Synthesis of Allosteric Modulators for Nicotinic Acetylcholine Receptors

College of Arts and Sciences Undergraduate Research ScholarshipNicotinic acetylcholine receptors (nAChR) can be found throughout the human nervous system. The receptors regulate a multitude of functions, including development, inflammation, and movement. They also serve as the receptor site for nicotine, an extremely addictive drug. Novel therapeutic strategies for breaking this addiction involve synthesis of negative allosteric modulators that could deactivate the binding site for nicotine on these receptors. However, because many subtypes of the nAChR exist, it is difficult to target one without affecting others. This study aims to synthesize a series of analogs of compound 16, an arylsulfonyl piperazine-containing compound that was previously shown to display selectivity for the Hα4β2 nAChR compared to the Hα3β4 nAChR receptor subtype. Synthetic pathways are focused on amide bond formation between substituted arylsulfonyl piperazines and aryl amines. Nine derivatives of 16 have been synthesized. Results confirm the identity of these compounds by 1H, 13C, m/z, and elemental analyses. Biological testing of these compounds has, thus far, shown that the analogs retain the potency of 16 for the Hα4β2 nAChR, but have lost selectivity for that receptor subtype. Future work will focus on exploring different hypotheses regarding the basis of 16 receptor subtype selectivity through the synthesis and evaluation of additional analogs.College of Arts and SciencesNIH Grant R21 DA029433No embarg

A Web-based Approach to Music Library Management

This application utilizes modern standards developing in web browsers to create a desktop-like application for managing a music library online. The server side application is written in a model-view-controller style using Python backed by a MySQL database. The client side JavaScript was designed around a modular concept interfacing several third-party frameworks and libraries. By taking advantage of developing browser features such as persistent local storage, this web application was designed to handle a large library of music

A retrospective study of school success : voices of successful Aboriginal professionals

This qualitative study was designed to explore the perceptions of Aboriginal professionals in various work sectors as they reflect on their educational experiences in high school and the nature of success. Questions guiding this research were: What is Aboriginal student success? What factors affect success? To what or whom do professionals attribute their successfulness? What can make others successful? Prompting this study was the latest statistics about Aboriginal people released on September 24, 2003. The Aboriginal Peoples Survey was compiled by Statistics Canada in 2001. The survey stated that the number of off reserve Canadian Aboriginal students who are dropping out of school is 52%. In comparison to the Non-Aboriginal population, the overall high school dropout rate is 26%. What is alarming is that the drop out rate has not changed since the previous study in 1996. Some of the research conducted has focused on finding barriers to Aboriginal students dropping out of school. Although this research assumed that if barriers can be identified, and removed they have only insignificantly decreased the dropout rate. This study gives voice to aboriginal professionals' success experiences by having them share their stories through in-depth interviews. Rather than focus on barriers, this study emphasizes positive high school experiences of Aboriginal professionals and factors that led to their success. In-depth interviews were conducted initially with professionals in various work sectors that include human service sectors. A second interview was held with these professionals to clarify and further develop ideas emerging from the initial sets of interviews. Descriptive memos and reflective notes were kept throughout the process with the analysis of data following traditions of qualitative methods. The results of the study showed that the nature of success was complex, intricate, and idiosyncratic. Each participant had their own unique definition of success based upon distinct factors including a mindset, cultural orientation, spiritual connections, marginalization, and colonization. The definitions of success varied with changing variables of the participants. Not surprisingly, the study related student success to the biological, social, physical and spiritual factors including Aboriginal spirituality; to external factors including culture, curriculum, instructional approaches, role models, relevant education, and relationships; and to the internal factors attitude, goal setting, motivation and inquiry. In their suggestions of how others can be successful, each participant shared words of wisdom about education, stability, balance and a work ethic. The study offers teachers, parents, and students practical suggestions for increased student success and provides a list of implications produced by the study

Code Generation: An Introduction to Typed EBNF

Errors and inconsistencies between code components can be very costly in a software project. E orts to reduce these costs can include the use of tools that limit human interac- tion with code by generating it from a description. This paper introduces two new works to address these issues: (1) an input speci cation called Typed EBNF (TEBNF), and (2) a prototype tool that demonstrates how TEBNF can be used to generate code. The tool generates code for a console application as described by a TEBNF grammar. An application built from the generated code will be able to receive input data, parse it, process it, and output it as needed

IDENTIFICATION OF HIGH COLLISION LOCATIONS FOR THE CITY OF REGINA USING GIS AND POST-NETWORK SCREENING ANALYSIS

In 2010, the American Association of State Highway and Transportation Officials (AASHTO) released the first edition of the Highway Safety Manual (HSM). The HSM introduces a six-step safety management process which provides engineers with a systematic and scientific approach to managing road safety. The first step of this process, network screening, aims to identify the locations that will most benefit from a safety improvement program. The output obtained from network screening is simply a list of locations that have a high concentration of collisions, based on their potential for safety improvement. The ranking naturally tends to lead to the assumption that the most highly ranked locations are the obvious target locations where road authorities should allocate their often-limited road safety resources. Though these locations contain the highest frequency of collisions, they are often spatially unrelated, and scattered throughout the roadway network. Allocating safety resources to these locations may not be the most effective method of increasing road safety. The purpose of this research is to investigate and validate a two-step method of post-network screening analysis, which identifies collision hotzones (i.e., groups of neighboring hotspots) on a road network. The first step is the network screening process described in the HSM. The second step is new and involves network-constrained kernel density estimation (KDE), a type of spatial analysis. KDE uses expected collision counts to estimate collision density, and outputs a graphical display that shows areas (referred to here as hotzones) with high collision densities. A particularly interesting area of application is the identification of high-collision corridors that may benefit from a program of systemic safety improvements. The proposed method was tested using five years of collision data (2005-2009) for the City of Regina, Saskatchewan. Three different network screening measures were compared: 1) observed collision counts, 2) observed severity-weighted collision counts, and 3) expected severity-weighted collision counts. The study found that observed severity-weighted collision counts produced a dramatic picture of the City's hotzones, but this picture could be misleading as it could be heavily influenced by a small number of severe collisions. The results obtained from the expected severity-weighted collision counts smoothed the effects of the severity-weighting and successfully reduced regression-to-the-mean bias. A comparison was made between the proposed approach and the results of the HSM’s existing network screening method. As the proposed approach takes the spatial association of roadway segments into account, and is not limited to single roadway segments, the identified hotzones capture a higher number of expected EPDO collisions than the existing HSM methodology. The study concludes that the proposed two-step method can help transportation safety professionals to prioritize hotzones within high-collision corridors more efficiently and scientifically. Jurisdiction-specific safety performance functions (SPFs) were also developed over the course of this research, for both intersections (three-leg unsignalized, four-leg unsignalized, three and four-leg signalized), and roadway segments (major arterials, minor arterials, and collectors). These SPFs were compared to the base SPFs provided in the HSM, as well as calibrated HSM SPFs. To compare the different SPFs and find the best-fitting SPFs for the study region, the study used statistical goodness-of-fit (GOF) tests and cumulative residual (CURE) plots. Based on the results of this research, the jurisdiction-specific SPFs were found to provide the best fit to the data, and would be the best SPFs for predicting collisions at intersections and roadway segments in the City of Regina

Mapping olive varieties and within-field spatial variability using high resolution QuickBird imagery

[Abstract]: The growth of the Australian olive (Olea europaea L.) industry requires support from research to ensure its profitability and sustainability. To contribute to this goal, our project tested the ability of remote sensing imagery to map olive groves and their attributes. Specifically, this study aimed to: (a) discriminate olives varieties; and to (b) detect and interpret within-field spatial variability. Using high spatial resolution (2.8m) QuickBird multispectral imagery acquired over Yallamundi (southeast Queensland) on 24 December 2003, both visual interpretation and statistical (divergence) measures were employed to discriminate olive varieties. Similarly, the detection and interpretation of within-field spatial variability was conducted on enhanced false colour composite imagery, and confirmed by the use of statistical methods. Results showed that the two olive varieties (i.e. Kalamata and Frantoio) can be visually differentiated and mapped on the enhanced image based on texture. The spectral signature plots showed little difference in the mean spectral reflectance values, indicating that the two varieties have a very low spectral separability. In terms of within-field spatial variability, the presence or absence of Rhodes grass (Chloris gayana) was detected using visual interpretation, corroborated by the results of quantitative statistical measures. Spatial variability in soil properties, caused by the presence of a patch of sandy soil, was also detected visually. Finally, the “imprint” of former cover-type or land-use prior to olive plantation establishment in 1998 was identified. More work is being done to develop image classification techniques for mapping within-field spatial variability in olive varieties, biomass and condition using hyperspectral image data, as well as interpreting the cause of observed variability

Comparing Infrared Star-Formation Rate Indicators with Optically-Derived Quantities

We examine the UV reprocessing efficiencies of warm dust and polycyclic aromatic hydrocarbons (PAHs) through an analysis of the mid- and far-infrared surface luminosity densities of 85 nearby H$\alpha$-selected star-forming galaxies detected by the volume-limited KPNO International Spectroscopic Survey (KISS). Because H$\alpha$ selection is not biased toward continuum-bright objects, the KISS sample spans a wide range in stellar masses ($10^8$-$10^{12}\rm{M}_\odot$), as well as H$\alpha$ luminosity ($10^{39}$-$10^{43}\rm{ergs/s}$), mid-infrared 8.0$\mu$m luminosity ($10^{41}$-$10^{44}\rm{ergs/s}$), and [Bw-R] color (-.1-2.2). We find that mid-infrared polycyclic aromatic hydrocarbon (PAH) emission in the Spitzer IRAC 8.0$\mu$m band correlates with star formation, and that the efficiency with which galaxies reprocess UV energy into PAH emission depends on metallicity. We also find that the relationship between far-infrared luminosity in the Spitzer MIPS 24$\mu$m band pass and H$\alpha$-measured star-formation rate varies from galaxy to galaxy within our sample; we do not observe a metallicity dependence in this relationship. We use optical colors and established mass-to-light relationships to determine stellar masses for the KISS galaxies; we compare these masses to those of nearby galaxies as a confirmation that the volume-limited nature of KISS avoids strong biases. We also examine the relationship between IRAC 3.6$\mu$m luminosity and galaxy stellar mass, and find a color-dependent correlation between the two.Comment: 15 pages, 10 figure