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Description
Ethinyl estradiol, (EE) a synthetic, orally bio-available estrogen, is the most commonly prescribed form of estrogen in oral contraceptives (Shively, C., 1998), and is found in at least 30 different contraceptive formulations currently prescribed to women (Curtis et al., 2005). EE is also used in hormone therapies prescribed to menopausal

Ethinyl estradiol, (EE) a synthetic, orally bio-available estrogen, is the most commonly prescribed form of estrogen in oral contraceptives (Shively, C., 1998), and is found in at least 30 different contraceptive formulations currently prescribed to women (Curtis et al., 2005). EE is also used in hormone therapies prescribed to menopausal women, such as FemhrtTM (Simon et al., 2003). Thus, EE is prescribed clinically to women at ages ranging from puberty through reproductive senescence. Here, in two separate studies, the cognitive effects of cyclic or tonic EE administration following ovariectomy (Ovx) were evaluated in young, female rats. Study I assessed the cognitive effects of low and high doses of EE, delivered tonically via a subcutaneous osmotic pump. Study II evaluated the cognitive effects of low, medium, and high doses of EE administered via a daily subcutaneous injection. For these studies, the low and medium doses correspond to the range of doses currently used in clinical formulations, and the high dose corresponds to the range of doses prescribed to a generation of women between 1960 and 1970, when oral contraceptives first became available. For each study, cognition was evaluated with a battery of maze tasks tapping several domains of spatial learning and memory. At the highest dose, EE treatment impaired multiple domains of spatial memory relative to vehicle treatment, regardless of administration method. When given cyclically at the low and medium doses, EE did not impact working memory, but transiently impaired reference memory during the learning phase of testing. Of the doses and regimens tested here, only EE at the highest dose impaired several domains of memory; this was seen for both cyclic and tonic regimens. Cyclic and tonic delivery of low EE, a dose that corresponds to doses used in the clinic today, resulted in transient and null impairments, respectively, on cognition.
ContributorsMennenga, Sarah E (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Baxter, Leslie C. (Committee member) / Olive, Michael F. (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Efficiency of components is an ever increasing area of importance to portable applications, where a finite battery means finite operating time. Higher efficiency devices need to be designed that don't compromise on the performance that the consumer has come to expect. Class D amplifiers deliver on the goal of increased

Efficiency of components is an ever increasing area of importance to portable applications, where a finite battery means finite operating time. Higher efficiency devices need to be designed that don't compromise on the performance that the consumer has come to expect. Class D amplifiers deliver on the goal of increased efficiency, but at the cost of distortion. Class AB amplifiers have low efficiency, but high linearity. By modulating the supply voltage of a Class AB amplifier to make a Class H amplifier, the efficiency can increase while still maintaining the Class AB level of linearity. A 92dB Power Supply Rejection Ratio (PSRR) Class AB amplifier and a Class H amplifier were designed in a 0.24um process for portable audio applications. Using a multiphase buck converter increased the efficiency of the Class H amplifier while still maintaining a fast response time to respond to audio frequencies. The Class H amplifier had an efficiency above the Class AB amplifier by 5-7% from 5-30mW of output power without affecting the total harmonic distortion (THD) at the design specifications. The Class H amplifier design met all design specifications and showed performance comparable to the designed Class AB amplifier across 1kHz-20kHz and 0.01mW-30mW. The Class H design was able to output 30mW into 16Ohms without any increase in THD. This design shows that Class H amplifiers merit more research into their potential for increasing efficiency of audio amplifiers and that even simple designs can give significant increases in efficiency without compromising linearity.
ContributorsPeterson, Cory (Author) / Bakkaloglu, Bertan (Thesis advisor) / Barnaby, Hugh (Committee member) / Kiaei, Sayfe (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Class D Amplifiers are widely used in portable systems such as mobile phones to achieve high efficiency. The demands of portable electronics for low power consumption to extend battery life and reduce heat dissipation mandate efficient, high-performance audio amplifiers. The high efficiency of Class D amplifiers (CDAs) makes them particularly

Class D Amplifiers are widely used in portable systems such as mobile phones to achieve high efficiency. The demands of portable electronics for low power consumption to extend battery life and reduce heat dissipation mandate efficient, high-performance audio amplifiers. The high efficiency of Class D amplifiers (CDAs) makes them particularly attractive for portable applications. The Digital class D amplifier is an interesting solution to increase the efficiency of embedded systems. However, this solution is not good enough in terms of PWM stage linearity and power supply rejection. An efficient control is needed to correct the error sources in order to get a high fidelity sound quality in the whole audio range of frequencies. A fundamental analysis on various error sources due to non idealities in the power stage have been discussed here with key focus on Power supply perturbations driving the Power stage of a Class D Audio Amplifier. Two types of closed loop Digital Class D architecture for PSRR improvement have been proposed and modeled. Double sided uniform sampling modulation has been used. One of the architecture uses feedback around the power stage and the second architecture uses feedback into digital domain. Simulation & experimental results confirm that the closed loop PSRR & PS-IMD improve by around 30-40 dB and 25 dB respectively.
ContributorsChakraborty, Bijeta (Author) / Bakkaloglu, Bertan (Thesis advisor) / Garrity, Douglas (Committee member) / Ozev, Sule (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Though for most of the twentieth century, dogma held that the adult brain was post-mitotic, it is now known that adult neurogenesis is widespread among vertebrates, from fish, amphibians, reptiles and birds to mammals including humans. Seasonal changes in adult neurogenesis are well characterized in the song control system of

Though for most of the twentieth century, dogma held that the adult brain was post-mitotic, it is now known that adult neurogenesis is widespread among vertebrates, from fish, amphibians, reptiles and birds to mammals including humans. Seasonal changes in adult neurogenesis are well characterized in the song control system of song birds, and have been found in seasonally breeding mammals as well. In contrast to more derived vertebrates, such as mammals, where adult neurogenesis is restricted primarily to the olfactory bulb and the dentate gyrus of the hippocampus, neurogenesis is widespread along the ventricles of adult amphibians. I hypothesized that seasonal changes in adult amphibian brain cell proliferation and survival are a potential regulator of reproductive neuroendocrine function. Adult, male American bullfrogs (Rana catesbeiana; aka Lithobates catesbeianus), were maintained in captivity for up to a year under season-appropriate photoperiod. Analysis of hormone levels indicated seasonal changes in plasma testosterone concentration consistent with field studies. Using the thymidine analogue 5-bromo-2-deoxyuridine (BrdU) as a marker for newly generated cells, two differentially regulated aspects of brain cell neogenesis were tracked; that is, proliferation and survival. Seasonal differences were found in BrdU labeling in several brain areas, including the olfactory bulb, medial pallium, nucleus accumbens and the infundibular hypothalamus. Clear seasonal differences were also found in the pars distalis region of the pituitary gland, an important component of neuroendocrine pathways. BrdU labeling was also examined in relation to two neuropeptides important for amphibian reproduction: arginine vasotocin and gonadotropin releasing hormone. No cells co-localized with BrdU and either neuropeptide, but new born cells were found in close proximity to neuropeptide-containing neurons. These data suggest that seasonal differences in brain and pituitary gland cell neogenesis are a potential neuroendocrine regulatory mechanism.
ContributorsMumaw, Luke (Author) / Orchinik, Miles (Thesis advisor) / Deviche, Pierre (Committee member) / Chandler, Douglas (Committee member) / Arizona State University (Publisher)
Created2012
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Description
In this thesis, a digital input class D audio amplifier system which has the ability

to reject the power supply noise and nonlinearly of the output stage is presented. The main digital class D feed-forward path is using the fully-digital sigma-delta PWM open loop topology. Feedback loop is used to suppress

In this thesis, a digital input class D audio amplifier system which has the ability

to reject the power supply noise and nonlinearly of the output stage is presented. The main digital class D feed-forward path is using the fully-digital sigma-delta PWM open loop topology. Feedback loop is used to suppress the power supply noise and harmonic distortions. The design is using global foundry 0.18um technology.

Based on simulation, the power supply rejection at 200Hz is about -49dB with

81dB dynamic range and -70dB THD+N. The full scale output power can reach as high as 27mW and still keep minimum -68dB THD+N. The system efficiency at full scale is about 82%.
ContributorsBai, Jing (Author) / Bakkaloglu, Bertan (Thesis advisor) / Arizona State University (Publisher)
Created2015
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Description
Elevated triglycerides (TG) are a hallmark of insulin resistance, which is generally caused by lower lipoprotein lipase (LPL) activity in the vasculature. LPL hydrolyzes TGs into free fatty acids in plasma for use and/or storage in tissues (i.e., adipose tissue, skeletal muscle). Plasma apolipoproteins (Apos) C3 and C2 interact with

Elevated triglycerides (TG) are a hallmark of insulin resistance, which is generally caused by lower lipoprotein lipase (LPL) activity in the vasculature. LPL hydrolyzes TGs into free fatty acids in plasma for use and/or storage in tissues (i.e., adipose tissue, skeletal muscle). Plasma apolipoproteins (Apos) C3 and C2 interact with LPL to modulate its function, and by inhibiting or activating LPL, respectively. Therefore, these proteins play key role in plasma lipid metabolism, but their role in regulating LPL activity in human insulin resistant (IR) (i.e., pre-diabetic) state is not known. Thus, the purpose of this research was to evaluate the concentrations of ApoC3 and ApoC2 in plasma along with the endothelial-bound LPL availability and activity in IR humans and in healthy, insulin sensitive (IS)/control humans. Insulin resistance was evaluated from plasma insulin and glucose responses to an oral glucose tolerance test, and by calculating the Matsuda index. Subjects were placed in the following groups: IR subjects, Matsuda index <4.0 (N=7; 4 males, 3 females); IS, Matsuda index >7.0 (N=11, 9 males, 2 females). IR and IS subjects received an intravenous infusion of insulin (1 mU/kg/min and 0.5 mU/kg/min, respectively) for 30 minutes to stimulate LPL activity. Whole-body endothelial-bound LPL was released from the vasculature by intravenous infusion of heparin. Plasma samples were collected 10 minutes after heparin infusion and analyzed for LPL concentration and activity, and ApoC3 and ApoC2 concentrations. Although plasma LPL concentrations were not different between groups (IR = 457 ± 17 ng/ml, IS = 453 ± 27 ng/ml, P = 0.02), plasma LPL activity was higher in the IR subjects (IR = 665 ± 113 nmol/min/ml, IS = 365 ± 59 nmol/min/ml, P = 0.02). IR subjects had higher concentrations of plasma ApoC3 (IR = 3.6 ± 0.5 mg/dl, IS = 2.7 ± 0.2 mg/dl, P=0.03). However, ApoC2 concentration was not different between groups (IR = 0.15 ± 0.03 mg/dl, IS = 0.11 ± 0.01 mg/dl, P = 0.11). These findings suggest that circulating APOC3 and ApoC2 are not key determinants regulating LPL activity during hyperinsulinemia in the vasculature of insulin resistant humans.
ContributorsJohnsson, Kailin Alexis (Author) / Katsanos, Christos (Thesis advisor) / Herman, Richard (Committee member) / De Filippis, Elena (Eleanna) (Committee member) / Arizona State University (Publisher)
Created2023
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Description
Introduction: The incidence of type 2 diabetes (T2D) in youth is projected to increase through 2060, especially in minority youth. Every Little Step Counts (ELSC) has demonstrated efficacy in reducing T2D risk factors in Latino youth. Documenting the adaptation of ELSC to a family diabetes prevention program (FDPP) could support

Introduction: The incidence of type 2 diabetes (T2D) in youth is projected to increase through 2060, especially in minority youth. Every Little Step Counts (ELSC) has demonstrated efficacy in reducing T2D risk factors in Latino youth. Documenting the adaptation of ELSC to a family diabetes prevention program (FDPP) could support future adaptation and scaling of FDPPs.Purpose: To describe the process that guided the adaptation of a culturally grounded evidenced-based DPP tailored to Latino families, with the aim of using the Framework for Reporting Adaptations and Modifications-Enhanced (FRAME) to classify adaptations. Methods/Design: The approach that guided the adaptation involved community-based participatory research (CBPR) and phases commonly used to adapt health interventions. Inductive and deductive content analysis guided by the FRAME was conducted on data collected throughout the phases to identify and classify adaptations. Data was then triangulated with the entities involved in the adaptation, analyzed to determine the frequency and proportion of adaptations across the FRAME categories and levels, and cross tabulated. Results: A total of N=66 adaptations were identified. Adaptations occurred with the highest frequency during the grant preparation and after the pilot study. Most adaptations were led by both the academic institution and community partners. Content modifications were most common. Prominent reasons for adaptation included organization/setting time constraints and integrating community partners’ and interventionists’ feedback. Discussion: Study results align with the CBPR approach that guided the adaptation and the ELSC core tenet of integrating community partnerships throughout all aspects of the intervention. To efficiently track adaptations, consensus as to what constitutes varying levels of adaptation granularity (i.e., macro, meso, micro) is needed. While tracking adaptations can be time and resource intensive, tracking adaptations may support the development of strategies to tie adaptations to outcomes. Conclusion: It is critical to determine when adaptations are needed to avoid a “culture of adaptation hyperactivity”. There is an opportunity to analyze past and future ELSC adaptations to better understand the intervention’s core tenets and the relationship between adaptations and outcomes. Future ELSC adaptations would benefit from considering how to incorporate feedback from diverse stakeholders and populations in preparation for scaling.
ContributorsDiaz, Monica (Author) / Shaibi, Gabriel Q (Thesis advisor) / Bruening, Meg (Committee member) / Shepard, Christina (Committee member) / Arizona State University (Publisher)
Created2024
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Description
Of the 2.87 million traumatic brain injuries (TBI) sustained yearly in the United States, 75% are diffuse injuries. A single TBI can have acute and chronic influences on the neuroendocrine system leading to hypothalamic-pituitary-adrenal axis (HPA) dysregulation and increased affective disorders. Preliminary data indicate TBI causes neuroinflammation in the hippocampus,

Of the 2.87 million traumatic brain injuries (TBI) sustained yearly in the United States, 75% are diffuse injuries. A single TBI can have acute and chronic influences on the neuroendocrine system leading to hypothalamic-pituitary-adrenal axis (HPA) dysregulation and increased affective disorders. Preliminary data indicate TBI causes neuroinflammation in the hippocampus, likely due to axonal damage, and in the paraventricular nucleus of the hypothalamus (PVN), where no axonal damage is apparent. Mechanisms regulating neuroinflammation in the PVN are unknown. Furthermore, chronic stress causes HPA dysregulation and glucocorticoid receptor (GR)-mediated neuroinflammation in the PVN. The goal of this project was to evaluate neuroinflammation in the HPA axis and determine if GR levels change at 7 days post-injury (DPI).

Adult male and female Sprague Dawley rats were subjected to midline fluid percussion injury. At 7 DPI, half of each brain was post-fixed for immunohistochemistry (IBA-1) and half biopsied for gene/protein analysis. IBA-1 staining was analyzed for microglia activation via skeleton analysis in the hypothalamus and hippocampus. Extracted RNA and protein were used to quantify mRNA expression and protein levels for GRs. Data indicate increased microglia cell number and decreased endpoints/cell and process length in the PVN of males, but not females. In the dentate gyrus, both males and females have an increased microglia cell number after TBI, but there is also an interaction between sex and injury in microglia presentation, where males exhibit a more robust effect than females. Both sexes have significant decreases of endpoints/cell and process length. In both regions, GR protein levels decreased for injured males, but in the hippocampus, GR levels increased for injured females. Data indicate that diffuse TBI causes alterations in microglia morphology and GR levels in the hypothalamus and hippocampus at 7 DPI, providing a potential mechanism for HPA axis dysregulation at a sub-acute time point.
ContributorsRidgway, Samantha (Author) / Thomas, Theresa C (Thesis advisor) / Newbern, Jason (Thesis advisor) / Bimonte-Nelson, Heather A. (Committee member) / Arizona State University (Publisher)
Created2019