FAS Theses and Dissertationshttps://nrs.harvard.edu/1/49276032024-03-19T03:47:09Z2024-03-19T03:47:09ZFrom Dynasty to Nation: A Historiography of the Dueling Portraits of Nguyễn Huệ and Nguyễn ÁnhNguyen, Vinh Quochttps://nrs.harvard.edu/1/373779372024-03-13T09:00:05Z2024-01-29T05:00:00ZFrom Dynasty to Nation: A Historiography of the Dueling Portraits of Nguyễn Huệ and Nguyễn Ánh
Nguyen, Vinh Quoc
This dissertation is an exercise in historiographical exegesis to explore the dynamics of the evolving reconstruction of the lives and afterlives of Nguyễn Huệ 阮惠 (1753-1792) and Nguyễn Ánh 阮暎 (1762-1820) who dominated the histories of the last thirty years of the eighteenth century in Vietnam. It seeks to understand the discursive dynamics behind the articulation of historical truth claims as new stories about the dueling portraits of these two men get continually retold over the past two centuries. This search for usable pasts in the service of an inventive narrative of political legitimation has unfolded through a pivotal shift in historiographical paradigms from traditional Confucian to modern nationalist and Marxist modes.
As dynastic founders Nguyễn Huệ and Nguyễn Ánh offered different solutions to the historical legacy of their predecessor: the Lê 棃 dynasty (1428-1789) with its tension-filled history of regional conflict through three centuries of alternating wars and peace. Their localized regiocentric solutions for self-fashioning dynastic legitimization in the nineteenth century were subsequently derailed by the supranational westerncentric impact of French colonialism, which induced a nationalistic backlash in the twentieth century. This reactive reassertion of a local tradition had been transformed by new varieties of nationalism and would be bifurcated by competing regional identities and visions of victorious destinies during the Vietnam War. This dissertation brings attention back to the centrality of region and regionalism in that historiographical process to understand the necessity of regiocentrism as a deep structure in the process of discursive and identity formation through the inventive manipulation of collective memory. Through six phases over nearly two centuries, the lives and afterlives of these two protagonists alternatingly took center stage in a story of cyclical rise and fall within a linear narrative progression from the Việt Nam state to the Vietnamese nation.
The story of modern Vietnam cannot be fully understood except in the context of residual regional strains through the alternative solutions that Nguyễn Huệ and Nguyễn Ánh brought to the legacy of Đại Việt. Retracing the evolution of their dueling portraits provides a key to understanding the regiocentric deep structure of modern Vietnamese historiography. Instead of “rescuing history from the nation” (Duara) or moving “beyond histories of nation and region” (Taylor) this dissertation dissects the persistent search for narrative coherence through these heuristic devices. This exercise provides a cautionary reminder about the historicity of dynasty and nation and their ensuing varieties of historiography as epistemic and ideological constructs. A better understanding of the underlying deep structure of regiocentrism can bring us a new appreciation for and reappraisal of a fluctuating southern turn/return against the predominant northern pull in Vietnamese historiography. The story of the dueling portraits of Nguyễn Huệ and Nguyễn Ánh attests to the multiplicity and contingency of historiographical truth claims, to the rise and fall, and indeed the reinvention, of new icons for different places and times, in war and in peace. Insights into this process of discursive formation can therefore enrich our understanding of Nguyễn Huệ and Nguyễn Ánh not only as agents and products of their time but also as crystallizing catalysts for new meanings for times to come.
2024-01-29T05:00:00ZB-MYB and FOXM1 drive cell division through cooperative regulation of cell cycle genes.Rivas, Hemblyhttps://nrs.harvard.edu/1/373779362024-03-13T08:59:16Z2024-03-12T04:00:00ZB-MYB and FOXM1 drive cell division through cooperative regulation of cell cycle genes.
Rivas, Hembly
Transcription facilitates cell cycle division and progression as it orchestrates the timely expression of genes crucial for each cell cycle phase. Two waves of gene expression prime the cell for replication: the first wave (DNA replication genes) produces the needed cell machinery for DNA replication, and the second wave of gene expression (mitotic genes) encodes the mitotic regulators required for cell division. The B-MYB/MuvB(MMB)-FOXM1 complex coordinates the expression of mitotic genes. This dissertation investigates the inter-dependence between B-MYB and FOXM1 and their requirement for mitosis.
We show that knockout of MMB-FOXM1 complex components B-MYB, LIN54, or FOXM1 confers resistance to CHK1 and ATR inhibition. In addition, we demonstrate that the loss of B-MYB impedes arrest following contact inhibition. Cell cycle kinetic studies reveal that the knockout of B-MYB or FOXM1 has profound effects on the progression of every cell cycle phase. These findings indicate the MMB-FOXM1 complexes function as global coordinators of cell cycle progression and establish the MMB-FOXM1 as a crucial signaling node in response to cellular stress.
During early S phase, B-MYB binds to MuvB to form the MMB complex. The MMB complex recruits FOXM1, and both B-MYB and FOXM1 contribute to activating mitotic genes. In this dissertation, we extend these findings by showing that MMB enhanced FOXM1 binding to DNA, and B-MYB-mediated recruitment of FOXM1 was critical for the onset of mitotic gene expression. We found that FOXM1 was required to properly dissociate B-MYB from DNA in G2 and degradation of B-MYB and other DNA machinery in mitosis. These findings prove that B-MYB and FOXM1 functionally cooperate and rely on mutually interdependent interactions to activate mitotic genes.
The CHR motif, recognized by the MuvB complex, is primarily enriched at mitotic gene promoters, while canonical MYB and forkhead DNA motifs are less abundant. Current models propose that B-MYB and FOXM1 stabilize MuvB complexes at CHR elements by binding largely non-sequence-specific DNA. Using high-resolution chromatin profiling, we show that B-MYB and FOXM1 binding is correlated but also distinct. We observed that B-MYB binding was enriched at mitotic gene promoters and contained canonical MYB and CHR DNA recognition motifs. In addition, we found that MuvB component LIN9 binding follows the pattern of BMYB rather than FOXM1. We demonstrate that FOXM1 binds to mitotic and DNA damage gene promoters. FOXM1 gene targets were enriched for canonical forkhead DNA recognition motifs. Combining nascent transcript analysis (PRO-seq), RNA-seq, and Cut\&Run sequencing, we define FOXM1 as a critical transcriptional driver of cell cycle gene expression. Collectively, these findings indicate that B-MYB and FOXM1 cooperatively regulate the expression of cell cycle genes, where the MMB complex defines mitotic genes through association with MYB and CHR recognition motifs and enhances recruitment of FOXM1 to mitotic gene promoters, where FOXM1 drives transcription of mitotic genes and DNA repair genes.
2024-03-12T04:00:00ZMultimodal and Context-Aware Computational PathologyChen, Richardhttps://nrs.harvard.edu/1/373779352024-03-13T08:58:43Z2024-03-12T04:00:00ZMultimodal and Context-Aware Computational Pathology
Chen, Richard
Cancers are defined by hallmark histopathological, genomic, and transcriptomic heterogeneity in the tumor and tissue microenvironment that contributes towards variability in treatment response rates and patient outcomes. The current clinical paradigm for cancer classification and prognostication is the manual assessment of histopathologic features such as tumor invasion, immune-infiltrates, and necrosis, which has been demonstrated to suffer from large inter- and intra-observer variability. Current advances in artificial intelligence (AI) for computational pathology (CPath) have demonstrated clinical-grade performance of AI workflows that exceed human pathologist performance in the objective characterization of histopathologic biomarkers in whole-slide images (WSIs) for diagnostic tasks. However, in prognostic tasks such as survival outcome prediction and response-to-treatment assessment, such tasks entail capturing contextual and multimodal information in the tumor microenvironment, which present challenging barriers for CPath workflows seeking clinical translation. In this dissertation, we expand the prognostic capabilities of current techniques, ranging from: (1) combining histology and genomics via multimodal deep learning, to (2) modeling contextual relationships based on permutation-equivariant aggregation techniques in set-based deep learning. For multimodal integration, we explored multimodal fusion architectures for resolving the data heterogeneity gap between WSIs and bulk molecular features, developing a computational technique that spatially deconvolves molecular pathway features onto a WSI. These data highlight not only superior prognostic performance over unimodal approaches, but also capabilities in finding image-omic biomarkers and visualizing feature interactions between morphology and molecular pathways. To model context, we explored set-based architectures for learning relationships between histology features, developing a computational technique based on Transformer attention for learning hierarchical cell-tissue relationships in the tumor microenvironment. These data highlight not only improved prognostic performance over traditional CPath techniques across diverse tumor types, but also clinical interpretability for characterizing contextual relationships in pathology. Together, these studies study two important gaps for cancer prognosis in CPath workflows: (1) multimodal integration and (2) modeling context, serving as a basis for harnessing pathology for prognosis and biomarker discovery.
2024-03-12T04:00:00ZSpace for Democracy?: School Governance in the 21st CenturyReid, Ellishttps://nrs.harvard.edu/1/373779342024-03-13T08:58:06Z2024-01-30T05:00:00ZSpace for Democracy?: School Governance in the 21st Century
Reid, Ellis
The education of young people is a vital task in a democracy with significant implications for both for young people themselves and for the state. How authority over schooling should be shared and organized is, therefore, a vital question in a democracy. This dissertation takes on that question and ultimately defends a broadly democratic account of schooling, insisting on democratic school governance as a critical component of collective self-government. Nevertheless, this dissertation further contends that democratic theorists have paid insufficient attention to the significant democratic deficits of our contemporary institutions of local governance in light of the significant spatially embedded inequalities in the US and have, therefore, failed to develop theory that can truly be action-guiding.
My argument begins with an account of the nature of schooling and the interests relevant to thinking about how the school system should be organized. Building on work by Amy Gutmann, chapter two ultimately defends democracy in school governance grounded in the good of collective self-government. I then turn to our existing institutions of school governance and present a normative assessment of local control—the institutional rules and norms that structure governance of the state-sponsored school system today. In light of the contemporary patterns in the social geography of the US, shaped by a long history of discriminatory federal policy, I argue that local control: (1) leads to injustice in the distribution of educational goods, (2) reliably undermines the kind of democratic culture necessary for realizing meaningful deliberation among citizens, and (3) encourages privileged citizens to rely on “exit” over “voice.”
Finally, I turn to the question of what we should do now. In chapter four, I argue that efforts to reform our school governance arrangements should be guided by a contextual analysis centered on whether those reforms are likely to encourage democratic responsiveness among citizens, contending that policymakers attend to three particular areas of concern: (1) the distribution of the burdens of educational provision; (2) the salience of stigmatizing stereotypes about marginalized groups; and (3) the quality of representation at multiple levels of government. I end by applying these insights to an analysis of school reform in New Orleans. Chapter five offers some concluding thoughts and future directions for research.
2024-01-30T05:00:00Z