Type 2 diabetes (T2D) is a complex metabolic disease that disproportionately affects African Americans. Obesity is a major risk factor for T2D, and it is postulated that chronic inflammation possibly stemming from adipose tissue macrophages and T cells plays a key role. Genome-wide association studies (GWAS) have identified over 20 disease loci that contribute to T2D in European Americans but few studies have been performed in admixed populations. We first performed a GWAS of 1,563 African Americans from the Vanderbilt Genome-Electronic Records Project and Northwestern University NUgene Project as part of the electronic Medical Records and Genomics (eMERGE) network. We successfully replicate an association in TCF7L2, previously identified by GWAS in our African American dataset. We were unable to identify novel associations at p<5.0x10-8 by GWAS. Admixture mapping disease loci in recently admixed populations is a powerful method used to identify disease loci in African Americans. Using admixture mapping, we sought to identify novel disease loci in the genome with T2D. Our admixture scan revealed multiple candidate genes with T2D, including TCIRG1, a T-cell immune regulator expressed in the pancreas and liver and not previously implicated in T2D. We performed a subsequent fine-mapping analysis to further assess the association with TCIRG1 and T2D in >5,000 African Americans. We successfully identified 13 independent associations in TCIRG1, CHKA, and ALDH3B1 genes on chromosome 11. Our results suggest a novel region on chromosome 11 identified by admixture mapping associated with T2D in African Americans and warrants additional replication and validation in this region.

Thesis--PlanB (M.S.)--University of Wisconsin--Stout, 2002. / Includes bibliographical references.

Thesis (Ph. D.)--Texas A & M University, 2003. / "Major Subject: Interdisciplinary Engineering." Title from author supplied metadata (automated record created on Apr. 30, 2004.). Vita. Abstract. Includes bibliographical references.

Angelman Syndrome (AS) is a devastating neurodevelopmental disorder characterized by developmental delay, speech impairment, movement disorder, sleep disorders and refractory epilepsy. AS is caused by loss of the Ube3a protein encoded for by the imprinted Ube3a gene. Ube3a is expressed nearly exclusively from the maternal chromosome in mature neurons. Mouse models have helped determine the molecular defects in AS, however findings have been inconsistent across laboratories. Work in our laboratory suggested that environmental factors may play a role in the phenotypes observed in AS model mice. As a result, we evaluated the possibility of non-genomic causes of variation in phenotypes observed in AS model mice. Here we demonstrate that maternal status and diet play a large role in the magnitude of a hypomyelination phenotype observed in these mice.

In this thesis we first briefly explore the barrier properties of monolayer graphene. We investigate how films of graphene can be used to decouple underlying metallic (Cu, Ni) substrate from the environment to passivate corrosion. In the remaining part of the thesis we explore the effects of the environment on electrical transport and optical properties of monolayer MoS2. In particular, we investigate the role of the underlying substrate, metallic contacts to MoS2 and phonons on intrinsic transport properties (e.g. carrier mobility) of MoS2. We then investigate the interplay between gate-induced charge carriers and excitons in MoS2 and discover the tunability of MoS2 optical properties (absorption/photoluminescence). Such strong electron-exciton interaction in MoS2 also opens up the possibility to study interesting quasi particles like trions and biexcitons in a 2D system. Finally, we thoroughly investigate Förster resonant energy transfer (FRET), a uniquely efficient long-range optical process, between quantum dots and monolayer MoS2. We discover that modest gate-induced variation in the excitonic absorption of MoS2 leads to large (~500%) changes in the FRET rate and allows modulation of quantum dot photoluminescence intensity.

Gallium Nitride or GaN-based high electron mobility transistors (HEMTs) is currently the most promising device technology in several key military and civilian applications due to excellent high-power as well as high-frequency performance. Even though the performance figures are outstanding, GaN-based HEMTs are not as mature as some competing technologies, which means that establishing the reliability of the technology is important to enable use in critical applications. The objective of this research is to understand the physical mechanisms affecting the reliability of GaN HEMTs at moderate drain biases (typically Vds < 30 V in the devices considered here). The degradation in device performance is believed to be due to the formation or modification of charged defects near the interface by hydrogen depassivation processes (due to electron-activated hydrogen removal) from energetic carriers. A rate-equation describing the defect generation process is formulated based on this assumption. A combination of ensemble Monte-Carlo (EMC) simulation statistics, ab-initio density functional theory (DFT) calculations, and accelerated stress experiments is used to relate the candidate defects to the overall degradation behavior (Vt and gm). The focus of this work is on the semi-ON mode of transistor operation in which the degradation is usually observed to be at its highest. This semi-ON state is reasonably close to the biasing region of class-AB high power amplifiers, which are popular because of the combination of high efficiency and low distortion that is associated with this configuration. The carrier-energy distributions are obtained using an EMC simulator that was developed specifically for III-V HFETs. The rate equation is used to model the degradation at different operating conditions as well as longer stress times from the result of one short duration stress test, by utilizing the carrier-energy distribution obtained from EMC simulations for one baseline condition. This work also attempts to identify the spatial location of these defects, and how this impacts the Vt shift and gm degradation of the devices.

The Department of Energy (DOE) is responsible for the cleanup of nuclear waste at former nuclear weapons sites across the United States. Cleanup activities of particular interest include the containment of waste in near surface disposal facilities. There is a need to build confidence in the predictive nature of long-term cover performance models, particularly when considering long-term impacts from climate change. This research aimed to develop an approach to assessing long-term performance of near surface disposal facilities under climate change impacts. This was accomplished by: (1) defining a methodology using historical precipitation and temperature data; (2) using a Monte Carlo approach to assess performance based on past events; (3) performing a proof of concept application; and (4) developing and assessing future climate change scenarios relative to percolation thresholds. From this research, it was determined that the HELP model is a useful tool to assess the hydrological performance of near surface disposal facilities in humid climates when degradation of designs is considered by modifying various hydraulic inputs. In addition, changes in both precipitation and temperature have been found to influence landfill cover performance; in many cases, the potential negative effects of additional precipitation on landfill cover performance can be offset by warmer temperatures. These developments and findings can have meaningful implications on future regulatory policies and guidelines when considering naturally occurring climatic change and anthropogenic forcing.

No description available.

Williams syndrome (WS) is a rare, neurodevelopmental disorder caused by the deletion of 26 genes on chromosome 7q11.23. WS has a well-defined auditory phenotype, characterized by a strong attraction and emotional reactivity to music, abnormal sensitivity to sounds (hyperacusis) and an aversion to or avoidance of sounds (phonophobia). Auditory abnormalities reported in WS also affect a wide range of neurodevelopmental, neuropsychiatric and neurological disorders. Little is known about sensory modulation, or the demonstration of maladaptive emotional and behavioral responses to sensory stimuli in WS. This study aims to describe a neural basis for impaired sensory modulation in atypical auditory processing characteristic of the WS phenotype. </p> To define functional and structural connectivity between brain regions involved in auditory processing, we recruited 18 individuals with WS and 18 controls, ages 16-50, for neuroimaging. In the absence of external stimuli, resting state fMRI (rs-fMRI) measures blood oxygenation level dependent (BOLD) signal that reflects baseline neuronal activation in functionally connected networks of brain regions, including the auditory processing network. We used rs-fMRI to identify a network of functional brain regions involved in auditory processing in WS. White matter (WM) integrity was assessed by DTI parameters providing a quantitative measure of water diffusion through axonal membranes. We used DTI to identify structural integrity differences in WM fiber tracts underlying auditory processing in WS. To provide a basis for understanding sensory modulation impairments in WS, 56 caregivers of individuals with WS, ages 5-49, were recruited to quantitatively describe sensory processing patterns, independent of clinical diagnoses. Atypical auditory response patterns, based on a self-report of sensory processing, were correlated with group differences in functional and structural connectivity in WS. This study constitutes the most comprehensive investigation of patterns of sensory processing in WS, spanning a wide age range, and provides a uniquely developmentally-informed basis for understanding behavioral difficulties and the clinical interventions that could address them. Investigating the relationship between patterns of auditory sensory responses and functional and structural connectivity measures elucidates a brain-behavior relationship related to atypical auditory processing.

Phosphors have been used for radiation detection before, but only for non-ionizing ra- diation. In fact, many phosphors are designed to be radiation-resistant so they can be used long-term and in harsh environments unaffected. Furthermore, many of the phosphors used in radiation environments are subjected to ionizing radiation. Our goal, however, is to find a material that changes permanently by non-ionizing radiation and that can be used as a record for radiation exposure. Ideally the material will be sensitive to a wide range of flu- ences as well as selective to different types and doses of radiation exposure. To determine if radiation can damage phosphors, we systematically exposed several materials to x-rays, alpha particles, protons, and neutrons. We expect radiation to cause displacement dam- age and change the structure of the material. Since phosphor luminescence intensity and lifetime are mainly governed by the arrangement of luminescent centers in the host lattice and the local crystal environment of each luminescence center, the optical properties can be used to detect these structural changes. The results of these experiments provide insight into the possible mechanisms of damage and instruct how to adjust our approach to developing a material with the desired interactions with radiation.