequences on the Orai channel gating. The immune response is triggered by a decline in Ca2+ concentration within the endoplasmic reticulum (ER) that is followed by the opening of the calcium release-activated channels (CRAC), thus increasing the intracellular Ca2+ concentration. Stromal interaction molecule (STIM) has been identified as a Ca+2 sensor in the ER activating the CRAC channel via physical interaction with Orai, the pore unit of the CRAC channel. In this study, we showed that the forces from STIM binding allosterically propagate through Orai helices, which lead to opening of the basic region of the pore. Moreover, we demonstrated important interactions that maintain the open structure of the Orai channel./nOverall, this study provides valuable insights into the molecular mechanisms that contribute to the activation of mechanosensitive proteins involved in leukocyte adhesion and firm adhesion.

Advisor: Mofrad, Mohammad RK
Thwarting Sophisticated Enterprise Attacks: Data-Driven Methods and Insights

This dissertation builds new defenses to thwart digital attacks on enterprises. Specifically, we develop a set of data-driven insights and methods that enable organizations to uncover and stymie three prominent enterprise attacks: spearphishing, lateral phishing, and lateral movement. For each of these threats, we present new conceptual models that deconstruct each attack into a set of fundamental actions that an attacker must perform in order to succeed, enabling organizations to more precisely search for signs of such malicious activity. The successful detection systems we construct based on these models highlight the value of decomposing and pursuing attacks along two facets: preventing attackers from gaining entry into an enterprise’s network and hunting for attacker activity within an organization’s internal environment./nEven with a clear specification of what to look for, uncovering sophisticated attacks has long eluded enterprises because such attacks give rise to a detection problem with two challenging constraints: an extreme class imbalance and a lack of ground truth. In particular, targeted enterprise attacks occur at a low rate, reflect the work of stealthy attackers (and thus frequently remain unknown and unlabeled), and transpire amidst a sea of anomalous-but-benign activity that inherently occurs within modern enterprise networks. This setting poses fundamental challenges to traditional machine learning methods, causing them to detect an insufficient number of attacks or produce an intractable volume of false positives. To overcome these challenges, we present a new approach to anomaly detection for security settings, specification-based anomaly detection, which we use to construct new detection algorithms for identifying rare attacks in large, unlabeled datasets./nCombining these algorithms with the attack models we develop, we design and implement a set of detection systems that collectively form a defense-in-depth approach to unearthing and mitigating enterprise attacks. Through collaborations with three large organizations, we validate the efficacy and practicality of our approach. Given the ability of our systems to detect a wide-range of attacks, the low volume of false positives they generate, and the real-world adoption of many of our ideas, this dissertation illustrates the utility and promise of a data-empowered approach to thwarting enterprise attacks.

Advisor: Paxson, Vern
Wagner, David
Non-Canonical Roles and Variants of Core Translation Initiation Factors

Translation initiation has been regarded as a tightly controlled point of commitment for protein synthesis. Dysregulation of the intricate orchestration of the factors responsible for translation initiation has been shown to be a contributing element in cancer progression, neurological disorders, and many more diseases. Throughout this body of work, we aim to better understand specialized translational regulation which can contribute to transcript selection shifts during times of stress and disease. We not only strive to understand novel non-canonical roles of these translation initiation factors, but also appreciate the unique mechanisms of regulation implemented through the diversification of these factors. We highlight an example of these non-canonical roles through the investigation of eukaryotic initiation factor 3 (eIF3) governed repression of FTL translation. We further this work by demonstrating how disruption of this repression is the molecular cause of a subset of hyperferritinemia cases. Additionally, we establish a platform to better understand the diversity of cap binding complexes and their control over the translatome. We focus on a poorly understood eIF4E1 family member, eIF4E3, and assess its consequences on cellular transformation. These projects aim to widen our appreciation and understanding of translation initiation, its regulation, and specialization under fluctuating environmental conditions.

Advisor: Cate, Jamie H
Ingolia, Nicholas T
Bioinspired Adhesives for Fetal Membrane Presealing

Fetal surgery can improve outcomes for severely affected fetuses, but carries a substantial risk of preterm birth. In order to perform surgery on the fetus, surgeons must breach the fetal membranes, a pair of fragile tissues that are susceptible to post-surgical rupture. Here, we sought to develop adhesives to seal this non-healing tissue, decreasing the overall risk of fetal surgery and making it an option for more families. The central challenge of fetal membrane sealing is achieving robust adhesion in a wet environment. In designing our adhesives, we took inspiration from marine mussels. Mussels secrete adhesive plaques rich in the amino acid 3,4- dihydroxyphenylalanine (DOPA) to adhere to diverse underwater surfaces, and we incorporated similar DOPA chemistry into our adhesives. We designed both injectable hydrogel adhesives and supramolecular adhesive patches and measured their adhesive strength and cytocompatibility. The adhesive hydrogels were also studied in a novel rabbit model of fetal membrane presealing. Membrane presealing is a proposed surgical approach in which the delicate fetal membranes are sealed prior to surgical puncture, stabilizing them, reducing the risk of membrane leakage and rupture, and decreasing the overall risk of fetal surgery. In this animal model, our mussel-inspired formulation appeared to be fetotoxic, but with an alternative adhesive, we found that fetal membrane presealing appeared facile and safe for mothers and fetuses. I also sought to understand how our materials interact with human fetal membrane tissues in vitro, and developed protocols to culture these tissues and their cells ex vivo. We used these cultures to analyze the cytocompatibility of our adhesives with clinically relevant primary cells and tissues, and took the initial steps to investigate the potential for a small molecule regenerative drug candidate (dihydrophenonthrolin-4-one-3-carboxylic acid, DPCA) to regenerate human fetal membranes in vitro. In this work, we created novel, mussel-inspired adhesive hydrogels and patches; established the feasibility of fetal membrane presealing in vivo; and developed human fetal membranes as an ex vivo tool for biomaterial-tissue compatibility evaluation.

Advisor: Messersmith, Phillip B
Pinned boundary piezoelectric micromachined ultrasonic transducers (PMUT)

Ultrasound technologies can be applied to a variety of applications, such as medical/nimaging/therapeutics, materials assessment, flow rate measurement and others. Piezoelectric/nmicromachined ultrasonic transducers (PMUTs) have advantages over the traditional bulk/ntransducers in wide bandwidth, small size, and low cost. This work proposes to boost/nPMUT’s acoustic performance further including vibrational amplitude, acoustic pressure and/nelectromechanical coupling by using the pinning boundary structure and to explore various/nnew applications./nThe equivalent circuit model for pinned boundary PMUTs has been developed and validated/nwith simulation results in terms of mode shape and displacement of the piezoelectric/ndiaphragm under the alternative electrical voltage inputs. Prototype devices with pinned/nboundary are then fabricated without adding any fabrication complexity as compared to the/nconventional fabrication process of PMUTs by modifying the mask designs. Fabrication/nlimitation of PMUTs with low resonant frequency is also investigated by fabricating/nprototype chips that operate at a resonant frequency of 338 kHz in air to experimentally detect/nobjects at 22 cm away. Furthermore, testing results show a measured 2.5 times improvement/nin center displacement and 3.3 times improvement in the pressure output as compared with/nthose PMUTs based on the traditional design with clamped boundary. The measured mode/nshape deformation results match well with the analytical and simulation results and a dualelectrode/npinned PMUT structure is proposed to enable a single chip for both transmitting/nand receiving functionality without sacrificing the improved acoustic performance./nIn the area of practical applications, a tilt angle sensing chip based on the PMUT device has/nbeen demonstrated based on the amplitude of signals from the receiver PMUT. It is found/nthat the measured sensing results match well with theoretical predictions with an average/nerror of ±0.7 degree within the tilting range of plate between -8 to 8 degrees. A wireless/npower transfer system is then proposed based on a pinned ring PMUT transmitting array to/nprovide a maximum efficiency of 57% at a focus point 2.7 mm away at a resonant frequency/nof 250 kHz.

Advisor: Lin, Liwei