VictorJuiz/thesis huggingface dataset:
Characterization of Differences in the Forelimb Motor Pools of the RNU Nude Rat

Immunodeficient “nude” rats are widely used for spinal cord injury research despite the lack of neuroanatomy characterization specific to this rat. This research has continued without characterization of the neuroanatomy because, from a neurological perspective, nude rats are assumed to be faithful models for non-immunodeficient rats. This assumption is made despite the neuroendocrine differences associated with nude rats being athymic, as well as other, more subtle differences that have been observed in the spinal column of nude rats. In this study we characterized the motor neuron pools which innervate the forelimb muscles of the RNU-/- nude rat and also investigated the extent to which the motor neuron pools differed in number and localization between RNU-/- nude rats and RNU+/- non-nude rats as a control. Using the tracer Fluoro-Gold, we performed retrograde tracing of four different forelimb muscles as well as behavioral testing. We ultimately found a 16-fold reduction in the number of labeled motor neurons innervating the forelimb muscles of nude rats in comparison to non-nude rats. We were also able to localize the forelimb motor neuron pools of the RNU rats for the first time, which appeared to span a longer range of vertebrae than has previously been described in other rats. These findings of neuroanatomical differences in the RNU-/- rat serve to demonstrate confounding variables that are not currently being accounted for in spinal cord injury research. Further, our characterization data supports the notion that the nude rat may have important differences to the non-nude rat.

Keywords:  Department of Biology
RNU nude rat
retrograde tracing
immunodeficient
forelimb neuroanatomy
motor neuron pools
Fluoro-Gold
Thesis
Advisor: Plant Giles
Luo Liqun
Characterization of Human Invariant Natural Killer T Cell Subset Heterogeneity via High-Dimensional Analysis

Human invariant natural killer T cells (iNKTs) are a set of innate-like lymphocytes that share the properties of both natural killer cells (NKs) and T cells. iNKTs exhibit a variety of different phenotypes and functions, with implications in autoimmunity, transplant tolerance, and the regulation of infections. However, in humans they are rare and not yet characterized adequately. In this thesis, a high-dimensional, data-driven approach was used to provide better clarity between the different iNKT phenotypes and their biomarkers, as well as their major functional population subsets. The data hint at a new combination of conventional and novel markers for these populations. Most saliently, a highly cytotoxic iNKT subset and a pro-inflammatory subset are both identifiable. The identification of these subsets is clinically relevant, as they may correlate with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (HCT).

Keywords:  Department of Biology
Biology
GVHD
aGVHD
iNKT
Transplantation
Tolerance
Autoimmunity
Transplant Tolerance
Thesis
Advisor: Meyer Everett
Jones Patricia
Chien Yueh-Hsiu
Characterization of hydrogel contact lens materials and their interaction with tear film proteins

The human tear film is a thin fluid film that coats the corneal epithelium of the eye, protecting it bacteria and debris. Maintaining a stable tear film is important for ocular health and comfort; issues associated with tear film stability and ocular surface health can result in feelings of dry eye and discomfort. These symptoms are especially common in patients using contact lenses and are the primary cause for contact lens dropout. To better understand some of the factors that may govern contact lens discomfort, this dissertation focuses on fundamental properties of contact lens hydrogel materials, the human tear film, and the interface between the tear film and contact lenses. Firstly, we wanted to better understand the complex chemistries present in various contact lens materials and we developed methods using solid-state NMR to do so. Using this method, we were able to estimate the molecular contributions of major lens components and were also able to estimate the uptake of a tear film protein, lysozyme, within contact lenses in an in vitro setting. The technique ultimately allowed us to demonstrate that a benzotriazole-based UV-blocker found within commercial contact lens materials also functions as an antioxidant and protects protein deposits from oxidation. The second half of this dissertation focuses on tear film stability, which we first studied in the presence of contact lenses. We investigated the effect of protein deposition on contact lenses on the stability of the tear film to understand if discomfort associated with protein deposition could be attributed to a physical instability in the tear film. Protein deposition was found to increase the surface wettability of contact lenses; however, contact lens surface wettability in saline was uncorrelated with fluid film stability in an artificial tear solution due to the interfacial fluid properties of the artificial tear film. Instead, evaporation from contact lenses was a better indication of the tear film stability in this in vitro setting. Finally, because some contact lens discomfort arises from inherent deficiencies in a patient's tear film, we also focused our efforts on the contribution of the mucin layer to tear film stability in the absence of contact lens materials. We found that mucins help contribute to tear film stability by altering the van der Waals forces within the film, giving rise to a disjoining pressure; additionally, in the presence of evaporation, there are thermal and solute gradients that cause surface-tension driven flow (Marangoni flow) which also stabilizes the film. Together, this dissertation sheds light on some of the potential contact lens and tear film factors that have been hypothesized to affect contact lens comfort in patients and introduces new methods to study additional physicochemical factors related to the tear film and contact lens materials.

Keywords: Chemical Engineering.
Advisor: Cegelski Lynette 
Fuller Gerald G.
Swartz James R.
Characterizing and Improving Transient Over-Expression Screens in Maize

Transcription factors (TFs) are key regulators of cell state changes. Understanding the role of different TFs in regulating cell state transitions can deepen knowledge of an organism’s developmental programs. In plants, numerous TFs have been found to play important roles in differentiation pathways (Schoof et al., 2000). Because plants have so many TFs (constituting approximately 10% of all genes) (Gonzalez, 2016), screening the function of each TF is difficult. In this thesis, my objective was to develop a screen that determines Zea mays TF function through ectopic expression of a TF gene in maize protoplasts followed by detecting transcriptome changes using an RNA-Seq readout. I used two genes with known roles in the maize anthocyanin pathway, R and C1, to validate the effectiveness of the screen. Additionally, I miniaturized the screen to permit scalability in future studies. Lastly, I tested the feasibility of a T7 expression system to induce high expression levels sufficient for enabling a pooled screen approach.

Keywords:  Department of Biology
Biology
Maize
Transcription Factors
Screen
Over-expression
T7
Thesis
Advisor: Walbot Virginia
Long Sharon
Characterizing mouse aging organism-wide with RNA-sequencing and single-cell RNA-sequencing

The cellular and molecular damage that defines aging is the single greatest cause of disease and suffering worldwide. Here I describe my initial efforts to unravel these complexities and characterize aging across all major organs and cell types in the mouse, Mus Musculus. This work so far encompasses single-cell RNA-sequencing in young mice, a database termed Tabula Muris, and whole organ RNA-sequencing at 10 ages across the lifespan, with single-cell RNA-sequencing across the lifespan currently underway. Tabula Muris provides a key transcriptomic resource for the field, and the whole organ transcriptomics unveil distinct aging dynamics among organ never before observed. Altogether, it is my hope that these data and findings will accelerate the development of therapies that keep us healthier, longer.

Advisor: Wyss-Coray Anton 
Palmer Theo 
Rando Thomas A.
Characterizing the Pro-Degenerative Functions of Rufy3 and p53 in Axon Degeneration

A key process shaping neurodevelopment is competition between individual axons for limited neurotrophic support. Local deprivation of trophic factors triggers caspase-dependent axon degeneration, which is carried out through apoptotic machinery present in axons. Although some effectors of degeneration have been defined, the complete pathways and molecular mechanisms remain undiscovered. In this project, I looked at two aspects of axon degeneration. First, in looking for potential effectors, I performed a CRISPR knockout screen to identify key effectors necessary for degeneration. I successfully identified Rufy3 as a neuron-specific effector in this caspase-based degeneration pathway, confirming an observation made in a preliminary shRNA screen. Next, I examined the upstream activating role of p53. Seeking to understand the temporal and spatial details of its involvement, I tested the effects of various p53 overexpression constructs on caspase activity. I demonstrated that cytoplasmic function of p53 is important for caspase activity, possibly through an acute mechanism. Taken together, these results provide new insights into the molecular mechanisms of programmed degeneration, a process which may contribute to the underlying pathology of neurodevelopmental disorders and neurodegenerative disease.

Keywords:  Department of Biology
Biology
neurobiology
axon degeneration
trophic deprivation
Rufy3
p53
Thesis
Advisor: Tessier-Lavigne Marc
Hynes Mary
Characterizing the role of NGLY1 and proteasomal inhibition in Nrf3 regulation

Nuclear Factor Erythroid 2 Like (Nrf) transcription factors are a family of cap n’collar factors that regulate several metabolic pathways. Recent research has illustrated Nrf1, a member of this family, as the proteasomal subunit regulator and a potential target for cancer therapeutics. Nrf1 is an endoplasmic reticulum (ER)-bound protein in its glycosylated state, when it has glycosylated asparagine residues, a post-translational modification regulatory mechanism. In its deglycosylated state, however, it localizes to the cytosol or nucleus in the case of proteasomal inhibition. N-glycanase 1 (NGLY1) is the human cytosolic enzyme responsible for cleaving N-glycans (i.e. deglycosylation).
Nrf3 is another member of this family with significant homology to Nrf1, and presumably, comparable glycosylation regulation patterns. While Nrf3’s normal cellular function and target genes are unclear, research implicates Nrf3 in carcinogenesis, but Nrf3’s mechanistic roles in these pathways are unknown. Here we investigate NGLY1’s impact on Nrf3’s cellular processing, localization, and target gene expression. Previous research shows Nrf3 protein of differential molecular weights and subcellular localization dependent upon PNGase F (a bacterial glycan-cleaving amidase) activity, suggesting glycosylated and deglycosylated forms; however, NGLY1’s role as the cellular deglycosylating enzyme in Nrf3 processing and localization has not been established. By inhibiting NGLY1 in breast cancer cell lines (MDA-MB 231) and treating them with a proteasomal inhibitor, carfilzomib, we investigated changes in Nrf3’s subcellular localization in the presence or absence of deglycosylating activity and cellular stress. Additionally, by exposing Ngly1-/- human embryonic kidney (HEK) cells to carfilzomib, we examined Nrf3 processing under the similar conditions.
We find that Nrf3 cleavage from the ER and nuclear localization occur in the presence and absence of NGLY1 activity, but that NGLY1’s deglycosylating activity could be necessary for Nrf3’s activation. and eventual target gene regulation. This insight into Nrf3’s regulation presents Nrf3 activity as an additional substrate of NGLY1, providing potential therapeutic target considerations in relevant cancers.

Keywords:  Department of Biology
Nrf3
NGLY1
glycosylation
carfilzomib
cellular stress
carcinogenesis
cellular biology
Thesis
Advisor: Bertozzi Carolyn
Dixon Scott
Chemical and electrochemical studies to improve homogeneous electrocatalysts

The electricity derived from renewable energy sources (e.g. solar, wind) is intermittent and not perfectly matched with consumer demand. The widespread adoption of these renewable energy sources as a replacement for fossil fuels subsequently depends upon the development of energy storage systems. Homogeneous electrocatalysts are promising energy storage systems as they can mediate the efficient interconversion of electrical and chemical energy in a highly tuneable fashion. In this thesis, various electrochemical and spectroscopic studies have been conducted in order to improve homogeneous electrocatalysts along various metrics of activity (i.e. turnover frequency, overpotential), selectivity (i.e. Faradaic efficiency), and stability. Chapter 1 reviews the electrochemical and spectroscopic techniques used to assess homogeneous electrocatalysts; highlights the key metrics by which electrocatalysts are evaluated; and provides selected examples of homogeneous electroreduction and electrooxidation catalysts relevant to the work presented in this thesis. Chapter 2 examines the reactivity of a cyclopentadienyl Co complex bearing a protonated phenylazopyridine ligand towards proton, hydride, and hydrogen atom transfer. Chapter 3 uses Co K-edge X-ray absorption spectroscopy (XAS), extended X-ray absorption fine structure (EXAFS), density functional theory (DFT), and time-dependent DFT methods to investigate the effect that various bidentate ligands have on the electrochemical and protonation properties of cyclopentadienyl Co complexes. Chapter 4 uses Mn K-edge XAS, Mn-Kβ X-ray emission spectroscopy (XES), and DFT to understand the impact that redox active ligands have on the electrochemical properties and speciation of Mn tricarbonyl complexes. Chapter 5 examines the ability of an electrochemically regenerable hydrogen atom transfer reagent to lower the overpotential of electrocatalytic alcohol oxidation. Chapter 6 investigates the use of an Fe-based acceptorless alcohol dehydrogenation catalyst for the electrooxidation of alcohols. Chapter 7 examines the factors that mediate demographic performance gaps and the impact that various pedagogical changes have had on student performance in the introductory chemistry sequence.

Keywords: Chemistry.
Advisor: Waymouth Robert M. 
Xia Yan
Zare Richard N.
Chemistry and mass spectrometry for protein structure determination in living cells

Protein structures speed discovery of life's molecular basis, but the artificial conditions of our structural techniques often disrupt natural protein behaviors. This could be sidestepped by chemically crosslinking adjacent residues together while a protein is still in its native cell. The protein could then be extracted and digested into mass spec--amenable peptides so the crosslinks can be seen by high-throughput mass spec. This would make a list of residue adjacencies useful to common structure determination software. Unfortunately, easily detectable crosslinkers are long and therefore vague about just how adjacent crosslinked residues are. This is because they facilitate detection by incorporating bulky moieties with distinctive behaviors during mass spec and purifiable tags. We show that a mass spec behavior ideal for crosslink detection can be encoded in a single well-placed atom in the crosslink. We also purify crosslinked peptides without adding anything to the crosslinker by inventing a method that isolates molecules with two peptidic N-termini. This frees us up to design crosslinking agents uncompromisingly tailored for high-resolution results. We synthesize these designs and investigate their utility.

Keywords: Biochemistry.
Advisor: Harbury Pehr 
Das Rhiju
Elias Joshua
Li Lingyin
Children, Childhood, and Neighborhoods in a Japanese Suburb: Toward Implications for Children’s Neighborhoods from Post-Humanist Perspectives

This paper aims to unpack processes through which children’s neighborhoods are constructed in a Japanese suburb. In this endeavor, I do not take for granted childhood which is often placed on developmentalism or regarded as a human embodiment of the future. Rather, in examining the forming processes of children’s neighborhoods, I pay particular attention to the relationality between children’s neighborhoods and childhood while contextualizing and denaturalizing childhood from post-humanist perspectives. The analysis based on an ethnographic data shows how the spatially, temporally, and socially intertwined separation between children and the general public and among children and parents dominantly takes place in the neighborhood while their integration also occurs to a limited extent. I contend that this dominant separation is prompted by the hegemony of childhood and the accompanying structures both of which are (re)produced within constant negotiation in the age of uncertainty. Further, with regard to that childhood, I showcase three modalities—the vulnerable child, the troublesome child, and the child-parent relationship—as significant aspects to shape children’s neighborhoods. This separation would, in turn, reinforce the hegemony of childhood and those structures, further (re)producing and maintaining itself. However, this separation is not a static phenomenon. Rather, since it is caused by dynamic and multilevel processes, it contains variances, particularly in a practical term. This variability produces a room that the integration instead takes place. Hence, in a Japanese suburb, children’s neighborhoods consist of the dominant separation and the limited integration both of which are the results of dynamic and complex negotiation processes revolving around childhood.

Keywords:  Stanford Global Studies
childhood studies
the modern family
neighborhood
suburb
Japan
post-humanism
Thesis
Advisor: Inoue Miyako
Chilnualna : numerology, speech orchestration, and natural sound

This dissertation consists of five musical works composed at Stanford University between 2014 and 2019. (1) Aux Imagistes II: Wide Arc -- Low in the Northern Sky (2016), String Octet, Ca. 13 min. Written for the JACK and Spektral Quartets; (2) Six Silver Rings of (((Aquamarine))) (2017), Flute, Clarinet, Electric Guitar, Percussion, Violin, Viola, Violoncello, Ca. 5 min. Written for Distractfold; (3) Songbird (2018), String Quartet and Birdsong (Tape), Ca. 10 min. Written for the JACK Quartet; (4) Linguaglossa (2018), Vocal Sextet, Narration, Film, Ca. 16 min. Written for Ekmeles Vocal Ensemble; (5) Chilnualna (2019), Two Voices, Natural Sound, Chamber Orchestra, Ca. 14 min. Written for Ensemble Dal Niente. In the following sections, I will outline the practices employed within individual pieces and sketch a broader trajectory spanning these works. Although beginning as poetic etudes in mimesis, my music becomes oriented towards a deeper introspective journey, in which each piece is understood as a pathway to self-discovery.

Keywords: Music.
Advisor: Applebaum Mark
Ferneyhough Brian
Ulman Erik
China's Belt and Road Initiative: The Malaysian Dilemma

The Malaysian Dilemma presents the case of a small, middle-income country’s engagement with China through the Belt and Road Initiative (BRI). While the BRI’s global reach and ambitions have drawn attention to the potential risks and benefits of Chinese investment, this thesis aims to study one partner country’s perspective through an analysis of the political economic logic and decision-making calculus of its top leaders. Malaysia provides an instructive case, with the leadership transition between Prime Ministers from Najib Razak to Mahathir Mohamad that catalyzed the evolution of the BRI locally. This opportunity for the Malaysian government to reshape its BRI involvement is evaluated through three in depth case studies: the high-profile East Coast Rail Link (ECRL), and the Melaka and Kuantan ports. The Malaysian government’s subsequent renegotiations and cancellations of BRI projects reflect the balancing of complex interests and opportunities for small states to advance their agenda through political maneuvering. Based on the analysis of Malaysian political economic logic surrounding these cases, further avenues for research and policy recommendations are proposed to address key BRI challenges surrounding good governance, transparency and sustainable development.

Keywords:  Stanford Global Studies
Stanford Global Studies
East Asian Studies
Belt and Road Initiative
China
Malaysia
East Coast Rail Link
Melaka Port
Kuantan Port
Policy
Political Science
Thesis
Advisor: Oi Jean
Choral orientations : spatial cognition and geopoetics in Pindar, Bacchylides, and Simonides

Cognition theory describes the human experience of space as dynamic both in terms of the many scales at which we perceive places and landmarks, and in terms of the many orientations through which we organize locations and distances within such scales. This is also the case for the presentation of space in late choral poetry. Such dynamism may be detected in the songs' construction of and interplay between different orientations within the visual and local scales of experience. Respecting the dynamic, network-bound nature of real experience and memory is part of what made this celebratory and occasional poetry appealing and believable to diverse audiences. "Choral Orientations" provides a critical method to support future work both on larger, regional spaces, and on multiscalar and multimodal narratives.

Keywords: Classics.
Advisor: Martin Richard P. 
Peponi Anastasia-Erasmia 
Shanks Michael
Chow groups and characteristic numbers on the space of complete quadrics

It is well-known that there are 3264 conics in P^2 that are tangent to 5 general smooth quadrics. This result can be proved by taking a suitable space that parametrizes conics in P^2 and computing C^5, where C is the divisor corresponding to the condition of being tangent to a general conic. To answer similar enumerative questions about quadrics in P^n, we use the space of complete n-quadrics, X_n. In this thesis we will give a brief overview of the equivalent ways of defining this space, determine ranks and generators of its Chow groups, and describe how one would use intersection theory on this space to compute the answers to enumerative problems involving hitting and tangency conditions.

Keywords: Mathematics.
Advisor: Vakil Ravi 
Kemeny Michael
Larson Eric
Circle method and the subconvexity problem

Munshi demonstrated the usefulness of the circle method in understanding the subconvexity problem, by exhibiting a subconvexity bound for GL3 automorphic forms twisted by a Dirichlet character. We take this idea further by exhibiting a subconvexity bound for GL2 X GL2 Rankin-Selberg L-functions using the circle method. We exhibit a subconvexity bound for the Rankin-Selberg L- functions in the level aspect when both the automorphic forms are varying independently (i.e the arithmetic conductors don't have a large common factor). We beat the best-known exponent for this problem using the circle method. We also use a different version of the circle method to exhibit a subconvexity bound in t-aspect.

Keywords: Mathematics.
Advisor: Soundararajan Kannan
Bump Daniel
Fox Jacob