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On the Analysis of Mouse BehaviorMurdaugh, Laura Bethany 16 January 2024 (has links)
Accurate and high throughput methods of measuring animal behavior are critical for many branches of neuroscience, allowing for mechanistic studies and preclinical drug testing. Methodological limitations contribute to narrow investigations, which may overlook the interplay between distinct but related behaviors, like affective behaviors and executive function (EF). To prevent such oversight, researchers can perform test batteries, or multiple assessments in one study. However, test batteries often exclude cognitive behaviors due to their lengthy testing period. This dissertation first reviews current evidence related to the investigation and relation of affective, pain-like, and operant behaviors in rodent models. Then, I demonstrate the use of traditional and novel test batteries to investigate these behavioral changes in multiple mouse models.
First, I investigated affective and pain-like behavior in mice lacking Nape-pld, a key enzyme that synthesizes lipid mediators which activate receptors in the endocannabinoid system. I found that these mice displayed reduced sucrose preference, but otherwise normal anxiety- and depression-like behavior, and had baseline differences in thermal nociception and inflammation response. Then, I investigated the affective, pain-like, and operant effects of chronic vapor exposure (CVE) to vehicle or nicotine (NIC). Regardless of NIC content, acute abstinence from CVE increased mechanical sensitivity and self-grooming, while chronic abstinence from NIC CVE resulted in motor stimulation. Other traditional anxiety- and depression-like behaviors were unchanged by CVE. In an operant test battery, acute abstinence from NIC CVE impaired acquisition, decreased sucrose motivation, and impaired the response to aversive rewards. Finally, I developed a protocol for the high throughput analysis of six operant tests which can be completed in as few as nineteen sessions, significantly fewer sessions than traditional operant tests. This battery investigates multiple aspects of goal-directed behavior and EF including operant acquisition, cognitive flexibility, reward devaluation, motivation via response to increased instrumental effort, cue devaluation or the extinction of learned behavior, and reacquisition. I validated several of these tests by demonstrating that lesions to specific subregions of the orbitofrontal cortex impaired cognitive flexibility and altered response to instrumental effort as observed in traditional operant tests. I then used this battery to investigate the effects of the P129T mutation, which results in a mutated version of the Fatty Acid Amide Hydrolase (FAAH) enzyme that is associated with addiction, in male and female mice. Knock-in animals displayed reduced activity in response to increasing instrumental effort, and reduced activity on the first day of an extinction test. Then, to encourage others to use this new operant battery I outlined how to efficiently collect data, shared a database for customizable analysis, and described common issues and how to solve them. This protocol has potential implications for many aspects of neuroscience including the investigation of novel therapeutics and the neural circuitry underlying behaviors.
Together, the information in this dissertation demonstrates the utility of multi-faceted behavioral assays and the combination of traditional and novel approaches to collect more comprehensive behavioral data, which will allow researchers to better investigate neural circuitry underlying behaviors or the behavioral changes associated with novel therapeutics. / Doctor of Philosophy / By measuring animal behavior researchers can gain insight into how specific brain regions interact to influence choice and action. Limitations in testing methods mean that researchers may fail to investigate the relationship between distinct aspects of behavior, like the influence of emotional state or pain on cognition. To prevent such oversight researchers can perform a test battery, a specific series of multiple tests that measures several different aspects of behavior. Traditional test batteries often overlook cognitive or operant (learning to perform an action for reward) behaviors due to time constraints, which limits their translational potential. This dissertation provides a brief overview of the ways that researchers investigate affective (emotional), pain-like (physical discomfort), and goal-directed behaviors. It further has a broad focus on mouse models related to addiction or the endocannabinoid system (ECS), which is shown to play a role in mood, pain (e.g., perception, relief, and inflammation), and cognition. Using a traditional test battery, we demonstrate that mice lacking a key enzyme in the ECS have altered responses to sugar, heat, and inflammation, but display otherwise normal performance in anxiety-, depression-, and pain-like tests. Next, we used a combined traditional and operant battery to investigate the effects of chronic vapor exposure (CVE) and nicotine in mice. We found that regardless of nicotine content, acute abstinence from CVE increased physical sensitivity and self-grooming but spared other anxiety- and depression-like behaviors. Acute abstinence from nicotine CVE resulted in motor stimulation, impaired operant learning, lower motivation for sucrose reward, and an impaired ability to withhold responding when presented with a bitter reward. Finally, I outline a novel operant test battery that addresses the limitations of current operant chamber- or place-based batteries. Using this battery, I first demonstrate that it captures similar behavioral changes to those seen in traditional operant chambers. Then, I demonstrate that mice containing an ECS mutation associated with problem drug use in humans display less motivation for food reward in response to increased effort, and more quickly inhibit a learned behavior when reward delivery is interrupted. I also found that in response to increased effort for reward or bitter rewards, male mice are more likely to alter their behavioral strategy. To encourage others to use this new operant battery I outlined how to efficiently collect data, shared a database for customizable analysis, and described common issues and how to solve them. This protocol has the potential to improve upon traditional tasks while opening cognitive research to more scientists. This has implications for many fields of neuroscience, especially the investigation of novel therapeutics and investigation of the neural circuitry underlying various disorders.
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THE DESIGN AND FABRICATION OF AUTONOMOUS POLYMER-BASED SURFACE TENSION-CONFINED MICROFLUIDIC PLATFORMSSwickrath, Michael J. January 2008 (has links)
No description available.
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IMPROVED TECHNIQUES IN GRAPH DRAWING USING FORCE DIRECTED METHODS FOR MODERATE SIZE GRAPHSJAIN, RACHANA 02 July 2004 (has links)
No description available.
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Studies toward the enantioselective total synthesis of pectenotoxin 2Bondar, Dmitriy A. 10 March 2005 (has links)
No description available.
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A Directed Evolution Strategy for Ligand Gated Ion Channel BiosensorsLePabic, Abdel Rahman 19 September 2022 (has links)
No description available.
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Graphs and Noncommutative Koszul AlgebrasHartman, Gregory Neil 25 April 2002 (has links)
A new connection between combinatorics and noncommutative algebra is established by relating a certain class of directed graphs to noncommutative Koszul algebras. The directed graphs in this class are called full graphs and are defined by a set of criteria on the edges. The structural properties of full graphs are studied as they relate to the edge criteria.
A method is introduced for generating a Koszul algebra Lambda from a full graph G. The properties of Lambda are examined as they relate to the structure of G, with special attention being given to the construction of a projective resolution of certain semisimple Lambda-modules based on the structural properties of G. The characteristics of the Koszul algebra Lambda that is derived from the product of two full graphs G' and G' are studied as they relate to the properties of the Koszul algebras Lambda' and Lambda' derived from G' and G'. / Ph. D.
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The Influence of Money on Goal Pursuit and Decision-Making: Understanding Money's Unique Impact on Goal PursuitMoran, Nora 07 May 2015 (has links)
Previous research suggests that activating concepts of money and wealth can increase motivation to achieve personal goals. In this dissertation, I investigate how money affects pursuit of important personal goals, and how this motivation may be affected by goal attainability. In eight studies, I show that priming concepts of money and wealth leads individuals to pursue important personal goals to a greater degree than control groups, but only when a goal is more attainable. In contrast, when a goal is less attainable, those primed with money will be less likely to work towards goals relative to control groups. Furthermore, I examine why money may have a detrimental effect on motivation when individuals are faced with less attainable but important goals, and argue those primed with money become more concerned with maintaining a sense of efficacy, and thus disengage from pursuit when success is less certain. Thus, this research identifies the needs made salient by activating money-"validating one's abilities. Finally, I show the relevance of these findings for consumer behavior, and discuss the additional implications of this work, as well as future research directions. / Ph. D.
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Electromagnetic Control of Biological AssemblySano, Michael B. 02 June 2010 (has links)
We have developed a new biofabrication process in which the precise control of bacterial motion is used to fabricate customizable networks of cellulose nanofibrils. This work describes how the motion of Acetobacter xylinum can be controlled by electric fields while the bacteria simultaneously produce nanocellulose, resulting in networks with aligned fibers. Since the electrolysis of water due to the application of electric fields produces the oxygen in the culture media far from the liquid-air boundary, aerobic cellulose production in 3D structures is readily achievable. Five separate sets of experiments were conducted to demonstrate the assembly of nanocellulose by Acetobacter xylinum in the presence of electric fields in micro and macro environments. This work demonstrates a new concept of bottom up material synthesis by control of a biological assembly process. / Master of Science
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Discrimination of Linguistic and Prosodic Information In Infant-Directed Speech by Six-Month-OldsTheaux, Heather M. 08 May 1997 (has links)
The purpose of the present study was to tease apart the paralinguistic from the linguistic aspects of infants' perception of infant-directed (ID) speech. Several studies have shown that infants beginning at a few days after birth discriminate native from nonnative speech and can discriminate specific contours (rising, falling, rising-falling) in ID speech. Some studies have also indicated that infants at 4.5 months of age prefer their own name over other names but at 6 months of age, fail to prefer a sentence with their own name embedded in it. Using a discrimination procedure, the current study investigated whether 6-month-old infants could detect a change in contour and/or a change in words when listening to ID utterances. Results indicated that 6-month-old infants detected both a contour and a word change. From these results, it is argued that as has been shown in other experiments, infants are extremely sensitive to subtle changes in speech. Furthermore, ID speech appears to facilitate infants' ability to discriminate small changes in ID speech (both linguistic and paralinguistic). It is suggested that future studies investigate more discrete changes in speech samples and a replication of this research with adult-directed (AD) speech. / Master of Science
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Assertion Training Groups: Therapist-Directed and Self-Directed Goal Orientation MethodsJarvis, Lawrence George 01 May 1980 (has links)
The present study was designed to investigate the effectiveness of two methods of goal specification in Assertion Training groups as assessed by two self-report measures, the Goal Attainment Scaling process and the Assertion Inventory. An Assertion Training group method having specific behavioral steps for approaching individualized goals was represented as the Therapist-Directed Assertion Training group. The second Assertion Training group was a Self-Directed group that allowed subjects to independently set and approach their own goals without the assistance of therapists in setting goals. Subjects were selected from among individuals who volunteered for the Assertion Training group in response to solicitation in general psychology classes, newspaper articles and circulars. Of the 76 subjects who filled out registration materials, 63 remained in the study, with 21 each assigned to the two treatment groups, and to a Waiting List Control group. While the Waiting List Control group participated in pre- and post-screening only, the Treatment groups underwent four weeks of group assertion training. The Self-Directed group was essentially encouraged to seek personally relevant goals, whereas the Therapist-Directed group members, with the help of a therapist, set up long- and short-range goals, which were monitored weekly by use of the Behavior Monitoring Progress Record. The level of assertion as assessed by the dependent measures appeared to be significantly enhanced by providing the Therapist-Directed group treatment or to a lesser extent by using the Self-Directed group method. The rationale for the study as well as the analysis of differences between groups are presented. Implications of the limitations and results of the present study are related to recommendations for future studies.
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