Population genetics of VNTR loci and their applications in evolutionary studies

Variable number of tandem repeats (VNTR) are genetic loci at which short sequence motifs are found repeated different numbers of times among chromosomes. To explore the potential utility of VNTR loci in evolutionary studies, I have conducted a series of studies to address the following questions: (1) What are the population genetic properties of these loci? (2) What are the mutational mechanisms of repeat number change at these loci? (3) Can DNA profiles be used to measure the relatedness between a pair of individuals? (4) Can DNA fingerprint be used to measure the relatedness between populations in evolutionary studies? (5) Can microsatellite and short tandem repeat (STR) loci which mutate stepwisely be used in evolutionary analyses?^ A large number of VNTR loci typed in many populations were studied by means of statistical methods developed recently. The results of this work indicate that there is no significant departure from Hardy-Weinberg expectation (HWE) at VNTR loci in most of the human populations examined, and the departure from HWE in some VNTR loci are not solely caused by the presence of population sub-structure.^ A statistical procedure is developed to investigate the mutational mechanisms of VNTR loci by studying the allele frequency distributions of these loci. Comparisons of frequency distribution data on several hundreds VNTR loci with the predictions of two mutation models demonstrated that there are differences among VNTR loci grouped by repeat unit sizes.^ By extending the ITO method, I derived the distribution of the number of shared bands between individuals with any kinship relationship. A maximum likelihood estimation procedure is proposed to estimate the relatedness between individuals from the observed number of shared bands between them.^ It was believed that classical measures of genetic distance are not applicable to analysis of DNA fingerprints which reveal many minisatellite loci simultaneously in the genome, because the information regarding underlying alleles and loci is not available. I proposed a new measure of genetic distance based on band sharing between individuals that is applicable to DNA fingerprint data.^ To address the concern that microsatellite and STR loci may not be useful for evolutionary studies because of the convergent nature of their mutation mechanisms, by a theoretical study as well as by computer simulation, I conclude that the possible bias caused by the convergent mutations can be corrected, and a novel measure of genetic distance that makes the correction is suggested. In summary, I conclude that hypervariable VNTR loci are useful in evolutionary studies of closely related populations or species, especially in the study of human evolution and the history of geographic dispersal of Homo sapiens. (Abstract shortened by UMI.) ^

Attitudes, stress and use of force in selected areas of Texas law enforcement

This research aimed to explore the extent to which police use of force was related to attitudes towards violence, agency type, and racism. Previous studies have found a culture of honor in the psychology of violence in the Southern United States. Were similar attitudes measurable among Texas professional line officers? Are there predictors of use of force?^ A self reported anonymous survey was administered to Texas patrol officers in the cities of Austin and Houston, and the Counties of Harris and Travis. A total of seventy-four questionnaires were used in the statistical analyses. Scales were developed measuring use of force, attitudes towards violence, and feelings on racism. Their relationship was examined.^ A regression model shows a strong and significant relationship between the officers' attitudes towards violence and the self-reported use of force. Further, agency type, municipal versus sheriff, also predicts use of force. Attitudes regarding race or racism, as measured by this study, were not predictive of use of force. ^

CIGARETTE SMOKING AMONG HIGH SCHOOL STUDENTS IN RURAL AREAS OF THAILAND

The purpose of this study was to identify the smoking prevalence among high school students in rural areas of Thailand and the factors associated with their smoking habits. The sample population was comprised of 946 volunteer students of both sexes enrolled in the twelfth grade classes of the 1981-82 school year in randomly chosen regional public high schools throughout the country. Data were obtained from a formal self-administered questionnaire survey. The comparisons were treated by classified smoking habits as "non-smoker," "trier," "ex-smoker," and "smoker."^ The study presented the low rate of cigarette smoking habits among female students, compared to male students. Significant differences of smoking-related habits were found among those who had exemplar models for smoking habits; fathers, siblings and peers were their reference groups. Parental approval was found to be a significant factor associated with students' smoking habits. The awareness of health hazards, the perceptions of the influence of cigarette advertisement, and the attitudes toward the concerns of government in cigarette manufacturing were also factors associated with cigarette smoking habits of high school subjects. ^

HEALTH CARE COST INCREASES IN METROPOLITAN AREAS

The research project is an extension of the economic theory to the health care field and health care research projects evaluating the influence of demand and supply variables upon medical care inflation. The research tests a model linking the demographic and socioeconomic characteristics of the population, its community case mix, and technology, the prices of goods and services other than medical care, the way its medical services are delivered and the health care resources available to its population to different utilization patterns which, consequently, lead to variations in health care prices among metropolitan areas. The research considers the relationship of changes in community characteristics and resources and medical care inflation.^ The rapidly increasing costs of medical care have been of great concern to the general public, medical profession, and political bodies. Research and analysis of the main factors responsible for the rate of increase of medical care prices is necessary in order to devise appropriate solutions to cope with the problem. An understanding of the community characteristics and resources-medical care costs relationships in the metropolitan areas potentially offers guidance in individual plan and national policy development.^ The research considers 145 factors measuring community milieu (demographic, social, educational, economic, illness level, prices of goods and services other than medical care, hospital supply, physicians resources and techological factors). Through bivariate correlation analysis, the number of variables was reduced to a set of 1 to 4 variables for each cost equation. Two approaches were identified to track inflation in the health care industry. One approach measures costs of production which accounts for price and volume increases. The other approach measures price increases. One general and four specific measures were developed to represent each of the major approaches. The general measure considers the increase on medical care prices as a whole and the specific measures deal with hospital costs and physician's fees. The relationships among changes in community characteristics and resources and health care inflation were analyzed using bivariate correlation and regression analysis methods. It has been concluded that changes in community characteristics and resources are predictive of hospital costs and physician's fees inflation, but are not predictive of increases in medical care prices. These findings provide guidance in the formulation of public policy which could alter the trend of medical care inflation and in the allocation of limited Federal funds.^

Addressing teenage pregnancy in rural areas: A case study from Liberty County, Texas

This study explores the issue of teenage pregnancy in a case study of Liberty County, a rural area in Texas with no public health department. It also describes the decision-making process and barriers faced in the beginning phases of adopting a sexual education program, and sets forth an implementation plan for two school districts on disseminating an evidence-based, comprehensive curriculum. Methods include a review of epidemiological data surrounding teenage pregnancy on the national, state, and county level; a literature review of factors related to teenage pregnancy and past interventions implemented in a rural community; a policy review of past and current bills in Legislature; and an analysis of barriers and decision making in implementing an evidence based program through qualitative observations, discussions with community members during meetings, presentations, and discussions. Results of this study indicate that there is a lack of research conducted in rural areas in the field of teenage pregnancy prevention and sexual education programs. Barriers experienced in Liberty County are shown to be consistent in scientific literature such as funding, logistical issues, and problems approaching the School Board in adopting a comprehensive sexual education program. This study fills a large gap in the literature on rural adolescents and attempts to analyze the process of decision-making in a rural area related to adoption of sexual education programming. In order to relieve this health disparity, further research should focus on rural areas to gain insight on the attitudes and behaviors of rural adolescents and beliefs among community stakeholders.^

Advanced Protein Modeling Method: Benchmarking and Applications in Computer-Aided Drug Discovery

Development of homology modeling methods will remain an area of active research. These methods aim to develop and model increasingly accurate three-dimensional structures of yet uncrystallized therapeutically relevant proteins e.g. Class A G-Protein Coupled Receptors. Incorporating protein flexibility is one way to achieve this goal. Here, I will discuss the enhancement and validation of the ligand-steered modeling, originally developed by Dr. Claudio Cavasotto, via cross modeling of the newly crystallized GPCR structures. This method uses known ligands and known experimental information to optimize relevant protein binding sites by incorporating protein flexibility. The ligand-steered models were able to model, reasonably reproduce binding sites and the co-crystallized native ligand poses of the β2 adrenergic and Adenosine 2A receptors using a single template structure. They also performed better than the choice of template, and crude models in a small scale high-throughput docking experiments and compound selectivity studies. Next, the application of this method to develop high-quality homology models of Cannabinoid Receptor 2, an emerging non-psychotic pain management target, is discussed. These models were validated by their ability to rationalize structure activity relationship data of two, inverse agonist and agonist, series of compounds. The method was also applied to improve the virtual screening performance of the β2 adrenergic crystal structure by optimizing the binding site using β2 specific compounds. These results show the feasibility of optimizing only the pharmacologically relevant protein binding sites and applicability to structure-based drug design projects.