Digital Commons Network^™

Applications Of Antioxidant And Anti-Inflammatory Polymers To Inhibit Injury And Disease, David B. Cochran

Theses and Dissertations--Chemical and Materials Engineering

There is an undeniable link between oxidative stress, inflammation, and disease. Currently, approaches using antioxidant therapies have been largely unsuccessful due to poor delivery and bioavailability. Responding to these limitations, we have developed classes of polymer and delivery systems that can overcome the challenges of antioxidant and anti-inflammatory therapy. In our initial studies, nanoparticles of poly(trolox), a polymeric form of trolox, were surface-modified with antibodies. This modification allows for specific targeting to endothelial cells, affording controllable and localized protection against oxidative stress. We have shown these targeted nanoparticles bind, internalize, and provide protection against oxidative stress generation and cytotoxicity from …

Influence Of Surface Modification On Properties And Applications Of Complex Engineered Nanoparticles, Binghui Wang

Theses and Dissertations--Chemical and Materials Engineering

Complex engineered nanoparticles (CENPs) are being used on various applications. Their properties are different from those of neat nanoparticles. The dissertation explores these differences from four aspects: 1) Modify carbon nanomaterials’ inert surfaces and investigate the effect on thermal and rheological behavior of their dispersions; 2) Generate self-assembly bi-layer structure of oxide nanoparticles via surface modification; 3) Study interaction between lysozyme and different surface-charged ceria nanoparticles; 4) Investigate the biodistribution and transformations of CENPs in biological media.

An environment-friendly surface modification was developed to modify surfaces of carbon nanomaterials for increasing their affinity to non-polar fluid. It can offset formation …

Reinforcing, Subjective, And Cognitive Effects Of Methamphetamine During D-Amphetamine Maintenance, Erika Pike

Theses and Dissertations--Psychology

Translational research suggests that agonist replacement may be a viable treatment approach for managing methamphetamine dependence. This study sought to determine the effects of d-amphetamine maintenance on methamphetamine self-administration in stimulant using participants. A cognitive battery was used to determine the performance effects of methamphetamine alone and during d-amphetamine maintenance. During each maintenance condition, participants first sampled a dose of intranasal methamphetamine then had the opportunity to respond on a progressive ratio task to earn portions of the sampled dose. Subject-rated drug-effect and physiological measures were completed prior to and after sampling methamphetamine. Methamphetamine was self-administered as function …

Examining The Interaction Of Neonatal Alcohol And Hypoxia In Vitro, Megan L. Carter

Theses and Dissertations--Psychology

Exposure to ethanol (ETOH) during fetal development results in a range of cognitive/behavioral deficits. There are differences in sensitivity to the effects of ETOH that could be explained by other factors, such as hypoxia. Similar mechanisms of damage underlie both ETOH, more specifically ETOH withdrawal, and hypoxia. Based on this overlap, it was hypothesized that sub threshold levels of these insults may interact to produce increased damage in sensitive brain regions. This study used a rodent organotypic hippocampal slice culture model to investigate the interaction of hypoxia and ETOH withdrawal and to determine possible developmental differences in the sensitivity to …

Does Botox Buffer The Negative Effects Of Social Rejection?: A Test Of The Facial Feedback Hypothesis, Vicki Sharif

Theses and Dissertations--Psychology

Can a common facial cosmetic procedure buffer against the negative impact of adverse social interactions? This pilot tested the hypothesis that an injection of botulinum toxin (Botox) to the corrugator supercilii muscles used in anger, compared to a placebo injection to the same location, will reduce the impact of social rejection on mood, self-esteem, control, meaningful existence, and aggression. Freezing facial musculature was hypothesized to alter the first physical signal of negative emotional reactions, thereby reducing the impact of social rejection on distress and aggression. This was the first study using Botox to examine the effects of reduced facial feedback …

The Mesocorticolimbic Dopamine Pathway Reconstituted In Vitro: Glutamate Receptors And Corticosteroid-Methamphetamine Neurotoxicity, Jennifer N. Berry

Theses and Dissertations--Psychology

Stress promotes the use of methamphetamine and other recreational substances and is often implicated in relapse to stimulant use. Thus, it is of critical importance to examine the consequences of the co-occurance of stress and methamphetamine use. Activity of the glutamatergic N-methyl D-aspartate (NMDA) receptor system appears to be involved in the neurotoxic effects of both chronic stress and methamphetamine exposure. The current studies investigated the hypothesis that chronic pre-exposure to the stress hormone corticosterone (CORT) results in an increase of NMDA receptor activity and that this will potentiate the neurotoxic effects of methamphetamine (METH). Co-cultures of the …

Investigation Of The Monty Hall Dilemma In Pigeons And Rats, Jessica P. Stagner

Theses and Dissertations--Psychology

In the Monty Hall Dilemma (MHD), three doors are presented with a prize behind one and participants are instructed to choose a door. One of the unchosen doors is then shown to not have the prize and the participant can choose to stay with their door or switch to the other one. The optimal strategy is to switch. Herbranson and Schroeder (2010) found that humans performed poorly on this task, whereas pigeons learned to switch readily. However, we found that pigeons learned to switch at level only slightly above humans. We also found that pigeons stay nearly exclusively when staying …

Characterizing Consumption, Dependence, And The Role Of Glucocorticoids In An Animal Model Of Voluntary Ethanol Consumption, Lynda Sharrett-Field

Theses and Dissertations--Psychology

Alcohol abuse disorders (AUD) represent a serious worldwide health problem with far reaching social, financial, and interpersonal implications. One of the most devastating facets of these disorders is the propensity to relapse following periods of abstinence. Ethanol withdrawal (EWD) is believed to promote relapse by increasing anxiety and craving, and may contribute to the development of cognitive decline associated with long-term dependence. Clinical data suggest that stress also plays a main role in both the development of AUD as well as relapse to drinking. As a physiological stressor, EtOH elevates levels of stress hormones (cortisol in humans, corticosterone (CORT) in …

The Whole Picture: Body Posture Recognition In Infancy, Alyson J. Hock

Theses and Dissertations--Psychology

Holistic image processing is tied to expertise and is characteristic of face and body processing by adults. Infants process faces holistically, but it is unknown whether infants process body information holistically. In the present study, we examined whether infants discriminate changes in body posture holistically. Body posture is an important nonverbal cue that signals emotion, intention, and goals of others even from a distance. In the current study, infants were tested for discrimination between body postures that differ in limb orientations in three conditions: in the context of the whole body, with just the limbs that change orientation, or with …

The Sexualized Girl: The Development Of An Expanded (Sexualized) Gender Stereotype Among Children, Ellen A. Stone

Theses and Dissertations--Psychology

The current study examined children’s stereotypes about sexualized girls. Elementary school children (n = 208) from the mid-South between the ages of 6 and 11 completed a survey assessing their stereotypes about sexualized girls and non-sexualized girls. Participants were asked to justify, in their own words, their responses to several stereotypic evaluations. Children’s cognitive development was analyzed through classification skill as a moderator of belief in stereotypes about girls. Results revealed that children perceived the sexualized girl to be more popular and better liked by boys than the non-sexualized girl. However, the sexualized girl was also rated as less athletic, …

Missing "Links": Investigating The Age And Gender Dimensions Of Development, Conservation, And Environmental Change In A Southern Zambian Frontier, Allison Harnish

Theses and Dissertations--Anthropology

This dissertation focuses on the lived, material realities of rural women, men, girls, and boys struggling to make a living in the context of changing national development priorities and changing environmental conditions in Southern Province, Zambia.

Over the last 20 years, Gwembe Tonga migrants living in the frontier farming area of Kulaale have witnessed significant declines in non-cultivated “bush” resources due to the conversion of forest and grassland to agricultural uses. This dissertation seeks to understand how women, men, boys, and girls differently experience these declines according to local gender- and age-based divisions of subsistence labor. Drawing on a variety …

Manufacturing Ceramics: Ceramic Ecology And Technological Choice In The Upper Cumberland River Valley, Melissa Ramsey

Theses and Dissertations--Anthropology

Ceramic material culture recovered from archaeological sites has more to offer the researcher than placing the site or strata into a cultural historic timeline. By examining the characteristics of ceramics manufactured during the Woodland Period in southern Kentucky, this thesis answers questions related to the behavior of the potters who lived and worked there. Using the theoretical basis of ceramic ecology and technological choice, this thesis examines the choices made by the potters of two sites, the Long (15Ru17) and Rowena (15Ru10) sites, located along the Cumberland River in Russell County, Kentucky. The two sites are also compared to one …

Late Archaic To Early Woodland Lithic Technology At The Knob Creek Site (12hr484), Harrison County, Indiana, Kyle E. Mullen

Theses and Dissertations--Anthropology

This study examines bifacial technology change at the Knob Creek site (12HR484) in Harrison County, Indiana, from the Late Archaic to Early Woodland periods. Through a statistical and attribute analysis of 2,620 lithic flakes it was possible to detect changes in the lithic reduction process over time. The analysis demonstrates that soft-hammer percussion becomes more prevalent during the Early Woodland component of the site. This is a significant change from the hard-hammer percussion industry of the Lower Late Archaic. The Terminal Archaic Riverton component in this study offers one of the few detailed flake-by-flake analyses for this poorly understood lithic …

Investigating The Impact Of Interactive Applets On Students’ Understanding Of Parameter Changes To Parent Functions: An Explanatory Mixed Methods Study, Robin R. Mcclaran

Theses and Dissertations--Science, Technology, Engineering, and Mathematics (STEM) Education

The technology principle in the Principles and Standards for School Mathematics (NCTM, 2000) states that technology plays an important role in how teachers teach mathematics and in how students learn mathematics. The purpose of this sequential explanatory mixed-methods study was to examine the impact of interactive applets on students’ understanding of parameter changes to parent functions. Students in the treatment classes were found to have statistically significantly higher posttest scores than students in the control classes. Although the data analysis showed a statistically significant difference between classes on procedural understanding, no statistically significant difference was found with regard to conceptual …

The Effect Of Augmented Reality Treatment On Learning, Cognitive Load, And Spatial Visualization Abilities, Nedim Slijepcevic

Theses and Dissertations--Curriculum and Instruction

This study investigated the effects of Augmented Reality (AR) on learning, cognitive load and spatial abilities. More specifically, it measured learning gains, perceived cognitive load, and the role spatial abilities play with students engaged in an astronomy lesson about lunar phases. Research participants were 182 students from a public university in southeastern United States, and were recruited from psychology research pool. Participants were randomly assigned to two groups: (a) Augmented Reality and Text Astronomy Treatment (ARTAT); and (b) Images and Text Astronomy Treatment (ITAT). Upon entering the experimental classroom, participants were given (a) Paper Folding Test to measure their spatial …

Choosing Home: International Pushes And Pulls For Malaysian Alumni Of U.S. Graduate Programs, Pauline Chhooi

Theses and Dissertations--Educational Policy Studies and Evaluation

Malaysians’ journeys to pursue graduate education in the U.S. generate more than just degree attainment. This dissertation looks at how experiences in the U.S., both in graduate school and in the workplace, influenced highly educated Malaysians, especially in their exploration of push and pull factors that influence their decisions to remain in the U.S. or to return to Malaysia. This study focuses on twenty-two participants comprised of those who have returned to Malaysia, those who are working in the U.S. on non-immigrant visas, those who became Permanent Residents and those who are naturalized U.S. citizens.

The first major finding demonstrates …

Education Policies And Migration Realities: Utilizing A State Longitudinal Data System To Understand The Dynamics Of Migration Choices For College Graduates From Appalachian Kentucky, Charles E. Mcgrew

Theses and Dissertations--Educational Policy Studies and Evaluation

Census data indicates people with higher levels of education are leaving Appalachian Kentucky as they do in other rural areas. Aside from anecdotal information and primarily qualitative community studies, there is little quantitative evidence of the factors which may influence these migration decisions. State policies and regional efforts to increase educational attainment of people in the region have focused on producing more college degrees however may be contributing to the out-migration of those with higher levels of education. The study incorporates community level data with demographic, academic, and employment data from a cohort of 2005-06 college graduates from Appalachian Kentucky. …

The Effect Of Acute Beetroot Juice Supplementation On Muscle Fatigue In Knee Extensor Exercise, Seungyong Lee

Theses and Dissertations--Kinesiology and Health Promotion

To examine the effect of acute beetroot juice supplementation on the rate of fatigue as measured by changes in peak torque.

Placebo-controlled, double-blind, cross-over study, 35 recreationally active subjects consumed beetroot (BR) juice or black currant juice (PL) 12 and 2.5 hours before the exercise procedure. Peak torque was measured on the BIODEX dynamometer by performing 50, maximal effort, concentric knee extensions at 90°/s. Blood pressure (BP) was recorded before and after exercise.

No significant difference between BR and PL in the rate of fatigue measured by change in peak torque. By stage 3, subjects retained 87.6±6.9% of strength with …

Effect Of Muscle Length On Cross-Bridge Kinetics In Intact Cardiac Trabeculae At Body Temperature, Nima Milani-Nejad, Ying Xu, Jonathan P. Davis, Kenneth S. Campbell, Paul M. L. Janssen

Physiology Faculty Publications

Dynamic force generation in cardiac muscle, which determines cardiac pumping activity, depends on both the number of sarcomeric cross-bridges and on their cycling kinetics. The Frank–Starling mechanism dictates that cardiac force development increases with increasing cardiac muscle length (corresponding to increased ventricular volume). It is, however, unclear to what extent this increase in cardiac muscle length affects the rate of cross-bridge cycling. Previous studies using permeabilized cardiac preparations, sub-physiological temperatures, or both have obtained conflicting results. Here, we developed a protocol that allowed us to reliably and reproducibly measure the rate of tension redevelopment (k_tr; which depends …

Successfully Climbing The "Stairs": Surmounting Failed Translation Of Experimental Ischemic Stroke Treatments, Michael Kahle, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

The Stroke Therapy Academic Industry Roundtable (STAIR) provided initial (in 1999) and updated (in 2009) recommendations with the goal of improving preclinical stroke therapy assessment and to increase the translational potential of experimental stroke treatments. It is important for preclinical stroke researchers to frequently consider and revisit these concepts, especially since promising experimental stroke treatments continue to fail in human clinical trials. Therefore, this paper will focus on considerations for several key aspects of preclinical stroke studies including the selection and execution of the animal stroke model, drug/experimental treatment administration, and outcome measures to improve experimental validity and translation potential. …

Orofacial Neuropathic Pain Mouse Model Induced By Trigeminal Inflammatory Compression (Tic) Of The Infraorbital Nerve, Fei Ma, Liping Zhang, Danielle Lyons, Karin N. Westlund

Physiology Faculty Publications

BACKGROUND: Trigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched. Although there are rodent trigeminal nerve research models to study orofacial pain, few models have been applied to studies in mice. A mouse trigeminal inflammatory compression (TIC) model is introduced here which successfully and reliably promotes vibrissal whisker pad hypersensitivity.

RESULTS: The chronic orofacial neuropathic pain model is induced after surgical placement of chromic gut suture in the infraorbital nerve fissure in the maxillary bone. Slight compression and chemical effects of the chromic gut suture on the portion of the infraorbital nerve contacted cause mild …

Global Profiling Of Alternative Splicing Events And Gene Expression Regulated By Hnrnph/F, Erming Wang, Vahid Aslanzadeh, Filomena Papa, Haiyan Zhu, Pierre De La Grange, Franca Cambi

Neurology Faculty Publications

In this study, we have investigated the global impact of heterogeneous nuclear Ribonuclear Protein (hnRNP) H/F-mediated regulation of splicing events and gene expression in oligodendrocytes. We have performed a genome-wide transcriptomic analysis at the gene and exon levels in Oli-neu cells treated with siRNA that targets hnRNPH/F compared to untreated cells using Affymetrix Exon Array. Gene expression levels and regulated exons were identified with the GenoSplice EASANA algorithm. Bioinformatics analyses were performed to determine the structural properties of G tracts that correlate with the function of hnRNPH/F as enhancers vs. repressors of exon inclusion. Different types of alternatively spliced events …

Effects Of Exercise On Ampk Signaling And Downstream Components To Pi3k In Rat With Type 2 Diabetes, Shicheng Cao, Bowen Li, Xuejie Yi, Bo Chang, Beibei Zhu, Zhenzhen Lian, Zhaoran Zhang, Gang Zhao, Huili Liu, He Zhang

Barnstable Brown Diabetes Center Faculty Publications

Exercise can increase skeletal muscle sensitivity to insulin, improve insulin resistance and regulate glucose homeostasis in rat models of type 2 diabetes. However, the potential mechanism remains poorly understood. In this study, we established a male Sprague-Dawley rat model of type 2 diabetes, with insulin resistance and β cell dysfunction, which was induced by a high-fat diet and low-dose streptozotocin to replicate the pathogenesis and metabolic characteristics of type 2 diabetes in humans. We also investigated the possible mechanism by which chronic and acute exercise improves metabolism, and the phosphorylation and expression of components of AMP-activated protein kinase (AMPK) and …

Luteolin Inhibits Human Prostate Tumor Growth By Suppressing Vascular Endothelial Growth Factor Receptor 2-Mediated Angiogenesis, Poyil Pratheeshkumar, Young-Ok Son, Amit Budhraja, Xin Wang, Songze Ding, Lei Wang, Andrew Hitron, Jeong-Chae Lee, Donghern Kim, Sasidharan Padmaja Divya, Gang Chen, Zhuo Zhang, Jia Luo, Xianglin Shi

Toxicology and Cancer Biology Faculty Publications

Angiogenesis, the formation of new blood vessels from pre-existing vascular beds, is essential for tumor growth, invasion, and metastasis. Luteolin is a common dietary flavonoid found in fruits and vegetables. We studied the antiangiogenic activity of luteolin using in vitro, ex vivo, and in vivo models. In vitro studies using rat aortic ring assay showed that luteolin at non-toxic concentrations significantly inhibited microvessel sprouting and proliferation, migration, invasion and tube formation of endothelial cells, which are key events in the process of angiogenesis. Luteolin also inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay (CAM) …

Doublesex Target Genes In The Red Flour Beetle, Tribolium Castaneum, Jayendra Nath Shukla, Subba Reddy Palli

Entomology Faculty Publications

Sex determination cascade in insects terminates with the production of sex-specific protein, Doublesex (Dsx). We identified the dsx homolog (Tcdsx) in Tribolium castaneum. The pre-mRNA of Tcdsx is sex-specifically spliced into three female (Tcdsxf1, Tcdsxf2 and Tcdsxf3) and one male-specific (Tcdsxm) isoforms. Cis-regulatory elements potentially involved in sex-specific splicing of the Tcdsx pre-mRNA were identified in the female-specific exon and the adjoining intronic sequences. All the three female-specific TcDsx proteins share common OD1 and OD2 domains and differ in their C-terminal sequences. Knockdown of Tcdsx resulted in a reduction in the oocyte development, egg production and hatching of eggs laid. …

Depletion Of Endothelial Or Smooth Muscle Cell-Specific Angiotensin Ii Type 1a Receptors Does Not Influence Aortic Aneurysms Or Atherosclerosis In Ldl Receptor Deficient Mice, Debra L. Rateri, Jessica J. Moorleghen, Victoria Knight, Anju Balakrishnan, Deborah A. Howatt, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Whole body genetic deletion of AT1a receptors in mice uniformly reduces hypercholesterolemia and angiotensin II-(AngII) induced atherosclerosis and abdominal aortic aneurysms (AAAs). However, the role of AT1a receptor stimulation of principal cell types resident in the arterial wall remains undefined. Therefore, the aim of this study was to determine whether deletion of AT1a receptors in either endothelial cells or smooth muscle cells influences the development of atherosclerosis and AAAs.

METHODOLOGY/PRINCIPAL FINDINGS: AT1a receptor floxed mice were developed in an LDL receptor -/- background. To generate endothelial or smooth muscle cell specific deficiency, AT1a receptor floxed mice were bred with …

The P2y(12) Antagonists, 2mesamp And Cangrelor, Inhibit Platelet Activation Through P2y(12)/G(I)-Dependent Mechanism, Binggang Xiang, Guoying Zhang, Hongmei Ren, Manjula Sunkara, Andrew J. Morris, T. Kent Gartner, Susan S. Smyth, Zhenyu Li

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: ADP is an important physiological agonist that induces integrin activation and platelet aggregation through its receptors P2Y(1) (Gα(q)-coupled) and P2Y(12) (Gα(i)-coupled). P2Y(12) plays a critical role in platelet activation and thrombosis. Adenosine-based P2Y(12) antagonists, 2-methylthioadenosine 5'-monophosphate triethylammonium salt hydrate (2MeSAMP) and Cangrelor (AR-C69931MX) have been widely used to demonstrate the role of P2Y(12) in platelet function. Cangrelor is being evaluated in clinical trials of thrombotic diseases. However, a recent study reported that both 2MeSAMP and Cangrelor raise intra-platelet cAMP levels and inhibit platelet aggregation through a P2Y(12)-independent mechanism.

METHODOLOGY/PRINCIPAL FINDINGS: The present work, using P2Y(12) deficient mice, sought to …

Reactive Oxygen Species Production And Brugia Pahangi Survivorship In Aedes Polynesiensis With Artificial Wolbachia Infection Types, Elizabeth S. Andrews, Philip R. Crain, Yuqing Fu, Daniel K. Howe, Stephen L. Dobson

Entomology Faculty Publications

Heterologous transinfection with the endosymbiotic bacterium Wolbachia has been shown previously to induce pathogen interference phenotypes in mosquito hosts. Here we examine an artificially infected strain of Aedes polynesiensis, the primary vector of Wuchereria bancrofti, which is the causative agent of Lymphatic filariasis (LF) throughout much of the South Pacific. Embryonic microinjection was used to transfer the wAlbB infection from Aedes albopictus into an aposymbiotic strain of Ae. polynesiensis. The resulting strain (designated "MTB") experiences a stable artificial infection with high maternal inheritance. Reciprocal crosses of MTB with naturally infected wild-type Ae. polynesiensis demonstrate strong bidirectional incompatibility. Levels of reactive …

Fak Is A Critical Regulator Of Neuroblastoma Liver Metastasis, Sora Lee, Jingbo Qiao, Pritha Paul, Kathleen L. O'Connor, B. Mark Evers, Dai H. Chung

Surgery Faculty Publications

Neuroblastomas express increased levels of gastrin-releasing peptide receptor (GRP-R). However, the exact molecular mechanisms involved in GRP-R-mediated cell signaling in neuroblastoma growth and metastasis are unknown. Here, we report that focal adhesion kinase (FAK), as a critical downstream target of GRP-R, is an important regulator of neuroblastoma tumorigenicity. We found that FAK expression correlates with GRP-R expression in human neuroblastoma sections and cell lines. GRP-R overexpression in SK-N-SH cells increased FAK, integrin α3 and β1 expressions and cell migration. These cells demonstrated flatter cell morphology with broad lamellae, in which intense FAK expression was localized to the leading edges of …

Intraspecific Diversity In Sinningia Speciosa (Gesneriaceae: Sinningieae), And Possible Origins Of The Cultivated Florist's Gloxinia, David Zaitlin

Kentucky Tobacco Research and Development Center Faculty Publications

BACKGROUND AND AIMS: The florist's gloxinia is a familiar houseplant in the Gesneriaceae, the botanical family that includes the African violet (Saintpaulia) and other ornamental species. The gloxinia's wild progenitor is Sinningia speciosa (Lodd.) Hiern, a Brazilian endemic. Although it has been cultivated for almost 200 years, little is known about the genetic diversity in S. speciosa, how the wild populations relate to one another or even where the cultivated forms originated. Using available wild collections, preliminary phenetic and phylogenetic investigations were conducted to elucidate the interspecific relationships within S. speciosa and to infer the origins of the cultivars.

METHODOLOGY: …