Differences in Abdominal and Liver Fat Accumulation Between Obesity-Matched Adults With and Without Type 2 Diabetes

Despite attempts to identify the mechanisms by which obesity leads to the development of Type 2 Diabetes (T2D), it remains unclear why some but not all adults with obesity develop T2D. Given the established associations between visceral adipose tissue (VAT) and liver fat with insulin resistance, we hypothesized that compared to age and obesity matched adults who were non-diabetic (NT2D), adults with T2D would have greater amounts of VAT and liver fat. The International Study of Prediction of Intra-Abdominal Adiposity and Its Relationship with Cardiometabolic Risk/Intra-Abdominal Adiposity (INSPIRE ME IAA) aims to study the associations between VAT and liver fat and risk of developing T2D and cardiovascular disease. Four thousand, five hundred and four participants were initially recruited; from this, 2383 White and Asian adults were selected for this ancillary analysis. The NT2D and T2D groups were matched for age, body mass index (BMI) and waist circumference (WC). The T2D and NT2D groups were also compared to participants with either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT; IFG/IGT)). Abdominal adipose tissue was measured by computed tomography; liver fat was estimated using computed tomography-derived mean attenuation. Secondary analysis determined whether differences existed between NT2D and T2D groups in VAT and liver fat accumulation within selected BMI categories for Whites and Asians. We report across sex and race, T2D and IFG/IGT groups had elevated VAT and liver fat compared to the NT2D group (p<0.05). VAT was not different between IFG/IGT and T2D groups (p>0.05), however liver fat was greater in the T2D group compared to the IFG/IGT group in both Whites and Asians (p<0.05). Within each BMI category, the T2D group had elevated VAT and liver fat compared to the age and anthropometrically matched NT2D group in both Whites and Asians (p<0.05). With few exceptions, abdominal subcutaneous adipose tissue was not different in the T2D or IFG/IGT groups compared to the NT2D group independent of sex and race. Compared to age and obesity-matched adults who are NT2D, we observe that White and Asian adults with T2D, and those with IFG/IGT, present with greater levels of both VAT and liver fat.

International Capital Flows and Monetary Policy Spillovers

This dissertation examines the drivers and implications of international capital flows. The overarching motivation is the observation that countries not at the centre of global financial markets are subject to considerable spillovers from centre countries, notably from their monetary policy. I present new empirical evidence on the determinants of the observed patterns of international capital flows and monetary policy spillovers, and study their effect on both financial markets and the real economy. In Chapter 2 I provide evidence on the determinants of a puzzling negative correlation observed between productivity growth and net capital inflows to developing and emerging market economies (EMEs) since 1980. By disaggregating net capital inflows into their gross components, I show that this negative correlation is explained by capital outflows related to purchases of very liquid assets from the fastest growing countries. My results suggest a desire for international portfolio diversification in liquid assets by fast growing countries is driving much of the original puzzle. In the reminder of my dissertation I pivot to study the foreign characteristics that drive international capital flows and monetary policy spillovers, with a particular focus on the role of unconventional monetary policy in the United States (U.S.). In Chapter 3 I show that a significant portion of the heterogeneity in EMEs' asset price adjustment following the quantitative easing operations by the Federal Reserve (the Fed) during 2008-2014 can be explained by the degree of bilateral capital market frictions between these countries and the U.S. This is true even after accounting for capital controls, exchange rate regimes, and domestic monetary policies. Chapter 4, co-authored with Michal Ksawery Popiel, studies unconventional monetary policy in a small open economy, looking specifically at the case of Canada since the global financial crisis. We quantify the effect Canadian unconventional monetary policy shocks had on the real economy, while carefully controlling for and quantifying spillovers from U.S. unconventional monetary policy. Our results indicate that the Bank of Canada's unconventional monetary policy increased Canadian output significantly from 2009-2010, but that spillovers from the Fed's policy were even more important for increasing Canadian output after 2008.

Design and Implementation of Tools for STM Studies in UHV and at the Solid-Liquid Interface

This thesis presents details of the design and development of novel tools and instruments for scanning tunneling microscopy (STM), and may be considered as a repository for several years' worth of development work. The author presents design goals and implementations for two microscopes. First, a novel Pan-type STM was built that could be operated in an ambient environment as a liquid-phase STM. Unique features of this microscope include a unibody frame, for increased microscope rigidity, a novel slider component with large Z-range, a unique wiring scheme and damping mechanism, and a removable liquid cell. The microscope exhibits a high level of mechanical isolation at the tunnel junction, and operates excellently as an ambient tool. Experiments in liquid are on-going. Simultaneously, the author worked on designs for a novel low temperature, ultra-high vacuum (LT-UHV) instrument, and these are presented as well. A novel stick-slip vertical coarse approach motor was designed and built. To gauge the performance of the motor, an in situ motion sensing apparatus was implemented, which could measure the step size of the motor to high precision. A new driving circuit for stick-slip inertial motors is also presented, that o ffers improved performance over our previous driving circuit, at a fraction of the cost. The circuit was shown to increase step size performance by 25%. Finally, a horizontal sample stage was implemented in this microscope. The build of this UHV instrument is currently being fi nalized. In conjunction with the above design projects, the author was involved in a collaborative project characterizing N-heterocyclic carbene (NHC) self-assembled monolayers (SAMs) on Au(111) films. STM was used to characterize Au substrate quality, for both commercial substrates and those manufactured via a unique atomic layer deposition (ALD) process by collaborators. Ambient and UHV STM was then also used to characterize the NHC/Au(111) films themselves, and several key properties of these films are discussed. During this study, the author discovered an unexpected surface contaminant, and details of this are also presented. Finally, two models are presented for the nature of the NHC-Au(111) surface interaction based on the observed film properties, and some preliminary theoretical work by collaborators is presented.

3D considerations for motion perception and visuomotor transformations

Moving through a stable, three-dimensional world is a hallmark of our motor and perceptual experience. This stability is constantly being challenged by movements of the eyes and head, inducing retinal blur and retino-spatial misalignments for which the brain must compensate. To do so, the brain must account for eye and head kinematics to transform two-dimensional retinal input into the reference frame necessary for movement or perception. The four studies in this thesis used both computational and psychophysical approaches to investigate several aspects of this reference frame transformation. In the first study, we examined the neural mechanism underlying the visuomotor transformation for smooth pursuit using a feedforward neural network model. After training, the model performed the general, three-dimensional transformation using gain modulation. This gave mechanistic significance to gain modulation observed in cortical pursuit areas while also providing several testable hypotheses for future electrophysiological work. In the second study, we asked how anticipatory pursuit, which is driven by memorized signals, accounts for eye and head geometry using a novel head-roll updating paradigm. We showed that the velocity memory driving anticipatory smooth pursuit relies on retinal signals, but is updated for the current head orientation. In the third study, we asked how forcing retinal motion to undergo a reference frame transformation influences perceptual decision making. We found that simply rolling one's head impairs perceptual decision making in a way captured by stochastic reference frame transformations. In the final study, we asked how torsional shifts of the retinal projection occurring with almost every eye movement influence orientation perception across saccades. We found a pre-saccadic, predictive remapping consistent with maintaining a purely retinal (but spatially inaccurate) orientation perception throughout the movement. Together these studies suggest that, despite their spatial inaccuracy, retinal signals play a surprisingly large role in our seamless visual experience. This work therefore represents a significant advance in our understanding of how the brain performs one of its most fundamental functions.

SINGLE STAGE LED DRIVER TECHNOLOGY WITH LOW FREQUENCY RIPPLE CANCELLATION

Because of high efficacy, long lifespan, and environment-friendly operation, LED lighting devices become more and more popular in every part of our life, such as ornament/interior lighting, outdoor lightings and flood lighting. The LED driver is the most critical part of the LED lighting fixture. It heavily affects the purchasing cost, operation cost as well as the light quality. Design a high efficiency, low component cost and flicker-free LED driver is the goal. The conventional single-stage LED driver can achieve low cost and high efficiency. However, it inevitably produces significant twice-line-frequency lighting flicker, which adversely affects our health. The conventional two-stage LED driver can achieve flicker-free LED driving at the expenses of significantly adding component cost, design complexity and low the efficiency. The basic ripple cancellation LED driving method has been proposed in chapter three. It achieves a high efficiency and a low component cost as the single-stage LED driver while also obtaining flicker-free LED driving performance. The basic ripple cancellation LED driver is the foundation of the entire thesis. As the research evolving, another two ripple cancellation LED drivers has been developed to improve different aspects of the basic ripple cancellation LED driver design. The primary side controlled ripple cancellation LED driver has been proposed in chapter four to further reduce cost on the control circuit. It eliminates secondary side compensation circuit and an opto-coupler in design while at the same time maintaining flicker-free LED driving. A potential integrated primary side controller can be designed based on the proposed LED driving method. The energy channeling ripple cancellation LED driver has been proposed in chapter five to further reduce cost on the power stage circuit. In previous two ripple cancellation LED drivers, an additional DC-DC converter is needed to achieve ripple cancellation. A power transistor has been used in the energy channeling ripple cancellation LED driving design to successfully replace a separate DC-DC converter and therefore achieved lower cost. The detailed analysis supports the theory of the proposed ripple cancellation LED drivers. Simulation and experiment have also been included to verify the proposed ripple cancellation LED drivers.

ENVIRONMENTAL INFLUENCES AND EPIGENETIC MECHANISMS IN RISK FOR DEPRESSION

Genetic and environmental factors interact to influence vulnerability for internalizing psychopathology, including Major Depressive Disorder (MDD). The mechanisms that account for how environmental stress can alter biological systems are not yet well understood yet are critical to develop more accurate models of vulnerability and targeted interventions. Epigenetic influences, and more specifically, DNA methylation, may provide a mechanism by which stress could program gene expression, thereby altering key systems implicated in depression, such as frontal-limbic circuitry and its critical role in emotion regulation. This thesis investigated the role of environmental factors from infancy and throughout the lifespan affecting the serotonergic (5-HT) system in the vulnerability to and treatment of depression and anxiety and potential underlying DNA methylation processes. First, we investigated the contributions of additive genetic vs. environmental factors on an early trait phenotype for depression (negative emotionality) in infants and their stability over time in the first 2 years of life. We provided evidence of the substantial contributions of both genetic and shared environmental factors to this trait, as well as genetically- and environmentally- mediated stability and innovation. Second, we studied how childhood environmental stress is associated with peripheral DNA methylation of the serotonin transporter gene, SLC6A4, as well as long-term trajectories of internalizing behaviours. There was a relationship between childhood psychosocial adversity and SLC6A4 methylation in males, as well as between SLC6A4 methylation and internalizing trajectory in both sexes. Third, we investigated changes in emotion processing and epigenetic modification of the SLC6A4 gene in depressed adolescents before and after Mindfulness-Based Cognitive Therapy (MBCT). The alterations from pre- to post-treatment in connectivity between the ACC and other network regions and SLC6A4 methylation suggested that MBCT may work to optimize the connectivity of brain networks involved in cognitive control of emotion as well as also normalize the relationship between SLC6A4 methylation and activation patterns in frontal-limbic circuitry. Our results from these three studies strengthen the theory that environmental influences are critical in establishing early vulnerability factors for MDD, driving epigenetic processes, and altering brain processes as an individual undergoes treatment, or experiences relapse.

Polymer Light-Emitting Electrochemical Cells with Embedded Bipolar Electrodes: Visualizing Bipolar Electrochemistry in Solid State

The work presented in this thesis examines the properties of BPEs of various configurations and under different operating conditions in a large planar LEC system. Detailed analysis of time-lapsed fluorescence images allows us to calculate the doping propagation speed from the BPEs. By introducing a linear array of BPEs or dispersed ITO particles, multiple light-emitting junctions or a bulk homojunction have been demonstrated. In conclusion, it has been observed that both applied bias voltages and sizes of BPEs affected the electrochemical doping from the BPE. If the applied bias voltage was initially not sufficiently high enough, a delay in appearance of doping from the BPE would take place. Experiments of parallel BPEs with different sizes (large, medium, small) demonstrate that the potential difference across the BPEs has played a vital role in doping initiation. Also, the p-doping propagation distance from medium-sized BPE has displayed an exponential growth over the time-span of 70 seconds. Experiments with a linear array of BPEs with the same size demonstrate that the doping propagation speed of each floating BPE was the same regardless of its position between the driving electrodes. Probing experiments under high driving voltages further demonstrated the potential of having a much more efficient light emission from an LEC with multiple BPEs.