VictorJuiz/thesis huggingface dataset:
Molecular Epidemiology of Human Immunodeficiency Virus Type 1 (HIV-1) in Southern Africa and Northern California

Human immunodeficiency virus type 1 (HIV-1) exhibits extraordinary genetic diversity that is driven by high rates of mutation and recombination, coupled with elevated rates of viral turnover and the persistent nature of infection. Through these mechanisms, HIV-1 group M, the group largely responsible for the global pandemic, diversified into nine distinct subtypes and additional circulating recombinant forms. Subtype C HIV-1, which accounts for approximately 50% of the estimated 37 million individuals living with HIV/AIDS worldwide, predominates the epidemics in southern Africa and South / Southeast Asia. In contrast, subtype B HIV-1, predominant in the United States and Europe, comprises 12% of the global HIV-1 prevalence./nCurrent US and, increasingly, international guidelines recommend that HIV genotypic sequencing be performed for newly-identified HIV-positive patients, in order to identify genetic mutations that may confer drug resistance and pose a barrier to effective antiretroviral therapy (ART). This practice has resulted in the generation of enormous amounts of genotypic data often linked with clinical, demographic, and geospatial information. Analyses of these large datasets, utilizing sophisticated statistical and computational methods, has enabled identification of important and previously unrecognized trends in epidemiologic and vertical transmission, persistence of HIV within and among distinct risk groups, and the accumulation and propagation of ART resistance. Results of these analyses, in turn, advance treatment and care for persons living with HIV./nThis thesis takes advantage of large, de-identified and anonymized datasets of HIV-1 genotypic and demographic information available through clinical testing and treatment programs in two distinct and epidemiologically important regions in the global HIV pandemic, northern California and southern Africa. Employing innovative and computationally intensive tools which combine experience from molecular biology, evolutionary biology and biostatistics, in-depth analyses were undertaken to explore and define risk factors, underlying epidemiologic features and clinical characteristics relevant to transmission and ART resistance. The final chapter provides a comprehensive literature review of the relevance of molecular epidemiologic principles and innovative biology to the complex and continued phenomenon of mother-to-child transmission of HIV, as a case study exemplifying the need for continued molecular studies grounded in solid epidemiologic principles. The findings presented here are ultimately intended to help guide domestic and global efforts to scale up ART treatment while considering well-known and lesser-known factors that may influence eventual clinical and epidemiologic outcomes.

Advisor: Reingold, Arthur
Water Effectiveness and Targeting: Insights from a Geospatial Dataset on Uganda Water Projects

Developing countries have long relied on foreign aid and international NGOs to provide/nsupplemental public goods such as communal drinking water points. Exploiting/na geospatial dataset of water projects in Uganda, I consider both eectiveness and/ntargeting of projects. To evaluate eectiveness as practiced at scale, I use a retrospective/ndesign that links placement of water projects with Demographic and/nHealth Survey (DHS) clusters, nding that over a ve year span, protected sources/nproduce statistically signicant improvement of weight-for-age, height-for-age, fever,/nand hemoglobin levels, but not of weight-for-height and diarrhea. In exploring poverty/ntargeting, I link water data with spatial poverty data and argue for a relative/ntargeting measure that compares dierent entity types to one another in terms of/nhow progressive their allocation of projects is. Finally, I use a similar procedure to/nanalyze placement in terms of its correlation with election outcomes.

Advisor: Miguel, Edward
A Contribution to the Study of Administrative Power in a Philosophical Perspective

This dissertation explores the challenges that administrative reasoning places on classical theories about the nature of law or adjudication, the structure of the legal process, and the separation of powers, particularly in its relationship with legality and the active role of the administrative power in modern governance. It describes how traditional theories about the nature of law and adjudication have explicitly addressed the philosophical foundations of judicial reasoning in hard cases, but they have been oblivious about how administrative decision-makers should decide them./nThis dissertation argues for an eclectic model where administrative reasoning should ideally be informed by publicly validated expert knowledge that requires a moral and political compass oriented towards the fulfillment of the purposes and aspirations of a democratic polity that lives under the rule of law. To that end, it proposes that the administrative power ought to decide hard cases regardless of the empirical, theoretical or meta-interpretive nature of the disagreement they may elicit. It suggests that, unlike the judiciary, the administrative power is ideally endowed with original or delegated lawmaking authority, vested with democratic legitimacy, and equipped with specialized expertise and the procedural mechanisms to allow the active participation of the citizenry in the administrative process./nFurthermore, it proposes that these features entail that administrative decision-makers should reason from principle and policy in deciding hard cases about the planning and allocation of valuable resources in a community by construing the grounds of law or deciding meta-interpretive disagreements based on publicly validated expertise. Finally, this dissertation ventures to speculate that the existence of administrative novelty may challenge the truism embraced by traditional jurisprudence according to which the solution to the tension between law’s certainty and its responsiveness is usually reserved to the interplay legislature-courts that regards the administrative power as a mere executor of legislation.

Advisor: O'Connell, Anne
Crystals and Mirror Constructions for Quotients

This thesis develops a new approach to computing the quantum cohomology of symplectic reductions of partial flag varieties $X$; such symplectic reductions are known as weight varieties. Motivated by a conjecture of Teleman \cite{Tel14}, we use a mirror family Landau-Ginzburg model $(M_{P},f_{P})$ of $X$ introduced by Rietsch \cite{Rie08} to give a conjectural explicit description of the quantum cohomology of weight varieties./nWe specialise to the class of polygon spaces $\mcP_{r,n}$, these are symplectic reductions of the complex Grassmannian of $2$-planes $\Gr_{\C}(2,n)$ by the maximal torus action. Polygon spaces in low rank have been classified and the quantum cohomology of these varieties is known. As a result, we are able to verify our conjectural description explicitly./nIn addition, we investigate the appearance of representation-theoretic combinatorial structures in the mirror symmetry of complete flag varieties. We show that, on the $B$-model side, the extended string cone $\underline{C}_{\rexi}$ introduced by Caldero \cite{Cal02} to define toric degenerations on the $A$-model can be recovered via a discretisation process known as tropicalisation. Specifically, using a non-standard parameterisation of $M_{B}$, tropicalisation recovers the precise inequalities defining $\underline{C}_{\rexi}$. This provides an explicit approach to results previously obtained by Berenstein-Kazhdan \cite{BK07}. We conclude with a description of a conjectural program relating these combinatorial structures on the $B$-model with hierarchies of integrable systems on the $A$-model.

Advisor: Teleman, Constantin
Decision Making Under Radical Uncertainty: A Multiple Case Comparison of Companies Creating New Technologies Featuring New Forms of Personal Data

How do companies creating new technologies featuring new forms of personal data respond to the radical uncertainty of designing data ecosystems and accompanying business models with that sensitive data?/nThis dissertation answers this question with an empirical, inductive, multiple case comparison of the development of pioneering fitness technologies by Suunto, Garmin, and Adidas. Cases draw on interviews with key product team members who created these technologies and related public artifacts./nTeams responded to this uncertainty in different ways, leading to varying data ecosystem designs that created value in varying ways. Evidence strongly supports that teams' responses are primarily explained by their interpretation of the relative importance of user needs, followed by their interpretations of the relative importance of information economics concepts and their own expertise, and lastly regulations regarding the collection and use of personal data./nThese findings pose implications for the creation of future technologies featuring new forms of personal data. Teams' responses will evolve as user needs evolve, and will offer insights into the dynamics and terms of teams' social license for their technologies. New regulations may impact how these ecosystem designs create value.

Advisor: Cheshire, Coye
The extension of bound state electronic structure methods to molecular resonances

In this thesis, we present our work in pursuit of black-box, \textit{ab initio} methods for computing positions and widths of molecular resonances. The method of complex basis functions is efficiently implemented and applied in the context of various electronic structure approximations. Within the static exchange approximation, basis set effects are investigated and the method is applied to a series of N-containing hetercycles. The extension to Hartree-Fock theory allows for more accurate calculations. These methods have been applied to several small molecules, and the computation of properties within this framework is discussed. The application of complex basis functions to shape and Feshbach resonances at correlated levels of theory including M\o ller-Plesset perturbation theory at second order and equation of motion coupled cluster singles and doubles is also investigated from a practical perspective, and the prospect of using these methods for computing accurate potential energy surfaces is explored. Finally, we describe some theoretical and practical aspects of computing positions and widths of low-energy shape resonances by analytic continuation in the coupling constant. We find that the properties of attenuated Coulomb potentials make them ideal for such calculations.

Advisor: Head-Gordon, Martin P.
Mapping Dysregulated Metabolic Pathways in Cancer Using Chemoproteomic and Metabolomic Platforms

Cancer cells reprogram cellular metabolism to support growth and maintain pathogenicity. Since Otto Warburg’s discovery nearly a century ago that cancer cells have heightened glucose uptake and aerobic glycolysis, many studies have identified additional metabolic alterations required to maintain proliferation and cancer pathogenicity, such as heightened de novo lipogenesis and glutamine-dependent anaplerosis. These studies have provided a foundation for understanding the metabolic alterations that support tumorigenesis and cancer pathogenicity, but additional studies are required to uncover novel dysregulated metabolic pathways to fully understand the biochemical consequences of cancer./nIn chapter one, we present several potential mechanisms that yield insight into the relationship between lipids and cancer. In chapter two, using an isotopic metabolomic platform, we elucidate the role of exogenous fatty acids in several types of cancer cells, putting forth an additional mechanism to describe the role of lipid metabolism in cancer. Although dysregulated lipid metabolism is a key feature of many cancers, the metabolic alterations in certain subtypes of cancer remain poorly understood. In chapter three, we use a reactivity-based chemoproteomic platform in combination with a metabolomic platform to identify GSTP1 as a novel metabolic enzyme target that is heightened in triple negative breast cancers (TNBCs), a highly malignant subtype of breast cancer that is poorly understood. Taken together, these studies highlight critical metabolic alterations in cancer to not only uncover novel metabolic pathways that drive cancer, but also lead to the development of novel therapeutic options for the treatment of cancer.

Advisor: Nomura, Daniel K
A Partial Characterization of $\square_\kappa$ for Plus-One Premice

We develop and refine the theory of plus-one premice, first introduced by Neeman and Steel in \cite{PIPM} and \cite{FSPIPM}. This culminates in a Condensation Lemma for iterable plus-one premice. We then apply Condensation to the construction of $\square_\kappa$ sequences in these premice; this is similar to Schimmerling and Zeman's $\square_\kappa$ construction in \cite{zeman square proof}, but the presence of long extenders complicates both the techniques and the results. Our main result is that for plus-one premice with finitely many long generators, $\square_{\kappa , 2}$ holds exactly when $\kappa$ is neither subcompact nor the successor of a $1$-subcompact cardinal.

Advisor: Steel, John R
Modeling of Planetary Interiors: From Microscopic to Global Scales

The inherent difficulty of making and interpreting measurements of the deep interior of the Earth and other planets necessitates constructing models of their structure and evolution. Properties of materials at actual planetary conditions are a key input to these models. For the Earth these conditions extend to the hundreds of GPa and thousands of Kelvin; for the energetic impact events and within the gas giants the range is extended to several TPa and perhaps tens of thousands Kelvin. Despite tremendous advances in experimental techniques, much of this range of conditions remains out of reach, and thus, computer simulations of materials play an important role in characterizing materials within planetary interiors./nThis thesis presents a variety of work using computational techniques to: 1) determine properties of planetary materials from first-principles simulations, and 2) apply these de- rived properties to models of large-scale planetary structure and processes. First-principles calculations are unique in their ability to simulate a nearly unbounded range of pressure-temperature conditions, including those beyond the capacity of any experimental techniques./nIn this thesis, I discuss the physics and numerical techniques I have used and developed to simulate planetary materials at high pressures and temperatures, and to interpret and condense the results of these calculations. I also present results of studies applying the first-principles techniques to specific problems in planetary science. I test the stability of compact rocky cores in the metallic hydrogen-helium envelopes of gas giants, finding that such cores are likely to undergo dissolution and erosion. I then explore the miscibility of terrestrial cores and mantles at extreme temperatures. I predict that this mixed rock-metal state is would be of importance in catastrophic giant impacts, which are now thought to be commonplace in the early history of the terrestrial planets, or deep inside “super-Earth” exoplanets./nI continue by detailing studies applying material equations of state from simulation and experiment. I describe work towards developing a more comprehensive thermo-chemical model of liquid iron alloys integrated with models of Mercury's thermal history and magnetic field energetics. I then describe the derivation and implementation of a new numerical, non-perturbative method for precise calculations of gravitational field strength for a rotating, liquid planet with tides. I then look at the consequences of this new method for the tidal responses of Jupiter and Saturn, finding a significant, previously uncharacterized contribution arising from the influence of rotation. Finally, I detail an ongoing effort using interior structure models of Jupiter to interpret the drastically improved measurements of Jupiter’s gravity by the Juno spacecraft mission, which finds some evidence for the existence of a dilute core in spite of difficulties reconciling first-principles equations of state with observations of the planet’s atmosphere.

Advisor: Militzer, Burkhard
Actomyosin mediated tension orchestrates thermogenic programs in adipocytes

Innovative approaches to shift energy balance are urgently needed to combat metabolic disorders such as obesity and diabetes. One promising approach has been the expansion or activation of thermogenic adipose tissues to improve metabolic homeostasis. My doctoral studies presented in the following text have identified novel approaches to translate adipose based metabolic therapeutics and the underlying mechanisms by which thermogenic adipocytes establish their therapeutically applicable metabolic capacity./nIn chapter I, I present a novel biomaterial technology optimized to expand metabolically beneficial thermogenic adipose depots in vivo. This system enabled me to determine the degree of metabolic enhancement possible with the exogenous expansion of thermogenic adipose depots. To generate therapeutic adipose implants I modified hyaluronic acid-based hydrogels to support the differentiation of white fat derived multipotent stem cells (ADMSCs) into lipid accumulating, uncoupling protein 1 (UCP1) expressing thermogenic adipocytes. Subcutaneous implantation of the synthetic tissues successfully attracted host vasculature and persisted for several weeks and the implant recipients demonstrated elevated core body temperature during cold challenges, enhanced respiration rates, improved glucose homeostasis, and reduced weight gain demonstrating the therapeutic merit of this highly translatable approach./nIn chapter II, I outline the experimentation leading to the discoveries presented in chapter III as well as thoroughly review pertinent tissue engineering strategies. Specifically, I sought to define the mechanism by which synthetic ECM components identified in chapter I could alter differentiation outcomes of preadipocytes to yield greater thermogenic capacity./nIn chapter III, I demonstrate that actomyosin-based mechanical responses provide a critical differentiation cue for the development of thermogenic adipocytes. Since I had determined that the hydrogel optimization techniques described in chapter I were likely acting through cytoskeletal-mediated processes I examined the role of cytoskeletal structure and tension in thermogenic adipose development. I identified that the muscle-like gene expression patterns of UCP1+ adipocytes are critical for the acute induction of oxidative metabolism and uncoupled respiration and regulate mechanosensitive transcriptional co-activators, YAP/TAZ, that control thermogenic gene expression./nThis dissertation establishes the role of physical mechanics in the development and function of thermogenic adipocytes which may engender future metabolic therapeutics.

Advisor: Stahl, Andreas
Don't Show A Hyena How Well You Can Bite: Performance, Race and the Animal Subaltern in Eastern Africa

This dissertation explores the mutual imbrication of race and animality in Kenyan and Tanzanian politics and performance from the 1910s through to the 1990s. It is a cultural history of the non-human under conditions of colonial governmentality and its afterlives. I argue that animal bodies, both actual and figural, were central to the cultural and political project of British colonialism in Africa – and in particular eastern Africa, which continues to be imagined in many circles as both “safari country” and the “cradle of humankind.” I build on extensive archival research to suggest that artistic and scientific activity in colonial Kenya, from the amateur and professional theatre to the natural-historical research conducted at the Coryndon Memorial Museum, helped to define a category of sub-political being that I call “the animal subaltern.” The animal subaltern is a concatenation of all forms of animal life lived below the horizon of “the human.” During the colonial period, this included the wildlife of eastern Africa, the pre-human hominids whose fossilized remains paleoanthropologists like Louis Leakey unearthed, and “natives,” whose political subjectivity the colonial state was determined to suppress. I argue that the forced contiguity of these variously inflected forms of life had a pervasive, if uneven, racializing effect: all of these beings became black. In the post- Second World War struggle for political, cultural and economic independence in eastern Africa, members of the animal subaltern contested their exclusion from the category of the human. I read the work of the Kenyan writer and intellectual Ngũgĩ wa Thiong’o and the Tanzanian playwright Ebrahim Hussein as important interventions into this unfolding struggle and its implications for the postcolonial future of their communities. Finally, I consider the environmental activism of Kenya’s “Rhino Man,” Michael Werikhe, whose performative blurring of the distinction between human and animal in the 1980s and 1990s helped to inaugurate a new model of interspecies solidarity that continues to play itself out to this day.

Advisor: Cole, Catherine
The Influence of Age and Alzheimer’s Pathology on Hippocampal Function

An abundance of research has demonstrated that aging is associated with declines in cognition, particularly episodic memory. A similarly large body of work has highlighted the underlying age-related functional alterations that occur within the hippocampus and surrounding medial temporal lobes (MTL) that may give rise to memory impairment. However, aging is also associated with the accumulation of Alzheimer’s disease pathology, namely beta-amyloid plaques (Abeta) and tau neurofibrillary tangles, which have been associated with a host of neural and behavioral changes, even in those without the disease. As such, it is unclear to what extent our understanding of age-related decline is attributable to the accumulation of pathology. Using a combination of neuropsychological assessment, structural and functional magnetic resonance imaging, and positron emission tomography, I will present two projects which seek to quantify hippocampal function in cognitively normal older adults, assess how Abeta and tau interact to alter neural activity, and define a functional mechanism through which pathology leads to episodic memory decline./nThe first project focuses on a function commonly attributed to the hippocampus called pattern separation. Here, using a lure discrimination memory paradigm, I demonstrate that cognitively normal older adults exhibit a behavioral shift from pattern separation towards pattern completion that is associated with elevated neural activity in the hippocampus and MTL. Additionally, I show that Abeta and tau are uniquely associated with two measures of neural function during memory encoding, suggesting that Abeta and tau pathology likely interact to produce aberrant neural activity in older adults. In the second project, I use a technique called representational similarity analysis to explore the relationship between memory encoding and retrieval. Here, I demonstrate that older adults exhibit greater neural similarity between encoding and retrieval for incorrect lures (i.e. false alarm) relative to correct lures. I also demonstrate that false alarm similarity is associated with tau, but only in older adults without Abeta. This suggests that, independent of Abeta, tau can disrupt memory function, specifically by altering the relationship between neural activity during encoding and retrieval. In sum, this research indicates that Alzheimer’s pathology alters hippocampal function in a way that leads to episodic memory impairment in cognitively normal older adults, and should be considered when addressing future questions about aging and memory.

Advisor: Jagust, William