Digital Commons Network^™

Physical Frailty And White Matter Abnormalities: The Aric Study, Emma L. Ducca

Theses and Dissertations

Physical frailty is associated with increased risk for dementia and other neurologic sequelae. However, the neurobiological changes underlying frailty and frailty risk remain unknown. The association of cerebral white matter structure with current and future frailty was examined. Atherosclerosis Risk in Communities Study Neurocognitive Study participants who underwent 3T brain MRI were included. Frailty status was classified according to the Fried criteria. Cerebral white matter integrity was defined using white matter hyperintensity (WMH) volume and microstructure, measured using diffusion tensor imaging fractional anisotropy (FA) and mean diffusivity (MD). Multivariable linear regression was used to relate baseline frailty to white matter …

Long-Term Stability Of Baseline Impact Scores In High School Football Players Across Age Groups, Christopher Thomas Burley

Theses and Dissertations

In recent decades, the increased awareness of the prevalence of concussions has resulted in significant advancements in concussion assessment and treatment, including annual or bi-annual pre-season computerized baseline assessments. However, limited research has focused on the differences in stability of baseline neurocognitive performance among different age groups in adolescence. The main purpose of the present study was to explore the long-term stability of ImPACT baseline assessments across one-year intervals in multiple age groups within a sample of high school football players. Subjects who completed two baseline assessments between the ages of 14 and 17 who had completed two baselines one …

N, N-Dimethylacetamide Targets Neuroinflammation In Alzheimer’S Disease In In Vitro And Ex Vivo Models, Zenghui Wei

Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative disorder with no cure, accounting for 60-80% of cases of dementia. While the two pathologic hallmarks of AD, senile plaques from extracellular deposition of amyloid β-protein (Aβ) and tau-based neurofibrillary tangles (NFT), have been known for decades, the pathogenesis of AD remains unclear. In recent years, anti-neuroinflammatory treatment has entered the spotlight in AD research. In previous studies, we have shown that N,N-dimethylacetamide (DMA), a common drug excipient, is a potent anti-inflammatory agent. In the current work, we investigate the effect of DMA on neuroinflammation and its mechanism of action in in-vitro and ex-vivo …

Repurposing Of Small Molecule Inhibitor Ym-155 Inhibits High-Risk Neuroblastoma Growth By Directly Inhibiting Survivin Protein, Danielle Crystal Rouse

Theses and Dissertations

High-risk neuroblastoma (NB) is an aggressive pediatric tumor which develops from the extracranial sympathetic nervous system and accounts for almost 15% of all childhood cancer-related deaths. Current therapies include high-dose chemotherapy and radiation which have long-term toxic side-effects. Despite these intensive therapies, the overall survival rate of NB is less than 50%. Therefore, developing novel therapeutic approaches by directly targeting the molecular mechanisms that drives NB progression is very important. In the present study, we analyzed genomic datasets of 1235 NB patients and discovered that overexpression of survivin coding gene BIRC5 strongly correlates with poor overall and event-free survival of …

Human Otop1 Proton Channel Can Function As A Monomer, Gabriella Abigail Ulloa

Theses and Dissertations

Otopetrins (OTOP) represent a new family of eukaryotic proton channels that do not share structural similarities with other renowned ion channels. Otop1 was initially known for its involvement in vestibular function and its significance for otoconia formation before it was established as a bona fide sour taste receptor. The cryo-EM structures for several Otop channels have been determined and demonstrated Otop1 as a homodimer comprised of two subunits. Each subunit constitutes twelve transmembrane helices that can be further partitioned into two structurally similar six transmembrane domains designated as the N and C domains. Molecular dynamic simulations have also previously shown …

An Examination Of School Characteristics Related To Racial Disparities In Special Education Identification In New York State, Teresa Ann Mcgrath

Theses and Dissertations

This study examined special education numbers for public school populations of White, Black, and Hispanic students in New York State and factors hypothesized to contribute to identification and subsequent disproportionality of minority students in special education. Data from the Civil Rights Data Collection (CDRC), combined with data from the National Center of Education Statistics (NCES) for New York state public schools in the academic school year of 2015-2016 are evaluated. Histograms of the percent difference in IDEA status of White and Black/Hispanic students are considered to identify if there is disproportionality in the schools in New York. The implication of …

Neural Plasticity For Speech Sound Processing In Adults: The Effect Of Transcranial Direct Current Stimulation, Garrett Sweitzer

Theses and Dissertations

We examined the possible modulatory effect of tDCS on the automatic processing of speech sounds by evaluating the components of two ERP waveforms (P1-N1-P2 and T-Complex. The P1-N1-P2 components were measured at frontocentral sites F3, F4, C3, C4, Cz, and Fz while the T-Complex components were measured at temporal cortices T7 and T8. A 64-channel sensor cap from Electrical Geodesics, Inc was placed on each of the participants’ scalp. The 17 young adults (12 females, 5 males) sat comfortably during the EEG measurements within an electrically shielded and sound-attenuated booth while watching a silenced movie with subtitles delivered through a …

Benjamin Percy And Queer Ecomasculinities: Ideas Of The Short Story From Hemingway To The Present, Thomas Edward Hahn

Theses and Dissertations

The 21st Century has ushered in a need to problemetize and challenge traditional boundaries between social and philosophical realms. It is therefore more important now than ever to revisit the classification of literary genres, specially the short story. Through the intersection of queer, literary, and ecocritical theory, this book reexamines the current identity of the contemporary American short story in order to posit that it is a queer formation, a hybrid of both the novel and the poem, among the generic literary landscape. Through this queer literary form, the short story subsequently has the ironic potential to reveal insight into …

Does Empathic Anger Motivate People To Act On Pro-Defending Cognitions?, Adir Pinchot

Theses and Dissertations

Recent theoretical and empirical work suggests that empathic anger represents a form of anger that motivates bystanders to intervene and defend victims of aggression. Prior research on defending behavior has identified cognitive correlates of defending, but most studies failed to distinguish between different forms of defending and did not evaluate how these cognitions interact with emotions, such as empathic anger, in motivating or inhibiting defending behavior. This study attempted to address these lacunae by analyzing whether empathic anger moderates the associations between cognitions associated with defending (i.e., perspective taking, moral disengagement, and self-efficacy for defending) and different types of defending …

Racial Bias In The Association Of Externalizing Symptoms With Black And White Children: The Development And Application Of An Implicit Association Test, Maura Francis

Theses and Dissertations

The objective of this study was to test the hypothesis that school and mental health professionals more strongly associate externalizing behaviors with Black children compared to White children. To test this hypothesis, we developed an implicit association test to determine if there was a difference in the reaction times in classifying symptoms as externalizing when the symptoms were paired with the word “Black Child” as opposed to paired with the word “White Child”. In a sample of 54 school and mental health professionals, we found clear evidence in support of our hypothesis. The existence of this implicit bias may explain …

Social Attention And Memory In Youth With Asd, Adnp Syndrome, And Foxp1 Syndrome, Megan L. Braconnier-Krupa

Theses and Dissertations

The current study used eye tracking and behavioral measures to examine social attention and recognition memory in two rare genetic disorders commonly associated with autism spectrum disorder (ASD): ADNP syndrome and FOXP1 syndrome. Impairment in social functioning is considered a core deficit in ASD. Although individuals with ADNP syndrome and FOXP1 syndrome typically present with symptoms of ASD, research suggests several dissimilarities in symptom presence and severity between the groups. Thus, there is a need to clarify disorder-specific patterns of social attention and their relationships to observed social skills. A visual paired comparison eye tracking task was used to assess …

The Internal And External Expectancies Scale: Development And Validation., Joanne Raptis

Theses and Dissertations

Healthy lifestyle habits are widely known to improve physical and psychological wellbeing, but many struggle to regularly practice these behaviors. As an overarching solution has yet to emerge, it may prove more fruitful to instead personalize behavior change recommendations and interventions. The present study examined whether individual responsiveness to internal and external expectations can be measured, as it could be a useful behavioral factor to target with tailored treatment recommendations. This construct was first postulated by popular author Gretchen Rubin (2015) but has yet to be studied empirically. For the current project, the Internal and External Expectancies Scale (IEES) was …

“You Think You Know What Nature Is”: The Literary And Historical Ecologies Of Lake Hopatcong, Peter Astras

Theses and Dissertations

This dissertation examines the unseen effects between human activity and nature, and more broadly the relationship between humans and a single local environment, Lake Hopatcong. My methodology is archival, drawing whenever possible on an array of sources to articulate a broad set of time periods and perspectives. This study utilizes foundational ecocritical texts as anchor points and referential lenses with which I examine the contextual and situational “truth” of each period. To get a comprehensive look, there are historical texts, scientific reports, travel journals, tourist materials and newspapers, along with archival materials at the Hagley Center in Wilmington, Delaware. Through …

The Prevalence Of Writing In Elementary Teacher Preparation Courses In The Pacific Northwest, Chelsea Mabie

Theses and Dissertations

Writing continues to be an underserved content area within English Language Arts instruction in elementary school classrooms. This sequential mixed-methods study was designed to develop a current state of practice for writing pedagogical training within the Pacific Northwest. Course descriptions were analyzed for specific references to writing, or terms inclusive of writing, from five teacher preparation programs in Oregon, Washington, and British Columbia. Grounded in expertise theory, the implications for this work are aimed at schools of education as well as teacher licensing bodies reflecting on if their training practices are supportive in developing a solid foundation for preservice educators …

Posthuman Queer Ecosexuality: Shakespeare And Earthly Consummation, Lisa Robinson

Theses and Dissertations

“Posthuman Queer Ecosexuality” explores the culminating productivity of a queer landscape fertilized by dead bodies. Tragedy as a genre provides a higher queer possibility simply because it does not contend with picture perfect happy endings. By seeing an inherent connection between queerness and death, the paired couples of the specific Shakespearean tragedies explored in this project, King Lear (1605), Othello (1604), and Antony and Cleopatra (1607), fertilize the respective landscapes within their plots. These main six characters are queered by forced connections to nature due to their gender, race, or function as a ruling body. Once they are placed in …

Regulation Of Interferon- Induced Interleukin-8 And Pd-L1 Expression In Ovarian Cancer Cells, Sveta Padmanabhan

Theses and Dissertations

Interferon-γ (IFNγ) is a pleiotropic cytokine that has a crucial role in immune response and tumor immunity. Because of its anti-tumor effects, IFNγ has been used in cancer treatment. However, IFNγ also has tumor-promoting functions that are less well understood. Here, I show that IFNγ induces expression of the pro-inflammatory and pro-angiogenic chemokine interleukin-8 (IL-8, CXCL8) in ovarian cancer (OC) cells. The IFNγ-induced IL-8 expression is dependent on JAK1, STAT1, and p65 NFκB, and is associated with an increased occupancy of K314/ 315 acetylated p65 NFκB and Ser-727 phosphorylated STAT1 at the IL-8 promoter. Neutralization of IL-8 using anti-IL-8 antibody …

Pbk/Topk Inhibitor Ots964 Resistance Is Mediated By Abcg2- And Abcb1-Dependent Transport Function In Cancer, Yuqi Yang

Theses and Dissertations

Accumulating evidence has suggested that multi-drug resistance (MDR) in cancer cells is a phenotype whereby cancer cells have attenuated sensitivity to drugs. ATP-binding cassette super-family G member 2 (ABCG2/BCRP) and ATP-binding cassette sub-family B member 1 (ABCB1/P-gp) are members of the ATP-binding cassette (ABC) transporter family and involved in MDR. OTS964 is a potent inhibitor targeting to PDZ-binding kinase (PBK)/T-lymphokine-activated killer cell-originated protein kinase (TOPK). Herein, we aimed to explore the relationship between MDR-associated ABC transporters, including ABCG2 and ABCB1, and the regulation of OTS964 efficacy. PBK/TOPK inhibitor OTS964 resistance is mediated by ABCG2-dependent transport function in cancer: in vitro …

The Craft Of Language: An Analysis Of Associations Between A Metalinguistic Writing Course And Reading Comprehension, Anna Incognito

Theses and Dissertations

This study examines associations between writing instruction with a focus on explicit sentence syntax and reading comprehension in a sample of students receiving special education services. While the outcome data does not show direct causation between student enrollment in a treatment writing course using Systemic Functional Linguistics and reading scores on state testing, the significant associations between variables imply possibilities for improvements in reading pedagogy. Reading comprehension depends on how accurately readers capture an author’s intended meaning while reading. Current research shows this has less to do with decoding words in a sentence, and more to do with recognizing communicative …

Dithiocarbamates Mancozeb And Disulfiram Induce Striated Muscle Myopathy And Neuropathy In Long-Evans Rats, Olivia Stephenson

Theses and Dissertations

Mancozeb (MZ), an ethylene bis-dithiocarbamate complexed with the metals manganese and zinc, is a broad-spectrum fungicide used primarily on orchards and vineyards. Disulfiram (DS, Antabuse®), a diethyldithiocarbamate, is an FDA-approved drug used for alcohol aversion therapy. Both dithiocarbamates (DTCs) have shown neurological effects including motor impairment, muscle weakness, and hind-limb paralysis, although the mechanism of toxicity is not understood. The purpose of this study is to determine how these neurotoxic compounds are damaging striated muscle of rats. Adult, male Long-Evans rats were administered either 250mg/kg MZ or 750mg/kg DS via oral gavage 3x/week for four weeks. Animals were euthanized 24 …

Tepotinib Reverses Abcb1- And Abcg2-Mediated Multidrug Resistance In Cancer, Zhuoxun Wu

Theses and Dissertations

Overexpression of ATP-binding cassette (ABC) transporters ABCB1 and ABCG2 in cancer cells have been linked to the development of multidrug resistance (MDR), an obstacle to cancer therapy. Therefore, it is important to inhibit ABCB1/ABCG2 activity in order to maintain an effective intracellular level of chemotherapeutic drugs in drug-resistant cancer cells. Tepotinib is an ATP-competitive MET kinase inhibitor approved for the treatment of adult patients with metastatic non–small cell lung cancer harboring MET exon 14 skipping alterations. In the present study, we identified that the MET inhibitor tepotinib can reverse ABCB1- and ABCG2-mediated MDR by directly binding to the drug-binding site …

The Ethylenebis(Dithiocarbamate) Backbone Of Mancozeb Alters Glutathione Status And Divalent Essential Metal Homeostasis In Rat, Benjamin Kistinger

Theses and Dissertations

Mancozeb is a fungicide used globally on a variety of crops. Studies on mancozeb attribute its toxicity to oxidative stress. There is debate if oxidative stress is caused by mancozeb’s metal components, manganese and zinc, its ethylenebis(dithiocarbamate) backbone, or both together. The ability of mancozeb to alter metal homeostasis and chelate copper has also been implicated in its toxicity. Manganese, zinc, copper, and iron are essential in the body such that deficiency results in disease. However, these metals in excess have toxic consequences. We sought to study the mancozeb’s ability to alter essential metal homeostasis, induce oxidative stress, and affect …

Maternal Literacy Practices And Beliefs Impact Infant Development, Deirdre Cruz

Theses and Dissertations

Infancy is a pivotal time in the development of a human’s cognitive ability. There is a lack of research in this area, specifically on mothers and their beliefs about literacy practices and the home learning environment. By utilizing Bronfenbrenner’s ecological framework, this study explores the beliefs of mothers and how they impact the infants’ preliteracy skills and knowledge, which are paramount to success in kindergarten and beyond. Using a phenomenological study, the researcher interviewed mothers on their views of literacy, their infant’s home learning environment, and how they perceive their culture and mothering style impact their infants.

Functional Modulation Of The Cav3.1 Calcium Channel By Alternative Splicing At The C-Terminus, Ruizhi Wang

Theses and Dissertations

The CACNA1G gene encodes for Cav3.1, the alpha-1G subunit of a low-voltage-activated T-type calcium channel, which plays crucial roles in cardiac and smooth muscle cells and neurons by influencing the transmembrane potentials and regulating intracellular Ca2+ signaling. Heterozygous missense mutations in the CACNA1G gene cause spinocerebellar ataxia-42 (SCA42), a heterogeneous group of neurodegenerative disorders characterized by brainstem and cerebellum degeneration, and mice that are null for this gene present severe motor coordination defects, abnormal electrical conductance in the heart, aberrant action potentials in the brain, disrupted sleeping patterns, and absence epilepsy. Different splice variants of Cav3.1 have been described, and …

Structural Modification Of The Propyl Linker Of Cjoc42 For Enhanced Gankyrin Binding And Anti-Cancer Activity, Tejashri Chavan

Theses and Dissertations

Gankyrin was first identified as an oncoprotein in hepatocellular carcinoma but was later found to be overexpressed in multiple cancer types. Gankyrin’s oncogenic ability is primarily manifested through its interactions with tumor suppressor proteins, regulation of transcription factors, and ability to moderate various signaling pathways. Additionally, gankyrin has been shown to decrease tumor suppressor protein levels (e.g., Rb and p53) in liver cancer cells. Cjoc42 was the first small molecule inhibitor of gakyrin; however, it also demonstrated poor anti-proliferative activity against liver cancer cells. Molecular modeling studies of cjoc42 with gankyrin suggests cjoc42 adopts a U-shape conformation upon binding to …

Repurposing An Anti-Epileptic Drug For The Treatment Of Glioblastoma, Anjali Yadav

Theses and Dissertations

Glioblastoma multiforme (GBM) is a grade IV malignant glioma. It is a highly proliferative form of brain tumor with 5-year survival rate ~ 5% indicating a high mortality rate. Current treatment strategies for GBM include surgery, radiation, and chemotherapy. Surgical resection is challenging due to vital function of brain and as GBM often metastasizes in different brain regions. Additionally, development of resistance against the standard of care drug temozolomide (TMZ) is a major challenge in GBM management. GBM is also shielded with the blood brain barrier (BBB) which prevents the entry of several drugs. Therefore, a new drug must overcome …

Understanding Language Use Patterns Of People With Chronic Pain: A Novel Assessment Approach, Jodie Maccarrone

Theses and Dissertations

It is estimated that 35% of Americans or 116 million people report experiencing chronic pain daily (Nahin, 2015). Due to the unique and individualized nature of chronic pain, successful treatment of this condition is difficult to achieve. The heterogeneity and complexity in presentation may help explain why, as all methods of treatment have fallen short of providing consistent and reliable outcomes (Finnerup et al., 2015; Lumley & Schubiner, 2019), resulting in unsuccessful treatment approaches that can lead to compounding negative consequences such as hyperalgesia (Garland et al., 2013) and even death (Scholl, Seth, Kariisa, Wilson, & Baldwin, 2019). As such, …

Viral Overexpression Of Rprd2 In Mouse Nucleus Accumbens Induces Anxiety-Like Behavior And Regulates Genes Associated With Microtubule Transport, Claire Nuhad Atiyeh

Theses and Dissertations

Anxiety disorders are the most prevalent mental illness in the United States with many individuals underdiagnosed and undertreated (Anxiety & Depression Association of America, 2021; Bandelow et al., 2017). While stress is a known risk factor for developing anxiety disorders, there is emerging evidence that biological variability in the expression of key proteins in the brain may contribute to regulating an organism’s stress-related behaviors. Earlier work from our laboratory identified a protein, called Regulation of Nuclear Pre-mRNA Domain Containing 2 (RPRD2), that was differentially expressed in the brain of mice stratified in terms of their phenotypic response to chronic stress …

Alternatively Spliced Csf3r In Human Health And Disease, Borwyn A. Wang

Theses and Dissertations

Elevated alternative colony stimulating factor 3 receptor (CSF3R) isoforms are observed in myelodysplastic syndromes (MDS) and other myeloid neoplasms, but their role in driving disease progression has not been fully explained. In this study we report on the role of an MDS-associated splicing factor SRSF2 and its effects on the production of Class III and Class IV CSF3R isoforms and granulopoiesis. Class IV add-back in Csf3r-null mice showed impaired neutrophil differentiation with increased number of CFU-G, which largely consisted of metamyelocytes, while Class III showed greater dysgranulopoiesis accompanied by dysmorphic neutrophils. Alternative CSF3R isoforms were elevated in …

The Role Of Irf-1 In Spontaneous Mouse Glioma, Aakash B. Vaidya

Theses and Dissertations

Glioblastoma Multiforme has been shown to be one of the deadliest primary brain cancers. One of the reasons why GBM is so deadly, is a unique immunosuppressive tumor microenvironment that promotes GBM growth and progression. Both astrocyte and microglia have been implicated in immunosuppression. In this study, we explored the role of Interferon Regulatory Factor 1 (IRF-1) in astrocytes and glioma cells on the growth of spontaneous glioma tumors. IRF-1 is regulated by the JAK/STAT pathway and induces expression of Programmed death ligand 1 (PD-L1). PD-L1 downregulates immune responses to glioma. We found that IRF-1 had no effect on spontaneous …

Racism Experiences And Mental Health: An Examination Of Direct, Vicarious, And Appropriated Racism Experiences On Mental Health Symptom Expression, Christina Barnett

Theses and Dissertations

The current study aimed to corroborate existing models of racism-related experiences by creating an explanatory model that operationalized direct, vicarious, and appropriated racism experiences. This study explored whether the factors of direct and vicarious racism experiences influenced mental health outcomes via appropriated racism experiences in a sample of Black women. This association was not present. However, results showed a positive association between vicarious and direct racism experiences, as well as predictive relations between direct and vicarious racism experiences and depression and trauma symptoms. Results, limitations, implications, and recommendations for future research are included.

Keywords: vicarious racism, appropriated racism, direct racism, …