VictorJuiz/thesis huggingface dataset:
Understanding the Mechanobiological Regulation of Brown and Beige Adipocytes

Obesity, defined as abnormal or excessive fat accumulation, has become a global epidemic. Although some obese individuals are metabolically healthy a majority develop several co-morbidities such as type II diabetes, hypercholesterolemia, and cardiovascular disease. Diet and exercise can be effective strategies to lose weight, but many individuals have difficulty making lifestyle changes. Thus, new therapeutic strategies are needed to combat the growing prevalence of obesity. Our lab has focused on understanding the biological function of brown adipose tissue (BAT) and beige adipose tissue (BeAT), which are promising therapeutic tissues to combat obesity and obesity related diseases. Unlike white adipose tissue which serves a purpose of storing energy for later use, BAT and BeAT catabolize fat and glucose, uncoupling the electron transport chain from ATP production, instead generating heat. BAT and BeAT depots are primarily activated by cold exposure via β-adrenergic receptor signaling. Targeting β-adrenergic signaling to activate BAT and BeAT was a promising therapeutic approach, however β-adrenergic receptors are also found in the heart preventing widespread therapeutic use. A deeper biological understanding of BAT and BeAT may lead to new therapeutic targets. Our lab previously uncovered a novel role for actomyosin mediated-tension facilitating thermogenesis in BAT. This novel mechanism became the basis for three projects described within this dissertation. First, we probed the importance of type II myosin activity in BeAT development and thermogenic function; type II myosin 9 (Myh9) was found to regulate UCP1 mRNA expression, mitochondrial function, and lipid metabolism. Second, in collaboration with the company Atomwise we screened novel type II myosin activators in BAT to determine whether pharmacologically activating type II myosins could increase thermogenesis. Third, we sought to understand the function of the mechanosensitive transcriptional paralogs YAP and TAZ in regulating BeAT differentiation.

Advisor: Stahl, Andreas
Investigating Regulators of Daughter Cell Size Asymmetry in the C. elegans Q Neuroblast Lineage

Asymmetric cell division (ACD) is an important mechanism that generates cellular diversity during development. Not only do asymmetric cell divisions produce daughter cells of different fates, many can produce daughters of different sizes, which we refer to as Daughter Cell Size Asymmetry (DCSA). In C. elegans, apoptotic cells are frequently produced by asymmetric divisions that exhibit DCSA, where the smaller daughter dies. We focus here on the divisions of the Q.a and Q.p neuroblasts, which produce apoptotic cells and divide with opposite polarity using both distinct and overlapping mechanisms. The PIG-1/MELK and TOE-2 proteins both regulate DCSA and specify the apoptotic cell fate in both the Q.a and Q.p divisions. In many asymmetric cell divisions, the non-muscle myosin NMY-2 is involved in properly positioning the cleavage furrow to produce daughters of unequal size. It was previously reported that NMY-2 is asymmetrically distributed and required for the DCSA of Q.a but not Q.p. In this study, we examined endogenously tagged reporters of NMY-2, TOE-2, and PIG-1 and found that all were asymmetric at the cortex during both the Q.a and Q.p divisions. TOE-2 and NMY-2 were biased toward the side of the dividing cell that would produce the smaller daughter, whereas PIG-1 was biased toward the side that would produce the larger daughter. We used temperature-sensitive nmy-2 mutants to determine the role of nmy-2 in these divisions and found that these mutants only displayed DCSA defects in the Q.p division. We generated double mutant combinations between the nmy-2 mutations and mutations in toe-2 and pig-1. The nmy-2 mutations did not significantly alter the DCSA of the toe-2 and pig-1 mutants but did alter the fate of the Q.a and Q.p daughters. This finding suggests that NMY-2 functions together with TOE-2 and PIG-1 to regulate DCSA but plays an independent role in specifying the fate of the Q.a and Q.p descendants.

Advisor: Garriga, Gian
Computational understanding of ionic systems for advanced energy storage materials

Ionic systems, in various states of order, are of great scientific and technological importance,and computation can help us understand these specifics to atomic-level resolution. However, in choosing a computational approach, it is important to use physics-based methods with chemical accuracy. We begin our evaluation of ionic systems by introducing the approximations underlying an exact theory, density functional theory, and investigate the origins of accurate ground state crystal structure prediction. We apply our findings and form an ab initio study on a partially disordered spinel system with excellent electrochemical properties. Such a system is essential for advanced battery materials development as it utilizes only earth-abundant manganese and does not require well-ordered, layered structures. These restrictions are exactly what anchor existing state-of-the-art materials to continued reliance on critical minerals, namely cobalt and nickel./nTo understand the partially disordered spinel system in all states of (de)lithiation and withcharge disordering, we create the largest cluster expansion ever constructed and suggest that cluster expansion models should instead scale with configuration space size. By applying the CE Hamiltonian with canonical and semi-grand canonical Monte Carlo sampling in large unit cells, we understand what constitutes a partially disordered spinel system in terms of its short-range-order and medium-range lithium transport network. New channels for lithium transport are uncovered and they work with a largely intact spinel transport network to move lithium. We establish that future manganese-based disordered ionic systems for advanced electrodes should intentionally incorporate partial spinel ordering to improve lithium diffusion. Finally, we conclude with a computational analysis on an earth-abundant, sodium-ion based electrode for application in grid energy storage where materials weight is not of concern, and find a fascinating, atomic-level interaction which may promote phase stability at high state of charge. The computational understandings reached in the partially disordered spinel and layered sodium-ion cathode systems guide future design of high performance advanced battery materials.

Advisor: Ceder, Gerbrand
Trade-offs and heterogeneities in host-parasite interactions

One question that has endlessly fascinated ecologists and evolutionary biologists is why there is so much biotic diversity on earth. At the advent of the field, Darwin grappled with these questions to propose that trade-offs between fitness traits constrained the evolution of hypothetical all-fit organisms termed ‘Darwinian demons’. Trade-offs in the co-evolution of antagonistic biotic partners are thought to be particularly important for diversification processes. Despite the centrality of trade-off theory to evolutionary biology, the genetic underpinnings of and selection dynamics on trade-offs remain poorly understood./nMy dissertation therefore focuses on trade-offs: what forms them, what influences them, and how they interact. To do this, I use experimental evolution methods in the Plodia interpunctella, or Indian meal moth, and granulosis virus model system. I focus on two trade-offs—one for each partner in a host-parasite interaction./nOn the host side, I focus on the trade-off to resistance to viral in infection. Understanding this trade-off is important for predicting when we expect to see resistance evolve and how it would alter ecological dynamics or persist in the absence of the pathogen. In chapter 1 of the dissertation, I ask whether the trade-off to resistance is symmetric such that selection for the longer development time phenotype constituting a cost to resistance produces symmetric gains in resistance. In chapter 2 of the dissertation, I ask why resistance inconsistently evolves in the system and how time scales and resource levels affect such resistance evolution and its costs. With these two chapters, I find that the shape of the trade-off between resistance to infection and development time can change depending on the population’s specific selection conditions when trade-offs are influenced by many genes. This is important because such differences in trade-off shape would alter the outcome of evolution./nOn the virus side, I examine how trade-offs between adaptation to different host genotypes influences host range evolution in our system. This trade-off is important because specificity in biotic interactions promotes diversity in co-evolutionary systems. In chapter 3, I examine the genetic and phenotypic dynamics of host genotype specialization in the granulosis virus. In chapter 4, I experimentally evolve granulosis virus in mesocosms of its Plodia interpunctella host with varying degrees of spatial structure and host genetic diversity. With these two chapters, I show that trade-offs between host genotypes might not follow simple functions and may depend on their interactions with other selection pressures. This is important because it suggests that costless generalism can exist in some evolutionary and ecological scenarios, thus interrupting evolutionary dynamics that depend on specialist interactions.

Advisor: Boots, Mike
Bold Fantasy: The Macaronic Epic of Teofilo Folengo Between Ariosto and Rabelais

The Baldus, a lengthy macaronic epic crafted over the course of a lifetime by one of Italy's greatest poets, is a masterpiece of Christian serio ludere which presents to readers a rousing and protracted rebuttal to the Platonic critique of poetry. This dissertation performs a three-chapter examination of the language, genre, and text of the four editions of the Baldus, those curated by Teofilo Folengo, with the aim of illuminating how the diachronic and synchronic features of his epic, as well as his use of a mixed-language style, Macaronic, in dozens of texts linked to this central project, are not simply `symptomatic' expressions of the convergence and conflation of humanist cultures, vernacular literary traditions, and ancient and medieval Latinities in a single text, but are rather highly generative, extraordinarily influential, and totally coherent parts of an anti-epic whose fictitious author, Merlin Cocaio, aims to outdo both Virgil and Homer---the greatest poets of the Western classical tradition---in macaronic verse. I demonstrate how three aspects of this poem---its language, genre, and textual presentation---interact with 'para'- and intertextual materials in the macaronic book and with an encyclopedic range of sources, to form a poem, collection, and even formalized prosodic system for Macaronic. Known to modern readers by way of the final, posthumous edition (1552), the Phantasia Macaronicon as the Baldus was titled in the 1521 'Toscolana' edition) was not only read by many of the most prominent Italian poets of its moment, but is alluded to and imitated by important writers operating outside of Italy's tightly-controlled borders, including Rabelais and Cervantes.

Advisor: Ascoli, Albert R.
Essays on Development Economics and Political Economy

This dissertation studies the impacts of quid pro quo relationships between politiciansand their supporters on public policy and the labor market of public servants. Chapter 2 investigates the effects of a temporary shock in the likelihood of detecting officeholders’ misbehavior on the composition of public expenditures and reelection rates of incumbent politicians, taking into consideration the existence of an ongoing relationship between lawmakers and campaign contributors. This shock derives from an experiment developed by Zamboni and Litschig (2018) that temporarily and randomly increased the likelihood of selection of Brazilian municipalities into a preexisting audit program against corruption. I document a reduction in the probability that treated municipalities engaged in construction projects during the experiment, with a partial reversal in the reelection year, as the audit risk returned to its baseline mark. I report that the threat of audit mostly impacted the actions of politicians in locations with previous experience in the anti-coruption program and where mayors had close relationships with historically corrupt campaign donors, such as construction companies. Moreover, I estimate a large contraction in the likelihood of contribution from these donors to the reelection campaigns of treated mayors and a sizeable reduction in their reelection rates. Chapter 3, co-authored with Thiago Scot, analyzes the effects of a change in power at the local level on the employment of health care workers in Brazil. It compares municipalities where the incumbent party barely won a bid for reelection with those where the incumbent party barely lost, in order to estimate the effects of political turnover on the labor market for public servants. It reports a larger rate of termination of employment contracts in municipalities affected by these shocks, in comparison to the control group. It shows that employees are more likely to leave the health care labor force permanently after political turnover and that public employees on unstable career tracks drive most of the disruption in the employment contracts.

Advisor: Finan, Frederico
Application of Bayesian Methods in Cosmological Data Analysis: Parameter Constraint Forecasts for Stage-IV Surveys and Bayesian Large-Scale Structure Inference

The application of Bayesian methodology in cosmological data analysis has gained enormous popularity, as the Bayesian interpretation of statistics is particularly appealing to the field of cosmology in which its subject, the Universe, is unique. In the coming decade, unprecedented size of data observed from forthcoming Stage-IV experiments - e.g. galaxy surveys such as DESI, Euclid, Roman, and LSST and CMB surveys such as SO and CMB-S4 - will call for the development of more advanced statistical analysis tools, and the Bayesian framework is expected to provide a key to decoding information hidden in the dataset. This will enable us to unlock the fundamental mysteries of the Universe, which include the nature of dark matter and energy, the neutrino mass scale, and inflationary physics./nWithin a Bayesian framework, this thesis develops numerical and statistical tools in preparation for Stage-IV cosmological surveys. First, we forecast the constraining power of combining LSST clustering and CMB-S4 lensing; we find that the constraint on the neutrino mass sum of 25meV can be achieved without optical depth information, and its constraint on the dark energy equation of state parameter is comparable to the LSST tomographic cosmic shear forecast. In the remainder of this thesis, we build an efficient, reliable analysis pipeline for growth of structure measurements from large-scale structure dataset, which can be useful for upcoming galaxy redshift surveys. This includes: hybrid covariance matrix generated by integrating the analytic disconnected part and the data-driven connected part, optimization-based numerical method for posterior inference, and the use of the halo perturbation theory model to provide RSD measurements from the power spectrum multipoles of SDSS-III BOSS DR12 galaxies. With the pipeline developed in this thesis, we find a tight constraint on $f\sigma_8$ corresponding to $S_8 = 0.821 \pm 0.037$ or an overall amplitude error of 4\% at $k_{\mathrm{max}} = 0.2\ h$Mpc$^{-1}$, within 0.3 sigma of Planck's $S_8 = 0.832 \pm 0.013$. We also show that on smaller scales ($k_{\mathrm{max}} = 0.4\ h$Mpc$^{-1}$) the constraint improves considerably to an overall 2.7\% amplitude error (with $S_8 = 0.786 \pm 0.021$), but there is some evidence of model misspecification. Such RSD measurements provide one of the most powerful cosmological probes by testing dark energy and different gravity models. Finally, we discuss the fundamental plane effect, which is claimed to be an important systematics of RSD analyses, and show that its impact on growth of structure constraints is insignificant.

Advisor: Seljak, Uros
Anatomy Inspired Hardware for Magnetic Resonance Imaging

Magnetic Resonance Imaging (MRI) is a powerful and non-invasive imaging modality that is widely used in medicine. MRI uses a static magnetic field, radiofrequency (RF) pulses, and linearly varying gradient fields to create high quality images of internal anatomy. Despite the ability to safely image soft tissue, MRI inherently suffers from low signal to noise ratio (SNR) which causes long scan times. In addition, the time required to perform multiple scans implies that most imaging is qualitative in nature. Instead of extracting the true value of quantitative parameters like T1, T2, and susceptibility, most MR images capture a single snapshot that is only weighted by these parameters. Speeding up and extracting more information from MR scans is an active area of research. In order to test new reconstruction methods and pulse sequences, it is necessary to have high quality phantoms that accurately mimic human anatomy. SNR of the scan can also be improved with form fitting receive coils since the signal drops off as a cubic function of the distance between the subject and the receiver./nTo improve the SNR of MRI scans, this dissertation will discuss two methods for patterning receive coil arrays on complex three-dimensional surfaces. The first method involves spray coating conductive inks and dielectric materials onto a 3D printed surface. The second method uses vacuum forming, sandblasting, and electroless copper plating to deposit conductive traces onto curved polycarbonate substrates. To account for the deformation of vacuum forming, a graphical simulation to pre-distort trace designs was developed. Both processes produce coils that have similar performance to coils made with conventional methods./nThis dissertation also discusses the development of slice phantoms that provide a more accurate representation of human anatomy compared to phantoms that are commercially available. A method is presented for preparing and 3D printing these phantoms with any segmented imaging data. A reproducible calibration process is described for creating agar gels that mimic a wide range of T1 and T2 values found in the body.

Advisor: Lustig, Michael
Arias, Ana C
Harmonic Activation and Transport

Harmonic activation and transport (HAT) is a random process which rearranges a set, one element at a time. More precisely, for integers n ≥ 2 and d ≥ 1, and given an n-element subset U of Zd, HAT is a Markov chain with the following dynamics. HAT removes x from U according to the harmonic measure of x in U, and then adds y according to the probability that a simple random walk from x, conditioned to hit the remaining set, leaves from y when it first does so. This process is then repeated for the resulting set, and so on. We are primarily interested in the classification of HAT as recurrent or transient, as the dimension d and number of elements n in the initial set vary./nChapter 2 concerns HAT in two dimensions. When d = 2, HAT exhibits a phenomenon we call collapse: Informally, the diameter shrinks to its logarithm over a number of steps which is comparable to this logarithm. Collapse implies the existence of the stationary distribution of HAT, where configurations are viewed up to translation, and the exponential tightness of diameter at stationarity. Additionally, collapse produces a renewal structure with which we establish that the center of mass process, properly rescaled, converges in distribution to two-dimensional Brownian motion./nTo characterize the phenomenon of collapse, we address fundamental questions about the extremal behavior of harmonic measure and escape probabilities. Among n-element subsets of Z2, what is the least positive value of harmonic measure? What is the probability of escape from the set to a distance of, say, r? Concerning the former, examples abound for which the harmonic measure is exponentially small in n. We prove that it can be no smaller than exponential in n log n. Regarding the latter, the escape probability is at most the reciprocal of log r, up to a constant factor. We prove it is always at least this much, up to an n-dependent factor./nChapter 3 concerns HAT in higher dimensions. When d ≥ 5 and n ≥ 4, HAT is transient. We prove that, remarkably, transience occurs in only one ``way'': The initial state fragments into clusters of two or three elements—but no other number—which then grow indefinitely separated. We call these clusters dimers and trimers. Underlying this characterization of transience is the fact that, from any state, HAT reaches a state consisting exclusively of dimers and trimers, in a number of steps and with at least a probability which depend on d and n only./nTogether, our results establish that HAT exhibits a phase transition in both d and n, in the sense that HAT is positive recurrent when d ≤ 2 or n ≤ 3, but transient when d ≥ 5 and n ≥ 4. Specifically, the phase boundary has a ``corner'': There are d ≥ 3 and n ≥ 4 for which HAT is transient, but HAT is positive recurrent for any smaller d or n.

Advisor: Hammond, Alan
Ziqpu-stars and Cuneiform Knowledge: Meaning, Applications, Contexts

This dissertation is a comprehensive study of a set of stars called ziqpu-stars in Babylonian astronomy. These stars were a tool devised and employed by astronomers during the first millennium BCE (or perhaps as early as the late second millennium BCE) in Mesopotamia. The culmination of the ziqpu-stars, or when they reach their highest point during their daily journey across the skies, was correlated with other celestial phenomena, such as a lunar eclipse or the first appearance of a star over the course of the year. In effect, these stars were used as a way to indicate or describe time of specific phenomena that were of interest to Babylonian astronomers.The present study examines all known sources featuring the ziqpu-stars. It explores the different contexts in which ziqpu-stars were used as well as the developments that took place within this tradition. This dissertation also investigates the underlying practices that are reflected in the texts, and advocates that the primary method to producing and utilizing knowledge of the ziqpu-stars was by means of abstract models rather than empirical observation. Approaching the topic of ziqpu-stars by means of models highlights the similarities between these kinds of texts and texts that belong to the so-called mathematical or theoretical astronomy of the Late Babylonian period. It also brings the study of Babylonian astronomy closer to current discussions in the philosophy of science and reaffirms the place of Babylonian astronomy within the history of science.

Advisor: Rochberg, Francesca