Predicting the potential distribution of Amblyomma americanum (Acari: Ixodidae) infestation in New Zealand, using maximum entropy-based ecological niche modelling

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Ligand binding to G protein-coupled receptors (GPCRs) 1. 1,8-naphthyridine analogs binding to the cannabinoid CB2 receptor 2. Pharmacophore model development for aminoalkylindole binding to a novel GPCR

G-protein coupled receptors (GPCRs) are transmembrane receptors found in eukaryotes that control many cellular signaling events. The cannabinoid receptors, CB1 and CB2, are both GPCRs. These are the receptors that are activated by Δ9-THC, the principal psychoactive compound in marijuana. CB1 is found mainly in neuronal cells and its activation is thought to lead to the negative, psychoactive side effects of marijuana. CB2 is found in immune cells and in small concentrations in brain tissue. Beneficial effects of activating the cannabinoid receptors include reduction in intraocular pressure, analgesia, antiemesis, and effects on bone density. Designing a drug that can selectively activate CB2, without activating CB1 should lead to analgesia without the negative side effects of CB1. Recent studies have shown the potential of CB2 in treating neurodegenerative diseases such as Parkinson's and Alzheimer's; increasing the importance for developing CB2 selective drugs. Analogs were developed using the 1,8-naphthyridine scaffold that are selective for CB2. These analogs had different activities at CB2 based on their structures. One goal of my thesis project was to develop a model for the binding of 1,8-naphthyridine analogs binding at CB2 and to develop a hypothesis concerning the structural requirements for their production of agonism or antagonism at CB2. The analogs were synthesized and tested by our collaborator, Dr. Clementina Manera at the University of Pisa. Computational modeling techniques were used to generate conformations of the 1,8-naphthyridine compounds. An automated docking program, Glide, was used to generate the ligand-receptor complexes. The model showed that the presence of a substituent at the C-6 position of the 1,8-naphthyridine ring prevents CB2 from adopting an activated state. Project 2. Aminoalkylindole Pharmacophore Model A second goal of my thesis was to develop a pharmacophore model for the newly discovered aminoalkylindole (AAI) receptor. WIN 55212-2 is the prototypical aminoalkylindole (AAI) and is known to act as an agonist at both CB1 and CB2. Recently, our collaborator, Dr. Nephi Stella (University of Washington) discovered that WIN 55212-2 and other AAI compounds bind to a non-CB GPCR found in HEK 293 and T98G cells. AAI analogs were developed to generate a structure activity relationship (SAR). These analogs and their binding data were used to generate a pharmacophore model that explains how these AAI compounds are binding to this new receptor. A pharmacophore model is a set of chemical features and their spatial arrangement that explains how a set of compounds bind to a protein. Computational modeling techniques were used to generate conformations of the AAI compounds. The pharmacophore model was developed in PHASE (Schrodinger, Inc.) using a conformational approach on a set of active compounds. The pharmacophore model shows the importance of four aromatic features, a hydrogen bond acceptor feature, and a hydrophobic feature corresponding to the C-2 position of the indole ring

My journey into intercollegiate athletic administration : how it was influenced by feminist consciousness-raising

The successful combination of the raising of a feminist consciousness and a career in intercollegiate athletic administration is the problem to be addressed. Questions about gender development that are struggled with during my consciousness-raising are explored. Investigating how those questions, and the resulting recontructing of my identity, have influenced my professional responsibilities, decision-making and leadership style are central to the study. Qualitative research methodology was employed to explore the topic of gender identity deconstruction and reconstruction. The primary method used for this study was autobiography. From notes and a journal kept at the recommendation of the chair of my committee, observations were made. Autobiography is not the traditional scientific methodology often used in dissertations; however, in this case, it was most appropriate. In research, the approach is to select a problem, and then, select the most appropriate method for studying that problem

An investigation into the relationship between locomotor dynamics and adaptability

Over the last 40 years, a new paradigm has been posited where the variability observed in physiological systems is a consequence of the interactions occurring between the various components that affect the system. While quantifying the magnitude of variability can be useful, analyses that measure how the structure of the variability (dynamics) changes over time have been posited to reflect the health of the system. Many researchers interpret the results of these analyses to be indicative of the system’s adaptive capacity. While there is ample indirect evidence to support this notion, a lack of direct findings has left the literature lacking a definitive foundation to move forward with this interpretation. While many physiological systems are too invasive to safely perturb, the movement-based systems are routinely perturbed in real-world environments without dire consequences. Of particular interest is the locomotor system, which is constantly challenged in real-world environments via slips and trips. Furthermore, the locomotor system can be safely and validly perturbed in the laboratory. A range of locomotor dynamics-based measures have been used to describe differences between various clinical populations, but none have been directly associated with a person’s ability to remain upright when perturbed. The objectives of this study are to (1) examine the relationship between locomotor dynamics/stability to overall fall-risk prior, (2) examine how locomotor dynamics relate to the ability to recover from a trip via global stability, and (3) determine the extent to which an acute trip-training session alters locomotor dynamics and global stability. Forty healthy, older adults (75.2±4.9 yrs) were recruited by convenience from the local community. The participants completed a variety of clinical assessments in order to determine overall fall-risk. Afterwards, they participated in three walking trials consisting of: 1) a 15-minute unperturbed walking session, 2) a 10-minute unperturbed walking session (control) or a 10-minute trip-training session (intervention), and 3) a 15-minute unperturbed walking session. Various measurements of locomotor dynamics and adaptability were calculated from full-body 3-D kinematics collected at 100Hz. Multiple regression and repeated measure analysis of variance models were calculated to determine to what extent locomotor dynamics and adaptability relate to one another and how an acute trip-training session affects their relationship. The results from our first experiment suggested that locomotor dynamics and stability during steady state do not significantly relate to overall fall-risk. However, the second experiment showed that locomotor dynamics are predictive of an individual’s ability to recover from a trip. Our last experiment showed the feasibility of using an acute trip-training session to alter locomotor dynamics and stability. These data represent the first direct evidence of physiological variability being indicative of adaptive capacity in the locomotor system. Further investigation will be necessary to determine the robustness of the analyses to indicate adaptive capacity across perturbations and populations

The impact of an action research study on deficit thinking in an elementary school

In education, the government has raised the bar related to expectations placed upon school districts to ensure that school letter grades are high, schools meet growth measures, and proficiency increases. While the bar is heightened, so is the student achievement gap between white students and students of color. Currently, there is not an existing policy, program, or practice that has resulted in the achievement gap closing. Therefore, instead of looking for external solutions, school leaders must look within their school buildings to identify what perceptions, biases, attitudes, and beliefs educators bring with them into the school that influence the work they do with students, especially those within marginalized populations. Deficit thinking is the practice of holding lower expectations for students with demographic, linguistic, and socioeconomic characteristics that do not align with the American dream, also known as the American way. Deficit thinking asserts that the low academic achievement of low-income students from culturally, racially, and socioeconomically different backgrounds is to be blamed on these external factors— factors not related to the school and the work done within the four walls of a classroom. Those whose thought is based in a deficit perspective attempt to “fix” marginalized students by assisting in their assimilation. School leaders must help educators search within to recognize the biases, perceptions, attitudes, and beliefs that they possess that are laced with deficit notions. This action research study examined the benefits of a focus group within an elementary school setting in which educators and the principal worked together to discuss their thoughts and practices aligned with deficit thinking. The goal was for the dialogue about race, deficit thinking, and achievement to spark educators to take action in which they would eliminate deficit thinking and practices within their classrooms and seek ways to spread the dialogue to their peers to do the same. Based on the findings, recommendations include having intentional discussions about deficit thinking to create school settings that promote a safe and supportive space for all students, including those who are often marginalized

The heat of transfer of some slightly soluble salts from water to tert-Butanol--water mixtures

A group of slightly soluble salts have been investigated as probes in the study of water structure in organic--aqueous solvent systems. The probe reactions were run in pure water as well as tert-butanol—water mixtures at about 25°C. The enthalpies for AgI, AgTPB, and TPAsTPB precipitation were plotted versus mol % tert-butanol and these exhibited exothermic maxima at approximately 5.3 mol % tert-butanol. The maxima observed are discussed in terms of the contributions to the overall enthalpy change, and thought to be dependent on the structure of the solutions and the structure altering characteristics of the ions involved. From the results of this investigation it was apparent that precipitation reactions can be useful in the study of water structure and water—solvent interaction. The precipitation reactions of AgTPB and TPAsTPB showed very large maxima of about 15 and 27 kcal respectively for the heats of transfer. Therefore AgTPB and TPAsTPB are shown to be excellent probes and should prove very useful in the investigation of other organic—aqueous binary systems. A further, tentative result is that TPB appears to be a structure making ion, from ?S calculations in pure water

Who Brinser? and other stories

This thesis is comprised of three short stories written during the last two years. The stories have little in common with each other except the author's style and even that changes somewhat from one to the next. Their settings are, respectively, an unnamed army base, a fictional New England town, and New York City, specifically Greenwich Village, Harlem, and Morningside Heights. Two of the stories are written through the point of view of soldiers in the United States Army and a lesser character in the third is also a soldier. The time of the stories is either the present or the immediate past

The legal aspects of dismissal of noncertificated personnel

The problem of dismissal of noncertificated staff for boards of education and school administrators is a relatively recent occurrence. Declining enrollments and determined, economy-minded voter-taxpayers are forcing educators to dismiss staff due to reductions in budgets. While teacher contracts and tenure laws prescribe dismissal procedures for professional staff, a void exists for procedures on dismissal of noncertificated staff. This study presents an historical perspective of the legal aspects of dismissal of noncertificated staff. A legal background is presented for the analysis of court decisions concerning dismissal of noncertificated staff in six major areas: (1) reduction in force, (2) incompetency, (3) insubordination, (4) neglect of duty, (5) immorality and (6) disability

That Grand Canyon and other stories

Unloading a half ton of manure had made Melvin's shoulders and arms ache, and he rested his elbows against his legs, holding the steering wheel with one hand as he drove. His mother had done it deliberately, he figured. There was no other way to figure it; the chicken house certainly hadn't needed cleaning that badly. And even if it had, she wouldn't have told the men to clean it on Saturday afternoon if she hadn't known that he wanted to use the truck that night. But now it was all done. He had given up supper and unloaded it, but his mother's ridicule still resounded in his mind: "You're a torn-fool. I no more'n got you out of your diapers, and here you think you're big enough to be seeing girls. Dating, you say: Hal If your father..." She always mentioned his father when she really wanted to shame him. She knew the effect it would have, and Melvin always gave her the satisfaction of seeing that effect, outwardly, at least. He would take on a saddened, reflective look—letting his shoulders drop slightly— and stare at the floor. It was a kind of conditioned response that signaled his complete surrender to her. But this time he hadn't surrendered; he'd waved his flag of truce as always, but he continued fighting

From Childhood Sexual Abuse to Adult Risky Sexual Behavior

This study attempted to establish that the depressive effect of childhood sexual abuse on self-esteem mediates the established relationship between childhood sexual abuse and adult abuse victims' engagement in risky sexual behavior. Overall self-esteem did not significantly mediate this relationship. However, one factor of self-esteem, interest in maintaining a healthy lifestyle, significantly mediated the relationship between childhood sexual abuse and one factor of risky sexual behavior, engaging in sex acts with unknown partners