VictorJuiz/thesis huggingface dataset:
Understanding material limits for encapsulated combo sensor design and fabrication [electronic resource]
Keywords: Mechanical Engineering.

Due to growing demand in the consumer space, there has been a push to create combo sensors and to reduce overall chip size. The 'epi-seal' process, developed by Robert Bosch GmBH and Stanford University, enables wafer-scale packaging of devices in an environment that has shown no long-term aging effects, using a thin-film encapsulation that results in the smallest reported package size. In order for this process to become truly viable for co-fabrication of sensors with different design constraints, we made several process modifications to produce sensors with high-sensitivity but low cross-sensitivity between different environmental factors. To prove this concept, we co-fabricate X/Y and Z-axis accelerometers, a pressure sensor, and resonant thermometer, where cross-sensitivity is improved by more than 700x; remaining cross-sensitivities can then be compensated based on real-time measurements from other sensors. In order for sensors to scale down and sustain sensitivity performance, I examine two material limits that can be prohibitive to sensor miniaturization: stiction and fatigue. Stiction studies with as-fabricated epi-seal devices reveal adhesion forces between contacting surfaces that are asperity-dominated and on average 35 μN. In order to overcome this force, I investigate several dynamic anti-stiction methods that lead to effective stiction forces being reduced by over 60%. Fatigue studies using high-displacement resonators fabricated in the epi-seal process were performed to observe any potential aging effects in single-crystal silicon. In contrast to literature, long-term (> 10^10 cycles) fatigue experiments with these devices showed no signs of fatigue damage up to 7.5 GPa. A cross-comparison with these literature results reveals that fatigue can indeed be prevented, only with atomically smooth side-walled devices that are fabricated in a packaging technology that prevents stress corrosion.
Understanding the Language of Genomes through Taxonomic Classification of Protein Domain Architectures
Keywords:  Department of Biology
Biology
Domain Architecture
Protein Sequence
Protein Structure
Structural Genomics
Thesis

The protein universe, or the set of all proteins of all biological organisms on earth, is vast, rapidly growing, and largely uncharacterized. To better study the millions of proteins that have been sequenced, we utilize domain architectures, which annotate proteins with sequence profiles that correlate with structural domains. If proteins are considered to be the language of a genome, we can think of sequence profiles as “words” and domain architectures with more than one sequence profile as “sentences” (Scaiewicz & Levitt, 2015). This linguistic analogy allows us to use text classifiers to classify proteins into taxonomic groups or kingdoms. We built three text classifiers: (1) dependent only on word content of a domain architecture and based off Naïve Bayes, (2) dependent only on word order in a domain architecture and based off Markov chains, and (3) a combination of the first two. We found that Archaea and Viruses performed better with the order-independent classifier (1), indicating that their vocabulary is the defining feature of their language. Eukaryotes and Prokaryotes performed better using the combination method (3), showing that word order (a very simple grammar) also plays a role in their languages. We found significant relationships between fraction of unique words and sentences in a language to the ability to predict that language. The relationship was linear between unique sentences and prediction ability but logarithmic between unique words and prediction ability. Kingdoms of Life (Eukaryotes, Prokaryotes, Viruses and Archaea) occupied the horizontal portion of the logarithmic curve that approached perfect prediction, but plants also were on that part of the curve (between Archaea and Viruses), establishing the vocabulary of plants as almost as distinct as that of a kingdom. Language analysis on proteins has assisted in identifying trends in a vast, poorly understood, but very important area of science.
Understanding the role of histone H3 lysine 36 methylation in chromatin regulation and cancer [electronic resource]
Keywords: Biology.

Methylation of histone H3 at lysine 36 (H3K36) is found at gene bodies of actively transcribed genes, but the state of methylation at this residue defines distinct biological outcomes. Trimethylation of this site (H3K36me3), which is mediated by the KMT SETD2 in humans, is involved in regulation of RNA processing. Loss of SETD2 and H3K36me3 is a recurring phenomenon in clear cell renal cell carcinoma (ccRCC) and other cancers, suggesting a tumor suppressor role for SETD2. In contrast, the specific molecular functions associated with H3K36me2 are unclear. However, elevated levels of this modification lead to aberrant activation of normally silenced genes, and upregulation of this mark is linked with numerous cancer types including acute myeloid leukemia, multiple myeloma, lung cancers, breast cancers, and glioblastomas. Given their clear implications for opposing roles in disease, it is important to understand the molecular functions of H3K36me2 and H3K36me3 in both their normal physiological roles and disease states. In my thesis, I first compare the roles of H3K36me2 and H3K36me3 in the regulation of actively transcribed genes. Using analyses of RNA-seq datasets from cells depleted of each modification, I show H3K36me3, but not H3K36me2, plays an important role in regulating gene expression and splicing processes. Then, I characterize the effects of H3.3 K36M, an oncohistone, on global regulation of H3K36 methylation. I demonstrate that this mutation depletes not only H3K36me3 (as previously reported) but also H3K36me2, and that the K36M mutant mimics loss of H3K36me2 alone in proliferation assays. Assaying H3K27me3 levels under H3K36 depletion indicates that the crosstalk between H3K27 and K3K36 methylation is largely mediated by H3K36me2, not me3 as previously assumed. This work points to an important role of H3K36me2, not just H3K36me3, in the dysregulation of chromatin modifications mediated by the H3.3 K36M oncohistone. Lastly, I identify the first reader for the H3K36me2 modification. I show that a PWWP domain on the NSD2 protein preferentially binds to H3K36me2. This PWWP-H3K36me2 interaction seems to be important for the stability of NSD2 at chromatin, as well as its ability to increase global H3K36me2 levels in cells and promote cell proliferation. Based on these data, I propose a model for H3K36me2 propagation by NSD2 sensing its own catalytic product and spreading it through chromatin regions.
Understanding the role of intestinal immunoglobulin A in utilization of a dietary polysaccharide by the model gut symbiont bacteroides thetaiotaomicron VPI-5482 [electronic resource]
Keywords: Microbiology and Immunology.

Intestinal IgA is one of the major host factors that shapes our gut microbiota composition and functionality. However, the actual mechanisms involved in the IgA-commensal interaction remain understudied. Our current work uses a model gut commensal, Bacteroides thetaiotaomicron VPI-5482 (Bt), in a gnotobiotic mouse model system to identify Bt antigens that prime a specific gut IgA response. Our study shows that the gut IgA targets a diverse set of bacterial proteins involved in a variety of functions that are thought to be important for bacterial colonization, survival and competition in the host intestine. Our IgA screen identified Bt proteins involved in utilization of dietary fructans that allow Bt to thrive in the gut lumen, when fructans are present in the host diet. Specifically, we identified the outer membrane machinery (OMM) involved in degradation and uptake of β2-6 fructans to be an active target of specific IgA. Biochemical and genetic analysis of this operon in closely related Bacteroides thetaiotaomicron strains demonstrated that the genes encoding the OMM determines fructan specificity, and thus the type of fructan that is utilized by a given organism. Further, comparative genomic analysis of the fructan utilization loci in closely related Bacteroides spp., revealed that the OMM is variably conserved. Using gene transfer experiments we were able to establish that the OMM acts as functional unit that can be transferred among closely related Bacteroides, which allows gain of a new specificity by the recipient organism. Our study further demonstrated that the OMM determines bacterial competitiveness in the gut in presence of specific fructans. Inquiry into the role of IgA in targeting this OMM demonstrated that specific IgA causes reduced expression of the fructan operon in presence of dietary fructans. We propose that this mechanism should allow the host to prevent bacterial overgrowth in presence of specific fructans. Our study thus highlights a novel mechanism by which the host regulates the growth of gut commensals, and could serve as an important pathway to control the gut microbial composition in the wake of dietary disturbances. Further our study also demonstrated that the natural, polyreactive IgA secreted in the mouse gut showed weak binding to Bt antigens. Analysis of the fructan operon expression in presence of this natural IgA indicated that the operon was upregulated in the early stages of bacterial colonization, even in absence of specific fructans. We propose that the natural IgA acts as a cue for Bt to non-specifically upregulate its nutrient utilization pathways in order to compete in the high bacterial density environment that it normally faces in a conventional host gut. Our current works sheds new light on the mechanism by which the gut IgA controls bacterial functionality in the gut lumen in order to maintain gut homeostasis.
Unhousing in Marilynne Robinson's Housekeeping
Keywords:  Department of English
Stanford University
Department of English
English
Marilynne Robinson
Housekeeping
house
escape
American
gothic novel
second wave feminism
20th century
20th century literature
feminist literature
female author
house
domesticity
domestic sphere
cult of domesticity
Thesis

This thesis analyzes Marilynne Robinson's first novel, Housekeeping, as both a new American gothic novel and a feminist text. Through the function and trajectory of the house in the novel, Housekeeping borrows from the gothic tradition. However, through the ultimate destruction of the physical structure and the metaphysical sense of home, this novel's female characters achieve a level of freedom not granted in the gothic tradition. This thesis proposes that by destabilizing traditional understandings of domesticity, Robinson imagines a possible escape for the woman trapped in the house and breaks the societal bind between women and the domestic sphere.
Universal dipolar scattering and spin-orbit coupling in ultracold gases of dysprosium [electronic resource]
Keywords: Applied Physics.

Ultracold atomic gases are powerful systems for studying and simulating quantum phenomena, and the magnetic lanthanide atom dysprosium is a promising atom for new areas of quantum simulation owing in part to its large magnetic moment, large spin, and variety of optical transitions. This thesis presents several studies with ultracold dysprosium. We have charac- terized both elastic and inelastic scattering properties of dysprosium. In bosonic dys- prosium we measured the s-wave scattering lengths via cross-dimensional relaxation and directly imaged the dipolar differential cross section. In fermionic dysprosium we have cooled identical fermions to quantum degeneracy via elastic dipolar collisions. We have also measured inelastic dipolar collision rates in bosonic and fermionic dys- prosium with excellent agreement with rates predicted under the first Born approxi- mation, revealing universal scattering behavior. In particular, we demonstrated the fermionic suppression of inelastic dipolar collisions. Finally, we have shown dyspro- sium to be a promising candidate for fermionic spin-orbit coupling studies due to gas lifetimes as long as 400 ms.
Unselfing interpreted [electronic resource] [electronic resource] : altered states and the ethics of insight from Valéry to Khatibi
Keywords: French and Italian.

Altered states of selfhood pervade French and Francophone literature in the twentieth century, from Henri Michaux's mescaline experiments in Paris, to Yolande Mukagasana's harrowing hallucinations during the Rwandan genocide, to Abdelkebir Khatibi's mystical union with the bilingual lover in Morocco. Both desirable experiences (sexual ecstasy, religious experience, and drug-induced visions) and undesirable ones (debilitating thirst, traumatic pain, and incapacitating fear) are recounted in the same phenomenological mode. This dissertation theorizes unselfing -- self-transcendence or self-loss -- in order to undertake the new work of analyzing these diverse accounts together under the same philosophical structure. If we think of Saul's transformation into Paul as a canonical example of the conversion model for unselfing, this project analyzes four other models that emerge in the twentieth century: disruption (Chapter One: Paul Valéry and Charlotte Delbo), mutation (Chapter Two: Henri Michaux and Yolande Mukagasana), fragmentation (Chapter Three: Hélène Cixous and Abdelkebir Khatibi), and destruction (Chapter Four: Georges Bataille and Simone Weil). Studying self-inflicted altered states alongside imposed ones exposes the unexpected convergences in the narrative strategies that writers use to testify to the extremes of the human experience. Moreover, this study offers a new perspective on the limits of empathy. It shows that there is more to altruism than reduced self-interest, and although unselfing may facilitate the sharing of mental states, it does not necessarily increase caring for others. What emerges is a constellation of French-speaking writers who attempt to think through ethics without the self at the center.
"An unusual accommodation" [electronic resource] : affect, reason, and relationality in black humor
Keywords: Education.

An Unusual Accommodation advances a theory of black political humor that deviates from established and under-contested interpretations of black comedic response to racial oppression. With attention to the affective, logical, and relational dimensions of humor, this study challenges the premise that black humor proceeding from and attending to conditions of racial subjugation must be enacted as a cathartic exercise in grief and rage; as a counter-narrative clarifying the utter absurdity and illogic of racism; or as a ritual of antagonistic counter-objectification. Looking to comedic film, literature, and stand-up performance, this dissertation instead proposes a "Humor of Unusual Accommodation" which finds black humorists approaching anti-blackness in subtle, riskily unusual ways. More specifically, the sense of humor observed among the black cultural producers of this study is animated by non-cathartic affects like curiosity, which conjures amusement toward and amidst the troubles of black social and political life, maintaining a critical emotive distance that stops just short of resigned and yielding apathy but avoids the presumed cathartic affects of black rage and grief. This sense of humor also derives from an agonistic pluralism whereby the legitimacy of white anti-black logics and ideological grammars are acknowledged alongside the legitimacy of directly opposing (pro-)black views, and the plurality of legitimacy is itself a rich source of comedy. In that the subjects/objects among and against whom racial ideologies are expressed or carried out are positioned in highly consequential, power-inflected relationships, the Humor of Unusual Accommodation also privileges an adversarial relation, a positionality that does not recuperate or reverse the subject/object positions of whiteness and blackness nor feigns a systemic leveling of the dynamics of racial power, but it does allow for shared oppositional laughter in an unironic "face-to-face" relation. Closely reading texts like Toni Morrison's Sula, the stand-up comedy of Dave Chappelle, Chris Rock, and Dominique Witten, and the sly humor lacing jazz genius Sun Ra's Space is the Place, this dissertation and the comedic objects explored therein hazard a set of political lessons that, despite their precarious proximity to surrender, ultimately offer a viable method of comedic coping amid the inevitabilities of racial struggle.
The US health insurance market after the Affordable Care Act [electronic resource]
Keywords: Economics.

The recent nation-wide health reform --- Patient Protection and Affordable Care Act, or simply ACA --- drastically altered the functioning of the health insurance industry in the US, opening many questions about how the system should be designed and regulated. While previous literature largely focused on health insurance provided through public programs or employer-sponsored insurance, in this dissertation I study the health coverage provision for outsiders: the twenty-one percent of the US population who as of 2013 were not offered insurance through their job, were not covered by the government, and yet did not purchase coverage in the so-called individual market. After the ACA, market institutions were largely redesigned with attention to this group, and policymakers are still dealing with great uncertainty about the efficacy of the new system and its costs for taxpayers in future years. In this context, my research advances our knowledge in two directions. On the one hand I provide empirical results of immediate policy relevance; on the other, I develop economic and statistical models to be used in this novel institutional environment. I consider three of the main channels through which, since 2014, the government affects the individual market for health insurance. First, state authorities determine how the geography of the state is divided in the local geographic markets in which insurers can participate and compete. Second, the ACA limits premium adjustments based on age or other observable characteristics of buyers. Third, the Federal government provides a large premium subsidy for all buyers whose income is between 133 and 400% of the Federal povery level. My dissertation contains three chapters, each of them analyzing the interaction of these three policies with the incentives of private health insurers.
Using CRISPR/Cas9 and human haploid genetic screens to identify host factors essential for dengue virus infection [electronic resource]
Keywords: Microbiology and Immunology.

Dengue virus (DENV) is an emerging pathogen worldwide, causing an estimated 100 million symptomatic infections annually, yet recent large clinical trials for a DENV vaccine candidate have showed only partial protection. Additionally, no licensed antiviral drugs are available, motivating our approach to evaluate host functions to accelerate development of antiviral therapies. We applied tools for unbiased discovery of host functions exploited by DENV to replicate and spread by performing two genome-scale knockout screens in parallel: one using CRISPR/Cas9 mutagenesis and one using gene trap mutagenesis in haploid human cells. We identified distinct ER-associated multi-protein complexes, which are critically required for DENV infection involved in protein translocation, N-linked glycosylation, and ER associated degradation. We observed that DENV replication was almost completely eliminated in cells deficient in the oligosaccharyltransferase (OST) complex. Additionally, other Flaviviruses, particularly Yellow Fever Virus, West Nile Virus and Zika Virus, also showed partial dependence on the OST complex. Our studies of the interaction mechanism between these Flaviviruses and the OST complex revealed that viral RNA replication was the critical step dependent on the OST complex possibly through interactions with viral nonstructural proteins. Entry or translation of the virus did not require the OST complex. We created catalytic dead mutants and found that dengue virus replication was efficiently rescued in knockout cells. Thus, we reveal a function of the OST in viral replication that is independent from its cellular function in N-linked glycosylation. This striking feature of the OST complex establishes it as a host target for antiviral drug development and targeting the OST complex will result in a higher barrier of resistance compared to drugs targeting viral proteins.
Using Growth Factors to Treat Chronic Tympanic Membrane Perforation in a Mouse Model
Keywords:  Department of Biology
Biology
Growth Factors
Hb-EGF
EGF
FGF-2
Tympanic Membrane Perforation
Thesis

Hearing loss can occur at any age, and is caused by a multitude of factors. One common source of conductive hearing loss is due to the rupture or perforation of the eardrum. Such perforations of the eardrum [or tympanic membrane (TM)] are caused by trauma or disease and can be classified as either acute or chronic. Acute perforations are temporary and can heal spontaneously, whereas chronic perforations may require surgical intervention (usually a grafting procedure called a tympanoplasty) to repair. A non-surgical treatment for chronic TM perforation would benefit those unable to access surgery and would reduce the cost. Previous work using nonsurgical growth factor treatments has involved the use of epidermal growth factor (EGF) or fibroblast growth factor 2 (FGF-2) to reinitiate wound healing in the TM. However, results from these studies are difficult to interpret since the experiments used acute TM perforations, which tend to heal spontaneously. Here, we explore whether heparin binding epidermal growth factor like growth factor (HB-EGF) heals chronic TM perforations with greater efficacy than FGF-2 and EGF in a validated mouse model of chronic tympanic membrane perforation. To test this, we surgically created chronic perforations in the mouse tympanic membrane and administered the above growth factors via an injectable hydrogel polymer. Relative TM closure was observed macroscopically and histologically over a three-month period. HB-EGF showed to be significantly more effective in closing chronic TM perforations over EGF and FGF-2. The healing rates of the TMs after treatment compared to control were 83.3% with HB-EGF, 15.8% with EGF, 31.6% with FGF-2 and 27.8% with control (no growth factor). An effective nonsurgical treatment, such as use of applied growth factors for chronic TM perforations, would provide a safer and cost-effective alternative for those unable to have surgery.