Browsing by Subject "Tolerance"
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Item Affective responses in cocaine-experienced rats reveal cue-induced drug craving and cocaine reward magnitude(2011-08) Maier, Esther Yvonne; Duvauchelle, Christine L.; Schallert, Timothy; Gonzales, Rueben A.; Gore, Andrea C.; Monfils, Marie H.The development and persistence of cocaine dependence are greatly influenced by emotional affect and cocaine associative learning. Cocaine is known to enhance nucleus accumbens (NAcc) dopamine, serve as a positive reinforcer and produce negative effects, such as anxiety that may influence cocaine intake behavior. In the first study, I investigated the effects of the anxiolytic, diazepam on NAcc dopamine levels and cocaine self-administration behavior. These are two factors associated with cocaine rewarding effects. Diazepam has no effect on NAcc dopamine, but affects cocaine self-administration. This supports the notion that decreasing the anxiogenic effects of cocaine increases the rewarding value in a dopamine independent manner. Therefore, increasing the aversive effects of cocaine might be a novel approach to fight cocaine dependence. In the second study, I studied cocaine-induced associative learning and changes in affect during cocaine conditioning and extinction. 50-kHz ultrasonic vocalizations (USVs) in rats are thought to reflect positive affect and occur upon appetitive stimuli and with cocaine delivery. First, I explored whether USVs might be elicited in anticipation of impending drug delivery. Shortly into conditioning, rats elicited USVs when placed in the cocaine-associated environment. USVs progressively increased, indicating a growing learned association between cocaine intake and cocaine-associated cues. This suggests that USVs may be a useful model for investigating cocaine craving and serve as a pharmacological target for interventions aimed to reduce cocaine craving and relapse. I then examined the effects of short-term deprivation of cocaine and cocaine cues on cocaine-conditioned USVs, which were both exaggerated after abstinence. The results may have clinical implications, in that intermittently avoiding cues or context may enhance drug cue salience and increase the probability of relapse. Motivational aspects of cocaine were assessed comparing commonly measured lever response rate and locomotion with cocaine-induced USVs during cocaine administration and extinction. In agreement with prevailing findings, lever responding for cocaine and cocaine-induced locomotor activity increased across conditioning sessions. However, the number of USVs evoked in response to cocaine infusion decreased with cocaine experience. These findings suggest growing tolerance to the rewarding properties of cocaine. These studies underscore the value of USV assessment during drug dependence studies.Item A compilation of design principles and guidelines for selective laser sintering(2016-05) Pradhan, Nivedita; Seepersad, Carolyn C.; Crawford, Richard HThe term Additive Manufacturing (AM) is used to describe several manufacturing technologies that share the same basic principle of producing parts directly from their CAD models without the need for special tooling, by adding material selectively one layer at a time. Current research focuses on one such technology called Selective Laser Sintering (SLS) where thin layers of powdered thermoplastic material are fused using a laser beam. With no part-specific tooling required, the product development cycle is drastically shortened. This lack of tooling, coupled with freedom of placement of material, opens the door to several design opportunities unique to AM such as increased geometrical design freedom and the ability to manufacture low production volumes economically. Gradual improvements in process accuracy and selection of materials over time have resulted in a shift in application of AM from rapid prototyping to direct manufacturing and even ‘democratization’ of the product development process in which even non-professional users can rapidly manufacture products as long as there is a CAD model for the part. However, the move to direct manufacturing of end-use parts also means that part quality in terms of conformance to product specification becomes important for the product to successfully perform its function. The research in this thesis is focused on documenting these manufacturability capabilities and limitations for Selective Laser Sintering. It focuses specifically on thermoplastics, especially Nylon 12 polyamide materials known by the trade names PA 2200 and Duraform PA. While several design resources have been created based on industry best practices developed through experience, they are scattered throughout the literature and are not readily available to designers. It is also difficult to compare and draw quantitative inferences from existing guidelines as they are developed independently under dissimilar process conditions. Therefore, a prime focus of this research is to synthesize and compile existing guidelines into a comprehensive document. The first objective of this research is to compile a user-friendly resource, in the form of design principles and guidelines, to help designers make early process selection decisions, optimize part quality and minimize manufacturing cost. A systematic literature review of available guidelines, exploratory studies and case studies is conducted to develop actionable design recommendations that are within the scope of the designer. The second objective of this research is to address the lack of adequate process tolerance information that can reliably predict the quality of parts produced by the selective laser sintering process. This information is important to accurately evaluate the process during early process selection. A test part is proposed to measure dimensional deviations for various features (such as holes, gaps, cylinders, walls, clearances, etc.) across a range of dimensions and along different orientations. Finally, a sampling plan that represents sources of variability in the process is put forward to collect statistical data in an economical manner.Item Cross national exploration of the relationship between education and tolerance(2013-08) Kolloju, Neeraja; Johnson, Doyle P.; Bradatan, CristinaEducation is considered to affect tolerance levels in a positive way almost universally, as observed by numerous authors. It is assumed to be universally creating intrinsically tolerant attitudes among its members. This study challenges the assumed positive effects of education on attitudes by emphasizing contextual placement of educational institutions in different societies. Considering the combination of culture and politics in each country as unique, it is shown in this study that education affects attitudes of tolerance differently in different countries. A regression analysis done on around thirty five countries shows that in a majority of politically free countries, i.e. democracies, education increases tolerance levels and in a majority of less free countries, education does not have any effect or has a negative correlation with tolerance levels. This study emphasizes that a country is an open system. A variety of societal factors, among which political orientation is significant, act together to produce difference in the organizational fields of the educational systems, thus affecting the relationship between education and tolerance.Item Diazepam binding inhibitor and tolerance to ethanol in Drosophila melanogaster(2012-12) Robles, Roseanna Beth; Atkinson, Nigel (Nigel S.); Aldrich, Richard; Duvauchelle, Christine; Mihic, John; Zakon, HaroldTolerance to ethanol is an endophenotype of alcoholism, allowing the study of a complex psychiatric condition using animal models. To identify new genes involved in the acquisition of tolerance, I designed an automated and high-throughput tolerance assay and screened a collection of deficiency mutants for the inability to develop tolerance. The screen yielded several “regions of interest” where more than one overlapping deficiency failed to develop tolerance. One of these regions comprised nine genes, and testing the expression levels of each gene revealed that diazepam binding inhibitor (Dbi) showed grossly increased expression in the deficiency mutant compared to wild type. Another mutant stock, with a P-element transposon inserted downstream of the Dbi gene, both failed to develop tolerance and showed further increased expression of Dbi. There are two insulator binding sites flanking Dbi, and the P-element transposon also contains insulator binding sites. Based on these results, it was hypothesized that an insulator complex kept Dbi expression low in wild type flies and that disrupting the insulator complex allowed aberrantly high expression of Dbi in the mutants. Furthermore, we assumed that induction of Dbi blocked tolerance by making the mutants resistant prior to the first sedation. A UAS-DBI transgene was constructed to over-express Dbi. Induction of the UAS-DBI with a heat shock gal4 driver induced resistance to ethanol sedation; a similar response was observed in the parental control, but the effect was smaller. Although driving UAS-DBI with the neural elav-gal4 driver did not block tolerance, the experimental stock was resistant to ethanol sedation compared to the parental controls, indicating that increased Dbi expression produced “pre-tolerance.” To confirm the theory that insulator disruption was responsible for the increase in Dbi and the resulting no-tolerance phenotype, the P-element in the second mutant was mobilized by introducing a transposase source. These offspring lines were analyzed using qualitative PCR to determine whether the transposon excised precisely, left a portion of the transposon behind, or removed some of the flanking region. A precise excision mutant was identified, but this mutation did not rescue tolerance as predicted. This result might indicate that genetic background was the cause of the no-tolerance phenotype, or it might indicate that the excision was not exactly precise and removed the native insulator binding site, causing the insulator complex to remain disrupted.Item Influence of corn hybrids and water stress on yield and nutritive value(2009-05) Montgomery, Randall; Xu, Wenwei; Thorvilson, Harlan G.; Wester, David B.; Allen, Vivien G.Silage corn (Zea mays) in Texas has increased from 16,000 ha harvested in 1985 to 53,000 ha harvested in 2005. All corn in the Texas High Plains is irrigated with water from the Ogallala Aquifer. Due to the declining water level of the Ogallala Aquifer and rising energy costs, corn silage producers need new hybrids that require less water and respond to improved crop management practices. As the dairy industry continues to grow in West Texas, producers must supply a high-quality, high-yielding corn forage that meets the nutritional demands of the dairy industry. The objective of this study was to compare the responses in regards to grain yield, forage yield and quality of five Texas Agricultural Experiment Station (TAES) corn hybrids and three widely grown commercial hybrids (Garst 8288, P31B13, and DKC66-80) under full and limited irrigation treatments. This experiment was conducted in 2005 and 2006, at Halfway, TX and Etter, TX. There were two irrigation treatments (well-watered and drought-stressed) at Etter and Halfway in both years. Drought stress was imposed by reducing the amount of irrigation water by one-half compared to well-watered plots from V10 to R3 growth stages. Plots were two-rows 5.5 m long and spaced 1 m apart at Halfway and 0.76 m apart at Etter. After planting, plots were thinned to 66,947 plants/ha at Etter and 57,383 plants/ha in Halfway. Data was collected on grain yield, silage yield, plant height, ear height, days to pollen, neutral detergent fiber (NDF), acid detergent fiber (ADF), crude protein and numerous other forage quality traits. Whole plant corn samples were collected and sub-samples were analyzed by Dairy One Forage Laboratory (Ithaca, NY) using Near Infrared Reflectance Spectroscopy (NIRS). The basic experimental design for this analysis was a randomized complete block design with two blocks (locations); irrigation treatments (100ET and 50ET) represented the main plot factor of a split-plot arrangement, and hybrid was a subplot factor. No three-way interactions were observed among year, irrigation, and hybrid for any of the variables analyzed. Additionally, interactions between irrigation and hybrid, and between irrigation and year, were not present for any of the variables analyzed. Effects of hybrids depended on the year of the experiment (year X hybrid interaction) for percentage ADF, NDF, TDN, and DM. For grain yield, per plant fresh weight (FW plant-1), DTP, PHT and EHT, differences among hybrids were independent of other factors included in this study. Thus, differences among hybrids were averaged over each yr and effects of hybrid and irrigation treatment were examined. Differences among hybrids were observed for grain yield (kg ha-1), FW plant-1, DTP, PHT, and EHT. When analyzing grain yield, the commercial check P31B13 (8703 kg ha-1) was the highest yielding hybrid with the exception of C3A654 x B110 (7800 kg ha-1) and DKC66-80 (8044 kg ha-1). In terms of FW plant-1, S1W x CML343 yielded a greater fresh weight per plant than any other hybrids except DKC66-80, while C3A654 x B110 yielded the least fresh weight per plant. Also, S1W x CML343 was the latest maturing hybrid when compared to all others and took an average of 80 d to anthesis (DTP). In terms of plant height, S2B73 x NC300 was a taller hybrid than Tx205 x B110 (230.6) and C3A654 x B110 (210.3) as it averaged 244.4 cm, while, C3A654 x B110 was statistically the shortest when compared to all other hybrids as it measured just over 210 cm on average. Drought stress (50% ET irrigation) did affect both ADF and NDF in terms of forage quality. Both cell wall (NDF) and cell wall minus hemicelluloses (ADF) were higher in hybrids subjected to water stress than hybrids irrigated at 100% ET. Irrigation level did not affect percentage CP and TDN. Grain yield was reduced about 50% by the low irrigation treatment compared with full irrigation. Surprisingly, there were no statistical differences found in the forage yield (FW plant-1) or in DTP with the imposition of drought. Effects of year and hybrid interacted with each other for ADF, NDF, TDN and DM. For DM, hybrids were similar (P > 0.1560) in 2005 and differed (P < 0.0001) in 2006. However, for ADF, NDF and TDN, hybrids differed in each year. In future studies the integration of brown mid-rib hybrids should be made a priority. Some hybrids from this study did show promise and should be considered for future studies as well. Although S1W x CML343 lacked the quality traits that some of the other hybrids, it should not be ruled out on that premise alone. It did appear to be one of the higher yielding hybrids and should be considered for future studies. While C3A654 x B110 did appear to produce higher quality forage, it also had the shortest plants and might lack the overall forage production when being considered for future studies. Also, SPG3 x B110 appeared to have quality traits that would be very desirable and at the same time may include some higher yielding traits and should be used in potential studies. A major limitation in this study was the inclusion of only two blocks, although the two locations did serve as valid blocks. More research and detailed analysis must be performed in order to select for high yielding, high producing corn forage that might potentially use less water. This study may help to serve as a reference to future researches.Item Mechanisms of benzyl alcohol tolerance in Drosophila melanogaster(2009-12) Alhasan, Yazan Mahmoud; Atkinson, Nigel (Nigel S.); Zakon, Harold H.; Gonzales, Rueben A.; Singer, Michael C.; Bergeson, Susan E.Proper neuronal function requires the preservation of appropriate neural excitability. An adaptive increase in neural excitability after exposure to agents that depress neuronal signaling blunts the sedative drug effects upon subsequent drug exposure. This adaptive response to drug exposure leads to changes in drug induced behaviors such as tolerance, withdrawal and addiction. Here I use Drosophila melanogaster to study the cellular and neuronal components which mediate behavioral tolerance to the anesthetic benzyl alcohol. I demonstrate that rapid tolerance to benzyl alcohol is a pharmacodynamic mechanism independent of drug metabolism. Furthermore, tolerance is a cell autonomous response which occurs in the absence of neural signaling. Using genetic and pharmacological manipulations I find the synapse to play an important role in the development of tolerance. In addition, the neural circuits that regulate arousal and sleep also alter benzyl alcohol sensitivity. Beyond previously described transcriptional mechanisms I find a post-translational role of the Ca2+-activated K+-channel, slowpoke in the development of tolerance. Finally, I explore a form of juvenile onset tolerance, which may have origins that differ from rapid tolerance. The implications of this study go beyond tolerance in Drosophila melanogaster to benzyl alcohol and can shed light on human drug tolerance, withdrawal and addiction.Item Optical Filter Design: Gain Analysis and Tolerance Analysis(2011-10-21) Vandrasi, VivekThree components, gain analysis, tolerance analysis in-depth, and a brief non- linearity analysis, are presented. In the first component, the effects of an Erbium doped waveguide amplifier in a microring are investigated using a time domain simulation. Methods to simulate the gain versus average input signal power in the microring are studied, given that it has a long lifetime compared to the short delay time of the microring. The methods are based on the dependence of the gain on the power of the signal being fed to the ring. An algorithm is proposed to perform a thorough tolerance analysis on any optical circuit with respect to any optical parameter. The algorithm, based on Monte Carlo Simulation, is implemented on a complex optical circuit that is designed to obtain a bandpass filter response of given specifications. It is also tested on similar designs for a comparative study between them. The parameters and the structure of the designs used for the analysis are presented in detail. The results are presented in terms of the yield with respect to the parameter being varied, against their tolerance value. Algorithms for studying the effects of two types of non-linearities are presented. The Kerr nonlinearity and the two-photon absorption are included in the bandpass filter designs used for the tolerance analysis. The algorithms are based on the power circulating in different regions of the circuit under consideration. The variation in the original response because of the loss due to nonlinearity is observed and analyzed for different power levels of the input signal.Item Tolerance as a way of life(2008-08) Clark, Jeffrey Nawrocki; Tsai, Yung-Mei; Johnson, PaulThe purpose of this study will be to redefine the nature and source of tolerance through an analysis of the complex patterns of interdependence that develop in urban environments. Some of the most crucial developments in this process include the following: 1) Increased need for interaction among diverse types of people, 2) symbols and other forms of commonality external to the individual, and 3) development of institutions and mechanisms for regulating such interaction and upholding such symbols. First, literatures on urban sociology and research on civil liberties are used to create an urbanism- tolerance paradigm. Short comings of urbanism are discussed through more detailed views of the composition of populations and the potential for subcultural development. I then argue that past efforts to explain tolerance have been biased by attitudinal measures of the extension of civil liberties. Review of the historic context of urbanism and tolerance show that toleration of differences, at the structural level, is quite prevalent and that tolerant behavior is, in fact, a way of life.