Medicine and Health Sciences Commons^™

Rna-Dependent Selenocysteine Biosynthesis In Eukaryotes And Archaea, Sotiria Palioura

Yale Medicine Thesis Digital Library

Selenocysteine (Sec), the 21st genetically encoded amino acid, is the major metabolite of the micronutrient selenium. Sec is inserted into nascent proteins in response to a UGA codon. The substrate for ribosomal protein synthesis is selenocysteinyl-tRNASec. While the formation of Sec-tRNASec from seryl-tRNASec by a single bacterial enzyme selenocysteine synthase (SelA) has been well described, the mechanism of Sec-tRNASec formation in archaea and eukaryotes remained poorly understood. Herein, biochemical and genetic data provide evidence that, in contrast to bacteria, eukaryotes and archaea utilize a different route to Sec-tRNASec that requires the tRNASec-dependent conversion of O-phosphoserine (Sep) to Sec. In this …

Reminiscence Of An Elderly Woman: An Artistic Inquiry, Cathy Gamby-Weideman

Creative Arts Therapies Theses

This thesis explores the clinical value to the elderly population of combining reminiscence and dance. This five month collaboration between a recently widowed elderly female and a dance/movement therapy intern culminated in a 13 minute choreographed dance performance. Themes that emerged during this art-based study were her relationship with her husband, her role as his primary caregiver and her grief after his death. Eric Erikson identifies integrity vs. despair as the struggle or crisis to be grappled with in the last stage of human development, old age. This theoretical framework has been incorporated in this study.

Dance/Movement Therapy And Responsive Classroom: A Theoretical Synthesis, Shawna L. Solsvig

Creative Arts Therapies Theses

This theoretical synthesis combines concepts from Chacian dance/movement therapy and the Responsive Classroom approach to teaching and learning, and suggests a proactive behavioral management style for dance/movement therapists that incorporates aspects from these two frameworks. For this synthesis, Chacian dance/movement therapy and Responsive Classroom techniques were adapted and implemented. Through combining these two methods, the researcher suggests a unique treatment model as a way to prevent and confront violent and aggressive behaviors of children that present in a dance/movement therapy session.

Inviting Consciousness: Authentic Movement And The Injured Brain, Ande Welling

Creative Arts Therapies Theses

This thesis is guided by curiosity regarding the possibility of incorporatingAuthentic Movement into a neuro-rehabilitation treatment program. Using Authentic Movement as part of one client's dance/movement therapy treatment, this qualitative case study explores and documents how mover consciousness, the first layer of Authentic Movement, develops and is taught to one client surviving brain injury. Data includes the researcher's journal entries, embodied knowledge, and notes written using a technique called embodied writing, as well as client journal entries, verbal responses, and the art work produced during each session. Data were analyzed by reviewing the material, embodying the data in my personal …

New Target Genes For Tumor Suppressors P53 And P73 In Regenerating Liver, Svitlana M. Kurinna

Dissertations & Theses (Open Access)

The p53-family of proteins regulates expression of target genes during tissue development and differentiation. Within the p53-family, p53 and p73 have hepatic-specific functions in development and tumor suppression. Despite a growing list of p53/p73 target genes, very few of these have been studied in vivo, and the knowledge regarding functions of p53 and p73 in normal tissues remains limited. p53+/-p73+/- mice develop hepatocellular carcinoma (HCC), whereas overexpression of p53 in human HCC leads to tumor regression. However, the mechanism of p53/p73 function in liver remains poorly characterized. Here, the model of mouse liver regeneration is used to identify new target …

Glycan Shielding Of The Influenza Virus Hemagglutinin Elicits Evasion Of The Adaptive Immune Response And T-Cell-Driven Pathology, Keith C. Wanzeck

Theses and Dissertations (ETD)

Three separate influenza pandemics have emerged in the human population since 1918, each characterized by viruses that lack N-linked glycosylation sites on the globular head of the hemagglutinin protein. In contrast, recent non-pandemic isolates have acquired such sites. Here we constructed isogenic viruses containing differing numbers of additional N-linked glycosylation sites to assess the impact on the host immune response. These studies show that mice infected with a glycosylated virus remain susceptible to challenge with a non-glycosylated virus, glycosylated viruses elicit an inferior immune response, and in this context T-cell pathology and death may occur. We conclude from these data …

H5n1 Influenza Virus Induces A Parkinsonian Pathology, Haeman Jang

Theses and Dissertations (ETD)

The greatest threat for an influenza pandemic at this time is posed by the highly pathogenic H5N1 avian influenza virus. To date, 63% of the 436 known human cases of H5N1 infection have proven fatal. Animals infected by H5N1 viruses have demonstrated acute neurological signs ranging from mild encephalitis to motor disturbances and coma. However, no studies have examined the longer-term neurologic consequences of H5N1 infection. We show that this virus travels from the peripheral nervous system into the central nervous system (CNS) to higher levels of the neuroaxis, using C57BL/6J mice that are infected by the A/VN/1203/04 H5N1 virus …

Predictors Of Pap Smear Utilization Among Female Mexican American College Students, Sylvia M. Morales

Theses and Dissertations - UTB/UTPA

The Pap smear is a diagnostic screening test that detects abnormal cell growth, which may lead to cervical cancer. Pap smears are performed at a consistently lower frequency among Hispanic than non-Hispanic American White women, potentially contributing to a 70% higher rate of cervical cancer in Hispanic Americans. This study examined possible predictors of Pap smear utilization among 165 Mexican American female college students aged 18 to 30 attending the University of Texas-Pan American situated near Texas’s United States – Mexico border. Significant predictors were: recommendation by a health care professional; sexual activity; mother’s educational level; and external locus of …

Mysticism And Mystery Moves: An Examination Of Flow Theory, John Michael Trembley

Masters Theses

This study takes a phenomenological approach to squirt kayaking. It looks to examine mystical states of consciousness, as defined by William James, and flow theory, as defined by Mihaly Csikszentmihalyi, and focuses on what these experiences mean for participants of the squirt kayaking community. The study poses three research questions. (1) Do squirt kayakers experience mystical states of consciousness through squirt kayaking, and what does this experience mean? (2) Do squirt kayakers experience flow states of consciousness through squirt kayaking, and how was this experienced? (3) What is the mystery zombie or the mystery trance state, and how is it …

Grade Point Average As A Predictor Of Timely Graduation From Associate Degree Registered Nursing Programs, Delores J. Jackson

Dissertations

The purpose of this study was to determine if admission selection strategies that utilize cumulative and/or pre-requisite GPA are predictive of timely graduation for associate degree nursing (RN-AD) students. Data were obtained from de-identified records of 437 associate degree nursing students enrolled in three Midwest community colleges from 2003-2006. Of the total sample, only 44% of the students graduated on time (i.e., in four semesters or two years). Although a statistically significant difference was found for timely graduation rates between colleges (ranging from 29% in College B to 54% in College A), no relationship was found for cumulative GPA, pre-requisite …

Assessing Sleep Quality In Young Adult College Students, Aged 18 - 24 In Relation To Quality Of Life And Anthropometrics, Douglas Mathews

Electronic Theses and Dissertations

Little is known about the impact of sleep on quality of life and anthropometrics in young adults. College students (n=218) were recruited through a variety of methods for a study on weight management for obesity prevention and randomized into control (n=108) or treatment (n=110) groups. Of those, 152 (71%) completed pre- and post-tests, including the Pittsburg Sleep Quality Index (PSQI), scored 0-4 =normal and 5-21=disordered, (a=0.80), the General Health Questionnaire-12 (GHQ), scored from 0-14=good quality of life to 15-36=poor quality of life, (ct=0.87), and anthropometrics. Statistical analyses included linear regression, one way ANOVA, chi-square analysis, and Pearson's Product-Moment Correlation. Significance …

Thoracic Radiotherapy Treatment Planning With Cine Pet/Ct, Adam C. Riegel

Dissertations & Theses (Open Access)

Purpose: Respiratory motion causes substantial uncertainty in radiotherapy treatment planning. Four-dimensional computed tomography (4D-CT) is a useful tool to image tumor motion during normal respiration. Treatment margins can be reduced by targeting the motion path of the tumor. The expense and complexity of 4D-CT, however, may be cost-prohibitive at some facilities. We developed an image processing technique to produce images from cine CT that contain significant motion information without 4D-CT. The purpose of this work was to compare cine CT and 4D-CT for the purposes of target delineation and dose calculation, and to explore the role of PET in target …

Role Of Protein Kinase C Isotypes In 1,25-Dihydroxyvitamin D3 Mediated Signal Transduction Through The 1,25d3 Membrane Associated, Rapid Response Steroid Binding Receptors In Chick Intestinal Cells, Sakara Tunsophon

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

It is now accepted that 1,25(OH)2D3 mediates its rapid actions on the control of phosphate and calcium homeostasis through its membrane receptor termed the 1,25D3-MARRS (membrane associated rapid response steroid binding) protein. I determined the various PKC isotypes involved in the rapid regulation of phosphate uptake and calcium extrusion in chick intestinal cells. 1,25(OH)2D3-mediated phosphate uptake was stimulated within 1 min after addition of the hormone. Western blot analyses on isolated intestinal cells treated with steroid hormone resulted in dose-dependent increases in PKC alpha and PKC beta in postnuclear centrifugation fractions, but not in the low speed centrifugation fractions. The …

The Effect Of Static Stretching And Order Of Warm-Up On The Isokinetic Peak Torque Of The Knee Extensors, Eric J. Sobolewski

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The purposes of these studies were to determine if an acute static stretch influenced isokinetic peak torque (IPT), and to examine if the order in which the warm up routine was performed affected peak knee extension torque. Twenty trained college male students performed maximal isokinetic knee extensions under four conditions: a control consisting of no stretching, a stretch only trial, jog then stretch, and stretch then jog conditions. Each stretch was held for a total volume of 360 s. Measurements were taken on a Biodex System 3 isokinetic dynamometer at speeds of 60º s^-1 and 300º s^-1. …

Mechanisms Of The Extreme Sensitivity Of Turkeys To Aflatoxin B1, Sumit Rawal

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The pathogenesis of hepatotoxic and hepatocarcinogenic actions of the mycotoxin aflatoxin B1 (AFB1) involves initial bioactivation by microsomal cytochrome P450s (P450) to a reactive and electrophilic intermediate, exo-aflatoxin B1-8,9-epoxide (exo-AFBO). Poultry, especially turkeys, are extremely sensitive to AFB1, a condition associated with efficient epoxidation by P450s. The purpose of this research was to 1) discover and characterize the P450s in turkey liver responsible for AFB1 bioactivation, and 2) determine the relative importance of these P450s in turkey liver.

Initial investigations led to the discovery of CYP1A5. We then identified CYP3A37, a human CYP3A4 homologue from turkey liver, …

Thioester Hydrolysis Reactivity Of Metal Complexes, James Justin Danford

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Glyoxalase II is one of two metalloenzymes found in the glyoxalase pathway and is responsible for catalyzing the hydrolysis of a thioester substrate. Its bimetallic active site is found to contain a variety of metal combinations, including Fe(III)Zn(II). A recent report indicates that human glyoxalase II, while containing a Fe(II)Zn(II) center, is catalytically active as a mononuclear Zn(II) enzyme. Detailed mechanistic studies of glyoxalase II enzymes are limited due to uncertainty in the metal ion content of recombinantly prepared samples. The research presented in this thesis is focused on gaining mechanistic insight into thioester hydrolysis promoted by well-characterized metal complexes …

Library Synthesis Of Anticancer And Antibacterial Agents Via Azide Chemistry, Jianjun Zhang

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Various anticancer and antibacterial agents have been synthesized via azide chemistry by taking advantage of carbohydrate. Starting from the synthesis of 14 glycosyl azides, a library of carbohydrate-oxazolidinone conjugates and a library of carbohydrate-cyclopamine conjugates with biological interests were synthesized based on a highly efficient "click reaction" assisted by sonication. Some of the conjugates have improved solubility and enhanced anticancer activity.

A library of neomycin B derivatives with various modifications at the 5" position has been synthesized. Two leads exhibit prominent activity against both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Antibacterial activities were measured when combined with other …

The Hypericum Perforatum Herb As An Antimycobacterial Agent And Its Implications As An Additional Tuberculosis Medication, Trent W. Mortensen

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

An immediate demand exists for new tuberculosis (TB) antibiotics due to the ever-increasing spread of drug-resistant strains. The drug-development process goes through four phases, the first (Phase 0) of which is to demonstrate and investigate drug effectiveness and toxicity. This research investigated the effectiveness of the Hypericum perforatum herb (commonly St. John's wort (SJW)) in its growth inhibition of mycobacteria and its viability effect on human lung cells.

Organic-solvent SJW extracts were effective at inhibiting every nonpathogenic genetically sequenced Mycobacterium isolate currently available (six isolates) in preliminary studies. Quantitative studies of five Mycobacterium isolates showed an order of concentration sensitivity …

The Abortion Attitudes Of Counselor, Social Worker, And Nursing Trainees, Mary J. Ball

Dissertations

This study examined the similarities and dissimilarities in abortion attitudes among counselors (CTs, n = 51), social workers (SWTs, n = 42), and nurses in training (NTs, n = 78), based on profession, age, race, gender, and religion. Data were analyzed using analysis of variance and standard multiple regression. It was predicted that profession, religion, age, gender, and race would predict the abortion attitudes of CTs, SWTs, and NTs in training. It was also predicted that the attitudes of CTs and SWTs would be most similar, and that both of these groups would hold more positive abortion attitudes than NTs. …

Experimental Analysis Of Gambling Using A Concurrent-Schedules Procedure, Andrew Ellis Brandt

Dissertations

Gambling has been experimentally investigated using various types of gambling simulations designed to mimic the contingencies found in real-world games of chance. Findings from past risky choice research suggest that certain procedures used in existing gambling simulations may systematically increase levels of gambling. Two of these characteristics, the use of a participant stake and the type of options available during gambling, were tested in four experiments in which participants had the opportunity to gamble using tokens exchangeable for entries into a $50 lottery. Experiments 1 and 2 tested persistence on a gamble option when either a single-option or a concurrent …

Evaluation Of Medication Effects On Academic Performance, Sleep, And Core Adhd Symptoms In Children, Tina K. Head

Dissertations

Idiosyncratic effects of Vyvanse™ (lisdexamfetamine dimesylate) and placebo were evaluated in a double-blind alternating treatments experimental design in this 4-week study. Direct, objective measures were combined with traditional behavior ratings to provide data sets to assess whether or not the prescribed stimulant medication showed detectable therapeutic effects for a child whose positive response to medication was not obvious via traditional subjective methods. Effects of medication on core ADHD symptoms, academic performance, and sleep in four children ages 10-12 with attention deficit/ hyperactivity disorder. Potential side effects were also measured. Daily measures included parent rating scales, side effects checklist, sleep journal …

Hospital Quality Of Care And Patient Satisfaction As A Function Of Physician Membership On Boards Of Directors, Austin W. Whitaker

Chancellor’s Honors Program Projects

No abstract provided.

Prenatal Care Of Hispanic Mothers, Craig A. Bleakney

Chancellor’s Honors Program Projects

No abstract provided.

The Design And Synthesis Of Novel Antimicrobial Agents For Use In The Battle Against Bacterial Resistance, Joshua Randal Brown

Theses and Dissertations (ETD)

There is an ever increasing need to develop new antimicrobial agents with novel mechanisms of action. These new agents will help to combat the steady rise of antibiotic-resistant bacteria which are becoming more and more difficult to treat due to the dwindling number of antibiotics available to treat such organisms. This body of work brings to light the many ways in which medicinal chemistry plays a vital role in the discovery of novel antimicrobial agents. Chapter 1 is an introduction into antimicrobial agents. It provides a brief history of the discovery of antimicrobial agents, and delves into reasons why new …

Systems Biology Approach To Identifying Host Interactive Pathways Modulating The Severity Of Streptococcal Sepsis, Nourtan Fatthy Abdeltawab

Theses and Dissertations (ETD)

Clinical outcomes of infectious diseases are controlled by complex interactions between the host and the pathogen. Epidemiological, genetic and molecular studies in my mentor’s laboratory provided evidence that in invasive Group A streptococcal (GAS) infections, genetic variations in both bacteria and patients influenced the severity of GAS sepsis. Allelic variations in class II human leukocyte antigens (HLA) contributed significantly to differences in the severity of group A streptococcal sepsis caused by the same virulent strain of the bacteria. HLA class II molecules present streptococcal superantigens (SAgs) to T cells, and variations in HLA class II molecules can strongly influence SAg …

Robotic Simulation Of Disc Arthroplasty Surgery: Influence Of Surgical Placement On Motion Segment Dynamics, Braham K. Dhillon

Theses and Dissertations (ETD)

A variety of total disc replacement (TDR) designs exist for the treatment of disc pathologies. A key design parameter for a constrained ball and socket device is the location of the fixed center of rotation (COR). A previous study demonstrated that intact motion segment unit (MSU) mechanics and range of motion (ROM) were sensitive to the location of a prescribed sagittal plane rotational axis. Mal-alignment between the implant COR and the COR of the MSU may lead to an overloaded or over constrained condition.

Two paradigms exist for the placement of a fixed COR TDR device relative to MSU anatomy: …

Pain Management In Nursing Home Residents With Cancer And Dementia With And Without Hospice Services, Todd Bryant Monroe

Theses and Dissertations (ETD)

Aims: We sought to identify differences in pain management between two groups; nursing home residents with malignant cancer and dementia with and without hospice services.

Methods: Decedent records from 2003-2009 were assessed for diagnosis of dementia and cause of death as cancer. Ten malignant cancer diagnoses were determined a priori from the CDC 2004 data on the top 10 malignant cancers for all races and genders. Fifty-five decedents from 10 nursing homes were included in the final sample. Four instruments were used: Minimum Data Set (MDS) a standardized assessment tool required of most U.S. nursing homes. A large …

Discovery Of Quinic Acid Derivatives As Oral Anti-Inflammatory Agents, Kui Zeng

Theses and Dissertations (ETD)

Quinic acid (QA) esters found in hot water extracts of Uncaria tomentosa (a.k.a. Cat’s claw) exert anti-inflammatory activity through mechanisms involving inhibition of the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB). Herein, we described the synthesis and biological testing of novel QA derivatives. Inhibition of NF-κB was assessed using A549 (Type II alveolar epithelial-like) cells that stably express a secreted alkaline phosphatase (SEAP) reporter driven by an NF-κB response element. A549- NF-κB cells were stimulated with TNF-α (10 ng/mL) in the presence or absence of QA derivative for 18 hours followed by measurement of SEAP activity. Amide substitution at …

Tamoxifen: Mechanisms Of Resistance, Cyrus Mccoy Adams

Theses and Dissertations (ETD)

The role of estrogen in breast cancer has been recognized for decades. The selective estrogen receptor modulator tamoxifen was the first targeted therapy for the treatment of breast cancer. It was also the first drug approved by the FDA for the reduction of breast cancer risk. While tamoxifen has extended the lives of countless patients with breast cancer, resistance to tamoxifen remains a significant clinical problem. Work over the last two decades has greatly enhanced our understanding of the molecular mechanisms by which breast cancer cells may become resistant to tamoxifen treatment. Here I review our current understanding of the …

Characterization And Optimization Of Antigen-Specific T Cell Responses During Ex Vivo Expansion Of Melanoma Tumor-Infiltrating Lymphocytes, Yufeng Li

Dissertations & Theses (Open Access)

Treatment of metastatic melanoma with tumor reactive T cells (adoptive T cell therapy, ACT) is a promising approach associated with a high clinical response rate. However, further optimization of this treatment modality is required to increase the clinical response after this therapy. ACT in melanoma involves an initial phase (pre-REP) of tumor-infiltrating lymphocyte (TIL) expansion ex vivo from tumor isolates followed by a second phase, “rapid expansion protocol” (REP) generating the billions of cells used as the TIL infusion product. The main question addressed in this thesis was how the currently used REP affected the responsiveness of the CD8+ T …