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A Neuron in the Visual System That Provides Feedback About Limb Movement
Sensory stimuli can arise from the environment and also, predictably, from an organism’s own movements. The ability to distinguish between self-generated and external sensory stimuli is essential for normal behavior, but the neural circuits that anticipate and cancel responses to self-motion are not well understood in most organisms and modalities. This study focuses on a previously uncharacterized group of neurons in the Drosophila visual system known as LT52 cells. LT52 cells receive the majority of their input from the optic lobes and provide strong inhibitory input to a specialized circuit in the central brain that mediates the visual pursuit of moving objects. To our surprise, we found that LT52 neurons are strongly activated when flies groomed their heads – even in the absence of an external visual stimulus. By comparing activity in genetically blind and control flies, we determined that this activity is partially driven by a non-visual signal. We found that the non-visual component of the response is specifically related to the movement of the ipsilateral foreleg, suggesting that it arises from internal self-motion signals, specifically proprioceptive feedback and/or copies of ipsilateral motor commands. In terms of visual tuning, we found that LT52 neurons respond best to large, fast-moving stimuli with vertically extended edges and have a strong directional preference for motion in the front-to-back direction. We show that these tuning properties overlap with the visual stimulus generated by the fly’s leg as it sweeps back and forth across the eye during head grooming, suggesting that LT52 activity during head grooming is also partly driven by visual reafference. The visual tuning of LT52 complements the tuning of its postsynaptic targets, which are small object motion detectors that respond to slower, more ethologically-relevant speeds. Taken together, our results suggest that LT52 neurons serve to inhibit the postsynaptic population’s response to large, fast-moving stimuli that the downstream circuit might otherwise confuse for the movement of a visual target. The movement of the fly’s own leg represents a special kind of visual “distractor” whose appearance can be predicted by a combination of visual reafference and internal self-motion signals input to LT52.Medical SciencesMedical Science
Reparative, Resentful, Queer, Parasitic: Varieties of Rewriting, 1900–Present
My dissertation project asks why contemporary authors continue to reread and adapt classic texts and why modernist authors have come to wield special power as precursors. Rewriting takes many forms: stories may be retold from another character’s perspective, transposed to a new setting, or simply continued from where the author left off. Memoirs and anti-biographies rewrite a canonical author to better suit contemporary sensibilities, while many novelistic rewrites pitch themselves as the text as it "should" have been written. Whether it is to imbue an old story with new political energy or to give marginalized characters a happier ending, rewriting emerges in the 20th century as a paradigm distinct from the models of influence and adaptation. I argue that rewriting must be understood on its own terms and that a more robust taxonomy is needed for theorizing this ever-growing practice, whose origins I trace to British modernism. Despite certain commonalities, rewrites mediate past and present through varied means. They can be simple forms of tribute or avenues for self-help. Their intent is, frequently, "reparative"—to rewrite stories to be more inclusive and just—but just as often "resentful"—bound up with a desire to react against and contradict a predecessor. Very often they are "queer"—unstraightforward, ambiguous, neutral, fraught. And, sometimes, they are "parasitic"—nakedly opportunistic in mining the canon for material and cultural prestige. I take a trans-periodizing approach, tracing how modernism resurfaces and informs contemporary fiction and nonfiction. Through case studies of Virginia Woolf, D. H. Lawrence, and E. M. Forster, I show that rewriting, instead of being a strictly postmodern or postcolonial concern, is a useful conceptual framework for understanding modernist literature. Methodological approaches to rewriting are limited. The phenomenon is usually dismissed as the byproduct of a risk-averse publishing industry or seen as a liberal “rescue mission” to recuperate characters who have not been given their due. The useful, but limited, frameworks of postcolonial “writing-back,” postmodern “pastiche,” and feminist “re-vision” do not account, however, for the full range of rewriting. My goal is to taxonomize several varieties of rewriting, argue for its centrality to the modernist period, and account for critiques that have emerged at the turn of the twenty-first century in the work of A. S. Byatt and J. M. Coetzee. Viewing the history of twentieth century literature through the lens of rewriting allows me to retell the story of modernism anew, while establishing why this practice has such a firm hold on literary culture today. My intervention is to show that rewriting is a spectrum, that individual rewrites cannot be praised or vilified according to a single political or aesthetic framework, and that the pivotal moment in its ascendancy is not the 1960s, but the early twentieth century
Discovery of ultra-low-signal variants to study human evolution and epilepsy
Next-generation sequencing (NGS) has revolutionized research on human evolution and brain-related diseases. With DNA-sequencing data available from humans at different time periods and affected tissues in the disease of interest, researchers have been able to conduct more quantitative analyses to answer questions such as which genetic variants likely contribute to higher functionality of the human brain and which genetic variants occurring in which parts of the brain potentially cause epilepsy. However, challenges in variant detection and interpretation remain and require significant efforts to develop novel computational methods accompanied by experimental techniques. Highly degraded short DNA templates and non-even sequencing depth lead to difficulty in detection of transposable elements (TEs) from ancient humans, while somatic mutations, i.e., non-hereditary mutations that arise during human development, can be present at very low variant allele fractions and elude detection.
In this thesis, I reliably detect underappreciated genetic variants due to their low signal-to-noise ratio from NGS data and reveal how these variants can contribute to the genetic basis of human evolution and different types of epilepsy. In Chapter 1, I show that our new machine learning method can reliably detect TEs in highly degraded and unevenly sequenced ancient human DNA, which provides some clue of how they can affect human evolution. In Chapter 2, I describe our efforts to capture weak signals of somatic mutations from hippocampus and present strong evidence that these mutations in cancer-related genes can cause temporal lobe epilepsy. In Chapter 3, I report our success in detecting known and novel somatic mutations from trace DNA adhering to single seizure-monitoring electrodes from pediatric epilepsy patient brains. These results have paved the way for alternative genetic explanations of human evolution, revealed the surprising crosstalk between cancer signaling pathways and non-tumor associated epilepsy, and advanced early and minimally invasive molecular diagnosis of epilepsy.Medical SciencesMedical Science
Marriage in Contemporary Northeast Brazilian Popular Poetry and Comedy
This dissertation analyzes five works of northeast Brazilian cordel poetry (popular verse poetry in chapbooks) and three northeast Brazilian stand-up comedy performances through the lens of their respective treatment of the theme of marriage. It poses and answers three questions: how does each work characterize marriage, how do these characterizations tend to differ between the two genres, and what do those tendencies reveal about the nature, status, and direction of each genre? It also newly identifies commonalities between northeast Brazilian cordel poetry and stand-up comedy. Finally, it proposes new questions for future consideration, based on this study’s conclusions.
This dissertation is innovative in several respects: it is the first academic study of northeast Brazilian stand-up comedy; it is the first in-depth analysis of the theme of marriage in northeast Brazilian cordel; it is the first work to compare the two genres; and all eight of the works that it analyzes have never been written about before. These eight works were selected because they are representative of the genres and because they focus on the theme of marriage. The five selected poems are also representative of the diversity of cordel poets, as they include works by authors of different ages, genders, sexual orientations, and geographic areas of northeast Brazil. The five cordel poems analyzed are: O romance de João Besta e a Jia da lagoa by Francisco Sales Arêda (circa 1950); O sacrifício do amor ou o noivo ressussitado by Manoel d’Almeida Filho (1977); O casamento do boiola by José Francisco Borges (1985); Romance de Amanda e Mara by Graciele Castro (2020); and As ninfas da cachoeira ou o castigo da ambição (2001) by José Mapurunga. The three stand-up comedy performances analyzed are: “Um show de comédia standup” by Paulo Araújo’s (2018); “Adulto” by Whindersson Nunes (2019); and “Comédia da vida casado” by Kedny Silva (2022). Other active northeast Brazilian comedians, including Arianna Nutt and Max Petterson Monteiro, are referenced but not analyzed, as they have not yet published extensive recordings of their stand-up comedy performances.
The analysis of the five cordel poems through the lens of marriage reveals diverse approaches, styles, identities, and perspectives. Each poem depicts marriage from a different angle and in a different light; moreover, each one does so with nuances and layers of meaning that only a close reading can reveal. Arêda presents happy marriage as a reward for the protagonist’s supposed humility, whereas d’Almeida Filho frames marriage as a social obligation in which the protagonist repays female devotion by offering marriage in return. Borges, in his whimsically vulgar poem, leverages gay marriage to satirize the clergy, while mocking homosexuality as a “modern” aberration. Castro, on the other hand, in sharing her personal story about meeting and marrying her wife, celebrates marriage, including gay marriage, as a sincere expression of love. Mapurunga, meanwhile, frames marriage as an imperative: he grants prosperous marriage as a reward for his protagonist’s honesty and obedience, while also directly exhorting his (ostensibly male) reader to embrace monogamy and settle down. Furthermore, analysis of the poems’ wording and rhymes reveals subtleties that complicate and transcend the above interpretations.
The three stand-up comedians, on the other hand, all jokingly characterize marriage in mostly the same manner, dwelling on a negative, pessimistic depiction of marriage centered on conflict and tension. They present personal anecdotes from their marriages in that light, and they extrapolate those alleged experiences to general affirmations. In doing so, they focus on a single trope: the henpecked, emasculated husband in a passionless relationship who lives in fear of his wife’s anger and eventually capitulates to her manipulation and demands. Only Nunes ventures beyond that characterization, employing the theme of marriage as a basis for affirming and joking about his low-income upbringing, regional and socioeconomic class contrasts in Brazil, and the opulence of Brazilian elites along with the greed of those who profit from them. The creativity, originality, and ingenuity of the comedians’ stand-up comedy performances are to be found not in the plot, framework, or underlying messages of the material, but rather in the unique details of the comedians’ respective anecdotes, in the cleverness of their wordplay, and in the flourishes of their delivery that successfully evoke the audience’s laughter.
This study has generated new questions that only further study and the passage of time will answer. Could northeast Brazilian stand-up comedy, like cordel, become more diverse and innovative? Specifically with regard to the comedians’ treatment of the theme of marriage, why is there such uniformity and negativity? Nutt, in her few published video clips of her stand-up comedy performances, makes jokes about marriage and divorce that align with the three male comedians’ characterizations. Is there something about the imperative of generating laughter that requires the comedians to base their marriage jokes, at least to some extent, on depictions of interpersonal conflict? Are those characterizations currently necessary or most effective for generating humor for Brazilian audiences, or are they prevalent for other reasons? To what extent is the trope of marital strife, and its usage in northeast Brazilian stand-up comedy, a localized phenomenon, and to what extent is it characteristic of stand-up comedy more broadly? Will northeast Brazilian stand-up comedy on the topic someday consist of more material beyond that trope? And when, and in what ways, will gay marriage form a substantive part of the material of northeast Brazilian stand-up comedians? If there is to be a transformation in how marriage is portrayed, what, or who, will drive it? More generally, how and why will northeast Brazilian stand-up comedy evolve? Will it diversify mainly due to an increase in the diversity of its comedians, or might diversification occur for other reasons – such as increased maturity of the genre over time, along with more experienced audiences that are fatigued by well-worn tropes and that seek out new approaches? Finally – whether with or without such an evolution of the genre’s content and approaches – will Brazilian stand-up comedy, including that of northeast Brazilian comedians, attract the scholarly and critical attention that today it still lacks? Might Brazilian stand-up comedy’s foreign origin, as well as the “discovery” and appreciation of it by foreign scholars, inspire Brazilian intellectuals to recognize Brazilian stand-up comedy (including northeast Brazilian stand-up comedy) as an art form worthy of study – in the same way that Brazilian scholars, motivated by the constructed myth of Brazilian cordel’s foreign origin and by the interest of foreign researchers, embraced cordel poetry and enthusiastically began researching it in the 1960s after having mostly ignored it for over half a century?
As for northeast Brazilian cordel poetry, how will the genre evolve? And how might it be influenced, if at all, by the rise of stand-up comedy in the region? Will the two genres continue to flourish and evolve in parallel? This dissertation argues that stand-up comedy is in some ways an heir to cordel, given that the genres share a number of key attributes, and considering that northeast Brazilian stand-up today has some characteristics that northeast Brazilian cordel used to possess but no longer does (or at least not to the same extent). Both stand-up comedy and Brazilian cordel poetry are characterized by the commercialization of published products (videos and chapbooks), by the use of themes and techniques that generate or suggest intimacy so as to compensate for the distance between the performer and the audience, and by the inclusion or simulation of direct dialogue or interaction, however limited in scope, between the artist and the viewer or reader. Meanwhile, northeast Brazilian stand-up comedians perform to live audiences and publish recordings that reach millions of viewers, whereas cordel poetry nowadays is rarely recited publicly as it once was, and it no longer has the readership that it once did. This is not at all to say, however, that cordel poetry has been superseded by stand-up comedy. Although stand-up comedy may have overtaken cordel in terms of live performances, distribution, and audience size, it has by no means challenged cordel poetry with regard to the literary genre’s cultural significance and identification with the region. Moreover, the immensity and diversity of the cordel poet community, including the presence of many young poets, attests to the continued relevance and dynamism of the genre – even though the genre has evolved away from live performance, and even if fewer chapbooks are sold today than decades ago. How might northeast Brazilian cordel poetry and stand-up comedy converge, or diverge, or coexist, in the coming decades? Might there be a resurgence of live performances of cordel, in the form of poetry readings and theatrical presentations? Or will the cordel universe continue on the path toward becoming an entirely written genre, leaving the element of performance to other genres? Meanwhile, will the pursuit and presence of humor increase in cordel as a consequence of competition or influence from stand-up? Or will cordel authors instead focus mainly on conveying new opinions and perspectives, ceding the realm of humor and laughter to stand-up? Finally, might it be the northeast Brazilian stand-up comedians who change course, maintaining humor and laughter while more purposefully selecting and diversifying the premises of their jokes? These are some of the questions for future consideration that emerge from this study’s analysis of eight works in two genres of northeast Brazilian popular cultural production
Tracing Earth’s Oxygen Cycle through High-Precision Multiple-Isotope Analyses
The oxygen cycle is fundamental to the past, present and future of Earth’s climate. This thesis focuses on three central components of the oxygen cycle: seawater sulfate (Chapter 1), molecular oxygen (Chapter 2), and odd-oxygen (Chapter 3). Together, these components encompass oxygen cycling in all regions of the fluid Earth (solid-fluid Earth interface, ocean, and atmosphere), and on timescales from geologic to transient. The study of each is enabled by emerging, high-precision multiple-isotopologue analyses.
Chapter 1: Seawater sulfate is a major carrier of oxidizing capacity, and its budget is therefore a critical control on Earth’s redox state. Here, the influence of submarine hydrothermal systems on seawater sulfate is investigated through triple-oxygen-isotope analyses. These analyses suggest that the seawater sulfate budget may contain a significant, and previously overlooked, hydrothermal contribution.
Chapter 2: The flux of O2 generated by gross primary production is critical to Earth’s oxygen and carbon cycles, but accurate estimation of this flux remains challenging. Here, triple-oxygen-isotope analyses of O2 are used to characterize the uncertainty in current estimates. A new method for estimating gross productivity, based on the fractionation of multiply-substituted O2 isotopologues (17O18O or 18O18O), is then proposed. This may reduce current uncertainties in gross primary production by a factor of 4.
Chapter 3: Odd-oxygen (i.e. atomic oxygen, O, and ozone, O3) is a central control on atmospheric oxidising capacity and therefore on climate. Reconstruction of recent changes in atmospheric odd-oxygen is inhibited by the short lifetime of each species. Here, experiments are used to identify signals of odd-oxygen photochemistry in the relative abundances of 18O18O and 17O18O. The experiments are used to propose that atmospheric 18O18O and 17O18O may provide unique constraints on past and present O3 cycling
A minimax approach to one-shot entropy inequalities
One-shot information theory entertains a plethora of entropic quantities, such as the smooth max-divergence, hypothesis testing divergence and information spectrum divergence, that characterize various operational tasks and are used to prove the asymptotic behavior of various tasks in quantum information theory. Tight inequalities between these quantities are thus of immediate interest. In this note we use a minimax approach (appearing previously for example in the proofs of the quantum substate theorem), to simplify the quantum problem to a commutative one, which allows us to derive such inequalities. Our derivations are conceptually different from previous arguments and in some cases lead to tighter relations. We hope that the approach discussed here can lead to progress in open problems in quantum Shannon theory, and exemplify this by applying it to a simple case of the joint smoothing problem.Accepted Manuscrip
Enhancing Clinical IVF Embryo Selection through the Integration of Artificial Intelligence and Bayesian Statistics
Despite major advancements in IVF technologies, the success rate of IVF remains low at around 35% and the main challenge of clinical IVF is embryo selection. Our approach to improve embryo selection leverages the advantages of AI, its ability to analyzing large and complex datasets, and Bayesian statistics, its ability to robustly infer causal relationships in complex problems. First, we enhanced the precision and efficiency of Time-Lapse Microscopy (TLM) image analysis through the implementation of Computer Vision (CV) techniques. We developed AI algorithms to automate the extraction of morphokinetic features from TLM movies of human embryos, providing a more objective evaluation of embryo quality. Second, we integrated these CV networks into BlastAssist, a pipeline designed to measure comprehensive, quantitative, and clinically-relevant features in IVF. To validate our pipeline, we conducted detailed comparisons between BlastAssist measurements and manual assessments by human experts, annotations from embryologists during routine treatments, outcomes of single embryo transfer (SET) cycles, and live birth outcomes of transferred embryos. Lastly, using the unprecedentedly large dataset generated by the BlastAssist pipeline in conjunction with electronic health record (EHR) data from three IVF labs, we constructed probabilistic graphical models (PGMs) for the complex IVF process across three key stages: ovarian stimulation,
fertilization, and embryo development. These graphical models elucidate causal relationships among variables in clinical IVF, providing valuable insights for directing future clinical research.Overall, this project has the potential for significant clinical impact. The BlastAssist pipeline has the potential as a powerful tool to streamline the IVF image analysis process and assist embryologists in embryo selection. The integration of AI and Bayesian statistics can enhance our understanding of
this complex process and help us identify key clinical predictors and improve clinical outcomes
Seeds of Societal Progress: Essays on Economic Inequality, Criminal Justice, and Climate Change
Significant economic and social problems threaten 21st-century America, including economic inequality, historic levels of incarceration, and climate change. This dissertation integrates economic theory, econometric techniques, experimental methods, and machine learning to explore how the general public—via public opinion and social networks—can influence, mitigate, or even foster such societal problems. The first chapter develops a social network employment model and shows that minorities suffer disadvantages in economic and social opportunities, all else equal, simply because their social group is smaller—even given the absence of discriminatory intent. I term this phenomenon social network discrimination. The second chapter exploits variation in the timing of district attorney (DA) elections during the steepest rise in U.S. incarceration (roughly 1986–2006) to show that, on average, being in a DA election year increased per capita admissions and months sentenced to state prisons. Interacting results with county characteristics suggests sentencing outcomes respond to public opinion—including anti-Black/pro-White racial bias and preferences regarding the harshness of courts. The third chapter designs and runs a nationally representative survey on 2,430 respondents across the U.S. both to study what factors matter most for U.S. public engagement in climate action, as well as to experimentally test divergent approaches to mobilizing climate action. I find that either communicating a vision for climate change mitigation or communicating its projected damages (or doing both) increases various measures of climate-friendly attitudes. I employ machine learning techniques to identify which groups of Americans are best targeted by such climate-friendly interventions
Obsessive-Compulsive Symptoms and Morningness-Eveningness Variation in Healthy Individuals
The present study proposes to answer the following question: Do people without OCD and a late chronotype have more obsessive-compulsive symptoms than people with earlier chronotypes? Individuals with obsessive-compulsive disorder (OCD) are more likely than healthy individuals to exhibit habitually delayed sleep schedules, sometimes diagnosed as Delayed Sleep Phase Disorder. Additional research suggests that this trend may also be present in people without OCD. Individuals with habitually later bedtimes may exhibit more subclinical obsessive-compulsive symptoms than those with earlier bedtimes. Given that high levels of subclinical symptoms may constitute a risk factor for developing OCD, it is important to understand if delayed sleep schedules play a role in the progression of the disorder from subclinical to clinical. Individual preference for later sleep and wake patterns, called eveningness or late chronotype, has been associated with worse mental health outcomes such as depression, but has yet to be compared with chronotype in healthy individuals.
This study surveyed 57 participants recruited online from the general population to submit reports on their sleep quality, chronotype, and obsessive-compulsive symptoms. Participants also submitted additional daily sleep diaries for one week to confirm sleep habits. Overall, increased eveningness significantly predicted increased reports of obsessive-compulsive symptoms and worse sleep quality. However, poorer sleep quality was a more substantial indicator of symptoms than eveningness, and grouping individuals into chronotype categories was less predictive of symptoms than the
morningness-eveningness scores. Sleep midpoint, a value that is indicative of differences in sleep schedules, was strongly associated with chronotype but was also a better indicator of symptom reports. Total sleep duration, age, and gender did not appear to significantly influence the outcome variables. More research is needed to better understand these relationships in a healthy population sample, especially using objective measurements of sleep timing and quality