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Coronavirus Proteases As Therapeutic Targets: Development Of Biosensors To Detect Inhibition Of Protease Activity And Separation Of The Multiple Functions Of Coronavirus Papain-Like Proteases, Andrew Kilianski

Dissertations

Coronaviruses are important human pathogens and have the potential to severely impact public health on an international scale. The emergence of SARS-CoV and MERS-CoV highlight the need for research to identify antivirals and vaccines against coronaviruses. To develop therapeutics against current and potentially emergent coronaviruses, I utilized two approaches targeting the proteases encoded within all coronaviruses. The papain-like protease and 3C-like protease of coronaviruses are responsible for cleaving viral polyproteins early during infection, and this step is required for viral replication. To quantitatively assess the inhibition by small-molecule compounds on MERS-CoV protease activity, I developed a luciferase-based biosensor to monitor …

The Restorative Justice Talking Circle Process With Probation Officers: A Phenomenological Approach, Constance Marie Sheehan

Dissertations

Restorative justice seeks to bring together stakeholders in the justice system by acknowledging harm caused by offending behavior and finding ways to repair that harm. The activities associated with restorative justice create the potential for meaningful and positive outcomes for all stakeholders within the system. Restorative justice asks, what is the harm?, who are the stakeholders?, and, how can the harm best be repaired? A particular restorative practice - the talking circle - is a common practice of restorative justice efforts. The potential for restorative justice practices, like the talking circle, is developing of a new way of understanding for …

Effects Of Cultural Awareness Training In Conjunction With An Established Bullying Prevention Program, Megan Kallie Polanin

Dissertations

While many school bullying prevention programs have been designed to thwart school bullying perpetration, victimization, and physical aggression, empirical support is limited. To date, few researchers have addressed bullying within the context of children's cultural systems, and cultural awareness training has not yet been utilized as a mechanism to decrease bullying behaviors in the context of school bullying prevention programs.

This study examined the utility of incorporating multicultural training aimed at reducing prejudice within the context of school bullying prevention programming efforts within a diverse educational setting. This researcher hypothesized that the addition of meaningful culture curriculum would further reduce …

Regulation And Targeting Of Fyn In Human Cutaneous Squamous Cell Carcinoma, Sarah Fenton

Dissertations

Fyn, a member of the Src family kinases, is an oncogene in murine epidermis and is associated with cell-cell adhesion turnover and migration. Introduction of active H-Ras(G12V) into the HaCaT human keratinocyte cell line resulted in upregulation of FYN mRNA (200-fold) and protein, but did not increase the expression of other SFKs. We identified two nucleotides 74 bases upstream of the human FYN gene transcription start site as necessary for FYN upregulation in HaCaT-Ras cells. Further studies identified Lef-1 as the transcription factor most likely binding to this site and mediating FYN upregulation.

Transduction of active Ras or Fyn was …

Dynamics Of Shrub Fires Investigated Via Physics Based Modeling, Ambarish Dahale

Dissertations

A physics based model, capable of predicting fire spread through a multiphase porous media, is formulated and described in detail. The resulting governing equations of fluid dynamics, combustion, heat transfer and thermal degradation of solid fuel, are solved using discrete numerical methods. The burning of an isolated chamise (Adenostoma fasciculatum) shrub approximately 1 m in height, similar to previously reported experimental study, was investigated using this physics based model. Global quantities including burning time, total mass consumed, time history of mass loss rate and time to reach maximum mass loss rate are found to be in good agreement with experimental …

Assessing The Fishery And Ecology Of Sharks In The United Arab Emirates, Rima W. Jabado

Dissertations

Large scale shark population declines have been documented worldwide due to overexploitation and the lack of adequate management frameworks to conserve shark stocks. This study aimed at gaining an understanding of the national shark fishery and the trade in shark products from the United Arab Emirates (UAE). Data were collected from June 2010 to October 2012 through interviews with local fishermen, market and landing site surveys, fishery independent surveys, and stomach content analysis. Interviews with local fishermen (n=126) provided information on the fishery characteristics and established that sharks were increasingly targeted due to their high value in the global fin …

Diplomatic Solutions: Land Use In Anglo-Saxon Worcestershire, Kevin Anthony Caliendo

Dissertations

My dissertation is a study of the charters of the Worcester diocese from its foundation in approximately 680 to the tenth century. Bishops of Worcester, men is control of one of the wealthiest sees in Anglo-Saxon England, used charters to acquire land, obtain rights and privileges for their existing estates, and manage trade within limits imposed by the king. Rights associated with bookland, land held by charter, gave bishops and their agents the ability to direct settlement and field systems in order to maximize estate productivity and encourage trade through a system of urban and rural marketing of timber, salt, …

Catalytic Mechanism And Maturation Of The Metalloenzyme Nitrile Hydratase, Natalie I. Gumataotao

Dissertations

Nitrile hydratases are metalloenzymes that catalyze the hydration of nitriles to their corresponding amides in a specific manner at ambient pressures and temperatures at neutral pH. Traditional industrial methods require high temperature and pressure, extreme pH, and heavy metals. NHases are used as biocatalysts in the large scale industrial production of amide precursors to textiles, animal feedstock, and polymers. Notably, NHase is used in the production of ~100,000 tons of acrylamide annually by the Mitsubishi Corporation.

Despite being used extensively in industry, questions remain about NHase. The catalytic mechanism is not defined. Understanding the way in which the nitrile is …

Moral Philosophy And The Art Of Silence, Kristina Grob

Dissertations

In this dissertation I begin with the claim that silence is part of moral life. Moral philosophy must make every attempt to bring within it all that is part of moral life. The dissertation produces a methodology for learning how to see some of the silences that I claim for moral life and it shows the importance of silence to continuing moral self-formation.

Urban Agriculture And Sustainability In Chicago, Matthew Hoffmann

Dissertations

Sustainability is increasingly informing the organization of urban life. In the past 15 years, cities have sought to alleviate the dual effects of environmental degradation and a changing economy by introducing sustainable development initiatives. Policy makers and environmental activists have often praised these efforts, pointing to the enhancement of quality of life, the mitigation of industrial pollution, and these initiatives' capacity to address poverty in a post-welfare state. Most popular depictions of the experiences of sustainability come from the perspective of white, middle class, college-educated volunteers and, increasingly, social entrepreneurs such as artisans, farmers, and other producers connected to "local" …

The Symptom Experience Of Patients Receiving Epidermal Growth Factor Receptor Inhibitors, Josephine Ann Howard-Ruben

Dissertations

This study explored the symptom experience of patients receiving epidermal growth factor receptor inhibitors (EGFRIs) for breast, colon, head and neck, and colon cancer. EGFRIs are targeted therapies used at various points along the treatment continuum for these solid tumors, and may be first, second or third-line agents which can be used as single agents or in combination with other therapies. The most common side effect of these agents include dermatologic effects, such as rashes, hair, and nail changes, but they can also contribute to other side effects such as fatigue, anxiety and diarrhea. Most previous work has addressed the …

Peripubertal Binge Ethanol, Age And Sex Modulate Microrna Expression In The Ventral And Dorsal Hippocampus Of The Adolescent Rat, Sarah Arianne Prins

Dissertations

Adolescent binge ethanol (EtOH) abuse induces long-term changes in gene expression, resulting in an increased risk for the development of adult mood disorders. microRNAs (microRNAs) are small, noncoding RNAs that regulate gene expression by translational repression. microRNA altered in response to EtOH and puberty in the developing brain. The biogenesis of mature 22-24 nucleotide (nt), single-stranded microRNAs involves Drosha and Dicer enzymatic processing of microRNA precursors. A mature microRNA imperfectly base pairs with messenger RNA (mRNA) target genes,which leads to mRNA cleavage or translational repression. Our lab has found that repeated binge EtOH exposure alters gene expression in the hypothalamus …

Investigating The Role Of The Pgf2 Alpha/Calcineurin-Signaling Pathway In The Regulation Of Adipogenesis, Damodaran Annamalai

Dissertations

Prostaglandin F2α (PGF2α) is a potent physiological inhibitor of adipocyte differentiation. In previous studies, we demonstrated that PGF2α inhibits adipogenesis via activation of the calcium-regulated protein phosphatase, calcineurin. In this current study, we have now extended these findings to identify the IL-11 cytokine and the Nurr1 orphan nuclear hormone receptor as functionally important downstream transcriptional targets of the PGF2α/calcineurin-pathway involved in the inhibition of adipocyte differentiation. In the case of IL-11, we show that this cytokine acts in an autocrine fashion to inhibit adipogenesis via the essential actions of the gp130 cytokine co-receptor signaling subunit. Further, by using a well-characterized …

Predicting Emotion Regulation In Early Childhood: The Impact Of Maternal Well-Being, Infant Crying, And Dyadic Mutuality, Tiffany Burkhardt

Dissertations

Learning adaptive emotion regulation skills in early childhood has been identified as fundamental to social competence, academic success, and psychological well-being. Because children learn to regulate their emotions through interactions with their caregivers, dyadic mutuality between the mother and infant may influence child emotion regulation capacity more than maternal behavior alone. To better understand the impact of maternal well-being and infant crying on the development of emotion regulation, parenting stress, maternal self-efficacy, maternal depression, and infant crying were examined with dyadic mutuality in the parent-child interaction to predict emotion regulation capacity.

A racially and socioeconomically diverse community sample of 149 …

Psychometric Evaluation Of The Neonatal Pain, Agitation, And Sedation Scale (N-Pass) Tool In Infants And Children Age One To Thirty-Six Months In The Post-Anesthesia Care Unit, Patricia A. Hummel

Dissertations

The purpose of this study was to investigate the Neonatal Pain, Agitation, and Sedation Scale (N-PASS) tool for evidence of validity and reliability in infants and children aged one to thirty-six months in the Post-Anesthesia Care Unit (PACU). This study design was a prospective, non-experimental psychometric evaluation of the N-PASS tool.

The research was conducted at a Midwestern Medical Center. The sample analyzed comprised forty subjects aged one to thirty-six months.

Data collection involved the evaluation of participants every five minutes, utilizing the N-PASS sedation subscale along with the University of Michigan Sedation Scale (UMSS) and the N-PASS pain/agitation subscale …

The Molecular Components Of Estrogen Receptor Beta (Erβ) Signaling In Neuronal Sytems, Natasha Mott

Dissertations

With increasing life expectancy, women are now living upwards of 50 years without circulating estrogens, therefore, it is essential to investigate how the brain is changed by estrogen deprivation and also how aging influences these changes. The Women's Health Initiative (WHI) study spurred rigorous debate regarding estrogen therapy for postmenopausal women due to dichotomous effects of estrogens in menopausal and post-menopausal women. Meta-analyses of the WHI study revealed that after circulating estrogens are depleted for many years re-exposure may cause aberrant, negative health effects, indicating that there is an age-related `switch' in estrogen signaling around menopause. These age-related effects of …

The Affective Consequences Of Expressing Moral Convictions, Lisa Diana Sandberg

Dissertations

This project examined the affective consequences of expressing moral convictions to an opposing majority. It was predicted that moral conviction would function as a buffer to the common negative emotions that occur when speaking out against majority opinion (e.g., fear; Asch, 1956; Berns, et al., 2005). It was also hypothesized that moral conviction would enhance positive feelings among those who speak out (e.g., pride). Two studies were conducting using two different research paradigms. Study 1 used a normative influence paradigm modeled after Hornsey, Smith, and Begg (2007). Participants' opinions and strength of moral conviction about the target issue (torture of …

2 Peter 2:4-16: The Redaction Of The Biblical And Intertestamental References Dependent On Jude 5-11 And Their Overall Significance For The Document, Jenny Devivo

Dissertations

For some time now, scholars have noted the close literary connection between Jude and 2 Peter, with thirteen of Jude's twenty-five verses paralleled in 2 Peter. One could say that the argument over the direction of dependency makes it the `synoptic problem' of the Catholic Epistles. Although the literary evidence is overwhelmingly supportive of 2 Peter's dependency on Jude, the prominence of the figure of Peter in Christian history seems to have influenced certain scholars to propose the contrary.

The arguments for the dependence of 2 Peter upon Jude will be addressed immediately in this dissertation since the focus of …

Recipe For Resilience: Factors Contributing To Urban African American Males' Post-Secondary Academic Achievement, Melvin Thomas Hargrett

Dissertations

The present research sought greater understanding of and contributes additional insights into supporting the academic success of African American males in urban public high schools and in higher education. The findings based on eight world life interviews of successful African American males from an urban community adds valuable information about the community factors (family, church, schools and community organizations) that contribute to the development of resiliency among African American males. Additionally, the research sought to provide a detailed account of the community wisdom (messages and methods) that informed resilience. Lastly, the transformative nature of resilience was explored in collegiate settings, …

Purpose And Design In Organisms And Artifacts: The Search For A Unified Philosophical Theory Of Function, Mark L. Bourgeois

Dissertations

This work examines the concept of function in both biological organisms and designed artifacts. Function is routinely attributed within both kinds of systems, yet it is unclear whether it can mean the same thing within each, and indeed whether function attribution within natural systems is legitimate at all. Function is typically understood to have teleological content; yet in true teleological causation, the end is somehow the cause of its own means. In artifacts the consciously envisioned design of an artifact is taken to be the cause of its parts and their roles. Yet in naturalistic science there is no prior …

Just Water: A Feminist Catholic Response To The Commodification Of Water, Rachel Noelle Hart Winter

Dissertations

Any Catholic ecological ethic today that does not focus sustained attention to our worldwide water crisis is inadequate, for it fails to engage one of today's core social justice violations and neglects to offer any moral guidance for one of the human family's most pressing challenges. A responsible Catholic approach to water justice that addresses the problems stemming from a commodified view of water must be informed by ecofeminist concerns and by the Catholic social justice tradition of moral reasoning. As populations grow and water sources run dry, access to water has become a pressing ethical issue. Today, nearly one …

Host Entry Factors For Human Coronaviruses, Taylor Heald-Sargent

Dissertations

Coronaviruses infect a diverse range of animals from birds to pigs and cats to humans. Coronaviruses employ RNA-based replicative processes and as such are genetically adaptable to acquire novel host ranges. A coronavirus from one species can jump to another by shifting its entry requirements. As we learned from the Severe Acute Respiratory Syndrome (SARS) pandemic, this shift in species can have detrimental consequences. Thus, it is imperative that we understand the virus-host interaction during the entry process.

This dissertation focuses on host entry factors that influence human coronavirus entry. Recently, a new class of proteases, the type II transmembrane …

Journey To The Neighborhood: An Analysis Of Fred Rogers And His Lessons For Educational Leaders, Jeana Lietz

Dissertations

Millions of children worldwide grew up watching Fred Rogers, aka “ Rogers,” as their childhood neighborhood friend on the television show Mister Rogers’ Neighborhood . How was a man able to produce one of the most successful, longest running children’s television programs and stay true to his moral principles? This study examines the life and work of Fred Rogers, and identifies the leadership attributes of Fred Rogers and the implications for educational leaders, through the lens of the five sources of authority described in Moral Leadership: Getting to the Heart of School Improvement by Thomas Sergiovanni (1992).

The central research …

Mutations In Phospholamban Alter The Structure And Function Of The Calcium Atpase Regulatory Complex, Neha Abrol

Dissertations

Phospholamban (PLB) is an integral membrane protein that plays an important role in regulation of cardiac calcium handling and contractility. PLB exists as a homopentamer in the membrane, which upon deoligomerization into active monomers reversibly inhibits sarco/endoplasmic reticulum calcium ATPase (SERCA). Mutations in PLB that change the PLB monomer-pentamer equilibrium result in dysregulation of SERCA. To determine the structural and regulatory role of the C-terminal residues of PLB in the membranes of living cells, we fused fluorescent protein tags to PLB and SERCA. We then studied the effect of C-terminal alanine substitutions and truncation mutations on PLB oligomerization and SERCA …

Re-Examining The Female Voice In Chaucer's Italian-Sourced Works: A Study In Paleography, Textual Transmission, And Masculinity, Stacee Bucciarelli

Dissertations

Research on women in medieval literature is abundant but often focused on broad questions of narrative and character development. Among the areas seldom examined is what I will term "female voice," a term that encompasses the thoughts and speech of women in literature. This project analyzes the representation of female voice in Chaucer's work, and it explores alterations to female voices within the largely male worlds (both actual and literary) in which they were created.

This study broadens the analysis from the restrictive and traditional realm of women's studies and contextualize these alterations on a grander scale of textual and …

Luxury Romanticism: The Quarto Book In The Romantic Period, Matthew Hale Clarke

Dissertations

This dissertation explores the cultural presence of the quarto book in Romantic-era Britain and argues that the format classed the period's defining literary ideologies--from sentimentalism, to liberalism, to Wordsworthian Romanticism, to orientalism--as luxuries meant exclusively for the nation's wealthiest consumers. Chapter 1 situates the quarto within the context of the period's luxury debates and advances a conception of the quarto as the era's predominant luxury format. Focusing on Oliver Goldsmith's The Deserted Village, Chapter 2 argues that early quarto editions of the poem classed the sympathetic feeling it celebrated as the unique privilege of a readerly elite and describes how …

Investigation Of Pharmaceutical Mass Transfer Phenomena Using Molecular Dynamics Simulations, Yi Gao

Dissertations

Molecular dynamics (MD) simulation has been widely used in understanding the physical basis of the structure and function of biological macromolecules. However, its application in pharmaceutical research is still at an early stage. This dissertation attempts to establish the use of MD simulation in studying several important pharmaceutical mass transfer processes. The three-series study included (1) the understanding of drug crystal dissolution at molecular level, (2) the elucidation of an unique mechanism for facile polymorphic transformation of crystalline drugs in solutions, and (3) the determination of drug-polymer interactions at water-crystal interface and the implications to crystallization inhibition.

A drug crystal …

Identification And Analysis Of Omentum Derived Suppressor Cells In Regards To Th17 Inhibition, Nick Huang

Dissertations

Omentum has been harnessed by surgeons for hundreds of years, providing an ideal environment for graft healing and acceptance. However, little is known about the cellular mechanisms that promote the tolergenic environment of the omentum. We examined the cellular composition and role of activated omentum in regards to T-cell immunomodulation. We then tested activated omentum as a cellular therapy in a mouse allogenic lung transplantation model.

Our findings demonstrated activated omentum is mostly comprised of non-hematopoietic cells resembling mesenchymal stem-like cells (MSCs) and myeloid derived suppressor cells (MDSCs). Activated omentum exhibited anti-inflammatory properties through suppression of Th1 and Th17, while …

Functional Importance Of Oxidative Post-Translational Modifications Of Ryanodine Receptor In Cardiac Sarcoplasmic Reticulum Ca2+ Handling During Oxidative Stress, Stefan R. Mazurek

Dissertations

Free ionic calcium (Ca2+) plays an essential role as a second messenger that initiates muscle contraction in the heart. Ryanodine receptor (RyR2) acts as the primary Sarcoplasmic Reticulum (SR) Ca2+ release channel in the heart. In the event that intracellular SR Ca2+ handling is compromised, both the contractility and electrical excitability of the heart can be altered. As a consequence, heart function may not be able to maintain the necessary cardiac output to meet the metabolic demand of the body.

Increased oxidation of RyR2 has been implicated in abnormal Ca2+ handling that promotes the onset and progression of cardiovascular disease. …

Multifunctional Coronavirus Papain-Like Proteases As Targets For Antiviral Therapeutics And Vaccines, Anna Maria Mielech

Dissertations

Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle Ease Respiratory Syndrome coronavirus (MERS-CoV) pose a severe threat to humans because of high mortality. Despite the risk of coronavirus (CoV) emerging in the human population there are no antiviral drugs or vaccines to combat coronavirus infection. The focus of my dissertation was to study the multifunctionality of papain-like proteases (PLPs) encoded within coronavirus genomes to facilitate the development of antiviral drugs and vaccines. The viral PLPs are critical for processing the amino-terminal end of the replicase during virus replication and are attractive targets for antiviral therapies.

In my research, I analyzed …