VictorJuiz/thesis huggingface dataset:
Probabilistic inference in the era of large models
Keywords: Engineering.

Recent progression in generative artificial intelligence has witnessed a ballooning in model size and data dimensionality. These large models, however, come with increased computational demands which prohibit the use of many traditional probabilistic inference algorithms. There is a pressing need for new inference algorithms that are efficient enough to run on large models and modern architectures, and powerful enough to work with high dimensionalities and large datasets. In this dissertation, we address this challenge by designing algorithms using ingredients that are compatible with model scale, such as parallelization, amortized inference, and neural function approximations. We present a variety of techniques to improve sampling and inference, leading to faster sample speed, better flexibility of sample queries, and more accurate estimation of inference targets. Our methods are applicable to large models across a range of architectures such as diffusion, autoregressive, and masked-autoencoder models. We demonstrate these findings on applications spanning image and text generation, game-playing, and robotics domains. These insights lead to practical improvements and novel perspectives for efficiently deploying large-scale generative models.
Progress towards cavity-based X-ray free-electron lasers : demonstration of cavity ringdown and microbunch rotation out-coupling
Keywords: Humanities and Sciences.
Applied Physics.

Current X-ray Free-Electron Lasers (XFELs), including the Linac Coherent Light Source (LCLS) at SLAC, are single-pass SASE (self-amplified spontaneous emission) machines, where electrons produce X-rays as they pass through an undulator line just once. The exponential gain of X-ray power in an XFEL occurs as X-rays act on the electron beam, causing it to form microbunches at the X-ray wavelength. In a SASE XFEL, the X-rays which initiate this process come from noise in the beam, and thus X-rays produced by current XFELs are transversely coherent, but longitudinally noisy. In proposed cavity-based XFELs (CBXFELs), by contrast, X-rays are spectrally filtered and returned by mirrors from the end of the undulator line to the beginning, so a strong X-ray pulse is used to seed the FEL process on subsequent passes. Future X-ray light sources based on CBXFELs can thus improve longitudinal coherence and spectral brightness, and promise to be more stable than current XFELs. In this thesis I discuss the requirements to build a CBXFEL cavity and several aspects of CBXFEL development. I cover in detail the characterization of CBXFEL-quality diamond mirrors, two cavity out-coupling methods including active cavity Q-switching and microbunch rotation, and a demonstration of a 14 m Bragg-reflecting cavity.
Proximal proteomics identifies novel subcellular localization and protein-protein interactions in Raf1-dependent cancers and SARS-CoV-2 infection
Keywords: Medicine.

Protein-protein interactions are essential to communication of information within cells. These interactions are altered in response to extracellular stimuli, intracellular differences in the presence of metabolites, and numerous other cell-state differences. Dysregulation of proteoforms and the complexes they form occurs in any disease state and restoring appropriate function to cells requires understanding how these signaling pathways and quaternary protein structures are disrupted. To understand the dependence of various tumors on the Raf-1 protein, proximity proteomics strategies were used. These experiments identified a novel mitochondrial localization of Raf-1 and an interaction with glutaminase. To better understand this localization and novel interaction, experiments that force Raf-1 localization to various compartments are used to decouple its canonical MAPK pathway capability and the novel glutaminase-altering function and further demonstrate its importance for cancer. Beyond tumorigenesis, protein-protein interactions are also critical for viral infection and pathogenesis. To understand these processes, BioID proteomics was performed on 17 SARS-CoV-2 proteins. This work identified several pathways by which SARS-CoV-2 suppressed cellular immunity, novel subcellular localization for some of the SARS-CoV-2 proteins, and points of difference between CoV-2 and other coronaviruses.
Reading and writing neural computation : from silent speech to holographic optogenetics
Keywords: Medicine.

This thesis presents a collaborative and interdisciplinary approach to understanding and manipulating neural computation across species. The work is divided into three main projects, each contributing to the overarching goal of improving human-computer interaction and deepening our understanding of neural dynamics. The first project explores Silent Speech Interfaces (SSIs) as a noninvasive alternative to brain-computer interfaces for soundless verbal communication. This work seeks to improve the performance of SSIs by using novel loss functions and large language models (LLMs) to significantly reduce word error rates in silent speech recognition on an open vocabulary. The development introduces Multimodal Orofacial Neural Audio (MONA) and LLM Integrated Scoring Adjustment (LISA), improving the state- of-the-art word error rate on silent speech from 28.8% to 12.2%. This demonstrates that SSIs are a viable alternative to automatic speech recognition and offers potential communication solutions for people with speech impairments. The second project focuses on translational research in SSIs at the intersection of chemical engineering and machine learning. We introduce a novel surface elec- tromyography (sEMG) sensor system that employs stretchable, sticky conductive polymers for high-fidelity adherence to the skin. In tandem with sensor development, this project also advances the application of high-speed state-space machine learning models for decoding sEMG on a 50-word vocabulary. This dual focus on advanced sensor technology and new machine learning methods opens new avenues for more reliable and human-centered wearable devices for biomedical applications. The third project shifts focus to the bioengineering of transgenic zebrafish to facilitate whole-brain optogenetics and holographic control of neural circuits. Through the creation of stable transgenic lines that express novel optogenetic actuators, this work enables the manipulation and observation of neural activity throughout the entire brain of a larval zebrafish. We also develop statistical and machine learning models to predict and denoise calcium dynamics in neural tissue. This project provides insight into a neural circuit involved in anxiety and depression, offering a new tool to dissect the functional organization of vertebrate brains. Together, these projects make advances in the fields of machine learning, bio- engineering, chemical engineering, and neuroscience in the pursuit of developing new modalities for human-computer interaction. From translational research in silent speech recognition for humans and basic research in neural circuit manipulation in zebrafish, this thesis contributes to the development of novel technologies for interfacing with the nervous system while drawing inspiration from the principles underlying neural computation.
Rewriting the mammalian genome : a user's guide
Keywords: Medicine.

In this dissertation, I embark on an explorative journey to unravel the complexities and unlock the potential of "rewriting the mammalian genome." This odyssey commences with a philosophical reflection on the questions that first inspired me towards this pursuit and an exploration of the current landscape of site-specific engineering technologies, tracing both their origins and evolution (Chapter 1). This is followed by an examination of the successes and challenges I have encountered in trying to apply these tools to "rewrite the mammalian genome" both ex vivo (Chapter 2) and in vivo (Chapter 3). Leveraging insights I have gained from my experience with both approaches, I amalgamate them into something new (Chapter 4). Along the way I also outline hurdles posed by both innate cellular (Chapter 2) and adaptive immune systems (Chapter 5) to "rewriting the mammalian genome" as well as potential avenues to overcome them. Finally, the narrative culminates in a distillation of the work I have performed and the lessons I have learned along the way to outline a comprehensive framework by which I believe "rewriting of the mammalian genome" can be achieved (Chapter 6). The dissertation encapsulates work conducted across various fields, emphasizing the lessons I have learned in my endeavor to "rewrite the mammalian genome." It offers reflections and insights into the complexities, challenges, and triumphs encountered in my quest to push the frontiers of genetic engineering in mammals, charting a course to fully realize the immense potential that "rewriting of the mammalian genome" holds.
RF-ultrasound relay for wireless powering and communication with retinal and brain implants
Keywords: Engineering.
Electrical Engineering.

Next generation neural interfaces including retinal and brain implants have the potential to treat vision loss and neurological disorders. To do so effectively, large arrays of electrical stimulation and recording channels are needed to manipulate and capture electrical activity at cellular resolution. To wirelessly power and communicate with these devices, a couple challenges need to be overcome. First, wireless power must pass through two mediums for retinal and brain implants: air and eye tissue, or skull and brain tissue. Current single modality solutions are limited in either depth or by the interface between the two mediums. Second, recording neural activity over a large array generates a huge data volume that needs to be transmitted from the implant. In this work, we will address these two challenges using a new RF-ultrasound relay architecture. First, to overcome the challenge of transmitting across two mediums, the relay architecture uses a combination of RF and ultrasound to overcome the interface loss and to transmit at depth. New rectifier and power amplifier designs are introduced in a custom CMOS chip to increase the power conversion efficiency from RF to ultrasound, and beamforming is implemented to make it more robust to implant movement. Second, we will introduce an implant compatible high data rate uplink. A 12 Mbps uplink ultrasound MIMO system is presented to handle the data volume from the recording array. The MIMO receiver is integrated onto the CMOS chip and is robust to movement and wireless power. The custom CMOS chip integrates both wireless power and data relaying capability to enable these next generation implants.
Scalable open-air processing of electron transport layers for perovskite solar cells
Keywords: Engineering.
Materials Science and Engineering.

This dissertation explores open-air processing of perovskite solar cells, specifically on the electron transport layer deposited above the perovskite layer. An inorganic titanium dioxide electron transport layer is first explored using an open-air chemical vapor deposition process. The titanium dioxide demonstrates improved mechanical stability and barrier properties against ingress of environmental species. The development of an open-air ultrasonic spray process for the deposition of an organic electron transport bilayer on top of perovskite is presented next. The successful spray deposition and resultant film quality is highly dependent on solvent composition and the inclusion of a near-infrared heating module to accelerate film drying. In addition, the second half of the bilayer is an ultrathin (sub 10 nm) film that requires sophisticated characterization to ensure that the film is of the appropriate thickness and surface morphology. The sprayed organic electron transport bilayer is integrated into perovskite solar cell devices exhibiting high efficiencies > 20%. Finally, the spray process is included in a previously developed cost model resulting in significant manufacturing cost savings.
Seismic signatures of volcanic eruptions
Keywords: Humanities and Sciences.
Physics.

Increases in seismic wave radiation coincident with explosive volcanic eruptions demonstrate that eruptive processes exert forces on the surrounding earth, exciting seismic waves. Studies of seismic radiation from volcanoes have been done to gain insight into internal dynamics that cannot be directly observed. However, traditional seismogram interpretation is nonunique and often ambiguously related to eruptive processes, which limits the amount of information we can learn from the seismic signal. In this dissertation, I develop a theoretical framework to rigorously connect internal fluid dynamics to associated seismic radiation in order to calculate synthetic seismograms from simulated eruptions. Based on this theoretical work, I present the procedure to translate wall shear traction and pressure changes into force and moment histories, which are then convolved with numerical Green's functions to calculate seismograms. This is referenced as the synthetic seismogram calculation workflow. This process allows for direct connection between an eruptive process and its seismic signature. This workflow is one of the first instances of using unsteady conduit flow models to quantitatively study seismicity. I then apply this workflow in the study of potential sources of commonly observed types of seismic signals at volcanic eruptions: very-long-period (VLP) waveforms and incoherent eruptive tremor. I demonstrate that rupture of a magmatic plug and fragmentation of high viscosity magma yield distinct signatures in the VLP frequency band with coincident modulations in mass eruption rate, providing observationally testable predictions. I explore an existing model for eruptive tremor based on particle impacts and turbulence in the upper conduit using steady-state conduit flow models and more rigorous treatment of wave propagation, finding extreme parameter values are required to match observed tremor amplitudes. I present a study of a potential alternative mechanism for eruption tremor due to fluctuating fragmentation, finding that stochastic fluctuations in fragmentation arising from advection of heterogeneous magma yield stochastic seismic signals.
Sensitivity analysis in structured optimization problems methods and applications to power systems models
Keywords: Engineering.
Electrical Engineering.

This work presents developments in differentiable optimization, with applications to the computation of marginal emissions in power system models. First, we discuss how recent results in differentiable optimization can be used readily to compute any emissions sensitivity metric (including marginal emissions) in optimization-based models. Second, we develop a general decentralized scheme for differentiation of graph-structured optimization problems. The methodology is efficient and can be made fully distributed, with convergence guarantees. Finally, we come full circle and illustrate the benefits of the decentralized framework in the computation of marginal emission factors. Using historical data, we demonstrate how the proposed approach allows for efficient computation of marginal emissions in large network models.
A sensory neuron driver circuit in the colon
Keywords: Engineering.
Chemical Engineering.

Within the gastrointestinal (GI) tract resides an entire nervous system devoted to coordinating its function autonomously, and which does not require any instruction from the brain. The enteric nervous system is composed of motor neurons, interneurons, and crucially its own intrinsic sensory neurons. These sensory neurons respond to local stimuli and coordinate movement of contents along the GI tract by instructing motility circuitry to relax and contract the gut. Additionally, in the colon, widespread synchro-nous oscillatory 1-2Hz activation of the ENS occurs at a set pace, every few minutes, resulting in rhythmic contractions all along its length. This motility pattern is called the colonic motor complex (CMC). Though sensory neurons were initially proposed as drivers of CMCs, that theory has long been discounted for a lack of further evidence of sensory neuron interconnectivity, synaptic input, or participation in CMCs. Here, I iden-tify cadherin-6 (Cdh6) as a novel marker of colonic sensory neurons, confirmed by im-munohistochemical, morphological, and electrophysiological methods, including the first recording of IH, a rhythmicity-associated current, in mouse colonic sensory neurons. A homophilic synaptic cell adhesion protein, Cdh6 expression only in sensory neurons suggests the presence of an interconnected sensory neuron network. I then show that optogenetic activation of Cdh6+ sensory neurons is sufficient to evoke CMCs. Finally, I demonstrate that pharmacologic blockade of IH in sensory neurons abolishes spontane-ous CMCs. These results revive a largely abandoned decades old theory of a sensory neuron driver circuit in the colon, and place sensory neurons firmly back in control of the entire ENS, not just local microcircuits.
Soot mitigation potential of multiple injection strategies for fuel-rich combustion in compression-ignition engines
Keywords: Engineering.
Mechanical Engineering.

Conventional direct-injection, compression-ignition (DI/CI) engines operate at overall lean equivalence ratios (Phi < 0.7) to avoid excessive amounts of engine-out soot emissions. In order to overcome this equivalence ratio barrier, while keeping the soot levels low, oxygenated fuels (such as methanol and ethanol) have previously shown promising results in stoichiometric DI/CI combustion strategy. Although these fuels are difficult to autoignite, utilizing thermal barrier coatings on in-cylinder surfaces have resulted in reliable operation at stoichiometric conditions while keeping the soot emissions orders of magnitude below the soot levels for Diesel fuel. Moreover, these developments have enabled the use of DI/CI engines as work-producing, fuel-reforming devices operating at fuel-rich regimes. This work presents original data collected on single-cylinder, low-heat rejection (LHR), direct-injection, compression-ignition engine using ethanol and E85 (a mixture of 85% ethanol and 15% gasoline by volume) in stoichiometric to fuel-rich equivalence ratios. The equivalence ratio sweep data show that ethanol soot concentrations continue to increase up to an equivalence ratio of 1.4 and exhibit a plateau beyond this point. The E85 soot concentration profile shows a similar trend. However, compared to ethanol, the presence of longer chain hydrocarbon components and aromatics in the E85 increases the soot levels dramatically. The experiments in this study focus on investigating soot mitigation potential of multiple injection strategies for ethanol in fuel-rich and E85 in stoichiometric operations. Furthermore, the effects of multiple injection strategies on engine performance and other engine-out emissions in fuel-rich and stoichiometric equivalence ratios are discussed. Experimental findings show that it is possible to mitigate engine-out-soot by at least a factor of two without hindering the engine performance in both fuel-rich and stoichiometric DI/CI operation. In order to be able to interpret the experimental findings, a phenomenological model referred to as Multi-Zone NSL (MZ-NSL) model for DI/CI engines was developed to capture the in-cylinder inhomogeneity and to accommodate multiple injection operating conditions. The model was able to capture the trends of exhaust species and in-cylinder pressure of multiple injection experiments.
Species-specific characteristics of biological processes in development and aging
Keywords: Medicine.
Genetics.

The evolutionary process of speciation divides a population into separate groups, which with time, develop characteristics that differentiate it from each other. Despite this, they contain remnants, whether it be physical characteristics or at the molecular level, which tie them to a common ancestor. These similarities have allowed us to use model organisms to deduce biological phenomena in different species. This is an extremely valuable and important resource, especially for understanding human biology, where the study of certain biological processes, such as early development using human embryos, is ethically prohibited. However, despite the availability of these resources, many of these processes remain understudied. And while species with shorter evolutionary distance often retain more of the same physical features, this does not guarantee that all biological processes function the same. This reminds us to proceed with caution as we make cross-species interpretations. This thesis addresses these issues by interrogating the similarities and differences between species through two different angles. (1) The first is a direct comparison of the same biological process, early pregnancy, in various species. Through this work, we identify and characterize these novel species-specific features. (2) I will also hone in on the biological process of one species to identify how both conserved and species-specific characteristics can change depending on the experimental environment (in vivo and ex vivo) and with aging. To do this, I look at mouse hematopoiesis, blood cell production, identifying these changes throughout the whole organismal life span, starting from development to aging. Both approaches shed a new light on our understanding of what factors underly species specificity and conserved characteristics.