Medicine and Health Sciences Commons^™

High Resolution Mass Spectrometry (Hrms) Based Investigation Of Small Molecule, Bioactive Secondary Metabolites As Probes In The Examination Of Bacterial Resistance And Virulence, Jerrod Stephen Scarborough

Theses and Dissertations (ETD)

The widespread availability of antimicrobial chemotherapeutics over the last half of the twentieth century has offered dramatic increases in life expectancy. Unfortunately, many pathogenic agents are exhibiting ever increasing resistance to many frontline antibiotics. New chemotherapeutic agents are urgently needed to combat this threat; this work seeks to illustrate applications in which mass spectrometric techniques may be applied to the investigation of novel, small molecule chemotherapeutics for the treatment of bacterial infections. Chapter 1 contains an introduction to mass spectrometry, as well as an overview of relevant chromatographic techniques. Chapter 2 introduces the bacterium F tularensis and M ulcerans and …

Verification Of The Accuracy Of Electronic Mandibular Movement Recording Devices: : An In Vitro Investigation, Joshua Heath Balch

Theses and Dissertations (ETD)

One goal of restorative dentistry is to truly capture maxillomandibular relationships that accurately reproduce mandibular border movements and that would prescribe the best occlusal interface. Registration of horizontal and sagittal movements of the patient allows maximum cusp height and fossae depth with proper placement of occlusal ridges and grooves. The goal is to develop an occlusion that is interference free and entails the concepts of organic occlusion. Methods to transfer patient information to a highly adjustable articulator include mechanical recorders, mechano-electronic recorders and optoelectronic recorders. The purpose of this study is to verify the accuracy of electronic mandibular movement recording …

The Effect Of Timbre And Vibrato On Vocal Pitch Matching Accuracy, Sirisha Duvvuru

Theses and Dissertations (ETD)

Research has shown that singers are better able to match pitch when the target stimulus has a timbre close to their own voice. This study seeks to answer the following questions: 1. Do classically trained female singers more accurately match pitch when the target stimulus is more similar to their own timbre? 2. Does the ability to match pitch vary with increasing pitch? 3. Does the ability to match pitch differ depending on whether the target stimulus is produced with or without vibrato? 4. Are mezzo sopranos less accurate than sopranos? Stimuli: Source signals were synthesized with a source slope …

In Vitro Staining Of Denture Liners And Potential For Color Correction Using Commonly Available Denture Cleansers, Russell D. Morrell

Theses and Dissertations (ETD)

Background: Denture liners are routinely used as part of immediate denture therapy, following surgery involving edentulous tissues, and to improve the function and stability of existing removable prostheses. Appropriate application of denture liners can facilitate patient comfort during prolonged therapy and prior to placement of definitive restorations. However, concern has been raised regarding the susceptibility of common denture liners to agent-induced color change which, in turn, adversely impacts the esthetic appeal of the associated removable prosthesis.

Objective: The purpose of the study was to evaluate the color stability of denture liners exposed to commonly encountered food stains and commonly used …

The Health Of Rural Grandparents Raising Grandchildren, Kimberly Y. Robitaille

Theses and Dissertations (ETD)

Introduction: Grandparents are becoming increasingly responsible for raising their grandchildren. Previous studies have noted physical and mental health limitations for custodial grandparents. Grandparents face numerous challenges in raising grandchildren and consequently, experience high stress levels. However, coping and social support have been found to mediate grandparent stress. Rural custodial grandparents have been an understudied population. Using the Stress Process Model, this study extends the knowledge of rural grandparents raising grandchildren by describing the relationships among physical and mental health, stressors, coping, and social supports for custodial grandparents living in Western Kentucky.

Methods: A mixed methods approach was used to examine …

Predictors Of Drug Court Client Graduation, Marie E. Gill

Theses and Dissertations (ETD)

Background: Substance use disorder in the United States adversely effects society by burdening the justice system with offender incarceration for drug-related crimes, it also strains in the healthcare system with costs in excess of $216 billion dollars for treatment of drug-related mental and physical illnesses. Many offenders of nonviolent crimes with substance use disorder have been diverted to Drug Court (DC) for year-long supervised community-based drug addiction treatment as an alternative to incarceration for non-violent drug-related crimes. Drug Court program outcomes, however, have been studied as a criminal justice intervention, rather than a primary care mental health intervention. The majority …

Hematopoietic Stem Cell Threshold Sensing Controls Regulatory Pathways Facilitating Clinically Relevant Ex Vivo Expansion For Stem Cell Transplantation, Andrew D. Lasiter

Theses and Dissertations (ETD)

The ex vivo expansion of hematopoietic stem cells (HSCs) for transplantation has threefold importance: 1.) First, because of the rarity of stem cells there often isn’t a sufficient supply obtainable from common sources for larger children and adults. 2.) Secondly, patient morbidity and time to hematopoietic reconstitution following myeloablative preconditioning is improved by administering a larger pool of HSCs. 3.) Lastly, gene therapies for hematological diseases still require a robust supply of HSCs to offset varying degrees of inefficiency in vector mediated transfection protocols. These reasons, and others, have been an impetus for many discoveries made within four primary subdivisions …

The Role Of Bip Nucleotide Exchange Factor Sil1 In Immunoglobulin Biosynthesis, Tyler Sanford

Theses and Dissertations (ETD)

BiP is an essential endoplasmic reticulum resident molecular chaperone of the HSP70 family that binds exposed hydrophobic regions of unfolded proteins. Substrates bound by BiP are protected from dangerous non-specific interaction with other unfolded proteins via their aggregation prone exposed hydrophobic regions, which are normally buried in the native state, and act as BiP binding targets. For these substrates to mature into the native state, BiP must be released. Like all HSP70 family members, cycles of BiP binding and release are nucleotide dependent and facilitated by two genres of cochaperones, HSP40s, and nucleotide exchange factors (NEFs). HSP40s function in stimulating …

Effect Of Compression Force On Agglomeration Of Micronized Active Pharmaceutical Ingredients: Techniques To Prevent Api Agglomeration During Compression, Suresh Potharaju

Theses and Dissertations (ETD)

Micronization is one of the common processes for size reduction to increase surface area of poorly soluble Active Pharmaceutical Ingredient’s (API). This size reduction improves the dissolution rate and permeability thereby increasing the bioavailability for hydrophobic API’s.

Tablets and capsules are the most marketed and easy to manufacture solid dosage forms. During manufacturing of tablets, high compression forces are applied uniaxially on the powder bed to get a coherent consolidated compact with good tensile strength. So, diluents are required to mix with API’s and compress into tablets. When this mixture is compressed into tablets, there is a possibility of agglomeration …

An Innovative Testing Protocol To Study Foot And Ankle Kinetics During Early Stance Phase Of Gait, Thomas E. Stewart

Theses and Dissertations (ETD)

The objective of this study was to improve upon existing testing platform limitations with respect to foot and ankle mechanics in the sagittal plane during dorsiflexion and plantar flexion. The intent was to develop a multi-loading protocol that simulated aspects of early stance phase of walking gait. This data were used to evaluate the influence an Achilles load has on the kinematic profile of the ankle complex. Also, resulting kinematic profile data can be used to evaluate ligament/tendon effects, ankle arthroplasty, and various surgical techniques.

A pair of cadaveric human feet, from the same donor, 50 years of age were …

Metabotropic Glutamate Receptor 5 In The Medial Prefrontal Cortex: Role In Cocaine Sensitization And Addiction, Kristin Marie Timmer

Theses and Dissertations (ETD)

Cocaine sensitization is associated with cocaine-induced hyperexcitability of pyramidal projection neurons within the medial prefrontal cortex (mPFC). Such hyperexcitability presumably results in increased glutamatergic input to reward-affiliated brain regions such as the ventral tegemental area (VTA) and nucleus accumbens (NAc), consequently facilitating drugseeking behavior. Metabotropic glutamate receptor 5 (mGluR5) has been implicated in cocaine addiction and demonstrated to increase neuronal excitability, therefore, the aim of the present study was to investigate the effect of intra-mPFC mGluR5 manipulation on behavioral and neurochemical sensitization and drug-seeking. Bilateral cannulae were implanted into the mPFC of male Sprague-Dawley rats and mGluR5 antagonist MTEP (15 …

Nanotherapies For Treating Prostate Cancer, Michael Danquah

Theses and Dissertations (ETD)

Current prostate cancer treatment remains ineffective primarily due to ineffectual therapeutic strategies and numerous tumor-associated physiological barriers which hinder efficacy of anticancer agents. Therefore, the focus of this study was to investigate a new combination therapy approach for treating prostate cancer and develop polymeric nanocarriers to facilitate anticancer drug and nucleic acid delivery.

It was hypothesized that simultaneously targeting androgen-androgen receptor (AR) and X-linked inhibitor of apoptosis protein (XIAP) signaling pathways would be effective in treating prostate cancer. The effect of bicalutamide (antiandrogen) and embelin (XIAP inhibitor) on the growth of prostate cancer cells in vitro and in vivo was …

N200 And P300 Evoked By Stimuli Straddling Category Boundary In Lexical Context, Ji Young Lee

Theses and Dissertations (ETD)

Background and Objectives: Event-related potentials (ERPs) like N200 and P300 have been reported to reflect the categorical perception of speech. The purpose of the present study is to explore whether these ERP components reflect the influence of lexical context on categorical perception. Findings may provide evidence for bottom-up or top-down processing of speech. Methods: On a seven step series of the /bi/-/pi/ continuum, a two-forced choice labeling test was administered in two conditions: /bi/ context (e.g. bee sting) and /pi/ context (e.g. pea soup). From the labeling results, Stimulus 1which is a prototypical /bi/ was selected for standard stimuli, and …

Mrp4 Is A Crucial Regulator Of Testosterone Biosynthesis, Jessica Ann Morgan

Theses and Dissertations (ETD)

The physiological role of multidrug resistance protein 4 (Mrp4) in the testes is unknown. It was discovered that Mrp4 is expressed primarily in mouse and human Leydig cells; however, there is no current evidence that Mrp4 regulates testosterone biosynthesis. The role of Mrp4 was investigated in Leydig cells where testosterone production is regulated by cAMP, an intracellular second messenger formed when the luteinizing hormone (LH) receptor (Lhr) is activated. As Mrp4 regulates cAMP, we compared testosterone levels in our Mrp4 WT and KO mice. Prepubertal KO mice had significantly reduced testicular testosterone, impaired gametogenesis, and disrupted cAMP homeostasis, resulting in …

Anti-Apoptotic Mcl-1 Localizes To The Mitochondrial Matrix And Couples Mitochondrial Fusion To Respiration, Rhonda Perciavalle

Theses and Dissertations (ETD)

MCL-1, an anti-apoptotic BCL-2 family member that is essential for the survival of multiple cell lineages, is also among the most highly amplified genes in cancer. Although MCL-1 is known to oppose cell death, precisely how it functions to promote survival of normal and malignant cells is poorly understood. Here, I report that different forms of MCL-1 reside in distinct mitochondrial locations and exhibit separable functions. On the outer mitochondrial membrane, a MCL-1 isoform acts like other anti-apoptotic BCL-2 molecules to antagonize apoptosis, whereas an amino-terminally truncated isoform of MCL-1 that is imported into the mitochondrial matrix is necessary to …

Using Grounded Theory To Reveal Tacit Knowledge For Nurse Educators In An Unfamiliar African Setting, Ramona B. Patterson

Theses and Dissertations (ETD)

There is a gap in evidence to guide individuals as they prepare for a nursing education partnership in an unfamiliar setting. Much of the existing knowledge base is contained within institutional or organizational confines. Individuals new to the field need access to existing expertise and tacit knowledge. The purpose of this research was to generate a grounded theory to guide aspiring nursing faculty in developing the necessary knowledge base to fulfill the nurse educator role in an unfamiliar setting. Ghana, Africa, was specified as the unfamiliar setting and context for this study.

Purposive sampling identified individuals from North America and …

The Role Of The Yxxφ Motif In Cd82 Trafficking And Function, Mekel Marie Richardson

Theses and Dissertations (ETD)

CD82, a tetraspanin, is a tumor metastasis suppressor. Tetraspanins are membrane spanning proteins that play critical roles in diverse biological and pathological processes, e.g., the regulation of cancer metastasis. CD82 is ubiquitously expressed in various types of tissues, but its expression becomes down-regulated or lost in a majority of metastatic tumors. It inhibits tumor metastasis without affecting primary tumor growth. Cancer patients whose tumors contain CD82 exhibit minimal metastasis. We know that CD82 functions as a tumor metastasis suppressor but the mechanism by which this occurs is largely unknown. CD82 can be found on the plasma membrane as well as …

Development Of The Sustained Release Analgesic Formulations For Rodents And A Novel In Vitro Model For Parenteral Formulations With The Character Of A Level A Ivivc, Jin Xu

Theses and Dissertations (ETD)

Laboratory animals are often subjected to various painful surgical procedures such as laparotomy, thoracotomy or orthopedic procedures as well as non-surgical procedures such as the induction of arthritis. Any procedure that causes pain in humans is assumed to cause pain in animals too. It is the ethical obligation of all research personnel to reduce or preferably eliminate pain and distress by using analgesics. Furthermore, the Institutional Animal Care and Use Committee (IACUC) requires that appropriate anesthetics and/or analgesics must be used to minimize or eliminate pain and distress for animals undergoing painful procedures.

The oral administration route is the most …

Discovery Of Dihydroartemisinin And Dasatinib Drug Combination To Cure Pooroutcome Bcr-Abl+ Acute Lymphoblastic Leukemia, Harpreet Singh

Theses and Dissertations (ETD)

Oncogenic signaling by the Philadelphia chromosome-encoded BCR-ABL fusion kinase initiates and drives both Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myelogenous leukemia (CML). Food and Drug Administration (FDA)- approved BCR-ABL-specific kinase inhibitors (BCR-ABL–KIs) imatinib, dasatinib and nilotinib induce prolonged remissions in CML but poor leukemia-reduction and relapse-control in Ph+ ALL. The relative primary BCR-ABL–KI-resistance in Ph+ ALL patients carrying predominantly BCR-ABLWT disease cannot be attributed to drug-resistant BCR-ABL mutations (BCR-ABLMUTANTS), and remains poorly understood.

We established a cell-based platform to evaluate the modulation of anti-Ph+ ALL activity of drugs by both tumor-extrinsic cytokines normally present in the leukemia …

Improving Literacy Through Instruction And Community Experiences: : The Effect Of A Summer Program On Literacy Outcomes Of Students From Low Ses Homes, Lisa Delozier Bowers

Theses and Dissertations (ETD)

Among the academic challenges faced by students from low socio-economic (SES) homes is the loss of academic skills during the summer months. Unfortunately, the public schools are often unable to provide summer learning opportunities because limited space, funding, and teacher availability. Established community organizations frequently provide summer programs, however, there is little research to indicate that they can be used to address summer learning loss.

A summer program was designed to improve oral and written narrative skills for students from low SES homes. This program was based in a local community ministry and was designed to use thematic units that …

Inhibition Of Breast Cancer Angiogenesis And Metastasis Ay Targeting Hypoxia-Inducible Factor-1Α, Chikezie O. Madu

Theses and Dissertations (ETD)

The current clinical chemotherapy agents are not ideal for breast cancer as they are not curative, but only provide a modest extension of survival with sometimes a severely adverse effect on the patient’s quality of life. There is, therefore, an urgent need to search for new and more effective anti-breast cancer drugs. However, the existing screening system is inefficient and time-consuming despite the extremely large amount of small molecule compounds in database currently available, and thereby hindering the effort for selecting new and effective anti-cancer drugs.

The majority of locally advanced solid tumors contain regions of reduced oxygen availability. Hypoxia …

Investigation Of Enhancement Of Furosemide Solubilization With Cyclodextrins And A Novel Octenyl Succinate Anhydride Starch, Rui Zhu

Theses and Dissertations (ETD)

Solubility behavior is one of the most challenging aspects for drug commercialization and often the main reason of drug that do not reach to its full potential. Now nearly 60% new chemical entities possess solubility problems, whereas practically no drug products with less than 10 µg/ml solubility in 70’s or 80’s. There is an ever increasing need to develop new formulation techniques and exicipients with novel mechanisms of action. Various techniques have been applied to enhance the drug solubility such as co-solvents, particle size reduction, lipid based drug delivery systems, nanosuspension, use of surfactants, salt formation, cyclodextrin complexes and solid …

Independent Component Analysis Of Event-Related Electroencephalography During Speech And Non-Speech Discrimination: : Implications For The Sensorimotor ∆∞ Rhythm In Speech Processing, Andrew Lee Bowers

Theses and Dissertations (ETD)

Background: The functional significance of sensorimotor integration in acoustic speech processing is unclear despite more than three decades of neuroimaging research. Constructivist theories have long speculated that listeners make predictions about articulatory goals functioning to weight sensory analysis toward expected acoustic features (e.g. analysis-by-synthesis; internal models). Direct-realist accounts posit that sensorimotor integration is achieved via a direct match between incoming acoustic cues and articulatory gestures. A method capable of favoring one account over the other requires an ongoing, high-temporal resolution measure of sensorimotor cortical activity prior to and following acoustic input. Although scalp-recorded electroencephalography (EEG) provides a measure of cortical …

The Effect Of Progesterone Only Contraception On The Accuracy Of Cervical Cytologic Interpretation, Michelle Reneé Collins

Theses and Dissertations (ETD)

Abstract Introduction: Papanicolaou screening is the standard of care for the detection of abnormal cervical cells. Early detection and treatment of cervical neoplasia depends on the accurate interpretation of the cytologic sample. Diagnosis of dysplasia is made by histology interpretation to confirm the results of cytology screening. Cervical cells are susceptible to change as a result of hormonal exposure, and this has the potential to affect cytologic interpretation. Cervical cells may be exposed to exogenous progesterone if the woman uses injectable depot medroxyprogesterone acetate or a progesterone intrauterine device. Previous study results have been inconsistent regarding the effect of progesterone …

Rankl And Osteoprotegerin Levels In Response To Orthodontic Forces, Katherine Ann Hart D.D.S.

Theses and Dissertations (ETD)

Orthodontic tooth movement is mediated by interactions between PDL cells and those of the alveolus. One protein—the receptor activator nuclear factor kappa B ligand (RANKL)—is critical for osteoclastogenesis, and osteoprotegerin (OPG) is a decoy ligand that competitively inhibits RANKL. A higher RANKL/OPG ratio is associated with areas of bone resorption, while a lower ratio occurs in areas of bone deposition and homeostasis. There have been almost no clinical studies of RANKL and OPG expression in human subjects undergoing orthodontic tooth movement. The purpose of this study was to quantify changes in the levels of RANKL and of OPG expression in …

A Secular Increase In The Tempos Of Tooth Formation: 1980-2010, Kevan Michael O'Neill

Theses and Dissertations (ETD)

Introduction: Improved environments in the U.S. have resulted in taller, larger, and heavier children and adults compared to past generations. Studies of other skeletal-dental dimensions have shown increases across generations, and our perception is that teeth now are forming faster. The purpose of this study is to test for a secular trend towards faster tempos of tooth mineralization in a sample of U.S. white adolescents over the past quarter century (1980-85 to 2005-10).

Materials: Two cohorts of 200 children each were identified, each with an age range of 10-to- 15 years, one group from 1980-85 and the more recent group …

Skeletal And Dental Components Of Class Ii Division 1 Correction With The Mara Compared To The Standard Edgewise Appliance, Zachary Paul Pitcher

Theses and Dissertations (ETD)

Many tools are available to correct Class II dental relationships. A functional orthopedic appliance is a popular type of Class II corrector that is thought to correct Class II dental relationships both dentally and skeletally by enhancing mandibular growth. The purpose of the study was to quantify differences in the amounts of skeletodental change based on treatment (MARA and Standard Edgewise) in Class II Division 1 patients. The sample consisted of 2 groups of Class II Division 1 patients: 51 patients treated with the MARA followed by an Edgewise appliance and another group of 51 patients treated with the Standard …

Pronthocyanidin-Rich Cranberry-Fractioninduced Alteration Of Periodontal Pathogen Lipopolysaccharide Functions, Vreiti Sangha

Theses and Dissertations (ETD)

The cranberry (species: Vaccinium macrocarpon, family: Ericaceae) is a polyphenolicrich berry fruit native to North America and exhibits numerous beneficial properties for human health, such as inhibition of human cancer cell line proliferation and prevention of urinary tract colonization by bacterial pathogens. The proanthocyanidin rich cranberry fraction has long been speculated to possess the capacity to reduce the production of inflammatory mediators by LPSstimulated macrophages and gingival fibroblasts and to inhibit host extracellular matrix destructive enzyme production and activity.

The purpose of this investigation was to examine the effect of cranberry non dialyzable material (NDM), which was shown to be …

Oropharyngeal Airway Volume Following Orthodontic Treatment: Premolar Extraction Versus Non-Extraction, Thomas Patrick Shannon

Theses and Dissertations (ETD)

Orthodontic correction of tooth size versus arch size discrepancy (TSASD) can be achieved with two distinct methods of treatment. The first involves the extraction of teeth to gain the space needed for tooth alignment. The second relies on arch expansion to gain the space needed for correction. In recent decades, arguments for and against the extraction of teeth for orthodontic purposes have become increasingly important, particularly in regards to oropharyngeal airway size. Purpose: The purpose of this study is to determine whether there is a decrease in oropharyngeal dimensions following the extraction of four premolars and subsequent orthodontic therapy. Methods: …

Oropharyngeal Airway Volume Following Orthodontic Treatment: Premolar Extraction Versus Non-Extraction, Thomas Patrick Shannon

Theses and Dissertations (ETD)

Orthodontic correction of tooth size versus arch size discrepancy (TSASD) can be achieved with two distinct methods of treatment. The first involves the extraction of teeth to gain the space needed for tooth alignment. The second relies on arch expansion to gain the space needed for correction. In recent decades, arguments for and against the extraction of teeth for orthodontic purposes have become increasingly important, particularly in regards to oropharyngeal airway size. Purpose: The purpose of this study is to determine whether there is a decrease in oropharyngeal dimensions following the extraction of four premolars and subsequent orthodontic therapy. Methods: …