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    Unsung Heroes: A Qualitative Inquiry into the Intersections of Literacy, Identity, and Community at Summer Camp

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    This dissertation explores student engagement in literacy practices at a mythology-themed summer day camp. It draws on literacy and identity theories to examine how academic skill-building is developed through social means and interactions. Multiliteracy and Multimodal scholarship further animate this research on participant perceptions of and interactions with the curriculum they encountered in the research setting. Interview and observation data were analyzed using Cope and Kalantzis\u27 Multiliteracies schema, Janks’ Domination, Access, Diversity, and Design framework, and Street’s Ideological Literacy model to understand whether and how advanced literacy skills are developed by centering student’s identities in community-focused pedagogical practices that reconstitute reading as a shared endeavor

    The \u27florin.ms\u27 Project

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    Penn Library\u27s LJS 456 - [Kitāb al-Siyāsah fī tadbīr al-riyāsah]. (Video Orientation)

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    https://repository.upenn.edu/sims_video/1197/thumbnail.jp

    Elucidating the Determinants of Alveolar Epithelial Cell Fate from Lung Development to Regeneration

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    The alveolus is the functional unit of gas exchange in the lung and home to two major epithelial cell lineages: alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. Large, squamous AT1 cells cover the vast majority of the adult lung surface area, creating the gas diffusible interface between the external environment and the vasculature. Cuboidal AT2 cells secrete pulmonary surfactant to reduce surface tension at this air-liquid interface to prevent alveolar collapse. These cells are essential for lung function, and many are lost upon lung injury. Thus, understanding the signals required to generate and regenerate these cells is vital to develop interventions to support long term pulmonary health. In this dissertation, I use a combination of epigenetic and transcriptomic profiling, in vivo mouse genetic and injury models, ex vivo organoid assays, and human patient tissue to define essential mediators of the developmental emergence, lineage commitment, and plasticity of AT1 and AT2 cells. I demonstrate that Dnmt1 ensures the proper specification and compartmentalization of proximal and distal epithelial cell lineages during development. Developing a method to segment heterogeneously injured adult lung tissue into distinct zones by severity, I define specific injury niches and characterize the spatially restricted cellular responses to damage intensity in mice and humans. I determine that Fgfr2 maintains early AT2 cell identity and balances AT2 cell proliferation and differentiation during lung regeneration. Additionally, I demonstrate the extent of AT1 cell plasticity during neonatal and adult regeneration to generate AT2 cells. Finally, I show that Klf5 regulates AT1 cell lineage commitment during both lung development and regeneration. This work defines essential factors that determine alveolar epithelial cell fate and reveals how these choices impact both lung development and regeneration

    The Perpetual Fragility of Creeping Hillslopes

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    Hills in nature are wrapped in a blanket of grains. Over geologic time, soil upon these hills slowly creep, but appear immobile and frozen at a glance. In this dissertation, I test this perception directly with experiments wherein grains are poured on a table and left to sit. Surprisingly, grains are not still—but slowly creep under gravity alone, with rates that are comparable to hillslope soils. I demonstrate that additional features of complexity found in nature—variable grain shapes and sizes, boundary roughness, and the presence of weak disturbances—do not extinguish creeping motions, but rather paint a picture of a slowly relaxing glass. This phenomenology is resilient and robust, and offers a new view of soil creep as the deformation of an amorphous solid, poked and prodded by disturbances in the environment that maintain soil in a perpetually fragile state. At a conceptual level, this work seeks a transfer of concept between soft-matter physics and geophysical contexts, and also provides new directions in the treatment and interpretation of field data, preparing the ground for future work examining dynamics upon Earth\u27s surface

    Mechanisms Regulating Amyloid Processing Enzymes in HIV-Associated Neurotoxicity

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    Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND), cognitive impairment seen in approximately 50% of HIV+ patients, shares similar pathological hallmarks with Alzheimer’s disease (AD). Extracellular plaques composed of amyloid-beta (Aβ), which are produced by cleavage of amyloid precursor protein (APP) by the secretases BACE1, are observed in the brains of HAND. Aβ production is precluded by cleavage of APP by the non-amyloidogenic secretase ADAM10. BACE1 is increased in HAND as well as in our cell culture model of HIV neurotoxicity. Additionally, ADAM10 is decreased in response to excitotoxicity, a process crucial to HAND pathology, suggesting that there might be a shift in APP secretases contributing to HIV-mediated neurotoxicity. Therefore, understanding the mechanisms by which APP secretases are regulated is crucial in understanding and possibly developing therapies for HAND pathology. To address this, primary rat cortical neurons were treated with supernatants from HIV-infected human macrophages (HIV/MDMs). We found that HIV/MDMs decreased levels of both ADAM10 and Sirtuin1 (SIRT1), an enzyme shown to regulate ADAM10 levels, in primary neurons. Both ADAM10 and SIRT1 reductions were mediated through NMDA receptors. Furthermore, SIRT1 protein levels decreased earlier than ADAM10 and this early SIRT1 reduction was via proteasomal degradation. We also explored PKR-like Endoplasmic Reticulum Kinase (PERK), one of three effectors of the unfolded protein response (UPR), as a potential regulator of APP secretases as it has an established role in modulating BACE1. Using PERK inhibitors, we found that the ADAM10 decrease with HIV/MDMs was not through the PERK pathway. Interestingly, we found that a pharmacological PERK activator exacerbated HIV/MDM and NMDA-mediated decreases of ADAM10 as well as neurotoxicity. Activation of the PERK pathway in combination with other HIV-associated insults could contribute to neurotoxicity and Aβ production in HAND. This work reveals the mechanisms by which APP secretases are dysregulated in a cell culture model of HAND and provides new avenues for exploration

    Methods for Investigating Transport of Nanoparticles and Ions at Polyelectrolyte Interfaces

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    As a method development focused thesis, the goal of this dissertation is to develop new methods to study nanoparticle and counterion transport at the polyelectrolyte-solution interface that researchers can use to characterize material performance in separations and ion transport applications. We start by describing the fundamental interactions that drive adsorption and desorption and thus impact the transport of nanoparticles in solution near solid interfaces. Next, in a model study of negatively charged gold nanoparticles (AuNPs, 20 nm, zeta potential = -58.3 mV) adsorbing to a positively charged weak polyelectrolyte layer-by-layer (LbL) film (85 nm, zeta potential = +14.5 mV), we show that a new label-free microscopy technique, interferometric scattering microscopy (iSCAT), gives single nanoparticle insight into the adsorption process by directly measuring adsorption events. We enhance the applicability of iSCAT by improving particle detection capabilities in imaging adsorption events at rough interfaces where stage movements complicate image analysis with machine learning. We complement the single particle iSCAT studies with ensemble measurements of AuNP adsorption to LbL films with quartz crystal microbalance with dissipation (QCM-D) and unite the results of the single particle iSCAT and ensemble QCM-D measurements by accounting for transport differences using finite element analysis (FEA). The union of a label-free single particle technique like iSCAT and an ensemble method like QCM-D through FEA simulations provides a novel workflow other researchers can use to characterize the performance of coating materials for nanoparticle separations technologies. In the last chapter, we develop a coarse-grained model that retains the chemical specificity of a strong polyelectrolyte in poly[(2-(methacryloyloxy)ethyl) trimethylammonium chloride] (PMETAC) using the MARTINI forcefield. We then build simulations of salt-free (only enough counterions to balance charge on the brush) 150 monomer MARTINI PMETAC brushes at experimentally relevant grafting densities of σ = 0.05, 0.10, 0.20, and 0.40 chains/nm2. Using 5 microsecond simulations, we investigate the effects of σ on brush and counterion structure, ion dissociation dynamics, polymer mobility, and counterion diffusivity. Results show that counterion diffusivity is controlled by three factors: electrostatic interactions, polymer mobility, and steric hindrance. The interplay of these factors leads to diffusivity that depends non-monotonically on σ in both the lateral and axial directions with the counterion diffusivity peaking at σ = 0.10 chains/nm2. The PE brush simulations developed here are easily modifiable and we propose other variables for future studies for all chapters as we conclude in Chapter 6

    Study of the Interplay of Symmetry and Strong Correlations in Excitonic Insulator Candidates

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    Strongly correlated material systems have been at the forefront of condensed matter physics for a few decades, and yet the physics of correlated systems is not fully understood. Theoretically, it is difficult to model these systems fully analytically since the dynamics of many-body interactions that are required to model the electron-electron or electron-phonon physics, for example, quickly become intractable beyond limits one dimensional limit. However, with the advent of novel and improved experimental techniques, it has now become possible to access these phases of matter and study the physics of real materials. More specifically, optoelectronic methods have become invaluable tools to probe the physics of strongly correlated materials beyond what traditional transport techniques can achieve. In this thesis we use optoelectronic measurements to study two strongly correlated material systems – the excitonic insulator (EI) candidate Ta2NiSe5, and the charge density wave (CDW) system 1T-TiSe2. We discover a novel form of circular photogalvanic effect (CPGE) in centrosymmetric material systems, which we name quadrupolar CPGE or QCPGE, and use this novel variant of CPGE to demonstrate that the crystalline symmetry in Ta2NiSe5 is lower than previously reported in literature. We also demonstrate that light or applied bias can fundamentally alter the phase of matter being studied in systems with strong correlations, as we observe clear signatures of disruption of the CDW phase in 1T-TiSe2 in the presence of optically excited carriers, which lowers the symmetry of the crystalline phase due to strong electron-electron correlations in the CDW system. We thus show it to be necessary for future studies to carefully consider the interaction between the probes used and the system under study in order to get a much better understanding of the intrinsic behavior of the correlated material as well as result in more ways to control the phase of matter in these complex systems. In conclusion we demonstrate that circular photogalvanic effect and its higher order variants are an incisive probe of the underlying physics of strongly correlated material systems, and a better understanding of the intrinsic light-matter interaction in correlated systems is essential to further discover new physics in these systems

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