VictorJuiz/thesis huggingface dataset:
Acousto-optics in thin-film lithium niobate
Keywords: Applied Physics.

Thin-film lithium niobate has opened the doors to new opportunities in integrated acousto-optics. Low-loss, wavelength-scale waveguides enable devices of an unprecedented size and efficiency. In this thesis, I develop a general framework for treating acousto-optic waveguides and design tools for the piezoelectric transducers that drive them. This work culminates in two demonstrations: a collinear acousto-optic modulator in suspended lithium niobate with a record figure-of-merit, and an integrated acousto-optic deflector for on-chip beam-steering in lithium niobate-on-sapphire
Adaptability and regulation of the ubiquitin-proteasome system
Keywords: Biochemistry.

Aging, disease, and environmental stressors are associated with failures in the ubiquitin-proteasome system (UPS), yet a quantitative understanding of how the UPS senses and addresses proteotoxic stressors is lacking. We assessed UPS performance and adaptability in yeast under stressors using quantitative measurements of the proteolytic stress response (PSR), a transcriptional program driven by the protein Rpn4 that expresses the UPS. We found that the UPS productively adapts to different proteotoxic stressors using separate mechanisms. Proteolytic stressors cause Rpn4 stabilization while folding stressors increase RPN4 transcription without increasing UPS demand. We also probed the genome for modulators of the PSR using the reverse genetic method ReporterSeq. We identified several PSR regulators, including thioredoxin reductase (Trr1), which had no known role in UPS regulation. Unlike all known mechanisms for Rpn4 regulation, which regulate Rpn4 levels, we found that Trr1 modulates the molecular activity of Rpn4 and does so in response to oxidative stress. Together, this work reveals the distinct effects of proteotoxic stressors on the UPS and illuminates the genetic landscape through which cells signal it
Adaptable stem cell differentiation in the adult Drosophila intestinal epithelium
Keywords: Developmental Biology.

Adult organs must be able to adapt rapidly to physiological changes including injury and changes to food availability. Resident stem cells replace damaged and dying cells by dividing and differentiating, stimulated by signals emanating from the dying cells themselves. How stem cells precisely tune their differentiation to match division and death rates in real time remains a largely open question. First, I present a novel method for live imaging the adult Drosophila midgut while still intact in the living organism. With this method I am able to monitor in real time the dynamics of stem cell divisions, differentiation, and loss in the midgut. I am able to precisely measure Notch activity over time and find that a threshold level of Notch defines stem cells from their intermediate progenitors, enteroblasts. Second, I find that injury alters differentiation rates and blurs normally distinct features of stem cells, enteroblasts and terminally differentiated enterocytes. I measure rates of Notch activation and deactivation, indicators of where cells are in the differentiation process and find that both are accelerated in injured midguts. Injury raises Notch activity in mitotic stem cells beyond the enteroblast threshold and maintains Notch activity longer in maturing cells. The injury response pathway JAK-STAT appears to play a role in the acceleration of Notch deactivation kinetics and blurring between enteroblast and enterocyte characteristics, suggesting that JAK-STAT plays more of a role in regulating enterocyte maturation than enteroblast specification. Finally, I find that food consumption affects population wide Notch activity levels and excessive activation of insulin signaling might also lead to blurring between stem and enteroblast identities
Adaptive Conservative Local Time-stepping Scheme for Multiphase Flow and Transport In Porous Media
Keywords:  Energy Resources Engineering
School of Earth Energy &amp; Environmental Sciences
multiphase flow and transport
adaptive local time integration
reservoir simulation
Thesis

Accurate and efficient simulation of the fluid flow and transport in the subsurface remains a challenging task. In implicit pressure explicit saturation (IMPES) formulation, the elliptic flow equation is discretized implicitly, whereas the hyperbolic transport equation is explicit. To ensure stability, the latter requires the choice of a sufficiently small timestep size, such that the local Courant-Friedrichs-Lewy (CFL) condition is not violated. This restriction leads to a large number of small global timestep sizes which drives the simulation very expensive. In order to take advantage of the local nature of the CFL condition, many local time-stepping methods were proposed. In this thesis we extend the use of the Adaptive Conservative Time Integration (ACTI) scheme devised by Jenny [1] for applications in reservoir simulation. We eliminate the most expensive step of the original algorithm and describe the details of local timestep size assignment to ensure stability for non-convex non-monotone flux functions. We investigate the performance of the scheme for a number of model problems with various physics including the tracer problem, immiscible two-phase flow in presence of buoyancy and the black oil model. We show that with modified ACTI, the size of the global timestep for explicit update of the transport can be chosen several orders of magnitude larger than that of standard IMPES. As a result, a speed-up of an order of magnitude is achieved in the number of flux and cell updates while maintaining negligible discrepancies in the solution when compared to conventional IMPES.
[1] P. Jenny, Time adaptive conservative finite volume method," Journal of Computational Physics, vol. 403, p. 109067, 2020.
Adaptive Evolution in Cancer Metastasis
Keywords:  Department of Biology
Biology
Cancer
Metastasis
Genetics
Evolution
Thesis

Metastasis is the spread of cancer from primary sites to distant regions of the body, called metastatic sites, and is responsible for nearly 90% of cancer deaths. Nevertheless, there exist few therapeutic options for the treatment of metastatic cancer. Thus, understanding of metastasis is critical to developing new clinical insights and therapeutic options. Cancer and metastasis are evolutionary processes driven at least in part by genetic changes that are generated under drift and selection. Somatic copy number alterations (SCNAs), the most common genetic change in the cancer genome, occur when multiple copies of the genome are gained or lost and have been shown to strongly influence cancer gene expression. While previous studies have predominantly focused on SCNAs and gene expression patterns in primary cancer, fewer studies have investigated their role in metastatic cancer. This study focused on SCNAs and identified gene expression patterns under selection during the process of metastasis, in which the corresponding genes were hypothesized to underlie metastasis. We developed a statistical approach based on the quantitative trait loci sign test, a well-established method to detect selection, to identify SCNAs and gene expression patterns under selection specifically in metastasis. We found 4,588 genes under selection more in metastatic cancer than primary cancer, including SMAD9, PLAC1, TTC28, TSTD3, and SMO. Importantly, we found that the genes under selection more in metastatic cancer than primary cancer were up-enriched for tolerance induction, a process that inhibits the immune system, and down-enriched for opsonization, a process that marks targets of the immune system. This suggests that the evasion of the immune system may be a critical process that allows metastasis to occur. In sum, this study identified candidate driver genes that underlie metastasis. Identifying such driver genes may contribute to the development of new clinical insights and therapeutic options, and ultimately reduce the massive contribution of metastasis to cancer morbidity and mortality.
Adaptive experiments and a rigorous framework for type I error verification and computational experiment design
Keywords: Statistics.

What wouldn't we give for faster access to life-saving drugs, cancer cures, or pandemic-ending vaccines? In recent decades, modern statistics has found something to trade: at the price of additional complexity and the loss of Gaussian behavior of our estimators, we can get faster, more robust, more flexible, and more efficient experiments through the use of adaptive designs. This thesis covers breakthroughs in several areas of adaptive experiment design: (i) (Chapter 2) Novel clinical trial designs and statistical methods in the era of precision medicine. (ii) (Chapter 3) Multi-armed bandit theory, with applications to learning healthcare systems and clinical trials. (iii) (Chapter 4) Bandit and covariate processes, with finite and non-denumerable set of arms. (iv) (Chapter 5) A rigorous framework for simulation-based verification of adaptive design properties
Adaptive games for education: performance and engagement in preschoolers
Keywords:  Symbolic Systems Program
active learning
adaptive games
Department of Psychology
Symbolic Systems Program
Thesis

Active learning—allowing learners to direct their own studies—is a key part of some educational theories and practices but is not well-understood in terms of its underlying mechanisms or effectiveness at different ages. Meanwhile, cognitive psychology studies have found that adults can benefit from being given self-direction in some types of tasks, and school-aged children can also benefit in simplified versions of these paradigms. Here I extend these past studies in two ways: studying younger children, whose metacognitive skills (which likely play a role in effective self-directed learning) are still developing, and using real-world stimuli for which children may have varying degrees of prior knowledge. In this multi-session study, I explore whether an active learning advantage can be found in preschoolers (ages 3-4) using a tablet game that teaches letter and number recognition over a week. I compare performance and engagement in two conditions: active learners are able to control time allocation between letter and number games that adapt to their level of knowledge; control learners follow a standard curriculum with no adaptive game dynamics. Despite the challenges presented by the adaptive curriculum, I find that active learners performed just as well as their peers who followed a standard curriculum.
Adaptivity and efficiency in the design of sequential experiments
Keywords: Electrical Engineering.

Sequential experiments that take place in many practical settings are often characterized by an exploration-exploitation tradeoff that is captured by the multi-armed bandit framework. This framework has been studied extensively in the literature and applied in various application domains including revenue management, service operations, online retail, recommender systems, and healthcare. We study fundamental problems where there are uncertainties about key characteristics governing the sequential experimentation environment, such as the information acquisition process, the payoff structure, and the feedback structure. Furthermore, we design and analyze near-optimal dynamic optimization policies that are adaptive with respect to these characteristics
Advances in data-driven financial econometrics and item response theory : theory and applications
Keywords: Management Science and Engineering.

Although option market is becoming increasingly important, its complex structure and abundant underlying assets make it very difficult to obtain relatively accurate pricing formulas or algorithms. The first part of this thesis focuses on a theoretical stochastic volatility model for option pricing. We propose a continuous-time stochastic volatility model based on an arithmetic Brownian motion: a one-parameter extension of the normal stochastic alpha-beta-rho (SABR) model. Using two generalized Bougerol's identities in the literature, the study shows that proposed model has a closed-form Monte-Carlo simulation scheme and that the transition probability for one special case follows Johnson's SU distribution---a popular heavy-tailed distribution originally proposed without stochastic process. It is argued that the SU distribution serves as an analytically superior alternative to the normal SABR model because the two distributions are empirically similar. The second part of this thesis gives a bias corrected algorithm of the least square Monte Carlo (LSM) algorithm for pricing American options. The traditional LSM estimator contains undesirable look-ahead bias, and the conventional technique of removing it necessitates doubling simulations. We present the leave-one-out LSM (LOOLSM) algorithm for efficiently eliminating look-ahead bias. We also show that look-ahead bias is asymptotically proportional to the regressors-to-simulation paths ratio. Our findings are demonstrated with several option examples, including the multi-asset cases that the LSM algorithm significantly overvalues. The LOOLSM method can be extended to other regression-based algorithms that improve the LSM method. In addition to option pricing, the third part of this thesis studies item response theory (IRT) and its application to foraging data analysis. A fundamental problem in biology is to understand how the differences among components, or variation in function, contribute to collective behavior. To tackle this problem, we first give a new approach to latent trait modeling in IRT, then design corresponding experiments and finally apply IRT to data analysis. We also give detailed explanation and further discussion for experiment results
Advancing access to non-visual graphics : haptic and audio representations of 3D information and data
Keywords: Mechanical Engineering.

Graphical representations are pervasive in Science, Technology, Engineering and Math (STEM) content, often serving as cognitive aids for spatial reasoning tasks. Examples include data charts, 3D models and simulations, physics diagrams, and maps. The vast majority of this content is highly visual and often inaccessible to people who are Blind and Visually Impaired (BVI). Alternative representations are mostly text-based (e.g. image descriptions) or static and difficult to update, produced by skilled specialists (e.g. embossed graphics). The inaccessibility gap is growing as more content moves to a digital format and offers sighted users capabilities for interactive manipulation and exploration. This dissertation aims to increase access to non-textual information for BVI people by investigating representations of spatial information that exploit haptic and/or auditory perception towards supporting enhanced understanding, interaction, and manipulation. I explore these accessibility challenges motivated by two activity domains: 3D design (Part 1) and data visualization on the web (Part 2). In Part 1, I investigate supporting 3D information consumption as well as authoring through the development of a novel 2.5D haptic shape display. This display consists of a grid of 12x24 actuated pins that can render shapes at interactive rates. With this system, I conduct studies to assess haptic object recognition and spatial navigation of large-format layouts. Working with BVI co-designers, I develop interaction techniques to support 3D design tasks, allowing users to create and manipulate models. An evaluation demonstrates how the proposed 3D design workflow enables BVI makers to quickly understand 3D design concepts and apply them in creating their own designs. In Part 2, I investigate increasing the accessibility of data visualizations on the web. With the goal of understanding BVI users' current experiences when accessing data-driven media on the web, I present findings from two studies, an online survey and a remote contextual inquiry. I outline challenges with existing accessible data representations, and discuss compromises users make between the modalities and technology they would prefer for access vs. the practical feasibility of their availability. To address the need for data representations on the web that are updatable and multimodal, I propose an algorithmic approach to generating data narratives, combining textual descriptions and sonification (the mapping of data to non-speech sounds). This approach is driven by co-design workshops with BVI users and principles in auditory perception. An evaluation of this approach demonstrates that data narratives support users in better understanding and gaining insights from auditory graphics compared to the standard representation
Advancing photonic communication and sensing through novel 3D silicon photonic devices
Keywords: Electrical Engineering.

From consumer products to specialized technology, it seems like everybody wants devices that are more powerful and yet smaller at the same time. Reliance on metallic devices and components serves to bottleneck any progress towards achieving both goals. One solution is to incorporate photonic technology and especially photonic crystals (PhCs), taking advantage of the speed, efficiency, and lossless nature of photons. PhCs, specifically three-dimensional (3D) PhCs, offer a promise of complete control over light inside a device through photonic band gap (PBG) confinement. But a big obstacle to integrating 3D PhCs into current processing and architecture is fabrication. Fabricated 3D PhCs (prior to this author's work in 2019) are not developed in a way that is considered silicon-compatible (Si-compatible) - using methodology that would fit into already-established silicon processing methods. Before widespread integration can be realized, a highly-customizable Si-compatible method for developing 3D photonic devices needs to be introduced. This dissertation explores the world of PhCs, offering novel fabrication methods and analyses of 3D silicon PhC devices. Both pure bulk 3D PhC structures and 3D PhC defect devices are examined, using theory and literature to provide a solid foundation and then building upon that foundation with new and innovative designs. The first truly Si-compatible fabrication of a 3D PhC is explored, yielding a wide omnidirectional and complete band gap. Then by introducing intentional defects into the device and still maintaining Si-compatible methodology, this thesis provides an avenue for a breadth of research applications to use 3D PhC defect devices that control light through PBG confinement
Advancing retinal prostheses from two to three dimensions
Keywords: Electrical Engineering.

Advanced age-related macular degeneration (AMD) results in loss of central vision due to the gradual demise of photoreceptors. Currently, no therapy exists for such condition, and the loss of sight is permanent. Subretinal prostheses aim to restore sight via electrical stimulation of the surviving secondary neurons in the retina. This is a rapidly expanding area of research, especially with the boom of neural interfaces in recent years, with many groups focusing on various aspects of such devices. Our group is pursuing a full-system approach, from fabrication of the devices to in-vivo testing and to clinical trials. In our system, silicon photovoltaic pixels convert light into electrical current to stimulate the nearby neurons. Clinical trial of the first version of such implants having 100 µm pixels confirmed safety and feasibility of this approach and demonstrated prosthetic acuity closely matching the sampling limit of such arrays (20/420). Further improvement of visual acuity requires miniaturization of the pixels and faces many challenges. Simply scaling the pixel size down with flat bipolar arrays decreases the penetration depth of the electric field into the tissue, increasing the stimulation threshold beyond the capacity of even the best charge-injection material. To enable smaller pixels, moving from flat electrodes into a three-dimensional configuration helps mitigate these issues. Additionally, with planar junction diodes isolated by deep reactive ion etched (DRIE) trenches, carrier recombination at the pixel side walls may limit the light-to-current efficiency, and growing side-wall oxide results in oxidation-related stress in the Si, especially as pixels scale down. We addressed these limitations by transitioning from planar to vertical junction diodes. In this thesis, I will discuss the limitations on reducing the pixel size and overcoming these limitations by using (1) pillar electrodes, (2) honeycomb electrodes, and (3) vertical junction diodes validated ex-vivo and in-vivo. I present the design and fabrication processes of such devices and also demonstrate the resulting photodiode functionality, electrode performance, retinal integration with 3-D devices in-vivo and electrophysiological responses. This work will enable prostheses with pixels down to 20 µm, which corresponds to visual acuity exceeding 20/100. I conclude by discussing the remaining work toward full utilization of such devices and moving toward single-cell resolution
The age of the perplexed : translating nature and bodies between the Ottoman Empire and Europe, 1650-1730
Keywords: History.

"The Age of the Perplexed: Translating Nature and Bodies between the Ottoman Empire and Europe, 1650-1730" examines scholarly engagements across cultures as a lens onto debates about the relationship between knowledge and uncertainty in the early modern world. It reveals the intertwined stories of religious conflict, natural history, medical authority, and translation which illustrate an important episode of intellectual genealogy fostering the idea of human difference in physical, spiritual, and moral domains. Over the course of their increasing interactions stimulated by religious, diplomatic, commercial, and intellectual agendas, Ottoman and European scholars faced a set of questions that still continues to resonate. Do all human beings have an essential nature? Were human bodies interchangeable in the medical context, or were "Turkish" bodies essentially different both emotionally and physically? Perplexed by the dilemma of understanding one other, both Ottomans and Europeans saw cultural encounters as an opportunity to raise questions about the universality of knowledge and human nature. This project demonstrates the boundaries of what constituted knowledge exchange in an age of early modern globalization and religious turmoil. I approach the question of knowledge exchange from the differing perspectives of a diverse community of Ottoman and European scholars, historians, physicians, natural philosophers, apothecaries, drug traders, preachers, and jurists between Istanbul and Europe. Each of these episodes reveals how efforts to bridge and differentiate distinct human societies were conducted through the medium of translation. Rather than seeing translation as a unidirectional process, this dissertation delineates what made translations successful or contingent failures by explaining how they created new perceptions of nature, human bodies, faith, and uncertainty, both in the Ottoman Empire and Europe. "The Age of the Perplexed" advances scholarship on the history of knowledge and history of early modern science and medicine. While a growing number of Ottoman and European scholars were certain about why having foreign knowledge would make a difference for them, they also realized that knowledge in circulation was too unstable and uncertain to be definitive. Consequently, the rhetoric of uncertainty became a new mode of inquiry and a highly productive strategy; factual and trustworthy knowledge was not necessarily the first intention in cross-cultural scholarly engagements. The knowledge that emerged at the nexus of the Islamic world and Europe, with all of its contradictions and ambiguities, raised critical questions about the limits of human knowledge. Fundamentally, these seventeenth-century conversations offered new possibilities to accommodate anxieties about what it meant to essentialize other societies—the people, their bodies, and their faith.