VictorJuiz/thesis huggingface dataset:
A synthetic batrachotoxin derivative as a novel molecular probe to study slow inactivation in voltage-gated sodium channels
Keywords: Chemistry.

Voltage-gated sodium channels (NaVs) are obligatory transmembrane proteins responsible for electrical signaling in biology. By transitioning between different conformational states, NaVs initiate the rising phase of the action potential. A large array of neurotoxins target specific conformational states of the channel or disrupt transitions between them. Among the most powerful of these pharmacological tools is batrachotoxin (BTX), the active ingredient in poison-tipped darts used by the indigenous people of Colombia. Every measurable aspect of channel function is disrupted when this potent small molecule binds in the NaV central pore. Using de novo synthesis, we sought to perform structure-activity relationship (SAR) studies to uncover the molecular underpinnings of the action of this potent toxin. SAR studies focused on derivatizing the C20-ester of BTX. Synthetic toxin analogues were characterized using whole-cell voltage clamp electrophysiology. Using this technique, the efficacy of BTX against a recombinantly expressed single channel isoform was measured for the first time. The ester derivatives show comparable ability to the natural product in their ability to hyperpolarize NaV activation potential, indicating changes to this region of the molecule are tolerated. A BTX derivative having a conformationally flexible ester, BTX-yne, uniquely alters NaV inactivation. With the exception of BTX-yne, BTX and all synthetic ester derivatives completely eliminate both fast and slow inactivation, distinct mechanisms that regulate NaV availability. In contrast, BTX-yne selectively eliminates fast inactivation while allowing channels to undergo slow inactivation. Electrophysiology experiments with rNaV1.4 and a prokaryotic sodium channel, NaVAe, were performed to fully characterize the behavior of this novel pharmacological tool compound. A novel sodium channel mutant, rNaV1.4 A438K, that is incapable of fast inactivation was characterized. The behavior of unmodified A438K resembles that of wild-type channels modified by BTX-yne, demonstrating that slow inactivation can be studied without the influence of fast inactivation with small molecules and mutant NaVs. The experiments in this thesis lay the groundwork for future work to understand the molecular elements underlying the dynamic conformational rearrangements that underlie channel gating.
System-driven circuit design for ADC-based wireline data links
Keywords: Electrical Engineering.

In the era of connectivity, wireline I/O has been a key technology underpinning the aggressive performance improvements of computer and communication systems. All standards, ranging from electrical to optical, long haul to short reach interconnects, have increased their aggregate bandwidth at a rate of about 2x every 4 years. This trend drives the usage of multi-level modulation schemes, such as PAM4. As a result, ADC-DSP based links are gaining more attention and are now heavily investigated. ADC links also take advantage of the intrinsic bandwidth and area improvements from process technology scaling. It is becoming very difficult for conventional mixed-signal links to meet the bandwidth and performance requirements of next-gen systems. As equalization is moved into the digital domain for ADC-based links, the ADC needs to be very fast, have reasonably high resolution and yet be very power efficient. Consequently, these stringent requirements pose significant challenges in both ADC links' architecture and circuit design. In this thesis, we focus on a statistical framework for understanding ADC nonidealities, including quantization and nonlinearity, and their impact in a link context. We will then present studies on equalization locations along the link's signal path, motivating the need of pre-equalization before the ADC. With the importance as well as the implementation challenges of pre-equalizers in mind, we present the first inverterbased analog front-end (AFE) for 56Gb/s transceivers for both PAM2 and PAM4 vapplications. Such AFEs include continuous time linear equalizers (CTLE), programmable gain amplifiers (PGA) and the ADC's track and hold circuits (T/H). The inverter-based AFE is process scaling friendly, consumes smaller power and achieves significant area reduction over prior art. Finally, system identification (SID) methodologies are used with silicon measurements to show validity of the before-mentioned analysis. SID-based bit error rate (BER) estimation method is also presented to compare measured and predicted link performance for different ADC resolutions.
Tailored metal-organic interactions for energy harvesting
Keywords: Chemical Engineering.

A preponderance of data indicates that humanity's reliance on fossil fuels for energy is deleterious to the longevity of our species and habitats. To counter this dependence, efficiency improvements are needed in the sustainable generation of energy as well as in energy conversion and with materials that are cost-competitive with traditional carbon-heavy energy sources. Organic electronic materials, with their lightweight, ubiquitous elements and promising performance, could meet these demands. However, ongoing challenges like poor conductivity due to lack of long-range order and air-instability through reactions with ambient water and oxygen undermine their efficacy. By structuring organics to better mimic inorganic systems or developing hybrid organic/inorganic materials, we can overcome some of these limitations. First, we develop a model hybrid polymer-metal system to achieve the electrode performance of a conventional metal system at a tenth of the cost. Incorporation of this system into an organic solar cell results in a 7x improvement in the power conversion efficiency over a bare silver electrode without the need for additional costly evaporation steps. Second, we consider materials for thermoelectric energy harvesting, a compelling technology because of its capability to directly convert waste heat into electrical energy. However, the widespread application of this technology has yet to be realized due to challenges associated with achieving a material that features low thermal conductivity despite high electrical conductivity with strong temperature dependence. The intrinsically low thermal conductivity of organic systems makes them appealing for thermoelectric applications; however, their performance is generally impeded by low charge mobility, arising from a lack of long-range order. We investigate a solvent treatment method for inducing greater order in the conductive polymer PEDOT:PSS that results in record electrical conductivities in excess of 8000 S/cm. By tuning the solvent and other parameters, we are able to double the previous record for solution-processable organic thermoelectric performance. Lastly, we explore a newly emerging class of hybrid thermoelectric materials: conductive metal-organic frameworks (MOFs). The long-range order in MOFs coupled with their intrinsic porosity hints a path toward high thermoelectric performance. However, full utilization of this promising material system requires greater understanding of how each of the elements in the MOF affects performance. We use the M-HAB family (HAB = hexaaminobenzene, M = Co, Cu, Ni, Zn) to explore how the character of the metal ion and its preferred coordination geometry impact thermoelectric performance and the air-stability thereof.
A tale of two drugs discovered from natural products : an aldehyde dehydrogenase 3A1 small molecule activator for mitigating radiation-induced injury and a botanical drug for ulcerative colitis
Keywords: Chemical and Systems Biology.

Approximately 50% of currently available drugs approved by the U.S. Food and Drug Administration (FDA) have been discovered from natural products derived from plants, animals, or microorganisms. Although the pharmaceutical industry has focused modern discovery efforts on screening synthetic libraries, natural products may be a continuing source for new drug discovery. This thesis provides two examples of pharmaceutical agents that were discovered from Traditional Chinese Medicine (TCM). The first, in Part I of this thesis, describes the identification of a single small molecule activator (Alda-341) of aldehyde dehydrogenase 3A1 (ALDH3A1) common to several TCM extracts for the treatment of radiation-induced injuries. The second, in Part II, describes a complex natural mixture (SA100) accepted as an FDA Botanical Investigational New Drug (IND) that was evaluated in a Phase 1b clinical study in patients with ulcerative colitis (UC).
Taobao Villages: A Sustainable Form of Rural Development?
Keywords:  Stanford Global Studies
CEAS
China
Taobao
E-commerce
Thesis

This paper explores the challenges of e-commerce as a lever for rural development, as well as the socio-economic problems faced by individual sellers and migrants in Taobao Villages (villages in China with a high concentration of Taobao sellers). Much of the official reports surrounding e-commerce, such as those by the Chinese government and AliResearch, are positive in nature and do not focus on the uneven patterns of e-commerce development. However, I use the data published by AliResearch, online public sentiments, academic papers and field experience to question two prevailing hypotheses of Taobao Villages: (1) that e-commerce is an effective tool for rural development, (2) and that the participation of sellers, including migrants, in a Taobao Village, automatically generates noticeable improvement of their socio-economic situation.
This conclusion of this paper is that e-commerce is actually thriving in villages along the urban coast, rather than within the inland or western parts of China. Moreover, owing to the type products that rural dwellers sell – namely agricultural produce – and the lack of high consumer demand for these goods, there is little room for rural sellers to scale up their businesses. On an individual level, Taobao’s business model favours incumbent sellers who are given opportunities to generate even more sales, perpetrating a “rich gets richer, poor gets poorer” phenomenon among sellers, irrespective of geography or product category.
Targeted long-read RNA sequencing and allele-specific gene silencing in cardiovascular disease
Keywords: Genetics.

As diagnostic genetic sequencing becomes more prevalent and as new genetic technologies rapidly develop towards clinical applicability, studies of the basic science behind these tools in human samples and model systems are increasingly important. In this dissertation, I explore the current state of cardiovascular precision medicine as it relates to genetics, and describe two experimental research projects that I have conducted over the past five years that focus on the use of gene silencing and sequencing technologies with a therapeutic and diagnostic perspective. The first project uses targeted long-read RNA sequencing to examine the effects of a rare mutation on MYBPC3 splicing in hypertrophic cardiomyopathy (HCM). This project describe new alternative splicing patterns in MYBPC3 that arise as a result of this mutation in a lowly characterized region of the protein, and stands as a case study for the importance of RNA sequencing in clinical settings. The second project examines two methods of allele-specific MYH7 silencing in HCM, using a human induced pluripotent stem cell derived cardiomyocyte (iPSC-CM) model. We use biophysical assays to probe not only the effects of an MYH7 mutation on iPSC-CM contractility, but also how therapeutic silencing may ameliorate disease phenotypes. This experiment finds a dissociation between allele-specificity and phenotypic effect in iPSC-CMs. Both of these projects use genetics to probe the underlying biology of HCM and highlight how genetic technologies, including sequencing and silencing, are poised to play important roles in the clinical cardiovascular world.
Targeting microenvironmental dependencies for cancer therapy : a role for the nervous system in glioma growth and progression
Keywords: Cancer Biology.

High-grade glioma (HGG) is the leading cause of brain tumor death in both children and adults. Active neurons exert a mitogenic effect on normal neural precursor and oligodendroglial precursor cells, the putative cellular origins of high-grade glioma (HGG). We demonstrate here that active neurons similarly promote HGG proliferation and growth in vivo using optogenetic control of cortical neuronal activity in a patient-derived pediatric glioblastoma orthotopic xenograft model. Activity-regulated mitogen(s) are secreted, as the conditioned medium from optogenetically stimulated cortical slices promoted proliferation of pediatric and adult patient-derived HGG cultures. The synaptic protein neuroligin-3 (NLGN3) was identified as the leading candidate mitogen; soluble NLGN3 was sufficient and necessary to promote robust HGG cell proliferation. NLGN3 induced PI3K-mTOR pathway activity and feed-forward expression of NLGN3 in glioma cells, providing mechanistic insight into its surprising role as a mitogen. NLGN3 expression levels in human HGG negatively correlated with patient overall survival. These findings indicate the important role of active neurons in the brain tumor microenvironment and identify secreted NLGN3 as an unexpected mechanism promoting neuronal activity-regulated cancer growth. We next demonstrate the striking dependence of HGG growth on microenvironmental neuroligin-3 in vivo, elucidate signaling cascades downstream of neuroligin-3 binding in glioma and determine a therapeutically targetable mechanism of secretion. Patient-derived orthotopic xenografts of pediatric glioblastoma (GBM), diffuse intrinsic pontine glioma (DIPG), and adult GBM fail to grow in Nlgn3 knockout mice. Neuroligin-3 stimulates numerous oncogenic pathways, including early focal adhesion kinase activation upstream of PI3K-mTOR, and induces transcriptional changes including upregulation of numerous synapse-related genes in glioma cells. Neuroligin-3 is cleaved from both neurons and oligodendrocyte precursor cells via the ADAM10 sheddase. ADAM10 inhibitors prevent release of neuroligin-3 into the tumor microenvironment and robustly block HGG xenograft growth. This work defines a promising strategy for targeting neuroligin-3 secretion, which could prove transformative for HGG therapy.
The taste of inequality : food and the reproduction of social class
Keywords: Sociology.

Growing inequality manifests in what individuals eat. Indeed, significant dietary and diet-related health disparities in the United States follow a socioeconomic gradient. Scholars commonly account for these dietary inequities using structural explanations that highlight differences in people's geographic and financial access to healthy food. These explanations emphasize food's material value to people with the underlying assumption that people eat simply to nourish themselves, and thus survive. But eating is about much more than physical nourishment: food also has significant symbolic, emotional and cultural value. We eat not only to live, but to fulfill other functions, among them, to provide for loved ones, to cultivate belonging, to show care and affection, and to achieve and signal status. Drawing on in-depth interviews with 160 parents and adolescents and over 100 hours of participant observations with families across socioeconomic status, this dissertation shows how food's symbolic, emotional and moral meanings help drive dietary disparities and contribute to the reproduction of inequality.
Tate duality in positive dimension and applications
Keywords: Mathematics.

In Part I, we generalize classical Tate duality (local duality, nine-term exact sequence, etc.) for finite discrete Galois modules (i.e., finite etale commutative group schemes) over global fields to all affine commutative group schemes of finite type (the "positive-dimensional" case), building upon recent work of Cesnavicius generalizing Tate duality to all finite commutative group schemes (the "zero-dimensional" case). We concentrate mainly on the more difficult function field setting, giving some remarks about the easier number field case along the way. In Part II, we give applications of this extension of Tate duality to the study of Picard groups, Tate-Shafarevich sets, and Tamagawa numbers of linear algebraic groups over global function fields.
Techniques for building predictable stream processing pipelines
Keywords: Electrical Engineering.

This dissertation presents techniques for easily building real-time parallel stream processing pipelines with predictable performance. These techniques enable automatically finding layouts of pipelines onto parallel-processing hardware that guarantee required performance and use resources efficiently. The automated workflow replaces tedious and error-prone process of laying out pipelines by trial-and-error. The key to the automated workflow is a novel performance modeling approach for stream processing pipelines based on two simple principles. First, pipelines are built out of components with predictable performance that also compose in predictable ways. Second, pipelines are built entirely out of compute and data-transfer as the basic operations. A large class of stream processing pipelines can be built following those principles. For any pipeline built in such a manner, techniques presented in this dissertation enable development of accurate models that can predict the performance of parallelized layouts. In turn, those models enable automated search for efficient pipeline layouts that can meet target performance requirements. The dissertation also includes design and implementation of two challenging real-time stream processing pipelines from the context of software-defined wireless networks - a WiFi data-plane and an LTE control-plane. Those pipelines are built following the proposed principles and techniques, thus demonstrating their effectiveness. The WiFi data-plane pipeline meets performance requirements of processing 20 million samples per second with latency bounds of tens of microseconds. This pipeline is built using Atomix, a novel programming framework for predictable signal processing embodying the proposed principles. The design and implementation of Atomix is presented along with that of the WiFi data-plane pipeline. The LTE control-plane pipeline meets peak performance requirements of processing event streams from 3,000 LTE base-stations with sub-second latency with processing load varying over two orders of magnitude daily. This pipeline is built using Trevor, a novel auto-scaling system for distributed stream processing leveraging the proposed principles. The design and implementation of Trevor is presented along with that of the LTE control-plane pipeline and similar pipelines realized using Trevor. The principles and techniques contained in this dissertation streamline continuous development, predictable execution, and efficient operation of parallel stream processing pipelines at scale through automated workflows. The two specific pipelines used to illustrate those techniques stretch the limits of real-time stream processing and demonstrate the power of model-based pipeline development. The contributions presented here apply broadly to real-time parallel stream processing in both multi-core and distributed settings.
Testing theories of forgetting: The effect of memory suppression strategies on associative memory
Keywords:  Symbolic Systems Program
Symbolic Systems
Stanford University
Memory
Suppression
Psychology
Associations
Thesis

Associative memory is the ability to form an association between two items and later recall one of the associates given the other. The strength of the association is a major contributor to successful recall. However, the way in which association strengths are strengthened and weakened is not fully understood. We were interested in exploring how attempts of suppression, where one intentionally tries to forget an association, affect the strength of associations. In an attempt to gain understanding of how associations can be influenced by suppression, we ran 2 experiments. Experiment 1 served as a replication of a classic memory suppression study, where we attempted to elicit a suppression effect following repeated intentional attempts at suppressing associations. Our results from Experiment 1 were consistent with previous findings, where cued retrieval performance on word pairs was significantly impaired after multiple attempts at suppressing the associations between pairs. The magnitude of impairment for the suppressed associations was found to be independent of the specific suppression instructions. Following the results from Experiment 1, we conducted an experiment to better understand how the suppression attempts were mechanistically affecting the association strengths of the targeted word pairs. We found that when subjects were instructed to directly suppress an association, they were significantly better at learning new associations with the suppressed associate as compared to subjects who were instructed to divert their thoughts during suppression attempts. Overall, our results suggest that directly suppressing an association weakens the strength of the association, thus reducing the amount of impairment present when new associations sharing one of the associates are being formed and retrieved.
The Conscious Consumption Act
Keywords:  Public Policy Program
Stanford University
Humanities and Sciences
Public Policy Program
Sustainability
environment
policy
labeling
life cycle assessment
legislation
behavioral economics
values
norms
Thesis

Perhaps the greatest threat to human well-being is current consumption behavior. We consume products from which the personal benefit we derive is far outweighed by the negative costs, largely environmental, to both ourselves and society. Ideally, prices would influence consumption decisions by incorporating the full lifecycle environmental costs to society into the price of a product. But most initiatives to incorporate environmental costs into product prices are failing. A complementary approach to influence consumption patterns is to provide the consumer with information as to the lifecycle environmental impact of a product in a manner that intrinsically motivates the consumer to change their purchasing behavior.
I propose legislation, the Conscious Consumption Act, that mandates all companies divulge information representing the environmental impact of the lifecycle of each of their products to the consumer. This legislation calls for the development of standards regulating the methodology lifecycle impact quantification and provides guidance based on behavioral economics and social psychology for designing and implementing eco-labeling initiatives leveraging social norms, individual values and emotions to inspire consumer behavior change. This paper provides background contextualization and discusses the key steps in the design and adoption of eco-labeling legislation.
The Death and Life of "The Hinterland"--an Exploration of the Development of Realistic Literature in Contemporary China
Keywords:  Stanford Global Studies
contemporary Chinese literature
realism literature in China
Chinese neorealism
Sino-Japanese War literature
Thesis

Through a case study of the first officially-banned novel in the history of the P.R.C –“The Hinterland” (《腹地》) written by the anti-Japanese War (the second Sino-Japanese War) writer Wang Lin (王林), this thesis examines the internal track of the developing trajectory of realism literature in contemporary China, and provides different insights on the current realism literature landscape in China.