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The average human lungs take ~22,000 breaths and inhale ~2,000 gallons of air each day. This organ is the primary conduit for the transfer of oxygen to the internal organs, making it crucial for the sustainment of life. Consequently, mechanical malfunction of the lungs and/or pollution of inhaled air negatively impact internal organ function and ultimately put survival in jeopardy. Epigenetics, by nature, is a plastic phenomenon in which environmental stimuli influence short term, long term, and generational gene expression patterns. Chronic exposure of harmful stimuli to the lung epithelium has also been shown to alter epigenetic pathways, engender aberrant lung cell differentiation, and manifest into long term diseases. Chronic Obstructive Pulmonary Disease (COPD) is a progressive, incurable lung disorder that is pathologically rooted in chronic inflammation and aberrant lung cell differentiation. Polycomb Repressive Complex 2 (PRC2) is a key epigenetic regulator of lung stem cell fate during development, but little is understood of its role in adult lung. In the following chapters, I will expound on how I utilized human patient samples, ex vivo lung organoids, and murine in vivo models to better elucidate how PRC2 controls lung cell biology and offer insight into potential therapeutic avenues to combat lung disease. To understand the role of PRC2 in COPD, we first analyzed patient and control lung tissues. Using quantitative immunohistochemistry and immunofluorescence, we observed a very significant decrease in the Polycomb Repressive Complex 2 catalytic mark, histone H3 lysine 27 tri-methylation (H3K27me3) in bronchiolar epithelium of COPD patients. Furthermore, H3K27me3 staining was strongly inversely correlated with markers of basal and goblet cells in patient samples. Next, we developed a new mouse model of conditional deletion of the Polycomb Repressive Complex 2 enzyme, EZH2, and used this model to interrogate lung stem cell function in organoid cultures and in vivo. Single cell RNA-sequencing of organoid cultures revealed the appearance of Krt17-negative basal cells and loss of the newly identified Krt8-positive progenitor cells in Ezh2-null cultures. Gene signatures associated with immune response were increased is Ezh2-heterozygous cultures, and genes enriched in EZH2 deficient organoids were enriched in human emphysemic lung. Furthermore, when we used this Ezh2 conditional knock-out mouse to interrogate the role of EZH2 in lung homeostasis and allergen response in vivo, we found that Ezh2-heterozygous mice had increased response to ovalbumin allergen and showed hallmarks of COPD including bronchiolar epithelial thickening and club to goblet cell transdifferentiation. Lastly, we sought to learn the mechanism of decreased PRC2 activity in COPD patients. We used human bronchiolar epithelial cells to interrogate the role of the redox-sensitive enzyme, cystathionine beta synthase (CBS), in controlling EZH2 levels and gene expression modulation. In the patient samples, we found that CBS was significantly higher in COPD lung. Excitingly, we identified shared transcriptional profiles between human bronchiolar epithelial cells that over-express CBS and mouse organoids with Ezh2 loss, offering insight into how redox stress may drive aberrant epigenetic reprogramming. Taken together, these findings suggests that PRC2 is integral to facilitating proper lung stem cell differentiation in adult humans and mice.

As the #MeToo movement swept the nation from Hollywood to Washington, within less than a week's time in November of 2017, longstanding news anchors, Matt Lauer and Charlie Rose were fired from their respective news networks because of sexual harassment allegations. As a result, each network had to grapple with repairing a destroyed image while simultaneously fulfilling the duty to report on news objectively. This qualitative analysis examined NBC and CBS's response to the allegations of sexual harassment against each anchor, allegations of withholding information and allegations of ignoring complaints through the lens of image repair theory in order to identify if any of the strategies were present in the networks' response. Applications of image repair discourse to news media organizations is a relatively novel examination and it highlights the complex duality of an organization's right to uphold its image but obligation to present the news objectively, even when it has become the news.

Introduction: Therapeutic strategies targeting protein aggregations are ready for clinical trials in atypical parkinsonian disorders. Therefore, there is an urgent need for neuroimaging biomarkers to help with the early detection of neurodegenerative processes, the early differentiation of the underlying pathology, and the objective assessment of disease progression. However, there currently is not yet a consensus in the field on how to describe utility of biomarkers for clinical trials in atypical parkinsonian disorders. Methods: To promote standardized use of neuroimaging biomarkers for clinical trials, we aimed to develop a conceptual framework to characterize in more detail the kind of neuroimaging biomarkers needed in atypical parkinsonian disorders, identify the current challenges in ascribing utility of these biomarkers, and propose criteria for a system that may guide future studies. Results: As a consensus outcome, we describe the main challenges in ascribing utility of neuroimaging biomarkers in atypical parkinsonian disorders, and we propose a conceptual framework that includes a graded system for the description of utility of a specific neuroimaging measure. We included separate categories for the ability to accurately identify an intention-to-treat patient population early in the disease (Early), to accurately detect a specific underlying pathology (Specific), and the ability to monitor disease progression (Progression). Discussion: We suggest that the advancement of standardized neuroimaging in the field of atypical parkinsonian disorders will be furthered by a well-defined reference frame for the utility of biomarkers. The proposed utility system allows a detailed and graded description of the respective strengths of neuroimaging biomarkers in the currently most relevant areas of application in clinical trials.

Computational chemistry lies at the intersection of chemistry, physics, mathematics, and computer science, and can be used to explain the behavior of atoms and molecules, as well as to augment experiment. In this work, computational chemistry methods are used to predict structural and energetic properties of small molecules, i.e. molecules with less than 60 atoms. Different aspects of computational chemistry are examined in this work. The importance of examining the converged orbitals obtained in an electronic structure calculation is explained. The ability to more completely describe the orbital space through the extrapolation of energies obtained at increasing quality of basis set is investigated with the use of the Sapporo-nZP-2012 family of basis set. The correlation consistent Composite Approach (ccCA) is utilized to compute the enthalpies of formation of a set of molecules and the accuracy is compared with the target method, CCSD(T,FC1)/aug-cc-pCV∞Z-DK. Both methodologies are able to produce computed enthalpies of formation that are typically within 1 kcal mol-1 of reliable experiment. This demonstrates that ccCA can be used instead of much more computationally intensive methods (in terms of memory, processors, and time required for a calculation) with the expectation of similar accuracy yet at a reduced computational cost. The enthalpies of formation for systems containing s-block elements have been computed using the multireference variant of ccCA (MR-ccCA), which is designed specifically for systems that require an explicit treatment of nondynamical correlation. Density functional theory (DFT) has been used for the prediction of the structural properties of a set of lanthanide trihalide molecules as well as the reaction energetics for the rearrangement of diphosphine ligands around a triosmium cluster.

From a media industries, fan studies, and emerging socio-cultural public relations perspective, this project pulls back the Hollywood curtain to explore two questions: 1) How do TV public relations practitioners and key tastemaker/gatekeeper media define, create, build, and maintain fandom?; and 2) How do they make meaning of fandom and their agency/role in fan creation from their position of industrial producers, cultural intermediaries, members of the audience, and as fans themselves? This project brings five influential, working public relations and media professionals into a conversation about two case studies from the 2010-2011 television season – broadcast network CBS’ Hawaii Five-0 and basic cable network AMC’s The Walking Dead. Each of these shows speaks to fandom in particular ways and are representative of the industry’s current approaches in luring specific audiences to TV. This study shows that the relationship between entertainment publicists and media is dynamic, intertwined, complex, and historically hidden.

Autism has been declared an urgent public health concern by the U.S. government and an epidemic by some advocacy groups. Determining autism’s diagnostic criteria, prevalence, and causes have been challenging. It is important to examine how the U.S. media have contributed to the public’s understanding of autism. Previous research found that British media coverage of the theory that vaccines cause autism was shown to contribute to the decline of vaccination rates in Britain (Lewis & Speers, 2003). This study examined U.S. television news media coverage using an agenda-setting theory and media framing perspective. A content analysis was conducted of national television evening news broadcasts airing on ABC, CBS, and NBC from 1994, when autism was first recognized as a spectrum disorder through April 2010, the time of this study. Specifically, this study examined the saliency of autism stories and how autism was framed in terms of prevalence and causes.

The American media system needs to be reformed. While the media are supposed to be a powerful force in preserving our democracy, certain components have not been as vigilant lately. In the name of capitalism, once separate media companies have merged to form a powerful few. The so-called Big Six – AOL Time Warner, Disney, General Electric, News Corporation, Columbia Broadcasting Service and Viacom – control the mainstream media in the United States. Not only do these companies control television stations, but also publishing companies, newspapers, and Internet websites. Additionally, Rupert Murdoch’s News Corporation has its hands in every form of media across the globe. Thus, a select few are controlling a large portion of the message to the American people. As a result of this corporate expansion, the state of journalism has suffered with the emphasis now on the bottom line instead of honest and respectable journalism. The mainstream media have degenerated into partisan reporting on both sides of the political spectrum. Americans are beginning to consider political pundits, like Glenn Beck or journalistic lightweights like Barbara Walters, actual journalists. The healthcare reform debate highlights just how important the media are and how corrupted certain media groups have become. As the reform debate continues, the desire for profits appears to drive the media rather than a desire to report the truth. This can only prove deleterious to the American political system.