VictorJuiz/thesis huggingface dataset:
Machine learning-based acceleration of monogenic disease diagnosis

Monogenic diseases are genetic diseases caused by mutations to single genes in the human genome. There are currently over 5,000 described monogenic diseases with a known causative gene, and thousands more likely monogenic diseases with an unknown causative gene. Patients with monogenic diseases are affected by a wide spectrum of disease-associated phenotypic abnormalities such as intellectual disability, developmental delays, skin, heart, or facial abnormalities. A handful of monogenic diseases occur fairly frequently: e.g., sickle cell anemia, which affects up to 3% of newborns in some parts of Africa, and cystic fibrosis, which occurs in one out of approximately 3,000 white infants in the United States. However, most monogenic diseases are very rare, occurring at a frequency of less than 1 in 10,000 newborns. Since they are individually so rare, physicians may not recognize the symptoms immediately, making rare monogenic diseases hard to diagnose. This leads to so-called diagnostic odysseys, where patients seek an explanation for their symptoms for months or years. With the rise of genome sequencing, diagnosis of a monogenic disease is becoming more and more synonymous with identifying the causative gene in the patient's genome. Diagnosis, in particular by identification of the causative gene, can help predict the course of the disease, treatment options, provide a sense of closure to the patient and their relatives, and in the age of gene editing even provide a first hope for a cure. In this dissertation, I present multiple computational methods that accelerate the diagnosis of patients with suspected monogenic disease. I describe the computational discovery of a novel disease-causing mutation, the automatic curation of monogenic disease-related data directly from the primary literature and patient medical records, and novel computational methods for accelerating the discovery of causative genes directly from patient data. I hope that the findings presented here will help patients affected with monogenic diseases, their relatives, physicians, and genetic counselors, to achieve the best possible care.

Advisor: Bejerano Gill
Bernstein Jonathan A.
Jurafsky Dan
Managing flood risk in a changing climate

Climate change threatens the livelihoods and wellbeing of people around the world. Communities and individuals can limit the damages by adapting their policies, infrastructure, and behaviors for hotter temperatures, heavier downpours, and higher sea levels. In three chapters, this dissertation examines the potential impacts of climate change and evaluates different adaptation strategies. In my first chapter, I focus on high-tide floods, an emerging consequence of sea level rise, and provide novel quantitative estimates of how these recurrent floods affect local economic activity. My second chapter analyzes managed retreat, the relocation of people and infrastructure away from hazardous places to reduce risk. I synthesize global experience with managed retreat and identify associated drivers and barriers. In the final chapter, I conduct the first national evaluation of the effect of flood risk maps on property values, uncovering how real estate disclosure laws, insurance prices, and flood damage influence the extent to which markets price flood risk. In sum, the empirical findings of this dissertation contribute to evidence-based decision-making for climate change adaptation.

Advisor: Burke Marshall 
Field Christopher B. 
Lobell David
Mach Katharine J.
Mapping the genomic distribution of RNA : DNA hybrids

R-loops are three-stranded nucleic acid structures consisting of an RNA-DNA hybrid and a displaced single strand of DNA, formed when single stranded RNA invades double stranded DNA. They are typically thought to form during transcription, when nascent mRNA pairs with its template. R-loops have recently been implicated both in aiding certain genomic processes, and in causing DNA damage within certain contexts. Possibly due to this tendency to cause damage, a variety of cellular mechanisms prevent R-loops from forming, or resolve them once formed. These resolution mechanisms maintain a constant turnover of R-loops in a cell, making them dynamic structures whose levels are subject to change within different cell types or during different growth conditions. Thus, to understand the biology of these structures, it is critical to understand where they form at any given point in time. A variety of next-generation sequencing techniques have been developed to map genomic RNA:DNA hybrids. All together, this work shows new insights into R-loop biology that have been gained from next-generation sequencing approaches, reviews these approaches, and provides a new technique that addresses a major challenge in the field. In particular, as more R-loop perturbations are tried, we hope that this last technique will be useful in providing accurate, quantitative and interpretable results about where and how R-loops are changing

Advisor: Cimprich Karlene
Curtis Christina
Jarosz Daniel
Wysocka Joanna
Mapping the neural basis of motivated behavior

Understanding what in the brain establishes specific motivational states, and how these states cause animals to pursue particular goal-directed behaviors, are central goals of behavioral neuroscience. Fully determining the mechanisms underlying these processes will require a comprehensive description of how the brain operates at different levels spanning multiple spatial and temporal scales, from the expression of individual genes within single cells to the coordinated activity of brain-wide networks of neurons. As a step towards this ultimate goal, this dissertation proposes several new approaches to map and understand the structural, functional, and molecular properties of neural circuits. These approaches are applied to study the circuits underlying motivated behavior, with an emphasis of thirst motivation. This work is divided into several parts. (1) I de-scribe the application of a method for labeling neural circuits defined by activity (TRAP) in combination with whole-brain clearing and imaging technology to map the location of neurons activated by a particular experience throughout the brain, and study their structural and molecular properties. (2) Extending the idea of brain-wide imaging to study dynamics, I introduce two new approaches to perform large-scale in vivo imaging of neural activity across the surface of the mouse brain, to study cell-type-specific cortical dynamics involved in production of a simple thirst-motivated choice behavior. (3) I dis-cuss an improved approach to TRAP, and apply this technique to measure and manipulate a crucial node in the neural circuit underlying the sensation of thirst to reveal how activity in this circuit induced by water deprivation produces an aversive drive that is diminished through water consumption. (4) I develop a new approach to spatially map the expression of up to 1,000 genes simultaneously in three dimensions within single cells in a tissue section, and show that this approach is compatible with activity measurement using activity regulated genes as a post hoc reporter of neural activity. (5) Finally, I develop an approach using large-scale electrophysiology to study spatially-localized activity dynamics from cells distributed throughout the entire mouse brain. I apply this technique to study brain-wide neural dynamics during thirst motivated choice behavior, revealing how thirst motivational state is represented throughout the brain and how this state gates the flow of information from sensory to motor regions.

Advisor: Deisseroth Karl 
Luo Liqun
Hestrin Shaul
Newsome William T. 
Shenoy Krishna V. (Krishna Vaughn)
Market Concentration, Earnings and Turnover: No-Poaching Clauses in the Quick Service Restaurant Industry

I analyze the impact of Quick Service Restaurant franchisors’ no-poaching clauses on historical employee earnings and turnover for the Restaurants and Other Eating Places industry. I examine the 41 largest Quick Service Restaurant franchisors and the labor markets of 10 major U.S. cities over 11 years from 2006 to 2016. No-poaching clauses restrict intra-franchisor movement of employees and, if in use, can be found in a brand’s franchise disclosure documents. I create a panel dataset using no-poaching agreements data, industry data on earnings and turnover, and business establishments’ employment data. Using a panel regression with fixed city and time effects, I determine that no-poaching clauses have an insignificant effect on turnover but do exhibit a statistically significant effect on earnings. Specifically, a 25 percent increase in market concentration related to no-poaching agreements results in a 2-6 percent decrease in average monthly earnings, depending on employment status, age, and education level.

Keywords: Department of Economics
No-Poaching Clauses
Market Concentration
Quick Service Restaurant
Franchisor
Turnover
Earnings
Herfindahl-Hirschman Index
Group-Specific Labor Index
United States
Thesis
Market Timing: A Myth or a Possibility? Individual Investor and Mutual Fund Performance in the Stock Market

Investors are always looking for ways to increase their portfolio returns, ideally without taking on additional risk. Some investors pay others to manage their money, while other investors turn to market timing strategies, believing they can pick individual stocks or funds that will do better than a market benchmark. However, the current literature is divided on whether these market timing strategies are effective in reality. This paper analyzes a new market timing strategy for individual investors that uses changes to the Federal Funds rate target to indicate market entry and exit. The results of this analysis show that individuals cannot use these simple signals in order to consistently achieve higher portfolio returns than market benchmarks. This paper also analyzes allocation and return data for a new set of actively managed mutual funds. The results from these correlative analyses suggest that mutual funds also do not have positive market timing ability even though they have more capital and resources. Overall, this paper supports research claiming that investors, whether as individuals or as part of a fund, do not have the ability to consistently time the market and achieve significant and positive returns above market benchmarks.

Keywords: Economics
finance
investing
stock market
Federal Reserve
mutual fund
Thesis
Markets, Money and Might: Chinese Economic Statecraft and a Case Study of the 21st Century Maritime Silk Road Initiative

Economic statecraft is a state’s deliberate manipulation of economic interaction or deployment of economic resources to defend its national interests and further its strategic goals. The practice of economic statecraft on a globally significant scale is changing both the nature of diplomacy and the logic and operation of markets. Some contend that the introduction of geopolitical logic into commercial deals render once-distinct security and economic considerations harder to disentangle, raising the risk that disagreements in one field can trigger a reaction in another. China has often been described as the world’s leading practitioner in geoeconomics. The increasing and diversified incidences of the use of economic statecraft as China’s tool of influence in the game of international politics, coupled with the lack of clarity and underlying mistrust regarding the current and future intentions and capabilities of this rising power, have prompted allegations that these less conventional shows of national strength are aimed at potentially upending the extant international order and have stoked concerns that these acts could undermine the laws and norms governing the conduct of international relations. Some of these allegations and concerns are legitimate, some misguided, and others overdrawn. It is, therefore, the modest aim of this thesis to lend some perspective to these concerns. With a view to analytically separate speculation from substance, this thesis assesses several of these claims in the specific context of the 21st Century Maritime Silk Road or Maritime Silk Road Initiative (“MSRI”). As one of China’s foremost displays of economic statecraft, the MSRI provides an important empirical arena in which to observe the interplay between strategic and economic considerations, and serves as a bellwether for the successes and limits of the tools of economic statecraft.

Keywords:  Stanford Global Studies
Stanford Global Studies
East Asian Studies
Chinese foreign policy
Chinese law
Belt and Road Initiative
state-business relations
port governance
Thesis
Advisor: Miller Alice
Matching in online market platforms

The thesis contains three parts which provide for an in depth study of problems that are motivated from challenges faced by online platforms. The first two parts study matching problems in decentralized and centralized environments respectively and the third part is concerned with the aggregation of preferences. The first part of the thesis considers the problem of assortment planning in two-sided platforms, where self-interested agents are present on each side of the platform. While assortment planning has been studied extensively in the revenue management literature, it is concerned with the problem of assigning menus of goods (as opposed to people who can reject) to agents. In our problem, agents' utilities are derived from a random utility choice model (RUM). Two different design settings are explored - simultaneous (both sides propose at the same time) and sequential (one side proposes first). The optimal menu is completely characterized for the case of a single customer where a greedy algorithm is shown be optimal. Both design settings turn out to be NP-Hard for multiple customers. Two heuristics are proposed and a constant factor approximation algorithm is provided for the sequential setting. The second part of the thesis considers a centralized marketplace, where agents (drivers and passengers) arrive in an online manner and are matched after a possible delay. Agents arrive at a given set of locations which form a metric (distance between points satisfying the triangle inequality) and the platform needs to minimize the sum of distance and waiting costs. A natural trade-off that arises is the following: matching agents faster reduces waiting costs but waiting for more agents to arrive allows to create better matches. A randomized and a deterministic algorithm are proposed on the tree metric (that has been embedded from the original metric); both of which achieve a constant competitive ratio on the tree metric leading to a logarithmic competitive ratio on the general metric. The third part of the thesis looks at pairwise comparisons among agents specifically in the context of intransitivity. The goal is to develop and analyze parametric models that can support intransitivity. The key result is that such models have non-concave likelihood functions. Next, taking inspiration from the Condorcet paradox, a majority vote model is proposed. The majority vote model can support strong and arbitrarily long intransitive cycles and shows comparable performance against other parametric models which support intransitivity on publicly available datasets.

Keywords: Management Science and Engineering.
Advisor: Ashlagi Itai 
Goel Ashish 
Saban Daniela
Mathematical and physical space in Kantian idealism

Kant's transcendental idealism aims to explain how we have mathematical knowledge. It frames space and time as pure 'forms' of our ability to acquire sensations, rather than as independently existing entities or their properties. This is then also supposed to explain how we can anticipate formal features of experience. The space we study in geometry is the very one in which objects appear to us. In the last several decades, however, scholarship has implicitly recognized Kant's notion of space is not as unified as this picture would suggest. In particular, the straightforward assumption that there is just one space - both mathematical and physical - has implicitly come under scrutiny. I locate grounds for this scrutiny within Kant's direct and indirect proofs for transcendental idealism. However, I argue the disunity of space actually strengthens Kant's doctrine. I clarify how Kant intends to incorporate Newtonian matter theory while responding to Leibnizian rationalism. To do this, I specify the evidential hurdles Newton faced in determining whether gravity is a well-founded physical magnitude. I suggest Kant's evolving criticisms of physical monadology gradually include more of Newton's matter theory. The inclusions reflect Kant's growing clarity on his precise disagreements with Leibniz. The core of these, I argue, is the distinction between matter and form as it applies to thought.

Keywords: Philosophy.
Advisor: Friedman Michael
Anderson R. Lanier 
Ryckman Thomas 
Smith George E. (George Edwin)
Measurement and control of non-adiabatic dynamics a study in the acetylene dication

Non-adiabatic structural dynamics occur in lighter molecules and are often described using Conical Intersections (CI) in molecules with at least three atoms. Light that is resonant near regions of strong non-adiabatic coupling can play an important role in controlling and understanding these dynamics. This thesis presents both simple model simulations and experimental data in the acetylene dication to analyze how light interacts with non-adiabatic dynamics. A key parameter that relates how the nuclear energy changes in time compared to the relative electronic energy is used to explain and predict the role that dipole coupling has in controlling non-adiabatic dynamics.

Keywords: Physics.
Advisor: Bucksbaum Philip H. 
Hollberg Leo (Leo William)
Martinez Todd J. (Todd Joseph)
Measurement and maintenance of human cell size

How cells reach and maintain the right size is a longstanding question in biology. Moreover, the many ways in which cell size may influence cellular physiology have received insufficient attention. Research has been hindered by inadequate tools for measuring size in living cells. In this dissertation, a novel strategy is developed to measure the size of single human cells using a nuclear-localized fluorescent protein expressed from a constitutive promoter. This method is validated by comparing it to established alternatives, with the result that the fluorescence measurements are more robust and less dependent on image segmentation than the commonly-used measurement of nuclear volume. Then, this strategy is applied to understand the size dependence of a crucial part of the cell cycle -- the transition from G1 to S phase -- and how it contributes to cell size homeostasis. One hypothesis is that titration of a size-proportional factor against a size-independent molecular factor could function as a "molecular ruler" to create a size-dependent biochemical signal. Several cell cycle regulatory proteins are tested as candidates and it is observed that one of them, the retinoblastoma protein Rb, is unique in its size-nonscaling behavior: Rb is diluted during G1 phase. This property of Rb is a consequence of its synthesis, partitioning, and degradation pattern. Finally, it is demonstrated that Rb concentration is a size-dependent determinant of cell cycle progression. Future areas of inquiry include the phenomenology of cell growth, mechanisms of size scaling, and in vivo size homeostasis.

Keywords: Biology.
Advisor: Skotheim Jan
Cyert Martha S.
Dixon Scott
Lipsick Joseph Steven
Measurements with optically levitated microspheres

I discuss the development of optically levitated microspheres as a tool for precision measurements and tests of fundamental physics. Micron-scale dielectric spheres are trapped by the radiation pressure at the focus of a Gaussian laser beam, where the optical suspension enables thermal, electrical, and mechanical isolation from the surrounding environment at high vacuum. Forces and torques can be measured from changes in the angle and polarization of light both transmitted through and reflected by the trapped particle. Additionally, the charge of the particle can be controlled with single electron precision. We have used these methods for the following three purposes: to search for fractionally charged particles and dark energy, to develop measurement techniques for surface potentials, and to construct an electrically driven micro-gyroscope.

Keywords: Physics.
Advisor: Gratta Giorgio 
Fox John D. 
Kasevich Mark A.
Measuring, mitigating, and modeling the impact of skin treatments and solar exposure on the barrier function of human stratum corneum

The biomechanical behavior of human stratum corneum (SC), the outermost layer of skin, is critical for its large role in providing the barrier function of human skin. The degradation of the SC's natural biomechanical function can thus lead to painful skin conditions such as atopic dermatitis, exacerbated wounds and scarring, and reduced compatibility of wearable electronic devices. However, the effects of synergistic environmental exposures and most topical cosmetic treatments on key mechanical properties such as stress and intercellular cohesion in the SC have not been previously quantified and their mechanisms of action remain poorly understood. Consequently, the first step necessary to make informed designs of protective or stress mitigating treatments is to elucidate the underlying mechanism in the SC of mechanical stress, the driving force for damage to the skin barrier function. As a result, the critical connection between water volume loss during drying and stress development is introduced. The effect of treatment molecules, such as emollients and moisturizers, on macroscopic stress and cohesion is then analyzed through the presented framework, thus significantly clarifying the treatment characteristics necessary to mitigate SC damage. After establishing the role of treatments to protect the skin, the impact of simultaneous ultraviolet (UV) light and heat exposure (to approximate infrared radiation) is quantified to demonstrate the ability of synergistic solar damage processes in the SC to enhance stress and reduce intercellular cohesion, thus increasing the risk of barrier function degradation. In this context, the efficacies of UVB absorbing molecules (and their carrier vehicle) to protect the SC biomechanical properties from UV damage is investigated. This results in a new understanding of multiple mechanisms (i.e. water loss, treatment molecule diffusion, environmental damage, photoabsorber protection) that may simultaneously affect SC biomechanics, a vital step towards the successful protection and maintenance of a healthy skin barrier function.

Keywords: Materials Science and Engineering.
Advisor: Dauskardt R. H. (Reinhold H.) 
Appel Eric (Eric Andrew) 
Chaudhuri Ovijit
Measuring political connections in Brazil

This paper investigates the returns of contributions to electoral campaigns on the market value of firms. The hypothesis is that contributing to a federal representative or senator leads to higher stock returns for the firms that made these contributions. I implement an event study strategy using data from the Supreme Electoral Court on campaign contributions and from the São Paulo Stock Exchange on historical prices to test my hypothesis. I find some evidence that firms that contribute to campaign winners have returns higher than one would expect right after the election. The intensity of this impact seems to be influenced by how much a firm contributed to campaign winners and by how many campaign winners a firm contributed to.

Keywords:  Department of Economics
Department of Economics
Brazil
political connections
campaign finance
Thesis
Advisor: Dupas Pascaline