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    Negotiating Between Shell and Paper: Wampum Belts as Agents of Religious Diplomacy

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    In a dialogue between the material and the textual, can objects speak over texts? This project examines nine devotional wampum belts produced as cross-cultural mediators between Catholic ecclesiastics and Indigenous people in northeastern North America between the seventeenth and nineteenth centuries. Following Haudenosaunee, Huron-Wendat, Abenaki, and Anishinaabe epistemologies, wampum belts have been considered as both symbols of Native American and First Nations sovereignty, and as non-human beings doted with agency and willpower. When Indigenous Christians sent wampum belts to religious communities in France, Belgium, and Italy, these objects embodied diplomatic requests presented to Christian saints worshipped at these sites. Did these wampum belts function as independent diplomatic agents, without the presence of Indigenous interpreters? If so, what were these belts meant to do? I suggest that there may be heretofore unexamined messages, embedded in the material and documentary record, that reveal the agency and potency of these objects. Closer engagements with wampum materiality can offer insights that are missing from earlier historical studies of missionary-Indigenous relations. To discern this, I examined construction techniques that may reveal Indigenous makers’ agency in articulating political demands. I conducted archival research and re-examined historical translations, while consulting with the Indigenous communities in Canada who created these wampum belts, to assess how wampum messaging impacts the consciousness of humans around it. These diverse sources illuminate the transfers of agency that take place during wampum diplomacy, showing the embodied innovations and continuities that allowed these materials to speak across space and time. These wampum belts constitute an alternative archive of both Indigenous and missionary strategies. The objects and associated papers show savvy Indigenization of Catholic stories and practices to secure new alliances and territories, at the same time that religious orders recorded different understandings of these relationships in French colonial archives. When these belts and papers have survived side by side in collections, they have continued to mediate various relationships, the most significant being between generations of Indigenous peoples who relate to their ancestors through them

    Resource-Constrained Synchrony: Kuramoto Oscillators Competing for Shared Resources

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    Many systems of biological interest exhibit oscillatory behavior, from the beating of a heart to the firing of neurons to the flashing of fireflies. Further, these oscillatory agents are rarely isolated from one another, and so may interact with one another. In the presence of such interactions, one possible outcome is synchronization of the oscillatory motions. Such synchrony may be observed in the simultaneous flashing of a great many fireflies, or the simultaneous firing of many neurons during an epileptic seizure. A classic model that captures this synchronization is the Kuramoto model. However, the Kuramoto model is a toy model, and thus much work has been directed to extending the model by introducing additional dynamics. In the dissertation, we will present two extensions of the Kuramoto model that make it more appropriate to the study or neural systems. The first extension will add a resource dependence to the Kuramoto dynamics, making the internal dynamics of the oscillators more complex, and thereby introducing novel phases into the Kuramoto phase diagram (Chapter 2). The next extension will allow the oscillators to compete for a shared supply of resources, creating a secondary avenue of communication between the oscillators (Chapter 4). This additional communication pathway will generate correlations in behavior, which may have some relevance for the differences observed between functional and structural connectivity measures in the brain. These two studies serve to elucidate some interesting results on the dynamics of Kuramoto oscillators competing for shared resources, and so serve as my primary contribution to the study of the physics of synchronizable systems. Further, as a scientist-educator, I am also interested in and committed to the education of young physicists, and so I have pursued a separate line of inquiry that studies the learning of students in a cross-disciplinary network-neuroscience course using the tool of concept networks (Chapter 6). We will find that student-drawn concept networks are a useful tool in studying the learning process at a high level, but that more thought needs to be put toward optimizing the collection task in order to bring out the full power of this tool. Collectively, these three studies --- two in the physics of dynamical systems and one in education --- have enabled me to develop in my role as a scientist-educator

    Experimental and Computational Analyses of Locomotor Rhythm Generation and Modulation in Caenorhabditis elegans

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    Neural circuits coordinate with muscles and sensory feedback to generate motor behaviors appropriate to its natural environment. Studying mechanisms underlying complex organism locomotion has been challenging, partly due to the complexity of their nervous systems. Here, I used the roundworm C. elegans to understand the locomotor circuit. With its well-mapped nervous system, easily-measurable movements, genetic manipulability, and many human homologous genes, C. elegans has been commonly used as a model organism for dissecting the circuit, cellular, and molecular principles of locomotion. My work introduces two separate approaches to probe the mechanisms by which the C. elegans motor circuit generates and modulates undulations. First, I quantified C. elegans movements during free locomotion and during transient muscle inhibition. Undulations were asymmetrical with respect to the duration of bending and unbending per cycle. Phase response curves induced by brief optogenetic head muscle inhibitions showed gradual increases and rapid decreases as a function of phase at which the perturbation was applied. A relaxation oscillator model was developed based on proprioceptive thresholds that switch the active muscle moment. It quantitatively agrees with data from free movement, phase responses, and previous results for gait adaptation to mechanical loads. Next, I characterized a proprioception-mediated compensatory behavior during C. elegans forward locomotion: the anterior body bending amplitude compensates for the change in midbody bending amplitude by an opposing homeostatic response. I demonstrated that curvature compensation requires dopamine signaling driven by PDE neurons. Calcium imaging experiments suggested a proprioceptive functionality for PDE in sensing midbody curvature. Downstream of PDE dopamine signaling, curvature compensation requires D2-like dopamine receptor DOP-3 in the interneurons AVK. FMRFamide-like neuropeptide FLP-1, released by AVK, regulates SMB motor neurons via receptor NPR-6 to modulate anterior bending amplitude. These results revealed a mechanism whereby proprioception works with dopamine and neuropeptide signaling to mediate homeostatic locomotor control. Together, through a consolidation of experimental and computational approaches, I found C. elegans utilizes its circuitry not only to act motor behaviors but to adjust/correct its ongoing behaviors in its natural contexts

    Geometry of Gradient Flows for Analytic Combinatorics

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    Analytic combinatorics in several variables (ACSV) analyzes the asymptotic growth of generating function coefficients in a direction r. It uses Morse theory on the pole variety V := {H = 0} ⊆ (C∗)d to deform the torus T in the multivariate Cauchy Integral Formula via the downward gradient flow for the log-linear function h = hr = –∑dj=1 rj log :zj:, giving a homology decomposition of T into cycles around critical points of h on V . The deformation can flow to infinity at finite height when the height function is not a proper map. This happens only in the presence of a critical point at infinity (CPAI): a sequence of points on V approaching a point at infinity, and such that log-normals to em\u3eV converge projectively to r. The CPAI is called heighted if the height function also converges to a finite value. The central questions that I have attempted to answer involve analyzing whether all CPAI are heighted, and in which directions CPAI can occur. I attempted to answer these questions by examining sequences converging to faces of the toric compactification defined by a multiple of the Newton polytope P of the polynomial H. The idea is to show that any projective limit of log-normals of a sequence converging to a face F must be parallel to F. This turns out to be true but only under further hypotheses. It implies that CPAI must always be heighted and can only occur in directions parallel to some face of P. The extra hypotheses hold in smooth cases under generically satisfied conditions. In addition, I show under a smoothness condition, that a point in a codimension-1 face F can only be a CPAI for directions parallel to F, and that the directions for a codimension-2 face can be a larger set, which can be computed explicitly and still has positive codimension. The question of whether non-heighted CPAI exist in general is left open; I conjecture that they do not exist

    Role of Type II Phosphatidylinositol 4-Kinases in Endosomal Tubule Dynamics during Melanosome Biogenesis

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    Melanosomes are pigment cell-specific lysosome-related organelles (LROs) in which melanin pigments are synthesized and stored. Melanosome maturation requires biosynthetic delivery of melanogenic enzymes (e.g. TYRP1), transporters (e.g. OCA2), and SNAREs (e.g. VAMP7) from early endosomes (EEs). One essential pathway requires the multisubunit complex, BLOC-1, on EEs to generate tubular transport carriers to deliver cargos to melanosomes. The molecular mechanisms by which BLOC-1 facilitates tubule formation are not entirely known, but several studies suggest that phosphatidylinositol-4-phosphate (PtdIns4P) and the type II PtdIns-4-kinases, PI4KIIα and PI4KIIβ, may play a role. Moreover, PI4KIIα and PI4KIIβ interact respectively with AP-3 and AP-1, both of which control BLOC-1-dependent cargo sorting. We hypothesized that type II PtdIns-4-kinases support BLOC-1-dependent tubule formation via PtdIns4P to regulate melanosome biogenesis. We found that depletion of either PI4KIIα or PI4KIIβ in melanocytes reduced melanin content and impaired the melanosomal localization of TYRP1, OCA2, and VAMP7 by immunofluorescence microscopy (IFM) and bright-field microscopy. TYRP1 was largely mislocalized to late endosomes/lysosomes in PI4KIIα- or β-depleted cells, and not exclusively to EEs as observed in BLOC-1-/- melanocytes. This suggested that type II PtdIns-4kinases are not absolutely required for BLOC-1-dependent cargo exit from EEs but function downstream of BLOC-1. Consistently, depletion of PI4KIIα or PI4KIIβ in BLOC-1-deficient cells did not affect TYRP1 accumulation in EEs by IFM, and depletion of PI4KIIα or PI4KIIβ in wild-type melanocytes did not affect BLOC-1 association with membranes by subcellular fractionation. Rescue studies revealed that enzymatic activity and AP-binding abilities of both PI4KIIα and PI4KIIβ are necessary for TYRP1 localization to melanosomes. Live cell imaging showed that PI4KIIα associates with tubules from the onset of tubule formation, whereas PI4KIIβ accumulates after the tubule has formed, suggesting that PI4KIIα acts earlier than PI4KIIβ. Depletion of either PI4KIIα or PI4KIIβ reduced PtdIns4P on endosomal tubules and impaired tubule elongation. These data together suggest that PI4KIIα and PI4KIIβ function sequentially and non-redundantly downstream of BLOC-1 by generating PtdIns4P on endosomal tubules during tubule elongation and that both isoforms are necessary for efficient melanosome contact and content delivery to melanosome. Our study demonstrates the important roles of PtdIns4P and both type II PtdIns-4-kinases in BLOC-1-dependent tubular cargo transport for melanosome biogenesis and extends the cohort of effectors required for LRO biogenesis

    Dovish Reputation Theory: When Fighting to Demonstrate Resolve Backfires

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    According to traditional, hawkish reputation theory, states inevitably harm their reputation for resolve by backing down and enhance or maintain it by choosing to stand firm and engage in military conflict. This logic has been used, at least in part, to justify consequential interventions like the Vietnam War, which resulted in tens of thousands of deaths and hundreds of billions of dollars spent. However, is it always true that states maximize their reputation for resolve by refusing to back down? In other words, is fighting to demonstrate resolve always a logical reason to go to war? I advance a new theory of reputation—dovish reputation theory—that argues the answer is no. My theory can be summarized in two steps. In the first step, choosing to fight rather than back down in the past can lead to war-weariness that reduces a country’s future level of resolve. In the second step, foreign actors can observe the signs of war-weariness and therefore downgrade their estimates of a country’s reputation for resolve. I test my theory using a multi-method research design that includes survey experiments conducted on the general public and members of the United Kingdom Parliament; large-N statistical analyses of political parties’ election manifestos and militarized interstate disputes; and historical case studies of World War I and the First Iraq War. My analysis yields four key findings. First, the experience of a previous conflict can harm a state’s future resolve. Second, backing down, all else equal, does undermine a state’s reputation for resolve. Third, choosing to fight can also erode a state’s reputation for resolve if signs of war-weariness develop. Fourth, the reputation for resolve costs associated with war-weariness can equal or outweigh the reputation for resolve benefits of not backing down. This means states do not always enhance or maintain their reputations for resolve by engaging in military conflict rather than backing down. The most important implication of this project is that the benefits of using military force are lower than the common wisdom suggests

    Covenantal Connections: Visualizing Mosaic Law in the Middle Ages

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    This dissertation examines iconography related to the Mosaic covenant in Jewish and Christian contexts of western Europe, specifically the regions of northern France and the Holy Roman Empire from circa 1150 to 1348. While there is more than one covenant in the Hebrew Bible, this project discusses the Mosaic covenant—ratified by the Tablets of Law delivered to Moses and the Israelites at Mount Sinai—which holds essential concern for both Jewish and Christian communities of the later Middle Ages. By situating the imagery of the Mosaic covenant within internal developments pertinent to both communities, this study illuminates how such covenantal iconography was intricately tied to current concerns, shaped by matters of the day, and key to fashioning their respective identities. Building on and departing from past literature, this study focuses on how Jewish communities in medieval Ashkenaz perceived themselves in relation to the Mosaic covenant vis-à-vis their own internal communal developments, in dialogue with liturgical practices. This study is the first to examine a corpus of six festival prayerbooks (mahzorim) from medieval Ashkenaz, particularly the imagery and liturgy for Shavuot (“Festival of Weeks”), the holiday that commemorates the biblical event of Moses and the Israelites receiving the Ten Commandments on the Tablets of Law at Mount Sinai. Mahzorim, used by the Jewish communities in liturgical practice, furnish valuable evidence for reconstructing a living tradition when almost all other evidence has been lost. This dissertation investigates the different visual strategies deployed for illustrating the scene of the revelation of the Law and argues that the mahzorim, contextualized within the pertinent liturgy and ritual practices, aided the Jewish communities of medieval Ashkenaz in asserting their ongoing covenantal connections within their contemporary Jewish practice

    Improving Molecular Diagnosis of Suspected Mendelian Disorders with RNA Splicing Analysis

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    Exome sequencing is the most advanced standard-of-care genetic test for people with suspected Mendelian disorders. Yet, the diagnostic rate of exome sequencing is only 31%. RNA sequencing (RNA-seq) is a promising molecular test for detecting potentially pathogenic changes in RNA splicing as part of obtaining a molecular diagnosis. In this dissertation, I develop new computational tools and perform analyses towards improving how we detect these potentially pathogenic changes in RNA splicing with the goal of improving the molecular diagnostic rate. First, in Chapter 1, I review background on how we diagnose patients and how RNA splicing and RNA-seq could be used to improve this process. Then, in Chapter 2, I describe my contributions to MAJIQ v2 as methodology to study RNA splicing from large and heterogeneous RNA-seq datasets. Afterwards, I use MAJIQ v2 in Chapter 3 to evaluate how tissue-specific expression and splicing affects what clinically-relevant splicing changes we can identify from clinically-accessible tissues. Then, in Chapter 4, I describe the limitations of MAJIQ v2 for our approach to detect splicing aberrations and the development and evaluation of MAJIQ v3 to address these challenges. With MAJIQ v3, I develop MAJIQ-CLIN in Chapter 5 to identify and prioritize splicing aberrations in patient RNA-seq data and compare our method to previous approaches. Finally, in Chapter 6, I discuss overall conclusions for the work and exciting areas for future work. Together, the work in this dissertation pushes forward how we can study and use RNA-seq to improve the diagnostic rate of patients with suspected Mendelian disorders

    The Digital Bahdala: Recoding National Humiliation Across Postrevolutionary Lebanon and Egypt

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    This dissertation analyzes three transnational social media scandals in the postrevolutionary contexts of Egypt and Lebanon. It offers these as cases of digital bahdala, or the didactic performative mode and state of humiliation, embarrassment, or shame which utilize the affordances and imaginaries of digital media platforms. It examines the rhetorical techniques, performances, and symbols used by transnational publics on three different social media platforms around these scandals. It finds that audiences engage in recoding, or the cultivation of alternative feeling states, to repair national imaginaries which are exposed as incompatible with a cosmopolitanism which was once promised. It also finds that activists can leverage the digital bahdala and its reliance on digital affordances meet demands for national accountability in exploitative labor conditions. In doing so, it offers digital bahdala as a diagnostic for a national belonging which is threatened but which carries the potential for repair

    Glass-Boxing Computing with Electronic Textiles: Teaching and Learning with Notional Machines in an Introductory Computing High School Classroom

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    Developing a conception of the invisible and abstract internal processes that translate computer programs into observable outcomes is essential yet challenging for learners. Notional machines are simplified notions that educators adopt to make transparent or glass-box program dynamics to learners while teaching. In this thesis, I examined teaching and learning with notional machines during a 14-week online introductory electronic textiles unit in a charter high school. Two broad groups of research questions guided this dissertation—one, exploring teaching, and two, examining student learning with notional machines. Research questions on teaching included: (1) What notional machines did the teacher adopt? (2) What forms did the notional machines take in practice? Research questions on student learning included: (3) How did students interact with notional machines during the unit? (4) Did notional machines support students’ development of computing conceptual agency? If so, how? (5) How did students’ conceptions of computing systems shift after learning with notional machines? Multimodal data—online class recordings, student pre- and post-unit interviews, and student-generated artifacts—were qualitatively analyzed to answer the questions posed. Overall, observational data analysis provided one of the first frameworks to capture notional machines in practice. Notional machines belonged to one of the five themes depending on the electronic textiles concept being simplified and differed along the levels of granularity. Also, notional machines took two distinct representational forms—verbal explanations and participatory roleplays. Analysis of student interactions with notional machines highlighted the agentic roles learners took: questioning, adopting, explaining notions, and roleplaying program execution. Further, student pre- and post-unit interviews indicated that students’ conceptions of program dynamics shifted from being simplistic to more advanced in a set of everyday physical computing devices, showing promise for student sense-making of computing devices outside their immediate programming context. Overall, findings from this study point to future research directions to further explore teaching and learning with notional machines and their potential to expand computing learning beyond classroom contexts

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