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Description
Nicotine is thought to underlie the reinforcing and dependence-producing effects of tobacco-containing products. Nicotine supports self-administration in rodents, although measures of its reinforcing effects are often confounded by procedures that are used to facilitate acquisition, such as food restriction, prior reinforcement training, or response-contingent co-delivery of a naturally reinforcing light. This study examined whether rats acquire nicotine self-administration in the absence of these facilitators. A new mathematical modeling procedure was used to define the criterion for acquisition and to determine dose-dependent differences in rate and asymptote levels of intake. Rats were trained across 20 daily 2-h sessions occurring 6 days/week in chambers equipped with active and inactive levers. Each active lever press resulted in nicotine reinforcement (0, 0.015, 0.03, 0.06 mg/kg, IV) and retraction of both levers for a 20-s time out, whereas inactive lever presses had no consequences. Acquisition was defined by the best fit of a logistic function (i.e., S-shaped) versus a constant function (i.e., flat line) for reinforcers obtained across sessions using a corrected Akaike information criterion (AICc) as a model selection tool. The results showed an inverted-U shaped function for dose in relation to the percentage of animals that acquired nicotine self-administration, with 46% acquiring at 0.015 mg/kg, 73% at 0.03 mg/kg, and 58% at 0.06 mg/kg. All saline rats failed to acquire as expected. For rats that acquired nicotine self-administration, multiple model comparisons demonstrated that the asymptote (highest number of reinforcers/session) and half learning point (h; session during which half the assymptote had been achieved) were justified as free parameters of the reinforcers/session function, indicating that these parameters vary with nicotine dose. Asymptote exhibited an inverted U-shaped function across doses and half learning point exhibited a negative relationship to dose (i.e., the higher the dose the fewer sessions to reach h). These findings suggest that some rats acquire nicotine self-administration without using procedures that confound measures of acquisition rate. Furthermore, the modeling approach provides a new way of defining acquisition of drug self-administration that takes advantage of using all data generated from individual subjects and is less arbitrary than some criteria that are currently used.
ContributorsCole, Natalie (Author) / Neisewander, Janet L (Thesis advisor) / Sanabria, Federico (Thesis advisor) / Bimonte-Nelson, Heather A. (Committee member) / Olive, Michael F (Committee member) / Arizona State University (Publisher)
Created2011
Description
In this thesis, I present a lab-on-a-chip (LOC) that can separate and detect Escherichia Coli (E. coli) in simulated urine samples for Urinary Tract Infection (UTI) diagnosis. The LOC consists of two (concentration and sensing) chambers connected in series and an integrated impedance detector. The two-chamber approach is designed to reduce the non-specific absorption of proteins, e.g. albumin, that potentially co-exist with E. coli in urine. I directly separate E. coli K-12 from a urine cocktail in a concentration chamber containing micro-sized magnetic beads (5 µm in diameter) conjugated with anti-E. coli antibodies. The immobilized E. coli are transferred to a sensing chamber for the impedance measurement. The measurement at the concentration chamber suffers from non-specific absorption of albumin on the gold electrode, which may lead to a false positive response. By contrast, the measured impedance at the sensing chamber shows ~60 kÙ impedance change between 6.4x104 and 6.4x105 CFU/mL, covering the threshold of UTI (105 CFU/mL). The sensitivity of the LOC for detecting E. coli is characterized to be at least 3.4x104 CFU/mL. I also characterized the LOC for different age groups and white blood cell spiked samples. These preliminary data show promising potential for application in portable LOC devices for UTI detection.
ContributorsKim, Sangpyeong (Author) / Chae, Junseok (Thesis advisor) / Phillips, Stephen M. (Committee member) / Blain Christen, Jennifer M. (Committee member) / Arizona State University (Publisher)
Created2011
Description
Phase contrast magnetic resonance angiography (PCMRA) is a non-invasive imaging modality that is capable of producing quantitative vascular flow velocity information. The encoding of velocity information can significantly increase the imaging acquisition and reconstruction durations associated with this technique. The purpose of this work is to provide mechanisms for reducing the scan time of a 3D phase contrast exam, so that hemodynamic velocity data may be acquired robustly and with a high sensitivity. The methods developed in this work focus on the reduction of scan duration and reconstruction computation of a neurovascular PCMRA exam. The reductions in scan duration are made through a combination of advances in imaging and velocity encoding methods. The imaging improvements are explored using rapid 3D imaging techniques such as spiral projection imaging (SPI), Fermat looped orthogonally encoded trajectories (FLORET), stack of spirals and stack of cones trajectories. Scan durations are also shortened through the use and development of a novel parallel imaging technique called Pretty Easy Parallel Imaging (PEPI). Improvements in the computational efficiency of PEPI and in general MRI reconstruction are made in the area of sample density estimation and correction of 3D trajectories. A new method of velocity encoding is demonstrated to provide more efficient signal to noise ratio (SNR) gains than current state of the art methods. The proposed velocity encoding achieves improved SNR through the use of high gradient moments and by resolving phase aliasing through the use measurement geometry and non-linear constraints.
ContributorsZwart, Nicholas R (Author) / Frakes, David H (Thesis advisor) / Pipe, James G (Thesis advisor) / Bennett, Kevin M (Committee member) / Debbins, Josef P (Committee member) / Towe, Bruce (Committee member) / Arizona State University (Publisher)
Created2011
Description
The past two decades have been monumental in the advancement of microchips designed for a diverse range of medical applications and bio-analysis. Owing to the remarkable progress in micro-fabrication technology, complex chemical and electro-mechanical features can now be integrated into chip-scale devices for use in biosensing and physiological measurements. Some of these devices have made enormous contributions in the study of complex biochemical processes occurring at the molecular and cellular levels while others overcame the challenges of replicating various functions of human organs as implant systems. This thesis presents test data and analysis of two such systems. First, an ISFET based pH sensor is characterized for its performance in a continuous pH monitoring application. Many of the basic properties of ISFETs including I-V characteristics, pH sensitivity and more importantly, its long term drift behavior have been investigated. A new theory based on frequent switching of electric field across the gate oxide to decrease the rate of current drift has been successfully implemented with the help of an automated data acquisition and switching system. The system was further tested for a range of duty cycles in order to accurately determine the minimum length of time required to fully reset the drift. Second, a microfluidic based vestibular implant system was tested for its underlying characteristics as a light sensor. A computer controlled tilt platform was then implemented to further test its sensitivity to inclinations and thus it‟s more important role as a tilt sensor. The sensor operates through means of optoelectronics and relies on the signals generated from photodiode arrays as a result of light being incident on them. ISFET results show a significant drop in the overall drift and good linear characteristics. The drift was seen to reset at less than an hour. The photodiodes show ideal I-V comparison between photoconductive and photovoltaic modes of operation with maximum responsivity at 400nm and a shunt resistance of 394 MΩ. Additionally, post-processing of the tilt sensor to incorporate the sensing fluids is outlined. Based on several test and fabrication results, a possible method of sealing the open cavity of the chip using a UV curable epoxy has been discussed.
ContributorsMamun, Samiha (Author) / Christen, Jennifer Blain (Thesis advisor) / Goryll, Michael (Committee member) / Yu, Hongyu (Committee member) / Arizona State University (Publisher)
Created2011
Description
An accurate sense of upper limb position is crucial to reaching movements where sensory information about upper limb position and target location is combined to specify critical features of the movement plan. This dissertation was dedicated to studying the mechanisms of how the brain estimates the limb position in space and the consequences of misestimation of limb position on movements. Two independent but related studies were performed. The first involved characterizing the neural mechanisms of limb position estimation in the non-human primate brain. Single unit recordings were obtained in area 5 of the posterior parietal cortex in order to examine the role of this area in estimating limb position based on visual and somatic signals (proprioceptive, efference copy). When examined individually, many area 5 neurons were tuned to the position of the limb in the workspace but very few neurons were modulated by visual feedback. At the population level however decoding of limb position was somewhat more accurate when visual feedback was provided. These findings support a role for area 5 in limb position estimation but also suggest that visual signals regarding limb position are only weakly represented in this area, and only at the population level. The second part of this dissertation focused on the consequences of misestimation of limb position for movement production. It is well known that limb movements are inherently variable. This variability could be the result of noise arising at one or more stages of movement production. Here we used biomechanical modeling and simulation techniques to characterize movement variability resulting from noise in estimating limb position ('sensing noise') and in planning required movement vectors ('planning noise'), and compared that to the variability expected due to noise in movement execution. We found that the effects of sensing and planning related noise on movement variability were dependent upon both the planned movement direction and the initial configuration of the arm and were different in many respects from the effects of execution noise.
ContributorsShi, Ying (Author) / Buneo, Christopher A (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Santello, Marco (Committee member) / He, Jiping (Committee member) / Santos, Veronica (Committee member) / Arizona State University (Publisher)
Created2011
Description
Fibromyalgia (FM) is a chronic musculoskeletal disorder characterized by widespread pain, fatigue, and a variety of other comorbid physiological and psychological characteristics, including a deficit of positive affect. Recently, the focus of research on the pathophysiology of FM has considered the role of a number of genomic variants. In the current manuscript, case-control analyses did not support the hypothesis that FM patients would differ from other chronic pain groups in catechol-O-methyltransferase (COMT) and mu-opioid receptor (OPRM1) genotype. However, evidence is provided in support of the hypothesis that functional single nucleotide polymorphisms on the COMT and OPRM1 genes would be associated with risk and resilience, respectively, in a dual processing model of pain-related positive affective regulation in FM. Forty-six female patients with a physician-confirmed diagnosis of FM completed an electronic diary that included once-daily assessments of positive affect and soft tissue pain. Multilevel modeling yielded a significant gene X environment interaction, such that individuals with met/met genotype on COMT experienced a greater decline in positive affect as daily pain increased than did either val/met or val/val individuals. A gene X environment interaction for OPRM1 also emerged, indicating that individuals with at least one asp allele were more resilient to elevations in daily pain than those homozygous for the asn allele. In sum, the findings offer researchers ample reason to further investigate the contribution of the catecholamine and opioid systems, and their associated genomic variants, to the still poorly understood experience of FM.
ContributorsFinan, Patrick Hamilton (Author) / Zautra, Alex (Thesis advisor) / Davis, Mary (Committee member) / Lemery-Chalfant, Kathryn (Committee member) / Presson, Clark (Committee member) / Arizona State University (Publisher)
Created2011
Description
Over recent decades, euthanasia has been a topic of increasing debate. With legalization of euthanasia in the states of Oregon and Washington and attempted reform in several other U.S. states and nations worldwide, it has become increasingly important to understand the roles and values of helping professionals who might be working with clients considering this option. The current study targeted 85 undergraduate students, 54 doctoral students in counseling psychology, and 53 doctoral-level professionals in psychology to assess both their personal values regarding euthanasia and their willingness to allow a client the autonomy to make a decision about euthanasia. Several factors were analyzed in regards to their relation to client autonomy and attitudes toward euthanasia, including age of client and sex of client. These variables were manipulated in vignettes to create four scenarios: a 24 year old male, 24 year old female, 80 year old male, 80 year old female. Other factors included level of education of the participant, spirituality and strength of religiosity of the participant, and personal experiences with deaths of friends or family members. Results indicated that more education was associated with greater support for euthanasia and that stronger religiosity and spirituality were related to less support for euthanasia. This study also found that participants did not exhibit differential levels of support based solely on the age or the sex of the client depicted in the vignette. Results further indicated that for doctoral students and professionals the loss of a loved one, regardless of cause of death, did not have a significant effect on their attitudes toward euthanasia. It is important for training programs to be aware of these findings in order to monitor trainees in terms of personal biases in the therapy relationship. With objectivity a high priority while working with clients, it is necessary to be aware of outside factors potentially influencing one's work with clients surrounding this value-laden issue.
ContributorsBevacqua, Frank (Author) / Robinson-Kurpius, Sharon (Thesis advisor) / Kinnier, Richard (Committee member) / Homer, Judy (Committee member) / Arizona State University (Publisher)
Created2011
Description
The current study was a benefit cost analysis that examined mental and behavioral health and prescription drug service use data of 347 participants (212 youth and 135 caregivers) from a bereavement intervention, the Family Bereavement Program (FBP).The preliminary goals of the current study were to compare the FBP intervention and the Literature Control (LC) groups at the six year follow-up on: (a) number of participants using mental/behavioral health services and prescription drugs, (b) the frequency of use of mental/behavioral health services and prescription drugs, and (c) the costs of mental/behavioral health services and prescription drugs. The final, and primary goal, was to (d) calculate the benefits of the FBP by analyzing the monetary difference between the LC and FBP groups in terms of cost of services used and then by applying those benefits to the cost of the intervention. Data representing participating youths' and caregivers' mental health service use and prescription drug use at the sixth year post-intervention were collected, as were the costs of those services. Results indicated that fewer FBP participants used services and prescription drugs than the Literature Control (LC) participants, but FBP participants, particularly the youth, used some low intensity services more frequently whereas the LC youth used more intensive and costly services more frequently. Consequently, service costs were greater for participants in the LC group than for participants in the FBP group. The benefit cost ratio revealed that the FBP, as delivered, saved society between $.15 and $.27 in mental and behavioral health costs for every dollar spent on the intervention. Implications of these findings and directions for future research are discussed.
ContributorsPorter, Michèle M (Author) / Hanish, Laura D. (Thesis advisor) / Sandler, Irwin N. (Committee member) / Wolchik, Sharlene A (Committee member) / Johnson, William G. (Committee member) / Arizona State University (Publisher)
Created2011
Description
Anticipatory planning of digit positions and forces is critical for successful dexterous object manipulation. Anticipatory (feedforward) planning bypasses the inherent delays in reflex responses and sensorimotor integration associated with reactive (feedback) control. It has been suggested that feedforward and feedback strategies can be distinguished based on the profile of grip and load force rates during the period between initial contact with the object and object lift. However, this has not been validated in tasks that do not constrain digit placement. The purposes of this thesis were (1) to validate the hypothesis that force rate profiles are indicative of the control strategy used for object manipulation and (2) to test this hypothesis by comparing manipulation tasks performed with and without digit placement constraints. The first objective comprised two studies. In the first study an additional light or heavy mass was added to the base of the object. In the second study a mass was added, altering the object's center of mass (CM) location. In each experiment digit force rates were calculated between the times of initial digit contact and object lift. Digit force rates were fit to a Gaussian bell curve and the goodness of fit was compared across predictable and unpredictable mass and CM conditions. For both experiments, a predictable object mass and CM elicited bell shaped force rate profiles, indicative of feedforward control. For the second objective, a comparison of performance between subjects who performed the grasp task with either constrained or unconstrained digit contact locations was conducted. When digit location was unconstrained and CM was predictable, force rates were well fit to a bell shaped curve. However, the goodness of fit of the force rate profiles to the bell shaped curve was weaker for the constrained than the unconstrained digit placement condition. These findings seem to indicate that brain can generate an appropriate feedforward control strategy even when digit placement is unconstrained and an infinite combination of digit placement and force solutions exists to lift the object successfully. Future work is needed that investigates the role digit positioning and tactile feedback has on anticipatory control of object manipulation.
ContributorsCooperhouse, Michael A (Author) / Santello, Marco (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Buneo, Christopher (Committee member) / Arizona State University (Publisher)
Created2011
Description
During adolescence, friends are a central part of adolescents' daily lives, they serve as significant sources of emotional support and companionship (Keefe & Berndt, 1996; Way & Robinson, 2003) as well as provide opportunities to negotiate interpersonal conflicts and disagreements (Laursen & Pursell, 2009). This study was designed to examine the nature and correlates of friendships, capturing the multidimensional nature of these relationships. Specifically, three goals were proposed: (a) to use a pattern-analytic approach to identify different profiles of adolescents' friendships along three dimensions: intimacy, negativity, and involvement; (b) to examine linkages between profile membership and adolescents' cultural orientations and values; and (c) to explore the relation between profile membership and adolescent well-being. Participants were 246 Mexican-origin adolescents (M = 12.50 years; SD = 0.58) who participated in home interviews and a series of nightly phone calls. Adolescents reported on their friendship qualities, their cultural orientations and values, as well as their depressive symptoms, risky behaviors, and on their current grades (GPA). Adolescents' time spent with best friends was calculated from the seven nightly phone calls. Results revealed three distinct latent profiles: Positive Engagement, Moderate Engagement, and Low Involvement. Profile membership was not linked to adolescents' cultural orientations and values. Further, associations emerged between profile membership and adolescents' GPA, but not their risky behaviors and depressive symptoms.
ContributorsRodriguez, Sue Annie (Author) / Updegraff, Kimberly (Thesis advisor) / Umana-Taylor, Adriana (Committee member) / Bradley, Robert (Committee member) / Arizona State University (Publisher)
Created2011