VictorJuiz/thesis huggingface dataset:
Optogenetic Applications in Retinal Glia and Neurons

Optogenetics, the ability to control cells with light, has revolutionized neuroscience by endowing researchers with hyper precise tools which can dissect neural circuits. However, the use of optogenetic effectors is not limited to academic studies on neurons. This dissertation examines two alternative applications of optogenetics: to study glia-neuron interactions and to therapeutically restore light sensitivity to degenerate retinas. In order express these optogenetic effectors, Adeno-Associated Virus (AAV) was used to deliver transgenes./nOver the course of these studies, the ability to specifically target certain types of cells became paramount. Specifically, special AAV capsid variants had to be used in order to transduce Müller glia, the principal glia cell of the retina. The capsid variants, 7m8 and ShH10, are not specific for Müller cells, so different glial promoters were investigated. Two promoters evaluated, GLAST and gfaABC1D, had unexpected expression profiles. Although GLAST is a Müller cell specific protein, the GLAST promoter was unable to restrict transgene expression to Müller glia. However, the smaller the gfaABC1D promoter was able to completely restrict transgene expression to retinal glia in both health and disease./nWith new methods to selectively transduce Müller glia, their role in glutamate uptake was investigated. The electrogenic transporters used to transport glutamate against its concentration gradient require a hyperpolarized membrane potential made possible through high expression of potassium channels. If glutamate uptake was dependent on Müller cell membrane potential, then transient depolarization of the Müller glia should inhibit glutamate uptake. To transiently depolarize Müller cells, they were targeted to express a bistable channelrhodopsin2 (ChR2) mutant (C128S/D156A, “BiChR2”). The effect of BiChR2 induced Müller glia depolarization on the retinal light response was investigated by examining the electroretinogram (ERG). While there were no significant changes to the ON-bipolar cell generated ERG B-wave, subtle temporal changes in arose that should be investigated further./nOptogenetics have a therapeutic potential to restore vision in degenerate retinas. People with late stage retinal degenerative disease lose sight as a consequence of photoreceptor death. However, other retinal cells remain. Endowing the surviving retinal cells with the ability to sense light through optogenetics could restore sight. The effectiveness of optogenetics tools used for vision restoration were analyzed based on their light and temporal sensitivity.

Advisor: Flannery, John G
Broadband mm-Wave Transceivers for Sensing and Communication

Scaling in silicon semiconductor process technology, although driven by digital applications, has also enabled the operation of analog integrated circuits (ICs) at higher and higher frequencies. Over the past 15-20 years, ICs operating at millimeter-wave (mm-Wave), the frequency range between 30 GHz and 300 GHz, have been demonstrated with increasing performance and complexity./nOne important application for mm-Wave ICs has been in automotive radar, where they have been used to make accurate measurements of distance and velocity with minimal processing required. There also has been significant interest in adapting this technology for non-vehicular applications, such as gesture recognition, room occupancy detection, or heart-rate monitoring, where performance and energy efficiency are both important. The first part of this thesis describes a custom IC for gesture recognition radar demonstrating state-of-the-art energy efficiency. The IC consists of four transmitters and four receivers with shared frequency generation circuitry, and is packaged onto a 1.2x1.2cm antenna module containing eight antennas./nThe other key application for mm-Wave technology has been for wireless communication. Products are finally coming to the market now that offer nearly 5 Gigabits per second of wireless data throughput for indoor wireless LAN applications, and mm-Wave technology will likely play a role in the next generation of wireless cellular standards as well. To demonstrate the possibility for yet-higher data rates to be achieved, a broad-bandwidth custom integrated circuit transceiver has been designed targeting a factor of 10 improvement in wireless data throughput beyond commercially available technology. The second half of this thesis will discuss the details of a transceiver and antenna design for broad-bandwidth and high data rate operation.

Advisor: Niknejad, Ali M
Locality in Gravity

The research presented in this dissertation is primarily focused around the study of locality in quantum gravity. The emergence of locality is intimately tied to many important questions in the field, including the emergence of the bulk in the Anti-de Sitter/Conformal Field Theory correspondence, and to holography in more general spacetimes, as well as the contradictions presented in the AMPS argument of the black hole information paradox. In particular, this thesis starts by studying the gauge redundancy related to the observer dependence in quantum gravity as well as its implications in the distribution of gravitational degrees of freedom. This picture is then applied to the black hole information paradox presenting a picture discussing deviations of local effective field theory around the horizon. Following the apparent fundamental role taken by the holographic entanglement proposal in AdS/CFT, I then present a generalization of this proposal to general spacetimes, proving that the appropriate a generalization satisfies the inequalities associated with von Neumann entropy. This picture is then used to study the Hilbert space structure of such theories. In chapter 4, I also present a model that suppressed isocurvature fluctuations present for interesting parameter ranges for axions in high scale inflation scenarios. Finally, the last chapter concludes with the reconstruction of bulk operators in AdS/CFT, where such a reconstruction has no prior knowledge of bulk geometry as a starting point. The result uses intimate connections to quantum error correction and obtains the bulk conformal metric as a byproduct of the construction.

Advisor: Nomura, Yasunori
Evaluation and Design of Robust Neural Network Defenses

Neural networks provide state-of-the-art results for most machine learning tasks. Unfortunately, neural networks are vulnerable to test-time evasion attacks adversarial examples): inputs specifically designed by an adversary to cause a neural network to misclassify them. This makes applying neural networks in security-critical areas concerning./nIn this dissertation, we introduce a general framework for evaluating the robustness of neural network through optimization-based methods. We apply our framework to two different domains, image recognition and automatic speech recognition, and find it provides state-of-the-art results for both. To further demonstrate the power of our methods, we apply our attacks to break 14 defenses that have been proposed to alleviate adversarial examples./nWe then turn to the problem of designing a secure classifier. Given this apparently-fundamental vulnerability of neural networks to adversarial examples, instead of taking an existing classifier and attempting to make it robust, we construct a new classifier which is provably robust by design under a restricted threat model. We consider the domain of malware classification, and construct a neural network classifier that is can not be fooled by an insertion adversary, who can only insert new functionality, and not change existing functionality./nWe hope this dissertation will provide a useful starting point for both evaluating and constructing neural networks robust in the presence of an adversary.

Advisor: Wagner, David
Principles of Tactile Stimulus Integration in the Rodent’s Whisker Somatosensory Cortex

Understanding how cortical circuits process sensory information and support perception is a fundamental problem in neuroscience. Rodents, being tactile experts, actively use their whiskers to sense complex tactile features like surface texture, object shape and location. In this dissertation I address how cortical neurons integrate sensory information from individual whiskers to support accurate and precise representations of complex tactile features./nNatural whisking during tactile exploration generates complex spatiotemporal sequences of whisker stimulation. Objects with different textures and shapes result in different patterns of whisker stimulation, sequentially stimulating different combinations of whiskers across time. I thus hypothesized that individual neurons in primary whisker somatosensory cortex (S1) are sensitive to specific features of tactile sequences. Chapter 2 describes the timescales at which S1 neurons integrated sensory input while rats discriminated between whisker impulse sequences that varied in single-impulse kinematics. While discrimination performance was consistent with integration at a relatively slow timescale (approximately 150ms), most S1 neurons integrated whisker input at a fast timescale (<20ms), generating a precise code for vibrotactile sequences in S1. Neurons with slower integration windows (>60ms) did not accurately represent the stimulus but were instead related to the rat’s behavioral choice. These findings show that S1 neurons encode whisker input at a fast timescale and suggest that areas downstream of S1 temporally integrate this information to guide perceptual discrimination./nGiven the precise representations of tactile sequences in S1, Chapter 3 explores the elementary computations underlying tactile stimulus integration by S1 neurons. Tactile sequences vary in spatial identity of stimulated whiskers and inter-whisker-deflection-intervals (Δt). Dense stimulation of local whisker pairs over a physiological range of Δt revealed a somatopically organized rate code for whisker combinations that was precise in space and coarser in time. Sublinear suppression for suboptimal combinations sharpened tuning relative to that expected from linear integration alone; analogous to the computation of motion direction selectivity in many visual circuits, thus suggesting a common computation for spatiotemporal feature extraction. Taken together, this dissertation shows that S1 neurons integrate sensory input in space and time to generate robust tuning for spatiotemporal features of tactile scenes.

Advisor: Feldman, Daniel E
Knowing Yourself is Something You Do

Why do your self-attributions of beliefs and intentions ordinarily constitute authoritative self-knowledge? You can self-attribute a belief or an intention transparently. For instance, you can transparently self-attribute a belief that p by judging that p. You can transparently self-attribute an intention to Φ by deciding to Φ. However, recognizing just this much does not completely explain the epistemology of transparent self-attributions./nSelf-attributions of this kind count as authoritative knowledge because they involve a form of practical knowledge. You can intentionally control the kind of attitude you take up in conscious thought, and when you do that, you know what kind of attitude you are taking up in conscious thought. Then, in the context of transparent self-attribution of belief or intention, a judgment that p or a decision to Φ can have a complex identity. A judgment that p can also be a self-attribution of a belief that p, and a decision to Φ can also be a self-attribution of an intention to Φ. To explain how this can be the case I introduce the linked notions of embedded mental action and content plurality./nThe view of self-knowledge that emerges also explains why there are contents involving belief attributions that are absurd to assert or to judge even though they can be true. These contents are Moorean absurdities for belief. I argue that there are no corresponding Moorean absurdities for intention, even though you also have transparent self-knowledge of what you intend to do. This points to an important attitudinal distinction between belief and intention: intentions are not beliefs./nThe difference between first-personal and third-personal methods of attributing attitudes is subtle. The specialness of the first-personal perspective cannot be explained in terms of epistemic groundlessness, as many have tried to do. You must also make third- personal groundless attributions of belief to understand others’ intentional behavior./nDespite philosophical skepticism on this point, transparent self-knowledge really is valuable, in a special sense. Having complete diachronic transparent self-knowledge involves having no hidden attitudes and having a diachronically unified self of the kind that is required for evaluation in terms of authenticity./nThe epistemology of self-knowledge relies crucially on the fact that you can do things in thought. Knowing yourself is something you do because intentional action is indispensable to authoritative, knowledgeable self-attribution of beliefs and intentions.

Advisor: Campbell, John
Stroud, Barry
ENGINEERING JUSTICE: CITIES, RACE, AND 21ST CENTURY WASTEWATER INFRASTRUCTURE

Public works across the country are reaching the end of their life-cycle. Water infrastructure systems, particularly those in older cities, are not equipped to deal with population growth nor the potential consequences of climate change. Wastewater planning methods of the past will not sufficiently address environmental degradation or keep up with user demands. As officials look to improve their water infrastructure, scholars are advocating for “soft path” or “Water 4.0” approaches to decentralize infrastructure and management. Calls for greater equity, however, are often absent in uses of these frameworks. Furthermore, scholarship’s focus on the impacts of old and new infrastructure neglects repair as a necessary site for critical engagement. Repair can perpetuate social and spatial inequalities; it is also an opportunity to reimagine and create infrastructure that is environmentally just./nThis dissertation enters this timely junction by asking how responding to environmental justice claims benefits wastewater infrastructure rebuilding in older cities. I investigate this question through an examination of San Francisco’s Sewer System Improvement Program (SSIP), a 20-year, $6.98 billion capital improvement project. Using interviews, original document review, and participant observation, I focus on the years from 2009 to 2017 of five rebuilding phases: project objectives, environmental review, project selection, project implementation/construction, and monitoring and evaluation. I build on environmental justice scholarship that identifies the equity implications of capital improvement plans. I also apply a structural racism lens to highlight the inter-institutional relationships and processes that create racialized outcomes./nI find that the pursuit of racial justice in rebuilding projects reveals cumulative impacts, enhances organizational capacity, involves activating more substantive forms of sustainability, unlocks the anchor potential of public works agencies, and is implicated in gentrification trends. Findings are used to develop a heuristic framework to engineer justice through the consideration of procedural and distributive justice in each phase of planning. This approach to confronting structural racism elucidates the political relationships within which infrastructure is embedded. It also enhances conventional planning and engineering practice.

Advisor: Corburn, Jason
N6-methyladenosine modification and the YTHDF2 reader protein play cell type specific roles in lytic viral gene expression during Kaposi’s sarcoma-associated herpesvirus infection

More than 100 types of RNA modifications are known to exist, regulating key aspects of cellular biology and metabolism. First discovered to be present on viral RNAs in the 1970s, methylation at the N6 position of adenosine (m6A) is the most abundant internal modification within eukaryotic mRNAs, and is proposed to be dynamically regulated during times of cellular stress. However, the transcriptome-wide distribution and function of m6A in the lifecycle of a dsDNA virus had not been explored. In Chapter 1, I review how human herpesviruses manipulate host pathways in order to replicate, with particular emphasis on gammaherpesviruses. I also discuss the diverse roles played by RNA modifications in gene expression, focusing on enzymes that install m6A (writers), and proteins that bind m6A modified mRNA (readers). In Chapter 2, I present a detailed investigation of how the m6A pathway impacts the lifecycle of the oncogenic human virus Kaposi’s sarcoma-associated herpesvirus (KSHV). Mass spectrometry and transcriptome-wide m6A-sequencing revealed enrichment of m6A in viral transcripts upon lytic reactivation, including in the lytic transactivator ORF50. Depletion of the writer METTL3 and reader YTHDF2 in three different KSHV reactivation models had differential pro- and anti-viral impacts on viral gene expression depending on the cell-type analyzed. Finally, in Chapter 3, I put my findings in the broader context of the literature examining m6A modifications in viral lifecycles. I discuss technical challenges that have hindered research to-date, and potential reasons for the diverse pro and anti-viral effects ascribed to the m6A pathway, including a discussion of why the m6A pathway may have cell-type specific effects. I highlight the impact of m6A deposition on host transcripts, including those of the innate immune system. Overall, this study demonstrates the critical importance of m6A modifications in regulating KSHV lytic gene expression and sets the stage for future studies to elucidate more mechanistic details, including the potential for discrete impacts at different stages of the viral lifecycle.

Advisor: Glaunsinger, Britt A
Towards Cooperative SLAM for Low-Cost Biomimetic Robots

Bio-inspired millirobots exhibit unique locomotion modalities that allow them to traverse complex, unstructured terrain that traditional robots cannot./nThis makes them potentially useful in urban search and rescue, structure inspection, environmental monitoring, and surveillance, all of which require some level of situational awareness./nThe low-cost, lightweight design and difficult-to-model dynamics of these robots also create unique challenges when applying state-of-the-art Simultaneous Localization and Mapping (SLAM) approaches usually used to gain this awareness./nIn this thesis, we develop a collection of estimation and control techniques that addresses these challenges, allowing teams of millirobots to localize within and map complex, unstructured environments./nThe analysis covers several facets of the problem, including low-cost millirobot team design, motion modeling, cooperative state estimation, and mapping./nWe first show the utility of disposable low-cost robots in hazardous environments by using teams of “picket” and “observer” robots for exploration./nNext, we explore a data-driven motion modeling approach to approximate the non-linear stochastic dynamics of legged millirobots./nThen we develop an inter-robot pose estimation technique using monocular vision and active markers that can operate in visually feature-poor environments, and can scale to teams of computationally constrained robots./nWe demonstrate this technique first on autonomous underwater vehicles, and then extend it to a team of ground robots cooperatively navigating three-dimensional terrain./nFinally, we explore a simple scanning laser technique that can leverage cooperating robots with cameras to map an environment.

Advisor: Fearing, Ronald S
Flexible Integrated Architectures for Frequency Division Duplex Communication

The explosion in demand for wireless capacity has been a strong driver for cellular network modification. Previous solutions to this problem have involved an increase in available channel spectrum to each user and an increase in bands used for cellular communication. This practice has led to an extremely crowded low-frequency spectrum, where the significant problems now are not processing high bandwidths in a mobile device, but instead managing the interference caused by high-traffic scenarios./nOne of the most challenging instantiations of this interference mitigation problem is Frequency Division Duplex (FDD) communication in the Long Term Evolution (LTE) standard, where a cellular device both transmits and receives information simultaneously, but in separate frequency bands. Globally, there are 40 LTE FDD bands, and in the worst cases, the center-to-center spacing of transmit (TX) and receive (RX) bands is only twice the bandwidth. With 120dB of dynamic range between the TX and RX signals, without significant isolation, the RX is heavily desensitized or even damaged by the high power TX signal. This problem is currently solved with fixed external duplexers, which provide high TX/RX isolation, but at the cost of frequency tunability. Due to the large number of TX/RX frequency band pairings present in the LTE standard globally, using fixed filters for isolation is infeasible if a phone is to operate well internationally./nIn this thesis, a fully-integrated, highly frequency-flexible method for TX self-interference cancellation is proposed, where a mixed-signal canceller is employed at the input of the RX. This technique is shown to allow the receiver to tolerate high TX power levels over a large variety of channel and transceiver nonidealities. The deterministic TX-band interference signal is shown to be mitigated within this system, along with the non-deterministic sources of interference from TX phase noise and canceller thermal noise. Finally, further reduction in TX interference in the digital backend using digital modelling of the PA, canceller, and duplex network is shown.

Advisor: Niknejad, Ali M.
Towards Predictive Medicine — On Remote Monitoring, Privacy and Scientific Bias

The current healthcare model in the United States of America (US) is reactive in nature. That is, individuals usually seek medical attention after symptoms manifest. In 2015, the total cost of healthcare in the US was $3.2 trillion (17.8% of US Gross Domestic Product), which amounts to $9,990 per capita. In the same year, the 30-days all-condition rate of unplanned rehospitalizations in patients in the Medicare fee-for-service program was around 17.9%; and between October 1, 2003 and December 31, 2003, 3.5% of patients in the same program died within 30 days of initial discharge./nAlternatively, a healthcare model that utilizes medical intervention based on personalized predictions of the patient's clinical status and possible deterioration could potentially decrease costs, unplanned rehospitalizations and mortality rates. This model also has the potential to improve the overall quality of care. We refer to this model as the predictive healthcare model./nIn this dissertation, we examine three outstanding challenges towards fully realizing the predictive healthcare model as the prevalent care model. Namely, i) we investigate means to streamline the costly longitudinal epidemiological studies using remote mobile monitoring and introduce the Berkeley Telemonitoring project; ii) we investigate the privacy challenge that is particular to the remote monitoring model and introduce the Private Disclosure of Information (PDI) semantic privacy model; and iii) we investigate the problem of publication bias in empirical sciences (including biomedicine) that hinders the credibility of empirical scientific findings and introduce a statistical test that detects bias in a sample of scientific publications which utilize the Student t-test.

Advisor: Bajcsy, Ruzena