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Measuring the production of three massive vector bosons in the four-lepton channel in pp collisions at √s= 13 TeV with the ATLAS experiment at the LHC
No full textThe Standard Model (SM) of particle physics, while describing fundamental matter constituents and their interactions, remains incomplete. By examining the production of three massive vector bosons, we can directly investigate the non-Abelian gauge structure of the SM electroweak sector, probing the SM triple and quartic gauge couplings. Deviations from the expected values in these rare processes might offer clues to new physics phenomena.
This dissertation measures the production of three massive vector bosons (WWZ, WZZ, and ZZZ), focusing on events with four reconstructed leptons. The study uses 140 fb⁻¹ of proton-proton collisions at √s = 13 TeV with the ATLAS detector at the Large Hadron Collider. Machine learning is employed to distinguish signal from background events and increase the statistical significance
Iterative Coordination and Innovation: Prioritizing Value over Novelty
No full textAn innovating organization faces the challenge of how to prioritize distinct goals of novelty and value, both of which underlie innovation. Popular practitioner frameworks like Agile management suggest that organizations can adopt an iterative approach of frequent meetings to prioritize between these goals, a practice we refer to as iterative coordination. Despite iterative coordination’s widespread use in innovation management, its effects on novelty and value in innovation remain unknown. With the information technology firm Google, we embed a field experiment within a hackathon software development competition to identify the effect of iterative coordination on innovation. We find that iterative coordination causes firms to implicitly prioritize value in innovation: Although iteratively coordinating firms develop more valuable products, these products are simultaneously less novel. Furthermore, by tracking software code, we find that iteratively coordinating firms favor integration at the cost of knowledge-creating specialization. A follow-on laboratory study documents that increasing the frequency and opportunities to reprioritize goals in iterative coordination meetings reinforces value and integration, while reducing novelty and specialization. This article offers three key contributions: highlighting how processes to prioritize among multiple performance goals may implicitly favor certain outcomes; introducing a new empirical methodology of software code version tracking for measuring the innovation process; and leveraging the emergent phenomenon of hackathons to study new methods of organizing. Supplemental Material: The online appendix is available at https://doi.org/10.1287/orsc.2021.1499.Version of Recor
Book of Adam, Gospel of Eve
No full textBook of Adam, Gospel of Eve reimagines the story of the Garden of Eden. It is told in part from the perspective of Adam, who knows nothing of the world outside the walls of the garden, and in part from the perspective of Eve, who lived in the city of Eden for two decades prior to her confinement in the garden.
The ‘author’ witnessed the deaths of Adam and Eve in the final days of the garden and remains alive today. Both stories are written in the third person, and the author, Ye, excerpts additional archaic sources to complete and enrich both books that make up this text.
To Adam and Eve, as well as the author, the god of Eden was a man until he contracted a beneficial contagion that gave him immortal life. The god, Etana, is complicated—capable of giving others the gift of eternal life through baptism, but equally willing to kill indiscriminately. Etana and all who are baptized become sanguivorous, and the centrality of blood in the world of the baptized gives the text its core motif and explains many of the miracles in the holy texts of Judaism, Christianity, and Islam.
Lucifer, the grandson of Etana, baptizes Eve and then Adam before he tempts both of them with the one forbidden substance in the garden. The seven Seraphim assist Etana and oversee the garden, while the Dominion, a lesser rank of angels, maintains the garden’s perfection.
Though Ye’s Book of Adam, Gospel of Eve is aware of its context in a broader world, it focuses on and gives life to a story that is both familiar and sparse.
This thesis includes the first twenty-two pages of Gospel of Eve and the first forty-three pages of Book of Adam. Each is expected to be between thirty-five and forty- five thousand words in length when completed
A Shell of a Good Time: A Design Framework for Oyster Sanctuaries and Playful Parks
No full textOysters play a crucial role in maintaining healthy marine ecosystems through their ability to filter water and provide habitat for various species. The Billion Oyster Project, a New York-based initiative, has been working tirelessly to educate the public about the importance of oysters and restore their populations in the waters around the city. This project combines education and restoration efforts, with a mission to engage both marine life and people in a symbiotic relationship. The central inquiry of this architectural thesis is: How do we design spaces that harmoniously coexist with marine life and serve as recreational and educational resources for the public? In the context of contemporary discourse, this research question addresses critical issues of marine conservation, urban environmental reclamation, and flood protection, as well as modular design and fabrication. The rapid depletion of oyster populations, the reclamation of post-industrial waste sites, and the need for resilient coastal infrastructure have become pressing concerns. By exploring a novel approach that integrates oyster restoration, public engagement, and architectural design, this thesis aims to bridge the existing gaps in these crucial domains. This thesis envisions the creation of an educational and recreational park for the Billion Oyster Project using modular forms inspired by existing wave dissipation blocks. While providing oysters with a habitat to thrive and filter the surrounding water of what was historically an industrial waste dumping site, the modularity also considers replicability and fabrication, as issues of marine conservation and coastal resilience are not endemic to only New York City. The park not only contributes to oyster restoration but also offers a unique platform for public education and recreation. The project postulates that architecture can be a catalyst for the synergy between human and marine life. The outcomes of this research project provide a conceptual framework for future urban waterfront development that can balance the needs of marine ecosystems and human communities
Circulating Follicular Helper T Cells: Evaluating Potential Clinical Biomarkers in Patients with Autoimmunity
No full textBackground
Circulating T follicular helper (cTfh) cells are pivotal in facilitating high-affinity antibody generation and autoimmunity. Variations in the distribution of CD4(+)T cells expressing the C-X-C chemokine receptor type 5 (CXCR5) and their subsets (cTfh1, cTfh17, cTfh1/17, cTfh2) have been documented in various autoimmune diseases. Despite the prominent role of TSH receptor autoantibody (TRAb) production and lymphocytic infiltration in Graves disease (GD), the involvement of cTfh cells in its pathogenesis remains incompletely understood. This study investigated the clinical utility of measuring cTfh subsets in managing patients with GD.
Methods
We conducted an observational study of cTfh cell profiles in pediatric patients diagnosed with GD. Our objective was to delineate potential clinical correlates, including disease activity and TRAb positivity, associated with patterns of cTfh skewing. We identified protein biomarkers potentially implicated in GD using the 7k SomaScan Assay v4.1, principal component analysis and pathway enrichment analysis with Enrichr. To validate the SomaScan findings, we performed enzyme-linked immunosorbent assays (ELISAs) for von Willebrand Factor (vWF) and actinin-alpha-2, selected based on their potential relevance to GD across the entire GD cohort.
Results
We enrolled a cohort of 38 patients with GD and 50 controls without any history of autoimmunity or immunologic disorders. Among the GD cohort, 89% were female, with a median age of 18 years. At the time of enrollment, 50% of the patients had active disease, 21% were in remission, and 29% had undergone definitive therapy. The most frequent comorbidities were obesity and Trisomy 21. Overall, CD4(+)CXCR5+ cTfh cell percentages were normal, with 15% exhibiting CD4(+)CXCR5+CXCR3+CCR6+ cTfh1/17 skewing. Levels of vWF, a marker of endothelial dysfunction or inflammation, were elevated in patients with active GD and significantly higher in those with Trisomy 21.
Conclusions
Increased percentages of cTfh1/17 cells and the presence of platelet dysfunction markers showed significant correlations with active GD, particularly evident in patients with Trisomy 21. cTfh cells and vWF levels could be potentially relevant biomarkers in patients with Trisomy 21. Targeting T cell activation pathways may offer therapeutic benefits in certain subgroups of patients with GD
Critical Friendship After the Pandemic
No full textAre critique and the “art of governing” antithetical? The aim of this article is to examine this tension that was laid bare by the Covid-19 pandemic by introducing “critical friendship” as a conceptual framework for a constructive interdisciplinary engagement with science in a post-pandemic era. It does so by drawing on several works and insights: (i) Michel Foucault’s notion of “critical attitude” as well as his assessment of philosophy as providing a “diagnosis of the present;” (ii) Bruno Latour and colleagues’ idea of a “critical zone” or what I call a horizontal epistemology of critique; (iii) Aristotle’s notion of friendship as being necessary for the “common good;” and finally (iv) Jacques Derrida’s interpretation of the messianic character of friendship in the constitution of progressive democracies. Whereas critical theory has been described as either “explanatory-diagnostic” or “emancipatory-utopian,” a critical friendship approach aims to be both diagnostic and emancipatory in an age of uncertainty and democratic backsliding.Version of Recor
Political Corruption: An Explanation for Latin American Migration
No full textThis study examines the intricate relationship between political corruption and migration. While existing research focuses mostly on the economic determinants of emigration, this explores the often-understudied political aspects acting as push factors, particularly political corruption as a driver of emigration from Latin America. Using the gravity model with cross-sectional data on yearly migration and corruption patterns of 16 Latin American countries from 2012 to 2021, this analysis reveals a strong relationship between political corruption and migration patterns. The study distinguishes between non-immigrants (tourists, business travelers, and students), who sometimes overstay visas to become informal migrants, and unauthorized migrants apprehended by border patrol entering the United States. For both groups, an increase in corruption in the origin country is associated with increased emigration rates, though also being shaped by other factors like the minimum wage and GDP per capita. This study also introduces the concept of the “shock element” to the decision-making process to emigrate. Corruption scandals are a mechanism that incentivizes individuals to consider emigration. Individual-level survey data on the motives for emigration from Guatemala shows that corruption is a primary incentive, particularly corruption scandals within a given year explain migration patterns from the country
Expertise and Empire: Fortification Building and the English Ordnance Office, 1660-1714
No full textThis dissertation examines the integral role played by military engineers, and the state institution that deployed and oversaw them, in the making of the British Empire. The second half of the seventeenth century was a formative moment of English imperial expansion. As England accumulated a growing number of colonies and extended its claims farther into indigenous territories, the state simultaneously sought to centralize the empire’s administration from London. In this contradictory moment of expansion and consolidation, military engineering emerged as a means of imposing English power on distant and diverse colonial territories.
To trace this history, the study focuses on a single government institution, the English Ordnance Office. Traditionally charged with the supply of arms for the army and navy, between 1660 and 1714, the Ordnance Office became the institutional center for fortification building both within England and throughout its empire, and it established and oversaw a cadre of engineers who managed building projects from Tangier to Ireland, Newfoundland to Jamaica. This profound transformation depended on complex negotiations among engineers, officials, and laborers with distinct fields of expertise, working across unfamiliar and unpredictable geographies far from the metropole. The dissertation toggles between England and its colonies to trace this growing, if tenuous, centralization of colonial fortification. Examining projects in North Africa, Ireland, North America, and the Caribbean, it reconstructs how the English state used engineer training, bureaucratic systems, visual representations, a global trade network, and the expertise of engineer-agents to weave together an engineering apparatus capable of defending—and constructing—an empire
Chemical Biology Strategies for Targeting Transcriptional Axes in Neurological Disorders
No full textTranscriptional dysregulation is a hallmark of numerous neurological disorders, offering targetable pathways with the potential to alter disease progression substantially. This Dissertation integrates chemical biology and precision medicine principles to discover and characterize small molecules capable of modulating dysregulated pathways.
Through a series of functional cell-based screening assays targeting key transcriptional axes, such as the Wnt signaling pathway, AP-1 transcription factors, and BET family members, this work identifies compounds that exhibit unexpected, often gain-of-function, mechanisms of action. These discoveries, which include potential therapeutics for neurological and neuropsychiatric disorders, highlight transcriptional vulnerabilities that would not have been attainable through genetic or in vitro screening alone. Building on these discoveries, we validated the therapeutic potential of these compounds through their characterization in patient-derived induced pluripotent stem cell models.
This work begins with the discovery of small molecules that reprogram BET family members for the enhancement of GRN (Chapter 2) and extends these investigations into a microglia-like cell type aided by the development of a microglia-
based PGRN-luciferase reporter line (Chapter 3). I next turn towards the discovery of a class of 3,5-disubstituted isoxazole carboxamides that can enhance Wnt signaling and describe our target identification efforts that converge on RNA-binding proteins (Chapter 4). Finally, I detail the characterization of covalent modifiers of the transcription factor ΔFosB and introduce a novel reporter line that aids in the discovery of small molecule AP-1 modulators (Chapter 5). Collectively, my studies demonstrate the utility of chemical biology approaches in identifying therapeutically relevant small molecules with unexpected mechanisms of action and highlight their potential within precision medicine frameworks
The Possibility of Critical Realism
No full textAn investigation into the potential incompatibility between critical metaphilosophy, the view that traditional philosophy violates the conditions of its own intelligibility, and realism, the view that (at least some) things are independent of us. I argue for their compatibility by working through important attempts to reconcile them made by Kant, Heidegger, and Putnam.
Philosophy is self-reflective. Part of the philosophical project is to consider the nature, scope, and limits of the project itself. Historically, this has led some philosophers to the view that philosophy is incapable of its traditional aspirations (e.g., to gain knowledge of the world by a priori means). In its distinctively post-Kantian form, which I call critical metaphilosophy, the view is that traditional philosophy violates certain limits to thought or language. For example, purely a priori theorizing lacks a requisite grounding in our experience or activity.
Critical metaphilosophy faces historically recurring problems that have tended to make it seem rationally unacceptable. One such problem is its potential incompatibility with realism. The need to ground meaningful discourse in our experience or activity threatens to leave us incapable of meaningfully affirming that things exist independently of that experience or activity. I investigate this problem by working through three important attempts at critical realism: Immanuel Kant’s empirical realism, Martin Heidegger’s ontical realism, and Hilary Putnam’s internal realism.
I argue that Kant’s attempt fails due to his transcendental idealism, on which independence and intelligibility turn out to be mutually exclusive. But the failure is instructive. The issue with Kant’s attempt isn’t his experiential conception of independent reality, but the idealistic commitments accompanying it. We can open up a route to critical realism by clearing away such commitments. Then, we can argue that the most realism can intelligibly require is that, given the conditions of intelligibility, things are intelligible as independent of us – according to experiential or practical standards. To demand more is to demand the unintelligible.
I argue that Heidegger and Putnam both pursue this sort of strategy. For Heidegger, our understanding of being – in particular, of ‘presence-at-hand’ – makes it possible for us to experience things as independent of our involvement with them. In abstraction from our understanding, he argues, things aren’t intelligible as either independent or dependent. Heidegger’s attempt is undermined by his commitment to temporal idealism, the view that time depends on us, but I argue that the strategy itself is separable from that commitment.
For Putnam, similarly, things are intelligible as independent of us with – and unintelligible without – some conceptual scheme in place. Putnam’s attempt is undermined by his commitment to an ‘interface’ model of cognition, which implies that things are scheme-dependent. But, again, I argue that the strategy is separable from that commitment. Insofar as Putnam rejects temporal idealism and Heidegger rejects the ‘interface’ model, they can serve as mutual correctives. And each of them, in fact, moves in the other’s direction in his respective later work