A novel three dimensional stereoselective descriptor for use in ligand-based computer-aided drug design (CADD) is presented in this thesis. CADD is an important tool for drug discovery and ligand-based CADD involves the computational analysis and representation of known active compounds for the prediction of novel active compounds. Several approaches are available for ligand-based CADD including quantitative structure-activity relationship (QSAR) which seeks to describe molecules numerically using descriptors. Stereochemistry is an important determinant of a molecules biological activity but presents a challenge for QSAR applications. Presented is the novel 3D-QSAR descriptor termed EMAS (Enantio-selective Molecular ASymmetry) that is capable of distinguishing between enantiomers and describing stereochemistry in a physically meaningful way. The descriptor aims to measure the deviation from an overall symmetric shape of the molecule. EMAS showed good predictability when tested with a dataset of thirty-one steroids commonly used to benchmark stereochemistry descriptors (r2=0.89, q2= 0.78). Additionally, EMAS improved enrichment of 4.38 versus 3.94 without EMAS in a simulated virtual high-throughput screening (vHTS) for inhibitors and substrates of cytochrome P450.

This study examined the issues of barriers and employment retention in a rural county welfare-to-work setting, the Missoula, Montana WoRC Program. Qualitative research (study one) was conducted, to interview clients regarding reasons why they had lost jobs in the past, and, to elicit their suggestions regarding new services the WoRC Program could offer to help with employment retention at future jobs. Study one results indicated that the primary barriers resulting in job loss were: family issues; medical problems; mental health disorders; work site difficulties; and other (i.e. boredom, attitude problems). Work adjustment proved to be an underlying barrier to employment retention. Study one results demonstrated that the clients wanted three primary services to help resolve barriers and improve job retention: life skills classes teaching work adjustment; job coaching; and post-TANF supportive services (i.e. clothing and gas vouchers). Quantitative research (study two) was conducted to analyze 90 variables via logistic regression and determine whether or not the WoRC Program assisted clients with gaining employment, and if so, what the characteristics of those clients were. The results of the logistic regression indicated that the WoRC Program helped clients gain employment exactly 50% of the time. Statistically significant variables for clients that gained employment were: study one participant; female; on TANF 4+ months; final status (case closed at time of study); merit (not sanctioned); no short term training months; no learning disability; no domestic violence; and no chemical dependency. Linear regression was utilized to determine whether or not the employment WoRC clients gained paid better than the minimum wage. The results of the linear regression demonstrated that the mean wage for the employed study two clients was $7.16/hr. The Federal minimum wage at the time of the study was $5.15/hr. To place this study in context, the literature review traced the development of the welfare system from ancient times to the present day, with special emphasis on the topics of cycling, barriers and retention, as well as intangible factors that may have contributed to the study results.

Rules, originally a means toward group solidarity, are the alternative to the need for ongoing physical dominance. Seemingly omnipresent in modern life, rules can be overt or subtle, explicit or tacit, rigidly enforced or overlooked. They may clash with our autonomy. This thesis names and explores different functional types of rules: safety, personal, socio-cultural, legal-religious, and technical. Rules in general are discussed from social and ethical theoretical viewpoints and using ideal type methodology. Understanding that there are different types of rules and the authority behind them makes it easier to determine ones obligations to follow them, especially with the notion of prima facie duties. A century after Max Weber wrote of his admiration--and fear--of bureaucratic authority, we should be alarmed at the march toward bureaucratic, algorithmic rule by a rule that, in its attempts toward fairness and certainty, in fact dominates us by turning us into standardized machines rather than thoughtful, intuitive, creative people.

Cardiovascular disease (CVD) accounts for 37.1 percent of all deaths in the United States. Physical activity is inversely related to both CV event risk and to many of the individual CVD risk factors. The inverse relationship between physical activity and CVD risk is well established. However, much dispute remains about the optimal physical activity intensity and duration related to health benefits and to lower CVD risk. The ability to objectively measure intensity and duration may clarify the inverse relationship between physical activity and CVD. The purpose of this collection of studies was to explore the association of physical activity with CVD and attempt to identify some specifics of this complex relationship. Results: In healthy sedentary individuals aged 31 to 66, 2 different activity accumulation programs were effective in increasing physical activity and resulted in improved fitness and blood glucose. However, the improvement in activity was not of sufficient intensity to provide changes in multiple heart disease risk factors or inflammation. In a cross-section sample of males and females aged 18 to 65, both active and sedentary, the relationship between physical activity and CVD risk varied by age group. The inverse relationship between physical activity and CVD risk was confirmed. However, reaching higher intensity levels for 1 minute periods at least 5 minutes a day appears to be better related to lower risk of CVD than longer durations of moderate or vigorous activity per day, particularly in younger individuals. In a sample of stroke survivors aged 50 to 72, 3 out of 6 of the modifiable risk factors for CVD were present. In these stroke survivors, physical activity intensity and duration were well below current recommendations and insufficient for CVD risk reduction. Conclusions: Accumulating activity can be effective in meeting physical activity recommendations however both duration and intensity requirements must be achieved. Combinations of higher intensities for shorter durations may also be effective in CVD risk reduction.

Using the 2004 Montana State Needs Assessment Prevention Youth Survey data, a cross-sectional sample of 8th, 10th, and 12th grade Montana Native American public school children (n=1611), this study examines hypotheses pertaining to the ability and influence of measures drawn from social bonding, social learning, and social disorganization theories to account for variations in self-reported lifetime and thirty day use of alcohol, marijuana, and illicit drugs of Native American youth residing on and off reservations. The results derived from ordinary least squares regression equations show significant predictability for family, peer, and community variables and the results for the independent sample t-test show significant differences in the influence of the theoretical indicators between the on and off reservation sub-samples. The results suggest there are multiple influences of protective factors on self-reported use of alcohol, marijuana, and illicit drugs and these differ for Native American adolescents who reside on and off reservations. Contributions to the literature along with suggestions for future research are discussed.

Cultural Geographers have written extensively on Diaspora, heritage, identity and their contributions greatly discuss how these theories integrate. The majority of what is available does not address the Palestinians specifically, hence my study fills a void in that it empirically addresses the Palestinian people and the role of their dialect and how it ties to Palestinian Diaspora, heritage and identity. Most of the literature has not viewed Diaspora, heritage, and identity thru the lens of language or language as a major player, an important one or perhaps vital. To produce these findings will contribute to the knowledge base on the issue to the Palestinians specifically and to the concept itself and its variable elements/components that integrate and act to define it. (Hubbuch, 2004, pp. 138-139). This Thesis will argue, from the historical and cultural record of Palestine, that among the multiple aspects of Palestinian culture, language is the most crucial bearer of identity and group cohesion. In addition to this central claim about the importance of language, the thesis will draw specific conclusions about the role and use of the Levantine dialect of Arabic by analyzing the data gathered in a semi-structured online interview in which thirty nine respondents offered their shared experiences and ideas regarding their Levantine dialect of Arabic. Palestinian relationship to language is deeply associated with place, family, history, heritage, and pride in self and in community. These associations are ones that speakers of the Levantine dialect of Palestine are remarkably self-aware about; that is, the diasporic condition makes language more visible as a pivot of culture and more precious because it is under threat.

This study seeks to evaluate the merits of collaborative zoning in rural areas by juxtaposing a case where zoning efforts failed to one where zoning was successfully passed by the community. While zoning practices vary greatly in different parts of the country, this study is focused entirely on rural zoning in the Rocky Mountains. There are specific obstacles and challenges when undertaking land-use planning in the West--and rural areas in particular--and this paper extracts and presenting the lessons learned in both communities.

Pluralism, the dominant theory in citizen involvement in the United States Forest Service since the 1950s, has prolonged the process of determining the public interest by promoting the use of appeals and lawsuits. The advent of more collaborative public involvement strategies in the past fifteen years offers the opportunity to assess whether participatory democracy offers a better paradigm for determining the public interest. This research focused on four cases of reported successful collaboration in Region One of the Forest Service and involved in-person interviews with 17 Forest Service officials and 24 citizen and interest group leaders. The researcher translated pluralist and participatory democracy paradigms into characteristic human actions and behavior in the setting of Forest Service public involvement, then analyzed reported actions and behaviors accordingly. Interviewees were asked to choose between two contrasting descriptions of group culture to characterize interactions with the Forest Service, one drawn from the rational choice model in the pluralist paradigm, the other from collaborative literature in the participatory democracy paradigm. Collaboration was rejected as a term for analysis because it lacked specific definition among both Forest Service and public interviewees. Instead, the researcher analyzed the cases using characteristics of participatory democracy drawn from civic republican theorists that also encompassed the characteristics contained in textbook descriptions of collaboration. Two of the cases had all characteristics and provided empirical examples of participatory democracy at work. Another of the cases used stakeholder negotiation that contained some of the aspects of participatory democracy, but lacked the characteristics of being voluntary and of fostering a sense of community. The last case used informed consent and was found to be a combination of participatory culture and synoptic administration. Based on these cases, the researcher concluded that public involvement that uses a participatory democracy paradigm has the potential to increase public trust in the Forest Service and to minimize appeals and lawsuits by creating strong diverse support for Forest Service decisions. The research also examined characteristics of the leadership in the cases and found trust and integrity to be essential to creating a participatory democracy paradigm.

Educational travel forms the basis for novel learning experiences that enhance adolescent development by enabling students to make choices about their own survival in an unfamiliar setting. This biological adaptation is driven by stimulation of the midbrain which produces high levels of dopamine, the chemical associated with learning. The elements of educational travel that promote sustained adolescent learning are: clear communication, commitment and action, communal trust and respect, maturity developed through assigned responsibilities and exposure to varied life circumstances, flexibility, and transition back to traditional school environments.

The purpose of this study consisting of three projects was to determine the effects of long-term strenuous exercise on oxidative DNA damage and proteinuria in trained individuals. In the first project, four successive triathlons accompanied by long-term training in a triathlete was chosen as the experimental design and procedure. In the second project, repeated 5-h bouts of cycling exercise at 52 %VO2peak and a 40 km time trial with carbohydrate and potential antioxidant supplementation (fenugreek seed extract) were carried out with trained individuals. In the third project, a wildland firefighting three-day work shift was conducted with active duty military personnel. Assessment of oxidative DNA damage was based on urinary and muscle 8-hydroxy-2'-deoxyguanosine. Post-exercise proteinuria was determined with several biomarkers including urinary total protein, albumin, beta2-microglobulin, N-acetyl-beta-D-glucosaminidase, and creatinine. The overall results showed that there were significant whole-body DNA oxidation and post-exercise proteinuria after the half- and full-Ironman triathlon races, but these levels gradually returned to baseline. In contrast, no significant alterations were observed in either oxidative DNA damage at the muscle and tissue level or proteinuria after the 5 h of cycling exercise at 52 %VO2peak and the 40 km time trial. Arduous work during wildland fire suppression induced proteinuria, which tended to be accumulated as the work shift progressed. These findings indicate that moderate exercise may not reach the threshold to cause oxidative DNA damage and proteinuria, whereas long-lasting strenuous exercise appears to induce oxidative DNA modification and exceed normal range of urinary protein excretion.