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Washington, D.C., a Black Aesthetic, & the Politics of Renewal
No full textSince 2010, Washington, D.C. has undergone major shifts in its racial demographics and property value. What was once a city that boasted a seventy percent population of black residents in the 1970s, giving it the moniker “Chocolate City,” has become an urban landscape overrun by developers, construction sites, and new residents who assist in branding the “new” Washington. What does that branding include? Not only new buildings, but an investment in an aesthetics that makes use of “Chocolate City’s” past to define its new and “authentically urban” future. I argue that despite the intentional attempt at erasure of black life and culture from the capital’s landscape, native black Washingtonians continue to produce an aesthetic birthed out of the Chocolate City of the 1970s, but decidedly invested in the contemporary focus on specificity of place. To that end, “Washington, D.C., a Black Aesthetic, & the Politics of Renewal” is an excavation of literary, film and visual artistic production as a means by which to interrogate what I identify as a new practice in black aestheticism. I articulate that black aesthetic, which I term an aesthetics of loss, as existing alongside and despite ongoing displacement and dispossession of black people and black spaces, and I enact a multi-methodological approach to get at its nuance. My work centers around black cultural curators in Washington, D.C. who use literature, film, music, and visual art to inscribe themselves and their communities as in place in the face of systemic erasure. To be clear, by “in place” I mean taking up material place, not just ideological space, on the mapping of the District of Columbia. Ultimately, this dissertation asks: What does it mean to live when you have been pronounced dead
Mass Spectrometry Methods for Studying RNA Modifications and RNA-Protein Interactions
No full textThe central dogma of biology dictates that sequence information encoded in DNA is transferred via transcription to RNA and through translation encodes a protein. While this provides one level of control, the majority of DNA, RNA and proteins are fine-tuned through chemical modifications that modulate their structure and function. Proteomics by liquid chromatography/mass spectrometry (LC-MS/MS) is an unbiased view into the world of these modifications by providing a tool to uncover their regulation and function. Specifically, the study of RNA modifications has exploded due to the parallel advancement of next generation sequencing and LC-MS/MS, but these technologies are incomplete due to the inability to capture the full depth of RNA modifications in robust manner. In this work, we designed new methods for the study of RNA modifications by creating a platform focused solely on improving the RNA MS. Separately, we have applied new methods in LC-MS/MS to virus biology to uncover how post-translational modifications (PTMs) of proteins govern RNA-protein interactions (RPIs). To this end, we investigated how PTMs are globally affected by adenovirus infection and uncovered key PTMs required for viral protein function. We identified a striking loss of arginine methylation due to the shuttling of protein arginine methyl transferase 1 (PRMT1) into the cytoplasm, away from nuclear RBPs. Overall, both works provide advances in mass spectrometry methods and illustrate their application, providing the tools to ask deeper questions about RNA and protein modifications and viral biology
Machine Learning under Endogeneity
No full textRecent advances in machine learning literature provide a series of new algorithms that both address endogeneity and can be applied in high-dimensional environments, we call them MLIV. These algorithms are data-driven and exploit various forms of regularization to ameliorate the ill-posedness of the problem while maintaining the functional form flexibility. In this thesis, we discuss how MLIV estimators can be used to answer economic questions. In the first chapter, Causal Gradient Boosting: Boosted Instrumental Variables Regression, we propose an MLIV algorithm called boostIV that builds on the traditional gradient boosting algorithm and corrects for the endogeneity bias. The algorithm is very intuitive and resembles an iterative version of the standard 2SLS estimator. The second chapter, Automatic Debiased Machine Learning in Presence of Endogeneity, introduces an approach for performing valid asymptotic inference on regular functionals of MLIV estimators. The approach is based on construction of an orthogonal moment function that has a zero derivative with respect to the MLIV estimator. We develop a penalized GMM estimator of the bias correction term necessary to obtain asymptotically normal debiased estimates and derive its convergence rate. We also give conditions for root-n consistency and asymptotic normality of the debiased MLIV estimator of the functional of interest. Finally, in the third chapter, Flexible Demand Estimation using Machine Learning, we demonstrate how to estimate substitution patterns in the market for sodas using the debiasing procedure from the second chapter. These three chapters are highly interconnected. The first chapter proposes a new MLIV algorithm for flexible estimation in presence of endogenous regressors. However, it focuses on the underlying structural function which in the majority of cases does not have a clear economic interpretation. While the second chapter develops a method to perform inference on functionals of MLIV estimators, which have a clear economic interpretation and can be used to answer various economic questions of interest. Finally, the third chapter investigates an important applied question of flexible estimation of demand for differentiated goods, which is a perfect example of a high-dimensional problem with endogenous regressors. As a result, we get a full picture about the potential of MLIV methods in economics
Fermionic Diagonal Coinvariants
No full textLet W be a complex reflection group of rank n acting on its reflection representation V ≅ Cn. The doubly graded action of W on the exterior algebra ∧(V ⊕ V*) induces an action on the quotient by the ideal generate by W-invariants with vanishing constant term FDRW = ∧ (V ⊕ V*) / ⟨ ∧ (V ⊕ V*)W_{+} ⟩. We describe the bi-graded W-module structure of FDRW and introduce a variant of Motzkin paths that descends to the standard monomial basis of FDRW with respect to certain term order. The top degree of FDRW exhibits the Narayana refinement of Catalan numbers. When W = Sn, the symmetric group, FDRSn ≅ Rn,0,2, where Rn,0,2 is the special case of the Boson-Fermionic diagonal coinvariants with two sets of Fermionic variables. In this case, the (i,j)-th degree component is a difference of Kronecker product of two hook Schur functions. In addition we consider a module Mn,m spanned by m-ary strings of length n. When m = 2, as a vector space, Mn,2 ≅ C[Xn] / ⟨ x12, ... , xn2 ⟩. The trivial component of drn ⊗ Mn,2 is a weighted sum of q,t-Narayana numbers which is a different q,t-Catalan number than the alternant of drn. At t = 1, the trivial component equals the inversion generating function for 321-avoiding permutations
Regulation of Genome Topology in Notch-Mutated Cancers
No full textSpatiotemporal regulation of gene expression governs cellular development and malignant transformation. Compared to the understanding of cis-regulatory elements on the linear chromatin, our knowledge about the three-dimensional (3D) organization of the human genome is still limited. Recent advances in chromatin conformation capture techniques coupled with high-throughput sequencing and fluorescence in situ hybridization combined with high-content microscopy greatly advanced the mapping of 3D genome at kilo-base resolutions. However, the mechanisms of the establishment and maintenance of genome folding and the implications of their disruption in cancer are largely unexplored. Moreover, besides a few architectural proteins, the roles of other transcription factors in chromatin topology remain elusive. Here, I used three cancer types with oncogenic mutations in the signaling-dependent developmental transcription factor NOTCH1 as models to probe the contributions of genome misfolding to oncogenesis and anti-cancer therapy resistance. By subjecting triple-negative breast cancer and mantle cell lymphoma cells to short-term Notch inhibition and reactivation, I discovered that beyond its known role in activating distal enhancers, Notch can dynamically reposition distal enhancers to the promoters of pro-survival genes such as MYC but has limited impact on higher-order chromatin structures including topologically associated domains (TADs) and compartments. Interestingly, in T-cell acute lymphoblastic leukemia (T-ALL), short-term Notch inhibition only diminishes MYC enhancer activity but not looping to the promoter, suggesting that Notch mediates chromatin loops in a lineage- and locus-specific manner. In contrast to short-term treatment, I identified widespread refolding of compartments, TADs and loops in T-ALL cells that acquire resistance to long-term Notch inhibition. These events closely coincide with redistribution of chromatin activity and architectural protein and are reversible when Notch inhibitor is removed. Finally, using a combination of sequencing, imaging and genetics approaches, I provided direct evidence that the B-cell lineage determining factor EBF1 is repositioned from the transcriptionally repressive nuclear lamina to the interior during long-term Notch inhibition. Activated EBF1 thus instructs reorganization of the linear and 3D genome to promote therapy resistance. My studies in Notch-mutated cancers advanced the mechanistical understanding of non-architectural transcription factors in cancer genome folding, which can potentially provide insights into their functional roles during normal development
Penn Library\u27s Ms. Codex 1663 - Libro per brevem : apprend[ere] le discipline... (Video Orientation)
No full texthttps://repository.upenn.edu/sims_video/1141/thumbnail.jp
Penn Library\u27s LJS 388 - [Mulakhkhaṣ fī al-hayʼah]. = [ملخص في الهيئه]. (Video Orientation)
No full texthttps://repository.upenn.edu/sims_video/1144/thumbnail.jp
Penn Library\u27s Ms. Codex 1671 - [Collection of alchemical works on distillation] (Video Orientation)
No full texthttps://repository.upenn.edu/sims_video/1150/thumbnail.jp
Collation Model for Oversize Ms. Codex 97: Libro della divina potentia [manuscript].
Get PDFThe text is on f. 2r-49v. Folios 50r-52r contain a chapter list, a slightly later addition in a different hand. Folio 52r also contains a 14-line poem, titled : Nella sala de priore e scritto questo sonetto. Two charts for linking dates with days of the week and a lunar table appear at the end of the volume (f. 52v-53v).https://repository.upenn.edu/sims_models/1035/thumbnail.jp
Collation Model for Ms. Codex 983: Chronica de la edificatione et destructione...
Get PDFCollection of historical accounts of the sieges of Ancona. The main work (ff. 25r-130r) is Biagio\u27s account of the construction, siege, and destruction of the citadel of Ancona between 1348 and 1383. The main work is preceded by an Italian translation of Boncompagno\u27s Latin work on the siege of 1174, with the translation attributed to Biagio, as well as Italian translations of two shorter passages on Ancona. A note laid in by an unidentified mid-19th century English owner describes one of these as enlarged extracts from the Doge Andrea Dandolo (f. 17r); the other is attributed in the text to Meser Francesco Petrarcha nel suo libro de la imperatori et pontifici (f. 21r). At the end of the volume is a copy of the Latin text of the letter from the Florentines to the people of Ancona, written by Coluccio Salutati, offering congratulations for the victory of 1383, with its conclusion missing.https://repository.upenn.edu/sims_models/1039/thumbnail.jp