Medicine and Health Sciences Commons^™

Prediction Of Human Systemic, Biologically Relevant Pharmacokinetic Properties Based On Physicochemical Properties Of Calcium Channel Blockers, Tafif Abdullah Al

Theses and Dissertations

This research explored quantitative relationships (QSPKR) between different molecular descriptors and pertinent, systemic PK properties for 14 calcium channel blockers (CCB). Physicochemical properties (PC) such as molecular weight (MW), molar volume (MV), calculated logP (clogP), pKa, calculated logD7.4 (clogD), % ionized at pH 6.3 and pH 7.4, hydrogen bond donors (HBD), hydrogen bond acceptors (HBA), and number of rotatable bonds (nRot) were chosen as possible predictor variables for systemic PK properties for CCB, obtained from pertinent literature, assessing the PK of CCB after intravenous administration to healthy humans. All PC properties and molecular descriptors were computed using ACD-solubility/DB 12.01. Total …

Development Of Natural Cyclic Peptide Inhibitors Of Xrcc4/Xlf Interaction For Radio-Sensitization Of Breast Tumor Cells, Mohaini Mohammed Al

Theses and Dissertations

Breast cancer is the second leading cause of cancer death in women according to the American Cancer Society. The standard treatment regimen for breast cancer involves ionizing radiation combined with surgery and chemotherapy. Ionizing radiation induces a complex signaling response in cells resulting in either growth arrest, senescence or cell death, and the cell killing after exposure to radiation results largely from DNA double-strand breaks (DSBs). There are two main mechanisms in mammalian cells responsible for repairing the DSBs; the primary mechanism is non-homologous end joining (NHEJ) and the secondary mechanism is homologous recombination (HRR). Previous studies showed that breast …

Preparation And Evaluation Of Deconstruction Analogs Of 7-Deoxykalafungin As Akt Inhibitors, Sudha Korwar

Theses and Dissertations

Pyranonaphthoquinone lactones have been recently found to be selective inhibitors of the serine-threonine kinase AKT/PKB. AKT/PKB plays a major role in tumorigenesis, hence these compounds have a great potential to act as anti-cancer agents. They act by a novel bioreductive alkylation mechanism of inhibition of AKT/PKB. In this work, 7-deoxykalafungin, a pyranonaphthoquinone lactone and its deconstruction analogs were synthesized. The structural features of the compounds necessary to inhibit AKT1 potently and selectively were determined. It was observed that compounds with a pyran ring were more potent in inhibiting AKT1. Conversely, flexible compounds were found to be weak inhibitors of AKT1. …

Towards Understanding The Mechanism Of Action Of Abused Cathinones, Rakesh Vekariya

Theses and Dissertations

The dopamine transporter (DAT) mediates reuptake of dopamine from the synaptic cleft into the presynaptic terminus and plays a critical role in maintaining the normal function of dopaminergic neurons. DAT is the major target of widely abused psychostimulant drugs, including cocaine and amphetamine. DAT also figures into disease states, and it is a target for therapeutic drugs. It is known that cathinone and methcathinone, β-keto analogs of amphetamine and methamphetamine, respectively, produce pharmacological actions similar to amphetamine. Cathinone and methcathinone analogs are recently gaining in popularity on the clandestine market (e.g. ‘bath salts’). Cathinone and methcathinone analogs as well as …

Role Of Nucleosome Remodeling Factor (Nurf) In Tumorigenesis Using A Breast Cancer Mouse Model, Aiman Alhazmi

Theses and Dissertations

Understanding the impact of epigenetic mechanisms on tumorigenesis is essential, as epigenetic alterations are associated with tumor initiation and progression. Because epigenetic changes are reversible, they are potential targets for cancer therapy. Nucleosome Remodeling Factor (NURF) is a chromatin-remodeling complex that regulates gene expression by changing nucleosome positioning along the DNA sequence. Previous studies have shown a role for NURF in embryonic development as well as regulating genes involved in tumor progression. In this work we investigated the impact of eliminating NURF function in tumorigenesis in vivo. BALB/c mice challenged with syngeneic 67NR breast cancer cell lines, injected into the …

Cell Death And Growth Arrest Pathways Mediating The Actions Of Stilbene 5c In Hct-116 Colon Cancer Cells, Moureq Alotaibi

Theses and Dissertations

Abstract The stilbene derivative, cis-3, 4’, 5-trimethoxy-3’-aminostilbene (stilbene 5c), is a potentially potent antitumor agent that acts via binding to the colchicine-binding pocket in microtubules. Earlier studies have shown that stilbene 5c induces cell death in ovarian cancer cells and leukemic cells. The present study was designed to investigate the effectiveness of this microtubule poison against the HCT-116 human colon cancer cell line and its mechanisms of action. Time course studies demonstrated that stilbene 5c produces a biphasic decrease in cell viability. The capacity of the cells to proliferate was not restored upon removal of the drug after 6 days …

Small Molecules As Negative Allosteric Modulators Of Alpha7 Nachrs, Osama Alwassil

Theses and Dissertations

Alpha7 Neuronal nicotinic acetylcholine receptors (nAChRs) are involved in essential physiological functions and play a role in disorders such as Alzheimer’s disease. MD-354 (3-chlorophenylguanidine; 21), the first small–molecule negative allosteric modulator (NAM) at alpha7 nAChRs, served as a lead in developing structure–activity relationships for NAMs at a7 nAChRs. MD-354 (21) also binds at 5-HT3 receptors. Analogs of MD-354 with structural features detrimental to 5-HT3 receptor affinity were evaluated in patch-clamp recordings and an aniline N-methyl analog resulted in a more potent and selective NAM than MD-354. A new N-methyl series of compounds was synthesized in which the 3-position was replaced …

Transferrin Binding Protein B Structure, Function, And Export In Neisseria Gonorrhoeae, Meredith L. Weck

Theses and Dissertations

Iron, an essential nutrient for most microorganisms, is sequestered in the host by iron-binding proteins, such as lactoferrin and transferrin. Neisseria gonorrhoeae utilizes transferrin as an iron source and its iron acquisition system is composed of two transferrin binding proteins: TbpA and TbpB. TbpA is a TonB-dependent, outer membrane transporter and TbpB is a bilobed, surface exposed lipoprotein. TbpB can distinguish between apo- and holo-transferrin which is involved in increasing the efficiency of iron uptake through the Tbps. It is anchored in the outer leaflet of the outer membrane by its lipid moiety. We aimed to identify the mechanism of …

The Role Of Tetraspanin-8 In Astrocyte Elevated Gene-1 Mediated Progression Of Hepatocellular Carcinoma, Maaged Akiel

Theses and Dissertations

Hepatocellular carcinoma (HCC) is a devastating form of liver cancer that accounts for 80% of liver cancers. HCC has a poor prognosis with five-year survival of less than 12% in the United States. We in previous studies have identified Astrocyte Elevated Gene-1 (AEG-1) as an aberrantly overexpressed gene in many cancers including HCC, regulating tumor progression. Microarray studies identified the small transmembrane protein, tetraspanin8 (TSPAN8) as a downstream of AEG-1. TSPAN8 belongs to the family of TETRASPANINS with the characteristic of crossing the membrane four times, and regulating a wide range of cellular phenomena. TSPAN8 is implicated in metastasis and …

Outcomes Of A Social Communication Intervention On The Use Of Emotion Words, Amy Tucker Cornett

Theses and Dissertations

Children with language impairment (LI) have often been identified as having social communication breakdowns. A number of these problems are likely the result of deficits in emotional competence. This thesis examines a social communication intervention designed to target the emotional competence of children with LI. Three elementary school-aged children with LI were recruited to receive twenty, 20-minute intervention sessions over the course of four months. Each intervention session involved a combination of activities targeting emotion recognition and emotion inferencing using story retell, story exploration, story enactment, perspectives charts, journal entries, emotion labeling, and personalization. These activities revolved around Mercer Mayer's …

Development Of Psychometrically Equivalent Speech Audiometry Materials For Measuring Speech Recognition Thresholds In Native Tagalog Speakers, Brandon Brian Taylor

Theses and Dissertations

In addition to the use of pure-tones for testing hearing, speech signals are highly valuable diagnostic tools for identifying and evaluating hearing impairment. Speech audiometry involves the implementation of such signals in the measurement of hearing acuity. One aspect of speech audiometry involves assessment of the speech recognition threshold (SRT) which evaluates an individual's ability to hear and understand speech. While live speech has been used in the past to assess SRT, recorded materials are preferred and have been shown to be advantageous over live speech. High-quality digitally recorded speech audiometry materials have been available in English for some time, …

Effect Of A Humanoid Robot During Therapy On Responding To Joint Attention With Children With Autism Spectrum Disorder, Katherine Lowe

Theses and Dissertations

This study examined the use of a humanoid robot to engage two children with Autism Spectrum Disorder (ASD) on responding language behaviors including language, affect, imitation, and eye contact. The robot was integrated into each child's regular intervention in low-doses (10 min of a 50 min session). The goal was to increase responding language behaviors in the children with their conversational partners. The two children participated in pre and post assessment sessions as well as 16 intervention sessions. The data from these sessions were coded into two main categories including how the children interacted (Initiating Engagement, Responding to …

Relationship Of Demographic Characteristics And Bmi With Health Literacy In Pacific Islander Care-Giving Adults, Sharla E. Morgan

Theses and Dissertations

Purpose: Health literacy and obesity are major global issues. Vulnerable populations, such as those with low health literacy, have the highest rates of obesity. Native Hawaiian and other Pacific Islander (NHOPI) nations have the highest prevalence of obesity in the world. This study describes the relationship between health literacy and demographic variables in a sample of NHOPI caregiving adults. Methods: We conducted a correlational study of 364 NHOPI adults. Each was a caregiver of at least one NHOPI child. Data were collected at grocery stores and a preschool in two Hawaiian Islands (n=209) and at NHOPI events in Utah (n=155). …

Angiogenesis In Response To Varying Fiber Size In An Electrospun Scaffold In Vivo., Damien Brown

Theses and Dissertations

Injury to the spinal cord results in partial or complete loss of sensory perception and motor function. After spinal cord injury (SCI), damaged tissue dies and a cavity will form. This cavity prevents the regeneration of tissue and any functional recovery. One way to address the cavity is the insertion of an electrospun scaffold that our lab has created. This provides a substrate for regenerating tissue to grow on, and it is thought that reestablishing the blood supply within the scaffold will allow cells necessary for regeneration to thrive. This could ultimately lead to meaningful recovery for patients who have …

Evaluating The Effectiveness Of A Workshop/Support Group For Parents Raising Children With Type 1 Diabetes, Christina Marie Yazzie

Theses and Dissertations

The purpose of this study was to evaluate the effectiveness of a workshop/support group for parents raising children with type 1 diabetes mellitus (T1DM). Diagnosis of a chronic disease in a child generally arouses acute anxiety and stress in parents. Parental stress when raising a child with type 1 diabetes is often centered on worry about their child's health and parents' ability to maintain the care activities needed by these children. Parents are the primary caregivers of children with Type 1 diabetes, and the effect of stress on parents can impact the health of both children and parents. The present …

The Relationship Between Select Demographic Characteristics And Body Mass Index Among Native Hawaiian And Other Pacific Islander Caregiving Adults, Katrina Duncan

Theses and Dissertations

Purpose: Native Hawaiian and other Pacific Islanders (NHOPIs) have the highest prevalence of overweight and obesity in the world. This study identified the proportion of our NHOPI sample in each body mass index (BMI) category and explored relationships between demographic characteristics and BMI. Design: This descriptive correlational study included 364 NHOPI caregiver adults in Utah (n=155) and Hawaii (n=209). We gathered demographic information with a questionnaire. Height and weight were measured for BMI calculations. Results: According to the CDC's BMI categories, 84.3% of our sample was overweight (BMI=25.0-29.9) or obese (BMI ≥30). Participants in Utah had significantly higher BMIs than …

Reliability Of The Mean Length Of Utterance Measure In Samples Of Children's Language, Katherine Marie Bigelow

Theses and Dissertations

Mean length of utterance (MLU) is widely used in child language sample analysis as a way to quantify language development. The current study examines the split-half reliability of MLU and two alternative measures: MLU2 and median length of utterance (MdLU). The effects of utterance segmentation into phonological units (P-units) or communication units (C-units) on reliability were also studied. Sixty conversational child language samples were used which included ten children with language impairment. All measures were found to have high levels of split-half reliability, with MLU and MLU2 having higher levels of reliability than MdLU. There was no significant difference between …

Superhydrophobic Nanostructured Coating For Anti-Icing Applications, Khedir R. Khedir

Theses and Dissertations

In this work, anti-icing superhydrophobic (SHP) tungsten nanorod (WNR) surfaces were fabricated. The fabrication of WNR surfaces as rough surfaces was carried out using the Glancing Angle Deposition (GLAD) technique. Using the magnetron- sputtering deposition method, the deposition Ar pressure, Ar flow rate, and substrate tilting angle were varied to fabricate WNRs with different surface morphologies and porosities. The surface energy of the WNR films was lowered by coating them with a nano-layer (10-15nm) of Teflon AF2400 using an effusion cell. Static contact angle (SCA) measurements of the sessile water droplet gently dispensed on surfaces were used to characterize the …

Investigation Of Advanced Nanostructured Multijunction Photoanodes For Enhanced Solar Hydrogen Generation Via Water Splitting, Hidetaka Ishihara

Theses and Dissertations

As the worldwide demand for fossil-based fuel increases every day and the fossil reserve continues to be depleted, the need for alternative/renewable energy sources has gained momentum. Electric, hybrid, and hydrogen cars have been at the center of discussion lately among consumers, automobile manufacturers, and politicians, alike. The development of a fuel-cell based engine using hydrogen has been an ambitious research area over the last few decades-ever since Fujishima showed that hydrogen can be generated via the solar-energy driven photo-electrolytic splitting of water. Such solar cells are known as Photo-Electro-Chemical (PEC) solar cells. In order to commercialize this technology, various …

Characterizing The Role Of Nucleosome Remodeling Factor (Nurf) In Tumorigenesis And Metastatic Progression Using Mouse Models Of Breast Cancer., Suehyb Alkhatib

Theses and Dissertations

Increasingly the role of epigenetic machinery as a bridge between underlying DNA sequence and cellular phenotype is being discovered. The establishment of a myriad of unique cellular types sharing identical gene sequences in a multicellular organism gives a broad sense for the inherent role of epigenetic influence on cell differentiation. Importantly, the epigenetic mechanisms involved in establishing cell identity unsurprisingly contribute to diseased states, including cancer. Recent research continues to elucidate contributory roles of epigenetic mechanisms, such as DNA methylation, histone modification, and microRNA regulation, in human cancers. Additionally, chromatin remodelers, such as the Nucleosome Remodeling Factor (NURF), have been …

Cohort Membership, Dental Insurance And Utilization Of Dental Services In Adults Age 47 And Over Receiving Dental Care At Virginia Commonwealth University’S School Of Dentistry, Patricia Brown Bonwell

Theses and Dissertations

This cross-sectional, non-experimental study evaluates associations between cohort membership, type of dental coverage, and utilization of dental services in all patients age 47 and over who received dental care at Virginia Commonwealth University’s (VCU) School of Dentistry in 2011. Structural Lag Theory poses that society’s institutions lag behind the actuality of a healthy and capable older adult population. The two dynamisms of the Structural Lag Theory were used for this study. The Dynamism of Changing Lives is represented by Cohort differences. Cohort differences include cohort size, people living longer and retaining more of their natural teeth along with different attitudes …

Development And Comparison Of Risk-Adjusted Models To Benchmark Antibiotic Use In The University Healthsystem Consortium Hospitals, Omar Moh'd Musa Ibrahim

Theses and Dissertations

Background. Infectious diseases societies recommend that hospitals risk-adjust their antimicrobial use before comparing it to their peers, a process called benchmarking. The purpose of this investigation is to apply and compare 3 risk-adjustment procedures for benchmarking hospital antibacterial consumption (AbC). Two standardization of rates procedures, direct and indirect standardization, are compared with one another as well as with regression modeling. Methods. Total aggregate adult AbC for 52 systemic antibacterial agents was measured in 70 hospitals that subscribed to the University HealthSystem Consortium Clinical Resource Manager database in 2009 and expressed as days of therapy (DOTs) per either 1000 patients days …

Cyberspace And Real-World Behavioral Relationships: Towards The Application Of Internet Search Queries To Identify Individuals At-Risk For Suicide, Casey C. Miller

Theses and Dissertations

The Internet has become an integral and pervasive aspect of society. Not surprisingly, the growth of ecommerce has led to focused research on identifying relationships between user behavior in cyberspace and the real world - retailers are tracking items customers are viewing and purchasing in order to recommend additional products and to better direct advertising. As the relationship between online search patterns and real-world behavior becomes more understood, the practice is likely to expand to other applications. Indeed, Google Flu Trends has implemented an algorithm that accurately charts the relationship between the number of people searching for flu-related topics on …

Emergency Department Nurses' Suggestions For Improving End-Of-Life Care, Robert D. Wood

Theses and Dissertations

Introduction: Death is not an uncommon outcome for patients who seek immediate care in an emergency department. Although death is common in the emergency department there is little literature regarding end-of-life care in the emergency department. The purpose of this research study is to determine what changes emergency nurses would suggest to improve end-of-life care for dying patients and their families in emergency departments.

Background: A national, geographically dispersed, random sample of 1000 emergency nurses were sent a questionnaire entitled, "Emergency Nurses' Perceptions of End-of-Life Care." Inclusion criteria included nurses who were members of the Emergency Nurses Association, could read …

Elucidating Genetic And Environmental Influences On Alcohol-Related Phenotypes, Jacquelyn Meyers

Theses and Dissertations

Decades of work has led researchers to believe that risk for complex behavioral phenotypes, such as alcohol use disorders, is likely influenced by multiple genes of small effect acting in conjunction with each other and the environment. Currently, the field of psychiatric genetics is developing methodologies for the identification of genetic risk variants that predispose individuals to the development of complex behavioral disorders. Several challenges related to the complex and polygenic nature of these phenotypes, must be considered. This dissertation study attempts to address these important challenges in the context of alcohol use disorders and related phenotypes. A rich twin …

Social Circles Of Children With Language Impairment, Erin Whitworth

Theses and Dissertations

Children with language impairment (LI) often demonstrate difficulties in social communication. The purpose of this pilot study was to examine the quantity and quality of the social interactions of children with LI and their typical peers through an analysis of the social networks or circles of each child. Eight children with LI as well as eight children with typically developing language and their parents were interviewed. Children's social networks were organized by social circles to effectively paint a picture of each child's social communication (Blackstone & Hunt Berg, 2003). Children with LI were found to have overall fewer contacts in …

Unique Features And Neuronal Properties In A Multisensory Cortex, W. Alex Foxworthy

Theses and Dissertations

UNIQUE FEAUTRES OF ORGANIZATION AND NEURONAL PROPERTIES IN A MULTISENSORY CORTEX Multisensory processing is a ubiquitous sensory effect that underlies a wide variety of behaviors, such as detection and orientation, as well as perceptual phenomena from speech comprehension to binding. Such multisensory perceptual effects are presumed to be based in cortex, especially within areas known to contain multisensory neurons. However, unlike their lower-level/primary sensory cortical counterparts, little is known about the connectional, functional and laminar organization of higher-level multisensory cortex. Therefore, to examine the fundamental features of neuronal processing and organization in the multisensory cortical area of the posterior parietal …

Postpartum Depression In Immigrant Hispanic Women: A Comparative Community Sample, Laura Mae Shellman

Theses and Dissertations

Purpose: This study was initiated to verify whether a remarkably high rate of postpartum depression (PPD), previously found in immigrant Hispanic women receiving health care at a community clinic, would also be found in a community sample with a similar demographic.

Data Sources: Sixty immigrant Hispanic women who had recently given birth were recruited from local community settings. The Beck Postpartum Depression Screening Scale-Spanish version (PPDS-S) and the General Acculturation Index (GAI) were used to screen for PPD symptoms and to collect demographic data. These data were then compared with previously published data from the community clinic sample.

Conclusions: Sixty …

The Correlation Between Spectral Moment Measures And Electropalatographic Contact Patterns For /S/ And /Ʃ/, Benjamin James Marshall

Theses and Dissertations

Spectral Moment Analysis has helped further our understanding of the spectral properties of obstruent speech production; however, the physiologic correlates of these spectral measures are not well understood. The aim of the present study was to examine the possible correlations between the linguapalatal contact patterns used to produce the fricatives /s/ and /ʃ/ and the resulting spectral characteristics. Using spectral moment analysis and electropalatography (EPG), the real-word productions of eight speakers of American English were investigated. The spectral measures for the fricative tokens in the present study were found to be similar to data reported in previous research with adult …

The Effect Of An Artificially Flattened Fundamental Frequency Contour On Intelligibility In Speakers With Dysarthria, Emily E. Redd

Theses and Dissertations

Prosody plays an important role in speech communication. Many individuals with motor speech disorders have decreased prosodic control and thus lower overall intelligibility. Few studies have examined the effect of a flattened prosodic contour on the intelligibility of dysarthric speech, and little is known about the role that listener gender plays in understanding disordered speech. The purpose of this study was to quantify the impact of artificial prosodic manipulation on the intelligibility of dysarthric speech as a function of the extent of fundamental frequency (F0) contour flattening. A further goal was to examine the influence of listener gender on intelligibility. …