VictorJuiz/thesis huggingface dataset:
Genomic analysis of benign prostatic hyperplasia implicates cellular re-landscaping in disease pathogenesis

Benign prostatic hyperplasia (BPH) entails growth in the central regions of the prostate gland and is common among older men. BPH obstructs urinary outflow, resulting in voiding symptoms and bladder and kidney damage for which current treatments, that target prostate physiology, are only partially effective. A better understanding of BPH may suggest new treatment strategies that target its pathophysiology. Here, we used next-generation sequencing to gain insight into BPH. By RNAseq, we uncovered transcriptional heterogeneity among BPH cases, where a 65- gene BPH stromal signature correlated with symptom severity. Compared to normal prostate, stromal signaling molecules including BMP5 and CXCL13 were enriched in BPH tissues, while estrogen regulated pathways were depleted. Addition of BMP5 to prostatic myofibroblast cells in culture altered their expression profile towards a BPH profile that included the BPH stromal signature. Our RNAseq analysis also suggested an altered cellular milieu in BPH, which we verified by immunohistochemistry and single-cell RNAseq. In particular, BPH tissues exhibited enrichment of myofibroblast subsets, with concurrent depletion of neuroendocrine cells and an estrogen receptor (ESR1)- positive fibroblast cell type residing near epithelium. Finally, by whole exome sequencing, we uncovered somatic single nucleotide variants (SNVs) in BPH, of uncertain significance in pathogenesis, that were indicative of clonal cell expansions consistent with cellular relandscaping. Thus, our genomic characterization of BPH has identified a clinically-relevant stromal signature and new candidate disease pathways (including a likely role for BMP5 signaling), and reveals BPH to be not merely a hyperplasia, but rather a fundamental re-landscaping of cell types.

Advisor: Pollack Jonathan D.
Brooks James (James D.)
Lipsick Joseph Steven
West Robert (Data scientist)
Genomic and mechanistic interrogation of novel genes and gene signatures in non-small cell lung cancer [electronic resource]

Lung cancer is the leading cause of cancer deaths worldwide, with 1.7 million deaths per year. Moreover, lung cancer is comprised of several histological subtypes, with non-small cell lung cancer (NSCLC) making up ~85% of the cases. Presently, the most important prognosis of NSCLC is the stage of disease. However, a vast majority of patients have locally advanced or metastatic disease at the time of diagnosis. Despite the number of current therapies consisting of chemotherapy, radiation, and surgery, patients with locally advanced NSCLC have heterogeneous outcomes. Recently, the advent of targeted therapies against specific genetic mutations or rearrangements have improved response rates and overall survival but there remains an unmet need to uncover novel genes involved in this disease. We have applied bioinformatics approaches to better elucidate the role of various genes or gene signatures in non-small lung cancer in several capacities -- 1) to uncover gene expression signatures to improve risk stratification and outcome in those diagnosed with early stage NSCLC; 2) to identify de novo genomic fusions and breakpoints from targeted paired-end DNA sequencing data; and 3) elucidate the function of a novel splicing factor mutation in non-small cell lung cancer. In the first application, we obtained gene expression profiles from 1106 non-squamous NSCLCs for the generation and internal validation of a 9-gene molecular prognostic index (MPI). This was validated on an independent cohort of FFPE tissues from 98 NSCLC patients. As a second application, we demonstrate a practical and robust identification method of DNA rearrangements resulting in gene fusions through the development of a Fusion And Chromosomal Translocation Enumeration and Recovery Algorithm (FACTERA). Some of these recurrent fusions involving ALK, ROS1, RET, and NTRK1 have been identified in NSCLC, leading to the development and approval of targeted therapies. Lastly, the third application identifies a novel recurrent splicing factor mutation in non-small lung cancer. We have characterized the binding and splicing properties of this splicing factor and functional changes associated with the mutation. The approaches described here can be applied to uncover other gene or gene expression signatures in NSCLC and be expanded to other cancer indications.

Advisor: Alizadeh Ash
Diehn Maximilian
Giaccia Amato J.
Pollack Jonathan D.
Genomic methods and studies in epidermal differentiation

Multicellular organisms are composed of diverse, functionally specialized cell types. However each cell contains essentially the same DNA sequence, the genetic information which encodes instructions for constructing the cellular machinery and guiding cellular behavior. How do cells achieve such diverse functions and behaviors from the same genetic endowment? A key part of the answer lies in selective usage of the genetic material (the genome) -- while one cell may act on a subset of the genome, a neighboring cell may act on a largely distinct subset of the genome in order to achieve distinct functions. This thesis describes insights into the molecular machinery that cells employ to achieve selective usage of the genome as well as novel methods to interrogate this machinery.

Advisor: Khavari Paul A. 
Diehn Maximilian
Majeti Ravindra
Germline-Targeting HIV-1 Immunogen Design

Human immunodeficiency virus type 1 (HIV-1) has caused one of the worst pandemics in human history. Although treatments can slow the progression of HIV-1, no cure exists and infected patients must live with the virus for life. Moreover, HIV-1 continues to spread rapidly in certain regions of the world, making vaccine development a global health priority. Because of HIV-1's high antigenic diversity, an effective vaccine must be able to elicit broadly-neutralizing antibodies (bnAbs). BnAbs against the CD4 binding site of the HIV envelope glycoprotein 120 (gp120) have been isolated from rare HIV-infected individuals, but attempts to elicit such bnAbs through vaccination have failed. This lack of bnAb induction is largely due to viral features that obstruct germline (gl) antibody binding and thereby prevent maturation into high-affinity bnAbs. Guided by computational modeling, we engineered a germline-targeting immunogen based on gp120's outer domain. This construct is able to bind multiple mature bnAbs with high affinity in addition to a predicted germline precursor, making it a strong vaccine candidate.

Keywords:  Department of Bioengineering
HIV
Immunogen
Vaccine
gp120
Rational Design
Stanford School of Engineering
Department of Bioengineering
Thesis
Advisor: Huang Possu
Kim Peter S.
Giftedness and Race at Lowell High School: Ho v. San Francisco Unified School District (1998)

Lowell High School is often viewed as one of San Francisco’s most academically gifted and selective schools. In the wake of Brown v. Board of Education (1954), a nationwide movement to desegregate public schools called Lowell’s GPA and test-based admissions process was called into question, resulting in the addition of a race-conscious admissions policy in 1983. I focus on a court case that successfully challenged this affirmative action measure, Ho v. San Francisco Unified School District (SFUSD) , in which two Chinese-American families accused the district of discriminating against their children through the use of race-conscious admissions. The result of this case was the elimination of race-conscious policies in the district altogether and the creation of a race-neutral “diversity index” for Lowell High School admissions specifically. My project is a historical study that analyzes the Ho v. SFUSD court documents, the demographic data of Lowell High School and the SFUSD, and Elizabeth Anderson’s philosophical framework of social equality to determine the effectiveness of the diversity index. My results demonstrate that the elimination of explicitly race-conscious policies led to a sharp decrease in the Black and Latinx student populations in Lowell. While the Latinx population was able to recover to its original percentage in the school before Ho v. SFUSD after twenty years of the diversity index, the Black population was not. Both remain disproportionately low for the city of San Francisco. This case study shows that we must understand the role that gifted schools and race-neutral admissions play in demonstrating and perpetuating racial inequality.

Keywords: Graduate School of Education
desegregation
integration
philosophy
Anderson
San Francisco
Lowell
Lowell High School
Asian American
Chinese American
gifted
Thesis
Advisor: Callan Eamonn
Willinsky John
Girls ∈ Math: An Investigation of Middle School Girls' Sense of Belonging in Mathematics

This thesis addresses the quest for equity in mathematics education through the lens of female students’ experiences of belonging before, within, and after an 18-day, algebra-based summer camp. The curriculum and teaching practices employed in the intervention were intentionally designed around open, visual mathematics combined with explicit growth-mindset messaging. Seven middle school girls from the same summer classroom were analyzed through numerous interviews and artifacts. Building on previous literature and the major takeaways from the data as a whole, I propose a framework for understanding the dynamics and interactions of a student’s development of learning identity and relationship to mathematics. Specifically, the framework represents my interpretation of Markus and Conners’ “Culture Cycle” applied to the context of the math classroom. Analyzed in light of this model, the seven case studies illustrate unique ways in which each girl negotiated her realtive sense of belonging to mathematics. The research suggests that what Dr. Jo Boaler has termed a “mindset mathematics” curriculum and teaching practice provides multiple pathways to belonging and success, significantly impacting students at varying achievement levels and backgrounds. While focusing specifically on female students due to the explicit systemic barriers facing women in mathematics, this thesis establishes that the curriculum and teaching practices employed in the youcubed summer camp effectively promoted equity in developing students belonging, which logically extends beyond the experiences of just girls.

Keywords: Graduate School of Education
Undergraduate Honors Thesis
secondary mathematics education
equity
gender
women in STEM
compulsory education
mindset
belonging
youcubed
identity
learning
mathematics
Thesis
Glimpsing the narco monster : Mexico's horror and the anachronism of narrative

The central argument of "Glimpsing the Narco Monster" is that the story of the narco violence ravaging contemporary Mexico is a horror story. That is, as a necessary condition it implies the presence of a monster. In traditional works of horror, the humans regard the monsters they meet as abnormal, as disturbances of the natural order. However, in this present study I argue that the particular monster in this particular work of horror can and must be understood as a product of the specific environment (historical, economic, socio-political) that bred it; its "ecology". With what I heuristically term the Narco Monster, the goal of this project is to reveal aspects of both the monster and the ecology of its production. Accordingly, each of the three chapters in this study describes one formal feature of this construction: the monstrous, the neoliberal, and the spectacular. When Pontecorvo shot The Battle of Algiers (1966), detailing the Algerian struggle for independence from the occupying French in the 1950s, he used a pseudo-documentary style that offered a case study of modern warfare, achievable because the content and the form were near contemporaries. This is no longer the case. As such, the present approach is to analyse various types of film and visual media paratactically; that is, to study individual scenes as fragments (or events) that dialogue not with the rest of the narrative of the specific film but instead function as glimpses of the ecology of the Narco Monster and its horror story. It is through his methodology that I will offer new readings of key Mexican (and Mexican-American) cinematic productions of the current century: Señorita extraviada (2001), Backyard: El traspatio (2009), Miss Bala (2011), Heli (2013), El infierno (2010).

Keywords: Iberian and Latin American Cultures.
Advisor: Ruffinelli Jorge 
Hoyos Ayala Héctor 
Rocha Marília Librandi
Global and seasonal effects of lightning-induced electron precipitation

Surrounding the Earth are two shells of high-energy electrons and ions known as the Van Allen Radiation Belts, the dynamics of which are governed by a complex balance of sources and loss processes, collectively resulting in populations which persist between days and months. The global distribution of lightning discharges has been theorized to be an important loss function for radiation belt electrons through a process known as Lightning- Induced Electron Precipitation (LEP). However, a lack of in situ measurements has precluded a quantitative global study. We present an investigation of the spatial and temporal morphology of lightning-induced electron precipitation. We seek to quantitatively determine the regions in space, time, and electron energy, where LEP may be of importance, using a combination of numerical raytracing and resonant interaction modeling, driven by a realistic measurement of global lightning activity from the GLD360 lightning detection network. First, using cold plasma numerical raytracing, we provide an estimate of the persistent radio energy in the near-Earth space environment due to whistler-mode, VLF waves generated by terrestrial cloud-to-ground lightning flashes. Variation is explored with respect to L-shell, longitude, frequency, and geomagnetic activity using the Kp index. We include updated ionospheric absorption curves and an improved 4-dimensional interpolation algorithm. We find that the persistent energy decays logarithmically with increasing L-shell and frequency. We then apply our raytracing and interpolation apparatus to simulate the precipitating electron flux resulting from single lightning strokes, and extrapolate over the GLD360 dataset to determine estimated locations of elevated electron precipitation. We compute the estimated lifetime of geomagnetically trapped electron populations, subject solely to LEP-induced losses, as a function of L-shell and electron energy. Our estimates are consistent with measurements in the 100keV -- 1 MeV energy range; however our results suggest that LEP may be a substantial loss mechanism for lower energy, suprathermal electrons in the 100 eV -- 10 keV range. We do not find any notable enhancement in the slot region, suggesting that resonant interactions with lightning-generated whistlers are not a significant contributor to slot region morphology. Finally we present a design for a VLF radio receiver, intended for deployment on a 3-unit CubeSat bus, which can be used in conjunction with an onboard electron energy spectrometer to make direct, in situ measurements of precipitating electrons and their causative whistler waves. The receiver is designed with radiation tolerance in mind, and includes a novel onboard data processing system, implemented entirely in an field-programmable gate array (FPGA) using the Verilog hardware description language.

Keywords: Electrical Engineering.
Advisor: Close Sigrid
Fraser-Smith A. C. (Antony C.) 
Marshall Robert
Golden Dawn, Dark Horizon: Exploring the Rise of Greece’s Ultra-Right Party In the Context of Simultaneous Crises

Over the past decade, Greece has undergone two simultaneous crises. The first is economic, triggered by the global financial crisis of 2008. Since then, gross domestic product has shriveled by a quarter, and the average Greek has become forty percent poorer. The second crisis is related to immigration: Greece has, over the past decade, become the favored point of entry for most illegal migrants seeking to reach Europe, resulting in an ongoing demographic shift in a previously homogenous country. It is in this climate of political and social upheaval that the Golden Dawn, a far-right, neo-Nazi political party, has risen to national prominence, becoming the country’s third most-popular party in the 2015 elections. In this thesis, I seek to determine whether either or both of these crises have influenced Golden Dawn’s sudden electoral success. I argue that, although the economic crisis laid a foundation for the party’s rise, Golden Dawn’s success is not simply a function of its ability to garner support from the country’s most economically disadvantaged. Instead, the party has found success by campaigning on a platform that promises the return of Greek society to its pre-crisis status quo, both economically and demographically. Specifically, the Golden Dawn shapes itself as a response to the cultural threat imposed by both the economic and immigration crises, as both have induced feelings of status loss among the Greek electorate.

Keywords:  Center for Democracy
Golden Dawn
Greece
xenophobia
ultra-right
Center for Democracy
Development
and the Rule of Law
CDDRL
Thesis
Advisor: Stedman Stephen
Greco-Roman urban form in its global context

The grid plan has long been considered the hallmark of the Classical city, but grid plans are common to cultures around the world. This misconception arises from the fact that the Classical city is often studied in cultural isolation. To remedy this, the arrangements of Greek and Roman cities are compared with those of other ancient societies, with an eye towards how plans delimit space and control movement and how the forms of cities reflect the balance of power between centralized authorities and individual residents to shape and maintain the urban space. This reveals distinctive spatial organizational characteristics underlying the forms of Classical sites: street networks that allow for free circulation and a lack of large-scale zones of restricted access between public and private spaces. On the basis of this new urban morphological model, the Greco-Roman grid plan is recast not as a defining feature of the Classical city, but as a preferential feature implemented in select contexts.

Keywords: Classics.
Advisor: Morris Ian
Netz Reviel 
Trimble Jennifer
Guided randomized search over programs for synthesis and program optimization

The ability to automatically reason about programs and extract useful information from them is very important and has received a lot of attention from both the academic community as well as practitioners in industry. Scaling such program analyses to real system is a significant challenge, as real systems tend to be very large, very complex, and often at least part of the system is not available for analysis. A common solution to this problem is to manually write models for the parts of the system that are not analyzable. However, writing these models is both challenging and time consuming. Instead, we propose the use of guided randomized search to find models automatically, and we show how this idea can be applied in three diverse contexts. First, we show how we can use guided randomized search to automatically find models for opaque code, a common problem in program analysis. Opaque code is code that is executable but whose source code is unavailable or difficult to process. We present a technique to first observe the opaque code by collecting partial program traces and then automatically synthesize a model. We demonstrate our method by learning models for a collection of array-manipulating routines. Second, we tackle automatically learning a formal specification for the x86-64 instruction set. Many software analysis and verification tools depend, either explicitly or implicitly, on correct modeling of the semantics of x86-64 instructions. However, formal semantics for the x86-64 ISA are difficult to obtain and often written manually with great effort. Instead, we show how to automatically synthesize formal semantics for 1,795 instruction variants of x86-64. Crucial to our success is a new technique, stratified synthesis, that allows us to scale to longer programs. We evaluate the specification we learned and find that it contains no errors, unlike all manually written specifications we compare against. Third, we consider the problem of program optimization on recent CPU architectures. These modern architectures are incredibly complex and make it difficult to statically determine the performance of a program. Using guided randomized search with a new cost function we are able to outperform the previous state-of-the-art on several metrics, sometimes by a wide margin.

Advisor: Aiken Alexander 
Mitchell John C. 
Sridharan Manu
Guides to Abstraction: Wallace Stevens, Marianne Moore, and Adonis

What is poetic abstraction? This thesis attempts a partial answer to this question by teasing out some criteria for why one poetic gesture of abstraction holds richer speculative possibilities than the next. Through readings of three modernist poets, Wallace Stevens, Marianne Moore, and Adonis, I identify two general modes of abstraction, which I call immanent and a priori abstraction, placing Stevens and Moore in the former category and Adonis in the latter. These methods of constructing and exploring poetic worlds are linked to the different ways they treat the real, which here designates poetry’s impasses or horizons of possibility. Beyond its contributions to studies of each individual poet, this paper's original methodology--based on the axiom that all poetry participates in a generic activity of abstraction--opens doors to a reconceptualization of "world literature."

Keywords:  Department of Comparative Literature
Comparative Literature
Division of Literatures Cultures and Languages
Arabic Literature
American Literature
World Literature
Abstraction
Modernism
Poetry
Wallace Stevens
Marianne Moore
Adonis
Thesis
Advisor: Key Alexander
Greene Roland
Guns, Rubles, and Oil: A Statistical Approach to Understanding Russia’s Military Modernization Programs

By using oil prices as a simple economic proxy, this research attempts to assess the future of Russia’s defense modernization programs through a basic statistical regression between defense spending and oil prices. From there, it builds 5 potential oil price scenarios and examines how overall defense spending might react in each of the 5 scenarios. Additionally, the analysis is extrapolated to 2 primary defense projects — the Borei and Yasen submarines. The financial burden of both programs on the Naval defense budget is then used to assess the feasibility that Russia will be able to successfully complete either project within the scope of the next 10-year modernization plan given each of the 5 budget scenarios. The research then attempts to contextualize the statistical results within the contemporary Russian landscape. This landscape includes a background of Russia’s oil-based economy, its Soviet legacy, and its highly centralized administration. Ultimately, the goal is to assess the probability that Russia will meet its military spending objectives over the next 10 years in each of the 5 budget scenarios while using the specific examples of the two submarine projects to demonstrate how budget constraints and prioritization might take place.

Keywords: Russia’s defense modernization
oil
defense budget
Russia’s oil-based economy
Thesis
Advisor: Blacker Coit
Holloway David