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Design, Synthesis, and Optimization of Allosteric Inhibitors of HIV-1 Integrase
No full textThe human immunodeficiency virus type 1 (HIV-1) infection remains a global health crisis, necessitating the development of innovative antiviral strategies. During the integration step, HIV-1 integrase (IN) interacts with viral DNA and the cellular cofactor LEDGF/p75 to effectively integrate the reverse transcript into the host chromatin. Recently, a novel class of antiretroviral agents called Allosteric Inhibitors of HIV-1 Integrase (ALLINI) compounds has emerged as a promising avenue in the fight against HIV-1. While originally designed to inhibit IN-LEDGF/p75 interactions, these compounds have been shown to also impact late-stage viral maturation severely through IN multimerization. Induction of IN multimerization interferes with virion maturation through misvocalization of vRNA rendering them noninfectious. ALLINI compounds have shown potent antiviral activity against a broad range of HIV-1 strains, including drug-resistant variants. This abstract provides an overview of the use of the ALLINI compounds based on quinoline scaffold derivatives which have been shown to exhibit enhanced potency, prolonged antiviral activity, and reduced likelihood of resistance. Additionally, this research explores the inclusion of covalent warheads with the aim to optimize these compounds and explore their applications as a part of therapeutic strategies for HIV-1, offering new avenues for effective treatment strategies and their integration into future combination antiretroviral therapies
“The Wonderful Improvement”: Landscape and Morals in Jane Austen’s Mansfield Park
Get PDFThis thesis examines how Jane Austen uses depictions of landscapes and estates in her novel Mansfield Park to explore questions of morality, comment on society, and explore humanity\u27s relationship with the natural world. While previous scholarship has analyzed Austen\u27s symbolic use of places like Sotherton and Mansfield Park itself, this study provides a more comprehensive investigation by closely reading the descriptions and judgments passed on two other estates featured in the novel not analyzed by the scholarship explored. Developing a nuanced definition of landscape,” the analysis is grounded in Austen\u27s verbal depictions that imbue the physical settings with moral significance. The historical context of the picturesque aesthetic movement and ethical notions of aristocratic estate stewardship further illuminate Austen\u27s aims. By contrasting the attitudes and actions of characters like Fanny Price, Edmund Bertram, Henry Crawford, and James Rushworth regarding the preservation or alteration of an estate’s grounds, a nuanced commentary on virtues like humility, restraint, and respect for nature arises. Crucially, the thesis argues that through her characterization, Austen endows the socially powerless Fanny Price with the greatest moral discernment and appreciation for judicious land stewardship. While male characters like Edmund and Henry evolve in their perspectives, Fanny remains the steadfast champion of preserving the estates\u27 natural and pastoral qualities against excessive, destructive improvements. In enshrining the low-born Fanny as the arbiter of landscape ethics, Austen mounts a subversive challenge to the patriarchal privilege of aristocratic landownership. The analysis ultimately posits that the symbolic role of landscapes in Mansfield Park allow Austen to dramatize an emerging proto-ecological consciousness that presaged later landscaping philosophies advocating sustainable stewardship over the domination of nature. Through her deployment of intricately detailed estates and grounds, the novel portrays the moral consequences of remaking the land purely for vanity and fashion. In elevating Fanny\u27s humble ethos of conservation, Austen crafted an enlightened voice of harmony between humanity and the natural world
The Effects that Dietary Intake and Cardiorespiratory Fitness has on Insulin Resistance in Adults
Get PDFInsulin resistance can impair bodily responses to insulin and the uptake of glucose within the human body. This imparity has many consequences and can more commonly cause Type II Diabetes.1 This study focuses on how different lifestyle modifications can be used to combat the sensitivity to insulin within the body. The sample included forty-one adults whose ages varied from 18 to 35 years old. The participants completed a VO2max test, blood glucose test, and a 31- item food frequency survey. These tests and survey questions revealed the correction between the participants’ age, blood glucose levels, VO2max score, and diet score. A statistically significant correlation was found between the VO2max results and the diet score; the r=0.720 and its p=0.001. The next significant correlation was with the blood glucose test and the diet score (r=-0.663, p=0.001). Also, the variables between the VO2max results and the blood glucose test created a r= -0.188 and a p= 0.240. From this, the study found that individuals with a higher diet score and a more balanced diet had an increase in their VO2max levels (which equates to a better physical fitness). Also, a good diet was also correlated with a decrease in glucose levels within participants. Meanwhile, a low VO2max score, and unbalanced diet increase blood glucose levels. From these findings, it was concluded that if a healthy and well-balanced diet is combined with sufficient physical activity, the effects of insulin resistance will decrease within young adults
Advances in Biomedical Research and Treatments: What is Acceptable?
Get PDFThis study investigated the technology acceptance (TA) of twenty-first century biomedical treatments by adults in the United States. A new TA instrument was created, using five distinct levels: (1) Healing and Prevention, (2) Replacement Organs, (3) Enhancements-Medical, (4) Enhancements-Discretionary, and (5) Transhumans. An on-line survey produced 353 usable responses, which showed distinct patterns for each of five biomedical treatment levels. There was clear support for Levels 1–3, but very strong opposition to Levels 4–5. The TA finding draws the line between which human interventions are acceptable versus others that should be prohibited through public policies and medical guidelines
Applying the Disaster Risk Assessment Framework to Sargassum Inundation in Barbados
Get PDFEpisodic influxes of pelagic Sargassum into the Caribbean result in inundation of coastlines with significant negative impacts to the environment, society, and economy. The spatial complexities of this issue demand a strategy that combines spatial planning with an analytical framework that can systematically unpack the underlying factors to inform effective management. We test the application of the United Nations Disaster Risk Reduction (UNDRR) conceptual framework for disaster risk assessment to Sargassum inundation, with a focus on the hazard and exposure components of risk, using Barbados, a Caribbean Small Island Developing State (SIDS), as a case study. We first consider in general terms how assessment of hazard, exposure, and ultimately vulnerability would contribute to management and broader spatial planning. As a trial, we use publicly available remotely sensed images to develop Sargassum inundation hazard maps together with spatially explicit secondary data on fisheries, tourism, and coastal ecosystem assets to examine their exposure to this hazard. This research establishes a proof of concept for application of the DRR framework to Sargassum inundation. Despite the data poor environment, the resulting broad coverage, low resolution hazard and exposure map outputs are useful planning tools, and the approach provides a template for future iterations, replications, and/or expansions, while highlighting important data needs. This trial application should be of considerable interest to the many developing countries affected by Sargassum inundation who typically have low capacity and budgets for data collection and technological tools to support management planning necessary to deal with this emergent marine hazard
Assessing The Impacts Of Grazing By Piney Woods Cattle And Controlled Burning On The Herbaceous Layer In An East Gulf Coastal Plain Longleaf Pine Woodland
Get PDFFire and grazing are two disturbances which influence vegetation composition and diversity in many ecosystems. In the southeastern United States, longleaf pine plant communities are adapted to frequent fires and are likely to have been grazed by bison in the past. Though bison have been extirpated from this region, Pineywoods Cattle, which were introduced by the Spanish in the 16th Century, have been fulfilling a similar role in many of these communities. This study examines the effects that combined grazing and controlled burning have on plant diversity, biomass, and community similarity in a longleaf pine savanna in the East Gulf Coastal Plain.
For this study, controlled burning combined with grazing yielded the highest diversity, with no burning with grazing yielding the lowest diversity. Controlled burning did not significantly affect biomass, while grazing had a significant positive effect on biomass. Treatment and sampling date had a significant effect on community similarity, with a Non-Metric Multidimensional Scaling plot visualizing the similarity of groups with each other.
Overall, fire combined with grazing appears to yield the highest levels of diversity with a community composition similar to that of ungrazed-burned plots. On the other hand, unburned plots with grazing yielded the lowest diversity and was most similar to unburned-ungrazed plots. Controlled burning is an effective management tool of longleaf pine communities and is enhanced by grazing
Elevating Commodity Polymers to Advanced Applications in Polymer Photonics and Polymer-Derived Porous Materials
Get PDFSince the inception of synthetic polymers, polymer-derived materials have permeated into essentially all aspects of our daily lives. The most commonly thought of examples of polymer materials involve single-use, disposable products to increase shelf lives of perishable items, act as personal protective equipment, or provide some degree of convenience for the consumer. However, as we have furthered our understanding of polymer chemistry and polymer physics to develop increasingly sophisticated polymer systems, polymer materials have been employed in incredibly advanced applications. These include solid electrolytes for energy storage, matrices for aerospace grade carbon fiber-reinforced composites, membranes for liquid and gas separations, among countless others. Oftentimes, developing polymers for these advanced applications can require complex synthetic approaches or additional challenges in processing the materials into products for end-use applications. Throughout this dissertation, the goal is to elevate commodity polymers into materials for advanced applications through simple processing methods in order to develop high performance materials that can be easily adopted due to their low cost and ease of fabrication. Specifically, this work first focuses on developing a simple and cheap approach to fabricating high reflectance and stimuli-responsive, 1- dimensional polymer photonic crystals with spatial control over structural color for applications in anticounterfeiting and sensing technologies. This is accomplished through developing a two-component polymer system from commercially available fluoropolymers and phenolic resins with high refractive index contrasts and leveraging spatially controlled surface functionalizations to selectively deposit polymer films in desired patterns. The second portion of this work is centered around establishing synthetic methods for
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converting commodity polyolefins into carbon materials that can be leveraged for applications in environmental remediation, energy storage, and heterogeneous catalysis. Specifically, a sulfonation-induced crosslinking method for preventing thermal degradation and enabling the conversion to carbon at elevated temperatures for polypropylene and various olefinic thermoplastic elastomers is demonstrated to produce carbon fibers and mesoporous carbons through scalable methods. Altogether, this work provides multiple avenues for developing functional materials derived from scalable processing methods and commodity precursors for advanced applications
Polecats, Poison, and Prejudice: Naturalized Anti-Judaic Tropes in Chaucer\u27s Pardoner\u27s Tale
No full textThe Pardoner’s Tale, one of Geoffrey Chaucer’s Canterbury Tales, is a fourteenth-century allegory against gluttony, told by a corrupt, gluttonous pardoner to the rest of the pilgrims on their way to St. Thomas Becket’s shrine at Canterbury. In the Pardoner’s initial description, the narrator compares the Pardoner to a hare, a goat, a gelding, and a mare to make conjectures concerning his gender identity. The comparison of the Pardoner to animals to suggest defining traits about his character invites closer attention to his tale’s use of animal imagery.
This thesis examines animal imagery and cultural signifiers related to the Black Death in The Pardoner’s Tale to illuminate the Pardoner’s anti-Judaic storytelling techniques, which support his argument about how Christians should behave. Building on prior scholarship establishing the anti-Judaism of The Pardoner’s Tale, I draw together additional threads of scholarship on medieval bestiary lore, blasphemy, poison, the Black Death, to further characterize the cultural prejudices against Jews present in The Pardoner’s Tale and its reflection of the intensity of religious prejudice entrenched in fourteenth-century English storytelling. As a result, I argue that The Pardoner’s Tale’s subtle anti-Judaic stereotypes, which align Jews with the bestial, reveal how commonplace anti-Judaic ideas were in Chaucer’s England
Under The Root
No full textUnder the Root is a collection that explores the experience of trauma through stories that majorly take place in/are inspired by the American South. These stories feature characters who are affected by the traumas of generational inheritance, addiction, poverty, and racism, as well as sexual, physical, and verbal abuses. As a collection, Under the Root displays how trauma manifests within the collective psyche of the American South, utilizing satire to argue that these manifestations of trauma are directly connected to the conservative culture of this region. Every story in this collection centers around a character with a different trauma and explores how trauma can manifest within both the experience of these characters and the narrative/lingual structure of each story.
The critical preface to Under the Root introduces how the “trauma plot” is utilized within this collection and discusses my creative work in the critical contexts of aesthetics, creative writing craft, contemporary satire, and clinical psychology. This essay analyzes scholarship on the therapeutic benefits of expressive nonfiction within a clinical setting and connects these findings to writing about trauma and anxiety within the fictional mode. Analyzing my personal experience and creative process for crafting this collection, this preface interprets my particular approach to aesthetics, humor, and form as having specific therapeutic applications when one draws from their personal anxieties and traumas when writing fiction